Journal of Neurology最新文献

{"title":"Sex differences in antiseizure medications response in people with epilepsy: a systematic review.","authors":"Loretta Giuliano, Elena Zambrelli, Vania Durante, Giulia Battaglia, Bruna Nucera, Vincenzo Mastrangelo, Irene Pappalardo, Federica Ranzato, Emanuele Cerulli Irelli, Barbara Mostacci","doi":"10.1007/s00415-025-13250-6","DOIUrl":"https://doi.org/10.1007/s00415-025-13250-6","url":null,"abstract":"<p><strong>Purpose: </strong>As a part of a wider project aimed to assess sex-related differences in adverse effects and efficacy of antiseizure medications (ASMs), we performed a systematic review focusing on differences in response to ASMs between males and females with epilepsy.</p><p><strong>Method: </strong>We conducted a comprehensive literature search in the PubMed database. The search was conducted without restriction on publication date, and all results up to September 2022 were included. We included all the articles written in English, Italian, Spanish, or French language evaluating the response to ASMs in people with epilepsy (PWE), with specific mention of the two sexes. The Newcastle-Ottawa Scale and the Jadad Scale were used to assess study quality.</p><p><strong>Results: </strong>A total of 1778 studies were identified. Of these, 60 studies searched for sex differences and among those, 46 (76%) did not identify statistically significant differences. Only 14 studies (23%) identified sex as a statistically significant variable in ASM efficacy. Among those, a greater number of studies reported higher rates of seizure reduction or seizure freedom in males using different ASMs, with 9 studies vs 5 in which drug response was higher in males.</p><p><strong>Conclusions: </strong>Our study has identified male sex as a predictor of drug response in epilepsy in the majority of studies that found sex differences. However, the scarcity of data found in the literature highlights the need for a systematic evaluation of sex as a variable influencing the response to medications in clinical research.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"518"},"PeriodicalIF":4.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659464","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":"Ludwik Eliasz Bregman (1865-1941).","authors":"Małgorzata Górecka-Politańska, Krystyna Makowska, Sławomir Gonkowski","doi":"10.1007/s00415-025-13244-4","DOIUrl":"https://doi.org/10.1007/s00415-025-13244-4","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"517"},"PeriodicalIF":4.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659462","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":"New genotype-phenotype correlations and transcriptomic findings in limb-girdle muscular dystrophy R9.","authors":"Qingyue Yuan, Zhihao Xie, Yunlong Lu, Chang Liu, Yanyu Lu, Xu Han, Zhenyu Li, Wei Zhang, Zhaoxia Wang, Yun Yuan, Zhiying Xie","doi":"10.1007/s00415-025-13252-4","DOIUrl":"https://doi.org/10.1007/s00415-025-13252-4","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to comprehensively investigate the clinical, genetic, muscle imaging, and pathological characteristics of limb-girdle muscular dystrophy R9 (LGMDR9) in a large cohort of Chinese patients. In addition, we sought to delineate the muscle transcriptomic landscape of LGMDR9 which has not been investigated.</p><p><strong>Methods: </strong>In total, 44 genetically confirmed Chinese LGMDR9 patients were enrolled. They underwent a detailed clinical, imaging, and pathological assessment, followed by customized bioinformatics analyses of genome-wide transcriptome data.</p><p><strong>Results: </strong>LGMDR9 patients presented with heterogeneous clinical manifestations, including hyper-creatine kinase-emia without weakness (n = 15), as well as mild (n = 11), moderate (n = 7), and severe (n = 11) weakness subgroups determined by hierarchical analysis. Eleven of the 35 pathogenic FKRP variants identified in our cohort were novel, with the c.545A > G variant being the most common found in 72.7% (32/44) patients. Hierarchical analysis revealed that 15 patients harboring null variants (frameshift, nonsense, and large deletions) exhibited a more severe phenotype compared to those with missense/inframe variants in FKRP. Muscle biopsy showed a dystrophic pattern in 19 patients, necrotizing myopathy in 5 patients, and mild myopathic changes in 9 patients. Muscle magnetic resonance imaging analysis showed a concentric pattern of fatty infiltration in 60.7% (17/28) patients. Transcriptomic profiling of 12 muscle samples showed significant upregulation of genes related to inflammation/immune response and extracellular matrix remodeling (P < 0.05). Furthermore, weighted gene co-expression network analysis identified a \"turquoise\" module enriched in immune cell proliferation and inflammatory markers, which were strongly correlated with histopathological inflammatory scores validated by immunohistochemical staining.</p><p><strong>Conclusion: </strong>Our findings indicate that null variants in FKRP may be associated with a severe phenotype. We also provide the first transcriptomic and experimental evidence of an immune-activated inflammatory microenvironment in LGMDR9 muscle tissue, which support the potential utility of immunomodulatory therapies in managing this condition.