Antonino Uncini, Tiziana Cavallaro, Gian Maria Fabrizi, Fiore Manganelli, Jean-Michel Vallat
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.
{"title":"Conduction slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies: Electrophysiology meets pathology","authors":"Antonino Uncini, Tiziana Cavallaro, Gian Maria Fabrizi, Fiore Manganelli, 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":null,"pages":null},"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}
Isaac R. L. Xu, Matt C. Danzi, Ariel Ruiz, Jacquelyn Raposo, Yeisha Arcia De Jesus, Mary M. Reilly, Andrea Cortese, Michael E. Shy, Steven S. Scherer, David N. Herrmann, Vera Fridman, Jonathan Baets, Mario Saporta, Reza Seyedsadjadi, Tanya Stojkovic, Kristl G. Claeys, Pooja Patel, Shawna Feely, Adriana P. Rebelo, Inherited Neuropathy Consortium, Maike F. Dohrn, Stephan Züchner
Background
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.
Methods
We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics.
Results
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.
Interpretation
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.
{"title":"A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot–Marie–Tooth neuropathy 1A","authors":"Isaac R. L. Xu, Matt C. Danzi, Ariel Ruiz, Jacquelyn Raposo, Yeisha Arcia De Jesus, Mary M. Reilly, Andrea Cortese, Michael E. Shy, Steven S. Scherer, David N. Herrmann, Vera Fridman, Jonathan Baets, Mario Saporta, Reza Seyedsadjadi, Tanya Stojkovic, Kristl G. Claeys, Pooja Patel, Shawna Feely, Adriana P. Rebelo, Inherited Neuropathy Consortium, Maike F. Dohrn, 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":null,"pages":null},"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}
Abigail L. D. Tadenev, Courtney L. Hatton, Robert W. Burgess
Background
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.
Aims
Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of Hdac6 on mice carrying a humanized knockin allele of Gars1, a model of CMT-type 2D.
Methods
Gars1ΔETAQ mice were bred to an Hdac6 knockout strain, and the resulting offspring were evaluated for clinically relevant outcomes.
Results
The genetic deletion of Hdac6 increased α-tubulin acetylation in the sciatic nerves of both wild-type and Gars1ΔETAQ mice. However, when tested at 5 weeks of age, the Gars1ΔETAQ mice lacking Hdac6 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 Gars1ΔETAQ mice with intact Hdac6.
Interpretation
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.
{"title":"Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D","authors":"Abigail L. D. Tadenev, Courtney L. Hatton, 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><sup>ΔETAQ</sup> 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><sup>ΔETAQ</sup> mice. However, when tested at 5 weeks of age, the <i>Gars1</i><sup>ΔETAQ</sup> 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><sup>ΔETAQ</sup> 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":null,"pages":null},"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}
Jeroen W. Bos, Ewout J. N. Groen, Henny G. Otten, Kevin Budding, Ruben P. A. van Eijk, Chantall Curial, Tineke Kardol-Hoefnagel, H. Stephan Goedee, Leonard H. van den Berg, W. Ludo van der Pol
Background and Aims
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.
Methods
We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.
Results
The genotype frequencies of rs28371582, a 21-bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p .009; Del/Del genotype 16.8% vs. 7.7%, p .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, p .019). The presence of CD59 rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083–1.80, p .032).
Interpretation
MMN susceptibility is associated with a 21-bp deletion in the CD55 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.
{"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, Ewout J. N. Groen, Henny G. Otten, Kevin Budding, Ruben P. A. van Eijk, Chantall Curial, Tineke Kardol-Hoefnagel, H. Stephan Goedee, Leonard H. van den Berg, 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":null,"pages":null},"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}
Jack R. Fennessy, Gabrielle A. Donlevy, Marnee J. McKay, Joshua Burns, Kayla M. D. Cornett, Manoj P. Menezes
Background and Aims
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.
Methods
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.
