Search

Background and Purpose: Patients presenting at the emergency room (ER) with headache often encounter a hostile atmosphere and experience delays in diagnosis and treatment. The aim of this study was to design a protocol for the ER with the goal of optimizing the care of patients with urgent headache to facilitate diagnosis and expedite treatment., Methods: A narrative literature review was conducted via a MEDLINE search in October 2021. The "Code Headache" protocol was then developed considering the available characteristics and resources of the ER at a tertiary care center within the Spanish National Public Health system., Results: The Code Headache protocol comprises three assessments: two scales and one checklist. The assessments identify known red flags and stratify patients based on suspected primary/secondary headaches and the need for pain treatment. Initial assessments, performed by the triage nurse, aim to first exclude potentially high morbidity and mortality etiologies (HEAD1 scale) and then expedite appropriate pain management (HEAD2 scale) based on scoring criteria. HEAD1 evaluates vital signs and symptoms of secondary serious headache disorders that can most benefit from earlier identification and treatment, while HEAD2 assesses symptoms indicative of status migrainosus, pain intensity, and vital signs. Subsequently, ER physicians employ a third assessment that reviews red flags for secondary headaches (grouped under the acronym 'PEACE') to guide the selection of complementary tests and aid diagnosis., Conclusions: The Code Headache protocol is a much needed tool to facilitate quick clinical assessment and improve patient care in the ER. Further validation through comparison with standard clinical practice is warranted., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months., Methods: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response., Results: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models., Conclusions: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: EC has received honoraria from Novartis, Chiesi, Lundbeck, MedScape; his salary has been partially funded by Río Hortega grant Acción Estratégica en Salud 2017–2020, Instituto de Salud Carlos III (CM20/00217). He is a junior editor for Cephalalgia. GE received travel grants and honoraria from Eli-Lilly, Novartis, Lusofarmaco, New Penta and Ecupharma. CNC has received honoraria for advisories, educational or commercial symposia from: Abbvie-Allergan, Kern Pharma, Chiesi, Lilly, Lundbeck, Novartis and Teva Pharmaceuticals And has participated as subinvestigator in Clinical Trials for: Abbvie-Allergan, Amgen, Biohaven, Lilly, Lundbeck, Pfizer and Teva Pharmaceuticals. JAM has received honoraria as consultant and/or speaker for Lilly, Novartis, Teva. FS-C received honoraria from Novartis, Lilly, TEVA, Abbvie. AM has received honoraria from Teva, Lilly, Roche, UCB, Bial, Chiesi, Allergan, Esai, Zambon, Kern Pharma, Pfizer, Biogen Idec, Novartis, TEVA, Merck, Janssen, Neuraxpharm, Genzyme, Sanofi, Bayer, Almirall and/or Celgene. JS received honoraria from Allergan, Lilly, Teva, Novartis. IBB received honoraria for presentations from Novartis, Lilly, Teva, Lundbeck and Abbvie. MW-P received honoraria from Pfizer, Allergan-Abbvie, TEVA, Polpharma. MW-P is member of Editorial Board: The Journal of Headache and Pain. LP received honoraria from Pfizer, Lilly, Abbvie, TEVA, Novartis. AL-R received honoraria for Abbvie, Lilly, Novartis and Teva. IL received honoraria from Novartis, Abbvie, Teva, Eisai, Tecnifar and Bial. LD received honoraria as a speaker for Allergan, Lilly, Teva and Lundbeck. MRA-E, received honoraria from ABBVIE, Lilly, and Novartis. AM has no COI to declare. The University Clinic Hamburg got an unrestricted scientific grant from Novartis (2019-2023). IPM has received honoraria