Journal of Neurology最新文献

{"title":"A 24-week prospective, multicenter, real-world study on eptinezumab's effectiveness and safety in migraine prevention (EMBRACE II).","authors":"Piero Barbanti, Cinzia Aurilia, Gabriella Egeo, Alberto Doretti, Florindo d'Onofrio, Paola Scatena, Steno Rinalduzzi, Luisa Vinciguerra, Mattia Sansone, Rosario Vecchio, Valeria Drago, Giovanna Viticchi, Marco Bartolini, Angelo Ranieri, Monica Bandettini di Poggio, Francesco Baldisseri, Davide Mascarella, Fabio Brusaferri, Luigi Caputi, Stefano Messina, Massimo Autunno, Alessandro Valenza, Bianca Orlando, Marisa Distefano, Laura Borrello, Francesca Pistoia, Cecilia Camarda, Gennaro Saporito, Giacomo Querzola, Paola Torelli, Antonio Salerno, Francesca Gragnani, Barbara Petolicchio, Antonio Carnevale, Roberta Messina, Massimo Filippi, Sofia Tavani, Giulia Fiorentini, Stefano Bonassi, Sabina Cevoli, Alice Mannocci","doi":"10.1007/s00415-025-13095-z","DOIUrl":"10.1007/s00415-025-13095-z","url":null,"abstract":"<p><strong>Introduction: </strong>We evaluated the effectiveness, tolerability, and safety of eptinezumab in preventing high-frequency episodic migraine (HFEM) and chronic migraine (CM) over 24 weeks in real-world. We also assessed its impact during the first treatment week, in patients failing monoclonal antibodies targeting the calcitonin gene-related peptide (anti-CGRP mAbs), and the effects of dose escalation to 300 mg in patients requiring enhanced control.</p><p><strong>Methods: </strong>EMBRACE II is a multicenter (n = 22), prospective, 24-week, real-world study involving consecutive patients with HFEM or CM who had failed > 3 preventive treatments. Eptinezumab (100 mg, with the option for escalation to 300 mg at week 12) was administered quarterly.</p><p><strong>Primary endpoint: </strong>change in monthly migraine days (MMD), for HFEM or monthly headache days (MHD), for CM, between weeks 21-24 and baseline. Secondary endpoints: changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates.</p><p><strong>Results: </strong>Of the 215 participants who had received ≥ 1 eptinezumab dose, 74 were treated for ≥ 24 weeks and considered for effectiveness analysis. Eptinezumab significantly (p < 0.001) reduced MMD/MHD (- 10.5), MAI (- 15.6), NRS (- 2.2), HIT-6 (- 9.9), MIDAS (- 48.7), and MIBS-4 (- 4.3). ≥ 50% responders were 69%, ≥ 75% responders 39.2%, and 100% responders 4.1%. Comparing the first week with the last baseline week, a significant reduction in migraine days was observed (- 3.7; p < 0.001). Significant improvements were seen in patients failing anti-CGRP mAbs (32.4%) and in those escalating to 300 mg (33.8%). Half of the subjects reported being \"very much improved\" or \"much improved\". The adverse events were infrequent (2.8%).</p><p><strong>Conclusions: </strong>This real-world study documents that 24-week eptinezumab treatment is rapidly effective and well tolerated in migraine patients with multiple therapeutic failures (including anti-CGRP mAbs). One-third of patients escalated to 300 mg at week 12, achieving further significant migraine-related disability reduction.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"382"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDA vs. EMA: evaluating donanemab and the global debate on accelerated approvals.","authors":"Prakriti Pokhrel, Aakriti Jindal, Qadeer Ahmed","doi":"10.1007/s00415-025-13131-y","DOIUrl":"10.1007/s00415-025-13131-y","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"378"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976709","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}

{"title":"Need for awareness and surveillance of long-term post-COVID neurodegenerative disorders. A position paper from the neuroCOVID-19 task force of the European Academy of Neurology.","authors":"Dániel Bereczki, Ádám Dénes, Filippo M Boneschi, Tamar Akhvlediani, Francesco Cavallieri, Alessandra Fanciulli, Saša R Filipović, Alla Guekht, Raimund Helbok, Sonja Hochmeister, Tim J von Oertzen, Serefnur Özturk, Alberto Priori, Martin Rakusa, Barbara Willekens, Elena Moro, Johann Sellner","doi":"10.1007/s00415-025-13110-3","DOIUrl":"10.1007/s00415-025-13110-3","url":null,"abstract":"<p><strong>Background: </strong>Neuropathological and clinical studies suggest that infection with SARS-CoV-2 may increase the long-term risk of neurodegeneration.</p><p><strong>Methods: </strong>We provide a narrative overview of pathological and clinical observations justifying the implementation of a surveillance program to monitor changes in the incidence of neurodegenerative disorders in the years after COVID-19.</p><p><strong>Results: </strong>Autopsy studies revealed diverse changes in the brain, including loss of vascular integrity, microthromboses, gliosis, demyelination, and neuronal- and glial injury and cell death, in both unvaccinated and vaccinated individuals irrespective of the severity of COVID-19. Recent data suggest that microglia play an important role in sustained COVID-19-related inflammation, which contributes to the etiology initiating a neurodegenerative cascade, to the worsening of pre-existing neurodegenerative disease or to the acceleration of neurodegenerative processes. Histopathological data have been supported by neuroimaging, and epidemiological studies also suggested a higher risk for neurodegenerative diseases after COVID-19.