Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
BMC cardiovascular disorders
Clinical spectrum, cardiac phenotypes, and outcomes of FHL1-related cardiomyopathies: a systematic review
BACKGROUND: Mutations in the Four-and-a-Half LIM Domains 1 (FHL1) gene are increasingly recognized as a rare cause of inherited cardiomyopathies, often associated with skeletal myopathy and adverse cardiac outcomes. The phenotypic spectrum and clinical implications of FHL1 variants remain poorly defined. OBJECTIVE: To systematically review published cases of FHL1-related cardiomyopathy and characterize the clinical, genetic, and pathological features. METHODS: We conducted a systematic literature search in PubMed and EMBASE up to July 2025 using predefined criteria to identify studies reporting clinical cases of patients with FHL1 mutations and cardiac involvement. Data on genotype, phenotype, cardiac and neuromuscular features, and clinical outcomes were extracted and synthesized. RESULTS: Twenty-two studies were included, comprising 114 patients with pathogenic or likely pathogenic FHL1 mutations. Most patients were male (69%), with a median age of onset of 18 (IQR 10-26) years. Cardiac involvement consisted in left ventricular hypertrophy (56%), followed by arrhythmias (51%), and conduction abnormalities (8%). The incidence of sudden cardiac death was 7%, and heart transplantation was reported in 5% of patients. Skeletal muscle involvement was present in 75%, ranging from mild contractures to more severe myopathic phenotypes with functional impairment. Creatine kinase levels were variably elevated. Truncating variants were reported in several severe cardiac presentations in young males, while isolated cardiac disease occurred with selected variants. CONCLUSIONS: FHL1-related cardiomyopathy is a rare but important diagnosis. Genetic testing should be considered in patients with cardiac hypertrophy and neuromuscular features. Further research is needed to define prognostic markers and guide management.
19 June 2026
Read appraisal →Neurology
Vamorolone Safety, Pharmacokinetics, and Exploratory Efficacy in Duchenne Muscular Dystrophy: A Phase II, Nonrandomized, Multiple-Dose Study in 2-<4-Year-Old Boys
BACKGROUND AND OBJECTIVES: Vamorolone is a dissociative corticosteroid (CS) approved by the US Food and Drug Administration in 2023 for treating Duchenne muscular dystrophy (DMD). This study evaluated the safety, tolerability, and pharmacokinetics (PK) of vamorolone in young boys with DMD; exploratory objectives included efficacy and patient-reported outcomes. METHODS: A 12-week, phase II, open-label, multiple-dose study (VBP15-006) enrolled CS-naive boys with DMD aged 2-<4 years in Canada. Participants received 2 or 6 mg/kg/d oral vamorolone. An ongoing expanded access protocol (EAP) provided longer-term data. Primary end points were the occurrence of treatment-emergent adverse events (TEAEs) and changes from baseline to week 12 in height, weight, and body mass index (BMI); other end points included PK and effects of vamorolone on muscle function. RESULTS: Twenty boys (mean age [SD] 3.4 [0.39] years) with similar baseline characteristics were enrolled; all completed VBP15-006 and 19 continued to receive vamorolone through EAP Canada. TEAEs were mostly mild, with no deaths, serious TEAEs, or TEAEs leading to drug discontinuation during VBP15-006. TEAEs were more frequent with 6 mg/kg/d vamorolone than with 2 mg/kg/d, with gastrointestinal disorders and infections/infestations, respectively, most reported. Vamorolone use was associated with morning serum cortisol reductions in all patients, more pronounced with 6 mg/kg/d. Stable growth trajectories were observed at both doses throughout VBP15-006 and the EAP Canada follow-up period, with a total median (Q1; Q3) exposure to vamorolone of 2 years (1.7; 2.3). By EAP Canada last visit, 8/19 patients had weight and BMI z-scores changes >0.5, suggestive of excessive weight gain over time. Vamorolone displayed a dose-dependent PK profile with rapid absorption and no accumulation. Dose-dependent improvements in motor function (measured by Bayley-III gross motor scaled score) were observed. Glucose metabolism and bone turnover biomarkers remained stable. Ease of administration was rated favorably. DISCUSSION: Vamorolone was well tolerated in 2-<4-year-old boys with DMD, with no new safety concerns identified. A dose-dependent PK profile was observed, consistent with previous studies. Exploratory evidence suggested dose-dependent improvements in gross motor function. These findings are consistent with potential therapeutic benefit of vamorolone for young boys with DMD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT05185622 (VBP15-006; clinicaltrials.gov/study/NCT05185622), NCT03863119 (EAP; clinicaltrials.gov/study/NCT03863119). First submitted November 9, 2021. First patient enrolled: March 21, 2022. CLASSIFICATION OF EVIDENCE: The VBP15-006 study provides Class IV evidence that in boys with DMD aged 2-<4 years, 12-week treatment with vamorolone was not associated with serious adverse events or changes in weight, height, or BMI. Gastrointestinal events and infections were the most reported TEAEs.
