Cluster Headache and Other Trigeminal Autonomic Cephalalgias
IHC-OR-040
Efficacy and safety of fremanezumab for the prevention of episodic cluster headache: results of a randomized, double-blind, placebo-controlled, phase 3 study
Richard B. Lipton1,2,*, Hans C. Diener3, Piero Barbanti4,5, Jimmy Schiemann6, Steve Barash6, Joshua M. Cohen6, Andrew H. Ahn6 and Peter J. Goadsby7
1Albert Einstein College of Medicine
2Montefiore Medical Center, Bronx, NY, United States
3Universitätsklinikum Essen, Essen, Germany
4Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele Pisana
5San Raffaele University, Rome, Italy
6Teva Pharmaceuticals, Frazer, PA, United States
7NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College London, London, United Kingdom
Objective: To evaluate efficacy, tolerability, and safety of fremanezumab for preventive treatment of episodic cluster headache (ECH) in this study.
Methods: Eligible patients (pts) with a ≥12-month (mo) history of ECH were randomized (1:1:1) to high-dose (HD) fremanezumab (mo 1/2/3, 900 mgIV/225 mgSC/225 mgSC), lower-dose (LD) fremanezumab (675 mgSC/PBO/PBO), or matched monthly PBO. The primary efficacy endpoint was mean change from baseline (BL) in weekly (wkly) average number of CH attacks during the first 4 weeks (wks). This study was terminated early for futility based on interim analyses (presented here).
Results: Prior to termination, 169 pts were randomized. With PBO, LD, and HD fremanezumab, BL wkly average numbers of CH attacks were 13.0, 13.3, and 12.7, respectively. The primary endpoint was not met; mean changes from BL in wkly average CH attacks during 4 wks were not significantly different for HD (−7.6) or LD (−5.8) fremanezumab vs PBO (−5.7; P ≥ 0.1). The reduction in wkly average CH attacks at 3 wks with HD fremanezumab was −8.5 vs −5.8 with PBO (P = 0.0930). With HD fremanezumab vs PBO, there was also a significant decrease in acute medication use from BL during 12 wks and wkly over the first 8 wks (P < 0.05, not multiplicity adjusted). No safety signals were identified.
Conclusion: Though this study was terminated because an interim analysis for the 4-wk primary endpoint demonstrated futility, results suggest that HD fremanezumab may have improved outcomes for ECH pts at wk 3. A low BL attack frequency, high PBO response, and the selection of wk 4 vs wk 3 for the primary endpoint may have contributed to the lack of separation between fremanezumab and PBO. Results also suggest CH may require higher monoclonal antibody doses than migraine. This negative study provides insight into the design of future studies in CH.
Disclosure of Interests: R. B. Lipton is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. Dr. Lipton receives research support from the NIH, the Migraine Research Foundation and the National Headache Foundation. Dr. Lipton serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. Dr. Lipton holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. Dr. Lipton receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. H.C. Diener has served as an investigator on clinical studies sponsored by Teva Pharmaceuticals. In the last 3 years, H.C. Diener received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from: Alder, Allergan, Amgen, Autonomic Technology, Bristol-Myers Squibb, CoLucid, Electrocore, Ipsen Parma, Lilly, Medtronic, MSD, Novartis, Pfizer, Sanofi, Schaper and Brümmer, Teva and Weber & Weber. Financial support for research projects was provided by Allergan, Electrocore, MSD and Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF) and the European Union. H.C. Diener has no ownership interest and does not own stocks of any pharmaceutical company. H.C. Diener serves on the editorial boards of Cephalalgia and Lancet Neurology. H.C. Diener chairs the Clinical Guidelines Committee of the German Society of Neurology and is member of the Clinical Trials Committee of the IHS. P. Barbanti serves as consultant, advisory board member, investigator on clinical studies, or has received honoraria from Amgen, Alder, Allergan, Bayer, Electrocore, Eli Lilly, GSK, Lusofarmaco, New Penta, Novartis, Teva Pharmaceuticals, Visufarma. J. Sciemann, S. Barash, J.M. Cohen, and A.H. Ahn are employees of Teva Pharmaceuticals. P.J. Goadsby reports grants and personal fees from Amgen and Eli Lilly and Company, and personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Electrocore LLC, eNeura, Impel Neuropharma, Mundipharma, Novartis, Teva Pharmaceuticals, Trigemina Inc., medicolegal work, Massachusetts Medical Society, UpToDate, Oxford University Press, and Wolters Kluwer; he holds a patent for magnetic stimulation for headache assigned to eNeura without fee.
Comorbidity of Primary Headaches
IHC-OR-028
Functional and metabolic changes in visual snow syndrome: a combined BOLD fMRI and MR-spectroscopy study
Francesca Puledda1,2,*, Dominic Ffytche3, David J. Lythgoe4, Owen O'Daly4, Christoph Schankin5, Steve C. Wlliams4 and Peter J. Goadsby1,2
1Headache Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, United Kingdom
2NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital, London
3Department of Old Age Psychiatry
4Centre for Neuroimaging Sciences, Dept. of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, United Kingdom, London, United Kingdom
5Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, Bern, Switzerland
Objective: Patients with visual snow (VS) suffer a pan-field visual disturbance described as continuous tiny flickering dots with frequent additional visual symptoms. A previous [18F]-FDG PET neuroimaging study in patients with VS showed increased glucose metabolism in the right lingual gyrus.
In order to understand more about the pathophysiology of visual snow and to confirm previous neuroimaging results, we performed a combined magnetic resonance spectroscopy (MRS) and functional MRI study in patients with VS compared to healthy volunteers. By placing the MRS volume of interest over the right lingual gyrus, we investigated the neurochemical properties of this area. Blood oxygenation level dependent (BOLD) responses were studied in response to visual stimulation in all subjects.
Methods: Subjects with VS (n = 24) and healthy volunteers (n = 24), matched by age and gender, took part in the study. Scanning was performed on a 3T General Electric MR750 MRI scanner. For MRS, proton spectra were acquired using a point resolved spectroscopy (PRESS) protocol. BOLD responses were obtained with a single fMRI experiment consisting of a 40 seconds on/off block-design, characterized by a simulation of visual snow alternated with darkness. The study was approved by the London – City & East Research Ethics Committee (Reference number: 16/LO/0964). Imaging was analysed using SPM 12 and MRS using LC model.
Results: There was a significant increase in lactate concentrations in the VS group with respect to controls (0.64 ± 0.9 mmol/L vs. 0.08 ± 0.2 mmol/L; p = 0.006). We found BOLD signal deactivation in VS patients but not controls in the left anterior insula in a whole brain analysis (k = 291; p = 0.025; x = −34, y = 12, z = −6) and, following SVC, in the contralateral insula as well (k = 100; p = 0.003; x = 44, y = 14, z = −2). Furthermore, there was a significant negative correlation between lactate concentrations and BOLD response in the right lingual gyrus (p = 0.001; r = −0.46), in VS patients only.
Conclusion: These results suggest that patients with VS have a localised disturbance in extrastriate anaerobic metabolism, which may cause a decreased metabolic reserve for the regular processing of external visual stimuli. As shown by the BOLD analysis, visual snow is also characterized by a difference in bilateral insular response in the on or off phase of a visual stimulus mimicking VS itself; this could be due to altered interoception and disruptions within the salience network.
Disclosure of Interest: None Declared.
Headache Pathophysiology – Basic Science
IHC-OR-032
Extracranial injections of onabotulinumtoxinA in combination with iv injection of atogepant attenuates activation of HT and WDR neurons by CSD
A Melo-Carrillo1,2, A M. Strassman1,2, A J. Schain1,2, A Adams3, M F. Brin3,4, R Burstein1,2,*
1Anesthesia, BIDMC
2HMS, Boston, United States
3Allergan, Ireland, Ireland
4UCI, LA, United States
Objective: The goal of the current study was to determine the effects of a combination therapy with onabotulinumtoxinA (BoNT-A) and atogepant (Ato) on the responsiveness of central (SpV) trigeminovascular neurons to CSD; a goal that partially depends on knowing BoNT-A effects on activation of nociceptors by CSD.
Methods: In the BoNT-A/Ato experiments, we studied responses to a single wave of CSD in 22 dura-sensitive neurons in SpV (11 HT, 11 WDR) of animals treated with saline (injected 7–11 d before recording) and vehicle (PEG 400) injected iv 1 h before CSD (control group), or BoNT-A and Ato injected at same timepoints (BoNT-A/Ato group). In the BoNT-A only experiments we studied responses to CSD in 54 C- and Ad-meningeal nociceptors pretreated with BoNT-A or saline.
Results: All central neurons: In control animals, a single wave of CSD activated 70% of all central trigeminovascular neurons, whereas in the BoNT-A/Ato group, it activated only 8.3% (X2 = 0.002). In the control group, the mean firing increased >230% 1 and 2 h after CSD. In the BoNT-A/Ato group, the mean firing remained unchanged after CSD.
HT neurons: CSD activated 80% of the neurons in the control group, and 16.6% in the BoNT-A/Ato group (X2 = 0.035). The mean firing increased 162.1 (1 h) and 251.1% (2 h) after CSD in the control group and remained unchanged in the BoNT-A/Ato group.
WDR neurons: CSD activated 60% of the neurons in the control group, and 0% in the BoNT-A/Ato group (X2 = 0.026). The mean firing increased 542.9 (1 h) and 199.4% (2 h) after CSD in the control group and remained unchanged in the BoNT-A/Ato group.
BoNT-A only, C and Ad neurons: BoNT-A reduced significantly the prolonged firing of the C-but not the Ad fibers after CSD.
Conclusion: The combination therapy of BoNT-A and atogepant prevents the activation of both HT and WDR neurons by CSD. These findings raise the possibility that chronic migraine aura patients may benefit from treatment approach that combines BoNT-A and blockade of CGRP signaling.
Disclosure of Interests: This study was supported by Allergan, and NIH grants R37-NS079678, RO1 NS069847, RO1 NS094198 (RB).
IHC-OR-036
Fremanezumab, an anti-CGRP monoclonal antibody, reduces stimulated CGRP release from rat cranial dura mater
Birgit Vogler1, Julika Nakajima1, Kimberly Mackenzie2, Jennifer Stratton2, Karl Messlinger1,*
1Institute of Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
2Teva Biologics, Redwood City, United States
Objective: Calcitonin gene-related peptide (CGRP) is regarded as an important mediator in migraine. CGRP is released from trigeminal neurons during migraine pain, inhibition of the CGRP mediator system is therapeutic in migraine and infusion of CGRP can induce migraine-like headache in migraineurs. Most recent developments in migraine therapy aim at blocking CGRP or its receptor with monoclonal antibodies. To clarify the effects of CGRP sequestering in the trigeminal system, the stimulated release of CGRP from meningeal tissues was studied in an animal model.
Methods: Fremanezumab, an anti-CGRP monoclonal antibody (30 mg/kg) or an isotype control antibody was subcutaneously injected into adult Wistar rats. One, 3 and 10 days later rats were intraperitoneally injected with glycerol trinitrate (GTN, 5 mg/kg) or vehicle and 4 hours later sacrificed for measurement of CGRP release from the cranial dura mater in the hemisected head preparation stimulated by the TRPV1 agonist capsaicin (5 × 10−7 M). In addition, the total CGRP content of excised trigeminal ganglia was measured using an ELISA.
Results: The basal as well as the stimulated CGRP release were significantly lower in rats treated with fremanezumab compared to the isotype control. These differences were pronounced 3 days after antibody treatment, in animals injected with GTN and in females compared to males. The weight-normalized CGRP content in the trigeminal ganglia was not significantly different between fremanezumab and the isotype control but was higher after GTN treatment and in males compared to females.
Conclusion: Following treatment with fremanezumab, the CGRP release from meningeal afferents measured by ELISA is reduced, particularly when CGRP is upregulated after provocation with the “NO donor” GTN. Fremanezumab reduces the free CGRP and may interrupt trigeminal afferent sensitization induced by high levels of CGRP in the tissue.
Disclosure of Interests: Kimberly Mackenzie and Jennifer Stratton are employed at Teva Biologics.
Headache Pathophysiology – Imaging and Neurophysiology
IHC-OR-029
Effect of pituitary adenylate cyclase-activating polypeptide-27 on cerebral hemodynamics in healthy volunteers: a 3T MRI study
Hashmat Ghanizada1,*, Messsoud Ashina1 and Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
1Neurology, Danish Headache Center, Glostrup, Denmark
Objective: Pituitary adenylate cyclase-activating polypeptide (PACAP) has emerged as an important signaling peptide in migraine pathogenesis. Recently, we have shown that the less-abundant PACAP isoform, PACAP27, induced migraine and headache in patients equipotently to PACAP38. The present study examined the effect of PACAP27 on cerebral hemodynamics in healthy volunteers using high resolution magnetic resonance angiography (MRA).
Methods: Eighteen healthy volunteers received infusion of PACAP27 (10 pmol/kg/min) or placebo over 20 min and were scanned repeatedly in fixed intervals for 5 hours in a double-blind, randomized, placebo-controlled study. The circumference of extra-intracerebral arteries was measured and compared with PACAP38 data.
Results: We found significant dilation of middle meningeal artery (MMA) (p = 0.019), superficial temporal artery (p = 0.001) and external carotid artery (p = 0.039) after PACAP27 infusion compared to placebo. Whereas the middle cerebral artery (MCA) (p = 0.011) and internal carotid artery (ICA) (pICAcervical = 0.015, pICAcerebral = 0.019) were constricted. No effects on basilar artery (p = 0.708) and cavernous portion of ICA were found. Post hoc analyses revealed significant larger area under the curve for MMA after PACAP38 compared to PACAP27 (p = 0.033). We also found that PACAP27 induced headache in nine out of twelve (75%) volunteers and one (17%) after placebo.
Conclusion: In conclusion, PACAP27 induced headache and dilated extracerebral arteries (>5 h) and slightly constricted MCA in healthy volunteers. Post hoc analysis of PACAP38 data compared with PACAP27 showed that PACAP isoforms dilates MMA with significantly different magnitude.
Disclosure of Interest: None Declared.
IHC-OR-033
Central pain processing is altered in Persistent Idiopathic Facial Pain
Christian Ziegeler1,*, Laura H. Schulte1 and Arne May1
1Systems Neuroscience, UNIVERSITY MEDICAL CENTER HAMBURG-EPPENDORF, Hamburg, Germany
Objective: Persistent Idiopathic Facial Pain (PIFP) is a poorly understood chronic pain syndrome of the face, formerly known as atypical facial pain. It is characterized by a constant painful sensation without neurological abnormalities and without clinically objectifiable cause. Similarities to neuropathic pain conditions have been discussed and are currently thought to be relevant for the pathophysiology of this disease. In this study we aim to characterize the altered central pain processing in PIFP via functional magnetic resonance imaging (fMRI).
Methods: 22 patients suffering from PIFP and 15 healthy controls (HC) underwent a standardized and well-established paradigm of painful stimulation of the trigeminal nerve using gaseous ammonia. Functional images were acquired within a 3T MRI scanner using an optimized protocol for high resolution echoplanar brainstem imaging.
Results: PIFP patients show a significantly stronger activation to painful stimulation in the spinal trigeminal nucleus (sTN). Furthermore, our data point towards a bilateral activation of medial nuclei of the thalamus in these patients and in contrast to that towards a stronger activation of the insula in healthy controls as a response to painful stimulation. These two latter findings however did not reach statistical significance.
Conclusion: Our data suggest that abnormal central pain processing plays a role in the pathophysiology of PIFP. An integration of these findings into neuropathic pain models might help to gain a better general understanding of the pathophysiology of PIFP.
Disclosure of Interests: CZ received speaker honoraria and from Novartis, Teva, Allergan and Lilly and received consulting fees from Novartis and Teva. LHS received speaker and consulting fees from Allergan. AM is the editor-in-chief of Cephalalgia and reports no conflicting interests.
Migraine Acute Therapy
IHC-OR-038
Acute Treatment Patterns Among New Triptan Treatment Users and Potential Triptan-Insufficient Responders
Anand R. Shewale1, Steven C. Marcus2, Richard B. Lipton3, David W. Dodick4,*, Hema N. Viswanathan1 and Jalpa A. Doshi2
1Allergan plc, Irvine, CA
2University of Pennsylvania, Philadelphia, PA
3Albert Einstein College of Medicine, Bronx, NY
4Department of Neurology, Mayo Clinic, Phoenix, AZ, United States
Objective: To examine real-world patterns of acute treatment of migraine among new triptan users and potential triptan-insufficient responder (TIR) patients.
Methods: Adult patients in the United States were selected if they had ≥1 triptan claim between 1/1/2013 and 31/12/2013 (first claim = index date) and 12 months of pre- and 24 months of post-index continuous enrollment in the 2012–2015 Clinformatics Data Mart (CDM)™ claims database. Patients were required to have ≥1 migraine diagnosis but no triptan claims in the pre-index period. Potential TIR patients were identified as patients who either (i) did not refill a triptan but used a nontriptan medication or (ii) refilled a triptan but augmented it with a nontriptan medication over the 24-month follow-up. Patients who continued filling triptan therapy only were categorized as triptan-only continuers. Treatment patterns of triptans, ergots, butalbital, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids filled within 15 days of a medical claim with a migraine diagnosis were examined over 6-, 12-, and 24-month periods.
Results: Of 10,509 new triptan users, 3102 (29.5%) were potential TIR patients, 4371 (41.5%) were triptan-only continuers, and the remainder (29%) did not refill either triptans or other acute medications. In the overall sample, 6.5%, 9.5%, and 13.9% switched to or added a different triptan over 6, 12, and 24 months, respectively. Even among potential TIR patients, only 11% and 15% tried a different triptan within 6 and 12 months, respectively, which represents 3.3% and 4.5% of the overall sample. Opioids were the most commonly used nontriptan medication by TIR patients within the first 12 months: 52% filled an opioid medication, 69.5% of whom were new opioid users.
Conclusion: High rates of triptan discontinuation, minimal use of ≥2 different triptans, and high opioid use among new triptan users suggest potentially suboptimal response or tolerability issues with current standard of care and the need for new acute treatments.
Disclosure of Interests: Sponsorship: Allergan plc, Dublin, Ireland.
Anand S. Shewale is a full-time employee and shareholder of Allergan. Steven C. Marcus is a consultant for Allergan. Richard B. Lipton serves on the editorial boards of Neurology and Cephalalgia and as senior advisor to Headache. He has received research support from the NIH. He also receives support from the Migraine Research Foundation and the National Headache Foundation. He has reviewed for the NIA and NINDS, and has served as consultant or advisory board member for or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, and Vedanta. He receives royalties from Wolff’s Headache (8th Edition, Oxford University Press), Informa, and Wiley. He holds stock options in eNeura Therapeutics and Biohaven. David W. Dodick, MD, within the last 36 months, reports personal fees from Acorda, Amgen, Alder, Allergan, Autonomic Technologies, Biohaven, Colucid, Eli Lilly, eNeura, Foresight Capital, Neurolief, Zosano, WL Gore, Vedanta Associates, Promius Pharma, Magellan Healthcare, CC West Ford Group, Nocira, Novartis, NuPathe, Supernus, Electrocore, Tonix, Teva, Alcobra, Insys, Ipsen, Charleston Laboratories, Biocentric, Theranica, Xenon, and ZPOpco; travel expense reimbursement and speaking fee from Sun Pharma; anticipated income from consulting within the next 3 weeks not previously reported from Impel Pharmaceuticals (currently under review by Mayo Clinic Medical Industry Relations Committee); compensation for activities related to a data safety monitoring committee from Axsome; speaking fees or fees related to CME content development from Healthlogix, Medicom Worldwide, Medlogix Communications, MedNet, Miller Medical Communications, PeerView Operation Services America, Web MD/Medscape, American Academy of Neurology, American Headache Society, PeerView Institute for Medical Education, Chameleon Communications, Academy for Continued Healthcare Learning, Universal Meeting Management, Haymarket Medical Education, Global Scientific Communications, UpToDate, and Meeting LogiX; royalties from editorial or book publishing from Oxford University Press, Cambridge University Press, Wiley Blackwell, Sage, and Wolters Kluwer Health; and a consulting use agreement through his employer with NeuroAssessment Systems and Myndshft. He holds equity in Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, and Epien, and serves on the board of directors of King-Devick Technologies and Ontologics. Hema N. Viswanathan is a full-time employee and shareholder of Allergan. Jalpa A. Doshi is a consultant for Allergan.
IHC-OR-041
Acute Treatment with Rimegepant 75 mg Confers Clinically Relevant Improvement in Migraine-Related Disability: Results from a One Year, Open-Label Safety Study (BHV3000-201)
Gilbert Litalien1,*, Robert Croop1, Elyse Stock1, Alexandra Thiry1, Meghan Lovegren1, Chris Jensen1, Kathryn Cowie2, Vladimir Coric1 and Richard Lipton3
1Biohaven Inc, New Haven
2Wake Forest, Winston-Salem
3Neurology, Albert Einstein College of Medicine, New York, United States
Objective: Epidemiologic studies have shown that migraine is among the most disabling neurologic conditions, burdening adults in their most productive years. The effect of rimegepant 75 mg oral tablet on migraine-related disability was assessed over 52 weeks of use as an acute treatment.
Methods: BHV-3000-201 is a multicenter, 1 year, open-label safety study of rimegepant 75 mg oral tablet. Eligible subjects include adults with ≥1 year history of migraine (ICHD-3 beta) who have been instructed to treat migraine attacks of any pain intensity with rimegepant 75 mg up to once daily as-needed for up to 52 weeks. Disability was assessed at baseline and Weeks 12, 24, 36, and 52 via the Migraine Disability Assessment (MIDAS), a validated 5-item instrument that queries migraine-related absenteeism and lost productivity at work, school, and home, as well as missed family, social, and leisure activities. Mean changes from baseline in total scores were analyzed post-hoc with paired t-tests, with decreasing scores signifying benefit.
Results: A total 1789 subjects was assessed. At Weeks 12, 24, 36, and 52, populations of 1631, 1211, 1085, and 917 subjects respectively were analyzed. Baseline mean total MIDAS score was 33.0 ± 0.8 (SEM) corresponding to the grade of severely disabled. Mean [95% C.I.] change from baseline in total MIDAS score was −12.5 [−13.9, −11.1] at Wk 12; −14.2 [−15.8, −12.6] at Wk 24; −14.8 [−16.6, −13.1] at Wk 36; and −14.1 [−15.9, −12.2] at Wk 52. Improvements in migraine-related disability were clinically and statistically significant at all time points p < .0001).
Conclusion: Acute treatment with rimegepant 75 mg confers significant improvement in migraine-associated disability, transitioning patients from severe to moderate disability within 3 months. This improvement was sustained out to one year. Observed changes exceeded the minimum clinically important difference (5 disability days/3mos) by nearly three-fold at all time points. These benefits would favorably impact healthcare costs, workplace productivity, and patient wellbeing.
Disclosure of Interests: GL, RC, ES, CJ, VC are employees and shareholders of Biohaven; RL is a consultant and shareholder to Biohaven.
IHC-OR-043
Long-term Safety of Qtrypta for the Acute Treatment of Migraine – 1-year Safety Results of Nearly 6,000 Treated Attacks
Stephanie Nahas1,*, Pete Schmidt2, Jean Engels2 and Donald Kellerman2
1Thomas Jefferson University, Philadelphia
2Zosano Pharma, Fremont, United States
Objective: Qtrypta is an intracutaneous microneedle formulation of zolmitriptan developed for acute migraine. Efficacy for freedom from pain and most bothersome symptom (MBS) at 2 hours was demonstrated in a previous randomized double-blind placebo-controlled trial. Our objective was to evaluate the safety of repeated use of Qtrypta 2 × 1.9 mg for migraine attacks.
Methods: During a 2-week run-in, migraine diagnosis and attack frequency of at least 2/month were confirmed via e-Diary. Subjects then recorded migraine symptoms, treatment effectiveness, and application site skin observations at 30 minutes, 2, 12, 24, and 48 hours post- dose. They completed the Migraine Assessment of Current Therapy (M-ACT) at all scheduled visits. Standard safety procedures and investigator assessment of application sites were done at each visit. Labs and ECGs were performed at beginning and end of study.
Results: In all, 342 subjects qualified, 335 treated at least one attack, 257 completed 6 months, and 127 completed 12 months. The average number of treatments/month was 1.9. The most frequent reason for premature discontinuation was not having 2 attacks/month (n = 79). Sixty subjects discontinued between 6 and 12 months once goals were achieved. Sixteen subjects discontinued due to adverse events (AEs); 5 of these were application site reactions, all of which were mild lasting one day or less. The most commonly reported AEs were mild erythema and swelling at the application site (approximately 90% of subjects); more than 80% of both resolved by 48 hours. Application site pain was reported by 14% of subjects on the first treatment, but by only 1% on the 25th. Grading of skin findings did not change appreciably across the 1st, 5th, 15th or 25th treatment. No neurologic adverse event exceeded 2%. Dizziness was reported by 1.8% of subjects. Pain freedom was achieved in 44% of attacks, and MBS freedom was achieved in 62%. M-ACT scores averaged 3.6 out of 4, demonstrating excellent efficacy and subject satisfaction.
Conclusion: Qtrypta was effective and well-tolerated throughout repeated use for the acute treatment of migraine. The most common AEs were mild application site erythema and edema which resolved quickly.
Disclosure of Interests: SN is on the advisory board for Zosano. PS, JE and DK are employees of Zosano.
IHC-OR-027
Efficacy of IV Hydromorphone versus IV Prochlorperazine plus Diphenhydramine for Migraine-associated Symptoms
Fred Cohen1,* and Benjamin W. Friedman2
1Department of Medicine
2Department of Emergency Medicine, Montefiore Medical Center, New York City, United States
Objective: Parenteral opioids are commonly used to treat migraines in acute care settings. We conducted a randomized trial of IV hydromorphone, an opioid, versus IV prochlorperazine, an anti-dopaminergic anti-emetic. The objective of this study is to compare improvement in migraine-associated symptoms (nausea, photophobia, and phonophobia) between the two groups.
Methods: This was a randomized, double-blind comparative effectiveness study conducted in two emergency departments in the Bronx, NY, USA. Patients who met ICHD3 criteria 1.1 for migraine without aura, or ICHD3 criteria 1.5.1 for probable migraine without aura were eligible for participation. Patients were excluded if they had used an opioid within the previous month. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV. Diphenhydramine was administered to prevent akathisia (a common side effect of IV prochlorperazine). The outcomes of interest were sustained symptom relief for nausea, photophobia, and phonophobia. Sustained relief was defined as having that particular symptom at baseline with complete improvement within two hours after medication administration and no symptom relapse within the subsequent 48 hours.
Results: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15 out of 49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95%CI: 20%–57%, p = 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13 out of 62 (20.9%) in the hydromorphone arm (ARR = 20.8%, 95%CI: 4.3%–37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16 out of 59 (25.4%) in the hydromorphone arm (ARR = 17.5%, 95%CI: 0.26%–34.8%, p = .049).
Conclusion: IV prochlorperazine plus diphenhydramine is significantly more effective than IV hydromorphone for the acute treatment and complete resolution of migraine-associated symptoms.
Disclosure of Interest: None Declared.
IHC-OR-035
Acute Actions of Caffeine in the Trigeminocervical Complex Relevant to Headaches
Tatiane Takahashi1,*, Alina Miedzik1 and Anna P. Andreou1,2
1Headache Research, Wolfson CARD, King's College London
2Headache Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
Objective: Caffeine, an adenosine receptor antagonist, is often used as an analgesic of headache attacks. Here we aimed to investigate its actions in the trigeminocervical complex (TCC), a key relay centre in headache’s pathophysiology.
Methods: The presence of A1 and A2 adenosine receptors in the trigeminal ganglia and TCC was investigated utilising qPCR and immunofluorescence. Caffeine at 10 and 60 mg/kg was injected in the trigeminovascular migraine model and activation of second order neurons in the TCC in response to Aδ- and C-fibre activation was assessed. In a different set of experiments, the actions of caffeine at 60 mg/kg were investigated on the number of Fos-positive cells in the TCC following trigeminovascular stimulation, assessed using immunohistochemistry.
Results: The A1 but not the A2 receptor was found to be present in both trigeminal ganglia and TCC. Caffeine at 10 and 60 mg/kg induced an initial facilitation of spontaneous neuronal firing (P < 0.05), which was in line with a rapid drop of blood pressure within the first 5 min of administration. Caffeine at both doses significantly inhibited Aδ-fibers activation in response to trigeminovascular stimulation (P < 0.05), while it had little effect of C-fibre evoked activity (P ≤ 0.49). Caffeine at 60 mg/kg reduced significantly the number of Fos-positive cells in the TCC following trigeminovascular stimulation (P < 0.05).
Conclusion: Acute caffeine at high doses blocks activation of the ascending trigeminovascular pathway, potentially by blocking the A1 receptor activity.
Disclosure of Interest: None Declared
Migraine Preventive Therapy
IHC-OR-039
Sustained efficacy and long-term safety of erenumab in patients with episodic migraine: 4+ year results of a 5-year, open-label treatment period
Messoud Ashina1, Peter J. Goadsby2, Uwe Reuter3, Stephen Silberstein4, David W. Dodick5, Denise E. Chou6, Shaloo Pandhi7, Fei Xue6, Feng Zhang6, Sunfa Cheng6, Daniel D. Mikol6,*
Objective: Erenumab (AMG334; Aimovig™, Amgen®, Novartis Pharma AG) is a fully human monoclonal antibody specifically designed for the prophylactic treatment of migraine. Long-term efficacy and safety data of erenumab for prevention of migraine are limited.
Methods: We conducted an efficacy and safety analyses at an interim 4+ years of a 5-year, open-label treatment period (OLTP) with erenumab in patients with episodic migraine (EM). In the OLTP, patients initially received erenumab 70 mg monthly (QM), and later (protocol amendment after ∼2 years) switched to 140 mg QM.
Results: Of the 250 patients who switched from erenumab 70 mg to 140 mg, 221(88%) completed OLTP or remained on 140 mg at 4+ years. Mean[SD] change from baseline, in monthly migraine days (MMD; 8.7[2.7]) to end of year 4+ was −5.8[3.8], and in acute migraine-specific medication treatment days (baseline: 6.1[2.7]) was −4.6(3.3). A ≥50%/≥75%/100% reduction in MMD at 4+ years was achieved by 77%/56%/33% of patients, respectively. The median(Q1, Q3) exposure for 383 patients who received ≥1 dose of erenumab 70 mg or 140 mg was 58.5(17.0, 62.2) months. The exposure-adjusted incidence rate/100 patient-years of AEs and serious AEs was 124.9 and 3.8, respectively. AEs were less frequent vs. placebo; nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7) were the most frequent. Rate of SAEs during OLTP was similar to that observed for erenumab and placebo during shorter term period. Compared to shorter term period, the exposure-adjusted incidence rate/100 patient-years for constipation did not increase during OLTP (Table) and no new safety signals or increase in incidence of AEs or SAEs were observed. 19(5.0%) patients discontinued due to an AE.
Conclusion: In a 4+ year interim analysis of the OLTP with erenumab in EM, long-term treatment demonstrated sustained reductions in migraine frequency, and was well tolerated and safe.
Disclosure of Interests: This study (NCT01952574) was supported by Amgen Inc. Erenumab is codeveloped by Amgen and Novartis.
Messoud Ashina – Consultant or scientific advisor for Allergan, Amgen, Alder, ATI, Novartis, and Eli Lilly; primary investigator for Amgen, and GM-11 gamma-Core-R trials; grants from Lundbeck Foundation, Research Foundation of the Capital Region of Copenhagen, Danish Council for Independent Research-Medical Sciences and Novo Nordisk Foundation; Peter J. Goadsby – Consulting fee, speaking/teaching fee, and/or research grants: Akita Biomedical, Alder Biopharmaceuticals, Allergan, Allergan, Amgen, Autonomic Technologies, Avanir Pharmaceuticals, Cipla Ltd, CoLucid Pharmaceuticals, Inc., Dr. Reddy's Laboratories, electroCore, Inc., Eli Lilly, eNeura, Inc., Journal Watch, Massachusetts Medical Society, Medico-Legal Journal, Novartis, Oxford University Press, Pfizer, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina, Inc., UpToDate, Wolters Kluwer; Uwe Reuter – consulting fee, speaking/teaching fee, and/or research grants: Allergan, Amgen, Autonomic Technologies, CoLucid, ElectroCore, Novartis, Pharm Allergan, Eli Lilly, and Teva Pharmaceuticals; Stephen Silberstein – Consultant and/or advisory panel member for and/or honoraria from Alder, Allergan, Amgen, Avanir, Dr. Reddy’s, eNeura, ElectroCore Medical, Medscape, Medtronic, Mitsubishi Tanabe Pharma America, NINDS, Supernus, Trigemina, and Teva; David W. Dodick – Within the last 12 months,personal fees from Amgen, Alder, Allergan, Autonomic Technologies, Biohaven, Eli Lilly, eNeura, Foresight Capital, Neurolief, Zosano, WL Gore, Vedanta Associates, Promius Pharma, Nocira, Novartis, Electrocore, Teva, Ipsen, Impel, Satsuma, Theranica; Compensation for activities related to data safety monitoring committee from Axsome; Compensation related to CME content development: Healthlogix, Medicom Worldwide, Medlogix Communications, MedNet, Miller Medical Communications, PeerView Operation Services America, Web MD/Medscape, American Academy of Neurology, American Headache Society, PeerView Institute for Medical Education, Chameleon Communications, Academy for Continued Healthcare Learning, Universal Meeting Management, Haymarket Medical Education, Global Scientific Communications, UpToDate, Meeting LogiX; Royalties from editorial or book publishing: Oxford University Press, Cambridge University Press, Wiley Blackwell, Sage, Wolters Kluwer Health; Consulting use agreement through employer: NeuroAssessment Systems, Myndshft; Equity (stock options): Aural Analytics, Healint, Theranica, Second Opinion/Mobile Health, Epien, Ontologics. Board of Directors position: King-Devick Technologies, Epien, Ontologics; Denise E. Chou – employee of and stockholder in Amgen; Shaloo Pandhi – employee of and stockholder in Novartis; Fei Xue – employee of and stockholder in Amgen; Feng Zhang – employee of and stockholder in Amgen; Sunfa Cheng – employee of and stockholder in Amgen; Daniel D. Mikol – employee of and stockholder in Amgen.
