Journal of Neurology最新文献

{"title":"Camptocormia in Parkinson's disease: state of the art and future directions.","authors":"Valeria Sajin, Mark Goodall, Antonella Macerollo","doi":"10.1007/s00415-025-13396-3","DOIUrl":"https://doi.org/10.1007/s00415-025-13396-3","url":null,"abstract":"<p><p>Camptocormia is a frequent axial postural deformity in Parkinson's disease (PD) that is prevalent in up to 18% in the PD population. Camptocormic PD patients have a lower quality of life and higher risks of falls, back pain and spondylarthrosis. Camptocormia is probably induced by brain changes caused by PD. Despite the myopathic changes in camptocormic PD patients' spine muscles and camptocormia's clinical similarity with dystonic postures, its pathophysiology seems to be different from myopathy and dystonia. The exact pathogenesis is however unclear. There is no consensus for treatment of PD-related camptocormia, although some nonpharmacological (e.g., backpack weight, back extensors and physiotherapy), pharmacological (e.g., levodopa, istradefylline and botulinum toxin) and surgical approaches (surgical corrections and deep brain stimulation) were elaborated upon with variable effects. There are still many gaps in data regarding clinical predictors, pathophysiology, the treatment and prevention of camptocormia. Multicenter studies (particularly on nonpharmacological therapy, on preventing strategies, and on favorizing factors) are needed. We identified an unexpectedly limited number of publications on camptocormia in PD. As of August 2025, the search strategy with MeSH terms related to camptocormia, on PubMed returned only 220 results. After screening, only 138 of the titles and abstracts were relevant to the topics. Of all these publications, only 27 (19.6%) were reviews, and more than half of which (15 reviews) focused on some characteristics of camptocormia (e.g., surgical treatment, deep brain stimulation, and prevalence or etiology) but did not elucidate on all its complex aspects. The present narrative review aims to describe different aspects of camptocormia ranging from its prevalence to the pathophysiology and treatment possibilities and provide a comprehensive image of this disorder.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"638"},"PeriodicalIF":4.6,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102938","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":"Delineating the pathogenic threshold and phenotypic spectrum of SCA27B: findings from a large French-Canadian cohort.","authors":"Pablo Iruzubieta, David Pellerin, Catherine Ashton, Felipe Villa, Mathilde Renaud, Marie-Josée Dicaire, Matt C Danzi, Mayra Aldecoa, Jean Mathieu, Rami Massie, Colin H Chalk, Anne-Louise Lafontaine, François Evoy, Marie-France Rioux, Jean-Denis Brisson, Kym M Boycott, Henry Houlden, Matthis Synofzik, Roberta La Piana, Stephan Zuchner, Antoine Duquette, Bernard Brais","doi":"10.1007/s00415-025-13387-4","DOIUrl":"10.1007/s00415-025-13387-4","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant spinocerebellar ataxia 27B (SCA27B), caused by an intronic (GAA•TTC) repeat expansion in FGF14, is a common cause of late-onset cerebellar ataxia, but its genotypic and phenotypic spectrum remains to be fully established.</p><p><strong>Methods: </strong>We analysed the FGF14 (GAA•TTC) repeat expansion in a cohort of 134 patients with ataxia and 822 controls from Quebec. We conducted segregation study in large families to further characterize intergenerational repeat instability.</p><p><strong>Results: </strong>We found a significant enrichment of (GAA•TTC)_≥200 alleles in the ataxia cohort compared to controls (53.0%, 71/134, vs 3.6%, 30/822, p < 0.0001), including for (GAA•TTC)_200-249 alleles (8.2% vs 2.6%, p = 0.0026). We identified 12 ataxic patients with a phenotype compatible with SCA27B carrying a (GAA•TTC)_200-249 expansion supporting the pathogenicity of these alleles in some patients. We further delineated the phenotype of 125 symptomatic individuals from 69 families who carried an FGF14 (GAA•TTC)_≥200 repeat expansion. Patients with (GAA•TTC)_200-249, (GAA•TTC)_250-299, and (GAA•TTC)_≥300 had a similar phenotype. We observed that 14% of patients with episodic symptoms (13/92) had severe episodes that were initially misdiagnosed as stroke, vestibular neuritis, Wernicke's encephalopathy, or seizures.</p><p><strong>Discussion and conclusion: </strong>This large cohort demonstrates that (GAA•TTC)_200-249 alleles are enriched in patients with ataxia compared to controls and can be pathogenic for SCA27B, supporting the need to define a lower pathogenic threshold in the presence of specific clinical criteria.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"636"},"PeriodicalIF":4.