Muscle & Nerve最新文献

Introduction/aims: Amyotrophic lateral sclerosis (ALS) lacks reliable biomarkers to predict disease trajectories or guide therapeutic strategies. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase implicated in cytoskeletal destabilization and neuroinflammatory pathways in preclinical ALS models, represents a promising yet unvalidated biomarker candidate. We aimed to translate preclinical findings by validating SIRT2's role in ALS.

Methods: A cross-sectional cohort study was conducted, comparing serum SIRT2 levels, measured via enzyme-linked immunosorbent assay (ELISA), between 182 ALS patients and 65 healthy controls. Clinical progression rates were derived from the ALS Functional Rating Scale-Revised (ALSFRS-R), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

Results: SIRT2 levels were significantly elevated in ALS patients versus controls, though diagnostic accuracy was modest (AUC = 0.620). Furthermore, SIRT2 levels showed a weak but significant positive correlation with disease progression rate (r = 0.182, p = 0.014) and inverse correlations with cognitive scores on both MMSE (r = -0.250, p = 0.032) and ECAS (r = -0.286, p = 0.031). Notably, SIRT2 demonstrated a limited but detectable ability to stratify patients into fast- and slow-progressing subgroups (AUC = 0.635).

Discussion: These findings provide preliminary clinical evidence linking elevated serum SIRT2 to disease progression and cognitive impairment in ALS, thereby supporting its role in disease heterogeneity. This work lends clinical support to preclinical insights, suggesting SIRT2 may aid in prognosis prediction and may represent a potential therapeutic target, necessitating further studies.

Introduction/aims: It has been demonstrated that muscle echo intensity quantification and needle electromyography (EMG) produce disparate results. The aim of this study was to investigate whether a more detailed muscle ultrasound texture analysis is associated with electrophysiological parameters in EMG.

Methods: We retrospectively analyzed muscle ultrasound and EMG data from consecutive subjects > 18 years of age suspected of myopathy or neurogenic disease, and healthy controls. Muscles with inconsistent ultrasound presets or missing EMG data were excluded. Texture parameters encompassed grayscale level histograms, second-order features (contrast, entropy, correlation), and higher-order features (short-run frequency and gray-level distribution, local entropy). EMG data included motor unit size index (SI), polyphasia, recruitment, and the presence of active denervation.

Results: We analyzed 156 muscles from 64 individuals (median age 55 years [IQR 45-69], 51% female). In neurogenic processes the SI correlated moderately and positively with contrast (r = 0.62, p = 0.002), whereas reduced recruitment was associated with a higher frequency of short runs. In non-inflammatory myopathies polyphasia was moderately and negatively correlated with entropy (r = -0.46, p = 0.003), while in inflammatory myopathies brightness correlated weakly and negatively with SI (r = -0.39, p = 0.014) and was increased in muscles that showed active denervation on EMG (p = 0.018).

Discussion: Muscle ultrasound texture parameters correlate with certain EMG findings, possibly reflecting underlying pathology. This study advances the use of ultrasound textural parameters beyond grayscale measurements to potentially bridge the gap between imaging and electrophysiology.

Introduction/aims: Guidelines for the management of chronic inflammatory demyelinating polyneuropathy (CIDP) recommend corticosteroids, intravenous immunoglobulin (IVIg), or plasma exchange for first-line therapies and subcutaneous immunoglobulin (SCIg) as a maintenance option. Literature on clinical experience with SCIg in CIDP maintenance therapy is limited. This study outlines practical approaches to SCIg transition and management optimization, considering the varying dosing recommendations in prescribing information and clinical guidelines.

Methods: This retrospective, multicenter study analyzed anonymized patient medical records from eight US centers. Patients with CIDP who transitioned to SCIg were included, and clinical practices regarding SCIg therapy management were analyzed.

Results: These 20 cases presented practical and clinical considerations for successful SCIg transition and maintenance. Switching decisions were guided by patient-physician assessment of treatment goals, benefits, and risks. The most common reason for switching (70%) was preference for site of care. Eight patients (40%) transitioned to a dose equivalent to their baseline IVIg dose. Overall, 12/19 patients (63%) remained stable following transition. Relapse-free rates were higher in patients who transitioned to a higher (67%) or lower (75%) than baseline dose versus those who received an equivalent dose (50%). All relapsed patients restabilized after increasing their SCIg dose. The final mean (SD) SCIg dose was 0.32 (0.15) g/kg/week. SCIg was well tolerated; 11 patients (55%) reported better tolerance versus IVIg.

Discussion: These patient cases provide practical guidance for SCIg therapy in CIDP maintenance, emphasizing individualized dosing strategies, ongoing monitoring, and patient-centered engagement. The findings help inform clinical decision-making to optimize long-term therapeutic outcomes.

