Background: Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking.
Objectives: This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation.
Methods: A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed.
Results: A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON).
Conclusion: This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.
{"title":"Phenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India.","authors":"Ganaraja Valakunja Harikrishna, Hansashree Padmanabha, Kiran Polavarapu, Ram Murthy Anjanappa, Veeramani Preethish-Kumar, Bevinahalli Nanjegowda Nandeesh, Seena Vengalil, Saraswati Nashi, Dipti Baskar, Aneesha Thomas, Mainak Bardhan, Gautham Arunachal, Deepak Menon, Sai Bhargava Sanka, Nisha Manjunath, Atchayaram Nalini","doi":"10.3233/JND-230021","DOIUrl":"10.3233/JND-230021","url":null,"abstract":"<p><strong>Background: </strong>Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking.</p><p><strong>Objectives: </strong>This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation.</p><p><strong>Methods: </strong>A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed.</p><p><strong>Results: </strong>A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON).</p><p><strong>Conclusion: </strong>This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"935-957"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537938","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}
N M van de Velde, Y D Krom, J Bongers, R J A Hoek, N A Ikelaar, M van der Holst, K J Naarding, J C van den Bergen, E Vroom, A Horemans, J G M Hendriksen, I J M de Groot, S L S Houwen-van Opstal, J J G M Verschuuren, H A van Duyvenvoorde, R R Snijder, E H Niks
Background: Duchenne and Becker muscular dystrophy lack curative treatments. Registers can facilitate therapy development, serving as a platform to study epidemiology, assess clinical trial feasibility, identify eligible candidates, collect real-world data, perform post-market surveillance, and collaborate in (inter)national data-driven initiatives.
Objective: In addressing these facets, it's crucial to gather high-quality, interchangeable, and reusable data from a representative population. We introduce the Dutch Dystrophinopathy Database (DDD), a national registry for patients with DMD or BMD, and females with pathogenic DMD variants, outlining its design, governance, and use.
Methods: The design of DDD is based on a system-independent information model that ensures interoperable and reusable data adhering to international standards. To maximize enrollment, patients can provide consent online and participation is allowed on different levels with contact details and clinical diagnosis as minimal requirement. Participants can opt-in for yearly online questionnaires on disease milestones and medication and to have clinical data stored from visits to one of the national reference centers. Governance involves a general board, advisory board and database management.
Results: On November 1, 2023, 742 participants were enrolled. Self-reported data were provided by 291 Duchenne, 122 Becker and 38 female participants. 96% of the participants visiting reference centers consented to store clinical data. Eligible patients were informed about clinical studies through DDD, and multiple data requests have been approved to use coded clinical data for quality control, epidemiology and natural history studies.
Conclusion: The Dutch Dystrophinopathy Database captures long-term patient and high-quality standardized clinician reported healthcare data, supporting trial readiness, post-marketing surveillance, and effective data use using a multicenter design that is scalable to other neuromuscular disorders.
{"title":"The Dutch Dystrophinopathy Database: A National Registry with Standardized Patient and Clinician Reported Real-World Data.","authors":"N M van de Velde, Y D Krom, J Bongers, R J A Hoek, N A Ikelaar, M van der Holst, K J Naarding, J C van den Bergen, E Vroom, A Horemans, J G M Hendriksen, I J M de Groot, S L S Houwen-van Opstal, J J G M Verschuuren, H A van Duyvenvoorde, R R Snijder, E H Niks","doi":"10.3233/JND-240061","DOIUrl":"10.3233/JND-240061","url":null,"abstract":"<p><strong>Background: </strong>Duchenne and Becker muscular dystrophy lack curative treatments. Registers can facilitate therapy development, serving as a platform to study epidemiology, assess clinical trial feasibility, identify eligible candidates, collect real-world data, perform post-market surveillance, and collaborate in (inter)national data-driven initiatives.</p><p><strong>Objective: </strong>In addressing these facets, it's crucial to gather high-quality, interchangeable, and reusable data from a representative population. We introduce the Dutch Dystrophinopathy Database (DDD), a national registry for patients with DMD or BMD, and females with pathogenic DMD variants, outlining its design, governance, and use.</p><p><strong>Methods: </strong>The design of DDD is based on a system-independent information model that ensures interoperable and reusable data adhering to international standards. To maximize enrollment, patients can provide consent online and participation is allowed on different levels with contact details and clinical diagnosis as minimal requirement. Participants can opt-in for yearly online questionnaires on disease milestones and medication and to have clinical data stored from visits to one of the national reference centers. Governance involves a general board, advisory board and database management.</p><p><strong>Results: </strong>On November 1, 2023, 742 participants were enrolled. Self-reported data were provided by 291 Duchenne, 122 Becker and 38 female participants. 96% of the participants visiting reference centers consented to store clinical data. Eligible patients were informed about clinical studies through DDD, and multiple data requests have been approved to use coded clinical data for quality control, epidemiology and natural history studies.</p><p><strong>Conclusion: </strong>The Dutch Dystrophinopathy Database captures long-term patient and high-quality standardized clinician reported healthcare data, supporting trial readiness, post-marketing surveillance, and effective data use using a multicenter design that is scalable to other neuromuscular disorders.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"1095-1109"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731218","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}
