Abstract
Alejandro Labastida-Ramírez, Eloisa Rubio-Beltrán, Philip R. Holland and Jan Hoffmann
Headache Group, King's College London, London, United Kingdom
Introduction
Migraine is two to three times more prevalent in women than in men. Although the mechanisms involved in this sex disparity are still poorly understood, a dysfunctional interaction between sex hormone fluctuations and the trigeminovascular system seems to be involved.
Objectives
Investigate in an in vivo model the role of amylin 1 (AMY1) receptor activation in the modulation of the trigeminal nociceptive system in rats during rising and falling estrogen levels across the estrous cycle, and compare it to the responses observed in males.
Methods
We recorded neuronal activity in male and female rats with extracellular electrodes placed within the trigeminocervical complex and examined the effects of targeting the AMY1 receptor on ongoing spontaneous and dural-evoked firing rates of central trigeminovascular neurons. The selective AMY1 receptor agonist pramlintide and AMY1 receptor antagonist AC187, were used for the present study. The different stages of the estrous cycle were identified and assigned by a blinded experimenter through two Cresyl violet-stained vaginal smears.
Results
Compared to males (n = 6), intravenous administration of pramlintide (6 µg/kg) significantly augmented the ongoing spontaneous activity and dural-evoked neuronal responses in the trigeminocervical complex, only during phases of the female estrous cycle that are characterized by falling estrogen levels (n = 12, n = 6 per phase group), whereas this effect was not observed in the high-estrogen phases (n = 18; n = 6 per phase group). Moreover, compared to vehicle (0.9% NaCl, n = 5), intravenous administration of AC187 (6 µg/kg) significantly decreased the ongoing spontaneous and dural-evoked firing rates of central trigeminovascular neurons in males and females (n = 4 each).
Conclusion
Our data support that activation of the AMY1 receptor modulates the trigeminal nociceptive system and that this effect is most pronounced during phases of the menstrual cycle in which estrogen concentrations are falling. The findings support selective AMY1 antagonists as novel and potentially effective targets for the treatment of migraine.
Disclosure of Interest
None Declared.
References
Marie-Louise K. Søborg1, Nunu L. T. Lund1,*, Anja S. Petersen1, Malthe F. Wandall-Holm2, Rigmor H. Jensen1 and Mads C. J. Barloese3
1Department of Neurology, Danish Headache center
2Department of Neurology, The Danish Multiple Sclerosis Registry, Glostrup
3Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic Imaging and Research, Hvidovre, Denmark
Introduction
The diagnostic criteria for Cluster headache differentiates between an episodic and a chronic variant depending on the duration of the remission periods (1). From the clinic and few cross-sectional studies, it has been observed that patients can convert between the two subtypes during the course of the disease, however, estimates of transition rates ranges from 2–32% (2, 3, 4) and predictors have not been identified (4, 5).
Objectives
We aimed to describe how many patients change phenotype, elucidate possible predictors for this transition and identify differences in clinical features between primary and secondary phenotypes.
Methods
A total of 540 well-defined cluster headache patients recruited from the Danish Headache Center, diagnosed according to current ICHD-criteria completed a cross-sectional semi-structured interview.
Results
The total transition-incidence for the cohort was 20.7%. Conversion into secondary episodic phenotype was reported for 6.3% of patients, and transition into secondary chronic phenotype for 14,4% with side shifting of attacks constituting the only predictor for secondary chronification (p = 0.007). Compared to primary chronic patients, secondary chronic patients had significantly more frequent (60 vs 34 pr. month, p = 0.0487), but shorter-lasting (60 vs. 90 minutes, p = 0.041) attacks per month. Secondary episodic patients experienced shorter remission-periods than primary episodic patients (6 vs 11 weeks, p = 0.010).
Conclusion
Cluster headache is not stationary as a fifth of our cohort experienced at least one phenotype change during course of disease. Apart from attack side shifts, no predictors for transition were identified. Severity and remission periods differed between primary and secondary subtypes. Overall, there is an urgent need for a better understanding of Cluster headache in order to improve prognosis, treatment and disease burden.
Disclosure of Interest
M.-L. Søborg Conflict with: Current sub-investigator for a study supported by Lundbeck, N. Lund Conflict with: Travel grant from Pfizer, A. Petersen Conflict with: Prior and current sub-investigator for studies sponsored by Eli-Lilly and Lundbeck, M. Wandall-Holm: None Declared, R. Jensen Conflict with: principal investigator in studies sponsored by Eli Lily, Novartiscand Lundbeck , Conflict with: lectures for Eli-Lily, ATI, Lundbeck, Novartis, Allergan, Pfizer, Berlin-Chemie, Norspan, Merck and TEVA., M. Barloese: None Declared.
References
Ana Echavarría Íñiguez, Henar Ruiz Saez, Álvaro Sierra Mencia, Leticia Sierra Martinez, Luisa Hurtado Rebollo, Cristina García Iglesias, Ana González Celestino, Yesica González Osorio, Andrea Recio García, Ángel L. Guerrero Peral and David García Azorín
Headache Unit, Hospital Clínico Universitario Valladolid, Valladolid, Spain
Introduction
Headache is one of the neurological symptoms most frequently associated with Covid-19. It appears early and has been proposed to determine a better prognosis for Covid-19. Its clinical phenotype may adopt either a tension-type or a migraine-like characteristics. Its median duration is around 7–14 days, however in some patients it may adopt a chronic pattern. It is also often disabling with a response not always adequate to symptomatic and preventive treatments.
Over the last 2 years, most countries have established massive vaccination plans against Covid-19. Previous vaccination has been reported to decrease the severity of the infection and mortality related to it. But the influence of vaccines on the neurological manifestations of this disease, including headache, have not been determined.
Objectives
We aim to evaluate if previous vaccination changes the clinical phenotype of headache related to Covid-19 and its duration.
Methods
Results
A total of 453 patients were enrolled, including 103 vaccinated and 350 unvaccinated.
Among the patients with a previous headache, 46.2% of the vaccinated and 58.3% of the unvaccinated did not find a similarity between the headache related to Covid19 and their usual one.
The duration of the headache was shorter in vaccinated patients. The frequency of anosmia and diarrea was lower in vaccinated patients and the frequency of weakness, cough myalgia, arthralgia, expectoration and rhinorrhea was higher in this group.
The attached table shows the most characteristic clinical data.
Conclusion
In our population, vaccination against Covid-19 changed the clinical phenotype of the headache decreasing its duration. This represents an additional argument to recommend vaccination to prevent Covid-19 disease.
Disclosure of Interest
None Declared.
Gina Dumkrieger1,*, Ryotaro Ishii2 and Peter J. Goadsby3,4
1Neurology, Mayo Clinic, Phoenix, United States
2Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan
3NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital, London, United Kingdom
4Neurology, University of California, Los Angeles, United States
Introduction
Headache frequency in migraineurs is known to vary over time, a variation not well studied. Natural variation is explicitly considered in the classification of individuals as having chronic or episodic migraine, a diagnosis with potentially significant impacts on the individual.
Objectives
This study investigates variation in reported headache frequency in a migraine population and proposes a model for classifying individuals by frequency while accounting for natural variation.
Methods
The American Registry for Migraine Research (ARMR) was a longitudinal multisite study of US adults with migraine. Study participants completed quarterly questionnaires and daily headache diaries. A series of hidden Markov models (HMMs) were fit to monthly headache frequency data calculated from the diary data of ARMR.
A HMM directs the path of an entity through a series of unobservable states. Observable emissions from each state vary according to a probability distribution. The entity remains in a state or transitions to a new state at each time interval. Here a migraineur moves between states representing overlapping monthly headache frequency probability distributions.
Results
Changes in monthly headache frequency tended to be small, with 48% of transitions resulting in a change of 0 or 1 day. A significant portion (28%) of months showed daily headache with individuals ever reporting daily headache likely to report daily headache consistently.
A four-state HMM with three Poisson (λ = 3.37, 10.09, 20.4 days/month) and one constant (28 days/month) emission distributions had the best fit of the models tested. This model had individual mean frequency and individual frequency variation that more closely matches the historical data than random selections from an empirical distribution or a HMM with truncated normal distributions.
Of sequential month to month headache frequency transitions, 12.0% were across the 15-day chronic migraine cutoff. Under the HMM 38.7% of those transitions involved a change in HMM state and the remaining 61.3% of the time a change in chronic migraine classification was not accompanied by a change in HMM state.
Conclusion
A hidden Markov model has appealing properties for classifying individuals according to their headache frequency while accounting for natural variation in frequency.
This approach has potential application in the diagnosis of chronic migraine, assessment of significant worsening or improvement of headache, and resolution of chronic migraine or post-traumatic headache.
Disclosure of Interest
G. Dumkrieger Conflict with: Amgen, R. Ishii Conflict with: Ryotaro Ishii, within the last 12 months, has served as a consultant for Amgen K.K., Eli Lilly Japan K.K., DAIICHI SANKYO COMPANY, LIMITED, and Otsuka Pharmaceutical Co., Ltd. He has received lecture fees from Amgen K.K., Eli Lilly Japan K.K., DAIICHI SANKYO COMPANY, LIMITED, Otsuka Pharmaceutical Co., Ltd, and Takeda Pharmaceutical Co., Ltd., P. Goadsby Conflict with: Eli-Lilly and Company, Celgene, Conflict with: Eli-Lilly and Company, Aeon Biopharma, Allergan/Abbvie, Biohaven Pharmaceuticals Inc., CoolTech LLC, Dr Reddys, Epalex, Impel Neuropharma, Lundbeck, Novartis, Praxis, Sanofi, Satsuma and Teva Pharmaceuticals.
Diana Y. Wei1,2,*, Owen O'Daly3, Fernando O. Zelaya3 and Peter J. Goadsby1,2
1Headache Group, Wolfson Centre for Age-Related Diseases, King's College London
2NIHR Wellcome Trust King's Clinical Research Facility, King's College Hospital
3Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
Introduction
Cluster headache patients endure repeated attacks of severe ipsilateral pain with cranial autonomic symptoms and agitation.
Objectives
To identify cerebral functional connectivity (FC) changes during nitroglycerin (NTG)-triggered cluster headache attacks
Methods
A cohort of cluster headache subjects between 18 and 60 years old was recruited and received an intravenous NTG infusion (0.5mg/kg/min over 20 minutes). Those for whom NTG successfully triggered an attack were invited to attend two subsequent scanning visits. They received either a single-blinded intravenous NTG or an equivalent volume of intravenous 0.9% sodium chloride over 20 minutes. A total of 16 paired NTG-triggered cluster headache attacks and placebo multi-echo gradient-recalled echo-planar images scans were obtained. Data was preprocessed using Statistical Parametric Mapping (SPM) version 12 and denoised using the TE-dependent ICA-based denoising from the Multi Echo Independent Component Analysis (MEICA) package. Connectivity maps were generated by calculating the voxelwise Pearson’s correlation from pre-determined seeds chosen based on previous hypotheses and anatomical regions of interest in cluster headache. As cluster headache attacks in this cohort were exclusively unilateral, analyses were performed so that all the right-sided attacks were identified, and their connectivity maps were flipped on the y-axis. A two-factor (time and infusion), repeated measures 2 x 2 ANOVA model was used to assess the main effects of and interactions between the effect of NTG-triggered attack vs placebo and time (post-administration and baseline pre-administration) on the connectivity maps. Results were considered significant if they survived familywise error correction (PFWE < 0.05) based on cluster extent, using an uncorrected voxel-wise cluster-forming height threshold of P < 0.001.
