Neuromuscular Disorders最新文献

Spinal muscular atrophy types 2 and 3 encompass a wide spectrum of motor abilities ranging from non-sitting to sitting and walking. This study refines a functional group termed high functioning sitter-standers, positioned between traditional categories, and examined in relation to both the Revised Hammersmith Scale and a World Health Organization motor milestone-based framework. Among 178 participants completing 618 assessments, 109 were classified as type 2, 59 as type 3a, and 10 as type 3b, with ages ranging from 1 to 17.5 years. Twenty-seven non-sitters completed 54 assessments, 110 sitters completed 347, and 50 walkers completed 169, while the high functioning sitter-standers accounted for 48 assessments of 21 individuals. This newly defined group scored significantly lower than walkers and higher than both sitters and non-sitters, highlighting a distinct and measurable functional profile. Although no significant differences in age distribution were observed between the high functioning sitter-standers and walkers or non-sitters, sitters were notably younger. This intermediate phenotype captures patients with partial standing and assisted walking abilities, often overlooked in previous analyses. Recognition of this group is important for understanding emerging functional trajectories in treated spinal muscular atrophy and for informing future outcome measures and quality of life assessments.

Immune-mediated necrotizing myopathy (IMNM) associated with antibodies against 3‑hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is typically a severe autoimmune myopathy requiring immunosuppressive therapy. Rare spontaneous remissions after discontinuation of statins have been reported, suggesting that the disease course may be more heterogeneous than previously assumed. We retrospectively identified four patients with anti-HMGCR-positive IMNM who experienced full recovery without immunosuppressive treatment. All had developed proximal muscle weakness and markedly elevated creatine kinase levels (8-80 times the upper limit of normal) during statin therapy, and they fulfilled the histopathological criteria of IMNM, except for the p62-pattern. After statin withdrawal, all patients recovered within 6-12 months without specific treatment. Two later relapsed after statin re-exposure and again improved after statin discontinuation. One patient relapsed after a flu-like illness. During long-term follow-up of up to ten years, three patients remained asymptomatic, two despite persistently elevated antibody titers, and one patient was started on intravenous immunoglobulins. These findings indicate that a subset of anti-HMGCR IMNM may follow a self-limited or relapsing-remitting course. While these cases broaden the clinical spectrum of anti-HMGCR IMNM, their implications for management remain uncertain and warrant further investigation.

We report clinical and genetic features in four patients from 3 independent families with an ultra-rare autosomal recessive myopathy associated with biallelic pathogenic or likely pathogenic variants in MSTO1. Exome or genome sequencing was used to identify genetic variants in patients with suspected hereditary myopathy who had negative results on targeted genetic panels. Age at diagnosis ranged from 13 to 30 years. All patients exhibited myopathy of variable severity. Two had congenital hypotonia and global developmental delay, while the remaining two developed muscle weakness at ages 2 and 5. Magnetic resonance imaging evidence of cerebellar atrophy was noted in Patient 3. The most common non-neurologic abnormality noted in our cases was skeletal abnormalities. MSTO1-related disease presents primarily as an early-onset myopathy, occasionally accompanied by cerebellar atrophy and skeletal abnormalities. As genome-wide sequencing is increasingly becoming a first line test for unexplained myopathy, further characterization of the phenotypic spectrum is likely.

Dysphagia often threatens the health of individuals with inclusion body myositis (IBM), significantly contributing to premature mortality. Quality evidence defining IBM-associated dysphagia remains scant and restricted to reports of limited utility. To address this gap, our group recently published a preliminary dysphagia profile for IBM using semi-quantitative impression-based kinematic analysis. In the current study, we offer updated evidence that combines our prior approach with quantitative pharyngeal kinematic analysis to better delineate swallowing features associated with dysphagia in IBM. This prospective, cross-sectional study leveraged the Modified Barium Swallow Impairment Profile (MBSImP) and the Analysis of Swallowing Physiology: Events, Kinematics & Timing (ASPEKT) method to perform videofluoroscopic kinematic analysis. We analyzed data from 15 individuals with IBM-associated dysphagia (9 males; mean age = 72.7 years [SD = 5.9]), compared their performance against normative data, and identified measures of clinical concern. A constellation of kinematic disruptions emerged across the swallowing continuum, but pharyngeal impairments were most pervasive and diffuse. Both MBSImP and ASPEKT findings suggest that bolus clearance mechanics were the primary or early culprit. Nonetheless, we identified subclinical airway response deficiencies that warrant clinical monitoring. This evidence provides new quantitative insights into better understanding IBM-associated dysphagia that can meaningfully guide targeted treatment.

We determined the proportion of adults with late-onset Pompe disease (LOPD) with clinically important changes in 6-minute walk distance (6MWD) and/or forced vital capacity (FVC) after switching from alglucosidase alfa (alg) to cipaglucosidase alfa plus miglustat (cipa+mig) in PROPEL (NCT03729362). This post hoc analysis (95 patients) used published anchor- and distribution-based minimal clinically important differences for 6MWD (in meters for anchor-based; % predicted for distribution-based) and a 3 % threshold for FVC (% predicted). For 6MWD, a higher percentage of patients improved after switching to cipa+mig versus alg plus placebo (alg+pbo) (anchor-based: 29.2 % versus 13.3 %; distribution-based: 33.8 % versus 13.3 %), fewer patients worsened (anchor-based: 12.3 % versus 26.7 %; distribution-based: 7.7 % versus 13.3 %). For FVC, 27.7 % versus 0.0 % improved for cipa+mig versus alg+pbo, 27.7 % versus 53.3 % worsened. Overall, 50.8 % versus 13.3 % of patients experienced improvements in 6MWD (% predicted) and/or FVC with cipa+mig versus alg+pbo, 30.8 % versus 56.7 % worsened. For combined responses from 6MWD (% predicted) and FVC (% predicted), the odds of a better versus a lower response category (improvement > stability > worsening) were 4.05 (95 % confidence interval 1.73-9.51) times higher for cipa+mig than alg+pbo (P = 0.0013). Adults with LOPD switching from alg to cipa+mig have greater chances of clinically relevant motor and lung function improvements than those remaining on alg.

Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid α-glucosidase deficiency, leading to glycogen accumulation in skeletal muscle. Reliable biomarkers for monitoring disease progression and treatment response are lacking. Urinary glucose tetrasaccharide (Glc4), a marker of glycogen turnover, is well established in infantile-onset Pompe disease, but its prognostic value in LOPD under longitudinal real-world conditions remains uncertain. Urinary Glc4 was evaluated in 35 genetically confirmed LOPD patients followed for four years with annual functional assessments, spirometry, and quantitative muscle MRI. Glc4 was measured by liquid chromatography-tandem mass spectrometry and normalized to creatinine. Associations with changes in six-minute walk test (6MWT), forced vital capacity (FVC), and thigh fat fraction (FF) were analyzed. Receiver operating characteristic (ROC) analysis assessed the ability of baseline Glc4 to predict clinically meaningful motor decline (>30 m reduction in 6MWT). Multivariate linear regression evaluated whether baseline Glc4 independently predicted 6MWT decline. Glc4 levels were elevated in all patients and showed considerable intra-individual variability. Higher baseline Glc4 was associated with greater functional decline and increased muscle fat replacement. ROC analysis showed good predictive performance (AUC 0.78), with an optimal threshold of approximately 13 mmol/mol creatinine. Baseline Glc4 remained an independent predictor of 6MWT decline in multivariate analysis (p = 0.042). Baseline urinary Glc4 provides relevant prognostic information in LOPD and may serve as a complementary biomarker for routine disease monitoring.