European Journal of Neurology最新文献

{"title":"Risk factors of dementia in a cohort of individuals with mild cognitive impairment in the Italian Interceptor project.","authors":"Claudia Carrarini, Naike Caraglia, Davide Quaranta, Fabrizio Vecchio, Francesca Miraglia, Guido Maria Giuffrè, Chiara Pappalettera, Alessia Cacciotti, Lorenzo Nucci, Nicola Vanacore, Alberto Redolfi, Daniela Perani, Patrizia Spadin, Fabrizio Tagliavini, Maria Cotelli, Stefano Cappa, Camillo Marra, Paolo M Rossini","doi":"10.1111/ene.16591","DOIUrl":"https://doi.org/10.1111/ene.16591","url":null,"abstract":"<p><strong>Background: </strong>The Italian Interceptor project is aimed at identifying a prodromal dementia phase and developing a nationwide organizational model. This study compares the sociodemographic and neuropsychological characteristics of mild cognitive impairment non-converters (MCI-NC) and MCI-converters (MCI-C) to dementia, including Alzheimer's disease (AD), enrolled during the Interceptor project.</p><p><strong>Methods: </strong>Sociodemographic, clinical, and neuropsychological data of MCI individuals were collected at baseline (December 2018 to October 2020) and every six-month follow-up visit for 3 years. Logistic regression and Random Forest classifier were used to describe the study population.</p><p><strong>Results: </strong>From 356 participants, 104 were MCI-C, whereas 252 were MCI-NC. Compared to MCI-NC, MCI-C were predominantly female (p = 0.020), older (p < 0.001), and more cognitively impaired (p < 0.001). Higher physical activity was protective for progression (p < 0.001), but no difference was observed for smoking exposure (p = 0.312) between the two groups. Similar results were found for AD individuals compared to MCI-C/non-AD. The ROC curve based on a Random Forest classifier distinguishing MCI-C from MCI-NC showed an area under the curve (AUC) of 0.7347.</p><p><strong>Conclusions: </strong>Our findings confirm previous evidence in literature and may increase the insight on dementia pathology and help in defining intervention strategies to prevent or slow down disease progression.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 2","pages":"e16591"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079131","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":"Riluzole is associated with reduced risk of heart failure.","authors":"Kibum Kim, Sodam Kim, Margaret Katana, Dmitry Terentyev, Przemysław B Radwański, Mark A Munger","doi":"10.1111/ene.70033","DOIUrl":"10.1111/ene.70033","url":null,"abstract":"<p><strong>Background: </strong>Reduction of intracellular Na⁺ accumulation through late Na⁺ current inhibition has been recognized as a target for cardiac Ca²⁺ handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, an Na⁺ channel blocker with enhancement of Ca²⁺-activated K⁺ channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca²⁺ leak and therefore may improve cardiac function.</p><p><strong>Objectives: </strong>The study aim was to investigate whether riluzole lowers HF incidence.</p><p><strong>Methods: </strong>Rates of HF incident were compared using a commercial insurance and Medicare supplement claims databases. Patients with a filled riluzole prescription (treatment) between 06/2009 and 12/2019 were compared to those with no-riluzole (control). We excluded HF patients during the 180-day baseline period. Study endpoint was the first HF diagnosis from the index riluzole prescription or ALS diagnosis. HF onset was compared between the propensity score matched treatment and control cohorts.</p><p><strong>Results: </strong>The matched cohort consisted of 4060 pairs of riluzole/control patients. The 24-month cumulative incidence of HF onset for riluzole versus control patients was 4.96% versus 7.27%, calculating hazard ratio (HR) [95% CI, p-value] of 0.55 [0.40-0.76, p < 0.01]. The HR estimates favoring riluzole over the ALS control were consistent across the 3 months to 2-year follow-up. The clinically and statistically significant effect on HF onset was driven by the lower rate of HFrEF with the 2-year HR [95% CI] of 0.46 [0.21-0.99].