Inflammation is increasingly recognized in the pathogenesis of diabetic neuropathy (DN). Circulating miR-27a-3p levels are closely related to inflammation and increased in patients with diabetic nephropathy and retinopathy. miR-27a-3p has a predicted binding site in the 3 UTR of Netrin-1 mRNA, an anti-inflammatory nerve growth factor whose levels correlate with small nerve fiber loss in patients with DN.
Methods
Eighty-two participants with (DN+) and without (DN-) small nerve fiber damage and 45 healthy controls underwent measurement of plasma miR-27a-3p, PBMC levels of NF-kB and NLRP3, serum Netrin-1, TNFα, IL-1β, and IL-10 levels.
Results
Corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) were significantly lower in the DN- and DN+ groups compared to controls (p < 0.001). Plasma miR-27a-3p and PBMC NF-kB and NLRP3 expression were significantly higher in the DN+ group, and miR-27a-3p identified DN+ with an area under the curve (AUC) of 89%. Serum Netrin-1 and IL-10 levels were lower, while TNFα and IL-1β levels were higher in the DN+ group. miR-27a-3p levels correlated negatively with CNFL and Netrin-1 and positively with NF-kB and NLRP3.
Conclusion
miR-27a-3p levels are elevated in subjects with DN and correlate with markers of inflammation, Netrin-1, and corneal nerve loss. miR-27a-3p could be a biomarker for DN, and miR-27a-3p/Netrin-1 crosstalk may be a promising therapeutic target for DN.
{"title":"miR-27a-3p Upregulation and Netrin-1 Deficiency Drive Inflammatory Responses and Nerve Degeneration in Patients With Diabetes","authors":"Asif Mondal, Sucharita Banerjee, Somnath Naskar, Chiranjit Bose, Chinmay Saha, Subhasish Pramanik, Bidisha Mukherjee, Piyali Jati, Pranab Kumar Sahana, Rayaz A. Malik, Satinath Mukhopadhyay","doi":"10.1111/ene.70449","DOIUrl":"10.1111/ene.70449","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammation is increasingly recognized in the pathogenesis of diabetic neuropathy (DN). Circulating miR-27a-3p levels are closely related to inflammation and increased in patients with diabetic nephropathy and retinopathy. miR-27a-3p has a predicted binding site in the 3 UTR of Netrin-1 mRNA, an anti-inflammatory nerve growth factor whose levels correlate with small nerve fiber loss in patients with DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty-two participants with (DN+) and without (DN-) small nerve fiber damage and 45 healthy controls underwent measurement of plasma miR-27a-3p, PBMC levels of NF-kB and NLRP3, serum Netrin-1, TNFα, IL-1β, and IL-10 levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) were significantly lower in the DN- and DN+ groups compared to controls (<i>p</i> < 0.001). Plasma miR-27a-3p and PBMC NF-kB and NLRP3 expression were significantly higher in the DN+ group, and miR-27a-3p identified DN+ with an area under the curve (AUC) of 89%. Serum Netrin-1 and IL-10 levels were lower, while TNFα and IL-1β levels were higher in the DN+ group. miR-27a-3p levels correlated negatively with CNFL and Netrin-1 and positively with NF-kB and NLRP3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>miR-27a-3p levels are elevated in subjects with DN and correlate with markers of inflammation, Netrin-1, and corneal nerve loss. miR-27a-3p could be a biomarker for DN, and miR-27a-3p/Netrin-1 crosstalk may be a promising therapeutic target for DN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687221","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}
Rok Berlot, Livia Asan, Timothy R. Nicholson, Biba Stanton, Thomas A. Pollak, Mark J. Edwards
Background
Following COVID-19, an increased risk of neurological and psychiatric sequelae has been reported. Viral illnesses commonly trigger functional neurological disorder (FND). However, mechanisms beyond immediate biological effects may contribute to FND after COVID-19. While FND cases have been observed after COVID-19, the overall risk and contributing factors remain unclear. In this retrospective cohort study, we compared the rates of FND post-COVID-19 to other respiratory tract infections (RTIs), assessed the influence of disease severity, and the characteristics of newly diagnosed patients.
Methods
We used TriNetX, a global electronic health record network. In total, 2,740,094 COVID-19 cases and 1846 post-COVID-19 FND cases were analysed. We compared FND incidence between 2 weeks and 6 months after COVID-19 to other RTIs and across cohorts of varying COVID-19 severity. Characteristics of individuals with new diagnoses of FND and migraine following COVID-19 were compared.
Results
The incidence of FND was higher in COVID-19 patients with records of hospitalisation (OR 2.165; 95% CI 1.691–2.773) and emergency department visits (OR 1.412; 95% CI 1.069–1.864). Incidence was higher following COVID-19 compared to other RTIs, both in the first 2 years of the pandemic (0.033 vs. 0.021%, OR 1.555, 95% CI 1.271–1.902) and subsequently (0.038 vs. 0.027%, OR 1.394, 95% CI 1.173–1.657). Medical, neurological, and psychiatric comorbidities were more common in newly diagnosed post-COVID-19 FND compared to migraine.
