Abstract
EP-01-001
Ambient light color variably influences migraine pain intensity and discomfort in the ictal and interictal phase.
Kiyoshi Niwa1,*, Fumihiko Sakai1,2, Tatsuya Ishikawa1, Nobuaki Shinohara1 and Chikako Kawaguchi1
1Tokyo Headache Clinic, Tokyo
2Saitama International Headache Center, Saitama, Japan
Objectives
Light stimuli exacerbate migraine headache. Previous studies also speculated that the sensitivity to light during attacks of migraine may be color-dependent. In patients with photophobia, light in the blue, red, amber and white increased migraine headache, while green light decreased the intensity of migraine headache. Since previous studies used direct application of light to the patient, we studied the effect of different colors of ambient light on aversiveness and migraine pain intensity during the ictal and interictal phase, respectively.
Methods
The study involved 936 patients with chronic headaches both during the headache and interictal phase. Subjects aged 12-77 years old were eligible for this study if they met ICHD-3beta. Episodic migraine (EM) was 392 patients and chronic migraine (CM) was 152 patients. For comparison 203 patients with tension type headache (TTH) and 74 with chronic TTH, 73 with trigeminal autonomic cephalalgias (TACs), 42 with new daily persistent headache (NDPH) were also evaluated. The intensity of light was 100 cd m−2 (equivalent to a normally lit office space) and the different colors were provided by using Macintosh hue system (Philips Hue, version 1.12.2, 2015). Patients were exposed to a fixed sequence of colors (yellow, white, gray, blue green, and red sequentially) for a period of 30 seconds. Yellow was chosen as the reference color because this color light is present in the waiting room. To evaluate the degree of discomfort, patients were asked to choose from six grades 0 (none), 1 (slight), 2 (mild), 3 (moderate), 4 (severe), to 5 (unbearable) for each color. The colors transitioned from one to another immediately in order to minimize additive effects. When the headache intensity was worsened by any color stimulus, the color of light was turned to the initial yellow once again at the end of each color stimulus, so that the patients could be given sufficient time to return to the baseline level of headache intensity.
Image:
Results
White, blue and red lights aggravated discomfort to color during both ictal and interictal phases and increased pain during migraine. Green light reduced discomfort during the interictal phase and pain intensity during the ictal phase only in patients with migraine (Figure) regardless of the presence or absence of photophobia. Significant change was seen both in EM and CM patients. CTTH patients demonstrated mild but significant discomfort only from white light in ictal phase (Figure). TACs and NDPH patients demonstrated no intensification of discomfort by any color light stimuli either in the interictal or headache phase.
Conclusion
Ambient light color, specifically blue and white, exacerbated discomfort and headache in patients specifically with migraine. These results support the observation that migraine photophobia may originate in cone-driven retinal pathways and be dependent on its luminous sensitivity. We hypothesize that ambient light color may be an important exacerbating factor in patients with migraine. In addition, surrounding green light may be a nonpharmacological treatment of migraine. The absence of discomfort or light induced exacerbation of pain in patients with other primary headache disorders is a novel finding and warrants further exploration.
Disclosure of Interest
None Declared.
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-002
Chronic migraine is mediated by the Hypothalamus
Laura Schulte1,*, Angie Allers1 and Arne May1
1Department of Systems Neuroscience, University Medical Center Eppendorf, Hamburg, Germany
Objectives
Chronic migraine is a debilitating disease. Identifying the pathophysiological characteristics of chronic migraine is thus of vast importance. Using a recently developed protocol for high resolution brainstem imaging of standardized trigeminal nociceptive stimulation1 we aim at elucidating mechanisms of migraine chronification.
Methods
17 chronic migraineurs (CM), 18 episodic migraineurs (EM) and 19 healthy controls (HC) underwent a standardized paradigm of painful stimulation of the left nostril using gaseous ammonia. Functional images were acquired within a 3 T MRI scanner using an optimized protocol for high resolution echoplanar brainstem imaging2.
Results
The anterior right hypothalamus (HT) was significantly stronger activated in CM as compared to Con. We then compared all migraineurs with headaches (EM and CM) with all migraineurs without headaches (EM and CM) and Con, to exclude that the headache on the day of the scanning was a prime mediator of the observed hypothalamic activation, and found a more posterior region of the HT to be stronger activated during headaches.
Conclusion
Our data corroborate a crucial role of the HT for migraine chronification as well as for the sustainment of acute migraine pain3. While the more posterior part of the HT seems to be a mediator of the acute pain stage, the more anterior part seems to be important for the pathophysiology of chronic migraine.
Disclosure of Interest
None Declared
Stankewitz A, Voit HL, Bingel U, et al. A new trigemino-nociceptive stimulation model for event-related fMRI. Cephalalgia 2010; 30: 475–485.
Schulte LH, Sprenger C, May A. Physiological brainstem mechanisms of trigeminal nociception: An fMRI study at 3T. NeuroImage 2015; 124: 518–525.
Schulte LH, Allers A, and May A. The hypothalamus as a mediator of chronic migraine: Evidence from high resolution fMRI. Neurology 2017 in press
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-003
TMS evoked potentials demonstrate altered cortical excitability in migraine with aura
Matthijs Perenboom1,*, Robert Helling2, Prisca Bauer2, Johannes Carpay1, Josemir Sander2, Michel Ferrari1, Gerhard Visser2 and Else Tolner1
1Neurology, Leiden University Medical Centre, Leiden
2Stichting Epilepsie Instellingen Nederland - SEIN, Heemstede, Netherlands
Objectives
Migraine is associated with altered processing of sensory input that may be due to cortical hyperexcitability. Cyclical changes in cortical excitability have been suggested around the migraine attack. The visual cortex is believed to be of particular interest, especially in migraine patients with visual aura. Transcranial magnetic stimulation with concomitant electroencephalography recordings (TMS-EEG) is a new method to measure cortical excitability from the direct response to non-invasive stimulation over the skull. Recent studies have shown that phase clustering in EEG responses is linked to cortical excitability. We quantified differences in TMS evoked EEG potentials (TEP) between healthy controls and patients with migraine with aura, to study TEP’s possibility as biomarker of cortical excitability in migraine.
Methods
We included nine patients with migraine with aura and nine age- and sex-matched healthy controls. All underwent single-pulse TMS on the vertex with simultaneous 64-channel EEG recording. Migraine patients were recorded interictally (at least three days before and after an attack). On average 300 pulses were delivered between -8% and +8% of the resting motor threshold. We compared averaged TEP waveforms and phase clustering over trials between the groups of participants.
Results
TEP waveforms differed between migraine patients with aura and healthy controls around the N100 and P180 peaks, mostly located at frontal and centro-parietal regions respectively. Hundred ms after the stimulus, phase clustering in the occipital lobe remains stronger in healthy controls than in patients, indicating reduced phase consistency after the N100 peak in migraine patients.
Conclusion
Patients with migraine with aura show different cortical responses to non-invasive magnetic stimulation compared to healthy controls. This suggests that cortical excitability is altered in migraine with aura, also between migraine attacks. Our findings are in line with studies that used indirect cortical stimulation with e.g. visual or somatosensory inputs and magnetic stimulation with peripheral readouts. We conclude that TMS-EEG could be useful to directly study changes in cortical excitability during the migraine cycle.
Disclosure of Interest
None Declared
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-004
Normalization of the Resting-State Network of Ventral Posteromedial Nucleus in Patients with Chronic Migraine Is Associated with Good Clinical Outcome to Prevention
Kuan-Lin Lai1,2,*, David M. Niddam3, Jong-Ling Fuh2,4, Wei-Ta Chen3,4 and Shuu-Jiun Wang3,4
1Neurology, Taipei Municipal Gan-Dau Hospital
2Neurology
3Institute of Brain Science, National Yang-Ming University
4Neurology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
Objectives
Chronic migraine (CM) affects about 2% of the general population. Previous task functional magnetic resonance image (fMRI) and electrophysiological studies suggested hyperactivation of the ventral posteromedial nucleus (VPM) of thalamus to pain stimuli play an important pathophysiology role in CM. However, the resting-state network (RSN) of VPM in patients with CM (PT) has not been studied yet. Thus, we aimed to evaluate (1) the difference of the VPM-RSN between control subjects (CS) and PT prior to prevention, and (2) the change of the VPM-RSN in PT before and after prevention within the regions derived from the first aim.
Methods
Experimental design: PT were recruited from the Headache Clinic of Taipei Veterans General Hospital. Upon first visit, all potential participants completed a structured headache questionnaire. Once the diagnosis of CM was considered, the subjects were asked to keep headache diaries for the following 2 weeks (T0) in order to confirm the headache profile. Subjects who had ≥7 days of headache, and migrainous headache on ≥4 of these days proceeded to undergo the 1st MRI scan. Afterwards, PT received preventive treatment, either Topiramate 50 mg/d or Flunarizine 10 mg/d, in divided doses. A 2nd MRI scan was arranged 2 weeks after prevention. After a treatment course of 8 weeks (T1 - T4, 2-week each), the effectiveness was determined, i.e. those with ≥50% reduction of migraine days (T4 vs. T0) were categorized as responders while those without were non-responders.
MRI acquisition and analysis: Anatomical and resting-state fMRI (rs-fMRI) data were acquired on a 3 Tesla MRI scanner. RS-fMRI data were preprocessed and analyzed by statistical parametrical mapping (SPM8) and the DPARSF toolbox. A seed-based correlation analysis was performed, with bilateral VPM (averaged signal) as seeds. Initially, the VPM-RSN was generated in the CS group. We then evaluate (1) the difference of the VPM-RSN between CS and PT prior to prevention, and (2) within these regions, the changes after prevention in responder and non-responder groups.
Results
Fifty-six PT and 32 age- and gender-matched CS were recruited. The anatomical images of all subjects showed no gross abnormality except for some white matter lesions. The VPM-RSN derived from CS group included nearly whole brain structure, which is consistent with previous studies.
Before prevention, there existed enhanced functional connectivity (FC) between VPM and bilateral occipital as well as auditory cortices in PT as compared to CS. No correlation between the FC and disease severity (including baseline migraine disability assessment score [MIDAS], T0 migraine or headache days) or CM duration was found.
Three PT failed to undergo the 2nd MRI scan due to claustrophobia (n = 1), or severe migraine attack on the scheduled day (n = 2). Three other PT responded to prevention with marked fluctuation during T3 and T4, and were also excluded from the analysis of treatment effects. In the remaining 50 PT, 33 were responders. The average FC between VPM and occipital region (results from aim 1) showed significant reduction after prevention in responder group. While in non-responder group (n = 17), the FC remained unchanged.
Conclusion
In this study, enhanced resting FC between VPM and visual as well as auditory cortices were found in patients with CM. Moreover, the observation that a reduction of such hyper-connectivity early after prevention is associated with good clinical outcome may provide clinicians an early neuroimaging biomarker for treatment efficacy.
Disclosure of Interest
None Declared
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-005
Alterations in regional cerebral blood (rCBF) during the premonitory stage of nitroglycerin (NTG) triggered migraine attacks assessed using arterial spin-labelled (ASL) functional magnetic resonance imaging (fMRI)
Nazia Karsan1,2,*, Pyari Bose1,2, Fernando O. Zelaya3 and Peter J. Goadsby1,2
1NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital
2Headache Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience
3Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
Objectives
The premonitory stage of migraine is an increasing area of interest within headache research, because of the insights it can offer into the early pathophysiology of the migraine attack, which could then lead onto identification of novel therapeutic targets.
We aimed to study the phenotype and imaging characteristics of this stage of the migraine attack using NTG triggered attacks, which have been shown to be phenotypically similar in premonitory symptomatology and headache phenotype. We used the methodology of pulsed continuous Arterial Spin Labelling (pCASL), performed on a 3T General Electric MR750 MRI scanner.
Methods
Subjects (n = 18) were recruited following screening and informed consent. Each subject was exposed to either a 0.5 mcg/kg/min NTG infusion over 20 minutes or placebo, depending on randomisation. Each subject received both infusions on two different visits and was blinded to which treatment was being administered. Following the infusion, the timeline and phenotype to development of premonitory and headache symptoms was documented. A standardised physician administered symptom checklist was used for data collection.
The premonitory stage of migraine was defined as the presence of at least 3 premonitory symptoms without the presence of migraine headache which the subject would usually associate with a spontaneous attack. Migraine headache was defined as moderate-severe headache which developed after the infusion and was associated with other migraine symptomatology that the subject would usually associate with spontaneous attacks.
Imaging (structural T1, T2 and FLAIR, resting state blood oxygen level dependant (rsBOLD) imaging and two six minute ASL scans) was conducted over 30-40 minutes at baseline, with ASL and rsBOLD scans acquired during the premonitory stage and during migraine headache. For the placebo visit the imaging was conducted at the same times following infusion in the absence of symptoms.
Images were analysed using SPM 12 (www.fil.ion.ac.uk/SPM). Voxel-wise analysis of all subjects’ premonitory scans compared to baseline was carried out.
Results
Significant increases in rCBF were detected in a large cluster that included the medial and superior frontal gyri and anterior cingulate cortices (p = 0.001 corrected for multiple comparisons at the cluster level). Small volume correction revealed significant increases in blood flow in the hypothalamus (p = 0.028), consistent with a previous investigation using Positron Emission Tomography (PET) imaging.
Significant reductions in rCBF were detected in the middle occipital gyrus (p = 0.019).
Conclusion
The premonitory stage of migraine is associated with significant areas of increased rCBF compared to baseline, in frontal cortex, anterior cingulate cortex and hypothalamus, before the onset of migraine pain. These areas are functionally consistent with some of the main symptoms displayed during this phase, including mood and cognitive change, neck stiffness and yawning.
