Eur J Neurol. 2022 Jan 31. doi: 10.1111/ene.15260. Online ahead of print.
Authors: Luigi Francesco Iannone, Davide Fattori, Silvia Benemei, Alberto Chiarugi, Pierangelo Geppetti, Francesco De Cesaris
Background: Guidelines for migraine prophylaxis suggest stopping medication after 6-12 months to reevaluate treatment appropriateness. The Italian Medicines Agency (AIFA) set a mandatory regulation to stop anti-CGRP (calcitonin gene related protein) pathway monoclonal antibody (anti-CGRP mAbs) treatments for 3 months after 12-months of treatment. Herein, we assess the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients, evaluating predictive factors of sustained response.
Methods: A monocentric prospective cohort study, enrolling 44 severe (resistant to ≥3 preventive treatments) chronic migraine patients (all with medication-overuse), treated with erenumab (54.5%) or galcanezumab (45.5%) for 12-months, who discontinued treatment for three months and then restarted for one month.
Results: Overall, patients reported an increasing deteriorating trend during the three months of discontinuation. Monthly migraine days (MMDs), number of analgesics, days with at least one analgesic used, a ≥50% response rate (reduction in MMDs), and MIDAS and HIT-6 total scores, remained lower than baseline values, but increased if compared to month-12 of treatment. All outcome measures decreased again during the month of retreatment. Patients who did not meet criteria for restarting treatment had lower MIDAS (p=0.03) and HIT-6 (p=0.01) scores at baseline and better outcome measures during discontinuation compared to patients who restarted treatment.
Conclusions: In most patients, the 3-month discontinuation of anti-CGRP mAbs resulted in progressive migraine deterioration that was rapidly reverted by retreatment. However, one-fourth of patients, who reported better quality of life indices before treatment, showed a sustained beneﬁt during discontinuation and did not need retreatment.
• PMID: 35098620
Ther Adv Chronic Dis. 2022 Jan 24;13:20406223211065235. doi: 10.1177/20406223211065235. eCollection 2022.
Authors: Yohannes W Woldeamanuel 1 , Robert P Cowan
Background: Computerized migraine diagnostic tools have been developed and validated since 1960. We conducted a systematic review to summarize and critically appraise the quality of all published studies involving computerized migraine diagnostic tools.
Methods: We performed a systematic literature search using PubMed, Web of Science, Scopus, snowballing, and citation searching. Cutoff date for search was 1 June 2021. Published articles in English that evaluated a computerized/automated migraine diagnostic tool were included. The following summarized each study: publication year, digital tool name, development basis, sample size, sensitivity, speciﬁcity, reference diagnosis, strength, and limitations. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was applied to evaluate the quality of included studies in terms of risk of bias and concern of applicability.
Results: A total of 41 studies (median sample size: 288 participants, median age = 43 years; 77% women) were included. Most (60%) tools were developed based on International Classiﬁcation of Headache Disorders criteria, half were self-administered, and 82% were evaluated using face-to-face interviews as reference diagnosis. Some of the automated algorithms and machine learning programs involved case-based reasoning, deep learning, classiﬁer ensemble, ant-colony, artiﬁcial immune, random forest, white and black box combinations, and hybrid fuzzy expert systems. The median diagnostic accuracy was concordance = 89% [interquartile range (IQR) = 76-93%; range = 45-100%], sensitivity = 87% (IQR = 80-95%; range = 14-100%), and speciﬁcity = 90% (IQR = 77-96%; range = 65-100%). Lack of random patient sampling was observed in 95% of studies. Case-control designs were avoided in all studies. Most (76%) reference tests exhibited low risk of bias and low concern of applicability. Patient ﬂow and timing showed low risk of bias in 83%.
Conclusion: Different computerized and automated migraine diagnostic tools are available with varying accuracies. Random patient sampling, head-to-head comparison among tools, and generalizability to other headache diagnoses may improve their utility.
• PMID: 35096362
J Neurol Sci. 2022 Jan 26;434:120170. doi: 10.1016/j.jns.2022.120170. Online ahead of print.
Authors: Todd D Rozen, Zlatko Devcic, Beau Toskich, Melanie P Caserta, Sukhwinder J S Sandhu, Thien Huynh, Young Erben
Objective: To determine if a speciﬁc population of patients with a daily persistent headache from onset have underlying nutcracker physiology and to propose a pathogenesis model for their headaches utilizing a novel MRI protocol.
Background: A single case report of a daily persistent headache associated with nutcracker syndrome was recently published. As the left renal vein has a connection to the spinal lumbar veins and secondarily to the spinal epidural venous plexus, one could hypothesize that renal vein compression could lead to persistent headache by altering spinal and cerebral venous pressure with secondary alterations in CSF pressure. The authors have published on a series of patients with a unique subtype of daily persistent headache from onset that appears to be caused by an abnormal reset of CSF pressure to an elevated state. The goal of the present study was to look for the presence of nutcracker physiology in this unique patient subgroup and to propose a pathogenesis model utilizing a novel MRI protocol to evaluate for retrograde lumbar vein ﬂow and regional spinal epidural venous plexus congestion.
Materials and methods: Case series of patients with a daily persistent headache from onset, head pressure, and whose headaches worsened in the Trendelenburg position. Patients were imaged with a 3 T MRI in the supine position from the lower diaphragm to the top of the pelvis with a dynamic angiogram centered over the left L2 lumbar vein.
Results: 12 patients were studied of which 8 were positive for left renal vein compression, lumbar vein dilation and early spinal epidural venous plexus enhancement. All were women. Mean age of headache onset was 39 years. Six of the 8 patients had a lumbar puncture, and all had a normal opening pressure. All improved with CSF volume removal although pain resolution lasted from hours to 6 months. The patient's headaches were marked by holocranial pressure and the majority displayed migrainous associated symptoms although none had a prior headache history. They did not complain of typical symptoms or signs of nutcracker syndrome.
Conclusion: We suggest that patients with a daily persistent headache from onset who worsen in the Trendelenburg position may have underlying nutcracker physiology. From our imaging ﬁndings, it can be hypothesized that left renal vein compression leads to retrograde ﬂow through the valveless lumbar vein which then leads to spinal epidural venous congestion and subsequently causes congestion of the cerebral venous system leading to an elevation of CSF pressure and to a daily headache. What appears to be unique about these patients is that a daily headache is their only manifestation of nutcracker physiology.
• PMID: 35093724
Lancet Neurol. 2022 Jan 27;S1474-4422(21)00409-9. doi: 10.1016/S1474-4422(21)00409-9. Online ahead of print.
Authors: Linda Al-Hassany, Peter J Goadsby, A H Jan Danser, Antoinette MaassenVanDenBrink
Migraine is the second most disabling disorder across all age groups worldwide. Since 2018, two classes of drugs that inhibit the actions of calcitonin gene-related peptide (CGRP), which is implicated in migraine pathophysiology, have become available: gepants (CGRP receptor antagonists) and monoclonal antibodies directed against CGRP or its receptor. Despite phase 3 clinical trials and some real world evidence, knowledge of the pharmacology and related clinical effects of these drugs is low, and trial data are not necessarily generalisable to all populations. Additionally, several pharmacodynamic processes affected by both gepants and monoclonal antibodies to CGRP and its receptor are not fully understood. Sex, body-mass index, age, ethnic background, and other characteristics, which are subject to considerable variation, might affect the pharmacokinetics of these therapies, especially gepants. If studies conﬁrm this possibility, these characteristics could assist clinicians in choosing the optimal treatment for patients with migraine. The choice between a gepant or monoclonal antibody should be made carefully, taking into consideration a patient's comorbidities and preferences. As more becomes known about CGRP-targeted therapies, management based on the characteristics of patients could have a more prominent role in the treatment of migraine.
• PMID: 35093196
J Headache Pain. 2022 Jan 29;23(1):19. doi: 10.1186/s10194-022-01391-2.
Authors: Xinyu Tao, Zeya Yan, Jiahao Meng, Wei Wang, Qiling Dai, Qiufeng Zhou, Zhifeng Wang, Zhong Wang
Background: Migraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efﬁcacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies.
Methods: MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study.
Results: We pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a signiﬁcant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no signiﬁcant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo.
Conclusions: Atogepant has shown good efﬁcacy and safety in the prophylactic treatment of migraine, and further studies are expected.