M. Honda, F. Shimizu, Ryota Sato, Masayuki Nakamori
Purpose of review: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes: dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), immune-mediated myopathy (IMNM), inclusion body myopathy (IBM), and overlap myositis. Myositis-specific autoantibodies were detected for the diagnosis and classification of IIM. This review highlights the pathogenic contributions of the complement system, microangiopathy, and inflammation in IIM. Recent findings: Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury. A recent study using human muscle microvascular endothelial cells showed that Jo-1 antibodies from ASS induce complement-dependent cellular cytotoxicity in vitro. Based on both clinical and pathological observations, antibody- and complement-mediated microangiopathy may contribute to the development of DM and anti-Jo-1 ASS. Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy. Several serum biomarkers that reflect the IFN1 signature and microangiopathy are elevated in patients with DM. The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM. A recent report showed that an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells by secreting proinflammatory cytokines, such as tumor necrosis factor α. Summary: The deposition of complement in muscles and capillaries is a characteristic feature of DM, ASS, and IMNM. Microangiopathy plays a pathogenic role in DM, possibly resulting in perifascicular atrophy. Further understanding of the detailed pathomechanism regarding complement, microangiopathy, and inflammation may lead to novel therapeutic approaches for IIM.
{"title":"Contribution of Complement, Microangiopathy and Inflammation in Idiopathic Inflammatory Myopathies","authors":"M. Honda, F. Shimizu, Ryota Sato, Masayuki Nakamori","doi":"10.3233/jnd-230168","DOIUrl":"https://doi.org/10.3233/jnd-230168","url":null,"abstract":"Purpose of review: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes: dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), immune-mediated myopathy (IMNM), inclusion body myopathy (IBM), and overlap myositis. Myositis-specific autoantibodies were detected for the diagnosis and classification of IIM. This review highlights the pathogenic contributions of the complement system, microangiopathy, and inflammation in IIM. Recent findings: Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury. A recent study using human muscle microvascular endothelial cells showed that Jo-1 antibodies from ASS induce complement-dependent cellular cytotoxicity in vitro. Based on both clinical and pathological observations, antibody- and complement-mediated microangiopathy may contribute to the development of DM and anti-Jo-1 ASS. Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy. Several serum biomarkers that reflect the IFN1 signature and microangiopathy are elevated in patients with DM. The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM. A recent report showed that an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells by secreting proinflammatory cytokines, such as tumor necrosis factor α. Summary: The deposition of complement in muscles and capillaries is a characteristic feature of DM, ASS, and IMNM. Microangiopathy plays a pathogenic role in DM, possibly resulting in perifascicular atrophy. Further understanding of the detailed pathomechanism regarding complement, microangiopathy, and inflammation may lead to novel therapeutic approaches for IIM.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"34 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138957226","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}
L. Otto, M. Froeling, R. V. van Eijk, R. Wadman, I. Cuppen, Danny R van der Woude, B. Bartels, F. Asselman, Jeroen Hendrikse, W. L. van der Pol
Background: Spinal muscular atrophy (SMA) is caused by deficiency of survival motor neuron (SMN) protein. Intrathecal nusinersen treatment increases SMN protein in motor neurons and has been shown to improve motor function in symptomatic children with SMA. Objective: We used quantitative MRI to gain insight in microstructure and fat content of muscle during treatment and to explore its use as biomarker for treatment effect. Methods: We used a quantitative MRI protocol before start of treatment and following the 4th and 6th injection of nusinersen in 8 children with SMA type 2 and 3 during the first year of treatment. The MR protocol allowed DIXON, T2 mapping and diffusion tensor imaging acquisitions. We also assessed muscle strength and motor function scores. Results: Fat fraction of all thigh muscles with the exception of the m. adductor longus increased in all patients during treatment (+3.2%, p = 0.02). WaterT2 showed no significant changes over time (–0.7 ms, p = 0.3). DTI parameters MD and AD demonstrate a significant decrease in the hamstrings towards values observed in healthy muscle. Conclusions: Thigh muscles of children with SMA treated with nusinersen showed ongoing fatty infiltration and possible normalization of thigh muscle microstructure during the first year of nusinersen treatment. Quantitative muscle MRI shows potential as biomarker for the effects of SMA treatment strategies.
