Lidón Carretero-Vilarroig, Rafael Sivera, Raquel Baviera, Carmen Espinós, Nuria Muelas, Juan Francisco Vazquez-Costa, Elena Aller, Luis Bataller, Teresa Jaijo
Background
Hereditary spastic paraparesis (HSP) encompasses a genetically and clinically heterogeneous group of neurodegenerative disorders, primarily characterized by progressive lower limb spasticity and weakness of the lower limbs. Although more than 80 genes have been associated with HSP, achieving definite genetic diagnosis remains challenging, limiting effective patient care, genetic counseling, and understanding of genotype–phenotype correlations. This study aimed to investigate the diagnostic yield of clinical exome sequencing (CES) in a cohort of Spanish individuals with suspected HSP and to explore genotype–phenotype correlations.
Methods
A total of 139 non-related Spanish individuals with HSP underwent standardized clinical evaluation and CES. Genetic analyses were performed using a virtual panel containing 129 HSP-associated genes, complemented by phenotype-driven filtering through the Human Phenotype Ontology. Statistical analyses were performed on core clinical and paraclinical features.
Results
After clinical review, 108 index cases were included. Male patients were slightly more represented and mean age at onset was 33 years. Pure HSP forms were more prevalent. The most frequent presenting symptoms were gait disturbance and recurrent falls. A genetic diagnosis was achieved in 57 patients (52,8%), with SPAST and SPG7 being the most frequently mutated genes. In total, pathogenic/likely pathogenic variants were identified across 21 genes, including 8 novel variants. HSP with autosomal recessive inheritance was more common than autosomal dominant (29 vs. 25 cases), while dominant/recessive X-linked disease forms were rare (3 cases).
Conclusions
CES combined with HPO-based filtering is an effective strategy for achieving genetic diagnosis in patients with suspicion of HSP.
{"title":"Diagnostic Yield and Genotype–Phenotype Correlations of Clinical Exome Sequencing in Hereditary Spastic Paraparesis: Experience From Eastern Spain","authors":"Lidón Carretero-Vilarroig, Rafael Sivera, Raquel Baviera, Carmen Espinós, Nuria Muelas, Juan Francisco Vazquez-Costa, Elena Aller, Luis Bataller, Teresa Jaijo","doi":"10.1111/ene.70475","DOIUrl":"10.1111/ene.70475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary spastic paraparesis (HSP) encompasses a genetically and clinically heterogeneous group of neurodegenerative disorders, primarily characterized by progressive lower limb spasticity and weakness of the lower limbs. Although more than 80 genes have been associated with HSP, achieving definite genetic diagnosis remains challenging, limiting effective patient care, genetic counseling, and understanding of genotype–phenotype correlations. This study aimed to investigate the diagnostic yield of clinical exome sequencing (CES) in a cohort of Spanish individuals with suspected HSP and to explore genotype–phenotype correlations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 139 non-related Spanish individuals with HSP underwent standardized clinical evaluation and CES. Genetic analyses were performed using a virtual panel containing 129 HSP-associated genes, complemented by phenotype-driven filtering through the Human Phenotype Ontology. Statistical analyses were performed on core clinical and paraclinical features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After clinical review, 108 index cases were included. Male patients were slightly more represented and mean age at onset was 33 years. Pure HSP forms were more prevalent. The most frequent presenting symptoms were gait disturbance and recurrent falls. A genetic diagnosis was achieved in 57 patients (52,8%), with <i>SPAST</i> and <i>SPG7</i> being the most frequently mutated genes. In total, pathogenic/likely pathogenic variants were identified across 21 genes, including 8 novel variants. HSP with autosomal recessive inheritance was more common than autosomal dominant (29 vs. 25 cases), while dominant/recessive X-linked disease forms were rare (3 cases).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CES combined with HPO-based filtering is an effective strategy for achieving genetic diagnosis in patients with suspicion of HSP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009388","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}
Emilie Cardot-Martin, Jean Baptiste Chanson, Cédric Lenormand, Pierre Boyer, Yves Hansmann, Jean Sibilia, Benoit Jaulhac, Marc Scherlinger
Context
B-cell-depleting therapies such as rituximab and newer anti-CD20 agents may impair humoral immune responses and reduce the reliability of serological testing. This systematic review aims to summarize reported cases of Lyme borreliosis and relapsing fever (RF) Borrelia infections in patients receiving B-cell-depleting therapies, focusing on clinical manifestations, diagnostic challenges, and treatment outcomes.
Methods
A systematic literature search was conducted using PubMed and the Web of Science Core Collection employing search terms linking B-cell-depleting therapies to Lyme borreliosis and to RF Borrelia infections.
Results
The most reported cases in the literature were neurological infections due to Borrelia; there were 11 cases of Lyme neuroborreliosis and 8 cases of neurological infections due to B. miyamotoi reported. Lyme neuroborreliosis cases all exhibited negative serology. Pleocytosis of cerebrospinal fluid (CSF) was, however, always present, and PCR could confirm the diagnosis in 8 cases. Diagnosis in all B. miyamotoi cases relied exclusively on direct detection methods. All patients responded to standard antibiotic regimens, although persistent symptoms were reported in some cases. The other infections were 7 erythema migrans (EM), 4 disseminated Lyme borreliosis, and 3 cases of relapsing fever.
Conclusion
Neurological Borrelia infections may be underrecognized in patients on B cell-depleting therapies due to atypical presentations and negative serologies. Early consideration of direct diagnostic methods such as PCR or indirect methods such as CSF CXCL13 levels is critical. Neurologists should maintain a high index of suspicion for Borrelia infections in immunocompromised patients presenting with CSF pleocytosis and neurological symptoms.