9 June 2026
Read appraisal →Neurology
Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial
BACKGROUND AND OBJECTIVES: Vamorolone demonstrated similar efficacy for Duchenne muscular dystrophy (DMD) compared with prednisone in a 24-week exploratory analysis and may reduce key side effects compared with classic corticosteroids. In this study, we compare the efficacy and anthropometric effect of vamorolone 6 mg/kg/d with prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d in steroid-naïve boys aged 4 to <7 years using data from 2 trials. METHODS: VISION-DMD was a phase 2b, 48-week randomized, double-blind trial assessing vamorolone 2 and 6 mg/kg/d vs placebo and prednisone 0.75 mg/kg/d to 24 weeks. Finding the Optimum Steroid Regimen for DMD (FOR-DMD) was a double-blind, parallel-group randomized trial comparing daily prednisone 0.75 mg/kg/d, daily deflazacort 0.9 mg/kg/d, and intermittent prednisone 0.75 mg/kg (10/10 days on/off). Entropy balancing generated weighted data for mixed model for repeated measures analyses that compared VISION-DMD vamorolone 6 mg/kg/d efficacy and anthropometric outcomes with FOR-DMD prednisone and deflazacort outcomes at 6 and 12 months. Inclusion criteria were boys with genetically confirmed DMD, age 4 to <7 years, ambulatory, and able to complete a time-to-stand (TTSTAND) assessment in <10 seconds at baseline. RESULTS: All interventions showed motor improvements relative to baseline at 6 and 12 months. Using the weighted cohorts and at 12 months, vamorolone 6 mg/kg/d (n = 28) had similar changes in TTSTAND velocity, the primary motor endpoint component in both trials, vs daily prednisone (n = 50) or deflazacort (n = 55; mean baseline age 5.42 years all groups), but with CIs overlapping minimal clinically important thresholds of 0.023 rises per second (TTSTAND velocity least squares mean [LSM] difference [95% CI]: vamorolone 6 mg/kg/d vs prednisone 0.75 mg/kg/d, 0.004 rises per second [-0.025 to 0.032] and vs deflazacort 0.9 mg/kg/d, 0.001 rises per second [-0.027 to 0.028]). Body mass index (BMI) Z-scores increased in all groups, greatest with vamorolone (12-month LSM difference [95% CI]: vamorolone vs prednisone 0.57 [0.24-0.90]; vamorolone vs deflazacort 0.29 [0.03-0.56]), whereas growth slowdown occurred in prednisone- and deflazacort-treated boys but not vamorolone (12-month LSM difference in height Z-scores [95% CI]: vamorolone vs prednisone 0.57 [0.24-0.90]; vamorolone vs deflazacort 0.72 [0.53-0.91]). DISCUSSION: Vamorolone demonstrated numerically similar TTSTAND velocity changes to prednisone and deflazacort at 1 year; however, interpretations of differences are limited by 95% CIs crossing minimally important difference thresholds. Further evidence of the growth-protective effect of vamorolone was observed; however, all treatments increased BMI. Vamorolone provides a linear growth-protective classic corticosteroid alternative. TRIAL REGISTRATION INFORMATION: NCT03439670; NCT01603407. CLASSIFICATION OF EVIDENCE: This Class III study did not definitively identify differences in efficacy between vamorolone and classic corticosteroids but found that vamorolone protects linear growth in boys with DMD.
