Muscle & Nerve最新文献

{"title":"Mitochondrial genome variants associated with amyotrophic lateral sclerosis and their haplogroup distribution.","authors":"Marcelo R S Briones, João H Campos, Renata C Ferreira, Lisa Schneper, Ilda M Santos, Fernando M Antoneli, James R Broach","doi":"10.1002/mus.28230","DOIUrl":"10.1002/mus.28230","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Amyotrophic lateral sclerosis (ALS) may be familial or sporadic, and twin studies have revealed that even sporadic forms have a significant genetic component. Variants in 55 nuclear genes have been associated with ALS and although mitochondrial dysfunction is observed in ALS, variants in mitochondrial genomes (mitogenomes) have not yet been tested for association with ALS. The aim of this study was to determine whether mitogenome variants are associated with ALS.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) in mitogenomes of 1965 ALS patients and 2547 controls.</p><p><strong>Results: </strong>We identified 51 mitogenome variants with p values <10^-7, of which 13 had odds ratios (ORs) >1, in genes RNR1, ND1, CO1, CO3, ND5, ND6, and CYB, while 38 variants had OR <1 in genes RNR1, RNA2, ND1, ND2, CO2, ATP8, ATP6, CO3, ND3, ND4, ND5, ND6, and CYB. The frequencies of haplogroups H, U, and L, the most frequent in our ALS data set, were the same in different onset sites (bulbar, limb, spinal, and axial). Also, intra-haplogroup GWAS revealed unique ALS-associated variants in haplogroups L and U.</p><p><strong>Discussion: </strong>Our study shows that mitogenome single nucleotide variants (SNVs) are associated with ALS and suggests that these SNVs could be included in routine genetic testing for ALS and that mitochondrial replacement therapy has the potential to serve as a basis for ALS treatment.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"862-872"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913325","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":"Diagnostic workup of rhabdomyolysis: Genetic testing should precede neurophysiological testing.","authors":"Nicol C Voermans, Salman Bhai, Pascal Laforet, John Vissing","doi":"10.1002/mus.28205","DOIUrl":"10.1002/mus.28205","url":null,"abstract":"","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"727-730"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phantom radiculopathy: An electrodiagnostic challenge.","authors":"Alexander De La Rosa-Cabral, Christopher Bonilla-Durango, Anelys Torres-Rivera, Ana Cintrón-Rodríguez","doi":"10.1002/mus.28217","DOIUrl":"10.1002/mus.28217","url":null,"abstract":"","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"873-874"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural changes and contractility in muscle assessed by magnetic resonance imaging in individuals with ryanodine receptor 1-related rhabdomyolysis or myalgia.","authors":"Zhe Lyu, Tuva Åsatun Solheim, Nanna Scharff Poulsen, Anne-Sofie Vibæk Eisum, Gry Hatting Beha, Freja Fornander, Annarita Ghosh Andersen, Nanna Witting, John Vissing","doi":"10.1002/mus.28219","DOIUrl":"10.1002/mus.28219","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Ryanodine receptor 1 (RYR1)-related myopathies associated with variants in the RYR1 gene present with a wide range of symptoms and severity. Two of the milder phenotypes associated with dominant pathogenic variants in RYR1 are rhabdomyolysis and myalgia. Only a few studies have investigated the muscle function and structure of individuals with RYR1-related rhabdomyolysis/myalgia objectively, showing inconsistent results. This study aimed to describe structural changes and contractility of muscles in individuals with RYR1-related rhabdomyolysis/myalgia.</p><p><strong>Methods: </strong>We investigated 15 individuals with dominant variants in the RYR1-gene and compared them with 15 age-, sex-, and body mass index (BMI)-matched controls using MRI, stationary isokinetic dynamometry, and comprehensive clinical evaluation.</p><p><strong>Results: </strong>No significant differences were found between individuals with RYR1-related rhabdomyolysis/myalgia and healthy controls in peak torque, fat fraction, cross-sectional area, contractile cross-sectional area, or contractility (p > .05) in muscles of the lower back (MRI data only), thigh, or calf. On clinical examination, three individuals exhibited weakness in hip or back extension on the Medical Research Council (MRC) test and eight had muscle hypertrophy. Individuals with weakness were not hypertrophic.</p><p><strong>Discussion: </strong>Most individuals with RYR1-related rhabdomyolysis/myalgia have close to normal strength, and normal fat fraction and contractility of muscles, and therefore constitute a mild phenotype of RYR1-related myopathies.