Abstract
Big Data
PO-02-001
Headache Version 2.0 Common Data Element (CDE) Recommendations: Updates to the National Institute of Neurological Disorders and Stroke (NINDS) Headache CDEs
Sarah Tanveer1,*, Sherita Ala’i1, Joy Esterlitz1, Katelyn Gay1 and Michael L Oshinsky2; on behalf of Headache V2.0 CDE Working Group
1The Emmes Corporation, Rockville
2National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, United States
Objectives
The National Institute of Neurological Disorders and Stroke (NINDS) Headache Common Data Elements (CDE) project was initiated to specifically develop data standards for clinical research within the neurological community. The vision of this initiative is to create common data elements and definitions so that information is consistently captured and recorded across studies in order to: increase the efficiency and effectiveness of clinical research studies and clinical treatment, increase data quality, facilitate data sharing across studies, more effectively aggregate information into significant metadata results, significantly reduce study start-up time, and help educate new clinical investigators. Since the 2011 release of Version 1.0 (V1.0) of the Headache CDEs, the research community felt that updates were necessary to better serve the purpose of harmonizing data collection. In July 2017, the Headache Version 2.0 (V2.0) CDEs will be released; the intent of the revisions are to provide updated recommendations based on the current state of headache research.
Methods
In 2016, a Headache V2.0 working group (WG) was established to review the CDEs and associated recommendations from 2011. The updates to the headache CDEs are based on clinical advancements and developments in the field of headache research, as well as user feedback of existing CDEs.
The Headache V2.0 WG, consisting of 42 worldwide experts, met monthly from August 2016 to May 2017 to review, revise and add to the headache-specific V1.0 CDEs. WG members selected and recommended instruments and assessments, and also refined and added to existing field-tested data elements from national registries and studies. Recommendations were revised and posted to the NINDS CDE website for public use.
Results
This second iteration of Headache CDE recommendations spans the following five domains: Biomarkers; Demographics; Imaging and Neurophysiology; Therapies and Intervention; and, Diagnostics and Characteristics. Headache V2.0 CDEs will be released to the NINDS CDE website in July 2017.The latest information provided at this meeting includes examples of how headache CDEs may be used by researchers, and how to navigate and select CDEs from the NINDS CDE website.
Conclusion
The NINDS CDEs are an evolving resource that is constantly being updated as research progresses. NINDS encourages use of CDEs by the clinical research community in order to standardize the collection of research data across studies. Through the development of the Headache V2.0 CDEs, the initiative strives to promote CDE standards designed to assist researchers in the various stages of design, implementation, and interpretation of their clinical study data.
Disclosure of Interest
S. Tanveer: None Declared, S. Ala’i: None Declared, J. Esterlitz: None Declared, K. Gay: None Declared, M. Oshinsky Conflict with: National Institute of Health
Big Data
PO-02-002
N = 1 statistical approaches to examine risk factor profiles of ICHD-3beta classified headaches versus migraines within individuals
Ty Ridenour1, Francesc Peris2, Gabriel Boucher2, Alec Mian2,3, Stephen Donoghue2,* and Andrew Hershey3
1RTI International, Research Triangle Park
2Curelator Inc., Cambridge
3CCHMC, Cincinnati, United States
Objectives
To what extent do migraines vs non-migraine headaches (distinguished by ICHD-3beta criteria) differ in underlying pathophysiology? This study examines risk factors associated with the (a) incidence (onset) and (b) severity of both migraine vs non-migraine headaches. Because profiles of headache triggers vary greatly among patients, statistical analyses were conducted at the individual level and the individual-level results were then used to draw sample aggregate conclusions.
Methods
Participants were 750 individuals with migraine identified by clinician referral or via the internet and registered to use a novel digital platform (Curelator HeadacheTM). Participants completed baseline questionnaires and then entered daily data on headache occurrence and severity (level of pain), ICHD-3beta migraine criteria, and exposure to 70 migraine risk factors. Nearly 88% of the sample was female. Risk factors spanned emotions, sleep qualities, environmental and weather factors, lifestyle, diet, substance use, travel, and three additional triggers selected by each patient. Cox regression hazard ratios tested associations between occurrence of a migraine (binomial) and the triggers. A form of hierarchical linear modeling tailored for N = 1 analysis (termed mixed model trajectory analysis or MMTA) tested associations between triggers and pain severity of (non)migraine headaches. MMTA statistically controlled for patient-specific time-related trends in pain severity, autocorrelation, and used statistical tests that generate conservative estimates for N = 1 analyses. Severity of headache was rated by patients on a mild – moderate – severe scaling.
Results
Among the individual-level associations between a risk factor and severity of pain from a headache, 50% of risk factors were associated with both migraine and non-migraine headaches whereas the other half were unique to one form of headache or the other. The particular risk factors that were associated with either form of headache varied greatly among individual patients.
Conclusion
Results suggest that triggers of onset of migraine attacks both overlap and differ from the risk factors that are associated with the severity of migraine pain. Moreover, these associations differ between migraine and non-migraine headaches. These observations imply that etiological factors differ between types of headaches. They further suggest that treatment of migraine headaches could aim to not only prevent the incidence of attacks, but also reduce the pain (and thus impairment) that patients experience during a migraine headache.
Disclosure of Interest
T. Ridenour: None Declared, F. Peris Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., G. Boucher Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., A. Mian Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., S. Donoghue Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., A. Hershey Conflict with: Alder, Amgen, Depomed, Impax, Eli Lilly, Upsher-Smith, Conflict with: Avanir, Curelator, Impax, Supernus
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-003
Clinical profile of SUNCT/SUNA in Japan - a clinic-based study
Shoji Kikui1,*, Jun-Ichi Miyahara1, Hanako Sugiyama1, Kentaro Yamakawa1, Yoshihiro Kashiwaya1, Kumiko Ishizaki2, Daisuke Danno3 and Takao Takeshima1
1Department of Neurology, Headache Center, Tominaga hospital, Osaka
2Department of Rehabilitation, Kaikoukai Rehabilitation Hospital, Aichi
3Department of Neurology, Hyogo College of Medicine, Hyogo, Japan
Objectives
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are rare primary headache syndromes, classified as trigeminal autonomic cephalalgias (TACs). Most studies of SUNCT/SUNA have focused on Caucasian populations, and thus, little is known about the characteristics of SUNCT/SUNA in patients from Asia. We characterized the clinical profile of SUNCT/SUNA in Japan by surveying patients with SUNCT/SUNA registered at a Japanese regional headache center.
Methods
The classification and clinical features of 20 consecutive patients with SUNCT (8 males, 3 females; mean age, 59.5 ± 20.5 years) and SUNA (5 males, 3 females; mean age, 51.3 ± 18.4 years) visiting a tertiary Headache center (Tominaga hospital) from February 2011 to January 2017 were analyzed. The diagnosis of headache was established in accordance with ICHD-2 or 3beta.
Results
Eight cases were previously diagnosed as cluster headache (CH), 7 as trigeminal neuralgia (TN), and 2 as migraine at clinics or hospitals. Only 2 cases were diagnosed as SUNCT previously. The attacks were left-sided in 7 cases and right-sided in 13; none of the patients had bilateral or side-shifting attacks. All patients reported either brief clusters of separate attacks or a saw-tooth pattern of attacks. An episodic disease course was evident in 19/20 (95.0%) cases, whereas 1/20 (5.0%) had a chronic course. Mean attack duration was 91.9 ± 87.9 s, being <30 s in 6/20 (30.0%) cases, approximately 60 s in 5/20 (25.0%), approximately 120 s in 3/20 (15.0%), and >120 s in 6/20 (30.0%). Besides ipsilateral conjunctival injection and lacrimation, ipsilateral rhinorrhea occurred in 9/20 (45.0%) and facial sweating in 1/20 (5.0%). Three out of 20 (15.0%) patients were smokers and 4/20 (20.0%) were alcohol consumers. A good or excellent response to lamotrigine was seen in 9/9 (100%), but toxic eruption was seen in 2/9 (22.2%). Pregabalin was effective in 3/10 (30.0%), gabapentin in 4/5 (80.0%), topiramate in 2/3 (66.7%), and carbamazepine in 2/4 (50.0%). An intravenous lidocaine proved completely effective for acute attacks of SUNCT in 5/6 (83.3%). Poor response was seen in a chronic SUNCT case. Indomethacin was ineffective in 6/7 (85.7%) cases; the good response to indomethacin in one patient may be because of the coexistence of SUNA and paroxysmal hemicranias in that patient. Computed tomography was used for investigation in one patient and magnetic resonance imaging (MRI) in the remaining patients. In 11 cases, the MRI revealed ipsilateral trigeminal neurovascular compression (NVC). Five cases were thought to have been transformed from TN. One SUNCT case with ipsilateral trigeminal NVC was treated with microvascular decompression, and the pain relieved postoperatively.
Conclusion
As in Caucasian patients, lamotrigine is effective in the majority of cases, and intravenous lidocaine is useful as an acute medication for severe recalcitrant attacks in Japanese patients with SUNCT/SUNA. However, patients in this study showed a relatively low prevalence of chronic SUNCT/SUNA (5%). Chronic CH is reported to show relatively low prevalence in Asia. Thus, chronic TACs may show relatively low prevalence in Asia. MRI revealed ipsilateral trigeminal NVC in 11 cases, and 5 cases were thought to have been transformed from TN. Therefore, despite being considered distinct conditions, emerging clinical and radiological evidence supports a broader nosological concept for SUNCT/SUNA and TN. Further evidence is required to shed light on this nosological issue, given its potential impact on clinical practice and future studies.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-004
Reliability of a preliminary questionnaire for detecting cluster headache among primary headache disorders
Soo-Jin Cho1,*, Pil-Wook Chung2, Mi-Ji Lee3, Chin-Sang Chung3, Byung-Kun Kim4, Tae-Jin Song5, Byung-Su Kim6, Kwang-Yeol Park7, Heui-Soo Moon2 and Min Kyung Chu8; Korean Cluster Headache Registry Group
1Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong
2Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine,
3Neurology, Neuroscience Center, Samsung Medical Center, Sungkyunkwan University School of Medicine
4Neurology, Eulji University School of Medicine
5Neurology, Ewha Womans University School of Medicine, Seoul
6Neurology, Bundang Jesaeng Hospital, Seongnam
7Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine
8Neurology, Kanam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea, Republic Of
Objectives
Cluster headache is a severe debilitating form of primary headache disorder. Due to similarity to migraine and remission periods, cluster headache has been misdiagnosed and neglected. For early detecting cluster headache, we developed an 8-item self-administered tool and test its reliability among the patients with primary headache disorders.
Methods
The candidate items were selected from the diagnostic guidelines of cluster headache from the international classification of headache disorder 3rd edition beta version and expert opinions. The total score was calculated the sum of positive response to each items. Like the clinical setting of first visit patients for headache, the reliability and validity were tested among patients with various primary headache disorders
Results
In total, 342 patients were enrolled: 28 with cluster headache, 254 with migraine, 44 with tension-type headache, and 16 with primary stabbing headache. Cronbach alpha is 0.619 and the areas under the curve were 0.922 in receiver operating characteristic curves for all 8 items. Using the total score of 5 as cut-value, sensitivity and specificity were 78.6% and 81.4% for cluster headache disorder including probable and chronic subtypes and 83.3% and 90.9% for definite episodic cluster headache among 342 patients. The validity was similar in differentiating cluster headache from migraine. Remission or cluster period did not influence the detecting rate.
Conclusion
This preliminary self-administered questionnaire for cluster headache is reliable and useful tool. It may be suitable for detecting cluster headache among primary headache disorders.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-005
Cluster Headache – Clinical pattern and a new severity scale in a Swedish cohort
Anna Steinberg1, Carmen Fourier2, Caroline Ran2, Elisabet Waldenlind1, Christina Sjöstrand1 and Andrea Carmine Belin2,*
1Clinical Neuroscience
2Neuroscience, Karolinska Institutet, Stockholm, Sweden
Objectives
Cluster headache (CH) patients exhibit a broad variance regarding disease burden. The objectives of this study were to investigate clinical features of the CH population in the central part of Sweden and to construct a new scale for grading severity.
Methods
Subjects were recruited from central Sweden and identified by screening medical journals for patients with the ICD 10 code G44.0, i.e. cluster headache. The study was designed as an observational survey and health records were read to confirm that the diagnosis fulfilled the International Headache Society criteria. All participating research subjects filled in a questionnaire including personal, demographic and medical aspects as well as questions designed to assess the CH pattern. We constructed a novel scale for grading severity of CH: the Cluster Headache Severity Scale (CHSS). The scale included three score items; number of attacks per day, attack duration and period duration. The lowest total score summarizing these score items was three and the highest 12. We used the CHSS to grade 500 subjects suffering from CH and further implemented the scale by defining and characterizing a CH maximum severity (CHMS) subgroup with a CHSS score ≥9.
Results
Our data show that chronic CH patients have a later mean age at onset compared to episodic patients and a majority (66.7%) of the patients reported that attacks appear at certain time intervals. In addition we report that CH patients who are current tobacco users or have a history of tobacco consumption had a later age of disease onset (31.7 years) compared to non-tobacco users (28.5 years). The CHSS was higher in the patient group reporting sporadic or no alcohol intake, than in the groups reporting an alcohol consumption of 3–4 standard units/week or more. A larger proportion of episodic patients had a regular alcohol intake compared to chronic patients and alcohol was identified to be the most common trigger factor for cluster attacks during a bout. In addition, a large male dominance (68%) was found in the whole study population, in contrast to the most severely affected subgroup (CHMS) where the distribution was less shifted, 56.9% men compared to 43.1% women. CHMS patients were further characterized by a higher age at disease onset, greater use of prophylactic medication, reduced hours of sleep, and lower alcohol consumption compared to the non-CHMS group.
Conclusion
There was a wide variation of severity grades among CH patients, with very marked impact on daily living for the most profoundly affected.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-006
Illicit Drug use among Cluster Headache Patients compared to the Dutch Population
Willemijn Naber1, Ilse De Coo1, Joost Haan1,2, Michel Ferrari1 and Rolf Fronczek1,*
1Neurology, Leiden University Medical Centre, Leiden
2Neurology, Alrijne Hospital, Leiderdorp, Netherlands
Objectives
Many cluster headache patients believe that illicit drugs might be effective in treating and preventing attacks. We systematically determined the use and assessed the effects of illicit drugs in a cluster headache population in the Netherlands - where use of cannabis is tolerated.
Methods
This cross-sectional study was conducted as part of the Leiden University Cluster Headache neuro-analysis programme (LUCA). Persons with cluster headache (n = 756) received a questionnaire designed by the authors, involving lifetime use of illicit drugs (cannabis, cocaine, heroin, PSI, MDMA, LSD, amphetamine and GHB) and their effect on attacks. Results were compared with age-matched data from the Dutch general population (n = 30.000) from the ‘Dutch annual health survey’.
Results
The response rate was 85.1%. There were more illicit drug users among cluster headache patients than in the general population (all drugs 32% vs. 24% (P < 0.01); cannabis 30% vs. 23% (P < 0.01); cocaine 9% vs. 5% (P < 0.01); amphetamine 6% vs. 4% (P = 0.01), PSI 9% vs. 4% (P < 0.01); heroin 1% vs. 0.5% (P = 0.04). No difference in illicit drug use was found between episodic and chronic cluster headache (31% vs. 32%; P = 0.41). Among cluster headache patients and in the general population, males more often used illicit drugs (29% vs. 19%; P < 0.01 and 35% vs. 24%; P < 0.01). The age distribution of illicit drug use followed the same pattern among cluster headache patients as in the general population, with less use of illicit drugs in older age cohorts. A positive influence on attack frequency was reported in 56% of LSD users, while 18% of GHB users reported a negative influence. Decreased attack duration was reported in 50% of PSI and heroin users, while 4–11% of cocaine, GHB, cannabis and MDMA users reported a prolonged attack duration.
Conclusion
In a Dutch cluster headache population remarkably many patients use illicit drugs. This might either be due to an actual alleviatory effect on cluster headache attacks, or due to false believe among people desperately seeking relieve of their cluster headache.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-007
The Psycho-Social impact of living with Cluster headaches: A scoping study
Katie Clarke-Day1,* and Michelle Clarke-Day1
1Not Just a Headache, Nottingham, United Kingdom
Objectives
‘Cluster headache (CH) is commonly regarded as one of the most disabling headache conditions, and referred to as one of the most painful conditions known to humankind (Torkamani et al., 2015)’. There has been limited research exploring the severe impact of CH and the consequences this has on the more psychological and social aspects of life. The objective of this research is to identify the social and psychological issues faced by those living with a diagnosis of Cluster headache and begin to explore some resilience factors and opportunities to offer appropriate support and advice to those living with a CH diagnosis. The primary author is a Chronic CH/TAC sufferer as well as a Social worker & Health psychologist.
Methods
Initially an online survey was advertised through online CH support groups, this elicited 375 responses. Demographics were collected and a single open ended question was asked, asking participants to identify areas of their life affected by CH diagnosis. The responses were analysed using thematic analysis. Following this In depth interviews (n = 10) with a small sample of respondents were arranged to begin to explore the complexities of the themes. Finally 2 focus groups were arranged to allow individuals living bringing CH patients together. Themes identified in the first 2 stages were reviewed by the groups and they were asked what it was about CH that led to people having issues in these areas of their life. The participants shared their experiences of living with the issues identified by the themes presented. These participants were asked to discuss what has helped them cope and what they feel is missing in order for them to be able to cope.
Results
375 (48.66% Male, 51.34% female) completed an online questionnaire. All respondents had a formal diagnosis of CH (56.8% episodic and 4.2% chronic) and were asked ‘aside from the medical and physical impact of your CH diagnosis what areas of your life have been most affected by your CH diagnosis?’ Only 3 respondents said that their diagnosis has no impact on their lives. 13 key themes were identified in the analysis of the responses. During further analysis these themes were grouped together under 3 headings; ‘Work & career’, ‘Relationships’ and ‘Physical & mental wellbeing’. Further stages of the research reinforced these themes and allowed us to identify some of the complexities behind each theme. It became apparent that the themes identified were rooted in common experiences of CH patients including: pain; isolation; lack of/misunderstanding of the condition by health professionals and lay persons alike.
Conclusion
Patients with CH identified several areas where their day to day life was affected significantly by their diagnosis. Aspects of the condition such as pain and lack of sleep were identified as having consequences for psychological and social wellbeing. This reinforced the need for better management and ongoing support for patients living with CH by both medical and allied health professionals. The findings also concluded that better management by medical professionals would facilitate better self-management of the condition by the patient, the benefits of which are explored in this paper. There are additional challenges for patient groups and appropriate professionals to raise awareness of not only the identified psychological and social impact of a CH diagnosis but also a general increased awareness of the condition as this lack of understanding has a significant impact on patient wellbeing.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-008
Trigeminal Autonomic Cephalalgias in tertiary Multi-disciplinary Orofacial Pain clinic
Diana Y Wei1,*, Tara F Renton2 and Peter J Goadsby1,3
1Headache Group, Department of Basic and Clinical Neuroscience
2Oral Surgery, Institute of Dentistry
3NIHR Welcome Trust King’s Clinical Research Facility, King's College London, London, United Kingdom
Objectives
Patients with headache often present to different specialities and in particular Trigeminal Autonomic Cephalalgia (TACs) patients are often seen by dentists. Of patients with cluster headaches 45% have consulted a dentist prior diagnosis and many have had procedures performed for the pain.
To evaluate the final diagnosis made from patients seen at a tertiary Multi-disciplinary Orofacial Pain clinic.
Methods
A retrospective review of clinic letters of patients who have attended the Multidisciplinary Orofacial Pain clinic over a ten month period, from September 2015 till July 2016, looking specifically at the final diagnoses.
Results
Of patients (n = 126) seen in clinic, 34 were follow up assessments and excluded. New patients (n = 92) had an average age of 52 years, and most were female (n = 63, 68%). The most common diagnosis made in the Clinic was a TAC (38 %), followed by migraine (37%) and post-traumatic trigeminal neuropathy (10%). The most common TAC diagnosis was possible hemicrania continua (74%), three were confirmed with indomethacin testing (two had oral indomethacin trials), two were negative on placebo-controlled intramuscular indomethacin testing and two were inconclusive on placebo-controlled intramuscular indomethacin test, the rest are awaiting testing.
Conclusion
TACs are the most common diagnosis made by the Headache team in our Multidisciplinary Orofacial Pain clinic. We conclude the importance of a multidisciplinary team approach to these complex patients.
Disclosure of Interest
D. Wei: None Declared, T. Renton: None Declared, P. Goadsby Conflict with: Allergan, Amgen, and Eli-Lilly and Company, Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion, Conflict with: MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press and eNeura
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-009
Availability of effective evidence-based symptomatic treatments for cluster headache in the EU countries. A survey of the European Headache Alliance
Paolo Rossi1 and Elena Ruiz De La Torre2,*
1European Headache Alliance, Vice-President, Rome, Italy
2European Headache Alliance, President, Valencia, Spain
Objectives
Treating cluster headache can be tricky because the pain becomes extremely severe very quickly and only few evidence-based treatments can work. Recent data from IHS suggest that oxygen is not universally reimbursed or available for CH patients. The aim of this study was to assess the reimbursement option and accessibility of 4 effective medicines for CH (sumatriptan s.c, oxygen, sumatriptan spray and zolmitriptan spray) across EU
Methods
A brief survey investigating the availability of symptomatic treatments for CH was send on e-mail on January 2017 to at least one headache specialist for every single country of the EU. For a complimentary point of view In the countries where active CH patients’ associations exist the survey was completed by CH expert patients.
Results
The questionnaire was completed by 26 headache specialists (93% of the EU countries representing 99.75% of the European population) and 10 CH expert patients (representing 72% of the European population). The answers provided by the headache specialists and expert patients were coherent in every country. Availability of ETs was defined as: a) complete: both oxygen and sumatriptan vial fully reimbursable and accessible; b) restricted: partial reimbursment or inaccessibility of one between Oxy and Suma s.c; c) lacking: both oxygen and sumatriptan s.c not reimbursable and not accessible
Oxygen was reimbursable for 62.68% of the CH population. Oxygen device was reimbursable for 49% of the CH population. Sumatriptan s.c. was reimbursable for 65% and accessible without restrictions for 37.1% of the CH population. Sumatriptan spray was reimbursable for 64% and accessible without restrictions for 43.7% of the CH population. Zolmitriptan spray was reimbursable for 23.7% and accessible without restrictions for 30.9% of the CH population.
Availability of CH effective treatments resulted complete, restricted or lacking for 49%, 30% and 21% respectively of the CH European patients
Conclusion
Based on this survey only 50% of the EU population had an unrestricted access to CH effective treatments with unacceptable inequalities between eastern countries and the rest of Europe. Headache societies and patients’ associations should pressure European and national health authorities to improve the availability of effective symptomatic treatments for CH.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-010
Pre-attack symptoms in cluster headache
Agneta Snoer1,*, Nunu Lund1, Mads Barloese1,2, Rasmus P Beske1 and Rigmor H Jensen1
1Dept. of Neurology, Danish Headache Center
2Dept. of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Glostrup, Denmark
Objectives
In contrast to the premonitory phase of migraine, only little is known about the pre-attack (prodromal) phase of a cluster headache (CH). We aimed to describe the nature, prevalence and duration of pre-attack symptoms in CH.
Methods
Patients with episodic CH and chronic CH, according to ICHD III (beta), were invited to participate. To avoid unnecessary recall bias, only episodic patients in active cluster and chronic cluster headache patients were included in the study. Patients were divided with regards to gender and CH diagnosis for group comparisons. All patients underwent a semi-structured interview where they were asked about presence of 31 symptoms in relation to a typical CH attack. Symptoms included previously reported CH pre-attack symptoms, premonitory migraine symptoms and accompanying symptoms of migraine and CH. Symptoms were grouped into: local and painful, local and painless and general.
Results
Eighty patients, 29 (36.3%) episodic CH, and 49 (61.3%) men, were included in the study. Of these patients, 86.3% reported pre-attack symptoms. Local and painful symptoms, occurring on average 29 min before the attack was reported by 70% of patients, 43.8% patients reported local and painless symptoms on average 38 minutes before the attack and 62.5% reported general symptoms on average 42 minutes before an attack. Of the local and painless symptoms, reported by 32.5% of patients, lacrimation, nasal congestion and rhinorrhea occurred at a median time of 5 minutes before the subsequent attack. Patients experienced on average 4.25 (SD 3.9) pre-attack symptoms: local and painful: 1.06 (SD 0.9), local and painless: 1.03 (SD 1.6) and general: 2.16 (SD 2.5). Apart from a dull/aching sensation in the area of the subsequent attack being experienced significantly (p < 0.05) more among men and episodic patients, no differences in the prevalence of pre-attack symptoms were identified in between groups.
Conclusion
Pre-attack symptoms are frequent in CH. Since the origin of CH attacks is still unresolved, studies of pre-attack symptoms could contribute to the understanding of CH-pathophysiology. Furthermore identification and recognition of pre-attack symptoms could potentially allow earlier abortive treatment.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-011
Treatment of resistant cluster headache by sphenopalatine ganglion pulse radiofrequency ablation
Levent E İnan1,*, Nurten İnan2, Ceyla Ataç-Uçar1, Hanzade Ünal- Artık1, Gülçin Babaoğlu3 and Tahir K Yoldaş1
1Neurology, Ankara Research and Training Hospital
2Anesthesiology and Algology, Gazi Universtiy School of Medicine
3Algology, Ankara Research and Training Hospital, Ankara, Turkey
Objectives
We report a case of a treatment-resistant-episodic cluster headache-patient who was treated with various combinations of drugs and interventional methods including great occipital nerve (GON), supraorbital nerve (SON) and sphenopalatine ganglion (SPG) block and had remission with SPG pulse radiofrequency ablation finally.
Methods
A 25-year-old man presented with right-sided, periorbital, pulsating type headache accompanied with tearing, conjunctival injection, ptosis and nose stiffness ipsilaterally. His headache lasted 1–3 minutes with a frequency of 10–15 per day. He had headaches for five months occurring three times a week and then he had been asymptomatic for seven months. Next year he returned to our unit with the same type of headache with a longer duration (30–50 minutes) and a frequency of 3–5 times/day which lasted for six months. Following six years he had bouts of headache with the same characteristics starting November lasting till March. Regarding to changing headache characteristics he was diagnosed as paroxymal hemicrania evolving to episodic cluster headache. During six years of follow-up he had used verapamil, lithium, pregabalin for profilaxis. Because of having more severe headaches for the last three bouts, GON and SON blocks had also been tried. His remission periods were approximately five months but In his last bout he had extremetly severe headaches, his remissions lasted for a month and the headaches re-occured in spite of taking verapamil combined with methylprednisolone and pregabalin followed by GON and SPG block. The patient underwent SPG pulse radiofrequency ablation finally.
Results
Our patient had only six headaches in the last four months and the headaches’ severity decreased prominently.
Conclusion
SPG pulse radiofrequency ablation may be done when medical and interventional treatments are not effective enough for the management of intractable cases.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-012
Characteristics of SUNCT and SUNA in a Headache Clinic of Hong Kong
Ting Hin Adrian Hui1,* and Chun Kong Raymond Chan1
1United Christian Hospital, Kwun Tong, Hong Kong
Objectives
To report the clinical characteristics and treatment responses in a case series of Chinese outpatients diagnosed with SUNCT or SUNA in Hong Kong.
Methods
A prospective study was conducted to characterize the clinical phenotypes and treatment responses in patients diagnosed with SUNCT/SUNA by headache specialist in a headache clinic of Hong Kong between 2012 and 2016. The diagnosis was made according to the International Headache Society (IHS) diagnostic criteria.
Results
Eleven patients were diagnosed SUNCT (n = 5) or SUNA (n = 6) with a female to male ratio of 1.75 and a median age of onset at 55 (range 38 - 76). The median number of years to diagnosis was 6 (range 1–16). Pain occurred in V1 distribution alone in 36%, both V1 and V2 in 46%, V2 alone in 9% and both V2 and V3 in 9%. For cranial autonomic symptoms, lacrimation was the commonest feature in 100% subjects, followed by rhinorrhea(64%) and conjunctival injection(46%). Others included ptosis(18%), facial flushing(18%), periorbital swelling(9%), facial sweating(9%), nasal congestion(9%) and aural fullness(9%). Chewing(91%) was the most common trigger, followed by washing face(82%), brushing teeth (64%), wind blowing (55%), rubbing eye(27%), talking (27%), shower(14%), sneezing(14%), laughing(7%), shaving(7%) and exercise(7%). Neurovascular compression was demonstrated radiologically in 2 subjects(18%). Lamotrigine was the most effective(77%) prophylaxis in drug trials. Carbamazepine(effective in 57%) and pregabalin(25%) were also useful in reducing the pain intensity or frequency in our cohort. Adverse drug effect was the commonest reason of switching drugs in treatment trial.
Conclusion
In our cohort, female preponderance in SUNCT/SUNA is observed. The location of pain distribution, cranial autonomic symptoms, triggers and response rate to Lamotrigine are similar to those reported in the literatures. Our study demonstrated that it can take quite a long time to diagnose both conditions despite seeking early medical attention. This reflects the importance of recognizing the conditions and initiating treatment as soon as possible because the pain is debilitating and effective treatment is available.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-013
Trigeminal autonomic cephalalgia-like headache syndromes following surgery: a case series
Stacy V Smith1,* and Deborah I Friedman1
1Department of Neurology, UT Southwestern Medical Center, Dallas, Texas, United States
Objectives
The trigeminal autonomic cephalalgias (TACs) are primary headache disorders characterized by lateralized pain with associated cranial parasympathetic autonomic features. In a small number of patients, TAC-like headaches are a secondary headache syndrome. There are rare cases of new-onset TAC-like headaches following cranial surgeries. We report a case series of TAC-like headaches developing after surgery on extracranial structures innervated by the trigeminal nerve.
Methods
Case series
Results
Patient 1: A 42-year-old man presented with 3 years of episodic severe left eye pain. The first episode occurred 1–2 days after deviated septum repair and sinus drainage. Twice a month, he develops left orbital pressure building over 1–2 hours. He then experiences sharp, stabbing eye pains for 1–2 minutes 10–15 times per day for 3–15 days. Rarely, milder pain occurs in the right eye simultaneously. Interictal soreness remains until the episode resolves. Associated symptoms include nasal congestion and occasional bilateral conjunctival injection, as well as persistent photophobia and phonophobia. He lies down and places pressure over his eye until the pain passes. Trochlear blocks improve the acute attacks, and lamotrigine improved the frequency and severity of his pain episodes.
Patient 2: A 60-year-old man presented with 3 years of constant left eye pain that onset following left retinal detachment repair with intraocular gas bubble and gradually increased in severity. Subsequent epiretinal membrane removal, cataract extraction, intravitreal steroid injection, Seton tube shunt (for new intraocular hypertension), and corneal transplant did not help his vision or pain. He has constant left eye pain that gradually worsens throughout the day to a throbbing in the left supraorbital and temporal region. He also experiences multiple attacks of severe, stabbing pain like a “sharp poker in his eye” every day. Most attacks occur between 5:00 pm and 2:00 am. Each attack lasts a few seconds, with residual pain resolving after 15–30 minutes. During these attacks, he has photophobia, restlessness, and erythema and swelling of the left eyelid. Triggers include eye movement, bending over, lying flat, and stress. He did not respond to indomethacin, verapamil, carbamazepine, or lamotrigine. Sphenopalatine ganglion block and trochlear blocks temporarily improved the pain.
Patient 3: A 25-year-old man with a history of migraines and testicular cancer presented with 2 years of persistent headache after left macula biopsy for painless progressive vision loss suggestive of an autoimmune retinopathy. He has constant sharp left retrobulbar pain. Every two weeks, the pain acutely worsens with throbbing and electric-like jolts radiating to the back of his neck. He has tearing, ptosis, nausea, photophobia, dizziness, and irritability during the attacks, which last 4–10 hours. The severe pain may awaken him from sleep or be provoked by focusing. He did not improve on a low dose of indomethacin, but could not tolerate higher doses.
Conclusion
We describe three cases of TAC-like headaches following surgical procedures on trigeminally-innervated structures. The trigeminal nerve carries autonomic fibers, and direct injury, tissue swelling, or an inflammatory response may lead to dysregulation of the trigeminal-autonomic reflex. Without prompt recognition and treatment of the symptoms, uncontrolled pain may lead to long-term central sensitization reminiscent of the complex regional pain syndrome that can follow minor trauma to other parts of the body. Although acute post-surgical pain requires appropriate assessment, recognition and diagnosis of the headache syndrome based on its clinical features is key to preventing unnecessary surgical intervention that may further exacerbate the pain syndrome.
Disclosure of Interest
S. Smith Conflict with: Fight for Sight/NANOS research grant (not related to this submission), D. Friedman Conflict with: Merck, Eli Lilly, Autonomic Technologies Inc., Conflict with: Avanair*, Supernus*, Teva Pharmaceuticals*, Eli Lilly, Zosano*, Alder BioPharmaceuticals*, Amgen* (*advisory boards), Conflict with: Allergan, Avanair, Supernus, Teva Pharmaceuticals, Conflict with: Neurology Reviews Editorial Board, MedLink Contributing Author, American Headache Society Board of Directors, medical-legal work (expert witness for IIH cases). No direct conflicts of interest with this submission.
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-014
A Comparative Study of Cranial Autonomic Symptoms/signs (CAS) in Trigeminal Autonomic Cephalalgias
Amit S Singh1,*, Debashish Chowdhury1 and Geeta A Khwaja2
1Neurology, Headache Clinic, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India.
2Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India., New Delhi, India
Objectives
Patients with trigeminal autonomic cephalalgias (TACs) characteristically have side locked headache in V1 distribution and ipsilateral prominent one or more cranial autonomic symptoms/signs (CAS). However, there may be differences in occurrence, frequency, laterality, severity and consistency during the attacks between the subgroups.
The aim of this study was to study and compare the CAS in the 4 subgroups of TACs namely cluster headache (CH), paroxysmal hemicrania (HC), hemicrania continua (HC) and short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/Short lasting unilateral headache attacks with autonomic features (SUNA) as diagnosed by ICHD3β.
Methods
We analysed following 10 CAS features namely lacrimation, conjunctival injection, eyelid edema, nasal congestion, rhinorrhoea, facial/forehead sweating, facial/forehead flushing, drooping of eyelid, aural fullness and miosis. We noted their occurrence, laterality, frequency, extent of involvement, severity and consistency during the attacks.
Results
122 TACs patients were studied. Out of them, 44 patients had CH, 36 patients had PH, 16 had HC and 26 had SUNCT/SUNA. Analysis of CAS features and their comparison in individual TACs group is summarised in table 1.
Conclusion
Analysis of Cranial Autonomic Symptoms/Signs in Trigeminal Autonomic Cephalalgias
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-015
OCCIPITAL NERVE BLOCK: A MANDATORY TREATMENT IN CLUSTER HEADACHE
Diaz Insa Samuel1,*, Perez Julia1, Escutia Matilde1, Morales Lluis2, Argente Herminia2 and Boscá Isabel2
1Headache Unit - Neurology Service
2Neurology Service, Hospital Universitari i Politècnic La Fe, Valencia, Spain
Objectives
In recent years, occipital nerve block (ONB) has been proposed as a good option of treatment in cluster headache (CH) patients. It is a clean, cheap, quick and easy technique in general clinical practice. The objective of our study is to prospectively analyze its use in a recently stablished Headache Unit in order to manage CH patients.
Methods
Since 2014, our protocol in CH management included ONB as first line treatment as soon as posible (asap) when a cluster period begins. ONB is made with bupivacaine 4 cc + triamcinolone 1 cc ipsilateral to the headache and autonomic signs. We used it in any CH patient (either episodic (ECH) or chronic (CCH)) attending our headache clinic with an active period. ECH patients were advised to come asap when a cluster period begins. Outcome was measured as: Complete response (no need to use any other transitional or preventive medication and cluster aborted since ONB); Good response (>75% improvement in duration of CH period and rescue medication use); Partial response (25–75% improvement); and No response (<25% improvement).
Results
35 patients, 29 ECH and 6 CCH (17’1%) were attended. 27 males and 8 females (3’4:1). Mean age 42’4 years (16–64). Outcome is analyzed separately in CCH and ECH patients.
CCH: one patient rejected ONB, the resting 5 were injected 41 times (3–15, median 8); No patient got Complete response, 2 (40%) got a Good response, other 2 (40%) Partial and 1 (20%) got No response.
ECH: 11 patients out of 29 were not active at the moment of the visit, even all of them have been advised to return asap when a cluster period begins. In the resting 18 ECH patients ONB was made 48 times (1–8, median 2’7, just one time in 5 patients and two times in 7 patients); Complete response was achieved in 11 patients (61’1%), Good response in 6 patients (33’3%), Partial response in 1 patient (5’6%) and there was no patient with No response. The duration of the cluster period was dramatically reduced in this group from a mean of 73 days (based in previous history) to 7. In accordance, the use of rescue medication (usually sc sumatriptan or en zolmitriptan) and transitional (usually oral corticosteroids) or preventive (verapamil and others) medication was not necessary in the great majority of patients.
Conclusion
Even the short number of patients included in the study, it seems that ONB must be mandatory in the management of CH patients. It is somewhat useful to improve CCH patients poor quality of life, some of them feel this technique permits them a better management of the illness. In ECH, ONB has changed dramatically the natural history of the disease. It’s not just the numbers, which are stunning; it’s the patient perception of the spectacular outcome that ONB permits and the self-confidence it deserves to them compared to previous experiencies. ONB must be included as a first line treatment in the management of ECH patients. Used asap when the cluster period begins, as in our experience, cuts-off the headache in almost two-thirds of patients and shortens the duration of the cluster, reduces the use of rescue medication and oral preventive treatment in the rest.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-016
Visual Images – an additional tool for the screening of cluster headache
Alina Buture1,*, Lisa Dikomitis2, Jason Boland3 and Fayyaz Ahmed1
1Neurology, Hull Royal Infirmary, Hull
2School of Medicine and RI Primary Care and Health Sciences, Keele University, Keele
3Hull York Medical School, Hull, United Kingdom
Objectives
The project aims to determine if images could be used as part of a screening tool to diagnose patients with cluster headache. The project is a questionnaire based study that aims to test visual images depicting different pain levels on healthy subjects (subjects without a history of headache).
Methods
Six images were commissioned, drawn on the basis of real life pictures. Each image represents a different pain severity. In order to avoid bias, the images were subsequently drawn using the same artistic style, chromatic range and colour saturation. Three images picture women and three men. The six images were tested on 150 healthy people to test whether there is consensus for the pain severity (mild, moderate, severe or excruciating) depicted by each image.
Results
Two images were rated as showing excruciating pain, one image as severe pain, two images as moderate pain and one image as mild pain. The selected images depicted a range of pain severity from mild to excruciating.
Conclusion
The six images will be tested on patients with cluster headache and migraine in a subsequent study. Our hypothesis is that the images will differentiate between the severities of pain experienced by patients suffering from cluster headache and migraine.
Disclosure of Interest
A. Buture: None Declared, L. Dikomitis: None Declared, J. Boland: None Declared, F. Ahmed Conflict with: Allergan, Eneura, Electrocore, Novartis as Advisory Board member paid to British Association for the Study of Headache and the Migraine Trust, Conflict with: Educational Officer for British Association for the Study of Headache, Trustee of Migraine Trust, IHS Board Member
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-017
Effectiveness and tolerability of greater occipital nerve blocks for the prophylactic treatment of cluster headache – A retrospective study
Tijmen Balvers1,*, Patty Doesborg1, Roy Meilof1, Evelien Bartels2, Michel Ferrari1 and Rolf Fronczek1
1Neurology
2Aneasthesiology, Leiden University Medical Center, Leiden, Netherlands
Objectives
Greater occipital nerve(GON)-blocks have shown to be an effective prophylactic treatment for cluster headache in placebo controlled and observational studies. However, further evidence on its effectiveness is needed and consensus on its position within the treatment of cluster headache is lacking, i.e. add-on versus monotherapy. The aim of this observational study is to assess the effectiveness and safety of GON-blocks in our center.
Methods
All patients recieving GON-blocks for cluster headache in our center from January 1st 2014 to December 31th 2016 were identified. Medication used was 3 ml 2% lidocaine and 80 mg methylprednisolone. Patient histories were taken right before and six weeks after treatment as part of standard clinical care. Data on the type of cluster headache (eg. episodic vs chronic), response to previous therapy, headache severity and frequency and occurrence of adverse events were recorded.
Results
We identified 89 injections in 57 patients with cluster headache (67 injections in patients with chronic cluster headache, 19 in patients with episodic cluster headache and 3 in patients with an unspecified type of cluster headache). The majority of patients had not responded to standard (noninvasive) therapy. Complete remission was reported in 25% (n = 22), partial decrease in headache severity or frequency in 36% (n = 32), no response in 24% (n = 21) and an increase in headache severity or frequency in 3% (n = 3) of injections. Results were similar for episodic and chronic cluster headache. No effect data was documented for 12% (n = 11) of injections. Mild to moderate side effects, such as local pain and an increase of headache complaints, were reported after 28% (n = 25) of treatments. No serious adverse events were observed.
Conclusion
This observational study showed beneficial effects in 61% of GON-blocks in our patients with cluster headache and forms a base for prospective and placebo-controlled studies. In additional analyses, outcome will be correlated to response to previous treatments.
Disclosure of Interest
T. Balvers Conflict with: Novartis, P. Doesborg: None Declared, R. Meilof: None Declared, E. Bartels: None Declared, M. Ferrari: None Declared, R. Fronczek: None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-018
Forehead and facial flushing and sensation of fullness in the ear in cluster headache
Heui-Soo Moon1,*, Pil-Wook Chung1, Byung-Kun Kim2, Byung-Su Kim3, Jong-Hee Sohn4, Soo-Kyoung Kim5, Tae-Jin Song6, Jae-Moon Kim7, Jeong Wook Park8, Min Kyung Chu9, Kwang-Yeol Park10, Yunju Choi11, Mi-Ji Lee12, Chin-Sang Chung12, Dong-Woo Ryu8, Jin Young Ahn13 and Soo-Jin Cho14
1Department of Neurology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
2Department of Neurology, Eulji University School of Medicine, Seoul
3Department of Neurology, Bundang Jesaeng Hospital, Gyeonggi-do
4Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon
5Department of Neurology, Gyeongsang National University Hospital, Jinju
6Department of Neurology, Ewha Womans University School of Medicine, Seoul
7Department of Neurology, Chungnam National University College of Medicine, Daejeon
8Department of Neurology, Uijeongbu St.Mary’s Hospital, The Catholic University of Korea College of Medicine, Uijeongbu
9Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine
10Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul
11Department of Neurology, Presbyterian Medical Center, Chonju
12Department of Neurology, Neuroscience Center, Samsung Medical Center, Sungkyunkwan University School of Medicine
13Department of Neurology, Seoul Medical center, Seoul
14Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea, Republic Of
Objectives
In the international classification of headache disorder-3 beta (ICHD-3β), ipsilateral forehead/facial flushing and ipsilateral sensation of fullness in the ear were added to the cluster headache(CH) diagnostic criteria. We analyzed the diagnostic value of the two additional criteria and their association with existing autonomic symptoms.
Methods
Consecutive patients with cluster headache based on ICHD-3β were prospectively recruited from 4 headache clinics in South Korea from Oct. 2016. Questionnaire surveys with patients and interviews with headache specialists were conducted to analyze the distribution and association of eight associated symptoms including a sense of restlessness or agitation symptoms.
Results
A total of 22 patients of CH were enrolled (mean age, 36 ± 9.1 years; 90.9% male): 21 episodic CH, 1 chronic CH, 18 definite CH, and probable CH 4. Among them, 19 patients were in the cluster period. Associated trigeminal autonomic symptoms were conjunctival injection and/or lacrimation in 19(82.6%), nasal congestion and/or rhinorrhea in 14(60.9%), eyelid edema in 6(23.1%), forehead and facial sweating in 5(26.1%), miosis and/or ptosis in 6(26.1%), and a sense of restlessness or agitation in 11(47.8%) of patients. At least 1 autonomic symptom was present in 22(95.7%) of patients, and restlessness or agitation without autonomic symptoms was present in 1(4.3%) of patients. Forehead and facial flushing was present in 3 (13%) of the patients and no patient showed the sensation of fullness in the ear. All the three patients with forehead and facial flushing also had conjunctival injection and/or lacrimation.
Conclusion
The diagnostic usefulness of the additional two associated symptoms is low and forehead and facial flushing mainly appears in relation to conjunctival injection and/or lacrimation.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-019
Greater occipital nerve injections of methylprednisolone alone or in combination with lidocaine in episodic and chronic cluster headache
Valentina Favoni1, Sabina Cevoli2,*, Giulia Giannini1, Enrico Farinella1, Pietro Cortelli1 and Giulia Pierangeli1
1Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum – University of Bologna Italy, IRCCS Istituto delle Scienze Neurologiche
2IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy, Bologna, Italy
Objectives
Many series suggested an effect of greater occipital nerve (GON) injections for cluster headache (CH). Steroids alone or in combination with anesthetics can be used. The substance or combination that is most effective and the optimal technique still remain controversy [1]. The aim of our study was to evaluate the effect of GON injections of methylprednisolone alone or in combination with lidocaine as treatment in CH patients.