Conclusions
New-onset FND appears more likely after COVID-19 than other RTIs. Both the severity of the triggering illness and pre-existing individual vulnerability may contribute to the development of FND.
背景：据报道，在COVID-19之后，神经和精神后遗症的风险增加。病毒性疾病通常引发功能性神经障碍（FND）。然而，直接生物效应之外的机制可能有助于COVID-19后的FND。虽然在COVID-19之后观察到FND病例，但总体风险和影响因素仍不清楚。在这项回顾性队列研究中，我们比较了covid -19后FND与其他呼吸道感染（RTIs）的发生率，评估了疾病严重程度的影响以及新诊断患者的特征。方法：我们使用TriNetX，一个全球电子健康记录网络。共分析新冠肺炎病例274094例，新冠肺炎后FND病例1846例。我们比较了COVID-19后2周至6个月的FND发生率与其他rti以及不同COVID-19严重程度的队列。比较新诊断的FND和偏头痛患者的特征。结果：有住院记录（OR 2.165; 95% CI 1.691-2.773）和急诊科就诊记录（OR 1.412; 95% CI 1.069-1.864）的COVID-19患者FND发生率较高。与其他RTIs相比，COVID-19后的发病率更高，无论是在大流行的前2年（0.033 vs 0.021%, OR 1.555, 95% CI 1.271-1.902）还是随后（0.038 vs 0.027%, OR 1.394, 95% CI 1.173-1.657）。与偏头痛相比，新诊断的covid -19后FND中医学、神经学和精神病学合并症更为常见。结论：新型冠状病毒感染后新发FND的发生率高于其他RTIs。诱发性疾病的严重程度和个体先前存在的脆弱性都可能导致FND的发展。
{"title":"Functional Neurological Disorder Following COVID-19: Results From a Large International Electronic Health Record Database","authors":"Rok Berlot, Livia Asan, Timothy R. Nicholson, Biba Stanton, Thomas A. Pollak, Mark J. Edwards","doi":"10.1111/ene.70459","DOIUrl":"10.1111/ene.70459","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following COVID-19, an increased risk of neurological and psychiatric sequelae has been reported. Viral illnesses commonly trigger functional neurological disorder (FND). However, mechanisms beyond immediate biological effects may contribute to FND after COVID-19. While FND cases have been observed after COVID-19, the overall risk and contributing factors remain unclear. In this retrospective cohort study, we compared the rates of FND post-COVID-19 to other respiratory tract infections (RTIs), assessed the influence of disease severity, and the characteristics of newly diagnosed patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used TriNetX, a global electronic health record network. In total, 2,740,094 COVID-19 cases and 1846 post-COVID-19 FND cases were analysed. We compared FND incidence between 2 weeks and 6 months after COVID-19 to other RTIs and across cohorts of varying COVID-19 severity. Characteristics of individuals with new diagnoses of FND and migraine following COVID-19 were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The incidence of FND was higher in COVID-19 patients with records of hospitalisation (OR 2.165; 95% CI 1.691–2.773) and emergency department visits (OR 1.412; 95% CI 1.069–1.864). Incidence was higher following COVID-19 compared to other RTIs, both in the first 2 years of the pandemic (0.033 vs. 0.021%, OR 1.555, 95% CI 1.271–1.902) and subsequently (0.038 vs. 0.027%, OR 1.394, 95% CI 1.173–1.657). Medical, neurological, and psychiatric comorbidities were more common in newly diagnosed post-COVID-19 FND compared to migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>New-onset FND appears more likely after COVID-19 than other RTIs. Both the severity of the triggering illness and pre-existing individual vulnerability may contribute to the development of FND.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676768","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}
Karin Zebenholzer, Andreas Gleiss, Berthold Reichardt, Walter Gall, Christian Wöber
Background
Insurance data allow insights into dispensations of medications. This retrospective study over 49 months examined dispensations of monoclonal antibodies against calcitonin gene-related peptide (CGRP-mAbs).
Methods
Using nationwide insurance data, we examined dispensations of erenumab, fremanezumab, or galcanezumab from September 1, 2018 to September 30, 2022. We examined the duration of treatment and breaks (Kaplan–Meier curves, medians, quartiles), persistence (proportion of days covered), and switches, acute medications, and other preventatives.
Results
Of 8.8 million persons, 8934 were at least once dispensed a CGRP-mAb (83.5% women, median age 45 years). Median individual follow-up time was 710 days, median duration of treatment with any CGRP-mAb was 297 days, 42.9% had CGRP-mAbs for at least 1 year. Median duration of treatment with the first-ever CGRP-mAb was 327 days; 63.4% experienced a therapy break. Within 1 year after stopping, 53.5% resumed the same CGRP-mAb, 16.9% another CGRP-mAb, 29.6% did not resume any CGRP-mAb; 13.7% started a second CGRP-mAb and 1.7% a third. 22% definitively stopped therapy within their follow-up. Dispensation of triptans decreased during and after therapy with CGRP-mAbs; dispensation of other acute prescription medications was low without change. 11.4% had other preventatives before and 2.4% during CGRP-mAb therapy. The proportion of days covered was 96%.
