[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-440555-105":59,"doc-detail-440555-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","reply-to-the-comment-by-zhang-et-al-letter-to-the-editor","Reply to the Comment by Zhang et al - Letter to the Editor","","Reply letter from Bogdan Bjelica addressing comments by Zhang et al. on a multicenter observational study in adults with 5q-spinal muscular atrophy treated with nusinersen. The response agrees that population-level stability can conceal inter-individual heterogeneity, explains why CMAP amplitude may be less sensitive due to reinnervation, reports no significant between-type differences and no robust correlations after multiple-comparison correction, and invites review of missing references.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/reply-to-the-comment-by-zhang-et-al-letter-to-the-editor/440555/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/reply-to-the-comment-by-zhang-et-al-letter-to-the-editor/440555.png","ImageObject",300,407,{"name":92,"@type":93},"hdkawk","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why does the author question CMAP amplitude as a sensitive biomarker of nusinersen treatment response in adult SMA?","Question",{"text":112,"@type":113},"The author argues that surviving motor units can expand territories to reinnervate muscle fibers, restoring CMAP response toward near-normal levels, which reduces sensitivity to treatment effects. The author also notes cases where motor function improved despite worsening CMAP amplitudes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the letter address the concern that population-level stability may mask heterogeneity?",{"text":117,"@type":113},"The author agrees that population-level analyses can obscure meaningful inter-individual variability and supports this by using linear mixed-effects models with random intercepts and slopes. This approach models variability in baseline CMAP values and individual longitudinal trajectories.",{"name":119,"@type":110,"acceptedAnswer":120},"Did the study find differences in CMAP trajectories between SMA type 2 and type 3 patients or correlations with motor outcomes?",{"text":121,"@type":113},"The letter reports no significant differences in CMAP trajectories between SMA type 2 and type 3. Correlations between changes in motor scores (HFMSE and RULM) and changes in CMAP amplitude were not significant after correction for multiple comparisons, though an unadjusted positive correlation with RULM at month 10 was observed.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},440555,1790825941,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},3985747859855,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","European Journal of Neurology  \nLETTER TO THE EDITOR  OPEN ACCESS   \nReply to the Comment by Zhang et al  \nBogdan Bjelica1,2   \n1Department of Neurology, Hannover Medical School, Hannover, Germany | 2PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Development, Hannover Medical School, Hannover, Germany  \nCorrespondence: Bogdan Bjelica ([bjelica.bogdan@mh-hannover.de](bjelica.bogdan@mh-hannover.de))  \nReceived: 18 December 2025 | Revised: 18 December 2025 | Accepted: 24 December 2025  \nDear Editor,  \nWe read with great interest the comment by Zhang et al. on our recently published paper entitled “Compound Muscle Action Potential (CMAP) Amplitude Trajectories and Patterns in Adults with 5q-Spinal Muscular Atrophy Receiving Nusinersen Therapy: A Multicenter, Binational Observational Study.” In that paper, we concluded that although CMAP amplitude correlates with disease severity, it may not serve as a sensitive biomarker of treatment response in adult SMA patients, as CMAP amplitudes remained largely stable during nusinersen treatment and no differences in trajectories between SMA subgroups were observed.  \nZhang et al. commented that the observed population-level stability could potentially mask important heterogeneity in treatment response. We fully agree with this observation and thank the authors for highlighting this important aspect. Indeed, in the first paragraph of the Discussion section of our paper, we described a non-significant trend toward an increase in median and peroneal nerve CMAP amplitudes up to month 18, which may have paralleled observed clinical improvements [1] . However, our data do not support using CMAP amplitude alone for clinical decision-making regarding nusinersen efficacy in adults with SMA, and we therefore recommend relying on validated motor outcome measures. As discussed in the Discussion section of our paper, “in the context of slowly progressive denervation, such as in SMA, surviving motor units can expand their territories to reinnervate muscle fibers that have lost synaptic input. This reinnervation may adequately restore the CMAP response to near-normal levels, rendering CMAP a less sensitive measure.” In our dataset, some patients demonstrated motor function improvement despite worsening CMAP amplitudes (data not shown), suggesting that factors beyond CMAP amplitude contribute to functional outcomes. Nevertheless, we fully agree with Zhang et al. that population-level stability may  \nmask meaningful inter-individual variability, and we encourage further investigation of this issue in larger multicenter studies. Importantly, the linear mixed-effects models used in our study were specifically chosen to account for inter-individual heterogeneity by allowing for random intercepts and slopes. This approach explicitly models variability in baseline CMAP values as well as individual longitudinal trajectories [2], thereby at least at some point, addressing the concern that population-level analyses may obscure clinically relevant individual or subgroupspecific treatment responses.  \nZhang et al. also suggested that exploring whether early CMAP trends correlate with baseline characteristics or long-term functional outcomes might provide additional insights into treatment dynamics. In our study, we examined whether CMAP trajectories differed between SMA type 2 and type 3 patients and found no significant differences. We also assessed correlations between changes in motor scores (HFMSE and RULM throughout the treatment period) and changes in CMAP amplitude, but no significant associations remained after correction for multiple comparisons. To control for type I error, we applied Bonferroni correction, a highly conservative approach. Notably, in unadjusted analyses, we observed a positive correlation between change in RULM and median nerve CMAP at month 10  \n(ρ = 0.38; p = 0.016), consistent with the aforementioned early trend (data available in Table S4 of our paper [1]) .  \nLa","cbCairRl5rATrgLJ","https://ap.wps.com/l/cbCairRl5rATrgLJ","pdf",126409,"English","# Reply to the Comment by Zhang et al\n## Main points on CMAP amplitude as a biomarker\n## Analysis of treatment heterogeneity and correlations\n## Request to review missing references\n## Author contributions and disclosures","[{\"question\":\"Why does the author question CMAP amplitude as a sensitive biomarker of nusinersen treatment response in adult SMA?\",\"answer\":\"The author argues that surviving motor units can expand territories to reinnervate muscle fibers, restoring CMAP response toward near-normal levels, which reduces sensitivity to treatment effects. The author also notes cases where motor function improved despite worsening CMAP amplitudes.\"},{\"question\":\"How does the letter address the concern that population-level stability may mask heterogeneity?\",\"answer\":\"The author agrees that population-level analyses can obscure meaningful inter-individual variability and supports this by using linear mixed-effects models with random intercepts and slopes. This approach models variability in baseline CMAP values and individual longitudinal trajectories.\"},{\"question\":\"Did the study find differences in CMAP trajectories between SMA type 2 and type 3 patients or correlations with motor outcomes?\",\"answer\":\"The letter reports no significant differences in CMAP trajectories between SMA type 2 and type 3. Correlations between changes in motor scores (HFMSE and RULM) and changes in CMAP amplitude were not significant after correction for multiple comparisons, though an unadjusted positive correlation with RULM at month 10 was observed.\"}]","Reply to the Comment by Zhang et al - Letter to the Editor | PDF",1790692508]