• PMID: 35093013
J Headache Pain. 2022 Jan 29;23(1):18. doi: 10.1186/s10194-022-01389-w.
Authors: Nazia Karsan, Karthik Nagaraj, Peter J Goadsby
Background: Whilst cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalalgias (TAC's), they have also been reported in migraine. Identiﬁcation and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management.
Methods: Migraineurs seen in a tertiary headache service between 2014 and 2018 (n = 340): cohort one, and a separate cohort of headache patients seen between 2014-May 2021 reporting voice change, or throat swelling, or both, as CAS were selected (n = 64): cohort two. We performed a service evaluation of our records regarding age, sex, diagnosis, headache and CAS frequency and laterality as acquired from the ﬁrst consultation, during which a detailed headache history is taken by a headache trained physician.
Results: Cohort 1: Mean age 43 (range 14-94, SD 15). The most common diagnosis was chronic migraine (78%). Median monthly headache frequency was 26 days (IQR 15-75). At least one CAS was reported in 74%, with a median of two (IQR 0-3). The most common were nasal congestion (32%), lacrimation (31%) and aural fullness (25%). Most patients reported their most common headache as unilateral (80%) and with it strictly unilateral CAS (64%). There was a positive association between headache and CAS laterality (χ21 = 20.7, P
< 0.001), with a positive correlation between baseline headache frequency and number of CAS reported (r
= 0.11, P = 0.047). Cohort two: mean age 49 (range 23-83, SD 14). Diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described trigeminal distribution pain; 25% involving all three divisions. Throat swelling was reported by 54, voice change by 17, and both by 7. The most common CAS reported were lacrimation (n = 47), facial swelling (n = 45) and rhinorrhoea (n = 37). There was signiﬁcant agreement between the co-reporting of throat swelling (χ21 = 7.59, P = 0.013) and voice change (χ21 = 6.49, P = 0.02) with aural fullness.
Conclusions: CAS are common in migraine, are associated with increasing headache frequency and tend to lateralise with headache. Voice change and throat swelling should be recognized as possible parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic endophenotype.
• PMID: 35093009
J Headache Pain. 2022 Jan 26;23(1):16. doi: 10.1186/s10194-021-01365-w.
Authors: Astrid Wiggers, Håkan Ashina, Nouchine Hadjikhani, Abhay Sagare, Berislav V Zlokovic, Martin Lauritzen, Messoud Ashina
Migraine is a ubiquitous neurologic disease that afﬂicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experimental data have conﬁrmed that intravenous infusion of these vasoactive peptides induce migraine attacks in people with migraine, but it remains a point of scientiﬁc contention whether their site of action lies outside or within the central nervous system. In this context, it has been hypothesized that transient dysfunction of brain barriers before or during migraine attacks might facilitate the passage of migraine-inducing peptides into the central nervous system. Here, we review evidence suggestive of brain barrier dysfunction in migraine pathogenesis and conclude with lessons learned in order to provide directions for future research efforts.
• PMID: 35081902
Curr Pain Headache Rep. 2022 Jan 25;1-6. doi: 10.1007/s11916-022-01005-1. Online ahead of print.
Authors: Kuan-Po Peng, Shuu-Jiun Wang
Purpose of review: The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years.
Recent ﬁndings: Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies conﬁrmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms.
• PMID: 35076874
Headache. 2022 Jan 25. doi: 10.1111/head.14259. Online ahead of print.
Authors: Richard B Lipton, Robert A Nicholson, Michael L Reed, Andre B Araujo, Dena H Jaffe, Douglas E Faries, Dawn C Buse, Robert E Shapiro, Sait Ashina, M Janelle Cambron-Mellott, John C Rowland, Eric M Pearlman
Objective: The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States.
Background: Regularly updating population-based views of migraine in the United States provides a method for assessing the quality of ongoing migraine care and identifying unmet needs.
Methods: The OVERCOME (US) 2018 migraine cohort involved: (I) creating a demographically representative sample of US adults using quota sampling (n = 97,478), (II) identifying people with active migraine in the past year via a validated migraine diagnostic questionnaire and/or self-reported medical diagnosis of migraine (n = 24,272), and (III) assessing consultation, diagnosis, and treatment of migraine (n = 21,143). The current manuscript evaluated whether those with low frequency episodic migraine (LFEM; 0-3 monthly headache days) differed from other categories on outcomes of interest.
Results: Among the migraine cohort (n = 21,143), 19,888 (94.1%) met our International Classiﬁcation of Headache Disorders, 3rd edition-based case deﬁnition of migraine and 12,905 (61.0%) self-reported a medical diagnosis of migraine. Respondents' mean (SD) age was 42.2 (15.0) years; 15,697 (74.2%) were women. Having at least moderate disability was common (n = 8965; 42.4%) and around half (n = 10,783; 51.0%) had consulted a medical professional for migraine care in the past year. Only 4792 (22.7%) of respondents were currently using a triptan. Overall, 8539 (40.4%) were eligible for migraine preventive medication and 3555 (16.8%) were currently using migraine preventive medication. Those with LFEM differed from moderate and high frequency episodic migraine and chronic migraine on nearly all measures of consulting, diagnosis, and treatment.
Conclusion: The OVERCOME (US) 2018 cohort revealed slow but steady progress in diagnosis and preventive treatment of migraine. However, despite signiﬁcant impact among the population, many with migraine have unmet needs related to consulting for migraine, migraine diagnosis, and getting potentially beneﬁcial migraine treatment. Moreover, it demonstrated the heterogeneity and varying unmet needs within episodic migraine.
• PMID: 35076091
Neurol Sci. 2022 Jan 24;1-7. doi: 10.1007/s10072-022-05910-6. Online ahead of print.
Authors: Emanuele Spina, Gioacchino Tedeschi, Antonio Russo, Francesca Trojsi, Rosa Iodice, Stefano Tozza, Aniello Iovino, Francesco Iodice, Gianmarco Abbadessa, Francesco di Lorenzo, Giuseppina Miele, Elisabetta Maida, Giovanni Cerullo, Maddalena Sparaco, Marcello Silvestro, Letizia Leocani, Simona Bonavita, Fiore Manganelli,
Luigi Lavorgna, Digital Technologies, Web and Social Media Study Group of the Italian Society of Neurology (SIN)
Background: Migraine affects more than a billion people all over the world and requires critical employment of healthcare resources. Telemedicine could be a reasonable tool to manage people suffering from headaches, and it received a big push from the COVID-19 pandemic.
Objective: This review aims to propose a practical approach for the virtual management of these patients.
Methods: To do this, we conducted a literature search, including 32 articles relevant to the topic treated in this review.
Results: The most challenging step in telemedicine applied to practical neurology remains the clinical assessment, but through a careful headache history and a recently proposed entirely virtual neurological assessment, this hitch can be easily overcome. Electronic diary compilations and virtual administration of disability-measuring scales, conversely, are the key features of effective long-term follow-up although we do not have apps that met the criteria of scientiﬁc reliability. Furthermore, tele-rehabilitation seems to be effective and has demonstrated to be a solution to alternatively treat chronic patients at home, and can be considered part of the remote management of headache patients. Moreover, virtual management of headaches ﬁnds an application in speciﬁc communities of patients, as pediatric patients and for rural communities of low- and middle-income countries suffer from health disparities, with inadequate resources and knowledge gaps.
Conclusion: Telemedicine could be promising for patients with no regular or convenient access to headache specialists and seems to be a priority in managing migraine patients to avoid non-urgent hospitalizations.
• PMID: 35075575
Curr Pain Headache Rep. 2022 Jan 22. doi: 10.1007/s11916-022-01015-z. Online ahead of print.
Authors: Pedro Augusto Sampaio Rocha-Filho, José Luiz Dias Gherpelli
Purpose of review: To review the literature on the clinical characteristics of the symptoms other than headache that occurs during a migraine attack in childhood and adolescence.
Recent ﬁndings: Premonitory symptoms (42-67%) and postdrome phase (82%) are frequent. The most frequent auras were visual. There was no association between age or sex and the occurrence of auras. Cranial autonomic symptoms are also frequent (40-70%) and are most often bilateral. Most studies suggest that age is not associated with the frequency of nausea, vomiting, photophobia, and phonophobia. Cephalic cutaneous allodynia (15-37%) and osmophobia (20-53%) are common symptoms in children with migraine. Osmophobia has low sensitivity and high speciﬁcity for the diagnosis of migraine and is associated with the severity of the migraine. Migraine is a complex disease, and although headache is its best-known symptom, other symptoms also occur frequently during migraine attacks in children and adolescents.
