Muscle & Nerve最新文献

Introduction/aims: Although the association between certain lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) has been recognized, the potential mechanism underlying it remains unexplored. This study aimed to identify the metabolic signature indicative of lifestyle factors related to ALS, to examine its association with ALS risk, and to evaluate the mediating effects of muscle strength underlying these associations.

Methods: This study used UK Biobank data, including ALS diagnoses, potential ALS-related factors, metabolomics, and hand grip strength. A total protective factor score was calculated from lifestyle data. Multivariable Cox regression analyzed associations between the score, its components, and ALS risk. ALS-related metabolic signatures were identified via elastic net regression. ALS risk across signature levels was compared by log-rank tests. Mediation analysis assessed the role of baseline hand grip strength.

Results: 248,222 participants were included in this study. Among lifestyle factors, the total protective factor score, no military service, and higher body mass index were significantly associated with reduced ALS risk. The metabolic signature derived from 163 metabolites indicative of potential ALS-associated protective factors was identified and found to be associated with lower ALS risk. Baseline hand grip strength of both hands was also associated with reduced ALS risk. Mediation analysis revealed that right-hand grip strength significantly mediated the associations between the total protective factor score, the metabolic signature, and ALS risk.

Discussion: Our study highlights the potential of the metabolic signature as a biomarker for early disease identification and underscores the importance of lifestyle-based prevention strategies.

Introduction/aims: The value of electrodiagnostic subtyping of Guillain-Barré syndrome (GBS) is still debated. This study aimed to determine the diagnostic yield, timing, and changes of the electrodiagnostic subtyping in patients with GBS in serial nerve conduction studies (NCS).

Methods: Data were extracted from the International GBS Outcome Study (IGOS) database. Serial NCS were available for 469 patients. For the serial NCS analysis, the intervals between the first and second study were defined as ≥ 7 and ≤ 42 days after onset of weakness. All NCS were classified according to the electrodiagnostic criteria sets of Hadden et al. and Rajabally et al.

Results: In NCS conducted within 3 days of onset of weakness, an axonal or demyelinating subtype could be demonstrated in 58.4% (Hadden) and 52.1% (Rajabally). NCS performed at a later timepoint demonstrated a similar yield of axonal and demyelinating subtypes. In patients with motor-sensory and motor GBS, the electrodiagnostic subtype changed on serial NCS in 37.8% (Hadden) and 44.7% (Rajabally). As the subtypes changed in multiple and opposite directions, the total proportion of axonal and demyelinating subtypes remained stable across time points. In patients with motor GBS, both axonal and demyelinating subtypes were found.

Discussion: This study demonstrates the highly dynamic disease course of GBS. The role of NCS remains to support the clinical diagnosis of GBS and should be performed as quickly as possible after onset of weakness. If these early NCS are non-diagnostic, repeating the study should be considered. Electrodiagnostic subtyping offers no additional value.

CNTNAP1 encodes the Contactin-Associated Protein 1 (CNTNAP1), also known as Caspr1, which is a transmembrane protein critical for nervous system function. CNTNAP1 is localized to the paranodal regions of all myelinated axons, flanking either side of the node of Ranvier. It plays a vital role in axonal domain organization and is essential for the propagation of action potentials along nerve fibers. This specialized arrangement of axonal domains, which contain distinct molecular complexes, enables saltatory conduction and significantly increases the speed and efficiency of neuronal communication. To date, there are 47 children with biallelic CNTNAP1 variants who have been reported exhibiting a wide spectrum of phenotypes including congenital hypomyelinating neuropathy, hypotonia, and joint contractures among other clinical features. In this review, we compiled all previously published cases and detailed the specific genetic variants of every known individual, including clinical manifestations. Additionally, we present seven new cases of individuals identified through direct collaborations with clinicians and families, bringing the total to 54 individuals who harbor biallelic variants in CNTNAP1. This review and the additional case studies demonstrate that while children with CNTNAP1 mutations can present with a broad spectrum of symptoms, there is a recurrence of key clinical features across these cases. These key features commonly include respiratory distress, generalized hypotonia, hypomyelination, intellectual disabilities, and reduced life expectancy. These newly described cases provide valuable insights into the phenotypic diversity of CNTNAP1 variants, deepening our understanding of the clinical impact in patients with this rare genetic disorder.

Introduction/aims: Direct involvement of the neuromuscular junction (NMJ) in the inflammatory process of Guillain-Barré syndrome (GBS) has been described. Despite this, the NMJ very rarely serves as a target for direct medical intervention in GBS. Here, we report the use of an acetylcholinesterase inhibitor, pyridostigmine, in four pediatric patients with axonal GBS.

Methods: All patients received standard immune therapy. Pyridostigmine treatment was started 7 weeks to 5 months after disease onset, and 5-11 weeks from reaching the plateau phase. Treatment efficacy was monitored by the 6-min walk, quadriceps femoris and hamstring strength (manual muscle testing), the pediatric evaluation of disability inventory-functional skills, and the GBS disability score. All tests were performed before and during drug intervention.