from Allergan Teva, Novartis, Lundbeck and Eli Lilly for lecturing or participating in advisory boards; is principal investigator for phase IV trials sponsored by Novartis, Lundbeck and Teva. CS has received personal fees for lectures/ advisory boards: Novartis, Abbvie and TEVA. PI received honoraria from TEVA, Novartis, Lilly, Abbvie, Lundbeck, Exeltis. ALR received honoraria from TEVA. ABG-V has received speaker honoraria and/or clinical advisor from Novartis, Lilly, TEVA, Exeltis, Chiesi, Abbvie, Pfizer and Lundbeck. RR has received travel grants and/or honoraria for lectures or advisory boards from Allergan/AbbVie, Hormosan, Lilly, Lundbeck, Novartis, Pfizer and Teva. SS reports consultant, speaker or advisory board fees from Abbott, Allergan/Abbvie, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, Medscape, Medtronic, Novartis, Pfizer, Starmed, Teva and Uriach. EC-G received honoraria from TEVA. DGA has received personal compensation for consulting/advising from the WHO. Non-profit board membership in the Spanish Society of Neurology, and the European Union of Medical Specialist section of Neurology. Research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain and Carlos III institute, Madrid, Spain. Speaker/travel grants/ clinical trials from Teva, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Biohaven. JP has received honoraria from Abbvie, Lilly, Lundbeck, Novartis and Teva. RG-G received honoraria from Allergan/ Abbvie, Lilly, Lundbeck, Novartis, Pfizer, Tecnifar, Teva. MH-V has received honoraria for participating on advisory boards and for collaborations as consultant, scientific communications, speaker, research support as well as funding for travel and congress-attending expenses for Abbie-Allergan, Novartis, Lundbeck, Lilly, Almirall, Chiesi, Esai, Exeltis, Kern Pharma, Menarini, TEVA and Zambon. His research group has received research grants from Abbie-Allergan and has received funding for clinical trials from Lilly, Novartis, TEVA. JVR received honoraria from Novartis, Abbvie, Lilly, TEVA, Lundbeck. SS-L received honoraria from Allergan, Almirall, Amgen, Chiesi, Eisai, Exeltis, Lilly, Lündbeck, Novartis, Pfizer y Teva. MG-S has received honoraria and been involved in research, education and advisory boards with Teva, Lily, Novartis and Abbvie. CT received personal fees for participating in advisory or for speaking at scientific events from AbbVie, Allergan, Biohaven, Dompé, Eli Lilly, Lundbeck, Novartis and Teva. CT has received research funding from the European Commission, the Italian Ministry of Health and Migraine Research Foundation. JDdT has received honoraria as consultant and/or speaker for Lilly, Novartis, Teva. SDI has received honoraria for advisories, educational or commercial symposia from: Abbvie-Allergan, Fundació Universitat-Empresa, Ipsen Pharma, Kern Pharma, Lilly, Lundbeck, MSD-Organon, Novartis and Teva Pharmaceuticals And has participated as PI in Clinical Trials for: Abbvie-Allergan, Alder, Amgen, Biohaven, Ipsen Pharma, Lilly, Lundbeck, Pfizer and Teva Pharmaceuticals. CGO participated in clinical trials from Novartis, St Jude Medical, Lilly, Lundbeck; TEVA, Biohaven, Pfizer. CGO received honoraria as consultant for Novartis, Lilly, Allergan-abbvie, Lundbeck, TEVA, Pfizer. CGO received honoraria as speaker for Allergan-Abbvie, TEVA, Novartis,Lilly, Chiesi, MSD, Almirall. PB reports personal compensation for consulting, serving on a scientific advisory board, speaking, research support, collaborated for clinical trials or other activities with Abbvie, Alder, Allergan, Amgen, Angelini, Assosalute, Bayer, Biohaven, ElectroCore, Eli-Lilly, Fondazione Ricerca e Salute, GSK, Lundbeck, Lusofarmaco, 1MED, MSD, New Penta, Noema Pharma, Novartis, Pfizer, Stx-Med, Teva, Visufarma, Zambon and serves as President with Italian Association of Headache