{"title":"Safety concerns of maternal antiseizure medications exposure on perinatal and offspring outcomes: a disproportionality analysis based on FDA adverse event reporting system.","authors":"Yanbin Zeng, Wanlong Lin, Wei Zhuang","doi":"10.1007/s00415-025-13172-3","DOIUrl":"https://doi.org/10.1007/s00415-025-13172-3","url":null,"abstract":"<p><strong>Background: </strong>Many women are exposed to antiseizure medications (ASMs) during pregnancy, raising concerns about pregnancy and offspring health risks. The current safety data remain insufficient, necessitating further investigation.</p><p><strong>Methods: </strong>Using data from the FDA Adverse Event Reporting System (2010-2023), this study employed both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) for disproportionality analysis of pregnancy and offspring toxicity related to maternal ASM exposure. In addition, we performed signal adjustment by excluding polytherapy cases, and drug-drug interaction (DDI) signals of two ASMs were identified using Ω Shrinkage measures and Chi-square tests.</p><p><strong>Results: </strong>3,459 mothers were exposed to 23 ASMs, resulting in 10,910 adverse events. 59 malformation signals, 27 adverse perinatal outcome signals, and 35 dysplasia signals were identified. Among traditional ASMs, valproic acid (VPA) and carbamazepine (CBZ) exhibited the highest number of signals, while levetiracetam (LEV), lamotrigine (LTG), lacosamide, gabapentin, and topiramate (TPM) predominated among newer ASMs. Signals for cardiac malformations, adverse neurodevelopment, and adverse offspring growth outcomes were widespread, with the strongest signals for specific outcomes observed for zonisamide [ROR = 14.82, 95% CI: 5.43-40.41], gabapentin [ROR = 52.52, 95% CI: 15.68-175.95], and brivaracetam [ROR = 22.96, 95% CI: 8.42-62.61], respectively. Six DDI signals displayed ≥ 3, including LTG + LEV/VPA associated with malformation, CBZ + lacosamide/LTG, and VPA + clonazepam associated with fetal loss.</p><p><strong>Conclusions: </strong>The potential risks associated with LEV and LTG surpass expectations, warranting further evaluation, particularly in combination therapy. In addition, ASMs with widespread signals, such as VPA, CBZ, TPM, and lacosamide, warrant heightened attention.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"429"},"PeriodicalIF":4.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ferdinando Clarelli, Andrea Corona, Kimmo Pääkkönen, Melissa Sorosina, Alen Zollo, Fredrik Piehl, Tomas Olsson, Pernilla Stridh, Maja Jagodic, Bernhard Hemmer, Christiane Gasperi, Adil Harroud, Klementy Shchetynsky, Alessandra Mingione, Elisabetta Mascia, Kaalindi Misra, Antonino Giordano, Maria Laura Terzi Mazzieri, Alberto Priori, Janna Saarela, Ingrid Kockum, Massimo Filippi, Federica Esposito, Filippo Martinelli Boneschi
{"title":"Correction: Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.","authors":"Ferdinando Clarelli, Andrea Corona, Kimmo Pääkkönen, Melissa Sorosina, Alen Zollo, Fredrik Piehl, Tomas Olsson, Pernilla Stridh, Maja Jagodic, Bernhard Hemmer, Christiane Gasperi, Adil Harroud, Klementy Shchetynsky, Alessandra Mingione, Elisabetta Mascia, Kaalindi Misra, Antonino Giordano, Maria Laura Terzi Mazzieri, Alberto Priori, Janna Saarela, Ingrid Kockum, Massimo Filippi, Federica Esposito, Filippo Martinelli Boneschi","doi":"10.1007/s00415-025-13108-x","DOIUrl":"https://doi.org/10.1007/s00415-025-13108-x","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"423"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claudio Gasperini, Diego Centonze, Antonella Conte, Paolo Gallo, Alessandra Lugaresi, Francesco Patti, Maria Trojano, Maria Pia Amato, Massimo Filippi
{"title":"Personalized therapy in multiple sclerosis: an Italian Delphi consensus.","authors":"Claudio Gasperini, Diego Centonze, Antonella Conte, Paolo Gallo, Alessandra Lugaresi, Francesco Patti, Maria Trojano, Maria Pia Amato, Massimo Filippi","doi":"10.1007/s00415-025-13173-2","DOIUrl":"https://doi.org/10.1007/s00415-025-13173-2","url":null,"abstract":"<p><strong>Objective: </strong>The increasing availability of disease-modifying therapies (DMTs) may provide more personalized treatment options for multiple sclerosis (MS) based on various factors, including patients' characteristics, prognostic indicators, comorbidities, and safety. In Italy, recent efforts focused on promoting interdisciplinary, patient-centered care and equitable access to optimized therapies, as reported in the 2023 Barometer of Multiple Sclerosis and Related Diseases from the Italian Multiple Sclerosis Association. A key challenge is ensuring equitable access to homogeneous and personalized therapeutic strategies.