IHC-OR-042
A Randomized, Placebo-Controlled Study of Galcanezumab in Patients with Treatment-Resistant Migraine: Double-Blind Results from the CONQUER Study
Wim M. Mulleners1,*, Byungkun Kim2, Miguel J. Láinez3, Michel Lanteri-Minet4, Sheena K. Aurora5, Russell M. Nichols5, Shufang Wang5, Antje Tockhorn-Heidenreich6 and Holland C. Detke5
2Neurology Department, Eulji Hospital, Seoul, Korea, Republic Of
3Hospital Clínico Universitario, Universiada Católica de Valencia, Valencia, Spain
4Pain Department CHU Nice and FHU InovPain Côte Azur University, Nice, France
5Eli Lilly and Company, Indianapolis, United States
6Eli Lilly and Company, Windlesham, GU20 6PH, United Kingdom
Objective: The CONQUER study assessed galcanezumab efficacy and safety in patients with episodic or chronic migraine who had multiple migraine preventive treatment failures.
Exposure-adjusted incidence rate/100 patient-years for constipation.
Placebo
Erenumab 70 mg
Erenumab 140 mg
During the 12 weeks of shorter-term studies*
4.3
5.6
13.3
During the 4+ years of the OLTP
–
1.3
2.6
Pooled results across 4 placebo-controlled studies; OLTP, open-label treatment period.
Methods: In this phase 3, double-blind study, patients were aged 18–75 years, met criteria for episodic or chronic migraine, had 4–29 migraine headache days per month, and had 2–4 migraine preventive medication category failures in the past 10 years. Eligible patients were randomized 1:1 to receive galcanezumab 120 mg/month (with 240-mg loading dose; N = 232) or placebo (N = 230). Headache information was captured in a daily electronic diary. Primary endpoint was overall mean change from baseline in number of monthly migraine headache days across Months 1–3. Key secondary endpoints included ≥50%, ≥75%, or 100% reduction in monthly migraine headache days and change on the Migraine-Specific Quality of Life-Role Function Restrictive domain.
Results: Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo. The galcanezumab group averaged 4.1 fewer monthly migraine headache days from a baseline of 13.4, and the placebo group averaged 1.0 fewer from a baseline of 13.0 (between-group difference −3.1; p < 0.0001; 95% CI: −3.9, −2.3; effect size = 0.72). Galcanezumab was superior to placebo on all key secondary endpoints. There were no statistically significant differences in treatment-emergent adverse events except for those reported more frequently in the placebo group. One galcanezumab-treated patient discontinued early due to an adverse event (rash).
Conclusion: Galcanezumab was superior to placebo in preventive treatment of migraine and was safe and well tolerated in patients who had previous failures to standard-of-care preventive treatments.
Disclosure of Interests: Wim M. Mulleners: Financial compensation for a Lilly European Advisory Board.
ByungKun Kim: Advisory role from Eli-Lilly, Teva, Novartis, Allergan and National Pension Service of Korea and received the honoraria for speeches from Allergan, SK chemicals, YuYu, and Sandoz Pharma.
Miguel JA Láinez: Honoraria, consultation fees and research grants from: Allergan, Amgen, ATI, Bayer, Bial, Boehringher, Chiesi, ElectroCore, Eli Lilly, Medtronic, Novartis, Otsuka, Roche, Teva and UCB.
Michel Lanteri-Minet: In the last five years, received honoraria for advisory boards, speaker panels or investigation studies from Allergan, Amgen, Astellas, ATI, BMS, Boehringer, Boston Scientific, CoLucid, Convergence, Glaxo-SmithKline, Grunenthal, Lilly, Medtronic, Menarini, MSD, Novartis, Pfizer, ReckittBenckiser, Saint-Jude, Sanofi-Aventis, Teva, UCB, Zambon.
Sheena K. Aurora: Employee and minor stockholder of Eli Lilly and Company.
Russell M. Nichols: Employee and minor stockholder of Eli Lilly and Company.
Shufang Wang: Employee and minor stockholder of Eli Lilly and Company.
Antje Tockhorn-Heidenreich: Employee and minor stockholder of Eli Lilly and Company.
Holland C. Detke: Employee and minor stockholder of Eli Lilly and Company.
IHC-OR-025
Treatment of chronic migraine with Erenumab alone or as an add on therapy; a real world prospective observational study
Guy P. Boudreau1,* and Demers Catherine1
1Neurology, Clinique des céphalées de Montréal, Montreal, Canada
Objective: We treated chronic migraineurs that have failed more than 3 preventive drugs with Erenumab alone or as an add on therapy to reduce the frequency of monthly headache days, to evaluate If the add on of Erenumab to another preventive therapy is superior to Erenumab alone, and assess all adverse events related to the use of Erenumab.
Methods: Migraineurs with 15–30 headache days per month at baseline with or without an actual preventive drug, were clustered in 3 categories. Failure of Erenumab was defined as no improvement in the frequency of monthly headache days. Group I: no preventive therapy, prior to the start of Erenumab. (No botox cohort),Group II: on Botulinum Toxin A (Botox), prior to the add on therapy with Erenumab. (Botox cohort),Group III: on an oral preventive drug, prior to the add on therapy with Erenumab. (No Botox cohort).
Results: Patients were evaluated after the 4 th injection session. A total of 158 patients were involved in this study. 118 patients (75%), received Erenumab 140 mg., and 40 patients (25%) received 70 mg., In the Botox cohort, of 650 patients, 90 (13%) patients were eligible. In the no Botox cohort, 533 patients, 83 (15%) patients were eligible. From all cohorts; 53pts/158(34%) obtained no improvement. 36pts/158 (23%); obtained a reduction in intensity of headache only. 69pts/158 (43%); reduced the frequency of their monthly headache days. 57% of patients failed the primary end point. The primary objective being the reduction of monthly headache days, of these 69 patients: in group I: 16patients (26%), reduced their monthly hea dache days. In group II, 45 patients (65%), and group III, 11 patients (15%) reduced their monthly headache days by 5–7 days. In group II and III all patients became episodic, in group I, 25% stayed chronic, 75% became episodic. 72 adverse events were experienced during the 4 months of treatment, mostly with the 140 mg. dose. The most frequent were: constipation 34%, fatigue 19%, itching 7.5%, muscle cramps 6.3%, increased headache 4.4%, rhinitis 4.4%, injection site discomfort 3.7%, lack of energy 3.1%
Conclusion: In this study the add on of Erenumab to a preventive therapy is more effective than Erenumab alone, Botulinum toxin A with the add on of Erenumab was the most effective combination.
Disclosure of Interests: principle investigator in a Lilly clinical trial with galcanezumab
IHC-OR-026
The Aimovig “Wear-Off” Effect: A Retrospective Analysis
Rose Duncan1,*, Naveen George1 and Deborah Reed1
1Neurology, University Hospitals Cleveland Medical Center, Cleveland, United States
Objective: Recently, the class of Anti-CGRP monoclonal antibodies has been approved for use in the treatment of migraine headaches. With the advent of this migraine specific medication class, many chronic migraine patients have started this preventative treatment. The first FDA approved in this class is Aimovig (erenumab). As demonstrated in collaborative research, a small cohort of patients on this medication have been found to have a “wear-off” effect where Aimovig was found to not be as effective by the end of the month as it was at the beginning of the month. The primary objective of this study was to identify trends in demographics, migraine characteristics, and comorbidities among patients who experienced an Aimovig “wear-off” effect.
Methods: Through retrospective chart review, we identified patients that were started on Aimovig 140 mg monthly injections that had an initial response to medication at the beginning of the month, followed by an increase in frequency and severity of headaches by the end of the month. Patient demographics, BMI, migraine type, and comorbidities were assessed to identify trends among this cohort of patients experiencing an Aimovig “wear-off” effect.
Results: Of the 190 patients started on Aimovig in this outpatient headache specialty clinic, 17 were identified as having a “wear-off” effect. Of these 17 patients, patient age range spanned 30–76 years, however 76.5% were between the ages of 45 and 65. 76.5% were female, and 100% were Caucasian. 100% suffered from chronic migraine, and 94.1% had migraines without aura. 41.2% had an overweight BMI, and 23.5% were obese. 41.2% had cardiovascular comorbidities, 52.9% had psychiatric comorbidities, and 26.3% had BPPV. 64.7% had non-headache pain syndromes, including 23.5% with cervical dystonia and 23.5% with cervical radiculopathy.
Conclusion: Among patients with Aimovig “wear-off”, the vast majority were middle-aged, Caucasian, and female, and all but one denied migraine aura. Over half of patients had psychiatric comorbidities, and an even larger portion of patients had comorbid non-headache pain syndromes. BPPV, cervical dystonia, and cervical radiculopathy were surprisingly prevalent among this cohort. While many trends were identified, additional information is still necessary in order to further predict and identify patients at risk of this Aimovig “wear-off” effect.
Disclosure of Interest: None Declared
Other Primary Headache Disorders
IHC-OR-034
Analgesic effect of intranasal oxytocin in a rat model of trigeminal neuralgia
David C. Yeomans1,* and Mikhail Klukinov1
1Anesthesiology, Stanford University, Stanford, United States
Objective: Trigeminal neuralagia (TN), is a chronic syndrome manifesting primarily in episodes of “lightning like”-sharp pain, usually the results of trigeminal root compression (TRC) by an adjacent artery. Current therapy often provides incomplete management.
We have shown that nasally applied oxytocin concentrates in the trigeminal nerve and ganglia, and inhibits firing of peripheral and central trigeminal nociceptive neurons. The purpose of this study was to determine whether nasally applied oxytocin would attenuate the exquisite facial mechanical hypersensitivity that is observed in a rodent model of trigeminal neuralgia.
Methods: Male rats were prepared using a trigeminal neuralgia model (Klukinov and Yeomans, 2012), wherein crystals of a super absorbent polymer were stereotaxically placed between the trigeminal nerve root and the crista petrosa of the temporal bone. Over the next few days, the polymer absorbed moisture and expanded to form a compressing mass, resulting in exquisite hypersensitity to touch with a fine artists brush in the peri-oral region, which is assessed by blinded scoring of the response to stimuli. In order to establish the pharmacologic validity of the model, the effects of 4 days of daily high dose of carbemazepine (30 mg/kg, IP), the first line drug for the treatment of trigeminal neuralgia, was tested on perioral brush sensitivity was tested. In other similarly prepared rats, the effects of a single administration of nasal oxytocin (1.0 IU) was similarly tested.
Results: Behavioral Phenotype: Application of polymer crystals to the trigeminal nerve root produces a resident mass which compressed the trigeminal nerve root resulting in a behavioral phenotype highly reminiscent of human trigeminal neuralgia, including exquisite peri-oral hypersensitivity to brush.
Behavioral Pharmacology: Both daily treatment with carbamazapine for 4 days significantly and a single dose of nasal oxytocin both significantly decreased responsiveness to brush stimulation of the peri-oral face.
Conclusion: These results indicate that the trigeminal neuralgia-like behavioral phenotype consequent to chronic compression of the trigeminal nerve root of rats can be attenuated by nasal application of oxytocin, implying the potential of this treatment for patients suffering from TN.
Disclosure of Interests: Founder and shareholder Trigemina, Inc.
Post-Traumatic Headache
IHC-OR-037
CGRP dependent- and independent-mechanisms of acute and persistent post-traumatic headache following mild traumatic brain injury in mice
Jill Rau1,*, Edita Navratilova2, Janice Oyarzo1, Jason Tien3, Kimberly Mackenzie3, Jennifer Stratton3, Bethany Remeniuk2, Todd Schwedt1, Trent Anderson4, David Dodick1 and Frank Porreca1,2
1Mayo Clinic AZ, Scottsdale
2University of Arizona, Tucson
3Teva Biologics, Redwood City, CA
4University of Arizona College of Medicine, Phoenix, United States
Objective: The underlying physiological mechanisms of post-traumatic headache (PTH) and persistent PTH (PPTH) remain unknown, and there are no currently approved therapies for these often debilitating conditions. The aim of this study is to explore the efficacy and timing of intervention with a murine anti-calcitonin gene related peptide (CGRP) monoclonal antibody (mAb) in novel mouse models of PTH/PPTH.
Methods: Male C57Bl/6 J mice received sham or mild TBI (mTBI) from a weight drop that allowed free head rotation. Periorbital and hindpaw tactile stimulation were used to assess cutaneous allodynia (CA). Mice were challenged with stress, a common aggravator of migraine and PTH, by exposure to bright lights (i.e., bright light stress, BLS) 2 weeks after mTBI; CA was again assessed. A murine anti-CGRP mAb was administered after mTBI with different dosing regimens to investigate the effect of either early and sustained CGRP sequestration or late administration on CA.
Results: mTBI-mice, but not sham-mice, displayed acute periorbital and hindpaw CA. After resolution of CA, exposure to BLS evoked CA in mTBI-mice only. Early and repeated administration of an anti-CGRP mAb attenuated the development of acute CA and prevented BLS-induced CA. A single administration of an anti-CGRP mAb, prior to BLS challenge, did not prevent BLS-induced CA.
Conclusion: In clinically-relevant, novel models, mTBI-mice demonstrated transient periorbital and hindpaw CA suggestive of PTH-related pain and central sensitization; subsequent exposure to BLS re-established CA, suggestive of PPTH-related pain. Continuous early sequestration of CGRP prevented both PTH and PPTH. A single, delayed anti-CGRP mAb treatment was ineffective in preventing PPTH-like pain. These observations suggest that CGRP-related mechanisms underlie the symptoms of PTH and drive the development of central sensitization, increasing vulnerability to headache triggers and promoting PPTH. Early and continuous CGRP blockade following mTBI may represent a viable treatment option for PTH and for the prevention of PTH persistence.
Disclosure of Interests: This study was funded by Teva Pharmaceutical Industries Ltd.
Psychological and Behavioural Factors and Management
IHC-OR-030
Loneliness in migraine: results from a case-control study
Tim P. Jürgens1,*, Maria Dick1, Laura-Marie Brill1, Julia Rager1, Florian Rimmele1, Peter Kropp2 and Britta Müller3
1Dept. of Neurology, Headache Center North-East
2Institute of Medical Psychology and Medical Sociology
3Institute of Medical Psychology and Medical Sociology, University Medical Center Rostock, Rostock, Germany
Objective: While there is solid evidence for a bilateral correlation between psychiatric comorbidities and migraine, loneliness has been only been examined sparsely in migraine. Increased rates of loneliness have been reported in elderly patients with migraine. Importantly, loneliness correlates also with depression, physical activity and sleep. The aim of this study was to examine the correlation between migraine and loneliness in a case-control study.
Methods: In a case-control study, 112 patients (80% females, mean age 42 years) with migraine according to the ICHD-3 treated at a tertiary referral center and 107 controls (55% females, mean age 41 years) were recruited. Loneliness was determined with the German translation of the UCLA Loneliness Scale (20 items with a 5 point Likert scale with a sum score between 20–100 with higher scores indicating greater loneliness). Additionally, depression was assessed with the PHQ-9 (9 items). To detect statistical differences, a general linear model was used.
Results: The level of loneliness was higher among participants with migraine (M = 34.64, SD = 12.69) compared to controls (M = 29.04, SD = 7.18) and differed significantly (F(1,209) = 11.39, p < .001). There was no statistically significant difference in loneliness sum scores for the different age groups (F(2,208) = 0.48, p = .619), for sex (F(1,209) = 1.89, p = .171) and for the interaction case/control*sex (F(1,209) = 0.11, p = .740) and the interaction case/control*age group (F(2,208) = 0.39, p = .675). An additional linear regression was conducted which showed that depression is a predictor of loneliness ((β = .42, p < .001), while a group specific effect cannot be found anymore (β = −.06, p = .441).
Conclusion: Loneliness is more pronounced in patients with migraine and not related to age or sex in this sample. However, depression seems to predict loneliness. These results are important as both loneliness and depression are relevant comorbidities of migraine and underline the need of proper psychiatric assessment in migraine patients and rigorous treatment. Additional analyses on the influence of social networks will reveal further insights into this potentially relevant finding.
Disclosure of Interests: None.
Big Data
IHC-LB-001
Effect of digital smartphone application “Migräne App” on therapy decisions, compliance, treatment quality and headache parameter
Hartmut Göbel1,*, Bettina Frank1, Axel Heinze1, Anna Göbel1,2, Carl Göbel1,2, Sarah Karstedt1, Wiebke Zimmermann1, Johann Brunkhorst3 and Klaus Rupp4
1Kiel Migraine and Headache Center, Heikendorfer Weg 9–27, 24149 Kiel
2Clinic for Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562 Lübeck
3Techniker Health Insurance Company, Chief of Federal State Representation Schleswig-Holstein, Hopfenstraße 2c, 24114 Kiel
4Techniker Health Insurance Company, Chief of Supply Management Department, Bramfelder Straße 140, 22305 Hamburg, Germany
Objective: Tension-type headache and migraine are among the most prevalent disorders. The use of smartphones enables “apps” for digital therapy accompaniment. In this study, the use of the “migraine app” will be examined in the treatment of migraine and headache patients in an extensive population sample.
Methods: An online survey was developed. It contains socio-demographic variables, course of headache disorders, previous treatment as well as usage of the migraine app. The app establishes compliance to recommended therapy, treatment plan, and therapeutic rules devised by the treating physician. The data was compared to pen-and-paper documentation, prior to using the migraine app.
Results: 1.464 users participated in the study. Average age was 47.19 ± 11.37 years (87.4% female). Users suffered from headaches for 27.28 ± 13.6 years. Most (76.5%) were seen by general practitioners. 70.9% reported presentation of data from the app to their physician on consultation. 76.4% reported the app helped to adhere to treatment plan and rules designed with their physician. A significant reduction of headache days per months prior to usage (13,30 ± 7,45) in comparison to the time of survey conduction (10,03 ± 7,30) and significant reduction of intake of acute medication was seen (before: 7.61 ± 5.58 vs. ongoing: 6.78 ± 4.72 days). No gender/age differences were observed. A significant reduction of mean headache hours/month and headache intensity was ascertained (p < 0.0001)
Conclusion: The data shows that the digital treatment control for therapy decisions made by the physician is highly relevant. Therapy compliance is improved and possible complications such as medication-overuse headache are reduced. Overall, a marked improvement of treatment quality due to more easily available information and self-help tools can be observed.
Disclosure of Interest: None Declared.
IHC-LB-002
Is migraine frequency correlated with its periodicity? An annual follow-up of how migraine cycles
Víctor J. Gallardo1,*, Xim Cerda-Company1, Marta Torres-Ferrus1,2, Alicia Alpuente1,2, Jérôme Trochet3 and Patricia Pozo-Rosich1,2
1Headache Research Group, Vall d'Hebron Research Institute (VHIR)
Objective: To analyze the cyclic evolution of migraine patients over a 12-month period.
Methods: Prospective observational study. Patients were recruited according to completion of a digital migraine calendar, available on the midolordecabeza.org website, over a 12-month period. Basic clinical characteristics were recorded. A comparative trimestral analysis, identifying the variation coefficient (VC) and fold-change (FC) as a function of basal frequency intervals, was executed.
Results: 97 patients (83.5% female; mean age 44.0 ± 11.6 years) were analyzed: 71.1% met criteria for episodic migraine (EM) with a mean monthly frequency (MMF) of 8.1 ± 3.5 and 28.9% for chronic migraine (CM) with a MMF of 22.9 ± 4.9. At follow up, a 20.6% of participants were using preventative treatment. Patients with EM presented increased heterogeneity (VC) as compared to those with CM (EM-28% vs. CM-16%, p < 0.05). There were no differences in FC in respect to diagnosis. A negative correlation between frequency and FC (p < 0.05) was identified, which permitted us to detect that a MMF between 6–15 days co-occurred with a higher FC (p < 0.01) and worse disease progression (≤5d: 11.1%, 6–15d: 46.2% y >15d: 14.8%; p < 0.01). Factors associated with increased heterogeneous periodicity and exacerbation of symptoms include: younger age (p < 0.01), absence of aura (p < 0.05) and increased stress (p = 0.05).
Conclusion: EM patients with a basal frequency between 6–15 days present increased trimestral cyclical heterogeneity as compared to EM with <6 days and CM. In addition to the basal frequency, a younger age, absence of aura and higher stress levels are correlated with increased oscillatory behavior of trimestral frequency. Increased cyclical heterogeneity would therefore appear to imply an increased risk for disease progression.
Disclosure of Interest: None Declared.
IHC-LB-049
Network Analysis of Headache Literature Citations
Pengfei Zhang1,*
1Neurology, Rutgers Robert Wood Johnson Hospital, New Brunswick, United States
Objective: Citation analyses of headache literature have usually been conducted through direct keywords or topic searches of “headache” and/or “migraine” in databases. This method systematically excludes non-headache publications and may offer an incomplete view of areas influencing headache research. We seek to resolve this shortcoming by analyzing all PubMed Central (PMC) articles discovered through citations, up to 2 degrees of separations, from known headache articles.
Methods: We obtain an initial list of PMC articles, or seed articles, through keyword searches for “headache” and “migraine”. We then identify all PMC articles that each of our seed articles references. New articles discovered through this process are documented and their citations are also identified for the purpose of discovering more articles. We identify new articles through this process for a total of 2 iterations. The set of all articles obtained are included in our study.
We generate a network model as follows: each article is considered a “node” in the model; if one article references another then an “edge” exists between the two. We obtain the 10 most important articles based on 3 measures of interconnectedness: Degree centrality identifies nodes with the most edges. Between-ness centrality identifies nodes serving as bridges between subgroups. Closeness centrality identifies nodes occupying the shortest distances to all other articles in the network.
Results: Our model has 79666 nodes and 143154 edges. Top 10 articles by closeness centrality include: 6 research articles on either migraine genetics or aura pathophysiology, 4 review articles on migraine pathophysiology and burden of diseases. Top 10 articles by between-ness centrality include: 3 research articles on migraine genetics or aura pathophysiology, 3 review articles on migraine pathophysiology, 4 review article on migraine and cardiovascular diseases, pharmacology, and burden of diseases. Top 10 articles by degree centrality include review articles on topics of epidemiology, migraine and sleep pathophysiology, pharmacology, and molecular biology.
Conclusion: Review articles on migraine pathophysiology as well as original researches on migraine aura and migraine genetics serve as major brokers of ideas in PMC headache literature. Non-headache literature influencing headache research comprise mostly of review articles in epidemiology and pharmacology.
Disclosure of Interests: Consultant for BoardVitals Inc., Consultant for Fieve Clinical Research.
Cluster Headache and Other Trigeminal Autonomic Cephalalgias
IHC-LB-003
Clinical Evidence for Peripheral and Central Nervous System Sensitization in Hemicrania Continua
Eric J. Eross1,*
1Glia Sciences, INC. / Phoenix Headache Institute, Scottsdale, United States
Objective: Determine the clinical evidence for both peripheral and central nervous system (trigeminal nucleus caudalis, thalamus, and limbic system) sensitization in subjects with hemicrania continua (HC).
Methods: A total of 108 subjects (hemicrania continua [n = 34], tension-type headache [n = 54] and non-headache [n = 20]) participated in this clinical investigation. All subjects completed an extensive medical history which included quantitative measures of headache related disability (Migraine Disability Assessment Scores [MIDAS], cutaneous allodynia (Allodynia Symptom Checklist [ASC-12]), misophonia (Misophonia Assessment Questionnaire [MAQ]), trypophobia (Trypophobia Image Score [TIS]), modified Lee, Cole and Wilkins Trypophobia Score [mLCWTS]) and TES (Emotional Response to Various Surfaces Score [ERVSS]).
Results: Average MIDAS were 0.2, 1.4, and 64 for non-headache (NH), tension-type headache (TTH) and hemicrania continua (HC) respectively. Headache days in the last ninety ranged from an average of 0.2 (NH), 1.4 (TTH) and 57 (HC). Average pain intensity also varied depending on headache type: NH (1.1), TTH (1.7) and HC (5.2). Seventy-nine percent of HC subjects described their pain as “throbbing” and 65% claimed routine physical activity made their pain worse. Average ASC-12 scores were <0.5 in NH and TTH groups and 5.4 in HC. HC subjects reported both cephalic (54%) and extra-cephalic (18%) cutaneous allodynia. Allodynia was confined to the side of their headache 79% (cephalic) and 29% (extra-cephalic) of the time. The average MAQ scores were <0.7 in NH and TTH and 7.7 in HC. TIS and mLCWTS were lower in NH (0.3/18) and TTH (0.2/17) as compared to HC (1.4/20). ERVSS were higher in HC (1.9) versus NH (0.5) and TTH (0.6).
Conclusion: HC subjects commonly reported a “throbbing” pain exacerbated by routine physical activity which supports a capacity for peripheral sensitization. Likewise, HC subjects had average allodynia scores ∼18x greater than NH subjects. Both cephalic and extra-cephalic allodynia were reported in HC subjects supporting central sensitization at the level of both the trigeminal nucleus caudalis and the thalamus. Finally, limbic system sensitization can be implicated in HC as evident by misophonia, trypophobia and TES scores that were ∼19x, ∼4.7x and ∼3.8x (respectively) more severe compared to NH subjects.
Disclosure of Interest: None Declared.
IHC-LB-004
Evaluating the Treatment of Cluster Headache with Oxygen
Helin Gosalia1,2, Calvin Chan1,2,*, Diana Y. Wei1,2 and Peter J. Goadsby1,2
1Headache Group, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
2NIHR-Wellcome Trust King’s Clinic Research Facility, SLaM Biomedical Research Centre, London, United Kingdom
Objective: To identify the phenotypical features of patients with cluster headache that predict therapeutic response and rebound attacks with oxygen therapy.
Methods: A questionnaire study was conducted in the South Central region of the UK from a database of 489 patients receiving oxygen for the indication of cluster headache. The diagnosis of cluster headache was made using the International Classification of Headache Disorders (ICHD-3). The questionnaire was validated by telephone follow-up interview of 20% of respondents randomly selected. Oxygen therapy satisfaction, reporting of rebound attacks after oxygen therapy, patient characteristics and cluster attack characteristics were collected and tabulated. Differences were examined by Mann Whitney U, Kruskal- Wallis and χ2 tests.
Results: From the database, 170 patients consented to receiving questionnaires, of which, 77 responded. All respondents met the ICHD-3 criteria for cluster headache; 62% male and 28% with chronic cluster headache. Current or ex-smokers accounted for 49%. In association with cluster headache attacks, 97% reported presence of at least one cranial autonomic symptom, 93% report agitation, 55% reported photo-sensitivity, 46% reported phonophobia and 41% reported nausea.
Rebound attacks after acute treatment with oxygen was reported by 67% of patients.
We identified that patients reporting 5 or more cranial autonomic symptoms (p = 0.049), conjunctival injection (p = 0.048) or ptosis (p = 0.047) were more likely to be satisfied with oxygen treatment.
We did not identify a cluster headache phenotypic feature nor patient characteristic that was significantly different in patients who reported rebound attacks.
Conclusion: Cluster headache patients who report 5 or more cranial autonomic symptoms with attacks, particularly conjunctival injection or ptosis are more likely to be satisfied with treatment of oxygen. Previously reported predictors of oxygen response were not found to be significant. These findings suggests the importance of the parasympathetic pathway in oxygen response.
Disclosure of Interests: Helin Gosalia, Calvin Chan and Diana Y Wei have no conflicts of interest to disclose.
Peter J Goadsby reports, over the last 36 months, grants and personal fees from Amgen and Eli-Lilly and Company, and personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr Reddy's Laboratories, Electrocore LLC, eNeura, Impel Neuropharma, MundiPharma, Novartis, Teva Pharmaceuticals, Trigemina Inc., WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and a patent magnetic stimulation for headache assigned to eNeura without fee.
IHC-LB-005
Evaluation of the Computerized Headache Assessment Tool (CHAT-III) for the Diagnosis of Cluster Headache
Morris Maizels1,* and Robert Wold2
1Providence St Joseph Health, Everett
2ClusterBusters.org, Lombard, United States
Objective: The diagnosis of cluster headache is often delayed for years, leading to delay in effective therapy. The Computerized Headache Assessment Tool (CHAT) is an algorithm-based instrument that screens for primary headache disorders. CHAT was previously validated in a primary care population. The present study was designed to evaluate CHAT in a population of individuals with known cluster headache.
Methods: Phase 1 was an exploratory phase, to test the algorithm in individuals with known cluster headache, recruited from the website of ClusterBusters.org. Subjects whose CHAT diagnosis differed from their clinical diagnosis were asked to participate in a diagnostic interview. Self-reported diagnoses were also compared to CHAT diagnoses. Discordant results were reviewed, and led to changes in the algorithm. Phase 2 was designed to test the modified questionnaire.
Results: Phase 1. 93 subjects completed the survey and 17 completed a diagnostic interview. The mean age was 43.2 years, and 65% were males. Of the 89, 57 received a CHAT diagnosis of cluster headache, 8 a trigeminal autonomic cephalgia not classified as cluster headache (TAC), and 28 a non-cluster headache diagnosis. 22 subjects reported a clinical diagnosis of cluster headache but received either a diagnosis of a non-cluster headache (n = 12), probable cluster headache (N = 3), or a TAC (n = 7). 15 subjects who received other CHAT diagnoses did not participate in a diagnostic interview.
Reasons for CHAT misdiagnosis were caused by: survey responses of headache duration greater or less than ICHD-III criteria; or attack frequency greater or less than ICHD-III criteria. Responses to questions during diagnostic interview often differed from responses to the survey (eg, indicating attacks “never go away”).
Modifications were made to the diagnostic algorithm of CHAT, to allow it to query for diagnostic criteria for cluster headache, even if headache duration or frequency are atypical, if headaches occur in cycles.
Phase 2 will evaluate the diagnostic accuracy of CHAT with the revised algorithm.
Conclusion: CHAT-III is highly specific for the diagnosis of cluster headache in a population of individuals with known cluster headache. Modifications to the algorithm will be studied to demonstrate increased sensitivity.
Speakers Bureau for Lilly, Teva, and Amgen/Novartis
Disclosure of Interests: Study funded by Lilly, Inc.
IHC-LB-050
Peripheral Nerve Blocks for the treatment of headache disorders in the UK: An Audit of BASH members’ practice
Luis Idrovo1,*, Marc Randall1, Fayyaz Ahmed2, Stuart Weatherby3; on behalf of BASH, Peter J. Goadsby4 and on behalf of BASH and BASH
2Neurology, Hull University Teaching Hospitals NHS, Hull
3Neurology, University Hospitals Plymouth NHS, Plymouth
4Neurosciences, King's College London NHS, London, United Kingdom
Objective: To obtain information about the current practice of peripheral nerve blocks-PNB’s- for the treatment of headache disorders in the UK.
Methods: Cross-sectional survey (Survey Monkey®) delivered to BASH members about their clinical practice using PNB’s. The survey included 11 multiple choice questions about the headache practitioner's geographical location and role, indications and technical aspects of PNB’s, clinical setting, safety and outcome measures.
Results: Electronic invitations were sent to registered BASH members without financial incentives, of whom 48% provided data. Of the responders, 80% performed PNB’s mostly in dedicated PNB's injection clinics. Responders were: consultant neurologists (51%) and GP’s and Nurses (28%); most were from London area, Yorkshire and the south of England. The headache disorders treated were episodic/chronic cluster headache (83%), chronic migraine (80%), occipital neuralgia (60%), PH/HC (51%), status migrainosus and headaches during pregnancy (46%). Practitioners perceived that cluster headaches responded better to PNB’s than any other headache disorder. The most common PNB performed was greater occipital nerve GON (98%) followed by lesser occipital nerve (48%), supraorbital (35%) and supratrochlear (28%) nerve blocks. The most common agents used for GON blocks were lidocaine +/− bupivacaine + methylprednisolone, and for other PNB's was lidocaine only. Local pain/minor bleeding 55%, headache exacerbation 42% and dizziness/presyncopal symptoms 36% were the most frequently reported side effects. Patient satisfaction (68%), headache diaries (50%) and HIT 6 scores (38%) were used more frequently by practitioners as treatment outcome measures.
Conclusion: PNB’s are frequently used by UK practitioners for the treatment of headache disorders with variability on their practices. This first collaborative BASH member’s survey may serve as an initiative to provide foundations for developing a practical and evidence-based consensus for PNB’s, a safe and widespread headache treatment option.
Disclosure of Interests: No Disclosures.
IHC-LB-051
Distinguishing Clinical Features Between Hemicrania Continua and High Frequency Chronic Migraine
Eric J. Eross1,*
1Glia Sciences, INC./Phoenix Headache Institute, Scottsdale, United States
Objective: Determine clinical features beneficial in distinguishing between hemicrania continua (HC) and high frequency chronic migraine (HFCM)
Methods: A total of 68 subjects (HC [n = 34] and HFCM [n = 34]) completed an extensive medical history and differences were explored. HFCM was defined as experiencing over 23 days of headache per month, at least eight of which fulfilled the criteria for migraine.