Methods
Patients suffering from active chronic (CCH) and episodic (ECH) CH were prospectively recruited. During active bouts, patients received three repeated GON injections every other day of methylprednisolone (A) or a single injection of a 80 mg of methylprednisolone mixed with 2 mL of 2 % lidocaine (B). Responders were classified as having a total remission for at least one month. A or B injections could be repeated either because of failure of the first treatment or recurrence of headaches.
Results
A total of 71 patients (48 ECH and 23 CCH) were enrolled in this study. Out of these, 59 patients (45 ECH and 14 CCH) received treatment A and 20 (12 ECH and 8 CCH) treatment B. 8 patients (5 ECH and 3 CCH) received both treatments. No serious adverse event were reported. Responders were 49/59 (83%) in A e 12/20 (60%) in B. Comparing ECH and CCH, A was effective in 87% vs 71% and B in 83% vs 25%. Among patients that received both treatments, 6 of 8 achieved the same effect either with A or B. Remission lasted between 2 months and 30 months in both A and B.
Conclusion
Our data suggest that GON injections of methylprednisolone alone or in combination with lidocaine are both effective in treating cluster headache, with long term effect. Moreover, GON injections of steroids are superior to steroids in combination to anesthetics in treatment of chronic CH.
Disclosure of Interest
None Declared
Referenecs
Leroux E, Ducros A. Occipital injections for trigemino-autonomic cephalalgias: evidence and uncertainties. Curr Pain Headache Rep. 2013;17(4):325.
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-020
Diagnostic delays and mismanagement in cluster headache
Michail Vikelis1,* and Alan M Rapoport2
1Glyfada Headache Center, Glyfada, Greece
2The David Geffen School of Medicine at UCLA, Los Angeles, United States
Objectives
Despite being considered the most excruciating primary headache syndrome, cluster headache (CH) is internationally reported to be often misdiagnosed, undertreated or mistreated. The objective of our study was to draw capture under-management, under-treatment and mis-treatment often encountered in clinical practice and hence improve recognition and successful treatment of cluster patients by Greek neurologists and other physicians.
Methods
Data on consecutive CH patients (n = 302) were prospectively recorded from February 2007 until June 2015. Patients came from all geographical regions of Greece, mainly through self-referral (84.7%). All patients were examined by the same headache specialist (MV).
Results
In the majority of our patients (175/302) a diagnosis of CH had not been previously made and was established during consultation at our center for the first time. The median time from disease onset to diagnosis in our cohort was 5 years (range 0–45, mean 7.2 years). Overall, time to diagnosis significantly improved with decade of onset, for the current decade being just one year (median), compared to 5 years for the 2000s, 12 years for the 1990s and 20 years for onset before 1990. The median number of physicians seen prior to diagnosis was 3 (range 0–15, mean 3.5) and significantly improved with decade of onset, from a median of 7 doctors seen prior to diagnosis for onset before 1989 to a median of 5, 3 and 1 for onset between 1990–1999, 2000–2009 and after 2009, respectively (p = 0.001 for all comparisons). Factors identified as significantly correlated with greater number of years lapsed to diagnosis included earlier decade of onset, presence of side shift between bouts, pain location in the jaw, cheek, lower teeth or ear area, presence of photophobia, forehead and facial sweating, pain aggravation by physical activity and absence of typical cluster headache autonomic features. In addition, factors associated with a greater number of physicians prior to diagnosis included presence of CCH, earlier decade of onset, pain location in upper teeth, cheek, lower teeth, neck, nose, ear, shoulder or vertex, presence of eyelid oedema, miosis/ptosis and aggravation by physical activity. Among the total group, 188 patients (62.7%) had received pharmaceutical treatment of any type prior to CH diagnosis and 42 patients (14.0%) had undergone unnecessary procedures, mainly by dentists (10.2%) and ENT specialists (9.9%), most commonly tooth extractions, fillings, sinus washout or surgery for nasal septum deviation, in all cases without success. Among the 127 previously diagnosed patients, only a minority had been offered treatment with subcutaneous sumatriptan or high flow oxygen for acute attacks or verapamil, corticosteroids or lithium for prevention. In addition, a substantial proportion was offered treatment with carbamazepine, flunarizine, antidepressants or alternative treatments. Use of recommended treatments, such as sc sumatriptan, O2 inhalation, corticosteroids or verapamil did not seem to be much more common even among previously diagnosed patients who had been diagnosed by a neurologist.
Conclusion
CH patients in Greece may remain misdiagnosed or undiagnosed for rather lengthy periods of time, but time to diagnosis has improved recently. Even after diagnosis, treatment received is commonly suboptimal.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-021
Baseline characteristics of medically intractable chronic cluster headache patients participating in a trial on occipital nerve stimulation
Patty G Doesborg1,*, Leopoldine A Wilbrink1, Ilse F de Coo1, Frank J Huygen2 and Michel D Ferrari1; The ICON Study group
1Neurology, Leiden University Medical Centre, Leiden
2Anaesthesiology, Erasmus University Medical Center, Rotterdam, Netherlands
Objectives
About 10% > 15% of chronic cluster headache patients are refractory or intolerant to standard prophylactics. Here we present the 3-month baseline observation characteristics of 116 patients with medically intractable chronic cluster headache participating in the ICON study assessing the prophylactic efficacy of occipital nerve stimulation.
Methods
Participants completed weekly headache diaries during a 3 month baseline-period. Data were prospectively collected and included several clinical characteristics including attack frequency, pain intensity, additional clinical characteristics, medication use, smoking habits, and alcohol consumption.
Results
Attack frequency was analysed in 108 patients (65.5% male). Complete diary data could not be retrieved in 6.9% (n = 8) of the patients. Mean attack frequency was 21 attacks per week +/- 17.8 SD (median 16.1, interquartile range 16.1). Median disease duration of cluster headache was 8 years (interquartile range 6.8) (n = 93) and median disease duration of chronic cluster headache was 4 years (interquartile range 4.5). Additional analyses still to conduct and to be presented at the meeting will include variability over the three month follow-up in attack frequency and intensity.
Conclusion
Clinical 3-month baseline observation characteristics of medically intractable chronic cluster headache patients participating in the ICON trial are presented.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-022
Remission of Cluster Headache Periods with Topiramate in Developing Country: A Case Report
Devi A Sudibyo1,*, Isti Suharjanti1 and Sadewi Puspitasari1
1Neurology, Airlangga University, Surabaya, Indonesia
Objectives
Cluster headache is a primary headache with high morbidity related to its intensity of pain and almost 80% patients report some limitations in doing their activities daily living. Headache is one of the most common diseases in Neurology Outpatient Clinic Dr. Soetomo General Hospital Surabaya which is the main referral hospital in eastern Indonesia.Various options of treatments according to IHS recommendations have been used to treat cluster headache either as acute or preventive. Cluster headache treatments in patients with various comorbidities is difficult. Moreover, the availability of the drug is quite difficult in our healthcare facilities.We describe the case of successful treatments of cluster headache using topiramate.
Methods
Male 55-years old with severe right periorbital pain that he never felt before. Pain was felt like a hard object pressed around his right eye radiated to the right temple, and followed by redness and lacrimation. The pain was almost daily in the last two months and lasted twice a day, especially at night with mean duration of attacks was 15–45 minutes followed by pain free between attacks. He had chronic gastritis and hypertension since couple years ago. There was no history of alcohol consumption and has stopped smoking since three years ago. Physical and neurological examination were normal. Numeric Rating Scale (NRS) was 10 during acute attacks. Head MRI and MRA with contrast were perform to rule out intracranial abnormalities, because the first onset of headache was quite old. He was referred from primary healthcare service and ever treated with paracetamol, ibuprofen and valproic acid but no reduction either in intensity or frequency of pain. Then he was given a combination of paracetamol with tramadol, and topiramate in our hospital.
Results
Patients had remission of cluster headache period within 14 days of treatment with combinations of paracetamol with tramadol as abortive treatments, and topiramate 50 mg once daily as a preventive treatment. There was no cluster attacks anymore. NRS reduce until zero. Topiramate has various mechanisms of actions include inhibition glutaminergic transmissions, inhibition of voltage-gated calcium channels and voltage gated sodium channel. Topiramate enhances the activity of GABA, inhibits carbonic anhydrase and also has inhibitory effects on the nociceptive trigeminovascular system on animal experiment. Therapeutic use of paracetamol and opioid in this case was due to limited availability of specific drugs for abortive treatments of cluster headache in our healthcare facilities. Using opiod for cluster headache must be considered carefully due to the possibility of medication overuse headache and should be combined with specific preventive drugs. Topiramate was selected as a preventive drug due to patient’s comorbidities. Prednisone, as the first line preventive drug, was not used because history of chronic gastritis. Verapamil has a beneficial effect in this case due to hypertensive comorbidity but the drug availability is rare and uncommon.
Conclusion
Despite patient’s comorbidities and limited availability of specific abortive treatment in our healthcare facilities which is the main referral hospital in eastern Indonesia, a combination treatments of weak opioid (tramadol) and paracetamol for abortive treatment with topiramate 50 mg once daily as a preventive drug could treat episodic cluster headache within 14 days.
Disclosure of Interest
None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-023
Refractory post-surgical SUNCT responsive to lacosamide
Michael J Marmura1,* and Clinton Lauritsen1
1Neurology, Thomas Jefferson University, Philadelphia, United States
Objectives
To report a patient with post-surgical headache with Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) characteristics who improved dramatically after treatment with lacosamide.
Methods
Case report
Results
A 46 year-old woman developed severe headaches starting immediately after sinus surgery in 2012. She presented with stereotyped severe left-sided, headaches lasting 1–2 minutes with severe ipsilateral lacrimation swelling, injection, rhinitis and ptosis without agitation. The pain is located around the left eye but radiates to the left temple and face. There is no refractory period between attacks, but no significant background pain between attacks. Her attacks occurred spontaneously with no apparent triggers. Over the next 6 years she experienced between 25–85 attacks per day, with an average of about 50.
The patient tried many treatments for headache without significant improvement. Intravenous lidocaine was somewhat helpful in the hospital but her attacks persisted at a lower level after 5 days and did not significantly improve after discharge. She experienced little to no improvement with medications such as lithium, indomethacin, lamotrigine, verapamil, phenytoin, oxcarbamazepine, carbamazepine, mexiletine, divalproex sodium, duloxetine, gabapentin, pregabalin, amantidine, nortriptyline, baclofen, amitriptyline, topiramate and zonisamide. She also had little relief with peripheral nerve blocks, onabotulinumtoxina injections, and repeated sphenopalatine ganglion blocks. Olanzepine and corticosteroids were modestly effective during exacerbations, and extended-release diclofenac and clomiphene citrate modestly improved pain severity. She underwent a microvascular decompression which did not reduce attack frequency over the next few months.
As an alternative treatment for SUNCT she began lacosamide, titrating to a dose of 200 mg twice daily. On the 400 mg/day dose, her attacks began to improve. In the first few weeks the attacks decreased to 33/day, then 18/day the next month, then 5/day after that. She remains in this pattern of 5 attacks/day for the last 4 months and both the pain and autonomic symptoms during attacks are much milder.
Conclusion
Lacosamide is an anticonvulsant which acts via voltage-gated sodium channels and modulation of collapsin response mediator protein 2. It does not affect or modulate other receptors or neurotransmitters important in pain such as GABA-A/GABA-B, serotonin, dopamine, norepinephrine, cannabinoids, and potassium or calcium currents. Although clinical trials using lacosamide for the treatment of migraine have not demonstrated significant benefit, it may be worth considering it as a treatment for SUNCT, especially in those with inadequate response or poor tolerability with sodium channel blockers such as lidocaine or mexiletine.
Disclosure of Interest
M. Marmura Conflict with: Teva, eNeura, Conflict with: Supernus, Teva, C. Lauritsen: None Declared
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
PO-02-024
Definition of Allodynia in TACs patients through Turkish Version of the Allodynia Checklist
Osman Ozgur Yalin1,*, Nevra Oksuz2, Derya Uluduz3 and Aynur Ozge4
1Neurology Department, Istanbul Education and Research Hospital, Istanbul
2Neurology Department, Mersin University School of Medicine, Mersin
3Neurology Department, Istanbul University, Cerrahpasa School of Medicine
4Neurology Department, Mersin University School of Medicine, Istanbul, Turkey
Objectives
Allodynia refers to central pain sensitization following normally non-painful stimulation. Cutaneous allodynia (CA) is also expression of central sensitization and commonly associated with migraine disease. Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by unilateral pain at trigeminal distribution accompanied by ipsilateral cranial autonomic features. In this clinical study rare TACs including paroxysmal hemicrania (PH), short-lasting unilateral neuralgiform headache attacks (SUNCT) and hemicranial continua (HC) are considered. Allodynia is clinical expression of central sensitisation and associated with chronicity. It’s present up to 2/3 of migraine patients, however allodynia is not comprehensively studied in SUNCT, Paroxysmal Hemicrania and Hemicrania continua. In this prospective study we aimed to define if there is association with TACs by the first valid Turkish allodynia assessment questionnaire.
Methods
The study performed in Mersin University School of medicine and Istanbul Training and Research Hsopital, Neurology Departments, Headache outpatient clinics. All patients evaluated by experienced neurologists. Diagnosis based to International Classification of Headache Disorders (ICHD)-3 beta version. SUNCT, SUNA, Hemicrania continua and Paroxysmal Hemicrania patients included to study. The first valid Turkish allodynia assessment questionnaire based on 12-item allodynia symptom checklist is translated from allodynia symptom checklist (ASC) according to our cultural adaptation by headache specialists.
Results
We used Turkish allodynia symptom checklist to evaluate 37 TACs patients including 14 (37,8%) SUNCT patients, 16 (43,2%) PH patients and 7 (18,9%) HC patients. The study group comprised 20 female (54,0%) and 17 male (46,0%), the mean age of subjects was 37,8 ± 12,8 years, median of education was estimated 8 (4–9) years. Cut-off value for ASC-12 regarded as ≥3 points. Cutaneous Allodynia observed at 8 patients (21,6%). The most common allodynia subtype was mechanical allodynia. There was no association of allodynia with age, headache subtype, frequency of headache.
Conclusion
The trigeminal autonomic cephalalgias (TACs) are rare headache syndromes. Typically in TACs patients the pain is usually located retroorbital, temporal and most often in the ophthalmic distribution (V1). Atypically patients with TACs have pain in other cranial areas, including top, side or back of head, the nose, trigeminal V2 and V3 regions, the teeth, the neck and the ear. In our study despite of the neurologic examination is normal in patients with TACs, we found abnormal sensation and allodynia in trigeminal V1 or V2 distrubition in the face at the pain located side. We observed that allodynia is common and a Turkish version of the allodynia symptom checklist was found to be convenient for the identification of allodynia in TACs patients. This study confirmed that CA is closely related to TACs patients. There is need to broad studies to reveal association of allodynia in TACs.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-025
Olfactory hallucination in association with migraine
Yasushi Shibata1,*
1Neurosurgery, University of Tsukuba, Mito, Japan
Objectives
Visual hallucinations and osmophobia are well known symptoms of migraine. Olfactory hallucinations are rarely reported in association with primary headache.
Methods
We experienced 3 cases involving migraine patients with olfactory hallucinations.
Results
The first patient was a 28-year-old woman. She had experienced migraine without aura since she had been in junior high school. Her headaches were frontal pulsatile, associated with nausea and frequently occurred before and after her menstrual period. A neurological examination and brain MRI and MRA showed no abnormalities. Treatment with lomerizine and triptan was effective. She reported that she occasionally smelled smoke even though there were no smokers around her. This olfactory hallucination was not associated with her migraine attacks and was observed before the initiation of migraine therapy at our hospital. She experienced these olfactory hallucinations, which were not affected by migraine therapy, several times a year.
The second patient was a 45-year-old man. He had experienced migraine without aura with nausea and photo hypersensitivity for 10 years. Triptan was effective. The patient had undergone the surgical removal of a front-temporal atypical meningioma 7 years previously and had undergone surgery 3 years previously for recurrence. He reported experiencing olfactory hallucinations several times a year in which he perceived the smell of urine. His olfactory hallucination was not associated with his migraine attacks. This olfactory hallucination was not affected by treatment for meningioma or the administration of anticonvulsants.
The third patient was a 22-year-old woman. She had been diagnosed with thrombocytopenic purpura and was treated with prednisolone. She visited our hospital with severe frontal headache and vomiting. A neurological examination and brain CT showed no abnormalities. We diagnosed the patient with migraine without aura. Treatment with sumatriptan was effective. She reported experiencing olfactory hallucinations in which she perceived a sweet smell; however, her hypersensitivity was not remarkable.
Conclusion
Olfactory hypersensitivity, which typically presents as osmophobia or olfactophobia, is well known symptom of migraine. Olfactory or gustatory hallucinations, which are phantosmias, differ from olfactory hypersensitivity and are observed in the patients with temporal lobe epilepsy, Parkinson’s disease and schizophrenia. Although the olfactory hallucinations in patients with schizophrenia are not experienced as real smells, the olfactory hallucinations experienced by migraine patients are sensed as a real, unpleasant smell. In our 2 patients, the olfactory hallucinations were not associated with migraine attack; thus, they did not represent a symptom of aura. Although most olfactory hallucinations that are reported in association with migraine are associated with aura, olfactory hallucinations that not related to migraine attacks have been reported in some cases. Olfactory hallucinations have also been reported in association with cluster headache and hemicranias continua. Although the pathophysiology of these olfactory hallucinations is not clear, dysfunction and/or hypersensitivity of the temporal lobe or olfactory structures and the degeneration and/or dysmodulation of the dopaminergic, serotonergic and cholinergic systems are suspected to be involved. Olfactory hallucination has been included in the International Classification of Headache Disorders (ICHD) 2 appendix, but was deleted in ICHD 3b. Since some data supported the high specificity of olfactory hallucination in the diagnosis of migraine, it should be included in ICHD 3b.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-026
Visual Snow syndrome is associated with reduced amplitudes and lack of habituation of visual evoked potentials independent from comorbid migraine
Ozan Eren1, Veronika Rauschel1, Ruth Ruscheweyh1, Andreas Straube1 and Christoph Schankin2,*
1Department of Neurology, University of Munich Hospital, Grosshadern, Munich, Germany
2Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Objectives
Visual Snow syndrome is highly comorbid with migraine and typical migraine aura. Patients suffer from a continuous TV-snow-like visual disturbance and additional visual symptoms. Currently, there is no established treatment. Its pathophysiology is unknown, but might overlap with the mechanism of migraine or migraine aura. Functional brain imaging has shown hypermetabolism of the lingual gyrus suggesting a dysfunction of visual processing. Here, we tested the hypothesis that Visual Snow is associated with altered cortical excitability by assessing visual evoked potential (VEP) habituation and magnetic suppression of perceptual accuracy (MSPA).
Methods
Patients with Visual Snow were compared to age- and migraine-matched controls. For pattern-reversal VEPs, N75–P100 and P100-N145 amplitudes were measured over six consecutive blocks of 75 VEPs each. Block 1 amplitude, amplitude regression slopes (n = 18 per group) and block 6-to-1 ratios (n = 17 per group) were used to quantify VEP habituation. Visual accuracy (n = 17 per group) was assessed by letter recognition with prior transcranial magnetic stimulation delivered to the occipital cortex at intervals of 40, 100 and 190 ms. After confirmation of normal distribution using Kolmogorov-Smirnov-test, two-sample t-test was used to assess group differences between patients and controls. The study was approved by the University of Munich ethics committee.
Results
VEP block 1 amplitudes were reduced in Visual Snow patients (N75-P100 amplitude: 7.4 µV vs 11.8 µV, p = 0.004; trend for P100-N145 amplitude: 8.1 µV vs 11.7 µV, p = 0.07). Further, VEP habituation of P100-N145 amplitudes was significantly reduced in Visual Snow patients compared to controls (amplitude regression slope: −0.02 vs −0.36, p = 0.048). There was no difference for N75-P100 habituation (slope: −0.15 vs −0.17, p = 0.88), block 6-to-1 ratios (N75-P100: 100.5 vs 96.8, p = 0.73; P100-N145: 108.9 vs 99.7, p = 0.52) and MSPA (40 ms: 70.7% vs 70.9%; 100 ms: 52.5% vs 48.4%; 190 ms: 74.9% vs 77.5%).
Conclusion
This study demonstrates differences in visual cortical processing in patients with Visual Snow syndrome when compared to migraine-matched controls. This supports the view that Visual Snow syndrome is - though highly comorbid with - distinct from migraine. Patients’ main symptom is a TV-noise-like visual disturbance of continuously flickering black and white dots in the entire visual field. Additional visual symptoms include poor night-vision, which could be explained by noise reducing the contrast during low light conditions. The substantial reduction of VEP block 1 amplitude in our study is consistent with such decrease of contrast in pattern-reversal VEP. This might be the first objective electrophysiological correlate of the patients’ subjective symptoms reinforcing that Visual Snow syndrome is not a psychogenic problem. Further, VEP amplitude could represent a useful parameter for monitoring treatment progress in prospective studies. The reduced VEP habituation might be a correlate of the subjective visual overload experienced by our patients. The source of the P100-N145 component of the VEP is thought to be in the extrastriate cortex, which would be in accordance with previous functional imaging showing hypermetabolism of the visual association cortex in Visual Snow syndrome. This suggests that the pathophysiology of the disorder is associated with dysfunctional visual processing. Understanding the mechanism of the cortical dysfunction demonstrated here might offer insights into how to treat this disabling condition.
Disclosure of Interest
O. Eren Conflict with: German Migraine and Headache Society, Eye On Vision Foundation, V. Rauschel: None Declared, R. Ruscheweyh: None Declared, A. Straube: None Declared, C. Schankin Conflict with: German Migraine and Headache Society, Eye On Vision Foundation
Comorbidity of Primary Headaches
PO-02-027
The Relationship Between Sleep Disorders and Migraine: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study
Dawn C Buse1,*, Jeanetta C Rains2, Jelena M Pavlovic3, Kristina M Fanning4, Michael L Reed4, Aubrey Manack Adams5 and Richard B Lipton3
1Montefiore Medical Center, Bronx
2Elliot Hospital, Center for Sleep Evaluation, Manchester
3Albert Einstein College of Medicine, Bronx
4Vedanta Research, Chapel Hill
5Allergan plc, Irvine, United States
Objectives
This cross-sectional analysis from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study compared the rates of sleep disturbances and sleep apnea (SA) among men vs women with migraine.
Methods
CaMEO participants were recruited from an online US panel using quota sampling and completed baseline and follow-up surveys every 3 months over 1 year. Participants were aged ≥18 years and met ICHD-3beta criteria for migraine. The Comorbidities/Endophenotypes cross-sectional survey module assessed the risk of SA using the Berlin Scale for Sleep Apnea and obtained self-reported physician diagnosis of SA. Sleep disturbances and habits were measured using the Medical Outcomes Study (MOS) Sleep Scale. Participants were also asked to report what time of day their headache usually began. Results were stratified by episodic migraine (EM), chronic migraine (CM), body mass index (BMI), and sex and tested for significance using chi-square.
Results
Of 16,763 (99.8%) CaMEO Study respondents who received Comorbidities/Endophenotypes survey invitations, 12,810 (76.4%) provided valid data including 3,220 men and 9,590 women. Based on the Berlin Scale, 4,739 (37.0%) respondents were “at high risk” for SA. SA rates were significantly higher for men than women, for those with high BMI and in persons with CM vs EM (all P < 0.001; Table). Self-reported SA rates were higher in men (n = 580, 18.0%) than in women (n = 713,7.4%; P < 0.001). Among those reporting SA, 75.7% also self-reported a physician diagnosis: men (n = 440, 75.9% [13.7% of total]); women (n = 539, 75.6% [5.6% of total]). The mean ± SD MOS Sleep Index II (long form) was 41.3 ± 17.6 (men, 38.7 ± 17.2; women, 42.2 ± 17.7; P < 0.001), with higher scores for the overall index and the subscales indicating worse sleep problems, unless otherwise noted. Commonly endorsed MOS sleep subscales with significant gender differences were Snoring (men, 39.2 ± 33.5; women, 29.1 ± 31.4; P < 0.001), Shortness of Breath (men, 15.0 ± 21.2; women, 17.7 ±22.5; P < 0.001), Sleep Adequacy (men, 39.7 ± 22.6; women, 38.4 ± 22.2; P < 0.01, lower scores indicate worse sleep problems), and the average number of hours slept per night (men, 6.6 ± 1.4; women, 6.8 ± 1.4; P < 0.001, lower scores indicate less sleep). There was a significant difference in temporal headache patterns between men and women, with a lower proportion of men than women reporting their most severe headache typically started before or during waking or immediately after waking/getting up (n = 349 [12.2%] vs n = 1,446 [16.6%]; chi-square, 31.5; P < 0.001). Similarly a smaller proportion of men than women reported their most severe headache starts before or during waking, immediately after waking/getting up, or in the morning (n = 585 [20.4%] vs n = 1,977 [22.6%]; chi-square, 6.1; P < 0.05).
Conclusion
Compared with reported population prevalence rates of 35.1% of men and 21.0% of women at risk for SA, data from the CaMEO Study revealed an increased risk and potential underdiagnosis of sleep apnea and sleep disturbances among people with migraine. This phenomenon was often significantly more prominent in men compared with women and in those with CM compared with EM.
Disclosure of Interest
D. Buse Conflict with: Allergan, Avanir, Amgen, and Dr. Reddy’s Laboratories, Conflict with: Eli Lilly, Conflict with: Montefiore Medical Center, which in the past 12 months, has received research support funded by Allergan, Alder, Avanir, CoLucid, Dr. Reddy’s Laboratories, and Labrys via grants to the National Headache Foundation and/or Montefiore Medical Center, Conflict with: Editorial board of Current Pain and Headache Reports, the Journal of Headache and Pain, Pain Medicine News, and Pain Pathways magazine, J. Rains: None Declared, J. Pavlovic Conflict with: Honoraria from Allergan and the American Headache Society, K. Fanning Conflict with: Vedanta Research, which has received research funding from Allergan, Amgen, CoLucid, Dr. Reddy’s Laboratories, Endo Pharmaceuticals, GlaxoSmithKline, Merck & Co., Inc., NuPathe, Novartis, and Ortho-McNeil, via grants to the National Headache Foundation, M. Reed Conflict with: Managing Director of Vedanta Research, which has received research funding from Allergan, Amgen, CoLucid, Dr. Reddy’s Laboratories, Endo Pharmaceuticals, GlaxoSmithKline, Merck & Co., Inc., NuPathe, Novartis, and Ortho-McNeil, via grants to the National Headache Foundation. Vedanta Research has received funding directly from Allergan for work on the CaMEO Study, A. Manack Adams Conflict with: Allergan, Conflict with: Allergan, R. Lipton Conflict with: eNeura Therapeutics, Conflict with: NIH, Conflict with: Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven Inc, Boston Scientific, Colucid, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, Glaxo, Merck, GlaxoSmithKlein, Pfizer, Teva, Vedanta, Conflict with: Served on the editorial board of Neurology and as senior advisor to Headache. Received support from the Migraine Research Foundation and the National Headache Foundation. He has reviewed for the NIA and NINDS. Receives royalties from Wolff’s Headache, 8th Edition, Oxford Press University, 2009 and Informa
Comorbidity of Primary Headaches
PO-02-028
Effects of OnabotulinumtoxinA Treatment on Chronic Migraine Comorbidities of Depression and Anxiety
Andrew M Blumenfeld1,*, Stewart J Tepper2, Lawrence D Robbins3, Aubrey Manack Adams4 and Stephen D Silberstein5
1Headache Center of Southern California, The Neurology Center, Carlsbad
2Geisel School of Medicine at Dartmouth, Hanover
3Robbins Headache Clinic, Riverwoods
4Allergan plc, Irvine
5Jefferson Headache Center, Philadelphia, United States
Objectives
Chronic migraine (CM) is associated with comorbidities that may exacerbate the condition. This subanalysis of COMPEL addresses the effects of onabotulinumtoxinA prophylaxis on comorbid psychiatric symptoms of anxiety and depression.
Methods
The 108-week, multicenter, open-label COMPEL Study enrolled adult patients with CM in Australia, Korea and the United States receiving onabotulinumtoxinA 155 U with/without concomitant prophylaxis. Primary outcome was the reduction in headache frequency per 28-day period at 108 weeks (9 treatments). Anxiety symptoms were assessed using the Generalized Anxiety Disorder Assessment (GAD-7) with a total score ranging from 0–21 (best to worst) distributed as 0–4 (minimal), 5–9 (mild), 10–14 (moderate), and 15–21 (severe); a score ≥10 indicates probable GAD. Depression symptoms were determined using the Patient Health Questionnaire (PHQ-9) with a total score ranging from 0–27 (best to worst) distributed as 0–4 (minimal), 5–9 (mild), 10–14 (moderate), 15–19 (moderately severe), and 20–27 (severe); a score ≥15 was indicative of major depression. Adverse events (AEs) were recorded.
Results
Enrolled patients (N = 715) had a mean (range) age of 43 (18–73) years and were
predominantly female (84.8%, 606/715). Headache day frequency at week 108 (primary
endpoint) was significantly reduced from a baseline mean (standard deviation, SD) of
22 (±4.8) to 11.3 (±7.4) days (P < 0.0001). Patient baseline
mean (SD) GAD-7 score was 6.3 (±5.3). OnabotulinumtoxinA treatment significantly
reduced (improved) mean GAD-7 scores by −1.4 at week 12, −1.9 at week 24, −2.0 at
week 48, −2.8 at week 72, and −2.8 at week 108 (all P < 0.0001;
Conclusion
COMPEL Study results support the established effectiveness and safety profile of onabotulinumtoxinA treatment for reducing headache frequency in CM. Less established is our understanding of how effective preventive treatment can affect common comorbidities of CM. These findings demonstrate that onabotulinumtoxinA treatment improved the comorbid symptoms of anxiety and depression for up to 108 weeks (9 treatment cycles) in patients with CM.
Disclosure of Interest
A. Blumenfeld Conflict with: Allergan, Pernix, Teva, Avanir, Depomed, and Supernus, Conflict with: Received funding for travel, speaking, and/or royalty payments from Allergan, S. Tepper Conflict with: Alder, Allergan, Amgen, ATI, Avanir, ElectroCore, eNeura, Teva, Zosano, Conflict with: Acorda, Alder, Allergan, Amgen, ATI, Avanir, BioVision, ElectroCore, eNeura, Kimberly-Clark, Pernix, Pfizer, Teva and Zosano, Conflict with: Dartmouth-Hitchcock Medical Center, American Headache Society (AHS), Conflict with: Stock options, ATI, Conflict with: Received salary as Editor-in-Chief of Headache Currents from AHS and royalties for books published by Springer, L. Robbins Conflict with: Speaker for Avanir, Pernix, and Merck, A. Manack Adams Conflict with: Allergan, Conflict with: Allergan, S. Silberstein Conflict with: His employer receives research support from Allergan, Inc.; Amgen; Cumberland Pharmaceuticals, Inc.; ElectroCore Medical, Inc.; Labrys Biologics; Eli Lilly and Company; Merz Pharmaceuticals; and Troy Healthcare, Conflict with: Alder Biopharmaceuticals; Allergan, Inc.; Amgen; Avanir Pharmaceuticals, Inc.; eNeura; ElectroCore Medical, LLC; Labrys Biologics; Medscape, LLC; Medtronic, Inc.; Neuralieve; NINDS; Pfizer, Inc.; and Teva Pharmaceuticals
Comorbidity of Primary Headaches
PO-02-029
Headache and migraine in Parkinson’s disease: a multicenter cross-sectional study
Keisuke Suzuki1,*, Yasuyuki Okuma2, Tomoyuki Uchiyama1,3, Masayuki Miyamoto4, Ryuji Sakakibara5, Yasushi Shimo6, Nobutaka Hattori6, Satoshi Kuwabara7, Toshimasa Yamamoto8, Koichi Hirata1 and Kanto NMPD investigators
1Neurology, Dokkyo Medical University, Tochigi
2Neurology, Juntendo University Shizuoka Hospital, Tokyo
3Neuro-urology and Continence Center, Dokkyo Medical University Hospital
4Clinical Medicine for Nursing, Dokkyo Medical University School of Nursing, Tochigi
5Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura
6Neurology, Juntendo University School of Medicine, Tokyo
7Neurology, Chiba University Graduate School of Medicine, Chiba
8Neurology, Saitama Medical University, Saitama, Japan
Objectives
The prevalence of headache and migraine and their impact on disease course in patients with Parkinson’s disease (PD) remain unclear.
Methods
We analyzed prevalence of headache and migraine and their clinical correlates in 436 PD patients and 401 age- and sex-matched controls from the cross-sectional, multicenter study. Migraine was diagnosed by questionnaire made according to the International Classification of Headache Disorders-second version. Epworth sleepiness scale, PD sleep scale (PDSS)-2 and Pittsburgh Sleep Quality Index (PSQI) were administered to all the participants.
Results
Between patients with PD and controls, the prevalence of headache during the lifetime (38.5% vs. 38.9%, p = 0.91) and headache during the past year (26.1% vs. 26.2%, p = 0.99) did not differ. However, PD patients had a lower prevalence of migraine during the past year compared with controls (6.7% vs. 11.0%, p = 0.027). Also, we found a significant number of PD patients with headache and migraine reported improvement of intensity and frequency of their headache and migraine after the onset of PD. PD patients with migraine showed a higher rate of depression and higher score of PSQI and PDSS-2 than those without headache.
Conclusion
We found improved overall headache severity after the onset of PD and the association of migraine with sleep disturbances and depression in PD patients.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-030
Poor sleep quality among individuals with probable migraine: a population-based study
Min Kyung Chu1, Bohm Choi1,*, Won-Joo Kim2, Soo-Jin Cho3, Kwang Ik Yang4, Chang-Ho Yun5 and Tae-Jin Song6
1Neurology, Kangnam Sacred Heart Hospital, Hallym University
2Neurology, Gangnam Severance Hospital, Yonsei University, Seoul
3Neurology, Dongtan Sacred Heart Hospital, Hallym University, Hwaseong
4Neurology, Cheonan Hospital, Soonchunhyang University, Cheonan
5Neurology, Bundang Hospital, Seoul National University, Seongnam
6Neurology, Ewha Womans University School of Medicine, Seoul, Korea, Republic Of
Objectives
It has been reported that sleep or sleep-related problems were common among migraineurs. Both sleep quality and sleep quantity are related to health and well-being. Sleep studies among migraineurs have reported that sleep duration did not differ from that of non-migraineurs. Therefore, difference in sleep quality may cause for higher sleep disturbance among migraineurs than non-migraineurs. Probable migraine (PM) is a subtype of migraine which fulfilled all but one criterion of migraine. However, there is little knowledge of the association between sleep quality and PM. This study is to investigate the association of poor sleep quality among individuals with PM in comparison with those with migraine.
Methods
We used the data of Korean Headache-Sleep Study (KHSS) in the present study. The KHSS is nation-wide population-based survey regarding headache and sleep for adults aged 16–69 years. We defined poor sleep quality as Pittsburgh Sleep Quality Index (PSQI) score > 5.
Results
Headache frequency and headache intensity according to the presence of poor sleep quality among individuals with migraine and probable migraine.
Mean ± standard deviation, #median and 25% > 75% interquartile range
Conclusion
Approximately 1/3 of individuals with PM had poor sleep quality across a general population-based sample. Poor sleep quality was associated with increased headache frequency and more severe headache intensity among individuals with PM.
Disclosure of Interest
M. K. Chu Conflict with: Hallym University Research Fund, Conflict with: Advisory board for Teva, Conflict with: Allergan Korean and Yuyu Pharm, B. Choi Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, W.-J. Kim Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, S.-J. Cho Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, K. I. Yang Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, C.-H. Yun Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, T.-J. Song Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None
Comorbidity of Primary Headaches
PO-02-031
Validation of the Patients Health Questionnaire-9 (PHQ-9), PHQ-2, Generalized Anxiety Disorder-7 (GAD-7), and GAD-2 in patients with tension-type headache
Jong-Geun Seo1,*, Sun-Young Kim2, Hye-Jin Moon3, Jin Kuk Do4 and Sung-Pa Park1
1Department of Neurology, School of Medicine, Kyungpook National University, Daegu
2Department of Neurology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan
3Department of Neurology, Keimyung University School of Medicine, Dongsan Medical Center
4Department of Neurology, School of Medicine, Catholic University of Daegu, Daegu, Korea, Republic Of
Objectives
Tension-type headache (TTH) is the most common headache disorder and psychiatric comorbidity is frequently reported in patient with TTH. The association of headache with psychiatric comorbidity has a major influence on the clinical outcome and quality of life. Therefore, the early diagnosis and treatment of psychiatric comorbidity is important for the proper management of patients with TTH. The aim of this study was to evaluate the validity of the Patient Health Questionnaire-9 (PHQ-9), PHQ-2, Generalized Anxiety Disorder-7 (GAD-7), and GAD-2 in patients with TTH.
Methods
Patients with TTH were recruited from four tertiary-care hospitals. The Mini International Neuropsychiatric Interview-Plus Version 5.0.0 (MINI) was used to diagnose current major depressive disorder (MDD) and generalized anxiety disorder (GAD). Subjects completed several instruments, including the PHQ-9, the GAD-7, and the Headache Impact Test-6 (HIT-6). The receiver operating characteristic (ROC) analyses for the PHQ-9, PHQ-2, GAD-7, and GAD-2, over a range of cutoff scores, were performed for comparison to MDD and GAD diagnoses by the MINI.
Results
Among 160 subjects, 23.8 % had current MDD and 21.3% had current GAD as determined by the MINI. Cronbach’s α coefficients for the PHQ-9, PHQ-2, GAD-7, and GAD-2 were 0.858, 0.722, 0.868, and 0.626 respectively. Receiver operating characteristic analysis of the PHQ-9, PHQ-2, GAD-7, and GAD-2 exhibited an area under the curve of 0.876, 0.817, 0.933, and 0.888 respectively. The scale with the highest sum of sensitivity (89.5%) and specificity (67.2%) was the PHQ-9 with a cut point of 7 and the scale with the highest sum of sensitivity (73.7%) and specificity (77.9%) was the PHQ-2 with a cut point of 2. The scale with the highest sum of sensitivity (85.3%) and specificity (86.5%) was the GAD-7 with a cut point of 8 and the scale with the highest sum of sensitivity (76.5%) and specificity (83.3%) was the GAD-2 with a cut point of 2. The scores of the PHQ-9, PHQ-2, GAD-7, and GAD-2 were well correlated with the HIT-6 score.
Conclusion
The PHQ-9, PHQ-2, GAD-7, and GAD-2 are valid screening instruments for detecting MDD and GAD in patients with TTH.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-032
The prevalence of right to left shunts in Japanese patients with migraine: a single center study
Akio Iwasaki1,*, Keisuke Suzuki1, Hidehiro Takekawa1, Ryotaro Takashima1, Ayano Suzuki1, Shiho Suzuki1 and Koichi Hirata1
1Neurology, Dokkyo Medical University, Tochigi, Japan
Objectives
An increased prevalence of right-to-left shunt (RLs) in migraine patients, particularly those with aura has been reported. However, the prevalence of RLs and its clinical correlation in Japanese patients with migraine remain unclear. In this study, we conducted a single center study to investigate the prevalence of RLs in Japanese patients with migraine.
Methods
A total of112 consecutive patients with migraine were recruited from our headache outpatient clinic. Migraine with aura (MA) and migraine without aura (MWOA) were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta-edition). Contrast transcranial Doppler ultrasound was used to detect RLs, including patent foramen ovale (PFO). The associations between RLs and clinical background factors of patients MA and MWOA were assessed.
Results
MA patients were younger (p = 0.013) and had early onset age (p = 0.013) and increased prevalence of photophobia (p = 0.008) compared with MWOA patients. The overall prevalence of RLs and PFO in migraine patients was 54.5% and 43.8%, respectively. A significant increased prevalence of RLs and PFO in the MA groups was observed compared with MWOA groups (RLs, 62.9% vs. 44.0%, p = 0.046; PFO, 54.8% vs. 30.0%, p = 0.008).
Conclusion
In our study, over half of the Japanese patients with migraine showed RLs. Also, our study results suggest a possible association between RLs and MA.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-033
TREATMENT EFFECT IN VISUAL SNOW
Francesca Puledda1,*, Tze Lau1, Christoph Schankin2 and Peter J Goadsby1
1Headache Group, Department of Basic and Clinical Neuroscience, King’s College London, and NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital, King's College London, London, United Kingdom
2Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Objectives
Patients with Visual Snow suffer a pan-field, dynamic visual disturbance. Proposed diagnostic criteria require at least two additional visual symptoms from: palinopsia, entoptic phenomena, photophobia and nyctalopia (1). Little is known regarding useful pharmacological treatments for patients. The aim of this study was to gain knowledge on the effect of a number of commonly used medications on Visual Snow.
Methods
A questionnaire was prepared in collaboration with the patient group Eye-on-Vision and sent to subjects who had expressed an interest in research. It asked the participant to select from a list of drugs, including antiepileptics, antidepressants and benzodiazepines, the ones that had been used at least once since symptom onset. Participants were then asked to mark the effect of these treatments on their Visual Snow, particularly if there had been an improvement or a worsening. The questionnaire also enquired on the use of recreational drugs, including cannabis, and their effect on Visual Snow. The study was approved by KCL Research Ethics Panel.
Results
Two hundred and four patients returned the questionnaire, with the effect of one-hundred and twelve drugs recorded in 611 reports. Less than half of the subjects (n = 92) showed any response to medication, either in the form of an improvement or a worsening. Antidepressants and antiepileptics were the most commonly used medications; they showed no effect on Visual Snow in 55% and 57% of reports, respectively. When benzodiazepines had been used in the past, an improvement of Visual Snow symptoms was reported in 29% of cases. Recreational drug use, always subsequent to symptom onset, was reported 117 times and caused a transient worsening in symptoms in 32% of cases, although in the majority of cases (61%) no effect was reported.
Conclusion
Visual Snow is a highly disabling syndrome, for which there is no widely accepted treatment. Most of the commonly used medications available show little or no effect on symptoms. In the future more effort needs to be made in understanding the pathophysiology and biological basis of this disorder, in order to allow focused treatment strategies for patients.
References
1) Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ. Visual snow- a disorder distinct from persistent migraine aura. Brain. 2014;137:1419–28
Disclosure of Interest
F. Puledda: None Declared, T. Lau: None Declared, C. Schankin: None Declared, P. Goadsby Conflict with: Dr. Goadsby reports grants and personal fees from Allergan, Amgen, and Eli-Lilly and Company; and personal fees from Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion; and personal fees from MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press; and in addition, Dr. Goadsby has a patent Magnetic stimulation for headache pending assigned to eNeura.
Comorbidity of Primary Headaches
PO-02-034
Clinical Implications between Headache and Gastrointestinal Disorders: The Study using Hallym Smart Clinical Data Warehouse
Jong-Hee Sohn1,* and Sang-hwa Lee2
1Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Gangwon-do
2Department of Neurology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Gangwon-do, Korea, Republic Of
Objectives
The brain and gastrointestinal(GI) tract are strongly connected via neural, endocrine, and immune pathways. Previous studies suggest that headache, especially migraine may be associated with various GI disorders, including gastroparesis, irritable bowel syndrome, peptic ulcer, and celiac disease. But upper GI endoscopy in migraineurs have shown a low prevalence of abnormal findings. Also, most studies have not demonstrated any association between Helicobacter pylori (HP) infection and migraine, although a pathogenic role for HP infection in migraine has been suggested. Further knowledge about headache and GI disorders is important: it may affect therapeutic consequence. Thus, we sought to investigate possible associations between GI disorders and primary headache such as migraine and tension-type headache (TTH) using the Smart Clinical Data Warehouse (CDW) during 10 years.
Methods
We retrospectively investigated clinical informations using a clinical data analytic solution called Smart CDW at Chuncheon Sacred Heart Hospital from January 2006 to August 2016. In patients with migraine and TTH, diagnosis of GI disorders visiting at gastroenterology center, upper GI endoscopy findings and results of HP infection collected and compared to clinical data in patients with controls (subjects who had medical check-up without headache). The time interval between diagnosing headache at neurology and underwent examination at gastroenterology center not exceed maximum of one year.
Results
We identified total 387 eligible case subjects in patients with migraine (mean age 41.39, 80.8 % female) and TTH (mean age 52.83, 61.4% female) respectively. Among the diagnosis of GI disorders by gastroenterologist, gastroesophageal reflux disorder is more prevalent in migraine than in TTH groups, whereas gastritis and gastric ulcer are more common in TTH than in migraine group (p < 0.001). In Endoscopic findings, high numbers of reflux esophagitis showed in migraine group, whereas gastric ulcer was significantly higher in patients with TTH compared with controls (p < 0.05).But, no differences were observed the prevalence of HP infection between the groups.
Conclusion
The observed association may suggest that primary headache suffers such as migraine and TTH are predisposed to GI disorders and this may have clinical implications. Further research about etiology of association of headache and GI disorders is needed.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-035
Risk factors for syncope in a migraine cohort
Ai-Seon Kuan1,2,*, Jong-Ling Fuh1,2, Shih-Pin Chen1,2, Yen-Feng Wang1,2 and Shuu-Jiun Wang1,2
1Faculty of Medicine, National Yang-Ming University School of Medicine
2Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
Objectives
The co-occurrence of migraine and syncope is high. Studies have reported prevalence of between 5.3% and 46.0% for syncope in patients with migraine. Few studies have reported the risk factors for syncope. The present study aimed to estimate the comorbidity of syncope and investigate its clinical correlates in patients with migraine.