</p><p><strong>Materials and methods: </strong>Using a Delphi methodology, a panel of Italian neurologists with expertise in MS evaluated consensus on specific aspects of MS treatments, including personalized therapy, patient involvement in decision-making, treatment flexibility, self-management of therapies, perception of treatment efficacy and safety and therapeutic sequence management.</p><p><strong>Results: </strong>Of 166 votes, 116 statements reached consensus (68% positive, 2% negative), representing 70% of the total, whereas 50 (30%) highlighted areas of non-consensus. The findings emphasize the central role of neurologists, the importance of personalized therapy, the inclusion of patients in therapeutic choices to enhance adherence and quality of life, and managing both quality of life and caregiver burden. Most high-efficacy disease-modifying therapies (HE DMTs), like cladribine and anti-CD20 therapies, recognized for their efficacy and convenience of administration, received positive consensus, emphasizing their perceived value in individualized treatment approaches.</p><p><strong>Conclusions: </strong>This research highlights best practices and provides a roadmap for improving patient outcomes through tailored, well-communicated therapeutic strategies.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"428"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessio Facchin, Jolanda Buonocore, Giulia Sgrò, Alessia Cristofaro, Marianna Crasà, Chiara Camastra, Maria Grazia Vaccaro, Aldo Quattrone, Andrea Quattrone
{"title":"Eye movement abnormalities in normal pressure hydrocephalus: a video-oculographic study.","authors":"Alessio Facchin, Jolanda Buonocore, Giulia Sgrò, Alessia Cristofaro, Marianna Crasà, Chiara Camastra, Maria Grazia Vaccaro, Aldo Quattrone, Andrea Quattrone","doi":"10.1007/s00415-025-13171-4","DOIUrl":"https://doi.org/10.1007/s00415-025-13171-4","url":null,"abstract":"<p><strong>Background: </strong>Eye movement dysfunction has been widely observed in several neurodegenerative diseases. Normal pressure hydrocephalus (NPH) is a treatable condition showing marked clinical and radiological overlap with neurodegenerative parkinsonism and dementia syndromes, often posing diagnostic challenges. The current study employed video-oculography (VOG) aiming to comprehensively explore possible ocular dysfunction in NPH patients.</p><p><strong>Methods: </strong>Forty-two consecutive NPH patients and seventy-six healthy controls (HC) were enrolled in the study. Participants underwent a video-oculographic assessment including reflexive saccades and fixation tasks. Amplitude, peak velocity and latency of upward, downward, and vertical saccades were calculated, together with square wave jerks (SWJ) number and amplitude during fixation. Correlations between VOG data and clinico-radiological features were investigated.</p><p><strong>Results: </strong>NPH patients showed a significant (33.8%) increase in saccadic latency compared to HC, with no differences in saccadic amplitude and peak velocity. The number and amplitude of SWJ were also similar between NPH and HC groups. Saccadic latency was specifically associated with cognitive deficits, especially phonemic fluency and executive functions, in the NPH group.</p><p><strong>Conclusion: </strong>This study characterized ocular dysfunction in NPH patients, demonstrating an increase of saccadic latency in comparison with HC, strongly associated with cognitive impairment. These results identified saccadic latency as a rapid and quantitative VOG biomarker of cognitive deficits in NPH, holding potential for repeated assessment of cognitive status over time. On the other hand, saccadic amplitude and velocity were not affected in NPH, thus suggesting their possible role in the differential diagnosis between NPH and neurodegenerative parkinsonian syndromes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"425"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Josefin E Kaufmann, Lukas Mayer-Suess, David Seiffge, Michael Knoflach, Stefan T Engelter, Christopher Traenka
{"title":"Management of cervical artery dissection: new evidence and future directions.","authors":"Josefin E Kaufmann, Lukas Mayer-Suess, David Seiffge, Michael Knoflach, Stefan T Engelter, Christopher Traenka","doi":"10.1007/s00415-025-13166-1","DOIUrl":"https://doi.org/10.1007/s00415-025-13166-1","url":null,"abstract":"<p><p>Cervical artery dissection (CeAD) is a leading cause of ischemic stroke in young adults. Although its pathogenesis remains incompletely understood, advancements in CeAD patient care have been made in recent years. This review provides an updated overview of the latest evidence on hyperacute and (sub-)acute management of CeAD, highlighting aspects that have received limited attention, including vascular risk factors and mental health. Furthermore, we aim to outline future research directions to enhance patient outcomes and deepen our understanding of the disease.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"426"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Dolbow, Soheil El-Azzouni, Yiyi Zhang, Christopher Geiger