背景：b细胞消耗疗法如利妥昔单抗和较新的抗cd20药物可能损害体液免疫反应并降低血清学检测的可靠性。本系统综述旨在总结已报道的接受b细胞消耗治疗的患者的莱姆病和复发热（RF）伯氏疏螺旋体感染病例，重点关注临床表现、诊断挑战和治疗结果。方法：使用PubMed和Web of Science核心合集进行系统的文献检索，使用将b细胞消耗疗法与莱姆病和RF疏螺旋体感染联系起来的搜索词。结果：文献报道的病例以伯氏疏螺旋体引起的神经系统感染最多；报告莱姆病神经螺旋体病11例，宫氏贝氏菌引起的神经系统感染8例。莱姆病神经螺旋体病患者血清学均为阴性。但脑脊液（CSF）多细胞增多症始终存在，PCR可确诊8例。所有宫本氏杆菌病例的诊断完全依赖于直接检测方法。所有患者都对标准抗生素治疗方案有反应，尽管在一些病例中报告了持续的症状。其他感染为移行性红斑7例，播散性莱姆病4例，回归热3例。结论：在接受B细胞消耗治疗的患者中，由于不典型的表现和阴性的血清学，神经系统伯氏疏螺旋体感染可能被低估。早期考虑直接诊断方法，如PCR或间接方法，如CSF CXCL13水平是至关重要的。神经学家应该对出现脑脊液多细胞症和神经症状的免疫功能低下患者的伯氏疏螺旋体感染保持高度怀疑。
{"title":"Borrelia Infections Under B Cell-Depleting Therapies: A Systematic Review of Diagnostic Challenges and Outcomes With Special Focus on Neurological Forms","authors":"Emilie Cardot-Martin, Jean Baptiste Chanson, Cédric Lenormand, Pierre Boyer, Yves Hansmann, Jean Sibilia, Benoit Jaulhac, Marc Scherlinger","doi":"10.1111/ene.70483","DOIUrl":"10.1111/ene.70483","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Context</h3>\u0000 \u0000 <p>B-cell-depleting therapies such as rituximab and newer anti-CD20 agents may impair humoral immune responses and reduce the reliability of serological testing. This systematic review aims to summarize reported cases of Lyme borreliosis and relapsing fever (RF) <i>Borrelia</i> infections in patients receiving B-cell-depleting therapies, focusing on clinical manifestations, diagnostic challenges, and treatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was conducted using PubMed and the Web of Science Core Collection employing search terms linking B-cell-depleting therapies to Lyme borreliosis and to RF <i>Borrelia</i> infections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most reported cases in the literature were neurological infections due to <i>Borrelia;</i> there were 11 cases of Lyme neuroborreliosis and 8 cases of neurological infections due to <i>B. miyamotoi</i> reported. Lyme neuroborreliosis cases all exhibited negative serology. Pleocytosis of cerebrospinal fluid (CSF) was, however, always present, and PCR could confirm the diagnosis in 8 cases. Diagnosis in all <i>B. miyamotoi</i> cases relied exclusively on direct detection methods. All patients responded to standard antibiotic regimens, although persistent symptoms were reported in some cases. The other infections were 7 erythema migrans (EM), 4 disseminated Lyme borreliosis, and 3 cases of relapsing fever.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Neurological Borrelia infections may be underrecognized in patients on B cell-depleting therapies due to atypical presentations and negative serologies. Early consideration of direct diagnostic methods such as PCR or indirect methods such as CSF CXCL13 levels is critical. Neurologists should maintain a high index of suspicion for <i>Borrelia</i> infections in immunocompromised patients presenting with CSF pleocytosis and neurological symptoms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008746","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}
Zainab Rissan, Nadja Skadkær Hansen, Vlasta Vukovic-Cvetkovic, Louise Ninett Carlsen, Steffen Hamann, Marianne Wegener, Rigmor H. Jensen, Henrik Winther Schytz
Objectives
Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure and papilledema. If left untreated, it can lead to vision loss, and, timely detection of papilledema is of paramount importance. Direct ophthalmoscopy can be difficult to perform and interpret for non-ophthalmologists. Therefore, this study aimed to investigate the impact of combined fundus photography and perimetry (CFPP) on patients with suspicion of new-onset IIH or IIH follow-up.
Method
The study was based on a cross-sectional, retrospective chart review of all patients who underwent CFPP examination due to suspicion of new-onset IIH or IIH follow-up at the Danish Headache Center between 2020 and 2023.
Results
258 patients were included for analysis, 92% females aged 17–72 years (mean age: 35.8 years). CFPP was performed due to clinical suspicion of new-onset IIH (38%), worsening/relapse of IIH (24%), assurance check in known IIH (19%), subjective symptoms (5%) or other reasons (14%). Overall, 62% had normal fundus photos, 21% had optic disc edema, 10% had other coincidental findings in the retina and/or optic disc, and 6% had an optic disc status unchanged from previous examinations. The use of CFPP confirmed the suspicion of IIH in 8% of patients and disproved it in 40% of patients. The CFPP results changed the treatment plan in 28% and caused referral to a neuroophthalmologist in 16% of patients.
Conclusion
CFPP can be used as a time- and resource-saving screening tool in headache patients with suspicion of new-onset IIH or follow-up in a tertiary neurology setting.