Results: HC and HFCM subjects were predominantly female (85%/82%) and Caucasian (88%/85%). Average age and age of onset was 53/30 years for HC and 47/19 for HFCM. Without treatment HC subjects experienced a continuous (97%) one-sided (100%) headache compared with HFCM (38% and 74%). Migraine Disability Assessment Scores were 64 for HC and 99 for HFCM. Headache days per month and pain severity were 25/5.2 (HC) and 28/6.2 (HFCM). Allodynia Symptom Checklist scores were 5.4 (HC) and 6.5 (HFCM). Cephalic / extracephalic allodynia was more common in HFCM (21%/6%) than HC (15%/3%). Misophonia Assessment Questionnaire scores were 7.2 (HC) and 12.8 (HFCM). Trypophobia Image Scores were 1.4 (HC) and 0.6 (HFCM). Headache features for HC and HFCM were: pounding (79%/97%), severe (97%/100%), worse with routine physical activity (65%/91%), nausea and/or vomiting (74%/88%), photophobia (82%/94%) [worse on side of headache (74%/50%)], phonophobia (79%/100%) [worse side of headache (50%/25%)], ipsilateral “scratchy” eye (35%/21%), misophonia (50%/56%) [worse on side of headache (18%/6%), and trypophobia (20%/18%) [worse side of headache (6%/0%)].
Conclusion: Aside from an absolute response to therapeutic doses of indomethacin, it often can be difficult to clinically separate HC from HFCM. In this cohort, HFCM was associated with an earlier age of onset, more allodynia and increased misophonia. HC was characterized by its unilateral, continuous pain and predominance of ipsilateral associated features.
Disclosure of Interest: None Declared.
IHC-LB-052
Case Report: A 51-year-old Lady With Hemicrania Continua And A Swollen Tongue
Yichen Lee1,*
1Neurology, National Taiwan University Hospital Hsin-Chu Branch, HsinChu, Taiwan
Objective: To present a patient with hemicrania continua who has a swollen tongue during exacerbation.
Methods: The patient is a 51-year-old lady who has had persistent daily headache for seven years. She had a surgery for chronic frontal sinusitis three months prior to the onset of headache. She recalled that as the discomfort of frontal sinus gradually diminished, she started to felt pain over left neck and left upper teeth. The pain became persistent and never went away a few days later.
She described the pain as a moderate persistent aching pain with exacerbation to severe about three to four times a month. The exacerbation usually lasted hours to two days. During exacerbation, the pain would extend to left retro-orbital and whole left side head accompanied with left ptosis, left periorbital edema, and voice change. She also noticed that her tongue became swelling and even left teeth marks on it during exacerbations (Figure 1).
According to the patient, she has had many unremarkable image studies and has failed lots of medication in these years. She started to experience pain-free since the ninth day with indomethacin 75 mg three times a day. The diagnosis of hemicrania continua was established.
Results: The cranial autonomic features are very important accompanying features in hemicrania continua. To the best of our knowledge, tongue swelling has not been mentioned in the literature. Palatoglossus muscle, which is innervated by vagus nerve and inserted into lateral side of the tongue, may be involved.
Conclusion: Cranial autonomic features other than those listed in the ICHD-3, such as itching eye, aural fullness or aural swelling, had been reported in the literature. The broader symptomology we know may help us understand this unbearable pain better.
Disclosure of Interests: None.
Comorbidity of Primary Headaches
IHC-LB-006
Burden of comorbid depression and anxiety on migraine-specific health-related quality of life in adult migraine patients in the United States
Richard B. Lipton1,2,*, Ravi Iyer3, Joshua M. Cohen3, James Jackson4, Verena Ramirez-Campos3, Sarah Cotton4, Gary Milligan3 and Dawn C. Buse1
1Albert Einstein College of Medicine
2Montefiore Medical Center, Bronx, NY
3Teva Pharmaceuticals, Frazer, PA, United States
4Adelphi Real World, Bollington, Cheshire, United Kingdom
Objective: Depression and anxiety are often comorbid with migraine and are associated with reduced quality of life and increased overall disease burden. The objective of this study was to examine the impact of comorbid depression and/or anxiety on migraine-specific health-related quality of life (HRQoL) outcomes in the real world from a patient perspective.
Methods: Data were drawn from the 2017 US Adelphi Migraine Disease Specific Programme, which included primary care physicians and neurologists and their consulting migraine patients. Patients completed a questionnaire that included validated measures of migraine-specific HRQoL and general quality of life, such as the Migraine Disability Assessment (MIDAS), Migraine-Specific Questionnaire (MSQ), and the EuroQol 5-Dimension 5-Level (EQ-5D-5L). Depression/anxiety was derived from the EQ-5D domain, and patients were categorized as experiencing none, slight, or moderate-to-severe (moderate+) depression/anxiety. Linear regressions were performed on the EQ-5D visual analogue scale (VAS) and MSQ domains to assess the relationship between the severity of anxiety/depression and headache days on HRQoL outcomes. Poisson regressions were performed on the square root of MIDAS being closest to normality from a number of transformations.
Results: 873 persons with migraine from the Adelphi Migraine Disease Specific Programme provided information on depression/anxiety. More severe anxiety/depression and an increasing number of headache days were associated with poorer MSQ scores, including the overall MSQ score and all 3 MSQ domains (P < 0.01). Similarly, more severe anxiety/depression and an increasing number of headache days were associated with more severe disability, based on MIDAS scores (P < 0.001). Worse anxiety/depression was also associated with worse overall quality of life, based on EQ-5D VAS scores (P < 0.001).
Conclusion: In patients with migraine, higher levels of depression/anxiety were associated with significant reductions in both migraine-specific (MSQ) and generic (EQ-5D) HRQoL and increments in disability (MIDAS).
Disclosure of Interests: R. B. Lipton is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. Dr. Lipton receives research support from the NIH: 2PO1 AG003949 (mPI), 5U10 NS077308 (PI), RO1 NS082432 (Investigator), 1RF1 AG057531 (Site PI), RF1 AG054548 (Investigator), 1RO1 AG048642 (Investigator), R56 AG057548 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor), 1K01AG054700 (Mentor). Dr. Lipton also receives support from the Migraine Research Foundation and the National Headache Foundation. Dr. Lipton serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. Dr. Lipton has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. Dr. Lipton receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. R. Iyer, J. M. Cohen, and V. Ramirez-Campos are employees of Teva Pharmaceuticals. J. Jackson, S. Cotton, and G. Milligan are employees of Adelphi Real World, and worked on the current analyses, funded by Teva Pharmaceuticals. D. C. Buse has received grant support and honoraria from Allergan, Amgen, Avanir, Biohaven, Lilly, Promeius and Teva. D. C. Buse is on the editorial board of Current Pain and Headache Reports.
IHC-LB-007
Risk of Ischemic Vascular Events with DHE use in Chronic Headache
George O. Dickson1,*, Menai McDonald1 and Alok Tyagi1
1Neurology, Institute of Neurological Sciences, Glasgow, United Kingdom
Objective: Since 1925, ergotamines have been used in the treatment of primary headaches. Dihydroergotamine (DHE) was introduced as an adrenolytic agent in 1943; inspired by the vascular theory of an initial cerebral vasoconstriction followed by extracranial vasodilation (1). However, underlying cardiovascular diseases or risk factors represent the major limitation for their use in practice. DHE induces systemic vasoconstriction that may potentially cause serious ischemic events. DHE is still prescribed worldwide and evidence concerning the risk for serious ischaemic vascular events is scarce (2). Risk of vascular events in patients receiving DHE was explored within a tertiary Neurology Centre.
Methods: A retrospective audit was performed of all patients receiving two or more iv DHE infusions between January 2014 and June 2019 within a tertiary Neurology Centre. The case notes were examined for documentation of cardiovascular events and their risk factors including; hypertension; diabetes mellitus; ischaemic heart disease; smoking history; cerebrovascular disease; hypercholesterolaemia. Any ischemic vascular event was highlighted.
Results: 65 patients were identified; 23 of whom were identified as having risk factors for vascular events. The most prevalent risk factor in those experiencing an ischemic vascular event was a history of smoking. 7 of the 23 patients had a history of ischaemic heart disease or stroke, 4 of whom were diagnosed before commencing DHE. 20 of the 23 patients identified as having risk factors for vascular disease experienced no vascular events whilst receiving DHE. 3 patients who were identified to have had an ischemic vascular event had received DHE infusions between 2–5 years prior to the event. No patients experienced an ischemic vascular event while on treatment with DHE either during the infusion or in between regular treatment periods.
Conclusion: 23 out of 65 patients (35%) receiving DHE infusions had risk factors for vascular disease with 7 patients (10%) having had ischemic heart disease or stroke. No ischemic vascular events were experienced during DHE infusions or in between regular treatment periods. Our audit does not suggest any increased risk of ischemic vascular events with DHE treatment. However we would recommend that all patients who receive DHE treatment should be screened for cardiovascular risk factors.
Disclosure of Interests: Dr Tyagi- from Janssen Cilage, GSK, Allergan, Electrocore, Lily, AMGEN, Novartis, eNeura, Teva, Alder, Abbott, he has received:
– research grants.
– funding to conduct clinical trials.
– educational grants for meetings/teaching courses.
– funding to attend medical conferences.
– hospitality in and out of hospital premises
IHC-LB-008
Are Migraine and Benign Paroxysmal Positional Vertigo (BPPV) linked?
Dhruvkumar M. Patel1,*, Mukundkumar V. Patel2, Dr. Jayanti K. Gurumukhani3 and Chilvana Patel4
1Medicine, Smt. N.H.L. Municipal Medical College, Ahmedabad
2Associate professor of Medicine, Zydus Medical College and Hospital, Dahod
3Consultant neurologist, Jay Neurology and Physiotherapy Clinic, Bhavnagar, India
4Director, Neurophysiology Fellowship Training Program, UTMB, Houston, United States
Objective: Repeated migraine attacks may cause vestibular dysfunction and dislodge of otoconia from utricle to semicircular canal resulting in Benign Paroxysmal Positional Vertigo (BPPV). The aim of the present study was to evaluate risk factors and linkage of migraine in patients of BPPV
Methods: This observational case-control study was conducted at an outpatient private neurology clinic of Ahmedabad, India from January 2017 to April 2019. 18 to 60 years old patients of confirmed BPPV were evaluated for past or present history of migraine (case). The control was selected from volunteer blood donors of matched demographical features. Patients suffering from severe cervical spine disease, significant carotid artery stenosis, Meniere’s disease and acute ongoing strokes were excluded from the study. Latest version of SPSS software was used to analyse this data.
Results: 295 consecutive BPPV cases (250 posterior canals, 45 horizontal canals) and 300 control subjects were studied. Mean age was 42.32 ± 11.45 years in cases and 44.15 ± 12.30 years in the control group. Out of total subjects, 68% were females in cases and 66% in the control group. In the case group, 55 (18.64%) were having past or present migraine (45 migraines without aura, 8 migraines with aura and 2 migraine variants), while in control group 24 (8.0%) were having migraine (20 migraines without aura, 4 migraines with aura). Among BPPV patients, those associated with migraine were younger and more often females, with many having a history of diabetes mellitus and coronary artery disease. Migraine was 2.3 times higher in cases as compared to the control (OR 2.63, 95% C.I. 1.58–4.39, p = 0.0002) in unadjusted analysis. These results were significant even after multidiscipline adjustment of variables (OR 2.50, 95% C.I., 1.26–4.30)
Conclusion: Migraine was more than two times associated with BPPV as compared to control. Although BPPV and migraine both can present as vertigo, the coexistence of both the diseases is more likely particularly if patients are female, have a history of diabetes mellitus or coronary artery disease. However, our study data should be validated by further large scale trials.
Disclosure of Interest: None Declared
IHC-LB-053
Incidence of constipation in patients treated with commonly used migraine medications
Victoria Chia1, Andrew Park1, Vamshidar Goli1, Nichole Win1,*, Marco S. Navetta1 and Fei Xue1
1Amgen Inc, Thousand Oaks, United States
Objective: Constipation has been reported with newer migraine therapies targeting the CGRP pathway; however, older commonly used migraine medications may also be associated with constipation. The objective was to estimate incidence rates of constipation in patients with migraine treated with commonly used migraine medications.
Methods: A retrospective cohort study was conducted using the MarketScan® Research Databases. Patients with migraine were identified from 01/2010-12/2011 using ICD-9-CM codes and claims for migraine-specific acute medications (triptans or ergots). Constipation, identified using ICD-9-CM codes, was defined as any constipation (e.g. a constipation claim in an outpatient (OP), emergency room (ER), or inpatient (IP) hospital setting) or serious constipation (e.g. a constipation claim in ER or IP). Incidence rates per 100 person-years and 95% confidence intervals (CI) of constipation were estimated in 1) all migraine patients; 2) in migraine patients newly initiating various types of acute or preventive migraine medications; and 3) in migraine patients by number of preventive treatments received in the prior 12 months.
Results: In the 584,475 patients with migraine, incidence rates were 3.41 (95% CI 3.39, 3.44) per 100 person-years for any constipation and 0.63 (95% CI 0.62, 0.64) for serious constipation. Incidence rates per 100 person years of any and serious constipation were even higher when various types of commonly used acute or preventive migraine treatments were initiated: opioids (6.13 and 1.79 for any and serious constipation); non-steroidal anti-inflammatory drugs (4.81 and 0.87); amitriptyline (6.50 and 1.08); nortriptyline (6.70 and 1.14); topiramate (5.29 and 0.85); gabapentin (8.22 and 1.81); pregabalin (9.41 and 1.95); and propranolol (4.82 and 0.84). There was a trend of increasing incidence rates with number of preventive migraine medications used in the 12 months prior.
Conclusion: In a large US administrative claims dataset, among patients with migraine, incidence rates of constipation were elevated among patients initiating commonly used types of acute or preventive migraine medications compared to all migraine patients. These data suggest that constipation occurs in patients treated with commonly used acute or preventive migraine medications.
Disclosure of Interests: All authors are employees and shareholders of Amgen Inc.
IHC-LB-054
Altered postural control in patients with migraine under visual stimulation
Gabriela F. Carvalho1,2,3,*, Arne May2, Débora Bevilaqua-Grossi3, Tibor Szikszay1, Waclaw Adamczyk1, Annika Schwarz2 and Kerstin Luedtke1
1Academic Physiotherapy, University of Luebeck, Luebeck
2Department of Systems Neuroscience, University of Hamburg-Eppendorf, Hamburg, Germany
3Department of Health Sciences, Ribeirão Preto Medical School, Ribeirão Preto, Brazil
Objective: To assess the postural control of patients with migraine and controls under visual-induced movement.
Methods: Up to 27 headache-free participants and 34 migraineurs between 18 and 65 years old were recruited from the community and from the University Clinic Hamburg Eppendorf, Germany. Patients were diagnosed with migraine according to the ICHD-3 and subjects were excluded when presented concomitant headaches, BMI > 30, any neurological or vestibular disease, or also any lower limb dysfunction. A colored marker was placed on subjects’ head and their balance displacement was assessed with a camera recording in HD 30fps, positioned 30 cm above the head. The subjects were instructed to gaze a screen positioned 70 cm from the body at the eye level, during three conditions:rest, with a fixed circle in the screen; lift, with a roller coaster video in constant and linear movement; and stimuli, with a roller coaster video in several directions and velocities. Data were processed through CVMob software (Ufba, Brazil). The total displacement length and displacement area were calculated through MATLAB2019a. Groups and conditions were contrasted using ANOVA with repeated measurements corrected by multiplicity in the SPSS 21.0 software, at α = 5%.
Results: Interactions between groups and conditions were verified for both total displacement (F = 3.20, p = 0.04) and area (F = 3.04, p = 0.05). The migraine group presented greater displacement length and area in all the three conditions compared to controls (p < 0.05) and all subjects presented greater displacement in the stimulicondition compared to liftand rest conditions (p < 0.05). Furthermore, the liftcondition also was related to more displacement compared to the rest condition for all subjects (p < 0.05) (table 1).
Average and 95% Confidence Intervals of total displacement (cm) and area (cm2) among migraine patients and controls.*
Control group (n = 27)
Migraine group (n = 34)
Rest
Total displacement
20.08 (18.9 to 21.2)
24.85 (23.84 to 25.87)
Area
3.61 (2.75 to 4.48)
5.87 (5.09 to 6.64)
Lift
Total displacement
27.35 (25.61 to 29.08)
33.90 (32.35 to 35.44)
Area
7.19 (5.69 to 8.69)
11.50 (10.17 to 12.84)
Stimuli
Total displacement
56.69 (52.73 to 60.65)
66.92 (63.39 to 70.45)
Area
21.45 (17.49 to 25.41)
27.35 (23.82 to 30.88)
p < 0.05 in the comparison among groups and all conditions.
Conclusion: Visual motion stimulation can induce greater total displacement length and greater area of displacement in subjects with and without migraine. For all conditions, migraine patients had poorer postural control compared to headache-free participants.
Disclosure of Interests: None.
IHC-LB-055
The effect of sound stimulus on the balance control of patients with different subtypes of migraine
Carina F. Pinheiro1,*, Gabriela F. Carvalho1, Jessica R. Moreira1, Tenysson Will-Lemos1, Nicoly M. Maciel1, Renato Moraes2, Marcelo E. Bigal3, Fabiola Dach4 and Debora Bevilaqua-Grossi1
1Health Sciences, RIBEIRÃO PRETO MEDICAL SCHOOL- UNIVERSITY OF SÃO PAULO
2School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
3Ventus Therapeutics, Montreal, Canada
4Neuroscience and Behavioral Sciences, RIBEIRÃO PRETO MEDICAL SCHOOL- UNIVERSITY OF SÃO PAULO, Ribeirão Preto, Brazil
Objective: To assess the balance of patients with migraine and controls with and without sound stimulus.
Methods: Fifty women with migraine and twenty-two non-headache women were assessed. They were aged between 18–55 years, and the migraineurs were divided into three groups according to the migraine subtype: Migraine without aura (MoA, n = 18), migraine with aura (MA, n = 16) and chronic migraine (CM, n = 16). All participants were instructed to keep standing posture on a force plate for 30 seconds, with closed eyes, in two conditions: in a quiet room (QR) and with a sound stimulus between 84–94dBA (SS). The center of pressure (CoP) displacement area was calculated and analyzed through groups and conditions using ANOVA two-way with repeated measures and Bonferroni post-hoc. Also, the prevalence ratio (PR) was calculated to assess whether the sound stimulus was associated with a greater imbalance (p < 0.05).
Mean and SD of CoP displacement area (cm2) between groups and conditions.
Control (n = 22)
MoA (n = 18)
MA (n = 16)
CM (n = 16)
Quiet room (QR)
1.68 (0.96)
1.35 (1.09)
2.83 (2.68)
1.99 (1.24)
Sound stimulus (SS)
2.48 (2.26)
1.50 (0.76)
5.02 (4.42)*†
5.83 (6.46)†
MA versus MoA, SS p < 0.02.
SS versus QR, p < 0.001.
Results: We observed an interaction between group and condition (F3,69 = 3.07, p = 0.03). The MA group exhibited a greater CoP area than MoA group on the SS condition (p < 0.01). Both the MA group and the CM group presented a greater CoP area on the SS condition than QR (p < 0.001) (Table 1). The prevalence ratio analysis showed that the sound stimulus is associated with an increased CoP area for MA group and CM group (MA PR 2.55, CI95% 1.32 to 4.91, p = 0.00; CM PR 2.16, CI95% 1.07 to 4.33, p = 0.02).
Conclusion: In the absence of the visual system, the sound stimulus is a disturbing factor for the balance of patients with migraine with aura and chronic migraine, but not for migraineurs without aura and healthy controls.
Disclosure of Interests: The authors declare no conflicts of interest.
IHC-LB-056
Impact of insomnia on the prevalence and clinical presentation of depression: a population study
Kyung Min Kim1,*, Dong Hyun Lee2, Soo-Jin Cho3, Won-Joo Kim1, Kwang Ik Yang4, Chang-Ho Yun5 and Min Kyung Chu1
1Neurology, Yonsei University College of Medicine, Seoul
2Neurology, Yeungnam University College of Mecidine, Daegu
3Neurology, Hallym University College of Medicine, Hwaseong
4Neurology, Soonchunhyang University College of Medicine, Cheonan
5Neurology, Seoul National University Bundang Hospital, Seongnam, Korea, Republic Of
Objective: A close association has been reported between depression and migraine. However, information concerning the impacts of migraine on the clinical presentation and prevalence of depression in a population-based study is currently limited.
Methods: Data from the Korean Headache-Sleep Study, a nationwide survey about headache and sleep for adults aged 19–69 years were used. Depression was defined when Patient Health Questionnaire-9 score ≥ 10.
Results: Of 2,695 participants who included in this study, 116 (4.3%), 143 (5.3%), and 1130 (41.9%) had depression, migraine, and non-migraine headache, respectively. Migraine (25/116 [20.7%] vs. 118/2579 [4.6%], p < 0.001) and non-migraine headache (67/116 [57.8%] vs. 1063/2579 [41.2%], p < 0.001) was more prevalent in the group of participants with depression than among participants without depression. Among participants with depression, there was no statistically differences in total Patient Health Questionnaire-9 scores among migraine, non-migraine headache, and non-headache groups (median with interquartile range, 12.0 [10.3–17.8] vs. 13.0 [11.0–16.0] vs. 12.0 [11.0–15.5], p = 0.514). Among subcomponent scores of Patient Health Questionnaire-9, all subcomponent scores did not significantly differ by headache status except feeling tired or having little energy scores (non-migraine headache 2.0 [1.0–3.0] vs. non-headache 2.0 [1.0–2.0], p = 0.019).
Conclusion: Participants with depression exhibit an increased risk of migraine and non-migraine headache compared with participants without depression. Among participants with depression, the severity of depression did not significantly differ on the basis of headache status.
Disclosure of Interests: The authors declare that they have no conflicting interests.
Genetics and Biomarkers of Headache Disorders
IHC-LB-010
Zonulin: a possible driver of gut-brain axis in migraine
Cherubino Di Lorenzo1,*, Najat Youssef2, Cono Casale3, Giulio Sirianni2, Gianluca Coppola4, Debora Toshi4, Grazia Semeraro4 and Francesco Pierelli5,6
1IRCCS – Fondazione don Carlo Gnocchi, Milan
2Associazione Eupraxia
3Marilab, Rome
4Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina
5IRCCS – Neuromed, Pozzilli (IS)
6Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Rome, Italy
Objective: Gut symptoms (as constipation, inflammatory and irritable bowel disorders) are very frequent among patients with migraine, however the integrity of the gastrointestinal system is not yet very well studied.
Aim of this study is to analyze the link between zonulin serum concentration (a marker of gut barrier integrity) and type and frequency of headache in a population of patients with different gastrointestinal disorders.
Methods: In a group of patients who self-referred to a gastroenterologist for various disorders, we asked them to undergo to a neurological evaluation, looking for a possible headache diagnosis. We divided 104 patients in 3 groups. Group 1: 22 patients without headache. Group 2: 32 patients with tension-type headache. Group 3: 50 patients with migraine.
We compared among groups the zonulin serum concentration and analyzed its correlation with the frequency of headache.
Results: Differences in terms of zonulin serum concentration emerged among Group 1 and 3 (p < 0.001).
Further, we observed a positive correlation between zonulin serum levels and the frequency of migraine attacks (R = 0.54; p < 0.001). There was no significant correlation between zonulin serum levels and tension-type-headache attacks.
Conclusion: The observed links between zonulin and migraine could be explained by the role of zonulin as marker of gut inflammation. Alterations of zonulin pathway have been associated with the leaky gut phenomenon, which could lead to the passage of potentially systemic pro-inflammatory substances in the blood circulation, leading to a migraine worsening. Another possible explanation of the observed correlation is the link between zonulin release and the dysfunction of vagal system that is one of the principal driver in migraine pathophysiology.
Further prospective studies on patients without gastrointestinal symptoms should confirm our early observations and clarify the actual mechanism of action underpinning this link.
Disclosure of Interests: Authors declare no conflict of interests.
IHC-LB-057
Endogenous Glucocorticoids may be Potential Biomarkers for Migraine Chronification
Yohannes W. Woldeamanuel1,*, Bharati M. Sanjanwala1 and Robert P. Cowan1
1Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, United States
Objective: a) to identify difference in CSF and serum glucocorticoids among episodic and chronic migraine patients compared to controls.
b) to determine longitudnal changes in serum glucocorticoids among chronic migraine patients with remission to episodic migraine compared to those with persistent chronic migraine.
c) to determine migraine-related clinical features associated with glucocorticoid group differences.
Methods: CSF and serum cortisol and corticosterone levels were measured using liquid chromatography-mass spectrometry among age- and sex-matched adult patients with episodic migraine, chronic migraine, and healthy controls. Serum and CSF samples were collected from 26 and 4 participants in each group, respectively. Serum cortisol and corticosterone levels were measured at a second timepoint after 2 years among 10 of the chronic migraine patients – 6 of whom reverted to episodic migraine while 4 persisted as chronic migraine. Association analysis was conducted to determine link between glucocorticoid levels and clinical variables i.e. headache frequency, headache intensity, medication-overuse headache, depression, anxiety, pain catastrophizing, sleep quality, somatic symptoms, post-traumatic stress disorder, pain self-efficacy, migraine-related disability.
Results: Chronic migraine patients exhibited significantly elevated serum cortisol compared to episodic migraine patients (Holm-Sidak’s p < 0.001; Figure 1A).
Abstract number: IHC-LB-057
CSF cortisol and corticosterone were highest in chronic migraine, followed by episodic migraine, and control (Figure 1B). Chronic migraine patients with remission had their cortisol and corticosterone return to control or episodic migraine levels (p < 0.05). Chronic migraine patients with persistent chronic migraine showed continued elevated cortisol and corticosterone levels. Cortisol and corticosterone levels were directly related to headache frequency (p = 0.002) and migraine-related disability (p = 0.0001), while inversely associated to pain self-efficacy (p = 0.008).
Conclusion: Endogenous glucocorticoids may be used as potential biomarker for episodic to chronic migraine progression and for monitoring treatment response of chronic migraine remission. Improving socio-cognitive skills of pain self-efficacy may help optimize endogenous glucocorticoid levels which in turn may prevent migraine attacks.
Disclosure of Interests: None.
Headache Classification
IHC-LB-059
Rare migraine variants not defined in international classification of headache disorders (ICHD)-3: clinical case series
Mukundkumar Patel1, Dhruvkumar M. Patel2,* and Jayanti Gurumukhani3
1General medicine, Zydus Medical College and hospital, Dahod
2under graduate medicine, Smt. NHL Mun Med College, Ahmedabad, India, Ahmedabad
3Neurology, Jay Neurology Clinic, Bhavnagar, India
Objective: We evaluated unique migraine variant cases which have not been classified in the international classification of headache disorders.
Methods: Patients of 14 to 60 years of age with episodic neurological symptoms diagnosed as migraine variants during January 2017- March 2019 were included in the study. These cases were not defined by ICHD 3 guidelines.
Results: Case -1: A 30 year old female presented with recurrent episodes of spontaneous vertigo lasting for about 30 minutes. They were preceded by severe weakness and photophobia for about 5 to 10 minutes and were precipitated by eating fermented food products or inadequate sleep. 12 such episodes of vertigo occurred at work in the last 3 months.
Case 2: A 28 year old female presented with recurrent episodes of true vertigo lasting for 5 to 6 hours associated with nausea and heaviness of head, but not classical migraine headache. She has experienced about episodes 6 to 8 in a month.
Case 3: A 32 year female presented with 8 episodes of syncope in last three months. All episodes occurred on the day of fasting.
Case 4: A 30 year male presented with sudden onset drooping of left side of face 10 to 15 minutes. This upper motor neuron facial weakness recovered in next 20 minutes and was followed by severe left sided throbbing headache with vomiting. He had 4–5 such episodes per month in last 6 months.
In all these cases, clinical examination in between the episodes was normal and the diagnostic work up was unrevealing. All these cases improved significantly when they were treated with prophylaxis of migraine. And when the treatment of discontinued, the symptoms recurred re-emphasising the disorder as migraine variants. First two cases were unexplained vertigo and the third case was of undetermined neuro cardio reflex syncope. All three cases were not associated with headache and were suspected due to past or family history of migraine. Fourth case is of migrainous headache associated with upper motor neuron facial palsy with ipsilateral headache, which is a unique brainstem aura migraine variant.
Conclusion: Migraine should be suspected in any episodic neurological disorder of unexplained aetiology with normal neurological examination when investigations are undetermined.
Disclosure of Interests: Conflict of interest; Nil.
Headache Disorders in Children and Adolescents
IHC-LB-012
Comparison of the prevalence of infantile colic between pediatric migraine and other types of pediatric headache
Yoel Levinsky1,* and Tal Eidlitz-Markus1
1Pediatric Headache Clinic, Schneider's children medical center of Israel, Petah Tikva, Israel
Objective: To examine whether the reported association of infantile colic and migraine in children pertains also to other headache types.
Methods: A cross-sectional historical study was conducted of 226 patients aged 3–18 years who presented to a tertiary pediatric headache clinic in 2016–2018. Parents were asked a series of questions to determine if their child had had infantile colic as defined in the ICHD3-beta version. Findings were compared between children diagnosed with migraine or other headache types.
Demographic and clinical data of children with migraine versus other types of chronic headache (226 participants)
Parameter
Patients with migraine (N = 170)
Patients with other types of headache (N = 56)
p value
Gender (female)
104 (61.2%)
33 (58.9%)
0.874
Age (years)
12.49 ± 3.46
11.71 ± 3.48
0.147
Headache age onset (years)
9.58 ± 3.97
10.20 ± 3.90
0.311
Duration of attacks (hours)
15.96 ± 23.25
10.77 ± 24.08
0.1652
Headache frequency/month
13.70 ± 12.2
22.98 ± 11.72
0.853
Awakening pain
74 (43.5%)
13 (23.2%)
0.011
Nausea
108 (63.5%)
14 (25%)
<0.001
Dizziness
99 (58.3%)
18 (32.1%)
0.001
Attention deficit disorder
49 (28.8%)
7 (12.5%)
0.012
Organic comorbidity
57 (33.5%)
11 (19.6%)
0.064
Psychiatric comorbidity
70 (40.7%)
12 (21.4%)
0.006
History of infantile colic
45 (26.5%)
6 (10.7%)
0.016
Data are presented as n (%) or mean ± standard deviation.
Results: There were 137 girls (60.6%) and 89 boys (39.4%) of mean age 12.3 ± 3.47 years at presentation. Migraine headache was diagnosed in 170 patients (75.2%) and other types of headache (14 in total) in 56 (24.8%). Fifty-one patients had a history of infantile colic: 45 in the migraine group (26.5%) and 6 in the comparison group (10.7%); the difference in colic prevalence was statistically significant (p < 0.0161; OR 3, 95% CI 1.17–9.11). There was no association of specific migraine parameters or symptoms with infantile colic.
Conclusion: There appears to be an association of infantile colic with pediatric migraine but not with other types of pediatric headache. Our results reinforce the theory that infantile colic may have share a pathogenic pathway with migraine.
Disclosure of Interests: The authors have no coflicts of intrests to disclose.
IHC-LB-013
Cephalic cutaneous allodynia in children and adolescents with migraine of short duration: a retrospective cohort study
Yoel Levinsky1,* and Tal Eidlitz-Markus1
1Pediatrics Headache Clinic, Schneider's Children Medical Center Of Israel, Petah Tikva, Israel
Objective: Allodynia is prevalent in adults with migraine and has been associated with long disease duration and severe course. Studies of the pediatric population are sparse. The aim of this study was to evaluate the rate of cephalic cutaneous allodynia in children and adolescents within the first six months of migraine onset and to identify associated clinical and migraine-related parameters.
Methods: The electronic database of a tertiary pediatric headache clinic from 2014 to 2017 was retrospectively searched for all children and adolescents diagnosed with migraine headache within 6 months or less of symptom onset. Cephalic cutaneous allodynia was identified by validated questionnaire. Demographics, symptoms, and headache-related parameters were compared between patients with and without allodynia.
Results: The cohort included 119 patients, 69 girls (58.0%) and 50 (42.0%) boys, of mean age 11.6 ± 3.6 years. Mean time since onset of migraine attacks was 3.6 ± 1.8 months. Cephalic cutaneous allodynia was reported by 31.1% of patients. It was significantly associated with female gender (p = 0.03), older age at admission (p = 0.037), older age at onset (p = 0.042) migraine with aura (p = 0.002) and higher rate of awakening pain (p = 0.017).
Conclusion: Cephalic cutaneous allodynia may occur in children and adolescents already in the first 6 months of migraine onset. Contrary to adult studies, we found no association of allodynia with migraine frequency or long disease duration. Allodynia was significantly associated with migraine with aura, female gender, and awakening pain. A genetic tendency may contribute to the appearance of allodynia in the pediatric age group.
Parameter
Patients without allodynia (N = 82)
Patients with allodynia (N = 37)
p value
Gender (female)
42 (51.2)
27 (73.0%)
0.030
Age (years)
11.2 ± 3.5
12.7 ± 3.5
0.037
Migraine age onset (years)
10.9 ± 3.5
12.4 ± 3.5
0.042
Duration of attacks (hours)
10.9 ± 15.1
6.7 ± 5.4
0.393
Headache frequency/month
20.9 ± 12.0
18.6 ± 11.9
0.272
Chronic migraine (≥15 episodes/month)
28 (34.6%)
16 (45.7%)
0.300
Duration of disease before admission (months)
3.5 ± 1.7
3.8 ± 1.9
0.631
Migraine with aura
18 (22%)
19 (51.4%)
0.002
Unilateral pain
29 (38.2%)
11 (32.4%)
0.669
Phonophobia
62 (76.5%)
27 (79.4%)
0.811
Photophobia
43 (54.4%)
25 (71.4%)
0.101
Osmophobia
12 (27.9%)
7 (41.2%)
0.365
Awakening pain
29 (35.4%)
22 (59.5%)
0.017
Disclosure of Interests: The Autors have no interetsts to disclose.
IHC-LB-060
Ramosetron as a treatment for cyclic vomiting syndrome: A clinical trial
Toshiyuki Hikita1,2,*
1Hikita Pediatric Clinic, Kiryu, Gunma
2Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan
Objective: Cyclic vomiting syndrome (CVS) is characterized by severe, recurrent episodes of vomiting in otherwise healthy subjects, and is classified within the subgroup of episodic syndromes that may be associated with migraine. Ramosetron, a selective serotonin 5-HT3 receptor antagonist, has been applied clinically for treatment of irritable bowel syndrome (IBS). In this clinical trial, we evaluated the potential efficacy of ramosetron for treatment of CVS.
