Journal of the Peripheral Nervous System最新文献

{"title":"Genetic and clinical profile of 15 Chinese families with GDAP1-related Charcot–Marie–Tooth disease and identification of H256R as a frequent mutation","authors":"Zhongzheng Li,&nbsp;Sen Zeng,&nbsp;Yongzhi Xie,&nbsp;Xiaobo Li,&nbsp;Shunxiang Huang,&nbsp;Huadong Zhao,&nbsp;Wanqian Cao,&nbsp;Lei Liu,&nbsp;Mengli Wang,&nbsp;Qiaoyu Gong,&nbsp;Jun Liu,&nbsp;Pengfei Rong,&nbsp;Ruxu Zhang","doi":"10.1111/jns.12628","DOIUrl":"10.1111/jns.12628","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Mutations in ganglioside-induced differentiation-associated protein 1 (<i>GDAP1</i>) cause axonal or demyelinating Charcot–Marie–Tooth disease (CMT) with autosomal dominant or recessive inheritance. In this study, we aim to report the genotypic and phenotypic features of <i>GDAP1</i>-related CMT in a Chinese cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical, neurophysiological, genetic data, and available muscle/brain imaging information of 28 CMT patients with <i>GDAP1</i> variants were retrospectively collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 16 <i>GDAP1</i> pathogenic variants, among which two novel variants c.980dup(p.L328FfsX25) and c.480+4T&gt;G were first reported. Most patients (16/28) presented with AR or AD CMT2K phenotype. Clinical characteristics in our cohort demonstrated that the AR patients presented earlier onset, more severe phenotype compared with the AD patients. Considerable intra-familial phenotypic variability was observed among three AD families. Muscle atrophy and fatty infiltration in the lower extremity were detected by Muscle magnetic resonance imaging (MRI) scans in four patients. MRI showed two AR patients showed more severe muscle involvement of the posterior compartment than those of the anterolateral compartment in the calf. One patient carrying Q38*/H256R variants accompanied with mild periventricular leukoaraiosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, we conducted an analysis of clinical features of the <i>GDAP1</i>-related CMT patients, expanded the mutation spectrum in <i>GDAP1</i> by reporting two novel variants, and presented the prevalent occurrence of the H256R mutation in China. The screening of <i>GDAP1</i> should be particularly emphasized in Chinese patients with CMT2, given the incomplete penetrance and pathogenic inheritance patterns involving dominant and recessive modes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"232-242"},"PeriodicalIF":3.9,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856578","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":"Cutaneous biomarkers of therapeutic efficacy in early treatment of hereditary ATTR amyloid polyneuropathy with tafamidis","authors":"Karla Cárdenas-Soto,&nbsp;Xel-Ha Dominguez,&nbsp;Giovanni Cortes,&nbsp;Felix Tsai,&nbsp;Maria del Mar Saniger,&nbsp;Paola Guraieb-Chahin,&nbsp;Benjamín Torres-Ocatvo,&nbsp;Christopher Gibbons,&nbsp;Jeffery W. Kelly,&nbsp;Roy Freeman,&nbsp;Alejandra González-Duarte","doi":"10.1111/jns.12624","DOIUrl":"10.1111/jns.12624","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0-II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) −9.3 versus −4 points (&lt;i&gt;p&lt;/i&gt; = &lt;.00) in the patient's neuropathy total symptom score 6 (NTSS-6) questionnaire, (2) −2.5 versus +2.8 points (&lt;i&gt;p&lt;/i&gt; = &lt;.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus −0.6 (&lt;i&gt;p&lt;/i&gt; = .01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis-treated patients, whereas it rose across all the biopsies in the control group. At the 4-year follow-up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of −3.0 vs. −9.3 fibers/mm) and the distal leg (mean difference [MD] −4.9 vs. −8.6 fibers/mm). ADI in tafamidis-treated patients was also","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"221-231"},"PeriodicalIF":3.9,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857134","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":"Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review","authors":"Claudia Cutellè,&nbsp;Alberto De Lorenzo,&nbsp;Pietro Emiliano Doneddu,&nbsp;Maria Francesca Creta,&nbsp;Carlo Selmi,&nbsp;Giuseppe Liberatore,&nbsp;Andrea Giordano,&nbsp;Francesco Gentile,&nbsp;Gian Luca Erre,&nbsp;Eduardo Nobile-Orazio","doi":"10.1111/jns.12622","DOIUrl":"10.1111/jns.12622","url":null,"abstract":"<p>Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3–71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"124-134"},"PeriodicalIF":3.