Muscle & Nerve最新文献

Introduction/aims: The single simple question (SSQ), "What percentage of normal (0%-100%) do you feel regarding your disease?" has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes.

Methods: A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch-built Overall Disability Scale (RODS).

Results: The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = -.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%-70%, and 34% with SSQ >70%).

Discussion: The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length-dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP.

Introduction/aims: There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells.

Methods: We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs.

Results: MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs.

Discussion: We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

In order to understand abnormal gait, this article will first review normal gait, discuss how neuromuscular diseases disturb gait patterns and review orthotic interventions. In normal gait, concentric contractions accelerate and eccentric contractions decelerate the limb. Neuromuscular gait disorders can be grouped into (1) proximal weakness, (2) distal weakness, (3) nonlength-dependent or generalized weakness, (4) asymmetric weakness, and (5) sensory disorders. Identification of gait disturbance type in neuromuscular diseases leads to the appropriate orthotic prescription since orthotic strategies are grouped into (1) proximal weakness, (2) distal weakness, and (3) sensory disturbances. Orthotics is not indicated in all types of gait disturbance. Weakness in proximal hip musculature can be managed with gait aids such as walkers. In contrast, distal muscle weakness can be managed with orthotics. Preservation of gait assists in maintenance of daily function and integration in society.

Introduction/aims: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Methods: We conducted a multicenter retrospective cohort study, including adult ambulant patients with SMA3, data available on 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale-Expanded (HFMSE) at baseline and at least at 6 months of treatment with nusinersen. We investigated fatigability, estimated as 10% or higher decrease in walked distance between the first and sixth minute of the 6MWT, at baseline and over the 14-month follow-up.

Results: Forty-eight patients (56% females) were included. The 6MWT improved after 6, 10, and 14 months of treatment (p < 0.05). Of the 27 patients who completed the entire follow-up, 37% improved (6MWT distance increase ≥30 m), 48.2% remained stable, and 14.8% worsened (6MWT distance decline ≥30 m). Fatigability was found at baseline in 26/38 (68%) patients and confirmed at subsequent time points (p < 0.05) without any significant change over the treatment period. There was no correlation between fatigability and SMN2 copy number, sex, age at disease onset, age at baseline, nor with 6MWT total distance and baseline HFMSE score.

Discussion: Fatigability was detected at baseline in approximately 2/3 of SMA3 walker patients, without any correlation with clinical features, included motor performance. No effect on fatigability was observed during the 14-month treatment period with nusinersen.

Introduction/aims: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice.

Methods: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building.

Results: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset.

Discussion: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.

Introduction/aims: Early diagnosis of a chronic neuromuscular disease such as muscular dystrophy (MD) generally excludes an individual from active-duty military service. However, it is not known whether veterans are sometimes diagnosed with milder forms of MD at a later timepoint. We aimed to determine the prevalence of MD in a veterans health system.

Methods: We abstracted clinical and genetic test data on patients who received care for a diagnosis of MD at the North Florida/South Georgia Veterans Health System between 2008 and 2021. We then determined which of these individuals would meet criteria for a definite diagnosis of MD, based on electrodiagnostic testing, muscle biopsy, and genetic testing of the individual or an affected first degree relative.

Results: We identified 12 patients with definite MD and 36 with possible or probable MD. The definite cases included myotonic dystrophy type 1 (4), myotonic dystrophy type 2 (3), oculopharyngeal MD (2), Becker MD (1), distal MD (1), and facioscapulohumeral MD (1). At least five of the cases classified as definite developed symptoms after discharge from active duty.

Discussion: Clinicians who care for veterans should be knowledgeable about, and have access to, diagnostic testing and treatment options for MD. When conducting MD surveillance, it is important to include veterans health systems as a data source. Mild cases of MD and those of later onset appear to be compatible in some cases with successful completion of military service.

Introduction/aims: The development of high-resolution ultrasound (HRUS) has enabled the depiction of peripheral nerve microanatomy in vivo. This study compared HRUS fascicle differentiation to the structural depiction in histological cross-sections (HCS).