Methods: Six patients referred to Hikita Pediatric Clinic or Teikyo University Hospital and diagnosed with CVS and IBS were enrolled in this trial after obtaining informed consent. Treatment consisted of oral administration of 2.5–10 µg ramosetron. Patient responses to treatment for subsequent attacks were classified as: (i) complete (no vomiting following treatment), (ii) effective (frequency of vomiting reduced ≥50% relative to previous attack prior to initiation of treatment), or (iii) noneffective (frequency of vomiting not notably affected by treatment).
Results: One of the 6 patients had been experiencing abdominal pain every morning, and diarrhea prior to vomiting. She took ramosetron every morning for 3 months. She did not vomit during that 3-month period, but did suffer occasional constipation. Following a constipation episode, she temporarily stopped taking ramosetron daily, but did take it at prodrome phase if she experienced abdominal pain and headache. She did not start vomiting after taking ramosetron.
All 6 patients experienced prodrome symptoms such as abdominal pain and/or diarrhea, nausea, appetite loss, headache, or menstruation-associated headache or vomiting. Following ramosetron treatment during prodrome phase, 5 of the 6 patients showed essentially “complete” response (out of 39 attacks, there were 32 complete, 1 effective, and 5 noneffective responses), and 1 showed effective response (for 1 attack). Overall, 34 of the 39 responses (87.2%) were classified as complete or effective.
For 3 of the patients, ramosetron treatment was initiated after vomiting had started, in a total of 10 attacks. One of these 3 patients showed effective response (in 1 attack), while the other 2 showed noneffective responses (in 9 attacks).
Conclusion: Ramosetron, a serotonin receptor antagonist, is potentially effective for treatment of patients with CVS.
Disclosure of Interest: None Declared.
Headache Education for Clinicians and Patients
IHC-LB-014
A novel CTP-based quantitative tool for assessment of perfusional alteration in migrainous aura stroke mimic
Antonio Granato1,*, Laura D'Acunto1, Miloš Ajčević1, Giovanni Furlanis1 and Paolo Manganotti1
1Department of Medical Sciences, University Hospital and Health Services, Clinical Unit of Neurology, Trieste, Italy
Objective: Diagnosis of migrainous aura (MA) represents the third most common stroke mimic (SM) in Emergency Department (ED). The studies on computed tomography perfusion (CTP) in SM differential diagnosis are based only on qualitative data and highlights controversial perfusion patterns. Aim of the study was to investigate brain perfusion abnormalities in MA using a novel CTP-based quantitative approach in order to improve differential diagnosis.
Methods: A two-year retrospective analysis of the patients who accessed the ED of the Hospitals of Trieste with acute focal neurological symptoms was performed. All the patients performed in ED general and neurological examination, hematological tests, brain non-enhanced CT, CT angiography of the supra-aortic and intracranial arteries, and CTP within 4.5 hours from symptom onset. Patients with normal qualitative CTP and with a final diagnosis of migraine with aura were included. ROIs were delineated on CTP source image anatomical area compatible with MA symptoms, while control ROIs were automatically delineated symmetrically on the contralateral side. The differences between ROI on the MA side and contralateral in terms of asymmetry index (AI%) were automatically estimated by the newly developed tool for each of CTP parameters (MTT, CBF and CBV). The AI% ≥ 10% was considered significant.
Results: Fourteen patients (8 F, 6 M, mean age 47 years) were included. In 13 patients a significant hypoperfusion was observed by quantitative analysis in at least one of the CTP parameters. In 7 patients all three CTP parameters showed significant hypoperfusion. MMT AI% increase was observed in 11 (79%) patients (median MTT AI% = 13.9), while CBF AI% and CBV AI% decrease were observed in 12 (86%) (median CBF AI% = −21.4) and in 9 (64%) (median CBV AI% = −17.9) cases respectively. All CTP values were outside ischemic stroke core or penumbra range.
Conclusion: The quantitative analysis of CTP images during MA detects a slight hypoperfusion pattern in the cerebral regions compatible with MA. It could be helpful in differential diagnosis between MA and acute cerebrovascular disease.
Disclosure of Interest: None Declared.
IHC-LB-061
Experiences of a motivational focused patient education – A qualitative study
Louise Schlosser Mose1,2,*, Jane Orry Bornhøft2,3, Jette Primdahl4,5 and Bibi Gram2,4
1Department of Neurology
2Research Unit of Health Sciences
3Department of Endocrinology, University Hospital of Southern Denmark, Esbjerg, Denmark, Esbjerg
4Department of Regional Health Research, University of Southern Denmark, Odense, Denmark, Odense
5Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark and Hospital of Southern Jutland, University Hospital of Southern Denmark, Aabenraa, Denmark, Sønderborg, Denmark
Objective: Patient education is recommended as part of the treatment for medication-overuse headache (MOH), however, knowledge of patients’ experiences when participating in an educational programme is sparse. The objective of this study was to explore how patients with MOH experienced participation in a patient educational programme (PEP) focusing on coping strategies and motivation for behavioural changes.
Methods: A qualitative interview study based on a phenomenological-hermeneutical approach was conducted. Semi-structured interviews (n = 8) were conducted among patients with MOH who had attended a PEP in a randomised controlled trial. The PEP had Motivational Interviewing (MI) as the communicative approach and focused at behavioural changes and empowering coping strategies. The interviews explored how the patients experienced participation in the PEP and possible changes in their perceived coping strategies and/or any behavioural changes associated with headache.
Results: Three overall themes emerged from the analyses; Changing coping strategies after participation, Self-perception and feeling of stigmatization, Experience of motivation during the PEP. Generally, patients with MOH found the PEP relevant with respect to coping with headache. Patients shifted from focusing on medication only to include other ways of managing their headache. Ambivalent feelings of changing behaviour and involvement of relatives were of particular interest to the patients.
Conclusion: Participation in the PEP helped the patients cope with headache in new ways, relevant to their everyday lives and challenges. The individualized approach enabled by the MI was experienced as useful by the patients, as it actively involved them in the treatment. Knowledge regarding the patients’ perspectives is paramount in planning future educational interventions.
Disclosure of Interests: The authors declare no conflicts of interests.
Headache Epidemiology, Outcomes and Burdens
IHC-LB-015
Impact of an employer-provided migraine coaching program on burden and patient engagement: results from interim analysis
Leonhard Schaetz1,*, Timo Rimner2, Purnima Pathak3, Juanzhi Fang4, Deepak Chandrasekhar5 and Jelena Mueller1
1Novartis Pharma AG
2Medgate, Basel, Switzerland
3Novartis Ireland Ltd., Dublin, Ireland
4Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
5Healint Pte Ltd., Singapore, Singapore
Objective: This study aimed to assess the impact of Migraine Care support program offered by a healthcare company as a complimentary service to medical care for its Swiss based employees and their family members living with migraine.
Methods: Of 320 participants with a diagnosis or high probability of migraine who registered to the program till mid-June 2019, 120 enrolled into the study for retrospective analysis of their data collected in the program. All participants received personalized telecoaching by a specialized nurse for up to 6 months supported by an advanced version of the Migraine Buddy smartphone application. The study participants were evaluated through a series of questionnaires including Migraine Disability Assessment (MIDAS), Patient Activation Measure (PAM), and the more commonly used coaching lessons and implemented action plans.
Results: The interim results are presented for 70 participants who completed both baseline and 3-month follow-up assessment, of which 41 reached 6 months. The mean age (standard deviation, SD) at baseline were 38 (8) years with 67% females, 69% had a confirmed diagnosis of migraine, and 51% were not treated by a physician despite 73% having MIDAS grade 2 or higher. The total mean (SD) MIDAS score improved from 15.2 (14.3) at baseline to 13.7 (16.9) (p = 0.342) at 3 months and to 6.5 (8.1) (p = 0.001) at 6 months. The mean (SD) PAM scores also improved from 63.7 (11.0) at baseline to 67.5 (11.6) (p = 0.012) at 3 months and to 70.8 (12.1) (p = 0.0009) at 6 months. The most used coaching lessons focused on progressive muscle relaxation (75.7%), sleep (57.1%), general disease understanding (50.0%), stress (45.7%), and diet (38.6%). Similarly, the top action plans concentrated on drinking enough (80.0%), sleep (78.6%), diet (52.9%), daily routine (52.9%), and sports (41.4%).
Conclusion: The study results demonstrate that employer-initiated educational and counseling support can significantly decrease migraine-related disability and promote disease self-management among employees.
Disclosure of Interest: None Declared.
IHC-LB-016
Polish omnibus online survey on migraine conducted in a population of 2000 adults
Aurelia Lipa1, Izabela Domitrz2,*, Jacek Rozniecki3 and Adam Stepien4
1Teva Pharmaceuticals
2Medical University, Warsaw
3Medical University, Lodz
4Military Institute, Warsaw, Poland
Objective: The objective of the survey was to assess the prevalence of migraine in the adult population in Poland, the percentage of people who experience symptoms that may be indicative of migraine attacks and the extent to which patients seek treatment and medical advice.
Methods: An online, quantitative survey involving a representative sample of 2000 adults aged 18–69 years residing in Poland, conducted in January 2019. The participants completed an online questionnaire (CAWI). The study group was representative for adults in terms of age, region and the size of place of living. The participants declared that within the past 12 months they experienced headache or headaches lasting 4 – 72 hours (or shorter if treated), and that these headaches were accompanied by symptoms corresponding to diagnostic symptoms of migraine without aura and/or with aura.
Results: Twenty five % of the respondents reported the presence of symptoms indicative of migraine within the past 12 months, in particular: 2.5% of people experienced only attacks of migraine with aura, 6.4% only without aura, 16.2% experienced both. In total, 18.7% of adults experienced aura symptoms. The results obtained that 1% of the adult population suffer from chronic migraine. Thirty seven % of migraineurs declare that they had migraine diagnosed by a physician in the past. The following symptoms are reported most frequently: pulsating headaches – 85%, photophobia and phonophobia – 82%, headaches that are aggravated by routine physical activity – 80%. Forty three % of people suffering from migraine attacks received medical advice for their condition, in the majority of cases – from a primary care physician / general practitioner (71%), and rarer – from a neurologist (48%). Ninety six % of people with migraine attack/attacks declared taking acute analgesics. Considering the last 30 days, half of these people took analgesics for a total of several days, 22%–several days per week, and 3%–everyday. Twenty five % of people with migraine take medications for migraine prophylaxis.
Conclusion: The omnibus study conducted in the group of 2000 adults in Poland indicates the need to improve awareness of migraine and its modern methods of treatment, especially prophylactic treatment.
Disclosure of Interests: ID, JR, AS – Teva ad boards. JR, AS – Teva studies investigators. AL – Teva employee.
IHC-LB-017
Forecasting Migraine Using Weather: A Retrospective Study
George McLendon1,*, Russ Bodner1, Josh Phipps2, Shannon Stearman2 and Alex Dzeda2
1Atrium Health, Charlotte, United Sates
2Sensorrx, Davidson, United Sates
Objective: Migraine weather triggers were derived from 11,712 migraines paired with weather data. Weather-based neural network migraine forecasts are reported. The association between migraine and weather triggers is controversial. Using the smartphone app MigrnX, migraine weather triggers and migraine forecasting are explored.
Methods: Sample N = 89 met ICHD-3 criteria for migraine diagnosed by a Neurologist. A longitudinal study was conducted using de-identified patient data of MigrnX users from Atrium Health. The cohort reported headaches using MigrnX over 12 months. Records included GPS-based weather data. Analysis of migraine weather triggers used a Random Forest algorithm with relative risk >4. Baseline weather data for the algorithm used patients’ non-headache days. To forecast migraines, a training set with an average of 100 episodes/pt was compiled. Each model compares predicted headache days with observed headache days to calculate Positive Predictive Values (PPV).
Results: Analysis used an average of 130 migraines per pt, average <8 per month. Patients were aged 24–62 yrs; 80% White, 76% Female. Over 1 yr, MigrnX clinical data with subsequent improved diagnosis and treatment, monthly headaches per pt declined ca 40%. Weather triggers strongly correlate with migraine frequency in the following order: wind speed > humidity, barometric pressure > temperature. The results are multifactorial, and demonstrate varied, multiple weather factors contributing to migraine, and cautions against using any single trigger as a forecasting measure. Weather-based Migraine Forecast The prediction of migraine PPV for individual patients from the neural network is shown in Figure 1A. 28% of the population has high PPV values (70–90%) where prophylaxis based on such predictions could be medically recommended, as for menstrual migraine prediction. For patients with PPV values 50–70%, additional information might make a prediction medically actionable.
Conclusion: Real-time headache reports coupled to passive weather collection can identify weather triggers, and allow weather-based migraine forecasting. Advances in real-time data collection combined with machine learning methods could provide a new paradigm for prediction-based prophylaxis.
Disclosure of Interests: Officer of SensorRx Inc.
IHC-LB-018
Predictors of urgency in headache patients looking for assistance in low complexity emergency units in Brazil: An analysis of 163,207 emergency visits
Joao Jose, F. De Carvalho1,*
1Neurology, Hospital Geral de Fortaleza, Fortaleza, Brazil
Objective: In the last decade, hundreds of low complexity Emergency Care Units (UPA 24 h) were launched in Brazil. Distributed throughout the city, the UPA 24 h, are designed to provide care for patients with acute diseases. Headache is one of the most common symptom that lead patients to UPA 24 h. The Manchester protocol is the tool used in UPA 24 h to detect patients who will need urgent or critical care. This study aimed to evaluate predictors of urgency in patients seeking medical care for headache in UPA 24 h.
Methods: We evaluated the ED charts of 163,207 visits motivated by headache to nine UPA 24 h in the city of Fortaleza, Ceará, from April 13, 2013 to June 31, 2017.
Results: The 163,207 consultations represented 3% of all the UPA 24 h visits and were made by 118,623 patients (mean age of 37.2 ± 15.7; 69,4% women). On average, patients had the Manchester Risk Classification in 01 minute and 22 seconds and 1,276 (0,8%) were classified as blue, 84.443 (51.7%) as green, 60,844 (37.3%) as yellow, 16.640 (10.2%) as orange and only 4 cases were classified as red. Older patients (>40 years) (OR 1.563; 95% CI, 1.532–1.595; P < 0,0001), female sex (OR 1.474; 95% CI, 1.442–1.507; P < 0,0001), off hours (from 19 to 07) (OR 1.825; 95% CI, 1.789–1.863; P < 0,0001) and on weekends (OR 1,047; 95% CI, 1.024–1.070; P < 0,0001) were predictors of urgency. Those classified as yellow, orange and red received medical evaluation in a mean time of 16 minutes versus 01 hour and 17 minutes for the patients classified as blue and green.
Conclusion: In Brazil, low complexity Emergency Care Units (UPA 24 h) represent an important channel of care for patients with acute headache. While about half of the patients have pains that could be treated in primary care, the other half have emergency and urgency characteristics captured in the Manchester Classification. Older age, female sex, arrival time and weekend days are strong predictors of urgency in patients seeking UPA 2 h for headache.
Disclosure of Interest: None Declared.
IHC-LB-062
Clinical audit of premonitory and postdromal symptomatology in patients with migraine
Karthik Nagaraj1,*, Francesca Puledda1, Nazia Karsan1 and Peter Goadsby1
1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London and NIHR-Wellcome Trust King’s Clinical Research Facility, London, United Kingdom
Objective: To compare the range and duration of premonitory and postdromal symptoms in patients with migraine attending headache centre on a year by year basis.
Methods: We carried out an audit of migraine patients who attended a tertiary headache referral centre between 2014 and 2018 using clinical documentation.
Results: Of patients (n = 340), 78% (n = 264) had chronic migraine. The median age of the cohort was 44 years with an interquartile range (IQR) of 31–53. The median age of headache onset was 14 (10-20) years. Medication overuse was present in 39% of patients.
There was an increase in the total number of premonitory symptoms recorded in 2018 with respect to 2014 (median and IQR: 5 and 3–5 vs 2 and 0–4; p < 0.001). The five most common were concentration difficulty (66%), mood changes (56%), fatigue (42%), neck stiffness (42%) and yawning (31%). There was an increase in the total number of postdromal symptoms recorded in 2018 with respect to 2014 (median and IQR: 2 and 1–3 vs 0 and 0–1; p < 0.001). The five most common were lethargy (32%), tiredness (29%), feeling drained (29%), cognitive impairment (24%) and irritability (14%). The number and duration of premonitory and postdromal symptoms did not correlate with the frequency of headache days (Pearsons correlation) or presence of MOH (chi square test). There was a correlation between the number of premonitory and postdromal symptoms and number of both associated migrainous symptoms and cranial autonomic symptoms (CAS; Pearsons correlation – r = 0.32, p < 0.001)
Conclusion: The data shows an increase in the total number of premonitory and postdromal symptoms recorded over the course of four years. This difference may be due to increased awareness among patients and medical personnel. We also found a significant correlation between the number of premonitory and postdromal symptoms and associated migrainous symptoms and CAS. This is consistent with the underlying biological basis of the premonitory and postdromal symptomatology.
Disclosure of Interests: The authors have no conflicts of interest to declare for this study.
IHC-LB-063
Clinical characteristics, comorbidities and functional impact in patients with migraine treated in a headache center at Buenos Aires, Argentina
Ingrid K. García Gómez1, María C. Lembeye2, Fiorella Martin Bertuzzi1,*, Eduardo D. Doctorovich1, Pamela E. Seilikovich1, Marco Ostuni, Florencia Ines Aiello, Cecilia Fieiras, Sofia Ramírez, Claudia Nadia Panoso Carrasco, Paula Schwartz, Nahir Aucar, Braian Morris Beker, Juan Ignacio Kenny, Maria Aime Risso and Maria Fernanda Marti; Micaela Buratovich
1Neurology Department, Hospital Italiano de Buenos Aires, Capital Federal
2Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina
Objective: This study describes clinical characteristics of patients with migraine in a headache center at Buenos Aires, Argentina.
Methods: Transversal study, patients +18 years were asked to complete an auto administered questionnaire about clinical characteristics, quality of life, allodynia, hospital anxiety and depression (HAD) and Oviedo questionnaire of sleep (COS). Patients classified as migraine according to the IHC-III by a headache specialist were included.
Transversal study, +18 y/o patients with migraine acording IHC-III answered a questionnaire about clinical characteristics, quality of life, and comorbidities.
Results: 183 patients were included, 94% women, average age 40 years (±27,5). Frequency headaches was 10 days/month and intensity was 7/10 in average. 78% had episodic migraine, 55% referred aura with a predominance of visual symptoms. HIT-6 score was 59,5 (±13,3); impact was substantial in 21,9% and severe in 61.7%.
Pain localization: temporal (56,8%), frontal 48,1% and neck 48,1%. Unilateral pain was present in 78% of the patients. Characteristic of pain: oppressive (71%) and pulsatile (56,3%). Accompanying symptoms: Photophobia (71%) and phonophobia (62,8%). Triggers: stress (66,7%) and anxiety (60,7%). Comorbidities: anxiety (48%), depression (30,6%) and insomnia (23%) among the patients. Table 1 shows the diferences between episodic and chronic migraine.
183 patients, 94% women, age 40(±27,5) years. Frequency headache: 10 days/month. Intensity 7/10. Episodic migraine: 78%, 55% referred aura. HIT-6 score was 59,5 (±13,3); impact was severe in 61.7%. Characteristics: Localization: temporal (56,8%) and frontal (48,1%). Unilateral pain: 78%. Accompanying symptoms: Photophobia (71%) and phonophobia (62,8%). Triggers: stress (66,7%) and anxiety (60,7%). Comorbidities: anxiety (48%), depression (30,6%) and insomnia (23%). Table 1 shows diferences between episodic and chronic migraine.
Conclusion: Our population reflects similar results reported by other specialized centres in migraines. The majority of our patients with migraine present a severe functional impact and it is necessary to have more resources and studies.
Disclosure of Interest: None Declared.
IHC-LB-064
Knowledge about migraine headache prevention and disability among migraine patients
R M Lakshasarah1,*
1COLLEGE OF NURSING, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, India
Objective: Headache is the most disabling phase of migraine and after this phase patients feel drained-out. Prevention of migraine headache and reducing the severity of migraine attack can be achieved if patients know exactly what are the common semiology migraine shows and the triggers of migraine headache. This study also aims to identify knowledge regarding migraine headache prevention and disability due to migraine among migraineurs.
Methods: A total of 155 migraineurs were assessed regarding the prodromal symptoms, the triggers and the preventive strategies. The migraineurs were also assessed about the level of disability and the impact of migraine on work productivity using the Migraine Disability Assessment Scale and Headache Impact Test.
Results: The study findings showed moderate to severe disability was experienced by migraineurs in doing their daily activities and work productivity was also severely affected. 43% of migraineurs have poor knowledge regarding migraine headache prevention, especially regarding triggers.
Conclusion: This study reveals the knowledge level of migraineurs was poor among the rural population and the newly diagnosed patient who had a severe disability due to migraine which insists on the importance of patient teaching and education for prevention of disability among migraine patients.
Disclosure of Interests: There is no conflict of interest.
Headache Pathophysiology – Basic Science
IHC-LB-019
Potential Clinical Evidence for Limbic System Sensitization in Migraine
Eric J. Eross1,*
1Glia Sciences, INC. / Phoenix Headache Institute, Scottsdale, United States
Objective: Determine the clinical evidence for limbic system sensitivity (LSS) in migraine subjects as indicated by the incidence and severity of misophonia, trypophobia and tactile-emotional synesthesia (TES).
Methods: A total of 290 subjects (migraine [n = 195], tension-type headache [n = 54], probable migraine [n = 21] and non-headache [n = 20]) participated in this clinical investigation. All subjects completed a medical history including quantitative measures of misophonia (Misophonia Assessment Questionnaire [MAQ]), trypophobia (Trypophobia Image Score [TIS], modified Lee, Cole and Wilkins Trypophobia Score [mLCWTS]) and TES (Emotional Response to Various Surfaces Score [ERVSS]). These measures were explored in relation to headache type, frequency, severity, associated disability (Migraine Disability Assessment Scores [MIDAS] and cutaneous allodynia (Allodynia Symptom Checklist [ASC-12]).
Results: Average MIDAS were 0.2, 1.4, 51, 23 and 77 for non-headache (NH), tension-type headache (TTH), all migraine (M), episodic migraine (EM) and chronic migraine (CM) respectively. Average headache days in the last ninety were 0.2 (NH) to as high as 58 (CM). Average pain intensity was: TTH (1.7), M (5.7), EM (4.9) and CM (6.4). Average ASC-12 scores were <0.5 in NH and TTH groups and 5.7 (M), 5.3 (EM) and 6.0 (CM). MAQ showed average scores <0.7 in NH and TTH. Elevated average MAQ scores of 7.7, 6.2 and 9.1 were seen in M, EM and CM respectively. Trypophobia indicators (average TIS and mLCWTS) were lower in NH (0.3/18) and TTH (0.2/17) versus M (1.2/21), EM (1.2/20) and CM (1.3/21). Average ERVSS, a measure of TES, were higher in M (2.3), EM (2.4) and CM (2.3) versus NH (0.5) and TTH (0.6).
Conclusion: The clinical measures for LSS were elevated in subjects with M when compared to those with NH or TTH, and CM subjects were more affected than their EM counterparts. Misophonia, trypophobia and TES scores were ∼23 ×, ∼4.3 × and ∼4.6 × (respectively) more severe in the CM group compared to NH subjects. In addition, these scores increased with headache frequency, severity, associated disability and cutaneous allodynia. These findings suggest that not only is the limbic system hyperexcitable in migraineurs, but that dynamic changes may lead to limbic network sensitization within the migraine matrix like known to occur in trigeminal and thalamic structures.
Disclosure of Interest: None Declared.
IHC-LB-021
Increased phase-synchronization and power oscillatory activity in patients with episodic migraine during the interictal period
Adria Vilà-Balló1,*, Angela Marti-Marca1, Marta Torres-Ferrus1,2, Alicia Alpuente A1,2, Victor Jose Gallardo1 and Patricia Pozo-Rosich1,2
1Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute
Objective: To analyze Phase-Synchronization and Power of oscillatory activity in migraine during the presentation of auditory stimuli.
Methods: In this case-control exploratory study, we recorded 20-channel Event Related Brain Potentials (ERPs) during an Active Novelty Oddball Paradigm in women with episodic migraine (EM) without aura (ICHD-3), and healthy matched controls (HC) without family history of migraine. We collected sociodemographic and clinical data, disability, quality of life, anxiety and depression (HIT-6, MIDAS, MSQ, MIG-SCOG, STAI, BDI-II, BSI, ASRS). We calculated behavioural data including reaction times (RTs), hit rates, false alarms, and d-primes. Phase-Synchronization (Inter-Trial phase Coherence, ITC) and Power of oscillatory activity were separately obtained for standard, target and novelty stimuli, from Current Source Density Transformed ERPs (CSD-ERPs).
Results: We studied 21 – EM (22.0 ± 2.2 years) and 21-HC (23.0 ± 2.0 years). There were no significant differences at a behavioural level (p > 0.1). We found an increased Phase-synchronization in response to standard trials, in migraine with respect to controls, in several frequency ranges: theta (3-9 Hz; 100–400 ms; F(1,40) = 4.106, p = 0.049), alpha (9-12 Hz; 50–250 ms; F(1,40) = 4.137, p = 0.049) and low-beta (12-15 Hz; 50–250 ms; F(1,40) = 4.186, p = 0.047). Similarly, compared to controls, migraineurs showed increased theta (at Fz: t(40) = −2.206, p = 0.033), alpha (Cz at Block 1: t(40) = −2.379, p = 0.016) and low-beta power (Cz at Block 1: t(40) = −2.345, p = 0.024). However, in alpha and low-beta, the significant effect was observed only on the first blocks. No evidences of lack of habituation were encountered in the migraine group (p > 0.1).
Conclusion: Hypersensitivity to auditory stimuli during the interictal period in young female patients with episodic migraine might be defined by a higher Synchronization of neural activity together with a higher Power activity.
Disclosure of Interest: None Declared.
IHC-LB-065
Anti-CGRP Monoclonal Antibody Eptinezumab Does Not Engage Fcγ Receptors Involved in ADCC and ADCP, Nor Does It Activate the Complement Cascade
Carol J. Raport1,*, Jens Billgren1, Charlie Karasek1, Ethan Ojala1, Michelle Scalley-Kim1, Dan Allison1, John A. Latham1 and Leon F. Garcia-Martinez1
1Alder BioPharmaceuticals, Inc., Bothell, WA, United States
Objective: Eptinezumab is a therapeutic monoclonal antibody targeting CGRP peptide developed for the preventive treatment of migraine. It contains the Fc region of human IgG1 with a modification of amino acid Asn297 to prevent the canonical N-linked glycosylation that is normally present at this site. This glycosylation is essential for antibody interactions of wild-type IgG1 with Fcγ receptors (FcγR) to induce ADCC (antibody-dependent cellular cytotoxicity) or ADCP (antibody-dependent cellular phagocytosis). It is also important for interactions with complement proteins to activate CDC (complement-dependent cytotoxicity). Eptinezumab was specifically designed to avoid these interactions. A series of assays were conducted to test the hypothesis that eptinezumab does not support these immune-related processes.
Methods: Binding of eptinezumab to FcγR was assessed using surface plasmon resonance technology. FcγR-dependent cell-based assays were also used to evaluate the engagement of eptinezumab with FcγR in vitro. A cell viability assay was used to evaluate complement activation by eptinezumab.
Results: The collective results of binding and FcγR-dependent cell-based assays demonstrated the absence of engagement of eptinezumab with FcγR in vitro. In addition, there was no activation of complement-mediated cytotoxicity by eptinezumab.
Conclusion: These results confirm that eptinezumab does not induce ADCC, ADCP, or CDC.
Disclosure of Interests: All authors are full-time employees of Alder BioPharmaceuticals.
IHC-LB-066
Entrainment of neural band oscillations in patients with migraine
Angela Marti-Marca1,*, Adria Vilà-Balló1, Mireia Torralba2, Marta Torres-Ferrus1,3, Alicia Alpuente1,3, Victor Gallardo1, Salvador Soto-Faraco2,4 and Patricia Pozo-Rosich1,3
1Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute
2Multisensory Research Group, Center for Brain and Cognition, Universitat Pompeu Fabra
3Neurology, Hospital Universitari Vall d'Hebron
4Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Objective: To study, using electrophysiology, the entrainment of neural band oscillations to repetitive, visual stimuli in migraine.
Methods: This is an exploratory case-control study. We studied women with episodic migraine (EM) without aura (ICHD-3) and healthy matched controls (HC) with no family history of migraine. We collected sociodemographic, psychometric and clinical data (HIT-6, MIDAS, MSQ, MIG-SCOG, STAI, BDI-II, BSI, ASRS). EEGs were recorded using 64-channels during the realization of a visual entrainment paradigm with rhythmic and arrhythmic targets. We obtained behavioral data (reaction times, hit rates, d-primes, false alarms). Separate measures of alpha band activity (range 7–14 Hz) and entrainment (peak 12 Hz) were calculated at the Oz electrode: phase synchronization (inter-trial coherence), phase concentration (kappa and mean vector length) and the mean angular difference between rhythmic-arrhythmic time-points.
Results: We included 19-EM (23.85 ± 3.36 years) and 22-HC (22.09 ± 2.04 years). Despite a lack of group differences on behavioural measures and phase synchronization (p > 0.1), phase trended to be more concentrated in EMs than in HCs on catch trials (kappa concentration, p = 0.06; mean vector length, p = 0.068). In addition, the difference in phase mean angle (p = 0.039) between rhythmic and arrhythmic catch trials was closer to 180° in EMs than in HCs.
Conclusion: Enhanced oscillatory alpha synchronization and entrainment (phase-angle and concentration) indicates that migraineurs display an increased tendency to synchronize and predict external rhythms present in their natural environment, even when these stimuli are not present. This hyper-vigilance, linked to an augmented capacity for stimulus prediction, could in part explain the hyper-sensibility to sensory stimuli seen in migraine.
Disclosure of Interest: None Declared.
IHC-LB-067
Only 3.8% (19/464) of papers on migraine and headache published in Cephalalgia 2014–2018 concerned actual spontaneous or provoked migraine/headache attacks
Peer Tfelt-Hansen1
1Danish Headache Center, Rigshospitalet, Copenhagen, Denmark
Objective: Ideally, the mechanisms of migraine and other headaches should be investigated during actual attacks; but it is the impression that most scientific headache experts rarely, if ever, investigate spontaneous or provoked migraine/headache attacks. This bibliographic review was performed in order to document this problem.
Methods: The 494 original reports published in 5volumes of Cephalalgia (from 2014 to 2018) were screened by reading the abstracts, and if necessary, the whole paper; and classified as: (1) spontaneous acute migraine/headache; (2) provoked acute migraine/headache; and (3) reports on other aspects of migraine/headache. For each report in (1) and (2) the number of patients or volunteers were noted.
Results: As shown in Table 1 only 7/494 (1.4%) of papers reported on investigations of spontaneous and only 12/494 (2.4%) on provoked migraine/headache.
Number of original reports in Cephalalgia from 2014 to 2018 on spontaneous acute headaches, provoked experimental headaches, and papers on other subjects. Number of patients or volunteers are presented in brackets.
Year and (volume)
Type of paper
2014 (Vol. 34)
2015 (Vol. 35)
2016 (Vol. 36)
2017 (Vol. 37)
2018 (Vol. 88)
2014–18 (Vol. 34–38)
Spontaneous acute migraine/headache
1 [17]
1 [96]
1 [17]
2 [46]
2 [30]
7
Provoked acute migraine/headache
1 [24]
1 [30]
6 [324]*
4 [78]
12
Other papers
73
91
85
96
132
475
Total papers
75
92
87
102
138
494
Note: *In one study 163 males ascended by plane in two hours to 3700 m, and high altitude headache was studied.
Conclusion: This mini-review confirms that investigations of patients during spontaneous or provoked migraine/headache attacks are rarely performed.
If the pathophysiology of migraine and other headaches are to be fully elucidated there is an urgent need for investigations during actual attacks. Relevant imaging and functional methods have been developed and can be used in our patients. What is needed now is that headache experts prioritize the establishment of facilities at their headache centers for receiving acutely patients in migraine or other headache attacks; alternatively, provoked attacks can be investigated in these headache centers.
Disclosure of Interests: None.
Headache Pathophysiology – Imaging and Neurophysiology
IHC-LB-022
Cerebrovascular reactivity in patients with Migraine using Transcranial Doppler
Avinash ALASHETTY1,*, Jawahar Marimuthu1 and Lakshmi Narasimhan Ranganathan1
1Institute of neurology, Madras Medical College, CHENNAI, India
Objective: ·To assess cerebrovascular reactivity in interictal phase of migraine patients.
Methods: • This study was conducted over three months in institute of neurology, madras medical college. • 30 patients who satisfied the criteria for migraine as per IHS criteria were selected from headache outpatient clinic of our institute. • 30 controls were selected who were age and sex matched with patients. • Inclusion criteria: 1) age 20–70 years 2) Migraine as per IHS criteria 3) Willing to participate.
• All patients complete history was included,Complete clinical examination, routine investigations, imaging was done. • Transcranial doppler using 2 Hz probe was done was done in all patients in supine position. • The baseline Peak systolic velocity(PSV),Pulsality index(PI) was measured in Middle cerebral artery (MCA) and posterior Cerebral artery(PCA) in all patients. Photic stimulation using a flickering light was done for 100 seconds from a distance 1 m.
• After photic stimulation, PSV in MCA and PCA was measured, the highest PSV value was averaged.