{"title":"A practical guide to assessing functional motor weakness: a review of validated techniques.","authors":"James Dolbow, Soheil El-Azzouni, Yiyi Zhang, Christopher Geiger","doi":"10.1007/s00415-025-13139-4","DOIUrl":"https://doi.org/10.1007/s00415-025-13139-4","url":null,"abstract":"<p><p>Functional neurological symptom disorder, specifically, functional limb weakness, is a commonly seen condition in clinical neurological practice and requires careful examination for diagnosis. Specific and detailed examination techniques have been developed and validated over the past 100 years to help clinicians differentiate functional limb weakness from objective neurological weakness. These techniques vary in sensitivity, specificity, clinical application, and limitations. However, over time, the studied and/or validated forms of these exam techniques may have been lost and often not performed or taught in the way it was originally studied, thus decreasing the reliability of the examiner's findings. With many new examination techniques for functional limb weakness having been studied in recent years, it is important to not only review the form of each of these examination techniques, but also discuss the clinical applications, limitations, and utility of each. To date, there has been no comprehensive review demonstrating the exact form of all the studied and/or validated examination techniques for functional limb weakness and their proposed clinical utility. This review analyzes 9 examination techniques for functional limb weakness that have been studied for validity and provides readers with the exact technique of examination used to study each. It also outlines their sensitivity, specificity, clinical applications, and limitations to help clinicians accurately diagnose functional limb weakness.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"427"},"PeriodicalIF":4.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joaquín Arzalluz-Luque, Pauline Dumez, Géraldine Picard, Marie Benaiteau, Maxime Bonjour, Pierre Lardeux, Julian Theuriet, Florian Lamblin, Marie Rafiq, Jerome Honnorat, Romain Marignier
{"title":"Clinical course and long-term outcomes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.","authors":"Joaquín Arzalluz-Luque, Pauline Dumez, Géraldine Picard, Marie Benaiteau, Maxime Bonjour, Pierre Lardeux, Julian Theuriet, Florian Lamblin, Marie Rafiq, Jerome Honnorat, Romain Marignier","doi":"10.1007/s00415-025-13159-0","DOIUrl":"https://doi.org/10.1007/s00415-025-13159-0","url":null,"abstract":"<p><strong>Background: </strong>The aim was to describe the clinical course and long-term outcomes of the French cohort of patients with glial fibrillary acidic protein (GFAP) astrocytopathy.</p><p><strong>Methods: </strong>Patients with positive CSF GFAP antibody test were identified between May 2017 and February 2023. Those whose clinical presentation occurred < 2 years before the initiation of the study, with other diagnosis than GFAP astrocytopathy, and with missing clinical information were excluded.</p><p><strong>Results: </strong>Among the 74 patients included, 71 were alive at last follow-up. The median age at onset was 43 years (range 6-84), 44 patients were male (62%), and 11 (15%) had a neoplasia. The main initial syndrome was meningo-encephalitis (n = 41, 58%). The median follow-up was 28 months (range 1-129). The median mRS at presentation was 4 (range 1-5) and at last follow-up was 1 (range 0-4). Forty patients reported disability at last follow-up (56%). The most frequent sequelae were cognitive complaints (20/40, 50%) and gait disorder (19/40, 48%). 38/55 patients (69%) returned to school/work. Long-term immunoactive treatment was introduced in 40 patients (56%); the most commonly administered were oral corticosteroids (n = 35, 49%). Relapses were documented in 10 patients (14%) and occurred after a median follow-up of 9 months (range 3-46). The presence of concomitant tumor at onset was associated with relapse (HR 4.55, 95% CI 1.28-16.14, p = 0.03).</p><p><strong>Conclusions: </strong>This study suggests a greater impact than previously described in long-term outcomes of patients with GFAP astrocytopathy and reports concomitant tumor at presentation as a risk factor for relapse.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"421"},"PeriodicalIF":4.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federica Giofrè, Alessandra Lugaresi, Flavia Baccari, Elaine Lui, Stefanie Roberts, Charles Malpas, Tomas Kalincik