Sufferers. PP-R has received, in the last 3 years, honoraria as a consultant and speaker for: AbbVie, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva. Her research group has received research grants from AbbVie, Novartis and Teva; as well as, Instituto Salud Carlos III, EraNet Neuron, European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014-2020 - RIS3CAT; has received funding for clinical trials from AbbVie, Amgen, Biohaven, Eli Lilly, Novartis, Teva. She is the Honorary Secretary of the International Headache Society. She is in the editorial board of Revista de Neurologia. She is an associate editor for Cephalalgia, Headache, Neurologia, The Journal of Headache and Pain and Frontiers of Neurology. She is a member of the Clinical Trials Guidelines Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company. VJG, MMV, GV, JR-M, NFF, AJS, RO, GG, YG-O, GC, AL-B, FVJ, JR-V and VO reports no disclosures. RO reports personal fees from Eli Lilly, Novartis, Teva, and Pfizer, and non-financial support from Novartis, Teva, and Allergan/AbbVie. CT has received honoraria for lectures from TEVA, Lundbeck and for advisory boards from TEVA. He has received travel support from TEVA and Lundbeck. SS received honoraria from TEVA. AH declares no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. HB received honoraria from Novartis, Teva and Lundbeck. NPRP received honoraria from ABBVIE, Lilly and Novartis. CF received honoraria from Novartis and Abbvie. AAL received honoraria for Abbvie, Lilly, Novartis and Teva. EMS received a grant from the Portuguese Headache Society, supported by Teva. MTF has received honoraria from Allergan-AbbVie, Novartis, Chiesi and Teva. AA has received honoraria from Allergan-AbbVie, Novartis, Chiesi. PT received grants and honoria from Novartis, Teva, Eli-Lilly and Allergan. CA received travel grants from FB-Health, Lusofarmaco, Almirall, Eli-Lilly Novartis and Teva. RDI received speaker honoraria from Eli-Lilly, TEVA and Lundbeck. GS received personal fees as speaker or advisory board from Eli Lilly, Novartis, Teva, Lundbeck, Pfizer. SB has received honoraria from Teva. SC has received honoraria from Teva, Lilly, Roche, UCB, Bial, Chiesi, Allergan, Esai, Zambon, Kern Pharma, Pfizer, Biogen Idec, Novartis, TEVA, Merck, Janssen, Neuraxpharm, Genzyme, Sanofi, Bayer, Almirall and/or Celgene. EP reports personal fees from Novartis, Teva and Lilly. ALGP Research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain. Speaker/travel grants/ clinical trials from Teva, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, Pfizer and Biohaven. AS has received honoraria for advisory boards and lectures from Allergan/AbbVie, Hormosan, Lilly, Lundbeck, Novartis, Sanofi, Teva. AGM has received speaker honoraria from TEVA. SQ has received speaker honoraria from Novartis, Lilly and Exeltis. MSR has received consulting fees and honoraria for lectures/presentations from Eli Lily, Lundbeck, Novartis, Teva and Pfizer. Intellectual as Secretary of the European Headache Federation, Review Editor on the Editorial Board of Headache and Neurogenic Pain (specialty section of Frontiers in Neurology). Margarita Sanchez-del-Rio serves as a member of the Board of Directors in the European Headache Federation. ET has received personal fees for lectures/ advisory boards: Novartis, Eli Lilly, Abbvie, TEVA, Roche, Lundbeck, Pfizer, Biogen. Consultant for and owner of stocks and IP in Man & Science. Stocks and IP in Nordic Brain Tech and Keimon Medical. Non-personal research grants from EU, Norwegian Research Council, Dam foundation, KlinBeForsk. Commissioned research (non-personal): Lundbeck, Pfizer. BVP received honoraria from ABBVIE. AOD received honoraria from ABBVIE, Lilly, Teva, Novartis. MR received honoraria from Lilly, Novartis. BC received grants and honoria from