Results
Significant interactions were observed in the contralateral amygdala, hippocampus, lateral geniculate body of the thalamus, sub-gyral temporal lobe and bilateral midbrain using the ipsilateral anterior insula seed. Further significant interactions were also observed between the ipsilateral anterior insula and ipsilateral cerebellar culmen, posterior cingulate, parahippocampal gyrus, hippocampus, thalamus and sub-gyral limbic lobe. The post-hoc investigation demonstrated that the changes in connectivity were driven by significant decreases in the post NTG infusion triggered attack rather than the increases observed following the placebo infusion.
Conclusion
Our results suggest the excruciating pain experienced during cluster headache attacks may cause functional reorganization of networks, shifting emphasis away from networks not active or required during attacks, such as visual processing, to areas involved in pain processing. The recurrence of attacks could cause FC changes involving the amygdala and hippocampus and perhaps reflect the coping mechanism in cluster headache patients.
Disclosure of Interest
None Declared.
Jan Mehnert, Hauke Basedau and Arne May
Institute for Systems Neuroscience, UKE, Hamburg, Germany
Introduction
Robust activation of the cerebellum has continuously been shown when investigating pain processing, especially in imaging studies on primary headache diseases. A direct anatomical connection between the spinal trigeminal nucleus and the cerebellum has been shown and cerebellar morphology, activation and connectivities are altered in migraine, depending on the severity and phase of the migraine. Next to the trigeminal nerve, the greater occipital nerve (GON) seems to play an important role in the pathophysiology of primary headache. Whether the trigeminal nerve, the GON or indeed the trigemino-cervical complex is specifically represented in the cerebellum is not known.
Objectives
We aimed to disentangle the functional somatotopy of the human cerebellum during pain processing of the TCC in a preregistered study (clinicaltrials.gov: NTC03999060).
Methods
We stimulated the three main branches of the trigeminal nerve as well as the greater occipital nerve electrically during brainstem optimized functional magnetic resonance imaging in two independent cohorts (25 and 38 participants).
Results
We found a dominant effect of the first trigeminal branch in the cerebellum and somatotopic arrangements in bilateral cerebellar lobules I-IV, V, VIIb, VIIIa and Crus I as well as in the brainstem. The cerebellar areas form the two fractured cerebellar representations of the homunculus while the brainstem nucleus is thought to provide direct input from the TCC into the cerebellum.
Conclusion
Our study replicates previous findings of high overall cerebellar activity during trigemino-cervical pain processing in both cohorts and suggests that the cerebellum is an important hub in pain transmission. We demonstrate a high overlap of trigeminal and occipital representations but also can show a clear distinction for each nerve and even each branch of the trigeminal nerve. The dominant effect of the first trigeminal branch on the cerebellar somatotopy underpins its particular role for headache diseases.
Disclosure of Interest
J. Mehnert: None Declared, H. Basedau: None Declared, A. May Conflict with: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB 936 - 178316478 - A5.
Christopher M. Jensen1, Richard B. Lipton2, Andrew Blumenfeld3, Robert Croop1, Alexandra Thiry1, Gilbert L’Italien1, Beth A. Morris1, Vladimir Coric1 and Peter J. Goadsby4,5,*
1Biohaven Pharmaceuticals, New Haven, CT, United States
2Albert Einstein College of Medicine, Bronx, NY, United States
3Headache Center of Southern California, Carlsbad, CA, United States
4NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital/SLaM Biomedical Research Centre, King’s College, London, United Kingdom
5University of California, Los Angeles, Los Angeles, CA, United States
Introduction
For some patients triptans have been associated with inadequate response, relapse of symptoms, and adverse events; cardiovascular contraindications and risk of medication-overuse headache complicate prescribing. Rimegepant is an oral small molecule calcitonin gene-related peptide (CGRP) receptor antagonist that has demonstrated efficacy in three Phase 3 trials in the acute treatment of migraine.
Objectives
Assess the efficacy of rimegepant for the acute treatment of migraine in subjects with and without a history of insufficient response to triptans.
Methods
Three double-blind, placebo-controlled trials of similar design randomized adults with migraine to rimegepant 75 mg tablet (NCT03235479, NCT03237845) or ODT (NCT03461757) or placebo to treat 1 migraine attack of moderate to severe pain intensity. Subgroups with a history of insufficient response with 1 or ≥2 triptans and those without a history of insufficient response, including triptan-naïve and current triptan users, were analyzed. Triptan insufficient response was defined as self-reporting a history of discontinuing ≥1 triptan due to inadequate efficacy and/or poor tolerability. The co-primary endpoints were 2-hour freedom from pain and the most bothersome symptom (MBS).
Results
In the pooled population (n = 3507: rimegepant n = 1749, placebo n = 1758), 2272 (64.8%) subjects had no history of triptan insufficient response and 1235 (35.2%) had a history of insufficient response with ≥1 triptan. Results for the co-primary endpoints in each triptan subgroup are shown in the Figure. No differences in co-primary endpoints were found in pairwise comparisons of triptan subgroups in rimegepant-treated subjects.
Conclusion
Rimegepant was effective for the acute treatment of migraine in subjects with and without a history of an insufficient triptan response. The efficacy of rimegepant was consistent among those with insufficient response to 1 or ≥2 triptans and those who were triptan-naïve or currently using triptans.
Disclosure of Interest
C. Jensen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, R. Lipton Conflict with: Receives research support from the NIH, the FDA, the National Headache Foundation and the Marx Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; receives royalties from Wolff’s Headache (8th Edition, Oxford University Press) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache. Serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta. Holds stock options in Biohaven Pharmaceuticals and CtrlM, A. Blumenfeld Conflict with: Serves as a consultant for Alder, Allergan, Amgen, Aeon, Avanir, Biohaven, ElectroCore, Eli Lilly, Equinox, Impel, Lundbeck, Novartis, Pernix, Promius, Supernus, Revance, Teva, and Theranica, R. Croop Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, A. Thiry Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, G. L’Italien Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, B. Morris Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, P. Goadsby Conflict with: Receives grants and personal fees from Amgen and Eli-Lilly and Company, grant from Celgene, and personal fees from Alder Biopharmaceuticals, Aeon Biopharma, Allergan (Abbvie), Biohaven Pharmaceuticals Inc., Clexio, Electrocore LLC, eNeura, Epalex, GlaxoSmithKline, Impel Neuropharma, Lundbeck, MundiPharma, Novartis, Pfizer, Sanofi, Santara Therapeutics, Satsuma, Teva Pharmaceuticals, Trigemina Inc., WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and Gerson Lehrman Group.
Carlo Lastarria*
Introduction
To our knowledge there are scarce studies in Latin America about the usage of GON block in migraine treatment, this study will allow us to obtain local evidence to support its application.
Nerve blocks have been used by headache medicine practitioners in the treatment of primary headache disorders for very long (Ashkenazi, Headache 2010; 50: 943–952.). This technique offers the patients pain relief and could be useful as preventive medication as well (Miller S, Cephalalgia 2019;39:1488–99).
Objectives
To analyse the response of GON block in migraine acute phase and as migraine therapy 180 days after the injection.
Methods
This prospective cohort recruited sequentially patients in Vallesur – Auna Clinic in Arequipa, Peru since January 2021 to March 2022.
As the application of greater occipital nerve block is a common practice in the Neurology - Headache outpatient clinic, it was not considered an experimental procedure and did not need the approval of the ethics committee. All patients gave oral consent to participate in the study and agreed to receive the occipital nerve block.
All patients were injected bilaterally with lidocaine 2% on 3cc each side during the acute pain phase.
A total of 624 patients with migraine diagnoses. Only eighty-seven patients with migraine participated in the study.
Inclusion criteria: a) Age between 14 and 80, b) Episodic and chronic migraine following the ICHD-3 criteria, c) Acute pain presence with a VAS ≥2 during the evaluation, d) More than 4 migraine crisis per month e) Head pain enhancement for 2 or more weeks(any increase of intensity or frequency of pain basal pattern that obligates the patient to come to consultation).
Exclusion criteria: a) Individuals receiving preventive medication for migraine at the moment of the study for at least 1 month before the intervention (This criterion was emphasised because as we did not have a control group, we focused on selecting patients with no other factor that could alter the intervention response), b) Medication overuse headache, as defined by the ICHD- 3, c) Treatment with peripheral nerve blockade within the last 3 months, d) Allergy to local anaesthetics, e) History of neurosurgery or severe head trauma.
Results
A total of 87 patients were studied in the acute pain phase and received GON block. Acute pain reduction was found in 91% of the patients. The average pain reduction was 50% or more. Only 65 patients completed the follow-up. Eighty-eight percent of the patients experienced preventive efficacy by GON block. The median interquartile range without pain after the procedure was 12 weeks.
Conclusion
GON block could be an effective migraine treatment in the acute pain phase and also appears to be effective as a preventive migraine treatment. These results must be confirmed with randomized controlled trials.
Disclosure of Interest
None Declared.
Patricia Pozo-Rosich1,2,*, José Luis Poveda3, Sergio Sánchez4, Carlos Crespo4, María Martínez5 and Pablo Irimia6
1Headache Unit, Neurology Department, Vall d’Hebron University Hospital; Headache
2Research Group, VHIR, Universitat Autonoma de Barcelona, Barcelona
3Pharmacy Department, Hospital Universitari i Politècnic La Fe, Valencia
4Axentiva
5Novartis, Barcelona
6Department of Neurology, Headache unit, Clínica Universidad de Navarra, Pamplona, Spain
Introduction
Migraine is a common, recurrent headache disorder that can lead to greater disability and cost.
Objectives
To compare effectiveness and cost of erenumab 140 mg vs onabotulinumtoxinA for the prophylaxis of chronic migraine after at least one prior preventive treatment failure in Spain.
Methods
We developed a cost-effectiveness analysis using a 10-year Markov model based on an indirect comparison from the societal perspective. Health states were based on responder, defined as having a minimum 50% reduction in the number of monthly migraine days (MMDs). Patients included in the model were 80.5% women with a mean age of 41 years suffering 18.24 (SE 0.3) MMDs. We estimated quality-adjusted life years (QALY) and MMD over a 10-year time horizon. Incremental cost-effectiveness ratios based on MMD avoided and QALYs gained were performed. Resource use and costs (2022) were obtained from official data sources and were validated by an expert panel. Indirect cost was estimated with MIDAS Questionnaire. Sensitivity analysis was performed to validate the robustness.
Results
Absenteeism and presenteeism cost were 7,718.63 € and 9,117.48 € for erenumab, and 8,300.34€ and 9,761.17€ for onabotulinumtoxinA, respectively. Erenumab showed a total societal cost per patient of 3,497€ vs onabotulinumtoxinA. Patients treated with erenumab showed improved mean MMDs over time, down to 12.35 MMDs at 10 years, while onabotulinumtoxinA patients reduced to 13.21. Given the total reduction of migraine days with erenumab, the cost per MMD avoided with erenumab was 32€. QALYs were 5.46 for erenumab and 5.30 for onabotulinumtoxinA. Incremental cost per QALY gained with erenumab vs onabotulinumtoxinA was 23,652€, below the Spanish efficiency threshold. Sensitivity analysis with indirect cost using WPAI, showed an incremental cost per QALY gained of 23,378€.
Conclusion
Erenumab (Aimovig®) could be a cost-effective alternative vs onabotulinumtoxinA for chronic migraine from the societal perspective in Spain.
Disclosure of Interest
P. Pozo-Rosich Conflict with: Consultant paid by Novartis, J. L. Poveda Conflict with: Consultant paid by Novartis, S. Sánchez Conflict with: Consultant paid by Novartis, C. Crespo Conflict with: Consultant paid by Novartis, M. Martínez Conflict with: Maria report that she are currently employees at Novartis Spain. Novartis is the owner of erenumab., P. Irimia Conflict with: Consultant paid by Novartis.
