Pub Date : 2024-11-05DOI: 10.1016/j.nmd.2024.105239
Omar Ketranji, Issa Alawneh, Asmaa Alenizi, Elisa Nigro, Michal S Zimmer, Freddy Paiz, Hernan Gonorazky
Neuromyotonia, also known as Isaac syndrome, is a rare neurological disorder characterized by continuous muscle activity, stiffness, and spontaneous muscle contractions, it is very rare in children. We report a 16-year-old female patient with neuromyotonia. She presented with pain, stiffness, autonomic symptoms and muscle myokymia in both lower limbs. The patient was treated with a short course of methylprednisolone, IVIG over the course of 4 weeks, and symptomatic management which resulted in a dramatic improvement and relief of symptoms. A literature review for pediatric patients with neuromyotonia was conducted revealing 10 reported cases so far. All pediatric patients with neuromyotonia showed favorable prognosis despite using different treatment modalities. Although the association between neuromyotonia and malignancy is known in adult population, this has not been seen in the reported pediatric cases. Indeed, given the scarcity of data, we still do recommend screening for malignancy in pediatric patients with neuromyotonia.
{"title":"Neuromyotonia in a 16-year-old female with dramatic improvement after IVIG therapy: Case report and literature review.","authors":"Omar Ketranji, Issa Alawneh, Asmaa Alenizi, Elisa Nigro, Michal S Zimmer, Freddy Paiz, Hernan Gonorazky","doi":"10.1016/j.nmd.2024.105239","DOIUrl":"https://doi.org/10.1016/j.nmd.2024.105239","url":null,"abstract":"<p><p>Neuromyotonia, also known as Isaac syndrome, is a rare neurological disorder characterized by continuous muscle activity, stiffness, and spontaneous muscle contractions, it is very rare in children. We report a 16-year-old female patient with neuromyotonia. She presented with pain, stiffness, autonomic symptoms and muscle myokymia in both lower limbs. The patient was treated with a short course of methylprednisolone, IVIG over the course of 4 weeks, and symptomatic management which resulted in a dramatic improvement and relief of symptoms. A literature review for pediatric patients with neuromyotonia was conducted revealing 10 reported cases so far. All pediatric patients with neuromyotonia showed favorable prognosis despite using different treatment modalities. Although the association between neuromyotonia and malignancy is known in adult population, this has not been seen in the reported pediatric cases. Indeed, given the scarcity of data, we still do recommend screening for malignancy in pediatric patients with neuromyotonia.</p>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"46 ","pages":"105239"},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.nmd.2024.105238
Sam Geuens , Jeroen Van Dessel , Hermien E. Kan , Rosanne Govaarts , Erik H. Niks , Nathalie Goemans , Jurgen Lemiere , Nathalie Doorenweerd , Liesbeth De Waele
This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes. The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (n = 40; 9–18 years) and age-matched controls (n = 40). Comparisons were made between DMD vs. controls, daily vs. intermittent corticosteroid treatment (n = 20 each), and Dp140+ vs. Dp140- gene mutations (n = 15 vs. 25). MANCOVA, CAT12 3D statistics and Pearson correlations were conducted. DMD patients showed differences in volumes of distinct subcortical structures, left hemisphere cortical thickness, and gyrification in multiple brain areas compared with healthy controls. The daily treated DMD group exhibited differences in subcortical volumes and different patterns of cortical thickness, sulci depth, and gyrification compared to the intermittent treated DMD group. DMD Dp140+ patients displayed altered gyrification and sulci depth compared to DMD Dp140- patients. Finally, we found correlations between neurobehavioral outcomes and brain areas that showed differences in cortical morphology associated with corticosteroid treatment. Both genotype and corticosteroid treatment are associated with variations in subcortical volumes and cortical morphology, albeit in different ways. Corticosteroid treatment appears to have a more profound association with differences in gray matter characteristics of brain regions that are associated with functional outcomes.