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092037","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":"Diagnostic performance of the 2010, 2017, and 2024 McDonald criteria: clinical implications in multiple sclerosis.","authors":"Mario Habek, Ivan Adamec, Tereza Gabelić, Barbara Barun, Magdalena Krbot Skorić","doi":"10.1007/s00415-025-13395-4","DOIUrl":"https://doi.org/10.1007/s00415-025-13395-4","url":null,"abstract":"<p><strong>Objective: </strong>To compare the sensitivity, specificity, predictive value, and accuracy of the 2010, 2017, and 2024 revisions of the McDonald criteria in a cohort of patients who have experienced their first demyelinating event suggestive of MS.</p><p><strong>Methods: </strong>We included 118 participants (mean age 32.21 years, 71.2% female) with an average follow-up of 7.89 ± 2.65 years. The primary outcomes were to assess the sensitivity, specificity, predictive value, and accuracy of the 2010, 2017, and 2024 revisions of the McDonald criteria and to compare the effectiveness of these three sets of criteria in diagnosing MS.</p><p><strong>Results: </strong>The 2024 revision demonstrated higher sensitivity (90% vs. 86% vs 32% and 87% vs. 79% vs. 37%) and lower specificity (35% vs. 47% vs. 69% and 54% vs. 63% vs 92%) when compared to the 2017 and 2010 revisions, for the development of a relapse and new MRI lesion, respectively. The hazard of relapse and EDSS worsening for participants meeting the 2024 McDonald criteria was 3.464 times (95% CI 1.492-8.046), p = 0.004, and 3.395 times (95% CI 1.043-11.049), p = 0.042, higher compared to participants who did not meet the criteria. After adjusting for age, sex, and EDSS, the hazard of switching to HET for participants meeting the 2024 McDonald criteria was 4.617 times greater than that of participants not meeting the criteria.</p><p><strong>Conclusion: </strong>The findings indicate that the 2024 criteria have the highest sensitivity while retaining clinical applicability, especially in identifying disease activity through new MRI lesions.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"637"},"PeriodicalIF":4.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102669","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":"Clinical phenotype associated with A118V mutation of PRPN gene.","authors":"Thomas Giannelli, Anna Ladogana, Dorina Tiple, Luana Vaianella, Anna Poleggi, Giorgia Ruta, Dalila Totaro, Giancarlo Logroscino, Damiano Paolicelli, Alessandro Introna","doi":"10.1007/s00415-025-13397-2","DOIUrl":"10.1007/s00415-025-13397-2","url":null,"abstract":"<p><strong>Background: </strong>Creutzfeldt-Jakob disease (CJD) is the most common human prion disease, with genetic forms linked to PRNP gene mutations accounting for 10-15% of cases. We present a case of probable genetic prion disease associated with a novel PRNP mutation.</p><p><strong>Case presentation: </strong>A previously healthy 60-year-old woman developed gait ataxia and micrographia. Six months later, she experienced severe anxiety, emotional lability, and visual hallucinations. Brain magnetic resonance imaging (MRI) showed cortical ribboning in the frontal-insular regions. Her condition progressed to walking dependence and cerebellar dysarthria. She died 15 months after symptom onset. CSF analysis revealed elevated total-Tau (1933 pg/mL; reference < 450 pg/mL). RT-QuIC assay using full-length recombinant PrP was negative. Genetic testing revealed a Met/Val polymorphism at codon 129 and a novel heterozygous A118V mutation in the PRNP gene. A second RT-QuIC using truncated PrP confirmed abnormal prion seeds, supporting a probable diagnosis of prion disease.</p><p><strong>Conclusions: </strong>The compound heterozygous A118V and M129V PRNP variant had not previously been associated with prion disease. Family history was unobtainable, as relatives declined testing. The patient's presentation-cerebellar and psychiatric symptoms-resembled Gerstmann-Sträussler-Scheinker syndrome, though a definitive diagnosis was not possible without neuropathology. MRI and RT-QuIC findings supported prion disease. The positive result with truncated PrP highlights its diagnostic value, offering improved sensitivity. This case underscores the phenotypic diversity of PRNP mutations and the importance of molecular testing, especially when family history or neuropathology is unavailable. PRNP gene analysis should be considered in patients with rapidly progressive motor and cognitive symptoms suggestive of prion disease.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"635"},"PeriodicalIF":4.