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"516"},"PeriodicalIF":4.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659463","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":"Charcot-Marie-Tooth-like presentation in giant axonal neuropathy: clinical variability and prevalence in a large Japanese case series.","authors":"Takahiro Hobara, Masahiro Ando, Yujiro Higuchi, Jun-Hui Yuan, Akiko Yoshimura, Takashi Saito, Takashi Shiihara, Shiho Okuda, Naoki Fukushima, Hiroyuki Awano, Takahito Inoue, Chikashi Yano, Fumikazu Kojima, Kento Kodama, Yu Hiramatsu, Satoshi Nozuma, Tomonori Nakamura, Yusuke Sakiyama, Akihiro Hashiguchi, Jun Mitsui, Shoji Tsuji, Hiroshi Takashima","doi":"10.1007/s00415-025-13243-5","DOIUrl":"10.1007/s00415-025-13243-5","url":null,"abstract":"<p><strong>Background: </strong>Giant axonal neuropathy 1 (GAN) is a rare neurodegenerative disorder with autosomal recessive inheritance and significant phenotypic heterogeneity, ranging from milder presentations resembling Charcot-Marie-Tooth disease (CMT) to classical presentations involving central and peripheral nervous systems. We investigated the genetic and clinical spectrum of GAN in Japanese patients with inherited peripheral neuropathies (IPNs).</p><p><strong>Methods: </strong>We conducted genetic screening of 3315 Japanese patients diagnosed with IPNs between 2007 and 2023 using targeted next-generation or whole-exome sequencing. Variant pathogenicity, clinical features, and neurophysiological and neuroimaging findings were reviewed.</p><p><strong>Results: </strong>We identified seven biallelic GAN variants in five patients from four unrelated families, including one homozygous and three compound heterozygous genotypes. Two novel pathogenic variants were identified: c.922G > T (p.Glu308*) and c.456dup (p.Ala153Cysfs*27). Two families exhibited the classical phenotype, whereas the other two exhibited a CMT-like phenotype. Mean onset age was 4.4 years (range 1.5-8), and gait disturbance was the initial symptom. The most common findings included distal weakness (n = 5), sensory impairment (n = 4), scoliosis (n = 3), autonomic dysfunction (n = 2). Neurophysiologically, all patients had sensorimotor axonal polyneuropathy. One patient with mild phenotype maintained a CMT-like state without systemic involvement until the age of 43 years and was still alive at 72, representing the longest documented survival in GAN.</p><p><strong>Conclusion: </strong>This study expands the genetic and phenotypic spectrum of GAN by identifying novel variants and a long-term survivor. These findings underscore the importance of systematic genetic screening for GAN in pediatric-onset CMT, even in the absence of classical features.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"514"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642846","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":"Prevalence of hereditary transthyretin amyloidosis in CIDP patients with red flags: a multicenter genetic screening and misdiagnosis analysis.","authors":"Pietro Emiliano Doneddu, Giulia Moretti, Vincenzo Di Stefano, Yuri Falzone, Luca Leonardi, Marco Luigetti, Giorgia Mataluni, Luca Gentile, Marinella Carpo, Alessandro Barilaro, Massimiliano Filosto, Elisa Vegezzi, Maurizio Inghilleri, Fabrizio Canale, Filippo Brighina, Sabrina Matà, Adele Ratti, Francesca Forcina, Giovanni Siconolfi, Claudia Lozi, Anna Mazzeo, Ugo Mollo, Barbara Risi, Giuseppe Cosentino, Federica Moret, Carla Fasano, Vincenzo Todisco, Massimo Russo, Eduardo Nobile-Orazio","doi":"10.1007/s00415-025-13218-6","DOIUrl":"https://doi.org/10.1007/s00415-025-13218-6","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv) is a rare, multisystemic disorder often presenting with peripheral neuropathy and can be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), especially in non-endemic areas. While clinical red flags have been proposed to aid diagnosis, their predictive value remains uncertain. This study prospectively assessed the prevalence of TTR variants in CIDP patients with red flags for ATTRv and retrospectively analyzed features of genetically confirmed ATTRv cases initially misdiagnosed as CIDP.</p><p><strong>Methods: </strong>Thirteen Italian tertiary neuromuscular centers consecutively screened CIDP patients with at least one red flag for TTR gene variants. A retrospective analysis was also conducted on ATTRv patients initially misdiagnosed as CIDP, comparing clinical, electrophysiological, and treatment response features to confirmed CIDP cases.</p><p><strong>Results: </strong>No TTR variants were identified among 124 screened CIDP patients despite 65% presenting with ≥ 2 red flags and 14% not responding to standard therapies. Among 17 retrospectively identified ATTRv patients, 5 (29%) met electrodiagnostic criteria for CIDP. In nearly half, CIDP was diagnosed without fulfilling electrodiagnostic criteria or obtaining appropriate supportive investigations. Compared to confirmed CIDP patients, ATTRv cases exhibited significantly more red flags, later onset, more insidious and distal presentations, a progressive course, lower rates of demyelination criteria fulfillment, and no response to immunomodulatory therapy.