30 May 2026
Read appraisal →PloS one
Deep Learning outperforms physicians in myopathy and neuropathy classification based on Needle Electromyography Signal
Needle electromyography (nEMG) is a valuable tool for diagnosing patients with neuromuscular diseases. However, it is labor-intensive and is prone to diagnostic inaccuracies stemming from human biases. To address these challenges, we validated an nEMG diagnosis-aiding system with minimal preprocessing using deep learning model to classify patients into three categories: normal, myopathy, and neuropathy. Using 376 nEMG signals from 57 patients from a tertiary university hospital database through nested k-fold cross validation, deep learning model surpassed the classification performance of six electromyographers. The median patient classification accuracy, precision, sensitivity, and specificity of the deep learning model was 0.70, 0.70, 0.70, and 0.85, respectively, whereas those of the physicians were 0.55, 0.60, 0.54, and 0.78, respectively. Model interpretability and failure analysis showed that the deep learning model classifies based on relevant signal features. Despite higher accuracy of DL model, the number of unanimously misclassified cases were higher in the DL model than physicians. Our study validates deep learning is a fast, accurate, and practical application to aid physicians in diagnosing patients using nEMG signals.
20 May 2026
Read appraisal →The New England journal of medicine
A Phase 3 Trial of Brepocitinib in Dermatomyositis
BACKGROUND: Brepocitinib is a first-in-class, oral, selective TYK2-JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence. RESULTS: A total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, -2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial. CONCLUSIONS: In adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.).
15 May 2026
Read appraisal →European journal of pediatrics
Machine learning-based integration of respiratory oscillometry and spirometry for predicting clinical outcomes in spinal muscular atrophy
UNLABELLED: Assessing respiratory function in spinal muscular atrophy (SMA) is challenging due to the effort-dependent nature of traditional spirometry. While respiratory oscillometry offers a passive alternative, its clinical utility in predicting clinical status remains underexplored. This study evaluates the efficacy of integrating spirometric and respiratory oscillometric indices through machine learning (ML) to predict ambulatory status and the requirement for bilevel positive airway pressure (BiPAP) in SMA patients. We retrospectively analyzed forty-five patients with a genetically confirmed diagnosis of SMA. To address data imbalance, we utilized the SMOTETomek technique and validated Random Forest models through leave-one-out cross-validation. SHAP (SHapley Additive exPlanations) analysis was used to interpret the contribution of individual physiological markers. In univariate logistic regression, forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory flow at 75% of vital capacity (FEF75) were significant predictors for walking support. FEF25, FEF50, FEF75, and FEF 25-75 were associated with the requirement for BiPAP use. None of the respiratory oscillometric parameters reached statistical significance in regression models. However, ML models achieved high predictive accuracy, with SMOTETomek improving BiPAP requirement recall from 0.00 to 1.00. SHAP analysis revealed that respiratory oscillometry gained significant predictive weight that traditional models overlooked. R20Hz emerged as a key predictor for ambulatory status, while R5-20 Hz was identified as a decisive feature for predicting the BiPAP use. CONCLUSION: The integration of effort-independent respiratory oscillometry with traditional spirometry via ML has the potential to enhance risk stratification in SMA. WHAT IS KNOWN: • SMA requires lung function monitoring, but traditional spirometry is challenging due to the need for forceful expiratory maneuvers. • Respiratory oscillometry provides an effort-independent assessment of respiratory mechanics through tidal breathing. WHAT IS NEW: • Machine learning successfully integrates effort-independent respiratory oscillometry with spirometry to significantly enhance clinical predictions in SMA. • It identifies R20Hz and R5-20 Hz as critical physiological markers for predicting ambulatory status and the requirement for respiratory support, respectively.
