Journal of the Peripheral Nervous System最新文献

{"title":"Insight in the Unmet Needs Encountered During the Management of Chronic Inflammatory Demyelinating Polyradiculoneuropathy","authors":"Jeffrey A. Allen,&nbsp;Helmar C. Lehmann,&nbsp;Eduardo Nobile-Orazio,&nbsp;Luis Querol,&nbsp;Yusuf A. Rajabally","doi":"10.1111/jns.70067","DOIUrl":"10.1111/jns.70067","url":null,"abstract":"<p>Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare acquired immune-mediated disorder affecting peripheral nerves, manifesting most commonly as symmetric, proximal, and distal weakness with sensory loss. Although the 2021 European Academy of Neurology/Peripheral Nerve Society guidelines provide evidence-based and consensus-driven approaches to the diagnosis and treatment of CIDP, challenges to optimal patient care persist. This report aims to highlight the unmet needs in CIDP management. A structured analysis of existing evidence was conducted to map gaps in CIDP care pathways, emphasizing diagnostic criteria, assessment of the therapeutic response, and disease management. Recognized key gaps and unmet needs in CIDP include (1) the absence of specific biomarkers for CIDP, (2) weighing the relative value of various CIDP metrics and interpreting what those metrics say about disease activity and treatment response, and (3) understanding the optimal timing and approach to assess treatment efficacy (or failure). There exists variability in how diagnostic and treatment guidelines are utilized, as well as how (and if) outcome metrics are utilized to guide informed treatment decisions. At least part of the confusion stems from the absence of terms commonly used during the CIDP treatment journey, including “response,” “refractory,” “remission,” and “relapse.” To address these ambiguities, a consensus-driven effort is needed to establish standardized definitions for key treatment milestones in CIDP. Harmonizing terminology will not only facilitate more accurate clinical assessments but also promote more robust and comparable research outcomes, ultimately improving the care of individuals with CIDP. This report underscores the critical unmet needs in CIDP diagnosis and management. By identifying barriers and facilitators within the current CIDP landscape, we hope to optimize clinical decision-making and focus research efforts.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Easy Handgrip Test as a Tool for Assessing Motor Fatigability in Children With Charcot-Marie-Tooth Disease Type 1A","authors":"Ester da Silva Estevam,&nbsp;Emanuela Juvenal Martins,&nbsp;Camila Scarpino Barboza Franco,&nbsp;Karoliny Lisandra Teixeira Cruz,&nbsp;Tenysson Will de Lemos,&nbsp;Pedro José Tomaselli,&nbsp;Wilson Marques Junior,&nbsp;Ana Claudia Mattiello-Sverzut","doi":"10.1111/jns.70061","DOIUrl":"10.1111/jns.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Charcot-Marie-Tooth (CMT), the most common inherited neuromuscular disorder, causes progressive, symmetrical muscle weakness, often affecting distal extremities. Motor fatigability, characterized by a decline in maximal muscle force, is common in neuromuscular disorders but remains underexplored in children with CMT. This study aimed to evaluate the feasibility of a motor fatigability test using a bulb dynamometer in children and adolescents with CMT1A, assess test–retest reliability, and compare handgrip pressure, electromyographic parameters, perceived effort, and time to exhaustion between CMT1A and typically developing peers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational cross-sectional study included 107 children (aged 8–16 years; 19 with CMT1A and 88 typically developing). Participants performed a handgrip motor fatigability test using a bulb dynamometer, involving repetitive maximum voluntary isometric contractions (MVICs) at one-second intervals until exhaustion, with simultaneous electromyographic monitoring. Test–retest reliability was assessed using Bland–Altman plots and the Intraclass Correlation Coefficient (ICC). For comparisons between groups and test phases, ANCOVA and linear mixed-effects models were adjusted for sex, age, height, and weight.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A hundred and four children completed the test. The protocol was feasible, with both groups reaching significant exhaustion in 4 min and showing a significant decline in handgrip pressure (<i>p</i> &lt; 0.05). The decline in median power frequency observed during the fatigue test indicated reduced neural activation in both groups. The ICC was 0.824, indicating good test–retest reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The protocol shows promise for monitoring disease progression and treatment effects in children with CMT1A, and may serve as a functional marker. Future studies should include other CMT types.