• PMID: 35064917
Curr Pain Headache Rep. 2022 Jan 22. doi: 10.1007/s11916-022-01011-3. Online ahead of print.
Authors: Laura Papetti, Giorgia Sforza, Ilaria Frattale, Samuela Tarantino, Fabiana Ursitti, Michela Ada Noris Ferilli, Federico Vigevano, Massimiliano Valeriani
Purpose of review: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH).
Recent ﬁndings: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little speciﬁc data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conﬂicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to ﬁll this information gap.
• PMID: 35064916
Eur J Neurol. 2022 Jan 21. doi: 10.1111/ene.15256. Online ahead of print.
Authors: Judith A Pijpers, Dennis A Kies, Erik W van Zwet, Frits R Rosendaal, Gisela M Terwindt
Background: Medication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double-blind manner the efﬁcacy of a behavioural intervention during medication withdrawal therapy.
Methods: In this concealed, double-blind, randomised controlled trial in medication overuse headache, conducted at the Leiden University Medical Center, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising of education, motivational interviewing and value-based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum-toxin-A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period.
Results: We enrolled 179 patients (90 maximal; 89 minimal intervention). At week 12, most patients achieved withdrawal in both groups (82/90 (93%) maximal intervention versus 75/89 (86%) minimal intervention, OR 2.44 (95%CI 0.83;7.23), p=0.107). At week 24, patients in the maximal intervention group had fewer medication days (mean difference -2.23, 95%CI: -3.76;-0.70, p=0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (-6.75 versus -6.22).
Conclusions: This trial suggests modest beneﬁt of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effect.
• PMID: 35064733
Neurol Sci. 2022 Jan 22. doi: 10.1007/s10072-021-05837-4. Online ahead of print.
Authors: Migliore Simone, D'Aurizio Giulia, Altamura Claudia, Brunelli Nicoletta, Costa Carmelinda, Curcio Giuseppe, Vernieri Fabrizio
Migraineurs show impaired cognitive functions interictally, mainly involving information processing speed, basic attention, and executive functions. We aimed to assess executive impairment in migraine patients with different attack frequencies through a task-switching protocol designed to assess different sub-processes of executive functioning. We enrolled 42 migraine patients and divided them into three groups based on the attack frequency: 13 subjects had episodic migraine with a low frequency (LFEM, 4-7 migraine days per month), 14 subjects had high-frequency episodic migraine (HFEM, 8-14 days) and, ﬁnally, 15 subjects presented chronic migraine (≥ 15 headache days/month, CM); we compared them to 20 healthy control (HC), matched to both gender and education. Patients with high headache frequencies (CM and HFEM) showed worse performance than LFEM and HC controls, as indicated by poor accuracy, increased switch cost, and reaction times. Our study demonstrated a difference in task-switching abilities in patients with high frequency or chronic migraine compared with low-frequency episodic migraine and healthy controls. These difﬁculties in executive control processes could be related to altered functioning of the frontal cortex and its cortical and subcortical connections.
• PMID: 35064344
J Headache Pain. 2022 Jan 21;23(1):14. doi: 10.1186/s10194-022-01388-x.
Authors: Samita Giri, Erling Andreas Tronvik, Knut Hagen
Background: Few prospective population-based studies have evaluated the bidirectional relationship between headache and affective disorder. The aim of this large-scale population-based follow-up study was to investigate whether tension-type headache (TTH) and migraine had increased risk of developing anxiety and depression after 11 years, and vice-versa.
Methods: Data from the Trøndelag Health Study (HUNT) conducted in 2006-2008 (baseline) and 2017-2019 (follow-up) were used to evaluate the bidirectional relationship between migraine and TTH and anxiety and depression measured by Hospital Anxiety and depression Scale (HADS). The population at risk at baseline consisted of respectively 18,380 persons with HADS score ≤ 7 and 13,893 without headache, and the prospective data was analyzed by Poisson regression.
Results: In the multi-adjusted model, individuals with HADS anxiety (HADS-A) and depression scores (HADS-D) of ≥8 at baseline nearly doubled the risk of migraine (Risk rations (RR) between 1.8 and 2.2) at follow-up whereas a 40% increased risk (RR 1.4) was found for TTH. Vice versa, the risk of having HADS-A and HADS-D scores of ≥8 at follow-up were increased for TTH (RR 1.3) and migraine (RR 1.3-1.6) at baseline. Migraine with aura was associated with 81% (RR 1.81, 95% 1.52-2.14) increased risk of HADS-A score of ≥8.
Conclusions: In this large-scale population-based follow-up study we found a bidirectional relationship between anxiety and depression and migraine and TTH. For anxiety, this bidirectional association was slightly more evident for migraine than TTH.
• PMID: 35062883
J Headache Pain. 2022 Jan 21;23(1):13. doi: 10.1186/s10194-022-01385-0.
Authors: Nijasri C Suwanwela, Naruchorn Kijpaisalratana, Supatporn Tepmongkol, Wanakorn Rattanawong, Pongpat Vorasayan, Chutibhorn Charnnarong, Jarturon Tantivattana, Sirigunya Roongruang, Tatchaporn Ongphichetmetha, Poonnakarn Panjasriprakarn, Aurauma Chutinet, Wasan Akarathanawat, Jeffrey L Saver
Background: After the initiation of the COVID-19 vaccination program in Thailand, thousands of patients have experienced unusual focal neurological symptoms. We report 8 patients with focal neurological symptoms after receiving inactivated virus vaccine, CoronaVac.
Case series: Patients were aged 24-48 years and 75% were female. Acute onset of focal neurological symptoms occurred within the ﬁrst 24 h after vaccination in 75% and between 1-7d in 25%. All presented with lateralized sensory deﬁcits, motor deﬁcits, or both, of 2-14 day duration. Migraine headache occurred in half of the patients. Magnetic resonance imaging of the brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deﬁcits or structural brain injury.
Discussions: Here, we present a case series of transient focal neurological syndrome following Coronavac vaccination. The characteristic sensory symptoms, history of migraine, female predominant, and abnormal functional brain imaging without structural changes suggest migraine aura as pathophysiology. We propose that pain related to vaccine injection, component of vaccine, such as aluminum, or inﬂammation related to vaccination might trigger migraine aura in susceptible patients.
• PMID: 35062869
J Headache Pain. 2022 Jan 20;23(1):11. doi: 10.1186/s10194-021-01372-x.
Authors: Elena R Lebedeva, Anton V Ushenin, Natalia M Gurary, Denis V Gilev, Jes Olesen
Background: Deﬁning the relationship between a headache and stroke is essential. The current diagnostic criteria of the ICHD-3 for acute headache attributed to ischemic stroke are based primarily on the opinion of experts rather than on published clinical evidence based on extensive case-control studies in patients with ﬁrst-ever stroke. Diagnostic criteria for sentinel headache before ischemic stroke do not exist. The present study aimed to develop explicit diagnostic criteria for headache attributed to ischemic stroke and for sentinel headache.
Methods: This prospective case-control study included 550 patients (mean age 63.1, 54% males) with ﬁrst-ever ischemic stroke and 192 control patients (mean age 58.7, 36% males) admitted to the emergency room without any acute neurological deﬁcits or severe disorders. Standardized semi-structured interview forms were used to evaluate past and present headaches during face-to-face interviews by a neurologist on admission to the emergency room in both groups of patients. All headaches were diagnosed according to the ICHD-3. We tabulated the onset of different headaches before a ﬁrst-ever ischemic stroke and at the time of onset of stroke. We divided them into three groups: a new type of headache, the previous headache with altered characteristics and previous unaltered headaches. The same was done for headaches in control patients within one week before admission to the hospital and at the time of entry. These data were used to create and test diagnostic criteria for acute headache attributed to stroke and sentinel headache.
Results: Our previous studies showed that headache at onset of ischemic stroke was present in 82 (14.9%) of 550 patients, and 81 (14.7%) patients had sentinel headache within the last week before a stroke. Only 60% of the headaches at stroke onset fulﬁlled the diagnostic criteria of ICHD-3. Therefore, we proposed alternative criteria with a sensitivity of 100% and speciﬁcity of 97%. Besides, we developed diagnostic criteria for sentinel headache for the ﬁrst time with a speciﬁcity of 98% and a sensitivity of 100%.