13 May 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial
BACKGROUND: Autoantibody-mediated complement activation drives pathology in acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis. Newer targeted therapies lower overall antibody concentrations or inhibit complement activity. We aimed to evaluate an siRNA (cemdisiran) targeting complement component 5 (C5) as monotherapy and in combination with a C5 antibody (pozelimab) in generalised myasthenia gravis. METHODS: NIMBLE is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 86 centres in 13 countries. We enrolled patients aged 18 years or older with a diagnosis of generalised myasthenia gravis, positive serology for anti-AChR or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Patients were randomly allocated to receive cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group), pozelimab monotherapy (200 mg every 4 weeks; pozelimab group), combined cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group), or placebo, all administered subcutaneously, during a 24-week double-blind treatment period. The primary endpoint was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set (the first 245 randomly allocated patients who received any dose of study treatment and had at least one post-baseline assessment). A prespecified hierarchal statistical testing strategy was used; multiplicity was controlled for comparisons of cemdisiran versus placebo and combination versus placebo (pozelimab was not statistically tested against placebo and was used only to assess the contribution of components to the combination treatment). Safety was mainly assessed by recording of treatment-emergent adverse events in all patients who received any dose of study treatment. This study is registered with ClinicalTrials.gov (NCT05070858); the current status is active, not recruiting. FINDINGS: Between Jan 20, 2022 and July 18, 2025, 390 participants were screened and, as of the data cut-off presented in this report (July 8, 2025), 284 were randomly allocated to the cemdisiran group (79 [28%] patients), pozelimab group (50 [18%]), combination group (80 [28%]), and placebo group (75 [26%]). Of 277 patients who received any study treatment, 263 (95%) completed the double-blind treatment period. In the mITT primary analysis set, at week 24, the least-squares mean change from baseline in MG-ADL total score was -4·5 (SE 0·4) in the cemdisiran group (n=64), -4·0 (0·4) in the combination group (n=67), and -2·2 (0·5) in the placebo group (n=59). Placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were -2·3 (SE 0·7; 95% CI -3·6 to -1·0; p=0·0005) in the cemdisiran group and -1·7 (0·7; -3·0 to -0·4; p=0·0086) in the combination group. The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group. The most common adverse event in the cemdisiran group was upper respiratory tract infection (nine [12%] of 78 patients), which occurred at a similar incidence in the placebo group (eight [11%] of 70). No serious or meningococcal infections occurred in the cemdisiran group. Adverse events leading to treatment discontinuation occurred in two participants (3%) in the placebo group and one participant (2%) in the pozelimab group. No deaths occurred during the double-blind treatment period. Two deaths occurred after the double-blind treatment period, one of which was assessed as treatment-related by the investigator but not treatment-related by the sponsor. INTERPRETATION: Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis. FUNDING: Regeneron Pharmaceuticals.
10 May 2026
Read appraisal →Journal of neurology
Effect of exercise training on clinical and physiological variables in adults with myotonic dystrophy type 1: a systematic review and meta-analysis
Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disorder characterized by muscle weakness, fatigue, reduced endurance, and impaired quality of life. This systematic review and meta-analysis aimed to evaluate the effects of exercise training on clinical and physiological outcomes in adults with DM1. Six databases were searched for studies published between 2003 and 2023. Randomized controlled trials, quasi-experimental studies, and longitudinal cohort studies involving adults with DM1 undergoing aerobic or resistance training were included, and risk of bias was assessed. Meta-analyses used standardized mean differences with fixed- or random-effects models based on heterogeneity. Fourteen studies were included. Most studies demonstrated low risk of bias. Only one study reported any adverse events, and the incidence of these events was similar in occurrence between the intervention and standard care only groups. Meta-analysis demonstrated a moderate improvement in strength (p = 0.022). Endurance showed a large but non-significant pooled effect (p = 0.14). Meta-analyses for fatigue (p = 0.49) and sleep (p > 0.05) were inconclusive. Narrative synthesis indicated improvements in most clinical and physiological outcomes, while sleep outcomes showed minimal or inconsistent changes across studies. Exercise training appears safe and provides moderate benefits for strength and selected clinical and physiological outcomes in adults with DM1. Future well-powered trials with standardized protocols are needed to optimize exercise prescription.