Introduction/aims: A previous publication reported that the number of months of training and the number of patient studies independently influenced examination scores for the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) self assessment examination (AANEM-SAE). The purpose of this study was to explore additional questions regarding how electrodiagnostic (EDx) training impacts AANEM-SAE score.

Methods: This was a retrospective review of the 2024 and 2025 AANEM-SAE results. Participants were asked the number of: patient studies performed, months of training completed, hours of didactic training received, and hours they studied to prepare for the AANEM-SAE. There were also questions regarding neuromuscular ultrasound training.

Results: A total of 1530 participants completed the proctored examinations. Scores steadily improved with additional months of training but leveled off after 300-400 patient studies. Regression analysis indicated that higher numbers of patient studies and higher numbers of didactic training hours and study hours were correlated with higher examination scores even after accounting for the number of months of training. Of the 2025 participants, 56% received training in neuromuscular ultrasound, but most completed no more than 30 patient studies. No association was found between ultrasound training and performance on ultrasound questions, but the number of questions was small.

Discussion: EDx training program directors should continue to emphasize core elements of EDx training and design their curricula with attention to providing sufficient numbers of studies and hours of didactic instruction for trainees.

Introduction/aims: Although classically characterized as a motor neuron disease, spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder. We previously showed hepatocyte-intrinsic steatosis in SMA, raising the question of whether SMA carriers, who are typically asymptomatic, may also exhibit subclinical hepatic abnormalities.

Methods: We generated induced hepatocyte-like cells (iHeps) from induced pluripotent stem cells (iPSCs) derived from an SMA Type 2 proband, his isogenic wild-type (Iso-WT) line, and both carrier parents, comprised of three carrier lines from the father and one from the mother. Steatosis was assessed by Oil Red O staining and image analysis. Survival motor neuron (SMN) expression was evaluated by immunoblotting. Proteotranscriptomic profiling and mitochondrial respiration assays were performed. Risdiplam, an SMN2 splicing modulator, was used to assess reversibility of observed phenotypes.

Results: SMA and carrier iHeps demonstrated increased lipid accumulation compared to Iso-WT. Risdiplam reduced steatosis by 65.9% in SMA patient-derived iHeps and by 43.6% and 56.9% in father- and mother carrier-derived iHeps, respectively. Carrier and SMA iHeps exhibited downregulation of genes involved in lipid metabolism and liver function, along with altered expression of lipid-related proteins. Mitochondrial dysfunction was present only in SMA iHeps. Carrier-derived induced motor neurons showed normal viability under oxidative stress, consistent with preserved neuromuscular function clinically.

Discussion: Our data reveal hepatocyte-intrinsic lipid metabolic defects in SMA carriers, partially reversible with risdiplam. These findings suggest subclinical hepatic involvement in carriers and support further investigation into the systemic impact of SMN deficiency.

Introduction/aims: Previous studies of children with spinal muscular atrophy (SMA) have focused on the ulnar and median nerves, while lower-limb and proximal motor nerves remain insufficiently characterized. This study aimed to evaluate compound muscle action potential (CMAP) amplitudes in upper- and lower-limb motor nerves in children with SMA and changes after nusinersen treatment.

Methods: In this single-center retrospective study, CMAP amplitudes were collected from children with SMA and age-matched controls without neuromuscular disease. CMAP amplitudes of the tibial, peroneal, femoral, median, and ulnar nerves were assessed in children with SMA types 1-3. A cross-sectional analysis was conducted to assess CMAP amplitudes prior to treatment. Longitudinal changes after SMA disease-modifying therapies (nusinersen monotherapy or nusinersen plus risdiplam treatment) were evaluated.

Results: A total of 47 children with SMA were included. The baseline CMAP amplitudes of the peroneal, tibial, median, and ulnar nerves were the highest in type 3, followed by type 2, and lowest in type 1. Femoral nerve CMAP amplitudes were low in all SMA subtypes. At preliminary diagnosis, children with SMA had significantly reduced CMAP amplitudes for the five nerves compared with age-matched controls (n = 63, p < 0.05). After 18 months of nusinersen treatment, CMAP amplitudes showed significant increases from baseline in the peroneal, femoral, median, and ulnar nerves (p < 0.05).

Discussion: CMAP amplitudes can differentiate SMA disease severity and may increase after nusinersen treatment. Large-scale longitudinal studies are required to investigate CMAP amplitude as a biomarker of treatment response in patients with SMA.

Introduction/aims: Effective management remains lacking for recurrent episodes of acute weakness in hypokalemic periodic paralysis (HypoPP). We assessed the efficacy of a second-generation potassium channel agonist, XEN1101, to prevent and abort the low-K⁺ induced loss of force in mouse models of HypoPP.