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Predictors of Idiopathic Small-Fiber Neuropathy in Adolescent Patients With Chronic Pain","authors":"William S. Frye,&nbsp;Sydney R. Ward,&nbsp;Anh Thy H. Nguyen,&nbsp;Giovanni Cucchiaro,&nbsp;Dennis A. Hart","doi":"10.1111/jns.70066","DOIUrl":"https://doi.org/10.1111/jns.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Small-fiber neuropathy (SFN) affects thinly myelinated and unmyelinated nerve fibers and often presents with pain. While this condition is observed in pediatric chronic pain settings, it is unclear which patients are most appropriate for SFN testing, particularly for idiopathic cases. Skin biopsy is the most accurate diagnostic tool, but guidelines for its use are lacking. This study aimed to identify clinical and laboratory variables predictive of a positive skin biopsy for SFN in adolescents with chronic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study analyzed clinical, demographic, and laboratory characteristics of 104 adolescents with chronic pain who had undergone PGP9.5-immunolabeled distal-leg skin biopsy to assess for SFN. Fisher's exact tests, ANOVA, and logistic regression were used to identify predictive factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient mean age was 15 years old and 51.9% had positive diagnostic skin biopsies. Results indicated adolescents with positive biopsies were more likely to have Juvenile Idiopathic Arthritis (JIA) compared to those without (33.3% vs. 14.3%, <i>p</i> = 0.02) and had higher median angiotensin-converting enzyme (ACE) levels (<i>p</i> &lt; 0.01) and thyroid free T4 levels (<i>p</i> = 0.02). Logistic regression only showed increased odds of positive skin biopsies with JIA (OR = 3.27, <i>p</i> = 0.02). No clinical symptoms were predictive of positive skin biopsies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Findings suggest that common clinical observations and laboratory tests used to guide referrals for skin biopsies were not predictive of SFN diagnosis. Clinicians should consider the risks and benefits of skin biopsies for adolescents with chronic pain. Additional research is warranted to validate potentially predictive markers and improve diagnostic pathways for SFN in pediatric chronic pain settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Neurofilament Light Chain Level as an Indicator of Axonal Injury in Parsonage–Turner Syndrome (Neuralgic Amyotrophy)","authors":"Sophie C. Queler,&nbsp;Ek Tsoon Tan,&nbsp;Ari Green,&nbsp;Carlo Milani,&nbsp;Ahmed Abdelhak,&nbsp;Darryl B. Sneag","doi":"10.1111/jns.70063","DOIUrl":"10.1111/jns.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Parsonage–Turner syndrome (PTS), also known as neuralgic amyotrophy, is a peripheral neuropathy resulting in severe axonal loss. This study aimed to characterize initial elevation and longitudinal trends of serum neurofilament light chain (sNfL), a marker of neuro-axonal damage, in PTS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective cohort included 29 adults with electromyography (EMG)–confirmed PTS ≤ 6 months from symptom onset. Patients underwent sNfL testing and EMG at baseline (median 86 days from symptom onset) and again at 3- and 6-month follow-up intervals. Age- and BMI-adjusted <i>Z</i>-scores were analyzed. Linear mixed-effects models assessed associations between sNfL and time from onset, number of nerves involved, EMG metrics, and corticosteroid use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean sNfL <i>Z</i>-scores were significantly elevated (1.64, SD 1.32, <i>p</i> &lt; 0.001) compared with healthy controls at 0 (1.64, <i>p</i> &lt; 0.001) and 3 months (0.49, SD 1.06, <i>p</i> = 0.020). At 6 months, statistically significant elevations were not detected (0.39, SD 0.96, <i>p</i> = 0.106). sNfL declined by 0.17 <i>Z</i>-scores per month (95% CI: 0.11–0.23; <i>p</i> &lt; 0.001). On EMG, the presence of nascent motor units, reflecting reinnervation, was associated with lower sNfL (<i>p</i> = 0.043).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>sNfL elevation was detected in PTS patients within the first 6 months from symptom onset and decreased as reinnervation ensued. These findings suggest sNfL deserves further consideration as a blood-based biomarker for detection and monitoring of PTS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology, Presentation, Management and Outcomes in Chronic Inflammatory Demyelinating Polyneuropathy in Birmingham, UK: The Impact of Ethnicity","authors":"Zeinab Rajabally,&nbsp;Lydia Spencer,&nbsp;Niraj Mistry,&nbsp;Yusuf A. Rajabally","doi":"10.1111/jns.70065","DOIUrl":"10.1111/jns.