</p><p><strong>Conclusions: </strong>Due to the high prevalence of COVID-19 during the pandemic, healthcare systems should be aware of, and be prepared for a potential increase in the incidence of neurodegenerative diseases in the upcoming years. Strategies may include follow-up of well-described cohorts, analyses of outcomes in COVID-19-registries, nationwide surveillance programs using record-linkage of ICD-10 diagnoses, and comparing the incidence of neurodegenerative disorders in the post-pandemic periods to values of the pre-pandemic years. Awareness and active surveillance are particularly needed, because diverse clinical manifestations due to earlier SARS-CoV-2 infections may no longer be quoted as post-COVID-19 symptoms, and hence, increasing incidence of neurodegenerative pathologies at the community level may remain unnoticed.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"380"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The intersection of delirium and long-term cognition in older adults: the critical role of delirium prevention.","authors":"Zhongyuan Lu, Xiaoling Wang, Jiao Wang, Liang Zhao, Yichen Wu, Mingyang Sun, Jiaqiang Zhang","doi":"10.1007/s00415-025-13104-1","DOIUrl":"10.1007/s00415-025-13104-1","url":null,"abstract":"<p><p>Delirium, a neuropsychiatric syndrome characterized by an acute and usually reversible state of confusion, while dementia is a chronic, acquired cognitive impairment that significantly reduces a patient's ability to perform daily tasks, learn, work, and engage in social interactions. Previous studies indicates that individuals with dementia are more susceptible to delirium than the general population, and that delirium serves as an independent risk factor for the subsequent onset of dementia. However, a major controversy in this field concerns whether delirium is merely a marker of vulnerability to dementia, or whether delirium-induced adverse outcomes such as falls and functional decline contribute to dementia, or whether delirium directly causes permanent neuronal damage and lead to dementia. It is possible that all these hypotheses hold some truth. In this review, we examine the shared and distinct mechanisms of delirium and dementia by reviewing their clinical features, epidemiology, clinicopathological, biomarkers, neuroimaging, and recent experimental studies, and we discuss the importance of targeting delirium to explore new preventive and therapeutic strategies for reducing long-term cognitive impairment.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"381"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014940","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}

{"title":"Lipoprotein-a and white matter abnormalities: predicting small vessel disease in young patients with ischemic cerebrovascular events.","authors":"Paola Caruso, Marco Liccari, Gabriele Prandin, Pierandrea Vinci, Federica Pellicori, Nicola Fiotti, Emiliano Panizon, Giovanni Furlanis, Marcello Naccarato, Gianni Biolo, Paolo Manganotti","doi":"10.1007/s00415-025-13111-2","DOIUrl":"10.1007/s00415-025-13111-2","url":null,"abstract":"<p><strong>Introduction: </strong>Post-stroke cognitive impairment (PSCI) affects 15-70% of ischemic stroke survivors, with vascular dementia contributing significantly to long-term disability. Lipoprotein(a) [Lp(a)] has emerged as a key risk factor for cardiovascular and cerebrovascular diseases, but its role in cerebral small vessel disease (cSVD) remains unclear. This study investigates the association between elevated Lp(a) levels and Fazekas scores (≥ 2), a marker of white matter hyperintensities (WMHs) indicative of cSVD, in young patients (< 65 years) with ischemic stroke or transient ischemic attack (TIA).</p><p><strong>Methods: </strong>We retrospectively analysed data of 217 patients with ischemic stroke/TIA, age 18-65, and Lp(a) measurement within four weeks of the event. Data included clinical history, imaging (MRI Fazekas scores), and Lp(a) levels (> 50 mg/dL). Multivariable logistic regression and ROC analysis were performed to identify predictors of higher Fazekas scores.</p><p><strong>Results: </strong>Elevated Lp(a) levels were independently associated with Fazekas scores ≥ 2 (OR 2.83, 95% CI 1.13-7.10, p = 0.03) alongside older age, hypertension, prior stroke/TIA, and elevated non-HDL cholesterol. The predictive model demonstrated high accuracy (AUC = 0.81). Patients with elevated Lp(a) exhibited greater WMH burden, indicating advanced small vessel damage.</p><p><strong>Conclusions: </strong>Elevated Lp(a) levels are a significant biomarker for WMHs and cSVD in young stroke patients, offering prognostic value beyond traditional risk factors. Incorporating Lp(a) testing into routine stroke evaluations could enable early identification and tailored management strategies to mitigate further vascular damage and cognitive decline.