背景:脊髓性肌萎缩症(SMA)是由存活运动神经元(SMN)蛋白缺乏引起的。鞘内nusinersen治疗增加运动神经元中的SMN蛋白，并已被证明可改善有症状的SMA儿童的运动功能。目的:利用定量MRI技术了解治疗过程中肌肉的微观结构和脂肪含量，并探讨其作为治疗效果的生物标志物。方法:我们对8例2型和3型SMA患儿在治疗开始前和治疗第一年第4次和第6次注射nusinersen后进行定量MRI检查。MR协议允许DIXON, T2映射和扩散张量成像获取。我们还评估了肌肉力量和运动功能评分。结果:除长内收肌外，所有患者在治疗期间所有大腿肌肉的脂肪含量均增加(+3.2%，p = 0.02)。WaterT2随时间变化不显著(-0.7 ms, p = 0.3)。DTI参数MD和AD显示腘绳肌与健康肌肉相比显著降低。结论:nusinersen治疗的SMA儿童大腿肌肉在nusinersen治疗的第一年表现出持续的脂肪浸润和可能的大腿肌肉微结构正常化。定量肌肉MRI显示了作为SMA治疗策略效果的生物标志物的潜力。
{"title":"Monitoring Nusinersen Treatment Effects in Children with Spinal Muscular Atrophy with Quantitative Muscle MRI","authors":"L. Otto, M. Froeling, R. V. van Eijk, R. Wadman, I. Cuppen, Danny R van der Woude, B. Bartels, F. Asselman, Jeroen Hendrikse, W. L. van der Pol","doi":"10.3233/jnd-221671","DOIUrl":"https://doi.org/10.3233/jnd-221671","url":null,"abstract":"Background: Spinal muscular atrophy (SMA) is caused by deficiency of survival motor neuron (SMN) protein. Intrathecal nusinersen treatment increases SMN protein in motor neurons and has been shown to improve motor function in symptomatic children with SMA. Objective: We used quantitative MRI to gain insight in microstructure and fat content of muscle during treatment and to explore its use as biomarker for treatment effect. Methods: We used a quantitative MRI protocol before start of treatment and following the 4th and 6th injection of nusinersen in 8 children with SMA type 2 and 3 during the first year of treatment. The MR protocol allowed DIXON, T2 mapping and diffusion tensor imaging acquisitions. We also assessed muscle strength and motor function scores. Results: Fat fraction of all thigh muscles with the exception of the m. adductor longus increased in all patients during treatment (+3.2%, p = 0.02). WaterT2 showed no significant changes over time (–0.7 ms, p = 0.3). DTI parameters MD and AD demonstrate a significant decrease in the hamstrings towards values observed in healthy muscle. Conclusions: Thigh muscles of children with SMA treated with nusinersen showed ongoing fatty infiltration and possible normalization of thigh muscle microstructure during the first year of nusinersen treatment. Quantitative muscle MRI shows potential as biomarker for the effects of SMA treatment strategies.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"58 7","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587092","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}
Barbara Sitaš, Mirea Hancevic, Katarina Bilic, Hrvoje Bilić, E. Bilic
Background: Risdiplam is an orally administered treatment for spinal muscular atrophy which leads to an improvement in motor function as measured by functional motor scales compared with placebo. Although risdiplam has been registered since 2020, real-world data in adults is still scarce. There have been no new safety signals so far, with some results pointing that risdiplam may be effective Objective: The objective was to present real-world data of 31 adult patients with spinal muscular atrophy type 2 and type 3 treated with risdiplam in the Republic of Croatia Methods: Treatment effects were assessed with motor function tests and patient reported outcome measures, including Individualized Neuromuscular Quality of Life questionnaire, and Jaw Functional Limitation Scale. Side effects, as well as subjective improvements and symptoms, were noted. Results: Majority of patients did not report any side effects. During treatment, we have observed clinically meaningful improvements in some patients, with stabilization of motor functions in the remaining patients. The majority of patients with bulbar function impairment experienced bulbar function improvement, all patients reported an increased quality of life with treatment. An unexpected observed treatment effect was weight gain in a third of all patients with some patients reporting an increase in appetite and subjective improvement in digestion. Conclusions: Risdiplam treatment was well tolerated with subjective and objective positive outcomes registered as measured by functional motor scales and patient-reported outcomes. Since risdiplam is administered orally and acts as a systemic therapy for a multisystemic disorder, effects in systems other than neuromuscular can be expected and should be monitored. Due to systemic nature of the disease patients need multidisciplinary monitoring.