Apoorva Tomar*, Debashish Chowdhury1, Vaibhav Deorari1, Ashish duggal1, Anand krishnan2 and Arun koul1
1NEUROLOGY, GIPMER
2community medicine, AIIMS, Delhi, India
Introduction
Greater occipital nerve blockade for the prevention of chronic migraine has a limited evidence base. GONB therefore do not find a mention in various guidelines for the prevention of CM.
Objectives
This was a double-blind placebo controlled randomized trial comparing the efficacy and tolerability of GONB for prevention of CM.
Methods
This double-blind, placebo-controlled, parallel-group trial, following a baseline period of 4 weeks, randomly assigned patients of chronic migraine 1:1 to receive 4-weekly bilateral greater occipital nerve blockade with either 2 ml of 2% (40 mg) lidocaine (active group) or 2 ml of 0.9% saline (placebo) injections for 12 weeks. To ensure patient blinding, lignocaine jelly was applied locally at the site of GONB to mask the effect of numbness by lidocaine. The primary and key secondary efficacy endpoints were a change from the baseline in the mean number of headache and migraine days and the achievement of ≥50% reduction in headache days from baseline across the weeks 9–12. Safety evaluations included reporting of serious and other adverse events. Efficacy analyses were conducted in the modified intention-to-treat population, which included all randomly assigned patients who received at least one dose of a trial regimen and had at least 1 follow-up assessment. To control the type I statistical error rate at 0.05, a pre-planned hierarchical testing procedure was applied for primary and the two key secondary endpoints which are presented in the sequence in which they were evaluated. For the primary and secondary endpoints that were measured at three time points (4, 8, and 12 weeks), the least-squares mean (LSM) at each time point was calculated with a linear mixed-effects model that included participants as a random effect, and the number of headache days during the 4-week observation period and years since migraine onset as covariates. For the 50% responder secondary endpoint, stratified Cochran-Mantel- Haenszel test was used.
Results
Twenty-two patients each were randomly allocated to the active and the placebo group. Flow of the study is depicted in Figure 1. The mean age at presentation ± SD was 30.0 ± 9.8 years. Mean headache days at baseline (±SD) in the active and the placebo group were 23.4 ± 4.4 and 22.6 ± 5.0 days respectively. The active group compared to the placebo had a significantly greater least-squares mean reduction in the number of headache and migraine days [−4.2 days (95% CI: −7.5 to −0.8; p = 0.018) and −4.7 days (95%CI: −7.7 to −1.7; p = 0.003) respectively]. 40.9% of patients in the active group achieved ≥50% reduction in headache days as compared with 9.1% of patients receiving a placebo (p = 0.024). Overall, 64 mild and transient adverse events were reported.
Conclusion
Four-weekly greater occipital nerve blockade with 2% lidocaine for 12 weeks was superior to placebo in decreasing headache and migraine days in patients with chronic migraine with a good tolerability profile. Using a robust methodology, the findings of this study provide a new and cheaper alternative for the preventive treatment of CM.
Disclosure of Interest
None Declared.
References
Renato Oliveira*, Inês B. Marques and Raquel Gil-Gouveia
Hospital da Luz Lisboa, Lisboa, Portugal
Introduction
There is an epidemiological association between migraine and transient global amnesia (TGA). While TGA recurrence (rTGA) has been increasingly recognized it is not clear what are the predictive factors.
Objectives
To assess the role of migraine as a predictive factor for TGA recurrence.
Methods
Description of a clinical case and retrospective analysis of a case series of patients with the diagnosis of TGA in our neurology center in the last 10 years, identified through an anonymized database search. TGA was identified by applying Hodges and Warlow criteria.
Results
63-year-old male with history of migraine with aura and 2 episodes (10 years apart) of TGA associated with a migrainous attack. Retrospective analysis of 69 patients with TGA: most female (66.7%); 14 with history of migraine (20.3%). Mean follow-up was 16.5 months. Average TGA episode was four hours. Seven patients (10%) had hippocampus restriction on diffusion weighted MRI. Eleven patients had TGA recurrence (rTGA) (15.9%). Patients with rTGA were more likely have history of depression, and more likely to have history of migraine. There were not enough cases to assess association of migraine subtypes.
Conclusion
TGA remains one of the most enigmatic neurological syndromes. The evidence supports a correlation between migraine and TGA regarding both its etiology and recurrence. This may help to contribute to explain TGA pathophysiology. One hypothesis is the occurrence of a cortical spreading depression affecting the hippocampus causing a transitory neurotoxicity.
Disclosure of Interest
None Declared.
References
Renato Oliveira and Raquel Gil-Gouveia
Hospital da Luz Lisboa, Lisboa, Portugal
Introduction
The calcitonin gene-related peptide monoclonal antibodies [anti-CGRP(r) Mabs] are a revolutionary treatment for migraine prevention. There is, however, some concerns regarding its long-term side effects. There are potential neuroimmunological adverse effects, previous reported by other biologics such as tumor necrosis factor blockers; immune checkpoint-inhibitors.
Objectives
To explore the association between anti-CGRP(r) MAbs and CNS neuroinflammatory conditions.
Methods
Description of 2 cases of temporal association between starting anti-CGRP(r) MAbs and development of CNS neuroinflammatory conditions.
Results
Clinical case 1: 21-year-old female with history of episodic migraine without aura since 14 years-old. Previous failure of 3 oral preventive drugs. Under treatment with fremanezumab 225 mg. After 2 doses she is admitted to the neurology ward due to subacute right-sided discoordination. Investigation showed multiple white-matter lesions fulfilling McDonald criteria for multiple sclerosis (MS). Improvement with intravenous corticosteroids.
Clinical case 2: 34-year-old woman with chronic migraine and medication overuse headache (codeine). Previous failure of 4 oral preventive drugs. Additionally, history of radiological isolated syndrome, diagnosed 10 years before without detectable CSF oligoclonal bands (OCBs). After 7 doses of erenumab 140 mg she had an episode of left optic neuritis that responded to intravenous methylprednisolone. Brain MRI without new lesions and CSF again without OCBs.
Conclusion
We present two cases of CNS neuroinflammatory disease developing after the introduction of anti-CGRP(r) Mabs. Even considering the likely coincidence, we discuss the possibility of a potential dysregulation of the immune system induced by these drugs.
Disclosure of Interest
None Declared
John Rothrock and Alison Koutsandreas
Neurology, Inova Health/University of Virginia, Fairfax, United States
Introduction
Given the prevalence of headache and the relative scarcity of physician subspecialists available to evaluate and treat patients with headache, a more effective and efficient paradigm for patient management is required.
Objectives
To assess a) patient satisfaction with the traditional patient:physician paradigm versus a patient:nurse practitioner (NP)/physician paradigm, b) potential differences in physician productivity according to the paradigm utilized, c) diagnostic concordance between the NP and subspecialist physician, and d) potential differences in management option chosen.
Methods
We evaluated a consecutive series of patients presenting for the first time to a university-based headache clinic. Patients were randomized to be seen by a subspecialist physician (JFR) only or to be seen initially by an NP (AK) with 6 months of clinical and didactic training in headache medicine and then by the physician.
At the conclusion of the clinic visit, each patient was asked to rate his/her satisfaction with the evaluation according to a 5 point Likert scale. In addition, for the patient:NP/physician group the diagnosis and management plan initially offered by the NP was compared with the final those suggested by the subspecialist. Finally, the time the physician spent with each patient was recorded, and the mean times per paradigm subsequently were compared.
Results
We evaluated a consecutive series of 200 patients (100 via each of the 2 paradigms). Patient satisfaction with the NP/physician paradigm was slightly higher than it was with the patient:physician paradigm (4.8 versus 4.7). In 98 (98%) of the 100 patients seen by both providers, the NP's initial diagnosis matched the subspecialist’s diagnosis. There were no major differences in the management suggested. The mean time spent by the subspecialist physician with each patient was 37.5 minutes via the patient:physician paradigm versus 8.3 minutes via the NP/ physician paradigm.
Conclusion
Assessing paradigms for diagnostic evaluation that included an NP and a subspecialist physician versus a physician only, we found patient satisfaction to be essentially equal, diagnostic and management concordance high, and physician productivity to be increased more than 4-fold. This NP/subspecialist physician paradigm may represent one means of coping more effectively with the existing imbalance between migraine patients seeking expert care and the number of physicians devoted to-and capable of- providing such care.
Disclosure of Interest
None Declared
John Rothrock and Alison Koutsandreas
Neurology, Inova Health/University of Virginia, Fairfax, United States
Introduction
There is a prevalent belief amongst headache medicine providers that a relatively small minority of headache clinic patients generate the majority of communications requiring a response.
Objectives
To determine factors predictive of electronic task and message volume generated by headache clinic patients and to quantify the time required to complete those tasks
Methods
We evaluated a consecutive series of new headache clinic patients who remained actively under our care for the ensuing 6 months and evaluated the volume of tasks and messages generated by those patients over that 6 month period. We prospectively chose a number of variables to assess their influence on task volume, including patient gender, age and headache diagnosis, presence of active self-reported depression or anxiety, history of fibromyalgia, Ehlers-Danlos or POTS and type of healthcare insurance coverage (commercial versus non-commercial). We included only tasks ultimately assigned to the provider and excluded from consideration tasks involving routine medication refills. We arbitrarily chose 10 or more tasks per month as the cut-point for defining a “high task generator”.
In a randomly selected group of 100 consecutive tasks received we calculated the time expended by the provider in fulfilling those tasks.
Results
We evaluated 500 consecutive patients. A total of 2,887 assessable electronic tasks and messages were generated over the six month study period, an average of 5.8 tasks per patient and 481 tasks per month. One-hundred and seventy-two (34%) of the 500 patients were “high task generators”, accounting for 2,136 (74%) of the total tasks generated. In a paired analysis of the variables prospectively generated, only a diagnosis of chronic migraine (p < .01) or a reported diagnosis of fibromyalgia, Ehlers-Danlos or POTS (p < .01) correlated significantly with high task generation. In a subsequent multivariate analysis, only chronic migraine remained significantly associated with high task generation.
In the 100 consecutive tasks selected for assessment, the provider required an average of 3.5 minutes to fulfill a given task. The majority (79%) were related to the prior authorization/appeals process for therapies prescribed by the provider.
Conclusion
Our results suggest that in a university-affiliated headache clinic in a major urban center approximately one-third of the patient population will generate approximately three-quarters of the electronic tasks received. The only variable we identified in that population to be independently predictive of high electronic task generation was an initial diagnosis of chronic migraine.
In that same clinical setting, a provider expends approximately 28 hours/month fulfilling electronic tasks for which no direct financial compensation is received.
Disclosure of Interest
None Declared
Avinash Chandra and Ayush Chandra
Neurology, Bir Hospital,, National Academy of Health Sciences, Government of Nepal, Kathmandu, Nepal
Introduction
Migraine is a neurological disabling condition which is prevalent globally and it is a major reason sought for the medical care. Very few studies are reported in Nepal regarding this disorder. This study is conducted in order to explore the clinical and functional disability of patient with migraine among Nepali residents.
Objectives
Ojectives are to assess the socio-demographic characteristics of patient with migraine, to investigate the clinical manifestation of migraine and to determine the functional disability caused due to migraine using Migraine Disability Assessment (MIDAS) format.
Methods
Quantitative research methods were used to carry out this study. MIDAS questionnaire was used. Data was collected under Likert scale format. Data were analyzed by using descriptive statistical method by SPSS (version 20).