{"title":"The Use of Combined Fundus Photography and Perimetry for the Assessment of Patients Referred for Intracranial Hypertension or Follow-Up of the Diagnosis in a Tertiary Headache Center","authors":"Zainab Rissan, Nadja Skadkær Hansen, Vlasta Vukovic-Cvetkovic, Louise Ninett Carlsen, Steffen Hamann, Marianne Wegener, Rigmor H. Jensen, Henrik Winther Schytz","doi":"10.1111/ene.70478","DOIUrl":"10.1111/ene.70478","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure and papilledema. If left untreated, it can lead to vision loss, and, timely detection of papilledema is of paramount importance. Direct ophthalmoscopy can be difficult to perform and interpret for non-ophthalmologists. Therefore, this study aimed to investigate the impact of combined fundus photography and perimetry (CFPP) on patients with suspicion of new-onset IIH or IIH follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The study was based on a cross-sectional, retrospective chart review of all patients who underwent CFPP examination due to suspicion of new-onset IIH or IIH follow-up at the Danish Headache Center between 2020 and 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>258 patients were included for analysis, 92% females aged 17–72 years (mean age: 35.8 years). CFPP was performed due to clinical suspicion of new-onset IIH (38%), worsening/relapse of IIH (24%), assurance check in known IIH (19%), subjective symptoms (5%) or other reasons (14%). Overall, 62% had normal fundus photos, 21% had optic disc edema, 10% had other coincidental findings in the retina and/or optic disc, and 6% had an optic disc status unchanged from previous examinations. The use of CFPP confirmed the suspicion of IIH in 8% of patients and disproved it in 40% of patients. The CFPP results changed the treatment plan in 28% and caused referral to a neuroophthalmologist in 16% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CFPP can be used as a time- and resource-saving screening tool in headache patients with suspicion of new-onset IIH or follow-up in a tertiary neurology setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988691","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}
Elisabetta Indelicato, Beatriz Carmona-Hidalgo, Javier Quintero, Juan Darío Ortigoza Escobar, Anne Koy, András Salamon, Pawel Tacik, Laura Muñoz-Delgado, Giulia Giannini, Martin Reich, Alberto Albanese, Tobias Bäumer, Francisco Grandas, Robert Jech, Athanasios Leonardos, Pablo Mir, Belén Pérez-Dueñas, Javier Ricardo Perez-Sanchez, Francesc Valldeoriola, Ginevra Zanni, Marie Vidailhet, Rocío Rodríguez-López, Juan Antonio Blasco-Amaro, Carola Reinhard, Sylvia Boesch, the European Reference Network for Rare Neurological Diseases (ERN-RND)
Background
Deep brain stimulation (DBS) is an essential treatment option for disabling segmental or generalized dystonia. An underlying monogenic etiology is increasingly recognized as an important predictor of DBS outcomes. Moreover, the genetic background of dystonia is continuously expanding, posing new challenges in the tailored counseling of patients regarding advanced therapies.
Methods
To improve the quality of available evidence on the efficacy of DBS for treating monogenic dystonia, we conducted a systematic review in accordance with PRISMA guidelines. We applied a rigorous methodology and maximized the amount of information provided by including all patients, regardless of age or applied rating scale.
Results
Our findings confirm the high probability of a good DBS outcome in patients harboring TOR1A, SGCE, PANK2, and TAF1 variants. An intermediate response was associated with KMT2B and THAP1 variants. A particularly favorable outcome with > 80% improvement in dystonia symptoms was associated with a subset of DYT-TOR1A patients and few cases with SGCE-, KMT2B-, THAP1-, GNAO1-, and TAF1-related disease. Poor study quality, non-systematic assessment of DBS response, and pooling of patients with different genetic etiologies were among the encountered limitations.
Conclusions
Based on the collected evidence, we formulated recommendations for applying DBS in monogenic dystonia. Our findings, together with the cumulative literature, advocate the introduction of genetic testing in the pre-DBS work-up. They furthermore highlight the need to implement and report on systematic assessments of DBS outcomes, including mandatory patient-reported outcomes. These steps will ensure optimal counseling and continuous improvement in the care of patients with monogenic dystonia.