{"title":"Risdiplam Real World Data – Looking Beyond Motor Neurons and Motor Function Measures","authors":"Barbara Sitaš, Mirea Hancevic, Katarina Bilic, Hrvoje Bilić, E. Bilic","doi":"10.3233/jnd-230197","DOIUrl":"https://doi.org/10.3233/jnd-230197","url":null,"abstract":"Background: Risdiplam is an orally administered treatment for spinal muscular atrophy which leads to an improvement in motor function as measured by functional motor scales compared with placebo. Although risdiplam has been registered since 2020, real-world data in adults is still scarce. There have been no new safety signals so far, with some results pointing that risdiplam may be effective Objective: The objective was to present real-world data of 31 adult patients with spinal muscular atrophy type 2 and type 3 treated with risdiplam in the Republic of Croatia Methods: Treatment effects were assessed with motor function tests and patient reported outcome measures, including Individualized Neuromuscular Quality of Life questionnaire, and Jaw Functional Limitation Scale. Side effects, as well as subjective improvements and symptoms, were noted. Results: Majority of patients did not report any side effects. During treatment, we have observed clinically meaningful improvements in some patients, with stabilization of motor functions in the remaining patients. The majority of patients with bulbar function impairment experienced bulbar function improvement, all patients reported an increased quality of life with treatment. An unexpected observed treatment effect was weight gain in a third of all patients with some patients reporting an increase in appetite and subjective improvement in digestion. Conclusions: Risdiplam treatment was well tolerated with subjective and objective positive outcomes registered as measured by functional motor scales and patient-reported outcomes. Since risdiplam is administered orally and acts as a systemic therapy for a multisystemic disorder, effects in systems other than neuromuscular can be expected and should be monitored. Due to systemic nature of the disease patients need multidisciplinary monitoring.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"24 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594269","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 : 2023-06-16DOI: 10.17650/2222-8721-2023-13-2-64-71
S. N. Bardakov, N. Khromov-Borisov, A. Belskikh, I. Litvinenko, A. V. Slobodya
Background. Marcher’s digitalgia paresthetica is a neuropathy of the medial plantar proper digital nerve (nervus digita lis plantaris proprii medialis halluci) and in some cases is accompanied by the formation of Joplin’s neuroma. Despite the general population rarity, marcher’s digitalgia paresthetica is significantly common among the special military contingent, athletes and tourists.Aim. To assess the prevalence of medial digital nerve neuropathy among military personnel and to identify possible factors contributing to its development.Materials and methods. The study involved 125 male servicemen of the Russian Federation, with an average age 37 (37–40) years. A neurological examination was performed with a detailed assessment of sensory disorders in the lower extremities, electroneuromyography and ultrasound examination of the leg nerves.Results. In 83 cases, or 66 (55–76) %, of digitalgia paresthetica were identified. Among them asymptomatic – 51 people, or 61 (47–74) %. In 27 cases – 33 (21–47) % – violation of sensitivity was observed on one side. The maximum area of violation of the sensitivity of the innervation of the medial‑plantar surface of the big toes was determined in 57 cases – 68 (55–80) %. At the same time, in 14 (6–25) % of the examined, the distal part of the second toe was additionally involved.Conclusion. In our study, the hypothesis about the influence of the type of footwear, the average daily duration of wearing and the frequency of its forced removal on the likelihood of developing paresthetic digitalgia was not confirmed. It is important that doctors are informed about the possible development of this neuropathy and its benign course.