Conclusions: We suggest alternative diagnostic criteria for acute headache attributed to ischemic stroke and new diagnostic criteria for sentinel headache with high sensitivity and speciﬁcity.
• PMID: 35057731
Neurol Sci. 2022 Jan 19;1-12. doi: 10.1007/s10072-021-05831-w. Online ahead of print.
Authors: Masahito Katsuki, Chinami Yamagishi, Yasuhiko Matsumori, Akihito Koh, Shin Kawamura, Kenta Kashiwagi, Tomohiro Kito, Akio Entani, Toshiko Yamamoto, Takashi Ikeda, Fuminori Yamagishi
Objective: The medication-overuse headache (MOH) prevalence has not been investigated in a general Japanese population. We performed questionnaire-based survey and revealed MOH prevalence and its characteristics. We also performed clustering to obtain insight for MOH subgrouping.
Methods: In this cross-sectional study, the 15-64-year-old population was investigated in Itoigawa during their COVID-19 vaccination under the national policy. MOH was deﬁned as ≥ 15 days/month plus self-report of use of pain medications ≥ 10 or 15 days/month in the last 3 months. Ward method and k-means + + were used to perform clustering MOH patients.
Results: Among 5865 valid responses, MOH prevalence was 2.32%. MOH was common among females and the middle-aged. Combination-analgesic is the most overused as 50%. MOH had aggravation by routine physical activity, moderate or severe pain, and migraine-like, compared to non-MOH. The 136 MOH patients could be grouped into 3 clusters. Age and frequency of acute medication use were essential factors for clustering.
Conclusions: This is the ﬁrst study of MOH prevalence in Japan. Most MOH characteristics were similar to previous reports worldwide. Public awareness of proper headache treatment knowledge is still needed. Clustering results may be important for subtype grouping from a social perspective apart from existing clinical subtypes.
• PMID: 35043356
Neuromodulation. 2022 Jan;25(1):103-113. doi: 10.1111/ner.13465.
Authors: Adnan Al-Kaisy, Stefano Palmisani, Roy Carganillo, Samuel Wesley, David Pang, Anand Rotte, Angela Santos, Giorgio Lambru
Background: Refractory chronic migraine (rCM) is a highly disabling condition for which novel safe and effective treatments are needed. Safety and long-term efﬁcacy of paresthesia-free high cervical 10 kHz spinal cord stimulation (SCS) were here prospectively evaluated for the treatment of rCM.
Materials and methods: Twenty adults with rCM (mean numbers of preventive treatments failed: 12.2 ± 3.1) were enrolled in this single-center, open-label, prospective study and implanted with a 10 kHz SCS system (Senza™ system, Nevro Corp), with the distal tip of the lead(s) positioned epidurally at the C2 vertebral level. Safety and effectiveness outcomes, such as adverse events, headache and migraine reductions, responder rates, Migraine Disability Assessment (MIDAS), Headache Impact Test-6 (HIT-6), and Migraine-Speciﬁc Quality-of-Life (MSQ), were captured up to 52 weeks after implantation.
Results: Compared to baseline, at 52 weeks postimplantation, there was a signiﬁcant reduction of mean monthly migraine days (MMD) by 9.3 days (p < 0.001). Sixty percent and 50% of patients obtained respectively at least 30% and at least 50% reduction in mean MMD. By week 52, 50% of patients' chronic pattern converted to an episodic pattern. The proportion of subjects classiﬁed with severe headache-related disability on the HIT-6, decreased from 100% to 60% at week 52. Meaningful improvements of headache-related quality of life measured by the MSQ scale were observed with mean gain of 24.9 ± 23.1 (p < 0.001) points at 52 weeks. No unanticipated adverse device effects occurred. No patients required any additional device surgical revision.
Conclusion: 10 kHz SCS may a be safe and effective neurostimulation option for rCM patients. The paresthesia-free waveform constitutes an unprecedented advantage for future methodologically sound sham-controlled studies in headache neuromodulation.
• PMID: 35041579
Headache. 2022 Jan;62(1):4-10. doi: 10.1111/head.14250.
Authors: Ada R Artemenko, Elena Filatova, Yulia D Vorobyeva, Thien Phu Do, Messoud Ashina, Alexey B Danilov
Objective: In this narrative review, we summarize clinical and experimental data on the effect of light in migraine and discuss future prospects.
Background: Effective nonpharmacological treatment of hypersensitivity to light in migraine is an unmet clinical need. Current management strategies primarily consist of seeking a dark room and avoiding light exposure. Advances in the past 2 decades have improved our understanding of the underlying pathophysiology of how migraine is inﬂuenced by light. This may provide promising avenues for novel approaches in clinical management.
Methods: We searched MEDLINE for articles published from database inception up to September 1, 2021. We used the search term "migraine" with the search terms "light," "photophobia," "treatment," "trigger," "circadian rhythm," "environment," and/or "pathophysiology."
Results: Light is commonly reported as a trigger factor of migraine attacks, however, early manifestation of photophobia and false attribution is likely the actual cause based on data deriving from retrospective, prospective, and experimental studies. The most common photophobia symptoms in migraine are exacerbation of headache by light and abnormal sensitivity to light with the underlying neural pathways likely being dependent on ongoing activity in the trigeminovascular system. Clinical studies and experimental models have identiﬁed mediators of photophobia and uncovered narrow wavebands of the light spectrum that may reduce pain intensity during a migraine attack. Consequently, novel devices have undergone exploratory clinical trials with promising results.
Conclusion: False attribution is likely the reason why light is commonly reported as a trigger factor of migraine attacks, and a prospective conﬁrmation is required to prevent unnecessary avoidance. The observation that individuals with migraine are not equally photophobic to all wavebands of the light spectrum opens the potential for innovative pain management strategies. In this context, using human-centric lighting (also called integrative lighting) to mimic the natural daylight cycle and avoid harmful wavebands through modern technology may prove beneﬁcial. Future research should identify direct and indirect consequences of light and other environmental factors in migraine to ﬁll out knowledge gaps and enable evidence-based care strategies within institutions, work environments, and other settings.
• PMID: 35041220
Headache. 2022 Jan;62(1):57-64. doi: 10.1111/head.14251.
Authors: Holly Elser, Nils Skajaa, Vera Ehrenstein, Cecilia Hvitfeldt Fuglsang, Dóra Körmendiné Farkas, Henrik Toft Sørensen
Objective: The purpose of this study was to examine overall and site-speciﬁc cancer risk among individuals diagnosed with migraine compared with the general population.
Background: Current evidence regarding migraine and risk of cancer is sparse and inconclusive.
Methods: We conducted a nationwide population-based cohort study with data collected routinely and prospectively from Danish population-based registries from 1995 to 2017. We computed the age- and sex-standardized incidence ratio (SIR) as the ratio of observed to expected cancers among patients diagnosed with migraine in the study population overall, and by encounter type of ﬁrst diagnosis (inpatient, outpatient specialty clinic, and emergency department). Site-speciﬁc cancers were grouped according to etiology.
Results: We identiﬁed 72,826 patients with a ﬁrst-time hospital migraine diagnosis. There were 3090 observed overall cancer cases among individuals diagnosed with migraine as compared with 3108 expected cases (SIR 0.99, 95% conﬁdence interval [CI]: 0.96-1.03). The cumulative incidence of all cancers combined from 1995 to 2017 among those with a ﬁrst-time migraine diagnosis was 9.47% (95% CI: 9.08-9.87). The SIRs for most cancers were consistent with absence of an association: 1.00 (95% CI: 0.94-1.06) for hormone-related cancers, 0.96 (95% CI:
0.88-1.03) for smoking-related cancers, 1.10 (95% CI: 0.98-1.24) for hematologic cancers, and 0.95 (95% CI: 0.85-1.06) for immune-related cancers. Exceptions were SIRs for gastrointestinal cancers (0.78, 95% CI: 0.70-0.87) and for cancers of neurological origin (1.57, 95% CI: 1.40-1.76).
Conclusions: For most cancer groups, our results did not support an association with migraine. The exceptions were an increased risk for cancers of neurological origin and a decreased risk for gastrointestinal cancers. These ﬁndings may reﬂect a true difference in risk among individuals with migraine, or more plausibly they reﬂect other forces, such as differences in medication use, detection bias and reverse causation, or shared risk factors.