ASL is promising non-invasive imaging modality, using rCBF as a correlate of neuronal activity, and could be increasingly used in migraine research.
Disclosure of Interest
N. Karsan Conflict with: Dr Karsan is an Association of British Neurologists/Guarantors of Brain Clinical Research Training Fellow, P. Bose: None Declared, F. Zelaya: None Declared, P. Goadsby Conflict with: Dr. Goadsby reports grants and personal fees from Allergan, Amgen, and Eli-Lilly and Company; and personal fees from Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, eNeura, Electrocore LLC, Novartis, Pfizer Inc, Promius Pharma, Quest Diagnostics, Scion, Teva Pharmaceuticals, Trigemina Inc., Scion, Conflict with: personal fees from MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press; and in addition, Dr. Goadsby has a patent Magnetic stimulation for headache pending assigned to eNeura
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-006
Carbon monoxide inhalation induces headache in a human headache model
Nanna Arngrim1,*, Henrik Schytz1, Josefine Britze1, Mark Vestergaard2, Mikael Sander3, Karsten S. Olsen4, Jes Olesen1 and Messoud Ashina1
1Department of Neurology
2Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, Glostrup
3Department of Cardiology, Bispebjerg Hospital, Copenhagen
4Department of Neuroanaesthesiology, The Neuroscience Centre, Rigshospitalet Glostrup, Glostrup, Denmark
Objectives
Carbon monoxide (CO) is an endogenously produced signalling molecule which has a role in nociceptive processing and cerebral vasodilatation. We hypothesized that inhalation of CO would induce headache and vasodilation of cephalic and extracephalic arteries.
Methods
In a randomized, double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0–10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial Doppler, diameter of the superficial temporal artery (STA) and radial artery (RA) by high-resolution ultrasonography and facial skin blood flow by laser speckle contrast imaging.
Results
Ten volunteers developed headache after CO compared to six after placebo. The area under the curve for headache (0–12 hours) was increased after CO compared with placebo (P = 0.021). CO increased VMCA (P = 0.002) and facial skin blood flow (P = 0.012), but did not change diameter of STA (P = 0.060) and RA (P = 0.433).
Conclusion
In conclusion, the study demonstrated that CO caused mild prolonged headache but no arterial dilatation in healthy volunteers. We suggest this may be caused by a combination of hypoxic and direct cellular effects of CO.
Disclosure of Interest
None Declared
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-007
Unique Infra-Slow Oscillatory Activity in the Prodrome Phase of Migraine
Noemi Meylakh1,*, Kasia Marciszewski1, Flavia Di Pietro1 and Luke Henderson1
1UNIVERSITY OF SYDNEY, Sydney, Australia
Objectives
Migraine is a highly prevalent and debilitating neurological disorder, but the underlying mechanism responsible for its pathogenesis remains unclear. It is widely assumed that migraineurs exhibit altered brain function in spinal and trigeminal nociceptive pathways between attacks. However, no study has investigated brain changes in the critical period directly prior to a migraine attack. We have recently shown that another orofacial neuropathic pain condition, trigeminal neuropathy, is associated with altered resting activity (increased infra-slow frequency oscillations) within trigeminal nociceptive pathways and within parts of the thalamocortical circuity which we hypothesise is related to glial activation. It is possible that a similar situation also occurs in individuals with migraine and that this predisposes an individual to a migraine event. In this study, we aimed to investigate whether individuals in their prodrome phase showed alterations in brain function. Given this, we hypothesise that migraineurs will present with altered resting activity, characterized by increased infra-slow oscillatory power during the 24 hours before a migraine attack.
Methods
In twenty six subjects with migraine (21 females; mean age 31.2 ± 2.1 years [ ± SEM]) and 103 pain-free controls (69 females; mean age 30.7 ± 1.1 years) we measured resting blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) over the entire brain (180 volumes, TR = 2 seconds). All migraineurs were scanned during an interictal period, that is, at least 72 hours after and 24 hours prior to a migraine event. Eight of these migraineurs were scanned during the prodrome phase (within 24 hours prior to a migraine) and 11 during the postdrome phase (during the 72 hours following a migraine attack). Using SPM12, fMRI images were realigned, intensity normalized and spatially normalized to the Montreal Neurological Institute template. On-going signal intensity fluctuations of the whole brain were analysed by performing fast fourier transforms on each voxel using REST software. Significant differences in power in the frequency band 0.03-0.06 Hz in migraineurs compared with controls were determined using a random effects procedure (FDR p < 0.05).
Results
Significant increases in infra-slow oscillatory power occurred in migraineurs during the prodome phase compared with controls in the brainstem, hypothalamus and thalamus. During prodrome, increased oscillatory power occurred in the region of the right (ipsilateral to side of most frequent migraine) spinal trigeminal nucleus (SpV) extending into the rostral ventromedial medulla (RVM), dorsomedial pons, midbrain in the region of the midbrain periaqueductal gray matter (PAG), posterior hypothalamus and in the thalamus in the region of the somatosensory nucleus. Importantly, no change in infra-slow oscillatory power occurred during either the interictal or postdrome phases. Furthermore, in no brain region and during no migraine phase was infra-slow oscillatory power reduced in migraineurs compared with controls.
Conclusion
These findings provide evidence revealing altered brainstem and hypothalamic function in the period directly prior to a migraine attack. It is possible that increased infra-slow oscillatory power represent changes in underlying astrocytic modulation of synaptic function since activated astrocytes display similar infra-slow oscillatory activities. These on-going activity changes alone, or in combination with an external trigger, may underlie the initiation of a migraine attack and the presence of head pain.
Disclosure of Interest
None Declared
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-008
WHITE MATTER LESIONS IN CRONIC MIGRAINE ARE NOT ASSOCIATED WITH CEREBRAL VASOREACTIVITY.
Davinia Larrosa1, Angela Meilán2, César Ramón Carbajo1, Eva Cernuda Morollón3, Pablo Martínez-Camblor4 and Julio Pascual Gómez5,*
1NEUROLOGY
2Radiology, H.U.C.A.
3University of Oviedo, OVIEDO, Spain
4Statistical analysis, Geisel School of Medicine at Darmouth, Hanover, United States
5NEUROLOGY, H.U.M.V., Santander, Spain
Objectives
White matter lesions (WML) are more prevalent in migraine, it seems that mainly with a high attack frequency. A vascular etiology has been proposed, but the pathogenesis and clinical significance remains unknown. Cerebral Vasoreactivity (CVR) reflects the vasodilation of microvasculature mediated via endothelial pathway, and its impairment is a marker of endothelial dysfunction.
The aim of this study is to asses whether differences in CVR can explain the mechanisms behind the WML described in MRI studies in chronic migraine (CM) patients.
Methods
This series includes 91 women meeting current IHS diagnostic criteria for CM. CVR was assessed by Breath Holding Index (BHI) on transcranial Doppler in middle cerebral arteries (MCA), posterior cerebral arteries (PCA) and in the basilar artery (BA). MRIs were acquired on a 1.5T unit following the CAMERA protocol.
Results
58 patients (aged 46,76 ± 10,11 years) had WML whereas 33 patients (35,64 ± 11,98 years) did not. Except for age (p < 0.001), the rest of clinical features and comorbidities -including history of aura, vascular risk factors and acute/preventive treatments- were similar between both groups. BHI was within range in all arteries examined. In patients with WML, mean BHI was: MCA 1,512 ± 0,371, PCA 1,402 ± 0,382, BA 1,450 ± 0,322. In patient without WML, mean BHI was: MCA 1,597 ± 0,450, PCA 1,440 ± 0,391, BA 1,541 ± 0,240. There were no differences in mean BHI in any of the different arteries explored (MCA p = 0,423, PCA p = 0,697, BA p = 0,447) for patients with and without WML.
Conclusion
In our series of CM there were not differences in BHI values in the different arteries explored, according to the presence of WML. This finding does not support endotelial dysfunction alone as the underlying pathophysiology of WML.
Disclosure of Interest
D. Larrosa: None Declared, A. Meilán: None Declared, C. Ramón Carbajo: None Declared, E. Cernuda Morollón: None Declared, P. Martínez-Camblor: None Declared, J. Pascual Gómez Conflict with: Supported by the PI14/00020 FISSS grant (Fondos Feder, ISCIII, Ministry of Economy, Spain)
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-009
The resting state connectivity between default-mode network and insula encodes intensity of migraine headache
Gianluca Coppola1,*, Antonio Di Renzo1, Emanuele Tinelli2, Cherubino Di Lorenzo3, Anna Ambrosini4, Vincenzo Parisi1, Claudio Colonnese5, Jean Schoenen6 and Francesco Pierelli4
1Research Unit of Neurophysiology of Vision and Neurophthalmology, G. B. Bietti Foundation IRCCS
2Department of Neurology and Psychiatry, Neuroradiology section, Sapienza University of Rome, Rome
3Department of Neurology, Don Carlo Gnocchi Foundation, Milan
4Headache Clinic
5Neuroradiology section, IRCCS Neuromed, Pozzilli, Italy
6Headache Research Unit, Department of Neurology-CHR Citadelle, University of Liège, Liège, Belgium
Objectives
Previous functional magnetic resonance imaging (MRI) studies have revealed that greater ongoing clinical pain in different chronic pain disorders, such as fibromyalgia and chronic low-back pain, is associated with proportional greater resting default mode network (DMN) to insula connectivity. Here, we investigated seed-based resting state DMN-insula connectivity during the acute head pain that characterizes spontaneous recurrent migraine attacks.
Methods
Thirteen patients with untreated migraine without aura (MI) underwent 3T MRI scans during the initial 6 hours of a spontaneous full-blown migraine attack and were compared to a group of 19 healthy volunteers (HV). We collected seed-based resting state data in the four core regions consistently identified in the DMN: medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs). Moreover, we collected seed-based resting state data from the insula bilaterally.
Results
Compared to HV, MI patients showed stronger bilateral insula connectivity to the medial prefrontal cortex (MPFC) region of interest. In MI, the strength of insula-MPFC connectivity, as measured by calculating the correlation coefficient, was negatively correlated with pain intensity (visual analogue scale) during migraine.
Conclusion
We documented for the first time that greater subjective intensity of pain during migraine is associated with proportional weaker DMN-insula connectivity. Notably, this is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.
Disclosure of Interest
None Declared
Headache Pathophysiology - Imaging and Neurophysiology
EP-01-010
Alice In Wonderland Syndrome associated to aripriprazole administration: a 99mTc-HMPAO brain SPECT study.
Giulio Mastria1, Valentina Macini1, Viviana Frantellizzi2, Alessandro Viganò1, Nikolas Petsas1, Saadi Sollaku2, Martina Fanella1, Carlo Di Bonaventura1, Mauro Liberatore2 and Vittorio Di Piero1,*
1Neurology and Psychiatry
2Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza - University of Rome, Rome, Italy
Objectives
Alice in Wonderland Syndrome (AIWS) is a rare disorder characterized by misperceptions of external and internal milieu, visual illusions and disorder of consciousness and may be caused by many diseases, albeit it is often associated with migraine in adults (1). Among other drugs, antiepileptics (topiramate), psychoactive drug (dextromethorphan) and abuse substances (LSD) may cause AIWS (1). We investigated AIWS by a brain perfusione SPECT performed during an AIWS episode caused by acute intake of aripiprazole, an atypical antipsychotic with partial agonism on D2 and 5HT1A and antagonism on 5HT2A receptors (2).
Methods
We describe a case of a 47 years old woman presenting AIWS sympotms who performed a perfusional brain SPECT during the attack.
Results
The patient had a history of migraine with visual aura since she was adolescent. Her past medical history included hypothyroidism and, since 1997, major depression treated with excellent results with fluvoxamine 300 mg and lorazepam 2.5 mg daily. In 2007 her psychiatrist added aripripazole 15 mg. She started to report a progressive change in her visual aura with the onset of mosaic vision and elongation and dismemberment feeling in her left arm, often followed by headache. The average duration of these episodes was approximately 6-8 hours. The frequency of these episodes increased over time and a partial benefit was obtained by a preventive therapy with valproate. Valproate was administrated in 6-months cycles for 2.5 years. She assumed aripripazole in a very irregular way. In 2016, the patient started again aripripazole and noted that the intensification of the misperception phenomena in conjunction with the assumption of this drug. In particular, misperception episodes were more frequent to the resumption of the assumption of aripiprazole, or upon reaching her therapeutic dose of 15 mg daily. She did a control EEG and MRI/MRA that were normal.
Recently, she had a worsening of her psychiatric condition. In the day she restarted aripiprazole, as expected, she experienced AIWS characterized by her usual symptoms and also apraxia of the left arm. During the AIWS episode, we performed a video-EEG, resulted normal, and a 99mTc-HMPAO brain SPECT. The perfusion SPECT images showed a reduced activity of the whole right hemisphere, associated with a focal area of hyperactivity in right cuneus/precuneous regions and an area of severe hypoactivity in the right primary parietal regions. A control SPECT study was repeated 2 weeks later and showed a normal brain perfusion pattern.
Conclusion
To date, this is the first case of AIWS caused by aripriprazole, a drug that lowers the threshold of neuronal excitability (4). By using SPECT, we observed significant decrease in brain activity in the right hemisphere during the occurrence of a AIWS episode. This overall reduction may let us speculate that it is linked to a thalamic dysfunction. In addition, SPECT showed an area of hyperactivity of the cuneus/precuneus regions, which are involved in own body perception and awareness (3), as well as a severe hypoactivity in the primary sensory regions. These results may suggest the occurrence during AIWS of an imbalance between the lower and higher associative cortices.