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Whether ethnicity impacts on epidemiology, presentation, management, and outcome is unknown in chronic inflammatory demyelinating polyneuropathy (CIDP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the prevalence/incidence of CIDP in Asian (Indian/Pakistani/Bangladeshi) and white subjects in Birmingham, UK, and associations of ethnicity with demographics/deprivation/phenotype/treatment and outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>On 10th July 2025, CIDP prevalence was 6.18 per 100 000 (95% CI: 4.66–8.05). Prevalence was lower in Asian (Indian/Pakistani/Bangladeshi) compared to white subjects (2.64 per 100 000 vs. 10.15 per 100 000; RR: 0.260, 95% CI: 0.111–0.609; <i>p</i> &lt; 0.001). Prevalence in ≥ 50-year-olds was lower in Asian (Indian/Pakistani/Bangladeshi) compared to white subjects (8.00 per 100 000 vs. 46.68 per 100 000; RR: 0.172; 95% CI: 0.061–0.479; <i>p</i> &lt; 0.001) but similar in 18–49-year-olds (2.48 per 100 000 vs. 1.83 per 100 000; RR: 1.355, 95% CI: 0.273–6.712; <i>p</i> = 0.661). Mean incidence of CIDP was 0.54 per 100 000 per year (95% CI: 0.404–0.713). CIDP incidence was lower in Asian (Indian/Pakistani/Bangladeshi) than in white subjects (0.24 per 100 000 per year vs. 0.86 per 100 000 per year, RR: 0.278; 95% CI: 0.118–0.654; <i>p</i> = 0.002). Asian (Indian/Pakistani/Bangladeshi) ethnicity was independently associated with younger age (<i>p</i> = 0.037), greater social deprivation (<i>p</i> = 0.045), and noncompliance to treatment (<i>p</i> = 0.016). No association of Asian (Indian/Pakistani/Bangladeshi) ethnicity was found with CIDP sub-type, diagnostic delay, pretreatment disability, access to high-cost therapies, or posttreatment outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Subjects of Asian (Indian/Pakistani/Bangladeshi) ethnicity in the UK may have a lower risk of CIDP after 50 years of age, but an equivalent risk between 18 and 49 years, compared to white subjects. They may present younger, be more socially deprived, and be more likely noncompliant to treatment, compared to white subjects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rasch-Built Overall Disability Scale for IgM-Associated Polyneuropathy With and Without Anti-MAG Antibodies: IgM-RODS","authors":"Tatiana Hamadeh,&nbsp;Johannes P. M. van de Mortel,&nbsp;Janneke G. J. Hoeijmakers,&nbsp;David R. Cornblath,&nbsp;Alexander F. J. E. Vrancken,&nbsp;Catharina G. Faber,&nbsp;Nicolette C. Notermans,&nbsp;Perry T. C. van Doormaal,&nbsp;Ingemar S. J. Merkies,&nbsp;the IMAGiNe Consortium","doi":"10.1111/jns.70059","DOIUrl":"10.1111/jns.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>IgM monoclonal gammopathy-associated polyneuropathy with(out) anti-myelin associated glycoprotein (±anti-MAG) is a rare immune-mediated disease that may cause severe limitations in daily activities and quality of life. The absence of a systematic comparison between patients with/without anti-MAG IgM polyneuropathy, no disease-specific functional metric, and lack of international consensus regarding assessment and treatment of these patients are factors obstructing future clinical trials. Therefore, it was decided to develop an interval Rasch-built activity/participation scale specifically for IgM polyneuropathy ±anti-MAG (IgM-RODS) and examine its clinimetric properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pre-phase IgM-RODS questionnaire containing 146 activity/participation items, based on the WHO International Classification of Functioning, Disability and Health, was completed by participants (≥ 18 years) of the IMAGiNe observational registry that fulfilled international criteria for IgM-polyneuropathy ±anti-MAG. Data was subjected to Rasch analyses, and reliability/validity studies were performed as well.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pre-RODS data of 259 subjects (originating from 8 different countries) underwent quality assessment, and 244 remaining records were submitted to the Rasch model, evidencing the model's expectations. Based on requirements like exceeding fit residuals, misfit statistics, item bias, local dependency, and less face validity, we systematically removed items until the final 36-item IgM-RODS fulfilled all Rasch requirements and showed acceptable test–retest reliability, cross-cultural, construct and discriminant validity, and unidimensionality. Compared to the Inflammatory-RODS, the IgM-RODS showed lower standard errors across the metric, indicating greater sensitivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The 36-item IgM-RODS is a disease-specific interval measure suitable for detecting functional deficits in patients with IgM-polyneuropathy ±anti-MAG. Future studies are needed to determine its responsiveness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing and Implementing a Web-Based Platform for Accurate and Reliable Clinical Outcome Measures and Global Certification for Evaluating Charcot–Marie–Tooth disease","authors":"Kayla M. D. Cornett,&nbsp;Tim Estilow,&nbsp;Paula Bray,&nbsp;Melissa R. Mandarakas,&nbsp;Gabrielle A. Donlevy,&nbsp;Jennifer N. Baldwin,&nbsp;Kate Eichinger,&nbsp;Richard S. Finkel,&nbsp;Joshua Burns,&nbsp;Marnee J. McKay","doi":"10.1111/jns.70062","DOIUrl":"10.1111/jns.