• PMID: 35041219
Headache. 2022 Jan;62(1):36-56. doi: 10.1111/head.14249.
Authors: Evan L Reynolds, James F Burke, Lacey Evans, Faiz I Syed, Eric Liao, Remy Lobo, Wade Cooper, Larry Charleston 4th, Brian C Callaghan
Objective: The objective of this study was to understand current practice, clinician understanding, attitudes, barriers, and facilitators to optimal headache neuroimaging practices.
Background: Headaches are common in adults, and neuroimaging for these patients is common, costly, and increasing. Although guidelines recommend against routine headache neuroimaging in low-risk scenarios, guideline-discordant neuroimaging is still frequently performed.
Methods: We administered a 60-item survey to headache clinicians at the Veterans Affairs health system to assess clinician understanding and attitudes on headache neuroimaging and to determine neuroimaging practice patterns for three scenarios describing hypothetical patients with headaches. Descriptive statistics were used to summarize responses, stratiﬁed by clinician type (physicians or advanced practice clinicians [APCs]) and specialty (neurology or primary care).
Results: The survey was successfully completed by 431 of 1426 clinicians (30.2% response rate). Overall, 317 of 429 (73.9%) believed neuroimaging was overused for patients with headaches. However, clinicians would utilize neuroimaging a mean (SD) 30.9% (31.7) of the time in a low-risk scenario without red ﬂags, and a mean 67.1% (31.9) of the time in the presence of minor red ﬂags. Clinicians had stronger beliefs in the potential beneﬁts (268/429, 62.5%) of neuroimaging compared to harms (181/429, 42.2%) and more clinicians were bothered by harms stemming from the omission of neuroimaging (377/426, 88.5%) compared to commission (329/424, 77.6%). Additionally, APCs utilized neuroimaging more frequently than physicians and were more receptive to potential interventions to improve neuroimaging utilization.
Conclusions: Although a majority of clinicians believed neuroimaging was overused for patients with headaches, many would utilize neuroimaging in low-risk scenarios with a small probability of changing management. Future studies are needed to deﬁne the role of currently used red ﬂags given their importance in neuroimaging decisions. Importantly, APCs may be an ideal target for future optimization efforts.
• PMID: 35041218
J Headache Pain. 2022 Jan 17;23(1):10. doi: 10.1186/s10194-021-01378-5.
42 Authors: Karissa Johnston, Linda Harris, Lauren Powell, Evan Popoff, Vladimir Coric, Gilbert L'Italien, Curtis P Schreiber
Background: The objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks.
Methods: Eligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-speciﬁc quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free.
Results: One thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of
0.08 incremental QALYs were associated with rimegepant use.
Conclusion: For subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks.
• PMID: 35038983
Neurol Res. 2022 Jan 17;1-7. doi: 10.1080/01616412.2021.1981105. Online ahead of print.
Authors: Amir Sherafat, Adeleh Sahebnasagh, Roya Rahmany, Farhad Mohammadi, Fatemeh Saghaﬁ
Background and purpose: Migraine ranked as the eighth cause of disability worldwide. Statins with anti-inﬂammatory and vasodilatory endothelial effects have been introduced as an option for the prevention of migraine-type headaches. The current study aimed to assess the efﬁcacy and tolerability of atorvastatin for the prevention of migraine in adults.
Method: This prospective, triple-blind, randomized controlled clinical trial was performed in adult migraineurs from mid-July 2019 to late-April 2020. Patients were randomly assigned to receive atorvastatin or placebo in combination with nortriptyline for 24-weeks. The frequency of headache was the primary outcome, and intensity of the headache and quality of life (QOL) were the secondary outcomes for this study.
Results: With 34 patients in each arm, 68 patients with migraines based on the International Headache Society (IHS) criteria were enrolled in the study. At week 24, patients in the atorvastatin group experienced signiﬁcantly fewer migraine attacks than the placebo group (P-value = 0.004). Moreover, there were signiﬁcant differences between the two groups in QOL at follow-up intervals of 14 (P-value = 0.001) and 24 (P-value < 0.001) weeks. However, no signiﬁcant difference was observed in the intensity of headache was observed in both groups (P-value > 0.05). The most common adverse effects in intervention and control groups were constipation and insomnia, respectively.
Conclusion: In patients with migraine, prophylaxis with atorvastatin signiﬁcantly improved the frequency of headache and QOL over 24 weeks compared with placebo with no effect on the intensity of headache. Statins seem to be a potential promising drug for prophylaxis of migraine headaches.
• PMID: 35037597
Neurol Sci. 2022 Jan 15. doi: 10.1007/s10072-022-05888-1. Online ahead of print.
Authors: Fulya Basoglu Koseahmet, Burcu Polat, R Gokcen Gozubatik-Celik, Isil Baytekin, Muazzez Gokcen Soylu, Ayten Ceyhan Dirican, Musa Ozturk
Objective: Our purpose was to identify the ratio and severity of stigmatization in patients with migraine and epilepsy. We also collected demographic and clinical data to search for possible facilitators.
Methods: In total, 196 patients with migraine and 60 patients with epilepsy were enrolled. Neuro-QoL Stigma Scale was applied in an ofﬁce setting by a neurologist in 3 different centers. Stigma scores were calculated as standardized T scores (total, enacted, and internalized). Demographics, clinical characteristics, and treatment status of the patients were also compared in terms of stigma scores. Kruskal-Wallis test or Mann-Whitney U tests were applied for comparisons. Spearman's correlation analysis was used for the evaluation of inter-parameter correlations.
Results: Eighty-one percent of the patients with epilepsy and 72% of the patients with migraine reported being stigmatized. Total T scores were signiﬁcantly higher in the epilepsy group (50.78 ± 9.1) than the patients with migraine (44.9 ± 7.62), also than the chronic (45.86 ± 8.76) and episodic (44.7 ± 7.27) migraine subgroups (p < 0.05). T scores increased as the duration of disease increased; however, this correlation was signiﬁcant for the epilepsy group only (p < 0.05). Migraine group with prophylactic treatment had signiﬁcantly higher scores than the migraineurs without preventive therapy (p < 0.05). Enacted T scores were higher than internalized T scores in all analyzed groups and subgroups (p < 0.05).
Conclusion: Patients with migraine and epilepsy are subjected to stigma. The ratio and intensity can change in different countries. We need to increase the awareness and search for better solutions. The standardized tests are important to compare results between studies.
• PMID: 35034235
J Headache Pain. 2022 Jan 15;23(1):9. doi: 10.1186/s10194-021-01381-w.
Authors: Tiffani J Mungoven, Kasia K Marciszewski, Vaughan G Maceﬁeld, Paul M Macey, Luke A Henderson, Noemi Meylakh
Background: The precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.
Methods: Functional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.
Results: Despite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.
Conclusions: These data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.
• PMID: 35033014
Pain. 2022 Feb 1;163(2):e342-e348. doi: 10.1097/j.pain.0000000000002360.
Authors: Shuai Yuan, Iyas Daghlas, Susanna C Larsson
We conducted a Mendelian randomization study to assess whether alcohol and coffee consumption and smoking are causally associated with risk of developing migraine. Independent single-nucleotide polymorphisms associated with the potential risk factors at P < 5 × 10-8 in large-scale genome-wide association studies were selected as instrumental variables. Summary-level data for the associations of the selected single-nucleotide polymorphisms with migraine were obtained from the FinnGen consortium comprising 6687 cases and 144,780 noncases and the UK Biobank study comprising 1072 cases and 360,122 noncases. Estimates derived from the FinnGen and UK Biobank cohorts were combined using ﬁxed-effects meta-analysis. We found evidence for associations of genetically predicted alcohol consumption (odds ratio [OR] 0.54 per SD increase in log-transformed alcoholic drinks per week, 95% conﬁdence interval [CI], 0.35-0.82; P = 0.004), coffee consumption (OR 0.56 per 50% increase in coffee consumption, 95% CI, 0.45-0.70; P < 0.001), and smoking initiation (OR 1.15 for one SD increase in the prevalence of smoking initiation, 95% CI, 1.01-1.31; P = 0.038). These associations persisted in sensitivity analyses, including mutual adjustment in multivariable Mendelian randomization analyses. In reverse Mendelian randomization analyses, genetic liability to migraine was inversely associated with alcohol consumption but was not associated with coffee consumption or smoking initiation. This study provides genetic evidence in support of a protective role of moderate coffee consumption and a detrimental role of cigarette smoking in the etiology of migraine. The inverse association between alcohol consumption and migraine risk may be attributable to reverse causality.
