Muscle & Nerve最新文献

Introduction/aims: When spasticity occurs after a stroke, peripheral changes in spastic muscle architecture may develop. The primary objective was to determine if an association exists between spastic muscle echointensity (EI) measured by the Modified Heckmatt Scale (MHS) and changes in insertional activity detected by electromyography (EMG). The secondary aim was to investigate whether these changes are due to the effects of botulinum neurotoxin (BoNT).

Methods: A total of 55 patients with poststroke spasticity were enrolled from three outpatient spasticity clinics. Muscle EI and needle EMG insertional activity were assessed for 8 muscles in each subject. Chi-square tests or Fisher's exact tests for categorical variables were used to evaluate the association between muscle EI and EMG insertional activity, as well as the association between BoNT exposure and muscle changes.

Results: For MHS Grade 1-2 muscles, 91.7% had normal insertional activity compared to 46.4% of MHS Grade 3-4 muscles (p < 0.001). In muscles with abnormal insertional activity, reduced or absent insertional activity was seen in 67.3% of MHS 3-4 muscles compared to only 16.7% for MHS 1-2 muscles, while increased insertional activity was seen in 32.7% of MHS 3-4 muscles and 83.3% of MHS graded 1-2 muscles. Exposure to BoNT did not impact the observed association between MHS and abnormal EMG insertional activity.

Discussion: Increased EI is associated with abnormal EMG insertional activity. Exposure to BoNT does not explain the observed EI and EMG changes. Further research is needed to elucidate the significance and causes of muscle architectural and electromyographical transformation in poststroke spasticity.

Introduction/aims: Azathioprine (AZA) and mycophenolate mofetil (MMF) are the most commonly used non-steroidal immunosuppressants in patients with generalized myasthenia gravis (gMG) in North America but their relative effectiveness among disease subgroups is not known. We reviewed data in the Duke MG Clinic Registry to compare the effectiveness of AZA and MMF in subgroups of patients with gMG.

Methods: This is a retrospective comparative effectiveness study of patients with acetylcholine receptor positive gMG receiving recommended doses of AZA or MMF for at least 90 days. Treatment goal (TG) was achieving MGFA Post-Intervention Status Minimal Manifestations. Time-to-event analysis, inverse probability of treatment weighting, and Cox proportional hazards (CPH) modeling were performed.

Results: Among 320 cohort patients, 177 took AZA and 143 took MMF. TG was achieved by 66.1% taking AZA, median time 17.5 months, and 68.5% taking MMF, median time 10.5 months (p = 0.0004). Concomitant prednisone, taken by 2/3 of patients, increased the proportion of patients who reached TG with either drug (p < 0.0001). There was a positive correlation between disease duration at drug initiation and time to TG (Pearson r = 0.32, p = 2.3 × 10^-6).

Discussion: Two-thirds of patients treated with AZA or MMF achieved TG after a median of 14 months. Patients taking MMF achieved TG sooner than those taking AZA, and concomitant prednisone increased the proportion of patients who achieved TG with either drug. Patients with shorter disease duration at drug initiation reached TG sooner with either drug. These results emphasize the value of concomitant prednisone and early immunosuppressive treatment of patients with gMG.

Introduction/aims: The cross-sectional area (CSA) of the median nerve (MN) is a key parameter for confirming carpal tunnel syndrome (CTS) with ultrasound. This study evaluates the performance of a convolutional neural network (CNN) with a 2D U-Net architecture for automated MN CSA segmentation in both healthy individuals and patients with CTS. Automated segmentation supports large-scale analysis, improves standardization across centers, and may serve as a foundation for future diagnostic tools.

Methods: Three hundred static ultrasound images from 50 healthy participants and 300 from 74 patients with CTS were used to train and validate a five-layer U-Net model. Each CSA measurement was performed in triplicate. Model performance was evaluated using the Dice similarity coefficient (DSC) and by comparing automated with manually annotated CSA values. Prospective evaluation was conducted on a small, unseen dataset and on data acquired using a different ultrasound system.

Results: Manual CSA measurements showed excellent repeatability (ICC 0.982). The model achieved high DSCs (0.95 in controls, 0.96 in CTS) and showed no statistically significant difference from manual CSA measurements (p = 0.227). Segmentation inaccuracies in the test set were primarily attributable to minor contouring differences at the epineurial border. On unseen data, errors occurred in more proximally scanned images or scans showing intraneural hyperechogenicity.

Discussion: In line with current literature, a CNN with a 2D U-Net architecture demonstrates strong potential for MN segmentation on static ultrasound images. However, reduced accuracy on unseen data suggests overfitting. Further validation is required to ensure robustness across anatomical and technical variation before clinical implementation.

Introduction/aims: The association between low forced vital capacity (FVC) and cognitive impairment in ALS is ambiguous; it could be due to respiratory dysfunction and/or poor effort from cognitive deficits. We used the objective, non-volitional phrenic nerve motor response amplitude (PAmp) to clarify how cognitive status affects the relationship between diaphragmatic strength and FVC.

Methods: This retrospective study included 73 patients with ALS followed in our clinic. FVC and PAmp were measured, and cognitive status was assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Regression models tested for associations between FVC and distinct ECAS domains and whether these domains influenced the PAmp-FVC relationship.

Results: PAmp (β = 0.58, p = 0.001) and its interaction with an abnormal ECAS's Executive score (β = -0.20, p < 0.045) were significant predictors of FVC. The latter indicated that patients with abnormal executive function had lower FVC than cognitively normal patients at similar PAmp values. Moreover, in patients with abnormal executive function, a reduction in PAmp was associated with a shallower decline in FVC. Severe bulbar dysfunction was also negatively associated with FVC (β = -0.22, p = 0.024).

Discussion: FVC may underestimate respiratory capacity in cognitively impaired patients; therefore, we recommend non-volitional measures when evaluating ALS patients with executive dysfunction.

Small fiber neuropathy (SFN) presents with neuropathic pain, dysesthesia, and autonomic symptoms in the context of normal nerve conduction studies, necessitating specialized diagnostic approaches. This evidence-based review by the AANEM SFN Task Force evaluates the diagnostic utility of ancillary tests and appropriate screening laboratory investigations in the assessment of SFN. A comprehensive literature review was conducted using OVID MEDLINE and EMBASE from 1966 to January 2023. Studies were selected based on prespecified inclusion criteria requiring clinical symptoms consistent with SFN and normal large fiber conduction studies. Articles were independently reviewed and graded for evidence quality by multiple raters. Thirteen diagnostic and two laboratory screening studies met criteria. Skin punch biopsy assessing intraepidermal nerve fiber density showed Class II evidence (sensitivity 74%-78%, specificity 65%-80%). Additional metrics included intraepidermal fiber length and inter-fiber distance. Corneal confocal microscopy (CCM) showed potential (Class III) but lacked validation in isolated SFN. Indirect tests (laser/contact heat evoked potentials, cutaneous silent period) had variable sensitivity and high specificity. Lab screening identified metabolic/immune etiologies in up to 64%, though most evidence was Class III. Skin biopsy is the most validated direct diagnostic tool for SFN, though CCM and indirect assessments can aid in diagnosis. No test offers enough sensitivity or specificity to serve as a stand-alone gold standard. Despite limited high-level evidence, screening for metabolic and immune conditions may help identify etiologies. Standardized methods and population studies are needed to improve accuracy.

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.