Eli-Lilly, Novartis, Teva; SC received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Novartis, Teva, Lilly, Allergan, Abvie, Ibsa, Amgen, Angelini and Lundbeck; FF has received fees for participation on advisory boards, speaker honoraria or consulting activities from Angelini, Cristalfarma, Ecupharma, IBSA, Lundbeck, Novartis, PIAM, Teva; FdO received travel grant, honoraria as a speaker or for partecipating in advisory boards from Novartis, Teva, Neopharmed Gentili, Qbgroup srl, K link srl and Eli-Lilly; MA received grants from Novartis and Lilly; RR received honoraria for speaker panels from Teva, Lilly, Novartis, Allergan, Lundbeck; MZ received travel grants and honoraria from Novartis; MA received travel grants and honoraria from Novartis, Teva, Eli-Lilly and Lundbeck; CF received grants and honoraria from Novartis, Eli Lilly, TEVA, AIM group; AR received travel grants and honoraria from Teva and Eli-Lilly; SZ, RLP, MJRC, VGQ, HCO, SA, IKZ, DGA, IFL, BFP, SB, PRA, AC, AEU, AGG, IM, JPS, VC, AFR, YVE, MT, AS, AC, FZ and MA has no disclosures to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Migraine-related stigma is a pervasive issue impacting nearly half of chronic migraine patients, with significant consequences for their quality of life, disability and mental health. Despite its profound effects, migraine stigma remains under-recognised in both clinical practice and research. This narrative review explores the three primary types of stigmas affecting migraine patients: public, structural and internalised. Public stigma involves negative societal attitudes and stereotypes that trivialise the condition. Structural stigma is reflected in policies that restrict access to necessary care and resources. Internalised stigma occurs when patients absorb these negative views, leading to self-blame and diminished self-worth. Addressing these different types of stigmas is crucial for improving the understanding, diagnosis and treatment of migraine. Educational efforts, advocacy and policy reform are essential strategies in this context. A deep understanding of stigma is vital for developing effective interventions that enhance clinical management and patient quality of life. Ultimately, reducing stigma can lead to better health outcomes and a more comprehensive approach to migraine care.

Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the cortex. Concurrent functional magnetic resonance imaging can show changes in TMS-induced activity in the whole brain, with the potential to inform brain function research and to guide the development of TMS therapy. However, the interaction of the strong current pulses in the TMS coil in the static main magnetic field of the MRI produces high Lorentz forces, which may damage the coil enclosure and compromise the patient's safety. We studied the time-dependent mechanical behavior and durability of two multi-locus TMS (mTMS) coil arrays inside a high-field MRI bore with finite element modeling. In addition, coil arrays were built and tested based on the simulation results. We found that the current pulses produce shock waves and time-dependent stress distribution in the coil plates. The intensity and location of the maximum stress depend on the current waveform, the coil combination, and the transducer orientation relative to the MRI magnetic field. We found that 30% glass-fiber-filled polyamide is the most durable material out of the six options studied. In addition, novel insights for more durable TMS coil designs were obtained. Our study contributes to a comprehensive understanding of the underlying mechanisms responsible for the structural failure of mTMS coil arrays during stimulation within high static magnetic fields. This knowledge is essential for developing mechanically stable and safe mTMS-MRI transducers., (Creative Commons Attribution license.)