Methods
Patients who were newly diagnosed with migraine by neurologists in the headache clinic in the Taipei Veterans General Hospital between January 2015 and December 2016 were recruited into this study. Information on demographics, lifestyle and comorbid health conditions was collected through questionnaires, and detailed assessments of migraine, aura symptoms, allodynia, anxiety, depression, and syncope were conducted. The associations between these personal and clinical factors and syncope were studied using a case-control design, with the cases consisting of migraine patients with syncope, and the controls of migraine patients without syncope. Relative risks (RRs) were calculated using unconditional logistic regression. Statistical significance was defined as two-tailed p < 0.05.
Results
A total of 829 patients with migraine (219 cases and 610 controls) were recruited into this study. 26.4% of patients with migraine had syncope. The majority of these patients reported having first syncope after having first headache, with the events a median of 8.0 (interquartile range, 4.0–16.0) years apart. In multivariate analyses, being female and having migraine with aura were associated with a significantly increased risk of syncope, with adjusted RRs of 2.07 (95% CI 1.26–3.40) and 1.87 (95% CI 1.16–3.01), respectively. Age, smoking, drinking, body mass index, level of education, age at first headache, frequency of headaches, and headache intensity were not significantly associated with the risk of syncope. Among the 10 comorbid health conditions that were studied, suicidal ideation was associated with a significantly increased risk of syncope (adjusted RR 1.68, 95% CI 1.17–2.41), even after correcting for multiple testing. Worse scores for the Migraine Disability Assessment (p for trend [ptrend] = 0.032), Hospital Anxiety and Depression Scale for anxiety (ptrend = 0.010) and depression (ptrend < 0.011), Beck Depression Inventory (BDI) score (ptrend < 0.001), and higher number of sites of allodynia during migraine attack (ptrend = 0.049) were associated with an increased risk of syncope. Having two or more of the following factors: being female, migraine with aura, and suicidal ideations (or BDI score ≥ 19) was associated 3 times higher risk of syncope when compared with having none of them.
Conclusion
The prevalence of syncope is 26.4% in our cohort of migraine patients. Being female, having migraine with aura, suicidal ideations, greater disability caused by migraine and having more anxiety and depression symptoms are significant risk factors for syncope in migraine patients.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-036
Clinical relevance of salivary cortisol in patients with fibromyalgia
Wei-Ta Chen1,2,*, Jong-Ling Fuh1,2 and Shuu-Jiun Wang1,2
1Taipei Veterans General Hospital
2National Yang-Ming University, Taipei, Taiwan, Republic of China
Objectives
Chronic pain is associated with altered hypothalamic-pituitary-adrenal axis function. Some studies have linked fibromyalgia (FM) to hypocortisolism. However, the clinical relevance of cortisol remains undetermined in patients with FM.
Methods
Consecutive patients with FM aged 20–69 and fulfilling the Modified 2010 ACR Criteria were enrolled from Taipei Veterans General Hospital. At first visit, all patients completed a questionnaire assessment on fibromyalgia symptoms [Widespread Pain Index (WPI) and Symptom Severity (SS) scale], functional status [Revised Fibromyalgia Impact Questionnaire (FIQR)], mood [Hospital Anxiety and Depression Scale (HADS)], sleep [Pittsburgh Sleep Quality Assessment (PSQI)], and stress [Perceived Stress Scale (PSS)] as well as an evaluation of tenderness (18 tender points). On a scheduled day (<1 week after first visit) while patients engaged in usual daily activities, salivary cortisol was collected at four time-points: awakening, 30 minutes after awakening, 3 pm, and 9 pm (at bedtime). Individual basal cortisol level was computed using the area under the curve (AUC) with respect to ground. Individual cortisol variability was also calculated as the difference between morning (30 minutes after awakening) and evening (bedtime) values. Appropriate power transformation was carried out for positively skewed variables before analysis.
Results
A total of 126 patients joined this study (107F/19M; mean age 43.6 ± 10.2). The cortisol levels at four time-points did not correlate with any clinical variables or tenderness. The basal cortisol level was associated with SS scale (r = 0.204, p = 0.022) but not with any other clinical variables. Cortisol variability was positively correlated with depression severity (r = 0.190, p = 0.034) and negatively correlated with tenderness (r = −0.195, p = 0.030) and global PSQI score (higher score indicating poor sleep quality; r = −0.198, p = 0.034). After adjustment of depression, all the above clinical correlations disappeared except for PSQI, as shown by a linear regression analysis that a lower cortisol variety was independently related with poor sleep quality (beta: −0.243, p = 0.008).
Conclusion
Salivary cortisol is associated with sleep quality and depression but not with pain or tenderness in patients with FM. Future longitudinal studies must investigate the temporal relationship of cortisol and fluctuating fibromyalgia-related symptoms.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-037
The Anxious Brain in Pain: Increased Levels of Anxiety, Depression and Stress Associated with Chronic Daily Headaches Patients Presenting to University-based Headache Clinic
Natalia Murinova1,*, Daniel Krashin2 and Melissa Schorn1
1Neurology
2Psychiatry and Pain & Anesthesia, University of Washington, Seattle, United States
Objectives
The primary objective of this study was to survey patients referred to a university-based headache with chronic daily headaches (CDH) regarding perceived stress, anxiety and depression.Patients referred to specialty headache clinics are more likely to have CDH, to be intractable, and have medication overuse. These patients report increased rates of mood, anxiety, and stress issues.
Methods
All new patients at a tertiary headache clinic complete a detailed patient intake questionnaire prior to their first visit. Of the 1826 completed patient intakes, 1150 reported CDH. Headache triggers, Perceived Stress Scale (PSS) scores, PHQ-4 assessments of anxiety and depression were assessed.
Results
Patients with CDH report stress as their most common trigger (603, 52.6%). CDH patients had elevated PSS scores with a mean of 17.5 compared with a normative value of 13.7. When stratified according to PSS scores, 55% (613) had moderate stress (PSS 14 to 27) and 12% (142) severe stress (PSS > 27). Patients had elevated scores on the PHQ4 measurement of depression and anxiety, with a 3.8 mean. When we examined those patients with a PHQ4 score of 5 or above, which is suggestive of a diagnosable mood or anxiety disorder, they represented 33.7% of the chronic headache patients, with very elevated PSS scores with a mean of 24.3
Conclusion
Patients with CDH referred to a tertiary university headache clinic were noted to have elevated stress levels on the PSS and identify stress as their most significant headache trigger. Significant fractions of the CDH group reported either extremely high stress scores or high depression and anxiety scores. Since it is not realistic or helpful to simply counsel these patients to “avoid stress” or “avoid nervousness”, headache providers must be able to address these behavioral issues in their clinics or through referrals.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-038
Sleepy Brain in Pain: Prevalence of Sleep Problems in a University-Based Headache Clinic
Natalia Murinova1,*, Daniel Krashin2, Melissa Schorn1, Sau M Chan-Goh1 and Flavia Consens1
1Neurology
2Psychiatry and Pain & Anesthesia, University of Washington, Seattle, United States
Objectives
The primary objective was to study the nature and prevalence of sleep complaints with specific headache diagnoses in patients presenting to a university-based tertiary care headache clinic.
Methods
All new patients at a tertiary headache clinic complete a detailed patient intake questionnaire prior to their first visit. This questionnaire contains a section on sleep symptoms and previous sleep disorder diagnoses. Later the clinician makes a specific headache diagnosis using IHS beta 3, this is entered into the database as well.
Results
Of the 864 patients, 548 (63.5%) endorsed sleep problems. The most common sleep problems reported were trouble staying asleep (62.4%), waking up feeling not refreshed (61.3%), and insomnia (34.1%). When compared to the subpopulation of headache patients who did not report sleep problems, certain headache diagnoses were much more common, including: chronic migraine (71% vs 52%), medication overuse headache (48% vs 34%), and cervicogenic headache (10.6% vs 5.7%)
Conclusion
A majority of the patients presenting to the university-based headache clinic have significant comorbid sleep disorders, especially trouble staying asleep, waking up feeling not refreshed, and insomnia. It is important to pay attention to sleep comorbidities associated with headache, since sleep disorders have been identified as modifiable risk factors for migraine progression. These results suggest that sleep assessment and treatment should become an integral part of specialty headache care.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-039
The Association between Alexithymia, Depresion, Anxiety and Midas in Migraine patients
Pinar Yalinay Dikmen1,*, Elif Onur Aysevener2, Seda Kosak1, Elif Ilgaz Aydinlar1 and Ayse Sagduyu Kocaman1
1Neurology department, acibadem university, school of medicine, istanbul
2Psychiatry department, dokuz eylul university, faculty of medicine, izmir, turkey
Objectives
Alexithymia concerns difficulty or incapacity to express emotions through words. The co-existence of psychiatric comorbidities with migraine is well-known; however, few studies have yet addressed the relationship between migraine and alexithymia. To assess the relationships between migraine, depression, anxiety, alexithymia and migraine-related disability.
Methods
One hundred and forty five migraineurs (33.18 ± 8.6; 111 female, 34 males), and 50 control subjects (29.06 ± 7.6; 34 females, 16 males) were prospectively enrolled for the study.
The participants completed a sociodemographic data form and a migraine disability assessment scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory and Toronto Alexithymia Score-20 (TAS-20).
Results
Depression and anxiety scores in episodic migraine patients were normal except for chronic ones, while all migraineurs were more depressive (p = 0.01) and anxious (p = 0.001) than healthy subjects. The TAS-20 scores of the migraineurs and control group did not indicate alexithymia. The migraine-related disability of all `migraine patients was severe (27.84 ± 29.22).
Depression scores in the migraineurs were correlated with anxiety (r = 0.47, p = 0.001) and alexithymia (r = 0.48, p = 0.01) and all its subscales in turn: difficulty in identifying (r = 0.435, p = 0.001) (Factor 1) and describing feelings (r = 0.451, p = 0.001) (Factor 2), and externally oriented thinking (r = 0.3, p = 0.001) (Factor 3).
Anxiety scores positively correlated with difficulty in identifying and describing feelings, externally oriented thinking, TAS-20 and BDI scores, in turn; (r = 0.473, p = 0.001), (r = 0.398, p = 0.001), (r = 0.22, p = 0.008), (r = 0.46, p = 0.001), (r = 0.47, p = 0.001).
MIDAS total scores showed a positive correlation with difficulty in describing feelings, and BDI scores, respectively; (r = 0.21, p = 0.01),(r = 0.33, p = 0.001). Headache frequency in past 3 months (MIDAS A scores) were positively correlated with difficulty in describing feelings, TAS-20 and BDI scores, in turn; (r = 0.19, p = 0.02), (r = 0.17, p = 0.04), (r = 0.335, p = 0.001).
Conclusion
The present study demonstrates that alexithymia is mainly connected with psychiatric pathology, not with migraine. Moreover the severity and disability of migraine are linked to depression, alexithymia and difficulty in describing emotions. Our findings showed that alexithymia was not an associated risk factor on its own for migraine without comorbid depression and anxiety. The early identification and treatment of psychiatric comorbidities and negative affect may be benefical in preventing the chronification of migraine and reducing the economic burden of its effects.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-040
Noonan syndrome associated with migraine and cluster headache
Veselina Grozeva1,* and José Miguel Láinez2; Prof. José Miguel Láinez group
1MHATNP “St. Naum” Sofia, Sofia, Bulgaria
2Hospital Clínico Universitario de Valencia, Valencia, Spain
Objectives
Noonan syndrome is a genetic congenital disorder with phenotypic neurological features such as mental retardation, intracranial aneurysm, cavernous angioma, and Moyamoya disease. Although, a positive association between Noonan syndrome and migraine exists, NS with migraine and concurrent cluster headache has never been reported.
Methods
We present a a clinical case of a 35-year-old Caucasian woman with Noonan syndrome and migraine that associates with cluster headache.
Results
Our patient was diagnosed with Noonan syndrome at the age of 9. When she was 20, complaints of mild (pain intensity VAS = 3) left-sided fronto-temporo-parietal throbbing headache started. Each attack lasted around 5 hours, with frequency of 6 attacks per month. At the age of 29, a headache with different characteristics appeared along with the usual one. The new headache was more severe (VAS = 10). Pain was localized in the left retroorbital region. It was stabbing in character, accompanied by ipsilateral autonomic signs (conjuctival injection, lacrimation and eyelid edema). Attacks’ duration was around 2 hours. Frequency was twice daily. The headache was more likely to start late in the evening or during the night. The new attacks appeared in spring and autumn and the attack periods lasted for 2 months.
Conclusion
The described case provides evidence of co-existing migraine and cluster headache in a patient with Noonan syndrome. Although, unilateral cranial autonomic features may occur in migraine patients with longer disease progression, the last type of headache attacks of our patient fulfill the ICHD criteria for cluster headache. Similar pathogenetic mechanisms may be suggested between the two primary headaches in our patient. As Noonan syndrome is caused by missense mutations in the PTPN11 gene on chromosome 12, and migraine is often a co-morbid disease, other migraine and cluster headache genes can be studied in the same chromosome.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-041
Characteristic of headache in lacunar strokes in Kyrgyzstan and influence on outcome: short-term longitudinal study
Inna L Lutsenko1,* and Dayana Nazhmudinova1
1Kyrgyz State Medical Academy, Bishkek, Kyrgyztan
Objectives
Lacunar infarcts or small subcortical infarcts result from occlusion of a single penetrating artery and account for one quarter of cerebral infarctions, developed mostly in arterial hypertension cohort. In literature review headache in lacunar stroke is unspecific and not fully described.
To characterise headache in lacunar strokes, and to find a correlation between headache type, intensivity and stroke outcome.
Methods
We studied a sample of 68 patients with acute lacunar infarction according TOAST criteria and with lacunar lesion on DWI scans of MRI, scored NIHSS scale at onset.Fazekas scale was used for leukoareosis estimation. All patients were tested on the presence of headache in the onset of stroke, its localisation and severity was estimated according to Visual Analogue Scale (VAS). In 10 days after stroke NIHSS and VAS were repeatedly measured and statistical correlation between them was searched.
Results
Headache was present in 90 % of observed patients at onset, strongly connected with arterial hypertension (p = 0.0001). Systolic blood pressure higher than 156 mm was associated with increasing headache in sample (p = 0.01). Headache was diffused and “pressure type” in 78% of all headache patients. Mean baseline NIHSS score in patients with headache was 8 (±1.8), what is minor stroke and mean VAS was 6 (±2). There was no significant correlation between intensity of baseline headache and baseline NIHSS, and lacunar infarct localisation and headache intensity, but strong association of dull headache and infarcts with leukoareosis in 3rd stage. In 64% headache significantly decreased to 10th day of stroke (VAS 3 ± 0.9).
Conclusion
In patients with lacunar infarction, headache tends to be moderate, diffuse and “pressure type”, not correlates with infarction site and NIHSS scale. 3rd stage of leukoareosis we found strongly associated with headache (p = 0.001).
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-042
The Prevalence And Severity of Headache in Multiple Sclerosis Patients treated with Interferon Beta
Serla Grabova1,*, Redona Hafizi2, Ilir Alimehmeti3, Suela Dibra2 and Jera Kruja4
1Neurology, UHC Mother Teresa
2Pharmacy
3Family Medicine
4Neurology, University of Medicine, Tirana, Tirana, Albania
Objectives
Evaluation of the prevalence and severity of headache in patients under treatment with IFNβ
Methods
52 patients with RRMS treated with IFNβ (group 3) for at least three months in the Service of Neurology, at UHC “Mother Theresa”, Tirana were compared with two control groups, respectively with 37 patients with MS not under treatment with IFNβ (group 2) and 208 healthy individuals (group 1). Data on the clinical features of MS and about therapy were collected. An oral interview on headache and the MIDAS test were performed to the three groups. The patients with MS were evaluated with the EDSS scale of Kurtzke.
Results
The data indicate that the difference between the average values of MIDAS in group 3 and 1 is statistically significant (p = 0.0000), and the difference between these values lies in the Confidence interval of 95%. MIDAS score in people with MS under treatment with IFNβ is 8 times greater than in the healthy population. While there are large differences in the values obtained from the MIDAS test (p = 0.000) and in the presence or absence of headache (p = 0.05) between the group of patients with MS under treatment with interferon beta and the group of patients with MS which are not under treatment with interferon beta.
Conclusion
The study conducted on the importance of headache in patients with multiple sclerosis under treatment with interferon beta found that the prevalence of headache in this group of patients was 68%, while the severity of headache belonged to the third degree of the MIDAS test corresponding to a moderate disability.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-043
The association of epilepsy, headache and migraine: a case-control study
Renata G Londero1,* and Marino M Bianchin1
1Neurology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Objectives
Epilepsy and headache are commonly observed to occur together and they are perhaps comorbid pathologies. However, because of divergences in findings of a comorbid association between epilepsy and headache or migraine, and because of lack of reports from places where epilepsy is more common, the question of whether epilepsy and headache or epilepsy and migraine are linked remains unsolved, and a possible comorbid relationship between both conditions remains not fully understood. In this study, we have tried to investigate the association of headache and epilepsy using two different approaches. First, we studied frequencies of common types of headaches in focal or generalized forms of epilepsy, comparing results with individuals without epilepsy, but evaluated by the same neurologists who evaluated headache in patients with epilepsy, using the same tools. Secondly, we explored similarities and differences among risk factors for common types of headaches in epilepsy in order to understand better possible mechanisms of the associations observed.
Methods
This is a case-control study. Two hundred and forty-four consecutive patients with epilepsy were included in this study. One hundred and seventy-one healthy controls, selected among the healthy companions of other patients who came to our outpatient epilepsy clinic were invited as controls. Patients with cognitive deficits severe enough for difficult subjective evaluations were excluded from the study. All individuals, patients with epilepsy and controls, were submitted to the same semi-structured interview with specific questions focusing on health problems, medications in use, familiar history of diseases (epilepsy, headache and migraine), and specific questions about epilepsy or headache. For analysis, epilepsy was divided in focal or generalized type. Focal epilepsies were further divided in temporal and extra-temporal focal epilepsies. Multinominal logistic regression was used to stablish independence of associations observed.
Results
The mean age was 43.9 (SD = 14.8) for patients and 44.1 (SD = 15.1) for controls. As expected, patients with epilepsy were more often retired or not working. One hundred and eighty-one (75.1%) patients and 67 (39.2%) controls reported at least one episode of headache during the last year. Migraine occurred in 92 (38.2%) patients with epilepsy and 32 (18.7%) controls, a significant difference (OR = 2.63; 95% CI = 1.65–4.18; p < 0.0001). Tension-type headache was also more observed in patients with epilepsy when compared with controls (OR = 2.10; 95% CI = 1.08–4.10; p = 0.018). Headache affected predominantly women. After multinominal logistic regression, female sex, familial history of headache or migraine, and focal or generalized epilepsy were all independently associated with tension-type headache, with migraine and with the other types of headache grouped together. Migraine was more strongly associated with epilepsy. Our data support that, while migraine is more generally comorbid in epilepsy, tension-type headache or other forms of headaches are also independently associated with focal or generalized epilepsies.
Conclusion
In this study, we observed that tension-type headache, migraine and other less common forms of headache were all independently associated with focal or generalized epilepsies. Migraine showed the strongest relationship. Despite of the independence of these associations, when data are taken together for interpretation, our results support the view that, while migraine might share a more broad and common comorbid mechanisms with epilepsy, the other forms of headache also share common mechanisms with epilepsies and are also significantly increased in patients with focal or generalized epilepsies. Acknowledgements: this study was fully supported by Brazilian governmental agencies CNPQ, FAPERGS, HCPA-FIPE and CAPES.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-044
Greater occipital nerve block in the treatment of triptan-overuse headache: A randomized comparative study
Ömer Karadaş1, Akçay Övünç Özön2, Fatih Özçelik3 and Aynur Özge4,*
1Neurology, Gülhane Training and Research Hospital, Ankara
2Neurology, Kemerburgaz University
3Medical Biochemistry, Haydarpaşa Sultan Abdulhamid Training and Research Hospital, İstanbul
4Neurology, Mersin University School of Medicine, Mersin, Turkey
Objectives
This study aims to investigate the efficiency of a single and repeated greater occipital nerve (GON) block using lidocaine in the treatment of triptan-overuse headache (TOH), whose importance has increased lately
Methods
In the study, 105 consecutive subjects diagnosed with TOH were evaluated. The subjects were randomized into three groups. In Group 1(n = 35), only triptan was abruptly withdrawn. In Group 2(n = 35), triptan was abruptly withdrawn and single GON block was performed. In Group 3 (n = 35), triptan was abruptly withdrawn and three-stage GON block was performed. All patients were injected bilaterally with a total amount of 5 cc 1% lidocaine in each stage. During follow-up, the number of headache days per month, the severity of pain (VAS), the number of triptans used, and hsCRP and IL-6 levels were recorded three times; in the pretreatment period, in the second month post-treatment, and in the fourth month of post-treatment. They were then compared
Results
There was a statistically significant difference in the post-treatment fourth month in comparison with the pretreatment period in Group 3 (p < 0.05). Compared to Group 1, the number of headache days, VAS, and decrease in triptan need in Group 3 was statistically significant compared to Group 2 (p < 0.05). Compared to pretreatment, in the fourth month post-treatment, both hsCRP and IL-6 levels were lower only in Group 3 (p < 0.05)
Conclusion
We are of the opinion that repeated GON block in addition to the discontinuation of medication has significant efficacy for TOH cases
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-045
Carotid intima-media thickness and aortic pulse wave velocity in perimenopausal women with migraine: a cross-sectional study
Joao E Magalhaes1, Rodrigo Pinto Pedrosa2 and Pedro Sampaio Rocha Filho1,*
1Universidade Federal de Pernambuco e Universidade de Pernambuco
2Pronto Socorro Cardiológico de Pernambuco, Universidade de Pernambuco, Recife, Brazil
Objectives
Migraine is associated with increasead cardiovascular mortality. There is still an unexplained link between them. It is possible that both conditions share an underlying vascular dysfuntion. The aim of this study is to evaluate the association between migraine and increased carotid intima-media thickness (cIMT) and between migraine and arterial stiffness (increased aortic pulse wave velocity - aPWV) in perimenopausal women.
Methods
We recruited 304 consecutive women with more than 60 days of menstrual irregularity, aged 45 to 65 years-old who were submitted to a strict protocol, including a semi-structured interview, physical examination, blood tests, portable sleep study, high-resolution carotid ultrasound, and aortic pulse wave tonometry. We also used the hospital anxiety and depression scale, the general cardiovascular risk profile from the Framingham Heart Study, and the 6-item Headache Impact Test. The presence of increased carotid intima-media thickness was indicative of subclinical atherosclerosis and increased aPWV was indicative of arterial stiffness. All patients had given their informed consent. The study was approved by the Research Ethics Committee of the Oswaldo Cruz University Hospital.
Results
We included 277 women in the final sample. The prevalence of migraine and migraine with aura (MA) were respectively 40.1% and 16.5%. Women with migraine with aura (MA) were younger (51 ± 3 vs. 55 ± 7 years, p = 0.04) and had more diagnosis of arterial hypertension (76.1% vs. 59.1%, p = 0.04), depression (71.7% vs. 37.6%, p < 0.001), and anxiety (82.6% vs. 57.6%, p < 0.001) than those without migraine. Apnea-hypopnea index, diagnosis of obstructive sleep apnea and aPWV were not different between migraine, MA, or migraine without aura (MO) groups and non-migraine group. Six women (2.2%) presented increased cIMT which was more prevalent in MA group (6.5% vs. 1.2%, p = 0.04) than non-migraine group. After adjustment for confounding factors we found that MA increases seven-fold the risk of increased cIMT (OR 7.12, 95% IC1.05–48.49). We found no difference on overall median Framingham score between migraine subgroups and non-migraine group.
Conclusion
Migraine is not associated with arterial stiffness. Migraine with aura is associated with increased carotid intima-media thickness in perimenopausal women. Therefore, it is important to consider that cIMT could be a marker of endothelial dysfunction in migraineurs.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-046
Misclassification on the diagnosis of overweight/obesity in migraineurs using the body mass index as compared to body adiposity
Ane Minguez-Olaondo1,2,*, Sonia Romero Sánchez3,4, Francisco Carmona-Torre5, Camilo Silva Froján3, Laura Imaz Aguayo1, José Miguel Láinez2,6, Gema Frühbeck Martínez3,4 and Pablo Irimia Sieira1
1Neurology, Clínica Universidad de Navarra, Pamplona
2Neurology, Hospital Clínico Universitario de Valencia, Valencia
3Endocrinology, Clínica Universidad de Navarra
4CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII
5Microbiology and infectious diseases, Clínica Universidad de Navarra, Pamplona
6Neurology, Universidad Católica de Valencia, Valencia, Spain
Objectives
The prevalence of both episodic and chronic migraine is increased in obese individuals when compared to normal weight. Body mass index (BMI) is the diagnostic tool widely used to classify obesity, but this method underestimates its prevalence, defined as an increase in body fat percentage (BF%). We aimed to examine the potential misclassification regarding the diagnosis of overweight and obesity by using BMI as compared with the determination of BF% (Bod Pod®) in migraineurs.
Methods
Fifty-nine patients (18–49 years-old), 46 with episodic migraine and 13 with chronic migraine, underwent BMI and Bod Pod® exams. Patients with known comorbidities such as severe or systemic diseases, pregnancy or breastfeeding, major psychiatric disorders, immunosuppression or morbid obesity, according to BMI were excluded from the study. Bod Pod® parameters and anthropometric data were analysed. We performed a descriptive analysis to assess misclassification on the diagnosis of obesity using BMI as compared with BF% and Cohen's Kappa Coefficient Index to evaluate the quality of agreement.
Results
We found that 1 (1,7%) patient was classified as underweight, 43 (72,9%) normal weight, 11 (18,6%) overweight and 4 (6,8%) obese according to BMI. Using BF% 2 (3,4%) patients were classified as underweight, 19 (32,2%) patients as normal weight, 13 (22,0%) as overweight and 25 (42,4%) as obese. Cohen's Kappa Coefficient Index value was 0,220 which is no more than a fair degree of agreement.
Conclusion
Our findings suggest that a relevant number of migraine patients are missclassified according to BMI as compared with BF% because of the fair degree of agreement. Replications of present findings in wider population with different frequency of migraine are warranted.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-047
Demographic and clinical profile of chronic migraine in a low income population of Bogota, Colombia
Marta L Ramos1, Stephania Bohorquez1,*, Julia Cuenca1, Luisa F Echavarria1, Sandra Riveros1, Jesús Martinez1 and Fidel E Sobrino1
1Hospital Occidente de Kennedy - Universidad de la Sabana, Bogotá, Colombia
Methods
We conducted an observational, descriptive, and cross-sectional study from June to December of 2016. The data for patients with headache, attending the specialized headache consultation at the Hospital Occidente de Kennedy in Bogotá-Colombia. Diagnosis of headache was according to the International classification of headache disorders (ICHD-III).
Results
A total of 277 patients consulted for headache for first time at the headache unit. 40% (n:110) of patients meet criteria for chronic migraine. 83.6 % are women. The middle age was 47.7 (±13.9),most are single (63.3%), 26,4% did not have any type of education, 86.2% belongs to risk social population and 10% are special populations victims of armed conflict and forced displacement. Osmophobia (70%), medication overuse (51,4%), allodynia (47,7%), aura (46.4%), emesis (31.8%), depression (28,8%) and vertigo (28,4%) were more prevalent in the group of patients with chronic migraine (p < 0,05).
Conclusion
Our patients are part of a special group of vulnerable population, and at social risk. The presence of a high percentage of patients with osmophobia could be related with a central sensitization process. Also we have a significant prevalence of medical overuse related with free analgesic sale in our country. Aura, allodynia, emesis and vertigo were an important find in this population.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-048
Significance of fatigue in patients with migraine
Jong-Geun Seo1,* and Sung-Pa Park1
1Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Korea, Republic Of
Objectives
Fatigue is often stated as a headache trigger or migraine-specific symptom. We investigated predictors of fatigue and its impact on quality of life (QOL) in patients with migraine.
Methods
Patients with migraine were recruited from a headache clinic and completed psychosomatic instruments, including the 12-item Allodynia Symptom Checklist (ASC-12), the Migraine Disability Assessment Scale (MIDAS), the Patients Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI), the Fatigue Severity Scale (FSS), and Migraine-Specific Quality of Life Questionnaire (MSQ).
Results
Two hundreds twenty-six patients with migraine were eligible for the study. Pathologic fatigue was manifested in 133 patients (58.8%). The FSS score was significantly associated with age, age at onset, the Visual Analog Scale (VAS) depicting headache intensity, photophobia, phonophobia, and the scores of the ASC-12, the MIDAS, the ESS, the ISI, the PHQ-9 and the GAD-7. The strongest predictor for the FSS was the PHQ-9 (β = 0.432, p < 0.001), followed by age (β = −0.169, p = 0.002), the ISI (β = 0.151, p = 0.016), and the VAS (β = 0.139, p = 0.018). There was an inverse correlation between the FSS score and three dimensional scores of the MSQ (p < 0.001).
Conclusion
Appropriate interventions for depression, insomnia, and headache intensity are likely to lessen fatigue and improve QOL.
Disclosure of Interest
None Declared
Comorbidity of Primary Headaches
PO-02-049
Association of headache impact test with chronotypes, sleep quality index, anxiety and depression in migraine without aura patients
Karina Velez-Jimenez1,*, Minerva Lopez-Ruiz2,3; on behalf of Ortiz Carmen, Rodriguez-Leyva Ildefonso, Martinez-Gurrola Marco, Ojeda-Echeverria Manuel H, Santana-Vargas Daniel, Carmen Alcantara Ortiz1, Ildefonso Rodriguez-Leyva3, Marco Martinez-Gurrola1, Manuel H Ojeda-Echeverria1 and Daniel Santana-Vargas1
1Neurology, Hospital General of Mexico, City of Mexico
2Neurology, Academy Mexican of Neurology
3Neurology, Hospital General of Mexico, Mexico, Mexico
Objectives
To evaluate the role of chronotypes, sleep quality, anxiety and depression with the headache impact test in migraine without aura patients.
Methods
Twenty eight female pattients (mean age ± S.D. 38.1 ± 11.9 years; range 22–59 years) were enroled at the General Hospital of Mexico City. Diagnostic of migraine without aura were stablished following the criteria of the International Headache Society (HIS). Depression and anxiety, chronotypes and sleep quality were evaluated using the Hospital Anxiety Depression Scale (HADS), Morningness-eveningness Questionnaire (MEQ), and the Pittsburgh Sleep Quality Index (PSQI) respectively. Impact of headache pain was evaluated using the Headache Impact Test (HIT-6) Logistic regression modeling were used to analise these data.
Results
Results: Poor sleep quality (PSQI ≥ 5) was 82.1%, and global score of PSQI was 8.78 (S.D. ± 4.02). Anxiety and depression (HADS) was 50% and 57.1%, (mean 9.7, S.D. ± 2.27; mean 8.6 S.D. ± 2.77) respectively. Chronotypes were moderate (50%) and morning types (50%), mean score 58.1 ± S.D.7.13. Headache Impact test scores was severe in 18 patients (68.4%) and the total score was 60.28 (S.D. ± 8.05) Best predictors for severity of HIT-6 were anxiety (2.755) depression (1.875) while chronotype predicted negatively (−0.603) and sleep quality predicted positively (0.657). constant (0.370).
Conclusion
Impact of headache in daily activities are more influenced by anxiety and depression than chronotypes and sleep quality. Among stressors of migraine sufferers anxiety and depression comorbidity play a major role in migraine without aura probably associated to chronic pain rather than circadian rhythms
Disclosure of Interest
None Declared
Genetics and Biomarkers of Headache Disorders
PO-02-050
INVOLVEMENT OF THE MIGRAINE SNP rs1835740 IN CLUSTER HEADACHE
Caroline Ran1,*, Carmen Fourier1, Anna Steinberg2, Christina Sjöstrand2, Elisabet Waldenlind2 and Andrea C Belin1
1Neuroscience, Karolinska Institutet
2Clinical Neuroscience, Karolinska University Hospital, Stockholm, Sweden
Objectives
The pathophysiology and symptoms of cluster headache presents certain common features with other headache disorders such as migraine. For example, the activation of the trigeminal vascular system, inflammation and vasodilation of the large arteries of the brain. Genetic factors have been implicated in both migraine and cluster headache. In this study we chose to screen cluster headache patients for two genetic variants known to increase the risk for migraine in Sweden: rs2651899 in the PRDM16 (PR/SET domain 16) gene and rs1835740 closely located to MTDH (metadherin), in order to investigate whether these two disorders also share genetic factors of predisposition. Furthermore, we have studied the mRNA expression patterns of these two candidate genes in rodent tissue to achieve a better understanding of how they might affect headache pathophysiology.
Methods
We screened a Swedish cluster-headache case-control study population consisting of 541 cluster headache patients and 571 control subjects for two genetic variants, rs1835740 and rs2651899. Genotyping was performed with TaqMan real-time PCR on a 7500 Fast instrument, results for rs1835740 were further confirmed with pyrosequencing on a PSQ 96 System. Fisher’s test and Chi-square test were used in the statistical analysis. mRNA expression patterns were investigated using radioactive in situ hybridization in cryosections of fresh frozen rat tissue.
Results
We found that rs1835740, an intergenic SNP that is known to affect MTDH activity, was associated with increased risk for cluster headache in Sweden (p = 0.043). The association was stronger in patients suffering from both cluster headache and migraine (p = 0.031). rs2651899 in PRDM16, was not associated with cluster headache in Sweden. Preliminary data from the gene expression analysis shows that MTDH has a widespread expression in rats, covering the central nervous system and several peripheral tissues. Rat PRDM16 mRNA was absent in most peripheral and nervous tissues analysed, with the exception of the lateral septal nucleus, the stomach and the small intestine.
Conclusion
rs1835740 is associated to cluster headache. This variant was more common in patients with both migraine and cluster headache and might therefore constitute a marker for severe headache in general. rs2651899 on the contrary is specifically related to migraine in Sweden.
Disclosure of Interest
None Declared
Genetics and Biomarkers of Headache Disorders
PO-02-051
Genetic pleiotropy between migraine and motion sickness
Dale R Nyholt1,*; on behalf of the International Headache Genetics Consortium (IHGC)
1Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Australia
Objectives
Motion sickness is associated with migraine. In fact, two-thirds of migraine sufferers are prone to motion sickness. Furthermore, migraine sufferers are more susceptible than controls to symptoms evoked by visual simulation of movement, implying that migraine is associated with abnormal central integration of visual and vestibular cues. Given genetic factors may underlie the tendency to motion sickness and the neurotological symptoms of migraine, we examined whether the same genes are involved in both conditions.
Methods
We utilised data from a large genome-wide association (GWA) study on motion sickness (80,494 individuals) [Hromatka, et al. Hum Mol Genet. 2015;24(9):2700–8] and migraine (23,285 migraine cases and 95,425 controls) [Anttila, et al. Nat Genet. 2013;45(8):912–7] to investigate whether single nucleotide polymorphisms (SNPs) associated with motion sickness overlap with SNPs associated with migraine.
Results
SNP rs7518255 on chromosome 1p36.32, showing genome-wide significant association (P < 5 × 10−8) with motion sickness is also significantly associated with migraine. Also, two additional SNPs significantly associated with motion sickness, rs705165 on 10q26.13 and rs11696973 on 20q13.2, show genome-wide suggestive association (P < 1 × 10−5) with migraine. For all three SNPs, the same allele is associated with an increased risk for both traits. Of the 182 independent SNPs showing genome-wide suggestive association with motion sickness, 28 (15.38%) show nominal association (P < 0.05) with migraine—more than double the empirically derived null expectation of 6.89%, producing significant evidence for genetic overlap (pleiotropy) (P = 8.95 × 10−5).
Conclusion
The observed comorbidity between motion sickness and migraine can be explained, in part, by shared underlying genetically determined mechanisms. We are currently extending these findings by performing additional SNP- and gene-based analyses utilising results from a larger migraine GWA study (30,465 migraine cases and 143,147 controls) [Gormley, et al. Nat Genet. 2016;48(8):856–66.]. Preliminary analyses have identified three SNPs with novel genome-wide significant association, and suggest several genes and pathways to be involved in migraine and motion sickness etiology.
Disclosure of Interest
None Declared
Genetics and Biomarkers of Headache Disorders
PO-02-052
Value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in migraineur
Hisanori Kowa1,*, Hiroshi Takigawa1, Toshiya Nakano1 and Kenji Nakashima2
1Department of Neurology, Tottori University Faculty of Medicine, Yonago
2Department of Neurology, Matsue Medical Center, Matsue, Japan
Objectives
The mechanism of migraine is not yet fully understood but may involve in part cortical spreading depression and neurogenic inflammation. Previous studies have shown blood neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) to be simple biomarkers for acute phase of inflammation and to be associated with predictor or prognosis of various disease, such as ischemic heart disease, stroke, chronic kidney disease, and neoplastic disorders.
To analyze the role of inflammation in migraine, we evaluated blood NLR and PLR in migraineurs.
Methods
Twenty-eight patients suffering from migraine with aura (MA) (9 men, 19 women, mean age: 39.1 years), 125 with migraine without aura (MO) (24 men, 101 women, mean age: 41.6 years), and 26 tension-type headache (TH) (9 men, 17 women, mean age: 59.5 years) participated in this study. The diagnosis of headache was made according to the International Headache Society (IHS) criteria. The blood sample for NLR and PLR assessment was collected in each ambulatory care. Acute phase (AP) and intermittent phase (IP) cases were defined respectively as the day of migraine attack and the other days after migraine attack. Patients were classified the frequency of attacks; 0–8 headache days per month, 9–14 headache days per month and 15- headache days per month. Patients were also classified with or without medication overuse headache. Comparisons among groups were assessed by the analysis of multivariate statistics. The level of significance was set at p < 0.05.
Results
The mean NLR in MA, MO, and TH were 1.79, 2.00, and 2.26. The mean PLR in MA, MO, and TH were 136.0, 139.1, and 143.0. The mean NLR was significantly increased in AP than IP, especially with MO, while the mean PLR was also significantly increased in AP, especially with TH. As the frequency of attacks, there was no certain tendency in the mean value of NLR and PLR. There was no significant difference in NLR and PLR between subjects having medication overuse or not.
Conclusion
NLR and PLR can be easily calculated from the differential WBC count in outpatient clinic. NLR and PLR have considered simple biomarkers for acute phase of inflammation. Our results support the conclusion that increased NLR/PLR is associated with a kind of inflammation in acute phase of headache pain.
Disclosure of Interest
None Declared
Headache and Gender
PO-02-053
Maternally-inherited migraine and sex-hormone-related events: a clinical clue for possible role of chromosome X in migraine pathogenesis
Mi Ji Lee1,*, June S Moon2, Hanna Choi3 and Chin-Sang Chung1
1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Samsung Biomedical Research Institute, Seoul
3Department of Neurology, Eulji University Hospital, Daejeon, Korea, Republic Of
Objectives
Migraine is a heterogeneous clinical entity which has a female predominance. Recently, a new locus on chromosome X was first identified to be associated with migraine risk. We aimed to test the association of chromosome X with clinical manifestations of migraine.
Methods
In our prospective headache clinic registry, female migraineurs aged <65 years who first visited between October 2015 and January 2017 were identified. Patients were grouped based on their family history of migraine: maternally-inherited migraine, paternally-inherited migraine, and sporadic migraine (no family history). Patients with family history of migraine of sisters, brothers, aunts, uncles, or both parents, or with incomplete information were excluded. Clinical characteristics and sex-hormone-related events were compared between the three groups.
Results
From our registry of the study period, 298 females with maternally-inherited migraine, 51 with paternally-inherited migraine, and 458 patients with sporadic migraine were identified. There was no difference in age, age of onset, migraine type (with vs without aura), chronicity (episodic vs chronic migraine), headache frequencies, severity, and accompanying symptoms. Maternally-inherited migraine was associated with more menstruation-related migraine (46.4%) compared to paternally-inherited (38.3%) and sporadic (34.7%) migraine (p = 0.015). Maternally-inherited migraine was more frequently aggravated during the pregnancy (21.4%) and after the delivery (41.0%) than the other two groups (p = 0.023 and 0.039, respectively).
Conclusion
Women with maternally-inherited migraine had more sex-hormone-related events. This is the first evidence to suggest possible role of chromosome X on migraine phenotype.
Disclosure of Interest
None Declared
Headache and Gender
PO-02-054
Symptoms of premenstrual syndrome in women with and without with menstrual migraine
Kjersti G Vetvik1,2,*, E Anne MacGregor3, Christofer Lundqvist4,5 and Michael B Russell1,6
1Head and Neck Research Group
2Department of Neurology, Akershus University Hospital, Lørenskog, Norway
3Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom
4Research Center, Akershus University Hospital, Lørenskog
5Campus Akershus University Hospital
6Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Objectives
Menstrual migraine (MM) and premenstrual syndrome (PMS) are two conditions linked to specific phases of the menstrual cycle. The exact pathophysiological mechanisms are not fully understood, but both conditions are hypothesized to be triggered by female sex hormones. Co-occurrence of MM and PMS is controversial. The objective of this population based study was to compare self-assessed symptoms of PMS in female migraineurs with and without MM.
Methods
A total of 237 women from the general population with self-reported migraine in at least half of their menstruations were interviewed and diagnosed by a neurologist according to the International Classification of Headache Disorders II (ICHD II). All women were asked to complete a self-administered form containing 11 questions about PMS-symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. The number of PMS symptoms was compared among migraineurs with and without MM.
Results
A total of 193 women returned a complete PMS questionnaire, of which 67 women were subsequently excluded from the analyses due to current use of hormonal contraception (n = 61) or because they did not fulfil the ICHD-criteria for migraine (n = 6). Among the 126 migraineurs who were included in the analyses, 78 had MM and 48 non menstrually related migraine. PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs. 5.9, p = 0.37).
Conclusion
We did not find any difference in the number of self-reported PMS-symptoms between female migraineurs with and without MM.
Disclosure of Interest
None Declared
Headache and Gender
PO-02-055
Sex differences in prevalence, symptoms, impact and comorbidities in migraine and probable migraine: results from Korean Headache-Sleep Study
Min Kyung Chu1,*, Jiyoung Kim2, Won-Joo Kim3, Soo-Jin Cho4, Kwang Ik Yang5 and Chang-Ho Yun6
1Neurology, Kangnam Sacred Heart Hospital, Hallym University, Seoul
2Neurology, Pusan National University School of Medicine, Busan
3Neurology, Gangnam Severance Hospital, Yonsei University, Seoul
4Neurology, Dongtan Sacred Heart Hospital, Hallym University, Hwaseong
5Neurology, Cheonan Hospital, Soonchunhyang University, Cheonan
6Neurology, Bundang Hospital, Seoul National University, Seongnam, Korea, Republic Of
Objectives
The significant higher prevalence of migraine and probable migraine (PM) among women compared to The significant higher prevalence of migraine and probable migraine (PM) among women compared to men has been documented around the world. However, only few data on sex differences in headache characteristics, accompanying symptoms, impact of headache and their common comorbidities of migraine and PM are available in Asian region, an area that includes more than half the world’s population. Prevalence and clinical characteristics of migraine and PM in Asian countries were somewhat different from those of Western countries. This study is to investigate sex difference in prevalence, clinical symptoms, impact of headache and comorbidities of migraine and PM using a Korean nation-wide population-based sample.
Methods
The Korean Headache-Sleep Study (KHSS) is a nation-wide population-based door-to-door survey regarding headache and sleep. We used the data of the KHSS in the present study.
Results
Sex-specific headache frequency, headache intensity and impact of headache among individuals with migraine and probable migraine.
Mean ± standard deviation, #median and 25% > 75% interquartile range
Conclusion
Migraine and PM were more common in women than men in a Korean general population sample. Women with PM experience more severe headache intensity and higher impact of headache than men with PM. Some headache features of women with PM were different from those with men with PM.
Disclosure of Interest
M. K. Chu Conflict with: None, Conflict with: Hallym University Research Fund 2016, Conflict with: Adbisory board member for Teva, Conflict with: None, Conflict with: Honoraria from Allergan Korea and Yuyu Pharm., Conflict with: None, Conflict with: None, Conflict with: None, J. Kim Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, W.-J. Kim Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, S.-J. Cho Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, K. I. Yang Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, C.-H. Yun Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None, Conflict with: None
Headache and Gender
PO-02-056
Cold Extremities in Women with Migraine
Katie M Linstra1,2,*, Matthijs J. L Perenboom1, Floor van Welie1, Kiki de Jong1, Rolf Fronczek1, Martijn R Tannemaat1 and Gisela M Terwindt1
1Neurology, Leiden University Medical Centre, Leiden
2Internal Medicine - Division Vascular Medicine and Pharmacology, Erasmus Medical Center, Rotterdam, Netherlands
Objectives
Migraine is three times more prevalent in women than in men. Women with migraine have an increased risk for cerebro- and cardiovascular disease. Systemic vascular dysfunction has been suggested to be the underlying cause for this association. Interestingly, in general, women suffer more frequently from cold extremities than men. We hypothesize that cold hands and feet are a marker for vascular dysfunction in (female) migraine patients, and that the discomfort of having cold extremities leads to difficulties initiating sleep, which may influence migraine attack frequency.
Methods
A random selection of 1084 migraine patients and 348 controls (aged 22–65 years) from the LUMINA migraine cohort were invited to fill out the validated questionnaires on Thermal Discomfort and Cold Extremities (TDCE) and Difficulties Initiating Sleep (DIS). The association of migraine (subtypes) and attack frequency to TDCE and DIS was calculated for each gender.