• PMID: 35029599
J Headache Pain. 2022 Jan 12;23(1):5. doi: 10.1186/s10194-021-01371-y.
Authors: Noemi Meylakh, Luke A Henderson
Background: Migraine is a neurological disorder characterized by intense, debilitating headaches, often coupled with nausea, vomiting and sensitivity to light and sound. Whilst changes in sensory processes during a migraine attack have been well-described, there is growing evidence that even between migraine attacks, sensory abilities are disrupted in migraine. Brain imaging studies have investigated altered coupling between areas of the descending pain modulatory pathway but coupling between somatosensory processing regions between migraine attacks has not been properly studied. The aim of this study was to determine if ongoing functional connectivity between visual, auditory, olfactory, gustatory and somatosensory cortices are altered during the interictal phase of migraine.
Methods: To explore the neural mechanisms underpinning interictal changes in sensory processing, we used functional magnetic resonance imaging to compare resting brain activity patterns and connectivity in migraineurs between migraine attacks (n = 32) and in healthy controls (n = 71). Signiﬁcant differences between groups were determined using two-sample random effects procedures (p < 0.05, corrected for multiple comparisons, minimum cluster size 10 contiguous voxels, age and gender included as nuisance variables).
Results: In the migraine group, increases in infra-slow oscillatory activity were detected in the right primary visual cortex (V1), secondary visual cortex (V2) and third visual complex (V3), and left V3. In addition, resting connectivity analysis revealed that migraineurs displayed signiﬁcantly enhanced connectivity between V1 and V2 with other sensory cortices including the auditory, gustatory, motor and somatosensory cortices.
Conclusions: These data provide evidence for a dysfunctional sensory network in pain-free migraine patients which may be underlying altered sensory processing between migraine attacks.
• PMID: 35021998
Neuroepidemiology. 2022 Jan 12;1-9. doi: 10.1159/000520548. Online ahead of print.
Authors: Tissa Wijeratne, Win Sen Kuan, Anne Maree Kelly, Kevin H Chu, Frances B Kinnear, Gerben Keijzers, Richard Body, Mehmet A Karamercan, Sharon Klim, Sinan Kamona, Colin A Graham, Tom Roberts, Daniel Horner, Said Laribi, on behalf HEAD study group
Background and aim: Migraine headache is commonly diagnosed in emergency departments (ED). There is relatively little real-world information about the epidemiology, investigation, management, adherence to therapeutic guidelines and disposition of patients treated in ED with a ﬁnal diagnosis of migraine. The primary aim of the current study is to get a snapshot of assessment and management patterns of acute migraine presentations to the different settings of EDs with a view to raise awareness.
Methods: This is a planned sub-study of a prospective study conducted in 67 health services in 10 countries including Australia, New Zealand, Southeast Asia, Europe, and the UK investigating the epidemiology and outcome of adult patients presenting to ED with nontraumatic headache. Outcomes of interest for this study are demographics, clinical features (including severity), patterns of investigation, treatment, disposition, and outcome of patients diagnosed as having migraine as their ﬁnal ED diagnosis.
Results: The cohort comprises 1,101 patients with a mean age of 39 years (SD ± 13.5; 73.7% ) were female. Most patients had had migraine diagnosed previously (77.7%). Neuroimaging was performed in 25.9% with a very low diagnostic yield or signiﬁcant ﬁndings (0.07%). Treatment of mild migraine was in accordance with current guidelines, but few patients with moderate or severe symptoms received recommended treatment. Paracetamol (46.3%) and nonsteroidal anti-inﬂammatory drugs (42.7%) were the most commonly prescribed agents. Metoclopramide (22.8%), ondansetron (19.2%), chlorpromazine (12.8%), and prochlorperazine (12.8%) were also used.
Conclusions: This study suggests that therapeutic practices are not congruent with current guidelines, especially for patients with severe symptoms. Efforts to improve and sustain compliance with existing management best practices are required.
• PMID: 35021181
Neurol Sci. 2022 Jan 11. doi: 10.1007/s10072-022-05872-9. Online ahead of print.
Authors: Youjin Shen, Xiaokun Qi
Background: Vestibular migraine (VM) is considered the most common cause of spontaneous episodic vertigo and the second most common cause of vertigo. However, without a biomarker or a complete understanding of the pathophysiology, VM remains underrecognized and underdiagnosed. Therefore, deﬁnite diagnostic criteria are urgently needed. Meanwhile, VM should be clearly differentiated from other similar diseases. This paper may help clinicians improve the diagnostic rate of VM and reduce the rate of misdiagnosis. A PubMed search was performed using the following terms: vestibular migraine, migraine-associated vertigo/dizziness, migraine-related vertigo, migraine-related vestibulopathy, benign recurrent vertigo, vertiginous migraine, migraine, headache, vertigo, dizziness, and diagnosis. This paper also summarizes the diagnostic criteria and differential diagnoses of VM. The diagnosis of VM is based on the symptoms, degree, frequency, and duration of the vestibular episodes, a history of migraine, and the temporal association of migraine symptoms with vestibular episodes in at least 50% of cases, while ruling out what may be due to other reasons. In addition to vestibular symptoms and migraine, transient auditory symptoms, nausea, vomiting, and susceptibility to motion sickness may also be associated with VM. Thus, VM should be differentiated from other diseases such as Meniere's disease, benign paroxysmal positional vertigo, migraine with brainstem aura, vestibular neuritis, posterior circulation ischemia, multiple lacunar infarction, vestibular paroxysmia, motion sickness, and episodic ataxia type 2.
Conclusion: Only if the diagnostic criteria of VM and differential diagnosis can be mastered clearly, we can make a deﬁnite diagnosis and treat patients properly.
• PMID: 35015204
Neurol Sci. 2022 Jan 11. doi: 10.1007/s10072-022-05870-x. Online ahead of print.
Authors: Simona Guerzoni, Carlo Baraldi, Umberto Pensato, Valentina Favoni, Flavia Lo Castro, Maria Michela Cainazzo, Sabina Cevoli, Luca Pani
Background: Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor which has been found effective even for the treatment of chronic migraine (CM) complicated with medication overuse headache (MOH). According to the present guidelines, the treatment with erenumab should continue for up to 1 year. The aim of the present study is to explore the evolution of patients affected by CM and MOH at the baseline, after erenumab discontinuation.
Methods: One hundred and eighty-ﬁve patients affected by CM and MOH were recruited and followed up after erenumab discontinuation. The number of migraine days per month, the number of painkillers taken per month, the number of days in which one medication was used for a month were collected every 30 days for the 3 months following erenumab suspension.
Results: At the 3rd month after suspension, patients displayed a signiﬁcantly higher number of migraine days per month, a signiﬁcantly higher painkiller consumption, and a signiﬁcantly higher migraine-related disability. A high body mass index and the presence of aura were positively correlated with the relapse of CM and MOH.
Conclusion: Patients affected by CM and MOH at the baseline displayed a signiﬁcant worsening of their headaches after erenumab discontinuation.
• PMID: 35015202
Rev Neurol. 2022 Jan 16;74(2):55-60. doi: 10.33588/rn.7402.2021258.
[Article in Spanish].
Authors: R Lamas-Pérez, F J Viguera-Romero, F Sánchez-Caballero, J Martínez-Simón, A Gómez-Camello, C González-Oria
in English, Spanish
Introduction: The SARS-CoV-2 pandemic has given rise to a major change in healthcare and brought teleconsultation to the forefront. In neurology, headaches are the most frequent reason for visits.
Aim: To assess the impact of the COVID-19 pandemic on the structure of headache units in Andalusia and the adaptations made to healthcare that are potentially useful innovations that can continue to be developed when the pandemic is over.
Materials and methods: Cross-sectional observational study using an online survey of neurologists responsible for headache units and specialised consultations in Andalusia.