Disclosure of Interest
None Declared
References
1 Mastria et al. Biomed Res Int; 2016;8243145
2 Argo et al. Pharmacotherapy 2004;24(2):212
3 Cavanna et al. Brain 2006, 129, 564
4 Thabet et al Clin Neuropharmacol 2013; 36(1):29
Migraine Acute Therapy
EP-01-011
Sumatriptan Response and Predictors in Migraine Patients: A Large Clinic-Based Cohort Study
Shuu-Jiun Wang1,2,*, Kuan-Po Peng1,3, Jong-Ling Fuh1,2, Shih-Pin Chen1,2 and Yeng-Feng Wang1,2
1Faculty of Medicine, National Yang-Ming University School of Medicine
2Neurological Institute, Taipei Veterans General Hospital
3Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taipei, Taiwan, Republic of China
Objectives
Triptans are widely used in acute migraine treatment; however, individual effectiveness varies. Sumatriptan is the first in the genre, and remains the most widely used triptan worldwide. We aimed to the investigate sumatriptan efficacy and factors associated with its effectiveness in a large cohort.
Methods
We conducted an observational cohort study in a headache clinic in a tertiary medical center. This study is a collaborative study of the original genome-wide association study of migraine. Patients with migraine, who had been prescribed with sumatriptan were enrolled. Patients were asked to record their response after taking sumatriptan. Effectiveness of sumatriptan, i.e. responder, was defined as freedom from pain, or reduction to mild intensity in headache severity within 2 hours in at least 3 2 of 3 migraine attacks after the use of sumatriptan tablet (50mg). When sumatriptan was used in combination with other abortive medications, those who reported effectiveness were excluded, but those who reported no response were retained as non-responders.
Results
A total of 1,499 migraine patients were enrolled in the study, of whom 1,195 (79.7%) were women, with a mean age of 38.7 ± 11.3 years. Most patients (90.5%) were diagnosed with migraine without aura; while 33.4% fulfilled the diagnosis of chronic migraine, 21.5% medication overuse headache. Effectiveness of sumatriptan was reported in 1,033 (68.9%) of 1,499 patients. Compared to non-responders, sumatriptan responders were older (39.7 ± 11.3 vs. 36.5 ± 11.1 years old, p < 0.001), had a lower baseline headache frequency (9.8 ± 7.9 vs. 11.6 ± 9.1 days per month, p < 0.001), less likely to have chronic migraine (30.4 vs. 39.8%, p < 0.001), with lower psychiatric measures (Beck Depression Inventory 10.5 ± 7.8 vs. 11.8 ± 8.7, p = 0.007), and were less likely to have fibromyalgia (6.1% vs. 10.5%, p = 0.014). Regular coffee consumption was positively associated with effectiveness ( ≥ 1 cup per day vs. non-drinker, odds ratio = 1.603, p = 0.003). Gender or status of aura were not associated with sumatriptan response.
Conclusion
In our large cohort, two thirds of migraine patients responded to sumatriptan. Certain demographic data, severity measures and comorbidities measures were associated with triptan responses. A link to coffee consumption is interesting and worth further investigation.
Disclosure of Interest
None Declared
Migraine Acute Therapy
EP-01-012
Intranasal ketamine for abortive migraine therapy in pediatric patients: a case series
Adrian L. Turner1, Kimberly Tobin1, Ean Miller1, Austin Rock1, Dani Ball1 and Brian Ryals2,*
1Pharmacy
2Jane and John Justin Neurosciences Center, Cook Children's Medical Center, Fort Worth, United States
Objectives
Migraine is a common presentation in adolescents and children in emergency departments (EDs) and inpatient visits. It is often treated with nonsteroidal anti-inflammatory drugs, dopamine receptor antagonists, triptans, or dihydroergotamine. Some cases, however, are refractory to traditional medications and options become narrowed [1,2]. Restricting therapy further, dihydroergotamine is currently on indefinite shortage [3]. Ketamine, a lipophilic, rapid-acting, N-methyl-D-aspartate (NMDA) antagonist, has emerged as a promising therapeutic option [4,5]. Excitatory glutamate signaling may be inhibited by ketamine via NMDA antagonism. This action could suppress cortical spreading depression(CSD) and alleviate migraines with and without aura [5].
Reports in mixed migraine patient populations described statistically significant pain score reductions (7.1 to 3.8; p < 0.0001) with intermittent intravenous ketamine[6] and diminished severity with ketamine infusions (0.12-0.42 mg/kg/hour)[7] without serious adverse effects (AEs) [6,7]. Intranasal (IN) ketamine 25 mg in migraine patients with prolonged aura demonstrated statistically significant reduced aura severity (p = 0.032) [4]. Reports of efficacy and safety with IN ketamine (0.3-0.5 mg/kg/dose) in pediatric patients with various pain diagnoses have been published[8-13], but pediatric migraine data with IN ketamine is lacking. Given minimal evidence and therapeutic options, our experience with IN ketamine was recorded to better understand potential efficacy and safety.
Methods
A retrospective case series was performed in 8 pediatric patients (12-17 years old) with refractory migraine who received IN ketamine between December 2016 and February 2017. In total, 11 encounters were recorded. Pain scores were obtained utilizing a 0–10 numeric pain scale [14]. Ketamine 0.1-0.2 mg/kg/dose (mean = 0.15 mg/kg/dose) was administered intranasally every 15 minutes (maximum: 5 doses).
Results
Migraine resolution was seen in 63.6% of encounters (n = 7/11); most responders achieved their lowest pain score with dose four or five (n = 5/7; 71.4%). Mean pain reduction from admission to ketamine completion for responders was -6.8. Non-responders (n = 4) saw only -0.5 reduction.
Mean migraine duration at presentation was longer in responders versus non-responders (44.6 versus 4 days). Responders also had a nearly 50% shorter mean length of stay (LOS) compared to non-responders (2.4 versus 4.75 days, respectively). Ketamine was initiated in the ED for 7 encounters; 3 (42.9%) avoided inpatient admission.
Vitals were monitored during and 1 hour post-ketamine administration. The following transient abnormalities were noted: prehypertensive blood pressure[15] (n = 8; 72.7%); mild tachycardia[16] (n = 4; 36.4%); dizziness (n = 2; 18.2%); and dysphoria (n = 1; 9.1%). No serious AEs or readmissions within 72 hours were reported.
Conclusion
Intranasal ketamine appears to be safe and effective for pediatric migraine treatment, particularly in patients with prolonged migraine. Our experience supports efficacy with lower IN ketamine doses (0.1–0.2 mg/kg/dose) in abortive migraine therapy with minimal AEs. Larger trials are warranted to substantiate ketamine’s efficacy, optimal dose, and safety for abortive migraine therapy in pediatric patients.
Disclosure of Interest
None Declared
Migraine Preventive Therapy
EP-01-013
Efficacy of erenumab for the treatment of patients with chronic migraine in presence of medication overuse
Stewart J. Tepper1,*, Hans-Christoph Diener2, Messoud Ashina3, Jan L. Brandes4, Deborah T. Friedman5, Uwe Reuter6, Sunfa Cheng7, Dean Leonardi7, Robert A. Lenz7 and Daniel D. Mikol7
1Geisel School of Medicine at Dartmouth, Hanover, United States
2Department of Neurology, University of Duisburg-Essen, Essen, Germany
3Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
4Department of Neurology, Vanderbilt University School of Medicine, Nashville
5Neurology and Neurotherapeutics and Ophthalmology, University of Texas Southwestern Medical Center, Dallas, United States
6Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
7Amgen, Thousand Oaks, United States
Objectives
Efficacy of erenumab, a human anti-CGRP receptor antibody, was evaluated in chronic migraine (CM) patients with medication overuse (MO) in prespecified subgroup analyses of a phase 2 study (NCT02066415).
Methods
CM patients ( ≥ 15 headache [HA] days/month over 3 months with ≥ 8 migraine days) were randomized to erenumab (70 mg or 140 mg QM) or placebo for 12 weeks, stratified by region and MO. Data from patients with MO at baseline were used to assess changes in monthly migraine days (MMD), acute migraine-specific medication (AMSM) days, monthly HA hours, and proportion of patients achieving ≥50% reduction in MMD. P-values for pairwise comparisons were not adjusted for multiple comparisons.
Results
Of 667 patients randomized, 41% (n = 274) met MO criteria. Mean (SD) baseline MMD in the MO subgroup were 19.6 (4.4), 18.8 (4.6), and 18.8 (4.5) in the placebo, 70–mg, and 140-mg groups. Compared with placebo, erenumab 70-mg or 140-mg groups had a greater reduction in change in MMD at week 12 (LS mean [SE]: -6.6 [0.7] and −6.6 [0.7] vs −3.5 [0.6]; p < 0.001 for both) and a greater reduction in change in AMSM days (LS mean [SE]: -5.4 [0.6] and -4.9 [0.5] vs -2.1 [0.5]; p < 0.001 for both). In the placebo, 70-mg, and 140-mg groups, ≥ 50% reductions in MMDs were achieved by 18%, 36% (OR: 2.67; p = 0.004), and 35% (OR: 2.51; p = 0.007). Respective changes in monthly HA hours were -56.9 [10.6] and −69.7 [10.4] vs -42.0 [8.7] (p = 0.28 and p = 0.04).
Conclusion
Erenumab showed efficacy in CM patients with medication overuse in this study.
Disclosure of Interest
S. Tepper Conflict with: Allergan, Amgen, H.-C. Diener Conflict with: Allergan, Almirall, AstraZeneca, Bayer, Electrocore, GSK, Janssen-Cilag, MSD and Pfizer, Conflict with: Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Böhringer Ingelheim, Bristol-Myers Squibb, Chordate, Coherex, CoLucid, Electrocore, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Labrys Bioloogicals, Lilly, La Roche, 3M Medica, Medtronic, Menerini, Minster, MSD, Neuroscore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofi, St. Jude, Teva and Weber & Weber, M. Ashina Conflict with: Allergan, Amgen, ATI, Novartis, Conflict with: Allergan, Amgen, Novartis, J. Brandes Conflict with: Allergan, Amgen, Clinvest, Teva, Colucid, Zozano, Conflict with: Amgen, Supernus, Conflict with: Depomed, Pemix, Teva, Avanir, Conflict with: Avanir, Supernus, Teva,, D. Friedman Conflict with: Merk, Autonomic Technologies, Inc., Conflict with: Allergan, Teva, Eli Lilly, Avanir, Conflict with: Eli Lilly, Allergan, Teva, Zosano, Amgen, Alder, Supernus, Trigemina, U. Reuter Conflict with: Amgen, Autonomic Technologies, Inc., Novartis, Eli Lilly, CoLucid, Conflict with: Amgen, Novartis, Eli Lilly, CoLucid, Allergan, Teva, Conflict with: Amgen, Autonomic Technologies Inc., Novartis, Allergan, S. Cheng Conflict with: Amgen, Conflict with: Amgen, D. Leonardi Conflict with: Amgen, Conflict with: Amgen, R. Lenz Conflict with: Amgen, Conflict with: Amgen, D. Mikol Conflict with: Amgen, Conflict with: Amgen
Migraine Acute Therapy
EP-01-014
Efficacy of erenumab for the treatment of patients with chronic migraine and aura
Messoud Ashina1,*, David Dodick2, Peter J. Goadsby3, David Kudrow4, Uwe Reuter5, Stewart J. Tepper6, Sunfa Cheng7, Dean Leonardi7, Robert A. Lenz7 and Daniel D. Mikol7
1Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
2Dept Of Neurology, Mayo Clinic, Scottsdale, United States
3NIHR-Wellcome Trust King’s Clinical Research Facility, Kings College, London, United Kingdom
4California Medical Clinic for Headache, Santa Monica, United States
5Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
6Geisel School of Medicine at Dartmouth, Hanover
7Amgen, Thousand Oaks, United States
Objectives
Efficacy of erenumab, a human anti-CGRP receptor antibody, was evaluated in chronic migraine (CM) patients in a phase 2 study (NCT02066415). Here we report a subgroup analysis of patients with aura and patients without aura.
Methods
CM patients (≥15 headache [HA] days/month over 3 months with ≥8 migraine days) were randomized to erenumab (70 mg or 140 mg QM) or placebo for 12 weeks. Data from patients with at least one aura and patients without any aura during the 4-week baseline period were used to assess changes in monthly migraine days (MMD), acute migraine-specific medication days (MSMD), and proportion of patients achieving ≥50% reduction in MMD. Data from patients with and without history of aura were also analyzed. Nominal p-values are presented without multiplicity adjustment and not used for pre-planned hypothesis testing.
Results
Of 667 patients randomized, 49% (n = 328) had at least one migraine with aura during the baseline period. Mean (SD) baseline MMD in the aura subgroup were 18.6 (4.5), 18.5 (4.1), and 18.1 (4.7) in the placebo, 70–mg, and 140-mg groups. Respective baseline MMD in the non–aura subgroup were 17.8 (4.9), 17.5 (4.5), and 17.5 (4.7).
Compared with placebo, treatment with erenumab 70 mg or 140 mg resulted in greater change (reduction) in MMD at week 12 in both subgroups: patients with aura and patients without aura (Table 1). There was also a greater change (reduction) in acute MSMD in both patients with aura and patients without aura (Table 1). The responder rates (≥50% reductions in MMDs) in the placebo, 70-mg, and 140-mg groups were 23%, 41% (odds ratio [95% CI]: 2.5 [1.4, 4.4]; p = 0.003) and 40% (OR: 2.5 [1.4, 4.5]; p = 0.002) for patients with aura and 24%, 39% (OR: 2.0 [1.1, 3.5]; p = 0.020) and 42% (OR: 2.2 [1.3, 4.0]; p = 0.006) for patients without aura. Results from analyses based on history of aura showed a similar pattern.