Conclusions
In this nationwide study persistence with CGRP-mAbs was excellent; dispensations of triptans and other preventatives decreased during CGRP-mAb therapy. Therapy breaks were common, but the majority resumed CGRP-mAbs, which indicates the need for long-term prophylaxis.
{"title":"Prescription of Monoclonal Antibodies Against Calcitonin Gene-Related Peptide for the Prophylaxis of Migraine in Austria: A Retrospective, Longitudinal Analysis of Nationwide Insurance Data","authors":"Karin Zebenholzer, Andreas Gleiss, Berthold Reichardt, Walter Gall, Christian Wöber","doi":"10.1111/ene.70440","DOIUrl":"10.1111/ene.70440","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Insurance data allow insights into dispensations of medications. This retrospective study over 49 months examined dispensations of monoclonal antibodies against calcitonin gene-related peptide (CGRP-mAbs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using nationwide insurance data, we examined dispensations of erenumab, fremanezumab, or galcanezumab from September 1, 2018 to September 30, 2022. We examined the duration of treatment and breaks (Kaplan–Meier curves, medians, quartiles), persistence (proportion of days covered), and switches, acute medications, and other preventatives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 8.8 million persons, 8934 were at least once dispensed a CGRP-mAb (83.5% women, median age 45 years). Median individual follow-up time was 710 days, median duration of treatment with any CGRP-mAb was 297 days, 42.9% had CGRP-mAbs for at least 1 year. Median duration of treatment with the first-ever CGRP-mAb was 327 days; 63.4% experienced a therapy break. Within 1 year after stopping, 53.5% resumed the same CGRP-mAb, 16.9% another CGRP-mAb, 29.6% did not resume any CGRP-mAb; 13.7% started a second CGRP-mAb and 1.7% a third. 22% definitively stopped therapy within their follow-up. Dispensation of triptans decreased during and after therapy with CGRP-mAbs; dispensation of other acute prescription medications was low without change. 11.4% had other preventatives before and 2.4% during CGRP-mAb therapy. The proportion of days covered was 96%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this nationwide study persistence with CGRP-mAbs was excellent; dispensations of triptans and other preventatives decreased during CGRP-mAb therapy. Therapy breaks were common, but the majority resumed CGRP-mAbs, which indicates the need for long-term prophylaxis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667711","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}
Roopal Desai, Amber John, Emma Anderson, Jean Stafford, Aysha Mohamed Rafik Patel, Natalie L. Marchant, Georgina Charlesworth, Verena Zuber, Joshua Stott
Background
We aimed to systematically review the evidence for associations between the known modifiable risk factors and dementia based on Mendelian randomisation (MR) studies.
Method
Five databases were searched from inception to April 2024 investigating the association between the 12 risk factors identified in the Lancet Commission and dementia. Evaluable analyses were categorized into one of four levels (robust, probable, suggestive, insufficient) based on estimate significance level and concordance of direction of effect between main and sensitivity analyses. Evidence from clinically diagnosed dementia outcomes was synthesized separately from proxy outcomes. A post hoc sensitivity analysis excluded estimates with concerns over construct validity.
Results
A total of 47 studies were included, representing 240 MR associations (185 unique and evaluable). Over half (73.5%) of evaluable analyses were graded as providing insufficient evidence for a causal association. Among clinically diagnosed outcomes, the strongest evidence was for educational attainment (mainly probable evidence in a protective direction) and type 2 diabetes-related dysfunction (probable evidence in the risk direction). Smoking showed probable evidence of a protective association. Other risk factors, produced inconclusive or insufficient evidence. Proxy outcome analyses yielded weaker findings; in particular, the association between education and Alzheimer's disease reversed direction.
Conclusion
MR evidence for most Lancet Commission risk factors remains insufficient or inconclusive. The most consistent support for causal associations was observed for lower educational attainment and type 2 diabetes. Null findings should be interpreted cautiously given limitations in GWAS phenotyping, sample composition, and MR methodology.
{"title":"Evidence for Causal Links Between Known Modifiable Risk Factors and Dementia: A Systematic Review of Mendelian Randomisation Studies","authors":"Roopal Desai, Amber John, Emma Anderson, Jean Stafford, Aysha Mohamed Rafik Patel, Natalie L. Marchant, Georgina Charlesworth, Verena Zuber, Joshua Stott","doi":"10.1111/ene.70458","DOIUrl":"10.1111/ene.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We aimed to systematically review the evidence for associations between the known modifiable risk factors and dementia based on Mendelian randomisation (MR) studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Five databases were searched from inception to April 2024 investigating the association between the 12 risk factors identified in the Lancet Commission and dementia. Evaluable analyses were categorized into one of four levels (robust, probable, suggestive, insufficient) based on estimate significance level and concordance of direction of effect between main and sensitivity analyses. Evidence from clinically diagnosed dementia outcomes was synthesized separately from proxy outcomes. A post hoc sensitivity analysis excluded estimates with concerns over construct validity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 47 studies were included, representing 240 MR associations (185 unique and evaluable). Over half (73.5%) of evaluable analyses were graded as providing insufficient evidence for a causal association. Among clinically diagnosed outcomes, the strongest evidence was for educational attainment (mainly probable evidence in a protective direction) and type 2 diabetes-related dysfunction (probable evidence in the risk direction). Smoking showed probable evidence of a protective association. Other risk factors, produced inconclusive or insufficient evidence. Proxy outcome analyses yielded weaker findings; in particular, the association between education and Alzheimer's disease reversed direction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MR evidence for most Lancet Commission risk factors remains insufficient or inconclusive. The most consistent support for causal associations was observed for lower educational attainment and type 2 diabetes. Null findings should be interpreted cautiously given limitations in GWAS phenotyping, sample composition, and MR methodology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667647","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}
Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder linked to androgen receptor gene mutations, often associated with metabolic abnormalities. We aimed to investigate the incidence of fragility fractures and the underlying mechanisms in SBMA.