Results
About 219 patients were diagnosed with migraine in the period of 3 months. Majority of participants were in the age group of 20–29 years (29.7%) followed by age group of 30–39(27.9%) with the majority of female participants (79%).
About 36.52% of patients were in the category of episodic migraine and 63.47% were in the category of chronic migraine. Most of the subjects (84.5%) experienced the severe level of functional disability.
Conclusion
chronic migraine was found to be 3.4 times higher in disability called as level IV in comparison with level I also called as lower disability level and this relationship was statistically significant (OR = 3.4, 95%CI = 1.01–11.48).
It is concluded that chronic migraine was found to be 3.4 times higher in disability called as level IV in comparison with level I also called as lower disability level and this relationship was statistically significant (OR = 3.4, 95%CI = 1.01–11.48) as shown in Table below. The study was conducted on the group of patient who came in Out-patient department (OPD) based in the hospital within the certain period of time.
It is concluded that chronic migraine was found to be 3.4 times higher in disability called as level IV in comparison with level I also called as lower disability level and this relationship was statistically significant (OR = 3.4, 95%CI = 1.01–11.48) as shown in Table below. The study was conducted on the group of patient who came in Out-patient department (OPD) based in the hospital within the certain period of time.
Disclosure of Interest
None Declared.
Alicia Gonzalez Martinez1,*, Inés Muro García1, Sonia Quintas1, María Chaparro2, Javier Javier P. Gisbert3, Ancor Sanz4, María José Casanova5, Cristina Rubín de Célix6, José Vivancos7 and Ana Beatriz Gago-Veiga1
1Headache Unit, Hospital Universitario de la Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Madrid
2Gastroenterology Unit, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
3Gastroenterology Unit, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
4Data Analysis Unit, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Hospital Universitario de la Princesa
5Gastroenterology Unit, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
6Gastroenterology Department, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
7Department of Neurology, Hospital Universitario de la Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Madrid, Spain
Introduction
There is a complex bidirectional association between neurological and gastrointestinal (GI) disorders under the so called gut-brain axis. In patients with migraine GI comorbidities are common suggesting the important role of this putative association.
Objectives
In this study waimed to evaluate the prevalence of migraine according to Migraine Screening Questionnaire (MS-Q) among patients with inflammatory bowel disease (IBD) and describe the headache characteristics compared to a control goup.
Methods
We performed a cross-sectional study by online survey including patients with IBD from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine prevalence evaluation. Scale scores from HIT-6, HADS and ISI were also included.
Results
We included 66 patients with IBD and 47 controls. Among patients with IBD, 28/66 (42%) were women, mean age 42 years and 23/66 (64%) had ulcerative colitis and 43/66 (65%) Crohn's disease. MS-Q was positive in 13/66 (23%) of IBD patients and 4 (13%) of controls. We found that a female sex (p = 0.006), weight (p = 0.002), height (p = 0.002) and anti-TNF use (0.0035) were associated with MS-Q positive diagnosis.
Conclusion
The prevalence of migraine according to MS-Q is higher in patients with IBD compared to a control group. These results might be explained by the relationship between these entities through the gut-brain axis. Moreover, sveral demographic characteristics of patients with IBD could predict migraine. Our results highlight the importance of migraine detecion among patients with IBD which could improve management of this condition and the quality of life of these patients.
Disclosure of Interest
None Declared.
Alicia Gonzalez Martinez1,*, Javier Gálvez-Goicuría2, Josué Pagán3, Sonia Quintas4, Alba Vieira1, José Luis Ayala Rodrigo5, Ancor Sanz6, Mónica Sobrado1 and José Vivancos7
1Headache Unit, Hospital Universitario de la Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Madrid
2Electronic Engineering Department, Universidad Politécnica de Madrid
3Electronic Engineering Department, Universidad Politécnica de Madrid, Madrid, 16771 Madrid, Spain, 28040
4Headache Unit, Neurology Department,, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Madrid, 28006, Madrid, Spain
5Computer Architecture and Automation Department, Universidad Complutense de Madrid, 16734 Madrid, Comunidad de Madrid, Spain; CCS: Center for Computational Simulation, , Universidad Politécnica de Madrid, Comunidad de Madrid, Spain
6Unidad de Análisis de datos, Instituto de Investigación Sanitaria (IIS-Princesa), Hospital Universitario de la Princesa)
7Neurology Department, Hospital Universitario de la Princesa & Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Madrid, Spain
Introduction
Clinical characteristics of a migraine crisis have been described in several studies giving rise to the number of symptoms that can be present during a migraine crisis. However, to date, literature regarding the evolution of tha pain is scarce.
Objectives
In this study we aimed to evaluate the semiology of a migraine crisis according to the type of pain curve.
Methods
We classified the pain curve of patients with episodic migraine according to the current criteria (ICHD-III) ina prospective real time study using a smartphone application. The follow-up period was one month, the patient marked start/end of the pain and the intensity evolution in at least 5 points. Symptomatic treatment was allowed. At the end of a crisis, the patient completed the characteristics of the episode in the smartphone application. To generate the model K-means and supervised validation technique using a logistic model tree was used.
Results
A total of 344 migraine crisis were included from 51 patients (mean age 39 years, 90% somen). Using the maximum pain intensity, time to achieve the maximum pain intensity, the relationship between both parameters and the total duration, all episodes were categorized in four types according to the main characteristics: high intensity, acute onset, prolonged and intens or low intensity. Univariate analysis found statistically significant differences in the type of curve regarding the presence of nauseas (p < 0.001), sohophobia (p < 0.001), osmophobia (p < 0.03) and the number of simultaneous symptoms (p < 0.001).
Conclusion
The evolution of the pain crisis can be categorized in four types of curves, which represent different semiology characteristics of a migraine crisis.
Disclosure of Interest
None Declared.
Robert Croop1,*, Jennifer Madonia1, Jennifer Hould1, Linda Mosher1, Meghan Lovegren1, Vladimir Coric1 and Richard B. Lipton2
1Biohaven Pharmaceuticals, New Haven, CT, United States
2Albert Einstein College of Medicine, Bronx, NY, United States
Introduction
In the acute treatment of migraine, nonoral formulations are particularly useful in patients with nausea or vomiting, rapidly escalating headache pain, or inadequate response to oral formulations, as demonstrated by a lack of efficacy, poor tolerability, or slow onset of action. Although people with migraine commonly cite rapid relief as a high priority treatment goal, lack of efficacy, adverse events, and cardiovascular complications limit the clinical utility of existing nonoral alternatives (triptans, ergot alkaloids). Zavegepant is the only small molecule CGRP receptor antagonist (gepant) for intranasal administration in late-stage development for the acute treatment of migraine. Previously, a Phase 1 study in healthy subjects showed that zavegepant 10 mg nasal spray has a Tmax of approximately 30 minutes, and a Phase 2/3 dose-ranging study (NCT03872453) found that zavegepant 10 mg was the optimal therapeutic dose.
Objectives
Evaluate the safety of zavegepant 10 mg nasal spray in the acute treatment of migraine.
Methods
This was a Phase 2/3, 1-year open-label safety study (NCT04408794) of zavegepant for the acute treatment of migraine. Adults aged ≥18 years with a history of 2 to 8 moderate-severe monthly migraine attacks were eligible. Use of another gepant was prohibited. Subjects self-administered 1 dose of zavegepant 10 mg nasal spray per day as needed to treat migraine attacks of any severity, up to 8 times per month, for up to 52 weeks. Months were defined as 4-week intervals. Safety assessments included adverse events (AEs), vital signs, ECG, nasal inspection, and clinical laboratory tests. Subjects who took ≥1 dose of zavegepant were included in the analysis.
Results
Of the 608 subjects who entered the long-term treatment phase, 603 were treated with zavegepant 10 mg nasal spray. The treated population had a mean (SD) age of 42.1 (12.5) years and was 85.7% female and 83.3% white. At baseline, the mean (SD) number of moderate-severe attacks per month was 5.0 (1.89), and 18.1% of treated subjects were using preventive migraine medication. Treatment-emergent AEs reported in ≥5% of subjects (Table) were dysgeusia (39.1%); nasal discomfort (10.3%); COVID-19 (7.5%); nausea (6.1%); nasal congestion and throat irritation (5.5% each); and back pain (5.3%). In total, 6.8% of treated subjects discontinued due to AEs; 1.5% discontinued due to dysgeusia. The majority of AEs (96.4%) were mild to moderate in intensity. Of the 7 serious AEs reported, none was considered related to treatment by the investigators. Aminotransferases >3x the upper limit of normal (ULN) occurred in 2.6% of subjects, none of whom had concurrent elevations in bilirubin >2x ULN. Subjects took a mean (SD) of 3.1 (1.6) zavegepant doses per month.
Conclusion
This 1-year open-label safety study demonstrated favorable safety and tolerability for zavegepant 10 mg nasal spray for the acute treatment of migraine.
Disclosure of Interest
R. Croop Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, J. Madonia Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, J. Hould Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, L. Mosher Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, M. Lovegren Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, R. Lipton Conflict with: Received research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; receives royalties from Wolff’s Headache (8th Edition, Oxford University Press, 2009) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Biohaven, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, BDSI, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Pfizer, Teva, and Vedanta; holds stock or options in Biohaven Pharmaceuticals and Manistee.
Kathleen Mullin1, Robert Croop2,*, Jelena M. Pavlovic3, Linda Mosher2, Timothy R. Smith4, Jennifer Madonia2, Meghan Lovegren2, Vladimir Coric2 and Richard B. Lipton3
1New England Institute for Neurology and Headache, Stamford, CT, United States
2Biohaven Pharmaceuticals, New Haven, CT, United States
3Albert Einstein College of Medicine, Bronx, NY, United States
4StudyMetrix Research, St. Louis, MO, United States
Introduction
In the acute treatment of migraine, nonoral therapies are recommended for attacks that include severe nausea or vomiting or rapidly escalating headache pain, as well as for patients in whom oral forms are associated with inadequate response, slow onset of action, or poor tolerability. Because most patients with migraine refuse injectable formulations if they are given an alternative, and route of administration influences response to treatment, especially in the first hour postdose, intranasally administered antimigraine drugs can meet important needs in clinical practice. Zavegepant is the only small molecule CGRP receptor antagonist delivered by nasal spray in late-stage development for the acute treatment of migraine. In a Phase 1 study with healthy subjects, the 10 mg nasal spray was rapidly absorbed (Tmax ∼30 minutes). A dose-ranging study (NCT03872453) found that zavegepant 10 mg was the optimal dose.
Objectives
Compare the efficacy and safety of zavegepant nasal spray with placebo in the acute treatment of migraine.
Methods
This was a phase 3, double-blind, randomized, placebo-controlled trial (NCT04571060). Adults with a history of 2–8 moderate or severe monthly migraine attacks self-administered 1 dose of zavegepant 10 mg nasal spray or placebo to treat 1 migraine attack of moderate or severe pain intensity. The coprimary endpoints were the percentage of subjects with 2-hour freedom from pain and the most bothersome symptom (MBS).