Results: During the state of alarm, all respondents used teleconsultation. The vast majority (92.8%) maintained some face-to-face activity, mostly for invasive techniques and new patients, using individual protection measures and as a way to avoid crowds. Half of them (50%) maintained botulinum toxin administrations at the scheduled times and 78.6% continued to prescribe monoclonal antibodies against calcitonin gene-related peptide. Altogether 78.5% are generally satisﬁed with the use of teleconsultation and 57.1% think it could be quite useful in the future. The main advantages reported were avoiding the need for the patient to travel and time savings; the disadvantages were the absence of physical examinations and difﬁculties in communicating. The most frequently expressed need for improvement was the use of video-calls.
Conclusions: Some of the changes adopted during this time could continue to be useful in the future and, in the case of headaches, teleconsultation could be used as an option for following up patients who have already been diagnosed and do not require any invasive techniques.
Title: Adaptación de las unidades de cefalea de Andalucía a la pandemia por COVID-19. Análisis del Grupo de Estudio de Cefaleas de la Sociedad Andaluza de Neurología. Introducción: La pandemia por SARS-CoV-2 ha supuesto un gran cambio en la atención sanitaria y ha dado protagonismo a la teleconsulta. En neurología, las cefaleas constituyen el motivo más frecuente de consulta. Objetivo: Evaluar el impacto de la pandemia por COVID-19 en la estructura de las unidades de cefaleas de Andalucía y las adaptaciones asistenciales potencialmente útiles tras ella. Materiales y métodos: Estudio observacional transversal mediante encuesta en línea a los neurólogos responsables de las unidades y consultas monográﬁcas de cefaleas de Andalucía. Resultados. Durante el estado de alarma, todos los encuestados usaron teleconsulta. El 92,8% mantuvo alguna actividad presencial, fundamentalmente para técnicas invasivas y pacientes nuevos, utilizando medidas de protección individual y para evitar aglomeraciones. El 50% mantuvo las administraciones de toxina botulínica en los tiempos adecuados y el 78,6% siguió prescribiendo anticuerpos monoclonales frente al péptido relacionado con el gen de la calcitonina. El 78,5% se encuentra globalmente satisfecho con el uso de la teleconsulta y el 57,1% considera que podría ser bastante útil de cara al futuro. Las principales ventajas expresadas fueron evitar el desplazamiento de los pacientes y el ahorro de tiempo; los inconvenientes, la ausencia de exploración física y la diﬁcultad de comunicación. La
Neurol Sci. 2022 Jan 10. doi: 10.1007/s10072-021-05861-4. Online ahead of print.
Authors: Austėja Dapkutė, Jurgita Vainauskienė, Kristina Ryliškienė
Background: Despite development of new therapies, migraine remains an undertreated illness. It is important to understand patients' preferences and perceptions of using a certain therapy. We present data from a nationwide Lithuanian survey of patients' experience using erenumab for the treatment of high frequency episodic and chronic migraine.
Methods: An anonymous internet survey was distributed on February-March 2021 to the members of Migraine Association of Lithuania. All adult respondents who reported using at least one dose of erenumab were included in the study.
Results: Out of 145 respondents, 75.2% had chronic migraine, and 31.7% had medication overuse headache. Patients received an average of 6 (IQR 4-9) erenumab doses. 93.1% respondents found erenumab effective, and 72.6% experienced improvement during the ﬁrst month. MHDs were reduced by
9.8 (SD 6.0) (P < 0.001), and MMDs by 7.2 (SD 5.2) days (P < 0.001). 78.6% respondents achieved ≥ 50% reduction and 47.6% achieved ≥ 75% reduction of MMDs. 13.8% patients indicated a wearing-off effect during the treatment course, and 37.8% - some wearing-off between injections. Constipation was the most frequent adverse event (32.6%). 47.2% of patients who had a positive erenumab effect and discontinued treatment experienced migraine rebound in 6 (SD 2.0) weeks.
Conclusion: Erenumab is perceived as an effective and safe treatment. Further studies are needed to investigate a post-cessation deterioration of achieved improvement.
Highlights: • Vast majority of patients experience stable or increasing effect of erenumab. • Erenumab efﬁcacy usually becomes evident during the ﬁrst month of treatment. • Erenumab is perceived signiﬁcantly better than non-speciﬁc preventive medications. • Almost 40% of patients experienced some wearing-off between injections. • Almost half of patients experience migraine rebounds after treatment cessation.
• PMID: 35006445
Cephalalgia. 2022 Jan 9;3331024211068813. doi: 10.1177/03331024211068813. Online ahead of print.
Authors: Umer Najib, Timothy Smith, Nada Hindiyeh, Joel Saper, Barbara Nye, Sait Ashina, Candace K McClure, Michael J Marmura, Serena Chase, Eric Liebler, Richard B Lipton
Aim: Evaluate the efﬁcacy and safety of non-invasive vagus nerve stimulation for migraine prevention.
Methods: After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period.
Results: Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespeciﬁed modiﬁed intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was �60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, -0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespeciﬁed subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported.
Conclusions: These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability proﬁle of this therapy.Trial Registration: ClinicalTrials.gov (NCT03716505).
• PMID: 35001643
J Neurol. 2022 Jan 8. doi: 10.1007/s00415-021-10930-x. Online ahead of print.
Authors: Chester Yan Hao Ng, Benjamin Y Q Tan, Yao Neng Teo, Yao Hao Teo, Nicholas L X Syn, Aloysius S T Leow, Jamie S Y Ho, Mark Y Chan , Raymond C C Wong, Ping Chai , Amanda Chee Yun Chan, Vijay Kumar Sharma, Leonard L L Yeo, Ching-Hui Sia, Jonathan J Y Ong
Background: An increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events.
Methods: Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies.
Results: A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23-1.51; p
= < 0.001), unspeciﬁed stroke (hazard ratio, 1.30; 95% CI, 1.07-1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03-1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07-1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14-1.42; p = < 0.001).
Conclusion: Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.
• PMID: 34997286
J Headache Pain. 2022 Jan 6;23(1):3. doi: 10.1186/s10194-021-01377-6.
Authors: Mohammad Mozafarihashjin, Mansoureh Togha, Zeinab Ghorbani, Abolfazl Farbod, Pegah Raﬁee, Fahimeh Martami
Background: Several inﬂammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls.
Methods: From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index.
Results: Serum levels of NGF were signiﬁcantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were signiﬁcantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were signiﬁcantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were signiﬁcantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ=
-0.025 and P-value=0.850).
Conclusions: Our ﬁndings suggest that NGF, BDNF, PGE2, and VEGF may play a signiﬁcant role in migraine pathogenesis and/or chroniﬁcation, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these ﬁndings.
• PMID: 34991456
J Headache Pain. 2022 Jan 3;23(1):1. doi: 10.1186/s10194-021-01374-9.
Authors: Hao Chen, Xueqian Tang, Jin Li , Bangyan Hu, Wenqin Yang, Meng Zhan, Tengyun Ma, Shijun Xu
Background: Chronic migraine places a disabling burden on patients, which is extensively modeled by the nitroglycerin (NTG)-treated animal model. Although the NF-κB pathway is involved in an increase in CGRP levels and activation of the trigeminal system in the NTG model, the relationship between NTG and neuroinﬂammation remains unclear. This study aimed to optimize a chronic NTG rat model with hyperalgesia and the ethological capacity for estimating migraine therapies and to further explore the underlying mechanism of NTG-induced migraine.
Methods: Rats were administered different doses of NTG s.c. daily or every 2 d; 30 min and 2 h later, the mechanical threshold was tested. After 9 d, the rats were injected with EB or Cy5.5 for the permeability assay. The other animals were sacriﬁced, and then, brainstem and caudal trigeminal ganglion were removed to test CGRP, c-Fos and NOS activity; Cytokines levels in the tissue and serum were measured by ELISA; and NF-κB pathway and blood-brain barrier (BBB)-related indicators were analyzed using western blotting. Immunohistochemistry was performed to observe microglial polarization and IL-17A+ T cell migration in the medulla oblongata.
Results: NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition, resulting in progressive hyperalgesia and migraine behavior. TNC neuroinﬂammation with increases in cytokines, CGRP and c-Fos and activation of the NF-κB pathway was observed, and these changes were alleviated by ibuprofen. Furthermore, NTG administration increased BBB permeability by altering the levels functional proteins (RAGE, LRP1, AQP4 and MFSD2A) and structural proteins (ZO-1, Occludin and VE-cadherin-2) to increase peripheral IL-17A permeation into the medulla oblongata, activating microglia and neuroinﬂammation, and eventually causing hyperalgesia and migraine attack.