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092026","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":"Jirō Suzuki (1924-1990).","authors":"Mariam M Yousuf, Hidenori Endo, Jonathan D Santoro","doi":"10.1007/s00415-025-13393-6","DOIUrl":"10.1007/s00415-025-13393-6","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"633"},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092042","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":"Seesaw nystagmus in oculopalatal tremor.","authors":"Hyo-Jung Kim, Seoyeon Kim, So-Yeon Yun, Ji-Soo Kim","doi":"10.1007/s00415-025-13391-8","DOIUrl":"https://doi.org/10.1007/s00415-025-13391-8","url":null,"abstract":"","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"634"},"PeriodicalIF":4.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092059","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":"Evaluating the predictive potential of Th1 (IFN-γ⁺CD4⁺)/CD4⁺ in rapidly progressive amyotrophic lateral sclerosis.","authors":"Jiahui Zhu, Yuechen Zhang, Shuqi Hu, Xudong He, Xiaoqin Hong, Wan Wei, Song Shu, Huixia Zhou, Gaoyi Yang, Hao Zhang","doi":"10.1007/s00415-025-13361-0","DOIUrl":"10.1007/s00415-025-13361-0","url":null,"abstract":"<p><strong>Background: </strong>Th1 (IFN-γ⁺CD4⁺)/CD4⁺ cells exacerbate the release of pro-inflammatory cytokines, contributing to neuronal death. It is proposed that the peripheral immune system plays a pivotal role in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aims to develop an interpretable machine learning model based on blood Th1/CD4⁺ cells to predict rapidly progressive ALS.</p><p><strong>Methods: </strong>We enrolled 564 patients with sporadic ALS who met the eligibility inclusion criteria for further analysis. Immune cells and cytokines were quantified using flow cytometric cell counting and a flow cytometry-based fluorescent bead capture assay. Multivariate Cox proportional hazards models and restricted cubic spline analyses were applied to estimate the correlation between Th1/CD4⁺ cells and rapidly progressive ALS. The important variables identified through LASSO regression analysis were incorporated into the development of the machine learning model.</p><p><strong>Results: </strong>The multivariate Cox proportional hazards model revealed that, compared to the low Th1/CD4⁺ group (Th1/CD4⁺  < 16.21), the high Th1/CD4⁺ group (Th1/CD4⁺  ≥ 16.21) was positively associated with the rate of ALS progression (HR: 1.90, 95% CI: 1.34-2.70). Th1/CD4⁺ is also associated with the decline in forced vital capacity (r = 0.11, P = 0.01). The machine learning model was built using Th1/CD4⁺ in combination with the other 4 features. Xgboost performed best in the validation cohort, achieving an AUC of 0.804 and a G mean of 0.756.</p><p><strong>Conclusions: </strong>Th1/CD4⁺ (with an optimal cutoff value of 16.21) was established as an independent risk factor for rapid progression in ALS. The machine learning model incorporating Th1/CD4⁺ demonstrated strong predictive performance.</p><p><strong>Trial registration: </strong>The prospective cohort study is registered with the Chinese Clinical Trial Registry (ID: ChiCTR2400079885) ( http://www.chictr.org.cn/ ).</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"631"},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058504","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":"Genetic background of neurological disorders with basal ganglia calcification.","authors":"Maha Yektay Farahmand, Joel Wallenius, Johan Wasselius, Olof Gråhamn, Andreas Puschmann, Andreea Ilinca","doi":"10.1007/s00415-025-13344-1","DOIUrl":"10.1007/s00415-025-13344-1","url":null,"abstract":"<p><strong>Background: </strong>Bilateral basal ganglia calcifications (BGCs), if severe, are known hallmarks for idiopathic BGC disease (IBGC), but if milder, are often considered radiological findings of unknown significance. In previous studies, only a minority of patients with BGC had monogenic forms of IBGC.</p><p><strong>Methods: </strong>We studied consecutive patients from a tertiary neurology clinic with bilateral BGCs of variable severity, and their families. We analyzed known IBGC genes, and an extended panel of genes linked to monogenic stroke and metabolic conditions. Clinical, radiological, and genetic data were collected, including vascular risk factors, cerebrovascular events, imaging findings (total calcification score, white matter hyperintensities, ischemic/hemorrhagic lesions), and relevant family history.</p><p><strong>Results: </strong>Twenty-four families with BGCs and neurological symptoms were analyzed. Disease-causing variants were identified in 14 families (58.3%). Eight patients had IBGC (variants in SLC20A2, PDGFB, MYORG), 4 had mitochondrial disease (MT-TL1), and 2 had monogenic vascular conditions (GAL, MAP3K6). Three variants were novel. BGC severity was highest in IBGC cases, while vascular and mitochondrial cases had milder calcifications. White matter hyperintensities were seen in 94.7% of cases and correlated highly with the total calcification score. Clinical vascular events had occurred in 41.7% cases. No monogenic cause was found in 10 patients, although many of these showed clinical or radiological features suggestive of monogenic disease.