{"title":"Marching neuropathy of the nervus digitalis plantaris proprii medialis halluci among military personnel","authors":"S. N. Bardakov, N. Khromov-Borisov, A. Belskikh, I. Litvinenko, A. V. Slobodya","doi":"10.17650/2222-8721-2023-13-2-64-71","DOIUrl":"https://doi.org/10.17650/2222-8721-2023-13-2-64-71","url":null,"abstract":"Background. Marcher’s digitalgia paresthetica is a neuropathy of the medial plantar proper digital nerve (nervus digita lis plantaris proprii medialis halluci) and in some cases is accompanied by the formation of Joplin’s neuroma. Despite the general population rarity, marcher’s digitalgia paresthetica is significantly common among the special military contingent, athletes and tourists.Aim. To assess the prevalence of medial digital nerve neuropathy among military personnel and to identify possible factors contributing to its development.Materials and methods. The study involved 125 male servicemen of the Russian Federation, with an average age 37 (37–40) years. A neurological examination was performed with a detailed assessment of sensory disorders in the lower extremities, electroneuromyography and ultrasound examination of the leg nerves.Results. In 83 cases, or 66 (55–76) %, of digitalgia paresthetica were identified. Among them asymptomatic – 51 people, or 61 (47–74) %. In 27 cases – 33 (21–47) % – violation of sensitivity was observed on one side. The maximum area of violation of the sensitivity of the innervation of the medial‑plantar surface of the big toes was determined in 57 cases – 68 (55–80) %. At the same time, in 14 (6–25) % of the examined, the distal part of the second toe was additionally involved.Conclusion. In our study, the hypothesis about the influence of the type of footwear, the average daily duration of wearing and the frequency of its forced removal on the likelihood of developing paresthetic digitalgia was not confirmed. It is important that doctors are informed about the possible development of this neuropathy and its benign course.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"88 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80273469","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 : 2023-06-16DOI: 10.17650/2222-8721-2023-13-2-72-82
F. A. Abbasov, G. V. Zemtsova, P. A. Popov, K. I. Chekhonatskaya, D. V. Kukhno, M. Severova, M. Shmyreva, A. A. Kindarova, D. Schekochikhin
Necrotizing myopathies are a subtype of autoimmune myopathies characterized by muscle fiber necrosis with minimal infiltration by inflammatory cells on muscle biopsy. This group of myopathies is defined by flaccid palsies due to prima‑ ry skeletal muscle damage as well as extramuscular manifestations such as fever, rash, arthritis, Raynaud’s syndrome and interstitial lung disease. The presence of anti-SRP antibodies is associated with rapidly progressive refractory myositis predominantly affecting limb muscles and axial muscles.Objective of the work is to analyze the course of severe, refractory to several lines of immunosuppressive therapies anti-SRP associated necrotizing myopathy and to highlight an adequate treatment regime.Necrotizing myopathy was suspected in patients aged 39 and 56 years with rapidly progressive flaccid tetraparesis on the basis of clinical and anamnestic data, the results of needle electromyography and muscle magnetic resonance imaging, as well as the analysis of myositis-specific and myositis-associated autoantibodies. In both cases, a rapid development of atrophies, marked muscle weakness in the limbs, without involvement of the bulbar musculature, was observed. To achieve effective control of the disease progression, several lines of therapy were required: glucocorticosteroids, intravenous immunoglobulins, methotrexate and rituximab. Our observations are consistent with those in the literature.Our observations illustrate the clinical course of severe myopathy associated with anti-SRP antibodies. Early initiation of aggressive immunosuppression is crucial to control the disease progression. Treatment and rehabilitation allow achieving significant improvement of the patient’s condition.
{"title":"Anti-SRP antibody-associated necrotizing myopathy: 2 clinical cases","authors":"F. A. Abbasov, G. V. Zemtsova, P. A. Popov, K. I. Chekhonatskaya, D. V. Kukhno, M. Severova, M. Shmyreva, A. A. Kindarova, D. Schekochikhin","doi":"10.17650/2222-8721-2023-13-2-72-82","DOIUrl":"https://doi.org/10.17650/2222-8721-2023-13-2-72-82","url":null,"abstract":"Necrotizing myopathies are a subtype of autoimmune myopathies characterized by muscle fiber necrosis with minimal infiltration by inflammatory cells on muscle biopsy. This group of myopathies is defined by flaccid palsies due to prima‑ ry skeletal muscle damage as well as extramuscular manifestations such as fever, rash, arthritis, Raynaud’s syndrome and interstitial lung disease. The presence of anti-SRP antibodies is associated with rapidly progressive refractory myositis predominantly affecting limb muscles and axial muscles.Objective of the work is to analyze the course of severe, refractory to several lines of immunosuppressive therapies anti-SRP associated necrotizing myopathy and to highlight an adequate treatment regime.Necrotizing myopathy was suspected in patients aged 39 and 56 years with rapidly progressive flaccid tetraparesis on the basis of clinical and anamnestic data, the results of needle electromyography and muscle magnetic resonance imaging, as well as the analysis of myositis-specific and myositis-associated autoantibodies. In both cases, a rapid development of atrophies, marked muscle weakness in the limbs, without involvement of the bulbar musculature, was observed. To achieve effective control of the disease progression, several lines of therapy were required: glucocorticosteroids, intravenous immunoglobulins, methotrexate and rituximab. Our observations are consistent with those in the literature.Our observations illustrate the clinical course of severe myopathy associated with anti-SRP antibodies. Early initiation of aggressive immunosuppression is crucial to control the disease progression. Treatment and rehabilitation allow achieving significant improvement of the patient’s condition.