</p><p><strong>Conclusions: </strong>Red flags alone have limited predictive value in specialized settings. However, ATTRv should be considered in distal, progressive, treatment-resistant neuropathies, especially with multisystem features. Greater diagnostic rigor and increased awareness in non-specialist settings is essential to reduce misdiagnosis and improve access to therapy.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"515"},"PeriodicalIF":4.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649741","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":"Risk factors, clinical presentation, stroke subtype and short-term outcome following acute stroke in a multi-ethnic population: a 10-year study from Qatar.","authors":"Parsa Babaei Zadeh, Kim H Tran, Nabeela Khan, Ahmad Kamal, Naveed Akhtar, Ashfaq Shuaib","doi":"10.1007/s00415-025-13213-x","DOIUrl":"10.1007/s00415-025-13213-x","url":null,"abstract":"<p><strong>Background: </strong>Stroke remains a leading global cause of disability and mortality with over 100 million patients affected worldwide. Its incidence has risen in recent decades, especially in low- and middle-income countries (LMICs), due to limited education, healthcare, and effective prevention measures. This study investigates the association between ethnicity and outcomes of stroke in Qatar, a country with a heterogeneous population.</p><p><strong>Methods: </strong>Data from 18,174 stroke patients admitted to Hamad General Hospital from 2014 to 2024 were analyzed. We assessed patient characteristics, stroke types, comorbidities, and outcomes using the NIH Stroke Scale and modified Rankin Scale (mRS).</p><p><strong>Results: </strong>There were significant ethnic differences in stroke presentation and outcomes. Middle Easterns were older (59.7 ± 14.2) than South East Asian (50.1 ± 11.7) and Far Eastern (47.5 ± 9.85) patients; p < 0.001. Middle Eastern patients had a higher prevalence of stroke risk factors (diabetes, hypertension, obesity) and stroke mimics (39.8%) than Southeast Asian (21.7%) and Far Eastern (27.7%) patients (p < 0.0001). Far Eastern patients demonstrated a higher incidence (17.6%) of intracerebral hemorrhage compared to Middle Easterns (6.2%) and East Asians (10.6%); p < 0.0001. However, ischemic stroke was more common among Southeast Asians (58.6%) than Middle Eastern (43.8%) and Far Eastern (44.4%) patients; p < 0.0001. Lastly, there were significant differences in outcomes as measured by mortality and the mRS.</p><p><strong>Conclusion: </strong>There are significant ethnic differences in stroke presentation, management, and outcomes in Qatar, some of which may reflect underlying disparities driven by social and structural inequities. While genetic differences play a role, early management of vascular risk factors is a crucial, preventable measure to reduce stroke burden in LMICs and improve health outcomes.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"511"},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642849","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":"Environmental risk factors for multiple sclerosis: a comprehensive systematic review and meta-analysis.","authors":"Bruno Kusznir Vitturi, Maria Cellerino, Daniele Boccia, Emmanuelle Leray, Jorge Correale, Ruth Dobson, Ingrid van der Mei, Kazuo Fujihara, Matilde Inglese","doi":"10.1007/s00415-025-13248-0","DOIUrl":"10.1007/s00415-025-13248-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Its etiology may involve both genetic and environmental factors, including vitamin D levels, body mass index, infections, and smoking. This is the first comprehensive systematic review with meta-analysis that synthesizes and explore the role of many environmental risk factors in the etiology of MS.</p><p><strong>Methods: </strong>A systematic search of MEDLINE, SciVerse ScienceDirect and Web of Science were conducted for any original peer-reviewed article that included adult subjects diagnosed with and without MS that were exposed to any environmental risk factor. We did not set any time restrictions. Data were extracted and the quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies. All the information was synthesized qualitatively and quantitatively (meta-analysis). We used the random-effects model based on the binomial distribution to calculate the pooled effects sizes (ES) regarding the risk of developing MS according to each potential risk factor.</p><p><strong>Results: </strong>One-hundred thirty-two publications met all the eligibility criteria and were included in the review. Overall, 109,626 people with MS and 16,724,390 controls from 38 countries were included in the review. A total of 42 environmental risk factors were investigated as potential risk factors for MS. Among the various statistically significant associations, the pooled ES revealed a direct association between serological evidence of contact with EBV (ES = 1.96, 95% CI = 1.53-2.51), herpes virus type 6 (HHV-6) (ES = 2.84, 95% CI = 2.08-3.89) and varicella-zoster virus (ES = 1.33, 95% CI = 1.08-1.63) and the occurrence of MS. Similarly, smoking was associated with a greater likelihood of having MS (ES = 1.43, 95% CI = 1.27-1.61). Vitamin D levels at any time were negatively associated with the proportion of cases of MS and had a moderate pooled ES (g = - 0.48, 95% CI = - 0.88-0.09). Adult BMI was not associated with MS.