Results: Demographic data: We included 30 patients, 25 female and 5male patients. The average duration of headache was 2.3 years in patients. Of 30 patients 12 had history of aura and all were visual aura and 18 were without any aura. The systolic velocities in MCA, in patient and control group was compared. There was no significant difference between PSV MCA between patient and the control group at baseline. After photic stimulation there was increase in peak velocities, however it was not statistically significant with p value (0.08). The systolic velocities in PCA were compared between the patient and the control group. The basline velocities in patients was comparatively higher in patient group. After photic stimulation the increase in PSV in patient group was higher and statistically significant (p-0.001) but the PSV changes in control group was not significant. The velocities were also compared in between two subgroups that is aura and without aura, the baseline PCA PSV in patients with aura was higher compared to those without aura. After photic stimulation the velocities in patient with aura was higher and statistically significant. The PSV in MCA however was not significant before and after photic stimulation in between the two subgroups.
Conclusion: There was increased cerebrovascular reactivity in patients with migraine. There was further increase in Cerebrovascular reactivity in patients with aura. There was maladaptation of cerebrovascular reactivity in migraineurs, more so in patients with aura causing activation of the trigeminovascular system causing change in neurovascular homeostasis thereby inducing migraine attacks. Transcranial doppler can be useful tool to assess the cerebrovascular reactivity in migraineurs. This study demonstrates increased cerebrovascular reactivity in patients of migraine with aura using photic PSV. Photic PSV along with other indices can be valuable tool to assess CVR in patients with migraine.
Disclosure of Interests: Nil.
IHC-LB-068
Cyclic fluctuations of sensorimotor cortex sensory processing in migraine may be important for attack initiation: observations from event related EEG changes
Martin S. Mykland1,*, Marte Helene Bjørk2,3, Marit Stjern1,4, Petter M. Omland1,4, Martin Uglem1,4 and Trond Sand1,4
1Neuromedicine and Movement Science, NTNU, Trondheim
2Clinical Medicine, University of Bergen
3Neurology, Haukeland University Hospital, Bergen
4Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim, Norway
Objective: Migraineurs experience altered sensory perception throughout migraine phases. For the first time, we mapped cyclic changes of cortical responsivity with “event related synchronization and desynchronization” (ERS/ERD).
Methods: We recorded ERS/ERD changes during a motor test (M) and a sensorimotor test (SM) in 41 migraineurs. Longitudinal analyses compared the interictal phase to the preictal (<36 h before headache, n = 11) and ictal (n = 13) phase. We studied low beta (12–19 Hz) ERD, representing cortical excitability during sensory processing, and post movement beta synchronization (PMBS) which represents post-stimulation cortical inhibition.
Results: In the preictal phase, baseline beta power and beta-ERD in contralateral sensorimotor cortex were significantly increased (p < 0,049). PMBS on the other hand, tended to be increased at the ipsilateral side (SM p = 0,058), while post-hoc test of cortical PMBS-side difference was highly significant (p = 0,001). In the ictal phase the baseline beta activity was significantly increased, and PMBS was significantly decreased in the ipsilateral sensorimotor cortex (p < 0,045). Beta-ERD was not altered during the ictal phase.
Conclusion: Preictal findings indicate lower contralateral sensorimotor cortical pre-activation and increased responsivity during sensory processing, followed by increased inhibition of the ipsilateral sensorimotor cortex. The results support the theory of underlying cortical hyperresponsivity in migraine, interictally contained by inhibitory control. Decrease in preictal cortical pre-activation may cause higher thresholds for inhibitory control and consequent release of the underlying hyperresponsivity seen as increased beta-ERD. Meanwhile, ipsilateral sensorimotor cortex may compensate with increased post-stimulation inhibitory control.
During the ictal phase, cortical pre-activation and post stimuli inhibition ipsilateral to stimuli decrease, with contralateral normalization. We postulate that decreasing cortical activation with compensatory inhibitory thresholds culminating in ictal escalation may trigger headache attacks.
Disclosure of Interests: All authors declare no conflict of interest regarding this study and article.
IHC-LB-069
Aberrant Structural Network Architecture in Chronic Migraine
Danielle D. DeSouza1,*, Yohannes W. Woldeamanuel1, Bharati M. Sanajanwala1, Daniel Bissell1, James H. Bishop2 and Robert P. Cowan1
1Neurology and Neurological Sciences
2Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, United States
Objective: The goal of the current study was to assess structural interconnections in patients with CM and healthy controls (HC) using MRI measures of cortical thickness and subcortical volume combined with graph theoretical network analyses.
Methods: 100 participants (52 CM and 48 HC) were included in the study. Cortical thickness and subcortical volumes of 83 regions were extracted and included as nodes in the network analysis. Edges were computed as Pearson correlations setting the negative correlations to zero. Analyses were carried out on binary undirected graphs, controlling for densities from 5% to 40% in steps of 0.5. To assess differences between groups in network architecture, we examined both local (nodal) and global measures of centrality, segregation, and integration. Significant between-group differences in network measures were examined using non-parametric permutation tests with 1000 replications in combination with two-tailed p-values based on 95% confidence intervals.
Results: Several significant differences in both local and global network topology were evident between the CM and HC groups. Patients with CM had disrupted global network properties characterized by lower global and local efficiency and higher transitivity. Additionally, patients with CM demonstrated aberrant local network topology characterized by higher path length, lower closeness centrality, lower clustering, and lower local efficiency. These differences were most prominent in the limbic and insular cortices but also occurred in frontal, temporal, and brainstem regions.
Conclusion: Structural MRI measures of gray matter combined with graph theoretical network analysis revealed multiple significant network topology differences in patients with CM compared to HC. Our results suggest that aberrant structural brain networks in CM are less central, less efficient, more segregated, and less integrated. These findings contribute to an increased understanding of structural connectivity in CM and provide a novel approach to potentially track and predict the progression of migraine disorders.
Disclosure of Interests: None.
Migraine Acute Therapy
IHC-LB-023
Acute Migraine Treatment with Rimegepant 75 mg and Health Related Quality of Life in Migraine: Results from a Long-Term, Open-Label Safety Study (BHV-3000-201)
Gilbert Litalien1,*, Robert Croop1, Elyse Stock1, Alexandra Thiry1, Meghan Lovegren1, Chris Jensen1, Kathryn Cowie2, Vladimir Coric1 and Richard Lipton3
1Biohaven Inc, New Haven
2Wake Forest, Winston-Salem
3Neurology, Albert Einstein College of Medicine, New York, United States
Objective: Migraine is a painful and disabling condition, with substantive patient burden on health related quality of life (HRQoL). This study assessed the effects of rimegepant 75 mg oral tablet on migraine-specific quality of life over 52 weeks of use as an acute treatment.
Methods: This ongoing, multicenter, long-term, open-label safety study (Study 201) of rimegepant 75 mg oral tablet included adults with ≥1 year history of migraine defined by ICHD-3 beta criteria. Subjects treated attacks of any pain intensity with rimegepant 75 mg up to once daily as-needed for up to 52 weeks. A validated 14-item Migraine-Specific Quality of Life Scale (MSQoL) was administered at baseline and Weeks 12, 24, 36, and 52. The MsQOL is designed to measure how migraine affects and/or limits daily functioning across three domains: Role-Restrictive [RR]: 7 items assessing how migraine limits daily social and work-related activities; Role Preventative [RP]: 4 items assessing how migraine prevents activities; Emotional Role [ER]: 3 items assessing the emotional impact of migraine. Raw total scores were computed and rescaled from 0 to 100 with higher scores indicating better HRQoL.
Results: The analyses included 1795 subjects at baseline, 1634 at Week 12, 1215 at Week 24, 1087 at Week 36, and 920 at Week 52. Mean MSQoL scores at baseline were 52.7 for RR, 67.9 for RP and 60.9 for ER. By Wk 12, rimegepant-treated subjects showed clinically and statistically significant improvements: mean Δ from baseline of +14.5, +11.5, and +15.4, for RR, RP, and ER respectively, (p < 0.0001). These benefits were sustained at Wk 24: +15.4, +12.8, +15.8 (p < 0.0001), Wk 36: +17.4, +13.7+17.0, (p < 0.0001), and Wk 52: +17.6, +14.4, +17.2, (p < 0.0001) for RR, RP, and ER
Conclusion: Effective Acute Migraine Treatment with Rimegepant 75 mg is associated with clinically meaningful improvements in HRQoL when dosed as needed up to once daily. These improvements demonstrate that treated patients would achieve better overall function and reduced impediments to social and work related activities.
Disclosure of Interests: GL, RC, ES, ML, CJ, VC are employees and shareholders of Biohaven Inc. RL is a consultant and shareholder of Biohaven Inc.
IHC-LB-024
Concomitant Use of Serotonergic Drugs with Zolmitriptan in a One-year Safety Trial
Pete Schmidt1,*, Donald Kellerman1 and Jean Engels1
1Zosano Pharma, Fremont, United States
Objective: In the United States, all triptans carry a warning against concomitant use with serotonergic medications – specifically SSRIs and SNRIs – in the Warnings and Precautions section of the package insert. Similarly, many serotonergic drugs carry a warning against concomitant use with triptans. Despite these warnings, some believe that the risk of serotonin syndrome is not supported by reliable data (e.g. Orlova, Rizzoli and Loder, 2018).
Zosano is currently studying intracutaneous zolmitriptan (Qtrypta) for the acute treatment of migraine and completed a 1-year open-label safety trial in which subjects dosed with the Qtrypta 3.8 mg system an average of twice per month over the course of twelve months. Though some serotonergic medications were not allowed during the trial, several subjects initiated one of these drugs at some point in the trial. Thus, we sought to analyze whether concomitant use of these medications affected the safety of the study drug with regard to serotonin syndrome.
Methods: We analyzed the medication database for known serotonergic drugs. Using the Hunter Criteria for the diagnosis of serotonin syndrome, the adverse event database was queried for the following terms: clonus, agitation, diaphoresis, tremor, hyperreflexia, hypertonia or fever (MedDRA version 20.0); and the frequency of these terms was compared between the two groups.
Results: The safety population of the trial totaled 335. Twenty-two subjects reported being on serotonergic drugs while in the study (6.6%). One subject was on two serotonergic medications.
None of the serotonin syndrome diagnostic terms were reported in either group, nor were there any reports of serotonin syndrome.
Conclusion: The results of this analysis suggest that a certain proportion of migraine patients will use triptans and serotonergic drugs concurrently, despite the warnings in the respective package inserts. However, in this limited sample there were no reported cases of serotonin syndrome, presumably the most serious complication of concomitant use. These findings lend further support to the argument that the risk of serotonin syndrome with concomitant use of triptans and serotonergic medications may be overstated.
Disclosure of Interests: PS, JE and DK are employees of Zosano.
IHC-LB-025
Efficacy of Qtrypta (zolmitriptan intracutaneous system) Before and After the Initiation of CGRP Antibody Therapy in Subjects with Migraine – a Preliminary Assessment
Nada Hindiyeh1,*, Peter Schmidt2, Jean Engels2, Whitney Halladay2 and Donald Kellerman2
1Stanford University, Stanford
2Zosano Pharma, Fremont, United States
Objective: With the recent introduction of the highly effective CGRP antibodies for migraine prevention, it is important to evaluate their effect on the efficacy of abortive migraine therapy.
A 1-year open-label safety study of Qtrypta was ongoing in 2018 and 2019 at the time of market introduction in the U.S. of erenumab, galcanezumab, and fremenumab. Several subjects participating in the long-term safety trial requested one of these injectable CGRP antibodies and as there were no safety concerns, the sponsor granted permission for the subjects to receive this treatment and continue to participate in the long-term safety trial.
Methods: To assess the potential impact of CGRP antibodies on the efficacy of Qtrypta 3.8 mg, we evaluated the standard co-primary endpoints for acute treatment of migraine trials (pain freedom and most bothersome symptom freedom, both at 2 hours from subject-recorded eDiary symptom scores) for all migraine attacks treated prior to and after CGRP antibody therapy initiation.
Results: Ten subjects started CGRP antibody therapy during the trial: 9 erenumab, and 1 galcanezumab. Six of 10 subjects treated migraine attacks with Qtrypta after initiating erenumab. These subjects treated 72 attacks prior to initiating anti-CGRP treatment and 37 attacks post initiation. Results for pain and most bothersome symptom freedom at 2 hours pre-and post-initiation of CGRP antibodies for all attacks treated are shown in the table.
Conclusion: From limited data, it appears that Qtrypta remained highly effective in relieving acute migraine symptoms in subjects receiving prophylactic treatment with CGRP antibodies. Further studies are needed, but these data suggest that attacks are more successfully treated with rapidly absorbed triptans when subjects are being treated prophylactically with a CGRP antibody.
Disclosure of Interests: NH is on the advisory board of Zosano, PS, JE, WH and DK are employees of Zosano.
IHC-LB-026
The 200 mg dose, the highest dose of 3 doses of lasmiditan investigated in phase 3, has a pain-free effect after 2 h, comparable to sumatriptan 50 mg
Peer Tfelt-Hansen1,*
1Danish Headache Center, Rigshospitalet, Copenhagen, Denmark
Objective: Lasmiditan has not been compared with oral triptans in randomized, controlled trials (RCTs). The aim was therefore to evaluate the 3 doses of lasmiditan (50 mg, 100 mg, and 200 mg) relative to the triptans by comparing results from meta-analyses.
Methods: Lasmiditan results were obtained from 2 large phase 3 RCTs. Triptans results were obtained from meta-analyses. For pain-free (PF) after 2 h the therapeutic gain (effect after active drug minus effect after placebo) (TG) with 95% CI was calculated.
Results: As shown in Table 1 the TG of lasmiditan 200 mg (17%) was comparable to the TG for sumatriptan 50 mg (17%), but this dose of lasmiditan has a TG less than the TGs of sumatriptan 100 mg (21%), zolmitriptan 2.5 mg (20%), and rizatriptan 10 mg (32%). Any adverse events (placebo-subtracted) was 27% for lasmiditan 200 mg and this incidence of adverse events was higher than the incidences for rizatriptan 10 mg (10%), zolmitriptan 2.5 mg (15%), and sumatriptan 100 mg (19%).
Efficacy and tolerability of oral lasmiditan and 3 oral triptans.
PF after 2 h.
Adverse events (AEs)
Drug and dose
Active drug
Placebo
Therapeutic gain
Any AE placebo subtracted
Lasmiditan 200 mg
36%
18%a
17% (95% CI: 13–21%)
27% (95% CI: 23–30%)
Lasmiditan 100 mg
30%
18%a
12% (95% CI: 8–15%)
22% (95% CI: 19–26%)
Lasmiditan 50 mg
29%
21%a
7% (95% CI: 2–12%)
6% (95% CI: 2–10%)
Rizatriptan 10 mg
42%
10%
32% (95% CI: 29–34%)
10% (95% CI: 6–14%)
Zolmitriptan 2.5 mg
30%
10%
20% (95% CI: 18–21%)
15% (95% CI: 13–17%)
Sumatriptan 100 mg
32%
11%
21% (95% CI: 19–23%)
19% (95% CI: 16–23%)
Sumatriptan 50 mg
28%
11%
17% (95%CI: 15–19%)
7% (95% CI: 5–10%)
Note: a, this high placebo effect remains unexplained.
Conclusion: The comparison of lasmiditan with 3 triptans indicates that only lasmiditan 200 mg has a clinically relevant effect on migraine pain. One possible problem is the high incidence of AEs of lasmiditan 200 mg. Comparative RCTs of lasmiditan and triptans are needed.
Disclosure of Interests: No conflict of interests.
IHC-LB-070
Oral Rimegepant Produces No Significant Effect on Blood Pressure When Administered Concomitantly with SC Sumatriptan
Robert Croop1,*, Joseph Stringfellow2, Michael Hanna1, Christopher M. Jensen1, Andrea Ivans1 and Vladimir Coric1
1Biohaven Pharmaceuticals, New Haven
2Navitas Life Sciences, Pottstown, United States
Objective: To evaluate the effects of rimegepant, a small molecule calcitonin gene-related peptide receptor antagonist with efficacy in migraine, on resting blood pressure (BP) when administered concomitantly with sumatriptan in healthy volunteers.
Methods: This was a single center, Phase 1, randomized, partially-blinded, placebo-controlled study in adult nonsmokers aged ≥18 and ≤40 years (males) or ≥18 and ≤50 years (females) with BMI > 18.5 and <30.0 kg/m2 and weight ≥ 50.0 kg (males) or ≥45.0 kg (females). On Days 1 and 5, subjects received 12 mg of sumatriptan as 2 SC 6 mg injections separated by 1 h; Day 5 injections were administered 2 and 3 h after oral rimegepant 75 mg or matching placebo tablet. From Days 2 to 5, subjects received rimegepant or placebo once daily (randomized 6 to 1, rimegepant to placebo). Parameters for BP were the time-weighted average (TWA) of mean arterial pressure (MAP), diastolic BP (DBP), and systolic BP (SBP). Similar TWA of MAP was concluded if the upper bound of the 90% CI of the difference between rimegepant + sumatriptan on Day 5 and sumatriptan on Day 1 was <5 mmHg. Plasma concentrations of rimegepant (Days 4 and 5) and sumatriptan (Days 1 and 5) were used to calculate PK parameters (AUC, Cmax, Tmax, T½ el) by standard noncompartmental methods.
Results: All 42 subjects who enrolled were treated and analyzed. There were no significant differences in the TWA of MAP, SBP, or DBP and no clinically meaningful PK interactions between rimegepant and sumatriptan. Overall, 39 (92.9%) subjects experienced ≥1 AE; all but 3 (related to sumatriptan) were mild. The most common AE was injection site reaction (59.5%). Two subjects experienced mild increases in heart rate and BP. No other clinically meaningful changes from baseline in laboratory values, vital signs, or ECGs were identified.
Conclusion: No significant difference in BP parameters was detected between treatments with rimegepant + sumatriptan on Day 5 and sumatriptan on Day 1, and the TWA of MAP was similar. No clinically meaningful PK interactions were observed. Coadministration of rimegepant with sumatriptan was safe and well tolerated.
Disclosure of Interests: Robert Croop, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Joseph Stringfellow, MS, receives compensation from Biohaven Pharmaceuticals.
Michael Hanna, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Christopher M. Jensen, PharmD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Andrea Ivans, MHS, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Vladimir Coric, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.
IHC-LB-071
Nasal cavity evaporative cooling for the symptomatic relief of withdrawal headache during triptan detoxification, a randomized, double-blind, sham-controlled pilot-study
Laura de Ceuster1, Judith Pijpers1, Yvonne Raaijmakers1, Hille Koppen1,*
1Neurology, Haga Teaching Hospital, The Hague, Netherlands
Objective: Medication overuse, especially the overuse of triptans, is an important problem in a share of (chronic) migraine patients as it maintains their headaches. With intranasal evaporative cooling (Rhinochill by BrainCool) a beneficial effect on migraine-attacks was shown in an open label study previously. The aim of study was to evaluate the efficacy of intranasal evaporative cooling compared to sham treatment in reducing withdrawl headache during triptan detoxification.
Methods: 14 patients with both migraine (mean age 56, 64% female, 50% migraine with aura) and triptan-overuse headache according to the ICHD III criteria were admitted for inpatient detoxification for the first week of their 8 week triptan detoxification period and randomized to either intranasal cooling or sham treatment with the same device with normal temperature air. Both patients and all personnel were blinded for treatment status. Patients could use the RhinoChill device up to 4 times per 24 hours for up to 10 minutes during this first week of detoxification. Admission was on forehand limited to at most 7 days. The painscores (predefined as none, mild, moderate, severe) were recorded by patients on 3 time-points each use (before treatment, directly following 10 minute treatment and 60 minutes after treatment). Treatment success was defined as going from baseline moderate or severe pain to mild headache or no headache. Of the secondary endpoints only side effects are presented here.
Results: Baseline characteristics did not differ between active and sham-group. Triptans were used on average 21 days during the 4 week baseline period. Subjects in active group remained 3.3 (SD 2.5) days in hospital vs 3.7 (SD 2.1) in sham- group. Subjects in active arm treated a total of 4.5 (SD 3.1) headaches vs. 5.1(SD 2.1) in sham-group. Most of these headaches were rated as severe.
Primairy outcome: At least one attack with acute good effect (from moderate or severe to mild or less, 10 minutes after start of treatment) was reported by 50% in active group vs. 33% in sham group (p = 0.6). Only 38% of active treatment group reported this effect in at least 50% of treatments vs. 17% in sham group (p = 0.6). At least one attack with good effect at one hour timepoint (from moderate or severe to mild or less) was reported by 29% in active group vs. 33% in sham group (p = 1.0). Only 14% of active treatment group reported this effect at one hour in >50% of treatments vs. 17% in sham group (p = 1.0).
Side effects were reported by 38% in active treatment group and 50% in sham-group and generally mild. One subject receiving coolant reported epistaxis, two subjects (one in active group and one in sham-group) experienced nasal drip. Painfull stabs were reported by two subjects in sham group and one in active-group.
Conclusion: We could not demonstrate a therapeutic effect (at both t = 10 and t = 60 minutes) of intranasal cooling using Rhincochill device, compared to sham-treatment for migraine patients during in-hospital detoxification. We acknowledge the fact that this study was underpowered to detect a imaginable small therapeutic effect, as number of subjects was limited in this study. Intranasal cooling did not cause important side-effects limiting its use.
IHC-LB-072
Is the early therapeutic action of 75 mg orally disintegrating tablet of rimegepant clinically relevant? A comparison of rimegepant with oral triptans
Peer Tfelt-Hansen1,*
1Danish Headache Center, Rigshospitalet, Copenhagen, Denmark
Objective: In a recent paper in The Lancet (July 13, 2019) on a large randomized, controlled trial (RCT) on rimegepant (75 mg orally disintegrating tablet [ODT]), Tmax is 1.5 h, it is stated:” With early and sustained therapeutic action, the 75 mg ODT formulation of rimegepant should be clinically useful for the acute treatment of migraine” [1]. In order to evaluate the clinical relevance of the early effect of rimegepant was compared with the early (0.5 to 2 h) effect of sumatriptan 100 mg [2], and rizatriptan 10 mg [3].
Methods: The results (0.5–2 h), pain free (PF) and headache relief (HR) (decrease of headache from moderate or severe to none or mild) of the rimegepant paper [1] were compared with a Cochrane review of oral sumatriptan [2], and a meta-analysis of rizatriptan [3]. For each time point the therapeutic gain (effect for active drug minus effect for placebo) (TG) with 95% confidence intervals (95%CI) were calculated.
Results: An overview of the time-effect curves (from 0.5 h and 2 h) for the three drugs are shown in Table 1.
In a review of 4 RCTs with almotriptan 12.5 mg (Tmax 2.6 h) only detailed results after 0.5 and 2 h are presented.[4]: The TGs for HR after 0.5 and 2 h are 7% (95%CI: 3–10%) and 26% (95%CI: 26–32%). The TGs for PF after 0.5 and 2 h are 2% (95%CI: 0.2–3%) and 21% (95%CI: 16–26%), respectively.
Pain freedom (PF) and headache relief (decrease of headache from moderate or severe to none or mild) (HR) after ODT rimegepant 75 mg [1] (Tmax = 1.5 h), sumatriptan 100 mg [2] (Tmax = 1.5-2 h), and rizatriptan 10 mg [3] (Tmax = 1 h) from 0.5 h to 2 h. TG (effect for active drug minus effect for placebo) is presented in bold. In parentheses: 95% CI for TG.
0.5 h
1 h
1.5 h
2 h
Pain-free
Rimegepant 75 mg PF
8% (4–11%)
10% (7–14%)
Sumatriptan 100 mg PF
6% (4–7%)
20% (18–22%)
Rizatriptan 10 mg PF
1% (0.2–1.8%)a
9% (7–11%)
19% (17–21%)
31% (28–34%)
Headache relief
Rimegepant 75 mg HR
6% (0.5–11%)
12% (7–18%)
16% (11–21%)
Sumatriptan 100 mg HR
15% (12–17%)
29% (27% > 31%)
Rizatriptan 10 mg HR
6% (3–9%)
20% (17–23%)
29% (26–32%)
33% (30–36%)
Note: a, should be disregarded due to the small, not relevant magnitude, of the PF.
Conclusion: When judging time-effect curves for early effects of 2 acute drugs for migraine 2 factors should be evaluated: 1. When does a clinical relevant effect occur? 2. What are the TGs for PF (most relevant for patients) or HR at the same early time-points?
It can be questioned whether a TG of 6–7% for HR is clinically relevant effect, but the fact that this result was obtained 1 h after ODT rimegepant vs. 0.5 h after rizatriptan and almotriptan, strongly indicates an earlier effect for these 2 triptans. In addition, the TG ratios for HR for rimegepant/triptan at the same time-points (1, 1.5, and 2 h) varied from 0.3 to 0.5 (ratios in the same range was also observed for PF).
In summary, the onset of effect for ODT rimegepant is slower than the onset for the 2 triptans tested at 0.5 h postdose. The effect from 1 to 2 h for rimegepant is considerably lower for both HR and PF for sumatriptan and rizatriptan, see Table 1.
Disclosure of Interests: No interests of conflict.
IHC-LB-073
The Next Frontiers in Digital Therapeutics for Headache
Eran Schenker1,2,*
1Public Health, George Washington University, Washington DC, United States, Washington DC, United States
2Neurolief, Netanya, Israel
Objective: Neuromodulation is a rapidly developing therapeutic approach for migraine. In addition to providing an alternative to pharmacological treatment that is inadequate for many migraine sufferers, non-invasive adaptive multi-channel brain neuromodulation (MCBN) eco-system is pushing the frontier in the realm of digital health. In the context of neuromodulation, the next frontiers for digital health are prediction of migraine attacks, multichannel therapeutic electrical stimulation, and AI in the cloud.
Methods: Machine learning (ML) is emerging in the management of acute medical situations. In contrast with the classic scientific approach in which a hypothesis is formulated regarding possible associations between a disease attack and a triggering situation, ML systems can take a data mining approach. Utilizing data that come from sensors on the patient, from devices used by the patient, from the social media posts the patient and others, from electronic medical records, and from online descriptions of similar cases, ML systems potentially can “discover” associations that were not hypothesized in advance. To be sure, such an approach entails the risk of shining a spotlight to what is not really an association, but merely a coincidence due to the fact that if enough tests are performed, or enough test results checked, that a certain fraction of the results will be false positives.
Results: The MCBN eco-system is on the forefront in the realm of predicting attacks of medical conditions, in this case migraine attacks. Current understanding of migraine disorder suggests that the triggering of migraine attacks is linked with numerous subjective and objective events experienced by affected individuals. Many migraine sufferers experience an aura consisting of various sensorial disturbances, such as flashing of lights. These auras, as well as bodily changes of which the affected individual may not be aware, are linked to some overt physiological changes, but also numerous subtle changes.
Conclusion: Advancing data science in neurological and neuropsychiatric disorders, such as migraine, depression, ADHD and insomnia. AI, and ML technologies can enable advances that push the limit, in term of providing precise, personalized therapy, applied to migraine disorder.
Disclosure of Interests: Working with Neurolief LTD in the last two years building strategic partnership.
Inge Burger-Mulder1,*, Mei Li1, Tao Qin1, Takeshi Yanagisawa1, Kazutaka Sugimoto1, Arn van den Maagdenberg2, Michel Ferrari3 and Cenk Ayata4
1Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
2Neurology & Human Genetics
3Neurology, Leiden University Medical Center, Leiden, Netherlands
4Radiology & Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, United States
Objective: Migraine is a risk factor for cerebral and myocardial infarction. CGRP pathway inhibitors are emerging treatments for migraine. CGRP-mediated vasodilation is, however, a critical rescue mechanism in brain and cardiac ischemia. We, therefore, investigated whether gepants, small molecule CGRP receptor antagonists, worsen cerebral ischemia.
Methods: Middle cerebral artery was occluded by an endovascular filament for periods ranging 12–60 minutes in wild type and familial hemiplegic migraine type 1 (FHM1) mice. We compared infarct rates and volumes, collateral flow, and neurological outcomes after pretreatment with olcegepant (single or 10 daily doses of 0.1 or 1 mg/kg) or rimegepant (single doses of 10 or 100 mg/kg) versus vehicle.
Results: Olcegepant (1 mg/kg) increased infarct rates after 12–20-minute occlusions mimicking transient ischemic attacks (odds ratio 5.6, 95%CI: 1.4–26.1, p = 0.022), and infarct volumes (p = 0.031) and neurological deficits (p = 0.001) after 60-minute occlusions. Ten daily doses of 0.1 or 1 mg/kg olcegepant yielded similar results. Rimegepant 10 mg/kg increased infarct volumes after 20 minutes of ischemia (p = 0.03); 100 mg/kg caused 75% mortality after 60-minute occlusion versus none with vehicle. In FHM1 mice, olcegepant (0.1 or 1 mg/kg) dose-dependently increased infarct size after 30 min occlusion. Both gepants consistently diminished collateral flow during occlusion and reduced reperfusion success.
Conclusion: Gepants worsened experimental ischemic stroke in mice by inhibiting CGRP-mediated collateral vasodilation. CGRP pathway blockers might thus aggravate coincidental cerebral ischemic events. The cerebrovascular safety of these agents must therefore be better delineated, especially in patients with comorbid vascular disease and long-term CGRP inhibition for migraine prevention.
Disclosure of Interests: None.
IHC-LB-028
High Frequency Episodic Migraine Shift to Low Frequency Episodic Migraine in Patients Treated with Galcanezumab
Virginia Stauffer1,*, Jakub Jedynak1, Astrid Gendolla2, Eric Eross3 and Liequn Jin4
1Eli Lilly and Company, Indianapolis, United States
2Praxis Gendolla, Essex, Germany
3Phoenix Headache Institute, Scottsdale
4Covance, Inc., Bristol, United States
Objective: To assess the proportion of patients with episodic migraine (EM) who shift from high-frequency EM (HFEM) to low-frequency EM (LFEM) or very low-frequency EM (VLFEM) status after doses of galcanezumab.
Methods: EVOLVE-1 and EVOLVE-2 were double-blind, placebo-controlled, Phase 3 studies that enrolled 1773 patients with EM. Patients 18–65 years of age were randomized 2:1:1 to subcutaneous monthly injections of placebo, galcanezumab 120 mg (240 mg loading dose) or 240 mg, respectively, for up to 6 months. Data were pooled and endpoints were change from baseline in number of monthly migraine headache days (MHD) and patients who shifted from HFEM (8–14 MHD) to LFEM (≤7 MHD) or VLFEM (≤3 MHD).
Results: At baseline, patients with HFEM (66% of 1773 patients) had mean monthly migraine headache days of 11 days and Migraine Disability Assessment Score of 37 (severe disability). During the treatment phase, more galcanezumab-treated patients shifted to LFEM for 3 or more consecutive months and maintained LFEM until study end (68.4% and 69.2% for 120 and 240 mg/month, respectively; p < 0.001) vs placebo-treated patients (50.7%). Furthermore, significantly more galcanezumab-treated patients maintained LFEM for 3 or more consecutive months (75.2% and 77.1% for 120 and 240 mg/month, respectively; p < 0.001) vs placebo (58.3%).
Similarly, significantly more galcanezumab-treated patients shifted to VLFEM for 3 or more consecutive months during the treatment phase (47.7% and 47.7% for 120 and 240 mg/month, respectively; p < 0.001) vs placebo-treated patients (25.5%). Furthermore, more galcanezumab-treated patients shifted to VLFEM for 3 or more consecutive months and maintained VLFEM until study end (39.9% and 38.6% for 120 and 240 mg/month, respectively; p < 0.001) vs placebo (19.5%).
Conclusion: Both doses of galcanezumab were superior to placebo in the reduction of monthly migraine headache days, with significantly more patients shifting from HFEM to LFEM or VLFEM postdose. Results were similar between the galcanezumab doses.
Frequency of Shifts from High-Frequency Episodic Migraine to Low-Frequency Episodic Migraine or from High-Frequency Episodic Migraine to Very Low-Frequency Episodic Migraine Following Subcutaneous Injections of Placebo, Galcanezumab 120 mg or Galcanezumab 240 mg for ≥3 Consecutive Months to the End of the Study.
Sustained Response and Treatment
N
n
Percentage
Odds Ratio
95% CIs for Odds Ratioa
Shift from HFEM to maintenance of LFEM
Placebo
875
444
50.7%
Galcanezumab 120 mg/month
436
298
68.4%
2.21
(1.72, 2.84)
Galcanezumab 240 mg/month
428
296
69.2%
2.28
(1.77, 2.94)
Shift to maintenance of VLFEM
Placebo
875
171
19.5%
Galcanezumab 120 mg/month
436
174
39.9%
2.88
(2.21, 3.74)
Galcanezumab 240 mg/month
428
165
38.6%
2.69
(2.06, 3.50)
Abbreviations: CI = confidence interval; HFEM = high-frequency episodic migraine; LFEM = low-frequency episodic migraine; N = number of patients who had at least one non-missing post-baseline value; n = number of patients meeting sustained response definition among the number of patients; VLFEM = very low-frequency episodic migraine.
All p-values from logistic regression were <0.001, confirming the statistical significance of the results.
Studies were registered as NCT02614183 and NCT02614196 at ClinicalTrials.gov.
Disclosure of Interests: V. Stauffer and J. Jedynak are employees of Eli Lilly and Company; A. Gendolla is an employee of Praxis Gendolla; E. Eross is an employee of Phoenix Headache Institute, Consultant with: Allergan, Amgen, Teva, Novartis, Speaker for: Amgen, Teva, Novartis, Founder and President of Glia Sciences, Inc.; L. Jin is an employee of Covance, Inc.