</p><p><strong>Conclusions: </strong>Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70033"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11716981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946873","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":"Myotilin gene duplication causing late-onset myotilinopathy.","authors":"Marco Spinazzi, Marco Savarese, Franck Letournel, Lydia Sagath, Florence Manero, Agnès Guichet, Alexander Hoischen, Corinne Metay, Julien Gouju, Bjarne Udd","doi":"10.1111/ene.70029","DOIUrl":"https://doi.org/10.1111/ene.70029","url":null,"abstract":"<p><strong>Background: </strong>myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share a common alteration of the sarcomere organization at the level of the Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately muscle degeneration. Most reported cases are due to dominant missense mutations in the MYOT gene, two of which are largely recurrent.</p><p><strong>Methods: </strong>We describe the clinical, radiological, pathological, and molecular analysis including long-read sequencing of a family affected by late-onset dominant proximodistal myopathy and muscle hypertrophy.</p><p><strong>Results: </strong>We identified a duplication of the entire MYOT gene as the molecular cause of late-onset-myotilinopapthy with typical clinical and pathological features.</p><p><strong>Conclusions: </strong>This study expands the molecular spectrum of myotilinopathy and highlights the use of long-read sequencing in the diagnosis of genetic neurological diseases caused by duplications and genomic structural variants. Myotilinopathy as well as other myofibrillar and distal myopathies should be considered in the differential diagnosis of patients affected by distal muscle weakness, even when presenting at an old age.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70029"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930900","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":"Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.","authors":"Barbara Risi, Alberto Imarisio, Giada Cuconato, Alessandro Padovani, Enza Maria Valente, Massimiliano Filosto","doi":"10.1111/ene.70014","DOIUrl":"10.1111/ene.70014","url":null,"abstract":"<p><strong>Background: </strong>Several studies evaluated peripheral and cerebrospinal fluid (CSF) mtDNA as a putative biomarker in neurodegenerative diseases, often yielding inconsistent findings. We systematically reviewed the current evidence assessing blood and CSF mtDNA levels and variant burden in Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Multiple sclerosis (MS) was also included as a paradigm of chronic neuroinflammation-driven neurodegeneration.</p><p><strong>Methods: </strong>Medline, Embase, Scopus and Web of Science were searched for articles published from inception until October 2023. Studies focused on mtDNA haplogroups or hereditary pathogenic variants were excluded. Critical appraisal was performed using the Quality Assessment for Diagnostic Accuracy Studies criteria.</p><p><strong>Results: </strong>Fifty-nine original studies met our a priori-defined inclusion criteria. The majority of CSF-focused studies showed (i) decreased mtDNA levels in PD and AD; (ii) increased levels in MS compared to controls. No studies evaluated CSF mtDNA in ALS. Results focused on blood cell-free and intracellular mtDNA were contradictory, even within studies evaluating the same disease. This poor reproducibility is likely due to the lack of consideration of the many factors known to affect mtDNA levels. mtDNA damage and methylation levels were increased and reduced in patients compared to controls, respectively. A few studies investigated the correlation between mtDNA and disease severity, with conflicting results.</p><p><strong>Conclusions: </strong>Additional well-designed studies are needed to evaluate CSF and blood mtDNA profiles as putative biomarkers in neurodegenerative diseases. The identification of \"mitochondrial subtypes\" of disease may enable novel precision medicine strategies to counteract neurodegeneration.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70014"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002496","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":"Clot signature in patients with large vessel occlusion stroke and concomitant active cancer.","authors":"Malin Woock, Rosanna Rossi, Duaa Jabrah, Andrew Douglas, Petra Redfors, Annika Nordanstig, Turgut Tatlisumak, Erik Ceder, Dennis Dunker, Jeanette Carlqvist, István Szikora, Georgios Tsivgoulis, Klearchos Psychogios, Georgios Magoufis, Alexandros Rentzos, Karen M Doyle, Katarina Jood","doi":"10.1111/ene.70037","DOIUrl":"https://doi.org/10.1111/ene.70037","url":null,"abstract":"<p><strong>Background and purpose: </strong>Patients with active cancer face an increased risk of ischemic stroke. Also, stroke may be an initial indicator of cancer. In patients with large vessel occlusion (LVO) stroke treated with thrombectomy, analysis of the clot composition may contribute new insights into the pathological connections between these two conditions.