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Background and purpose: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP MAb) may be considered after 12–18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption. Methods: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti‐CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti‐CGRP MAb (T‐baseline); last month of first treatment period (T‐suspension); month of restart due to worsening (T‐worsening); and 3 months after resumption (T‐reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD. Results: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T‐baseline was 20 (13) and MMD was 5 (6); at T‐suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T‐worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T‐reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001). Conclusion: The results suggest that anti‐CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period. [ABSTRACT FROM AUTHOR]

Background and purpose: Short‐chain fatty acids (SCFAs) can have pro‐ or anti‐inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum. Methods: We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography–mass spectrometry. Results: Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non‐MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of <0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2–239.4, p < 0.01). Most nonrelapsing patients showed values of >0.36, which were similar to those in healthy pregnant women. Conclusions: Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period. [ABSTRACT FROM AUTHOR]

It has been suggested that bilingualism is beneficial for executive control and could have positive long-term effects by delaying the onset of symptoms of degenerative diseases. This research investigates, for the first time, the impact of bilingualism on executive control (monitoring and inhibitory control) in individuals with Multiple Sclerosis (MS), a neurodegenerative disease which commonly causes deficiencies in the cognitive system. Bilingual and monolingual adults, with and without an MS diagnosis, performed a flanker task with two degrees of monitoring demands (high monitoring vs. low monitoring). Results showed that bilingual MS patients had inhibitory control and monitoring abilities that were similar to healthy bilingual controls. In contrast, monolingual MS patients showed similar inhibitory control but significantly worse monitoring abilities compared to monolingual healthy controls. We propose that the similar behaviour between bilingual groups suggests that bilingualism might counteract cognitive deficits related to MS, especially with respect to monitoring. The high monitoring cost observed in monolingual patients seems related to underlying deficits in monitoring and possibly switching, executive control abilities commonly impaired in MS patients from early stages. Our findings provide some preliminary evidence for the cognitive reserve hypothesis in bilingual MS patients. [ABSTRACT FROM AUTHOR]

Background: Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. Objective: The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. Methods: We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. Results: Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6–41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. Conclusions: Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.)