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 6","pages":"379"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Core diagnostic features of stiff person syndrome: insights from a case-control study.","authors":"Shuvro Roy, Yishang Huang, Chen Hu, Kathryn C Fitzgerald, Yujie Wang, Scott D Newsome","doi":"10.1007/s00415-025-13103-2","DOIUrl":"10.1007/s00415-025-13103-2","url":null,"abstract":"<p><strong>Background: </strong>Stiff person syndrome spectrum disorders (SPSD) are rare, disabling neuroimmunological conditions with no consensus diagnostic criteria, making diagnosis challenging. Misdiagnosis often occurs due to the limited awareness of atypical symptoms and presentations. This study aimed to identify key clinical and paraclinical features most predictive of classic SPS and SPS-plus diagnosis and misdiagnosis patterns.</p><p><strong>Methods: </strong>We conducted a retrospective case-control study at Johns Hopkins SPS center, analyzing patient data from 1997-2021. A total of 154 classic SPS, 45 SPS-plus, and 66 control patients (evaluated for SPSD but given an alternative diagnosis) were included. Clinical assessments, autoantibody testing, electromyography (EMG), and other diagnostic studies were reviewed. Sensitivity, specificity, and diagnostic odds ratios were calculated, with logistic regression identifying the strongest diagnostic indicators of the SPS phenotypes.</p><p><strong>Results: </strong>Torso/lower extremity symptoms, hypersensitivity triggers, paravertebral stiffness, and gait dysfunction were common in both phenotypes. Classic SPS was most specifically associated with high-titer GAD65 antibodies (98%), cerebrospinal fluid GAD65 positivity (100%), characteristic EMG abnormalities (> 90%), and hyperlordosis (87%). SPS-plus specificity was highest for cerebellar (98.5%) and brainstem (100%) signs/symptoms. High-titer GAD65 antibodies were the strongest independent diagnostic factor for both phenotypes. Misdiagnosis was most common in patients presenting with upper extremity, brainstem, or cerebellar involvement.</p><p><strong>Conclusions: </strong>Recognizing key diagnostic and misdiagnosis patterns may help clinicians make accurate and timely diagnoses of SPSD. This could help prevent misdiagnosis/overdiagnosis, ensure timely treatment, and assure appropriate patient populations are included in future interventional SPS clinical trials. Further studies are needed to validate these findings and refine diagnostic criteria.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"377"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"William Henry Broadbent (1835-1907).","authors":"Andrew J Larner","doi":"10.1007/s00415-025-13119-8","DOIUrl":"https://doi.org/10.1007/s00415-025-13119-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"376"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004456","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}

{"title":"Intrathecal methotrexate in progressive multiple sclerosis: a phase 1 open-label study with long-term follow-up.","authors":"Hadar Kolb, Yuval Shachaf, Karin Fainberg, Maya Golan, Keren Regev, Ifat Vigiser, Lior Fuchs, Avi Gadoth, Meir Kestenbaum, Nurit Omer, Ludmila Shopin, Elissa L Ash, Moran Artzi, Dafna Ben Bashat, Orna Aizenstein, Arnon Karni","doi":"10.1007/s00415-025-13114-z","DOIUrl":"10.1007/s00415-025-13114-z","url":null,"abstract":"<p><p>Progressive multiple sclerosis (PMS) remains challenging to treat effectively. Intrathecal methotrexate (ITMTX) has emerged as a potential therapy for alleviating PMS symptoms. This study aimed to assess the safety, tolerability, and efficacy of ITMTX in PMS patients over short- and long-term periods. A 1-year, open-label, phase 1 study was conducted, administering ITMTX quarterly to eligible PMS patients. Primary endpoints included changes in Expanded Disability Status Scale (EDSS) scores, 25-Foot Walk (25FW), and Symbol Digit Modalities Test (SDMT) from baseline to 1 year. Secondary endpoints encompassed 6-month clinical changes, cerebrospinal fluid immune cell profiling, and MRI measures. Long-term follow-up included retrospective review of patients continuing ITMTX treatment beyond the initial study period. Twenty-two patients were initially enrolled, with 17 completing the 12-month treatment. ITMTX was well-tolerated, with post-LP headache being the most common adverse event (31.8%). No significant changes were observed in EDSS, 25FW, SDMT, CSF IgG levels, or immune cell counts over 12 months. Long-term follow-up of ten patients receiving ITMTX for 2-9 years (mean 4.1 ± 3.1 years) showed stable EDSS in seven patients, with three experiencing minimal worsening (0.5 points). The therapy was well-tolerated long-term, with no evidence of disease progression in most patients. These findings support ITMTX as a promising therapeutic approach for PMS, particularly for patients progressing despite approved disease-modifying therapies or unable to tolerate them. Further large-scale studies are warranted to confirm these results. Clinicaltrials.gov identifier: NCT02644044, year: 2015.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"374"},"PeriodicalIF":4.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997521","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}

