Muscle & Nerve最新文献

Introduction/aims: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care.

Methods: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs).

Results: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death.

Discussion: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis.

Results: Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline.

Discussion: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.

The landscape of care for children and adults with neuromuscular disorders (NMDs) is rapidly changing as more disease-modifying treatments (DMTs) become available. These DMTs provide hope and opportunity for evolving phenotypes, though none (yet) are curative. Rehabilitation has been the standard of care for patients with NMDs and should remain so, even with the advent of novel DMTs. An interdisciplinary rehabilitation approach is holistic and comprehensive, addressing functional needs, musculoskeletal complications, pain, durable medical equipment, and bracing needs. This care will continue to be essential for patients who experience impairments and disability, despite receiving DMTs. Additionally, we must consider how to care for a new rapidly expanding cohort of patients aging with NMDs. Children with NMDs are expected to live longer into adulthood; a population that we may not have the workforce to support at this time. At this point, we have the perfect opportunity to reemphasize the importance of rehabilitation in the care of persons with NMDs, while we reexamine historical rehabilitation practices and innovatively deliver services to optimize the effects of these high-cost DMTs.

Background: In motor nerve conduction studies (MNCS), proximal stimulation should give a longer duration and lower amplitude compound muscle action potential (CMAP) due to higher temporal dispersion. Yet the CMAP waveforms at the distal and proximal stimulation sites appear remarkably similar. The objective of this study was to confirm this anomaly and investigate its possible cause by studying the median and ulnar nerves.

Methods: Recordings from 50 subjects with normal electrodiagnostic studies were reviewed. The conduction velocity (CV) was measured using different points on the negative phase of the CMAP including its peak and baseline crossing. Collision studies were performed in three healthy subjects to measure the dispersion when nerve action potentials (APs) propagated from elbow to wrist.

Results: CV was relatively unaffected by the measurement point on the CMAP. The CMAP duration with elbow stimulation increased minimally compared to wrist stimulation. This was inconsistent with the dispersion of the AP from wrist to elbow measured in collision studies.

Discussion: The insignificant change in the CMAP in spite of axon AP dispersion is an enigma. We hypothesize that the terminal conduction time (TCT) (i.e., conduction in terminal axon branches, neuromuscular transmission, etc.) is independent of axon CV, represents a significant portion of the latency, masks AP dispersion, and reduces CMAP dispersion. This yields similar CMAPs with distal and proximal stimulation. The onset latency at the distal stimulation site does not depend on CV. Thus, onset latency and CV may not reflect the conduction properties of the fastest conducting axons.

Introduction: The epidermal growth factor receptor (EGFR; ErbB1), a membrane bound receptor tyrosine kinase, is hypothesized to have an inhibitory influence on peripheral nerve regeneration. This study examines the impact of EGFR inhibition on nerve regeneration using the commercially available small molecule inhibitor gefitinib.

Method: In vitro assays included neurite outgrowth of cultured dorsal root ganglion (DRG) neurons from adult C57Bl/6 wildtype mice on immobilized chondroitin sulfate proteoglycans (CSPG). Following forelimb median nerve injury, EGFR expression, number of regenerated neurons (using retrograde labeling) and myelination of motor and sensory neurons were compared between mice that received either gefitinib or vehicle. Functional recovery was assessed using grip strength.

Results: EGFR expression on DRG and spinal motor neurons was confirmed. Gefitinib significantly increased neurite outgrowth in medium sized (30-50 μm) DRG neurons, resulting in longer neurites (183 ± 36 μm) compared with CSPG alone (49 ± 9 μm). After median nerve injury, significantly greater numbers of sensory neurons (638 ± 112 vs. 301 ± 81), but not motor neurons (31 ± 12 vs. 42 ± 13) regenerated in animals treated with gefitinib compared with controls. Regenerated axons in gefitinib treated animals displayed significantly greater diameter and increased g-ratio compared with controls. Grip strength recovered more quickly in animals receiving gefitinib compared with controls (27.6 vs. 19.1 g 18 days post-injury).

Discussion: This study provides data supporting the role of EGFR as a negative regulator of sensory but not motor neuron regeneration. Further, it demonstrates versatile potential uses of existing pharmaceuticals.

Introduction/aims: Ultrahigh-frequency ultrasound (UHFUS) allows improved visualization and higher resolution images of nerve fascicles than standard high-frequency ultrasound. Dynamic UHFUS may detect the presence of fascicular entwinement, the recently described sonographic phenomenon of pathologic fascicular rotation seen in neuralgic amyotrophy. This pilot study aims to establish normative reference values and degrees of fascicular rotation for the proximal portions of commonly involved upper limb nerves in healthy controls using UHFUS.

Methods: Twenty healthy participants underwent sonographic examination of the median, musculocutaneous, and radial nerves on both upper limbs using UHFUS with a 48 MHz linear transducer. A single rater assessed the degree of fascicular rotation in each peripheral nerve.

Results: Fascicular rotation appears to occur in the proximal portion of each of these nerves. The mean degree of fascicular rotation for each of the measured nerves was median 94.5°, musculocutaneous 97.9°, and radial 50.9°. The maximum observed fascicular rotation in each nerve was 180°. Age, sex, height, weight, body mass index, and race did not predict degree of fascicular rotation (all p > .103). A single-factor ANOVA test showed the degree of fascicular rotation differed in median, musculocutaneous, and radial nerves (F = 4.748, p = .011).

Discussion: UHFUS allows quantification of fascicular rotation in healthy controls in the median, musculocutaneous, and radial nerves, and provides normative data. The data from this pilot study may serve as control data for future comparative studies in conditions where fascicular rotation occurs, such as neuralgic amyotrophy.