Results
Of 1405 randomized subjects, 1269 (mean age 41 years, 83% female) were evaluable for efficacy (zavegepant n = 623, placebo n = 646). Zavegepant was superior to placebo for the coprimary endpoints, 2-hour freedom from pain (23.6% vs 14.9%, P < .0001) and the MBS (39.6% vs 31.1%, P = .0012). Zavegepant was also more effective than placebo on the secondary endpoints of pain relief at 15 minutes (15.9% vs 8.0%, P < .0001) and 2 hours (58.7% vs 49.7%, P = .0012); return to normal function at 30 minutes (10.5% vs 6.1%, P = .0059) and 2 hours (35.8% vs 25.6%, P = .0001); sustained pain relief from 2 to 24 hours (40.6% vs 33.0, P = .0048) and 2 to 48 hours (36.1% vs 29.6%, P = .013); sustained pain freedom from 2 to 24 hours (14.6% vs 9.8%, P = .0076) and 2 to 48 hours (12.4% vs 8.7%, P = .0308); and phonophobia (41.0% vs 32.7%, P = .0123) and photophobia (37.1% vs 28.5%, P = .0018) at 2 hours. The Figure shows that zavegepant was more effective than placebo for pain relief from 15 minutes through 2 hours postdose. The most common (≥2%) adverse events (zavegepant vs placebo) were dysgeusia (20.5% vs 4.7%), nasal discomfort (3.7% vs 0.8%), and nausea (3.2% vs 1.1%). Most adverse events were mild or moderate; none were serious.
Conclusion
Zavegepant nasal spray was effective for the acute treatment of migraine, achieving its coprimary endpoints and providing a rapid onset of pain relief as early as 15 minutes postdose, sustained benefits to 48 hours postdose, and favorable safety and tolerability.
Disclosure of Interest
K. Mullin Conflict with: Serves as a consultant, advisory board member, or has received honoraria from Amgen, Biohaven, electroCore, and Eli Lilly, R. Croop Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, J. Pavlovic Conflict with: Consultant for Allergan and serves on the advisory board for Biohaven, L. Mosher Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, T. Smith Conflict with: Received fees for speaker's bureau from Amgen, Allergan/Abbvie, Biohaven, Novartis, and Lilly and for advisory boards or consultancies from Allergan/Abbvie, Biohaven, Amgen, Lilly, Alder/Lundbeck, Impel Neuropharma, Neurolief, Nocira, Theranica, Teva, and Vorso/Nesos; received research support from Amgen, Alder/Lundbeck, Lilly, Teva, Allergan/Abbvie, Biohaven, Electrocore, Novartis, Novo Nordisk, Impel Neuropharma, Aeon, Charleston Labs, Nocira, Teva, Theranica, and Vorso/Nesos, J. Madonia Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, M. Lovegren Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and own stock/stock options in Biohaven Pharmaceuticals, R. Lipton Conflict with: Received research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; receives royalties from Wolff’s Headache (8th Edition, Oxford Press University, 2009) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta; holds stock or options in Biohaven Pharmaceuticals, Manistee, and CntrlM.
Fred Cohen1, Hsiangkuo Yuan1,*, Kathryn Dent1, Matthew Beucherie1, William Connolly1, Maurice Driessen2, Lynda J. Krasenbaum3, Karen Carr4, Mary Hopkins1 and Michael Marmura1
1Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States
2Global Medical Affairs, Teva Netherlands B.V., Amsterdam, Netherlands
3Global Medical Affiars , Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA
4US Medical Affairs, Teva Pharmaceuticals, Parsippany, NJ, United States
Introduction
OnabotulinumtoxinA (onabotA) is approved for prevention of chronic migraine (CM); however, additional preventive medication may be necessary to achieve a successful clinical outcome. Due to different but complementary mechanisms of action, there may be an additive or synergistic effect when combining onabotA with a calcitonin gene-related peptide (CGRP) pathway-targeted monoclonal antibody (mAb).
Objectives
We investigated the effectiveness and tolerability of fremanezumab as an add-on therapy for patients already receiving onabotA as preventive treatment for CM.
Methods
In this pre-post retrospective chart review study, we reviewed medical records of adult patients with CM at the Jefferson Headache Center who first initiated fremanezumab treatment between October 2018 and May 2020 (date of first initiation = index date) and had ≥3 months (mos) of concomitant onabotA and fremanezumab usage. Study outcomes were changes in monthly headache days (MHD) and average pain intensity (PI; 0–10 numerical rating scale [NRS]) from the index date to 3, 6, and 9 mos and last available follow-up (last visit). Adverse events (AEs) were also evaluated. Outcomes were evaluated in the overall population and subgroups by prior CGRP pathway-targeted mAb exposure. P-values < 0.05 were considered statistically significant.
Results
Records of 236 patients were assessed for eligibility; 116 met the inclusion criteria.
Conclusion
Concomitant use of fremanezumab with onabotA for CM prevention is well tolerated and may together be a more effective treatment regimen than onabotA alone in patients with CM.
Disclosure of Interest
F. Cohen: None Declared, H. Yuan Conflict with: NIH (R44NS115460), consultation fees from Trillen, institutional support for serving as an investigator from Teva, and royalties from Cambridge University Press and MedLink, K. Dent: None Declared, M. Beucherie: None Declared, W. Connolly: None Declared, M. Driessen Conflict with: Employee of Teva Pharmaceuticals, L. Krasenbaum Conflict with: Employee of Teva Pharmaceuticals, K. Carr Conflict with: Employee of Teva Pharmaceuticals, M. Hopkins: None Declared, M. Marmura Conflict with: compensation for consultation from Alder/Lumbeck, Axsome, Supernus, Upsher-Smith, and Satsuma. He has participated in speaker bureaus for Eli Lilly, and Amgen/Novartis. He has received institutional support for serving as principal investigator from Teva, GammaCore and Allergan/AbbVie. He has received payments for authorship or royalties from Demos Medical, Cambridge University Press and MedLink
Beatriz Nunes Vicente1,*, Filipa Dourado Sotero1 and Isabel Pavão Martins1,2,3
1Neurology, Centro Hospitalar Universitário Lisboa Norte
2Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
3Centro de Estudo Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
Introduction
Menstrually-related migraine (MRM) attacks are consistently referred to as more disabling, longer duration and higher drug resistance than non-menstrual migraine attacks. A subgroup analysis of a randomized controlled trial showed the efficacy of monoclonal antibodies blocking CGRP-ligand or receptor (CGRP-mAbs) in MRM, but did not distinguish menstrual from non-menstrual days. Real world data suggests that women with chronic migraine on treatment with CGRP-mAbs had headaches more commonly in menstrual than in premenstrual or non-menstrual days.
Methods
We describe the clinical presentation of a 36-year-old female with a history of chronic migraine, treated with fremanezumab and evolving to a pure-menstrual migraine resistant to treatment.
Results
A 36-year-old female accounter had migraine with aura since the age of 12 years that evolved to chronic migraine in the last 3years with medication-overuse headache, with triptan and non-opioid analgesics. Attacks were resistant to several prophylactic treatments (amitriptyline, topiramate and flunarizine). Neurological examination and brain MRI were unremarkable. She was treated with fremanezumab for 9 months, in addition to amitriptyline 25mg and a progesterone pill. She reported a significant improvement in monthly headache days (from an average of 20 to 5 days/month), with almost disappearence of attacks except for the perimenstrual days, becoming a pure-menstrual migraine. As she interrupted fremanezemab due to pregnancy attacks returned to the previous almost daily pattern.
Conclusion
Our case showed that menstruation remains a trigger for migraine occurrence even after treatment with fremanezumab, even in those women who have a favorable response to the treatment. Evidence suggests that female sex hormones can modulate CGRP levels in women and CGRP blockade might be counterbalanced by an increased expression of CGRP in the days around the menstruation.
Disclosure of Interest
None Declared.
References
Jan Hoffmann1,2,*, Holger Kaube3, Florian Rimmele4, Tim P. Jürgens4, Charly Gaul5, Andreas Straube6, David Lewis7 and Arne May8
1Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London
2NIHR-Wellcome Trust King’s Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, United Kingdom
3Neurologie und Kopfschmerzzentrum Münchner Freiheit, Munich
4Department of Neurology, Headache Center North-East, University Medical Center Rostock, Rostock
5Headache Center Frankfurt, Frankfurt am Main
6Department of Neurology, Ludwig-Maximilians-Universität München, Munich
7Lewis Neurologie, Stuttgart
8Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Introduction
Targeting the trigemino-autonomic reflex and parasympathetic outflow for the preventive treatment of migraine has long been debated. This is supported by the observations that the infusion of parasympathetic neuropeptides such as PACAP and VIP can trigger migraine attacks and that the parasympathetic pathway may represent an effective treatment target. Kinetic oscillation of the nasal cavity induces a reliable cranial autonomic response reflected in the lacrimation it causes and repetitive use may therefore have a preventive effect on migraine.
Objectives
A multicentre, randomised, sham-controlled clinical trial was conducted to assess the efficacy of Kinetic Oscillation Stimulation of the nasal cavity as a preventive treatment for chronic migraine (n = 132). Herewith we report the results of a subgroup analysis on the findings obtained of all study participants recruited in Germany (n = 92).
Methods
Patients diagnosed with chronic migraine were randomised to either receive intranasal stimulation or sham stimulation once per week for 10 minutes per nostril over a period of 6 weeks. Primary outcome was the reduction of monthly headache days with moderate to severe intensity during weeks 3–6 compared to the 4-week baseline period in the treatment group versus the sham group. A secondary outcome parameter was the reduction of headache days with moderate to severe intensity during a 4-week follow-up period compared to baseline. Data was analyzed using ANCOVA followed by a van Elteren Test stratified for medication overuse.
Results
The subgroup analysis revealed that the 6-week intranasal Kinetic Oscillation Stimulation (n = 46) significantly reduces the number of monthly headache days with moderate to severe intensity from baseline when compared to sham stimulation (n = 46). The difference in least square means (LSQ) of the ANCOVA model, containing terms for treatment, baseline value, and medication overuse between the 4-week baseline period and treatment weeks 3–6 was −2.52 (CI95% = [−4.52; −0.52], p = 0.0140; using non-parametric, stratified van Elteren test p = 0.0092). During the follow-up period after ending stimulation the reduction in LSQ was −2.70 (CI95% = [−4.73;-0.68], p = 0.093; van Elteren test p = 0.0151) thereby showing a sustained improvement during this observation period. The treatment was well-tolerated with no severe adverse events.
Conclusion
This clinical trial shows that intranasal Kinetic Oscillation Stimulation is an effective and safe option for the preventive treatment of chronic migraine. The non-pharmacological nature of the treatment option positions Kinetic Oscillation Stimulation as a valuable expansion of the current therapeutic portfolio since most of the current preventive treatments have a significant risk of causing systemic unwanted side effects, which were not observed in this trial.
Disclosure of Interest
J. Hoffmann Conflict with: Bristol Myers Squibb, Conflict with: Jan Hoffmann reports honoraria for consulting activities and/or serving on advisory boards from Allergan, Autonomic Technologies Inc., Cannovex BV, Chordate Medical AB, Eli Lilly, Hormosan Pharma, Lundbeck, Novartis, Sanofi and Teva. He received personal fees for Medico-Legal work as well as from Oxford University Press, Quintessence Publishing, Sage Publishing and Springer Healthcare. He holds stock options from Chordate Medical AB. Jan Hoffmann serves as Associate Editor for Cephalalgia, Cephalalgia Reports, Journal of Oral & Facial Pain and Headache as well as for Frontiers in Pain Research. He is an elected member of the Board of Trustees of the International Headache Society (IHS) and serves as a Council Member and Treasurer of the British Association for the Study of Headache (BASH). , H. Kaube: None Declared, F. Rimmele: None Declared, T. Jürgens Conflict with: EFRE, Innovationsfonds-Gemeinsamer Bundesausschuss and Novartis, Conflict with: Tim P. Jürgens reports honoraria for consulting activities and/or serving on advisory boards from Allergan, Autonomic Technologies Inc., Lilly, Hormosan Pharma, Lundbeck, Novartis and Teva. He received personal fees for medico-legal work, Elsevier and Springer. He does not hold any stock options. He serves as Associate Editor for Frontiers in Neurology – headache and Neurogenic Pain on the Editorial Board of the The Journal of Headache and Pain. He is currently President of the German Migraine and Headache Society. , C. Gaul Conflict with: German Research Foundation (DFG), Conflict with: Charly Gaul has received honoraria for consulting and lectures within the past three years from Allergan Pharma, Lilly, Novartis Pharma, Hormosan Pharma, Grünenthal, Sanofi-Aventis, Weber & Weber, Lundbeck, Perfood, and TEVA. He does not hold any stocks of pharmaceutical companies. He is honorary secretary of the German Migraine and Headache Society., A. Straube Conflict with: Andreas Straube reports honoraria for consulting activities and/or serving on advisory boards and/or lectures from Allergan, Allergosan, Eli Lilly, Novartis, Sanofi and Teva., D. Lewis Conflict with: David Lewis reports honoraria for consulting activities and/or serving on advisory boards, lectures from Allergan, Hormosan, Lilly, Lundbeck, Novartis and Teva. He does not hold any stocks of pharmaceutical companies., A. May: None Declared.