12 Apr 2026
Read appraisal →Neurology
Efficacy of Pyridostigmine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial
BACKGROUND AND OBJECTIVES: Pyridostigmine, an acetylcholinesterase inhibitor, is a symptomatic drug approved for the treatment of myasthenia gravis (MG), but no randomized controlled trials substantiate its widespread use. We aimed to assess the efficacy and cost utility of pyridostigmine in patients with anti-acetylcholine receptor-positive MG (AChR MG). METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted at Leiden University Medical Center, a tertiary center for the treatment of MG in the Netherlands. Main eligibility criteria were current use of pyridostigmine and a stable dose of other MG treatments. Participants were assigned to a sequence of 2 treatment periods for 5 days separated by a 2-day washout, in which patients either first received placebo and then pyridostigmine, or vice versa. Pyridostigmine dosing matched each participant's prestudy regimen. The primary outcome was change in the Myasthenia Gravis Impairment Index (MGII) score. Secondary efficacy outcome measures included the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, the Quantitative Myasthenia Gravis (QMG) score, and the revised 15-item Myasthenia Gravis Quality of Life (MG-QOL15r) questionnaire. For the post hoc cost-utility analysis, a mathematical model was developed to translate the observed study results into long-term annual effect on societal costs and quality-adjusted life years (QALYs). RESULTS: A total of 19 patients (median age 59 years, 58% female) were recruited between March 23, 2023, and February 21, 2024. The estimated mean difference in the MGII score between pyridostigmine and placebo interventions was 5.3 (95% CI 1.9-8.7, p = 0.004). Secondary efficacy outcome measures showed estimated mean differences of 1.4 (95% CI 0.5-2.3) for the QMG score, 1.2 (95% CI 0.5-1.8) for the MG-ADL score, and 2.0 (95% CI 0.03-3.91) for the MG-QoL15r score. The post hoc cost-utility analysis showed lower annual societal costs (€6,565, 95% CI €328-€15,945) and annual improved QALYs (0.106, 95% CI 0.019-0.210) for patients using pyridostigmine. DISCUSSION: This trial showed that, in patients with AChR MG chronically treated with pyridostigmine, pyridostigmine demonstrated benefit over placebo across all efficacy outcome measures and substantially reduced societal costs. TRIAL REGISTRATION INFORMATION: The trial was registered at EudraCT (2021-004110-20, registration date: July 12, 2022) and ClinicalTrials.gov (NCT05919407, registration date: June 16, 2023). First patient enrolled: March 23, 2023. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, in adults with AChR ab-positive ocular or generalized MG on stable standard-of-care therapy and currently using pyridostigmine, pyridostigmine improves MG symptoms compared with placebo.
9 Apr 2026
Read appraisal →Neurology
Efficacy and Safety of Amifampridine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial
BACKGROUND AND OBJECTIVES: Amifampridine, a short-acting potassium-channel blocker, is the first-line treatment for Lambert-Eaton myasthenic syndrome. Its benefit as add-on to pyridostigmine in acetylcholine receptor (AChR)-positive myasthenia gravis (MG) has been proposed, but no randomized controlled trials have been conducted. We aimed to evaluate the efficacy and safety of amifampridine in AChR-MG with insufficient symptom control on pyridostigmine. METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted at Leiden University Medical Center, a tertiary center for the treatment of MG in the Netherlands, as part 2 of the IMPACT-MG trial. Eligible patients had either completed part 1 (pyridostigmine vs placebo) or failed the initial 2-day pyridostigmine washout, and had an Myasthenia Gravis Impairment Index (MGII) score >10. Participants were randomized (1:1:1) to 1 of 3 treatment sequences. Each treatment period lasted 5 days, with a 2-day washout between treatments, during which participants received either 30 mg or 60 mg of amifampridine modified release, or placebo. The primary outcome was the difference in MGII score between the 2 amifampridine dosages and placebo. Pharmacokinetics, safety, and tolerability were assessed throughout the trial. RESULTS: Between March 2023 and April 2024, 20 patients were enrolled (median age 60 years, 55% female). For the MGII score, the estimated mean