{"title":"Aging and the neuropsychiatry of multiple sclerosis: a cross-sectional study.","authors":"David E Freedman, Jiwon Oh, Gillian Einstein, Anthony Feinstein","doi":"10.1007/s00415-025-13116-x","DOIUrl":"10.1007/s00415-025-13116-x","url":null,"abstract":"<p><p>Aging in multiple sclerosis (MS) affects clinical and radiological disease activity. Yet, evidence is equivocal about the effects of aging on the neuropsychiatric sequelae of MS, including anxiety, depression, fatigue, and cognitive dysfunction. This study aimed to clarify how the neuropsychiatric symptoms of MS vary across ages. A consecutive cohort of 1194 people with MS (pwMS) underwent neuropsychological testing using the Minimal Assessment of Cognitive Function in MS, the Hospital Anxiety and Depression Scale sub-scales for anxiety (HADS-A) and depression (HADS-D), Modified Fatigue Impact Scale (MFIS), and the Perceived Deficits Questionnaire (PDQ) for cognitive complaints. Participants were stratified into age sub-groups: 18-29, 30-39, 40-49, 50-59 years. t-tests were undertaken to compare symptoms between the 18-29 and 50-59 sub-groups. Linear regression analyses, controlling for disability (Expanded Disability Status Scale; EDSS), sex, educational years, and high-efficacy disease-modifying therapy use, were used to evaluate whether age significantly predicted neuropsychiatric sequelae. Mean age was 42.15 years, 74.12% were female, and median EDSS was 2.00. Older pwMS had reduced HADS-A, PDQ, California Verbal Learning Test (CVLT), Brief Visuospatial Memory Test (BVMT), Symbol Digit Modalities Test (SDMT), and Delis-Kaplan Executive Function System (D-KEFS) scores, all p < 0.01. There were no age differences on the HADS-D, MFIS, Controlled Oral Word Association Test, Judgment of Line Orientation, or Paced Auditory Serial Addition Test. Controlling for covariates, older age independently predicted reduced HADS-A, CVLT, BVMT, SDMT, and D-KEFS scores, all p < 0.01. In summary, as pwMS age, anxiety declines and performance on learning, memory, processing speed, and executive function tests worsens.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"375"},"PeriodicalIF":4.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987940","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}

{"title":"Pathological laugher and crying in motor neuron diseases: a matter of bulbar and neurobehavioral involvement with sex imbalance.","authors":"Veronica Faltacco, Eleonora Dalla Bella, Anna Nigri, Alessandra Telesca, Giulia Gandini, Nilo Riva, Maria Vizziello, Jean Paul Medina, Greta Demichelis, Marina Grisoli, Susanna Usai, Giuseppe Lauria, Monica Consonni","doi":"10.1007/s00415-025-12959-8","DOIUrl":"10.1007/s00415-025-12959-8","url":null,"abstract":"<p><strong>Background: </strong>Emotional lability (EL), also known as pathological laughter and crying, is a common but understudied symptom in motor neuron diseases (MND): amyotrophic lateral sclerosis and primary lateral sclerosis. This study aimed to investigate the prevalence of EL in MND and to explore the independent frequency components of laughter and crying in relation to motor, cognitive, neuropsychiatric, and neuroimaging factors.</p><p><strong>Methods: </strong>A total of 198 incident MND patients were enrolled. The Centre of Neurological Study-Lability Scale was used to measure EL. Associations between EL and motor function, mood, neuropsychological variables, and structural MRI were examined, with cortical thinning measured on a subset of 48 patients.</p><p><strong>Results: </strong>EL was identified in 36% of patients showing more severe motor functional disabilities, heightened depressive and anxiety symptoms and behavioral changes than those without EL. Women exhibited more severe EL and altered mood with frequent crying episodes than men. EL was strongly correlated with bulbar involvement. Crying episodes were associated with mood disorders, while laughter correlated with disinhibition and emotional regulation difficulties. EL had a specific association with the thinning of frontal regions, including the right pars orbitalis, which was also linked to altered emotional and behavioral regulation.</p><p><strong>Conclusion: </strong>These findings underscore the role of corticobulbar and frontal pathways in EL pathophysiology. The study highlights the distinct mechanisms underlying pathological crying and laughter and their independency from general cognitive decline. It emphasizes the need for clinicians to recognize EL as an independent symptom, necessitating targeted management strategies to improve patient outcomes and support caregivers.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 5","pages":"372"},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016212","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}