Conclusion
These data indicate that erenumab has similar efficacy in patients with migraine with and without aura in terms of MMD, MSMD and ≥50% RR.
Change from baseline at week 12
Disclosure of Interest
M. Ashina Conflict with: Allergan, Amgen, ATI, Novartis, Conflict with: Allergan, Amgen, Novartis, D. Dodick Conflict with: Epien Medical (Stock), Second Opinion (stock), GBS (stock),, Conflict with: Allergan, Amgen, Alder, Dr Reddy’s, Merck, eNeura, Eli Lilly & Company, INSYS therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, and Boston Scientific, GBS, Merck, Colucid, Zosano, Conflict with: Neuroassessment systems (Know-how License with Employer-Mayo Clinic), Oxford University Press, Cambridge University Press, Web MD. UptoDate, P. Goadsby Conflict with: Allergan, Amgen, Eli-Lilly and Company, and eNeura; and personal fees from Ajinomoto Pharmaceuticals Co, Akita Biomedical, Alder Biopharmaceuticals, Autonomic Technologies Inc, Avanir Pharma, Cipla Ltd, Colucid Pharmaceuticals, Ltd, Dr Reddy's Laboratories, Electrocore LLC, Ethicon, US, WL Gore & Associates, Heptares Therapeutics, Novartis, Nupathe Inc, Pfizer Inc, Promius Pharma, Scion, Teva Pharmaceuticals, Trigemina Inc.; and personal fees from MedicoLegal work, Journal Watch, Up-to-Date, Oxford University Press., Conflict with: patent Magnetic stimulation for headache pending assigned to eNeura, D. Kudrow Conflict with: Amgen, Ely Lilly, Alder, Teva, Dr Reddy’s Lab, Co-Lucid, Topstone, Roche-Genentech,, Conflict with: Evidera, Conflict with: Ely Lilly, Amgen, U. Reuter Conflict with: Amgen, Autonomic Technologies, Inc., Novartis, Eli Lilly, CoLucid, Conflict with: Amgen, Novartis, Eli Lilly, CoLucid, Allergan, Teva, Conflict with: Amgen, Autonomic Technologies Inc., Novartis, Allergan, S. Tepper Conflict with: Allergan, Amgen, S. Cheng Conflict with: Amgen, Conflict with: Amgen, D. Leonardi Conflict with: Amgen, Conflict with: Amgen, R. Lenz Conflict with: Amgen, Conflict with: Amgen, D. Mikol Conflict with: Amgen, Conflict with: Amgen
Migraine Acute Therapy
EP-01-015
Early Onset of Efficacy in a Phase 2 Clinical Trial of Erenumab in Patients with Chronic Migraine
Uwe Reuter1,*, Stewart Tepper2, Peter Mcallister3, Messoud Ashina4, Dean Leonardi5, Thuy Vu5, Sunfa Cheng5, Daniel Mikol5 and Robert Lenz5
1Dept of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
2Geisel School of Medicine at Dartmouth, Hanover, NH
3New England Institute for Neurology & Headache, Stamford, CT, United States
4Dept of Neurology, Danish Headache Center, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark
5Amgen Inc., Thousand Oaks, CA, United States
Objectives
Erenumab 70 mg and 140 mg reduced monthly migraine days at all time points assessed (weeks 4, 8, and 12) in a phase 2 clinical trial of chronic migraine (NCT02066415). Here we evaluated efficacy prior to week 4.
Methods
Post hoc analyses evaluated achievement of ≥50% reduction in weekly migraine days and change from baseline in weekly migraine days. P-values for these endpoints are based on odds ratios or mean differences from placebo and are not adjusted for multiple comparisons. Also, to evaluate trends, a linear model was fitted to observed daily migraine days from days 1-7 (week 1) and pairwise comparisons of the slopes and moving averages were evaluated and overlaid with observed data.
Results
Both erenumab dose groups had a greater proportion of patients achieving ≥50% reduction in weekly migraine days by week 1 (26% for both doses compared with 16% for placebo [p ≤ 0.011]), increasing to 31%, 41%, and 21% in the 70 mg, 140 mg, and placebo groups, respectively, at week 2 (p ≤ 0.011). At weeks 1-4, reductions from baseline in weekly migraine days were observed for the 70 mg group (range: -1.5 to -0.9 days [4.5 days at baseline]) and 140 mg group (range: -1.5 to -0.8 days [4.5 days at baseline) compared with placebo (range: -0.8 to -0.5 days [4.6 days at baseline]; week 1: 70 mg p = 0.047, 140 mg p = 0.18; weeks 2-4 p ≤ 0.002 for both doses vs placebo). Moreover, 7-day moving averages of observed data showed that each treatment arm differed from placebo within the first several days. On pairwise comparisons, slopes for 140 mg differed from placebo by day 4 (p = 0.03). By day 6, both doses differed from placebo (p ≤ 0.03).
Conclusion
Erenumab showed early onset of efficacy with separation from placebo within the first week.
Disclosure of Interest
U. Reuter Conflict with: Amgen, Autonomic Technologies, Novartis, Eli Lilly, CoLucid, Conflict with: Amgen, Novartis, Eli Lilly, CoLucid; Pharm Allergan, TEVA, Conflict with: Advisory board for Amgen, Autonomic Technologies, Novartis, Pharm Allergan, S. Tepper Conflict with: ATI, Conflict with: Alder, Allergan, Amgen, ATI, Avanir, ElectroCore, eNeura, Scion NeuroStim, Teva, and Zosano, Conflict with: Acorda, Alder, Allergan, Amgen, ATI, Avanir, BioVision, ElectroCore, eNeura, Impax, Kimberly-Clark, Pernix, Pfizer, Scion NeuroStim, Teva, and Zosano, Conflict with: American Headache Society, Conflict with: Royalties from the University of Mississippi Press, Springer, P. Mcallister Conflict with: Amgen, Lilly, TEVA, Alder, Conflict with: Amgen, M. Ashina Conflict with: Allergan, Amgen, Novartis, Conflict with: Advisory Board for Allergan, Amgen, ATI, Novartis, D. Leonardi Conflict with: Amgen, Conflict with: Amgen, T. Vu Conflict with: Amgen, Conflict with: Amgen, S. Cheng Conflict with: Amgen, Conflict with: Amgen, D. Mikol Conflict with: Amgen, Conflict with: Amgen, R. Lenz Conflict with: Amgen, Conflict with: Amgen
Migraine Preventive Therapy
EP-01-016
Chronic Migraine Treatment with Erenumab: Responder Rates
Jan L. Brandes1,*, Hans-Christoph Diener2, David Dolezil3, Marshall C. Freeman4, Peter J. Mcallister5, Paul Winner6, Sunfa Cheng7, Dean Leonardi7, Robert A. Lenz7 and Daniel D. Mikol7
1Department of Neurology, Vanderbilt University School of Medicine, Nashville, United States
2Department of Neurology, University of Duisburg-Essen, Essen, Germany
3Prague Headache Center, Prague, Czech Republic
4Headache Wellness Center, Greensboro
5New England Institute for Neurology and Headache, Stamford
6Palm Beach Headache Center, West Palm Beach
7Amgen, Thousand Oaks, United States
Objectives
Erenumab (AMG 334) is a human anti-CGRP receptor antibody being evaluated as preventive treatment for chronic migraine (CM). When assessing efficacy of CM treatments by responder rates, there is an unmet need for more effective treatments.
Methods
In an analysis of data from a phase 2 study (NCT02066415) in patients with CM (≥15 headache days/month over 3 months with ≥8 migraine days), patients (N = 667) were randomized to erenumab (70 mg or 140 mg QM) or placebo. This analysis included calculation of proportions of patients with ≥50%, ≥75%, or 100% reduction in monthly migraine days (MMD) from baseline to last 4 weeks of a 12-week double-blind phase. P-values are based on odds ratios (OR) from placebo and are not adjusted for multiple comparisons.
Results
Mean (SD) baseline MMD were 18.0 (4.6). Significantly higher proportions of patients treated with erenumab 70 mg or 140 mg experienced a ≥50% reduction from baseline in MMD compared with placebo at week 12 (39.9% and 41.2%, vs 23.5%; OR: 2.2 [p < 0.001] and 2.3 [p < 0.001]). The ≥75% responder rates at week 12 were higher for patients treated with erenumab 70 mg or 140 mg compared with placebo (17.0% and 20.9%, vs 7.8%; OR: 2.4 [p = 0.002] and 3.1 [p < 0.001]). Likewise, the 100% responder rates were higher for patients treated with erenumab 70 mg or 140 mg compared with placebo (4.3% and 2.7%, vs 0.4%; OR: 12.6 [p = 0.002] and 8.1 [p = 0.026]).
Conclusion
Erenumab treatment resulted in higher proportions of patients with CM experiencing ≥50%, ≥75%, and 100% reduction in monthly migraine days as compared with placebo.
Disclosure of Interest
J. Brandes Conflict with: Allergan, Amgen, Clinvest, Teva, Colucid, Zozano, Conflict with: Amgen, Supernus, Conflict with: Depomed, Pemix, Teva, Avanir, Conflict with: Avanir, Supernus, Teva,, H.-C. Diener Conflict with: Allergan, Almirall, AstraZeneca, Bayer, Electrocore, GSK, Janssen-Cilag, MSD and Pfizer, Conflict with: Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Böhringer Ingelheim, Bristol-Myers Squibb, Chordate, Coherex, CoLucid, Electrocore, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Labrys Bioloogicals, Lilly, La Roche, 3 M Medica, Medtronic, Menerini, Minster, MSD, Neuroscore, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofi, St. Jude, Teva and Weber & Weber, D. Dolezil Conflict with: Amgen, Allergan, M. Freeman Conflict with: Alder, Amgen, Allergan, Avanir, Dr. Reddy Laboratories, Eli Lilly, Scion NeuroStim, Teva, Zosano Pharma, Conflict with: Avanir, Scion NeuroStim, Teva, Conflict with: Avanir, Teva, P. Mcallister Conflict with: Amgen, eli Lilly, Teva, Alder, Conflict with: Amgen, P. Winner Conflict with: Allergan, Amgen, A-Z, Teva, Pfizer, Novartis, Lilly, Conflict with: Avanir, Allergan, and Teva; Advisory Board: Avanir, Teva, and Supernus, S. Cheng Conflict with: Amgen, Conflict with: Amgen, D. Leonardi Conflict with: Amgen, Conflict with: Amgen, R. Lenz Conflict with: Amgen, Conflict with: Amgen, D. Mikol Conflict with: Amgen, Conflict with: Amgen
Migraine Acute Therapy
EP-01-017
Fremanezumab (formerly TEV-48125) reduces headache pain within the first week of beginning treatment in the phase 2 episodic migraine study
Marcelo Bigal1, Ernesto Aycardi1,*, Mirna McDonald2, Robert Noble3 and Pippa Loupe4; Investigators of the Fremanezumab (TEV-48125) HFEM Study
1Clinical Development, Teva Global Research and Development
2Statistics, Teva Global Medical Affairs, Frazer PA
3Statistics, Teva Global Medical Affairs, Hamilton OH
4Academic Affairs and Network, Teva Global Research and Development, Overland Park KS, United States
Objectives
Fremanezumab (formerly TEV-48125) is a fully humanized IgG2Δa monoclonal antibody that has been shown to selectively block both CGRP isoforms (α- and β) from binding to the CGRP receptor. In addition, fremanezumab inhibited neurogenic vasodilation induced by CGRP release in animal models. Fremanezumab was found to be effective and well-tolerated as a preventive migraine treatment for two 3 month placebo-controlled phase 2 studies. The present study evaluated in post-hoc analyses, the efficacy of two doses of subcutaneous fremanezumab (225 mg and 675 mg) during the first three weeks of therapy in patients with high frequency episodic migraine (HFEM).
Methods
In this multicenter, placebo-controlled, parallel-group study, patients with HFEM were first screened and trained to use an electronic headache diary during a 28 day run-in period. After the run-in period, participants who met inclusion criteria and were 80% compliant with daily diary intake were randomized, and treated once every 28 days for three months with either placebo, fremanezumab 225 mg or 675 mg treatment. Compared to placebo, both doses of fremanezumab significantly reduced the primary endpoint of the HFEM study, change in the number of migraine days in month 3 relative to baseline; herein we performed post-hoc mixed-effects model repeated measures (MMRM) analyses to assess the efficacy of each dose during the first 3 weeks of treatment for several headache parameters.
Image:
Results
The sample consisted of 296 subjects. Compared to placebo, decreases in the number of migraine days were seen during 1 week of therapy for both fremanezumab doses (p < 0.0001, Fig. 1, Panel A), a benefit that was maintained through the second and third weeks of therapy (p < 0.0001). Likewise, there were decreases in days with headaches of moderate to severe intensity for both doses at week 1 (p = 0.0062 and p = 0.0005, Fig. 1, Panel B), week 2 (p = 0.0032 and p = 0.0025) and week 3 (p = 0.0094 and p = 0.0042). Both doses decreased the number of days with headache of any severity within week 1 (p < 0.0001), this effect persisted at week 2 (p < 0.0001 and p = 0.0002) and week 3 (p = 0.0002 and p = 0.0011). For headache hours of least moderate or severe intensity and headache hours of any severity, the same pattern of efficacy was seen; there were decreases for both doses at weeks 1, 2, and 3 (all p < 0.01, Fig 2. Panels A and B).