Somayeh Nasergivehchi1,*, Fan Cheng2, Mariam Hussain2, Modar Khalil2 and Fayyaz Ahmed2
1Neurology, Tehran University of Medical Science, Tehran, Iran, Islamic Republic Of
2Department of Neurosciences, Hull University Teaching Hospitals, Hull, United Kingdom
Introduction
Chronic migraine (CM), is a disabling condition with significant morbidity affecting 1.4–2.2% of the population. Preventive therapies are the most powerful tools available to improve the well-being of people with migraine. CGRP is a neuropeptide that is involved in migraine pathogenesis and the development of monoclonal antibodies targeting CGRP or its receptor has transformed the preventive treatment of migraine. currently five CGRP monoclonal antibodies are available.
Objectives
Fremanezumab is licensed as preventive treatment in those with >4 days of headaches per month. We evaluated one year outcome on patients prescribed fremanezumab for CM.
Methods
Adult CM patients attending the Hull Migraine clinic were prescribed fremanezumab and followed up prospectively. Patients maintained a headache diary for at least 1 month prior to and continuously after commencing fremanezumab. All patients tried and failed at least 6 treatments with 93% failing OnabotulinumtoxinA. We measured monthly headache days (MHD), migraine days (MMD), headache-free days (HFD), analgesia medication (AMD) and triptan days (TD) and Headache Impact Test-6 (HIT6) scores at baseline and monthly during treatment for a year. The treatment was discontinued if they had <30% reduction in either MHD, MMD at the end of three months. At one year, those that continued were asked to stop treatment for three months if they had ≤4 headache days per month for the previous three months and treatment recommenced if any time in the subsequent three months, the headache days went above 4 per month.
Results
300 patients (221 F, 79 M), mean age 48.6 years (range 21–75), commenced fremanezumab between November 2020–April 2021. 243 patients (187 F, 56 M) at 3-month follow-up had baseline MHD, MMD and HFD of 28, 17 and 2 days, improving to 15, 6 and 15 days respectively were classed as responders and continued treatment for one year. The remaining 57 patients (34 F, 23 M) stopped treatment due to lack of response. At one year 225 (92.5%) patients (213 F and 12 M) were still getting ≥5 days of headaches per month and continued treatment and only 18 (7.5%) patients (12 F, 6 M) were able to stop treatment. All but 3 had to restart therapy as the headache days exceeded ≥5 or more between 1–3 months.
Conclusion
Even though many patients with CM are reverted to episodic migraine following fremanezumab therapy, almost all (99%) patients are required to continue treatment for the second year.
Disclosure of Interest
None Declared.
Reference
Richard B. Lipton1, David Kudrow2, Timothy Smith3, Jessica Ailani4, Peter J. Goadsby5,6,*, Lisa Kamen7, Alexandra Thiry7, Christopher M. Jensen7, Vladimir Coric7 and Robert Croop7
1Albert Einstein College of Medicine, Bronx, NY, United States
2California Medical Clinic for Headache, Santa Monica, CA, United States
3Study Metrix Research, Saint Peters, MO, United States
4Medstar Georgetown University Hospital, Washington, DC, United States
5NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital/SLaM Biomedical Research Centre, King’s College , London, United Kingdom
6University of California, Los Angeles, Los Angeles, CA, United States
7Biohaven Pharmaceuticals, New Haven, CT, United States
Introduction
Tolerability issues lead most patients to discontinue preventive treatment of migraine within 1 year. Rimegepant is an orally administered small molecule CGRP receptor antagonist with established efficacy in clinical trials for the acute and preventive treatment of migraine. Rimegepant was well tolerated in acute and preventive studies.
Objectives
Assess the safety and tolerability of rimegepant 75 mg dosed every other day (EOD) for the preventive treatment of migraine and as-needed (PRN) for acute treatment on nonscheduled dosing days.
Methods
This was the 1-year open-label extension phase of the 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) of rimegepant for the preventive treatment of migraine. Adults aged ≥18 years with a history of 4 to 18 moderate-severe monthly migraine attacks were eligible. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo EOD could continue with rimegepant 75 mg EOD for preventive treatment of migraine for 52 weeks. On nonscheduled dosing days, subjects could take rimegepant 75 mg up to once per day PRN for acute treatment of migraine. Safety assessments included adverse events (AEs) and clinical laboratory test evaluations, including liver function tests. Subjects recorded the occurrence and severity of migraine attacks, as well as use of rimegepant, in an electronic diary; in-person visits occurred at Weeks 2, 4, and every 4 weeks thereafter through Week 52 of the open-label extension phase (ie, overall study Week 64). Subjects who took ≥1 dose of open-label rimegepant were analyzed. Months were defined as 4-week intervals.
Results
Of the 741 subjects treated in the double-blind treatment phase, 603 (81.4% [rimegepant n = 301, placebo n = 302]) were treated in the open-label extension. The open-label population had a mean (SD) age of 42.6 (13.10) years and a mean (SD) history of 7.9 (2.74) monthly attacks; 82.7% were female. The most common AEs (Figure) were upper respiratory tract infection (7.1%), nasopharyngitis (6.3%), and back pain (4.3%). The rate of discontinuation due to AEs was 2.8%. Serious AEs in 2.2% of subjects were considered not related to rimegepant. Two deaths (0.3%), 1 due to aortic dissection related to Marfan syndrome and 1 due to sepsis, were also deemed unrelated to rimegepant. Aminotransferases >3x the upper limit of normal (ULN) occurred in 3.4% of subjects; none had concurrent elevations in bilirubin >2x ULN. Subjects took a mean (SD) of 14.6 (2.45) rimegepant doses per month; 81.4% used ≤16 rimegepant tablets per month.
Conclusion
One year of open-label rimegepant 75 mg every other day for preventive treatment of migraine plus PRN on nonscheduled dosing days for acute treatment up to once daily was safe and well tolerated with no liver safety concerns. Use of PRN treatment was limited, and more than 80% of subjects took ≤16 tablets per month.
Disclosure of Interest
R. Lipton Conflict with: Received research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; receives royalties from Wolff’s Headache (8th Edition, Oxford University Press, 2009) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta; holds stock or options in Biohaven Pharmaceuticals, Manistee, and CntrlM, D. Kudrow Conflict with: Received fees for advisory board from Alder, Biohaven, Eli Lilly, Amgen, and Xoc and for speaker’s bureau from Xoc, Teva, Amgen, Novartis, and Eli Lilly; received research support from Amgen, Novartis, Eli Lilly, Teva, Alder, Biohaven, Biogen, and Roche-Genentech, T. Smith Conflict with: Received fees for speaker's bureau from Amgen, Allergan/Abbvie, Biohaven, Novartis, and Lilly and for advisory boards or consultancies from Allergan/Abbvie, Biohaven, Amgen, Lilly, Alder/Lundbeck Impel Neuropharma, Neurolief, Nocira, Theranica, Teva, and Vorso/Nesos; received research support from Amgen, Alder/Lundbeck, Lilly, Teva, Allergan/Abbvie, Biohaven, Electrocore, Novartis, Novo Nordisk,, Impel Neuropharma, Aeon, Charleston Labs, Nocira, Teva, Theranica, and Vorso/Nesos, J. Ailani Conflict with: Received clinical trial grants as a principal investigator from Allergan/Abbvie, American Migraine Foundation, Biohaven, Eli Lilly, Satsuma, and Zosano; has received stock options for consulting from CtrlM, Conflict with: Received stock options for consulting from CtrlM; and has received honoraria from the following: Alder/Lundbeck (speaking, consulting), Allergan/Abbvie (speaking, consulting), Amgen (speaking, consulting), Biohaven (speaking, consulting), GlaxoSmithKline (consulting), Eli Lilly and company (speaking, consulting), Impel (consulting), Theranica (consulting), Axsome (consulting), Neso (consulting), Aeon (data advisory board), Teva (speaking, consulting), Satsuma (consulting), Current Pain and Headache Reports (section editor), NeurologyLive (editorial board), SELF (medical advisory board), Medscape (advisory board), P. Goadsby Conflict with: Reports grants and personal fees from Amgen and Eli-Lilly and Company, grant from Celgene, and personal fees from Alder Biopharmaceuticals, Aeon Biopharma, Allergan, Biohaven Pharmaceuticals Inc., Clexio, Electrocore LLC, eNeura, Epalex, GlaxoSmithKline, Impel Neuropharma, Lundbeck, MundiPharma, Novartis, Pfizer, Sanofi, Santara Therapeutics, Teva Pharmaceuticals, Trigemina Inc., WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and a patent magnetic stimulation for headache assigned to eNeura without fee, L. Kamen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, A. Thiry Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, C. Jensen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, R. Croop Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Jessica Ailani1, David Kudrow2, Timothy Smith3, Richard B. Lipton4, Peter J. Goadsby5,6,*, Alexandra Thiry7, Christopher M. Jensen7, Lisa Kamen7, Vladimir Coric7 and Robert Croop7
1Medstar Georgetown University Hospital, Washington, DC, United States
2California Medical Clinic for Headache, Santa Monica, CA, United States
3Study Metrix Research, Saint Peters, MO, United States
4Albert Einstein College of Medicine, Bronx, NY, United States
5NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College Hospital/SLaM Biomedical Research Centre, King’s College , London, United Kingdom
6University of California, Los Angeles, Los Angeles, CA, United States
7Biohaven Pharmaceuticals, New Haven, CT, United States
Introduction
Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of episodic migraine. In a 1-year open-label study, as-needed (PRN) acute treatment with rimegepant reduced monthly migraine days (MMDs); a 12-week double-blind study showed that scheduled every other day (EOD) dosing of rimegepant significantly reduced MMDs. In clinical trials of medications for the preventive treatment of migraine, the most common primary endpoint is the change from baseline in the frequency of MMDs. The percentage of subjects with ³50% reduction in MMDs from baseline is a clinically useful endpoint.
Objectives
Assess the effects of rimegepant 75 mg on MMDs through 52 weeks of open-label treatment when dosed EOD plus PRN on nonscheduled dosing days.
Methods
This open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study evaluating rimegepant 75 mg EOD for preventive treatment of migraine included adults aged ≥18 years with a history of 4–18 moderate-severe monthly migraine attacks. Subjects completing the 4-week observation period and 12-week double-blind treatment could continue with open-label rimegepant 75 mg EOD for preventive treatment of migraine for 52 weeks. On nonscheduled dosing days, subjects could take rimegepant 75 mg up to once per day PRN for acute treatment of migraine. Key outcomes were the mean change from the observational period in MMDs and the percentages of subjects with ≥50%, ≥75%, or 100% reductions from the observational period in moderate to severe MMDs. Months were defined as 4-week intervals.