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"753-760"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of voluntary and stimulated neuromuscular jitter studies in ocular myasthenia gravis.","authors":"Giuseppe Cosentino, Paolo Prunetti, Giulia Tammam, Chiara Zaffina, Matteo Gastaldi, Cristina Tassorelli, Enrico Alfonsi, Massimiliano Todisco","doi":"10.1002/mus.28202","DOIUrl":"10.1002/mus.28202","url":null,"abstract":"<p><strong>Introduction/aims: </strong>There is a lack of studies comparing the accuracy of neuromuscular jitter analysis during voluntary activation (v-jitter study) versus axonal stimulation (s-jitter study). The study aimed to compare these two techniques in the same population of patients with suspected ocular myasthenia gravis (OMG).</p><p><strong>Methods: </strong>Fourteen control subjects (mean age: 55.5 ± 15.2 years) and 34 patients with suspected OMG (mean age: 59 ± 13.9 years) were prospectively evaluated. Twenty spike pairs and 30 individual spikes were analyzed during v-jitter and s-jitter study, respectively. Two different criteria for abnormal individual jitter values were evaluated: ≥ or > than 10% values exceeding the upper normal limit.</p><p><strong>Results: </strong>OMG was diagnosed in 19 patients based on clinical and laboratory findings, without considering jitter measurements. In most patients, v-jitter and s-jitter analyses provided comparable results. The maximum sensitivity (89%) was achieved with s-jitter study using the ≥10% criterion, while the maximum specificity (93%) was found with v-jitter study using the >10% criterion.</p><p><strong>Discussion: </strong>Both v-jitter and s-jitter studies showed good to very good accuracy for the diagnosis of OMG, in the absence of any statistically significant difference. Therefore, the patient's cooperation level and examiner's experience should guide the choice of performing v-jitter or s-jitter analysis in patients with suspected OMG.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"733-743"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in corneal nerve fiber density and fiber length in patients with painful chronic idiopathic axonal polyneuropathy and diabetic polyneuropathy.","authors":"Mariska D Nieuwenhoff, Hoang-Ton Nguyen, Sjoerd P Niehof, Frank J P M Huygen, Ajay Verma, Erica S Klaassen, Malik Bechakra, Wouter J Geelhoed, Joost L M Jongen, Annette C Moll, Alexander F J E Vrancken, Axel Petzold, Geert Jan Groeneveld","doi":"10.1002/mus.28213","DOIUrl":"10.1002/mus.28213","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Corneal confocal microscopy (CCM) detects small nerve fiber loss and correlates with skin biopsy findings in diabetic neuropathy. In chronic idiopathic axonal polyneuropathy (CIAP) this correlation is unknown. Therefore, we compared CCM and skin biopsy in patients with CIAP to healthy controls, patients with painful diabetic neuropathy (PDN) and diabetics without overt neuropathy (DM).</p><p><strong>Methods: </strong>Participants with CIAP and suspected small fiber neuropathy (n = 15), PDN (n = 16), DM (n = 15), and healthy controls (n = 16) underwent skin biopsy and CCM testing. Inter-center intraclass correlation coefficients (ICC) were calculated for CCM parameters.</p><p><strong>Results: </strong>Compared with healthy controls, patients with CIAP and PDN had significantly fewer nerve fibers in the skin (IENFD: 5.7 ± 2.3, 3.0 ± 1.8, 3.9 ± 1.5 fibers/mm, all p < .05). Corneal nerve parameters in CIAP (fiber density 23.8 ± 4.9 no./mm², branch density 16.0 ± 8.8 no./mm², fiber length 13.1 ± 2.6 mm/mm²) were not different from healthy controls (24.0 ± 6.8 no./mm², 22.1 ± 9.7 no./mm², 13.5 ± 3.5 mm/mm², all p > .05). In patients with PDN, corneal nerve fiber density (17.8 ± 5.7 no./mm²) and fiber length (10.5 ± 2.7 mm/mm²) were reduced compared with healthy controls (p < .05). CCM results did not correlate with IENFD in CIAP patients. Inter-center ICC was 0.77 for fiber density and 0.87 for fiber length.</p><p><strong>Discussion: </strong>In contrast to patients with PDN, corneal nerve parameters were not decreased in patients with CIAP and small nerve fiber damage. Therefore, CCM is not a good biomarker for small nerve fiber loss in CIAP patients.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"782-790"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.","authors":"Johnnie Turner, Christine C Bruels, Audrey L Daugherty, Elicia A Estrella, Seth Stafki, Safoora B Syeda, Hannah R Littel, Lynn Pais, Vijay S Ganesh, Hart G W Lidov, Simon M L Paine, Paul Maddison, Rachel E Harrison, Volker Straub, Partha S Ghosh, Christina A Pacak, Louis M Kunkel, Isabelle Draper, Ana Topf, Peter B Kang","doi":"10.1002/mus.28214","DOIUrl":"10.1002/mus.28214","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.</p><p><strong>Methods: </strong>Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES).</p><p><strong>Results: </strong>The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.