Conclusion
In these post-hoc analyses, fremanezumab treatment resulted in a rapid preventive response in patients with HFEM, with improvements seen in several pain parameters within the first week of therapy initiation.
Disclosure of Interest
M. Bigal Conflict with: Teva Pharmaceutical Industries, Conflict with: Teva Pharmaceutical Industries, E. Aycardi Conflict with: Teva Pharmaceutical Industries, Conflict with: Teva Pharmaceutical Industries, M. McDonald Conflict with: Teva Pharmaceutical Industries, Conflict with: Teva Pharmaceutical Industries, R. Noble Conflict with: Teva Pharmaceutical Industries, Conflict with: Teva Pharmaceutical Industries, P. Loupe Conflict with: Teva Pharmaceutical Industries, Conflict with: Teva Pharmaceutical Industries
Migraine Acute Therapy
EP-01-018
Patient Preferences for Preventive Therapy in Headache Medicine
Melissa Schorn1,*, Natalia Murinova2, Daniel Krashin3 and Sau Mui Chan Goh1
1Neuroscience Institute, University of Washington Medical Center
2Neurology
3Psychology and Pain and Anesthesiology, University of Washington, Seattle, United States
Objectives
The primary objective of this study was to survey patients referred to a university-based headache clinic regarding treatment preferences.
Methods
All new patients at a tertiary headache specialty clinic completed a general patient reported outcomes questionnaire prior to their first visit (n = 1826). Treatment preferences are addressed in a section of this questionnaire. Patients chose from the following nine options when asked about preferences: preventive prescription medications, acute prescription medications, supplements/herbs/vitamins, Botox, other non-medication procedures, biofeedback or meditation, hypnosis, stress management or other preferences.
Results
Only a small percentage of patients preferred prescription medications only (64, 3.5%). A larger group preferred non-medication approaches (301, 16.5%). The majority of patients preferred an integrative approach, combining medications and complementary options (1235, 67.6%).
Conclusion
The majority of patients with headache are offered only medication treatment options, yet the preference of a majority of patients is an integrative approach that includes a combination of medication and non-medication treatments. Only a small minority of patients prefers medication only. It is important to open a conversation regarding patient preferences when partnering with patients to improve adherence to a treatment plan.
Disclosure of Interest
None Declared
Migraine Acute Therapy
EP-01-019
Migraine Preventive Benefits of ALD403 (eptinezumab) begin in the first 24 Hours Following Intravenous Administration
Peter J. Goadsby1,*, Jeff Smith2, David Dodick3, Richard Lipton4, Stephen Silberstein5, Roger Cady2 and Joe Hirman6
1Neurology, UCSF, San Francisco
2Alder BioPharmaceuticals, Bothell
3Mayo Clinic, Phoenix
4Neurology, Montefiore Headache Center, Albert Einstein College of Medicine, New York
5Neurology, Thomas Jefferson University Headache Center, Philadelphia
6Pacific Northwest Stats, Bothell, United States
Objectives
Current options for preventive treatment in chronic migraine (CM) fail to meet the needs of many patients. Calcitonin gene-related peptide (CGRP) is a promising target for treating CM. ALD403 (eptinezumab) is a genetically engineered humanized anti-CGRP antibody, for migraine prevention. Data from a Phase 2b trial demonstrated a persistent reduction in migraine days that was maintained through 12 weeks. During these trials, a reduction in migraine activity was observed 24 hours after intravenous (IV) administration of ALD403 (eptinezumab). Based on this observation, we conducted a further assessment of the time of onset for the migraine preventive action of ALD403 (eptinezumab) in patients with CM.
Methods
The time to onset of ALD403 migraine preventive efficacy was assessed by post hoc analysis of a parallel group, double-blind, placebo-controlled Phase 2b trial. Patients with CM were randomized to receive a single IV infusion of ALD403 or placebo. Self-reported migraine episodes and migraine hours were recorded daily in an eDiary at baseline and throughout the study. In this analysis, migraine episodes and migraine hours experienced 24 hours after a single IV infusion of ALD403 (300 mg or 100 mg) or placebo were compared to baseline.
Results
Of 665 patients randomized, 616 received treatment, and 588 treated patients who provided reliable data were included in this analysis. Analysis of the first full day (24 hours) following a single infusion indicated the percent of patients with a migraine was reduced from baseline in the ALD403 300 mg (59% to 27%) and in the ALD403 100 mg (60% to 29%) and from 59% to 49% in the placebo group. The reduction in daily migraine hours within the 24 hours after administration of study drug compared to the average baseline hours per day was also greater following treatment with ALD403 300 mg (6.1 to 2.9; -3.1 hrs) and 100 mg (6.1 to 2.8; -3.3 hrs) vs. placebo (6.1 to 5.1; -1.1 hrs). ALD403 was well-tolerated with no serious related adverse events reported.
Conclusion
In this post hoc analysis, on the first full day (24 hours) after administration of a single IV infusion, reductions in both the proportion of patients experiencing a migraine and the number of migraine hours experienced on that day were greater relative to baseline for patients receiving ALD403 (eptinezumab) compared to those receiving placebo. These observations suggest an early onset of migraine preventive efficacy, which may be related to IV administration, the unique pharmacokinetic and pharmacodynamic attributes of ALD403 (eptinezumab), the specific mechanism of action, or some combination of these attributes.
Disclosure of Interest
P. Goadsby Conflict with: Alder BioPharmaceuticals, J. Smith Conflict with: Alder BioPharmaceuticals, Conflict with: Alder BioPharmaceuticals, D. Dodick Conflict with: Alder BioPharmaceuticals, R. Lipton Conflict with: Alder BioPharmaceuticals, S. Silberstein Conflict with: Alder BioPharmaceuticals, R. Cady Conflict with: Alder BioPharmaceuticals, Conflict with: Alder BioPharmaceuticals, J. Hirman Conflict with: Alder BioPharmaceuticals
Neuromodulation for Headache
EP-01-020
Effect of cathodal transcranial direct current stimulation of the primary motor and sensory cortex on migraine
Mohammad Dawood Rahimi1,*, Javad Salehi Fadardi2, Imanolla Bigdeli2, Morteza Saeidi3, Mohammad Mahdi Ghasemi4 and Karim Nikkhah3
1Ferdowsi University of Mashhad and Mashhad University of Medical Sciences, Herat, Afghanistan
2Psychology, Ferdowsi University
3Neurology
4Ear, Nase, and throat, Mashhad University of Medical Sciences, Mashhad, Iran, Islamic Republic Of
Objectives
Transcranial direct current stimulation is a novel technological method that has been used in the scope of pain related diseases like migraine-as a prevalent and high burden disease extensively. The aim of the present study was to evaluate the effectiveness of cathodal transcranial direct current stimulation (c-tDCS) over the right primary motor (M1) and sensory (S1) areas of the cortex on decreasing the intensity, duration, and frequency of pain in migraineurs.
Methods
This study was based on a randomized, double-blind, and sham-controlled design, and it tested 15 seasons (every week three seasons; over 5 consecutive weeks) of c-tDCS (20 min/1000μA) on forty-five migraineurs (diagnosed according to the IHCD-II) into two experimental (nm = 1 5; ns = 15) and a control group (nc = 15).
Image:
Results
The results of a series of one-way ANOVA, c-tDCS showed significant (p < 0.05) reductions in all hypothesized aspects of pain in both experimental groups compared to the control one.
Conclusion
Therefore, it seems that c-tDCS can be used as a technological method in the treatment of migraine both therapeutically and prophylactically.
Disclosure of Interest
None Declared
Neuromodulation for Headache
EP-01-021
sTMS Blocks Cortical Spreading Depression by Suppressing Spontaneous Cortical Neuronal Firing and by Increasing the Threshold of Activation of the Occipital Cortex
J O. Lloyd1,*, B N. Okine1, M G. Jones2,3, G Lambru1,4, S B. McMahon2 and A P. Andreou1,4; Headache group, Wolfson CARD
1Headache Research-Wolfson CARD
2Neurorestoration Department-Wolfson CARD, King's College London
3Zenith Neurotech Ltd
4Headache Centre, Guy's and St Thomas' NHS Trust, London, United Kingdom
Objectives
Single-pulse transcranial magnetic stimulation (sTMS) is a non-invasive neuromodulation technique that has been shown to be a successful acute and preventative treatment for migraine patients with and without aura. In vivo, sTMS has been previously shown to block cortical spreading depression (CSD) and thalamic neuronal activity. sTMS uses a single magnetic pulse of 170 µs duration to induce weak electrical currents via electromagnetic induction, in the underlying cortical tissue.
Methods
All procedures were performed under a UK Home Office Licence in accordance to the 1986 Animal (Scientific Procedures) Act in anaesthetised male adult Sprague-Dawley rats. Spontaneous neuronal activity of the visual cortex was recorded using in vivo extracellular electrophysiological techniques. A rat-specific sTMS device was placed above the visual cortex and two pulses were applied at 100 V increments (100-600 V; ∼0.2-1.1 T). Spontaneous neuronal activity was recorded for up to 90 minutes post-sTMS and compared to baseline recordings. In a separate set of experiments, the CSD model of migraine with aura was utilised. CSD induction was monitored through recordings of cortical steady-state potentials and induced via electrical stimulation of the visual cortex. This was repeated following two 600 V (1.1 T) sTMS pulses to the visual cortex. The microcoloumbs needed to induce a CSD wave were recorded pre- and post- sTMS application. In an independent group, two pulses of sTMS were applied and the microcoloumbs needed to induce CSD were recorded and compared to a control group.
Results
sTMS inhibited spontaneous neuronal activity in a dose-dependent manner. The sTMS treatments with the highest voltage, 500 V (0.9 T) and 600 V (1.1 T) significantly decreased cortical neuronal activity (n = 6; P < 0.001). Additionally, sTMS significantly increased the electrical threshold required to induce CSD (n = 6; P < 0.05). Comparisons within the same group demonstrated that sTMS blocked CSD for up to 2 hours (n = 5; P < 0.001).
Conclusion
Twin sTMS pulses demonstrate a dose dependent inhibitory effect on cortical neuronal activity. sTMS also blocked electrically-induced CSD by increasing the threshold of activation required for the induction of a wave. Collectively, these findings suggest a potential mechanism by which sTMS treatment reduces cortical excitability and migraine aura known to occur in migraine patients.
Disclosure of Interest
J. Lloyd: None Declared, B. Okine: None Declared, M. Jones Conflict with: CEO of Zenith Tech. Ltd, Conflict with: Nevro Corp, G. Lambru Conflict with: Honorarium from Allergan, Autonomic Technologies, Inc., S. McMahon Conflict with: Wellcome Trust and MRC, Conflict with: Consultant for Bayer, Conflict with: Scientific Advisory Board member – Spinal Research, Afferent Pharma. Board member of MRC NMHB, A. Andreou Conflict with: Honorarium from eNeura Inc, Allergan, Autonomic Technologies, Inc.
Other Primary Headache Disorders
EP-01-022
Outcome of microvascular decompression in trigeminal neuralgia is highly dependent on sex and degree of neurovascular contact – A prospective systematic study using independent assessors
Tone B. Heinskou1,*, Stine Maarbjerg1, Per Rochat2, Frauke Wolfram3, Jannick Brennum2, Jes Olesen1 and Lars Bendtsen1
1Danish Headache Center, Department of Neurology, Rigshospitalet. Faculty of Health and Medical Sciences, University of Copenhagen., Glostrup
2Department of Neurosurgery, Rigshospitalet. Faculty of Health and Medical Sciences, University of Copenhagen., Copenhagen
3Department of Diagnostics, Rigshospitalet. Faculty of Health and Medical Sciences, University of Copenhagen., Glostrup, Denmark
Objectives
Microvascular decompression (MVD) is first choice neurosurgical treatment in medically refractory trigeminal neuralgia patients with an MRI verified neurovascular contact (NVC). There is a lack of high-quality prospective, systematic studies, using independent assessors of outcome of the procedure. Here we aimed to evaluate whether sex and degree of NVC can predict outcome of MVD.
Methods
Clinical characteristics and outcome data were systematically recorded prospectively from consecutive trigeminal neuralgia patients, using standardized semi-structured interviews and schemes. A pre-surgical 3.0 Tesla MRI was performed to evaluate the degree of NVC blinded to symptomatic side. The patients were assessed before and 3, 6 and 12 months after MVD by a neurologist at the Danish Headache Center. The Department of Neurosurgery had no influence on recording or evaluation of data. Data from a self-completed 12 months post-surgical questionnaire including items on pain intensity, complications and satisfaction, were also recorded. The primary outcome was pain relief according to the Barrow Neurological Institute pain score (BNI I-VB), table 1. Secondary outcome was patient satisfaction.
Results
From May 2012 to February 2016, 27 men and 33 women had completed one year follow-up. Mean age at operation was 59.9 years (range 28-80 years). Mean duration of disease was 6.6 years (range 1-40 years). Thirty-three patients (57%) had NVC with morphological changes.
Forty-three (72%) patients had an excellent outcome defined as ‘no pain, no medication’ (BNI I). Nine (15%) patients had a good outcome, while eight patients (13%) had poor outcome or failure.
At multiple logistic regression the odds ratio of NVC with displacement or atrophy of the trigeminal nerve and excellent outcome was 5.2 (95% CI 1.3 – 20.1, P = 0.0183) and the odds ratio between sex (male vs. female) and excellent outcome was 10.6 (95% CI 2.0 – 56.1, P = 0.0057). There was no significant interaction between sex and severe NVC (p = 0.56).