Methods
Consecutive genetically confirmed SBMA patients and healthy controls (HC) were enrolled. We surveyed fracture history and assessed motor function, bone metabolism markers, and bone mineral density (BMD) using dual-energy X-ray absorptiometry. Longitudinal BMD changes were also analyzed between SBMA patients and HC.
Results
A total of 109 SBMA patients and 21 HC were included. Fragility fractures in SBMA patients were mainly observed in cortical bone-dominant regions. Their lower limb BMD was significantly reduced (SBMA 1.10 g/cm, HC 1.19 g/cm; p < 0.05) and further decreased overtime. Despite low bone resorption markers, bone formation markers showed no difference between the groups, suggesting that SBMA patients exhibit characteristics of low turnover osteoporosis. Serum 25-hydroxyvitamin D levels were lower in SBMA patients than in HC (15.4 ng/mL vs. 19.4 ng/mL; p < 0.01). Longitudinal analysis revealed that SBMA patients had a higher incidence of fragility fractures than HC (log-rank test, p < 0.05), with the first fragility fracture occurring 10 years after the onset of muscle weakness. Low baseline BMD was a predictor of fragility fractures (adjusted OR = 0.32; 95% CI: 0.17–0.60; p < 0.05).
Conclusions
SBMA patients have a high fragility fracture incidence, particularly in cortical bone, with a progressive BMD decrease. Low bone turnover and vitamin D deficiency are associated with these fractures.
背景：脊髓和球性肌萎缩症（SBMA）是一种与雄激素受体基因突变相关的遗传性神经肌肉疾病，通常与代谢异常有关。我们的目的是调查脆性骨折的发生率和潜在的机制在SBMA。方法：连续纳入遗传确诊的SBMA患者和健康对照（HC）。我们调查了骨折史，并使用双能x线吸收仪评估了运动功能、骨代谢指标和骨矿物质密度（BMD）。还分析了SBMA患者和HC患者之间的纵向骨密度变化。结果：共纳入SBMA患者109例，HC患者21例。SBMA患者脆性骨折主要发生在皮质骨优势区。患者下肢骨密度显著降低（SBMA 1.10 g/cm, HC 1.19 g/cm）； p结论：SBMA患者脆性骨折发生率高，尤其是皮质骨，骨密度进行性降低。低骨转换和维生素D缺乏与这些骨折有关。
{"title":"Bone Fragility and Fracture Characteristics in Patients With Spinal and Bulbar Muscular Atrophy","authors":"Takahiro Kawase, Shinichiro Yamada, Yoshiyuki Kishimoto, Daisuke Ito, Shota Komori, Ayano Kondo, Madoka Iida, Itaru Kawashima, Yasuhiko Takegami, Atsushi Hashizume, Shiro Imagama, Masahisa Katsuno","doi":"10.1111/ene.70457","DOIUrl":"10.1111/ene.70457","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder linked to <i>androgen receptor</i> gene mutations, often associated with metabolic abnormalities. We aimed to investigate the incidence of fragility fractures and the underlying mechanisms in SBMA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consecutive genetically confirmed SBMA patients and healthy controls (HC) were enrolled. We surveyed fracture history and assessed motor function, bone metabolism markers, and bone mineral density (BMD) using dual-energy X-ray absorptiometry. Longitudinal BMD changes were also analyzed between SBMA patients and HC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 109 SBMA patients and 21 HC were included. Fragility fractures in SBMA patients were mainly observed in cortical bone-dominant regions. Their lower limb BMD was significantly reduced (SBMA 1.10 g/cm, HC 1.19 g/cm; <i>p</i> < 0.05) and further decreased overtime. Despite low bone resorption markers, bone formation markers showed no difference between the groups, suggesting that SBMA patients exhibit characteristics of low turnover osteoporosis. Serum 25-hydroxyvitamin D levels were lower in SBMA patients than in HC (15.4 ng/mL vs. 19.4 ng/mL; <i>p</i> < 0.01). Longitudinal analysis revealed that SBMA patients had a higher incidence of fragility fractures than HC (log-rank test, <i>p</i> < 0.05), with the first fragility fracture occurring 10 years after the onset of muscle weakness. Low baseline BMD was a predictor of fragility fractures (adjusted OR = 0.32; 95% CI: 0.17–0.60; <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SBMA patients have a high fragility fracture incidence, particularly in cortical bone, with a progressive BMD decrease. Low bone turnover and vitamin D deficiency are associated with these fractures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667649","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}
Laura Martikainen, Petra ljäs, Olli P. Suomalainen, Liisa Tomppo, Laura Mannismäki, Henrietta Törmänen, Maria Girfanova, Sami Curtze
Background and Aims
Previous randomized trials, such as CHANCE and POINT, have shown that dual antiplatelet therapy (DAPT) reduces ischemic event recurrence. However, its effectiveness depends on accurate dosage and timely administration. This study is a comprehensive quality assessment of the implementation of the DAPT protocol—specifically, treatment initiation within 48 h of symptom onset in patients with mild stroke or high-risk TIA—at our center.