{"title":"Efficacy of Deep Brain Stimulation for the Treatment of Monogenic Dystonia Symptoms: A Systematic Review","authors":"Elisabetta Indelicato, Beatriz Carmona-Hidalgo, Javier Quintero, Juan Darío Ortigoza Escobar, Anne Koy, András Salamon, Pawel Tacik, Laura Muñoz-Delgado, Giulia Giannini, Martin Reich, Alberto Albanese, Tobias Bäumer, Francisco Grandas, Robert Jech, Athanasios Leonardos, Pablo Mir, Belén Pérez-Dueñas, Javier Ricardo Perez-Sanchez, Francesc Valldeoriola, Ginevra Zanni, Marie Vidailhet, Rocío Rodríguez-López, Juan Antonio Blasco-Amaro, Carola Reinhard, Sylvia Boesch, the European Reference Network for Rare Neurological Diseases (ERN-RND)","doi":"10.1111/ene.70490","DOIUrl":"10.1111/ene.70490","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deep brain stimulation (DBS) is an essential treatment option for disabling segmental or generalized dystonia. An underlying monogenic etiology is increasingly recognized as an important predictor of DBS outcomes. Moreover, the genetic background of dystonia is continuously expanding, posing new challenges in the tailored counseling of patients regarding advanced therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To improve the quality of available evidence on the efficacy of DBS for treating monogenic dystonia, we conducted a systematic review in accordance with PRISMA guidelines. We applied a rigorous methodology and maximized the amount of information provided by including all patients, regardless of age or applied rating scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings confirm the high probability of a good DBS outcome in patients harboring <i>TOR1A, SGCE, PANK2</i>, and <i>TAF1</i> variants. An intermediate response was associated with <i>KMT2B</i> and <i>THAP1</i> variants. A particularly favorable outcome with > 80% improvement in dystonia symptoms was associated with a subset of DYT-<i>TOR1A</i> patients and few cases with <i>SGCE-, KMT2B-, THAP1</i>-, <i>GNAO1</i>-, and <i>TAF1</i>-related disease. Poor study quality, non-systematic assessment of DBS response, and pooling of patients with different genetic etiologies were among the encountered limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Based on the collected evidence, we formulated recommendations for applying DBS in monogenic dystonia. Our findings, together with the cumulative literature, advocate the introduction of genetic testing in the pre-DBS work-up. They furthermore highlight the need to implement and report on systematic assessments of DBS outcomes, including mandatory patient-reported outcomes. These steps will ensure optimal counseling and continuous improvement in the care of patients with monogenic dystonia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988633","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}
<p>We read with great interest the article by Bjelica et al., titled “Compound muscle action potential (CMAP) amplitude trajectories and pattern in adults with 5q-spinal muscular atrophy receiving nusinersen therapy” [<span>1</span>]. This multicenter, binational observational study provides invaluable longitudinal data on electrophysiological changes in a substantial cohort of adult spinal muscular atrophy (SMA) patients under nusinersen treatment. The investigation of CMAP as a potential biomarker in this context is highly relevant, and the authors are to be commended for their comprehensive analysis and the remarkably long follow-up period of up to 4.5 years, which significantly contributes to the understanding of treatment effects in adult SMA.</p><p>While the study is undoubtedly robust, we would like to raise several points for the authors' consideration that may further refine the interpretation of their findings. The observation that CMAP amplitudes remained stable throughout the treatment period, while a substantial proportion of patients demonstrated clinically meaningful improvements in motor function, presents an interesting clinical paradox. This dissociation between electrophysiological parameters and functional outcomes raises important questions about the practical utility of CMAP as a monitoring tool in clinical practice, where clinicians require sensitive biomarkers to track treatment response and make informed decisions about continuing therapy.</p><p>Building upon this point, we believe the conclusion that “CMAP may not serve as a sensitive biomarker for treatment response in adult SMA patients,” while supported by the group-level analysis, may benefit from additional nuance. Given that clinical decision-making ultimately occurs at the individual patient level, the observed population-level stability could potentially mask important heterogeneity in treatment response. The current analytical approach, while methodologically sound for detecting population trends, might not fully capture the existence of patient subgroups with different CMAP trajectories. Supplementary analyses exploring individual response patterns, perhaps by establishing thresholds for meaningful CMAP change and characterizing the proportion of patients meeting these criteria, could reveal important responder subgroups—particularly among patients with shorter disease duration or more preserved baseline function [<span>2, 3</span>]. Such analysis would help provide clinicians with more nuanced guidance for CMAP's application in practice while acknowledging its potential utility for specific patient populations.</p><p>Furthermore, considering the methodological rigor demonstrated throughout the study, we were particularly intrigued by the nonsignificant trend toward increased median and peroneal nerve CMAP amplitudes up to month 18. While appropriately noted as nonsignificant in the current analysis, this pattern aligns with emerging evidence suggesting that ce
{"title":"Moving Beyond Population-Level Analyses to Characterize Individual Heterogeneity in CMAP Responses Would Enhance the Assessment of Its Clinical Utility","authors":"Yujie Zhang, Jia Hu, Yuting Pu, Xue Bai","doi":"10.1111/ene.70503","DOIUrl":"10.1111/ene.70503","url":null,"abstract":"<p>We read with great interest the article by Bjelica et al., titled “Compound muscle action potential (CMAP) amplitude trajectories and pattern in adults with 5q-spinal muscular atrophy receiving nusinersen therapy” [<span>1</span>]. This multicenter, binational observational study provides invaluable longitudinal data on electrophysiological changes in a substantial cohort of adult spinal muscular atrophy (SMA) patients under nusinersen treatment. The investigation of CMAP as a potential biomarker in this context is highly relevant, and the authors are to be commended for their comprehensive analysis and the remarkably long follow-up period of up to 4.5 years, which significantly contributes to the understanding of treatment effects in adult SMA.</p><p>While the study is undoubtedly robust, we would like to raise several points for the authors' consideration that may further refine the interpretation of their findings. The observation that CMAP amplitudes remained stable throughout the treatment period, while a substantial proportion of patients demonstrated clinically meaningful improvements in motor function, presents an interesting clinical paradox. This dissociation between electrophysiological parameters and functional outcomes raises important questions about the practical utility of CMAP as a monitoring tool in clinical practice, where clinicians require sensitive biomarkers to track treatment response and make informed decisions about continuing therapy.</p><p>Building upon this point, we believe the conclusion that “CMAP may not serve as a sensitive biomarker for treatment response in adult SMA patients,” while supported by the group-level analysis, may benefit from additional nuance. Given that clinical decision-making ultimately occurs at the individual patient level, the observed population-level stability could potentially mask important heterogeneity in treatment response. The current analytical approach, while methodologically sound for detecting population trends, might not fully capture the existence of patient subgroups with different CMAP trajectories. Supplementary analyses exploring individual response patterns, perhaps by establishing thresholds for meaningful CMAP change and characterizing the proportion of patients meeting these criteria, could reveal important responder subgroups—particularly among patients with shorter disease duration or more preserved baseline function [<span>2, 3</span>]. Such analysis would help provide clinicians with more nuanced guidance for CMAP's application in practice while acknowledging its potential utility for specific patient populations.</p><p>Furthermore, considering the methodological rigor demonstrated throughout the study, we were particularly intrigued by the nonsignificant trend toward increased median and peroneal nerve CMAP amplitudes up to month 18. While appropriately noted as nonsignificant in the current analysis, this pattern aligns with emerging evidence suggesting that ce","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988681","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}
Giulia Tammam, Luisa Villa, Richard J. L. F. Lemmers, Jonathan Pini, Abderhmane Slioui, Laura Bouchareychas, Yann David, Mihai-Bogdan Ioncea, Leonardo Salviati, Michele Cavalli, Andra Ezaru, Angela Puma, Jan J. Verschuuren, Silvère M. van der Maarel, Sabrina Sacconi
Background
Facioscapulohumeral dystrophy (FSHD) and Myasthenia Gravis (MG) are well-known rare neuromuscular diseases of respectively genetic and acquired origin. Among muscular dystrophies, the co-occurrence of MG with FSHD is the most common, representing a non-negligible “double trouble”. Here, we aim to describe a series of patients with coexistence of these two rare disorders and combine this with a review of the literature to identify common elements which might provide useful clues when evaluating a FSHD patient with uncommon clinical presentation compatible with MG.