Conclusion
Based on high-quality prospective data collected by independent assessors we demonstrate that patients with morphological changes of the trigeminal nerve and male sex have a considerably better chance of an excellent outcome of MVD. The results should guide decision-making before neurosurgery.
Barrow Neurological Institute (BNI) pain intensity score. Outcome 12 month after microvascular decompression. N = 60.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-023
Interdisciplinary management of patients with Chiari Malformation Type I
Beatriz L. Kinjo1,*, Juan José M. Mezzadri2, Lourdes V. Molina1, Daniel H. Gestro1 and María D. L. Figuerola1
1Headache Center, Department of Neurology
2Craniospinal junction Disorders Programme, Division of Neurosurgery, Hospital de Clínicas "José de San Martín", Buenos Aires, Argentina
Objectives
In the study of the patients with headache, it is often included a neuroimaging. If a Chiari Malformation Type I (CMI) is observed, the headache is frequently attributed to it. We know that not all headaches in patients who have that malformation are a consequence of it. Together with the Department of Neurosurgery, patients with headaches and diagnosis of CMI using magnetic resonance imaging (MRI) were evaluated to determine if such symptom was caused by the malformation or if it was about a primary pain, and thus decide the right treatment.
Methods
Patients with diagnosis of CMI and associated headache derived from the Department of Neurosurgery were evaluated within March 2013 and December 2016. Patients with previous surgery of CMI and/or symptoms of syringomyelia were excluded.
During that period, a total of 73 patients with diagnosis of CMI and headache were received. Of them, 22 patients were excluded because they had a history of Chiari surgery (15 patients) and/or symptoms of syringomyelia (7 patients). There were 51 cases with a net predominance of the female sex (41/51) and ages between 17 and 70.
Through a semi-structured questionnaire and the complete physical examination, the spectrum of headaches associated with CMI were identified under the criteria of the International Headache Society (IHS).
Results
Of the 51 patients, 43 (84%) presented headaches not attributed to the CMI. The most frequently observed headache was the chronic headache secondary to analgesic abuse (22/51), followed by the migraine without aura (15/51), tension type headache (3/51), migraine with aura (1/51), temporomandibular joint disorder (1/51) and hemiplegic migraine (1/51). Only 8 of the 51 patients met diagnostic criteria of headache secondary to CMI (development and aggravation with the Valsalva maneuver). Of them, 5 patients underwent surgery with successful result and headache extinction, and 3 cases were lost to follow up.
Conclusion
In the majority of patients with evidence of CMI in the MRI the headache has another origin. Therefore, they should be evaluated by a neurologist previously to the surgery with the aim of excluding other causes of pain and avoiding an unnecessary surgical intervention. We consider that it is important to work jointly with neurosurgeons in order to indicate a right treatment.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-024
Pressure-related symptoms of isolated CSF hypertension in headache sufferers
Maria Rosaria Mazza1,*, Laura Rapisarda2, Maria Curcio3, Virginia Vescio4, Carlo Stanà4, Caterina Bombardieri4, Domenica Mangialavori5, Aldo Quattrone3 and Francesco Bono3
1Headache Group, Institute of Neurology, Magna Græcia University of Catanzaro
2Headache Group, Institute of Neurology, Magna Græcia University of Catanzaro
3Headache Group, Institute of Neurology, Magna Græcia University of Catanzaro
4Department of Medical and Surgical Sciences, Institute of Neuroradiology, Magna Graecia University of Catanzaro
5Department of Medical and Surgical Sciences, Institute of Ophthalmology, Magna Graecia University of Catanzaro, Catanzaro, Italy
Objectives
The absence of papilledema makes the diagnosis of isolated CSF hypertension (ICH) difficult and subject to much debate. The objective of this study is to identify the pressure-related symptoms of ICH without papilledema.
Methods
We prospectively performed short-term lumbar CSF pressure monitoring through a spinal needle in order to measure CSF opening pressures and to monitor, for 1 hour, the CSF pressure in 134 consecutive headache sufferers suspected of having high CSF pressure without papilledema. All patients underwent a complete neurological and ophtalmological evaluation, Trendelenburg positioning test, brain MRI, and cerebral MR venography before lumbar puncture.
Results
Of the 134 headache sufferers, 79 of these patients had isolated CSF hypertension without papilledema. The most of these (>90%) had postural headache with nocturnal head pain attacks. Severe headaches and visual disturbances with intracranial noise are common in 2 patients with higher CSF pressure (> 300 mmH2O), while chronic headache and vertigo occurred in 20 patients with CSF pressure between 250 and 300 mmH2O. Less severe CSF-pressure elevation (from 200 to 250 mmH2O) with abnormal CSF pressure waves was also detected in 57 patients with moderate chronic headache and tinnitus. Bilateral transverse sinus stenosis was detected in two third of the patients.
Conclusion
There is a continuous, graded relation between CSF pressure and the symptoms of isolated CSF hypertension without papilledema. Linked to posture/sleep-related changes in CSF pressure are postural and nocturnal headaches. While intracranial noise, tinnitus, and visual disturbances are symptoms fluctuating and variable linked to spontaneous intermittent daily CSF pressure elevation.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-025
White Matter Microstructural Changes Associated with Medication Overuse in Patients with Migraine
Tzu-Hsien Lai1,* and Kevin L.-C. Hsieh2
1Department of Neurology, Far Eastern Memorial Hospital, New Taipei City
2Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, Republic of China
Objectives
The objective of this study is to investigate the brain diffusion tensor magnetic resonance imaging (DTMRI) findings in patients with medication-overuse headache (MOH).
Methods
Twenty-three MOH cases and 19 healthy controls were recruited for the DTMRI. Diffusion indices were extracted from the data and clinical headache parameters were recorded for analysis.
Results
A significant difference in the parietal white matter (PWM) was observed between the groups. The fractional anisotropy (FA) value was significantly lower (p = 0.002) and the mean diffusivity (MD) and radial diffusivity (λ⊥) values were higher in MOH patients than in controls (p = 0.01). Several imaging features of PWM and inferior frontal white matter were selected to generate a receiver operating characteristic (ROC) curve. Using an optimal cut-off value, the sensitivity and specificity for predicting the occurrence of MOH were 79% and 84%, respectively. The FA values for PWM correlated inversely with the duration of analgesic usage (r = −0.50, p = 0.01) but not headache parameters such as headache duration, frequency or intensity.
Conclusion
Our study found that microstructural PWM damage is a distinct characteristic of MOH. These white matter changes could be useful for monitoring both tissue damage and therapeutic effects in patients with this disease.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-026
Post-dural puncture headache and CSF collection time for different needle types in migraineurs and healthy controls
Robin M. van Dongen1,*, Gerrit L. Onderwater1, W P. van Oosterhout1, Ronald Zielman1, Nadine Pelzer1, Gisela M. Terwindt1 and Michel D. Ferrari1
1Neurology, Leiden University Medical Center, Leiden, Netherlands
Objectives
Small atraumatic needles are associated with lower risk of post-dural puncture headache but longer cerebrospinal fluid (CSF) collection time. For biochemical CSF studies this might promote ex vivo metabolic breakdown. As part of an extensive biochemical research programme in CSF of migraineurs we prospectively assessed incidence and characteristics of post-dural puncture headache and CSF collection time for different needle types.
Methods
Lumbar punctures (14.6 mL) were performed for research purposes in 216 participants with migraine and 96 age- and sex-matched healthy volunteers. All participants were prospectively and proactively followed for at least three days. CSF collection time and incidence and duration of post-dural puncture headache were noted. The study was approved by the local ethics committee and all participants provided informed consent.
Results
The study population comprised of many subjects with increased risk of post-dural puncture headache (61.9% females with young mean age of 40.3 and normal mean BMI of 23.6). Incidence of post-dural puncture headache was substantially lower (OR 0.391; 95% CI 0.180 - 0.830; p = 0.018) for smaller 22G atraumatic needles (16.7%; 10/60) than for larger 20G traumatic (32.7%; 69/211) and 20G atraumatic needles (33.3%; 13/39). Median duration of headache was 3.5 days for 22G atraumatic needles, 4.0 days for 20G traumatic needles, and 4.0 days for 20G atraumatic needles. Mean collection time of 14.6 mL CSF was higher for 22G (9.06 min) than for 20G (3.47 min; p < 0.001).
Conclusion
In a high risk population 22 G atraumatic needles had substantially lower incidence of post-dural puncture headache and acceptable CSF collection time for biochemical studies.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-027
Clinical prediction model for medically urgent secondary causes of headache in children or adolescents presenting to the Emergency Department
Lawrence Richer1,*, Meghan Linsdell1, Lyndon Woytuck1, Amanda Greenwell1, Samiha Rahman1, Robyn Langevin2 and Jerome Yager1
1University of Alberta, Edmonton, Canada
2University of Washington, Seattle, United States
Objectives
Headache is one of the most common pediatric neurological presentations to the Emergency Department (ED). Children who present to the ED with headache and other focal neurological symptoms may be diagnosed with secondary causes like stroke or intracranial infection, but primary headache disorders like migraine with aura are more common. Uncertainty can lead to unnecessary neuroimaging or delayed diagnosis. A predictive model using routinely collected clinical features may help ED physicians more rapidly identify those at highest risk for a secondary cause of headache and help refine timely diagnosis and management. We hypothesize that routinely documented clinical features of children presenting with headache to the ED will predict those at highest risk for secondary headache disorders and may help to reduce uncessary neuroimaging.
Methods
A retrospective cohort was identified from hospital and ED administration databases using ICD10 codes for all children who were diagnosed with an acute neurological disorder and presented to the ED over one year. The hospital record for each case was manually abstracted for the presenting complaint, clinical features, final diagnosis, and validated for inclusion criteria. The analysis was performed on all cases with a presenting complaint of headache, no history of trauma in the last 7 days, and no previously diagnosed disorder causing headache (e.g. hydrocephalus). A stepwise logistic regression model of clinical predictors associated with secondary causes of headache was derived and validated on a random 33% sample not used in the derivation.
Results
From a total of 1134 presentations, 630 cases with a presenting complaint of headache were identified. The mean age was 11.5 years (SD 3.9; range 0-17). Characteristics of the cohort include: female (57%), history of recurring headache (33%), ambulance transport (8%), and fever (18%). Neuroimaging (CT or MRI) was ordered in 126 (20%) and was abnormal in 38 (29%). A total of 27 (4.4%, 95% CI 2.8 – 6) were diagnosed with a medically urgent secondary cause of headache including intracranial infection (n = 11), intracerebral hemorrhage or vascular malformation (6), tumour (5), stroke (2), hydrocephalus (2), demyelination (1), and inborn error of metabolism (1). Features positively associated with secondary causes of headache were ambulance transport (OR 8.5, 95% CI 1.7-42.8), decrease consciousness (OR 30.8, 95% CI 2.5-382), ataxia (OR 6.8, 95% CI 1.1-43.9), vomiting (OR 5.4, 95% CI 1.4-20), and progressive headache over days (OR 9.9, 95% CI 2.4-39.8). Age, fever, focal weakness, visual symptoms, and rapid onset headache were included in the model, but not significant. Negative predictors were prior history of headache (OR 0.1, 95% CI 0.01-0.85) and altered speech (OR 0.02, 95% CI 0.01-0.7). The model correctly classified 93% of the validation cohort (n = 200) with receiver operator curve (ROC) of 0.91. The optimal probability cut-off for a secondary cause was 0.15. The specificity was 95%, but sensitivity was low at 55% (false negative rate 45%) with PPV of 33% and NPV of 98%. The prediction model would have decreased the number of scans in the validation cohort by 55%.
Conclusion
The majority of children presenting to the ED with headache do not have medically urgent secondary causes and have normal neuroimaging. A prediction model of routinely collected clinical features was specific and could reduce the number of unnecessary neuroimaging studies by more than half. However, the sensitivity was unacceptably low. Ongoing research will refine the model with a larger cohort, but better predictors (e.g. biomarkers) may be needed to improve prediction in this age group.
Disclosure of Interest
None Declared
Other Primary Headache Disorders
EP-01-028
Developing a cerebrospinal fluid secretion assay using a genetically encoded biosensor to evaluate therapeutic and pathogenic molecules in idiopathic intracranial hypertension
Connar Westgate1, Hannah Botfield1,*, David Hodson1,2 and Alexandra Sinclair1,3
1Institute of Metabolism and Systems Research
2Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham
3Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
Objectives
Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and papilledema which primarily affects obese women of reproductive age. Treatment options are limited. Additionally, the aetiology is poorly understood but is driven by the imbalance of cerebrospinal fluid (CSF) secretion (predominantly at the choroid plexus) and CSF drainage.
We aimed to develop an in vitro CSF secretion assay that could be used to evaluate drug therapies, and potential pathogenic molecules of relevance to IIH. CSF secretion is dependent numerous ion channels and pumps where the Na/K ATPase is the rate limiting step. We aimed to develop a novel CSF secretion assay that measures Na/K ATPase activity, a validated surrogate marker of CSF secretion. Additionally, we sought to validate the assay with acetazolamide, a carbonic anhydrase inhibitor which reduces CSF secretion and is used therapeutically in IIH. Finally, our recent ex-vivo studies have highlighted raised serum testosterone in IIH: consequently we evaluated the effect of testosterone on CSF secretion.