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571129","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":"Conduction slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies: Electrophysiology meets pathology","authors":"Antonino Uncini,&nbsp;Tiziana Cavallaro,&nbsp;Gian Maria Fabrizi,&nbsp;Fiore Manganelli,&nbsp;Jean-Michel Vallat","doi":"10.1111/jns.12625","DOIUrl":"10.1111/jns.12625","url":null,"abstract":"<p>Nerve conduction studies are usually the first diagnostic step in peripheral nerve disorders and their results are the basis for planning further investigations. However, there are some commonplaces in the interpretation of electrodiagnostic findings in peripheral neuropathies that, although useful in the everyday practice, may be misleading: (1) conduction block and abnormal temporal dispersion are distinctive features of acquired demyelinating disorders; (2) hereditary neuropathies are characterized by uniform slowing of conduction velocity; (3) axonal neuropathies are simply diagnosed by reduced amplitude of motor and sensory nerve action potentials with normal or slightly slow conduction velocity. In this review, we reappraise the occurrence of uniform and non-uniform conduction velocity slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies attempting, with a translational approach, a correlation between electrophysiological and pathological features as derived from sensory nerve biopsy in patients and animal models. Additionally, we provide some hints to navigate in this complex field.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"135-160"},"PeriodicalIF":3.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570706","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":"A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot–Marie–Tooth neuropathy 1A","authors":"Isaac R. L. Xu,&nbsp;Matt C. Danzi,&nbsp;Ariel Ruiz,&nbsp;Jacquelyn Raposo,&nbsp;Yeisha Arcia De Jesus,&nbsp;Mary M. Reilly,&nbsp;Andrea Cortese,&nbsp;Michael E. Shy,&nbsp;Steven S. Scherer,&nbsp;David N. Herrmann,&nbsp;Vera Fridman,&nbsp;Jonathan Baets,&nbsp;Mario Saporta,&nbsp;Reza Seyedsadjadi,&nbsp;Tanya Stojkovic,&nbsp;Kristl G. Claeys,&nbsp;Pooja Patel,&nbsp;Shawna Feely,&nbsp;Adriana P. Rebelo,&nbsp;Inherited Neuropathy Consortium,&nbsp;Maike F. Dohrn,&nbsp;Stephan Züchner","doi":"10.1111/jns.12621","DOIUrl":"10.1111/jns.12621","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN-INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age-normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost-efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"202-212"},"PeriodicalIF":3.9,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570707","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":"Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D","authors":"Abigail L. D. Tadenev,&nbsp;Courtney L. Hatton,&nbsp;Robert W. Burgess","doi":"10.1111/jns.12623","DOIUrl":"10.1111/jns.12623","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot–Marie–Tooth disease (CMT). Inhibition of HDAC6 increases the acetylation of proteins important in axonal trafficking, such as α-tubulin and Miro, and has been shown to be efficacious in several preclinical studies using mouse models of CMT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of <i>Hdac6</i> on mice carrying a humanized knockin allele of <i>Gars1</i>, a model of CMT-type 2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Gars1</i>^ΔETAQ mice were bred to an <i>Hdac6</i> knockout strain, and the resulting offspring were evaluated for clinically relevant outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The genetic deletion of <i>Hdac6</i> increased α-tubulin acetylation in the sciatic nerves of both wild-type and <i>Gars1</i>^ΔETAQ mice. However, when tested at 5 weeks of age, the <i>Gars1</i>^ΔETAQ mice lacking <i>Hdac6</i> showed no changes in body weight, muscle atrophy, grip strength or endurance, sciatic motor nerve conduction velocity, compound muscle action potential amplitude, or peripheral nerve histopathology compared to <i>Gars1</i>^ΔETAQ mice with intact <i>Hdac6</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our results differ from those of two previous studies that demonstrated the benefit of the HDAC6 inhibitor tubastatin A in mouse models of CMT2D. While we cannot fully explain the different outcomes, our results offer a counterexample to the benefit of inhibiting HDAC6 in CMT2D, suggesting additional research is necessary.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"213-220"},"PeriodicalIF":3.9,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318589","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":"A 21-bp deletion in the complement regulator CD55 promotor region is associated with multifocal motor neuropathy and its disease course","authors":"Jeroen W. Bos,&nbsp;Ewout J. N. Groen,&nbsp;Henny G. Otten,&nbsp;Kevin Budding,&nbsp;Ruben P. A. van Eijk,&nbsp;Chantall Curial,&nbsp;Tineke Kardol-Hoefnagel,&nbsp;H. Stephan Goedee,&nbsp;Leonard H. van den Berg,&nbsp;W. Ludo van der Pol","doi":"10.1111/jns.12620","DOIUrl":"10.1111/jns.12620","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of <i>CD46</i>, <i>CD55</i>, and <i>CD59</i> in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The genotype frequencies of rs28371582, a 21-bp deletion in the <i>CD55</i> promotor region, were altered in patients with MMN as compared to controls (<i>p</i> .009; Del/Del genotype 16.8% vs. 7.7%, <i>p</i> .005, odds ratio: 2.43 [1.27–4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040–0.490, <i>p</i> .019). The presence of <i>CD59</i> rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, <i>p</i> .032).