Results
A total of 594 migraine patients and 206 controls completed the questionnaires (55% and 59% response rates). As expected, women were overrepresented in this study and significantly more women were present among migraineurs compared to controls (88% vs 61%). In women, TDCE was more often reported by migraine patients versus controls with an OR of 2.0 (95% > CI: 1.3–3.2) (34% vs 21%; p < 0,001). No difference in TDCE was found comparing migraine subtypes in women. In men, TDCE was not more often reported by migraineurs versus controls. DIS was reported more often in both genders suffering from migraine compared to healthy controls with an OR of 2.3 for women (1.6–3.5) and 2.2 for men (2.1–4.2). In general, positive outcome of TDCE was associated with DIS with an OR of 2.4 (1.8–3.3).
Conclusion
Our results suggest cold extremities to be a female-specific symptom for vascular dysfunction in migraine. A follow up study is needed to show whether changing thermoregulatory behaviour before going to sleep may be of benefit in migraine patients.
Disclosure of Interest
None Declared
Headache and Gender
PO-02-057
Redefining the Time Window of Perimenstrual Migraine Days Reveals Additional Inter- and Intra-Individual Differences
James S McGinley1, R. J Wirth1, Gabriel Boucher2, Dawn C Buse3, Stephen Donoghue2, Jelena Pavlovic3, E Anne MacGregor4 and Richard B Lipton3,*
1Vector Psychometric Group, LLC, Chapel Hill
2Curelator, Inc., Cambridge
3Albert Einstein College of Medicine and Montefiore Headache Center, Bronx, United States
4Barts and The London School of Medicine and Dentistry, London, United Kingdom
Objectives
To explore the possible advantages of an expanded, flexible Perimenstrual Migraine Day (PMD) time window applied to women with migraine.
Methods
Individuals meeting ICHD-3beta criteria for migraine who registered to use a novel digital platform (Curelator HeadacheTM), either directly or through a clinician referral program via website or the App Store (iOS only), entered headache/migraine occurrence, symptoms and variables potentially affecting migraine attacks daily. Data used included women’s daily reports of migraine (yes/no, assessed by ICHD-3b criteria) and menstrual bleeding (yes/no). We defined a four-part menstruation timing window that is specific to each individual’s monthly cycle: 1) Pre-menstruation (PRE): 2 days prior to bleeding, 2) Active Bleeding (AB): days actively bleeding, 3) Post-bleeding (POST): 3 days after the last day of bleeding; 4) Baseline (BL): days outside of the Pre, AB, and POST time periods. Two n = 1 methodologies were used to quantify and visualize between- and within-person risk for PMDs. Method 1 was a categorical time approach which directly contrasts the menstruation time periods (e.g., PRE vs. BL, AB vs. BL, and POST vs. BL). Method 2 was a continuous time approach that allowed each individual’s migraine risk to vary between and within the time periods. For example, women can differ in how much their migraine risk changes from day 1 to day 2 of PRE, through their AB days, and across their 3 POST days. Individual n = 1 logistic regression models were fitted using Method 1 and Method 2. Data visualizations were utilized to depict inter- and intra-individual differences in migraine risk related to menstruation.
Results
Our analysis sample consisted of n = 50 menstruating females (average age of 35.3 and 12% used contraceptives pills) reporting on a median of 200 days. Method 1, categorical time, showed substantial individual differences in migraine risk across the menstruation time-periods: 20% of women had greater than two-fold odds of having a migraine on a PRE day vs. a BL day; 44% for AB vs. BL; and 26% for POST vs. BL. Further, the level of migraine risk associated with the different time periods varied considerably across women. Method 2, continuous time, extended Method 1 by showing that each woman’s migraine risk often varied not only across menstrual stages (BL vs. PRE vs. AB vs. POST) but also within specific stages. Individual n = 1 plots visually depicted the individual differences in migraine risk related to menstruation and contrasted the unique inferences drawn from Methods 1 and 2.
Conclusion
Two different n = 1 analytic approaches can successfully be applied to analyze the association between migraine and menstruation and reveal inter- and intra-individual differences in migraine risk. The n = 1 methods showed strengths and weaknesses associated with treating time as a categorical versus continuous variable. A limitation of the current study is that we only considered a single extended time window. Future studies should empirically evaluate other potential timing structures for menstruation and examine how they relate to migraine.
Disclosure of Interest
J. McGinley Conflict with: Vector Psychometric Group, LLC, R. Wirth Conflict with: Vector Psychometric Group, LLC, Conflict with: Vector Psychometric Group, LLC, G. Boucher Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., D. Buse Conflict with: Allergan, Avanir, and Dr. Reddys, Conflict with: served on scientific advisory board and received compensation from Allergan, Amgen, and Eli Lilly; section editor for Current Pain and Headache Reports, S. Donoghue Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., J. Pavlovic Conflict with: Received honoraria from Allergan and American Headache Society, E. A. MacGregor: None Declared, R. Lipton Conflict with: National Institutes of Health, National Headache Foundation, and Migraine Research Fund, Conflict with: serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristol Myers Squibb, Cognimed, CoLucid, Eli Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, and Teva, Inc.; receives royalties from Wolff’s Headache, 8th Edition (Oxford University Press, 2009)
Headache Classification
PO-02-058
Clinical features and outcomes of benign paroxysmal vertigo in adults: a clinic longitudinal study of 84 patients
Yixin Zhang1,*, Xueying Kong1, Weiheng Wang1, Chaoyang Liu1, Qing Liu1, Huahua Jiang1 and Jiying Zhou1
1Neurology, The first affiliated hospital of chongqing medical university, Chongqing, China
Objectives
To explore the clinical features, treatment response, and prognosis as well as applicability of the International Classification of Headache Disorders, 3rd edition beta version (ICHD-3 beta version) of benign paroxysmal vertigo (BPV) in a Chinese cohort.
Methods
Consecutive patients with BPV were prospectively enrolled in a neurology clinic between June 2013 and December 2015. All patients underwent detailed clinical interview and neuro-otological examinations. Twenty-eight patients with cochlear symptoms were studied pure-tone audiometry (PTA). Follow-up was conducted through direct or semi-structured telephone interview after starting prophylactic treatment.
Results
Eighty-four patients (62 female/22 male, 52.1 ±11.8 years old) were identified with BPV. The majority of patients (63%) continued to have recurrent vertigo after a median follow-up of 22 months (range 10–41 months). Vertigo days (a day on which vestibular symptoms of at least moderate intensity occurred, regardless of the duration and frequency) were markedly reduced in 71% of patients who received flunarizine. Nine patients had chronic course (vertigo days ≥15 days per month for >3 months) and six of them reported overuse of symptomatic medications (on ≥15 days per month for >3 months). After discontinuing the excessive use of symptomatic medications and receiving flunarizine, these nine patients were noted a markedly improvement in vertigo days. Four patients developed migraine on follow-up, and all of them also fulfilled vestibular migraine in ICHD-3 beta version. Comorbid anxiety or depression predicted a poor outcome. Inconsistent with the ICHD-3 beta version, 10% of patients with BPV had abnormal vestibular functions between attacks.
Conclusion
The majority of patients still have recurrent vertigo in the long-term evolution of BPV. Withdrawal therapy plus preventive treatment may help reduce the vertigo days in patients with chronic course of BPV. The transformation of clinical characteristics between BPV and vestibular migraine suggests the similar migrainous mechanism.
Disclosure of Interest
None Declared
Headache Classification
PO-02-059
An auto-accumulating and matching database and a rule-based artificial intelligence expert system for the International Classification of Headache Disorders 3 Beta
Hiroyasu Furuyama1,*
1Neurology and Clinical Brain Research Laboratory, Sapporo Yamanoue Hospital, Sapporo, Japan
Objectives
The International Classification of Headache Disorders 3 Beta (ICHD-3b) includes all headache diagnoses. However, the association between each criterion and symptoms/treatments is still controversial for many diagnoses, especially those of secondary headaches. Thus, the accumulation of matching patterns using a very large number of patients is needed. Such a database requires the integration of inquiry, symptoms, and laboratory data with diagnosis, as well as accurate judgments from the headache specialists of the large diagnosis group ICHD-3b. However, the accumulation of this type of data is very difficult. This study aimed to create a system comprising an auto-accumulating and matching database of patient information and a rule-based artificial intelligence expert system that suggests a diagnosis derived from the database. We also evaluated the accuracy of the suggested diagnosis and the patient impressions of the usability of this system.
Methods
Quoting all items of ICHD-3b, we established a database system comprising a comprehensive headache questionnaire (CoQ), a clinicians’ judgment enrollment application (CJE), and a rule-based artificial intelligence expert system for ICHD-3 b (HEx), which automatically suggests headache diagnosis candidates based on the datasets derived from CoQ and CJE. All components work on a PHP + JAVAScript + MySQL system with WEB browsers. As a trial, the results of patients (23 females and three males) who tested the system were collated with diagnoses from a headache specialist. Simultaneously, the patients answered another questionnaire on their impressions of the number of questions (IN), their sense of sufficiency regarding the interview (SF; whether the CoQ could adequately identify their headache characteristics), and overall satisfaction (OS) of CoQ. They were also asked to answer the paper-based MIDAS and HIT-6 questionnaires. Finally, Spearman’s rank correlation coefficients (ρ) were calculated using the results of the trial.
Results
CoQ required 21.50 ± 6.86 (Mean ± SD) min as answering time (TM) for 134.92 ± 6.90 questions. HEx suggested 2.77 ± 1.48 candidate diagnoses, which included the same as the diagnosis provided by the headache specialist in all cases except one. OS correlated with SF (ρ = 0.7469; p < 0.0001) but not with TM and IN(ρ = 0.1465; p = 0.4751 and ρ = −0.0336; p = 0.8707, respectively). However, HIT-6 revealed an inverse correlation with OS (ρ = −0.4520; p = 0.0304).
Conclusion
CoQ can accumulate the properties of patients’ headaches and does not affect patient satisfaction. Moreover, HEx with CoQ and CJE can suggest accurate diagnoses and may be helpful for headache specialists in the diagnostic process. However, there is a possibility that the burden that the patients feel regarding CoQ worsens with the increase in their headache severity. Hence, it is important to reduce the number of questions in the questionnaire. For example, the Naive Bayes classifier or artificial intelligence with deep learning that can be used for all natural languages would be useful to reduce the burden that patients feel; however, they might have less accuracy than CoQ. To establish this type of machine learning, our current system can also provide a fundamental dataset of the properties and diagnoses of patients’ headaches.
Disclosure of Interest
None Declared
Headache Classification
PO-02-060
Chronic and Primary Persistent Vestibular Migraine - Two New Subtypes of the Disorder
Steffen Naegel1,*, Hsin-Chieh Chen1, Sebastian Wurthmann1, Hans-Christoph Diener1, Christoph Kleinschnitz1 and Dagny Holle1
1Department of Neurology, University of Duisburg-Essen, Essen, Germany
Objectives
Vestibular migraine (VM) is a common cause of vertigo affecting approximately 1% of the population. In collaboration Bárány-Society and the IHS developed diagnostic criteria for vestibular migraine which were added as appendix criteria to ICHD3-beta. Chronification of migraine headaches is a well-known condition. Clinical experience has shown, that vestibular migraine can also take a chronic course of disease. However, scientific data regarding this topic are sparse.
Methods
We retrospectively analysed records of patients diagnosed with vestibular migraine in a tertiary vertigo centre (vertigo centre Essen) between January 2011 and December 2016. Only patients suffering typical migraine headaches, fulfilling ICHD3-beta criteria for VM, and had vertigo/dizziness on at least 15 days per month were included into the analysis. Patients with concurrent vertigo disorders or psychiatric comorbidities were excluded.
Results
Thirty three (24 female) patient with chronic courses of vestibular migraine could be certainly identified. Patients age ranged from 18–72 years (average 35.82 years). On average vertigo was reported to be first recognized 42.37 [3–360] month before consultation in the vertigo center. On average patients suffered vertigo on 26.39 [15–30] days per month. If not persistent the duration of vertigo attacks was reported between min. 578 [10–2880] to max. 980 [10–4320] minutes. Fifteen patients reported their vertigo to be continuously present. A subset of 7 patients (=21.2%, age 34.29 years [19–53], 3 female) reported the vertigo as primary persistent (PPVM). Fifteen patients (=45%) reported to suffer typical visual auras at least occasionally. The frequencies of the reported vertigo-accompanying symptoms are summarized in the table.
Conclusion
We here for the first time present two new subgroups of patients suffering high frequent vertigo caused by vestibular migraine. These preliminary data stress the need to further study different courses of vestibular migraine, which here are proposed as chronic vestibular migraine and primary persistent vestibular migraine.
Disclosure of Interest
Vertigo-accompanying symptoms
(PPVM = primary persistent vestibular migraine, cVM only = chronic vestibular migraine without subset of PPVM patients)
Headache Classification
PO-02-061
Towards an improved diagnostic criterion for Menstrually Related Migraine (MRM)
Mathias Barra1,*, Gabriel Boucher2, E Anne MacGregor3 and Kjersti G Vetvik1
1Akershus University Hospital (Ahus), Lørenskog, Norway
2Curelator Inc., Cambridge
3Barts and the London SMD, London, United Kingdom
Objectives
The ICHD-III classifies MRM as a subtype of migraine without aura if migraine attacks occur on 2 out of 3 menstrual windows (defined as the five days centered on the first day of bleeding) in women who also have non menstrual attacks; we refer to this as the 2/3 criterion. Concerns exist that MRM diagnoses set by the 2/3 criterion may lead to unacceptable type-I and type-II error rates: MRM may be missed in women with sparse migraine patterns while women with frequent migraine may fulfill the 2/3 criterion spuriously.
Previous research has shown that in women with MRM, menstrual attacks last longer than non-menstrual attacks.1 The objective of this study was to compare the ability of a novel statistical method to diagnose MRM using this criterion (sMRM) against the ICHD-III 2/3 criterion (2/3MRM).
Methods
Data: We analyzed a pooled data set from 106 women using a digital platform [Curelator Headache™] during 2015–7 and 123 women attending the City of London Migraine Clinic during 1997–8, whose data have previously been published.2 All women had logged migraine attacks during at least 3 consecutive natural menstrual cycles. MRM was diagnosed by the standard ICHD-III criterion (2/3).
Subsequently, negative binomial (mixed effects) regression models were designed to investigate if either criterion was able to select women with prolonged menstrual attacks. One model explained attack length (unit days) by whether the attack was menstrual (beginning within a menstrual window), whether the women had 2/3MRM, and their interaction-term, and included random effects accounting for within-woman correlation. The second model was similarly specified, but used sMRM instead of 2/3MRM.
Results
The 229 women were mean age 38 years (SD 9), and had logged 158 (SD 98) migraine days; the mean number of menstrual cycles was 5 (SD 3), mean number of attacks was 14 (SD 12).
95 (41%) women had an MRM diagnosis and 71 (31%) had an sMRM diagnosis; 55 (24%) had both MRM and sMRM.
The regression model showed reasonable fit, though the skewed attack-length distribution was an issue for all models (Poisson and loglinear models were discarded). Table 1 gives the coefficients and the p-values for the main predictors.
The model coefficients indicate that sMRM selects women with prolonged menstrual attacks, while MRM was unable to isolate this trait in our data.
Conclusion
Both models suggest a cross-sample prolongation of menstrual vs. non-menstrual attack length regardless of MRM or sMRM diagnosis. However, the sMRM model had a significant (and positive) interaction term – an indication that sMRM might have better specificity. The sMRM allows sparse attack patterns while at the same time controlling the rate of spurious diagnoses. We think that the ICHD should consider incorporating statistical association into the diagnostic criterion of MRM, but further research of the merit of the method is needed.
Disclosure of Interest
M. Barra: None Declared, G. Boucher Conflict with: Curelator Inc., Conflict with: Curelator Inc., E. A. MacGregor: None Declared, K. Vetvik: None Declared
References
1Vetvik KG, et al. Cephalalgia
2015;
2MacGregor EA, Hackshaw A. Neurology
2004;
3Barra M, et al. Headache 2015;
Headache Classification
PO-02-062
A statistical criterion for Menstrually Related Migraine (MRM) without an independence-of-attacks assumption
Mathias Barra1,*, Fredrik A Dahl1, E Anne MacGregor2 and Kjersti G Vetvik1
1Akershus University Hospital (Ahus), Lørenskog, Norway
2Barts and the London SMD, London, United Kingdom
Objectives
The ICHD-III beta classifies MRM as a subtype of migraine without aura if migraine attacks occur on 2 out of 3 menstrual windows (defined as the five days centered on the first day of bleeding) in women who also have non menstrual attacks. Concerns that MRM-diagnoses thus obtained may lead to unacceptable type-I and type-II error rates have instigated scientific exploration of alternative criteria. As the etiology of MRM is unknown, the inclusion of spuriously diagnosed patients could hamper the advancement of a better understanding of this sub-type of migraine.
A promising probability-based criterion proposed by Marcus et al.1 was subsequently revised by Barra et al.2 However, this criterion assumes independence-of-attacks (IoA): i.e. that the probability of experiencing a migraine attack is unconditional on the previous day.
The aim of this study was twofold: 1. to investigate how restricting this assumption is; 2. to specify a statistical criterion for MRM that does not rely on IoA.
Methods
Simple Markov-chains for individual migraine-histories were tested, and data from 123 women attending the City of London Migraine Clinic during 1997–8, whose data have previously been published,3 was used for estimating conditional probabilities for recording migraine days.
The criterion from Barra et al. was redefined so as to be statistically sound also without the IoA-assumption.
Results
A clustering of migraines was observed and consistent with a simple 2-state Markov-chain with a baseline probability for a recorded migraine on a day after a migraine-free day, and an elevated for a recorded migraine on a day subsequent to a migraine-day. Setting and produced simulated data similar to the observed.
A re-specified statistical criterion that can accurately capture significant association between migraine and menstrual pattern on the individual level was obtained by modifying the method from Barra et al. by focusing on the day of an attack start rather than counting attack days. More precisely, the criterion developed by Marcus et al. and Barra et al. employs the statistically very simple Fischer’s exact test (with mid-p correction) for obtaining a conservative p-value representing the strength of the association between the catamenial cycle and the patient’s migraine attacks. Our new method keeps track of attack starts only (see table 1.)
This new accounting for attack starts retains the desirable properties developed by Barra et al. (exact and conservative) but avoids the IoA-assumption (which could increase Type-I errors when not satisfied.)
Conclusion
Our study show that the IoA is unrealistic, and that the criterion (sMRM) in Barra et al. may yield elevated type-I errors. An improved version, accommodating non-IoA, is presented here. To ensure minimizing diagnostic error the ICHD should consider integrating the improved sMRM in its future revisions.
Disclosure of Interest
None Declared
References
1Marcus DA, et al. Headache
2010;
2Barra M, et al. Headache 2015;
3MacGregor EA, Hackshaw A. Neurology
2004;
Headache Classification
PO-02-063
Discriminative Analysis of Migraine with Aura using Non-Linear SVM Classification
Mario Garingo1,*, Farhang Sahba2 and Mark Doidge3
1Research and Development, Cerebral Diagnostics Canada Inc, Toronto
2Faculty of Applied Science and Technology, Sheridan College, Brampton
3Cerebral Diagnostics Canada Inc, Toronto, Canada
Objectives
The objective of this work is to implement a technique of characterizing and extracting significant, robust and informative features from EEG signals which are representative of the non-pain migraine with aura (MwA) brain state. EEG signals are used because they contain critical spatial and temporal information about the neural bioelectricity.
Methods
The study was approved by the Ontario Institutional Review Board of Institutional Review Board Services. All subjects were recruited online and gave their informed consent prior to their inclusion in the study. The participants consisted of 24 MwA patients and 24 NC individuals with no history of migraines. Subjects with migraine symptoms were screened using the International Headache Society criteria before they were admitted into the study.
Thirty-two Ag/AgCl electrodes were secured onto a nylon electrode cap according to the standard 10–20 electrode system. The EEG signals were average referenced, amplified, and digitally sampled at 1024 Hz using a TMSI Refa 32 amplifier. All subjects underwent baseline recordings of 2 minutes of eyes closed no light. In all conditions, subjects were told to relax but remain alert.
The EEG signals were filtered using a high pass filter at 0.1 Hz to remove the DC drift and then subsequently decimated to 64 Hz. Independent component analysis was then applied to remove artifacts (eye blinks, ECG, muscle twitches) and 60 Hz notch filter to eliminate electrical interference. Finally, by visual inspection from an EEG expert, 30 seconds of clean EEG signal was selected to be analyzed.
Three electrical characteristic groups or features were obtained to characterize the EEG patterns: alpha phase synchronization (PLV), wavelet scale, and autoregressive (AR) based frequency statistics. Alpha phase synchronization was used to characterize the network structures of the brain. Wavelet scale was used to describe the transient activity and finally AR frequency statistics were used to obtain valuable time-frequency information.
Feature selection and reduction techniques were performed on the sub-features of these three mutually independent features, to combat the over-fit problem as well as maximize generality of the support vector machine classifier. Furthermore, extracted features were used as inputs to a 10-fold cross validated non-linear support vector machine (SVM) classifier. Interpretation of the reduced features adhered to previous migraine studies.
Results
As seen in the table, our proposed method consistently outperforms the classification of the individual features on our dataset. It is also important to note that though combining different features increased the classification performance of the individual features, our method is still superior improving accuracy by 10% to 20% compared to other methods. To further illustrate the discrimination capabilities of our proposed algorithm we plotted the decision hyperplane onto the features space, whereby each axis is comprised of each feature (see Figure). The hyperplane is shown in gray and it can be clearly seen separating MwA and NC.
Conclusion
Baseline benchmark comparison results of the binary classification task on various electrical characteristic combinations.
Disclosure of Interest
M. Garingo: None Declared, F. Sahba: None Declared, M. Doidge Conflict with: CEO
Headache Classification
PO-02-064
Four phenotypically distinct headache disorders in the same patient over 12 years follow up
Fan Cheng1,*, Alina Buture1, Ali J Ghabeli2 and Fayyaz Ahmed2
1Neurology, Hull York Medical School and Spire Hesslewood Clinic
2Neurology, Spire Hesslewood Clinic and Hull York Medical School, Hull, United Kingdom
Objectives
Although migrainous headache is considered the commonest form of primary headache disorder, there are uncommon primary headache disorders that often present in a tertiary headache clinic. Nonetheless, it is relatively rare for a patient to have more than two different forms of primary headache disorders. We describe a female patient who developed four distinct primary headache disorders over a period of 12 year follow up that were managed with appropriate treatment.
Methods
A 70 year old female presented with classical left sided (V2 V3) trigeminal neuralgia in 2001 that responded well to Carbamazepine. Her neuralgia was stable until she presented again in 2011 with recurrent episodes of stabbing left sided V1 pain at a frequency of six per hour each lasting 10–20 seconds with conjunctival injections and tearing. This was typical for SUNCT and responded well to lamotrigine 200 mg bd. Three months later she developed a new, episodic, excruciating pain in the left peri-orbital region 3–4 times each day, each episode lasting 20–45 minutes with restlessness and full set of autonomic features. A diagnosis of cluster headache was made and she responded dramatically to a short course of steroids and was able to go in remission with topiramate 50 mg bd. She has continued to have 4 weeks of cluster period every 3–4 months managed with either oral steroid or greater occipital nerve block. Since 2012 she developed a continuous left sided dull facial ache with no other associated symptoms and was treated as atypical facial pain that partly responded to pregabalin following no response to amitriptyline, gabapentin, epilim or indomethacin.
Results
The case report describes four distinct primary headache disorders in the same patient sequentially over 12 years timeframe.
Conclusion
To our knowledge, this is the first description in the literature of a patient who is simultaneously treated for four phenotypically distinct and rare headache disorders. Our case demonstrates the complexity of headache disorders that are managed in a tertiary headache clinic setting, and illustrates the importance that combinations of medication therapies plays in the appropriate management of patients with complex headache disorders.
Disclosure of Interest
F. Cheng: None Declared, A. Buture: None Declared, A. Ghabeli: None Declared, F. Ahmed Conflict with: Allergan, Eneura, Electrocore, Novartis as Advisory Board member paid to British Association for the Study of Headache and the Migraine Trust, Conflict with: Educational Officer for British Association for the Study of Headache, Trustee of Migraine Trust, IHS Board Member
Headache Classification
PO-02-065
Crying Headache: Frequency and clinical features among medical students
Marta L Ramos1, Fidel E Sobrino1,* and Alejandra Guerrero1
1Hospital Occidente de Kennedy, Bogotá, Colombia
Objectives
To describe the frequency an clinical features of crying headache among medical students
Methods
Observational, descriptive, cross-sectional study prospectively recording data from medical students in clinical practice at Hospital Occidente de Kennedy. A questionnaire was used for data collection which was then analyzed by statistical methods.
Results
A total of 105 students volunteered in the study (77 females and 28 males). Among the students, 79% complained of headache when they cry and 38% said that was the only type of headache they had suffered. About clinical features we found: Mean intensity 5.62 (SD 1.88), more common type of pain was pulsatile (37%)and in frontal localization (32%). More frequent associated symptoms were photophobia (32%), phonophobia (21%) and nausea (18%). Duration of each episode was less than 4 hours in all cases. Situations related with crying headache were angry (46.7%), stress (43.8%), sadness (41.9%) and physic pain (10.5%). None of the students has headache when they cry because of cooking (peel an onion). About treatment, 44.8% feel relive with rest, 41% use non-steroidal anti-inflammatory drug (NSAID), 21.9% has spontaneous relive, in 12.4% pain disappear when they stop crying and 7.6% use cold water.
Conclusion
Among our population of medical students, crying headache has a higher prevalence compare with literature [Blau (1995) y Fragoso (2003)]. About clinical features, crying headache was a short lasting headache (less than 4 hours), pulsatile, with photophobia and phonophobia as principal associated symptoms. Negative emotions were the trigger of pain, suggesting a possible physiopathology in where cortical and diencephalic structures were involved with sphenopalatine ganglion as principal intermediary between central and peripheral structures. Key Words: Headache, crying, medical students
Disclosure of Interest
None Declared
Headache Classification
PO-02-066
Improving discrimination between migraine with aura and transient ischemic attacks using the ICHD-3 beta appendix criteria
Carl Göbel1,*, Sarah Karstedt1, Thomas Münte1, Georg Royl1 and Jes Olesen2
1Department of Neurology, University Hospital Lübeck, Lübeck, Germany
2Department of Neurology, Rigshospitalet, Glostrup, Denmark
Objectives
Migraine with aura and transient ischemic attacks (TIAs) are two very different, hugely prevalent conditions encountering the neurologist in the emergency department on a daily basis. Distinguishing between the two is not always straightforward, however mistakes are very harmful: Misdiagnosing a migraine patient with a TIA renders him or her to an unnecessary expensive diagnostic work-up as well as lifelong antiplatelet and lipid-lowering therapy while misdiagnosing a TIA as a migraine with aura may result in an avoidable stroke. Monetary incentives, whereby the diagnosis of a TIA is reimbursed more than a migraine with aura, may also introduce conflicts of interest in the healthcare setting.
Methods
In this prospective study, 60 patients admitted to the Department of Neurology, University Hospital Lübeck, Germany with a suspected TIA were interviewed about their symptoms leading to admission. In a second step, both the main body and appendix criteria of ICHD-3 were applied to these patients.
Results
Our interim analysis shows that the appendix criteria in ICHD-3 beta had a significantly lower rate of false positive diagnoses (and thus higher specificity) than the main body criteria.
Conclusion
ICHD-3 appendix criteria for migraine with aura and migraine with typical aura are superior to the corresponding main body criteria in distinguishing between a migraine and a TIA. They serve as a robust tool both for the clinician as well as the researcher, and should be used to reduce rates of misdiagnosis.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-067
Prevalence of infantile colic and relationship to parental migraine in a Japanese population
Toshiyuki Hikita1,2,*
1Hikita Pediatric Clinic, Kiryu Gunma
2Pediatrics, Teikyo University School of Medicine, Tokyo, Japan
Objectives
Infantile colic is classified as a subgroup of migraine in the International Classification of Headache Disorders, 3rd Edition, beta version (ICHD-3 beta) (appendix), and is described in the Comments section as affecting approximately one out of five babies worldwide. The likelihood of having an infant with colic is 2.5 times higher for mothers with (vs. without) migraine, and 2 times higher for fathers with (vs. without) migraine. We examined the prevalence of infantile colic, and its relationship to parental migraine, in a Japanese population.
Methods
From June 2015 to February 2017, we interviewed all parents who brought healthy babies ≥5 months old to the Hikita Pediatric Clinic for vaccinations, using a standard questionnaire. Questions covered the following points: does baby have (or previously had) colic; [if so,] duration of colic (min); frequency of colic (times/wk); ages at which colic symptoms began and ended; parental migraine history. Possible disorders other than colic causing similar symptoms were ruled out. Questionnaire responses were analyzed to make diagnoses of infantile colic and parental migraine according to ICHD-3 beta criteria.
Results
The study included 105 babies (61 female, 44 male), with age range 150–281 days. Of the 105 babies, 67 (63.8%) showed no colic symptoms, and 38 (36.2%) (23 female, 15 male) showed some colic symptoms (irritability, fussing/crying episodes). Among the 38 babies with colic symptoms, median crying time was 30 min (range 0–300), median age at which colic symptoms began was 0 months (range 0–4), median colic frequency was 2 times/wk (range 0–7), and colic duration >3 wk was reported in 7 cases (range 3–84 wk). Among the 38 babies with some colic symptoms, 3 (2.9% of the 105 in the study) (all female) were diagnosed with infantile colic according to all three of the ICHD-3 beta criteria; i.e., crying time >3 hr/day; colic frequency >3 times/wk; colic duration >3 wk. The remaining 35 babies, who met two or fewer of the criteria, were broken down into the following groups: (i) crying time <3 hr/day; colic frequency >3 times/wk; colic duration >3 wk: n = 3. (ii) crying time >3 hr/day; colic frequency >3 times/wk; colic duration <3 wk: n = 1. (iii) crying time >3 hr/day; colic frequency <3 times/wk; colic duration >3 wk: n = 0. (iv) crying time <3 hr/day; colic frequency <3 times/wk; colic duration >3 wk: n = 14. (v) crying time <3 hr/day; colic frequency <3 times/wk; colic duration <3 wk: n = 17.
Of the 105 mothers in the study, 32 (30.5%) had a migraine history according to ICHD-3 beta criteria. These 32 cases consisted of 11 cases of migraine without aura, 17 of provable migraine without aura, 2 of migraine with aura, and 2 of probable migraine with aura. Of the 105 fathers in the study, 11 (10.5%) had a migraine history. These 11 cases consisted of 6 cases of migraine without aura, 3 of provable migraine without aura, and 2 of probable migraine with aura. For the 3 babies diagnosed with infantile colic (see above), neither parent had a migraine history.
Conclusion
Infantile colic is much less common in Japan (2.9% prevalence in our study population) than in most other countries. Among our study population (n = 105), 30.5% of the mothers and 10.5% of the fathers had a migraine history; however, these did not include either parent of the 3 babies diagnosed with infantile colic. Thus, we observed no relationship between infantile colic and parental migraine.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-068
Paroxysmal Headache as the only presenting feature of extensive Brain and spinal cord demyelination in an adolescent boy
Shantanu Shubham1,* on behalf of Dr Hrishikesh Kumar, Dr, Supriyo Chaudharu, Banashree Mondal, Koustav Chaterjee, Hrishikesh Kumar1, Supriyo Choudhury1, Banashree Mondal1, Koustav Chatterjee1 and Rebecca Banerjee1
1Neurology, Institute of Neurosciences, Kolkata, India
Objectives
Childhood demyelinating disorders usually present with encephalopathy, brainstem signs, long tract involvement or polysymptomatic presentations. We report clinical, laboratory and radiological features of a 15 year old boy with extensive demeyelination involving supratentotial region, brainstem and longitudinally extensive cervical and dorsal cord involvement presenting only with paroxysmal holocranial headache.
Systemic examination was normal. Fundus examination was normal. Visual acuity was normal. Power and deep tendon reflexes was normal. Cerebellar signs were absent. Sensory examination was normal.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-069
Co-morbid backbone pain localizations in adolescents with tension-type headache and migraine
Sergey Tereshchenko1,*, Nina Gorbacheva1, Olga Zaitseva1 and Margarita Shubina1
1Department of child's physical and mental health, Scientific Research Institute of medical problems of the North, Krasnoyarsk, Russian Federation
Objectives
Recurrent headache and backbone pain are common comorbidities in adolescents. Data regarding the association of backbone pain localizations in different headache types, however, are limited.
Methods
148 adolescents aged 12–18 years were examined to diagnose the headache types and recurrent functional backbone pain. Based on ICHD-II criteria, 55 % had migraine and 45 % had clinical relevant tension-type headache (TTH, including the subtypes “frequent episodic TTH, chronic TTH”). Recurrent functional backbone pain was defined as follow: (1) no organic cause; (2) pain frequency ≥2 in month; (3) typical pain severity ≥4 points on the 6-point visual pain scale. 119 age and gender matched adolescents with no headache complaint were examined as control group. Two-tailed chi-square and Fisher's exact tests were used.
Results
Significant positive associations were detected between recurrent upper (neck) back pain and recurrent headache (both for TTH and migraine; Table 1). Similar associations were found for middle (thoracic) back pain. Low back pain was reported by 22.4 % adolescents with TTH, which was significantly higher than in control (5.9 %, p = 0.002) and migraine (11.1 %, p = 0.08) groups.
Conclusion
Backbone pain localization in adolescents with different headache types
For ease of exposition, only p values <0.1 are displayed.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-070
The Development and Well-Being Assessment (DAWBA) screening for psychiatric comorbidity in urban Siberian adolescents with tension-type headache and migraine
Sergey Tereshchenko1,*, Margarita Shubina1 and Nina Gorbacheva1
1Department of child's physical and mental health, Scientific Research Institute of medical problems of the North, Krasnoyarsk, Russian Federation
Objectives
The Development and Well-Being Assessment (DAWBA) diagnostic tool was developed by R. Goodman et al. [J Child Psychol Psychiatry. 2000; 41: 645–655] as comprehensive semistructured interview for the diagnosis of psychiatric disorders and has been found to been an effective diagnostic tool in clinical and epidemiological settings. Data regarding the DAWBA estimated psychiatric symptoms in Russian adolescents with different headache types are limited.
Methods
224 urban Siberian (Krasnoyarsk, Russia) adolescents aged 12–18 attending a tertiary medical center for primary diagnosis of tension-type headache (n = 109, TTH, including the subtypes “frequent episodic TTH, chronic TTH”), migraine (n = 89), and mixed type (n = 26, TTH + migraine). All of them and 180 healthy matched controls completed computer-assisted DAWBA package of interviews. Each of psychiatric disorders was coded on a computer-generated 5-point probability scale. Data are shown as Mean (Mean–SE-Mean + SE) of computer-predicted probability. The Mann-Whitney U test is used to compare differences between groups.
Results
Significant positive associations were detected between all headache subgroups (TTH, migraine, and TTH + migraine) and posttraumatic stress disorder, generalized anxiety disorder, and depressive disorder probabilities (Table 1). Specific and social phobias were more characteristic for adolescents with TTH (TTH and TTH + migraine groups), whereas obsessive-compulsive disorder was more typical for migrainers (migraine and TTH + migraine groups).
Conclusion
Computer-predicted probability of psychiatric disorder, generated by the DAWBA, in adolescents with tension-type headache and migraine
* For ease of exposition, only p values ≤0.1 are displayed.
Reference:
1. Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry. 2000; 41: 645–655.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-071
Treatment of chronic headache disorders with greater occipital nerve injections in a large population of childhood and adolescent patients
Francesca Puledda1,*, Peter J Goadsby1 and Prab Prabhakar2
1Headache Group, Department of Basic and Clinical Neuroscience, King’s College London, and NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital, London, UK, King's College London
2Department of Paediatric Neurology, Great Ormond Hospital for Children NHS Foundation Trust, London, United Kingdom
Objectives
Chronic headache disorders in children are common and highly disabling, with chronic migraine affecting between 0.8% and 1.7% of subjects in pediatric age groups (1). Management can be challenging, with a lack of rapid and sustained treatment options. The objective of this clinical audit was to determine the efficacy and safety of greater occipital nerve injections in a large population of paediatric headache sufferers.
Methods
We performed a retrospective review of our clinic letters from children and adolescents seen within the Specialist Headache Service at Great Ormond Street Hospital, who received a greater occipital nerve injection between 2009 and 2016. We included first time and repeat injections. Infiltrations were always unilateral and consisted of 30 mg 1% lidocaine and 40 mg methylprednisolone acetate. The primary outcome measure of ‘benefit’ from the injection was defined as either a significant (more than one third) decrease in headache frequency and intensity or by a documented headache improvement in the clinical notes, determined by a neurologist specialized in headache.
Results
Two hundred and six patients received GONI injections (n = 841). Follow-up data was available for 145 patients (70%), who had 369 injections. Of the 145 patients, 117 (80%) had chronic migraine (migraine with aura, n = 21), 19 (13%) had New Daily Persistent Headache (NDPH), five (4%) had a chronic trigeminal autonomic cephalalgia, three (2%) had a form of secondary headache and one patient had chronic tension-type headache. Medication overuse was present in 37 (26%) subjects. The mean age was 15 ± 2 with a range between 8 and 18 years. Female to male ratio was 1.9:1. Mean number of headache years was 4 ± 3 and on average patients had tried at least two previous preventives with a range between 0 and 5.
A benefit was seen in 101 (69%) subjects. The mean duration of improvement was 9 ± 4 weeks. Benefit reached 70% in the chronic migraine population (n = 82) and was 63% in the NDPH subgroup. Four of the five patients with trigeminal autonomic cephalalgias benefitted from the injection. Side effects were reported in eleven patients: ten cases had a headache worsening and one case had soreness at the site of injection.
Conclusion
Greater occipital nerve injections are a safe, effective and useful strategy for chronic headache disorders in children. They appear more beneficial in the migraine and trigeminal autonomic cephalalgia subgroups. In the clinical approach to the treatment of chronic headache disorders in a paediatric setting, this strategy should be considered as first line management alongside the classic medications, which are often more side-effect prone.
References
1) Wöber-Bingöl. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep. 2013 Jun;17(6):341.
Disclosure of Interest
F. Puledda: None Declared, P. Goadsby Conflict with: Dr. Goadsby reports grants and personal fees from Allergan, Amgen, and Eli-Lilly and Company; and personal fees from Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion; and personal fees from MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press; and in addition, Dr. Goadsby has a patent Magnetic stimulation for headache pending assigned to eNeura., P. Prabhakar Conflict with: Consultancy work for AMGEN, GSK, BMS
Headache Disorders in Children and Adolescents
PO-02-072
Mathematical predicting of risk of chronic tension-type headache in adolescents
Kostiantyn Stepanchenko1,*
1Neurology, kharkiv medical academy of postgraduate education, Kharkiv, Ukraine
Objectives
Despite the fact that tension-type headache is the most common form of primary cephalgia in the population, including adolescents, there is no clear understanding of the risk factors and approaches to prediction the development of tension-type headache and its transition to a chronic form.
Methods
2,342 adolescent boys and girls aged 13–17 in schools in Kharkiv were examined. We used questionnaire to identify the headache. A group of adolescents with tension-type headache - 947 people (infrequent episodic tension-type headache - 854 people and chronic tension-type headache - 93 people) was selected. The control group included 246 healthy adolescents. Possible risk factors in the formation of tension-type headaches were divided into 4 groups: genetic, biomedical, psychosocial and welfare. Mathematical predicting of risk of tension-type headache in adolescents was performed using the method of normalization of E.N. Shigana intensive indicators, based on probabilistic Bayesian method. The result is presented in the form of prognostic coefficients.
Results
The most informative risk factors for developing tension-type headache were the pathology of the fetus and newborn, overweight, the presence of headache and autonomic disorders in the family history, traumatic brain injury, extragenital pathology of the mother before birth, stress. Diagnostic scale has been developed to predict the risk of tension-type headaches. It includes 22 prognostic factors with their grading and meaning of integrated measures of risk, depending on the strength of the effect of a single factor.
The risk of tension-type headaches ranged from 35,79 to 67,5 predictive coefficient values (low probability (35,79–46,37), the average probability (46,37–56,95) and high probability (56,95–67,53)).
Conclusion
The study of risk factors of chronic tension-type headaches, which were obtained by using an assessment and prognostic tables show the importance of overweight, diseases of the fetus and newborn, trauma of the head, stress, family history of headache and autonomic dysfunction in the development of chronic tension-type headache.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-073
Cerebrospinal Fluid Leak in Children and Adolescents
Masamichi Shinonaga1 and Masamichi Shinonaga1,*
1Neurosurgery, International University of Health and Welfare Atami Hospital, Atami, Shizuoka, Japan
Objectives
Reports of CSF (cerebrospinal fluid) leak in children were rare. CSF hypovolemia due to CSF leak occasionally causes longstanding disability in school life. The aim of this study was to clarify the cause, symptoms, radiological study and outcome.
Methods
70 children and adolescents (35 male, 35 female) were studied by brain and spinal MRI, RI cisternography and CT myerography. All patients with CSF leak were treated with epidural bloodpatch.
Results
Causes of CSF leak were sports 35%, traffic accident 20%, fall 20% and unknown 25%. Main symptoms were headache (66 cases), fatigue(59 cases), dizziness (40 cases), neck pain (30 cases), insomnia (29 cases) and loss of concentration (27 cases). Rate of neuroradiological positive findings were 45% in brain MRI, 71% in RI cisternography, 83% in CT myelography. Outcome after bloodpatch was cure 60%, good recovery 26%, recovery 10% and no change 0%.
Conclusion
This study revealed that CSF leak in children was not rare and bloodpatch was a very effective treatment. CSF leak is an important differential diagnosis in child headache.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-074
The Effect of Baseline Preventive Medications on the Efficacy and Safety of Zolmitriptan Nasal Spray (ZNS) in Adolescent Migraine Patients
Andrew Hershey1,*, Traci Sheaffer2, Sarita Khanna3, Suneel Gupta3, Heather Wray4 and Robert Rubens3
1Cincinnati Children's Hospital Medical Center, Cincinnati
2Raleigh Neurology Associates, Raleigh
3Impax Laboratories, Inc., Hayward, United States
4AstraZeneca, Molndal, Sweden
Objectives
To assess the use or non-use of baseline preventive migraine medications on the safety and efficacy of an acute migraine treatment (ZNS) in adolescent patients (aged 12 to 17 years) treated in the TEENZ study.
Methods
The TEENZ study was a global, multicenter, randomized, double-blind, parallel-group study of Zolmitriptan Nasal Spray (ZNS) compared with placebo (NCT01211145). Adolescents (12–17 years old) with an established diagnosis of migraine with or without aura by International Classification of Headache Disorders were enrolled. They were required to have at least 2 moderate to severe migraines per month for at least 1 year. Following a placebo challenge run-in period, non-responders were randomized to ZNS 5 mg, ZNS 2.5 mg, ZNS 0.5 mg, or placebo in a 5:3:3:5 ratio and given 10 weeks to treat a single migraine attack. After treatment of this migraine, patients completed a headache diary for 24 hours. The primary efficacy outcome measure was pain-free status at 2 hours post-treatment. In this post-hoc analysis, safety and efficacy (pain-free status and headache response at 2 hours) are evaluated across dosing groups based on the use or non-use of at least one baseline preventive migraine medication (divalproex/valproate, topiramate, metoprolol, propranolol, timolol, atenolol, nadolol, pindolol, amitriptyline, nortriptyline, venlafaxine, cyproheptidine, or verapamil).
Results
Of the 656 randomized patients (full safety analysis set), 84 (12.8%) were taking at least one preventive migraine medication on entry into the study. For the primary endpoint for randomized patients reporting use of preventive medications, the treatment group sample sizes were relatively small (approximately 30/group), making statistical conclusions challenging for this cohort. The two cohorts were fairly well matched in terms of demographics, except the cohort taking preventive medications had a relatively higher percentage of females (75.0% vs 59.4%; p = 0.0062) and whites (98.8% vs. 92.1%; p = 0.0252).
For the group not taking preventive medications (non-use), the primary endpoint is statistically significant in favor of ZNS 5 mg versus placebo. In the group taking preventive medications (use), this comparison (ZNS 5 mg vs. placebo) was not significant but the numbers were small (ZNS 5 mg, N = 27 and placebo, N = 32). A comparison of the 2-hour pain-free differences (active – placebo) in proportions (use: 10.3% vs. non-use: 13.2%) suggests little difference between the two cohorts. Similar statistical trends are observed for the ZNS 5 mg versus placebo 2-hour headache response, although, in this case, the cohort taking preventive medications showed a larger difference in proportions (use: 18.1% vs. non-use: 10.1%). The pattern of reported adverse events (AEs) was similar between the two cohorts. A higher percentage of placebo-treated subjects taking preventive medications reported at least 1 AE (31.3%) as compared with those placebo-treated subjects not taking preventive medications (13.1%).
Conclusion
Despite the migraine severity and frequency required by the study entry criteria, relatively few subjects reported use of migraine preventive medications and, consequently, this cohort was statistically challenging because of its small treatment group sample sizes. Notwithstanding, data from this post-hoc analysis suggests that the use or non-use of preventive migraine medications has little impact on the efficacy or safety of ZNS in adolescent migraineurs.