</p><p><strong>Discussion: </strong>This review furnishes a broad and detailed overview of the potential environmental risk factors associated with MS. Our findings hold notable implications for public health policies, clinical practices, and the focus of future research.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"513"},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642847","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":"Vestibular event monitoring in acute posterior circulation stroke: from emergency room to stroke unit and beyond.","authors":"Gülden Akdal, Benjamin Nham, Belinda Kwok, Pinar Özcelik, Andrew Bradshaw, Chao Wang, Gábor Michael Halmágyi, Miriam S Welgampola","doi":"10.1007/s00415-025-13163-4","DOIUrl":"10.1007/s00415-025-13163-4","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"510"},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642850","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":"Longitudinal evaluation of serum neurofilament light levels in normal healthy volunteers: defining a threshold of concern.","authors":"Thomas A Lanz, Klemens Ruprecht, Christopher J Somps, Jens C Göpfert, Tony Kam-Thong, Fetene Tekle, Kelly A Fader, Viviana A Carcamo Yañez, Volker Meyer, Sabine Friedrich, Katerina Vlasakova, Carolin Otto, Sara A Paciga, Sophia L Samodelov, Shashi K Ramaiah","doi":"10.1007/s00415-025-13246-2","DOIUrl":"10.1007/s00415-025-13246-2","url":null,"abstract":"<p><p>Neurofilament light (NfL) is a neuron-specific protein integral to neuronal cytoskeletons. Upon damage to the central or peripheral nervous system (NS), NfL is released into cerebrospinal fluid and blood. Elevated serum or plasma NfL levels have been reported in a variety of diseases and NS injury states. However, although intraindividual longitudinal NfL changes may be more meaningful than NfL measurements at a single timepoint, data on the longitudinal variation of NfL in normal healthy volunteers (NHV) are scarce. We investigated normal variation in NHV serum NfL and estimate an upper limit of normal (ULN) of NfL variation in longitudinal samples. An initial cross-sectional screening in sera from 270 NHV using a 4-plex assay detected NfL in 99.6% and glial fibrillary acidic protein (GFAP) in 100%, while Tau (67.4%), and Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCH-L1, 4.1%) were less frequently detectable. An age-dependent increase was found in NfL (2.36% per year) and GFAP (1.18% per year). Longitudinal evaluation of NfL was then conducted in a separate cohort of 80 NHV at baseline, day 14 (range 11-17), and day 28 (range 26-56). A 1.64-fold increase from baseline in serum NfL was calculated as the ULN. Putting this threshold into context with published reports on NfL across a large variety of injury and disease settings, the 1.64-fold threshold is well positioned to discriminate between healthy and NS injury. Altogether, these findings provide a framework for longitudinal monitoring of serum NfL as a biomarker for neuronal damage in multiple contexts of use, including drug-induced injury.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"512"},"PeriodicalIF":4.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642848","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":"Neurophysiological biomarkers of networks impairment in amyotrophic lateral sclerosis.","authors":"Antonio Fasano, Veria Vacchiano, Luigi Bonan, Roisin McMackin, Bahman Nasseroleslami, Orla Hardiman, Rocco Liguori","doi":"10.1007/s00415-025-13229-3","DOIUrl":"https://doi.org/10.1007/s00415-025-13229-3","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease involving motor system as well as cognitive domains. There is an urgent need for objective biomarkers that can subcategorize subjects into homogeneous groups based on disease pathobiology.In this review, we discuss novel neurophysiological techniques that provide detailed, multiscale and multidimensional insights into ALS networks impairment, spanning from the micro-columnar architecture of the motor cortex to motor and cognitive networks. Specifically, Transcranial Magnetic Stimulation (TMS) paradigms can be used to evaluate the status of excitatory and inhibitory networks within the layers of the motor cortex. Abnormalities in functional connectivity between the two motor areas, as well as within the frontal-temporal and frontal parietal networks, can be characterized using novel source-localization analysis of high-density electroencephalography (EEG). TMS and EEG techniques provide data that correlate with both motor and cognitive impairment. Furthermore, cortico-muscular coherence analysis can be used to assess functional dysregulation within the entire motor system, and novel surface electromyography (EMG) techniques, such as motor unit number estimation, motor unit number index, and nerve excitability testing studies provide useful insights into axonal loss and membrane ion channel dysfunctions in lower motor neurons.The integrated analysis of these biomarkers provides valuable insights into the clinical and biologic heterogeneity of the disease, aiding the intelligent design of next generation precision-based therapeutics.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"507"},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626594","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}