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>MMN susceptibility is associated with a 21-bp deletion in the <i>CD55</i> promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"193-201"},"PeriodicalIF":3.9,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288438","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":"Development of a functional outcome measure for riboflavin transporter deficiency","authors":"Jack R. Fennessy,&nbsp;Gabrielle A. Donlevy,&nbsp;Marnee J. McKay,&nbsp;Joshua Burns,&nbsp;Kayla M. D. Cornett,&nbsp;Manoj P. Menezes","doi":"10.1111/jns.12619","DOIUrl":"10.1111/jns.12619","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease-modifying therapies including genetic therapies. The Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS) is a well-validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children's Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. ‘Shoulder internal rotation’ and the ‘30-s sit to stand test’ were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single ‘Feet apart on a line eyes open’ balance item. ‘Pinprick sensation’ was removed due to a floor effect.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Interpretation&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 &lt;","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 2","pages":"185-192"},"PeriodicalIF":3.9,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039702","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":"Laura Feltri: In memoriam","authors":"Stefano C. Previtali,&nbsp;Carla Taveggia","doi":"10.1111/jns.12618","DOIUrl":"10.1111/jns.12618","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 1","pages":"4-5"},"PeriodicalIF":3.8,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972390","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":"Genetic diversity in hereditary axonal neuropathy: Analyzing 53 Brazilian children","authors":"Fernanda Barbosa Figueiredo,&nbsp;Pedro José Tomaselli,&nbsp;Jaime Hallak,&nbsp;Ana Cláudia Mattiello-Sverzut,&nbsp;Anna Paula Paranhos Miranda Covaleski,&nbsp;Cláudia Ferreira da Rosa Sobreira,&nbsp;Silmara de Paula Gouvêa,&nbsp;Wilson Marques Jr","doi":"10.1111/jns.12617","DOIUrl":"10.1111/jns.12617","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The genetic epidemiology of inherited neuropathies in children remains largely unknown. In this study, we specifically investigated the genetic profile of a Brazilian cohort of pediatric patients with pure or complex axonal neuropathies, a crucial knowledge in the near future for establishing treatment priorities and perspectives for this group of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-three pediatric patients who were assessed prior to reaching the age of 20, and who had clinical diagnoses of axonal hereditary neuropathy or presented with axonal neuropathy as the primary clinical feature, were included in the study. The recruitment of these cases took place from January 1, 2018, to December 31, 2020.</p>\u0000 \u0000 <p>The diagnosis was based on clinical and electrophysiological data. A molecular assessment was made using target-gene panel or whole-exome sequencing. Subsequently, segregation analysis was performed on available family members, and all candidate variants found were confirmed through Sanger.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A molecular diagnosis was reached in 68% of the patients (<i>n</i> = 36/53), considering only pathogenic and probably pathogenic variants. Variants in MFN2 (<i>n</i> = 15) and GJB1 (<i>n</i> = 3) accounted for half of the genetically confirmed patients (50%; <i>n</i> = 18/36). The other 18 genetically diagnosed patients had variants in several less common genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Apart from MFN2 and GJB1 genes, universally recognized as a frequent cause of axonal neuropathies in most studied population, our Brazilian cohort of children with axonal neuropathies showed an important genetic heterogeneity, probably reflecting the multi ethnicity of the Brazilian population. Diagnostic, counseling, and future interventions should consider this characteristic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 1","pages":"97-106"},"PeriodicalIF":3.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905865","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}