{"title":"Genotype and corticosteroid treatment are distinctively associated with gray matter characteristics in patients with Duchenne muscular dystrophy","authors":"Sam Geuens , Jeroen Van Dessel , Hermien E. Kan , Rosanne Govaarts , Erik H. Niks , Nathalie Goemans , Jurgen Lemiere , Nathalie Doorenweerd , Liesbeth De Waele","doi":"10.1016/j.nmd.2024.105238","DOIUrl":"10.1016/j.nmd.2024.105238","url":null,"abstract":"<div><div>This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes. The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (<em>n</em> = 40; 9–18 years) and age-matched controls (<em>n</em> = 40). Comparisons were made between DMD vs. controls, daily vs. intermittent corticosteroid treatment (<em>n</em> = 20 each), and Dp140<sup>+</sup> vs. Dp140<sup>-</sup> gene mutations (<em>n</em> = 15 vs. 25). MANCOVA, CAT12 3D statistics and Pearson correlations were conducted. DMD patients showed differences in volumes of distinct subcortical structures, left hemisphere cortical thickness, and gyrification in multiple brain areas compared with healthy controls. The daily treated DMD group exhibited differences in subcortical volumes and different patterns of cortical thickness, sulci depth, and gyrification compared to the intermittent treated DMD group. DMD Dp140<sup>+</sup> patients displayed altered gyrification and sulci depth compared to DMD Dp140<sup>-</sup> patients. Finally, we found correlations between neurobehavioral outcomes and brain areas that showed differences in cortical morphology associated with corticosteroid treatment. Both genotype and corticosteroid treatment are associated with variations in subcortical volumes and cortical morphology, albeit in different ways. Corticosteroid treatment appears to have a more profound association with differences in gray matter characteristics of brain regions that are associated with functional outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 105238"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.nmd.2024.08.006
Giorgia Coratti , Matthew Civitello , Annemarie Rohwer , Emilio Albamonte , Jacqueline Montes , Allan M Glanzman , Amy Pasternak , Roberto De Sanctis , Sally Dunaway Young , Tina Duong , Irene Mizzoni , Evelin Milev , Maria Sframeli , Simone Morando , Adele D'Amico , Michela Catteruccia , Noemi Brolatti , Marika Pane , Mariacristina Scoto , Sonia Messina , Eugenio Mercuri
The Revised upper limb module (RULM) has been increasingly used in clinical trials and in clinical settings. The aim of this study was to use the ‘shift analysis’ to assess the patterns of lost or gained abilities for each item on the RULM in an untreated cohort, stratified by SMA type, age, SMN2 copy number, and motor functional status. The analysis was performed on 222 12-month paired assessments from 129 individuals (115 assessment from type II and 107 from type III) who had at least two assessments at yearly intervals. There was a loss of one or more activities in 54% in type II and in 29% type III. A gain of one or more activities was found in 42% type II and in 22% type III. There were concomitant gains and losses in 27% in SMA II and in 9% in SMA III. Our results, measuring the number of abilities that are lost or gained, provide an additional method of detecting changes that can be used for the interpretation of the longitudinal data collected in treated SMA individuals.
修订版上肢模块（RULM）在临床试验和临床环境中的应用越来越广泛。本研究的目的是使用 "移位分析 "来评估未经治疗队列中 RULM 各项能力丧失或增强的模式，并根据 SMA 类型、年龄、SMN2 拷贝数和运动功能状态进行分层。该分析对 129 人（115 人来自 II 型，107 人来自 III 型）的 222 项 12 个月配对评估进行了分析，这些人每年至少进行两次评估。54%的 II 型患者和 29% 的 III 型患者丧失了一项或多项活动能力。42% 的 II 型和 22% 的 III 型患者增加了一项或多项活动。有 27% 的 SMA II 型患者和 9% 的 SMA III 型患者的能力同时增强和减弱。我们的结果测量了丧失或获得的能力数量，提供了一种检测变化的额外方法，可用于解释在接受治疗的 SMA 患者中收集的纵向数据。
{"title":"Upper limb function changes over 12 months in untreated SMA II and III individuals: an item-level analysis using the Revised Upper Limb Module","authors":"Giorgia Coratti , Matthew Civitello , Annemarie Rohwer , Emilio Albamonte , Jacqueline Montes , Allan M Glanzman , Amy Pasternak , Roberto De Sanctis , Sally Dunaway Young , Tina Duong , Irene Mizzoni , Evelin Milev , Maria Sframeli , Simone Morando , Adele D'Amico , Michela Catteruccia , Noemi Brolatti , Marika Pane , Mariacristina Scoto , Sonia Messina , Eugenio Mercuri","doi":"10.1016/j.nmd.2024.08.006","DOIUrl":"10.1016/j.nmd.2024.08.006","url":null,"abstract":"<div><div>The Revised upper limb module (RULM) has been increasingly used in clinical trials and in clinical settings. The aim of this study was to use the ‘shift analysis’ to assess the patterns of lost or gained abilities for each item on the RULM in an untreated cohort, stratified by SMA type, age, <em>SMN2</em> copy number, and motor functional status. The analysis was performed on 222 12-month paired assessments from 129 individuals (115 assessment from type II and 107 from type III) who had at least two assessments at yearly intervals. There was a loss of one or more activities in 54% in type II and in 29% type III. A gain of one or more activities was found in 42% type II and in 22% type III. There were concomitant gains and losses in 27% in SMA II and in 9% in SMA III. Our results, measuring the number of abilities that are lost or gained, provide an additional method of detecting changes that can be used for the interpretation of the longitudinal data collected in treated SMA individuals.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"44 ","pages":"Article 104449"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.nmd.2024.08.007