Methods
An immortalised rat choroid plexus epithelial cell line (Z310 cells) were infected with an adenoviral vector containing the ATP:ADP ratio sensor Perceval. Na/K ATPase activity was determined following acute administration of the specific Na/K ATPase inhibitor ouabain (1 mM) and measuring the change in ATP:ADP ratio, an indicator of ATP consumption of by the Na/K ATPase. The Z310 cells were treated with 1 mM acetazolamide or 100 nM testosterone (versus vehicle) to determine alterations in Na/K ATPase activity following acute ouabain administration.
Results
Initial experiments were conducted with ouabain and vehicle to determine if ouabain elicits a change in the ATP:ADP ratio. Ouabain increased the ATP:ADP ratio (P < 0.0001) compared to control and allowed resolution of the ATP formation rate. These data indicate that acute administration of ouabain allows detection of Na/K ATPase activity with the Perceval biosenor. Following two days of acetazolamide treatment, ouabain elicited a reduced change in ATP:ADP ratio (P < 0.05) and reduced ATP production (P < 0.05) compared to vehicle treated cells, indicating reduced Na/K ATPase activity. In contrast, following two days of 100 nM testosterone incubation, ouabain administration displayed an increased change in ATP:ADP ratio (P < 0.0001) with larger ATP production (P < 0.01) compared to vehicle treated cells, indicating increased Na/K ATPase activity.
Conclusion
We have developed a novel assay that can specifically measure Na/K ATPase activity through the change in ATP:ADP ratio elicited by ouabain. This assay of Na/K ATPase activity is a potential in vitro surrogate assay for CSF secretion with relevance to ICP, thus has a potential role for evaluating novel therapeutic agents aimed at lowering ICP through reduced CSF secretion. We demonstrate that Na/K ATPase activity can be manipulated with acetazolamide, causing a reduction in Na/K ATPase activity, indicating reduced CSF secretion. Furthermore, we identify testosterone as a molecule that can increase Na/K ATPase activity, indicating increased CSF secretion. Testosterone elevation in IIH may exert a pathogenic role in modulating ICP though increasing CSF secretion. Future work will examine the relationship of this assay to in vivo ICP measures.
Disclosure of Interest
None Declared
Post-Traumatic Headache
EP-01-029
Cortical Thickness in Patients with Persistent Post-traumatic Headache
Chia-Chun Chiang1,*, Todd J. Schwedt1 and Catherine Chong1
1Neurology, Mayo Clinic Arizona, Phoenix, United States
Objectives
Post-traumatic headache (PTH) is a common and disabling neurological disorder. Recent data from functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies indicate network connectivity abnormalities and white matter alterations in patients with PTH. However, whether patients with PTH might have changes specifically to the cortical grey matter is insufficiently understood. In this study, we interrogated cortical thickness, a proxy measure of cortical integrity, in patients who have persistent PTH attributed to mild traumatic brain injury.
Methods
Cortical thickness measurements were calculated from T1-weighted images obtained on a Siemens 3 Tesla scanner in 29 patients with PTH attributed to mild traumatic brain injury and 31 age-matched healthy controls. Data were post-processed using a FreeSurfer 5.3 pipeline. Multivariate analyses were performed to compare vertex-by-vertex cortical thickness in patients with PTH compared to healthy controls. Correlations between cortical thickness with headache frequency and time interval since onset of post-traumatic headache were calculated.
Image:
Results
Mean age of healthy controls was 33.7 years (SD = 7.2); mean age for PTH patients was 32.1 years, (SD = 10.5); p = 0.48. For patients with persistent PTH, the average headache frequency was 21.8 days per month (SD = 8.7) and average time interval since onset of post-traumatic headache was 80 months (SD = 103.3). Patients with persistent PTH had significantly less cortical thickness compared to healthy controls in left rostral middle frontal and bilateral precentral, superior frontal and caudal middle frontal areas [Figure 1] (p < 0.01, Monte Carlo corrected for multiple comparisons). For patients with PTH, there was a negative correlation between headache frequency and right superior frontal thickness (p = .032).
Conclusion
Results suggest bilateral changes in frontal pain processing regions in PTH. Furthermore, patients with more frequent headaches had less cortical thickness in the right superior frontal region suggesting that headache frequency might modulate brain integrity in PTH.
Disclosure of Interest
None Declared
Psychological and Behavioural Factors and Management
EP-01-030
Pain catastrophizing as predictor of response to topiramate in chronic migraine patients
Aldara Astorga1, Henar de la Red1, Marta Gómez-García1, Marina Ruiz1, Marta Hernández1, Eva Sotelo1 and Angel L. Guerrero1,*
1Headache Unit. Hospital Clínico Universitario de Valladolid, Valladolid, Spain
Objectives
Pain Catastrophizing (PC) is among psychological factors that might contribute to pain chronicity. It is defined by the presence of persistently negative cognitive and emotional responses to pain. It has been associated with increased pain intensity, mood disturbances, and analgesic overuse. There are three variables considered in PC: rumination, magnification and helplessness. We aimed to evaluate whether PC predicts the response to preventive therapy with topiramate in a population of chronic migraine patients.
Methods
We included patients firstly attended in a headache unit of a tertiary hospital. Chronic Migraine was diagnosed accordingly to International Classification of Headache Disorders, III edition, beta version (ICHD-III beta), and preventive therapy with topiramate was indicated. Inclusion period extended from January to June 2016. We collected clinical and demographic variables, including time from onset of migraine and chronic migraine. We excluded patients with a previous diagnosis of a psychiatric illness. We administered in each patient six-item Headache Impact Test (HIT-6) and Hospital Anxiety and Depression Scale (HADS), considering Anxiety or Depression when scored > 10 in any of the subscales. PC was assessed with Pain Catastrophizing Scale (PCS). In PCS, patients are asked to indicate the degree they experienced 13 thoughts or feelings when suffering pain, on 5-point scales with end points 0-not at all and 4-all the time. PCS score over 30 is considered clinically relevant catastrophizing. Topiramate was prescribed at a dose of 100 milligrams per day and the response was evaluated 3 months after initiation of treatment. The patient was considered a responder when a decrease in monthly headache days of at least 50% was achieved.
Results
We included 35 patients in the study. In eight cases topiramate was not tolerated during at least 3 months and they were excluded from the analysis. Among the 27 analyzed patients, 2 were male and 25 female. Age at inclusion was 36.7 ± 9.7 years (range: 18-57), time from migraine onset was 18.5 ± 10.2 years (1-37) and time since chronic migraine onset was 31.3 ± 34.4 months (3-120). Number of headache days per month was 23.8 ± 5.4 days (15-30) and 20 patients (74.1%) met criteria for symptomatic medication overuse. The scores on the administered scales were as follows: HIT-6: 63.5 ± 6.8 (50-74), HADS-anxiety: 9.1 ± 5.1 (1-19), HADS-depression: 4 ± 4.3 (0-15), and PCS: 23.4 ± 12.4 (1-45). 11 patients (40.7%) met criteria for anxiety and 3 (11.1%) for depression according to HADS, and 10 (37%) had a clinically relevant catastrophizing. Response to topiramate was achieved in 17 patients (63%). Scores on the HADS-depression scale (1.7 ± 2.2 vs 7.8 ± 4.5, p: 0.002) and PCS (19.6 ± 11.7 vs 29.8 ± 11.5, p: 0.041) were significantly lower among responders group. None of the other variables analyzed predicted response to treatment
Conclusion
Among our population of chronic migraine patients, a relevant catastrophizing is not uncommon. The presence of lower scores on the Pain Catastrophizing Scale predicted the response to preventive treatment with topiramate.
Disclosure of Interest
None Declared
Psychological and Behavioural Factors and Management
EP-01-031
Life traumatic experiences and stressful events in chronic migraine with medication overuse: Do they impact the outcome of a detoxification therapy?
Sara Bottiroli1,2,*, Michele Viana2, Grazia Sances2, Roberto De Icco1,2, Vito Bitetto2, Elena Guaschino2, Natascia Ghiotto2, Stefania Pazzi2, Giuseppe Nappi2 and Cristina Tassorelli1,2
1Department of Brain and Behavioral Sciences, University of Pavia
2Headache Science Centre, C. Mondino National Neurological Institute, Pavia, Italy
Objectives
In this study we evaluated the association between early life traumatic experiences and recent stressful events with the outcome following detoxification therapy in a 2-month follow-up in 171 subjects with medication overuse headache (MOH).
Methods
This study was conducted at the Headache Center of the C. Mondino National Neurological Institute in Pavia, Italy. All consecutive patients with chronic headache and medication overuse undergoing an inpatient detoxification program were enrolled and followed-up in a prospective study. Diagnosis was operationally defined according to ICHD-IIIβ. The protocol consisted in an inpatients detoxification treatment and a 2-month follow-up. Data on early life traumatic experiences – distinguished in term of physical and emotional traumas – and recent stressful events – rated according to the impact patients’ quality of life, from mild to very serious – were collected by means of self-report questionnaires. Data were analyzed with the analysis of variance.
Results
Of the 171 patients who completed the 2-month follow-up, 122 stopped overuse and their headache reverted to an episodic pattern (Group A), 30 stopped overuse without any benefit on headache frequency (Group B), and 19 failed to stop overuse (Group C). A higher number of early life traumatic experiences was detected in the patients who failed to stop overuse when compared to the other groups (Group A: M = 1.2 ± 1.3; Group B: M = 0.9 ± 0.9; Group C: 2.0 ± 1.5; p = .04). The type of stress reported was mainly of the emotional type, rather than physical. No differences were observed when comparing A and B Groups. As regards recent stressful events, a significantly higher number of patients in Group B reported very serious current life events as compared to patients in Group A and B (Group A: 19.7%; Group B: 46.7%; Group C: 15.8%; p = .005) The percentage of patients reporting life events with lower impact were instead similar in the three groups.
Conclusion
Withdrawal from overused drug is the treatment of choice for MOH, reverting the headache from chronic to episodic within two months. Many factors are involved in MOH prognosis and outcome, and their understanding is a topic of interest. MOH patients experience increased psychiatric comorbidity, such as anxiety, depression, or personality disorders (1, 2), even if this cause-effect relationship still needs to be understood. Even less is known about the role of these factors in the response to detoxification treatments. Our data are very interesting and suggest a different impact of life traumas and stressful events on the outcome of a detoxification program. The failure to cease overuse is related to the existence of childhood (mostly emotional) traumas, whereas recent life events, especially when very serious, do not seem to influence the capacity of the patient to stop overuse, but are associated to the persistence of chronic headache. These findings have important practical implications on how to treat these patients.
Disclosure of Interest
None Declared
1. Sances G et al. Factors associated with a negative outcome of medication overuse headache - a three-year follow-up (the “care” protocol). Cephalalgia 2013, 33: 1-13.
2. Bottiroli S et al. Psychological factors associated to failure of detoxification treatment in chronic headache associated with medication overuse. Cephalalgia 2016; 36: 1356-1365.
Psychological and Behavioural Factors and Management
EP-01-032
Interactions between affective measures and amygdala volume in chronic migraine: associations in the absence of group volumetric differences
Danielle D. Desouza1,*, Yohannes W. Woldeamanuel1, Addie M. Peretz1, Bharati M. Sanjanwala1 and Robert P. Cowan1
1Neurology and Neurological Sciences, Stanford University, Palo Alto, United States
Objectives
Previous studies examining brain structure in patients with chronic migraine (CM) have been mixed, with some reporting volumetric abnormalities compared to controls and others finding no differences. While many of these studies examined the relationship between pain symptoms and brain volumetrics, affective measures have been far less explored. The objective of the current study was to examine the relationship between affective measures and brain volumetry of the amygdala, a structure known for its role in affect, in patients with CM.
Methods
We conducted a cross-sectional case-control study comparing participants with CM to healthy controls. Sixty participants (30 patients (24 F, 6M, mean age ± SD: 40.5 ± 13.9) and 30 age- and sex- matched controls (mean age ± SD: 40.3 ± 14.6)) were recruited for this study. Patients had a diagnosis of CM according to the International Classification of Headache Disorders-3 beta criteria and controls had no history of chronic pain. All participants underwent MRI scans on a 3T GE scanner. A voxel-based morphometry (VBM) approach was implemented in FMRIB’s Software Library v. 5.0.8 and examined left and right amygdala volumes and subregional volumes (superficial, laterobasal, centromedial) as labeled by the Juelich histological atlas. Participants completed the following questionnaires to assess scores of depression, anxiety, and pain catastrophization, respectively: Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Pain Catastrophization Scale (PCS). Differences in affective measures between patients and controls were evaluated and a multiple linear regression analysis determined the relationship between the affective measures and amygdala volumes.
Results
The VBM results indicated that there were no significant differences in left or right amygdala volumes or in subregional amygdala volumes between CM patients and controls. When affective measures were compared between patients and controls, CM patients had significantly higher depression and pain catastrophization scores (p < 0.05). Furthermore, the multiple linear regression analysis revealed a significant group x depression interaction for right amygdala volume (p < 0.05), such that there was a positive association between right amygdala volume and depression in CM patients only. This relationship was also evident when right amygdala subregions were examined: centromedial (p < 0.01), laterobasal (p < 0.05), superficial (p < 0.05). A separate multiple linear regression analysis showed a significant group x PCS interaction for the right amygdala (p < 0.05), such that patients had a positive association between right amygdala volume and pain catastrophization. However, this relationship was only evident when the entire right amygdala volume was examined, but not for any of the subregions (p > 0.05). No significant interactions were found between amygdala volumes and anxiety scores (p > 0.05).