Introduction: Chronic cluster headache (CCH) is a relatively rare primary headache disorder whose management is often challenging. The prevalence of refractory CCH (rCCH) is unknown. Our aim is to describe the frequency of rCCH within a population of CCH, define the clinical profile of the refractory patients and the treatments they underwent., Methods: We conducted a cross-sectional study through a review of the medical records of CCH patients in six hospitals in Madrid, Spain. Data on epidemiological, clinical presentation, treatment and disease activity at the moment were collected. The European Headache Federation diagnostic criteria were used for rCCH definition. High disease activity was defined as having at least 3 severe attacks per week that impact quality of life despite treatment. Non-rCCH and rCCH groups were compared., Results: 88 CCH patients were analyzed, 68.2% (60/88) met rCCH criteria at some point in their evolution. A longer diagnostic delay (4.6 ± 7.1 vs. 3.2 ± 3.7 years, p = 0.017) was observed in rCCH. All rCCH patients tried therapies without established evidence from randomized clinical trials. OnabotulinumtoxinA and galcanezumab were initiated in 77.3% (68/88) and 5.7% (5/88), but discontinued in 52.9% (36/68) and 60.0% (3/5), respectively. Occipital nerve stimulation (ONS) was implanted in 29.6% (26/88), with 50.0% (13/26) still active. Other treatment options are described and discussed. Despite treatment, 60.2% (53/88) still have high disease activity., Conclusion: CCH is a disorder with poor prognosis, meeting refractoriness criteria in more than half. OnabotulinumtoxinA and ONS could be the effective in refractory patients., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response., Methods: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events., Results: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p  = 0.026) and a higher smoking rate (100% vs. 42.9%, p  = 0.006). Stational fluctuations (58.3% vs. 7.7%, p  = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p  = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks., Conclusions: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH., Competing Interests: Declaration of conflicting interestsJAM has received honoraria as a speaker from TEVA and Novartis and for advisory boards from Pfizer. AGM has received speaker honoraria from TEVA. ABGV has received honoraria for advisory boards and/or speaker panels from Novartis, Lilly, TEVA, Abbvie-Allergan, Lundbeck and Pfizer. JDT has received honoraria for advisory boards from speaker panels from Novartis, Lilly, TEVA, Abbvie-Allergan, Lundbeck Pfizer and Boston Scientific.

Background and Purpose: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine., Methods: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated., Results: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05)., Conclusions: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Preventive treatment for refractory chronic cluster headache (rCCH) is challenging and many therapies have been tried., Objective: To study what could be considered the therapy of choice in rCCH through a systematic review and meta-analysis., Methods: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in PROSPERO (ID CRD42021290983). A systematic search was performed in MEDLINE, Embase, Cochrane, clinicaltrials.gov, and the WHO's-International-Clinical-Trials-Registry-Platform. Studies on the preventive treatment for rCCH as defined by the European Headache Federation consensus statement were included. A meta-analysis of the pooled response rate was conducted for the different therapies., Results: Of 336 results, 45 were eligible for inclusion. Most articles studied the effect of neuromodulation as a preventive treatment for rCCH. The most studied neuromodulation technique was occipital nerve stimulation (ONS), with a pooled response rate in the meta-analysis of 57.3% (95% CI 0.481-0.665). Deep brain stimulation (DBS) was the second most studied treatment with a pooled response rate of 77.0% (95% CI 0.594-0.957). DBS results were more heterogeneous than ONS, which could be related to the different stimulation targets in DBS studies, and reported more serious adverse events than in ONS studies. The remaining therapies (anti-CGRP pathway drugs, warfarin, ketamine-magnesium infusions, serial occipital nerve blocks, clomiphene, onabotulinum toxin A, ketogenic diet, sphenopalatine ganglion radiofrequency or stimulation, vagus nerve stimulation, percutaneous bioelectric current stimulation, upper cervical cord stimulation, and vidian neurectomy) present weaker results or have less quality of evidence., Conclusions: The results of this systematic review and meta-analysis suggest that ONS could be the first therapeutic strategy for patients with rCCH based on the current evidence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), has demonstrated clinical benefit as a preventive treatment of episodic cluster headache (ECH) but not in chronic cluster headache (CCH) to this date. Our objective was to analyze our clinical experience of the compassionate use of galcanezumab in cluster headache and to conduct a narrative review of the published literature., Methods: We present a case series of patients with refractory ECH and CCH treated with 240 mg galcanezumab monthly in an outpatient headache clinic. We recorded epidemiologic and clinical data and analyzed the disease evolution after 3 and 6 months. The review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: We included three patients with ECH who were treated during a refractory cluster bout (mean duration of 83.7 days since the first attack, range 46.0-105.0 days) and six patients with CCH who had a high frequency of attacks (mean 35.8 attacks/week, range 7-56) and refractory to a mean of 5.2 preventive treatments (range, 3-9). In the CCH group, >50% frequency reduction was seen in 83% (5/6 patients) and the number of attacks per week showed a mean reduction of -24.2 at month 3 (range, -6 to -49) and -27.6 at month 6 (range, -7 to -49). In the ECH group, the bout ended a mean 17.3 days (range, 10-28) after galcanezumab administration. One third of patients reported mild adverse events, none of them leading to discontinuation., Conclusion: In conclusion, our clinical experience supports the use of galcanezumab in patients with refractory cluster headache. These results might encourage the possibility of continuing clinical development with randomized controlled trials of anti-CGRP treatments in patients with cluster headache., (© 2022 American Headache Society.)