Methods
For this single-center, retrospective analysis we screened all 11,180 consecutive patients from the Helsinki Stroke Quality Registry (HSQR) treated at the emergency department between 1st of January 2019 and 25th of January 2023. Patients with DAPT (ASA and clopidogrel) within 2 weeks of admission were included. Patients treated with i.v. thrombolysis, thrombectomy or if already on DAPT prior to admission were excluded. We analyzed the time of DAPT initiation, patient diagnoses and risk scores (NIHSS and ABCD2).
Results
Of 11,180 patients screened, 299 met the inclusion criteria. Among them, 263 (88.0%) had a final diagnosis of ischemic stroke or TIA, supporting DAPT use. Risk scores were documented in 193 (73.4%), and 197 (65.9%) initiated DAPT within 48 h of symptom onset per our institutional protocol. Overall, 137 (45.8%) fully adhered to all protocol criteria.
Conclusions
Fewer than half (45.8%) of patients fully adhered to the HUS protocol, and 65.9% initiated DAPT within 48 h from symptom onset. We propose that DAPT should be considered as part of the acute stroke treatment protocol for eligible patients to minimize delays in treatment initiation.
{"title":"Adherence to Dual Antiplatelet Therapy Protocol in Acute Ischemic Stroke","authors":"Laura Martikainen, Petra ljäs, Olli P. Suomalainen, Liisa Tomppo, Laura Mannismäki, Henrietta Törmänen, Maria Girfanova, Sami Curtze","doi":"10.1111/ene.70461","DOIUrl":"10.1111/ene.70461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Previous randomized trials, such as CHANCE and POINT, have shown that dual antiplatelet therapy (DAPT) reduces ischemic event recurrence. However, its effectiveness depends on accurate dosage and timely administration. This study is a comprehensive quality assessment of the implementation of the DAPT protocol—specifically, treatment initiation within 48 h of symptom onset in patients with mild stroke or high-risk TIA—at our center.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this single-center, retrospective analysis we screened all 11,180 consecutive patients from the Helsinki Stroke Quality Registry (HSQR) treated at the emergency department between 1st of January 2019 and 25th of January 2023. Patients with DAPT (ASA and clopidogrel) within 2 weeks of admission were included. Patients treated with i.v. thrombolysis, thrombectomy or if already on DAPT prior to admission were excluded. We analyzed the time of DAPT initiation, patient diagnoses and risk scores (NIHSS and ABCD<sup>2</sup>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 11,180 patients screened, 299 met the inclusion criteria. Among them, 263 (88.0%) had a final diagnosis of ischemic stroke or TIA, supporting DAPT use. Risk scores were documented in 193 (73.4%), and 197 (65.9%) initiated DAPT within 48 h of symptom onset per our institutional protocol. Overall, 137 (45.8%) fully adhered to all protocol criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Fewer than half (45.8%) of patients fully adhered to the HUS protocol, and 65.9% initiated DAPT within 48 h from symptom onset. We propose that DAPT should be considered as part of the acute stroke treatment protocol for eligible patients to minimize delays in treatment initiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667611","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}
Kristine Blix, Ida Laake, Ida Henriette Caspersen, Berit Feiring, Anna Hayman Robertson, Siri N. Skodvin, Siri Mjaaland, Per Magnus, Anker Stubberud, Marte-Helene Bjørk, Lill Trogstad
Background
Persistent headache after SARS-CoV-2 infections and vaccination has been reported. However, limited data exist on the risk of new-onset headache after these exposures compared to unexposed periods in the general population.
Methods
We used data from three population-based cohorts (N = 85,774, age 19–81 years). SARS-CoV-2 infections and vaccinations were obtained from national registries and questionnaires. Before and after Omicron emergence, participants stated whether they had been suffering from headache during the past year, reported headache characteristics, and time of onset. Time-dependent exposures were used to investigate the impact of SARS-CoV-2 infection and vaccination on the risk of new-onset headache. Headache subtypes were secondary outcomes.