George W. Padberg
{"title":"26th Meryon Lecture St Anne's College, Oxford, 5th July 2024 FSHD: The long road to DUX4","authors":"George W. Padberg","doi":"10.1016/j.nmd.2024.08.007","DOIUrl":"10.1016/j.nmd.2024.08.007","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"44 ","pages":"Article 104450"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.nmd.2024.105237
Wui-Kwan Wong , Denise Warner , Richard Webster
Laminin α2-related muscular dystrophies are autosomal recessive disorders with a spectrum of disease from congenital muscular dystrophy to adult-onset limb girdle muscular dystrophy. We report two cases of previously undiagnosed laminin α2-related muscular dystrophy presenting with acute weakness and elevated serum creatine kinase levels in association with coxsackievirus infections. One proband deteriorated at 10 days of age and required intubation. Another, unrelated proband presented at 17 months of age with acute weakness on a background of pre-existing gross motor delay. Both children had significant improvement in weakness and decreases in creatine kinase levels after the acute presentation with the second child returning to baseline strength. Trio whole exome sequencing subsequently identified pathogenic/likely pathogenic variants in the LAMA2 gene in each proband, confirming the diagnosis of laminin α2-related muscular dystrophy. This is the first report of acute illness-associated weakness in laminin α2-related muscular dystrophy.
{"title":"Acute weakness and elevated creatine kinase levels associated with coxsackievirus infection in LAMA2-related muscular dystrophy","authors":"Wui-Kwan Wong , Denise Warner , Richard Webster","doi":"10.1016/j.nmd.2024.105237","DOIUrl":"10.1016/j.nmd.2024.105237","url":null,"abstract":"<div><div>Laminin α2-related muscular dystrophies are autosomal recessive disorders with a spectrum of disease from congenital muscular dystrophy to adult-onset limb girdle muscular dystrophy. We report two cases of previously undiagnosed laminin α2-related muscular dystrophy presenting with acute weakness and elevated serum creatine kinase levels in association with coxsackievirus infections. One proband deteriorated at 10 days of age and required intubation. Another, unrelated proband presented at 17 months of age with acute weakness on a background of pre-existing gross motor delay. Both children had significant improvement in weakness and decreases in creatine kinase levels after the acute presentation with the second child returning to baseline strength. Trio whole exome sequencing subsequently identified pathogenic/likely pathogenic variants in the <em>LAMA2</em> gene in each proband, confirming the diagnosis of laminin α2-related muscular dystrophy. This is the first report of acute illness-associated weakness in laminin α2-related muscular dystrophy.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 105237"},"PeriodicalIF":2.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Variants in the CHRNE gene can lead to a condition called congenital myasthenic syndrome (CMS), which affects the neuromuscular junction (NMJ). CHRNE mutations are the most common cause of CMS. Seventy-seven patients with a possible diagnosis of CMS were referred to the neuromuscular clinic of Shariati Hospital affiliated with the Tehran University of Medical Sciences. We performed whole-exome sequencing (WES) to determine the underlying defect in a group of individuals with a possible diagnosis of CMS. Clinical features and morphological and molecular data on 33 patients with mutations in CHRNE were described. Age of onset, age at diagnosis, consanguinity, family history, motor milestone delay, ophthalmoparesis, generalized fatigue, dysphagia, neurophysiologic findings, and response to treatment of the patients were assessed. Nineteen CHRNE variants including 10 novel ones were identified. The most common mutations were c.1327del; (p.Glu443LysfsTer64) in four different families and c.1252–1267dup; (p.Cys423SerfsTer38) in three families. Clinical onset was mostly at birth or under one year with bilateral fatigable ptosis, ophthalmoplegia, bulbar weakness, and proximal muscle weakness. All patients were treated with pyridostigmine ± salbutamol, which resulted in improvement of motor function, dysphagia, and breathing.