IHC-LB-029
Safety and tolerability of erenumab in older migraine patients: A subgroup analysis of randomised trials
Christian Lampl1, Josefin Snellman2,*, Shannon Ritter3 and Jan Klatt2
1Headache Medical Centre, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria
2Novartis Pharma AG, Basel, Switzerland
3Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States
Objective: Erenumab (AMG334; Aimovig™, Amgen®, Novartis Pharma AG) is a fully human monoclonal antibody specifically designed for the preventive treatment of migraine, and has been used by over 250,000 patients since it was first made available. Migraine is a disabling neurological disease in all age groups, including older adults. Treatment of migraine in older patients requires further consideration due to possible comorbid medical conditions and concomitant medications. Here, we present a subgroup analysis of data including older patients (aged > 50 years) with chronic migraine (CM) or episodic migraine (EM).
Methods: Safety and tolerability of erenumab (70 mg or 140 mg) versus placebo was evaluated in subgroups of patients from two studies with CM (NCT02066415) or EM (NCT02456740, STRIVE). Subgroup analysis of patients in age groups 18–40, >40–50, >50–55 and >55 years was used to assess the safety and tolerability of erenumab during the 12-week double-blind period.
Results: Overall, the safety in the erenumab treatment groups was comparable to placebo across the age groups. Exposure-adjusted subject incidence rates were comparable between older (>50–55 and >55 years) and younger (18–40, >40–50) age groups. No notable imbalance was observed in the subject incidence of treatment-emergent adverse events (AEs), serious AEs or in the severity of AEs by age group. Safety and tolerability assessments for cardiovascular, cerebrovascular and peripheral vascular events were comparable across age groups. Common AEs such as sedation, cognitive dysfunction or anticholinergic syndromes associated with older patients were not seen in patients treated with erenumab.
Conclusion: Erenumab is safe and well-tolerated in older patients with CM and EM. Safety and tolerability in the erenumab treatment groups is comparable across different age groups.
Disclosure of Interests: Christian Lampl has received honoraria for planning and conducting clinical trials, participating in advisory board meetings and speaking for: Allergan, Eli Lilly, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi-Aventi and Teva. Josefin Snellman, Shannon Ritter, and Jan Klatt are employees and stockholders of Novartis.
IHC-LB-030
10-year cost-effectiveness analyses of response-based fremanezumab use in migraine patients with inadequate response to prior preventive treatments
Lee Smolen1,*, Stephen Thompson2, Timothy Klein1, Joshua M. Cohen2 and Sanjay K. Gandhi2
1Medical Decision Modeling Inc., Indianapolis, IN
2Teva Pharmaceuticals, Frazer, PA, United States
Objective: Cost-effectiveness (C-E) of fremanezumab for preventive treatment of chronic (CM) and episodic migraine (EM) in patients (pts) with inadequate response to 2–4 prior preventive treatment classes was examined, accounting for cessation of fremanezumab treatment for non-responders.
Methods: A semi-Markov C-E model (CEM) was developed with a 4-week (wk) cycle and 10-year (yr) analysis time horizon. Costs and benefits were discounted at 3.0% annual rates. Treatment efficacy was incorporated as reduction in mean migraine days(MDs)/28days vs placebo (PBO). Pt cohorts were distributed among MD categories (0–28MDs/28days) based on mean MD levels. The CEM estimated costs (fremanezumab acquisition and MD-related costs) and health-related-quality-of-life (MD- and treatment status–based utilities) for fremanezumab and no-treatment arms. Only background mortality was modeled. Analyses were performed on a combined CM(67%)/EM(33%) population. CM/EM patients not achieving 30%/50% reductions, respectively, in MDs/28days at 12 wks(non-responders) stopped treatment. The incremental C-E ratio (ICER) was reported as cost/quality-adjusted life-yr (QALY) gained between fremanezumab and no treatment. Fremanezumab MDs/28 day reductions vs PBO and 12-wk non-response rates were sourced from a network meta-analysis. In base-case analysis, fremanezumab was compared with constant no-treatment MD profiles. Fremanezumab was also compared with randomized-controlled trial (RCT)-sourced PBO-arm MD profiles.
Results: In base-case, 10-yr analysis time horizon, fremanezumab dominates no treatment (less costly, more effective): average cost savings, $3,492/pt; incremental QALYs, 0.22; reduction in MDs, 161.5MDs. Excluding indirect costs, fremanezumab resulted in a cost/QALY ICER of $13,606; average incremental costs, $2,998/pt. When PBO effects were included, fremanezumab dominates no treatment: average cost savings, $13,905/pt; incremental QALYs, 0.412; reduction in MDs, 353.9MDs.
Conclusion: Based on current pricing and RCT results, fremanezumab treatment is cost-effective versus no treatment, especially if discontinued at 12 wks for non-responders.
Disclosure of Interests: L. Smolen and T. Klein are employees of Medical Decision Modeling Inc., Indianapolis, Indiana, USA, which received payment for their work on these analyses from Teva Pharmaceuticals. S.K. Gandhi, S. Thompson, and J.M. Cohen are employees of Teva Pharmaceuticals.
IHC-LB-031
A Phase 2 Study of Galcanezumab in Japanese Patients with Episodic Migraine
Fumihiko Sakai1, Atsushi Kuga2,*, Akichika Ozeki2 and Vladimir Skljarevski3
1Saitama Neuropsychiatric Institute, Saitama
2Eli Lilly Japan K.K., Kobe, Japan
3Eli Lilly and Company, Indianapolis, IN, United States
Objective: Galcanezumab (GMB), a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, was investigated to determine superiority to placebo in the prevention of migraine headache in Japanese patients.
Methods: This study was a double-blind, 6 month (M) study in patients with episodic migraine (4–14 monthly migraine headache days [MHD]). Patients were randomized 1:1:2 to monthly subcutaneous injections of GMB 120 mg (N = 115), GMB 240 mg (N = 114), or placebo (N = 230). Primary endpoint was overall (M1–6) mean change from baseline in the number of monthly MHD (Mixed Models Repeated Measures analysis). Key secondary endpoints included overall rates of ≥50%, ≥75% and 100% reduction in monthly MHD and overall mean change from baseline in monthly MHD with acute migraine treatment, and mean change from baseline over M4–6 on the Migraine-Specific Quality of Life Questionnaire–Role Function-Restrictive domain (MSQ-RFR) and Patient Global Impression of Severity (PGI-S).
Results: Baseline mean of monthly MHD was 8.7 and was similar across treatment groups. Both GMB doses demonstrated a statistically significant improvement compared to placebo (p < .05) for overall mean change in monthly MHD (placebo = −0.59, GMB 120 mg = −3.60, GMB 240 mg = −3.36). Percentage of patients with MHD reductions of ≥50%, ≥75% or 100%, and reduction of monthly MHD with acute migraine treatment were significantly higher for each GMB dose relative to placebo. Mean change in MSQ-RFR was greater for each GMB dose versus placebo and in PGI-S for GMB 240 mg. There were no statistically significant differences between GMB and placebo on treatment-emergent adverse events except for a greater incidence of injection site-erythema, -pruritus, -swelling, -pain, influenza, and urticaria.
Conclusion: Both doses of GMB met the primary objectives and all key secondary objectives except for PGI-S. Efficacy and safety outcomes were similar across GMB doses. A very low placebo effect was observed. This study demonstrated that GMB provided clinical benefit, improved function, and was safe in Japanese patients with episodic migraine.
Disclosure of Interests: FS is an advisor of Eli Lilly Japan K.K.; AK and AO are full-time employees of Eli Lilly Japan K.K.; VS is a full-time employee of Eli Lilly and Company.
IHC-LB-032
User Acceptance of a Prefilled Auto-injector Device for Erenumab in Patients with Migraine
Ryan Dammerman1, Jennifer Mead1,*
1Amgen Inc., Thousand Oaks, CA, United States
Objective: Erenumab (AMG334; Aimovig™, Amgen®, Novartis Pharma AG) is a fully human monoclonal antibody specifically designed for the preventive treatment of migraine. Erenumab is approved for the preventive treatment of migraine in adults. Erenumab is available at doses of 70 mg and 140 mg as an auto-injector device for subcutaneous administration. The objective of this study was to evaluate the perceived ease-of-use of the device, the ability to learn self-injection, and the ergonomics of the single-dose, prefilled SureClick® auto-injector device for erenumab among patients with migraine.
Methods: Patients (aged 21–85 years old, inclusive) with migraine who were naïve to auto-injector or therapies targeting the CGRP pathway were recruited from 3 headache centers in the USA between March 04, 2019 and March 29, 2019. During a 30-minute 1:1 session, researchers demonstrated the SureClick® auto-injector device using a standard protocol-driven script under the supervision of research managers. Participants then practiced a simulated injection using a prototype device and were then asked to rate their agreement with 19 statements on the usability of the SureClick® auto-injector device on a 5-point Likert scale (1 = completely disagree, 2 = somewhat disagree, 3 = neutral, 4 = somewhat agree, 5 = completely agree).
Results: A total of 204 patients (73% female, 27% male) participated in the study. Over 90% of the participants agreed (somewhat agree or completely agree) on 17/19 statements on ease-of-use of the device, ability to self-inject, and size of the device with an average rating of >4.5 on a 5-point Likert scale (Table). Two statements relating to the size of device, “I like the size of the device,” and “The device is compact,” were rated 4.23 and 4.26, respectively.
Conclusion: The pre-filled SureClick® auto-injector device for erenumab, was well-received by patients with migraine. Following a 1:1 instructional session, participants with no prior experience of using an auto-injector device felt confident in their ability to self-inject with SureClick® auto-injector device.
Patients’ rating on the usability of the SureClick® device
Statement
Average rating*
% of Patients (N = 204) agreed (somewhat agree or completely agree)
Overall, the device is easy to use
4.75
96%
Overall, the device is simple to use
4.79
98%
It’s easy to inject by pressing the start button
4.79
96%
I feel confident in my ability to use the device
4.77
98%
I am confident in my ability to inject without the help of a caregiver
4.78
97%
The device is stable in my hand during administration
4.75
96%
Out of 5 on a Likert scale (1 = completely disagree, 2 = somewhat disagree, 3 = neutral, 4 = somewhat agree, 5 = completely agree).
Disclosure of Interests: Erenumab is co-developed by Amgen and Novartis.
The study was supported by Amgen Inc., Thousand Oaks, CA, USA, and Novartis Pharma AG, Basel, Switzerland.
Ryan Dammerman – used to provide services to Amgen during the conduct of the study;
Jennifer Mead – is an employee of Amgen.
IHC-LB-033
Consistency of Galcanezumab Efficacy Throughout a Month Over Time
Karen Samaan1, Patricia Pozo-Rosich2,*, Robert Nicholson1, Suchirita Rathmann1 and Eric Pearlman1
1Eli Lilly and Company, Indianapolis, United States
2Vall d’Hebron University Hospital and Vall d’Hebron Institute of Research, Barcelona, Spain
Objective: To determine if galcanezumab 120 mg once-monthly dosing maintains efficacy throughout the dosing interval.
Methods: This was a post-hoc analysis of 3 double-blind, placebo-controlled Phase 3 studies, in adult patients with chronic or episodic migraine. Patients received monthly subcutaneous galcanezumab 120 mg (initial loading dose of 240 mg) or placebo for 3 months (REGAIN; N = 835) or 6 months (EVOLVE-1 and -2; N = 1335). Endpoints for this study were the mean change from baseline in migraine headache days (MHDs), comparing the first 2 weeks and last 2 weeks in each month of the studies. Least squared mean changes were estimated using a mixed model for repeated measures analysis.
Mean Change from Baseline in Biweekly Number of Migraine Headache Days for the First and Last Two Weeks of the Last Month of the Study in Patients with Chronic or Episodic Migraine Following Injections of Galcanezumab or Placebo.
Chronic Migraine (Month 3 of REGAIN)
Episodic Migraine (Month 6 of EVOLVE-1 AND EVOLVE-2)
Period
Treatment
N
LS Means Change from Baseline (SE)
95% CI
Period
Treatment
N
LS Means Change from Baseline (SE)
95% CI
First Two Weeks
Placebo
509
−1.64 (0.20)
(−2.03, −1.25)*
First Two Weeks
Placebo
745
−1.46 (0.10)
(−1.65, −1.26)*
GMB 120 mg/month
262
−2.54 (0.25)
(−3.03, −2.04)*
GMB 120 mg/month
381
−2.28 (0.13)
(−2.53, −2.03)*
Last Two Weeks
Placebo
508
−1.79 (0.20)
(−2.19, −1.40)*
Last Two Weeks
Placebo
741
−1.49 (0.10)
(−1.68, −1.30)*
GMB 120 mg/month
263
−2.66 (0.26)
(−3.16, −2.15)*
GMB 120 mg/month
378
−2.34 (0.13)
(−2.59, −2.09)*
Abbreviations: CI = confidence interval; GMB = galcanezumab; LS = least squares; N = number of intent-to-treat subjects who have non-missing baseline value and at least one post-baseline value; SE = standard error.
Indicates statistical significance
Estimates were obtained using unstructured covariance structure. The Kenward-Roger approximation was used to estimate denominator degrees of freedom.
Results: Overall, reduction in MHDs observed in the first two weeks of the month was maintained during the last two weeks for chronic and episodic migraine. In patients with chronic migraine, mean MHDs were reduced by 1.84, 2.31, and 2.54 days with galcanezumab versus 0.73, 1.34, and 1.64 days with placebo in the first 2 weeks of Months 1, 2, and 3, respectively (p < 0.001; baseline monthly MHDs = 19.4. Similarly, in the last 2 weeks, mean MHDs were reduced by 1.98, 2.35, and 2.66 days with galcanezumab versus 1.15, 1.65, and 1.79 days with placebo, respectively, in Months 1, 2 and 3 (p < 0.001).
In patients with episodic migraine, mean MHDs were reduced by 1.80 and 2.28 days with galcanezumab versus 0.51 and 1.46 days for placebo in the first 2 weeks of Months 1 and 6, respectively (p < 0.001; baseline monthly MHDs = 9.1. Comparably, in the last 2 weeks, mean MHDs were reduced by 1.77 and 2.34 days with galcanezumab versus 0.86 and 1.49 days with placebo, respectively, in Months 1 and 6 (p < 0.001). The same pattern was seen across Months 2 to 5 (p < 0.001).
Conclusion: Galcanezumab 120-mg once monthly consistently maintains efficacy throughout each monthly dosing interval across months for chronic and episodic migraine. There is no difference in efficacy comparing the first and last halves of the month.
Studies were registered as NCT02614261, NCT02614183, and NCT02614196 at ClinicalTrials.gov.
Disclosure of Interests: K. Samaan, R. Nicholson, S. Rathmann, and E. Pearlman are employees of Eli Lilly and Company; P. Poso Rosich (PP-R) is an employee of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Research (Spain), PP-R has received honoraria as a consultant and speaker for: Allergan, Almirall, Chiesi, Eli Lilly, Novartis and Teva. Her research group has received research grants from Allergan and has received funding for clinical trials from Alder, Electrocore, Eli Lilly, Novartis and Teva. PP-R does not own stocks from any pharmaceutical company.
IHC-LB-034
First-Hand impressions of the new monoclonal antibody erenumab from patients in Germany
Heike Israel-Willner1,*, Katrin Schuh2, Mirja Koch2 and Charly Gaul3
1NFZB, Specialized Center of Neurology Berlin Sankt Gertrauden Hospital, Berlin
2Clinical Research Neuroscience, Novartis Pharma GmbH, Nuremberg
3Migraine and Headache Clinic, Koenigstein am Taunus, Germany
Objective: The growing importance of real-world evidence (RWE) data in the healthcare sector has been acknowledged for some years now. However, the value of capturing the patients’ benefit of a new therapeutic option is still largely underestimated. Therapy outcome in migraine treatment cannot solely be measured based on the reduction of migraine days. The quality of life including daily activity and time with the family, also the wellbeing of the patient are decisive factors driving migraine management. Thus, it is imperative to understand the patients’ perspective on treatment with the newly available fully human monoclonal antibody erenumab (Aimovig®), the first-in-class calcitonin gene-related peptide (CGRP) receptor inhibitor available since November 2018. This data collection aims to characterize the perception of erenumab from the patient's point of view.
Methods: An online survey will collect data from about 200–300 erenumab patients in Germany. Patients diagnosed with migraine will be questioned about their disease in general and their experience with pharmacological and non-pharmacological prophylactic therapies. Patients who have already been on therapy with erenumab for at least three months will be specifically surveyed.
Results: By September, data of the first interim analysis will be available. The use of erenumab will be characterized from the point of view of migraine patients with regard to therapy satisfaction, daily functioning, quality of life, changes in frequency and intensity of migraine and use of acute medication.
Conclusion: PERISCOPE will provide us the first real-world evidence data of German patients treated with erenumab and will provide insight into patient perspective regarding their experience controlling their migraine with the new prophylaxis erenumab, therapy satisfaction, therapy adherence and possible effects on the quality of life.
Disclosure of Interests: K. Schuh and M. Koch are employees of Novartis Pharma GmbH. Germany.
C. Gaul received honoraria for consulting and lectures within the past 3 years from Allergan Pharma, Ratiopharm, BoehringerIngelheimPharma, Eli Lilly, Novartis Pharma, DesitinArzneimittel, Cerbotec, Bayer Vital, HormosanPharma, electroCore, Grünenthal, Reckitt Benckiser, and Teva. He does not hold any stocks of pharmaceutical companies or medical device companies.
IHC-LB-035
Non-headache benefits of onabotulinumtoxinA in chronic migraine patients: PREEMPT pooled analysis
Hans-Christoph Diener1,*, Richard B. Lipton2, David W. Dodick3, Ronald E. DeGryse4, Aubrey Manack Adams4 and Stephen D. Silberstein5
1Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
2Department of Neurology, Albert Einstein College of Medicine, Bronx
3Department of Neurology, Mayo Clinic, Phoenix
4Allergan plc, Irvine
5Jefferson Headache Center, Thomas Jefferson University, Philadelphia, United States
Objective: To evaluate the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life.
Methods: A post-hoc analysis was conducted of pooled, 24-week data from the placebo-controlled, randomized, double-blind treatment phases of the PREEMPT clinical trials. The percentages of patients meeting responder status at 24 weeks for the change in headache days (≥50% reduction in headache-day frequency), the Headache Impact Test (HIT-6; ≥5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥1-point improvement on a 4-point ordinal scale where 0 = no pain and 3 = severe pain) were calculated. Percentages of patients meeting responder status in ≥1, ≥2, ≥3, and all 4 categories were calculated. Missing scores were estimated using modified last observation carried forward techniques.
Results: Patients (N = 1384) were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696) groups. Significantly more patients treated with onabotulinumtoxinA compared with placebo were responders with regard to change in headache days (44.8% vs 34.2%), HIT-6 (40.8% vs 25.3%), MSQ-RFR (59.0% vs 40.2%), and ADHS (35.5% vs 22.4%) at 24 weeks (all P < 0.001). At least 1 responder criteria was met by 72.1% and 56.6% of onabotulinumtoxinA and placebo patients, respectively (P < 0.001). All 4 criteria were met by 20.4% and 8.6% of onabotulinumtoxinA and placebo patients, respectively (P < 0.001). Linear regression analysis found approximately 20% of the variance in HIT-6 and MSQ-RFR improvement could be explained by improvement in headache days.
Conclusion: Change in headache days did not fully capture the benefit associated with 24 weeks of onabotulinumtoxinA treatment. While 45% of patients met responder criteria for monthly headache days, >70% of patients had clinically meaningful improvements on at least 1 outcome measure.
Disclosure of Interests: Support: Allergan plc, Dublin, Ireland.
Hans-Christoph Diener, MD, has received honoraria for participation in clinical trials and for contribution to advisory boards or oral presentations from Addex Pharma, Allergan, Almirall, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherex, CoLucid, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Lilly, La Roche, 3 M Medica, Medtronic, Menerini, Minster, MSD, Neuroscore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofi, St. Jude, and Weber & Weber. He has received financial support for research projects from Allergan, Almirall, AstraZeneca, Bayer, GSK, Janssen-Cilag, MSD, and Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. Dr. Diener has no ownership interest and does not own stock in any pharmaceutical company.
Richard B. Lipton, MD, serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta.
David W. Dodick, MD, reports personal fees from Acorda, Amgen, Alder, Allergan, Autonomic Technologies, Biohaven, Colucid, Eli Lilly, eNeura, Foresight Capital, Neurolief, Zosano, WL Gore, Vedanta Associates, Promius Pharma, Magellan Healthcare, CC West Ford Group, Nocira, Novartis, NuPathe, Supernus, Electrocore, Tonix, Teva, Alcobra, Insys, Ipsen, Charleston Laboratories, Biocentric, Theranica, Xenon, ZP Opco. Travel expense reimbursement and speaking fee from Sun Pharma. Anticipated income from consulting within next 3 weeks not previously reported: Impel Pharmaceuticals (currently under review by Mayo Clinic Medical Industry Relations Committee). Compensation for activities related to data safety monitoring committee from Axsome. Speaking fees, or fees related to CME content development: Healthlogix, Medicom Worldwide, Medlogix Communications, MedNet, Miller Medical Communications, PeerView Operation Services America, Web MD/Medscape, American Academy of Neurology, American Headache Society, PeerView Institute for Medical Education, Chameleon Communications, Academy for Continued Healthcare Learning, Universal Meeting Management, Haymarket Medical Education, Global Scientific Communications, UpToDate, Meeting LogiX. Consulting use agreement through employer: NeuroAssessment Systems, Myndshft.
Ronald E. DeGryse, MS, MA, and Aubrey Manack Adams, PhD, are full-time employees of Allergan plc and own stock in the company.
Stephen D. Silberstein, MD, is a consultant and/or advisory panel member for and has received honoraria from Alder Biopharmaceuticals, Allergan, Amgen, Avanir, eNeura, ElectroCore Medical, Labrys Biologics, Medscape, Medtronic, Neuralieve, NINDS, Pfizer, and Teva. His employer receives research support from Allergan, Amgen, Cumberland Pharmaceuticals, ElectroCore Medical, Labrys Biologics, Eli Lilly, Merz, and Troy Healthcare.
IHC-LB-036
Galcanezumab shows efficacy as early as Day 1 after initial treatment v. placebo for the prevention of episodic and chronic migraine
Anna P. Andreou1,2, Peter Wright3,*, Holland C. Detke3, Dustin Ruff3 and Uwe Reuter4
1Headache Centre, Guy's and St Thomas' NHS Foundation Trust
2Headache Research, Wolfson CARD, King's College, London, United Kingdom
3Eli Lilly and Company, Indianapolis, United States
4Charité Universitätsmedizin, Berlin, Germany
Objective: To evaluate onset of efficacy of galcanezumab (GMB) in patients with episodic or chronic migraine.
Methods: Migraine headache occurrence during the first 7 days including and following initial study treatment was analyzed for patients from 3 double-blind, Phase 3 studies. EVOLVE-1 (N = 858) and EVOLVE-2 (N = 915) were 6-month studies in patients with episodic migraine; REGAIN (N = 1,113) was a 3-month study in patients with chronic migraine. Patients were randomized 2:1:1 to monthly injections with placebo (PBO), GMB 120 mg with a 240 mg loading dose, or GMB 240 mg. Onset of efficacy was defined as the earliest time point at which GMB became superior to PBO and maintained that superiority for the primary outcome (change in migraine headache days [MHD]). Monthly and weekly analyses were based on mean change from baseline in MHD; daily analyses were based on the percent of patients with migraine headache on day of injection through 6 days post-injection. Percentages were modeled to control for baseline differences.
Results: As GMB was superior to PBO in reducing MHD starting at the first month and even as early as the first week of treatment, daily analyses were also conducted. In the baseline periods, a daily average of 30% of patients in the EVOLVE-1 and EVOLVE-2 trials, and 65% of patients with chronic migraine in REGAIN trial experienced migraine headache. At Day 1 post-injection, significantly fewer GMB-treated patients experienced MHD versus PBO-treated patients (EVOLVE-1: 14% in GMB vs 22% in PBO, p = .002; EVOLVE-2: 18% in GMB vs 24% in PBO, p = .038; REGAIN: 49% in GMB vs 58% in PBO, p = .004). GMB-treated patients continued to have significantly lower MHD rates for each remaining day during the first week of treatment compared with placebo-treated patients in all 3 studies (all p-values < 0.05).
Conclusion: GMB showed statistically superior efficacy to placebo starting at Day 1 after injection and the effect was sustained throughout the trials in both episodic and chronic migraine patients.
Disclosure of Interests: These studies were funded by Eli Lilly and Company.
PW, HCD, and DR are employees and minor stockholders of Eli Lilly and Company.
UR has received support from Eli Lilly, Amgen, Novartis, Alder, Allergan, TEVA, and Medscape for participation in clinical trials and speaking.
IHC-LB-037
10-year cost-effectiveness analyses of fremanezumab compared to erenumab as preventive treatment in episodic migraine for patients with inadequate response to prior preventive treatments
Lee Smolen1,*, Joshua M. Cohen2, Timothy Klein1, Sanjay K. Gandhi2 and Stephen Thompson2
1Medical Decision Modeling Inc., Indianapolis, IN
2Teva Pharmaceuticals, Frazer, PA, United States
Objective: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide, is approved for the preventive treatment of episodic migraine in adults. Cost-effectiveness of fremanezumab versus erenumab for the prevention of episodic migraine (EM) in patients who had responded inadequately to 2 to 4 classes of prior preventive treatments was examined.
Methods: A semi-Markov cost-effectiveness model (CEM) was developed with a 4-week cycle and 10-year analysis time horizon. Costs and benefits were discounted at 3.0% annual rates. Treatment efficacies were incorporated as reductions in mean migraine days (MDs)/28 days versus placebo. Patient cohorts were distributed among MD categories (0–28 MDs/28 days) based on mean MD levels. For this study, EM was defined as patients with 4 to 14 MDs per 28 days at the start of the study. The CEM estimated costs (fremanezumab and erenumab acquisition costs, MD-related costs [direct and indirect]) and health-related-quality-of-life (MD- and treatment status–based utilities) for fremanezumab and erenumab. Outcome measures were costs, reduction in MDs, and quality-adjusted life-years (QALYs). Only background mortality was modeled. Analyses were performed on an EM population with 2–4 prior treatment failures. The incremental cost-effectiveness ratios (ICERs) were reported as cost/QALY gained between fremanezumab and erenumab. Fremanezumab and erenumab (140 mg dosing) MDs/28-day reductions versus placebo were sourced from a Network Meta-Analysis (NMA). The analysis assumed the same discontinuation rate for fremanezumab and erenumab.
Results: In the base-case 10-year analysis time horizon, fremanezumab dominates erenumab (less costly, more effective), with an average incremental cost savings of $1,795/patient, incremental QALYs of 0.037/patient, and a reduction in MDs of 33.3 MDs/patient. Excluding indirect costs, fremanezumab still dominates erenumab, with an average incremental cost savings of $936.96/patient.
Conclusion: Based on current pricing and RCT results, fremanezumab treatment is cost effective versus erenumab.
Disclosure of Interests: L. Smolen and T. Klein are employees of Medical Decision Modeling Inc., Indianapolis, Indiana, USA, which received payment for their work on these analyses from Teva Pharmaceuticals. S.K. Gandhi, S. Thompson, and J.M. Cohen are employees of Teva Pharmaceuticals.
IHC-LB-038
Repeated peripheral nerve blocks reduce cutaneus allodynia symptoms, headache-related disability, depression, and anxiety in chronic migraine
Devrimsel H. Ertem1,*, Ulgen Y. tekan1, Yavuz altunkaynak2 and Derya uluduz3
1Neurology, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
2Neurology, Bakırkoy Psychiatric and Neurological Diseases Education and Research Hospital, Istanbul, Turkey
3Neurology, cerrahpasa school of medicine, istanbul, Turkey
Objective: Up to date, there is a lack of evidence whether the combination of trigeminal nerve branch blocks and occipital nerve blocks is more effective than greater occipital nerve blocks (GON) alone, or if the injections should only be inserted to the localization of the migraine pain. In this study, the effects of repeated trigeminal nerve branch and GON blocks on cutaneous allodynia (CA), migraine-related disability, depression and anxiety symptoms in chronic migraine were assessed.
Methods: Twenty patients with chronic migraine who failed adequate trials of at least 3 preventive drug classes were enrolled. Six months of results following repeated bilateral supraorbital nerve, auriculotemporal nerve, and GON blocks were evaluated. A total of 10 mL of 2 lidocaine HCL was injected each month. Change in the Numeric Pain Rating Scale (NPRS), Allodynia Symptom Checklist (ASC), Beck Depression and Anxiety Inventory, and MIDAS were used to assess the response to blocks.
Results: The mean age of patients was 46.25 ± 9.92, 95% were female. The mean number of headaches days/month was 21.10 ± 5.07 and following the 6th injection, mean headache days reduced to 6.1 ± 2.11 (p = 0.012). For analysing the mid-term effect of injections on ASC, NPRS, depression, anxiety, and MIDAS scores, Anova with repeated measures test was used. These differences were noted to be statistically significant (all p values < 0.05). Medication overuse headache and localization of migraine pain were not associated with ASC scores’ decline over time (p = 0.461).
Conclusion: This study demonstrates that repeated occipital plus trigeminal branch nerve blocks with local anaesthetics may be an effective option for management of chronic migraine, contribute to treatment of allodynia and prevent migraine chronification.
Disclosure of Interests: None.
IHC-LB-039
Cortical excitability in chronic migraine patients after preventive treatment measured by TMS
Ada Artemenko1,*, Vladlena Shevchenko1, Olga Shavlovskaya1, Alexey Kurenkov2, Nikolay Yahno1, Mikhail Bzhiljanski and Fedor Bushkov
1I.M. Sechenov First Moscow State Medical University (Sechenov University)
2Scientific Centre of Children’s Health, Moscow, Russian Federation
Objective: OnabotulinumtoxinA (OnabotA) and topiramate are regulatory approved effective medications for chronic migraine (CM) preventive treatment, however, the exact mechanisms of their antinociceptive action in CM are not fully understood.
Methods: 85 patients with CM (mean age 44, women 97%, diagnosis according to ICHD-III beta, 2013) were included in the open-label prospective study. We assessed motor cortex thresholds (MT r/l, % of maximal stimulator output), cortical silent period duration (CSP r/l, ms) by motor cortex stimulation with recording responses from abductor digiti minimi muscles r/l and phosphene threshold (PT, % of maximal stimulator output) by visual cortex stimulation. Clinical data were collected from headache diaries: number of headache days per month. TMS was performed twice: before and 3 months after OnabotA injections (according to the PREEMPT paradigm; n = 43) and Тopiramate (100 mg/day; n = 42).
TMS parameters in CM patients before/after OnabotA (n = 43) and Topiramate (n = 42)
OnabotA
Тopiramate
Parameter
Before
After
Before
After
MT, % Me (min-max) (25; 75%)
Right
40 (26–60) (37; 49)
45 (32–63) (38; 52)*
41 (27–56) (35; 47)
45 (28–57) (38; 48)*
Left
42 (26–61) (38; 51)
45 (33–62) (37; 52)*
40 (27–57) (33; 44)
45 (28–55) (37; 48)*
CSP duration, ms Me (min-max) (25; 75%)
Right
96 (47–161) (78; 114)
117 (73–167) (96; 138)*
94 (52–165) (80; 111)
92 (57–147) (83; 116)
Left
96 (47–170) (72; 120)
117 (75–170) (94; 141)*
85 (56–165) (70; 110)
87 (55–158) (72; 126)
PT
% Me (min-max) (25; 75%)
63 (40–95) (52; 74)
63 (46–93) (52; 77)
64 (40–94) (51; 73)
72 (49–95) (62; 84)*
- statistically significant difference between parameters before and after treatment in each group of CM patients.
Results: After OnabotA, MT r/l and CSP r/l significantly increased compared to baseline; after Тopiramate, MT r/l and PT significantly increased compared to baseline (Table 1).
The number of headache per month decreased significantly in both groups: OnabotA (before 29 days, after 12 days; p < 0,01) and Topiramate (before 25 days, after 12 days; p < 0,01).
Conclusion: The results of our study showed a combination of significant clinical parameters improvement with TMS parameters changes, reflecting cortical excitability and intracortical inhibition. This suggests that cortical mechanisms in CM “de-chronification” are obligatory involved, independently of primary peripheral (like OnabotA) or central (like Topiramate) action mechanism.
Disclosure of Interest: None Declared.
IHC-LB-074
CGRP Monoclonal Antibodies: First Year Results, Controversies, and Management Issues
Lawrence Robbins1,*
1Neurology, Chicago Medical School, North Chicago, United States
Objective: This is a retrospective review of the first year's use of fremanezumab and galcanezumab for the prevention of chronic migraine. Efficacy and side effects are reviewed. In addition, results from switching from one monoclonal antibody(mAb) to another will be presented. controversies and management issues will be discusse.
Methods: This is a retrospective, office based review of results after 3 months for 79 fremanezumab patients and 70 emgality patients. The results of 121 patients who had switched from one mAb to another were evaluated. IRB approval was obtained. Improvement was determined primarily by the number of headache days per month.
Results: 51% of patients achieved at least a 30% improvement in the number of headache days with the use of fremanezumab, and 60% with the use of galcanezumab. Side effects were frequent, with the most common ones being constipation, nausea, depression, and increased headache. When the patients were swtiched from one mAb to another, 27% did well if the switch was due to poor efficacy. 33% improved if the switch was because of side effects, while 58% did well if it was secondary to financial or insurance reasons.
Various management issues will be discussed, such as the use of onabotulinumtoxinA with the mAb, long-term efficacy, serious side effects, and others.
Conclusion: The efficacy of the mAbs is reasonably good, but the side effects are commonly enountered. There are a number of management issues and controversies that need to be addressed.
Disclosure of Interests: Speaker for Lilly, Teva, and Amgen.