Results
SARS-CoV-2 infection and first and second vaccine doses were associated with increased risk of new-onset headache. The three cohorts, representing different age groups, were analyzed separately. For pre-Omicron infections, the hazard ratio (HR) was 6.7 (95% confidence interval (CI) 4.8–9.2) and 6.5 (95% CI 3.8–11.1) among middle-aged women and men, respectively. For Omicron infection, HRs were 4.7 (95% CI 4.1–5.4) and 4.5 (95% CI 3.7–5.4), respectively. The risk increased with infection severity. Corresponding HRs for first and second vaccine doses, administered during low transmission, were 1.6 and 1.7, respectively, in women, and 1.5 for both doses in men. The third dose, given before the Omicron surge, was associated with 20%–40% protection against new-onset headache.
Conclusions
SARS-CoV-2 infection was strongly associated with new-onset headache. Primary vaccination was associated with a small increased risk of headache during a low-transmission period, whereas booster vaccination offered protection during high-transmission.
背景：已有SARS-CoV-2感染和疫苗接种后持续头痛的报道。然而，在普通人群中，与未暴露期间相比，这些暴露后新发头痛的风险数据有限。方法：我们使用的数据来自三个基于人群的队列（N = 85,774，年龄19-81岁）。SARS-CoV-2感染和疫苗接种数据来自国家登记处和调查问卷。在欧米克隆出现之前和之后，参与者陈述了他们在过去一年中是否患有头痛，报告的头痛特征和发病时间。使用时间依赖暴露来研究SARS-CoV-2感染和疫苗接种对新发头痛风险的影响。头痛亚型是次要结局。结果：SARS-CoV-2感染和第一次和第二次疫苗剂量与新发头痛的风险增加相关。代表不同年龄组的三个队列分别进行分析。对于欧米克隆前感染，中年女性和男性的危险比（HR）分别为6.7（95%可信区间（CI） 4.8-9.2）和6.5 （95% CI 3.8-11.1）。对于Omicron感染，hr分别为4.7 （95% CI 4.1-5.4）和4.5 （95% CI 3.7-5.4）。风险随着感染的严重程度而增加。在低传播期间接种第一剂和第二剂疫苗的相应hr在女性中分别为1.6和1.7，在男性中两剂分别为1.5。第三剂，在Omicron激增之前，对新发头痛有20%-40%的保护作用。结论：SARS-CoV-2感染与新发头痛密切相关。初次接种与低传播期头痛风险小幅增加相关，而加强接种在高传播期提供保护。
{"title":"New-Onset Headache After SARS-CoV-2 Infection and Vaccination: Results From Three Population-Based Cohorts in Norway","authors":"Kristine Blix, Ida Laake, Ida Henriette Caspersen, Berit Feiring, Anna Hayman Robertson, Siri N. Skodvin, Siri Mjaaland, Per Magnus, Anker Stubberud, Marte-Helene Bjørk, Lill Trogstad","doi":"10.1111/ene.70437","DOIUrl":"10.1111/ene.70437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Persistent headache after SARS-CoV-2 infections and vaccination has been reported. However, limited data exist on the risk of new-onset headache after these exposures compared to unexposed periods in the general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from three population-based cohorts (<i>N</i> = 85,774, age 19–81 years). SARS-CoV-2 infections and vaccinations were obtained from national registries and questionnaires. Before and after Omicron emergence, participants stated whether they had been suffering from headache during the past year, reported headache characteristics, and time of onset. Time-dependent exposures were used to investigate the impact of SARS-CoV-2 infection and vaccination on the risk of new-onset headache. Headache subtypes were secondary outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SARS-CoV-2 infection and first and second vaccine doses were associated with increased risk of new-onset headache. The three cohorts, representing different age groups, were analyzed separately. For pre-Omicron infections, the hazard ratio (HR) was 6.7 (95% confidence interval (CI) 4.8–9.2) and 6.5 (95% CI 3.8–11.1) among middle-aged women and men, respectively. For Omicron infection, HRs were 4.7 (95% CI 4.1–5.4) and 4.5 (95% CI 3.7–5.4), respectively. The risk increased with infection severity. Corresponding HRs for first and second vaccine doses, administered during low transmission, were 1.6 and 1.7, respectively, in women, and 1.5 for both doses in men. The third dose, given before the Omicron surge, was associated with 20%–40% protection against new-onset headache.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SARS-CoV-2 infection was strongly associated with new-onset headache. Primary vaccination was associated with a small increased risk of headache during a low-transmission period, whereas booster vaccination offered protection during high-transmission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12675824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667635","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}
Annexins are a family of calcium-dependent membrane-binding proteins implicated in membrane repair and inflammation, yet their immunoreactivity patterns in neuromuscular disorders remain poorly characterized. This study systematically examined the immunoreactivity profiles of annexins A1, A2, A4, A5, A6, A7, and A11 across various muscular dystrophies, including muscular dystrophies, inflammatory myopathies, lipid storage myopathy (LSM), and amyotrophic lateral sclerosis (ALS).