Methods
We retrospectively collected demographic, clinical, and laboratory data of patients affected by both FSHD and MG followed at the Nice University Center, and we performed a review of the literature.
Results
We identified 10 patients in our cohort, 7 females. All patients have a D4Z4 4qA allele of 7–10 RU, a disease onset > 45 years and a mean FSHD score of 9.6 ± 2 at the last evaluation. The mean age of onset of MG was 68.5 ± 7.6 years; all patients presented with anti-AChR antibodies and without thymic pathology, and MG appeared in all but two patients after FSHD. We identified 9 case reports in the literature. All of them presented with AChR positivity. The majority of them presented with a late and very late onset MG and without thymic pathology.
Conclusions
Our results underline the need for careful clinical evaluation to identify uncommon features, especially in elderly FSHD patients carrying a D4Z4 4qA allele of 7–10 RU to exclude the coexistence of other treatable neuromuscular conditions.
{"title":"Co-Occurrence of Myasthenia Gravis and Facioscapulohumeral Muscular Dystrophy: A Case Series and Review of Literature","authors":"Giulia Tammam, Luisa Villa, Richard J. L. F. Lemmers, Jonathan Pini, Abderhmane Slioui, Laura Bouchareychas, Yann David, Mihai-Bogdan Ioncea, Leonardo Salviati, Michele Cavalli, Andra Ezaru, Angela Puma, Jan J. Verschuuren, Silvère M. van der Maarel, Sabrina Sacconi","doi":"10.1111/ene.70477","DOIUrl":"10.1111/ene.70477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Facioscapulohumeral dystrophy (FSHD) and Myasthenia Gravis (MG) are well-known rare neuromuscular diseases of respectively genetic and acquired origin. Among muscular dystrophies, the co-occurrence of MG with FSHD is the most common, representing a non-negligible “double trouble”. Here, we aim to describe a series of patients with coexistence of these two rare disorders and combine this with a review of the literature to identify common elements which might provide useful clues when evaluating a FSHD patient with uncommon clinical presentation compatible with MG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively collected demographic, clinical, and laboratory data of patients affected by both FSHD and MG followed at the Nice University Center, and we performed a review of the literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 10 patients in our cohort, 7 females. All patients have a D4Z4 4qA allele of 7–10 RU, a disease onset > 45 years and a mean FSHD score of 9.6 ± 2 at the last evaluation. The mean age of onset of MG was 68.5 ± 7.6 years; all patients presented with anti-AChR antibodies and without thymic pathology, and MG appeared in all but two patients after FSHD. We identified 9 case reports in the literature. All of them presented with AChR positivity. The majority of them presented with a late and very late onset MG and without thymic pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results underline the need for careful clinical evaluation to identify uncommon features, especially in elderly FSHD patients carrying a D4Z4 4qA allele of 7–10 RU to exclude the coexistence of other treatable neuromuscular conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988631","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}
María Payá, Sofía Portela, Rafael Sivera, Marina Frasquet, Fernando Más-Estellés, Pilar Martí, Inmaculada Azorín, Karolina Aragon-Gawinska, María Tárrega, Herminia Argente-Escrig, Juan F. Vázquez-Costa, Roger Vilchez, Juan J. Vilchez, Teresa Sevilla, Nuria Muelas
Background
Distinguishing between distal myopathies (DMs) and distal hereditary motor neuropathies (dHMNs) can be challenging because clinical, EMG and biopsy findings sometimes overlap. This study aims to identify distinctive muscle MRI features that can guide the diagnosis.
Methods
We collected clinical, genetic and muscle MRI data from patients with a confirmed diagnosis of DM and dHMN. We analyzed potential MRI characteristics to distinguish these conditions and to guide molecular diagnosis, such as the texture and pattern of infiltration.
Results
Seventy-eight (71.5%) patients diagnosed with DMs and thirty-one (28.4%) with dHMNs were included. A length-dependent pattern of muscle involvement, a distal to proximal gradient of fat replacement along the length of the muscles and severe and widespread involvement of foot muscles were more common in patients with dHMNs. Muscle hypertrophy and asymmetry were more frequently observed in the DMs. A reticular pattern of fat infiltration was exclusive to patients with dHMNs, while the moth-eaten pattern predominated in DMs. Muscle islands were more commonly identified in dHMNs (54.8%) but were also observed in 32% of patients with DMs.