</p><p><strong>Methods: </strong>We compared the content of 64 consecutively retrieved clots from LVO stroke patients with concomitant active cancer and 64 clots from matched-control LVO stroke patients without a history of cancer. Clots were analyzed with respect to histological composition by Martius Scarlet Blue, von Willebrand factor (vWF), citrullinated histone H3 (H3Cit, a biomarker of NETS), CD42b, and CD3 expression by immunohistochemistry. Orbit Image Analysis was used for quantification. Differences between groups were tested using the Mann-Whitney U-test and Chi-square Test.</p><p><strong>Results: </strong>Clots from patients with concomitant cancer had a significantly higher content of vWF (median 26 [IQR13-38]% vs. 10 [4-18]%, p < 0.0001) and H3Cit (median 0.11 [IQR0.02-0.46]% vs. 0.05 [0.00-0.28]% p = 0.027) than controls. The presence of collagen >1% within the retrieved clots was highly indicative of cancer, occurring in 16/64 with active cancer and in 3/64 controls, p = 0.002. After correction for multiple comparisons, the statistical significance for H3Cit was lost. Red and white blood cells, platelets, fibrin, and expression of CD3 and CD42b did not differ between the groups.</p><p><strong>Conclusions: </strong>Clots from LVO patients with concomitant active cancer possess distinct characteristics, indicating an influence of cancer on the innate immune system, fibroblasts, and the vascular endothelium in the formation of LVO clots.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70037"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930894","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":"Impact of Sex on Clinical Outcomes of Tandem Occlusion in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy. A Propensity-Matched Analysis.","authors":"Lucio D'Anna, Matteo Foschi, Mariarosaria Valente, Liqun Zhang, Simona Sacco, Raffaele Ornello, Nina Mansoor, Matthew Fallon, Adelaida Gartner Jaramillo, Massimo Sponza, Vladimir Gavrilovic, Kyriakos Lobotesis, Gian Luigi Gigli, Soma Banerjee, Giovanni Merlino","doi":"10.1111/ene.70044","DOIUrl":"10.1111/ene.70044","url":null,"abstract":"<p><strong>Background: </strong>Although mechanical thrombectomy (MT) represents the standard of care for ischemic stroke due to large-vessel occlusion (LVO), the impact of sex on outcomes in tandem occlusions remains unclear. We investigated sex-based differences in outcomes after MT for tandem occlusions.</p><p><strong>Methods: </strong>This multicenter observational study included consecutive patients with tandem occlusion treated with MT across three stroke centers (2021-2023). Propensity score matching was performed. Primary outcomes were the 90-day favorable functional outcome (mRS 0-2) and mRS score shift. Secondary outcomes included favorable recanalization, 24-h early neurological improvement, and NIHSS median score. Safety outcomes were post-MT intracerebral hemorrhage and 90-day mortality.</p><p><strong>Results: </strong>Of 635 patients (46.8% women), 289 women were matched to 289 men. There were no significant differences in primary, secondary, or safety outcomes between sexes. Subgroup analysis showed a lower rate of favorable 90-day mRS scores in women with diabetes compared to men. Women not receiving emergent carotid treatment had higher rates of favourable outcomes. No significant sex differences were found in other subgroups.</p><p><strong>Conclusions: </strong>Women with anterior circulation tandem occlusions treated with MT have similar outcomes to men. However, women with diabetes and those treated with intracranial MT alone exhibited sex-specific differences. Further studies are needed to explore underlying mechanisms.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70044"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970224","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":"Cerebrotendinous xanthomatosis: A complex interplay between a clinically and genetically heterogeneous condition.","authors":"Emily O'Keefe, Matthew Kiernan, William Huynh","doi":"10.1111/ene.70006","DOIUrl":"https://doi.org/10.1111/ene.70006","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease characterized by abnormal bile acid synthesis. It often presents with systemic and neurological manifestations; however, atypical presentations can lead to significant diagnostic challenges. This case report highlights the diagnostic complexities and management considerations in a patient with an uncommon presentation of CTX.