Methods
Muscle biopsies from patients with dysferlinopathy, Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD), facioscapulohumeral muscular dystrophy (FSHD), LSM, inflammatory myopathies, and ALS, along with controls, were analyzed. Immunofluorescence and immunoblot assays were used to assess annexin localization and abundance, and quantitative immunoreactivity levels were statistically compared with controls.
Results
Dysferlinopathy showed a distinct upregulation of multiple annexins (A1, A2, A4, A5, A6, and A7). These annexins were primarily localized to the extracellular matrix, with additional cytoplasmic accumulation in atrophied fibers. Annexin A6 was strongly associated with the sarcolemma, while annexin A7 was diffusely distributed. In contrast, other myopathies such as OPMD and FSHD exhibited reduced or unchanged annexin immunoreactivity. Inflammatory myopathies partially mirrored the dysferlinopathy pattern, though annexin A2 levels were lower. ALS samples displayed minimal immunoreactivity, restricted to focal cytoplasmic annexin A1 and sparse sarcolemmal annexin A6.
Conclusions
These findings reveal a unique annexin signature in dysferlinopathy, suggesting a potential involvement in membrane repair and inflammatory modulation. The differential expression across disorders highlights the diverse roles of annexins in muscle pathophysiology and supports their utility as diagnostic biomarkers and therapeutic targets.
{"title":"Comprehensive Profiling of Annexins in Neuromuscular Disorders Reveals a Unique Signature in Dysferlinopathy","authors":"Qi-Fang He, Yu-hua Lin, Ze-ling Zheng, Ming-hui Zeng, Xin Lin, Xin-yi Liu, Kang-yang, Q I-jie Zhang, Min-ting Lin, Ning Wang, Zhi-qiang Wang, Feng Lin","doi":"10.1111/ene.70442","DOIUrl":"10.1111/ene.70442","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Annexins are a family of calcium-dependent membrane-binding proteins implicated in membrane repair and inflammation, yet their immunoreactivity patterns in neuromuscular disorders remain poorly characterized. This study systematically examined the immunoreactivity profiles of annexins A1, A2, A4, A5, A6, A7, and A11 across various muscular dystrophies, including muscular dystrophies, inflammatory myopathies, lipid storage myopathy (LSM), and amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Muscle biopsies from patients with dysferlinopathy, Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD), facioscapulohumeral muscular dystrophy (FSHD), LSM, inflammatory myopathies, and ALS, along with controls, were analyzed. Immunofluorescence and immunoblot assays were used to assess annexin localization and abundance, and quantitative immunoreactivity levels were statistically compared with controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dysferlinopathy showed a distinct upregulation of multiple annexins (A1, A2, A4, A5, A6, and A7). These annexins were primarily localized to the extracellular matrix, with additional cytoplasmic accumulation in atrophied fibers. Annexin A6 was strongly associated with the sarcolemma, while annexin A7 was diffusely distributed. In contrast, other myopathies such as OPMD and FSHD exhibited reduced or unchanged annexin immunoreactivity. Inflammatory myopathies partially mirrored the dysferlinopathy pattern, though annexin A2 levels were lower. ALS samples displayed minimal immunoreactivity, restricted to focal cytoplasmic annexin A1 and sparse sarcolemmal annexin A6.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings reveal a unique annexin signature in dysferlinopathy, suggesting a potential involvement in membrane repair and inflammatory modulation. The differential expression across disorders highlights the diverse roles of annexins in muscle pathophysiology and supports their utility as diagnostic biomarkers and therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12669908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653703","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}
Marco Michelutti, Hans-Jürgen Huppertz, Sarah Anderl-Straub, Heiko Volkmann, Daniele Urso, Benedetta Tafuri, Salvatore Nigro, Paolo Manganotti, Angela Rosenbohm, Albert C. Ludolph, Markus Otto, Giancarlo Logroscino, Hans-Peter Müller, Jan Kassubek
Background
We investigated whether diffusion tensor imaging (DTI) and atlas-based volumetry (ABV) could track specific patterns of brain white matter (WM) microstructure and gray matter (GM) volumes in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD).
Methods
MRI datasets from 65 bvFTD (including 19 with longitudinal MRI), 18ALS-FTD, and 39 controls were analyzed. White matter fractional anisotropy (FA) differences were assessed using unbiased Whole Brain-based Spatial Statistics (WBSS) and a hypothesis-driven complementary approach consisting of Tract-Wise FA Statistics (TFAS) in Tracts of Interest (TOIs) and ABV in Structures of Interest (SOIs). FA maps were correlated with disease severity (FTLD-CDR sum of boxes). A random forest algorithm classified participants employing TOI and SOI data.
Results
At baseline, both bvFTD and ALS-FTD exhibited WM changes in several tracts including the uncinate fasciculi, tracts originating in the corpus callosum, and the inferior and superior longitudinal fasciculi. Atrophy was most pronounced in the frontal lobes and caudate nuclei. Longitudinally, bvFTD demonstrated an antero-posterior spread of WM degeneration, particularly along the corpus callosum and inferior longitudinal fasciculus, with relatively modest cortical atrophy progression. Random forest analysis identified the most discriminative TOIs and SOIs including the uncinate fasciculus and the amygdala.