Conclusions
Analysis of MRI features can help distinguish between DMs and dHMNs. A reticular pattern is an early feature of dHMNs while muscle islands are identified in advanced stages and in some forms of DMs, though not specific to neurogenic conditions. We recommend including foot muscles in the MRI protocol as they show extensive involvement in most dHMNs, while in DMs their involvement correlates with greater fatty infiltration of lower leg muscles.
{"title":"Muscle MRI Contributes to the Differential Diagnosis Between Distal Myopathies and Distal Hereditary Motor Neuropathies","authors":"María Payá, Sofía Portela, Rafael Sivera, Marina Frasquet, Fernando Más-Estellés, Pilar Martí, Inmaculada Azorín, Karolina Aragon-Gawinska, María Tárrega, Herminia Argente-Escrig, Juan F. Vázquez-Costa, Roger Vilchez, Juan J. Vilchez, Teresa Sevilla, Nuria Muelas","doi":"10.1111/ene.70456","DOIUrl":"10.1111/ene.70456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Distinguishing between distal myopathies (DMs) and distal hereditary motor neuropathies (dHMNs) can be challenging because clinical, EMG and biopsy findings sometimes overlap. This study aims to identify distinctive muscle MRI features that can guide the diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected clinical, genetic and muscle MRI data from patients with a confirmed diagnosis of DM and dHMN. We analyzed potential MRI characteristics to distinguish these conditions and to guide molecular diagnosis, such as the texture and pattern of infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-eight (71.5%) patients diagnosed with DMs and thirty-one (28.4%) with dHMNs were included. A length-dependent pattern of muscle involvement, a distal to proximal gradient of fat replacement along the length of the muscles and severe and widespread involvement of foot muscles were more common in patients with dHMNs. Muscle hypertrophy and asymmetry were more frequently observed in the DMs. A reticular pattern of fat infiltration was exclusive to patients with dHMNs, while the moth-eaten pattern predominated in DMs. Muscle islands were more commonly identified in dHMNs (54.8%) but were also observed in 32% of patients with DMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Analysis of MRI features can help distinguish between DMs and dHMNs. A reticular pattern is an early feature of dHMNs while muscle islands are identified in advanced stages and in some forms of DMs, though not specific to neurogenic conditions. We recommend including foot muscles in the MRI protocol as they show extensive involvement in most dHMNs, while in DMs their involvement correlates with greater fatty infiltration of lower leg muscles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917266","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}
<p>We appreciate the thoughtful comments regarding our recent article, “Immediate Motor Control Enhancement via Pallidothalamic Tract (PTT) Circuit Ablation: A Dual-Target MR-Guided Focused Ultrasound Approach for Tremor-Dominant Parkinson's Disease” [<span>1</span>]. We welcome this opportunity to address concerns regarding the possible influence of order effects and carry-over phenomena in our intraoperative design.</p><p>All participants underwent ventral intermediate nucleus (VIM) ablation first, followed by PTT ablation within the same MRgFUS session. This sequence was deliberately selected based on safety and anatomical hierarchy. The VIM is a well-validated and relatively superficial target for tremor control, whereas the PTT lies deeper, adjacent to eloquent structures such as the Mammillothalamic tract (MTT) and subthalamic nucleus (STN). Performing VIM first ensured procedural safety, patient tolerance, and adequate acoustic transmission before proceeding to the deeper lesion.</p><p>To mitigate potential sequence bias, clinical evaluations were performed immediately before and after each step (VIM evaluation → PTT evaluation), allowing within-subject comparison. Distinct temporal and domain-specific effects were observed: all tremor subtypes improved primarily after VIM, while rigidity improved most prominently after PTT. These differential response patterns argue against a non-specific additive or order-driven gain.</p><p>We concur that transient edema or temperature-dependent conduction block may transiently influence immediate post-lesion testing. To minimize such effects, the VIM score used for analysis was obtained immediately before the first effective PTT sonication, with a latency of less than 10 min. Lesion overlap was also evaluated by post-op MRI, confirming confinement to the intended PTT zone.</p><p>While our study design cannot fully exclude microlesional carry-over, the parameter-specific dissociation (rigidity versus tremor) and the consistency across subjects support target-specific physiological effects rather than generalized intraoperative augmentation.</p><p>We fully agree that randomized or counterbalanced target order, standardized lesion metrics, and objective blinded kinematic assessments are essential to confirm causality. These refinements have already been incorporated into our upcoming multi-center trial, which will include a VIM-only intraoperative control arm to rigorously evaluate the incremental contribution of PTT lesioning.</p><p>Our present study was intended as a physiological feasibility investigation, not as a definitive randomized comparison. In clinical practice, patients with Parkinson's disease frequently present with a mixed motor phenotype in which disabling tremor coexists with varying degrees of rigidity and bradykinesia. For such individuals, our standard treatment algorithm prioritizes VIM ablation as the initial intervention, given its well-established efficacy in tremor suppression. How