Results: All treated patients showed marked improvement in their motor and functional abilities. After 1 month of treatment, quadriceps femoris and hamstring strength increased by at least two points, and walking distance increased by 10-272 m. The pediatric evaluation of disability inventory functional skills mobility test increased by 22.3-34.7 points. No serious side effects were documented.

Discussion: Pyridostigmine may be a safe and effective add-on treatment in pediatric patients with axonal GBS who show insufficient response to immune therapy, and may be effectively used even at a late stage. Additional, larger studies are needed.

Introduction/aims: Voluntary muscle contractions result in a temporary increase in twitch force, a phenomenon termed post activation potentiation (PAP). In rodents and other species, PAP is observed predominantly or exclusively in fast twitch muscles. However, it has been suggested that in humans, PAP occurs more or less independently of muscle fiber type.

Methods: Eighteen healthy men and women (27 ± 8 years) underwent an electrical stimulation protocol during which two sets of four twitches were elicited both pre and post 6 s maximal voluntary contractions of the triceps surae (60%-70% slow twitch) and triceps brachii (60%-70% fast twitch) muscles.

Results: Unpotentiated peak twitch torque (PTT) was higher in the larger triceps surae versus the smaller triceps brachii (i.e., 13.4 ± 5.3 vs. 3.4 ± 2.1 nm; p < 0.001), but time to peak torque was shorter (i.e., 84 ± 7 vs. 132 ± 14 ms; p < 0.001) and relative rate of torque development (RTD) was greater in the triceps brachii (2294 ± 257 vs. 1425% ± 102%/s; p < 0.001). PAP increased PTT by 172% ± 124% in the triceps brachii versus 20% ± 20% in the triceps surae (p < 0.001). Absolute RTD also increased more in the triceps brachii (i.e., 240% ± 170% vs. 31% ± 24%; p < 0.001). However, PAP-induced changes in half-relaxation time and relative rate of relaxation did not differ between muscle groups.

Discussion: We conclude that PAP influences contraction but not relaxation of human muscle in a fiber type dependent manner. This should be kept in mind when interpreting individual differences in the results of neuromuscular testing, response to varying warm-up protocols, etc.

Introduction/aims: Diagnosing neuromuscular disorders in children is challenging. Concentric needle electromyography (CNEMG) is the standard for electrophysiological assessments but has limitations in pediatric populations. High-density surface electromyography (HDsEMG) provides a noninvasive technique with superior spatial resolution, enabling the identification and analysis of motor unit (MU) firing dynamics throughout the entire period of MU activity. This study assessed the feasibility of HDsEMG MU decomposition in children and explored parameters that differentiate neuropathy, myopathy, and normal findings.

Methods: One hundred children (mean age 9.1 years, standard deviation [SD] 5.1) underwent CNEMG followed by HDsEMG. EMG signals were decomposed into individual MU spike trains, and MU yield, as well as firing properties (mean discharge rate [MDR], discharge rate variability [DRV]) were analyzed across diagnostic groups. Furthermore, correlations were assessed between MU action potential parameters obtained from CNEMG (MU amplitude and duration) and those obtained from HDsEMG.

Results: MUs were reliably identified in 86.0% of children, with an average of 7 (4.2) MUs per participant. Among MU firing parameters, DRV was significantly higher in children with myopathy (p = 0.005). Additionally, MU duration from HDsEMG correlated weakly with CNEMG values (r = 0.31) and successfully discriminated myopathy from normal and neuropathic groups (p = 0.02).

Discussion: HDsEMG MU decomposition is feasible in children with neuromuscular disorders, providing valuable insights into MU firing and MU action potential properties. This technique has the potential to improve diagnosis and monitoring of pediatric neuromuscular conditions. Nevertheless, further signal processing refinements are warranted to enhance its discriminative capacity for detecting neuromuscular disorders in children.

Introduction/aims: Juvenile myasthenia gravis (JMG) patients report symptomatic improvement following thymectomy; however, there is a lack of published literature on biomarkers for interval improvement. This study aimed to investigate the utility of single-fiber electromyography to quantify changes post-thymectomy.

Methods: This was a retrospective medical record review of JMG patients who underwent thymectomy at Children's Healthcare of Atlanta between 2014 and 2024. Pre- and post-thymectomy orbicularis oculi jitter values and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores were recorded. A two-sided paired t-test was used to compare results pre- and post-thymectomy and Pearson's correlations were calculated.