Results
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.
Interpretation
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.
{"title":"Development of a functional outcome measure for riboflavin transporter deficiency","authors":"Jack R. Fennessy, Gabrielle A. Donlevy, Marnee J. McKay, Joshua Burns, Kayla M. D. Cornett, Manoj P. Menezes","doi":"10.1111/jns.12619","DOIUrl":"10.1111/jns.12619","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 <","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"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, 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":null,"pages":null},"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}
Fernanda Barbosa Figueiredo, Pedro José Tomaselli, Jaime Hallak, Ana Cláudia Mattiello-Sverzut, Anna Paula Paranhos Miranda Covaleski, Cláudia Ferreira da Rosa Sobreira, Silmara de Paula Gouvêa, Wilson Marques Jr
Background and Aims
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.
Methods
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.
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.
Results
A molecular diagnosis was reached in 68% of the patients (n = 36/53), considering only pathogenic and probably pathogenic variants. Variants in MFN2 (n = 15) and GJB1 (n = 3) accounted for half of the genetically confirmed patients (50%; n = 18/36). The other 18 genetically diagnosed patients had variants in several less common genes.
Interpretation
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.
{"title":"Genetic diversity in hereditary axonal neuropathy: Analyzing 53 Brazilian children","authors":"Fernanda Barbosa Figueiredo, Pedro José Tomaselli, Jaime Hallak, Ana Cláudia Mattiello-Sverzut, Anna Paula Paranhos Miranda Covaleski, Cláudia Ferreira da Rosa Sobreira, Silmara de Paula Gouvêa, 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":null,"pages":null},"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}
Federica Rachele Danti, Emanuela Pagliano, Davide Pareyson, Maria Foscan, Alessia Marchi, Alessia Feoli, Fabio Bruschi, Giuseppe Piscosquito, Micheal E. Shy, Sindhu Ramchandren, Isabella Moroni, Tong Tong Wu
Background and Aims
The parent-proxy reports can offer complementary informations or be the only source of Quality of Life measurement in young children. The aim of this study was to provide and validate the Italian version of the recently published parent-proxy pCMT-QOL for patients aged 8–18 years old, making it available for possible trials in Italian speaking children.
Methods
The English-language instrument was translated and adapted into the Italian language using standard procedures: translation, transcultural adaptation, and back-translation. Parent-proxy pCMT-QOL was administered to parents of patients with a genetic diagnosis of CMT, aged 8–18 years old. All parents were retested 2 weeks later to assess reliability.
Results
A total of 21 parents of CMT patients (18 CMT1A, 2 CMT2A, 1 CMT2K) were assessed during their children clinical appointments. The Italian-pCMT-QOL showed a high test–retest reliability; none of the parents had any difficulties with the completion of the questionnaire and no further revisions were necessary after completion.
Interpretation
The Italian parent-proxy pCMT-QOL is a reliable, culturally adapted, and comparable version of the original English instrument. This questionnaire will improve the quality of the follow-up and will make it possible to monitor more accurately the severity of the disease in Italian-speaking families.