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"62 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84491861","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 : 2023-06-16DOI: 10.17650/2222-8721-2023-13-2-56-63
E. Dadali, T. Markova, V. Kenis, T. Nagornova, S. Nikitin
Background. Primary hypertrophic osteoarthropathy is a rare genetically heterogeneous disease with three clinical variants. The classic one is a combination of hyperostosis, arthropathy and pachyderma and two variants with damage to only bone structures or pachyderma. Two genes responsible for the occurrence of primary hypertrophic osteoarthropathy have been identified: HPGD (debut age up to one year) and SLCO2A1 (debut in puberty and adolescence), whose products are involved in prostaglandin E2 metabolism. Two recurrent variants were identified in the HPGD gene: c.175_176delCT(p.Leu59fs) in patients from Europe and c.310_311delCT in patients from China. There were no clinical and genetic correlations in patients with different variants in the identified genes, which may be due to a small number of observations. The analysis of clinical manifestations in patients with newly identified variants or previously unidentified combinations of variants in a compound‑heterozygous state helps to understand the pathogenesis and prognosis of the course of the disease.Aim. To present the clinical and genetic characteristics of two Russian patients with primary hypertrophic osteoarthropathy caused by a newly identified combination of nucleotide variants in a compound‑heterozygous state in the HPGD and SLCO2A1 genes.Materials and methods. Clinical examination, radiography of the skeleton and chest, electrocardiography, echocardiography. Confirmation of the pathogenicity of the identified variants and clarification of the type of disease was carried out using automatic Sanger sequencing.Results. The clinical and genetic characteristics of two unrelated patients with primary hypertrophic osteoarthropathy caused by an undescribed combination of variants in the compound heterozygous state in the HPGD and SLCO2A1 genes were analyzed. In a patient with variants in the SLCO2A1 gene, the disease debuts at the age of 14 with deformities of the fingers, nails on the hands and feet, followed by the addition of burning pain in the distal parts of the arms and legs. At the age of 33, the examination revealed deformity of the fingers of the hands and feet by the type of drumsticks and nails by the type of watch glasses, enlargement of the knee joints, pronounced arthralgia. There were no signs of pachyderma. The new generation sequencing revealed two variants in the SLCO2A1 gene c.764G>A(p.Gly255Glu) in exon 6 and c.1333C>T(p.Arg445Cys) in exon 10. These variants were identified earlier in a compound‑heterozygous combination with other variants in patients with the classical phenotype of the disease, which were not present in the patient we observed. A feature of the case was pronounced hyperhidrosis and burning pain in the extremities, which may be due to stimulation of nociceptors in the musculoskeletal structures.Deformities of the fingers, nails of the hands and feet occurred in a patient with variants in the HPGD gene at 6 months. At the age of 9 years, a change in shap
{"title":"Clinical and genetic characteristics of primary hypertrophic osteoarthropathy","authors":"E. Dadali, T. Markova, V. Kenis, T. Nagornova, S. Nikitin","doi":"10.17650/2222-8721-2023-13-2-56-63","DOIUrl":"https://doi.org/10.17650/2222-8721-2023-13-2-56-63","url":null,"abstract":"Background. Primary hypertrophic osteoarthropathy is a rare genetically heterogeneous disease with three clinical variants. The classic one is a combination of hyperostosis, arthropathy and pachyderma and two variants with damage to only bone structures or pachyderma. Two genes responsible for the occurrence of primary hypertrophic osteoarthropathy have been identified: HPGD (debut age up to one year) and SLCO2A1 (debut in puberty and adolescence), whose products are involved in prostaglandin E2 metabolism. Two recurrent variants were identified in the HPGD gene: c.175_176delCT(p.Leu59fs) in patients from Europe and c.310_311delCT in patients from China. There were no clinical and genetic correlations in patients with different variants in the identified genes, which may be due to a small number of observations. The analysis of clinical manifestations in patients with newly identified variants or previously unidentified combinations of variants in a compound‑heterozygous state helps to understand the pathogenesis and prognosis of the course of the disease.Aim. To present the clinical and genetic characteristics of two Russian patients with primary hypertrophic osteoarthropathy caused by a newly identified combination of nucleotide variants in a