Disclosure of Interest
A. Hershey Conflict with: Avanir, Curelator, Supernus, Conflict with: Alder, Amgen, Depomed, Impax, Lilly, Upsher-Smith, T. Sheaffer: None Declared, S. Khanna Conflict with: Impax Laboratories, Inc., Conflict with: Impax Laboratories, Inc., S. Gupta Conflict with: Impax Laboratories, Inc., Conflict with: Impax Laboratories, Inc., H. Wray Conflict with: AstraZeneca, Conflict with: AstraZeneca, R. Rubens Conflict with: Impax Laboratories, Inc., Conflict with: Impax Laboratories, Inc.
Headache Disorders in Children and Adolescents
PO-02-075
Benign intracranial hypertension in children can be due to hypoparathyroidism: a case-report
Giorgia Sforza1,2, Annalisa Deodati3, Laura Papetti2, Barbara Battan2, Paolo Curatolo4, Federico Vigevano2 and Massimiliano Valeriani2,5,*
1Child Neurology and Psychiatry Unit, Tor Vergata University
2Headache Center
3Endocrinology
4Child Neurology and Psychiatry Unit, Ospedale Bambino Gesu, Rome, Italy
5SMI Center, Aalborg University, Aalborg, Denmark
Objectives
To present the rare case of a girl with idiopathic intracranial hypertension (IIH) secondary to hypoparathyroidism (HPTH).
Methods
Workup of a 9-year-old girl with IIH and HPTH, including physical examination, blood tests, diagnostic imaging, and lumbar puncture.
Results
We present a 9-year old female patient who was hospitalized for headache associated with nausea and vomiting for 3 weeks. She underwent ophthalmologic examination which showed papilledema. She had never had cramps, paraesthesias or tetany. Lumbar puncture (LP) revealed an opening pressure of 65 cm H2O. CSF analysis and brain CT scan were normal. The patient was started on acetazolamide 375 mg/die. However, a low serum calcium level (6.3 mg/dL) was found, thus leading us to suspect HPTH. Indeed, phosphorus was 10.2 mg/dL, parathormone was very low (3 pg/mL). Chvostek and Trousseau signs scored positive. Neck ultrasonography showed normal thyroid, while parathyroids were not viewable. Oral supplementation with calcitriol (0.50 mcg/day) and calcium (500 mg/day) was started.
Conclusion
IIH is defined as an elevated intracranial pressure (>25 cmH2O) without clinical, laboratory or radiological evidence of hydrocephalus, infection, tumor or vascular abnormality. Annual incidence is 1–2 per 100,000. Several hypotheses have been proposed for the IIH pathophysiology, but none of them has reached a general consensus. Rare cases of IIH secondary to HPTH have been described (Aragones and Alonso-Valdés, 2014). It is supposed that hypocalcemia causes a decrease in the CSF absorption at level of the arachnoidal granulations (Sambrook and Hill, 1977). Interestingly, our patient did not present with the typical neurological HPTH symptoms, such as tetany, cramps, paraesthesias, seizures, behavioral disorders, and intracranial calcifications. Only the serum calcium dosage led us to suspect this condition. Therefore, we recommend that possible HPTH should be always checked in children with clinical findings of benign intracranial hypertension.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-076
Validity of the ICHD-IIIb criteria in the diagnosis of migraine with aura in children and adolescents
Martina Balestri1, Daniela Maiorani2, Alessandro Capuano1, Laura Papetti1, Samuela Tarantino1, Barbara Battan1, Federico Vigevano1 and Massimiliano Valeriani1,3,*
1Headache Center, Ospedale Bambino Gesu, Rome
2Pediatric Unit, Belcolle Hospital, Viterbo, Italy
3SMI Center, Aalborg University, Aalborg, Denmark
Objectives
Though common in pediatric age, migraine with aura (MA) has been scarcely studied in children. Our main aim was to test whether the International Classification of Headache Disorders criteria 3rd edition (ICHD-IIIb) are useful to diagnose MA in children and adolescents. Moreover, we aimed also at investigating: 1) the clinical characteristics of the aura in a cohort of MA children, and 2) the features of the headache associated with the aura.
Methods
The present study was based on data retrospectively collected from 164 MA children referred to our 3rd level Headache Centre.
Results
In our patients, aura mainly included visual symptoms, which were far more frequent (93%) than somatosensory, motor, and speech disturbances. Aura preceded the headache onset in most cases (69.1%) and its duration ranged from 5 to 60 minutes. We divided our patients in 4 different age groups (less than 7 years, between 7 and 10 years, between 11 and 14 years, more than 14 years). No difference in the aura characteristics was found between the groups (Table). On the other hand, when the headache type was classified according to the ICHD-IIIb criteria, migraine was diagnosed only in 40.2% of patients and the diagnosis remained undetermined in 4.3% of children. However, if headache duration was not considered, the headache could be classified as migraine in 67% of patients and in no child the diagnosis was undetermined.
Conclusion
Our pediatric population showed aura features that did not depend on the age and were similar to those of adult patients. Although the headache type was difficult to be classified if headache duration was considered, the new criteria reduce the importance of the headache type associated with the aura, thus allowing the diagnosis of MA also in children and adolescents.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-077
School Nurses's Management for Schoolchildren with Headache
Young-Il Rho1,*
1pediatrics, Chosun University Hospital, Gwangju, Korea, Republic Of
Objectives
Recurrent headaches are common among Korean students, causing absences from school or learning impediments. However, most school nurses are unable to provide appropriate diagnosis and treatment as they lack accurate information about the clinical aspects or treatment of headaches. The aim of this study was to investigate school nurses's clinical knowledge, assessment, and management of headache and educational needs in headache management.
Methods
This was a cross-sectional study targeting 250 school nurses who participated in the training lecture hosted by and were working at elementary, middle, and high schools. Surveys with insufficient data were excluded.
Results
Participants were 237 school nurses; 122 elementary school nurses, 62 middle school nurses, and 53 high school nurses, with an average age of 42.4 ± 8.8 years. In all, 58.2% of the school nurses responded that they had received headache education, 68.8% responded that they knew the classifications of a headache, and 38.4% responded that they knew a headache assessment method. Only, 29% had a protocol for headache treatment. The educational needs (0–7 points) of school nurses to manage students with headaches were 5.8 for headache knowledge education, 5.5 for acute pharmacotherapy, 5.0 for preventive pharmacotherapy, 6.0 for lifestyle modification, and 6.0 for complementary remedy.
Conclusion
School nurses had insufficient knowledge of headaches and high educational needs for headache management and had not a protocol for the headache management in the most cases. It suggests that headache knowledge education should be performed and the standardized headache management guideline should be developed to improve the performance of school nurses.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-078
New Daily Persistent Headache in children: a clinic- based study in a specialist headache service
Diana Y Wei1,*, Jonathan J Ong1,2, Peter J Goadsby1,3 and Prab Prabhakar4
1Headache Group, Department of Basic and Clinical Neuroscience, King's College London, London, United Kingdom
2Department of Medicine, Division of Neurology, National University Hospital, Singapore, Singapore
3NIHR Welcome Trust King’s Clinical Research Facility, King's College London
4Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
Objectives
As New Daily Persistent Headache (NDPH) is still poorly defined in the paediatric population, we conducted a clinic based review of our patients with NDPH, to understand better the clinical phenotype of this disorder.
Methods
This retrospective study was conducted as an audit in a tertiary paediatric headache centre. We identified the list of patients whose clinical features were consistent with NDPH by the International Classification of Headache Disorders 3rd edition (ICHD-3 beta) from 2004 until 2016. On reviewing the clinical notes, the relevant data was collated with a standardised data collection form.
Results
We identified 34 patients with NDPH, average age of NDPH onset 13 years old. The majority were female (n = 25, 74%). The median duration till diagnosis was 436 days, the interquartile range was 232–546 days, with the longest being 1960 days. Antecedent events were clearly identified by 26 patients, the most common being a preceding viral illness, such as upper respiratory tract infection); physical exertion, and situational events, such as a clear recollection of attending a prolonged history lesson class, visiting a London museum, long car journey. The majority of patients were able to identify the time of onset of their symptoms (n = 32, 94%). Migrainous symptoms were common with exacerbations: 71% had movement sensitivity, 68% had phonophobia, 65% had nausea, 59% had photophobia and 41% had vertigo, of which 29% could specify it was internal vertigo. Of the cohort, 18% had medication overuse.
Conclusion
Paediatric patients with NDPH often have migrainous symptomatology. Most often, there was a preceding history of viral illness or physical exertion. Medication overuse was not commonly implicated in our patients.
Disclosure of Interest
D. Wei: None Declared, J. Ong: None Declared, P. Goadsby Conflict with: Allergan, Amgen, and Eli-Lilly and Company, Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion, Conflict with: MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press and eNeura, P. Prabhakar Conflict with: AMGEN, GSK, BMS
Headache Disorders in Children and Adolescents
PO-02-079
The chief complaints and exacerbating factors of migraine in children and adolescents
Mariko Okada1,*, Hitoshi Mori1 and Katsuro Shindo1
1Neurology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
Objectives
Migraine is common in children and adolescents, with the reported prevalence between 3.8% and 13.5%. Both children and adolescents are unable to describe their symptoms exactly, and their chief complaints are diverse. To our knowledge, little is known about how children describe their migraine symptoms. This study aims to reveal the migraine symptoms and exacerbating factors of migraine in Japanese children and adolescents.
Methods
We retrospectively reviewed the clinical records of children and adolescents (12–20 years old) with migraine according to the ICHD-3 beta who visited the department of neurology in a single center from January 2014 to December 2016. We analyze their migraine symptoms and the reason for the visit (chief complaint). We also clarify their exacerbating factors of migraine.
Results
57 patients (18 boys, 39 girls) with the median age of 16 (range, 12 to 19) were included. 33 (58%) patients presented with a complaint of ‘headache’. Other chief complaints were visual aura (n = 11, 19%), nausea (n = 7, 12%), dizziness (n = 4, 7%), stomachache (n = 1, 2%), and photophobia (n = 1, 2%). Their exacerbating factors of migraine were regular examinations at schools (n = 12, 21%), and lack of sleep (n = 13, 23%). Twenty-nine (51%) patients had ‘unilateral’ headaches.
Conclusion
This study suggests 42% of children and adolescents with migraine presented with complaints other than ‘headache’. Stressful events such as examinations and lack of sleep are associated with the development of migraine in Japanese children and adolescents.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-080
United Kingdom NICE Quality Standards applied to a children and young person's headache clinic: always room for improvement
William Whitehouse1,2,*, Aikaterina Vraka2, Ian Brown3 and Manish Prasad2
1School of Medicine, University of Nottingham
2Paediatric Neurology
3Quality Improvement, Nottingham Children's Hospital, Nottingham, United Kingdom
Objectives
The UK’s National Institute for Health and Care Excellence (NICE) published their evidence based headache guideline (CG150) and Quality Standard (QS42, see https://www.nice.org.uk/guidance/qs42) recently. We therefore decided to undertake a clinical audit of our tertiary headache clinic, as part of our Quality Improvement programme.
Methods
Cases attending a tertiary headache clinic for the first time in 2013 and 2014, with at least 2 year’s follow-up, were ascertained from the headache clinic lists and data extracted from the digital health record clinic letters, using a standard proforma. Simple descriptive statistics were used. The clinical audit was registered with the hospital Trust.
Results
So far 82 patients’ records (52 female) have been reviewed. The ages ranged from 1–16 years (mean 12) on the 1st visit. 38/82 (46%) were referred by a paediatrician, 24/82 (29%) by another specialist, 18/82 (22%) by a Family Practitioner, and 2/82 were self-referred through an advertisement for a research project.
For 71/82 (90%), headache was the main presenting complaint, and in 66/71 (93%) the headache diagnosis was documented within 6 months.
The headache diagnoses observed were: “migraine” 54/71 (76%), “tension-type headache” 8/71 (11%) including “new daily persistent headache” 2/71 (3%), “paroxysmal hemicrania” 3/71 (4%), cluster headache 2/71 (3%). Secondary headache was diagnosed in 10/71 (14%), including “idiopathic intracranial hypertension” in 6/71 (8%), and “medication overuse headache” (MOH) in 1/71 (1%). Unclassified headache (not otherwise specified) was the diagnosis at last observation in 11/71 (15%). 14/71 (20%) were diagnosed with more than one type of headache.
Of the 60 with primary headache (migraine, tension, cluster, paroxysmal hemicrania) advice on preventing MOH was documented as in 34/60 (57%), and a head MRI or CT scan was only requested in 15/34 (44%) of those not already scanned before referral. Appropriate rescue treatment advise, i.e. a triptan together with a non-steroidal anti-inflammatory drug (NSAID) or paracetamol, was documented in 43/54 (83%) with migraine.
Conclusion
Migraine was the commonest diagnosis made in the headache clinic. More patients with primary headaches should have had advice on MOH documented, and fewer should have undergone brain imaging. However, appropriate rescue treatment advice for migraine was well documented.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-081
The relationship between adolescent and parental use of non-prescription analgesics for headache and somatic pain – a cross-sectional study
Synva N Hasseleid1, Jocelyne Clench-Aas2, Ruth K Raanaas1 and Christofer Lundqvist3,4,*
1Department of Landscape Architecture and Spatial Planning, Public Health, Norwegian University of Life Sciences, Ås
2Mental and physical health, Norwegian Institute of Public Health, Oslo
3Research Centre and Dept of Neurology, Akershus University Hospital, Lørenskog
4Institute of Clinical Medicine, Health Services Research, University of Oslo, Camapus Akershus University Hospital, Oslo, Norway
Objectives
Concern has been expressed about adolescents’ possible liberal attitude towards - and increasing use of non-prescription analgesics. Headache is the most common reason for analgesics use by adolescents. A high consumption of analgesics may be unfortunate in the headache setting as it may lead to medication induced worsening of headache (medication-overuse headache) in addition to other side effects. Several studies show that adolescents have a high consumption of non-prescription analgesics, such as paracetamol and non-steroid anti-inflammatory drugs (NSAIDs), which are often available as over the counter (OTC) non-prescription medication and are often, as in Norway, also available outside pharmacies. In order to address this challenge, it is necessary to achieve more extensive knowledge about adolescent consumption and in order to assess also OTC medication, prescription registries are not sufficient as direct user data is necessary. In the case of children and young adolescents, this necessitates information from both the parents and the children. Parental use of, and attitudes to analgesics have been suggested to affect the medication-related behavior of their children. The aim of this study was, in a general population sample, to examine adolescent use of non-prescription analgesics for headache, as well as the association between parental and adolescent use of analgesics, also taking other somatic pain states into account.
Methods
The study is based on data from two cross-sectional population-based data sets collected in 2005 and 2012 in Norway, including 646 adolescents, each with an accompanying parent. By using sample weights to correct for possible population bias in the sampling, the final weighted sample used in the analysis was 1326. Data was collected through postal questionnaires to parents and adolescents as well as parental telephone interviews. Questionnaires included questions on different pain locations and the pain for each location was graded according to how troubling the pain was. Medication data on prescription and non-prescription analgesics was from telephone interviews and was quantified based on the pattern over the past 4 weeks. No clinical examination of partcipants was made, thus diagnostic data of pain statess are based on self-reports. Multivariate logistic regression models and complex samples analyses were used.
Results
20% of adolescents were reported as using non-prescription analgesics during the previous 4 weeks, more commonly girls than boys. Headache was the most common pain state and was reported more frequently among girls. Other somatic pain locations except back pain were also reported more commonly for girls, boys more frequently reported back pain. 34% of adolescents with headache used non-prescription analgesics versus 19% of adolescents with other somatic pain and 14% of adolescents not reporting pain. 9% of adolescents reporting headache used non-prescription analgesics daily or almost daily versus 3% and 2% among those reporting other somatic pain or no pain, respectively. Parental use of non-prescription analgesics was a strong independent predictor of adolescent use (adjusted OR 1.69 for boys, 1.54 for girls). This relationship was stronger when the adolescents were less bothered by headache themselves.
Conclusion
Headache is the dominant medication-driving pain for non-prescription analgesics among adolescents but parental medication use of non-prescription analgesics also strongly influences adolescent use which is something parents should be made aware of. The risk of detrimental patterns of use of such analgesics leading to increased risk of medication-overuse headache later in life should be emphasized.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-082
Maternal alexithymia and attachment style: which relationship with their children's headache features and psychological profile?
Samuela Tarantino1,*, Laura Papetti1, Cristiana De Ranieri2, Francesca Boldrini2, Angela Rocco2, Valeria Valeriano2, Barbara Battan1, Federico Vigevano1, Simonetta Gentile2 and Massimiliano Valeriani1,3
1Headache Center, Division of Neurology
2Unit of Clinical Psychology, Ospedale Pediatrico Bambino Gesù, Rome, Italy
3SMI Center, Aalborg University, Aalborg, Denmark
Objectives
Migraine is a complex phenomenon where genetic, biological and environmental factors interact to each other. Attachment theory suggests that early interpersonal relationships may be important determinants of psychopathology and pain management. In a recent study, we found an association between ambivalent attachment style, migraine severity and psychological symptoms. Our findings supported the hypothesis that a dysfunctional parent-child interaction may be a common vulnerability factor for both pain severity and psychological symptoms, in young migraineurs. There is evidence that caregivers’ attachment styles and their way of management/expression of emotions (alexithymia traits) can influence children’s psychological profile and pain expression. To date, data dealing with headache are scarce. Aims of our study were to investigate the role of maternal alexithymia and attachment style on: 1) their children headache features (intensity and frequency), 2) children's psychological profile (anxiety, depression, somatization).
Methods
We enrolled 84 consecutive patients suffering from migraine without aura (female: 45, male: 39; age range 8–18 years; mean age 11.8 ± 2.4 years). Patients were divided into two groups according to frequency of the migraine episodes (high or low). Patients were divided into two groups according to headache attack frequency: (1) high frequency patients, having from weekly to daily episodes and (2) low frequency patients, showing ≤3 episodes per month. According to headache attack intensity, patients were classified into two groups: (1) mild pain, allowing the patient to continue his/her daily activities and (2) severe pain, leading to interruption of patient activities or forcing the child to go to bed. Children’s psychological profile was assessed by SAFA Anxiety, Depression and Somatization scales. Attachment style was measured by the semi-projective SAT test and children were divided in “secure” and “insecure” (“avoidant”, “ambivalent” and “disorganized/confused”) attachment patterns. We used ASQ and TAS-20 questionnaires to assess respectively the maternal attachment style and alexithymia levels.
Results
We found a significant higher score in maternal alexithymia levels in children classified as “ambivalent”, compared to those classified as “avoiding” (Total scale: p = 0.011). Alexithymia levels also correlated with children’s psychological profile. A positive correlation has been identified between mother's TAS-20 Total score and the children's SAFA-A Total Score (p = 0.026). In particular, positive correlations were found between maternal alexithymia and children's “separation anxiety” subscale (p = 0.009), “school anxiety” (p = 0.015). Maternal “externally oriented thinking” subscale correlated with SAFA-A “school anxiety” subscale (p = 0.050). ASQ analysis showed a negative relationship between “Confidence” (in self and others) subscale and “school anxiety” (p = 0.050). Our data did not show any relationship between TAS-20 and ASQ questionnaires and children’s migraine intensity and frequency.
Conclusion
Our results showed that maternal alexithymia and attachment style have no impact on children's migraine features but they influence their anxiety levels and attachment style. We can hypothesize that maternal difficulty in expression and management of emotions may inhibit the ability of their children to self-regulate their emotional states; consequently, children's increased subjective distress and focus on negative affects may have an impact on their migraine features.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-083
Clinical presentation and diagnostic evaluation of idiopathic intracranial hypertension in children and adolescents
Barbara Battan1, Laura Papetti1, Irene Salfa1, Federico Vigevano1 and Massimiliano Valeriani1,*
1Headache Center, Child Neurology Unit, Bambino Gesu’ Children’s Hospital, Rome, Italy
Objectives
Idiopathic intracranial hypertension (IIH) or pseudotumor cerebri is a syndrome characterized by signs and symptoms of increased intracranial pressure in the absence of a secondary cause (space-occupying mass lesion or venous thrombosis). IIH occurs mainly in young, fertile and overweight women but is not uncommon in children. The aim of this study is to report the IIH clinical presentation in children and adolescents presenting to our hospital during a 5-year period.
Methods
Retrospective study, between January 2012 and January 2017, of IIH patients, younger than 15 years, was conducted. Modified Dandy criteria were used for IIH diagnosis. The patients were analysed according to age (≤10 years and 11–15 years).
Results
Nineteen patients, ranging from 3.8 to 15 years, were included. Eight patients were younger than 11 years (42%), while 11 patients were 11–15 years old (58%). Fifteen patients (78%) were obese (weight centile ≥90%). Mean cerebrospinal fluid opening pressure was 400 mm H2O (260- 890 mmH2O). The most common presenting symptoms were headache (95%), vomiting (31%), dizziness (10%), blurred vision or diplopia (73%). Sixth nerve palsy occurred in 11 children (57%). In general, headache did not respond to pain medication. All our patients showed papilledema. Diagnostic evaluation included neuroimaging studies and ultrasound-based optic nerve sheath diameter (ONSD) measurement. In 3 patients (15%), MRI showed signs of empty sella syndrome, while in 5 patients (26%) ultrasound ONSD measurement showed optic nerve sheath distension. There were no significant differences between the age groups in both clinical presentation and instrumental findings. Treatment included weight loss and acetazolamide (maximum 5 mg/kg/die) in 16 patients (84%). Furosemide was added to acetazolamide in 3 patients (15%). All patients fully recovered and none of them complained visual loss in the follow-up.
Conclusion
Regardless of age sex and weight, IIH should be considered in children with new-onset headache. Clinical headache presentation can be variable, although vomiting and visual symptoms are frequently associated. To exclude a secondary cause, as intracranial mass lesion or venous thrombosis, neuroimaging should be performed. Ultrasound-based optic nerve sheath diameter measurement may be useful as an additional tool to identify patients with IIH. Early diagnosis and treatment for IIH can prevent potential visual loss that remains the major morbidity. Acetazolamide and weight loss remain the most effective treatments in children.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-084
Predictors of response to biofeedback therapy for persistent post-concussive headache in children
Anisha Chandra Schwarz1,*, Cora C Breuner2 and Heidi Blume1
1Neurology
2Adolescent Medicine, University of Washington/Seattle Children's Hospital, Seattle, United States
Objectives
Post-traumatic headaches represent a common, often disabling, and potentially difficult to treat consequence of pediatric concussion or mild traumatic brain injury. Biofeedback therapy is currently being used in children for the management of post-traumatic headaches. However, while biofeedback has been established as an effective tool for migraine, its utility has not yet been examined in children and adolescents with post-concussive headaches. This retrospective cohort study both measured the response to biofeedback therapy and examined factors associated with response in order to determine potential predictors of positive response to biofeedback in pediatric post-concussive headache.
Methods
Subjects were those children ages 8–18 that had completed at least two biofeedback therapy sessions for post-concussive headache at Seattle Children's Hospital from 2010–2016 and were identified through electronic medical record search. Additional data were collected via subsequent chart review. Response to biofeedback therapy was defined as either 50% reduction in headache frequency or at least 3-point drop in maximum Likert pain scale ratings between first and last biofeedback sessions. Variables identified in pediatric migraine and concussion populations as likely to be relevant to headache or biofeedback response were examined in the the responder and nonresponder groups in order to identify associations between these factors and treatment response.
Results
The study group was 77% female, with average age 15.5 (standard deviation (SD) 1.8) and a median time from injury to evaluation of 5.7 months (interquartile interval 3.9–10.8 months). 66% of children reported headache 7 days per week at their initial visit. We found a 46% response rate to biofeedback therapy. Of all subjects, 35% had a 50% reduction in headache frequency, 23% described at least a three-point drop in headache severity, and 12% experienced both. Responders were significantly more likely to have stayed in school (chi-squared = 5.52, p = 0.02), and were also significantly less likely than nonresponders to be taking selective serotonin reuptake inhibitors or tricyclic antidepressants at the time of biofeedback therapy (chi-squared = 3.86, p = 0.05). The response and nonresponse groups were not significantly different in age, sex, weight, BMI, therapist, personal or family headache history, depression or anxiety scales, number of headache days per week, or pain duration prior to biofeedback therapy.
Conclusion
This is one of the first studies to evaluate the efficacy of biofeedback therapy for the management of post-concussive headaches in a pediatric population. Initial data suggest that it may be effective for children and adolescents with persistent headaches secondary to mild traumatic brain injury. In addition, those children who responded to biofeedback were more likely to have remained in school and were less likely to be taking psychotropic medications at the time of therapy. We did not find an association between responder status and pain duration, indicating that positive response was unlikely to be related simply to the passage of time after concussion. These early data may help guide clinicians and institutions in identifying those children and adolescents who would be most likely to benefit from biofeedback. The implications of these findings may be widespread given that compared to pharmaceutical options, biofeedback therapy is safer, and skills learned can be used indefinitely for management of headaches over the lifespan.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-085
Evaluation of patient satisfaction among adolescents who received infusion treatment for headache
Jonathan Winkelman RN1,*, Sarah Ostrowski-Delahanty PhD1, Tami Cieplinski RN1, Mackenzie Feathers RN1, Pretti Polk CNP1, Kristine Woods PsyD1, M. Cristina Victorio MD1
1Neuro Developmental Science Center, Akron Children's Hospital, Akron, United States
Objectives
Currently, there is limited research data on infusion centers for pediatric headache. The objective of this study was to assess the satisfaction of adolescent patients who received infusion treatment for headache in an outpatient setting. Additional analyses examined differences between receiving infusion treatments in an outpatient setting versus in an emergency department (ED). Findings of this study may help gain a greater understanding of patient experiences during infusion treatments so that more effective and satisfactory care can be provided to patients acutely suffering from headache.
Methods
Institutional Review Board approval was obtained. Patients aged 12–17 years who received infusion treatment for headaches from September 9, 2015 to June 14, 2016 at Akron Children's Hospital NeuroDevelopmental Science Center (NDSC) were eligible for inclusion in this study. After obtaining consent, patients were administered a patient satisfaction questionnaire. Patients were asked to rate their satisfaction with factors such as pain alleviation, noise level, and overall comfort with respect to their infusion visit experience. Patients previously treated in an ED were asked to rate their satisfaction with the infusion visit compared to their visit(s) in the ED. Medical information was also collected, including the following data points at the time of the patient's infusion for which they completed the questionnaire: diagnosis, administered medications, number of ED infusions, and number of NDSC infusions. Data analyses were performed and results were compiled from both questionnaire responses and clinical data.
Results
A total of 43 patients (males = 7, females = 36) participated in the study. The average age of participants was 15.22 years (range = 12.30–17.70 years). Twenty-five (58%) patients received infusion for prolonged migraine/status migrainosus. Thirteen patients (30%) received infusion for post-traumatic headache; 4 patients (10%) for chronic daily headache and 1 patient (2%) for tension-type headache. The average baseline pain score prior to infusion was 6/10 and the average post-infusion pain score was 1/10. Twenty-four of the patients (56%) were headache-free after the infusion. Thirty-six of the patients (84%) experienced at least 50% reduction in their headache pain.
Based on the questionnaire responses, 91% reported significant pain relief with the infusion irrespective of pain score. The overall level of infusion experience satisfaction was an average of 8.86 [0 (least satisfied)-10 (most satisfied)]. Of those patients with a prior infusion history in an ED (n = 24), 17 (71%) reported greater success in pain alleviation in an outpatient infusion center than in an ED. Nearly 80% of patients (n = 19) reported greater overall comfort with the outpatient infusion center than with an ED infusion.
Conclusion
Our study shows that outpatient infusion treatment is viewed as a positive and beneficial therapy option for adolescents suffering from headache pain. It also suggests that headache infusion treatment in an outpatient center provides more pain relief and satisfaction when compared to headache treatment in the ED. The greater degree of pain relief and satisfaction may be due to a variety of factors, including medications given and the environment of the outpatient center, which tends to be quieter and more controlled than that of the ED.
Our study is limited to patients treated at one hospital, thereby possibly limiting its generalizability. Future studies should consider including data from multiple outpatient infusion centers as well as other EDs.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-086
Non-invasive Vagus Nerve Stimulation (nVNS) for the Acute Treatment of Migraine Without Aura in Adolescents: Preliminary Clinical Experience
Licia Grazzi1,*, Gabriella Egeo2, Eric Liebler3 and Piero Barbanti2
1Headache Center, Carlo Besta Neurological Institute and Foundation, Milan
2Headache and Pain Unit, Department of Neurological Motor and Sensorial Science, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Rome, Italy
3electroCore, LLC, Basking Ridge, United States
Objectives
Study results and clinical experience have demonstrated the safety, tolerability, and efficacy of non-invasive vagus nerve stimulation (nVNS; gammaCore®) for the acute and prophylactic treatment of primary headache disorders including migraine and cluster headache. nVNS is easy to use and has a favorable adverse event profile, making this therapy an attractive option for sensitive patient populations. We explored the safety, tolerability, and efficacy of nVNS as an acute treatment of migraine without aura in adolescents.
Methods
Nine 13- to 18-year-old patients who had migraine without aura according to International Classification of Headache Disorders, 3rd edition (beta version) criteria (4 to 8 migraine days per month) were recruited into this single-arm open-label study. The patients and their parents participated in a 1-hour training session where they were instructed on how to acutely treat attacks with nVNS for a 4-week period (4 to 8 episodes). For each attack, patients administered one 120-second nVNS stimulation on the right side of the neck. Within 1 hour of the first treatment, a second stimulation was allowed as needed if the patient was not pain free. Patients recorded the pain intensity of the treated attack at several pre-specified time points between 30 minutes and 24 hours after treatment. Rescue medication was allowed after 2 hours post treatment if the patients did not perceive a meaningful reduction in pain. At the end of the study, patients and their parents completed a questionnaire to rate the effectiveness, safety, and ease of nVNS use on a scale from 0 to 5 (where 0 was the lowest score and 5 was the highest score).
Results
Forty-seven migraine attacks were treated. Of these, 22 (46.8%) did not require rescue medication and were deemed treatment successes. Nineteen (40.4%) of the treated attacks were pain free at 1 hour. In an additional 3 attacks (6.3%), patients experienced pain relief (pain intensity reduction to mild) at 2 hours. In the remaining 25 treated attacks, insufficient pain relief or a patient’s fear of migraine progression led to his or her choice to take rescue medication within 1 hour after treatment with nVNS. Patients did not report any device-related adverse events. All patients and parents completed the questionnaire and rated nVNS as having the highest safety and ease of use (score = 5). More than half of the patients (5/9) were highly satisfied with the overall effectiveness of nVNS (score = 5). The remaining 4 patients were not at all satisfied (score = 0).
Conclusion
This preliminary study suggests that the use of nVNS in adolescents is safe, well tolerated, and practical for the treatment of migraine without aura. Acute nVNS treatment was effective in approximately half of the treated migraine attacks, none of which required rescue medication. As reported in previous studies, initiation of nVNS treatment when pain is milder in intensity is more likely to result in a pain-free outcome. This finding is particularly relevant given the rapid onset and short duration of attacks that occur in adolescents. Results of this pilot study are comparable to open-label data from other sensitive patient populations and provide a rationale for larger studies of nVNS as an acute treatment option for adolescents with migraine.
Disclosure of Interest
L. Grazzi Conflict with: Consultancy and advisory fees from Allergan, Inc., and electroCore, LLC, G. Egeo: None Declared, E. Liebler Conflict with: Receives electroCore, LLC, stock ownership, Conflict with: Employee of electroCore, LLC, P. Barbanti Conflict with: Consultancy fees from Allergan, Inc., electroCore, LLC, Janssen Pharmaceuticals, Inc., and Lusofarmaco, Conflict with: Advisory fees from Abbott Laboratories and Merck & Co., Inc
Headache Disorders in Children and Adolescents
PO-02-087
An app to describe headache and pain in children: A proposal
Alejandro Marfil1,*, Oscar De la Garza1 and Silvia Barrera1
1Servicio de Neurología, Facultad de Medicina, UANL, Monterrey, Mexico
Objectives
Children under 8 y/o cannot describe pain accurately. The diagnosis of painful states relies on indirect data from the mother or teachers, or from direct observation and deduction by the physician. In any case, there is uncertainty about the pain quality or other characteristics. In the headache field this is particularly important. At the present times, tablets and other gadgets are available or almost omnipresent and children learn to manipulate them at early ages. We thought that his could be used to evaluate pain.
Methods
We designed an app to help children to describe their pain, based on cartoons with their own picture and different sketches that depicte different pain descriptors.
Results
The app and preliminary results will be presented along with clinical examples.
Conclusion
We think this app will be useful in the evaluation of pain, specially headache. However, there could be cultural differences that deserve some variations. Clinical validation is currently under way.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-088
Accompanying migraineous features in pediatric migraine patients with restless leg syndrome
Derya Uluduz1,*, Aynur Ozge2, Seden Demirci3, Melih Sohtaoglu1, Hatice Onur4, Feray K Savrun1 and Baki Goksan1
1Neurology, Istanbul University Cerrahpasa Medical Faculty
2Neurology, Mersin University Medical Faculty, Istanbul
3Neurology, Suleyman Demirel University Medical Faculty, Isparta
4Child and Adolescent Psychiatry, Mersin University Medical School, Mersin, Turkey
Objectives
The aim of this study was to analyze the frequency of Restless legs syndrome (RLS) in pediatric patients with migraine and compare the results with those of tension-type headache (TTH) patients and healthy controls, and also compare migrainous accompanying symptoms, sleep characteristics, and serum ferritin levels between the pediatric migraine patients with RLS and those without RLS.
Methods
We included 85 consecutive patients with the diagnosis of migraine with or without aura (n = 65) and TTH (n = 20) and 97 headache-free children to our study. Demographics, clinical and laboratory data were recorded. The presence of primary headache was diagnosed using the ICHD-II criteria and RLS was determined with face-to-face interview by an experienced neurologist based on the revised International RLS Study Group criteria for pediatrics.
Results
The frequency of RLS in pediatric migraine patients and patients with TTH was significantly higher than in controls. (p = 0.0001, p = 0.025; respectively). The frequencies of allodynia, vertigo/dizziness and self-reported frequent arousals were significantly higher and serum ferritin levels were significantly lower in migraine patients with RLS compared to those without RLS (p = 0.05, p = 0.028, p = 0.02, p = 0.038; respectively)
Conclusion
Our study suggests that the frequency of RLS is higher in pediatric migraine and TTH patients compared to controls. Therefore, pediatric headache patients should be questioned about the presence of RLS, as this co-occurrence may lead to more frequent migrainous accompanying symptoms and sleep disturbances.
Disclosure of Interest
None Declared
Headache Disorders in Children and Adolescents
PO-02-089
Parental attitudes in children with primary headaches
Derya Uluduz1,*, Harika D Ertem1, Büşra Uğurcan1, Ayhan Bingöl1, Ismail Simsek2 and Aynur Ozge3
1Neurology
2Istanbul University Cerrahpasa Medical Faculty, Istanbul
3Neurology, Mersin University Medical Faculty, Mersin, Turkey
Objectives
To determine whether there is a relationship between migraine and tension-type headache, and depression, anxiety, and parents attitudes in the pre-adolescent pediatric population.
Methods
Participants included 195 children with headache and 43 healthy children ages between 10 and 15 years (mean 12.6 ± 1.1) and their parents who presented at headache clinic. A detailed self report questionnaire for sociodemographic variables, Visual Analogue Scale (VAS), Social Anxiety Scale for Adolescent, and Children's Depression Inventory were administered to the children. Parents were interviewed using validated Parents Attitude Scale which is an attitude measure specifically designed to evaluate psychological adjustment. The SPSS for Windows 23.0 program was used for analyses.
Results
According to the International Headache Classification (ICHD-III beta version), 38% of the patients were episodic migraine and 11% were chronic migraine, 34% were tension-type headache. There was no significant difference among headache groups and healthy subjects in terms of depression, anxiety and fathers’ attitude scale scores. However mothers’ attitude scale scores of migraine group, particularly chronic migraine, was significantly higher than controls (p = 0.04). VAS and depression scores had positive correlation (p = 0.009) and there was a direct relationship between anxiety and mothers’ attitude scale scores among children with migraine (p = 0.016). Both headache groups and controls had a significant correlation between fathers’ and mothers’ attitude scale scores (p = 0.000). Age of children with episodic migraine was correlated negatively with parents’ attitude scale and depression scores, and mothers’ attitude scale scores were correlated positively with children’s anxiety scores (p = 0.025).
Conclusion
Our findings support that mothers’ attitude has effects on migraine in children. Parental attitudes may elevate anxiety and depression symptoms and influence childrens’ perception of pain. In the management of treating childhood headaches, the association of psychiatric comorbidities should be considered.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-090
The Validation of a Self-Efficacy Scale for Chronic Headache: A methods study
Erica Sigman1, Lori Ginoza1 and Jenna Hankard1,*
1Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, United States
Objectives
Chronic headaches affect approximately 4% of the adult population in the United States, and have a debilitating impact on daily activities and quality of life1,2. Self-efficacy is a situation specific sense of self-confidence that one can perform needed actions to achieve desirable or avoid undesirable outcomes. Self-efficacy, or the ability to manage and control headaches, in patients with chronic headaches has been reported to be low3. Defining the level and specific elements of self-efficacy in patients with chronic headaches may help to reduce the disability associated with chronic headaches. We have developed a patient self-reported outcome measure to assess and define the factors of daily activities and behaviors related to self-efficacy in patients with chronic headaches, called the Chronic Headache Self-Efficacy Scale (CHASE).
The objective of this study is to assess the validity and reliability of the CHASE questionnaire in patients with chronic headaches.
Methods
The validity and reliability of CHASE will be examined in 100 patients with a diagnosis of chronic headache or chronic migraine. The patients will complete the CHASE, SF-12 (Short Form-12), HMSE (Headache Management Self-Efficacy Scale), HIT-6 (Headache Impact Test-6), GROC (Global Rating of Change), Patient Acceptable Symptom State (PASS), and questions related to history of treatment and frequency of headaches. Patients will complete the questionnaires at three time points: initial encounter, 24 to 72 hours after initial encounter, and 12 weeks after initial encounter. Statistical analyses will be performed to determine reliability, error estimates, validity, and responsiveness of the scale.
Results
To be completed after the study is completed.
Conclusion
Characterizing the reliability, error, and validity of this scale will provide practitioners with a means to assess the self-efficacy. Particularly, self-efficacy related to the ability to perform daily and lifestyle activities, as well as a variety of behaviors specific to the management of chronic headaches.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-091
Current gaps and challenges in migraine care in Canada: a multi-stakeholder perspective
Sophie Peloquin1, Elizabeth Leroux2,*, Gary Shapero3,4, Sara Labbé1, David W Dodick5 and Werner J Becker6
1Axdev Group, Brossard
2Headache Clinic, South Health Campus, Calgary
3The Shapero Markham Headache and Pain Treatment Centre, Markham
4Department of Family and Community Medicine, University of Toronto, Toronto, Canada
5Mayo Clinic, Phoenix, United States
6Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
Objectives
Despite migraine being a common reason for medical consultation, patients remain sub-optimally treated and managed. Lack of sufficient training in medical school and lack of continuing education training around migraine has been mentioned as an underlying cause for sub-optimal migraine care (Gladstone 2010). A Canadian study was conducted to identify challenges, clinical practice gaps and potential educational needs of health care providers caring for patients suffering from migraine, with the goal to inform the design of future educational activities and programs.
Methods
This IRB-approved educational and behavioural research study uses a mixed-methods (qualitative and quantitative) methodology with a multi stakeholders approach in four (4) provinces of Canada: Alberta, British-Columbia, Ontario and Quebec. The initial qualitative phase included multiple data sources: 1) literature review, 2) input from an expert working group & 3) semi-structured telephone interviews with: Neurologists (NEU) and General Practitioners (GPs), Nurses with special expertise in migraine (NUs), Pharmacists (PHs), Clinic Administrators (CAs), Policy Influencers or Payers (PIs) & Patient Advocates (PAs). Data sources were triangulated to obtain a comprehensive understanding of factors undermining optimal migraine care. The quantitative phase (survey) will validate the extent to which the identified gaps are present in a larger sample of healthcare professionals and will allow a comprehensive understanding of challenges and their causalities.
Results
29 participants were enrolled in the qualitative phase; NEU (n = 8), GPs (n = 7), NUs (n = 2), PHs (n = 4), CAs (n = 3), PIs (n = 3) & PAs (n = 2). A majority of Health care provider participants worked in community setting (65%) and had over 20 years of experience (60%). Caseload of patients with migraine varied from 10 to 100% of overall caseload. Six (6) preliminary key findings and their underlying causalities were identified in the patient's care pathway: (1) Challenges in differential diagnosis, (2) Challenges in selection of treatment (migraine specific vs. non-migraine specific), (3) Challenges in incorporating non-pharmacological therapy, (4) Challenges in monitoring treatment response, (5) Lack of availability of effective therapies and (6) Sub-optimal sharing or roles and responsibilities in migraine care. The underlying causalities identified for each challenge included specific knowledge and skills gaps, confidence and attitudinal issues, as well as system and contextual factors, all potentially contributing to impaired care. Results from the quantitative phase (survey), including validation of the aforementioned challenges and their causalities, will be integrated into the final findings and presented.
Conclusion
Six (6) preliminary key challenges and their causalities were identified in migraine care in 4 provinces of Canada. Findings from this study underline the need to examine how further support, resources and medical/health education interventions could be provided to health care providers involved in the care of patients suffering from migraine in Canada. A similar study is currently underway in US and Europe.
Disclosure of Interest
S. Peloquin: None Declared, E. Leroux Conflict with: Allergan, Tribute Pharmaceuticals, Eli Lilly, Teva Neurosciences, Conflict with: Allergan, Tribute Pharmaceuticals, Electro Core, Teva Neurosciences, G. Shapero: None Declared, S. Labbé: None Declared, D. Dodick Conflict with: Stock/options: Xalan-GBS, Epien, and Mobile Health., Conflict with: Allergan, Amgen, Alder, Dr Reddy’s, Merck, Dr Reddy’s, Promius, eNeura, Eli Lilly & Company, INSYS therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, Boston Scientific, GBS, Colucid, Zosano. CME companies honoraria: Haymarket Medical Education, Global Scientific Communications, HealthLogix, Academy for Continued Healthcare Learning. Consulting use agreement: NAS. Board position (advisory; no compensation): King-Devick Test, Conflict with: Royalties: Oxford University Press and Cambridge University Press (Book Royalty) Other Uptodate – editorial/honoraria, W. Becker Conflict with: Dr. Becker has served on advisory boards and/or received speaker's honoraia from Amgen, Allergan, Tribute, and ElectroCore.
Headache Education for Clinicians and Patients
PO-02-092
Neurology residents’ knowledge of the management of headache
Espen Saxhaug Kristoffersen1,2,*, Bendik Slagsvold Winsvold3,4 and Kashif Waqar Faiz2,5
1Department of General Practice, University of Oslo, Oslo
2Department of Neurology, Akershus University Hospital, Lørenskog
3Department of Neurology
4FORMI, Oslo University Hospital, Oslo
5Research Centre, Akershus University Hospital, Lørenskog, Norway
Objectives
Headache is a common complaint in the general population, and physicians should have a good knowledge of its management. Although the majority of patients are self-managed or treated in primary care, the most complicated cases are often referred to neurological outpatient clinics. Therefore, all physicians working within the field of neurology should be especially competent in the management of headache.
There is limited focus on headache in the curriculum at the four medical schools in Norway. Furthermore, approximately 50% of all residents in Norway have graduated from abroad.
The national five-year training program in clinical neurology has no mandatory headache program. Therefore, knowledge and expertise in headache management must be acquired during the everyday clinical neurology training.
The objectives of this survey were to investigate whether residents acquire the necessary knowledge about headache, and to evaluate experience in, and attitudes towards headache management.
Methods
The study was conducted as a questionnaire survey among residents in neurology at all the 17 neurological departments in Norway. A contact person at each department had the responsibility for distributing and collecting the forms. The study was reviewed by the ethics committee and approved by the Data Protection Official for Research, Norway.
Results
All the neurological departments participated, and the responder rate among residents was 84 %. In total, 138 residents participated, of which 60% were women. Mean age was 33 years. The respondents had on average almost three years clinical training in neurology. Residents answered questions about knowledge, attitudes and experiences related to headache management. Barriers to adequate headache treatment were investigated. The use of national treatment guidelines and the International Classification of Headache disorders were examined. Finally, various neurological diseases were compared with regards to their perceived social status among residents.
Conclusion
The results are currently being analysed and will be presented at the meeting.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-093
Headache Medicine Knowledge Assessment Survey of Primary Care Providers
Melissa Schorn1,*, Natalia Murinova2, Sau Mui Chan Goh1, Yongjie Locker3, Daniel Krashin4 and Jennifer Wax2
1Neuroscience Institute, University of Washington Medical Center
2Neurology
3Nursing
4Pain and Anesthesiology, University of Washington, Seattle, United States
Objectives
The objective of this study was to develop a survey to assess knowledge gaps in primary care regarding headache medicine. This is the first step in a process to develop a headache education program for primary care providers in a University-based healthcare system.
Methods
A survey for primary care providers was developed by two providers in a university-based specialty headache clinic (one physician board certified in headache medicine and one doctorate prepared nurse practitioner) in collaboration with a doctoral family primary care nurse practitioner student. The survey included questions regarding diagnosis and treatment of headache disorders and was distributed by Catalyst survey to 132 primary care providers throughout 12 primary care clinics within the university-based healthcare system.
