European Journal of Neurology最新文献

{"title":"Riluzole is associated with reduced risk of heart failure","authors":"Kibum Kim,&nbsp;Sodam Kim,&nbsp;Margaret Katana,&nbsp;Dmitry Terentyev,&nbsp;Przemysław B. Radwański,&nbsp;Mark A. Munger","doi":"10.1111/ene.70033","DOIUrl":"10.1111/ene.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The study aim was to investigate whether riluzole lowers HF incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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, <i>p</i>-value] of 0.55 [0.40–0.76, <i>p</i> &lt; 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Riluzole is associated with a lower rate of HF onset, suggesting a potential prevention strategy for early management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-09","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":"Delineating the genetic landscape of Charcot–Marie–tooth disease in Türkiye: Distinct distribution, rare phenotypes, and novel variants","authors":"Arman Cakar,&nbsp;Ayse Candayan,&nbsp;Gulandam Bagırova,&nbsp;Zehra Oya Uyguner,&nbsp;Serdar Ceylaner,&nbsp;Hacer Durmus,&nbsp;Esra Battaloglu,&nbsp;Yesim Parman","doi":"10.1111/ene.16572","DOIUrl":"10.1111/ene.16572","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic and clinical findings were recorded. Patients were initially screened for <i>PMP22</i> duplication. Targeted sequencing or whole-exome sequencing was performed in duplication-negative patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 311 patients from 265 families were included. Demyelinating CMT (67.4%) was more common than axonal (20.5%) and intermediate subtypes (11.7%). <i>PMP22</i> duplication was the most frequent mutation, followed by pathogenic variants in <i>GJB1</i>, <i>MFN2</i>, <i>SH3TC2</i>, and <i>GDAP1</i> genes. <i>MPZ</i>-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 <i>SH3TC2</i>, peripheral hyperexcitability in <i>HINT1</i>, and central nervous system findings in <i>GJB1</i>. Autosomal recessive CMT subtypes had higher CMTESv2 scores when compared to autosomal dominant ones (12.39 ± 4.81 vs. 8.36 ± 4.15, <i>p</i>: 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","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}

{"title":"Efficacy and safety of tirofiban in acute ischemic stroke patients with ideal reperfusion: A cohort study of LAA and CE subgroups","authors":"Chengsong Yue,&nbsp;Xiang Liu,&nbsp;Changwei Guo,&nbsp;Lilan Wang,&nbsp;Wenlong Zhao,&nbsp;Wenzhe Sun,&nbsp;Jiaxing Song,&nbsp;Jie Yang,&nbsp;Linyu Li,&nbsp;Nizhen Yu,&nbsp;Shihai Yang,&nbsp;Xiaolei Shi,&nbsp;Jiacheng Huang,&nbsp;Weiling Kong,&nbsp;Zhenqiang Li,&nbsp;Shunyu Yang,&nbsp;Shuang Yang,&nbsp;Wenjie Zi,&nbsp;Yi Lin,&nbsp;Fengli Li","doi":"10.1111/ene.70034","DOIUrl":"10.1111/ene.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Despite achieving ideal reperfusion (eTICI = 3) through endovascular treatment (EVT), some acute ischemic stroke (AIS) patients still experience poor outcomes. This study aims to evaluate the efficacy and safety of tirofiban in AIS patients with ideal reperfusion, focusing on its effects in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 474 AIS patients from the RESCUE-BT database were included. Patients were assigned to either the tirofiban or placebo group based on the treatment received. The primary outcome was favorable functional recovery at 90 days (mRS ≤2), and safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. Multivariable logistic regression was used to adjust for confounders, and subgroup and interaction analyses assessed tirofiban's efficacy in LAA and CE populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the overall population that achieved ideal reperfusion, Tirofiban did not improve clinical outcomes and did not increase the risk of mortality or incidence of sICH (<i>p</i> &gt; 0.05). However, subgroup analysis indicated potential clinical benefits for patients with higher NIHSS scores in the LAA group, especially in the subgroup with NIHSS scores &gt;13 (adjusted OR 4.671, 95% CI [1.545, 14.122]). No significant differences were found in the CE group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Tirofiban showed potential benefits for LAA patients with ideal reperfusion, especially those with NIHSS scores above 13. Careful patient selection is recommended.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946832","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 efficacy of remote ischemic conditioning for outcomes in ischemic stroke patients with or without prior stroke: A post hoc analysis of the RICAMIS trial","authors":"Liang Liu,&nbsp;Xiao-Yu Sun,&nbsp;Chang Cui,&nbsp;Miao Liu,&nbsp;Yu Cui,&nbsp;Hui-Sheng Chen","doi":"10.1111/ene.70032","DOIUrl":"10.1111/ene.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>To investigate the impact of a history of ischemic stroke or transient ischemic attack (TIA) on the effectiveness of remote ischemic conditioning (RIC) for outcomes in acute ischemic stroke patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a post hoc analysis of the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) trial. Patients in RICAMIS were categorized into two groups according to a history of stroke. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0–1 at 90 days. Instead of comparing patients receiving usual care alone, we investigated the association of the RIC effect with functional outcomes in each group and the interaction between the RIC effect and a history of ischemic stroke or TIA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included a total of 1695 patients, of whom 562 patients had a history of ischemic stroke or TIA and 1133 patients without prior ischemic stroke or TIA. In the Never Stroke or TIA group, a higher proportion of excellent functional outcomes was found in the RIC subgroup compared to the control subgroup (adjusted OR = 1.557 [95% CI 1.187–2.043], <i>p</i> = 0.001) but not in Prior Stroke or TIA group (adjusted OR = 1.299 [95% CI 0.893–1.888], <i>p</i> = 0.171). However, no significant interaction between the RIC effect and a history of ischemic stroke or TIA was found among the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first report suggesting that the RIC effect may be influenced by the history of ischemic stroke or TIA for patients with acute ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946877","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,&nbsp;Matthew Kiernan,&nbsp;William Huynh","doi":"10.1111/ene.70006","DOIUrl":"10.1111/ene.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70006","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":"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,&nbsp;Rosanna Rossi,&nbsp;Duaa Jabrah,&nbsp;Andrew Douglas,&nbsp;Petra Redfors,&nbsp;Annika Nordanstig,&nbsp;Turgut Tatlisumak,&nbsp;Erik Ceder,&nbsp;Dennis Dunker,&nbsp;Jeanette Carlqvist,&nbsp;István Szikora,&nbsp;Georgios Tsivgoulis,&nbsp;Klearchos Psychogios,&nbsp;Georgios Magoufis,&nbsp;Alexandros Rentzos,&nbsp;Karen M. Doyle,&nbsp;Katarina Jood","doi":"10.1111/ene.70037","DOIUrl":"10.1111/ene.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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 <i>U</i>-test and Chi-square Test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clots from patients with concomitant cancer had a significantly higher content of vWF (median 26 [IQR13-38]% vs. 10 [4–18]%, <i>p</i> &lt; 0.0001) and H3Cit (median 0.11 [IQR0.02–0.46]% vs. 0.05 [0.00–0.28]% <i>p</i> = 0.027) than controls. The presence of collagen &gt;1% within the retrieved clots was highly indicative of cancer, occurring in 16/64 with active cancer and in 3/64 controls, <i>p</i> = 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70037","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myotilin gene duplication causing late-onset myotilinopathy","authors":"Marco Spinazzi,&nbsp;Marco Savarese,&nbsp;Franck Letournel,&nbsp;Lydia Sagath,&nbsp;Florence Manero,&nbsp;Agnès Guichet,&nbsp;Alexander Hoischen,&nbsp;Corinne Metay,&nbsp;Julien Gouju,&nbsp;Bjarne Udd","doi":"10.1111/ene.70029","DOIUrl":"10.1111/ene.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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 <i>MYOT</i> gene, two of which are largely recurrent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a duplication of the entire <i>MYOT</i> gene as the molecular cause of late-onset-myotilinopapthy with typical clinical and pathological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70029","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How well is the female population represented in clinical trials with infusion therapies for Parkinson's disease? A systematic review and metanalysis","authors":"Katarzyna Smilowska,&nbsp;Vanessa Carvalho,&nbsp;Natalia Szejko,&nbsp;João Costa,&nbsp;Elena Moro,&nbsp;Angelo Antonini","doi":"10.1111/ene.70024","DOIUrl":"10.1111/ene.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a neurodegenerative disorder affecting both sexes, but differences exist between male and female in clinical manifestations, functional impact of symptoms and hormonal influences. Therefore, representativeness of females in PD trials indirectly determines the external validity of the clinical research in this field.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To estimate the representativeness of female in infusion therapy trials for advanced PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed and EMBASE databases were searched (1980 to September 2023), along with congress abstracts, to identify controlled clinical trials and large non-controlled studies on infusion therapies in PD enrolling &gt;100 patients. Random-effect meta-analysis was conducted to estimate mean pooled prevalence of females included in the studies. Subgroup analyses were conducted accordingly to study design and intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 15 studies (six studies on levodopa-carbidopa intestinal gel, six on subcutaneous levodopa, two on subcutaneous apomorphine, and one on levodopa-carbidopa-entacapone intestinal gel). Sex was not a randomisation stratification factor in any of these studies. Only one study explored differences in the outcome estimated according to sex. Overall, the proportion of female included was 38% (95% CI:33%–43%; <i>I</i>² = 74%), without differences between studies assessing different type of interventions (<i>p</i> = 0.72) or between study design (<i>p</i> = 0.35). In two studies, females represented the majority of included patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Female with advanced PD are underrepresented in infusion therapy trials. Most trials have overlooked sex-based biological differences that can impact clinical and functional outcomes, raising concerns about the generalizability of these findings to real-world contexts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930898","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":"Substantia nigra degeneration in spinocerebellar ataxia 2 and 7 using neuromelanin-sensitive imaging","authors":"Lydia Chougar,&nbsp;Giulia Coarelli,&nbsp;François-Xavier Lejeune,&nbsp;Pia Ziegner,&nbsp;Rahul Gaurav,&nbsp;Emma Biondetti,&nbsp;Sabrina Sayah,&nbsp;Rania Hilab,&nbsp;Alain Dagher,&nbsp;Alexandra Durr,&nbsp;Stéphane Lehéricy","doi":"10.1111/ene.70035","DOIUrl":"10.1111/ene.