{"title":"Parent-proxy pediatric CMT quality of life outcome measure: Validation of the Italian version","authors":"Federica Rachele Danti, Emanuela Pagliano, Davide Pareyson, Maria Foscan, Alessia Marchi, Alessia Feoli, Fabio Bruschi, Giuseppe Piscosquito, Micheal E. Shy, Sindhu Ramchandren, Isabella Moroni, Tong Tong Wu","doi":"10.1111/jns.12615","DOIUrl":"10.1111/jns.12615","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The parent-proxy reports can offer complementary informations or be the only source of Quality of Life measurement in young children. The aim of this study was to provide and validate the Italian version of the recently published parent-proxy pCMT-QOL for patients aged 8–18 years old, making it available for possible trials in Italian speaking children.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The English-language instrument was translated and adapted into the Italian language using standard procedures: translation, transcultural adaptation, and back-translation. Parent-proxy pCMT-QOL was administered to parents of patients with a genetic diagnosis of CMT, aged 8–18 years old. All parents were retested 2 weeks later to assess reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 21 parents of CMT patients (18 CMT1A, 2 CMT2A, 1 CMT2K) were assessed during their children clinical appointments. The Italian-pCMT-QOL showed a high test–retest reliability; none of the parents had any difficulties with the completion of the questionnaire and no further revisions were necessary after completion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The Italian parent-proxy pCMT-QOL is a reliable, culturally adapted, and comparable version of the original English instrument. This questionnaire will improve the quality of the follow-up and will make it possible to monitor more accurately the severity of the disease in Italian-speaking families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12615","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702839","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}
Andreas A. Argyriou, Jordi Bruna, Foteini Kalofonou, Roser Velasco, Pantelis Litsardopoulos, Montse Alemany, Garifallia G. Anastopoulou, Haralabos P. Kalofonos
Objective
To define the incidence and risk factors for developing chemotherapy-induced neuropathic pain (CINP).
Methods
Retrospective, file-based analysis on cancer patients who received any type of conventional chemotherapy and for whom neurological evaluation was asked to reveal the extent of chemotherapy-induced peripheral neurotoxicity (CIPN) with or without CINP. CINP was assessed by means of the PI-NRS and Douleur Neuropathique-4 questionnaire. The total neuropathy score-clinical version graded the severity of CIPN.
Results
The medical files of 500 chemotherapy-treated cancer patients were reviewed. Any grade chronic CIPN was disclosed in 343 (68.6%) patients and CINP in 127 (37%) of them, corresponding to an overall percentage of 25.4% among all 500 included patients. The logistic regression analysis identified as independent predictors for CINP development the presence of uncomplicated diabetes (OR: 2.17; p = .039) and grade 2–3 chronic CIPN (OR: 1.61; p < .001) as also the administration of combined paclitaxel plus cisplatin (reference variable), compared to oxaliplatin (OR: 0.18; p = .001) and taxanes (OR: 0.16; p < .001). The increased severity of acute OXAIPN was associated with CINP (OR: 4.51; p < .001). OXA-treated patients with persistent CINP presented a worst likelihood to improve after chemotherapy discontinuation, than patients receiving combined paclitaxel plus cisplatin (OR: 50; p < .001).
Conclusion
The incidence of CINP in our cohort was comparable to previous reports, with severities fluctuating upwards during chemotherapy and declined post-chemotherapy. Uncomplicated diabetes, the combined paclitaxel plus cisplatin treatment and the increased severity of acute oxaliplatin neurotoxicity mostly increase the risk for developing CINP. OXA-treated patients present less possibilities to recover from CINP after chemotherapy discontinuation, than other chemotherapies.