Results
Of the 741 subjects who were treated in the double-blind treatment phase, 603 (81.4% [rimegepant n = 301, placebo n = 302]) were treated in the open-label phase. The open-label population had a mean (SD) age of 42.6 (13.10) years and was 82.7% female, with a mean (SD) history of 7.9 (2.74) monthly moderate-severe attacks. Subjects took a mean (SD) of 14.6 (2.45) rimegepant doses per month; the most common AEs were upper respiratory tract infection (7.1%), nasopharyngitis (6.3%), and back pain (4.3%). Through 52 weeks of open-label rimegepant (Figure A), the frequency of MMDs consistently declined; the mean 95% (confidence interval) changes from the observation period in MMDs were −5.1 (−5.49, −4.74) in Weeks 1–4 and −6.9 (−7.31, −6.56) in Weeks 49–52. The percentage of subjects with ≥50% reduction in moderate-severe MMDs from the observation period ranged from 63.6% in Weeks 1–4 to 80.9% in Weeks 49–52, ≥75% reductions ranged from 44.1% in Weeks 1–4 to 65.8% in Weeks 49–52, and 100% reductions ranged from 25.6% in Weeks 1–4 to 49.3% in Weeks 49–52 (Figure B).
Conclusion
Scheduled every other day preventive treatment dosing with rimegepant 75 mg plus PRN acute treatment dosing on nonscheduled days through 52 weeks was associated with consistent reductions in MMDs. More than 80% of subjects experienced ≥50% reduction in moderate or severe MMDs and ∼50% experienced a 100% reduction by Week 52.
Disclosure of Interest
J. Ailani Conflict with: Received clinical trial grants as a principal investigator from Allergan/Abbvie, American Migraine Foundation, Biohaven, Eli Lilly, Satsuma, and Zosano; received stock options for consulting from CtrlM, Conflict with: Received honoraria from the following: Alder/Lundbeck (speaking, consulting), Allergan/Abbvie (speaking, consulting), Amgen (speaking, consulting), Biohaven (speaking, consulting), GlaxoSmithKline (consulting), Eli Lilly and company (speaking, consulting), Impel (consulting), Theranica (consulting), Axsome (consulting), Neso (consulting), Aeon (data advisory board), Teva (speaking, consulting), Satsuma (consulting), Current Pain and Headache Reports (section editor), NeurologyLive (editorial board), SELF (medical advisory board), Medscape (advisory board), D. Kudrow Conflict with: Received fees for advisory board from Alder, Biohaven, Eli Lilly, Amgen, and Xoc and for speaker’s bureau from Xoc, Teva, Amgen, Novartis, and Eli Lilly; received research support from Amgen, Novartis, Eli Lilly, Teva, Alder, Biohaven, Biogen, and Roche-Genentech, T. Smith Conflict with: Received fees for speaker's bureau from Amgen, Allergan/Abbvie, Biohaven, Novartis, and Lilly and for advisory boards or consultancies from Allergan/Abbvie, Biohaven, Amgen, Lilly, Alder/Lundbeck Impel Neuropharma, Neurolief, Nocira, Theranica, Teva, and Vorso/Nesos. He has received research support from Amgen, Alder/Lundbeck, Lilly, Teva, Allergan/Abbvie, Biohaven, Electrocore, Novartis, Novo Nordisk, Impel Neuropharma, Aeon, Charleston Labs, Nocira, Teva, Theranica, and Vorso/Nesos, R. Lipton Conflict with: Received research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; rreceives royalties from Wolff’s Headache (8th Edition, Oxford Press University, 2009) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta; holds stock or options in Biohaven Pharmaceuticals, Manistee, and CntrlM, P. Goadsby Conflict with: Reports grants and personal fees from Amgen and Eli-Lilly and Company, grant from Celgene, and personal fees from Alder Biopharmaceuticals, Aeon Biopharma, Allergan, Biohaven Pharmaceuticals Inc., Clexio, Electrocore LLC, eNeura, Epalex, GlaxoSmithKline, Impel Neuropharma, Lundbeck, MundiPharma, Novartis, Pfizer, Sanofi, Santara Therapeutics, Teva Pharmaceuticals, Trigemina Inc., WL Gore, and personal fees from MedicoLegal work, Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer; and a patent magnetic stimulation for headache assigned to eNeura without fee, A. Thiry Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, C. Jensen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, L. Kamen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, R. Croop Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals.
Fayyaz Ahmed1, Ho-Tin Wong2, Modar Khalil2 and Somayeh Nasergivehchi3,*
1Department of Neurosciences, Hull University Teaching Hospitals, Hull, UK 2 Hull York Medical School, Hull, UK
2Department of Neurosciences, , Hull University Teaching Hospitals, , Hull, United Kingdom
3neurology, Tehran University of Medical Science, Tehran, Iran, Islamic Republic Of
Introduction
Migraine affects women three times more than men, with migraine prevalence reaching 24% in females aged 30–39 years. Treatment of migraine, particularly during pregnancy, is challenging because of fetal and maternal risks. OnabotulinumtoxinA(Botox) is approved as a preventive treatment for adult patients with chronic migraine, although its impact on pregnancy is unknown.
Objectives
In this study, we will report the outcome of pregnant patients with CM exposed to onabotulinum toxin.
Methods
Previously, we reported a mean 3.5 years (3 months-7 years) follow-up of a cohort of 45 patients exposed to onabotulinumtoxinA for CM treatment during their pregnancy1. In the new update, 36 patients were added to the cohort of pregnant CM patients who suffered from CM and were treated with onabotulinumtoxinA(Botox). The toxin is administered as per PREEMPT paradigm. Same as the first phase of the study, all reproductive-age female patients who received onabotulinumtoxinA(Botox), were given advice on contraception because of the unknown impact of this toxin on pregnancy. They are asked to report pregnancy when they are appraised on the risk/benefit of treatment continuation. All patients are consented for access to their medical records and pregnancy outcome and those who wished to continue are asked to sign a disclaimer. Pregnancy outcome data were collected on all patients for the mode of delivery, birth weight and congenital malformation, and any other unexpected outcomes.
Results
the first report of this experience on 45 patients was published in 2020. Over 10 years period, 81 patients reported pregnancy while receiving onabotulinumtoxinA(Botox). Forty-seven patients received treatment in the first trimester, while 34 received treatment a few weeks before conception. Fifty-seven patients wished to continue with further treatment at the three-monthly interval, while 24 decided to stop the medicine. All patients were followed up three monthly. Those on treatment continued to show a good response (N = 57), and 20/24 who stopped treatment relapsed 4–6 months following the last treatment. Four remained in remission. 17/20 restarted treatment after pregnancy, while three decided to try oral prophylaxis. Apart from 1 miscarriage in the treatment group, all patients had full-term healthy babies of normal birth weight and no congenital malformations. The patient with miscarriage continued treatment and got pregnant twice after that with normal full-term deliveries.
Conclusion
Based on our experience with 81 pregnant patients with chronic migraines over the past 10 years, onabotulinumtoxinA(Botox) is a safe drug and could be considered a good treatment option for CM during pregnancy.
Disclosure of Interest
None Declared.
Reference
Kathleen Mullin1, Jelena M. Pavlovic2, Susan Hutchinson3, Richard B. Lipton2, Christopher M. Jensen4,*, Alexandra Thiry4, Lisa Kamen4, Vladimir Coric4 and Robert Croop4
1New England Institute for Neurology and Headache, Stamford, CT, United States
2Albert Einstein College of Medicine, Bronx, NY, United States
3Orange County Migraine & Headache Center, Irvine, CA, United States
4Biohaven Pharmaceuticals, New Haven, CT, United States
Introduction
Preference of medication, satisfaction with medication, and clinical global impression of change (CGI-C) are useful outcomes in migraine clinical trials. Rimegepant is an orally administered small molecule CGRP receptor antagonist for the acute and preventive treatment of migraine. Previously, subjects indicated preferences for and satisfaction with rimegepant 75 mg, and investigators rated it highly on the CGI-C.
Objectives
Assess preference for and satisfaction with open-label rimegepant as well as CGI-C over 1 year of use as a preventive treatment and acute treatment for migraine.
Methods
This 1-year open-label extension phase of a 12-week, phase 2/3, randomized, double-blind, placebo-controlled study (NCT03732638) included adults aged ≥18 years with a history of 4–18 moderate-severe monthly migraine attacks. Subjects completing 12 weeks of double-blind treatment with rimegepant 75 mg or placebo every other day could continue with open-label treatment with rimegepant 75 mg every other day for preventive treatment of migraine for 52 weeks. On nonscheduled dosing days, subjects could take rimegepant 75 mg up to once per day as needed for acute treatment of migraine. Exploratory objectives included evaluating the effect of rimegepant on Preference of Medication (PoM), Satisfaction with Medication (SM), and CGI-C scales. The PoM is a subject-rated measure of preference of study medication compared with previous medications to treat migraine pain. The SM is a subject-rated measure of satisfaction with the study medication to treat migraine headaches. The CGI-C is an observer-rated rating of subject total improvement since study entry. The PoM, SM, and CGI-C were evaluated at Weeks 12 and 52 of the open-label extension phase (ie, overall study Weeks 24 and 64).
Results
Of the 741 subjects treated in the double-blind treatment phase, 603 (81.4% [rimegepant n = 301, placebo n = 302]) were treated in the open-label extension phase. The open-label treated population had a mean (SD) age of 42.6 (13.10) years and was 82.7% female, with a mean (SD) history of 7.9 (2.74) moderate-severe monthly attacks. The percentages (95% CI) of subjects who preferred rimegepant to their previous migraine treatments at Week 12 (n = 357) and Week 52 (n = 246) were 82.6% (78.3, 86.2) and 85.2% (80.4, 89.0), respectively. The percentages (95% CI) of subjects completely satisfied with rimegepant at Week 12 and Week 52 were 32.7% (28.2, 37.6) and 47.2% (41.5, 53.0), respectively, and the majority of the other subjects reported being very satisfied. The percentages (95% CIs) of subjects considered improved on the CGI-C scale at Weeks 12 and 52, respectively, were 95.1% (92.9, 96.7) and 98.3% (96.4, 99.2). Results at Week 52 are shown in the Figure.
Conclusion
Large majorities of subjects who used open-label rimegepant for both preventive treatment and acute treatment of migraine over 1 year preferred rimegepant to prior migraine medications, were satisfied with rimegepant, and experienced clinical improvement.
Disclosure of Interest
K. Mullin Conflict with: Serves as a consultant, advisory board member, or has received honoraria from Amgen, Teva, Theranica, Vorso, Biohaven, electroCore, and Eli Lilly, J. Pavlovic Conflict with: Receives funding from the NIH/NIA, Conflict with: Served as a consultant and/or advisory board member for Allergan/Abvie, Alder/Lundbeck, Amgen/Novartis, Biohaven and Dr. Reddy’s Laboratories, S. Hutchinson Conflict with: Served as a consultant/advisory board member for Alder/Lundbeck, Allergan/Abbvie, Amgen, Biohaven, Currax, electroCore, Impel, Lilly, Novartis, Teva, Theranica, and Upsher-Smith and is on the speaker’s bureau for Allergan/Abbvie, Amgen, Biohaven, Impel, Lilly, Novartis, Teva, Theranica, and Upsher-Smith, and Teva, R. Lipton Conflict with: Received research support from the NIH; receives support from the Migraine Research Foundation and the National Headache Foundation; receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis; receives royalties from Wolff’s Headache (8th Edition, Oxford Press University, 2009) and Informa, Conflict with: Serves on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache but is not paid for his roles on Neurology or Headache; reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta; holds stock or options in Biohaven Pharmaceuticals, Manistee, and CntrlM, C. Jensen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, A. Thiry Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, L. Kamen Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, V. Coric Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals, R. Croop Conflict with: Employed by and holds stock/stock options in Biohaven Pharmaceuticals.