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Accurate, reliable and sensitive clinical outcome measures in rare neurologic conditions, such as Charcot–Marie–Tooth disease (CMT), are essential for monitoring disease progression and evaluating treatment efficacy. Ensuring measures such as the CMTPedS, CMTInfS and CMT-FOM are easily accessible removes a barrier to implementation. The aims of this project were to: (1) design a web-based platform to enable real-time scoring of CMT outcome measures; (2) implement co-designed training and quality assurance resources; and (3) establish a Global Certification Standard for clinical evaluators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A consultation process informed the design of the web-based platform and included a process evaluation of current users (<i>n</i> = 65). Training resources were co-designed with key stakeholders (<i>n</i> = 51) including CMT physicians and scientists, clinical evaluators, pharmaceutical representatives, and patients through a mixed-methods approach. A Global Certification Standard was developed through the co-design process and Master Trainer expertise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A web-based platform, www.ClinicalOutcomeMeasures.org was designed and implemented in June 2020 as a freely available trial readiness resource for clinicians and researchers. The platform now has &gt; 1400 registered users from &gt; 45 countries. Clinical evaluators identified a lack of accessible training resources as the top barrier to accurate and reliable administration of CMT outcome measures. Video demonstrations, online workshops, and labelled photographs were ranked as the top training methods. Five guiding principles for the Global Certification Standard for CMT outcome measures were established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The web-based platform provides real-time scoring of CMT outcome measures, access to standardized training, and a Global Certification Standard to support accurate and reliable assessment of disease severity, progression, and treatment efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor Neuropathy in a Patient With Mitochondrial Disease and a Novel TTC19 Variant: An Underrecognized Phenotypic Feature","authors":"Daniele Mandia,&nbsp;Charline Benoit,&nbsp;Tanya Stojkovic,&nbsp;Yann Nadjar","doi":"10.1111/jns.70060","DOIUrl":"https://doi.org/10.1111/jns.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>TTC19 encodes a mitochondrial protein involved in the assembly of complex III of the respiratory chain. Biallelic pathogenic variants cause a rare mitochondrial disorder typically associated with cerebellar ataxia, neuropsychiatric symptoms, and characteristic brain MRI findings within the Leigh syndrome spectrum. Peripheral motor involvement has been described in a minority of cases but has rarely been documented with detailed neurophysiological data. We report a novel TTC19 variant in a patient presenting with a distinctive combination of central and peripheral motor involvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>A male patient of Malian origin presented with cerebellar ataxia and attention deficits from early childhood. During adolescence, he developed additional features including dysarthria, dysphagia, dysexecutive syndrome, and signs of peripheral motor neuropathy. Brain MRI revealed T2-FLAIR hyperintensities in the basal ganglia and brainstem. Genetic testing identified a novel homozygous nonsense variant in TTC19 (c.235G&gt;T, p.(Gly79*)). At age 19, he experienced two acute deteriorations associated with respiratory infections, leading to severe tetraparesis and diaphragmatic weakness. Neurophysiological studies confirmed a diffuse, axonal, pure distal motor neuropathy. Follow-up imaging showed progression and cavitation of brainstem lesions. The patient died from respiratory failure at age 20.