differences were -1.0 (95% CI -4.1 to 2.0, p = 0.681) for amifampridine 30 mg vs placebo and -1.7 (95% CI -4.7 to 1.4, p = 0.379) for amifampridine 60 mg vs placebo. No statistically significant association was observed between pharmacokinetic parameters and the MGII. No serious adverse events were reported. Adverse events were more common with amifampridine 30 mg (12 patients [60%]) and 60 mg (15 patients [75%]), compared with placebo (6 patients [30%]), with paresthesia, fatigue, numbness, dizziness, and sleep disturbances most frequently reported. Three patients discontinued amifampridine early due to adverse events. DISCUSSION: The addition of amifampridine to pyridostigmine was not superior to treatment with pyridostigmine alone and was associated with a higher incidence of adverse events. TRIAL REGISTRATION INFORMATION: The trial was registered at EudraCT (2021-004110-20, registration date: July 12, 2022) and ClinicalTrials.gov (NCT05919407, registration date: June 16, 2023). First patient enrolled: March 23, 2023. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with AChRAb+ MG, the addition of amifampridine to pyridostigmine was not superior to treatment with pyridostigmine alone and was associated with a higher incidence of adverse events.
8 Apr 2026
Read appraisal →Journal of neurology
Accuracy of muscle ultrasonography in detecting fasciculations for the diagnosis of amyotrophic lateral sclerosis: a systematic review and meta-analysis
PURPOSE: This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of muscle ultrasonography in detecting fasciculations for the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: Following PRISMA-DTA guidelines, we systematically searched PubMed, Embase, Cochrane Library, Ovid Medline, Sinomed, Web of Science, CNKI and VIP for studies published up to July 8, 2025 that evaluated muscle ultrasonography to detect fasciculations for ALS diagnosis. The study protocol was registered in PROSPERO (CRD420251057866). Studies were screened using predefined inclusion and exclusion criteria and data were extracted. Risk of bias was assessed with QUADAS-2. Statistical analyses (Stata 16.0 and R 4.5.1 with the "midas," "metandi," and "mada" packages) were used to calculate pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). We constructed forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, summary ROC (SROC) curves and calculated the area under the SROC curve (AUC). Univariate meta-regression and subgroup analyses explored sources of heterogeneity. Publication bias was assessed using Deeks' funnel plot asymmetry test. Fagan nomograms were also used to illustrate the changes from pre-test to post-test probability and to enhance clinical interpretability. RESULTS: Thirteen studies involving 1176 participants met the inclusion criteria. Muscle ultrasonography for fasciculation detection in ALS yielded a pooled sensitivity of 0.87 (95% CI 0.83-0.91) and specificity of 0.91 (95% CI 0.86-0.94). The pooled LR+ was 9.81 (95% CI 6.25-15.40) and LR- was 0.14 (95% CI 0.10-0.19), with a DOR of 70.03 (95% CI 41.72-117.56). The area under the SROC curve was 0.94 (95% CI 0.91-0.95). Meta-regression identified scan duration as a primary factor influencing diagnostic accuracy, with scan durations ≥ 30 s associated with higher sensitivity but relatively lower specificity. Deeks' funnel plot showed no significant asymmetry (p = 0.61), indicating no notable publication bias. Fagan nomograms showed that, at a pre-test probability of 30%, the post-test probability increased to 81% after a positive MUS result and decreased to 6% after a negative result. CONCLUSION: Muscle ultrasonography demonstrates good pooled diagnostic accuracy for detecting fasciculations in ALS and may serve as a useful adjunct to electrodiagnostic evaluation. Scan duration appears to significantly affect the diagnostic performance, with longer scanning improving sensitivity at the cost of reduced specificity. We speculate that prolonged scanning may be more useful in clinical scenarios where fasciculations are subtle or atypical, whereas shorter scanning may be sufficient when fasciculations are already readily apparent. Nevertheless, further large-scale prospective studies are needed to validate standardized scanning protocols and to better define the clinical role of MUS in ALS diagnostic pathways.
7 Apr 2026
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