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Spinocerebellar ataxias (SCA) are neurodegenerative diseases with widespread lesions across the central nervous system. Ataxia and spasticity are usually predominant, but patients may also present with parkinsonism. We aimed to characterize substantia nigra <i>pars compacta</i> (SNc) degeneration in SCA2 and 7 using neuromelanin-sensitive imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ataxic and preataxic expansion carriers with SCA2 (n=15) and SCA7 (n=15) and healthy controls (n=10) were prospectively recruited. Volume and signal-to-noise ratio (SNR) values of the SNc were extracted from neuromelanin-sensitive images. ROC curves were used to determine the metrics that best differentiated SCA participants. Correlations between imaging measurements, clinical variables, and plasma neurofilaments light chain (NfL) levels were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SCA2 participants had lower SNR values in the SNc than controls (110.2 ± 1.3 versus 113.2 ± 1.4; <i>p</i> &lt; 0.001) and those with SCA7 (112.5 ± 2.1; <i>p</i> &lt; 0.01). SNR in SCA7 participants and controls did not differ. In ataxic patients, SNc volumes were lower in SCA2 (0.13 ± 0.04; <i>p</i> = 0.06) and SCA7 (0.10 ± 0.03, <i>p</i> = 0.02) patients compared to controls (0.17 ± 0.04). Signal decrease was detected at the preataxic stage in SCA2, but not in SCA7. SCA2 participants showed prominent involvement of the associative and limbic nigral territories. SNR discriminated ataxic and preataxic SCA2 participants from controls (AUC ≥0.94). SNc volume differentiated ataxic SCA7 participants from controls (AUC = 1), but not preataxic ones. In SCA7, correlations were observed between SNc volume and time to onset, CAG repeats, clinical severity scores, and NfL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Neuromelanin-sensitive imaging provides biomarkers of nigral degeneration in SCAs, detectable from the preataxic stage in SCA2, which could potentially serve as outcome measures in clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930903","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":"Carotid endarterectomy and the risk of perioperative stroke: The importance of chronic ischaemic lesions and small vessel disease","authors":"Henrietta Törmänen,&nbsp;Suvi Koskinen,&nbsp;Krista Nuotio,&nbsp;Pirkka Vikatmaa,&nbsp;Petri T. Kovanen,&nbsp;Lauri Soinne,&nbsp;Perttu J. Lindsberg,&nbsp;Petra Ijäs","doi":"10.1111/ene.16551","DOIUrl":"10.1111/ene.16551","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and purpose</h3>\u0000 \u0000 <p>Perioperative stroke is a well-recognized complication of carotid endarterectomy (CEA), but well-performing prediction models do not exist for it. Our aim was to identify novel predictors for perioperative ischaemic cerebrovascular events (iCVEs), emphasizing cerebrovascular imaging and potential biomarkers for stroke in carotid stenosis (CS) patients in a well-characterized prospective CS cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Helsinki Carotid Endarterectomy Study 2 is an observational prospective and consecutive cohort study of CS patients subjected to CEA during 2012–2015. The associations between perioperative stroke and transient ischaemic attack (iCVEs) and potential predictive factors were evaluated by univariate and Cox regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 488 operated CS patients, 33 (7%) sustained an iCVE including 21 (4%) ischaemic strokes. In univariate analysis, moderate ipsilateral CS (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.08–4.23), covert or chronic ipsilateral brain infarct in imaging (HR 2.27, 95% CI 1.09–4.76) and severe cerebral small vessel disease (HR 3.36, 95% CI 1.04–10.88) appeared as novel risk factors for perioperative iCVE. In Cox proportional hazards regression modelling, female gender (HR 3.03, 95% CI 1.30–7.04), a history of coronary heart disease (HR 3.59, 95% CI 1.52–8.47), covert or chronic ipsilateral infarct (HR 2.32, 95% CI 1.01–5.34) and severe small vessel disease (HR 2.63, 95% CI 1.07–6.47) were the strongest independent predictors of perioperative iCVE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In addition to the previously reported clinical risk factors, it was found that imaging markers of past cerebrovascular disease, covert or chronic ipsilateral infarct and severe small vessel disease, and moderate ipsilateral stenosis are associated with perioperative iCVEs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920807","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}