{"title":"The topography of infratentorial lesions in depression and anxiety in multiple sclerosis.","authors":"Federica Giofrè, Alessandra Lugaresi, Flavia Baccari, Elaine Lui, Stefanie Roberts, Charles Malpas, Tomas Kalincik","doi":"10.1007/s00415-025-13167-0","DOIUrl":"https://doi.org/10.1007/s00415-025-13167-0","url":null,"abstract":"<p><strong>Background: </strong>Depression and anxiety are highly prevalent in multiple sclerosis and significantly impact patient outcomes. However, their link to specific areas of demyelination remains unclear.</p><p><strong>Objectives: </strong>This study examines the association between infratentorial lesions and depression or anxiety, focusing on three regions of interest: raphe nuclei, locus coeruleus, and cerebellar lobule VIIA.</p><p><strong>Methods: </strong>Patients were recruited from the cognitive neuroimmunology clinic at the Royal Melbourne Hospital. Participants were categorised as belonging to the groups 'depression'/'no depression' and 'anxiety'/'no anxiety' based on SPECTRA Indices of Psychopathology. MRI scans were examined for lesion presence in regions of interest. Association analyses were performed using multivariable logistic regression, adjusting for demographics, clinical parameters, and therapy.</p><p><strong>Results: </strong>Of 73 patients, 21 (29%) had clinically relevant depressive symptoms, and 18 (25%) had anxiety. Depression was significantly associated with lesions in the raphe nuclei (47.6% vs. 17.3%, OR 10.5, 95%CI 1.9-57.5, p=0.007) and locus coeruleus (38.1% vs. 15.4%, OR 20.5, 95%CI 2.3-184, p=0.007). Anxiety showed a potential association with locus coeruleus lesions (38.9% vs. 16.4%, OR 8.62, 95%CI 0.9-79.2, p=0.057).</p><p><strong>Conclusions: </strong>Depression in multiple sclerosis is associated with lesions within serotoninergic and noradrenergic brainstem nuclei. No definitive anatomical substrate for anxiety was identified. These findings suggest that inflammatory structural changes may underlie mood disorders in multiple sclerosis, potentially serving as early imaging markers of susceptibility to depression.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"420"},"PeriodicalIF":4.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Best, Heidrun H Krämer, Marianne Dieterich
{"title":"Acute peripheral unilateral vestibulopathy of the whole nerve causes increased impairment of spatial orientation and poorer long-term outcome.","authors":"Christoph Best, Heidrun H Krämer, Marianne Dieterich","doi":"10.1007/s00415-025-13160-7","DOIUrl":"https://doi.org/10.1007/s00415-025-13160-7","url":null,"abstract":"<p><strong>Background: </strong>Acute peripheral unilateral vestibulopathy (UVP) is the third most common cause of peripheral vestibular vertigo. Etiologically, a viral inflammation is assumed. In most cases, an isolated dysfunction of the superior part of the vestibular nerve can be found (superior part UVP = sUVP), but an additional involvement of the inferior part has also been shown (whole nerve UVP = s+iUVP). The aim of the study was (a) to determine the prevalence of an additional inferior part involvement, (b) to quantify the extent of vestibular deficit comparing sUVP vs. s+iUVP and (c) to examine the long-term outcome focusing on psychological distress as well as long-lasting symptoms associated with dizziness.</p><p><strong>Methods: </strong>96 UVP patients were enrolled. They underwent a neuro-otological examination including measurements of cervical vestibular evoked myogenic potentials (cVEMP), subjective visual vertical (SVV), ocular torsion (OT), caloric testing and the clinical head impulse test (HIT) in the acute phase. The Symptom Checklist-90 R and the Vertigo Symptom Scale were examined at a mean follow-up interval of 4.0 years (± 0.4 years) after disease onset.</p><p><strong>Results: </strong>Among the 96 patients (47 female; mean age 58 ± 14 years), additional involvement of the inferior nerve part was found in 35 cases (36%). These patients showed a significantly greater tilt of SVV (6.3° ± 4.4° vs. 4.2° ± 3.7°; F = 5.581, p = 0.020) and a more pronounced OT (15.1° ± 8.2° vs. 11.3° ± 7.4°; F = 4.770, p = 0.032) in the acute stage of the disease. The proportion of pathological HIT was significantly higher in the s+iUVP group (82.9% vs. 67.2%; Chi-Square = 20.167, p < 0.001). cVEMPs showed significantly decreased amplitude on the affected side (124.8 µV (± 10.3 µV) vs. 408.4 µV (± 26.6 µV); F = 61.911; p < 0.001). At long-term follow-up, the patients with s+iUVP had significantly increased anxiety scores as compared to patients with isolated sUVP (SCL-90 score for anxiety: 48.4 ± 3.8 vs. 41.6 ± 0.5; F = 4.231, p = 0.026).</p><p><strong>Discussion: </strong>An additional lesion of the inferior part of the vestibular nerve led to increased vestibular dysfunction in acute UVP and might trigger long-lasting symptom persistence. Identifying these patients early might improve the clinical outcome, lead to a faster improvement and prevent secondary psychosomatic symptoms.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"422"},"PeriodicalIF":4.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}