IHC-LB-075
In Vivo Antagonistic Activity and Endogenous Target Engagement of an Anti-PACAP Monoclonal Antibody in Cynomolgus Monkeys
Cristina Moldovan Loomis1, Susan M. Pederson1, Daniel R. Boster1, Lisa Perrino McCulloch1, John A. Latham1, Leon F. Garcia-Martinez1,*
1Alder BioPharmaceuticals, Inc., Bothell, WA, United States
Objective: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that has been implicated in migraine pathophysiology. A role for PACAP in migraine is supported by clinical observations including human provocation studies that have demonstrated that PACAP triggers migraines and migraine-associated symptoms, such as photophobia, phonophobia, and nausea. In addition, clinical studies have reported increased ictal PACAP levels in the plasma of patients with migraine. We have discovered and engineered ALD1910, a humanized anti-PACAP monoclonal antibody for the preventive treatment of migraine. The amino acid sequence of PACAP is identical in human, cynomolgus monkey, rabbit, rat, and mouse; therefore, it is expected for ALD1910 to cross-react with PACAP across these species. Cynomolgus monkeys were chosen as a relevant pharmacology model to characterize the in vivo antagonistic effects of ALD1910 on PACAP-mediated biology. The objectives of this study were to determine the in vivo antagonistic activity and the target engagement ability of ALD1910 in cynomolgus monkeys.
Methods: The in vivo ability of ALD1910 to inhibit PACAP38-mediated dermal vasodilation in cynomolgus monkeys was determined via laser Doppler technology. The ability of ALD1910 to interact with cynomolgus monkey endogenous PACAP was determined via a sandwich ELISA.
Results: Our results show that ALD1910, administered by intravenous bolus injection in male cynomolgus monkeys, effectively inhibits PACAP38-induced dermal vasodilation as measured by laser Doppler technology. Target engagement of ALD1910 with endogenous cynomolgus monkey PACAP in vivo was confirmed through the detection of the [ALD1910:PACAP] complex.
Conclusion: Collectively, the data demonstrate that ALD1910 exhibits antagonistic in vivo activity and engages native endogenous PACAP when administered intravenously to cynomolgus monkeys.
Disclosure of Interests: All authors are full-time employees of Alder BioPharmaceuticals.
IHC-LB-076
Real-life management of chronic migraine with Erenumab: correlation of clinical improvement with biomolecular and neurophysiological parameters
Roberto De Icco1,2,*, Giuseppe Fiamingo1,2, Rosaria Greco1, Anna Zanaboni1,2, Elena Tumelero1, Sara Bottiroli1,3, Elena Guaschino1, Marta Allena1, Valentina Grillo1, Cristina Tassorelli1,2 and Grazia Sances1
1Headache Science Centre, IRCCS Mondino Foundation
2Department of Brain and Behavioral Sciences, University of Pavia, Pavia
3Faculty of Law, Giustino Fortunato University, Benevento, Italy
Objective: The aim of this study is the correlation of the clinical effectiveness of Erenumab, administered in a real-life setting, with changes in the expression of micro-RNA that are relevant for migraine and spinal central sensitization in subjects with chronic migraine (CM) with or without medication overuse (MO).
Methods: We enrolled 23 CM patients (19 female, age 48.1 ± 10.0 years), 19 of whom had MO. All patients were treated with 3 doses of Erenumab (every 28 days). The study protocol included: V1: baseline; V2: 28 days after V1; V3: end of study, 56 days after V2.
At V1, V2 and V3 we recorded headache days (HDs) and days of drug intake (DDs) using an ad hoc headache diary.
At V1 and V3 all subjects underwent neurophysiological recording of the Nociceptive Withdrawal Reflex (RTh: Reflex threshold, TST: Temporal Summation) and blood essays for the expression of micro-RNAs (using rtPCR): miR382-5p, implicated in the modulation of inflammation and mir34-5p implicated in the expression of GABA receptors.
Results: HDs markedly and progressively decreased over time (V1: 23.6 ± 5.4; V2: 16.1 ± 8.2; V3: 12.0 ± 8.1; p = 0.001), reaching the statistical level of significance already at V2. A similar pattern was observed for DDs, which significantly decreased over time (V1: 18.0 ± 8.0; V2: 8.1 ± 6.3; V3: 4.0 ± 2.5; F 20.110, p = 0.001) with a reduction that was already significant at V2.
At V3, we recorded a significant increase in both R-Th (V1: 15.9 ± 7.9, V3: 19.37 ± 8.9; p = 0.001) and TST (V1: 11.4 ± 5.7, V3: 12.8 ± 5.5; p = 0.003), with a parallel reduction in the expression of miR382-5p (V1: 7.8 ± 6.7, V3: 2.2 ± 2.9) and miR-34a-5p (V1: 25.8 ± 19.4, V3:4.7 ± 4.0), p = 0.001 for both.
Conclusion: This study provides the first report of the positive effects of Erenumab on biomolecular and neurophysiological alterations related to CM.
Disclosure of Interests: RDI, GF, RG, AZ, ET, SB, EG, MA, VG, and GS have no conflicts of interest to declare. CT received honoraria for the participation in advisory boards or for oral presentations from: Allergan, Electrocore, Eli-Lilly, Novartis and Teva. CT has no ownership interest and does not own stocks of any pharmaceutical company. CT serves as Chief Section Editor of Frontiers in Neurology – Section Headache Medicine and Facial Pain and on the editorial board of The Journal of Headache and Pain.
IHC-LB-077
Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination
Bianca Raffaelli1,2,*, Valeria Mussetto1, Heike Israel1, Lars Neeb1 and Uwe Reuter1
1Department of Neurology, Charité Universitätsmedizin Berlin
2Clinician Scientist Program, Berlin Institute of Health (BIH), Berlin, Germany
Objective: Monoclonal antibodies (mAbs) targeting the CGRP pathway are safe and efficacious therapies for the prevention of migraine. In this study we assessed the effects of discontinuation of preventive erenumab and galcanezumab treatment in patients with chronic migraine.
Methods: This retrospective pooled analysis included completers of the open-label extension study phase for the preventive treatment of chronic migraine with galcanezumab (NCT02614261; 9 months) and erenumab (NCT02174861; 12 months) in a single headache center. We compare migraine data until week 12 after open-label treatment completion, when patients did not have any pharmacological preventive medication, to study baseline values of the double-blind trial period, and to the last 4 weeks of the open-label extension. The assessment included changes in monthly migraine days, headache hours, days with severe headache and acute headache medication use.
Results: Data from 16 patients after galcanezumab (n = 9) and erenumab (n = 7) open-label treatment completion were analyzed. The mean number of monthly migraine days was 18.38 ± 3.74 at baseline, and 12.19 ± 4.53 in the last 4 weeks of the open-label extension (p < 0.001). Monthly migraine days remained significantly reduced compared to baseline during the entire 12-week observation period after open-label termination (p = 0.002), with a reduction of 5.38 ± 4.92 in weeks 1–4 (p = 0.001), 4.75 ± 4.15 in weeks 5–8 (p = 0.001), and 3.93 ± 5.45 in weeks 9–12 (p = 0.014). There was no significant difference in monthly migraine days between the 12 weeks after open-label termination and the last 4 weeks of the open-label phase (p = 0.228). All other analyses revealed numerical improvement through week 12 in comparison to baseline.
Conclusion: In this small, self-selected cohort, the results indicate a therapeutic effect of monoclonal antibodies targeting the CRGP pathway in chronic migraine prevention after treatment termination up to 12 weeks.
Disclosure of Interests: BR has received honoraria for consulting from Novartis Pharma. VM reports no disclosures. HI has received honoraria for consulting from Pharm Allergan and Autonomic Technologies. LN has received honoraria for consulting from Eli Lilly and Novartis Pharma, and for scientific presentations by Pharm Allergan, Desitin, Hormosan, Eli Lilly, Novartis Pharma and TEVA. UR has received honoraria for consulting from Amgen, Pharm Allergan, Autonomic Technologies, Co-Lucid, Eli Lilly, Medscape; StreaMedUp, Novartis Pharma and TEVA, and for scientific presentations by Amgen, Allergan, Eli Lilly, Co-Lucid, Medscape, Novartis Pharma and TEVA. BR, HI, LN and UR are involved as investigators in clinical trials with monoclonal antibodies from Amgen, Alder, Eli Lilly, Novartis, and TEVA without personal remuneration.
IHC-LB-078
Erenumab for Migraine Treatment – First Real World Data from Germany
Steffen Naegel1,2,*, Armin Scheffler1, Sebastian F. Wurthmann1 and Dagny Holle1
1Dept. of Neurology, University Hospital Essen, Essen
2Dept. of Neurology, University Hospital Halle, Halle, Germany
Objective: Erenumab is the only approved antibody against the CGRP receptor, and in Germany is used for the treatment of refractory migraine. Previously clinical trials showed that the substance is well tolerated and has a good efficacy. Data reflecting real world conditions are still scarce. This is especially relevant as clinical trials have not looked for these severely refractory patients in particular which are currently being treated due to reimbursement regulations. We here present real-world therapy response regarding headache and migraine days and intake of acute medication after 3-month Erenumab therapy.
Methods: 79 therapy refractory patients (non-response, side effects or contraindications of 4 or, in chronic migraine 5 prophylactic medication groups; 52 with chronic migraine, 27 with episodic migraine) were evaluated regarding their migraine before and after 3-month Erenumab therapy. The majority of patients started with a starting dose of 70 mg (N = 75 patients), the rest with 140 mg. Headache days, migraine days and the use of acute therapies were documented in the follow-up using headache diaries. Retrospective nonparametric analysis was performed on non-normally distributed data using the Wilcoxon-Mann-Whitney test.
Results: The analysis of all patients revealed a reduction in headache days (17.862 ± 7.072 vs. 12.914 ± 9.031; p < 0.001), migraine days (14.1692 ± 6.343 vs. 9.24 ± 7.684; p < 0.001), and days on which acute medication was taken (11.243 ± 6.094 vs. 7.018 ± 5.832, p < 0.001). 58% of patients with chronic migraine under therapy converted to episodic migraine within the three months follow up. The 50% response rate regarding headache days was 35.5%. The rate of patients who did not achieve any improvement under therapy or who increased the number of headache days was 27.6%.
Conclusion: As in clinical trials, under real conditions, a significant response to Erenumab therapy was demonstrated in our cohort. In particular, the conversion rate from chronic to episodic migraine is clinically relevant. However, almost one third of the patients did not respond to the therapy. The extent to which these patients could benefit from an increased dose, a longer therapy or a change of preparation to a CGRP ligand antibody is still unclear. The long-term course of therapy response needs to be investigated in more detail.
Disclosure of Interests: SN and DHL have received honorariums for advisory board and presentations from Novartis, Lilly and Teva Pharma.
IHC-LB-079
Single-pulse transcranial magnetic stimulation (sTMS) for the treatment of migraine: A prospective real world single-centre experience
Bethany Hill1,*, Joseph Lloyd2, Madeleine Murphy1, Anna P. Andreou1,2 and Giorgio Lambru1
1Headache Centre, Guy’s and St Thomas’ NHS Foundation Trust
2Headache Research, Wolfson CARD, King’s College London, London, United Kingdom
Objective: The Headache Centre at Guy’s and St Thomas’ NHS Foundation Trust is currently the only National Health System (NHS) service commissioned to offer sTMS to migraine patients in the United Kingdom (UK). The aim of this audit is to evaluate the effectiveness of sTMS (eNeura) as a non-pharmacological treatment modality in adults with chronic/high frequency episodic migraine in a real-world setting.
Methods: This is an open-label prospective ongoing single centre clinical audit. Patients with a diagnosis of episodic high frequency (≧8 migraine days/month) or chronic migraine were offered the therapy. A standard titration protocol for prevention and acute migraine treatment was given to patients in clinic. Data were collected prospectively using a headache diary and HIT-6 scale. Change in headache days (HD), migraine days (MD) and HIT-6 at 3 and 12 months of treatment compared to baseline were analysed. Adverse events and treatment compliance were collected.
Results: A total of 128 patients were treated with sTMS. Hundred-one patients completed the 3-month trial period and were analysed. Forty-three patients (43%) received sTMS after failing at least 3 oral preventives and Botox therapy, hence were considered refractory to medical treatments. At baseline, patients displayed an average of 18.3 HD/month, of which 14.7 were MD with a average HIT-6 score of 66. Following a 3-month trial, 22 patients achieved at least a 30% reduction in HD, while a total of 49 patients (49%) obtained a clinically meaningful benefit (−6.4 HD/month, – 6.7 MD/month and −8.8 points on HIT-6 score), hence continued the treatment. Fifty-two (51%) patients stopped the treatment due to lack of efficacy. Of those, the majority were refractory to medical treatments. (N = 34; 64%). Currently,18 patients continue sTMS treatment for over 12 months. Treatment compliance was satisfactory with sTMS used up to eight pulses three times a day. Side effects were minor and include: worsening of the headache (N = 3), transient mild dizziness during the treatment (N = 1), scalp tenderness (N = 2) and nausea (N = 1).
Conclusion: sTMS constitutes an effective and well tolerated preventive treatment option for high frequency/chronic migraine patients in a real world setting.
Disclosure of Interests: APA received sponsorship and equipment grant from eNeura. BH received sponsorship from eNeura.
IHC-LB-080
Evaluation of the efficacy of Topiramate in the treatment of vestibular migraine
Tatiana Ivanova1,* and Elena Filatova1
1Department of Neurology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Objective: to evaluate the efficacy of a therapeutic pathway for VM with Topiramate.
Methods: 152 patients with migraine with aura and without aura, average age 39.5 ± 13.1 years, females 122 were recruited. Their medical history and neurological status was analyzed. All patients filled up Dizziness Handicap Inventory (DHI) scale and headache (HA) diary. VM was diagnosed according to ICHD-3 beta version. Patients with VM had otoneurological examination to exclude peripheral vestibulopathy.
Results: The main group consisted of patients with VM – 13,8% (n = 21), and controls were patients with dizziness (D) – 42,2% (n = 64); 2,6% (n = 4) of patients had peripheral vestibulopathy and 41,45% (n = 63) of patients had no vertigo (V) or D. Less patients with episodic migraine (EM) suffered from V than patients with chronic migraine (CM) (23 people (31.9%) vs 40 people (51.9%), p = 0.01). In VM group CM was observed more often than in the group with EM (15 people (20.8%) vs 6 people (7.7%), p = 0.01). 16 of 21 patients with VM passed treatment with topiramate during 6 months: during the first month, the dose was gradually increased from 25 to 100 mg/day.
Results of treatment with topiramate of patients with VM.
Pretreatment n = 16
Posttreatment n = 16
p
Number of days with HA
11,63 ± 8,5
2,8 ± 1,04
p < 0,01
Number of days with V
14,88 ± 8,4
2,3 ± 2,4
p < 0,01
DHI F
17,23 ± 6,8
2,63 ± 0,8
p < 0,01
DHI E
11,88 ± 7,7
2,81 ± 0,8
p < 0,01
DHI P
15,5 ± 5,1
3,75 ± 2,2
p < 0,01
∑ DHI
45 ± 17,03
9,3 ± 2,5
p < 0,01
100% (n = 16) VM patients who got topiramate showed a significant decrease in the number of days with headache and vertigo per month and severity of dizziness by DHI.
Conclusion: Our data confirm high comorbidity of M and V. V in VM occurs during chronification. High efficacy of topiramate, in reducing both the frequency of migraine attacks and vertigo indirectly confirm the role of central sensitization in the pathogenesis of the VM.
Disclosure of Interest: None Declared.
IHC-LB-081
Long term safety profile of DHE use in chronic headaches
Menai McDonald1,*, Geroge Dickson2 and Alok Tyagi2
1Institute of Neurological Sciences, Glasgow, United Kingdom
2Neurology, Institute of Neurological Sciences, Glasgow, United Kingdom
Objective: Dihydroergotamine (DHE) has been used since 1943 in the treatment of migraine. Since the advent of triptans, its use has mainly been for medically refractory primary headaches. In 2013, the European Medicines Agency released a statement recommending restricting the use of ergot derivatives due to increasing concern over the risk of fibrosis. However it is an effective treatment for resistant primary headache. There is little published data on its safety profile to guide its use. By examining current practice within our tertiary Neurology Centre, we hope to explore this.
Methods: We performed a retrospective audit on all patients receiving IV DHE infusions between January 2014 and June 2019 in our tertiary Neurology Centre. We examined case notes to look at number of infusions received. For those who received 5 or more infusions (time equivalent of 2 years) we noted whether patients underwent an echocardiogram or CT chest/abdo/pelvis (CT CAP) to look for valvular, retroperitoneal or pulmonary fibrosis. Any fibrosis found was highlighted.
Results: Of 65 patients identified, 38 patients received 5 or more DHE infusions. 13 underwent an echo and a CT CAP (or US as per radiology). These patients had been on treatment for 121 to 373 weeks (mean 224 weeks/4.3 years) prior to surveillance scans and received on average 9.5 infusions. 3 patients had subsequent imaging 91, 96 and 107 weeks later. These patients received 12, 13 and 16 infusions respectively. 4 patients had an echo and chest xray. 4 patients had CT CAP only. A echo and CT CAP were performed for unrelated indications. No patients were found to have valvular or retroperitoneal fibrosis. One patient with pre-existing bronchiectasis was found to have pulmonary fibrosis, but after Respiratory Review, this was felt to be unrelated to DHE use. This patient, however received no further DHE treatment. 15 patients have undergone no surveillance scans, of which 6 remain on treatment.
Conclusion: None of our patients receiving DHE have had a fibrotic reaction directly attributed to their DHE treatment, however data is incomplete for 66%. It would be our recommendation that all patients should be screened for fibrotic reactions, however there is no clear guidance on mode of imaging or frequency. This would be an appropriate area for further research.
Disclosure of Interests: Dr Tyagi, from Janssen Cilage, GSK, Allergan, Electrocore, Lily, AMGEN, Novartis, eNeura, Teva, Alder, Abbott, has received: research grants, funding to conduct clinical trials, educational grants for meetings/teaching courses, funding to attend medical conferences, hospitality in and out of hospital premises.
IHC-LB-082
How effective is erenumab for patients with chronic migraine who failed onabotulinum toxin type A as prophylactic treatment?
Objective: In this single-center, retrospective database study, the efficacy and safety of erenumab was assessed in patients with chronic migraine (CM) who had failed prophylactic onabotulinum toxin type A and at least three other previous prophylactic treatments.
In the Netherlands, national guidelines recommend topiramate as the first-line prophylactic therapy for CM (ICHD-III), with onabotulinum toxin type A recommended as second-line therapy. However, reimbursement for onabotulinum toxin type A requires failure of at least three prior prophylactic treatments. Since November 2018, CM patients in the Netherlands failing at least four prophylactic treatments (beta-blockers, candesartan, topiramate, valproic acid and onabotulinum toxin type A) have had access to erenumab through a Managed Access Program (MAP).
Following both national guidelines and reimbursement requirements means that patients eligible for erenumab under the MAP have failed onabotulinum toxin type A and at least three other prophylactic treatments.
Methods: Of 152 (100%) patients with CM identified in our database, 47 (31 %) were treated with approved and reimbursed onabotulinum toxin type A. Of this group, 33 (70%) were successfully treated (i.e. satisfying criteria relating to reduction in the number of headache days, Headache Impact Test (HIT)/Migraine Disability Assessment (MIDAS) score, and anamnestic wellbeing). Fourteen patients (30%) did not improve. Diagnosis of CM was reconfirmed in this group of 14 patients prior to initiation of treatment with erenumab.
Results: At the end of 3 months follow up, there was a significant improvement in 11 of the 14 (79%) erenumab-treated patients, while 3 (21%) discontinued through lack of efficacy. There were no discontinuations due to adverse events.
Conclusion: Erenumab is a therapeutic option for migraine prophylaxis even in patients with CM who have failed multiple lines of prophylactic therapy, including onabotulinum toxin type A. Between November 2018 and the end of June 2019 this center has successfully treated 44 of 47 (94%) patients with CM who fulfilled the inclusion criteria for this new prophylactic treatment.
Disclosure of Interests: Consulting, boards and presentations for Allergan, Lilly, Novartis.
IHC-LB-083
Erenumab in chronic migraine: a conventional scheme versus erenumab + short dechronification – Pilot data
Maria Nicolodi1,*, Maria Stella Pinnaro2, Therapy on behalf of Foundation Prevention, Primary Pain, Florence, Vanessa S. Italy, Sandoval3
1Scientific Research
2Foundation Prevention and Therapy Primary Pain
3Scientific Research, Foundation Prevention and Therapy Primary Pain and Headache, Florence, Italy
Objective: Background In 1990s we detected increase of sensory neuropeptides like-immunoreactivity (LI), including CGRP-LI in trigeminal area fluids during headache attacks. We also evidenced a role of N-methyl-D-aspartate (NMDA) in migraine chronification. Since prevention with erenumab is known to carry a great variability and a not a dramatic significativity it seems interesting to improve this headache-specific therapy.
Aim To compare erenumab to CGRP–R-antibody after 5 days dechronification using 5Glu antagonists versus erenumab following 7 days wash-out in chronic refractory migraineurs. Focus: Migraine relief, side-effects.
Methods: Population: participation claim was made by using social media. Entry/exclusion criteria allowed to enroll 213 out of 587 chronic migraineurs refractory to conventional prophylactic treatments. Thus, 106 males, 107 females (age 31.8 ± 5.2SD) volunteered single blind 2 parallel-branches randomization: 104 assigned to 70-mg erenumab after 7 days wash-out (A), 109 to erenumab after fixed pre-treatment with NMDA antagonist (B). Treatments were administered twice. Informed consent was obtained, statements WMA Helsinki Declaration 2000 were followed.
Results: June 2019, 30 volunteers of both groups completed the observation.
Pain-Relief mean migraine-days/month.
Baseline vs. 1 month post-treatment.
20.8 ± 1.4SD vs17.3 ± 1.6SD Group A p > 0.00001
22.4 ± 2.1 SD vs 8.9 ± 2.2SD Group B p > 0.000001
By month 2 (2nd treatment), migraine/days/month.
16.4 ± 1.9SD Group A p > 0.00001
1.1 ± 1.8SD Group B p > 0.000001
Scores Migraine Physical Function Impact Diary: Group A = 30%, Group B = 100% (p > 0.00001)
Preference Index–Group B: sustained pain-free; 0–1 rescue/2months (ibuporfen mesylate 200 mg) p > 000001 vs baseline.
Group A rescue p > 0.004 (23.4 ± 4SD vs 16.9 ± 4.8SD)
Guideline on the preventive treatment of chronic migraine, chronic tension type headache, hemicrania continua and new daily persistent headache on belhaf of the Colombian Association of Neurology
Joe Munoz1,*, Mauricio Rueda2, Oscar Pradilla2, Michel Volcy3, Sergio F Ramirez1, Bernardo Uribe4, Natalia Hernandez3, Carolina Guerra3, Marta Ramos1, Gustavo Pradilla2, Fidel Sobrino1, Daniel Torres3, Juan D Jimenez5, Jose D Martinez3 and Gabriel Torres Torres1
1Neurology, acn, Bogota
2Neurology, ACN, Bucaramanga
3Neurology, ACN, Medellin
4Neurology, acn, Manizalez
5Neurology, acn, Pereira, Colombia
Objective: To recommend therapeutical options for the preventive treatment of chronic migraine, tension type headache, hemicrania continua and new daily persistent headache.
Methods: The Colombian association of neurology identified an expert group in order to develop recommendations. Alternatives with evidence-based information were analyzed through systematic review and GRADE methodology. In the case of options with clinical efficacy but without support based on well-designed clinical trials, the expert group performed the recommendations using delphy methodology.
Results: For chronic migraine we recommend topiramate, onabotulinun toxin and erenumab, Prednisone was not recommended in detoxification therapy (GRADE evaluation) Fig 1. Other alternatives are divalproate/valproic acid, amitirptiline, flunarizine and naratriptan (Consensus). Tension type headache could be treated with amitriptiline, imipramine and venlafaxine (Consensus). Indomethacine, topiramate and celecoxib are the pharmaceutical choices recommended to treat patients with hemicrania continua (Consensus). For new daily persistent headache we recommend gabapentin and doxicicline. According to clinical judgment craneal nerve blocks could be indicated in all the cases. Education and a comprehensive approach is essential in order to achieve better results.
Conclusion: The experts of the Colombian Association of Neurology present the therapeutic alternatives for the preventive treatment of primary chronic daily headache, although most of the informations is based on expert recommendations, this approach could improve the use of resources in the treatment of this condition. Further studies are needed in order to generate evidence which strength these recommendations.
Disclosure of Interests: None.
IHC-LB-085
Perampanel as prophylaxis treatment in refractory chronic migraine
Jose M. Sanchez Alvarez1,*, Rocio Alvarez Escudero1, David Fuentes Castanon1 and Pablo Siso Garcia1
1Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain
Objective: Chronic migraine is a disabling disease, with high impact in their quality of life. Current prophylactic treatments are often not effective or bad tolerated. Glutamate is elevated in chronic migraine, and AMPA receptor is implicated in the maintenance the pain. Perampanel, an antagonist of the AMPA receptor could have a preventive effect in chronic migraine.
Methods: We review the records of patients with refractory chronic migraine treated with Perampanel, and the results at third month.
Results: There were 35 patients (25 females), mean age 46,5 years (SD 11,8). All of them were not responders to, at least, Propranolol, Flunazine, Topiramate, Amitriptyline and Onabotulinumtoxin. The mean monthly migraine days (MMD), were 25,8 (SD 4,76). The dose was 4 mg/24 h but one patient who tolerated 6 mg/24 h. Five patients (14%), could not complete it due to adverse events (AEs). Only 10 (14%), did not complain of AEs. The AEs were drowsiness, dizziness and irritability.
After 3 months, 2 patients (6%), were slightly worse; one (3%), had reduced MMD by 30%; 5 (14%), by 50–74%; 9 (26%), ≥75%. Fifteen patients (43%), had converted to episodic migraine.
Conclusion: Even though the tolerance issue, 40% of the patients reduced MMD >50%. Perampanel might be an option in refractory chronic migraine. More studies are needed.
Disclosure of Interests: None.
IHC-LB-086
The role of botulinum toxin and anesthetic block in refractory neuralgies to medical therapy – Characterization of a sample
Isabel Luzeiro1,*, Alexandra Silva1 and Rita Machado1
1Neurology, CHUC, Coimbra, Portugal
Objective: Botulinum toxin administration and anesthetic block are minimally invasive interventions used for refractory pain when preventive drugs fail. Benefits of these administrations has been reported as temporary pain relief. This study’s aim is to caratherize the patients who underwent botulinum toxin and anesthetic block in neuralgic and cervicogenic headache in Headache outpatient clinic and verify the eficacy of these treatments.
Methods: Cohort study including patients with trigeminal and occipital neuralgia and cervicogenic headache over a 30 months period, who underwent botulinum toxin and anesthetic block. Data was obtained through the consultation records and contacting patients by telephone.
Results: 12 patients were included, mean age of 65.83 years, being 58.3% female. 50% were diagnosed with trigeminal neuralgia, 33.3% cervicogenic headache and 16.7% occipital neuralgia. 50% performed block with bupivacaine, 16.7% with botulinum toxin (follow the pain) and 33.3% did both. Patients who underwent anesthetic nerve block were back to the Clinic earlier (mean of 2 months).
33.3% didn’t need to take prophylactic pills anymore. 75% had prior drug abuse. The difference between the lenght of the pain during a week decreased from 5.5 days to 1.8 and need to use pills decreased from 5.5 days/week to 2.99. 91.7% reported no side effects, 8.3% reported pain worsening.
Conclusion: Botulinum toxin appears to be effective in cases of neuralgia, as anesthetic nerve block in cervicogenic headache. Although the effect of blockage with bupivacaina is transitory.
The neuralgia pain relief is partial with botulinum toxin, but allow a better life quality.
We need more patients treated with these new methods to achive new guidelines like what drugs should we use, how long and in what doses it can be effective.
Disclosure of Interest: None Declared.
Neuromodulation for Headaches
IHC-LB-040
Temporal migraine surgery: auriculotemporal and zygomaticotemporal nerves decompression under endoscopic guidance with preserving superficial temporal artery
Minchul Oh1,*
1Madiheal Neurosurgery Clinic, Seoul, Korea, Republic Of
Objective: Temporal region is the most common site in patients with migraine headache. However in a relatively large number of patients, treatment outcome remains insufficient and a drug intolerability of adverse effects further can limit the use of medication. For these patients, relatively simple decompression surgery with minimal complication can be considered as alternative and effective treatment.
Methods: The auriculotemporal and zygomaticotemporal nerves entrapment are the two primary pathology and the main surgical focus in the temporal area of migraine headache. We described and delineated the surgical procedure in eighteen patients with temporal migraine who were medically intractable and uncontrolled. All procedure were combined open decompression in auriculotemporal nerves and endoscopic decompression in zygomaticotemporal nerves with preserving superficial temporal artery under local anesthesia.
Results: Fourteen patients (77%) reported a successful surgery (>50 percent improvement of headache index) at least 6 months after surgery (mean follow-up, 8 months). Eight patients (44%) reported complete elimination of temporal migraine headache. There were no significant surgical complication or wound problem.
Conclusion: Decompression surgery of auriculotemporal and zygomaticotemporal nerve-triggered migraine headache should be considered in patients with medically uncontrolled migraine. In addition, superficial temporal artery preserving surgery showed nearly similar results compared with previous reports that coagulate or sacrifice superficial temporal artery.
Disclosure of Interest: None Declared.
IHC-LB-087
Neuromodulation with eTNS in migraine – the first Romanian experience
Bogdan I. Pana1,*, Andra Iosif1 and Adina Roceanu2
1Emerald Medical Center, Bucharest, Romania
2Emergency University Hospital, Bucharest, Romania
Objective: Neurostimulation is emerging as a credible alternative in migraine therapy and is considered to have a very favorable efficacy/safety ratio. Our goal was to examine the safety and preventive effect of eTNS (external trigeminal nerve stimulation) for migraine in Romanian patients. The end points of the study where: the percentage of responder patients (more than 50% reduction) in migraine hours, medium pain intensity, migraine attacks and rescue medication.
Methods: Patients were prospectively enrolled between January to July 2019, previously or “de novo” diagnosed with migraine, with or without aura, including patients with prophylaxis prescribed at least three months before the initiation of the study. All subjects were asked to use the device for 20 minutes every day in prevention mode and for 60 minutes in acute mode for a minimum period of 3 months. The patients were asked to complete a journal with the number of migraine hours each day, the intensity of the pain (from 1 to 10) and if they used the device and/or rescue medication. The baseline parameters where recorded anamnestically.
Results: From the 32 patients that fulfilled the inclusion criteria, 6.25% dropped out because of the pain during the sessions. Nine patients fully completed the migraine diary. 44% where observed for 3 months, 22% for 4, 11% for 5 and 22% for 7 months. The total number of migraine hours was significantly reduced in 55% at 3 months, but at 5, respectively 7 months 50% of the non-responders became responders. The medium pain intensity was significantly reduced in 22% at 3 months, 14% of the others becoming responders at 4 months and 28% at 7 months. None had a significantly reduced number of migraine attacks at 3 months, but 11% had at 5 months and 22% at 7 months. At baseline 66% used triptans as rescue medication, 66% of them did not used triptans at all after 3 months and the others achieved a reduction of 40%, respectively 45%.
Conclusion: The majority of the previously migraine prevention studies with eTNS (Cefaly) where conducted for a period of three months, using the device only on preventive mode. This study raises the question if the patients should be observed for longer periods using eTNS for both prevention and acute mode. The study was not externally funded.
Disclosure of Interests: None.
Other
IHC-LB-041
Efforts to accelerate the discovery and clinical development of non-addictive therapeutics for pain within the nih heal initiative
Smriti Iyengar1,*, Sarah A. Woller1, Clinton B. Wright1, Amir P. Tamiz1 and Barbara I. Karp1
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, United States
Objective: The NIH HEAL (Helping to End Addiction Long-term) Initiative is an aggressive, trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the Initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction and enhancing pain management. The trans-agency, multi-institute HEAL Initiative is being led by the National Institute of Drug Abuse (NIDA) and the National Institute of Neurological Disorders and Stroke (NINDS). Within HEAL, NIDA is focused on understanding, preventing, and treating addiction. NINDS is focused on understanding pain mechanisms and developing effective, non-addictive treatments for pain, including headache. Together, programs within the HEAL Initiative will reduce the burden of illness due to addiction and pain.
Methods: NINDS was tasked with the goal of enhancing pain management through identification of non-addictive pharmacologic and non-pharmacologic interventions. As a result, NINDS, along with multiple institutes across the NIH, built a collaborative infrastructure of therapeutic development programs designed to enhance our understanding of the development and prevention of chronic pain, including headache. These programs span the discovery process from target validation through clinical trials.
Results: Programs in the infrastructure include: (1) A Preclinical Screening Platform for Pain (PSPP) focused on the identification and profiling of non-addictive/non-opioid therapeutics for pain, and (2) an Early Phase Pain Investigation Clinical Network (EPPIC-Net), to test new therapeutics for pain conditions in adults and children. These programs will evaluate small molecules, biologics, devices, and natural products across a range of pain conditions including headache.
Conclusion: This presentation will describe the two NINDS/NIH HEAL Initiative programs and efforts to test new therapies for pain, including headache.
Disclosure of Interest: None Declared.
IHC-LB-042
Identifying self-management research needs through an exploration of the views of migraine patients and their carers about their role and the roles of others
Anne-Marie Logan1,*, Nan Greenwood2 and Mark Edwards1
1Molecular and Clinical Sciences Research Institute
2Faculty of Health, Social Care and Education, St George's University of London, London, United Kingdom
Objective: To explore what headache management roles migraine patients and carers identify as present, important or missing in order to identify future self-management research needs.
Methods: Patients were approached consecutively in two phases; those attending a secondary care headache service in phase one and those attending a third sector migraine primary care service in phase two. The discussion guide was developed by the author with patients and responses recorded by hand. Those who agreed to take part were asked if their responses could be used anonymously for dissemination by presentation/publication. Ethics approval was not needed as the work aimed to identify areas of research needs.
The first phase responses were analysed thematically using an inductive approach to group similar codes into themes. The results were reviewed with the patient advisor and the discussion guide was then adapted. The process was repeated in the second phase.