{"title":"CHRNE-related congenital myasthenic syndrome in Iran: Clinical and molecular insights","authors":"Narges Karimi , Aida Ghasemi , Akram Panahi , Bentolhoda Ziaadini , Shahriar Nafissi","doi":"10.1016/j.nmd.2024.105234","DOIUrl":"10.1016/j.nmd.2024.105234","url":null,"abstract":"<div><div>Variants in the <em>CHRNE</em> gene can lead to a condition called congenital myasthenic syndrome (CMS), which affects the neuromuscular junction (NMJ). <em>CHRNE</em> mutations are the most common cause of CMS. Seventy-seven patients with a possible diagnosis of CMS were referred to the neuromuscular clinic of Shariati Hospital affiliated with the Tehran University of Medical Sciences. We performed whole-exome sequencing (WES) to determine the underlying defect in a group of individuals with a possible diagnosis of CMS. Clinical features and morphological and molecular data on 33 patients with mutations in <em>CHRNE</em> were described. Age of onset, age at diagnosis, consanguinity, family history, motor milestone delay, ophthalmoparesis, generalized fatigue, dysphagia, neurophysiologic findings, and response to treatment of the patients were assessed. Nineteen <em>CHRNE</em> variants including 10 novel ones were identified. The most common mutations were c.1327del; (p.Glu443LysfsTer64) in four different families and c.1252–1267dup; (p.Cys423SerfsTer38) in three families. Clinical onset was mostly at birth or under one year with bilateral fatigable ptosis, ophthalmoplegia, bulbar weakness, and proximal muscle weakness. All patients were treated with pyridostigmine ± salbutamol, which resulted in improvement of motor function, dysphagia, and breathing.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"46 ","pages":"Article 105234"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/j.nmd.2024.105235
Lola E. R. Lessard , Emmanuelle Girard , Nathalie Streichenberger , Philippe Petiot , Cécile Acquaviva , Cécile Pagan , Peter Mulligan , Françoise Bouhour , Laurent Schaeffer , Arnaud Jacquier
We aimed to evaluate whether inherited mitochondrial dysfunction is associated with neuromuscular junction remodeling in patients with mitochondrial disorders.
Muscle biopsies from 15 patients with mitochondrial disorders and 10 control patients were analyzed through immunostaining for various neuromuscular junction components. The patient group, with a mean age of 49.9 years, exhibited various mitochondrial disorders including chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Patients with mitochondrial disorders had a high percentage of remodeled (p= 0.0001), neoformed (p= 0.0049) and dilated (p= 0.016) endplates. There was a trend toward an increased proportion of neuromuscular junctions with terminal Schwann cell extension in these patients (p= 0.052). No significant difference was found in myofiber diameter between the groups. The observed neuromuscular junction defects varied widely across different mitochondrial disorder phenotypes and were present even without accompanying muscle weakness or neuropathy.
This suggest that mitochondrial disorders are associated with a primary NMJ remodeling independent of muscle structural damage. Pathomechanisms underpinning this remodeling of the neuromuscular junction, as well as clinical factors predictive of this remodeling, remain to be fully characterized.
{"title":"Mitochondrial disorders are associated with morphological neuromuscular junction defects","authors":"Lola E. R. Lessard , Emmanuelle Girard , Nathalie Streichenberger , Philippe Petiot , Cécile Acquaviva , Cécile Pagan , Peter Mulligan , Françoise Bouhour , Laurent Schaeffer , Arnaud Jacquier","doi":"10.1016/j.nmd.2024.105235","DOIUrl":"10.1016/j.nmd.2024.105235","url":null,"abstract":"<div><div>We aimed to evaluate whether inherited mitochondrial dysfunction is associated with neuromuscular junction remodeling in patients with mitochondrial disorders.</div><div>Muscle biopsies from 15 patients with mitochondrial disorders and 10 control patients were analyzed through immunostaining for various neuromuscular junction components. The patient group, with a mean age of 49.9 years, exhibited various mitochondrial disorders including chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. Patients with mitochondrial disorders had a high percentage of remodeled (<em>p</em> <em>=</em> 0.0001), neoformed (<em>p</em> <em>=</em> 0.0049) and dilated (<em>p</em> <em>=</em> 0.016) endplates. There was a trend toward an increased proportion of neuromuscular junctions with terminal Schwann cell extension in these patients (<em>p</em> <em>=</em> 0.052). No significant difference was found in myofiber diameter between the groups. The observed neuromuscular junction defects varied widely across different mitochondrial disorder phenotypes and were present even without accompanying muscle weakness or neuropathy.</div><div>This suggest that mitochondrial disorders are associated with a primary NMJ remodeling independent of muscle structural damage. Pathomechanisms underpinning this remodeling of the neuromuscular junction, as well as clinical factors predictive of this remodeling, remain to be fully characterized.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 105235"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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