Results
A total of 51 participants completed the survey, a 40% response rate. Common areas of knowledge gaps were identified through data analysis. These areas included assessment and management of medication overuse headache, assessment of psychosocial co-morbidities, use of International Headache Society Beta 3 Diagnostic Criteria, acute pharmacological management, and non-pharmacological treatment of headache. Participants reported the highest confidence in diagnosing migraines, with nearly 50% of them reporting 4 or 5 on a confidence scale of 0–5 (0 being “not confident at all,” and 5 being “extremely confident”). They were the least confident in diagnosing cluster headache, chronic daily headache, and medication overuse headache. Participants were largely aware that NSAIDs, Tylenol, and opioids can cause medication overuse headache (MOH), but fewer than 60% of participants were aware that other medications can cause MOH, such as benzodiazepines, barbiturates, and ergotamines. Only 16% of the participants reported using the International Headache Society Beta 3 criteria when diagnosing headaches. Despite recommendations against prescribing opioids and barbiturates for headache relief, 24% of the participants would consider prescribing opioids, and 39% of them would consider prescribing barbiturates for acute headache management. Most participants actively assess for comorbid anxiety, depression and sleep disorders (85%, 98%, 93% respectively), however only a small number assess for comorbid elevated body mass index (39%). An overwhelming majority of primary care providers completing the survey (98%, n = 50) were interested in learning more about headache medicine through either online modules or in person training.
Conclusion
There are both significant learning opportunities and the desire to learn more about headache medicine among primary care providers in this university-based healthcare system. Primary topics for a headache training program are those which meet knowledge deficits and have the potential to significantly improve care, including medication overuse headache diagnostic criteria and treatment options, acute and preventive treatment options, use of International Headache Society Beta 3 Diagnostic Criteria for all headache diagnoses, and comorbid conditions important to assess and address in headache that may directly or indirectly impact treatment success.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-094
Patients and Carers Education - Cumbria Headache Forum
Jitka Vanderpol1,*
1Neurology, Cumbria Partnership NHS, Cumbria, United Kingdom
Objectives
Headache disorders are often disabling conditions impacting on all aspects of normal living. It can lead to decreased performance at work or school, depression, disability and decreased quality of life.
Cumbria Headache Forum (CHF), was established in 2013. It provides regular, three-monthly, large scale meetings regionally, open to all patients with headache and migraine as well as health professionals in Cumbria. CHF enables access to medical professionals with an expertise in the headache field from Cumbria as well as invited experts from the outside of Cumbria. This is an educational platform which aims to enable patients to take an active role in management of their often-debilitating condition.
Methods
The concept combines pharmacological and non-pharmacological approach, lifestyle advice, advice about stress management and diet. Invited speakers are headache experts, GPs with special interest, Headache Specialist Nurses, psychologist, physiotherapist and dietary nurse, nutritional therapis. CHF meetings are organised and chaired by Dr Vanderpol Consultant Neurologist with expertise in headache field who heads Headache Service in Cumbria. To establish benefit and gather qualitative data a survey was conducted with participants who attended headache forums between December 2014 and January 2016.
Results
In total 25 responded to the survey. 87.5% learned new information about headache or migraine which has helped them to better understand the condition. 83.33% have taken more active role in management since attending the forum. 96% participants would recommend to family or friend who suffers from headache or migraine to attend the forum.
Conclusion
This concept provides multidisciplinary approach enabling and supporting Self-Management. The aim was to create a comprehensive program to increase the likelihood of successfully managing headaches and provide support to patients who often felt left alone for many years with their condition. More than 3 years of experience of running CHF meetings and outcomes of the survey has shown very positive results. Positive feedback is provided after every meeting. The attendance of the meeting has been growing, many patients travel from neighboring regions far away, to get the needed help and support.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-095
Progressive Multifocal Cerebral Infarction Due to Reversible Cerebral Vasoconstriction Syndrome without Headache
Byung-Su Kim1,*, Mun Kyung Sunwoo1, Eun Hye Jung1, Hyun-Jeung Yu1 and Sook Young Roh1
1Neurology, Bundang Jesaeng General Hospital, Daejin Medical Center, Seongnam, Korea, Republic Of
Objectives
Multiple attacks of thunderclap headache are cardinal features of reversible cerebral vasoconstriction syndrome (RCVS). However, few studies reported that RCVS could occur without typical thunderclap headache. Here, we report on an unusual clinical course of progressive multifocal cerebral infarction probably due to RCVS without headache.
Methods
Case report.
Results
A 46-year old woman visited our emergency department due to 1-day history of suddenly developed visual field defect. She had no history of conventional vascular risk factors, such as hypertension, diabetes, and dyslipidemia, as well as migraine and other headache disorders. Initial magnetic resonance imaging (MRI) and angiography (MRA) revealed acute cerebral infarct in the left middle cerebral artery (MCA) territory that was likely embolic in nature and diffuse multivascular stenoses involving bilateral the proximal and distal segments of the MCAs, the anterior cerebral arteries (ACAs), and the posterior cerebral arteries. She was started on aspirin and clopidogrel initially. At the 2nd day of her admission, she reported sudden-onset left lower limb weakness; and follow-up MRI showed new acute ischemic stroke in the right ACA territory. Cerebral angiography was performed to further evaluate the multivascular stenotic lesions. Laboratory studies provide no evidence of systemic vasculitis and other autoimmune disease. Although she had never complaint any headache at all, she was treated with oral calcium channel blocker (nimodipine 30 mg bid). There was no subsequent cerebral infarction. Three-month follow-up MRI and MRA showed complete recovery of the multivascular stenoses.
Conclusion
This is an uncommon case of progressive cerebral infarction probably due to RCVS, despite the absence of headache. The clinico-radiological findings of our case suggest that RCVS can be a potential cause for cerebral infarction even if headache does not exist at all during clinical course.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-096
The Clinical Research Nurse: a 5-Year Experience in a 3rd Level Headache Centre
Monica Bianchi1,*, Vito Bitetto1, Grazia Sances1 and Cristina Tassorelli1
1Headache Science Centre, C. Mondino National Neurological Institute, Pavia, Italy
Objectives
The role of the headache nurse within the activities of a headache centre is becoming increasily important, even more so in those structures where care and research are institutional activities. I have been working as a clinical research nurse in such a structure for 5 years and I have dynamically adapted my supporting role within the research team with a multitude of tasks. The aim of this abstract is to illustrate my experience for the perusal of other centres and colleagues.
Methods
I have retrospectively analysed the type of activities and the organizational adaptations that have been put in place in order to support and expedite activities within the research team, focusing the attention also on the initiatives taken to optimize the management and wellbeing of patients during the procedures, with the aim to improve their satisfaction.
Results
My activities initially consisted mainly in sample collection and planning of patients’ appointments. Over the years, they increased in number and type. Today they can be associated to several domains, with different levels of responsibilities: protocol development, organization of activities, spaces, supplies and documents, distribution/collection of informed consents, patient recruiting and scheduling, data collection and safety reporting, tissue and sample collection, processing and mailing, remote follow-up of patients, triage of complaints. All of these activities require accurate planning. In addition, most, if not all, studies foresee a variable overlapping of research and care activities. In this frame it is very important to reach and keep a good balance between the requirements of the research and the needs of patients.
Conclusion
Being a clinical research nurse entails a large amount of responsibilities in the outcome of studies and in the quality of care delivered to patients. To perform the role at best, the clinical research nurse requires a large repertoire of clinical expertise, organizational skill and capability to critically evaluate problems and dynamically search for the possible solutions. An expert and well trained research nurse is pivotal for the conduction and completion of clinical studies in the field of headacge and greatly contributes to patient’s satisfaction.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-097
Barriers to Care among Indian Children with Recurrent Headache
Devendra Mishra1,*, Charu Jain1, Monica Juneja1 and Kirti Singh2
1Pediatrics
2Ophthalmology, Maulana Azad Medical College, Delhi, India
Objectives
Reasons which prevent headache patients from seeking healthcare are labelled Barriers to Care. Theris little information on these in the context of pediatric headache. This study was done to identify various barriers to care among children with recurrent headache attending a general pediatric OPD.
Methods
After IEC clearance and informed consent, consecutive children attending our Pediatric department with either Migraine or Tension-type headache (as per ICHD-3) were enrolled between April, 2014 to February, 2015. Complete history and physical examination was done in all children. Barriers to care were explored during a one-to-one interview with the parents using a list of previously described factors categorized as Clinical, Social, and Others,1 along with open-ended questions.
Results
Forty children (24 males) with mean (SD) age of 10.6 (1.7) year were enrolled. Migraine was diagnosed in 24. Majority of the headache patients (83.3% migraine, 100% TTH) had more than two barriers to care identified, and none was without an identified barrier.
The major group was Clinical barriers, with ‘wrong diagnosis’ (90%) and ‘improper treatment’ (75%) being common. Delayed referral was significantly higher (P < 0.001) among TTH patients than migraine. The Social barriers were also frequent, with ‘Wrong expectations’ observed in all patients, and ‘Frequent change of doctors’ being more in those with TTH (P = 0.039).
Conclusion
Identification of barriers is a step towards appropriate strategies for addressing these, provided similar community-based data is generated. Clinical barriers are amenable to intervention by improving teaching during clinical training and by CME programs for clinicians, though Social barriers will require more sustained public health awareness campaigns.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-098
Frequency of Vertigo in Pediatric Migraine
Katherine Hamilton1,* and Amy Gelfand1
1University of California, San Francisco (UCSF), San Francisco, United States
Objectives
In its appendix section, the International Classification of Headache Disorders, 3rd edition, beta (ICHD IIIb) has identified a new diagnostic category of vestibular migraine[1], which has been validated in adult populations[2]. However, the utility of this diagnosis among pediatric patients with migraine is unclear. Vertigo is a commonly reported symptom in children with migraine and may be as common as photophobia or nausea. The current study sought to establish the frequency of vertigo in pediatric patients seeking care for migraine.
Methods
This study is a retrospective chart review that includes all patients less than 18 years old with migraine who were seen at the University of California, San Francisco (UCSF) Pediatric Headache Clinic in 2014. Notes from patients’ initial encounters were reviewed, as all patients presenting to the clinic undergo a semi-structured interview that includes a specific query regarding the presence or absence of vertigo with their migraine attacks.
Results
Of 103 pediatric patients with migraine, the mean age was 13.4 years, 70% were girls, 21% had migraine with aura, 59% had chronic migraine, and the mean frequency of migraine days per month was 19. Among this population, 49 patients or 48% reported experiencing vertigo at least once in association with their migraine headaches.
Conclusion
The high percentage of pediatric migraine patients experiencing vertigo supports the hypothesis that vertigo is a common symptom in the pediatric migraine population. Of note, our sample was from a tertiary care center, and the majority of these patients had chronic migraine. Nevertheless, our finding should spur further research to determine whether a subset of migraine patients with vertigo would meet criteria for vestibular migraine and whether pediatric migraine patients with vertigo respond differently to acute and preventive treatments compared to those without vertigo.
Disclosure of Interest
K. Hamilton: None Declared, A. Gelfand Conflict with: from eNeura and Allergan, Conflict with: to Zosana and Eli Lilly, Conflict with: Travel expenses from Teva. Her spouse has received research support from Genentech, MedDay, and Quest Diagnostics and has received personal compensation for medical-legal consulting and consulting fees from Genentech.
References
[1] Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808.
[2] Radtke A, Neuhauser H, von Brevern M, Hottenrott T, Lempert T. Vestibular migraine–validity of clinical diagnostic criteria. Cephalalgia. 2011;31(8):906–913.
Headache Education for Clinicians and Patients
PO-02-099
Cycling Through Migraine Preventive Treatments: Implications to All-Cause Total Direct Costs
Janet Ford1,*, Allen Nyhuis1, Sheena Aurora1, Shonda A Foster1 and Krista Schroeder1
1Eli Lilly and Company, Indianapolis, IN, United States
Objectives
Migraine is a common and disabling neurological condition associated with a substantial economic burden. Currently available preventive migraine medications (PMM) are marginally effective and induce side effects that can lead to multiple PMM switches or discontinuation. It is unknown if cost differences exist among migraine patients when PMM switches occur. The aim of this study is to understand the cost burden of patients who cycle through 1 (PMM1), 2 (PMM2), or ≥3 (PMM3) unique PMM drug classes over a 12-month period compared to patients who are persistent on their initial PMM class.
Methods
This retrospective observational study used the Truven MarketScan U.S. Commercial and Medicare Supplemental claims database to identify adult migraine patients initiating their first PMM class (antidepressants, antiepileptics, beta-blockers, or neurotoxins) from 2011–2013 (index = first PMM claim), with a 1 year pre-index clean period established for all PMMs. Patients were required to have at least 2 (1 if inpatient) migraine diagnosis codes (ICD9: 346.xx) from 1 year pre-index to 1 year post-index with at least 1 code occurring pre-index. The inclusion criteria also required 12 months of pre- and post-index continuous medical and prescription enrollment. Patients were excluded if, during the 12 months before the first claim for any PMM class (index or switched drug), they received an ICD9 code for a non-migraine comorbidity treated by that PMM class (epilepsy and antiepileptics, hypertension/congestive heart failure and beta-blockers, depression and antidepressants). Based on the 2014 medical consumer price index, all-cause total direct costs (outpatient, inpatient, emergency room, and prescriptions) were estimated for the 3 PMM cohorts vs. the persistent (remained on initial therapy) cohort in the 12 months post-index. Propensity score bin bootstrapping controlling for patient baseline characteristics was used to compare costs between each PMM and persistent cohort. Bootstrap simulations were performed, resulting in adjusted calculations of each subgroup’s mean total costs and standard deviation (SD).
Results
The study population included 61,232 patients who received a PMM and met all other study inclusion/exclusion criteria. Study patients were mainly female (85%) with a mean age of 38.6 yrs and mean Charlson comorbidity index of 0.34. Adjusted mean all-cause total direct costs ± prescription costs for the 4 cohorts are presented in the table above; statistically significant differences were observed between each PMM group and the persistent cohort.
Conclusion
All-cause total direct USD costs: propensity score-adjusted comparisons
Disclosure of Interest
J. Ford Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, A. Nyhuis Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, S. Aurora Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, S. Foster Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, K. Schroeder Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company, Conflict with: Eli Lilly and Company
Headache Education for Clinicians and Patients
PO-02-100
Characteristics of patients newly initiating a preventive treatment for migraine: Baseline data from the Assessment of TolerabiliTy and Effectiveness in MigrAINeurs using Preventive Treatment (ATTAIN) study
Ariane K Kawata1, Neel Shah2, Jiat-Ling Poon1, Shannon Shaffer1, Sandhya Sapra2, Alex Mutebi3, Teresa K Wilcox1, Stewart J Tepper4, David W Dodick5 and Richard B Lipton6,*
1Evidera, Bethesda, MD
2Amgen
3Former Amgen employee, Thousand Oaks, CA
4Geisel School of Medicine at Dartmouth, Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
5Department of Neurology, Mayo Clinic Arizona, Phoenix, AZ
6Albert Einstein College of Medicine and the Montefiore Headache Center, Bronx, NY, United States
Objectives
To present baseline demographic and clinical characteristics, and patient-reported outcomes (PROs) of migraineurs initiating a preventive migraine medication and enrolled in a prospective observational study: Assessment of TolerabiliTy and Effectiveness in MigrAINeurs using Preventive Treatment (ATTAIN).
Methods
Subjects with a clinical diagnosis of episodic (EM) or chronic migraine (CM) and initiating a physician-prescribed preventive treatment at primary care or neurology clinics in the United States are currently being enrolled in a study to assess the tolerability and effectiveness of migraine preventive therapies. Subjects are enrolled onsite at clinical sites and complete baseline assessments online. Baseline assessments include: demographic forms, migraine history, healthcare resource use, and PROs including Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6™; score range: 36–78), Migraine Functional Impact Questionnaire (MFIQ; score range: 0–100), and Work Productivity and Activity Impairment Questionnaire (WPAI; score range: 0–100%). Migraine and treatment history are also reported by clinic staff through medical chart review. Subjects are followed for 6 months post-baseline, with monthly completion of questions related to migraine frequency, treatment tolerability, reasons for any change in treatment, and the PROs included at baseline. The enrollment target is 300 subjects. Summarized here are baseline characteristics of 101 subjects enrolled to date.
Results
The current sample includes 48 (47.5%) EM and 53 (52.5%) CM subjects, with mean ± SD age 42.0 ± 13.1 years. The majority are female (87.1%), white (73.3%), and employed full-time (58.4%). Mean ± SD age at first migraine diagnosis was 22.3 ± 11.1 years (EM: 23.5 ± 11.4; CM: 21.1 ± 10.8) and the majority have migraine without aura (65.3%). In the three months prior to enrollment, subjects reported mean ± SD of 15.8 ± 7.2 headache days per month (EM: 10.0 ± 2.4; CM: 21.1 ± 6.0), of which 11.4 ± 6.0 (EM: 7.6 ± 2.8; CM: 14.8 ± 6.2) were migraine days. Prior to enrollment, the majority of subjects (71.3%; EM: 75.0%; CM: 67.9%) were naïve to treatment with migraine preventive medications; 58.3% of treatment naïve subjects were initiated on topiramate. The most commonly prescribed migraine preventive treatments were topiramate (58.3%), beta blockers (14.6%), and tricyclic antidepressants (10.4%) for EM subjects, and topiramate (37.7%), onabotulinumtoxinA (24.5%), and tricyclic antidepressants (15.1%) for CM subjects. At baseline, EM and CM subjects reported severe headache impact (HIT-6 score >59; EM: 85.4%, CM: 92.5%) and severe disability (MIDAS Grade IV (≥21); EM: 64.6%, CM: 83.0%). Functional impacts on activity were also reported based on MFIQ Global item (EM: 55.2 ± 29.2; CM: 55.7 ± 27.1) and WPAI activity impairment score (EM: 58.5% ± 29.4; CM: 55.1% ± 29.6).
Conclusion
This web-based longitudinal, observational study is currently ongoing and seeks to generate insights into the real-world tolerability and effectiveness of preventive migraine treatments. Baseline assessments indicate high burden of illness among both EM and CM subjects, with migraine contributing to severe disability, functional impact, and activity impairment.
Disclosure of Interest
A. Kawata Conflict with: Employee of Evidera, N. Shah Conflict with: Amgen, Conflict with: Amgen, J.-L. Poon Conflict with: Employee of Evidera, S. Shaffer Conflict with: Employee of Evidera, S. Sapra Conflict with: Amgen Inc., Conflict with: Amgen Inc., A. Mutebi Conflict with: Stock in Amgen, Conflict with: Employee of Amgen at the time of study start, T. Wilcox Conflict with: Employee of Evidera, S. Tepper Conflict with: ATI, Conflict with: Alder, Allergan, Amgen, ATI, Avanir, Teva, Zosana, Conflict with: Consultant: Acorda, Alder, Allergan, Amgen, ATI, Avanir, Eli Lilly, Kimberly-Clark, Pernix, Pfizer, Teva, Zosana; Salary: American Headache Society, Conflict with: Advisors board: Allergan, Amgen, ATI, Avanir, BioVision, Dr Reddy's, Kimberly-Clark, Scion Neurostim, Teva, Pfizer, Conflict with: Receipt of royalties: University of Mississippi Press, D. Dodick Conflict with: Epien Medical (Stock), Second Opinion (stock), GBS (stock), Neuroassessment systems (Know-how License with Employer-Mayo Clinic), Conflict with: Served on advisory boards and/or has consulted for Allergan, Amgen, Alder, Dr Reddy’s, Merck, eNeura, Eli Lilly & Company, INSYS therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, and Boston Scientific, GBS, Merck, Colucid, Zosano., Conflict with: Amgen, Conflict with: Received editorial honoraria and/or royalties from Oxford University Press, Cambridge University Press, Web MD. UptoDate, R. Lipton Conflict with: eNeura Therapeutics, Conflict with: NIH, Migraine Research Foundation, National Headache Foundation, Conflict with: Consultant, advisory board, honoraria: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Colucid, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta, Conflict with: Receipt of royalties: Oxford Press University, Wiley, Informa
Headache Education for Clinicians and Patients
PO-02-101
Headaches in Argentina. Preliminary Study
Lourdes V Molina1,*, Beatriz L Kinjo1, Daniel H Gestro1 and Maria D. L Figuerola1
1Headache Center. Department of Neurology, Hospital de Clínicas “José de San Martín ”, Buenos Aires, Argentina
Objectives
According to the data from the WHO (World Health Organization) (2010) primary headaches are among the most prevalent diseases worldwide. We conducted a National headache survey during 2014 with the aim of establishing the prevalence and some epidemiologic data of headache in Argentina.
Methods
We conducted a descriptive epidemiological study in different geographic areas of Argentina through a standardized questionnaire. Face-to-face interviews were performed to the general population randomly between May and July 2014. Subjects, who answered to have headaches, were asked about pain duration, frequency and severity, as well as the quality of life and self-medication.
Results
A total of 2020 subjects were interviewed. In this study 92% respondents reported to have headaches (52% female subjects vs. 48 % male subjects) with no significant differences between the compared geographic areas. A total of 10% referred to have frequent headaches (more than 50 episodes/year), 22% reported to have moderate to severe pain, 94% missed work at least one day over the last year. 72% percent reduced their quality of life, and 80% were self-medicated. Only 38, 5% sought medical help.
Conclusion
Our study showed a similar prevalence of headaches in our country compared to data from WHO. Upon analysis of the data, we concluded that the impaired quality of life is associated with the high frequency and severity of headache episodes. The self-medication is related to the severity and duration of the pain, and/or the frequency of each episode. Among those who sought medical help, more than half of the patients consulted a general practitioner
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-102
Individual self-prediction of migraine attacks: longitudinal analysis of cohort of migraine patients using a digital platform
Pablo Prieto1,*, Gabriel Boucher1, Alec Mian1 and Noah Rosen2
1Curelator Inc., Cambridge
2Northwell Health, New York, United States
Objectives
As a critical component towards self-management of their condition we examine the individual ability of patients to predict their attacks 24 hrs in advance. Prediction of attacks might be expected to be difficult as migraine premonitory symptoms, and the potential risk factors that trigger them, show significant inter-individual variation (1) and possibly also intra-individual variation. Accurate prediction may impact quality of life, allow optimal timing of medication dosing and may also lead to understanding of the profiles and “best practice” of good predictors. Thus, the objective is to understand and compare ability of episodic migraineurs to self-predict attacks on an individual level.
Methods
Individuals with migraine registered to use a digital platform (Curelator Headache™) via website or the App Store (iOS only) and on a daily basis for at least 90 days entered about lifestyle factors, possible headaches, and medications as well as migraine expectation for the next 24 hours (low/moderate/high). Patients with at least 10 low and 10 high expectations instances of migraine were included in the analysis. Prediction was considered successful when 24 hr expectation of migraine was high and an attack occurred on the next day; or 24 hr expectation was low and was followed by a migraine free day.
Results
Of 497 episodic migraineurs examined in the study, 192 met the criteria for analysis. Good predictors were defined as having an accuracy of ≥75% at predicting an attack; bad predictors were defined as those with ≤25% accuracy predicting a migraine. In this study we found 18% (n = 34) were good predictors and 21% (n = 41) were defined as bad predictors, and both groups stood up as different from the rest of the sample with statistical significance (p < 0.001).
Conclusion
A substantial proportion (61%, n = 117) of users predict their migraine with only moderate accuracy (≥25% but ≤75%). A small group (21%, n = 41), were considered bad predictors with <25% accuracy. A somewhat smaller group (18%, n = 34) were found to be good predictors with >75% accuracy. A next step would be to understand the in possible differences risk factors and premonitory symptoms that these two groups may exhibit and are possibly using for prediction of their attacks.
Disclosure of Interest
P. Prieto Conflict with: Curelator Inc., Conflict with: Curelator Inc., G. Boucher Conflict with: Curelator Inc., Conflict with: Curelator Inc., A. Mian Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., N. Rosen Conflict with: Allergan, Avanir, Supernus, Promius and Curelator Inc
Reference
(1) Peris et al. Towards improved migraine management: determining potential trigger factors in individual patients. Cephalalgia (2016). May 14
Headache Education for Clinicians and Patients
PO-02-103
Reducing Impaired Days: Results from the STRIVE Trial, A Phase 3, Randomized, Double-Blind Study of Erenumab for Episodic Migraine
Asha Hareendran1, Dawn C Buse2, Richard B Lipton2,*, Martha S Bayliss3, Daniel D Mikol4, Dennis A Revicki5, Feng Zhang4, Pooja Desai4, Hernan Picard4 and Ariane K Kawata5
1Evidera, London, United Kingdom
2Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
3Optum, Lincoln, RI
4Amgen Inc., Thousand Oaks, CA
5Evidera, Bethesda, MD, United States
Objectives
To evaluate the effect of erenumab, a preventive treatment for episodic migraine (EM) in adults, on monthly days with impairment as measured by the Migraine Physical Function Impact Diary (MPFID).
Methods
The MPFID is a 13-item patient-reported outcome (PRO) measure that assesses the impact of migraine on two domains: everyday activities (EA) and physical impairment (PI), over the previous 24 hours. MPFID was completed using an electronic diary every evening during a global, placebo controlled double-blind, 6 month, phase 3 trial (STRIVE trial; NCT02456740) in which 955 adults with EM aged 18–65 years were randomized 1:1:1 to subcutaneous, monthly placebo or erenumab 140 mg or 70 mg. Reponses to items in the MPFID EA and PI domains are on a 1–5 scale, with higher numbers indicating greater negative impact. A day with a response ≥3 on at least one item in a domain was defined an “impaired day” (ID) for that domain, (i.e. EA-ID and PI-ID). Mean monthly number of IDs were summarized for the 4-week baseline period and each subsequent 4 week period. Changes from baseline in mean monthly EA-ID and PI-ID over the final 3 months (month 4–6) of the double-blind treatment phase (DBTP) were assessed as pre-specified exploratory endpoints in the STRIVE trial; primary and secondary endpoints are reported separately. All p-values are descriptive and were not adjusted for multiplicity.
Results
At baseline, subjects in the erenumab and placebo groups had a similar number of mean monthly EA-ID (140 mg: mean ± SD 6.62 ± 4.20; 70 mg: 7.21 ± 4.56; placebo: 7.12 ± 4.85) and PI-ID (140 mg: 5.81 ± 4.32; 70 mg: 6.09 ± 4.60; placebo: 6.20 ± 5.05). Over the final 3 months of the DBTP, greater reductions from baseline in EA-IDs and PI-IDs were observed in the erenumab 140 mg and 70 mg groups compared to placebo. For EA-IDs, subjects treated with erenumab 140 mg (LS mean = −3.01 days (95% confidence interval (CI): −3.45,−2.57)) and 70 mg (−2.83 days (−3.27,−2.39)) experienced larger reductions compared to placebo (−1.71 (−2.16,−1.27), p < 0.001 for both). Greater reductions in mean monthly PI-IDs days were also observed in the erenumab groups (140 mg: LS mean = −2.51 days (95% CI: −2.93,−2.09); 70 mg: −2.25 days (−2.68,−1.83)) compared to placebo (−1.16 (−1.59,−0.74), p < 0.001 for both).
Conclusion
Compared to the placebo group, EM subjects treated with erenumab 140 mg and 70 mg experienced greater reductions from baseline in mean monthly MPFID EA-ID and PI-ID during the 6 month DBTP of the STRIVE trial. Numerically greater reductions were observed in the 140 mg compared to the 70 mg group. Erenumab treated patients experience reductions in functional impairment due to migraine, as measured by MPFID, which complements improvements observed with standard efficacy measures.
Disclosure of Interest
A. Hareendran Conflict with: Pfizer Ltd, Conflict with: Employee of Evidera, D. Buse Conflict with: Buse has received grant support and honoraria from Allergan, Avanir and Eli Lilly. She is an employee of Montefiore Medical Center, which has received research support funded by Allergan, CoLucid, Endo Pharmaceuticals, GlaxoSmithKline, MAP Pharmaceuticals, Merck, NuPathe, Novartis, Ortho-McNeil, and Zogenix, via grants to the National Headache Foundation., Conflict with: Allergan, Avanir, Amgen, Dr. Reddy’s laboratories, Eli Lilly, Conflict with: Non-remunerative Positions of Influence: Buse is on the editorial board of the Current Pain and Headache Reports, Journal of Headache and Pain, Pain Medicine News, and Pain Pathways magazine., R. Lipton Conflict with: National Institutes of health, the National Headache Foundation, the Migraine Research Fund, Conflict with: Serves as a consultant, serves as an advisory board member, or has received honoraria from Alder, Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristo Myers Squibb, Cognimed, CoLucid, Eli Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, and Teva, Conflict with: Receipt of royalties: Royalies from Wolff's Headache, 8th Edition (Oxford University Press, 2009), M. Bayliss Conflict with: Martha Bayliss, MSc, is an employee of Optum, a division of UnitedHealth Group, which has consulting engagements with many pharmaceutical companies, including Amgen., Conflict with: Optum, a division of UnitedHealth Group, Conflict with: Non-remunerative Positions of Influence, D. Mikol Conflict with: Amgen Inc., Conflict with: Amgen Inc., D. Revicki Conflict with: Amgen, Conflict with: Amgen, Allergan, Conflict with: Employee of Evidera, F. Zhang Conflict with: Amgen Inc., Conflict with: Amgen Inc., P. Desai Conflict with: Amgen Inc., Conflict with: Amgen Inc., H. Picard Conflict with: Amgen Inc., Conflict with: Amgen Inc., A. Kawata Conflict with: Employee of Evidera
Headache Education for Clinicians and Patients
PO-02-104
Prevalence and Impact of Headache in Republic of Ireland
Niamh Murphy1,*, Ruth MacIver1, Esther Tompkins2 and Martin Ruttledge2,3
1Novartis Ireland, Dublin
2Beaumont Hosptial, Dublin 9
3Hermitage Medical Clinic, Dublin, Ireland
Objectives
Headache disorders such as migraine are among the most common disorders of the nervous system, bringing a heavy burden not only to individuals but also to society. The populaton of the Republic of Ireland is approximately 4.7 million however the impact and burden of headace disorders in Ireland is unknown
Methods
In order to estimate the prevalence and burden of headache within the republic of Ireland we conduced a telephone survey with a population sample that was generated by random digit dialling. The survey was answered by 1013 people. aged 15 or older. The population was spread across the four provinces of Ireland and balanced by age, sex and social demographic.
Results
226 (22.3%) of the respondents reported at least one headache episode in the previous year. Of those 150 (14.8%) fulfilled the criteria for migraine, with 44% having at least one migraine a month. There was a 3:1 ratio of women to men reporting headache. Only one third of the headache sufferers had received an appropriate diagnosis from a doctor or other healthcare professional. Over half were given a diagnosis of migraine and a further 10% were diagnosed with tension headache. Other headache sufferers were diagnosed with epilepsy and vertigo. 135 (60%) of those reporting a headache had taken a medication in the past month for their headache with 15% of those reporting that they were currently taking a prophylactic or preventative treatment. Headaches were reported to be significantly impacting on ability to work and participation in social activites. The impact was similar in both the migraine and non-migraine groups.
Conclusion
This study provides an estimate of the prevalence of primary headache and migraine in Ireland. As already shown in many other Western contries, primary headache is common and there is an under-diagnosis of this often disabling condition. This under-diagnosis is also apparent amonst those who have at least on headached a month. Migraine is the most disabiling neurological condition worldwide, causing significant impact on day to day functioning, quality of life and productivity.
Disclosure of Interest
N. Murphy Conflict with: Employee of Novartis, R. MacIver Conflict with: Employee of Novartis, E. Tompkins: None Declared, M. Ruttledge: None Declared
Headache Education for Clinicians and Patients
PO-02-105
Alcohol as a trigger for migraine
Gerrit Onderwater1,*, Willebrordus van Oosterhout1, Guus Schoonman2, Michel Ferrari1 and Gisela Terwindt1
1Neurology, Leiden University Medical Center, Leiden
2Neurology, Elisabeth-TweeSteden Hospital Tilburg, Tilburg, Netherlands
Objectives
To determine the self-reported prevalence of alcohol as a migraine trigger and self-restricted alcohol use in a large, well-defined, migraine cohort.
Methods
We conducted a cross-sectional, web-based, questionnaire study among 2197 migraine patients diagnosed according to ICDH-3. We assessed alcoholic beverages consumption and self-reported triggering potential, reasons behind alcohol abstinence, and time duration between alcohol consumption and migraine attack onset.
Results
Alcoholic beverages were reported as a trigger by 35.6% of migraine patients. One quarter of patients either stopped consuming or never consumed alcoholic beverages because presumed triggering effects. Wine, especially red wine (77.8% of patients) was recognized as the greatest trigger among the alcoholic beverages. However, in only 8.8% of patients red wine consistently led to an attack. Time of onset was rapid (<3 hours) in one third of patients, independent of beverage type.
Conclusion
Alcoholic beverages, especially red wine, are recognized as a migraine trigger factor by patients and have a substantial effect on patient behavior. Time of onset of provoked migraine attacks may suggest different mechanism than for hangover-headache. Low consistency of provocation suggest that alcoholic beverages acting as singular trigger is insufficient or fluctuations in the trigger threshold might cause variations in triggering success.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-106
Association between work-related stress and headache among medical staff in Ulaanbaatar
Selenge Enkhtuya1,*, Otgonbayar Luvsannorov1, Dorjkhand Baldorj2, Byambasuren Tsenddorj3, Bayarbat Magsar1 and Tsolmon Altankhuyag1
1Neurology, Mongolian National University of Medical Sciences
2Neurology, Sukhbaatar hospital
3Neurology, State Third Central Hospital of Mongolia, Ulaanbaatar, Mongolia
Objectives
The headache is the third cause of years lost due to disability. For primary headache in the workplace one of the most commonly identified trigger is stress. The goal of this study is to determine the association between stress and headache among medical staff in the Ulaanbaatar city hospitals, Mongolia.
Methods
A cross-sectional, hospital-based survey consisting of semi-structured questionnaires was administered to 159 medical staffs from randomly selected public hospitals during the period from January to February 2017. The first part of the questionnaires included demographic data and the one-year headache profile, including headache duration, frequency, location, characteristics of accompanying symptoms, and aggravating factors. The sub-typing questionnaire of primary headache was based on International Classification of Headache Disorders-III (ICHD-III) criteria. The questionnaire of the 22-item Maslach Burnout Inventory (MBI) was used to measure emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). The Student’s t-test, one-way analysis of variance (ANOVA), and chi-square test were used for statistical analysis.
Results
Seventy-six out of 156 responders (48.7%) had experienced primary headaches in the previous year. The prevalence rates of migraine, tension type headache (TTH), chronic headache and probable medication overuse headache, were 22.4% (n = 35), 26.3% (n = 41), 12.2% (n = 19) and 7.1% (n = 11), respectively. There were no demographic differences between the sufferers and non-sufferers. Most of staff had scores which indicated they were burnt out. Nearly one fifth (20.5%) reported EE, 22.4% reported DP while almost one quarter (26.3%) experienced reduced PA. Chronic Headache sufferers had more EE and PA than non-headache sufferers (p = 0.01). The primary headaches are triggered by changes in sleeping habits, stress and flu, most of responders commonly uses non-steroidal anti-inflammatory drugs to relieve their pain.
Conclusion
The primary headache prevalence is high among medical staff in Ulaanbaatar. Burnout, which results from prolonged exposure to chronic work stress, may be associated with chronic headache, further researches in this field is needed.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-107
Willingness to pay for effective headache treatment in Estonia – preliminary results
Kati Toom1,*, Aire Raidvee2 and Mark Braschinsky1; PRILEVEL study group
1Department of Neurology, Tartu University Hospital, Tartu, Estonia
2New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Objectives
The objectives of our study were to estimate the willingness to pay for effective headache treatment in Estonian population and investigate factors influencing the outcome.
Methods
The data were derived from a population based survey conducted in Estonia form January 2016 till March 2017. The participants were asked about their age, sex, education, monthly income, occurrence, frequency and intensity of headaches. Participants were asked to play a “bidding game”, which determined how much they would pay for effective headache treatment per month. The “bidding game” results were compared in respect to the age, sex, education, income, occurrence, frequency and intensity of the headaches of the participants using Kruskal-Wallis rank sum test, medians and means of the “bidding game” sum.
Results
672 participants completed the survey (379 (56.4%) women). Of all the participants, 311 (46.3%) had had headaches during the previous year (205 (65.9%) women). The “bidding game” sum was statistically significantly different in only 2 domains of the study – the occurrence of the headaches (means 24.8 vs 36.6 for people with headaches vs without headaches, p = 0.01) and the income of the participants (means 24.4, 33.2, 44.6, 44.7 and 54.2 for the income groups of 0–499, 500–999, 1000–1499, 1500–1999 and >2000€ per month respectively, p < 0.001). There were no statistically significant differences in the “bidding game” sum in respect to the age (means 28.6, 31.9, 35.1, 30.6 and 24.1 for the age groups of 18–29, 30–39, 40–49, 50–59 and 60–65 years respectively, p = 0,48), sex (means 33.4 and 29.2 for men and women respectively, p = 0.98), education (means 10.0, 28.3, 32.3, 28.1 and 32.4 for the primary, basic, secondary, vocational and higher education groups respectively, p = 0.70) or frequency (means 32.5, 25.8 and 32.6 for the frequency of 0–1, 2–14 and >15 days with headache per month respectively, p = 0.58) or intensity of the headaches (means 38.8, 29.0 and 34.1 for mild, moderate and severe pain respectively, p = 0.18).
Conclusion
Predictably, higher income was related to higher willingness to pay for effective headache care. Surprisingly, people who had not experienced headaches during the previous year showed higher readiness to pay for effective headache care than those who had had headaches. It might be speculated, that the reason for this is that those suffering from headaches are more incapacitated precisely because of the disorder and thus have a reduced socioeconomic capacity, which prevents them from using their limited resources for headache care. This in turn means that governmental support is essential in adequate headache care system in Estonia.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-108
“What’s under the hat?” Evaluation of an online European campaign for increasing public awareness for headache disorders. Perplexities about the usefulness of a story-telling approach for revealing the headache-related burden
Paolo Rossi1, Audrey Craven2 and Elena Ruiz De La Torre3,*
1European Headache Alliance, Vice President, Rome, Italy
2European Headache Alliance, Past President, Dublin, Ireland
3European Headache Alliance, President, Valencia, Spain
Objectives
“What’s under the hat?” is a headache awareness campaign conceived and launched in 2015 by the European Headache Alliance, an umbrella organisation of patient organisations. The aims of the campaign were a) to increase awareness of and compassion for the real and everyday impact of headache disorders amongst the general public; b) to help those affected by headache disorders to know that they are not alone and that headache disorders are treatable. The campaign asked those living with a headache disorder such as migraine or cluster headache, to share their story online in video or photo and text format, with the person wearing a hat. Stories were shared mainly on Facebook and Twitter with the tag #underthehat. In this study we evaluated if the patients’ participation and stories posted in a video or text format on the online campaign platforms reached the campaign objectives.
Methods
The participation to the campaign was evaluated by using social-media metrics. In addition we conducted a qualitative analysis of patient stories posted during the first 8 months of the campaign and asked a selected team to rate the stories based on their appropriateness, appeal and clarity.
Cristiana (Italy) “due to my hedaches I just can see the life running far from me…I’m not able to make any project for the future”
Elisabeth (Ireland) “when I was young I missed an enormous amount of school and felt isolated, guilty and frustrated. Being unable to imagine how I would function normally as an adult was terrifying.”
Lucia (Spain): “headache is like a demon that prevented me to study, to work, to have a family, to have a normal life…”
Nicki (Italy)): “I don’t tell anymore to my friends and colleagues that I got a headache…. They don’t understand …”
Michelle (Uk): “no treatment has been effective for me…I’m so angry…I would like to change this condition but I can’t do anything helpful”
Results
The facebook page reached less than 200 users, less than 400 interactions and 710
likes. In twitter 747 tweets were obtained with the #underthehat. The only active
organizations were from Italy, Spain, UK, Ireland and Finland Only 30 stories (15
videos), mainly posted by women (92%), were received analyzed. Most patients give an
account of the dramatic impact of headache on their working and private life.
Headache is often personified as an invisible persecutor that may be accepted but
not integrated in the self
Conclusion
Headache patients have shown to be reluctant to share their sufferings in a social media context. The personal stories posted online reached the campaign aims and represent a potential powerful source of information for educating the general public about the burden and impact of headache disorders. However, a concern emerged that the hopelessness evident in the stories may wrongly suggest that headache disorders whilst common and disabling cannot be managed or treated
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-109
Development of a novel, weighted and quantifiable scale for measuring QOL among patients with chronic migraine
Yasuo Terayama1,*, Masako Kudo1, Naoki Ishizuka1, Ayumi Saitoh1 and Satoko Obara1
1Neurology and Gerontology, Iwate Medical University, Morioka, Japan
Objectives
Lack of knowledge about chronic migraine headache may cause significant misunderstandings between patients and their healthcare providers. For patients with chronic migraine, a positive quality of life (QOL) may be continually threatened and disturbed. Attempts have been made to measure the effectiveness of headache therapy in number of ways. However, none of them are universally accepted or have been adopted as the gold-standard of QOL-oriented quantitative measures of severity of chronic migraine.
The purpose of the present study is to establish a novel, readily usable, quantifiable and reliable QOL-oriented scale for measuring the severity of chronic migraine headache.
Methods
Six variables including daily physical functioning, daily community activities, enjoyment of life, somatic symptoms which are found to predict QOL are selected from the review of scales currently available and from the opinion of 30 migraine experts (25 neurologists and 5 neurosurgeon).
After categorization of selected variables, evaluation of the distribution and sensitivity of variables utilizing 22 active patients (aged 27–52; 38.8 ± 12.3 years old, M:F = 10:12) who had frequent chronic migraine headache according to the criteria of the International Classification of Headache Disorders 3rd edition (Beta version).
After modification of the scale with modified variables, testing of inter- and intra-rater reliability by 8 pairs of doctors using 10 new stroke patients (aged 29–49; 37.2 ± 11.1 years old, M:F = 3:7).
Ranking of a set of 16 virtual patients with a different combination of variables according to severity by 27 presently symptomatic patients with chronic migraine (aged 27–58; 39.2 ± 12.4 years old, M:F = 10:17) and 30 headache specialists was performed.
From these rankings, conjoint analysis derived averaged importance and weights of each of the items of the scale.
Results
As a result of conjoint analysis, the relative importance against the QOL of migraineurs was calculated. For patients with chronic migraine, daily physical functioning (33.4%) was clearly the most important factor for determining the QOL of migraineurs. Somatic symptoms (20.6%), work-place efficacy (19.2%), corporeal pain (9.5%), enjoyment of life (9.3%), daily community activities (8.0%) are the next important factors for determining the QOL.
On the other hand, for migraine specialists, daily physical functioning (29.1%) was the most important factor for determining the QOL of migraineurs. Somatic symptoms (23.5%), corporeal pain (14.5%), work-place efficacy (12.7%), enjoyment of life (10.6%), daily community activities (9.6%) are the next important factors for determining the QOL of migraineurs.
Total score of the scale ranges from 12.8 (the best QOL) to 20.0 (the worst QOL).
Conclusion
The present study revealed:
1) The difference of relative importance against the QOL of migraineurs between doctors and patients.
2) The relative importance and weights of variables may be different among the countries and may change chronologically even in the same country.
3) The understanding of the difference between doctors and patients may lead to the better relationships for treatment with chronic migraine headache.
4) It also help the mutual understanding of medical practice and research in headache between nations.
The present study revealed the possibility of our scoring system to be universally accepted and reliable standardized system with higher consistency, reliable validity and superior quantitativeness from the Clinimetrical point of view.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-110
Medication use and overuse patterns in a cohort of US and UK migraine patients using a digital platform
Pablo Prieto1,*, Gabriel Boucher1, Stephen Donoghue1, Peter J Goadsby2 and Stephen D Silberstein3
1Curelator Inc., Cambridge, United States
2NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, United Kingdom
3Jefferson Headache Center, Thomas Jefferson University, Philadelphia, United States
Objectives
Overuse of acute medications may worsen migraine and lead to medication overuse headache (MOH) (1). Few population studies have studied the risk of MOH across migraine treatment classes, and drugs involved in MOH vary from region to region (2). Here we describe medication use and identification of overuse (MO) in users of a digital platform for migraine (Curelator Headache™). The objective is to compare medication use and possible overuse patterns in individuals’ with migraine from the US and the UK.
Methods
Individuals with migraine registered to use the platform (Curelator Headache™) via website or the App store (iOS only) and used it daily for at least 90 days, entering details about headaches and medications used acutely and chronically. Acute medication use was analyzed at the level of individual drug names and MO was defined according to ICHD-3 beta criteria; other reported drugs were not included in the analysis.
Results
Individuals from the USA (n = 261) and the UK (n = 216) entered 20,353 (USA) and 17,965 (UK) headache instances. Only 6 (2.3%) US and 4 (1.8%) UK users did not use any acute medication for their headaches. Triptans (29.8% US, 35.4% UK) and NSAIDs (27.8% US, 29% UK) were the most frequently used classes of medication: opioid use was significantly different in the US and UK (5.9% US, 0.8% UK, p < 0.0001). The top two medications used were sumatriptan and ibuprofen in both cohorts. Overall, potential overuse of acute medication was identified in 79 (30.3%) and 45 (20.8%) US and UK patients respectively. In individuals with headache on ≥15 days/month, MO was identified in 60% and 51% in the US and UK, respectively. In the US, individuals with MO used significantly more classes and individual medications than non-MO users (p < 0.0001). MO was more common with NSAIDs (41.2%) and analgesic combinations (29.4%) in the US, while in the UK NSAIDs (52.8%) and triptans (42.7%) were most frequently overused. In the US, top medications overused were ibuprofen (19.3%), oxycodone (16.6%), sumatriptan (15.2%) and tramadol (11.9%), while in the UK these were ibuprofen (33.1%), paracetamol/codeine (21.4%), naproxen (13.8%) and zolmitriptan (12.1%).