compound‑heterozygous state in the HPGD and SLCO2A1 genes.Materials and methods. Clinical examination, radiography of the skeleton and chest, electrocardiography, echocardiography. Confirmation of the pathogenicity of the identified variants and clarification of the type of disease was carried out using automatic Sanger sequencing.Results. The clinical and genetic characteristics of two unrelated patients with primary hypertrophic osteoarthropathy caused by an undescribed combination of variants in the compound heterozygous state in the HPGD and SLCO2A1 genes were analyzed. In a patient with variants in the SLCO2A1 gene, the disease debuts at the age of 14 with deformities of the fingers, nails on the hands and feet, followed by the addition of burning pain in the distal parts of the arms and legs. At the age of 33, the examination revealed deformity of the fingers of the hands and feet by the type of drumsticks and nails by the type of watch glasses, enlargement of the knee joints, pronounced arthralgia. There were no signs of pachyderma. The new generation sequencing revealed two variants in the SLCO2A1 gene c.764G>A(p.Gly255Glu) in exon 6 and c.1333C>T(p.Arg445Cys) in exon 10. These variants were identified earlier in a compound‑heterozygous combination with other variants in patients with the classical phenotype of the disease, which were not present in the patient we observed. A feature of the case was pronounced hyperhidrosis and burning pain in the extremities, which may be due to stimulation of nociceptors in the musculoskeletal structures.Deformities of the fingers, nails of the hands and feet occurred in a patient with variants in the HPGD gene at 6 months. At the age of 9 years, a change in shap","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"31 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87469388","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 : 2023-06-15DOI: 10.17650/2222-8721-2023-13-2-20-30
D. S. Astafyeva, Y. V. Vlasov, A. Strelnik, O. Chigareva, E. A. Markina, T. Shishkovskaya, D. Smirnova, A. Gayduk
Neuropathic pain affects 7 % of the general population worldwide, it is often resistant to analgesic treatments and is complicated with depressive states in 57–65 % of this patients’ cohort. Ongoing research of current therapeutic approaches, including repetitive transcranial magnetic stimulation (rTMS) use in neuropathic pain and depression, grants new data about the details of treatment protocols’ designs. The aim of our literature review was to evaluate those parameters of the treatment protocols which proved significant efficacy in the management of the neuropathic pain with comorbid depression.Focusing on the Scopus, Elsevier and PubMed databases search, we have found 639 peer‑review articles. 23 studies have been included into the data analysis, whereas others were excluded based on their heterogeneous study design. Across the data analysis we evaluated such rTMS parameters as the type of a coil, type of stimulation area, locus of gained evoked motor potential, amplitude of stimulation, duration of session, frequency/number of sessions per day/month, tie duration between sessions, number and frequency of trains, amount and frequency of pulses containing and efficacy of treatment. Those studies that performed repetitive transcranial magnetic stimulation using the figure‑of‑8 coil over the M1 brain area, for 10 or more daily sessions with duration from 7 up to 40 minutes, of 10–20 Hz frequency, intensity 80–90 % of resting motor threshold and total pulses number over 1500 per session demonstrated the greater efficacy in pain level decrease and depression scores reduction among neuropathic pain patients with comorbid depression. Conducting an additional maintenance phase of treatment prolonged the therapeutic effect of the course.Based on the data review, the parameters of the most efficient rTMS protocols’ designs in management of patients with neuropathic pain and comorbid depression have been revealed. Further research requires investigation of other promising indicators of rTMS efficacy use in neuropathic pain with comorbid depression, such as stimulation over multiple brain areas, the duration/timing of additional maintenance phase of treatment, and the figure‑of‑8 coil orientation options.
{"title":"Repetitive transcranial magnetic stimulation use in neuropathic pain with comorbid depression: a review of efficient treatment protocols’ parameters","authors":"D. S. Astafyeva, Y. V. Vlasov, A. Strelnik, O. Chigareva, E. A. Markina, T. Shishkovskaya, D. Smirnova, A. Gayduk","doi":"10.17650/2222-8721-2023-13-2-20-30","DOIUrl":"https://doi.org/10.17650/2222-8721-2023-13-2-20-30","url":null,"abstract":"Neuropathic pain affects 7 % of the general population worldwide, it is often resistant to analgesic treatments and is complicated with depressive states in 57–65 % of this patients’ cohort. Ongoing research of current therapeutic approaches, including repetitive transcranial magnetic stimulation (rTMS) use in neuropathic pain and depression, grants new data about the details of treatment protocols’ designs. The aim of our literature review was to evaluate those parameters of the treatment protocols which proved significant efficacy in the management of the neuropathic pain with comorbid depression.Focusing on the Scopus, Elsevier and PubMed databases search, we have found 639 peer‑review articles. 