Conclusion
We report significant interactions between right amygdala volumes and measures of depression and pain catastrophization in CM patients only. These findings highlight the importance of assessing for abnormal associations between brain volumetry and affective measures even in the absence of group volumetric difference. Additionally, the laterality of the findings and the specific subregional volumes involved may provide insight into the basic mechanisms of CM pathophysiology.
Disclosure of Interest
None Declared
Psychological and Behavioural Factors and Management
EP-01-033
Development and Acceptability of a Mindfulness-Based Cognitive Therapy for Migraine (MBCT-M) Individual Treatment Protocol
Alexandra B. Singer1,*, Dawn C. Buse2,3 and Elizabeth K. Seng1,3
1Ferkuaf Graduate School of Psychology, Yeshiva University
2Montefiore Headache Center
3Neurology, Albert Einstein College of Medicine, Bronx, United States
Objectives
To adapt existing Mindfulness-Based Cognitive Therapy (MBCT) protocols for migraine, develop a treatment manual for use for individual MBCT-M therapy and report on study enrollment and subject satisfaction to date in the Bronx MBCT-M clinical trial (NCT02443519).
Methods
The Bronx MBCT-M manualized study protocol was developed by 1) consulting with expert migraine treatment providers (medical and psychological) 2) converting existing MBCT group protocols for depression relapse (DR) and chronic headache pain (CHP) into session outlines, 3) adapting and creating session and homework materials for migraine, and 4) converting session format from group to individual (Table 1). Major protocol adaptations were made prior to study enrollment. Therapists (advanced doctoral psychology student) engaged in monthly peer-debriefing sessions identified common problems in implementation within the first three months of the trial (n = 4), which resulted in iterative clarification and increased specificity of the written treatment protocol.
Therapists (eight advanced doctoral psychology students) receive weekly individual and monthly group supervision from licensed psychologists. Participants are randomized to active treatment or a wait list control followed by treatment. Thirty eight participants (of a total goal of 80) have been enrolled, 15 completed the eight-item Client Satisfaction Questionnaire (CSQ-8), which assessed global satisfaction with treatment and provider, following sessions 1, 4 and 8.
Results
When developing content for the MCBT-M protocol two themes emerged: 1) The Migraine Experience, and 2) Treatment Expectations.
The Migraine Experience: Since migraine is a chronic disease with episodic attacks and few people have continuous or daily migraine, treatment rationales and educational components that presume continuous symptoms (chronic pain) were modified. Addition of migraine-specific content included 1) migraine phases with prodromal symptoms and 2) modifiable factors/triggers that contribute to migraine onset (reducing emphasis on Gate Control Theory of Pain). Yoga postures that could contribute to neck strain were replaced with the gentle mindful-movement used in MBCT-DR. Since anxiety is highly comorbid with migraine, we highlighted the Recognizing Aversion skills from MBCT-DR to address rumination.
Treatment Expectations: Expert feedback agreed that therapy would be more effective if delivered in individual rather than group format. 120 minute weekly group sessions were replaced with 75 minute weekly individual sessions. Each session maintained a 20-30 minute guided mindfulness practice (Mindful eating, Body-Scan Meditation, Breath Meditation, Three-Minute Breathing Space, Mindful Walking, or Mindful Moment).
Of the 18 participants randomized to MBCT-M treatment, 1 (5.6%) discontinued due to changes in preventive medications and of the 20 participants randomized to waitlist/treatment as usual 1 (5%) dropped out prior to follow-up phase. Client satisfaction with treatment has been high across sessions; Session 1 (Mdn = 28.5, IRQ = 25.5-31), Session 4 (Mdn = 28, IRQ = 24.75-32), and Session 8 (Mdn = 31, IRQ = 24.75-32).
Conclusion
The Bronx MBCT-M clinical trial is testing an individual session, migraine-specific adaptation of existing, validated group MBCT protocols for chronic headache pain and recurrent depression. Participants’ satisfaction with MBCT-M demonstrates acceptability of the treatment; feedback has been generally positive and attrition rates have been low and relatively equal across groups thus far.
Disclosure of Interest
MBCT-M Adaptation
Psychological and Behavioural Factors and Management
EP-01-034
Effectiveness of a multicomponent intervention on Quality of life of patients with Migraine- A pilot study
Vishnu Renjith1,*, Aparna Pai2 and Anice George1
1Manipal College of Nursing Manipal, Manipal University, Karnataka, India
2Neurology, Zulekha Hospital, Sharjah, United Arab Emirates
Objectives
Migraine headaches are the third most common medical problem in the world with a global prevalence of 14.7%. Migraine as ranked seventh as the highest cause of disability globally. Migraine is associated with substantial impairment in quality of life. Conventional management of migraine headache is suboptimal and overuse of episodic medication will lead to the development of chronic daily headache.This pilot trial was primarily designed to investigate the effectiveness of a multicomponent intervention in improving the quality of life of patients with migraine.
Methods
The study was a prospective, randomized, controlled, single-blinded trial with parallel arms. After obtaining the written informed consent, forty participants were randomized to intervention (n = 20) and control arms (n = 20) using block randomization. The participants randomized to the intervention arm received the multicomponent intervention along with routine pharmacological management. The multicomponent intervention comprised of a behavioral lifestyle modification program and sessions of pranayama (a form of yogic breathing exercise). Participants in the control group received the routine pharmacological management. The subjects were then followed up and the outcomes were assessed at 4th, 12th and 24th week. The primary outcome variable of this pilot study was the quality of life. The Migraine-Specific Quality of Life Questionnaire (MSQ) was used to assess the quality of life of the migraineurs. The outcome assessor was blinded to the allocation status of the study participants. The trial protocol has been reviewed and approved by the institutional ethics committee.
Results
Majority of the participants were in the age group of 18-30 years. There was a preponderance of female participants in the study with 90% of subjects being females in intervention and 75% in control arm. A positive family history was evident in majority of the study participants. The baseline mean (SD) quality of life scores for the subjects in intervention and control group were 29.95 (6.27) and 29.70 (5.20) respectively. However the mean (SD) posttest (at the 24th week) quality of life scores for the subjects in intervention and control group were 77.99(4.11) and 61.30(4.68). Repeated Measures ANOVA was done to evaluate the effectiveness of intervention quality of life of patients with migraine. The F ratio was 566.24 and the associated significance level was 0.001 (<0.05). Hence it is interpreted that the multicomponent intervention was effective in improving the quality of life of patients with migraine. Four paired samples t-tests were used to make post hoc comparisons between conditions, statistically, significant differences were obtained at all the four time points.
Conclusion
The research demonstrated that the multicomponent intervention had a positive impact on the quality of life of patients with migraine. The importance of intervention as demonstrated by this research should be considered for use by health professionals working in neurological settings.
Disclosure of Interest
V. Renjith Conflict with: Sigma Theta Tau International / Omicron Delta Research Grant, A. Pai: None Declared, A. George: None Declared
Psychological and Behavioural Factors and Management
EP-01-035
Cognitive beliefs about health and body and illness behavior in patients with chronic headaches
Yulia Migunova1,*, Elena Parfenova2, Elena Rasskazova1 and Alisa Andrushenko2
1Lomonosov Moscow State University
2I.M. Sechenov First Moscow State University, Moscow, Russian Federation
Objectives
Somatosensory amplification, catastrophization and subjective beliefs about bodily weakness as well as illness behavior are considered as factors of functional somatic symptoms especially in patients with somatoform and hypochondriac disorders (Rief et al., 1998, 2003). Different aspects of perception and interpretation of bodily sensations including pain were found to be changed in patients with chronic pain and headaches (Keefe, Lefebvre, 1994, Nicholson, 2010, Yalug et al., 2010) and are considered as targets for cognitive-behavioral therapy with pain (Francis, 1996)
The aim of the study was to compare cognitive beliefs about health and body and illness behavior in patients with chronic headaches and healthy controls and to reveal their relationship with quality of life.
Methods
104 patients (88 females, 18-70 years old) with chronic migraines and tension-type headaches and 41 participants without history of headaches and chronic somatic or mental illnesses (29 females, 18-70 years old) filled a brief version of Quality of Life and Enjoyment Questionnaire (Ritsner et al., 2005), Cognitions About Body and Health Questionnaire (Rief et al., 1998), Scale for the Assessment of Illness Behavior (Rief et al., 2003).
Results
Patient with headaches were not only less satisfied with their health, emotions and leisure time activity (but not with communication) than control group (t = 3.01-6.86, p < .01, d = .56-.26) but also reported higher somatosensory amplification, more autonomic sensations, higher concentration of their health habits, believed that their body is weak and vulnerable and more frequently catastrophized about bodily sensations (t = -5.95 - -2.07, p < .01, d = .38-1.10). There were two types of illness behavior that were more typical for patients with chronic headaches than for healthy controls: emphasize on availability of medication and medical emergency and changes in life due to symptoms and illnesses (t = -3.98 - -2.72, p < .01, d = .50-.73).
Moderation analysis revealed that in both groups higher belief in body weakness (β = -.32, p < .01) and lower belief in health habits (β = .14, p < .05) predicted lower satisfaction with health but the effect of belief in bodily weakness was marginally stronger in patients with headaches (β = .29, p < .09). Satisfaction with emotions was related to more consequences of symptoms for the personal life both in patients and healthy controls (β = -.38, p < .01) while satisfaction with leisure time activity was related to less beliefs in bodily weakness (β = -.30, p < .01) and satisfaction with communication – to higher somatosensory amplification (β = -.23, p < .01).
Conclusion
The level of cognitive beliefs (somatosensory amplification, autonomic sensations, bodily weakness, catastrophization) as well as some aspects of illness behaviour (illness consequences and medication) that are typical for somatoform and hypochondriac disorders (Rief et al., 1998) is high in patients with chronic headaches. However, their effect on the quality of life seems to be common for healthy subjects and patients. Data supports that somatosensory amplification, belief in bodily weakness and negative impact of somatic symptoms on personal life as well as refusal from health habits are related to satisfaction with life domains but these effects are not moderated by headaches. From the cognitive behavioural perspective it could be hypothesized that patients with chronic headaches are more vulnerable to the development of somatosensory amplification, concentration on health and body as well as illness behaviour that are related to more deterioration of their quality of life.
Research was supported by the Russian Foundation of Fundamental Research, project 17-06-00849.
Disclosure of Interest
Y. Migunova Conflict with: Research was supported by the Russian Foundation of Fundamental Research, project 17-06-00849., E. Parfenova: None Declared, E. Rasskazova Conflict with: Research was supported by the Russian Foundation of Fundamental Research, project 17-06-00849., A. Andrushenko: None Declared
Psychological and Behavioural Factors and Management
EP-01-036
Utilization of behavioral treatment in migraine patients who visit a Headache Center: A Cross-Sectional Study
Mia Minen1,*, Alexandra Boubour2, Audrey Halpern3, Thomas Berk3 and Elizabeth Seng4
1Neurology, NYU Langone Medical Center
2Barnard College, Barnard College, Columbia University
3NYU Langone Medical Center, 4Ferkauf Graduate School of Psychology, New York, United States
Objectives
Behavioral treatments (biofeedback, cognitive behavioral therapy, progressive muscle relaxation therapy) are level A evidence based treatments for the prevention of migraine. Research has shown that there are barriers for referring to behavioral therapy, and that these therapies are not widely used. As part of an ongoing study, we sought to (1) examine prior healthcare utilization (including treatment by a psychologist) of patients seen by headache specialist, (2) understand migraine patients' beliefs about their ability to prevent their migraines, and (3) examine migraine patients’ reasons for not undergoing behavioral therapy.
Methods
From July 2016-January 2017, consecutive patients diagnosed with migraine by a fellowship trained Headache Specialist in an academic Headache Center in NYC using the ICHD 3 beta criteria were invited to complete a study questionnaire at the end of the office visit. Questions included information about patient demographics and prior healthcare utilization (including use of behavioral treatment and whether treatment had previously been recommended), and Migraine Disability Assessment (MIDAS) score. Other questions ranked patients’ views on certain headache-related issues, including headache management, patient-doctor relations, and protective headache factors. There were blank spaces for writing reasons for not participating in behavioral therapy. Descriptive analyses were then performed.
Results
116 eligible patients were seen by the physician in the recruitment period and 67. 2% (78/116) took part in the study. 86. 5% (N = 64) were female. The average age of headache onset was 16. 8 years and of diagnosis was 26. 0 years. 84. 4% (65/77) of patients reported that they believed that there are things they can do to reduce headache pain. The average MIDAS score was 36. 6 (severe disability). The majority of patients (42/72, 58. 3%) were referred by the headache specialist for behavioral therapy. Prior to the current visit, patients reported seeking headache care from a variety of other specialists including ophthalmologists (32/78, 41. 0%), emergency department/urgent care providers (27/78, 34. 6%), chiropractors (15/78, 19. 2%), and psychologists (12/78, 15. 4%). 32/72 (44. 4%) patients reported previously engaging in behavioral headache treatment; of those who had not previously engaged in behavioral headache treatment, fewer than half (17/40, 42. 5%) reported having previously received a referral. Expense (13, 76. 5%) followed by time (6, 35. 3%) were the reasons cited for not participating in behavioral therapy. CBT was the most common behavioral treatment tried (13, 40. 6%) followed by biofeedback (12, 37. 5%) and progressive muscle relaxation (7, 21. 9%).
Conclusion
Most patients presenting to this headache center reported severe migraine disability. Patients reported seeing a wide variety of specialists; however, psychologists were among the least visited specialists. Of those who were previously recommended yet did not access behavioral treatment, they commonly shared that treatment was time consuming, too expensive, or not covered by insurance. More research is needed to determine rates and predictors of successful referral to behavioral treatment options.
Disclosure of Interest
None Declared