</p><p><strong>Discussion: </strong>Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"843-850"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788666","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":"Myasthenia gravis Lambert-Eaton overlap syndrome: Recommended modification for the diagnostic criteria.","authors":"Shin J Oh","doi":"10.1002/mus.28221","DOIUrl":"10.1002/mus.28221","url":null,"abstract":"<p><p>In 2016, MLOS (myasthenia gravis Lambert-Eaton overlap syndrome) was coined to represent an entity of overlap syndrome of myasthenia gravis and Lambert-Eaton myasthenic syndrome. Fifty-five MLOS patients have been identified. Modification of the diagnostic criteria for MG by adding MuSK positive antibody testing is recommended. Two MuSK positive MLOS patients were identified by the new diagnostic criteria.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"731-732"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible sex and racial disparities in myasthenia gravis care.","authors":"Shriya Suresh, Maya Watanabe, Evan L Reynolds, Brian C Callaghan","doi":"10.1002/mus.28215","DOIUrl":"10.1002/mus.28215","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Given the importance of early diagnosis and treatment of myasthenia gravis (MG), it is critical to understand disparities in MG care. We aimed to determine if there are any differences in testing, treatment, and/or access to neurologists for patients of varying sex and race/ethnicity with MG.</p><p><strong>Methods: </strong>We used a nationally representative healthcare claims database of privately insured individuals (2001-2018) to identify incident cases of MG using a validated definition. Diagnostic testing, steroid-sparing agents, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and thymectomy were defined using drug names or CPT codes. Steroid use was defined using AHFS class codes. We also determined whether an individual had a visit to a neurologist and the time between primary care and neurologist visits. Logistic regression determined associations between sex and race/ethnicity and testing, treatments, and access to neurologists.</p><p><strong>Results: </strong>Female patients were less likely to get a computed tomography (CT) chest (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.64-0.83), receive steroids (OR: 0.85, 95% CI: 0.75-0.97), steroid-sparing agents (OR: 0.84, 95% CI: 0.72-0.97), and IVIG or PLEX (OR: 0.80, 95% CI: 0.67-0.95). Black patients were less likely to receive steroids (OR: 0.78, 95% CI: 0.63-0.96). No significant disparities were seen in access to neurologists.</p><p><strong>Discussion: </strong>We found healthcare disparities in MG treatment with female and Black patients receiving less treatment than men and those of other races/ethnicities. Further research and detailed assessments accounting for individual patient factors are needed to confirm these apparent disparities.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"791-799"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No sex-based differences in odds of starting or time to treatment of generalized myasthenia gravis: A single center cohort study.","authors":"Benjamin Beland, Tefani Perera, Angela Lee, Jamie Greenfield, Lawrence Korngut, Gordon Jewett","doi":"10.1002/mus.28210","DOIUrl":"10.1002/mus.28210","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Females with generalized myasthenia gravis (gMG) report lower quality of life (QoL) and have more severe disease than males. Sex differences in disease characteristics exist, however whether there are sex differences in the treatment of gMG that may contribute to QoL disparities is unknown. Our objective is to determine whether there are sex differences in the treatment of gMG.</p><p><strong>Methods: </strong>We performed a single-center retrospective study of people diagnosed with gMG at the University of Calgary between 1997 and 2021. Primary outcome was proportion starting treatment and secondary outcome was time from diagnosis to treatment initiation. Treatments included pyridostigmine, prednisone, steroid sparing therapies (azathioprine, mycophenolate mofetil [MMF], methotrexate [MTX], or tacrolimus), intravenous immunoglobulin (IVIg), plasmapheresis, rituximab, eculizumab, cyclosporine, stem cell transplantation, and thymectomy. Multivariable logistic and Cox proportional hazards regression models were used to examine treatment associations with sex, adjusted for time from onset to diagnosis, age at diagnosis, presence of thymoma, and antibody status.</p><p><strong>Results: </strong>A total of 179 people with gMG were included (41.9% female). Odds of starting treatment were not statistically associated with sex after adjustment for confounders and correction for multiple testing. Results of the secondary analysis using time to treatment initiation as the outcome were similar.</p><p><strong>Discussion: </strong>We found no sex differences in odds of starting treatment or time to treatment initiation that might explain previously observed sex-based differences in QoL. Future work should capture physician and patient treatment preferences that may influence disease management.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"774-781"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759953","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}