</p><p><strong>Methods: </strong>We present a patient with a 25-year history of spastic paraparesis, initially suggestive of hereditary spastic paraplegia (HSP), ultimately diagnosed with CTX associated with a novel CYP27A1 variant of uncertain significance (VUS).</p><p><strong>Results: </strong>A 53-year-old Greek woman presented with a 25-year history of slowly progressive spastic paraparesis. Initial investigations were largely unremarkable, leading to a presumptive diagnosis of a hereditary spastic paraplegia (HSP)-like syndrome. After 5 years of slow disease progression, the patient developed right ankle swelling. MRI revealed significant enlargement of the Achilles tendon, suggestive of xanthoma infiltration. Subsequent genetic testing identified a homozygous variant of uncertain significance (VUS) in the CYP27A1 gene. Biochemical analyses revealed elevated cholestanol levels and cholestanepentol glucuronide in urine, confirming the diagnosis of CTX. Treatment with chenodeoxycholic acid stabilized her condition over 3 years, but advanced disease limited efficacy in improving disability.</p><p><strong>Conclusion: </strong>This case highlights the diagnostic challenges associated with CTX, stemming from its relative rarity and significant clinical heterogeneity. It emphasizes the importance of a comprehensive approach combining clinical suspicion, imaging, genetic testing and biochemical analyses for accurate diagnosis, interpretation of VUS and management of rare conditions like CTX.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70006"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930890","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":"Longitudinal trajectories of digital upper limb biomarkers for multiple sclerosis.","authors":"Yi Chao Foong, Daniel Merlo, Melissa Gresle, Chao Zhu, Katherine Buzzard, Jeannette Lechner-Scott, Michael Barnett, Bruce V Taylor, Tomas Kalincik, Trevor Kilpatrick, David Darby, Pamela Dobay, Johan van Beek, Robert Hyde, Steve Simpson-Yap, Helmut Butzkueven, Anneke van der Walt","doi":"10.1111/ene.70000","DOIUrl":"10.1111/ene.70000","url":null,"abstract":"<p><strong>Background: </strong>Upper limb dysfunction is a common debilitating feature of relapsing-remitting multiple sclerosis (RRMS). We aimed to examine the longitudinal trajectory of the iPad®-based Manual Dexterity Test (MDT) and predictors of change over time.</p><p><strong>Methods: </strong>We prospectively enrolled RRMS patients (limited to Expanded Disability Status Scale (EDSS) < 4). Longitudinal data was analysed using mixed-effect modelling and latent class mixed models. We then examined whether group membership in latent classes predicted confirmed slowing in MDT.</p><p><strong>Results: </strong>Seven hundred and twenty-one participants had complete data for analysis. At a population level, MDT remained stable over time. No practice effect was seen. Baseline disability and T2 lesion volume were the strongest predictors of longitudinal MDT performance. We identified two latent class trajectories of MDT. The slower latent class was typified by greater variability and a weak association with confirmed worsening of MDT and EDSS. When compared to trajectory analysis stratified by baseline MDT, latent class analysis (LCA) was able to identify those at greater risk of confirmed slowing, signifying the importance of latent processes in upper limb function in pwMS.</p><p><strong>Conclusion: </strong>In this cohort of mild to moderate RRMS, MDT scores remained stable over time with no evidence of a practice effect at a population level. Trajectory analysis based on LCA identified a cohort with greater variability and risk of disability progression and domain specific worsening. Our findings demonstrate the importance of latent processes in determining upper limb function in pwMS.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e70000"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876301","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 Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): Regression-based norms for German-speaking countries.","authors":"I K Penner, J Baijot, M Filser, S Bätge, L Raithel, E Toth, A Renner, G Nagels","doi":"10.1111/ene.16495","DOIUrl":"10.1111/ene.16495","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cognitive impairment in multiple sclerosis (MS) is common and is associated with problems in employment, driving ability, and quality of life. Since cognitive impairment at time of diagnosis is predictive of disability progression, early assessment and annual monitoring is recommended. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) was introduced as a time-efficient screening tool that can easily be applied in standard clinical care. However, besides application, tests need to be analysed and the raw values obtained must be interpreted accordingly. Since normative values have not been available for German-speaking countries, BICAMS has not been implemented in clinical routine. The aim of this study was to calculate German normative BICAMS data to improve the current diagnostic process for people with MS.</p><p><strong>Methods: </strong>Healthy control subjects in different age categories were recruited to enable regression-based norm analysis. Raw scores for each BICAMS test were converted into scaled scores before they were regressed for age, age squared, gender, and education. The obtained scores were then normalised to a z-score by dividing the difference between the scaled score and the predicted score by the root mean squared error of the model.</p><p><strong>Results: </strong>In all, 237 HCs were recruited (68.8% female, 31.2% male) and examined with BICAMS. Datasets entered the regression-based norms analysis and formed the basis for a final z-score calculation. To simplify handling in everyday clinical practice, nomograms and look-up tables were created which provide clinicians with age- and education-corrected norms.</p><p><strong>Conclusion: </strong>Our work fills the gaps between BICAMS application, evaluation and interpretation and will make a significant contribution to more regular cognitive assessment of MS patients.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e16495"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002501","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":"Delineating the genetic landscape of Charcot-Marie-tooth disease in Türkiye: Distinct distribution, rare phenotypes, and novel variants.","authors":"Arman Cakar, Ayse Candayan, Gulandam Bagırova, Zehra Oya Uyguner, Serdar Ceylaner, Hacer Durmus, Esra Battaloglu, Yesim Parman","doi":"10.1111/ene.16572","DOIUrl":"https://doi.org/10.1111/ene.16572","url":null,"abstract":"<p><strong>Background: </strong>Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. In this study, we aimed to analyze the genetic spectrum and describe phenotypic features in a large cohort from Türkiye.</p><p><strong>Methods: </strong>Demographic and clinical findings were recorded. Patients were initially screened for PMP22 duplication. Targeted sequencing or whole-exome sequencing was performed in duplication-negative patients.</p><p><strong>Results: </strong>Overall, 311 patients from 265 families were included. Demyelinating CMT (67.4%) was more common than axonal (20.5%) and intermediate subtypes (11.7%). PMP22 duplication was the most frequent mutation, followed by pathogenic variants in GJB1, MFN2, SH3TC2, and GDAP1 genes. MPZ-neuropathy was rare in our cohort (3.0%). Interestingly, CMT4 is the second most common type after CMT1. Lower extremity weakness and foot deformities were the most frequent presenting complaints. Striking clinical features included a high frequency of scoliosis in SH3TC2, peripheral hyperexcitability in HINT1, and central nervous system findings in GJB1. Autosomal recessive CMT subtypes had higher CMTESv2 scores when compared to autosomal dominant ones (12.39 ± 4.81 vs. 8.36 ± 4.15, p: 0.023). Twenty-one patients used wheelchairs during their last examination. Among them, 16 had an autosomal recessive subtype. Causative variants were identified in 31 genes, including 28 novel pathogenic or likely pathogenic changes.</p><p><strong>Conclusions: </strong>Our findings provided robust data regarding the genetic distribution of CMT in Türkiye, which may pave the path for building population-specific diagnostic gene panels. Rare autosomal recessive subtypes were relatively frequent in our cohort. By analyzing genotype-phenotype correlations, our data may provide clinical clues for clinicians.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":"e16572"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055881","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}