{"title":"Clarifying Order and Carry-Over Considerations in Dual-Target MRgFUS for Parkinson's Disease","authors":"Jui-Cheng Chen, Ming-Kuei Lu, Chon-Haw Tsai","doi":"10.1111/ene.70467","DOIUrl":"10.1111/ene.70467","url":null,"abstract":"<p>We appreciate the thoughtful comments regarding our recent article, “Immediate Motor Control Enhancement via Pallidothalamic Tract (PTT) Circuit Ablation: A Dual-Target MR-Guided Focused Ultrasound Approach for Tremor-Dominant Parkinson's Disease” [<span>1</span>]. We welcome this opportunity to address concerns regarding the possible influence of order effects and carry-over phenomena in our intraoperative design.</p><p>All participants underwent ventral intermediate nucleus (VIM) ablation first, followed by PTT ablation within the same MRgFUS session. This sequence was deliberately selected based on safety and anatomical hierarchy. The VIM is a well-validated and relatively superficial target for tremor control, whereas the PTT lies deeper, adjacent to eloquent structures such as the Mammillothalamic tract (MTT) and subthalamic nucleus (STN). Performing VIM first ensured procedural safety, patient tolerance, and adequate acoustic transmission before proceeding to the deeper lesion.</p><p>To mitigate potential sequence bias, clinical evaluations were performed immediately before and after each step (VIM evaluation → PTT evaluation), allowing within-subject comparison. Distinct temporal and domain-specific effects were observed: all tremor subtypes improved primarily after VIM, while rigidity improved most prominently after PTT. These differential response patterns argue against a non-specific additive or order-driven gain.</p><p>We concur that transient edema or temperature-dependent conduction block may transiently influence immediate post-lesion testing. To minimize such effects, the VIM score used for analysis was obtained immediately before the first effective PTT sonication, with a latency of less than 10 min. Lesion overlap was also evaluated by post-op MRI, confirming confinement to the intended PTT zone.</p><p>While our study design cannot fully exclude microlesional carry-over, the parameter-specific dissociation (rigidity versus tremor) and the consistency across subjects support target-specific physiological effects rather than generalized intraoperative augmentation.</p><p>We fully agree that randomized or counterbalanced target order, standardized lesion metrics, and objective blinded kinematic assessments are essential to confirm causality. These refinements have already been incorporated into our upcoming multi-center trial, which will include a VIM-only intraoperative control arm to rigorously evaluate the incremental contribution of PTT lesioning.</p><p>Our present study was intended as a physiological feasibility investigation, not as a definitive randomized comparison. In clinical practice, patients with Parkinson's disease frequently present with a mixed motor phenotype in which disabling tremor coexists with varying degrees of rigidity and bradykinesia. For such individuals, our standard treatment algorithm prioritizes VIM ablation as the initial intervention, given its well-established efficacy in tremor suppression. How","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932707","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}
<p>With great interest we read the current consensus overview, “The Spectrum of Headaches in Moyamoya Angiopathy: From Mechanisms to Management Strategies - A Consensus Review from the NEUROVASC Working Group” which provides a much-needed framework for managing headaches in patients with Moyamoya angiopathy (MMA).</p><p>As neurologists specializing in headaches, we agree that both acute and prophylactic treatment of headaches in patients with MMA is very challenging. The stroke mechanisms in MMA are hemodynamic, embolic, and haemorrhagic, all of which carry different risks for treatment. High-dose ASA, for example, may lead to an increased risk of bleeding in this patient group with a pre-existing increased risk. NSAIDs are suboptimal due to their interaction with ASA used for ischemia prophylaxis; metamizole may lead to hypotension, and triptans, due to their vasoactive properties, are not only formally contraindicated in this context. Regarding prophylactic treatment, we find calcium channel blockers and beta blockers difficult due to hypotension and the resulting hemodynamic risks.</p><p>However, our most important addition to the Consensus Review is our stricter assessment of calcitonin gene-related peptide (CGRP) antagonists. Although the authors adopted a cautious approach to the use of CGRP-based therapies, we believe that the severity of the inherent vascular risk in MMA requires an even more definitive stance against these agents.</p><p>The available evidence, while limited, points to a potential for harm that far outweighs the therapeutic benefit in this high-risk population.</p><p>The core pathophysiology of MMA involves progressive steno-occlusive disease of the intracranial carotid arteries and the compensatory formation of fragile collateral (Moyamoya) vessels. In this delicate, flow-compromised system, maintaining adequate cerebral blood flow (CBF) and oxygen delivery is paramount [<span>1</span>].</p><p>CGRP is one of the most potent endogenous vasodilators [<span>2</span>]. Its presence is particularly vital in the setting of ischemia, where it acts as a critical compensatory mechanism to maximize blood flow and perfusion pressure [<span>3</span>]. This appears to be of the utmost relevance when considering the pathophysiology of MMA. Blocking this compensatory mechanism carries an unacceptable theoretical risk of precipitating cerebral ischemic events. By dampening the body's intrinsic ability to induce vasodilation in areas of critical flow, CGRP-related therapies could potentially shift the delicate balance, leading to hypoperfusion, transient ischemic attacks (TIAs), or stroke, particularly in patients with borderline flow dynamics.</p><p>The risk here is not just theoretical, as Mulder and colleagues were able to document very clearly and convincingly that CGRP-blocking treatment leads to more severe strokes in animal models. Even transfer from bench to bedside is not straightforward. It appears reasonable that these data ma