</p><p><strong>Conclusions: </strong>Bilateral BGCs can occur in many neurogenetic disorders apart from IBGCs, and a broader genetic search increases the diagnostic yield. Patients with BGCs frequently had clinical cerebrovascular events, which emphasizes the role of cerebrovascular pathology in BGCs.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"632"},"PeriodicalIF":4.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064945","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 decline in striatal DAT binding in LRRK2 Parkinson's disease: connections with CSF α-synuclein seeding activity.","authors":"Jing Wang, Xixi Sun, Yunfei Yin, Ruihua Cao","doi":"10.1007/s00415-025-13359-8","DOIUrl":"10.1007/s00415-025-13359-8","url":null,"abstract":"<p><strong>Objective: </strong>Parkinson's disease (PD) associated with mutations in the LRRK2 gene exhibits considerable pathological heterogeneity and may not present with Lewy body pathology. The α-Syn seed amplification assay (SAA) performed on cerebrospinal fluid (CSF) has emerged as a reliable in vivo biomarker of α-Syn aggregation. In this study, we aim to investigate the longitudinal trajectories of striatal dopaminergic imaging in LRRK2 PD patients stratified by CSF α-Syn SAA status.</p><p><strong>Methods: </strong>Data were obtained from the Parkinson's Progression Markers Initiative. CSF α-Syn aggregation was assessed using SAA. Striatal DAT-specific binding ratios (SBR) were quantified using [¹²³I] FP-CIT SPECT at baseline, year 2, and year 4.</p><p><strong>Results: </strong>At baseline, the α-Syn SAA-negative LRRK2 PD group exhibited higher DAT binding in the contralateral putamen and ipsilateral putamen compared to the SAA-positive group with comparable disease duration. Longitudinally, linear mixed-effects models demonstrated that the α-Syn SAA-negative LRRK2 PD maintained significantly higher DAT binding in both the contralateral and ipsilateral putamen over time. A significant group × time interaction was identified in the contralateral caudate, suggesting a slower rate of DAT loss in the α-Syn SAA-negative group. Sensitivity analyses restricted to participants with complete baseline and follow-up imaging data largely confirmed the main LMEM findings.</p><p><strong>Conclusions: </strong>The observed differences in striatal dopaminergic degeneration between LRRK2 PD patients with and without detectable CSF α-synuclein aggregates may reflect region-specific vulnerability to underlying pathological processes. Our findings support the utility of CSF α-Syn SAA status as both a diagnostic and prognostic biomarker in LRRK2 PD.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"630"},"PeriodicalIF":4.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054074","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":"Amygdala-predominant Lewy bodies associate with cognitive decline and amygdala atrophy in Alzheimer's disease neuropathological change.","authors":"Francisco C Almeida, Alexandra Santos, Tiago Jesus, Kathryn Gauthreaux, Charles N Mock, Walter A Kukull, John F Crary, Tiago Gil Oliveira","doi":"10.1007/s00415-025-13360-1","DOIUrl":"10.1007/s00415-025-13360-1","url":null,"abstract":"<p><strong>Introduction: </strong>Amygdala-predominant Lewy body (LB) pathology occurs frequently in association with advanced Alzheimer's disease (AD). Its clinical significance is not yet fully clarified. We investigated the influence of amygdala-predominant LB in cognitive profiles and brain atrophy in the context of AD neuropathological change (ADNC).</p><p><strong>Methods: </strong>We performed a retrospective cohort study from the National Alzheimer's Coordinating Center dataset assessing the influence of amygdala-predominant LB and caudo-rostral LB stages in longitudinal neuropsychological and cognitive testing, as well as on regional brain volume in cross-sectional MRI.</p><p><strong>Results: </strong>Amygdala-predominant LB associated with specific deficits in neuropsychological testing compared with those without LB and with limbic LB (p ≤ 0.05). This was accompanied by focal atrophy of the right amygdala compared with those without LB co-pathology (p ≈ 0.02), although this result did not survive false discovery rate correction.</p><p><strong>Discussion: </strong>These results suggest that amygdala-predominant LB is an important form of co-pathology in ADNC, associating with cognitive decline and focal brain atrophy.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 9","pages":"629"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054010","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}