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This case, featuring a novel TTC19 variant and detailed electrophysiological data, further supports the presence of pure motor neuropathy within the phenotypic spectrum of TTC19-related disease. The co-occurrence of Leigh syndrome MRI findings and motor neuropathy represents a specific diagnostic clue that may help prioritize genetic testing in patients with overlapping central and peripheral motor involvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyneuropathy in Kidney Transplant Recipients: Accuracy of a New Clinical Diagnostic Scoring System","authors":"Svea Nolte,&nbsp;Naser B. N. Shehab,&nbsp;Stefan P. Berger,&nbsp;Celina Oldag,&nbsp;Ilja M. Nolte,&nbsp;Bianca T. A. de Greef,&nbsp;Fiete Lange,&nbsp;Marco van Londen,&nbsp;Catharina G. Faber,&nbsp;Stephan J. L. Bakker,&nbsp;Pieter A. van Doorn,&nbsp;Harmen R. Moes,&nbsp;Gea Drost","doi":"10.1111/jns.70058","DOIUrl":"https://doi.org/10.1111/jns.70058","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Polyneuropathy is highly prevalent among kidney transplant recipients (KTR), underscoring the need for an accurate yet easy-to-perform diagnostic method to improve understanding and enable early identification of treatable cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included KTR at least 12 months post-transplant at the University Medical Centre Groningen, the Netherlands. An expert panel assessed polyneuropathy through a structured neurological examination, quantitative sensory testing, and nerve conduction studies. The modified Toronto Clinical Neuropathy Score (mTCNS) was obtained from all participants. Logistic regression analyses with Firth penalization validated the mTCNS components. A new model, the Kidney Transplant Neuropathy Score (KTNS), was developed through stepwise elimination. Diagnostic performance was evaluated with bootstrapped metrics and ROC curve analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 160 KTR, 91 (57%) were diagnosed with polyneuropathy. All 10 mTCNS components were univariably associated with polyneuropathy; numbness (OR = 4.9 [1.8–18.0]), tingling (OR = 2.5 [1.2–5.9]), impaired nociception (OR = 1.5 [1.1–2.2]), and reduced vibration perception (OR = 1.5 [1.0–2.4]) remained independently associated in multivariable analysis. The mTCNS achieved an area under the curve (AUC) in ROC analysis of 0.83 [0.76–0.89]. Two KTNS were derived: the KTNS_Basic, including history of numbness, tingling in the feet, and pinprick and vibration perception testing (AUC–ROC: 0.85 [0.79–0.90]); and the KTNS_Advanced, replacing vibration perception with Achilles and patellar deep tendon reflex testing (AUC–ROC: 0.90 [0.85–0.94]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The mTCNS is a valid diagnostic tool for polyneuropathy in KTR. The KTNS offers a simplified alternative based on key symptoms and sensory tests, with reflex testing included in the KTNS_Advanced for settings with neurological expertise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT04664426</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Case of Nerve Biopsy Proven Wild Type Transthyretin (TTR) Amyloidosis","authors":"Catherine M. Daley,&nbsp;Michael P. Skolka,&nbsp;JaNean K. Engelstad,&nbsp;Karen L. Rech,&nbsp;P. James B. Dyck","doi":"10.1111/jns.70056","DOIUrl":"https://doi.org/10.1111/jns.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To report a novel case of biopsy-proven, mass spectrometry-confirmed, wild-type transthyretin amyloidosis (ATTRwt) in nerve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The patient was identified and evaluated in the peripheral nerve clinic. Our nerve laboratory's pathology database and the literature were searched for prior evidence of pathologically confirmed cases of ATTRwt.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 94-year-old man with a history of lumbar spinal stenosis presented to the neurology clinic with subacute-on-chronic progressive, upper limb predominant weakness along with numbness and tingling paresthesia. Electromyography (EMG) revealed multiple mononeuropathies involving the right median nerve at the wrist, right ulnar nerve, and right distal radial nerve superimposed upon an axonal predominant peripheral neuropathy along with multilevel lumbosacral radiculopathies. Extensive serology for causes of neuropathy and multiple mononeuropathies returned unremarkable. A diagnostic right superficial radial nerve biopsy was performed and showed congophilic material within a small epineurial vessel wall in the nerve tissue. Amyloid typing by mass spectrometry was performed and revealed ATTRwt. TTR gene sequencing returned normal. The patient was diagnosed with ATTRwt neuropathy and started on diflunisal therapy for neuropathy treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case confirms the presence of ATTRwt deposition directly in nerve tissue as the likely cause of the patient's large fiber and multiple mononeuropathies, expanding our current understanding of ATTRwt-associated disease. Proving the direct association of ATTRwt and neuropathy may open up amyloid-specific treatments for this disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}