{"title":"Letter to the Editor: Reaffirming Caution—The Unacceptable Vasoconstrictive Risk of CGRP-Related Therapies in Moyamoya Angiopathy","authors":"Charly Gaul, Steffen Naegel","doi":"10.1111/ene.70481","DOIUrl":"10.1111/ene.70481","url":null,"abstract":"<p>With great interest we read the current consensus overview, “The Spectrum of Headaches in Moyamoya Angiopathy: From Mechanisms to Management Strategies - A Consensus Review from the NEUROVASC Working Group” which provides a much-needed framework for managing headaches in patients with Moyamoya angiopathy (MMA).</p><p>As neurologists specializing in headaches, we agree that both acute and prophylactic treatment of headaches in patients with MMA is very challenging. The stroke mechanisms in MMA are hemodynamic, embolic, and haemorrhagic, all of which carry different risks for treatment. High-dose ASA, for example, may lead to an increased risk of bleeding in this patient group with a pre-existing increased risk. NSAIDs are suboptimal due to their interaction with ASA used for ischemia prophylaxis; metamizole may lead to hypotension, and triptans, due to their vasoactive properties, are not only formally contraindicated in this context. Regarding prophylactic treatment, we find calcium channel blockers and beta blockers difficult due to hypotension and the resulting hemodynamic risks.</p><p>However, our most important addition to the Consensus Review is our stricter assessment of calcitonin gene-related peptide (CGRP) antagonists. Although the authors adopted a cautious approach to the use of CGRP-based therapies, we believe that the severity of the inherent vascular risk in MMA requires an even more definitive stance against these agents.</p><p>The available evidence, while limited, points to a potential for harm that far outweighs the therapeutic benefit in this high-risk population.</p><p>The core pathophysiology of MMA involves progressive steno-occlusive disease of the intracranial carotid arteries and the compensatory formation of fragile collateral (Moyamoya) vessels. In this delicate, flow-compromised system, maintaining adequate cerebral blood flow (CBF) and oxygen delivery is paramount [<span>1</span>].</p><p>CGRP is one of the most potent endogenous vasodilators [<span>2</span>]. Its presence is particularly vital in the setting of ischemia, where it acts as a critical compensatory mechanism to maximize blood flow and perfusion pressure [<span>3</span>]. This appears to be of the utmost relevance when considering the pathophysiology of MMA. Blocking this compensatory mechanism carries an unacceptable theoretical risk of precipitating cerebral ischemic events. By dampening the body's intrinsic ability to induce vasodilation in areas of critical flow, CGRP-related therapies could potentially shift the delicate balance, leading to hypoperfusion, transient ischemic attacks (TIAs), or stroke, particularly in patients with borderline flow dynamics.</p><p>The risk here is not just theoretical, as Mulder and colleagues were able to document very clearly and convincingly that CGRP-blocking treatment leads to more severe strokes in animal models. Even transfer from bench to bedside is not straightforward. It appears reasonable that these data ma","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932675","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}
Renan Flávio de França Nunes, Thiago Junqueira Ribeiro de Rezende, Guilherme Soares de Oliveira Wertheimer, Wilson Marques Junior, Marcondes Cavalcante França Junior
Background
Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder characterized by TTR gene mutations, causing amyloid fibril deposition in peripheral nerves. Significant CNS involvement has been noted, emphasizing the necessity for advanced neuroimaging tools for early detection of CNS damage in ATTRv.
Methods
Comprehensive clinical assessments and multimodal MRI techniques, including FreeSurfer, TBSS and microbleed analysis, were utilized. The cohorts comprised 30 symptomatic patients (ATTRv-PN), 19 presymptomatic patients (pre-ATTRv-PN), classified based on neuropathic signs, and 44 age- and sex-matched controls. For cognitive assessment, we utilized the Addenbrooke's Cognitive Examination-Revised.
Results
The ATTRv-PN group had an average age of 51 years, while the pre-ATTRv-PN group averaged 41 years, with a sex ratio of 35% men to 65% women. Symptomatic patients experienced an average disease duration of 5 years, predominantly featuring the p.Val50Met genotype (73%). Brain imaging showed diffuse subcortical white matter alterations in ATTRv-PN, while cortical thinning and microbleeds were infrequent. Cognitive assessments revealed significant differences, with symptomatic scoring lower in memory and verbal fluency than presymptomatic.
Conclusion
ATTRv-PN involves cerebral white matter microstructural damage from early stages. Multimodal MRI serves as an accurate, non-invasive tool for detecting CNS damage, improving our understanding of the disease spectrum.
{"title":"Early Detection of Central Nervous System Involvement in ATTRv Using Multimodal MRI and Cognitive Assessments","authors":"Renan Flávio de França Nunes, Thiago Junqueira Ribeiro de Rezende, Guilherme Soares de Oliveira Wertheimer, Wilson Marques Junior, Marcondes Cavalcante França Junior","doi":"10.1111/ene.70427","DOIUrl":"10.1111/ene.70427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder characterized by <i>TTR</i> gene mutations, causing amyloid fibril deposition in peripheral nerves. Significant CNS involvement has been noted, emphasizing the necessity for advanced neuroimaging tools for early detection of CNS damage in ATTRv.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Comprehensive clinical assessments and multimodal MRI techniques, including FreeSurfer, TBSS and microbleed analysis, were utilized. The cohorts comprised 30 symptomatic patients (ATTRv-PN), 19 presymptomatic patients (pre-ATTRv-PN), classified based on neuropathic signs, and 44 age- and sex-matched controls. For cognitive assessment, we utilized the Addenbrooke's Cognitive Examination-Revised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ATTRv-PN group had an average age of 51 years, while the pre-ATTRv-PN group averaged 41 years, with a sex ratio of 35% men to 65% women. Symptomatic patients experienced an average disease duration of 5 years, predominantly featuring the p.Val50Met genotype (73%). Brain imaging showed diffuse subcortical white matter alterations in ATTRv-PN, while cortical thinning and microbleeds were infrequent. Cognitive assessments revealed significant differences, with symptomatic scoring lower in memory and verbal fluency than presymptomatic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ATTRv-PN involves cerebral white matter microstructural damage from early stages. Multimodal MRI serves as an accurate, non-invasive tool for detecting CNS damage, improving our understanding of the disease spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917250","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号