Methods: An ex vivo contractility assay was used to interrogate the efficacy of XEN1101 for preserving contractile force and for enhancing recovery of force in the setting of a low-K⁺ challenge for HypoPP mice carrying the sodium channel Na_V1.4-R669H or the calcium channel Ca_V1.1-R528H mutations.

Results: The acute loss of force for HypoPP muscle, triggered by a 2 mM K⁺ challenge, was prevented by low micromolar XEN1101, with an effective concentration of 0.30 μM for 50% protection. Application of 1 μM XEN1101, after the onset of 2 mM K⁺ induced weakness, restored the peak contractile force (70%-100% of baseline).

Discussion: The K_V7 potassium channel agonist XEN1101 is effective as both a prophylactic agent and as abortive therapy for management of low-K⁺ induced weakness in murine models of HypoPP. XEN1101 is more potent than the first-generation Kv7 agonist, retigabine, in our murine models of HypoPP and is also better tolerated in patients. These improvements provide a rationale for future clinical trials of XEN1101 in HypoPP patients.

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing phase, double support time, and estimated speed of gait were all computed.

Results: Lunar stance was characterized by 13.3 ± 3.6 SD to 14.3 ± 3.9 SD inch base of stance (based on a 6.5 or 7.0 in. shoe width, respectively), 39.3° ± 9.0° hip flexion, 42.2° ± 14.8° knee flexion, and 17.0° ± 7.5° ankle dorsiflexion. Upper torso anterior tilt was 16.4° ± 8.8°. Lunar gait demonstrated 14.0 ± 2.8 SD to 15.1 ± 2.9 SD base of gait, 0.42 ± 0.16 m/s speed of gait, and 15.4 ± 3.3 in. step length with 40% double support time. Stance phase was 69% and swing phase was 31% of the gait cycle.

Discussion: Decreased speed of gait with wide base, short steps, and increased double support time was seen in astronaut gait patterns. This pattern is adopted on Earth to increase stability and prevent falls.

Introduction/aims: Amyotrophic lateral sclerosis (ALS) affects military veterans at a higher rate than the general civilian population. The aim of the present study is to assess symptom burden and satisfaction with care among persons with ALS care enrolled in the US Veterans Health Administration (VA).

Methods: A custom online survey was created with questions about symptom prevalence and management as well as care satisfaction. A survey link was sent by email to all veterans with an ICD-10 diagnosis of ALS in the VA for whom an email address was available in the electronic health record.

Results: Responses were received from 413 individuals (16% response rate). Respondents reported high care satisfaction and higher prevalence of treatment of symptoms compared to prior surveys of persons with ALS in the United States. Self-reported outcomes, including treatment, education, and satisfaction, were better for Veterans receiving care exclusively within the VA compared to those receiving care at both VA and non-VA facilities or receiving care exclusively at non-VA facilities. Areas for further improvement identified in the survey include education on genetic testing and research and management of non-motor symptoms.

Discussion: This survey indicates that, overall, veterans with ALS receive comprehensive symptom-based care within the nationalized VA care system and report high levels of satisfaction. Furthermore, this study provides baseline data and findings that may be used for quality improvement efforts across a large healthcare system and may serve as a model for similar efforts in other health systems.

Introduction/aims: While neurofilament light chain is a promising biomarker in spinal muscular atrophy (SMA), its dynamics in presymptomatic patients have not yet been determined. This study aimed to analyze the plasma neurofilament light chain (pNfL) as a treatment response biomarker in patients with presymptomatic spinal muscular atrophy (SMA) undergoing nusinersen treatment.

Methods: Eight 5q-SMA patients with three SMN2 copies (four presymptomatic patients from newborn screening and four symptomatic patients) were prospectively enrolled from August 2022 to June 2023. All patients received nusinersen treatment and were followed up for 660 days. pNfL levels were measured at baseline and throughout the treatment, analyzing their temporal changes and correlation with motor function outcomes.

Results: At baseline, presymptomatic patients exhibited higher pNfL levels than symptomatic patients (388.74 ng/L vs. 113.60 ng/L). During the loading phase, pNfL levels decreased markedly in both groups, with greater reductions in presymptomatic patients (94.64% vs. 79.50%). All presymptomatic patients achieved age-appropriate motor milestones. Decreased pNfL levels correlated moderately with motor function improvements, as measured by CHOP INTEND (r = -0.548, p < 0.01) and HINE-2 scores (r = -0.635, p < 0.01).

Discussion: pNfL is a promising biomarker for monitoring treatment response in patients with presymptomatic SMA, highlighting the importance of early diagnosis and treatment through newborn screening.