Conclusions: This study conﬁrmed that NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition to provoke migraine, resulting in mechanical hyperalgesia and observable migraine-like behavior. Furthermore, IL-17A crossed the blood-brain barrier into the medulla oblongata, triggering TNC activation through microglia-mediated neuroinﬂammation. This process was a novel mechanism in NTG-induced chronic migraine, suggesting that IL-17A might be a novel target in the treatment of migraine.
• PMID: 34979902
J Headache Pain. 2022 Jan 3;23(1):2. doi: 10.1186/s10194-021-01367-8.
Authors: Pedro Augusto Sampaio Rocha-Filho, Pedro Mota Albuquerque, Larissa Clementino Leite Sá Carvalho, Mylana Dandara Pereira Gama, João Eudes Magalhães
Background: Neurological symptoms are frequent among patients with COVID-19. Little is known regarding the repercussions of neurological symptoms for patients and how these symptoms are related to one another.
Objectives: To determine whether there is an association between the neurological symptoms in patients with COVID-19, and to characterize the headache.
Method: This was a cross-sectional study. All hospital inpatients and health workers at the Hospital Universitario Oswaldo Cruz with a PCR-conﬁrmed COVID-19 infection between March and June 2020 were considered for the study and were interviewed by telephone at least 2-months after the acute phase of the disease. These patients were identiﬁed by the hospital epidemiological surveillance department. A semi-structured questionnaire was used containing sociodemographic and clinical data and the ID-Migraine.
Results: A total of 288 patients was interviewed; 53.1% were male; with a median age of 49.9 (41.5-60.5) years; 91.7% presented some neurological symptom; 22.2% reported some neurological symptom as the symptom that troubled them most during COVID-19. Neurological symptoms were: ageusia (69.8%), headache (69.1%), anosmia (67%), myalgia (44.4%), drowsiness (37.2%), agitation (20.8%); mental confusion (14.9%), syncope (4.9%) and epileptic seizures (2.8%). Females, those who presented with fever, sore throat, anosmia/ageusia and myalgia also presented signiﬁcantly more with headache (logistic regression). The most frequent headache phenotype was a non-migraine phenotype, was of severe intensity and differed from previous headaches. This persisted for more than 30 days in 18% and for more than 90 days in 10% of patients. Thirteen percent of those with anosmia and 11% with ageusia continued with these complaints after more than 90 days of the acute phase of the disease. Aged over 50 years, agitation and epileptic seizures were signiﬁcantly associated with mental confusion (logistic regression).
Conclusion: Headache is frequent in COVID-19, is associated with other symptoms such as fever, sore throat, anosmia, ageusia, and myalgia, and may persist beyond the acute phase of the disease.
• PMID: 34979899
J Neurol Sci. 2021 Dec 29;434:120122. doi: 10.1016/j.jns.2021.120122. Online ahead of print.
Authors: Sara Pérez-Pereda, Jorge Madera, Vicente González-Quintanilla, Marta Drake-Pérez, Clara Naima Marzal Espí, Carmen Serrano Munuera, Silvia Cusó García, Clara Aguilella Linares, María Fernández Recio, Gabriel Velamazán Delgado, Julio Pascual
Objective: To assess the frequency of symptomatic structural lesions and the diagnostic yield of conventional brain MRI in cluster headache (CH).
Background: In contrast to migraine, brain MRI is recommended in patients with CH to exclude potential mimics. The prevalence of symptomatic CH is not known.
Methods: We retrospectively analysed in detail the brain MRIs of patients diagnosed as CH in 3 Neurology Services in Spain and reviewed their clinical history. Clinical diagnoses were reassessed based on the ICHD-3 criteria.
Results: We included 130 patients: 113 (86.9%) were male; mean age at diagnosis being 41.4 years (range 7-82). Forty-nine (37.7%) showed some abnormal MRI ﬁnding. Only in two cases potential symptomatic lesions were found: one trigeminal schwannoma and one craneopharyngioma, but both presented atypical features (facial hypoesthesia on examination and episodes of prolonged duration that had progressed to continuous refractory pain without speciﬁc pattern, respectively) and therefore did not fulﬁl the ICHD-3 CH criteria. The remaining abnormal MRI ﬁndings were: white matter lesions (24 patients; 18.4%), sinus inﬂammatory changes (13; 10.0%), small arachnoid cysts (5; 3.8%), empty sella turca (3; 2.3%), and other unspeciﬁc ﬁndings (8; 6.2%). All of them were not symptomatic based on neuroimaging characteristics, clinical course and response to treatment.
Conclusions: Brain MRI in patients who meet ICHD-3 CH criteria, with no atypical clinical features, does not show any clinically-relevant ﬁndings, suggesting that these criteria are highly predictive of its primary origin and that systematic MRI is not useful for the diagnosis of typical CH.
• PMID: 34979370
J Headache Pain. 2021 Dec 31;22(1):158. doi: 10.1186/s10194-021-01368-7.
Authors: Maria Terhart, Jasper Mecklenburg, Lars Neeb, Lucas Hendrik Overeem, Anke Siebert, Maureen Steinicke, Bianca Raffaelli, Uwe Reuter
Background: Migraine preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs) has a positive effect on patients' health-related quality of life (HRQoL). The German treatment guidelines recommend discontinuing successful treatment with CGRP(-receptor) mAbs after 6-12 months. We aimed to evaluate headache-speciﬁc and generic HRQoL for three months after discontinuation of CGRP(-receptor) mAb treatment.
Methods: We conducted a prospective, longitudinal cohort study, including patients with migraine after 8-12 months of therapy with a CGRP(-R) mAb and before a planned discontinuation attempt. HRQoL was assessed at the time of the last mAbs injection (V1), eight weeks later (V2), and sixteen weeks later (V3). For headache-speciﬁc HRQoL, we used the Headache Impact Test-6 (HIT-6). Generic HRQoL was determined with the EuroQol-5-Dimension-5-Level (ED-5D-5L) form, and the Short-Form 12 (SF-12), which comprises a Physical Component Summary (PCS-12) and a Mental Component Summary (MCS-12). Questionnaires' total scores were compared across the three observation points using nonparametric procedures.
Results: The study cohort consisted of n = 61 patients (n = 29 treated with the CGRP-receptor mAb erenumab and n = 32 with the CGRP mAbs galcanezumab or fremanezumab). The HIT-6 sum score was
59.69 ± 6.90 at V1 and increased by 3.69 ± 6.21 at V3 (p < 0.001), indicating a greater headache impact on patients' lives. The mean total EQ-D5-L5 score declined from 0.85 ± 0.17 at V1 by - 0.07 ± 0.18 at V3 (p = 0.013). Both Mental and Physical Component Scores of the SF-12 worsened signiﬁcantly during treatment discontinuation: The PCS-12 total score decreased by - 4.04 ± 7.90 from V1 to V3 (p = 0.013) and the MCS-12 score by - 2.73 ± 9.04 (p = 0.003). Changes in all questionnaires' scores but the MCS-12 were already signiﬁcant in the ﬁrst month of the drug holiday (V2).
Conclusions: Our results show a signiﬁcant decline in headache impact and generic HRQoL of migraine patients after treatment discontinuation of a CGRP(-R) mAb. The observed deterioration is above the established minimally clinically important differences for each of the questionnaires and can therefore be considered clinically meaningful. Monitoring HRQoL during a discontinuation attempt could facilitate the decision whether or not to resume preventive treatment with CGRP(-R) mAbs.
• PMID: 34972502
Lancet Neurol. 2022 Jan 27;S1474-4422(21)00468-3. doi: 10.1016/S1474-4422(21)00468-3. Online ahead of print.
Author: Hans Christoph Diener
No abstract available
• PMID: 35093197
J Neurol Neurosurg Psychiatry. 2022 Jan 27;jnnp-2021-327992. doi: 10.1136/jnnp-2021-327992. Online ahead of print.
Authors: Simone de Vries Lentsch, Linda Al-Hassany, Michel Dominique Ferrari, Gisela Marie Terwindt, Antoinette MaassenVanDenBrink
No abstract available
• PMID: 5086941
Neurol Sci. 2022 Jan 14. doi: 10.1007/s10072-021-05827-6. Online ahead of print.
Authors: Licia Grazzi, Alberto Raggi, Paul Rizzoli
No abstract available
• PMID: 35028781