Background: To study the effect of greater occipital nerve (GON) block on migraine-associated photophobia levels. Photophobia is one of the most bothersome symptoms reported by migraine patients. Studies investigating the impact of migraine treatment on this symptom are scarce., Methods: This is an observational prospective case-control study. Patients with migraine and photophobia attending a Headache Clinic were recruited. Cases were defined as patients in whom GON block was performed, following usual clinical practice guidelines. All patients were evaluated with the Hospital Anxiety and Depression Scale, the Migraine Specific Quality of Life Questionnaire, the Utah Photophobia Symptom Impact Scale (UPSIS-12), and the Korean Photophobia Questionnaire (KUMC-8); both in the first visit (V1) and one week after (V2)., Results: Forty-one patients were recruited, 28 (68.3%) cases and 13 (31.7%) controls. At V1, there were no significant differences in the median [p25-p75] score of UPSIS-12 in cases vs controls (32.0 [21.0-34.0] vs 30.5 [22.0-37.0], P = 0.497) or KUMC-8 (6.5 [5.5-7.0] vs 7.0 [6.0-8.0], P = 0.463). At V2, cases experimented a significant improvement in UPSIS-12 of -5.5 [-8.8 to -1.3] and in KUMC-8 of -0.5 [-2.0 to 0], whereas there were no significant changes in the control group. Migraine with aura patients presented higher UPSIS-12 score at V1 (33.5 [24.5-37.0] vs 26.0 [16.0-35.0]) and lesser improvement at V2 after GON block compared with migraine without aura patients (-4.0 [-6.0 to -1.0] vs -8.0 [-17.0 to -2.0]), although statistical significance was not achieved ( P = 0.643 and P = 0.122, respectively). There was no significant variation in the remaining scales., Conclusions: Greater occipital nerve block improves migraine-associated photophobia, measured with UPSIS-12 and KUMC-8. Patients without aura may exhibit a greater improvement. Physicians could consider GON block for management of photophobia in migraine patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Background: Headache is a frequent symptoms of coronavirus disease 2019 (COVID-19). Its long-term evolution remains unknown. We aim to evaluate the long-term duration of headache in patients that presented headache during the acute phase of COVID-19., Methods: This is a post-hoc multicenter ambisective study including patients from six different third-level hospitals between 1 March and 27 April 2020. Patients completed 9 months of neurological follow-up., Results: We included 905 patients. Their median age was 51 (IQR 45-65), 66.5% were female, and 52.7% had a prior history of primary headache. The median duration of headache was 14 (6-39) days; however, the headache persisted after 3 months in 19.0% (95% CI: 16.5-21.8%) and after 9 months in 16.0% (95% confidence interval: 13.7-18.7%). Headache intensity during the acute phase was associated with a more prolonged duration of headache (Hazard ratio 0.655; 95% confidence interval: 0.582-0.737)., Conclusion: The median duration of headache was 2 weeks, but in approximately a fifth of patients it became persistent and followed a chronic daily pattern.