Results: Twelve JMG patients (6 female) with a mean age at diagnosis of 12.9 ± 4.5 (range 1.6-17.1) years, positive acetylcholine receptor antibodies, and normal thymus imaging underwent thoracoscopic thymectomy at 15.2 ± 3.3 (range 7.4-18.2) years. Post-thymectomy, there was a statistically significant decrease in mean jitter (interval 7.3 ± 7.4 months, mean difference -33.2 ± 32.6 μs, p = 0.04, n = 7) and MG-ADL scores (interval 2.5 ± 2.1 years, mean difference -2.2 ± 2.5, p = 0.02, n = 11). There were no significant correlations between timing of thymectomy after diagnosis and the change in mean jitter (r = 0.11, p = 0.8, n = 7) and MG-ADL (r = -0.19, p = 0.58, n = 11). No major post-surgical complications were observed.

Discussion: Thymectomy is well-tolerated and leads to both objective and subjective improvement in JMG patients.

Introduction/aims: Some patients diagnosed with juvenile myasthenia gravis (JMG) have corticosteroid-refractory myasthenia gravis (CRMG). The aim of this study was to evaluate the biomarkers of corticosteroid (CS) responsiveness and refractoriness in children, and the overall prognosis of patients after receiving nonsteroidal immunosuppressants (ISs).

Methods: This cross-sectional study was conducted at the Department of Pediatrics, Xiangya Hospital, Central South University. Data of the patients diagnosed with JMG from 2010 to 2023 were collected and analyzed.

Results: Two hundred and seventy-five patients were included in this study; 215 utilized CS, of whom 44.2% had CRMG. Ptosis only was an independent predictor of CS responsiveness (OR = 2.13, SE = 0.36, OR 95% CI = 1.05-4.32, p value = 0.003). The presence of acetylcholine receptor antibodies (AChR-Abs) was an independent predictor of CS refractoriness (OR = 2.78, SE = 0.48, OR 95% CI = 1.09-7.05, p value = 0.033). At last follow-up, 65.8% of the CRMG patients responded to ISs including tacrolimus, azathioprine, intravenous immunoglobulin, mycophenolate mofetil, and rituximab. About 71.0% of the patients that received ≤ 2 ISs were responders; however, only 14.3% of the patients that received subsequent ISs responded.

Discussion: This study provides an approximate prevalence of CRMG in children, as well as predictors of CS responsiveness and refractoriness, which can guide clinicians in prescribing alternative ISs in a timely manner. It can also help researchers understand the burden of CRMG in children when developing promising new therapies.

Neuromuscular junction (NMJ) disorders such as myasthenia gravis, Lambert-Eaton myasthenic syndrome, and botulism are characterized by impaired synaptic transmission leading to weakness. This review examines the electrodiagnostic evaluation of these conditions, emphasizing the importance of techniques such as repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG) for confirming the diagnosis and distinguishing presynaptic from postsynaptic defects. The reduced safety factor of neuromuscular transmission (NMT) in postsynaptic disorders produces a decrement in compound muscle action potential (CMAP) amplitude and area with low-frequency stimulation, whereas presynaptic disorders show small baseline CMAPs that increase markedly in amplitude and area (postactivation facilitation) after brief exercise or during high-frequency stimulation. SFEMG, the most sensitive test of abnormal NMT, measures neuromuscular jitter-temporal variability in action potential generation-and also reflects a compromised safety factor. Fiber density remains normal in primary NMJ disorders, distinguishing them from conditions with neuropathic reinnervation, such as motor neuron disease. Proper performance and interpretation of these electrodiagnostic studies are essential for accurate diagnosis, assessment of disease severity, and guiding management of NMJ disorders.

Introduction/aims: Natural history data for adult patients with spinal muscular atrophy (SMA) remain scarce, which is particularly relevant in the current therapeutic era. This study aimed to identify the most sensitive clinical, patient-reported, and neurophysiological measures to detect short-term disease progression in untreated adult SMA patients.

Methods: This prospective, one-year longitudinal study included 21 genetically confirmed adult patients with SMA types 2B and 3. Clinician-reported outcomes (CROs) included the Motor Function Measure (MFM), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module (RULM). Additionally, patient-reported outcomes (PROs) were assessed using the Modified Fatigue Impact Scale (MFIS). Neurophysiological evaluations included compound muscle action potential (CMAP) amplitude and motor unit number index (MUNIX) recorded from the ulnar nerve. Sensitivity to change was determined using standardized response means (SRMs), and associations between clinical and neurophysiological data were analyzed via Spearman correlation.

Results: The majority of participants were non-ambulatory (16/21). The MFM total score was the only outcome to show a statistically significant decline over 12 months (p = 0.02), with the highest SRM (-0.55), indicating superior sensitivity. MFM also demonstrated the strongest correlations with CMAP amplitude (ρ = 0.90) and MUNIX (ρ = 0.75), compared to other CROs. No significant longitudinal changes were observed in RULM, HFMSE, MFIS, CMAP, or MUNIX.

Discussion: Among evaluated outcome measures, the MFM was the most sensitive to short-term progression and most closely aligned with neurophysiological markers. These findings support the use of MFM as a primary outcome in clinical trials involving adult SMA patients.