Methods: A human cadaveric sciatic nerve was marked with 10 surgical sutures, and HRUS image acquisition was performed with a 22-MHz probe. The nerve was excised and cut into five segments for HCS preparation. Selected HCS were cross-referenced to HRUS, with sutures to improve orientation. Sciatic nerve and fascicle contouring were performed to assess nerve and fascicular cross-sectional area (CSA), fascicle count, and interfascicular distances. Three groups were defined based on HRUS fascicle differentiation in comparison to HCS, namely single fascicle (SF), fascicular cluster (FC), and no depiction (ND) group.

Results: On cross-referenced HRUS to HCS images, 58% of fascicles were differentiated. On HRUS, significantly larger fascicle CSA and smaller fascicle count were observed compared with HCS. Group analysis showed that 41% of fascicles were defined as SF, 47% as FC, and 12% as ND. The mean fascicle CSA in the ND group was 0.05 mm². Compared with the SF, the FC had significantly larger fascicle CSA (1.2 ± 0.7 vs. 0.6 ± 0.4 mm²; p < .001) and shorter interfascicular distances (0.1 ± 0.04 vs. 0.5 ± 0.3 μm; p < .001).

Discussion: While HRUS can depict fascicular anatomy, only half of the fascicles visualized on HRUS directly correspond to single fascicles observed on HCS. The amount of interfascicular epineurium appears to influence the ability of HRUS to differentiate individual fascicles.

Introduction/aims: Sodium phenylbutyrate-taurursodiol (PB-TURSO) was recently approved for treating amyotrophic lateral sclerosis (ALS). Third-party payors' coverage policies are evolving, and adverse events are just being fully assessed. The goals of this study were to evaluate patients' experiences in obtaining and continuing PB-TURSO and assess adverse events and medication adherence.

Methods: Medical records of 109 ALS patients who were considered PB-TURSO candidates by the treating physician at a tertiary ALS clinic from October 2022 to May 2023 were reviewed. Data was recorded for demographics, clinical, and insurance information. A survey was e-mailed to patients asking about out-of-pocket expenses for PB-TURSO, financial assistance, medication start and (if applicable) stop dates, and reasons for discontinuation.

Results: Insurance information was available for 91 patients [57 males (62%); mean age 64.8 years (range 25.7-88)]. Of 79 who applied for insurance approval, 71 (90%) were approved; however, 19 required 1-3 appeals. Among 73 patients with available data about medication status, 54 started PB-TURSO and 19 did not, most commonly due to personal choice or out-of-pocket expenses. About 44% of patients (24/54) stopped taking PB-TURSO, primarily due to adverse events. Monthly out-of-pocket expenses varied from $0 to $3500 and 36 patients qualified for financial assistance. Administrative and nursing staff devoted 7.2 hours/week to the insurance authorization process.

Discussion: Most patients received insurance approval for PB-TURSO, but one-fourth required appeals. Some out-of-pocket costs were very high. Investment of staff time was substantial. These findings have implications for insurance coverage of, and adherence to, future ALS treatments.

Introduction/aims: Paired-pulse stimulation provides clinically useful information regarding sensory inhibition. When supraorbital nerve stimulation is repeated within a short interval, the response to the second stimulation is reduced to varying degrees. This magnitude of change in stimulation response can be monitored by electromyogram (EMG) or by mechanomyogram (MMG) as in this report. MMG has some advantages such as being less time consuming and lacking stimulus artifact. We compared the use of MMG and EMG to validate MMG as an effective method of assessing blink reflex paired-pulse inhibition.

Methods: Eight volunteers participated. Participants received electrical stimulation to the supraorbital nerve of each side. A paired-pulse paradigm was employed, varying the conditioning-test interval between 5 and 800 ms. The R1 component of the induced blink reflex was simultaneously recorded by EMG using a pair of electrodes placed on the lower eyelid and by MMG using an accelerometer placed between the electrodes.

Results: The correlation coefficient of the R1 amplitude between MMG and EMG of the grand-averaged waveforms was 0.99. The average participant r value was .91 (range .76-.99). Similar analyses were performed for the amplitude variation of the second response relative to the first response. Results correlated well, yielding r values of .97 and .86 for the grand-averaged waveform and the average for each subject.

Discussion: The present results demonstrate that MMG could be an alternative to EMG in assessing paired-pulse inhibition of the electrical blink reflex R1 component.