In this work, a stream function inverse boundary element method (IBEM) has been used for designing different deep transcranial magnetic stimulation (dTMS)coils to activate the prefrontal cortex and the temporal lobe have been set as the target regions. In addition, the performances of these coils have been described and the electric field induced by them has been obtained by using a computational forward technique. These results show that the stream function IBEM is an ideal approach to design optimal dTMS coils capable of producing deep stimulation in the target brain regions. Clinical relevance - The design problem proposed here can be used to produce efficient dTMS stimulators for neurological disorders, which can overcome some of the currently existing limitations of the most common devices employed in TMS.

Importance: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive disorder caused by pathogenic variants in PLEC1, which encodes plectin. It is characterized by mild mucocutaneous fragility and blistering and muscle weakness. Translational readthrough-inducing drugs, such as repurposed aminoglycoside antibiotics, may represent a valuable therapeutic alternative for untreatable rare diseases caused by nonsense variants., Objective: To evaluate whether systemic gentamicin, at a dose of 7.5 mg/kg/d for 14 consecutive days, is clinically beneficial in a patient with EBS-MD., Design, Setting, and Participants: A single patient in Madrid, Spain, received 2 treatment courses with gentamicin on July 2019 and February 2020 with a follow-up period of 120 and 150 days, respectively., Results: In this case report of a woman in her 30s with EBS-MD, before gentamicin treatment, the patient had mucocutaneous involvement, skeletal and respiratory muscle weakness, and myalgia that negatively affected her quality of life. Outcomes were evaluated with extensive laboratory tests and clinical scales. No nephrotoxic or ototoxic effects were detected after intravenous gentamicin administration. Gentamicin treatment was followed by plectin expression in the skin for at least 5 months. Although minimal changes were noted in skeletal muscle function (as measured by the Hammersmith functional motor scale and its expanded version: 6/40 to 7/40 and from 10/66 to 11/66, respectively) and respiratory musculature (maximal inspiratory and expiratory pressures D0 vs D16, MIP: 2.86 vs 3.63 KPa and MEP: 2.93 vs 4.63 KPa), myalgia disappeared (VAS dropped from 6 to 0), and quality of life improved (EuroQoL-5D-3L pain and anxiety dropped from 2 to 1)., Conclusions and Relevance: The findings of this single case report suggest that gentamicin treatment may help suppress PLEC1 premature termination codons and induce plectin expression in EBS-MD primary keratinocytes and skin. Our study suggests that gentamicin may play an important role in treating EBS-MD owing to nonsense variants.

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The acute infection is characterised not only by respiratory symptoms, but also by multiple systemic manifestations, including neurological symptoms. Among these, headache is a frequent complaint. As the pandemic progresses and the population of patients recovering from COVID-19 grows, it is becoming apparent that the headache present in the acute stage of the infection may persist for an indeterminate period, becoming a major problem for the patient and potentially leading to disability. In this review we describe the pathophysiological and clinical aspects of persistent headache after COVID-19 based on the information currently available in the literature and the authors' clinical experience., (© 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U.)

Occipital nerve stimulation (ONS) is a surgical treatment proposed for drug-resistant chronic cluster headache (drCCH). Long-term series assessing its efficacy are scarce. We designed a retrospective observational study with consecutive sampling, evaluating the follow-up of 17 drCCH patients who underwent ONS. Our main endpoint was the reduction the rate of attacks per week. We also evaluated the pain intensity through the Visual Analogue Scale (VAS), patient overall perceived improvement and decrease in oral medication intake. After a median follow-up of 6.0 years (4.5-9.0), patients decreased from a median of 30 weekly attacks to 22.5 (5.6-37.5, p = 0.012), 7.5 at 1 year ( p = 0.006) and 15.0 at the end of follow-up ( p = 0.041). The VAS decreased from a median of 10.0 to 8.0 ( p = 0.011) at three months, to 7.0 ( p = 0.008) at twelve months and 7.0 ( p = 0.003) at the end of the follow-up. A total of 23.5% had an overall perceived improvement of ≥70% at 3 months, 41.2% at 1 year and 27.8% at the end of follow-up. Reducing prophylactic oral medication was possible in 76.5% and it was stopped in 17.7%. Triptan use decreased in all the responder patients and 17.7% stopped its intake. A total of 41.2% presented mild adverse events. In conclusion, our long-term experience suggests that ONS could be an interesting option for drCCH-selected patients, as it is a beneficial and minimally invasive procedure with no serious adverse events.