Results: Discussions were held with thirteen secondary care and 8 third sector patients. Patients spoke of the importance of their role. The reasons given for their role were “doing the GP’s job”, “the GP tried” or “most motivated person”, “the only solution”.
Discussions about treatment showed a power imbalance between the patient, GP and neurologist. Patients’ roles rarely mentioned treatment whereas GPs “should be able to give treatment” “alter medicines” but “do as they are told by the consultant”. It was thought that treatment “should be with the GP, not the consultant” however the neurologist was “guru” and was the one with a “range of treatment”.
The patient’s role related instead to lifestyle adaptations through awareness. “Day to day awareness”, “can I do this, can I go out?” linked to “leading the right lifestyle”.
Finally collaboration, “have to use medical side and your side together” was important in developing a “partnership”.
Conclusion: Patients were clear on their important role and a wish for active partnership with clinicians. They saw treatment access through neurologists but their roles concentrated on adaptation. There is a clear research need to identify ways to develop active partnerships between GPs and patients to enhance treatment in primary care.
Disclosure of Interest: None Declared.
IHC-LB-043
World Brain Day; Migraine Painful Truth WFN-IHS successful collaboration with a global impact
Tissa Wijeratne1,*, David Dodick2, Wolfgang Grisold3 and William Carroll4
1School of Psychology & Public Health. Department of Psychology & Counselling, La Trobe University, Bundoora, Australia
2Neurology, Mayo Clinic, Scottsdale, United States
3Neurology, Ludwig Boltzman Institute, Vienna, Austria
4Neurology, Perron Institute, Nedlands Perth, Australia
Objective: Annually, the World Federation of Neurology (WFN) celebrates World Brain Day (WBD) on July 22 (the official anniversary of WFN) with each year focusing on a different theme. 2019 the theme is “ Migraine, The Painful Truth”. Migraine is the leading cause of disability affecting people under the age of fifty years (the group with the highest contribution to the worldwide workforce). This makes migraine one of the highest negative economic impacts globally. The latest analysis from the Global Burden of Disease study, 3 billion people had a headache disorder in 2016, including 1.04 billion with migraine. The painful truth us despite the very high prevalence and public health burden, research in migraine remains the most underfunded area in neurology. People with migraine and other headache disorders experience substantial stigma. Migraine continues to be under-diagnosed and poorly managed, developed and especially in developing countries.
Methods: 2019 WBD campaign was organised by the IHS and WFN. This ambitious joint project between the IHS and WFN went on to develop the key messages, social media feeds, press releases, global webinar that was freely accessible to the member countries of both IHS and WFN.
Results: Local societies were provided with material and also suggestions for press mailings.
Together, we can ensure that those affected by migraine receive the help they need.
The 2019 World Brain Day campaign had been a resounding successJ. Over 100 countries took part in this well-coordinated campaign, culminating in a worldwide Webinar https://www.wfneurology.org/world-brain-day-2019 addressing the five key messages. as above. The webinar received very positive feedback from all over the world.
The social media impressions on world brain post surpassed the three million impression mark. Just over 100 national radio, TV, print, web-based presentations cut across the world, sharing the painful truth about migraine. Several national migraine walks were launched for the first time.
The successful campaign created an unprecedented opportunity of global advocacy program with huge potential for grassroots impact. The WBD committee expect continue the momentum throughout 2019.
Conclusion: 2019 IHS-WFN World Brain Day Campaign is a tremendous success. We hope to continue the momentum throughout the year with a view to tackle this pervasive disorder and find solution to the five key thems we raised.
Disclosure of Interests: TW, WC, WG nothing to disclose.
IHC-LB-088
Zolpidem-Induced Headache: A Case Series
Abdolhamid Parsa1, Mohammad Babaeian1,*
1School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic Of
Objective: The body of evidence and adverse effect reports of zolpidem is rapidly growing. The aim of presenting the current report is to discuss the possible causes of different types of headache observed in seven adults following the consumption of different doses of zolpidem with different patterns of use.
Methods: Two pharmacists have evaluated seven adults -age range 22–47 years- who self-reported different types of headache associated with zolpidem use. Every important and practical information obtained from the cases has been kept as confidential. Five electronic databases were searched to find and identify all available, accessible and relevant case reports and case series.
Results: The mean standard age of the cases was 31 years. Headache symptoms were observed in all the cases. 45 % of the affected cases had at least one type of primary headache before starting to use zolpidem. All of cases got better following zolpidem tapering down or withdrawal. The development of headache seemed to be associated with zolpidem consumption, especially when the used dose was exceeded than recommended.
Conclusion: Given that the occurrence of such complication was 100% of all cases, it let us conclude that headache should be counted as a significant adverse effect of zolpidem. Clinicians should be aware of this risk and advise their patients accordingly.
Disclosure of Interests: The Authors haven't anything to disclose.
IHC-LB-089
Neck pain associated with migraine attacks investigated in the interictal state – a search for the origin of pain
Jeppe Hvedstrup1,*, Lærke T. Kolding1, Samaira Younis2, Messoud Ashina2 and Henrik W. Schytz1
1Headache Diagnostic Laboratory
2Human Migraine Research Unit, Danish Headache Center and Department of Neurology, Copenhagen, Denmark
Objective: To investigate phenotypical differences between migraine patients with and without neck pain associated with migraine attacks in the interictal phase.
Methods: One-hundred migraine patients and 46 controls went through a semi-structured interview and sensory testing interictally. Pericranial muscle tenderness was determined using total tenderness score and local tenderness score. The occurrence of migraine attacks was prospectively recorded for the following seven days.
Results: Patients with neck pain associated with migraine attacks had increased tenderness of pericranial neck muscles compared to migraine patients without (P = 0.023). Neck pain associated with migraine attacks was not associated with migraine localization, tension-type headache or markers of central sensitization. Prospective data of 84 patients showed that tenderness of trigeminal sensory innervated muscles increased the migraine attack rate (P = 0.035).
Conclusion: The study suggests a possible peripheral influence on migraine pain in patients with neck pain associated with migraine attacks. The distinction of migraine patients based on the occurrence of neck pain associated with migraine attacks could be a useful biomarker in future migraine studies.
Disclosure of Interests: The authors have no conflict of interest to declare.
Other Primary Headache Disorders
IHC-LB-044
PCH-CU: Description of primary cough headache in a cough unit. A prospective study
Stephanie Becker1, David Moreno Ajona1,2,*, Jan Hoffmann1,2, Francesca Puledda1,2, Surinder Birring3 and Peter J. Goadsby1,2
1Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London
2NIHR-Wellcome Trust King’s Clinical Research Facility/SLaM Biomedical Research Centre
3Respiratory Medicine, King's College Hospital, London, United Kingdom
Objective: Description of characteristics, prevalence and comorbidities associated with cough headache in a Cough Unit.
Methods: From July 2018 to date, consecutive patients who attend the Cough Clinic were asked about the presence of headache with and without cough. The eligibility of the participants was determined via telephone interview. Neurological/ neuro-otological examination; and a modified Valsalva test were completed, MRI with cranio-cervical views. Results were tabulated and statistical analysis included χ2 and Pearson correlation coefficient.
Results: At interim analaysis, 245 patients completed the screening. Of these, 167 (68%) suffered from headache, of which 78 (47%) reported headache with cough. Fifty patients have completed the telephone interview (61% women, mean age of 45 ± 4 years) and 35 (70%) met the diagnostic criteria of cough headache according to the International Classification of Headache Disorders (ICHD-3). The remaining patients met the criteria for migraine. Among patients with cough headache, 90% had a previous history of migraine. Median time since headache onset was 6 years (range 3–11 years). The average attack duration was 1 hour, the most frequent location was occipital and cough was the only trigger in 65%. Associated symptoms included either vertigo, described as “spinning, whirling or being on a boat” (20%) or “dizziness”, described as “lightheadedness, giddiness or floating” (32%) for seconds in 52% of patients. The modified Valsalva test was positive in 37% but did not distinguish between primary and secondary headaches. The respiratory diagnosis: cough hypersensitivity syndrome was significantly related to the diagnosis of cough headache (χ2 = 5.2 p = 0.02). Four secondary headaches (8%) were identified: Chiari malformation, tuberculosis, fungal sinus infection and headache attributed to low CSF pressure.
Conclusion: In the presence of chronic cough, primary cough headache is more frequent in women with a history of migraine and could be related to cough hypersensitivity syndrome. Secondary cough headache was not as prevalent as in previous series. The modified Valsalva test was not capable of distinguishing primary from secondary headaches.
Disclosure of Interests: Stephanie Becker reports no conflicts of interest.
David Moreno-Ajona reports no conflicts of interest.
Jan Hoffmann has received honoraria for consulting and/or serving on advisory boards for Allergan, Autonomic Technologies Inc. (ATI), Atheneum Partners, Chordate Medical AB, Eli Lilly, Hormosan Pharma, Novartis and Teva. He has received honoraria for speaking from Allergan, Autonomic Technologies Inc. (ATI), Chordate Medical AB, Novartis and Teva. JH also received financial compensation for serving as an Associate Editor, reviewing and/or writing manuscripts from Cephalalgia (Sage Publishing), Journal of Oral & Facial Pain and Headache (Quintessence Publishing) and Oxford University Press.
Surinder Birring reports no conflicts of interest.
Peter J Goadsby reports, over the last 36 months, grants and personal fees from Amgen and Eli-Lilly and Company, and personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr Reddy's Laboratories, Electrocore LLC, eNeura, Impel Neuropharma, MundiPharma, Novartis, Teva Pharmaceuticals, Trigemina Inc., WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and a patent magnetic stimulation for headache assigned to eNeura without fee.
IHC-LB-090
Comparison of clinical profile of patients having chronic migraine with patients having new daily persistent headache of chronic migraine subtype
Karthik Nagaraj1,*, Francesca Puledda1, Diana Wei1, Nicolas Vandenbussche1, Jonathan Ong2, Sadaf Waheed1 and Peter Goadsby1
1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London and NIHR-Wellcome Trust King’s Clinical Research Facility, London, United Kingdom
2Department of Medicine, Division of Neurology, National University Hospital, Singapore, Singapore
Objective: To compare the clinical profile of patients having chronic migraine (CM) with patients having new daily persistent headache of chronic migraine type (NDPH CM)
Methods: An audit was conducted of the clinical letters of patients presenting with a phenotype of new daily persistent headache of chronic migraine type (NDPH-CM) and chronic migraine (CM) from a tertiary referral centre from 2014 to 2019.
Results: Patients with NDPH CM (n = 76) and CM (n = 257) were identified.
The age at first headache was lower in the CM group with respect to the NDPH-CM group (median and IQR: 14, 10–20 vs 19, 14–34; p < 0.001)
A total of 71% and 83% of the NDPH-CM and CM cohorts, respectively, were female (p = 0.022)
The total number of associated symptoms was greater in the CM group with respect to the NDPH-CM group (median and IQR: 6, 5–8 vs 5, 4–7; p < 0.001)
The total number of postdromal symptoms (median and IQR: 2, 1–3 vs 1, 0–2; p = 0.008) was greater in the CM group compared to the NDPH-CM group.
The total number of premonitory symptoms (median and IQR: 3, 2–5 vs 3, 2–4; p = 0.182) and cranial autonomic symptoms (median and IQR: 2, 1–4 vs 2, 0–4; p = 0.798) were not different in the 2 groups.
The total number of preventives used was also greater in the NDPH CM group compared to the CM group (median and IQR: 7,5-10 vs 6, 4–9; p = 0.01). Medication overuse was present in 33% of NDPH CM group and 51% of the CM subtype (p = 0.006)
Family history of headache was greater in the CM group compared to the NDPH-CM group (82% vs 53%) (p < 0.001).
Conclusion: There are significant differences between CM and NDPH-CM with regards to: age of headache onset, gender distribution, family history of headache, total number of associated symptoms, total number of postdromal symptoms and concomitant medication overuse.
Disclosure of Interests: The authors do not have any conflicts of interest for the above study.
IHC-LB-091
Clinical audit of patients with new daily persistent headache (NDPH)
Karthik Nagaraj1,*, Francesca Puledda1, Diana Wei1, Nicolas Vandenbussche1, Jonathan Ong2, Sadaf Waheed1 and Peter Goadsby1
1Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King’s College London and NIHR-Wellcome Trust King’s Clinical Research Facility, London, United Kingdom
2Department of Medicine, Division of Neurology, National University Hospital, Singapore, Singapore
Objective: To analyse the clinical symptomatology, therapeutic profile and outcome of a cohort of patients with a new daily persistent headache (NDPH) phenotype.
Methods: An audit of patients who presented with a phenotype of new daily persistent headache (NDPH) from a tertiary referral centre between 2014 and 2019 was conducted using clinic documentation.
Results: Of patients identified (n = 133), the chronic migraine (CM) subtype was identified in 87% (n = 115) and the featureless subtype in 2% (n = 2). Of the remaining patients, eight (6%) were under investigation for hemicrania continua, five (4%) were suspected to have low CSF pressure, one (0.7%) was found to have chronic paroxysmal hemicrania with migraine and one (0.7%) had idiopathic intracranial hypertension.
The median age of onset of NDPH was 24 years with an interquartile range (IQR) of 14–38. The median time to diagnosis was 3 (IQR:1-5) years. A past history of migraine was present in 45% of the cohort. A preceding event just before NDPH onset was found in 49% of patients. Within the CM subtype, 27% of patients had aura. The median number of cranial autonomic symptoms (CAS) was 1 (IQR: 0–3). The median number of premonitory symptoms among patients with the CM subtype was 2 (IQR: 1–4). The median number of postdromal symptoms within the CM subtype was 1 (IQR: 0–2).
Medication overuse was present in 33% of the cohort. The median number of preventives used were 5 (IQR: 3–8). At follow-up, four (3%) had gone into remission.
Conclusion: While the NDPH phenotype can be variable, the majority of patients have a CM subtype. They commonly present associated migrainous, cranial autonomic, premonitory and postdromal symptoms. A significant percentage of NDPH patients are refractory to treatment, requiring multiple preventive medications.
Disclosure of Interests: The authors do not have any conflicts of interest for the above study.
IHC-LB-045
Headache secondary to corticosteroid withdrawal: a case report
Braian M. Beker1, Agustina Saldarini1, Ostuni Marco1, Fiorella Martin Bertuzzi2,*, Marcelo F. Rugiero2 and Eduardo D. Doctorovich2
1Instituto Universitario del Hospital Italiano
2Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Objective: Headache attributed to increased cerebrospinal fluid pressure (ICP) is a syndrome characterized by an elevation of intracranial pressure without hydrocephalus, with normal cerebrospinal fluid (CSF) composition and no alterations in the brain parenchyma.
Most of these cases are considered idiopathic, several possible etiologies have arised. ICP secondary to corticosteroid withdrawal is poorly understood and rarely reported in the literature while observed primarily on pediatric population.
Methods: The following case presents an adult presentation of this unusual trigger of ICP.
Results: A 28-year-old male patient with a history of Crohn’s disease treated with stable doses of azathioprine, mesalazine and meprednisone (60 mg/daily) for over 6 months. No personal history of headache. In October 2018, corticosteroid withdrawal was started. At week four (10 mg/daily), patient referred right pulsatile hemicranial headaches, intensity 9/10, associated to photophobia and phonophobia, increasing with Valsalva maneuvers, did not worsen with dorsal decubitus nor awaken the patient at night. Initially improved with acetaminophen; but after corticoid suspension, became persistent and increased intensity. Brain and orbital magnetic resonance imaging (MRI): no parenchymal alterations, intrasellar arachnoidocele and increased right optic nerve sheath liquid and tortuosity. Intracranial MRI angiography: slight tortuosity on the transverse sinuses. Ophthalmologic evaluation: mild right hyperemic papilledema, confirmed by optical coherence tomography. Lumbar puncture (LP): opening pressure 260 mm, CSF analysis and cultures normal.
After 1 week of corticosteroid therapy reintroduction (20 mg/daily), with a more gradual tapering, headache was completely resolved and remained asymptomatic 6 months after complete withdrawal. The patient was interpreted as a 7.1.2 headache attributed to intracranial hypertension secondary to toxic cause, according to the IHC-3.
Conclusion: Our case shows an unusual presentation of ICP syndrome with unilateral symptoms associated with withdrawal of corticosteroids. Performance of an LP and fundoscopy should be considered on patients presenting a headache of recent onset while descending corticosteroid treatment.
Disclosure of Interest: None Declared.
Other Secondary Headache Disorders
IHC-LB-092
Systematic review and meta-analysis of efficacy, performance time, and accidental vascular puncture with ultrasound-guided versus fluoroscopy and CT-guided cervical medial branch blocks
Stephania Paredes1, Roderick J. Finlayson2, Sameh M. Hakim3, Dmitri Souza4,*, Nebojsa N. Knezevic1, Alex Feoktistov5, Daniel Adams4, Lynn Kohan6, Antoun Nader7, Imanuel Lerman8 and Samer N. Narouze9
1University of Illinois, Chicago, United States
2McGill University, Montreal, Canada
3Ain Shams University, Cairo, Egypt
4Western Reserve Hospital, Cuyahoga Falls
5Diamond Headache Clinic, Chicago
6University Of Virginia, Charlottesville
7Feinberg School of Medicine, Chicago
8University of California, San Diego
9Ohio University, Cuyahoga Falls, United States
Objective: Cervical medial branch blocks (CMBB) are useful in differentiating of facetogenic pain from other sources of cervicogenic headaches. The purpose of this systematic review and meta-analysis is to compare the efficacy, performance time and pain reduction with ultrasound-guided (US-guided) CMBB vs. other used methods such as fluoroscopy and CT guidance. Additionally, the study assesses some complications such as vascular puncture, intraarticular spread, intra-foraminal and other aberrant spreads of the local anesthetic.
Trials Pertaining to Ultrasound-Guided Cervical Facet/Medial Branch Blocks and Radiofrequency Ablation
Authors (Yr)
Study Type
Jadad Score
Blinded Assessment/ Sample Size Justification
Description
Number of Patients/Groups
Primary Outcome
Main Findings
Eichenberger et al. (2006)
RCT
5
Y/N
Volunteers underwent an USG TONB with LA on one side and saline in the other using an OOP approach.
11/ crossover trial
Presence of cutaneous hypoesthesia in the distribution of the TON, needle position relative to fluoroscopic target point
Needle was correctly placed over the C2/C3 joint in all but one case, similarly cutaneous hypoesthesia was seen in seen in all but one of the LA blocks.
Siegenthaler et al. 2011
CH
NA
N/Y
Examined the effect of a shortened fluoroscopic radiofrequency neurotomy procedure (fewer lesions), using of ultrasound assistance to guide cannula placement
15/1
Reduction in pre-procedural pain intensity.
A pain reduction of at least 80% was observed in 14 of the subjects at 15 days. Median duration of 50% pain relief was 44 weeks.
Siegenthaler et al. 2012
CH
NA
Y/Y
Volunteers underwent USG needle placements with contrast injection simulating CMBB and TONB using an OOP approach.
60/1
Needle tip position and contrast distribution relative to conventional fluoroscopic target points
Overall accuracy was 77% for needle placement and 84% for contrast distribution. Results varied by level and was lowest at C7.
Finlayson et al. 2012
CH
NA
Y/N
Two phase study examining the accuracy of USG TONB and CMBB (C3-C6) using an IP approach in patients with neck pain.
53/ 1
Needle tip position and contrast distribution as assessed by post-procedural X-rays.
Phase 1:80.9% of needles placed correctly; phase 2: contrast covered appropriate area in 94.5% of injections.
Finlayson et al. 2013
RCT
3
N/Y
Patients with suspected cervicogenic headaches underwent a TONB using either fluoroscopy or an IP USG technique
40/ 2
Performance time was the primary outcome and secondary outcomes included success rates as well as sensory distribution of the blocks.
Ultrasound guidance was associated with a significantly shorter performance time (212.8 vs 396.5 seconds; P = 0.000) and fewer needle passes (2 vs 6; P = 0.000). Both imaging modalities resulted in similar success rates (95% vs 100%).
Obernauer et al. 2013
RCT
3
N/N
Patients undergoing cervical intraarticular facet blocks were assigned to CT guidance or USG using an IP approach
40/2
Primary outcomes were performance time and accuracy (as assessed by CT control). Secondary outcomes include pain reduction at 30 min and 1 month.
USG was associated with 100% accuracy and significant reduction in performance times (04:46 versus 11:12 min p < 0.05), as well as radiation dose. Pain relief was similar in both groups.
Finlayson et al. 2014
CH
NA
N/N
Patients with cervical pain underwent an USG CMBB at the C5 and C6 levels using a bi-planar (IP) technique.
40/1
Contrast distribution, as assessed by a blinded observer on anteroposterior and lateral x-ray views.
Appropriate contrast distribution was seen in 100% and 97.5% of C5 and C6 levels respectively
Finlayson et al. 2015
RCT
3
N/Y
Patients undergoing a C7 CMBB were randomized to either ultrasound or fluoroscopic guidance.
50/2
Performance time was the primary outcome and secondary outcomes included success rates, number of needle passes, as well as pain relief
US guidance was associated with a shorter performance time (233.6 vs 390.6 seconds; P < 0.001) and fewer needle passes. Both pain relief and success rates (92% > 96%) were similar between groups.
Park et al. 2017
CH
NA
N/N
Retrospective chart review of patients with neck pain who had undergone CMBB with either fluoroscopic or USG (IP).
68 (USG) 58 (Fluoro)
Neck Disability Index and pain scores at 1,3 and 6 months after injection. Secondary measures included performance time, needle passes and complication.
USG was associated with a shorter performance time and fewer needle passes. Pain relief and functional improvement were similar for both groups. No major complications were noted.
Randomized control trial (RCT); cohort study (CH); third occipital nerve block (TONB); cervical medial branch block (CMBB); ultrasound-guided (USG); in-plane (IP); out-of-plane (OOP);
Methods: The protocol of this systematic review and meta-analysis was performed following the PRISMA recommendation data.
The following will be discussed in the presentation: protocol and registration, inclusion criteria, exclusion criteria, information sources and searches, study selection, data collection process, risk of bias in individual studies.
Results: The results demonstrate that US-guided CMMB is a reliable alternative to the fluoroscopy and CT – guided CMMB, with demonstrated advantages in the efficacy, early identification, and prevention of adverse effects. The meta-analysis and discussion will be unfolded in the presentation.
Conclusion: This study demonstrated benefits of US-guided CMBB compared to fluoroscopy and CT Scan.
Disclosure of Interests: None. The study results were not available until 25/05/2019.
Post-Traumatic Headache
IHC-LB-046
Non-Steroidal Anti-Inflammatory Drug Use and Post Traumatic Headache in Adults following a Concussion
Stephen Bunt1, Bert Vargas2, Nyaz Didehbani1, Kathleen Bell3, Hunt Batjer4, C M. Cullum1, Shamin Masrour5,*
1Psychiatry
2Neurology and Neurotherapeutics
3Physical Medicine and Rehabilitation
4Neurosurgery, UT Southwestern Medical Center Dallas
5UT Southwestern medical Center, Dallas, United States
Objective: Posttraumatic headache (PTH) is common after concussion and non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used for symptom relief. This study investigates the frequency and severity of PTH in concussed adults treated with NSAIDs during recovery and those who were not.
Methods: Concussed adults (n = 70) aged 19 to 78 with no history of treatment for PTH were evaluated within 30 days of injury at clinics in the North Texas Concussion Registry. Demographics, headache symptom severity (0-6), and NSAID use were recorded at initial evaluation and three-month follow-up. Chi square analysis and 2 (time) by 2 (NSAID use) repeated measures ANOVA with sex as a covariate were conducted to determine frequency and severity of headaches between PTH groups treated with NSAIDs and those that were not treated with medications at initial evaluation and follow-up.
Results: There was no difference in headache frequency at initial evaluation and three-month follow-up between subjects who used NSAIDs (n = 42) and those who did not (n = 30), (χ = 0.26, p = 0.61) regardless of sex. Subjects who used NSAIDs reported higher levels of headache symptoms initially than those who did not use NSAIDs, F (1, 67) = 5.29, p = 0.03. There was no interaction between time and NSAID use regarding headache severity, F (1, 67) = 1.83, p = 0.18. There was also no interaction between time and gender regarding headache severity, F (1, 67) = 3.64, p = 0.06. There was a main effect over time in reduction of headache severity, F (1, 67) = 54.51, p < 0.001. Differences in headache severity between the sexes was non-significant, F (1, 67) = 3.46, p = 0.07.
Conclusion: Regardless of sex, in this population of acutely concussed adults headache frequency was unchanged three months post-injury for who used NSAIDs compared to those who did not use any medication. Headache severity was initially higher for those who used NSAIDS, but not significantly so three months post-injury. Routine use of NSAIDs following a concussion may act to reduce symptoms but not frequency of headache during recovery in adults.
Disclosure of Interests: None.
Psychological and Behavioural Factors and Management
IHC-LB-047
Visual feedback to modulate pain perception in chronic migraine patients: a pilot study
Sara Bottiroli1,2,*, Marta Matamala-Gomez2,3, Grazia Sances2, Marta Allena2, Roberto De Icco2,4, Elena Guaschino2, Giorgio Sandrini2,4 and Cristina Tassorelli2,4
1Faculty of Law, Giustino Fortunato University, Benevento
2Headache Science Center, IRCCS MONDINO FOUNDATION, Pavia
3Department of Human Sciences for Education, University of Milano Bicocca, Milan
4Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
Objective: To investigate whether the exposure to different visual stimulating conditions may modulate pain perception assessed by the visual analogue scale (VAS) in chronic migraine patients.
Methods: To this aim we enrolled 10 female chronic migraine patients (mean age: 44.7 ± 12.4) recruited at the IRCCS C. Mondino Foundation in the study. Using a visual feedback system, subjects were randomly exposed to 4 different types of facial expression: positive (happy/relaxed facial expression), neutral (neutral facial expression), negative (sad/distorted face) and control (white screen). At baseline, patients were evaluated on personal, clinical, psychological (Positive and Negative Affect Schedule, Hospital Anxiety and Depression Scale) variables, level of pain (VAS) and body image perception (Body Image Questionnaire). Subsequently, they were exposed to a 1x4 within-subject study design where they had to observe the different visual stimuli presented 3 times in a randomized order (each condition lasted 40 seconds). After the observation of each visual condition, the level of pain was assessed using the VAS.
Results: A repeated measure analyse (mixed effects model test) and the following multiple comparisons by using the Scheffe test showed a significant difference in pain ratings between the positive (20.5 ± 25.0) and the negative (36.2 ± 24.9) facial expressions (z = −4.04, p = 0.001), and the positive facial expression (20.5 ± 25.0) and the white screen (35.3 ± 28.9) control condition (z = 3.82, p = 0.002).
Conclusion: Our results show that a positive visual feedback is a stimulus strong enough to modulate pain perception via the mediation of empathy mechanisms for positive emotions. Further, our study paves the way to the integration of conventional behavioral therapy with new cognitive behavioral training based on the adoption of visual feedback to further control pain perception in chronic migraine patients.
Disclosure of Interests: no conflict of interests.
IHC-LB-093
Systematic review of patient education and cognitiv behavioral treatment for adults with migraine
Ruth Meise1,2,*, Annika Schwarz3 and Kerstin Luedtke3,4
1Physiotherapy, University of Luebeck, Luebeck
2Department für Angewandte Gesundheitswissenschaften, University of Applied Sciences, Bochum
3Department of Systems Neuroscience, University Medical Center, Hamburg-Eppendorf, Hamburg
4Programme Director, Physiotherapy, University of Luebeck, Luebeck, Germany
Objective: To evaluate the content and effectiveness of patient education and cognitive behavioural therapy for adults with migraine.
Methods: Predefined search using key terms of information sources including MEDLINE, EMBASE, PsycINFO and CINAHL databases. RCTs of the last 10 years (to April 2019) were included. Two reviewers independently searched and evaluated publications. The methodological quality of studies was assed using the Cochrane Rob 2 tool.
Results: Across n = 11 studies, 1397 participants were recruited (84,2% females). Characteristics of education comprise explanations about links between thoughts and feelings, behaviour and relaxation techniques or aiming at improvements in life-style and stress coping, advices regarding diet, physical activity, or dealing with the pathophysiology of migraine, effective acute or prophylactic drug use. Professionals performing education were psychologists. The duration and frequency of education varied (three times for 1 h up to eight times for 2 h plus a retreat day). Different educational formats were used (workbooks, questionnaires, audiotapes, face-to-face sessions, online Behavioural Therapy, clinical visits, telephone contacts). Education was often enclosed in adjunct treatments (multi-modal therapy, prophylactic medical therapy, endurance training, relaxation techniques). Outcome measures related to pain (headache frequency, attack frequency, medication use (diary), function and disability (MIDAS; HIT-6), and psychosocial issues (e.g. HADS-anxiety, PHQ-9, Perceived stress scale-10). Due to strong heterogeneity the data could not be pooled for a meta-analysis.
Conclusion: Most of the studies with a good quality support a positive effect concerning the reduction of migraine frequency and improved quality of life. Behavioural approaches should be implemented in every treatment guideline. Besides psychologists also physical therapists specialized in the treatment of chronic pain should conduct the education. More randomized controlled trials are needed to evaluate the content and extend of education.
Disclosure of Interests: The authors declare no conflicts of interest.
IHC-LB-094
Could the migraine phase be predicted from the use of mobile phones? Social sensing in migraine
2Vall d’Hebron Research Institute, Barcelona, Spain
Objective: The use of smart phones is closely related to human interaction. Thus, individual mobile activity could be used to predict migraine attacks and to study some cognitive and social changes. These changes may help us to define the different migraine phases.
To study if there is a correlation between migraine attacks and the social and cognitive activity and use of a smartphone.
Methods: A prospective observational study. We included patients with episodic (EM) and chronic migraine (CM) during 3 months. A mobile app monitored the daily use of the smartphone and migraine attacks. Moreover, we collected both sociodemographic and clinical data. We performed a comparative analysis between the migraine days (M) and 24 hours before the attack (24B), 24 and 48 hours after (24A and 48A) and headache-free days (F).
Results: 32 patients were recruited: 68.8% had EM and 31.2% had CM. The patients registered 764 entries: 50.5% headache-free and 25.0% with headache, 8.7% 24B, 9.2% 24A and 6.4% 48A. CM patients use more time the mobile phone and the social apps than EM (p = 0.05). The time of the attacks is significantly different between diagnostics (CM: 23.5% in the early morning, EM: 38.1% in the morning, p = 0.01) and CM have a longer attack duration (p = 0.038). A reduction of the use of the mobile phone has been reported during migraine days (p = 0.01) with respect to other days (F, 24B, 24A and 48A), but the use of social apps was significantly increased in 24 hours before the attack (p = 0.05).
Conclusion: The use of the smartphone depends on the migraine phase and the diagnostic: lower use in migraine days and EM and increase of use of social media before the attack. New technologies allow us to predict migraine attacks from changes in the social behavior and cognitive activity because these changes according to the migraine phase. This could be correlated with changes in brain activity.
Disclosure of Interests: PP-R has received honoraria as a consultant and speaker for: Allergan, Almirall, Chiesi, Eli Lilly, Novartis and Teva. AA has received honoraria as a speaker for Allergan. The authors declare no conflicts of interest to this work.
Tension-type Headache
IHC-LB-048
Excessive daytime sleepiness in tension-type headache: a population study
Kyung Min Kim1,*, Jiyoung Kim2, Soo-Jin Cho3, Won-Joo Kim1, Kwang Ik Yang4, Chang-Ho Yun5 and Min Kyung Chu1
1Neurology, Yonsei University College of Medicine, Seoul
2Neurology, Pusan National University School of Medicine, Busan
3Neurology, Hallym University College of Medicine, Hwaseong
4Neurology, Soonchunhyang University College of Medicine, Cheonan
5Neurology, Seoul National University Bundang Hospital, Seongnam, Korea, Republic Of
Objective: Excessive daytime sleepiness (EDS) is a common sleep-related complaint in the general population and has been reported to be associated with headache. Tension-type headache (TTH) is the most commonly encountered headache and accounts for a significant amount of disease burden. A previous study reported a high prevalence of EDS in migraineurs and an association between EDS and migraine exacerbation. However, the association between EDS and TTH remains to be determined. In this study, we evaluated the prevalence of EDS in TTH individuals and examined the impact of EDS on the clinical presentation of TTH.
Methods: We used data from the Korean Headache-Sleep Study, a national survey that sought to identify headache and sleep characteristics in Korean adults. Participants with an Epworth sleepiness scale score greater or equal to 11 were considered as having EDS.
Results: Of the 2695 participants enrolled, 570 (21.2%) and 313 (11.6%) had TTH and EDS, respectively. EDS was highly prevalent in individuals with chronic tension-type headache (CTTH) than in those with non-headache (35.7% vs. 9.4%, p < 0.001). The prevalence of EDS in episodic tension-type headache (ETTH) individuals with a headache frequency <1 per month (8.3%, p = 0.511) and ETTH individuals with a headache frequency of 1–14 per month (13.5%, p = 0.054) was not significantly different from that in non-headache individuals (9.4%). TTH participants with EDS had a higher headache frequency (4.3 ± 8.1 vs. 1.7 ± 4.2, p = 0.013), more severe headache intensity (Visual Analogue Scale, 5.0 [3.0–6.0] vs. 4.0 [3.0–6.0], p = 0.008), a higher impact of headache (Headache Impact Test-6 score, 47.1 ± 7.3 vs. 43.5 ± 7.6, p < 0.001), and a higher prevalence of depression (12.7% vs. 3.2%, p < 0.001) compared to TTH participants without EDS.
Conclusion: Consequently, CTTH is associated with higher EDS prevalence compared to ETTH and non-headache. Moreover, TTH with EDS had more severe TTH symptoms compared to TTH without EDS.
Disclosure of Interests: The authors declare that they have no conflicting interests.