Conclusion
Using a digital platform (Curelator Headache™) MO was identified in 114 migraine subjects and could be used to alert patients and their clinicians, which is clinically useful (1). US and UK medication use and overuse patterns are different but within literature-reported rates. An electronic diary system may complement previous studies investigating the role of MO in developing chronic migraine or MOH.
Disclosure of Interest
P. Prieto Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., G. Boucher Conflict with: Curelator Inc., Conflict with: Curelator Inc., S. Donoghue Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., P. Goadsby Conflict with: Allergan, Amgen, Eli Lilly and Company, Conflict with: Akita Biomedical, Alder Biopharmaceuticals, Allergan, Amgen, Autonomic Technologies, Avanir Pharmaceuticals, Cipla Ltd, CoLucid Pharmaceuticals, Inc., Dr. Reddy's Laboratories, electroCore LLC, Eli Lilly and Company, eNeura, Journal Watch, Medico-Legal Journal, Novartis, Oxford University Press, Pfizer Inc., Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina, Inc., Up-to-Date, S. Silberstein Conflict with: Alder Biopharmaceuticals; Allergan; Amgen Inc.; Avanir Pharmaceuticals, Inc.; Curelator, Inc.; Depomed; Dr. Reddy's Laboratories; ElectroCore Medical, LLC; eNeura Inc.; INSYS Therapeutics; Pfizer, Inc.; Lilly USA, LLC; Supernus Pharmaceuticals, Inc.; Teva Pharmaceuticals; Theranica; Trigemina, Inc.; Labrys Biologics; Medscape, LLC; Medtronic, Inc.; Neuralieve; NINDS
References
(1) Tassorelli C, et al. Cephalalgia. 2016 Jul 20
(2) Thorlund K, et al. J Headache Pain. 2016 Dec;17(1):107.
Headache Education for Clinicians and Patients
PO-02-111
Epidemiology differences between migraineurs followed by the (Curelator HeadacheTM) who completed 3 months daily electronic follow up vs. drop-outs
Julio R Vieira1,*, Gabriel Boucher2 and Pablo Prieto2
1Neurology, Albert Einstein College of Medicine/Health Quest Neurology, Kingston
2Curelator Inc, Cambridge, United States
Objectives
Migraine is a very common condition with high prevalence throughout the world. An important issue of medical research is to obtain reliable data and adequate follow up. Data collection for headache research has been historically obtained by questionnaires utilizing retrospective data, which are not very reliable, given that data is not collected on real time and is prone to recall bias. Paper headache diaries, used clinically by physicians are also not completed daily and patients are prone to the same caveat when trying to report headache frequency and other factors during their office visit. Some attempts were made to develop and utilize electronic methods for recording data in a prospective way like the platform used here (Curelator Headache™), which requires users to enter data daily, irrespective of the presence of symptoms. Current technology utilizes smart phone as a personal data entry device and can function as a powerful tool to track headaches, however many patients end up losing interest and after a short period of time drop the use of these headache diaries. A platform that demands daily tracking of both risk factors and symptoms from users was used in this cohort, and sought to determine if there were differences between a group of individuals who completed a headache tracking period daily for at least 90 days and continued being tracked, and their counterparts who dropped out within 90 days.
Methods
The digital platform offered to headache patients in the present study (Curelator Headache™) was used to record profile demographic data, as well as real time daily collection of headache data including frequency, possible triggers, treatment and disability score (MIDAS) among other variables. Patients were followed daily for at least 90 days and those completing data collection at that time were defined “completers”, those who did not complete the 90 days data collection and stopped entering date were “non-completers”. Non-completers were further stratified in try-outs (≤3 tracked days), early drop-outs (>3 and ≤30 tracked days) and late drop-outs (>30 and <90 tracked days). Demographics and headache data between groups were compared statistically utilizing t-test and Mann-Whitney tests for continuous variables and chi-square for categorical variables.
Results
2678 individuals with migraine were registered with the platform, 88% were women. At 90 days, only 493 (18.4%) individuals reliably completed data entry, compared to 2185 drop-outs (1535 try outs, 702 early drop-outs and 304 late drop-outs). An additional 356 patients also enrolled and are ongoing data collection, but did not yet reach 90 days. Completers were older, less likely to be employed (36.9% vs 52.3%), had slight less severe pain, although they visited the ED less frequently (10% vs 16%), utilized less caffeine and smoked less cigarettes when compared to all non-completers (drop-outs). When comparing completers to late drop-outs, completers were older and less likely to be employed, but there was no difference in pain level, caffeine consumption, smoking and ED visits.
Conclusion
Disclosure of Interest
J. Vieira: None Declared, G. Boucher Conflict with: Curelator Inc, P. Prieto Conflict with: Curelator Inc
Headache Education for Clinicians and Patients
PO-02-112
Tyramine as a risk factor for migraine attacks: an exploration
Stephen Donoghue1,*, Gabriel Boucher1, Francesc Peris1, Alec Mian1 and Anne MacGregor2
1Curelator Inc., Cambridge, United States
2Barts and the London SMD, London, United Kingdom
Objectives
Since the initial study by Hanington in 1967 (1) which suggested an association between foods containing tyramine and migraine attacks, questions have been raised about the prevalence of this sensitivity in the migraine population (2). Adding to lack of clarity is that the tyramine content of food varies greatly depending on freshness and processing, not all foods containing tyramine are considered common migraine triggers and some foods have been incorrectly identified as containing tyramine (3). Hence despite much suspicion there is no agreement about whether tyramine is a migraine trigger. To explore this question we used a digital platform (Curelator HeadacheTM) to statistically compare daily intake of tyramine containing foods and occurrence of migraine attacks.
The objective of this study is to determine in individuals with migraine 1) how many suspect tyramine as a migraine trigger and 2) for how many an association of tyramine intake with attacks can be identified statistically.
Methods
Individuals with migraine registered to use Curelator Headache via website or the App Store (iOS only) and answered questions about personal suspected triggers, including tyramine, and their importance (1 = low; 10 = maximal). They then used Curelator Headache daily for 90 days, entering details about headaches and tracking factors that may affect migraine attack occurrence. After 90 days all factors were analyzed (univariate analysis - see Ref 4) and for each individual the association of tyramine intake with attacks was determined.
Results
Of 528 individuals with migraine, tyramine was suspected as a trigger by 240 (45.5%): it was mildly suspected (1–3) by 20.6%; moderately (4–6) by 18.2%; strongly (7–10) by 6.6%. Of those who suspected tyramine, 129 entered sufficient data and tyramine was shown to be associated with increased attack risk in 20 (15.5%), with decreased risk in 20 (15.5%) and no association was identified in 89 (69%). In the other 111 there was insufficient data for analysis, indicating either avoidance of tyramine or lack of reporting. There was no clear association between degree of suspicion of tyramine and the percentage of individuals in whom an association was identified.
Of 288 individuals who did NOT suspect tyramine as a trigger, 139 entered sufficient data for analysis and we found an association of increased risk in 14 (10.1%) and decreased risk in 13 (9.4%). In 149 there was not enough data for analysis - again indicating either avoidance of tyramine or lack of reporting.
Conclusion
Tyramine is widely suspected as a trigger but in only a small number of individuals was an association with attacks identified statistically. However intake of tyramine containing foods was reported infrequently by almost half of individuals making analysis for them impossible: this is possibly due to avoidance of such foods.
Disclosure of Interest
S. Donoghue Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., G. Boucher Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., F. Peris Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., A. Mian Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., Conflict with: Curelator, Inc., A. MacGregor: None Declared
References
(1) Hanington E. Br Med J. 1967;2:550–551
(2) Kohlenberg RJ. Headache 22:30–34, 1982
(3) McCabe-Sellers et al J Food Comp Analysis 2006;19:S58-S65
(4) Peris F et al. Cephalagia 2016; DOI: 10.1177/0333102416649761
Headache Education for Clinicians and Patients
PO-02-113
Characteristics of Migraine According to the Age: A Clinic-based Study in Korea
Hanna Choi1,*, Mi Ji Lee2 and Chin-Sang Chung2
1Department of Neurology, Eulji University Hospital, Daejeon
2Department of Neurology, Samsung Medical Center, Seoul, Korea, Republic Of
Objectives
Past studies suggested that the profile of migraine changes over the life span, and migraine remits in majority. We aimed to investigate if the core characteristics of migraine differ according to the age at onset.
Methods
Using the consecutive headache registry, we identified patients who were diagnosed with migraine in Samsung Medical Center headache clinic from October 2015 to April 2016. Patients were grouped into three categories; group A, patients younger than 50 years; group B, patients 50 years old or older with headache began before 50 years; and group C, patients with new-headache after 50. Components of diagnostic criteria for migraine were assessed using International Classification of Headache Disorders, 3rd edition (ICHD-III), beta version and compared between the groups.
Results
Three-hundred twenty patients were included in this study (190 for group A, 77 for group B, and 53 for group C). There were no significant differences in unilaterality, pulsatility, nausea and/or vomiting, and photophobia and phonophobia, and aura in three groups. Duration of attack and aggravation by routine physical activity were less typical in group C (85.3%, 81.8%, and 58.5% for group A, B, and C; 66.0%, 60.8% and 35.3%, for group A, B, and C; both p < 0.001). Intensity of headache were less severe in group B and C, compared with group A (85.9%, 70.0%, and 51.9%, for group A, B, and C, p < 0.001). The proportions of chronic migraine and medication overuse headache were not different among the groups.
Conclusion
In this cross-sectional study using a large number of migraine subjects, clinical features of unilaterality, pulsatility, nausea and/or vomiting, photophobia and phonophobia, and aura did not differ across the age or age of onset, serving as core features of migraine. Duration of attack and peripheral sensitization were less typical in late-onset migraine, while headache intensities decreased in older patients regardless of age of onset. These features may be helpful to easily identify migraine in patients older than 50 years presenting with new-onset headache.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-114
Study of Headache after the Great East Japan Earthquake in Iwate coast area. (2) The change of migraine-related factor (2012 ∼ 2015)
Masako Kudo1,*, Yasuhiro Ishibashi1, Hisashi Yonezawa1, Haruki Shimoda2, Kiyomi Sakata2, Seiichiro Kobayashi3, Akira Ogawa3 and Yasuo Terayama1
1Department of Neurology and Gerontology, Iwate Medical University
2Department of Hygiene and Preventive Medicine, Iwate Medigal University
3Iwate Medical University, Morioka, Japan
Objectives
To investigate related factors with migraine in the people lived in disaster area after the Great East Japan Earthquake.
Methods
We conducted medical inquiries concerning headaches every year from 2012 to 2015 headache-related factors among municipalities with the greatest earthquake-related damage in Iwate Prefecture including Yamada Town, Rikuzentakata City and Heita District of Kamaishi City. We got replies from 5915 individuals in 2012, 5588 in 2013, 5286 in 2014, 5318 in 2015. We investigated prevalence of migraine and compared about age, gender, mental factors (stress, nervousness, sleep disorder, and K6 score), habit of alcohol and smoking, daily physical exercise, post-traumatic stress disorder (PTSD)–related factors caused by the earthquake and social network factors (having friends, thinking of helping and trust neighbors each other) between the group with and without migraine.
Results
The prevalence of subjects who had migraine declined gradually from 2012 to 2015 (p < 0.05). Migraineurs were younger (p < 0.001) and more frequent in women (p < 0.001). Migraine was related with stress (p < 0.001), nervousness (p < 0.001), high score of K6 (p < 0.001) and PTSD by he earthquake (physical symptoms) (p < 0.05) in every year, and were related with nocturnal awakening (p < 0.05) in 2012, 2013, 2014 (p < 0.05). Migraine wasn’t related with habit of smoking and exercise, but was related with drink habit in every year (p < 0.05). Proportion of subjects who trust neighbors were few in migraineurs in every year. Proportion of subjects who can help each other and have friends (p < 0.001) were few in migraineurs in 2013, 2014 (p < 0.001).
Conclusion
The present study revealed that prevalence of migraine in subjects suffered by the Great East Japan Earthquake declined gradually from 2012 to 2015. Migraine was related with mental factors, PTSD and social network.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-115
Algorithms to improve identification of Idiopathic Intracranial Hypertension patients in the Swedish National Patient Registry
Anna Sundholm1,*, Sarah Burkill2, Shahram Bahmanyar2 and Ingela Nilsson Remahl3
1Department of Clinical Neuroscience, Department of Neurology, Karolinska Institutet, Karolinska University Hospital
2Centre for Pharmacoepidemiology, Department of Medicin, Solna, Karolinska Institutet
3Department of Clinical Neuroscience, Department of Neurology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
Objectives
Idiopathic intracranial hypertension (IIH) is a rare disorder mainly affecting young, obese females. By definition, the cause behind development of high intracranial pressure is unknown for IIH patients. Large scale studies are hard to conduct due to the rarity of IIH and because IIH is known to often be misdiagnosed, which has made assessment of risk factors difficult. The purpose of this study was to produce algorithms to better predict true IIH patients among those given an IIH diagnosis in the Swedish National Patient Register (NPR) to improve the validity of the IIH diagnosis in future register-based studies.
Methods
Individuals with a recorded IIH diagnosis between 2006 and 2013 in Stockholm County were identified using the NPR (ICD-10 code G93.2). Validation was done through medical record reviews, using the original modified Dandy Criteria. We randomized the patients into two groups, one group to produce the algorithm (algorithm group, n = 105) and one group for validation (test group, n = 102). We tested variables which it was possible to extract from registries (NPR and Prescription Register) and used forward stepwise logistic regression. The outcome was whether the diagnosis was correct or not. The model then provided a predicted probability of the diagnosis being correct for each patient.
Results
207 patients were identified of which 135 had confirmed IIH. This gave a positive predictive value (PPV) of 65.2% (95% CI: 58.4–71.4). The variables most useful for correctly identifying patients were; age, having received the diagnosis code twice or more and treatment with acetazolamide. The algorithm which included information from NPR and Prescription Register could predict the diagnosis correctly 88.2% (95% CI: 80.3–93.3) of the time when testing on the test group. When we reapplied the algorithm on the group used to make the predicted probabilities the percent correctly identified was slightly lower. Using only NPR data the probability of correct prediction was again slightly lower (see Table 1).
Conclusion
Algorithm predicting correct or incorrect if patients have IIH disorder or have been given a wrong diagnosis code
Disclosure of Interest
A. Sundholm: None Declared, S. Burkill: None Declared, S. Bahmanyar: None Declared, I. Nilsson Remahl Conflict with: Lectures and Advisory board for Allergan, Linde Healthcare
Headache Education for Clinicians and Patients
PO-02-116
Perception of the effect of exercise in patients with migraine at a Headache Clinic in Argentina
Fiorella Martin Bertuzzi1,* and Eduardo D Doctorovich1
1Neurology Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Objectives
Effect of physical activity on headache migraine
Improving of frequency, duration or intensity of migraine headaches with regular exercise
We aim to describe patients’ perception of the effect of physical activity (PA) in their pain. Secondarily, we tried to find a relationship between type of migraine, age or sex in the effect of exercise in migraine.
Methods
This study was conducted at a specialist Headache Center in Buenos Aires, Argentina, between August 2016 and January 2016. The participants were asked to complete a 3 questions self-administered survey. Patients were asked how PA impacts in a mild-moderate or severe migraine headache (PA was defined as “climb up a floor of stairs” or “walking fast 200 meters”) and wherever if they noted if regular exercise improves frequency, intensity or duration of migraine headaches.
Additionally, age and sex were requested and patients where classified in three categories, migraine without aura (MWOA), migraine with aura (MWA) and chronic migraine (CM), for a trained neurologist, according the International Classification of Headache Disorders version 3 beta.
Results
Overall, we evaluated 115 participants: 85 with MWOA (73,9%), 10 MWA (8,7%) and 20 CM (17,4%). Mean age was 40,1 years (range 17–70 years) and 87,8% were females. Patients answers are resumed in tables 1 and 2. In the analysis by groups, there was no correlation between effect of PA and type of migraine, sex or age.
Conclusion
Diagnostic criteria of migraine includes an item of “aggravation by or causing avoidance of routine physical activity”, but in clinical practices is not uncommon find patients without this classic characteristic. We find 55% of patients that report that mild to moderate headaches did not get worse, and even 16% getting better with PA. In our analysis, there were no differences in the effects of PA adjusted by type of migraine, age or sex. It is uncertain if the PA has a real effect on migraine treatment. In our experience over half of patients perceive that regular physical activity ameliorate their migraines.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-117
Dopaminergic symptoms in migraine: a case series on 446 consecutive patients
Piero Barbanti1,*, Cinzia Aurilia1, Aliaksei Kisialiou2, Gabriella Egeo1, Luisa Fofi1 and Stefano Bonassi2
1Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences
2Clinical and Molecular Epidemiology Unit, IRCCS San Raffaele Pisana, Rome, Italy
Objectives
Dopamine (DA) is considered to play a major role in migraine pathogenesis as suggested by clinical, genetic, biochemical and pharmacological evidence. The present study was designed to assess frequency and characteristics of DAergic pre-synaptic (yawning, somnolence, neck discomfort/stiffness) and post-synaptic (intense nausea, vomiting) symptoms in migraineurs during the different attack phases (prodromes, headache stage, postdromes), and to investigate whether migraineurs with DAergic symptoms represent a distinct migraine clinical phenotype.
Methods
We studied all patients affected by episodic and chronic migraine consecutively seen at our Headache and Pain Unit from 1 June to 31 December 2016. Following a careful physical and neurological examination, all patients were evaluated with face-to face interviews using a semi-structured questionnaire addressing three main issues: 1) life-style, behavioral and socio-demographic factors, including age, sex, civil status, occupation, body mass index, blood pressure, sport activity, use of coffee, alcohol, smoking, illicit drugs, sleep disturbances, menopause, contraceptive use; 2) comorbidities and concomitant medications; and 3) clinical migraine features encompassing family history, disease duration, site, quality and intensity of pain, attack duration and frequency, presence, type and duration of aura, prodromes, accompanying symptoms, postdromes, DAergic symptoms, allodynia, unilateral cranial parasympathetic symptoms, triggers and alleviating factors, previous and current acute or preventive treatments, patients’ satisfaction with triptans,. The presence of DAergic symptoms was determined by asking the following question: “During prodromes, headache stage or postdromes do you also have at least one of the following symptoms: yawning, somnolence, neck discomfort/stiffness, severe nausea or vomiting?”.
Results
We investigated 446 migraine patients (F/M: 348/98; migraine without aura: 269 pts; migraine with aura: 35 pts; chronic migraine: 142 pts; medication overuse headache, MOH: 114 pts). One-hundred-sixty-three of the them (DA+, 36.5%) reported the DAergic symptom during migraine attacks: 44 DA+ patients (27%) reported 1 symptom, 21 (12.9%) 2 symptoms and 98 (60.1%) ≥3 symptoms. Seventy out of 163 DA+ patients (42.9%) had both pre- and post-synaptic DAergic symptoms during the attack: the most frequent was yawning (94 pts, 57.7%) followed by somnolence (79 pts, 48.4%), severe nausea (71 pts, 43.6%), neck discomfort/stiffness (58 pts, 35.6%) and vomiting (40 pts, 24.5%). DAergic symptoms occurred during prodromes in 14.7% patients, headache stage in 74.3% and postdromes in 11%. DA+ patients had longer attack duration (p = 0.0052), more severe pain intensity (p = 0.0335) and more frequent osmophobia (p < 0.0001) than general migraine population, showing a positive trend for allodynia (p = 0.0576) and comorbidities (p = 0.0639). Migraineurs with and without DAergic symptoms did not differ for other migraine clinical variables.
Conclusion
This study, the first specifically aimed at identifying DAergic symptoms in migraine, reveals that more than 1/3 or migraineurs afferents to a headache center has DAergic symptoms (usually ≥3) during the different migraine attack phases. DAergic symptoms are usually presynaptic (yawing and somnolence being the most frequent) and occur mainly during the headache stage. Migraine attacks are longer, more severe and more frequently associate with osmophobia in DA+ patients than general migraine population.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-118
Quality indicators in headache care: an implementation study in six Italian specialist-care centres
Lanfranco Pellesi1,*, Silvia Benemei2, Valentina Favoni3, Chiara Lupi2, Edoardo Mampreso4, Andrea Negro5, Matteo Paolucci6, Timothy J Steiner7,8, Martina Ulivi6, Sabina Cevoli3 and Simona Guerzoni1; Young Italian Headache Network
1Università di Modena e Reggio Emilia, Modena
2Università degli Studi di Firenze, Firenze
3Università degli Studi di Bologna, Bologna
4Università degli Studi di Padova, Padova
5Università Sapienza
6Università Campus Biomedico, Roma, Italy
7Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway
8Division of Brain Sciences, Imperial College, London, United Kingdom
Objectives
Headache disorders are highly prevalent, and have a substantial and negative impact on health worldwide. They are largely treatable, but differences in structure, objectives, organization and delivery affect the quality of headache care. In order to recognize and remedy deficiencies in care, the Global Campaign against Headache, in collaboration with the European Headache Federation, recently developed a set of quality indicators for headache services. These require further assessment to demonstrate fitness for purpose. This is their first implementation to evaluate quality in headache care as a multicentre national study.
Methods
Between September and December 2016, we applied the quality indicators in six Italian specialist headache centres (Bologna, Firenze, Modena, Padova, Roma Campus Bio-Medico and Roma Sapienza). We used five previously developed assessment instruments, translated into Italian according to Lifting The Burden's translation protocol for hybrid documents. We took data by questionnaire and from the medical records of 360 consecutive patients (60 per centre), and by questionnaire from their health-care providers (HCPs), including physicians, nurses and psychologists.
Results
The findings, comparable between centres, confirmed the feasibility and practicability of using the quality indicators in Italian specialist headache centres. The questionnaires were easily understood by HCPs and patients, and were not unduly time-consuming. Diagnoses were almost all (>97%) according to ICHD criteria, and routinely (100%) reviewed during follow-up. Diagnostic diaries were regularly used by 96% of physicians. Referral pathways from primary to specialist care existed in five of the six clinics, as did urgent referral pathways. Instruments to assess disability and quality of life were not used regularly, a deficiency that needs to be addressed.
Conclusion
This Italy-wide survey confirmed in six specialist centres that the headache service quality indicators are fit for purpose. By establishing majority practice, identifying commonalities and detecting deficits as a guide to quality improvement, the quality indicators may be used to set benchmarks for quality assessment. The next step is extend use and evaluation of the indicators into non-specialist care.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-119
Visual Sensitivity and Cutaneous Allodynia in Migraine
Joris M Meijer1,*, Matthijs J. L Perenboom1, Johannes A Carpay2, Gisela M Terwindt1 and Michel D Ferrari1
1Leiden University Medical Center, Leiden
2Tergooi Ziekenhuis, Hilversum, Netherlands
Objectives
Migraine patients report visual sensitivity and cutaneous allodynia, during and in-between attacks. Allodynia is believed to be caused by central sensitisation, the process assumed to underlie the transformation from episodic to chronic migraine and likely causing enhanced cortical excitability. Increased visual sensitivity is thought to be caused by cortical hyperexcitability and may thus also result from central sensitization. We expected these phenomena of altered sensory processing to be correlated in migraine patients. Furthermore, we hypothesised a correlation between the number of migraine headache days and visual sensitivity and cutaneous allodynia.
Methods
Patients with episodic (N = 19) or chronic (N = 18) migraine who were screened for a clinical trial with prophylactic migraine treatment recorded the number of migraine headache days over 4 weeks using a headache diary. Ictal and interictal visual sensitivity and ictal cutaneous allodynia during the same timespan were recorded using the Leiden Visual Sensitivity Scale (L-VISS; range 0–36 points) and a questionnaire on allodynia (range 0–12 points), respectively. Spearman’s correlation coefficients between these parameters were calculated.
Results
Mean number of migraine headache days was 9.8 days (SD 4.3), the median ictal and interictal L-VISS scores were 18.0 (interquartile range 9.5) and 7.0 (interquartile range 9.5), respectively, and the median allodynia score was 3.0 (interquartile range 5.0). The number of migraine headache days correlated with ictal (R = 0.566, p < 0.001) and interictal (R = 0.397, p = 0.015) L-VISS score, but did not correlate with allodynia (R = 0.138, p = 0.415). Allodynia did however show a correlation with ictal (R = 0.514, p = 0.001) and interictal (R = 0.531, p = 0.001) L-VISS score.
Conclusion
We found an association between visual sensitivity and cutaneous allodynia in episodic and chronic migraine patients. In our cohort, ictal and interictal visual sensitivity but not ictal cutaneous allodynia were correlated with the number of migraine headache days. There appears to be a complex interaction between central sensitization, sensory processing and number of migraine headache days.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-120
Establishment of an italian chronic migraine database: a multicenter pilot study
Piero Barbanti1,*, Luisa Fofi1, Sabina Cevoli2, Paola Torelli3, Cinzia Aurilia1, Gabriella Egeo1, Licia Grazzi4, Domenico D'Amico4, Gian Camillo Manzoni3, Pietro Cortelli2, Francesco Infarinato5 and Nicola Vanacore6
1Headache and Pain Unit, IRCCS San Raffaele Pisana, Rome
2Headache Center, IRCCS Istituto delle Scienze Neurologiche, Bologna
3Headache Center, University of Parma, Parma
4Headache Center, Istituto Neurologico C.Besta, Milan
5Rehabilitation Bioengineering Laboratory, IRCCS San Raffaele Pisana
6National Institute of Health, Rome, Italy
Objectives
To optimize chronic migraine (CM) ascertainment, provide specific clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study coordinated by the Italian National Institute of Health, aimed to establish an Italian CM database, the first step for a future Italian CM registry.
Methods
We enrolled all consecutive patients affected by CM referred to 4 Italian headache centers. Using face-to-face interviews, detailed information were gathered on life-style, behavioral and socio-demographic factors, comorbidities and concomitant medications, migraine features before and after chronicization and healthcare resource use.
Results
We enrolled 63 patients affected by CM (F/M = 51/12;47.4 ± 14.6 yrs). Previous episodic migraine started at the age of 15.2 ± 6.6 yrs, had a frequency of 5.6 ± 5.4 days/month, and evolved into CM at the age of 36.6 ± 14.1 yrs. Chronicization factors included affective disorders (19%), stressful events (9.5%), menopause (4.8%), cancer (3.2%) and others (3.2%). Most frequent comorbidities were insomnia (30.2%), depression (22.2%), anxiety (17.5%), endocrine disorders (17.5%), hypertension (12.7%), dyslipidemia (11.1%) and previous head/cervical trauma (9.5%). Mean CM attack frequency was 23.6 ± 5.4 days/month. Migraine episodes were severe (60.3%), very disabling (92%), associated with photo- and phonophobia (84.1%), osmophobia (54%), allodynia (50.7%), nausea (73%) and vomiting (31.7%). CM patients used triptans (73%), NSAIDs (50.8%) and analgesic combinations (30.2%) as acute treatment. Most patients (58.5%) overused analgesics: triptans (33.2%), NSAIDs (11.1%), analgesic combinations (6.3 %), NSAIDs +triptans (4.7%), triptans + analgesic combinations (3.1%). Patients with CM had used on average 2 prophylaxis among anticonvulsants (66.7%), amitriptyline (50.8%), botulinum toxin (41.3%), beta-blockers (39.7%), calcium-antagonists (36.5%), acupuncture (20.6%), antiserotonin drugs (12.7%) and nutraceuticals (6.3%). Migraine treatments had been prescribed by GP in 50.8% of cases, headache specialists in 47.6% and other specialists in 19%. Self-medication had occurred in 41.2% of patients. Diagnostic procedures had been requested by headache specialists in 52.4% of cases, GPs in 49.2%, other specialists in 28.6%, or had been performed by patients themselves (19.04%): 57.1% had undergone brain MRI, 38% brain CT-scan, 26.9% EEG, 19% cervical MRI, 7.9% cervical spine or temporomandibular joint x-rays. 27% of patients had been hospitalized for CM, 9.5% admitted to DH, and 36.5% to ED. 11% of patients got illness benefit exemption or disability allowance.Univariate analysis revealed that patients affected by more severe CM (≥21 headache days/month) had more frequently MO (p = 0.01) and MO positive family history (p = 0.01), insomnia (p = 0.05), ipsilateral lacrimation during the attacks (p = 0.03) and had used more frequently topiramate (p = 0.05), valproate (p = 0.01) and antiserotonin drugs (p = 0.05) than those with mild CM (15–20 headache days/month). When considering monthly migraine days as independent variable, regression analysis showed that patients with severe CM had higher alcohol intake (p = 0.033), more frequent insomnia (p = 0.017) and analgesic overuse (p = 0.018) than those with mild CM.
Conclusion
This multicenter pilot Italian study on CM identifies areas with inadequate health care provision, indicates the need for rationalizing healthcare strategies and resource use and prompts for the establishment of an Italian CM registry.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-121
Follow-up study of 12–18 years on subtypes of headache in a population of children below 6 years old: preliminary results
Francesca Marchese1,*, Edvige Correnti1, Davide Trapolino1, Filippo Brighina2, Vincenzo Raieli3 and Francesca Vanadia3
1Child Neuropsychiatry School
2 Department of Clinical Neurosciences, University of Palermo
3Child NeuroPsychiatry Unit, PO “G Di Cristina” ARNAS Civico, Palermo, Italy
Objectives
Headache is a common problem in childhood; up to 25% of school children suffer from chronic recurrent headache but the diagnosis of early onset headache disorders can be delayed due to the non specific nature of symptoms. Studies about primary prescholar headaches are rare, As well as, in this paediatric population, there are only few follow-up studies. Aim of this study is to analyze the follow-up of a pediatric cephalalgic population below 6 years old, previously studied in depth.
Methods
We contacted a population of children admitted in our headache center, between 1997 and 2003, when they were below 6 years old. We evaluated the evolution over time of headache’s subtypes and using a 12–18 years-long follow-up study. we tried to identify a possible predictor throughout the duration of follow-up. We administered a semi-structured questionnaire by phone interview from November 2015. Children with secondary headaches have been excluded
Results
We found 96 children’s medical records. To date, only 22/96 (22,9%) patients responded to the semistructured interview. The actual mean age is 17 years old (range 22–14 years old). There were 12 males (54,54%) and 10 females (45,45%). We found 14 cases with of migraine, 2 patients with primary stabbing headache and 6 cases with more than one headache’s subtype. As preliminary result, we found that 4 of 22 (18,1%) patients without headache and 13 patients of 14 (92,8%) that still have migraine. 10/14 (71,4%) of migraineurs exhibited cranial autonomic symptoms
Conclusion
Description of the evolution of headache from childhood to adulthood has been a focus of interest for several authors; there is still a paucity of literature data on the evolution and prognosis of headache starting in childhood. From the preliminary result obtained in our study we found that of 14 patients with migraine interviewed, 92% today still suffers from migraines and 71% of these complains autonomic symptoms. This finding shows that prescholar migraineurs after a follow-up of several years, still complain migrainous attacks and they present a significant cranial parasympathetic involvement
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-122
Classification of cases with a diagnosis of acute headache, to emergency division in Regional Hospital Durres, Albania
Edlira Shemsi1,* and Ferid Domi2
1Neurology
2Emergency, Regional Hospital Durres, Durres, Albania
Objectives
Symptoms of headache that is relatively frequent to emergency care and assessment and differentiation of these cases are done by gravity pain and neurological signs that had accompanying.Evaluation of cases made with CT, MRI and EEG according to the evaluation of neurologist doctor. Often headache are considered a contingency of "small" in relation to major emergencies presented in the service of emergency. About 1–2% of the cases presented with acute headache have a life threatening Diagnose.
Methods
To demonstrate how often a strong acute headache may mask a serious pathology we have seen in our study cases presented with a diagnosis of the above in the period November 2014-December 2015, in the emergency care, in Regional Hospital Durres. In total where 70000 cases gone in emergency(al categories). With the diagnosis of cefalese were 3674 patients (5.2% of cases), of which 2612 cases (71%) were women, and 1062 (29%) males. From cases with headache 2645 patients (72%)had not accompanying with neurological deficits and were considered and treated as primary headache and were later flown home. In the case of the symptoms associated cefalea n = 1029 (28%) presented symptoms as ataxia, nystagem, meningitis, visual disturbance, cofusional state, convulsions, etc.). Of these 116 cases with associated symptoms (11.2%), or =3.1% of total cases with cefalea resulted in serious pathology.
Of these, 24 patients (20.6% of 116) were diagnosed bleeding subarachnoid, 6 cases (3.4%) intraparenchymal hemorrhage, 11 (9.4%) subdural hematoma 39 (33.6%) cerebral ischemia, 12 (10,3%) neuroinfection, 12 (11.2%) primary cerebral neoplasia, 5 cases with brain defects (4.3%), 1 case with carotid artery dissection (0.8%), 5 cases arachnoidal cyst (4 3%), 1 case with hydrocefalia (0.8%).
All cases were examined with CT and MRI of the head. Examinations made for other accompanied symptoms headache, had excluded cerebral serious problems.
Results
In the case of the symptoms associated cefalea n = 1029 (28% of all cases with headache), 116 of these (11.2%), or =3.1% of total cases with headache resulted in serious pathology. Examinations made for other accompanied symptoms headache, had excluded cerebral serious problems. n = 913 (88.8%)
Conclusion
These data show the importance of careful assessment of the cases presented with a diagnosis of acute headache in emergency service and the evaluation of each case suspicious of examinations appropriate to have the correct diagnosis, this and in collaboration with specialists other.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-123
Clinical profile of headache in a Displaced Population: A Case series of 26 patients in a public hospital of Bogotá, Colombia
Marta Liliana Ramos1,*, Stephania Bohorquez1, Julia Cuenca1, Luisa F Echavarria1, Sandra Riveros1, Jesús Martinez1 and Fidel E Sobrino1
1Hospital Occidente de Kennedy - Universidad de la Sabana, Bogotá, Colombia
Methods
We conducted an observational, descriptive, and cross-sectional study from July to December of 2016. The data for all patients were prospectively registered. Diagnosis of headache was according to the International classification of headache disorders, 3th edition (ICHD-3 Beta).
Results
Twenty-six (9,7%) out of 277 patients with headache in our headache unit, were victims of forced displacement. Ninety-six percent were women with mean age of 48,7 years(SD + −16). The mean time prior to consult was 12,4 years and 69,2% (n:18) of them meet the criteria for chronic daily headache(CDH). Among patients with CDH, 70.6% (n:12) complain about phonophobia (p 0,06), but there was no difference in other symptoms. 73% patients were classified as having primary headache being Chronic migraine the most frequent diagnosis (42.3% n:11). Pain tend to intensify with stress (58.3 %); 33,3(n:8) has medication overuse and 45% (n:10) complain about sleep disorders. In the group of secondary headache de most frequent diagnosis was posttraumatic headache.
Conclusion
In a displaced population, headache is a common cause of consultation and apparently, are more frequent the primary headaches as in the general population. In this population, the semiological profile is characterized by women with chronic daily headache, with phonophopia, medical overuse and sleep disorders. Phonophobia and posttraumatic headache may be related with armed conflict.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-124
A Retrospective Analysis of Emergency Department Visits and Revisits for Migraine in New York City
Mia T Minen1,*, Alexandra Boubour2 and Benjamin Friedman3
1Neurology, NYU Langone Medical Center
2Barnard College, Barnard College, Columbia University
3Emergency Medicine, Albert Einstein College of Medicine, New York, United States
Objectives
Headache is the fifth most common cause of emergency department (ED) visits; however, prior research demonstrates suboptimal care of headache patients in the ED. ED revisit rates are considered one marker of ED quality of care. We sought to examine (1) the number of revisits to the emergency department (ED), (2) the timeframe of revisits to the ED, and (3) whether poverty was associated with migraine ED revisits.
Methods
We conducted a retrospective analysis of patients with a diagnosis of migraine in 18 NYC EDs from 1/1/2015–6/30/2015. The primary outcome was headache revisit within 6 months. A secondary outcome was patient poverty status. Descriptive analyses were conducted.
Results
402,705 patients visited the EDs during this time period with any discharge diagnosis. 33. 2% (133,744/402,705) had one revisit and 24. 1%(96,811/402,705) revisited twice or more. Within our nested migraine cohort, there were 1052 migraine discharge diagnoses (80. 8% female). 26. 3% (277/1052) of migraine discharge diagnosis patients had one revisit and 12. 5% (131/1052) had two or more revisits. 92. 3% (971/1052) of the patients were below the federal poverty line, and 53. 1% were in the high or very high poverty group.
Conclusion
ED revisit rates for migraine discharge diagnoses were lower than the ED revisit rate for the overall discharge diagnosis for any disorder but the absolute numbers are still considerable. Over half of the patients who visited the 18 EDs in New York City are considered to be at a high or very high level of poverty based on the Federal Poverty Line.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-125
Prevalence and clinical characteristics of headache in general medicine and dental students in Kyrgyz State Medical Academy and International University of Kyrgyzstan
Inna L Lutsenko1,* and Maryam T Scherba2
1Neurology
2Pediatrics, Kyrgyz State Medical Academy, Bishkek, Kyrgyztan
Objectives
To determine prevalence and characteristics of all types of headache in students of 2nd, 3rd and 4th years of medical universities Kyrgyz State Medical Academy (KSMA) and International University of Kyrgyzstan, International School of Medicine (IUK, ISM) in Kyrgyzstan.
Methods
A questionnaire was administered to randomly selected students of general medicine and dental faculty, which included index HIT6, VAS, index HALT, Zung depression scale. Diagnoses were assigned according to the criteria of the International Headache Society.
Results
768 students participated in our study with mean age 21 ± 3.2 years, and 77% responded positively about headache, 49%males and 51% females. Among 592 students with headache, 56.7% had tension headache TH) with pericranial muscles tensions, 11.6% TH without pericranial muscles tensions, 23.8% had autonomic cephalgias, 7.2% had migraine. TH localised in frontal zone in 81% of students. Female students with migraine had menstrually related attacks more frequently than students with nonmigraine headache (78.1% versus 19.5%). Women students suffered from migraine-types of headache twice more than men (p = 0.001). Significant headache risk-factors were loud noise OR 4 (95%CI 2,11–3,18), lack of sleep OR 8 (95%CI 4,2–9,1), staying in suffocated room OR 7 (95%CI 5,6–8,9), staying in a crowdy place OR 5 (95% CI 3,2–6,2). Protective methods were massage OR 0,6 (95% CI 0,51 −0,9), warm shower OR 0,8 (95% CI 0,61 −0,82). 78% of students did not link use of alcohol with headache manifestation (p = 0.01), but the positive connection was found in starting of headache after 4th class (after 5 h of studying), p = 0.0001. We found positive correlation between long-term depression and headache (p = 0.001).KSMA students displayed more expressed and frequent headache in both genders than students of IUK ISM (p = 0.01). 38% of students do not use treatment. Among treatment students tend to use non-steroid anti inflammatory pills (68%).
Conclusion
Tension headache is prevalent in students of medical universities in both genders in Kyrgyzstan, it connects with long-term depression and more than 5 h of studying. We educated 238 students with headache post isometric relaxation techniques for pain relieving.
Disclosure of Interest
None Declared
Headache Education for Clinicians and Patients
PO-02-126
Burden of Chronic Migraine in Tertiary Headache Outpatient Clinics: Experience of 10 years a Multicenter Study
Osman Ozgur Yalin1,*, Derya Uludüz2, Mehmet A Sungur3 and Aynur Ozge4
1Department of Neurology, Istanbul Training and Research Hospital
2Department of Neurology, Istanbul University Cerrahpasa School of Medicine, Istanbul
3Department of Biostatistics, Duzce University School of Medicine, Duzce
4Department of Neurology, Mersin University School of Medicine, Mersin, Turkey
Objectives
The burden of headache is a major public health problem worldwide. Headache, more specifically chronic headache, is associated with direct and indirect costs and negatively effects on quality of life. International Classification of Headache Disorders (ICHD) diagnostic criteria had provided marked awareness about headache since firstly published. Classification schemes not only provide accurate diagnosis of headache subtype, but also comprehensively classified syndromes. This standardization facilitated multicenter-studies globally last decade and shed light on understanding of pathophysiology of headache. Population based studies report globally 45–50% of adult population have active headache, nearly 10% for migraine, %30–35 for tension type headache and 3% for chronic headache. However, distribution for tertiary headache centers expected to be different from many aspects.
In this large study we stated 10 years’ experience of three tertiary headache centers. We analyzed patient data retrospectively and re-classified subjects according to ICHD-3 beta. We aimed (1) to reveal distribution of primary and secondary headache, (2) to classify primary headache, (3) to state frequency of chronic headache according to ICHD-3 beta.
Methods
This study is conducted a part of ongoing Turkish Headache Database Study recording and analyzing headache syndromes according to ICHD standards at tertiary headache centers in Turkish population. Electronic database examined retrospectively for 2007–2017 years and 28546 enrolled patients’ data included to survey. The accurate diagnosis re-evaluated according to ICHD 3 beta by headache-experienced neurologists. To avoid mistakes, we excluded all patients whom have insufficient data or could not be diagnosed accurately.
Results
Study group consisted 8711 patients, 6954 women and 1674 men (80,6% and 19,4%). Mean age was 38.2 ± 14.2 years. The primary headache disorders covered 6959 patients (79,89%) and 1752 patients diagnosed secondary headache syndromes (%20,11). Secondary headache patients were significantly older, male/female ratio were significantly higher than primary headache patients (p < 0,001). Headache onset (months) were significantly longer at primary headache disorders (48 months & 24 months), (p < 0,001). Three thousand-six hundred and seventy four patients have migraine (42,18%), 3163 patients have tension type headache (36,1%), 90 patients have trigeminal autonomic cephalalgias (1,03%). Other primary headache syndromes observed rarely. Chronic migraine diagnosed 8,9% of study group, covered 775 patients (24,5% of migraine patients), when we added migraine plus medication overuse headache patients to chronic migraineurs (112 patients, 1,22%), chronic migraine frequency reached 28% of migraine patients and 10,2% of study group.
Conclusion
This study exposes that Chronic Migraine is more prevalent in Tertiary Headache centers and reached up to 10% of all patients. This high prevalence demonstrates urgent need to new arrangements for diagnosis and treatment schemes. Population-based studies report tension type headache is the most common headache syndrome, contrarily in this study the most frequent headache disorder was migraine.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-127
Elevation of apolipoprotein E during migraine attacks
Eiichiro Nagata1,*, Naoki Yuasa2, Natsuko Fujii1, Masatoshi Ito3, Hideo Tsukamoto3 and Shunya Takizawa1
1Neurology, Tokai University School of Medicine
2Neurology, Isehara Kyodo Hospital
3Support Center for Medical Research and Education, Tokai University, Isehara, Japan
Objectives
Our previous proteomics analysis revealed that the serum apolipoprotein E (Apo E) protein level during migraine attacks was significantly higher than the preictal level. In this study, we aim to compare the serum level of Apo E protein in migraineurs during attack and attack-free period with that of control subjects.
Methods
All patients were carefully interviewed and examined, and diagnosis was made using the ICHD-3 beta. Sera were prepared from peripheral blood samples obtained from 4 migraine with aura patients (MA) and 8 migraine without aura (MO), 5 tension type headache (TTH), and 3 healthy controls. We performed Western blot analysis for Apo E and α fodrin, the latter of which we previously reported as a possible migraine biomarker using an RNA microarray method.
Results
The protein levels of Apo E and α fodrin tend to be higher than those of controls (TTH patients and healthy controls). Notably, the level of α fodrin protein in the patients with MA during attack free-period was only significantly higher than controls and other types of headache patients.
Conclusion
These findings suggest that migraine attacks alter serum ApoE level. Moreover, Apo E may serve as a biomarker of migraine that is useful in differential diagnosis of headache disorders.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-128
5-HT2B-induced calcium increase and ERK phosphorylation in primary cells with relevance to a migraine mouse model
Maria Josten1,*, Miriam Kremser1 and Hermann Lübbert1; Department of animal physiology
1Ruhr-University Bochum, Bochum, Germany
Objectives
Recent research showed that the 5-HT2B receptor may play a crucial role in the pathophysiology of migraine. These findings are emphasized by clinical studies demonstrating, that mCPP (meta-chlorophenylpiperazine), a partial 5-HT2B receptor agonist, led to a migraine-like headache in migraine patients. We have established a chronic migraine model, in which hypoxic treatment sensitizes mice towards a migraine-like status in which mCPP can induce PPE (plasma_protein_extravasation) in the murine dura mater. This readout serves as an indicator for a sterile neurogenic inflammation of the dura mater in animal models.
Consequently, investigations of 5-HT2B receptor signalling pathways came into focus. Studies from heterologous cell systems provided some evidence that its activation may lead to ERK (extracellular-signal regulated kinase) phosphorylation and calcium release via IP3, but the latter was in contrast to the few results from experiments with endogenously expressing cells like pulmonary artery endothelial cells (ECs). To investigate this further, primary cell cultures of murine lung and dural ECs were established.
Methods
Calcium-imaging, western blotting (pERK/ERK), immunocytochemistry (pERK), single-cell PCR and primary murine endothelial cell culture.