Conclusions
Our findings demonstrate a similar pattern of structural and microstructural changes in bvFTD and ALS-FTD, with a specific involvement of the corticospinal tract for ALS-FTD, and support the utility of combined DTI and ABV in tracking disease progression across the FTLD spectrum.
{"title":"MRI-DTI Biomarkers Along the Continuum of Behavioral Variant Frontotemporal Dementia","authors":"Marco Michelutti, Hans-Jürgen Huppertz, Sarah Anderl-Straub, Heiko Volkmann, Daniele Urso, Benedetta Tafuri, Salvatore Nigro, Paolo Manganotti, Angela Rosenbohm, Albert C. Ludolph, Markus Otto, Giancarlo Logroscino, Hans-Peter Müller, Jan Kassubek","doi":"10.1111/ene.70438","DOIUrl":"10.1111/ene.70438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We investigated whether diffusion tensor imaging (DTI) and atlas-based volumetry (ABV) could track specific patterns of brain white matter (WM) microstructure and gray matter (GM) volumes in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRI datasets from 65 bvFTD (including 19 with longitudinal MRI), 18ALS-FTD, and 39 controls were analyzed. White matter fractional anisotropy (FA) differences were assessed using unbiased Whole Brain-based Spatial Statistics (WBSS) and a hypothesis-driven complementary approach consisting of Tract-Wise FA Statistics (TFAS) in Tracts of Interest (TOIs) and ABV in Structures of Interest (SOIs). FA maps were correlated with disease severity (FTLD-CDR sum of boxes). A random forest algorithm classified participants employing TOI and SOI data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, both bvFTD and ALS-FTD exhibited WM changes in several tracts including the uncinate fasciculi, tracts originating in the corpus callosum, and the inferior and superior longitudinal fasciculi. Atrophy was most pronounced in the frontal lobes and caudate nuclei. Longitudinally, bvFTD demonstrated an antero-posterior spread of WM degeneration, particularly along the corpus callosum and inferior longitudinal fasciculus, with relatively modest cortical atrophy progression. Random forest analysis identified the most discriminative TOIs and SOIs including the uncinate fasciculus and the amygdala.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate a similar pattern of structural and microstructural changes in bvFTD and ALS-FTD, with a specific involvement of the corticospinal tract for ALS-FTD, and support the utility of combined DTI and ABV in tracking disease progression across the FTLD spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647782","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}
Magdalena Vieregge, Anastasia Kuzkina, Annette Janzen, Wolfgang H. Oertel, Michael Sommerauer, Jens Volkmann, Kathrin Doppler
Background
Skin biopsies and seed amplification assays (SAA) provide a sensitive and potentially quantitative method to detect alpha-synuclein (a-syn) aggregation in peripheral nerve fibers in Parkinson's disease (PD). Relating to the previously published hypothesis that PD may either originate in the peripheral (body-first) or central (brain-first) nervous system, we investigated whether patients with clinical features that have been reported to be associated with a suspected body-first subtype of PD exhibit higher levels of a-syn aggregation in dermal nerve fibers compared to those without these features. Patients with isolated REM sleep behavior disorder (iRBD) representing a suspected premotor stage of body-first PD were studied in comparison to the PD cohort.
Methods
Patients were categorized on the basis of clinical features, and SAA parameters such as lag time, number of positive curves, and titers were analyzed and correlated with clinical features.
Results
Although patients with clinical features of suspected body-first PD showed slightly higher titers, significant differences were mainly observed between iRBD patients and PD patients.
Conclusions
Our data suggest that widespread α-syn aggregation in advanced PD limits the use of SAA in skin biopsies for subtype differentiation.
{"title":"Dermal Alpha-Synuclein Aggregation in Seed Amplification Assays for Parkinson's Disease Subtype Differentiation","authors":"Magdalena Vieregge, Anastasia Kuzkina, Annette Janzen, Wolfgang H. Oertel, Michael Sommerauer, Jens Volkmann, Kathrin Doppler","doi":"10.1111/ene.70453","DOIUrl":"https://doi.org/10.1111/ene.70453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skin biopsies and seed amplification assays (SAA) provide a sensitive and potentially quantitative method to detect alpha-synuclein (a-syn) aggregation in peripheral nerve fibers in Parkinson's disease (PD). Relating to the previously published hypothesis that PD may either originate in the peripheral (body-first) or central (brain-first) nervous system, we investigated whether patients with clinical features that have been reported to be associated with a suspected body-first subtype of PD exhibit higher levels of a-syn aggregation in dermal nerve fibers compared to those without these features. Patients with isolated REM sleep behavior disorder (iRBD) representing a suspected premotor stage of body-first PD were studied in comparison to the PD cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were categorized on the basis of clinical features, and SAA parameters such as lag time, number of positive curves, and titers were analyzed and correlated with clinical features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although patients with clinical features of suspected body-first PD showed slightly higher titers, significant differences were mainly observed between iRBD patients and PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data suggest that widespread α-syn aggregation in advanced PD limits the use of SAA in skin biopsies for subtype differentiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618978","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}
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