{"title":"Incidence and risk factors for developing chemotherapy-induced neuropathic pain in 500 cancer patients: A file-based observational study","authors":"Andreas A. Argyriou, Jordi Bruna, Foteini Kalofonou, Roser Velasco, Pantelis Litsardopoulos, Montse Alemany, Garifallia G. Anastopoulou, Haralabos P. Kalofonos","doi":"10.1111/jns.12616","DOIUrl":"10.1111/jns.12616","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To define the incidence and risk factors for developing chemotherapy-induced neuropathic pain (CINP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective, file-based analysis on cancer patients who received any type of conventional chemotherapy and for whom neurological evaluation was asked to reveal the extent of chemotherapy-induced peripheral neurotoxicity (CIPN) with or without CINP. CINP was assessed by means of the PI-NRS and Douleur Neuropathique-4 questionnaire. The total neuropathy score-clinical version graded the severity of CIPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The medical files of 500 chemotherapy-treated cancer patients were reviewed. Any grade chronic CIPN was disclosed in 343 (68.6%) patients and CINP in 127 (37%) of them, corresponding to an overall percentage of 25.4% among all 500 included patients. The logistic regression analysis identified as independent predictors for CINP development the presence of uncomplicated diabetes (OR: 2.17; <i>p</i> = .039) and grade 2–3 chronic CIPN (OR: 1.61; <i>p</i> < .001) as also the administration of combined paclitaxel plus cisplatin (reference variable), compared to oxaliplatin (OR: 0.18; <i>p</i> = .001) and taxanes (OR: 0.16; <i>p</i> < .001). The increased severity of acute OXAIPN was associated with CINP (OR: 4.51; <i>p</i> < .001). OXA-treated patients with persistent CINP presented a worst likelihood to improve after chemotherapy discontinuation, than patients receiving combined paclitaxel plus cisplatin (OR: 50; <i>p</i> < .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The incidence of CINP in our cohort was comparable to previous reports, with severities fluctuating upwards during chemotherapy and declined post-chemotherapy. Uncomplicated diabetes, the combined paclitaxel plus cisplatin treatment and the increased severity of acute oxaliplatin neurotoxicity mostly increase the risk for developing CINP. OXA-treated patients present less possibilities to recover from CINP after chemotherapy discontinuation, than other chemotherapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707035","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}
Volkan Tasdemir, Nermin Gorkem Sirin, Arman Cakar, Ayla Culha, Aysun Soysal, Ayse Deniz Elmali, Aysegul Gunduz, Beyza Arslan, Destina Yalcin, Dilek Atakli, Elif Kocasoy Orhan, Elif Sanli, Erdem Tuzun, Eren Gozke, Esra Gursoy, Feray Karaali Savrun, Ferda Ilgen Uslu, Fikret Aysal, Hacer Durmus, Hafsa Bulbul, F. Inci Ertas, Kayihan Uluc, Kemal Tutkavul, Leyla Baysal, Mehmet Baris Baslo, Meral Kiziltan, Metin Mercan, Nevin Pazarci, Nurten Uzun, Onur Akan, Ozlem Cokar, Pinar Kahraman Koytak, Reyhan Sürmeli, Sefer Gunaydin, Selahattin Ayas, Sezin Alpaydin Baslo, Vildan Yayla, Vuslat Yilmaz, Yesim Parman, Zeliha Matur, Zeynep Unlusoy Acar, Ali Emre Oge
Background and Aims
This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul.
Methods
Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed.
Results
One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019–February 2020) and 108 during the pandemic (March 2020–March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies.
Interpretation
Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.
{"title":"Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study","authors":"Volkan Tasdemir, Nermin Gorkem Sirin, Arman Cakar, Ayla Culha, Aysun Soysal, Ayse Deniz Elmali, Aysegul Gunduz, Beyza Arslan, Destina Yalcin, Dilek Atakli, Elif Kocasoy Orhan, Elif Sanli, Erdem Tuzun, Eren Gozke, Esra Gursoy, Feray Karaali Savrun, Ferda Ilgen Uslu, Fikret Aysal, Hacer Durmus, Hafsa Bulbul, F. Inci Ertas, Kayihan Uluc, Kemal Tutkavul, Leyla Baysal, Mehmet Baris Baslo, Meral Kiziltan, Metin Mercan, Nevin Pazarci, Nurten Uzun, Onur Akan, Ozlem Cokar, Pinar Kahraman Koytak, Reyhan Sürmeli, Sefer Gunaydin, Selahattin Ayas, Sezin Alpaydin Baslo, Vildan Yayla, Vuslat Yilmaz, Yesim Parman, Zeliha Matur, Zeynep Unlusoy Acar, Ali Emre Oge","doi":"10.1111/jns.12612","DOIUrl":"10.1111/jns.12612","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019–February 2020) and 108 during the pandemic (March 2020–March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, <i>p</i> = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, <i>p</i> = 0.007), and a more severe disease as compared with those without antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642355","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}
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