Results
Activation of the 5-HT2B receptor on murine pulmonary EC triggered ERK phosphorylation and elevation of cytoplasmic calcium in the analysed cell population. Single-cell analysis revealed mRNA expression of the 5-HT2B receptor in pulmonary and dural primary ECs.
Conclusion
Effects of 5-HT2B receptor activation on murine ECs may comprise cell proliferation and increased transcription, which may lead to dural vascularisation in the animal. An altered vascular system in the murine dura mater may contribute to the migraine-like status in the hypoxic mouse model.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-129
Both anti-CGRP and anti-CALCRL antibodies suppress cortical spreading depression
Minyan Wang1,*, Liwen Jiang2, Yan Wang2 and Fan Bu1,2
1Department of Biological Sciences
2Centre for Neuroscience, Xian Jiaotong-Liverpool University, Suzhou, China
Objectives
Cortical Spreading Depression (CSD), is a transient propagating synaptic excitation followed by depression, which is regarded as an important pathophysiological basis of migraine. Both calcitonin-gene related peptide (CGRP) and CALCRL-containing receptor are the known targets for migraine prophylaxis; however, their mechanism action in migraine is not fully understood. This study aimed to explore if CGRP and CGRP receptor could regulate cortex susceptibility to CSD in rodents.
Methods
CSD was induced by K+-medium. Intrinsic optical imaging was used for CSD recording in the mouse brain slice and electrophysiology for CSD recording in the rat.
Results
The results show that functional inhibition of CGRP by an anti-CGRP antibody markedly prolonged the CSD latency in the mouse brain slice; this inhibition was not observed when the antibody was co-incubated with exogenous CGRP. Corresponding to this, an anti-CALCRL antibody also prolonged the CSD latency in the mouse brain slice. Consistently, prolongation of CSD latency was also observed after pretreatment of the anti-CALCRL antibody perfused into the intracerebroventricle of rats in addition to a significant reduction of CSD number and propagation rate.
Conclusion
This data demonstrates that functional inhibition of both CGRP and CALCRL-containing receptors suppress cortex susceptibility to CSD, indicating their key role in central mechanism of migraine.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-130
Topical intranasal administration of local anaesthetics over the sphenopalatine foramen: Does this really block the sphenopalatine ganglion?
Joan Crespi1,*, Daniel Bratbak2, Kent A Jamtøy3, Irina Aschehoug4, Manjit Matharu5, David Dodick6 and Erling Tronvik7
1Neurology
2Neurosurgery
3Maxillofacial Surgery
4Institute for Neuroscience, Institute for Neuroscience, Trøndelag, Norway
5Neurology, National Hospital of Neurology and Neurosurgery, London, United Kingdom
6Neurology, NTNU, Arizona, United States
7Institute for Neuroscience, Trondheim, Norway
Objectives
Historical reports describe the sphenopalatine ganglion (SPG) as positioned directly under the nasal cavity mucosa. This localization is the basis for the topical intranasal administration of local anaesthetic (LA) towards the sphenopalatine foramen (SPF) which is hypothesized to diffuse a short distance to reach the SPG. This distance is reported to be as short as 1 mm. Nonetheless, the SPG is located in the sphenopalatine fossa, encapsulated in connective tissue, surrounded by fat tissue and separated from the nasal cavity by a thin bony wall. The sphenopalatine fossa communicates with the nasal cavity through the SPF, which itself contains neurovascular structures packed with connective tissue and is covered by mucosa in the nasal cavity. Endoscopically the SPF does not appear open. It has hitherto not been demonstrated that LA reaches the SPG
Methods
Our group has previously identified the SPG on 3 T-MRI images merged with CT. This enabled us to measure the distance from the SPG to the nasal mucosa covering the SPF in 20 Caucasian subjects on both sides (n = 40 ganglia). This distance was measured by two physicians. Interobserver variability was evaluated using the intraclass correlation coefficient (ICC).
Image:
Results
The mean distance from the SPG to the closest point of the nasal cavity directly over the mucosa covering the SPF was 6.77 mm (SD 1.75; range, 4.00–11.60). The interobserver variability was excellent (ICC 0.978; 95% CI: 0.939–0.990, p < 0.001).
Conclusion
The distance between the SPG and nasal mucosa over the SPF is significantly longer than previously assumed. These results challenge the assumption that the intranasal topical application of LA close to the SPF results in passive diffusion to and blockade of the SPG.
Disclosure of Interest
J. Crespi Conflict with: Our research group is currently developing a technique that aims to block the SPG using a New Neuronavigation-based Surgical Technique, D. Bratbak Conflict with: Our research group is currently developing a technique that aims to block the SPG using a New Neuronavigation-based Surgical Technique, K. Jamtøy Conflict with: Our research group is currently developing a technique that aims to block the SPG using a New Neuronavigation-based Surgical Technique, I. Aschehoug Conflict with: Our research group is currently developing a technique that aims to block the SPG using a New Neuronavigation-based Surgical Technique, M. Matharu: None Declared, D. Dodick: None Declared, E. Tronvik Conflict with: Our research group is currently developing a technique that aims to block the SPG using a New Neuronavigation-based Surgical Technique
Headache Pathophysiology - Basic Science
PO-02-131
Facial TRPM8 stimulation ameliorates thermal hyperalgesia in a mouse migraine model
Yohei Kayama1,*, Mamoru Shibata1, Tsubasa Takizawa1, Toshihiko Shimizu1, Haruki Toriumi1, Taeko Ebine1 and Norihiro Suzuki1
1Department of Neurology, Keio University School of Medicine, Tokyo, Japan
Objectives
Transient receptor potential cation channel melastatin 8 (TRPM8), a nonselective cation channel that mediates cool perception, is expressed in trigeminal ganglion (TG) neurons. Genome-wide association studies reproducibly identified TRPM8 as a candidate susceptibility gene for migraine. In the present study, we aimed to investigate the role of TRPM8 in migraine pathophysiology.
Methods
We produced a migraine model by dural inflammatory soup (IS: 1 mM each of histamine, serotonin, and bradykinin, and 0.1 mM prostaglandin E2 in 10 mM HEPES buffer, pH 5.5) administration in wild-type C57BL/6 and TRPM8 knockout (KO) mice. Sham-operated animals without IS administration were used as controls. Temporal profiles of facial heat pain threshold temperature were recorded using a peltier device-based apparatus with its surface temperature regulated by a computer. After baseline measurement, mice were subjected to 5 minute-long topical application of icilin solution (10 µM) or DMSO to the face prior to every threshold temperature determination. Measurement was carried out at 6 hours, 1 day, 2 days, and 6 days after IS administration or sham operation. A histological study using retrograde tracers (Fluorogold and DiI for the dura and face, respectively) was also performed to identify TG neurons innervating these regions. Furthermore, immunostaining for transient receptor potential cation channel vanilloid 1 (TRPV1), a marker for nociceptive neurons, was conducted. All numerical data were expressed as mean ± SD.
Results
In wild-type mice, the threshold temperature for heat pain was gradually reduced, reaching a nadir on Day 2 post-IS treatment (41.3 ± 1.9°C vs. 43.6 ± 1.0°C at the baseline, N = 30 each, P < 0.001, ANOVA with a Bonferroni correction). The IS-induced thermal hyperalgesia was abrogated by pretreatment with icilin in wild-type mice. Such an inhibitory effect of icilin was not observed in TRPM8 KO mice. In sham-operated mice, there were no significant changes in threshold temperature. Our tracer study revealed that 14.3 ± 10.8% of all TG neurons (N = 3015 from 12 animals) were labelled with Fluorogold, indicating that these neurons innervated the dura. Furthermore, 60.0 ± 28.8% of these TG neurons were found to send collaterals to the face as well. Of these TG neurons innervating both the dura and face, 46.1 ± 34.9% were positive for TRPV1.
Conclusion
TRPM8 activation is capable of correcting trigeminal nociceptive hyperactivity due to migraine-associated meningeal inflammation. Therapeutic interventions to the face seem to be an effective measure for modifying dural nociceptive neuronal activity. Taken together, TRPM8 activation in the facial region is likely to be a promising therapeutic strategy for migraine.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-132
Persistent Naproxen sodium treatment dose not induce mechanical allodynia in mice
Chonlawan Saengjaroentham1,*, Lauren C Strother1, Peter J Goadsby1 and Philip R Holland1
1Headache Group, Basic and Clinical Neuroscience, King’s College London, London, United Kingdom
Objectives
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for migraine treatment. The excessive intake of acute migraine therapy may lead to disease chronification and progression to medication overuse headache (MOH). NSAIDs have been proposed to be a risk factor for MOH in patients having high baseline migraine frequency. However, the study of prolonged NSAID induced MOH in animal models has not been fully established. To examine the effect of a long-acting NSAID on the progression of MOH-like phenotype in mice, we aimed to explore alterations in mechanosensitivity resulting from repeated exposure to naproxen sodium.
Methods
Male and female C57BL/6 J mice (N = 36) were injected intraperitoneally with naproxen sodium (100 mg/kg), sumatriptan (0.6 mg/kg) or saline control daily for 15 or 11 days, respectively, followed by a recovery period. Hind paw mechanical withdrawal thresholds were measured every second day using von Frey filaments. On the testing day, mice were acclimatized in the apparatus for 1 hour, followed by the application of filaments perpendicularly to the plantar surface of the hind paw for 3 seconds. Positive response was defined as lifting or flicking of the paw after stimulation, commencing with the 0.6 g filament and following the “up and down” method. To evaluate the mechanical threshold, the pattern of filaments was calculated using the Claplan analysis method. All behavioral testing occurred in light conditions between 09:00 and 12:00 to avoid circadian variations.
Results
We first demonstrated that repeated exposure to sumatriptan induced a latent sensitization of hind paw mechanical withdrawal thresholds (F(1, 140) = 11.92, P ≤ 0.001) in agreement with published data. However; there was no significant difference in mechanical withdrawal thresholds in response to sustained administration of naproxen sodium when compared to control mice (F(1, 21) = 1.39, P = 0.252).
Conclusion
Repeated exposure to daily naproxen for 15 days does not induce mechanical hypersensitivity in mice. This long acting NSIAD may represent an alternative therapeutic agent for those at risk of MOH or undergoing withdrawal.
This study was supported by the MRC grant (MR/P006264/1) and PhD funding from the Development and Promotion of Science and Technology Talents Project (DPST), the Royal Thai Government.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-133
The α6 subunit-containing GABAA receptors: A novel target for migraine treatment
Pi-Chuan Fan1,2,*, Pokai Huang3, Werner Sieghart4, Margot Ernst4, Daniel E Knutson5, James Cook5 and Lih-Chu Chiou6,7
1Department of Pediatrics, College of Medicine, National Taiwan University
2Department of Pediatrics, National Taiwan University Hospital, Taipei
3Department of Pediatrics, E-da Dachang Hospital, Kaohsiung, Taiwan, Republic of China
4Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Vienna, Austria
5Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
6Graduate Institute of Pharmacology
7Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
Objectives
The α6 subunit-containing GABAA receptors (α6GABAARs) are expressed in both neurons and satellite glia of the trigeminal ganglia (TG) in addition to cerebellar granular cells. The α6GABAAR-positive neuronal cell bodies in the TG project axons to the temporomandibular joint as well as to the trigeminal nucleus caudalis and upper cervical region (Vc–C1), which form the trigeminal cervical complex (TCC). Previous studies, including ours, have shown that activation of the TCC plays an important role in the pathogenesis of migraine. However, the pathophysiological role of α6GABAARs in migraine remains unclear. Recently, a pyrazoloquinolinone Compound 6 was identified to be a positive allosteric modulator (PAM) highly selective to α6GABAARs. We examined its effect on a migraine model induced by intra-cisternal injection (i.c.) of capsaicin to elucidate the role of α6GABAARs in the pathogenesis of migraine. Besides, two α6GABAAR PAMs, Ro15–4513 and loreclezole, were used as positive controls of Compound 6, and diazepam, an α6GABAAR-insensitive benzodiazepine, was used as negative control.
Methods
The migraine model induced by intra-cisternal (i.c.) capsaicin in Wistar rats (250–300 g) was used. The rat was pretreated with the drug or vehicle by intraperitoneal injection (i.p.) 30 min before being stimulated by i.c. instillation of capsaicin (10 nmol, 100 μl). Two hours after capsaicin instillation, the dura mater, TG and TCC in rats were dissected for immunohistochemical measurements. The neuronal number with positive immunoreactivity (ir) of c-Fos, an activated neuron marker, in the TCC was quantified by the formulas established in our previous study, representing the central end response of the trigeminovascular system (TGV). In the periphery, the immunoreactivity of calcitonin gene-related peptide (CGRP-ir) was measured by immunohistochemistry and immunofluorescence in the dura mater and TG, respectively.
Results
Capsaicin i.c. instillation significantly increased the c-Fos-ir neuronal number in the TCC, increased the CGRP-ir in the TG, and depleted the CGRP-ir in the dura mater. Compound 6, at 3 and 10 mg/kg (i.p.), but not 1 mg/kg, significantly attenuated the elevation in the number of c-Fos-containing TCC neurons and CGRP-ir of TG as well as reversed CGRP depletion in the dura mater. Importantly, all the three effects of Compound 6 were mimicked by Ro15-4513 and loreclezole, two α6GABAAR PAMs, but not by diazepam, an α6GABAAR-insensitive benzodiazepine.
Conclusion
These results showed that α6GABAAR PAM can attenuate capsaicin-induced responses in both central and peripheral ends of the TGV, suggesting α6GABAARs play a role in the pathogenesis of migraine, and are novel and promising targets of migraine treatment. α6GABAAR PAMs, like Compound 6, may be potential novel antimigraine agents.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-135
The CGRP receptor antagonist olcegepant modulates cortical spreading depression in vivo
Sajedeh Eftekhari1,*, Gayane M Kechechyan1, Guido Faas1 and Andrew Charles1
1Neurology, David Geffen School of Medicine at UCLA, Los Angeles, United States
Objectives
The neuropeptide calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology. CGRP is released during migraine attacks, and agents that inhibit CGRP signaling have demonstrated efficacy as migraine therapy. We examined the effects of the CGRP receptor antagonist olcegepant on the neural and vascular components of cortical spreading depression (CSD) in mice in vivo.
Methods
Neural and vascular responses to CSD in anesthetized mice were recorded using optical intrinsic signal (OIS) and local field potential recording techniques. The effects of systemically administered olcegepant (0.02 mg/kg IP) on spontaneous cortical bursting and accompanying vascular activity, and on single and repetitive CSD events were examined.
Results
Olcegepant did not have any significant effect on baseline spontaneous cortical bursting activity or accompanying vascular oscillations prior to CSD. Treatment with olcegepant significantly reduced (by 35%) repetitive CSD frequency evoked by continuous KCl stimulation as compared with vehicle treated controls. Examination of single CSD events before and after administration of olcegepant in the same animal showed that olcegepant increased the initial vasoconstriction associated with the CSD wave, and prolonged the sustained vasoconstriction that occurred after the initial CSD wave.
Conclusion
These findings support a role for CGRP in CSD, including both its neural and vascular components.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-136
Distribution of CGRP and its receptor components CLR and RAMP1 in the rat retina
Karin Warfvinge1, Lars Edvinsson1,2, Aneta Radziwon-Balicka1 and Frank Blixt2,*
1Department of Clinical Experimental Research, Glostrup research institute, Glostrup, Rigshospitalet Copenhagen, Copenhagen, Denmark
2Department of Clinical Experimental Sciences, Lund university, Lund, Sweden
Objectives
With CGRP and its growing role in migraine, it is vital to understand their roles in various parts of the retina since different visual phenomenon are found in migraine patients. This study aims to investigate the distribution of CGRP and its two receptor components in the rat retina.
Methods
Rat retinas were used and processed visually by immunohistochemistry and quantitatively with flow cytometry using antibodies against CGRP, CLR, or RAMP1.
Results
Immunohistochemistry showed that CGRP was mainly confined to ganglion cell layer, vessels in the innermost part of the retina and to occasional cells within the inner nuclear layer, while CLR and RAMP1 co-expressed in the optic nerve and in the inner most layer of the retina, specifically the nerve fiber layer. Retinal vessels showed CLR and RAMP1 immunoreactivity. Moreover, CLR expression dominated over RAMP1 and thereby revealing that CLR expression alone occurred. Double labelling with vimentin revealed co-expression between CGRP and vimentin, indicating that CGRP is expressed in Müller glial cells. No co-expression between vimentin and CLR or RAMP1 was found. Two-color flow cytometry showed that 13.6% of CLR-positive events were expressing RAMP1. Furthermore, 96.3% of RAMP1 positive events expressed CLR. These results suggest that almost all RAMP1 positive events expressed CLR.
Conclusion
The functional role of CGRP and its receptor is still unknown, but recent developments in antibody genetics and new antagonists may provide excellent tools to unravel this. However, our results indicate that CGRP is expressed in glial cells and the receptor elements in neurons. In addition, the localization of RAMP1/CLR immunoreactive cells gives a decent appreciation of functional CGRP receptors distribution in the rat retina.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-137
Trigeminal ganglia of familial hemiplegic migraine type 1 R192Q mutant mice express markers of the M1 macrophage polarisation stage
Luigi Balasco1, Sandra Vilotti1, Arn van den Maagdenberg2, Andrea Nistri1 and Elsa Fabbretti3,*
1International School for Advanced Studies SISSA, Trieste, Italy
2Departments of Human Genetics & Neurology, University Medical Centre, Leiden, Netherlands
3University of Nova Gorica, Nova Gorica, Slovenia
Objectives
One of the hallmarks of migraine are recurrent pain attacks, a condition supported by a tissue background prone to neuronal sensitisation and neurogenic inflammation. Transgenic mice that express a missense R192Q mutation in the a1A subunit of voltage-gated CaV2.1 calcium channels are the model of familial hemiplegic migraine type 1 (FHM1 R192Q mutant mice). Trigeminal ganglia from these mutant mice, compared to ganglia of wild type mice, are characterised by a larger number of Iba-immunopositive macrophages, higher expression levels of CD11b, ED1 and F4/80 markers in non-neuronal satellite glial cells and increased secretion of pro-inflammatory cytokine TNFα. Recent evidences suggest that the tissue balance of different macrophage polarisation stages is an important indicator for inflammation outcome.
Methods
We have used FHM1 R192Q mutant mice to study macrophage polarisation markers, namely the M1 pro-inflammatory markers CD16 and CD32 and the M2 pro-resolving CD206. Expression of the inducible form of the nitric oxide synthase gene (iNOS) was also tested. Real-time PCR analysis of intact trigeminal ganglia samples from FHM1 R192Q mutant and WT mice have been performed. All experiments were carried out in accordance with the regulations of the local Animal Welfare act accordingly to the 3R roles and following the ARRIVE guidelines.
Results
We observed a large heterogeneity of CD16- and CD206-expressing cells in ganglia from mutant mice compared to wild type ganglia. In addition, mutant mice expressed significantly larger amount of the pro-inflammatory CD32 and iNOS transcripts. In contrast, trigeminal ganglia from a CGRP knockout mice expressed significantly lower levels of the CD16 transcripts.
Conclusion
These results suggest that soluble mediators, such as CGRP, have a strong role in the control of the differentiation of pro-inflammatory monocytes in trigeminal ganglia. Pro-resolving strategies aimed at lowering the neurogenic inflammation background in the trigeminal ganglia could be considered to ameliorate migraine prognosis.
Supported by EU FP7 grant EUROHEADPAIN (#602633).
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-138
Exteroceptive suppression of voluntary masseter muscular activity in migraine: A pilot study
Pei Ru Chen1,2,*, Kwong-Kum Liao1,2, Kuan-Lin Lai1,2 and Shuu-Jiun Wang1,2
1Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
2Department of Neurology, National Yang-Ming University School of Medicine, taipei, Taiwan, Republic of China
Objectives
We aimed to explore the differences in the trigeminal system by studying the exteroceptive suppression of the voluntary masseter muscular activities between migraine patients and controls.
Methods
Ten patients (1M/9F, mean age 34 years old) with migraine without aura and 9 healthy volunteers (3M/6F, mean age 31 years old) were recruited into the study. In the exteroceptive suppression test, activities of the ipsilateral masseter muscle were recorded while the electric stimuli were applied to the area supplied by the infraorbital nerve (V2 branch). The exteroceptive suppression of voluntary masseter muscular activities constitutes dual phases of the silent periods in the electromyography (EMG), i.e. exteroceptive suppression period 1 (ES 1) and ES2. Between these two suppression periods, a period with transient increased EMG activities emerged, i.e. the interposed EMG activity (IE). The latency and duration of IE and the ratio of IE, defined as the ratio of the IE duration to the overall exteroceptive suppression duration (i.e. IE latency + IE duration + ES2 duration), were measured. In this study, we compared the difference in these measurements between migraine patients and controls. In addition, the measurements were correlated with the headache profile in patients with migraine.
Results
Both left and right mean IE durations were significantly longer in migraine patients than those in controls (left 31.02 ± 6.82 ms vs. 24.70 ± 6.89 ms, p < 0.001; right 27.3 ± 6.56 ms vs. 25.32 ± 8.22 ms, p = 0.02). A trend of shorter left IE latency (26.45 ± 2.8 ms vs. 27.1 ± 3.99, p = 0.126) and a significantly higher left IE ratio were found in migraine patients (0.33 ± 0.07vs. 0.28 ± 0.084, p < 0.001) compared to the controls. In patients with migraine, a positive correlation between right IE ratio and number of migraine days per month (r = 0.316, p = 0.037) and a negative correlation between left IE latency and number of days with painkiller usage per month (r = −0.302, p = 0.044) were demonstrated.
Conclusion
Our pilot study showed migraine patients, compared to the controls, had longer IE duration, shorter IE latency and higher IE ratio. These findings suggest hyper-excitability in the spinal trigeminal complex system in migraine patients. Further study recruiting more cases is warranted to confirm our results.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-139
Interictal levels of cgrp are no related with changes in cerebral vasoreactivity in cronic migraine
Davinia Larrosa Campo1, César Ramón Carbajo1, Eva Cernuda Morollón2, Pablo Martínez-Camblor3 and Julio Pascual Gómez4,*
1NEUROLOGY, H.U.C.A.
2University of Oviedo, OVIEDO, Spain
3Statistical analysis, Geisel School of Medicine at Darmouth, Hanover, United States
4NEUROLOGY, H.U.M.V., Santander, Spain
Objectives
CGRP is a potent vasodilator of cranial vasculature. Interictal CGRP (calcitonin-gene related peptide) levels have been reported as a reliable biomarker of chronic migraine (CM). Cerebral CO2 Vasoreactivity (CVR) reflects the vasodilation of microvasculature and its impairment is a marker of endothelial dysfunction. In CM, both an increase in CGRP levels and a decrease in CVR have been described.
The aim of this stady is to determine whether CGRP levels correlate with CVR in CM.
Methods
This series includes women meeting current IHS diagnostic criteria for CM. CGRP levels were determined in blood samples obtained from right cubital vein between 9–12 am with an ELISA kit from USCN following manufacturers instructions. CVR was assessed by Breath Holding Index (BHI) on transcranial Doppler in middle cerebral arteries (MCA), posterior cerebral arteries (PCA) and in the basilar artery (BA). To examine correlations between BHI and CGRP, Pearson correlation coefficient test was used.
Results
A total of 94 women fulfilling CM criteria (aged 43,09 ± 12,01 years) were included. CGRP levels were 64.51 ng/ml (range 11–157). Mean BHI were: MCA 1,528 ± 0,408, PCA 1,420 ± 0,406, BA 1,450 ± 0,352. There was no correlation between BHI and CGRP levels for the different arteries explored: MCA r = 0,000, PCA r = −0,024, BA r = −0,054 (p > 0,05)
Conclusion
In our series of CM there was not relationship between interictal CGRP levels and CVR. This finding suggest that CGRP alone is not responsible for the endothelial dysfunction described in migraine. The role of other neuropeptides alone or in combination with CGRP needs to be studied.
Disclosure of Interest
D. Larrosa Campo: None Declared, C. Ramón Carbajo: None Declared, E. Cernuda Morollón: None Declared, P. Martínez-Camblor: None Declared, J. Pascual Gómez Conflict with: Supported by the PI14/00020 FISSS grant (Fondos Feder, ISCIII, Ministry of Economy, Spain)
Headache Pathophysiology - Basic Science
PO-02-140
The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: evaluation in an animal model
Chiara Demartini1,2, Rosaria Greco1, Anna Maria Zanaboni1,2, Stefania Ceruti3, Germana Tonsi1, Oscar Francesconi4, Cristina Nativi4 and Cristina Tassorelli1,2,*
1Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Center, C. Mondino National Neurological Institute, Pavia
2Department of Brain and Behavioral Sciences, University of Pavia, Pavia
3Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan
4Department of Chemistry ‘Ugo Schiff’ and FiorGen, University of Florence, Florence, Italy
Objectives
To date, the pharmacological treatment of migraine remains somewhat unsatisfactory, partly because the pathophysiology of this disabling disease is still poorly understood. Clinical and experimental studies have pointed to the possible involvement of the transient receptor potential ankyrin type-1 (TRPA1) channels in migraine pain. The present study is aimed to further investigate the role of TRPA1 in the mechanisms of migraine pain in an animal model of migraine using a novel TRPA1 antagonist (ADM_12) as a probe.
Methods
The effects of ADM_12 on nitroglycerin-induced hyperalgesia at the trigeminal level were investigated in rats using the quantification of nocifensive behavior induced by the orofacial formalin test. Gene expression of CGRP and SP in peripheral and central areas relevant for migraine pain were also evaluated.
Results
The findings show that in rats made hyperalgesic with nitroglycerin, ADM_12 has an anti-hyperalgesic effect of in the second phase of orofacial formalin test. This effect is associated to a significant inhibition of nitroglycerin-induced increase in c-fos, CGRP and SP mRNA levels in medulla-pons, cervical spinal cord and in trigeminal ganglion.
Conclusion
The present findings support a critical involvement of TRPA1 channels in the pathophysiology of migraine, and show their active role in counteracting hyperalgesia at the trigeminal level.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-141
The role of peripheral CGRP on the vasculature in a preclinical mouse model of migraine
Bianca N Mason1,*, Anne-Sophie Wattiez2, Adisa Kuburas1, William J Kutschke3 and Andrew F Russo1
1Molecular Physiology and Biophysics, The University of Iowa
2Molecular Physiology and Biophysics, University of Iowa
3Anesthesia, The University of Iowa, Iowa City, United States
Objectives
The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. While migraine can be induced by peripherally administered CGRP (intravenous) and can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the central nervous system, we used a mouse model of photophobia. Photophobia is an abnormal discomfort to non-noxious levels of light and is experienced by approximately 90% of migraine patients. We have previously shown that peripheral (intraperitoneal, IP) injection of CGRP resulted in light aversive behavior in wild-type CD1 mice similar to aversion previously seen following central (intracerebroventricular, ICV) injection. Importantly, two clinically effective migraine drugs, the 5-HT1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. Our goal for this study, is to identify the mechanism of action of peripheral CGRP using light aversion.
Methods
Intraperitoneal injections 0.1 mg/kg CGRP, Vehicle, 1 mg/kg Phenylephrine, CGRP + Phenylephrine was given to mice 30 minutes prior to placement in the light aversion chambers.
Radio telemetry devices were implanted in mice and blood pressure was used as a readout for changes in vascular tone after injection of drugs in mice.
Results
As previously mentioned, ICV CGRP, but not IP CGRP, induced light aversion in mice that have elevated levels of the CGRP receptor component hRAMP1 in the nervous system. We have now used transgenic CGRP-sensitized mice that have globally elevated levels of hRAMP1 (global hRAMP1) in all tissues. Interestingly, sensitivity to low light after IP CGRP in these mice was observed.
We have now begun investigating the role of the vasculature in peripheral CGRP-induced light aversion by using two approaches (1) injection of phenylephrine to minimize vasodilation induced by CGRP (2) genetic overexpression of the CGRP receptor in the vasculature.
Conclusion
These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms. This also suggests that peripheral CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves and likely not on CGRP receptors in the nervous system to cause migraine-like photophobia.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-142
Peripheral CGRP-induced pain detection in a preclinical mouse model of migraine
Brandon J Rea1,*, Aaron M Fairbanks1, Bennett Robertson1, Cameron Brown1, William C Castonguay1, Jayme Waite1, Pieter Poolman1, Randy H Kardon1, Levi P Sowers1 and Andrew F Russo1
1University of Iowa, Iowa City, United States
Objectives
Migraine is a complex neurological disorder that afflicts over 6% of men and 18% of men in the United States. Having a myriad of symptoms, migraine is denoted by debilitating, unilateral pain, lasting up to 72 hours, and at least one of two symptoms: nausea and/or vomiting, or photophobia and phonophobia. Photophobia is a condition where low to normal levels of light cause discomfort and light aversion in the perceiver. This photosensitivity is a subjective experience for each migraineur and is a common trigger.
Calcitonin gene-related peptide (CGRP) is a neuropeptide that is elevated during migraine. Clinical evidence suggests that CGRP plays a key role in migraine etiology. In particular, intravenous injection of CGRP has been shown to induce migraine-like headache in migraineurs but only fullness-of-head in non-migraineurs. Currently we have an established mouse model for CGRP-induced photophobic behavior. However, we have yet to quantify pain expression post CGRP administration. We hypothesized that our mice would exhibit increased expression of pain after CGRP administration and that this expression may be increased in the presence of light.
Methods
Mice were acclimated to a customized restraint and recorded using multiple cameras during dark and light conditions. Mice were then given an intraperitoneal injection of CGRP (0.1–0.5 mg/kg) or PBS and underwent the same conditions. Using the Mouse Grimace Scale and point-to-point measurement software, mice were independently scored by blinded observers for pain expression. Additionally, mice were co-injected with Sumatriptan, the gold standard for migraine treatment, to observe if symptoms of pain would be alleviated.
Results
CGRP caused a significant increase in pain expression compared to saline control in both dark and light conditions. A difference between dark and light was not observed.
Conclusion
These data validate the grimace and squint assays as sensitive tools to measure CGRP induced discomfort in mice. The data further suggest that peripherally administered CGRP exerts an effect in a light-independent manner in addtion to its photophobia-inducing properties.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-143
Plasma CGRP, Histamine, L-Kynurenine and Kynurinic acid levels in migraine without aura patients
Deepak Kumar Bhatt1,2, Katrine Falkenberg1, Bhagwat Prasad2, Lau Underbjerg1, Isabel Engel1, Julie M Jacobsen1 and Jes Olesen1,*
1Neurology, Rigshospitalet-Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark
2Department of Pharmaceutics, University of Washington, Seattle, United States
Objectives
There is a great need to find and validate biomarkers in clinical migraine research. Currently, only description of headache intensities, location of headache and at least one of the associated symptoms like nausea, vomiting, photophobia and phonophobia, are the diagnostic criteria to verify migraine headache. A significant change in the plasma calcitonin gene-related peptide (CGRP), histamine, L-Kynurenine (LK) and Kynurinic acid (KA) are reported in migraine patients. But there are also conflicting studies showing no change in these markers during migraine attack. In present study, we wanted to study comprehensive list of potential biomarkers in the plasma of migraine without aura patients, both during attack and interictally, by using advance LC-MS/MS and ELISA methods.
Methods
Four sets of blood samples were collected from the cubital vein. The first set during a migraine attack, second set two hours after treatment with subcutaneous sumatriptan, third set after at least five migraine free days/free from any other headache for at least 24 hours and the last set after a cold pressure test. Plasma was immediately separated in tubes containing protease inhibitors. Samples were placed on dry ice and transported back to the hospital from patient’s home. Subsequently, samples were stored in -80-degree freezer. LC-MS/MS methods for CGRP, histamine, LK and KA were developed at the University of Washington, USA. CGRP ELISA assay was performed in-house at Rigshospitalet-Glostrup, Denmark.
Results
We have identified two surrogate peptides, NNFVPTNVGSK and SGGVVK, to detect human CGRP by LC-MS/MS. In human plasma samples, small peaks of NNFVPTNVGSK and SGGVVK, matching to spiked heavy labelled peptides, were identified. But peaks were below limit of quantification. Subsequently, CGRP was extracted from plasma and ELISA assay was performed. Pooled plasma from non-migraineurs was used as a matrix to get a CGRP standard curve. Lower limit of quantification for CGRP was 15 pg/ml. In most of the samples, CGRP concentration was below lower limit of quantification. Lower limit of quantification for histamine, KA and LK were 5 nM, 30 nM and 250 nM. Plasma histamine levels were below limit of quantification. There was no significant change in plasma KA (99 nM vs 96 nM) and LK (750 nM vs 730 nM) levels during and outside migraine attack.
Conclusion
CGRP and histamine levels were below limit of quantification. Recovery of spiked CGRP in plasma is approximately 10 %. We recommend that when recovery is low, unknown values should be calculated from standard curve derived from known amount of CGRP spiked in similar volume of plasma and extracted similarly as samples. There is a great need to come up with protocols harmonizing neuropeptide extraction from plasma and subsequent ELISA assay protocols. Our results cast considerable doubt upon previous positive studies of these markers during migraine attack.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-144
Cortical spreading depression alters expression of inflammatory gene transcript in the dura: (a) sex effects (b) effects of pretreatment with onabotulinumtoxinA
Agustin Melo-Carrillo1,2,*, Aaron Schain1,2, Manoj Bhasin3,4 and Rami Burstein1,2
1Anesthesia, Harvard Medical School
2Anesthesia Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center
3Harvard Medical School
4Medicine, Beth Israel Deaconess Medical Center, Boston, United States
Objectives
Cortical spreading depression (CSD) has long been thought to be the neural event that underlies migraine aura, the non-painful sensory phenomena that can precede the migraine attack. It is thought to initiate the headache phase of migraine by activating the nociceptive pathway that provides the sensory innervation to the intracranial meninges. We recently raised the possibility that cortical spreading depression (CSD) activates meningeal nociceptors indirectly, by changing the molecular environment in the dura. Accordingly, the purpose of this study was to determine whether CSD alters the molecular environment in the dura, and if so, how such changes respond to treatment with onabotulinumtoxinA.
Methods
To answer these questions, we first induced a single wave of CSD in naïve male and female mice, and an hour later removed the dura and measured expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses. We then repeated these experiments in male and female mice pre-treated with onabotulinumtoxinA seven days earlier. Gene expression was considered altered (elevated or suppressed) if the number of copies of mRNA of that gene was altered by more than 1.5 fold and a p value of <0.01.
Results
A comparison between mice in which CSD was induced (after craniotomy) and sham mice (in which craniotomy was performed but CSD was not induced) revealed that 31 genes were altered in female mice (27 were upregulated, 4 were downregulated) and 17 in male mice (7 were upregulated, 10 were downregulated). A comparison between OnabotulinumtoxinA-treated and untreated mice showed that onabotulinumtoxinA reversed some of the CSD effects. In female mice, it downregulated 7 of the upregulated genes. In male mice, it downregulated 4 of the upregulated genes, and upregulated 4 of the downregulated genes. Functional analysis revealed that the altered genes are involved in inflammatory responses, immune cell trafficking, and lymphoid tissue structure.
Conclusion
The findings suggest that CSD-induced activation of inflammatory pathways in the dura is more robust in females than males, and that pre-treatment with onabotulinumtoxinA can prevent such activation. In the context of migraine headache, it may be that activation of dural nociceptors by CSD is secondary to a so-called ‘inflamed’ environment. In the context of onabotulinumtoxinA mechanisms of action, the findings point to a possible involvement in ‘calming’ the environment in the dura by reducing inflammatory responses.
Disclosure of Interest
A. Melo-Carrillo: None Declared, A. Schain: None Declared, M. Bhasin: None Declared, R. Burstein Conflict with: TEVA, Allergan, Trigemina, SST, Depomed, Dr. Reddy, Conflict with: TEVA, Allergan, Trigemina, Dr. Reddy
Headache Pathophysiology - Basic Science
PO-02-145
Cortical spreading depression closes the paravascular space and impairs glymphatic flow: Implications for migraine headache and treatment
Aaron Schain1,2,*, Agustin Melo-Carrillo1,2, Andrew Strassman1,2 and Rami Burstein1,2
1Anesthesia, Harvard Medical School
2Anesthesia, Beth Israel Deaconess Medical Center, Boston, United States
Objectives
To determine the effect of cortical spreading depression (CSD), the neural correlate of migraine aura, on the physical and functional attributes of the brain’s “glymphatic” waste clearance system, a recently described network of paravascular space (PVS) tunnels through which cortical interstitial solutes are cleared from the brain.
Methods
Using of state-of-the-art 2-photon in vivo imaging through the lightly thinned skull, we studied the PVS, the blood vessel lumen, and the subarachnoid space before, during, and after CSD. We used ubiquitously expressing GFP or tdTomato mice which can be used to identify such fluid-filled spaces by lack of fluorescence. We then inject 3kDalton dextran dyes into the brain to determine the effect of CSD on the rate of flow through the glymphatic system.
Results
We show that CSD induces a closure of the paravascular space around cortical pial blood vessels, that is not related to the stereotypical changes in blood vessel lumen. The overlying subarachnoid space is less affected. This closure is accompanied by a reduction in the rate of clearance of intraparenchymal solutes from the cortex. We also show that the glymphatic system is unaffected by approved migraine prophylactics.
Conclusion
Our findings not only demonstrate a link between migraine and the glymphatic system, but also suggest a novel mechanism for regulation of glymphatic flow through PVS constriction or dilatation independent of vasculature. Because CSD is involved in the production of many potentially harmful interstitial molecules, the additional blockage of their route of clearance could exacerbate their effects on cortical structural changes, gliosis, and headache instigation.
Disclosure of Interest
A. Schain: None Declared, A. Melo-Carrillo: None Declared, A. Strassman: None Declared, R. Burstein Conflict with: TEVA, Allergan, Trigemina, SST, Depomed, Dr. Reddy, Conflict with: TEVA, Allergan, Trigemina, Dr. Reddy
Headache Pathophysiology - Basic Science
PO-02-146
Hydrogen sulfide as a new modulator in an animal model of trigeminal nociception
Christiane Teicher1, Roberto De Col1 and Karl B Messlinger1,*
1Institute of Physiology & Pathophysiology, UNIVERSITY OF ERLANGEN-NÜRNBERG, Erlangen, Germany
Objectives
Hydrogen sulfide (H2S) is a neuromodulator acting through nitroxyl (HNO) when it reacts with nitric oxide (NO). HNO activates TRP channels of the ankyrin type 1 (TRPA1) causing release of calcitonin gene-related peptide (CGRP) from primary afferents. Activation of meningeal nociceptors projecting to the human spinal trigeminal nucleus (STN) may lead to headaches. In a rodent model of meningeal nociception, the activity of STN neurons was used as readout for the interaction between H2S and NO.
Methods
In anesthetized rats extracellular recordings from single neurons in the STN were made. Na2S producing H2S in the tissue and the NO donor DEA-NONOate were infused intravenously. H2S was also locally applied onto the exposed cranial dura mater or the medulla. Endogenous production of H2S was inhibited by oxamic acid and NO production by L-NAME to manipulate endogenous HNO formation.
Results
Systemic administration of Na2S was followed either by increased ongoing activity (in 73 %) or decreased activity (in 27 % of units). Topical application of Na2S onto the cranial dura mater caused a short-lasting activation followed by a long-lasting decrease in activity in the majority of units (70 %). Systemic administration of DEA-NONOate increased neuronal activity, subsequent infusion of Na2S added to this effect, whereas DEA-NONOate did not augment the activity after Na2S. The stimulating effect of DEA-NONOate was inhibited by oxamic acid in 75 % of units, and L-NAME following Na2S administration returned the activity to baseline.
Conclusion
Individual spinal trigeminal neurons may be activated or (less frequently) inhibited by the TRPA1 agonist HNO, presumably formed by H2S and NO, whereby endogenous H2S production may be rate-limiting. Activation of meningeal afferents by HNO paradoxically tends to decrease spinal trigeminal activity, consistent with the elevation of the electrical threshold caused by TRPA1 activation in afferent fibers. The effects of H2S-NO-TRPA1 signaling seem to depend on the site of action and the type of central neurons, and the role of H2S in headache generation appears ambiguous.
Disclosure of Interest
None Declared
Headache Pathophysiology - Basic Science
PO-02-147
Presence of Oxytocin Receptors on PACP-38 positive Shenopalatine Ganglia Neurons
David C Yeomans1,* and Shashi Kori2
1Anesthesia, Stanford University, Stanford
2Trigemina, Inc, Moraga, CA, United States
Objectives
Objectives: Activation of parasympathetic sphenopalatine ganglia (SPG) neurons is implicated as a critical step in the pathogenesis of cluster and some migraine headaches. In particular, activation of these neurons appears to release PACAP-38 onto the dura matter, where it causes mast cell degranulation and subsequent vasodilation. When infused, PACAP-38 induces headache as well as facial flushing in patients. Thus, mechanisms by which inhibition of SPG neuronal activity and subsequent release of PACAP-38 is potentially of great clinical utility.
We have previously demonstrated that oxytocin, acting at oxytocin receptors on trigeminal ganglia neurons inhibits those neurons, reduces the release of CGRP and inhibits craniofacial pain in rodents and migraine headache in patients. Thus, it is of interest to determine whether SPG neurons also possess oxytocin receptors and whether these receptors are co-localized with PACAP-38. Here we performed immunohistochemical experiments examining the expression of oxytocin receptors and PACP-38 on SPG neurons.
Methods
Methods: Rats were injected bilaterally with 50 µL of CFA into the vibrissal pads to induce robust inflammation which has been shown to induce overexpression of oxytocin receptors. Two days later, rats were deeply anesthetized and transcardially perfused with fixative. Their SPG was removed and cryoprotected overnight in 20% sucrose. Thereafter SPG was cryosectioned (10 uM) and slices were processed for PaCAP-38 and oxytocin receptor immunofluorescence using specific antibodies. Sections were also stained with DAPI to show nuclei. Sections were then examined using epifluorescence microscopy for immunoreactivity to the two antigens. Z stacks were also created to determine intracellular localization
Results
Results: Examination of sections demonstrated clear expression of oxytocin receptors on most SPG neurons. In addition, as previously reported, many cell also showed expression of PACAP-38. Extracellular PACAP-38 was also observed. More than 50% of oxytocin receptor positive neurons were also positive for PACAP-38. Z-stack analysis demonstrated that while cellular PACAP-38 was primarily located cytoplasmically, oxytocin receptors were located along neuronal cell membranes as well as in the cytoplasm.
Conclusion
These results indicate oxytocin receptors are present on SPG neurons and that many of these neurons also contain PACAP-38. Given the demonstrated inhibitory effect of oxytocin on peripheral neuronal firing, it is possible that oxytocin might also inhibit the firing of SPG neurons, inhibit PACAP-38 release, and have a therapeutic effect on cluster headache.
Disclosure of Interest
D. Yeomans Conflict with: Trigemina, Inc., S. Kori Conflict with: Trigemina, Inc., Conflict with: Trigemina, Inc, Conflict with: Trigemina, Inc
Headache Pathophysiology - Basic Science
PO-02-148
Peripherally administered Calcitonin Gene-Related Peptide induces pain and pain-depressed behaviors in mice
Anne-Sophie Wattiez1,2,*, Brandon J Rea1, Bianca N Mason1, William C Castonguay1 and Andrew F Russo1,2
1Molecular Physiology and Biophysics, University of Iowa
2Veterans Affairs, Iowa City, United States
Objectives
Migraine is a complex neurological disorder inducing severe headaches that last for 4 to 72 h and has at least two of the following characteristics: unilateral localization, pulsating quality, moderate to severe pain intensity, and aggravation by movement. In addition, migraine is accompanied by at least one of two symptoms: nausea and/or vomiting, or photophobia and phonophobia. The neuropeptide calcitonin gene-related peptide (CGRP) is a well-established key player in migraine pathogenesis. CGRP levels are elevated during spontaneous migraine attacks, and peripherally administered CGRP antagonists are able to relieve both the pain and the associated symptoms of migraine. Interestingly, an intravenous injection of CGRP in migraineurs causes spontaneous migraine symptoms. To this day, the relevant sites of CGRP action remain unclear. Our team has previously shown that both peripherally and centrally administered CGRP induced an immediate light-aversive behavior in mice, in correlation with the photophobia observed in patients. The goal of the present study is characterize other migraine relevant symptoms in mice after peripheral CGRP injection.
Methods
We used the Mouse Grimace Scale in order to investigate pain induced by peripheral CGRP. Orbital tightening, nose bulge, cheek bulge, ear position and whiskers orientation were the different modalities scored on a scale of 0 to 2. We also used an activity wheel (number of wheel turns over 2 hours) in order to investigate whether mice would be discouraged to engage in an otherwise pleasurable activity (non-essential movements) after peripheral injection of CGRP, mimicking the clinical observation that movement exacerbates migraine symptoms. In complement, animals’ activity was recorded over time using an automated activity assay (essential movements).
Results
We report that peripheral administration of 0.1 mg/kg i.p. CGRP significantly induces pain in CD1 mice starting 10 minutes after the injection, compared to vehicle administrated animals. In those conditions, CGRP is also able to decrease the amount of wheel turns immediately after injection, and for at least 45 minutes. Preliminary results show that the overall activity of the animals is decreased during the first hour after the injection of CGRP. This decrease however is relatively small compared to the one observed with the activity wheel, suggesting a discrimination between essential and non-essential movements.
Conclusion
Peripheral injection of CGRP in mice seems to recapitulate many clinically relevant symptoms observed in migraine headache patients. Those findings further validate the possible action of CGRP in the periphery in the development of migraine symptoms.
Disclosure of Interest
None Declared