23 studies have been included into the data analysis, whereas others were excluded based on their heterogeneous study design. Across the data analysis we evaluated such rTMS parameters as the type of a coil, type of stimulation area, locus of gained evoked motor potential, amplitude of stimulation, duration of session, frequency/number of sessions per day/month, tie duration between sessions, number and frequency of trains, amount and frequency of pulses containing and efficacy of treatment. Those studies that performed repetitive transcranial magnetic stimulation using the figure‑of‑8 coil over the M1 brain area, for 10 or more daily sessions with duration from 7 up to 40 minutes, of 10–20 Hz frequency, intensity 80–90 % of resting motor threshold and total pulses number over 1500 per session demonstrated the greater efficacy in pain level decrease and depression scores reduction among neuropathic pain patients with comorbid depression. Conducting an additional maintenance phase of treatment prolonged the therapeutic effect of the course.Based on the data review, the parameters of the most efficient rTMS protocols’ designs in management of patients with neuropathic pain and comorbid depression have been revealed. Further research requires investigation of other promising indicators of rTMS efficacy use in neuropathic pain with comorbid depression, such as stimulation over multiple brain areas, the duration/timing of additional maintenance phase of treatment, and the figure‑of‑8 coil orientation options.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"80 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77463603","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 : 2023-06-15DOI: 10.17650/2222-8721-2023-13-2-42-55
A. Murtazina, P. N. Tsabay, G. Rudenskaya, L. Bessonova, F. Bostanova, D. Guseva, I. Sharkova, O. Shchagina, A. Orlova, O. Ryzhkova, T. Markova, A. S. Kuchina, S. Nikitin, E. Dadali
TRPV4‑associated neuromuscular diseases represent a clinical spectrum of neuropathies and motor neuron disorders. To date, 3 phenotypic forms are distinguished. There are Charcot–Marie–Tooth disease type 2C, distal hereditary motor neuropathy type 8 (DHMN8), scapulo‑peroneal spinal muscular atrophy (SPSMA). Here we report 3 families with DNMN8 and one family with SPSMA. In all cases, DNA‑analysis revealed single nucleotide variants in the TRPV4 gene previously reported as pathogenic. In 3 probands, a combination of signs of both motor and motor‑sensory neuropathies led to difficulties in the establishment of the clinical diagnosis. Patients had mild sensory disturbances in the feet, but in all of these cases nerve conduction study revealed normal sensory nerve action potentials. Considering the prevailing signs of motor neuropathy, these patients were diagnosed with DNMN8. Clinical signs of sensory disturbances are regarded as not contradicting the diagnosis, since they can be observed in various forms of distal motor neuropathies. The clinical features of SPSMA in one patient corresponded to those previously described in the literature. The involvement of the shoulder girdle muscles and the peroneal muscles and neurogenic changes in needle electromyography allow suspecting SPSMA clinically. A distinctive features of TRPV4‑associated neuromuscular diseases are the vocal cords paresis, sensorineural hearing loss and respiratory failure, however they are not obligatory according to our clinical reports.
{"title":"Phenotypic variability in TRPV4-associated neuropathies and neuronopathies: a case series","authors":"A. Murtazina, P. N. Tsabay, G. Rudenskaya, L. Bessonova, F. Bostanova, D. Guseva, I. Sharkova, O. Shchagina, A. Orlova, O. Ryzhkova, T. Markova, A. S. Kuchina, S. Nikitin, E. Dadali","doi":"10.17650/2222-8721-2023-13-2-42-55","DOIUrl":"https://doi.org/10.17650/2222-8721-2023-13-2-42-55","url":null,"abstract":"TRPV4‑associated neuromuscular diseases represent a clinical spectrum of neuropathies and motor neuron disorders. To date, 3 phenotypic forms are distinguished. There are Charcot–Marie–Tooth disease type 2C, distal hereditary motor neuropathy type 8 (DHMN8), scapulo‑peroneal spinal muscular atrophy (SPSMA). Here we report 3 families with DNMN8 and one family with SPSMA. In all cases, DNA‑analysis revealed single nucleotide variants in the TRPV4 gene previously reported as pathogenic. In 3 probands, a combination of signs of both motor and motor‑sensory neuropathies led to difficulties in the establishment of the clinical diagnosis. Patients had mild sensory disturbances in the feet, but in all of these cases nerve conduction study revealed normal sensory nerve action potentials. Considering the prevailing signs of motor neuropathy, these patients were diagnosed with DNMN8. Clinical signs of sensory disturbances are regarded as not contradicting the diagnosis, since they can be observed in various forms of distal motor neuropathies. The clinical features of SPSMA in one patient corresponded to those previously described in the literature. The involvement of the shoulder girdle muscles and the peroneal muscles and neurogenic changes in needle electromyography allow suspecting SPSMA clinically. A distinctive features of TRPV4‑associated neuromuscular diseases are the vocal cords paresis, sensorineural hearing loss and respiratory failure, however they are not obligatory according to our clinical reports.","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":"36 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87464717","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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