John Rothrock, Alison Koutsandreas and Lea Armstead
Neurology, Inova Health/University of Virginia, Fairfax, United States
Introduction
Serial injection therapy with onabotulinumA (BotoxA) is often effective for chronic migraine (CM), but some patients who improve frequently “plateau” at a level wherein their headache burden is still substantial.
Objectives
To determine whether the addition of atogepant 60 mg daily to ongoing treatment with BotoxA in partial positive responders to injection therapy is safe, well-tolerated and potentially synergistic
Methods
To a clinic population of CM patients who had been receiving serial BotoxA injection therapy for at least 1 year, who had experienced a partial positive response, and whose headache burdens had remained stable for the last two consecutive 12 week intervals between treatments we offered the option of adding atogepant 60 mg daily. A “partial positive response” was defined as at least a 50% reduction in mean monthly migraine days or at least a 50% reduction in migraine burden index relative to pre-Botox status.
In those patients electing to receive atogepant we assessed mean monthly migraine days, mean monthly headache days, mean monthly days of functionally incapacitating headache, mean monthly days of symptomatic medication use, MIDAS scores and mean “migraine burden index” (MBI: a calculation based on headache frequency and severity) for the 3 months preceding initiation of treatment with atogepant. For all patients we reassessed these same variables 12 weeks following initiation of treatment with atogepant, coinciding with the time of the patient’s next scheduled BotoxA treatment. Any other prophylactic therapy was stopped at least 1 month prior to study entry.
A patient was considered to be a positive responder to polytherapy with BotoxA and atogepant if he/she completed the 12 week treatment period and reported a 50% or greater reduction in mean monthly migraine days relative to their pre-atogepant status (primary endpoint).
Results
314 patients patients with CM met our criteria for participation. 234 (74.5%) elected to continue BotoxA and add atogepant.
Of the 234 patients, 211 (90%) completed the 12 week treatment period. 4 patients (2%) discontinued atogepant consequent to adverse events (nausea, non-specific “dizziness”, fatigue, constipation or some combination thereof), none of which were clinically serious.
Of the 211 patients, 132 (63%) achieved the primary treatment endpoint of a 50% reduction in mean monthly migraine days experienced over the 12 week treatment period relative to their pre-atogepant status. As for the secondary endpoints, mean monthly headache days declined by 6.6 days, mean functionally incapacitating headache days by 2.7 days, mean monthly days of symptomatic medication use by 5.4 days, MIDAS score by 21.6 and mean MBI by 16.6.
Conclusion
Adding atogepant 60 mg to the prophylactic regimen of CM patients receiving BotoxA and experiencing a partial positive treatment response to the neurotoxin represents a safe, well-tolerated and potentially synergistic treatment intervention.
Disclosure of Interest
None Declared.
Catarina Fernandes1,*, Isabel Costa2, Joana Lopes3, Bruno Silva4 and Isabel Luzeiro1
1Neurology, Hospitalar and University Center of Coimbra, Portugal
2Neurology, Hospitalar and University Center of Coimbra, Coimbra
3Neurology, Hospitalar Center of Baixo Vouga, Aveiro
4Neurology, Hospitalar Center of Leiria, Leiria, Portugal
Introduction
The onabotulinumtoxinA (onabotA) is an injectable preventive treatment of chronic migraine (CM), in 12 week’s intervals. The wearing-off effect has been previously described in the literature, usually in the two weeks before next treatment.
Objectives
The aim of our study was to evaluate the wearing-off and delayed-on phenomena in patients under onabotA treatment and to recognize possible predictive features of better therapeutical response.
Methods
We designed a retrospective study of patients with CM and at least two treatments with onabotA from January 2015 until December of 2021. We proceeded to demographic and clinical characterization and evaluation of onabotA therapeutic response. Statistical analyses were performed with SPSS software.
Results
We included 60 patients (95,1% female) diagnosed with CM with a mean age of migraine diagnosis of 31,8 ± 14,2 years. On average, before onaBotA treatment patients had around 20,0 attacks per month. In 45,3% we noticed a therapeutical response after the first treatment and 34 patients reported at least one adverse event after the injections, headache (25,0%) were the most reported. 50 patients (86,2%) showed a decrease in duration of headache attacks and a mean intensity of attacks decrease of 3 points in pain visual analog scale (VAS). However, 47 patients (85,5%) reported a subjective delayed onset of therapeutic effect, the most (52,7%) referred improvement only between 1 to 5 days after the onabotA administration. The wearing-off effect was noticed in 36 patients (66,7%) before the next injection of onabotA and the majority (50,9%) between the 10th to 12th week post treatment. No correlation was found between delayed-on and wearing-off effect in our cohort. All the patients that do not reported wearing-off were under the 195 units PREEMPT protocol, however statistic correlation was not found (p = 0,07).
Conclusion
To summarize, most patients with CM receiving onabotA experience a delayed onset of the therapeutical effect and a wearing-off effect in the last two weeks before next treatment. More studies are needed to discover clinical issues that predict a risk of loss of onabotA effect and to explore the possibility of shortening intervals or a different number of units protocol in selected patients.
Disclosure of Interest
None Declared.
References
Alvaro Sierra Mencia, Lucinia Colilla Cantalejo, Ana Echavarria Iñiguez, Andrea Recio Garcia, Yesica Gonzalez Osorio, Angel L. Guerrero Peral and David Garcia-Azorin
Headache Unit, Hospital Clinico de Valladolid, Valladolid, Spain
Introduction
Alcohol induced headache is one of the commonest secondary headaches. Delayed alcohol-induced headache, also known as hangover headache, is defined by the International Classification of Headache Disorders (ICHD) (code: 8.1.4.2) as a headache developing within 5–12 hours after ingestion of alcohol and resolving within 72 hours of onset. Phenotypic characteristics proposed by ICHD include bilateral location, pulsating quality, and aggravation by physical activity
A study carried out in our center, surveying 1108 students, described that the headache was more frequently holocranial and oppressive, and sometimes increasing when standing from decubitus, so suggesting a possible low cerebrospinal fluid pressure as the cause, at least in part, of this headache (1).
A prospective design, avoiding participant recall bias, could help to better elucidate the characteristics of this type of headache
Objectives
We aimed to evaluate the characteristics of delayed alcohol-induced headache and the factors associated with its presentation
Methods
Longitudinal, prospective study was carried out. Healthy volunteers aged 18–40 years were recruited. They freely decided to consume alcohol in a more than recommended amount in a recreational basis. In a first phase, demographic and clinical data were collected, including previous history of headache. They were instructed to complete a questionnaire during alcohol consumption, collecting the amount of alcohol ingested as well as other drinks and foods. Finally, in another questionnaire, they reported the characteristics of the headache present during the hangover, including its duration
Results
We included 32 participants, who recorded 96 episodes of alcohol consumption and hangover. The median age was 22 years (interquartile range (IQR): 21–24), 72% were women, and 47% had a previous history of primary headache, mainly migraine. The median alcohol intake during the episodes was 252 (IQR: 192–336) grams of pure alcohol.
Headache was reported as a hangover symptom in 55/96 (57%) episodes. The median duration of the headache was 2 hours (IQR: 2–3). Pain was holocraneal in 95% of episodes. The most frequent pain locations were frontal (98.2%) and temporal (36.4%). The most frequent pain character described were oppressive (67.2%) and stabbing (27.3%). Median pain intensity (visual analogical scale) was 6 (IQR: 4–6). Phonophobia and photophobia appeared respectively in 90.9% and 98.2% of the episodes. Appearance or increasing with orthostatism was observed in 49/55 (89%) of the episodes. Finally, 53.3% of patients with a history of primary headache described their hangover-related headache as like their previous headache
Conclusion
In our sample, headache phenotype of delayed alcohol-induced headache combined migraine and intracranial hypotension headache characteristics.
Disclosure of Interest
None Declared.
Reference
Catherine D. Chong, Simona Nikolova1, Gina Dumkrieger1, Teresa Wu2, Visar Berisha3, Jing Li4, Katherine Ross5 and Todd J. Schwedt1
1Neurology, Mayo Clinic, Phoenix
2School of Computing and Augmented Intelligence
3College of Health Solutions, Arizona State University, Tempe
4School of Industrial and Systems Engineering, Georgia Tech, Atlanta
5Neurology, Phoenix VA Health Care System, Phoenix, United States
Introduction
The thalamus plays an integral role in the pathomechanism of pain and headache. Post-traumatic headache (PTH), which often has a migraine-like phenotype, is the most common symptom following mild traumatic brain injury (mTBI), yet the role of the thalamus in PTH remains unclear.
Objectives
This study investigated subthalamic volume and iron accumulation using T1 and T2* magnetic resonance imaging (MRI) in individuals with PTH and healthy controls to determine whether these MRI measures associate with the presence and severity of post-mTBI symptoms including PTH.
Methods
107 participants underwent multimodal T1-weighted and T2* brain magnetic resonance imaging. Thalamic subfield volume and thalamic iron accumulation were explored in 52 individuals with acute PTH (mean age = 41.3; SD = 13.5), imaged on average 24 days post mTBI, and compared to 55 healthy controls (mean age = 38.3; SD = 11.7) without history of mTBI or migraine. Symptoms related to mTBI and headache characteristics were assessed between 0–59 days post-mTBI (n = 52) and again at 3-month follow-up (n = 46) using the Symptom Evaluation of the Sports Concussion Assessment Tool (SCAT-5) and a detailed headache history questionnaire.
Results
Relative to healthy controls, individuals with acute PTH had significantly less volume (p = 0.003) and more iron deposition (p = 0.048) in the left lateral geniculate nucleus (LGN). Post-hoc correlations in individuals with PTH revealed a positive relationship between left LGN T2* iron deposition and SCAT-5 symptom severity score at baseline (p = 0.039) and maximum headache severity at 3-month follow-up (p = 0.005).
Conclusion
Individuals with acute PTH had less volume and higher iron deposition in the left LGN relative to healthy controls. Higher iron deposition in the left LGN might reflect mTBI symptom load and poor headache recovery.
Disclosure of Interest
C. Chong Conflict with: Amgen, Conflict with: NIH and Department of Defense, S. Nikolova: None Declared, G. Dumkrieger Conflict with: Amgen, T. Wu: None Declared, V. Berisha Conflict with: co-founder and has equity in Aural Analytics, Inc, J. Li: None Declared, K. Ross: None Declared, T. Schwedt Conflict with: Amgen, DOD, NIH, Conflict with: serves on the Board of Directors for the American Headache Society and the American Migraine Foundation. He has received research support from the American Migraine Foundation, Amgen, Henry Jackson Foundation, Mayo Clinic, National Institutes of Health, Patient-Centered Outcomes Research Institute, and US Department of Defense. Within the past 12 months, he has received personal compensation for serving as a consultant or advisory board member for AbbVie, Axsome, Biodelivery Science, Collegium, Eli Lilly, Ipsen, Linpharma, Lundbeck, Novartis, and Satsuma. He holds stock options in Aural Analytics and Nocira. He has received royalties from UpToDate.