Objective: To describe the semiology of pain and its associated features in patients with coronavirus disease 2019 (COVID-19) and headache presenting to the emergency department who do not require urgent services., Background: Headache is one of the most frequent neurological symptoms reported in case series, epidemiological studies, and meta-analyses of COVID-19, with a prevalence ranging from 8 to 71.1%. Studies addressing the semiology of these headaches are lacking., Methods: We conducted a cross-sectional study in the emergency department of a tertiary hospital. Patients classified according to the Manchester Triage System as standard and non-urgent and those fulfilling the criteria for probable or confirmed COVID-19 according to World Health Organization guidelines who presented with headache were included. A standardized questionnaire was used for data collection., Results: Of the 145 confirmed and probable COVID-19 patients, 99 (68.3%) reported headache. A total of 54/99 (54.5%) were classified with probable COVID-19 and 45/99 (45.5%) with confirmed COVID-19. The mean age (44.7 ± 11.8 vs 40.4 ± 10.7, P = .061), sex distribution (35/54 [64.8%] vs 28/45 [62.2%] female, P = .768), and headache comorbidity (19/54 [35.2%] vs 17/45 [37.8%], P = .789) were similar between the probable and confirmed COVID-19 groups, along with other medical comorbidities and laboratory data. Patients with confirmed COVID-19 showed a higher incidence of anosmia (21/54 [38.9%] vs 28/45 [62.2%], P = .021) and pneumonia (10/54 [18.5%] vs 18/45 [40%], P = .018), headache at onset (32/54 [59.3%] vs 39/45 [86.7%], P = .002), and hospital admission (0/54 [0%] vs 2/45 [11.1%], P = .017). In most cases, the headache appeared simultaneously with other COVID-19 symptoms (57/99, 57.6%). It was bilateral (86/99, 86.9%), frontal or holocranial (34/99, 34.3% each) in location and intense (60/99, 60.6%, reported a visual analog scale [VAS] score ≥7). A total of 39/99 (39.4%) identified triggers, most commonly fever. The most frequent aggravating factors were physical activity (45/99, 45.5%) and coughing (43/99, 43.4%). Patients showed a propensity toward prostration (41/99, 41.4%), photophobia (29/99, 29.3%), and phonophobia (27/99, 27.3%). Partial (53/99, 53.5%) or total (26/99, 26.3%) responses to first-step analgesics were reported. A total of 25/99 (25.3%) patients had a prior history of migraine, presenting with headache different from the usual in 23/25 (92.0%) patients. Individuals with migraine were more likely to have earlier (headache at onset of the respiratory symptoms in 24/25 [96.0%] vs 57/74 [77.0%], P = .023 [95% CI: 0.067, 0.313]), longer (>24 hours of pain in 20/25 [80%] vs 25/74 [33.8%], P < .001 [95% CI: 0.272, 0.652]), and more intense (VAS score ≥5 in 25/25 [100%] vs 63/74 [85.1%], P = .043 [95% CI: 0.057, 0.213]) headaches than patients without migraine., Conclusions: Headache is a very prevalent COVID-19 symptom among patients presenting to the emergency room, most frequently presenting as holocranial or bifrontal moderate to severe, and pressing quality headache. Individuals with migraine tend to present with earlier, longer, and more intense headaches., (© 2020 American Headache Society.)