Muscle & Nerve最新文献

The high physiologic demands of sports create dynamic stress on joints, soft tissues, and nerves which may lead to injuries in the athlete. Electrodiagnostic (EDx) assessment is essential to identify the correct diagnosis, localization, and prognosis, to guide management of sports-related neuropathies. A comprehensive review was performed to provide the EDx medical consultant with a practical approach to the common peripheral nerve disorders seen in athletes. Sports-related neuropathies reviewed include transient traumatic irritation of the brachial plexus and/or cervical nerve roots ("Burners and stingers,") suprascapular and axillary neuropathies, ulnar neuropathy at the elbow (UNE) in throwers, ulnar neuropathy at the hand/wrist in cyclists, multi-ligamentous knee injury, and foot/ankle neuropathies including tarsal tunnel syndrome. A thorough understanding of peripheral anatomy, possible entrapment sites, mechanisms of injury, and key physical examination findings is essential for correct diagnosis. EDx assessments beyond routine studies are generally required for sports-related neuropathy, which may not necessarily follow typical entrapment patterns. Adjunct diagnostic imaging, such as point-of-care ultrasound and magnetic resonance imaging, are helpful tools to identify associated musculoskeletal pathology such as compressive cysts or nerve entrapment, which may be amenable to interventional or surgical treatment. When no clear reversible structural pathology exists, management of sports-related neuropathy is athlete-specific and generally multi-modal, involving a combination of physical rehabilitation techniques to address muscle imbalances, load management, protective equipment, and interventional pain procedures.

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: Medial femoral cutaneous (MFC) sensory nerve action potentials (SNAPs) can be easily recorded using distal stimulation. This study aimed to identify a new parameter using MFC SNAPs for the early electrophysiological diagnosis of length-dependent axonal polyneuropathy (LDAP) associated with uremic neuropathy.

Methods: Patients with chronic renal failure who were referred to the electrodiagnostic laboratory due to symptoms suggesting polyneuropathy were included. Assessments encompassed neurological examination, Michigan Neuropathy Screening Instrument (MNSI), and Semmes-Weinstein monofilament test. Antidromic radial, median, ulnar, MFC, sural, and superficial peroneal sensory; median, ulnar, tibial, and peroneal motor nerve conduction studies were performed. Sural-to-radial amplitude ratio (SRAR) and sural-to-medial femoral cutaneous amplitude ratio (SMFCAR) were calculated, and their diagnostic sensitivities were compared with the age and sex matched healthy controls.

Results: Thirty-two chronic renal failure patients (mean age 60.0 ± 9.6 years) and 37 controls (60.6 ± 9 years) were included. MNSI indicated clinical polyneuropathy in 59.4% of patients, while sural SNAP amplitude was diagnostic in 78%. Median SRAR and SMFCAR values were significantly lower in patients than controls (p < .001 for both). The cut-off values for SMFCAR and SRAR were <1.82 and <0.30, respectively, both with a sensitivity of 59% and a specificity of 94%.

Discussion: Sural SNAP is the most sensitive parameter in the diagnosis of LDAP. SMFCAR is not superior to SRAR. If the sural SNAP amplitude is normal, SMFCAR can serve as an alternative to SRAR in dialysis patients with bilateral arteriovenous fistulae or in those unable to undergo radial NCS.

Introduction/aims: Assessing upper limb muscle strength is important for understanding health outcomes, such as daily function and mortality. Ultrasound (US) is increasingly used to evaluate muscle health, but the relationship between its measures of morphology and isometric strength has not been thoroughly explored in upper limb muscles. The aim of this study was to evaluate the associations between US morphological measures and isometric strength in functionally relevant upper limb muscles in healthy adults.

Methods: Twenty-four healthy volunteers (30.0 ± 10.8 years) underwent B-mode, axial US scans of the first dorsal interosseus (FDI), flexor pollicis longus (FPL), biceps brachii (BB), brachialis (BR), and triceps brachii lateral head (TB). Participants performed corresponding maximal voluntary contractions (MVC), including first digit distal phalanx flexion, second digit abduction, and elbow flexion and extension. US images were segmented to obtain maximal muscle thickness (MT) and cross-sectional area (CSA).

Results: Strong positive correlations were found between muscle strength and BB MT (r = .83; p < .001), BR CSA (r = .84; p < .001), and TB MT (r = .70; p < .001). Moderate positive correlations were found for strength and FDI CSA (r = .67; p < .001), FDI MT (r = .47; p < .05), FPL CSA (r = .54; p < .01), and FPL MT (r = .42; p < .05). No significant correlation was found between strength and BR MT (r = .16; p > .05).

Discussion: Our data showed moderate-to-strong associations between US muscle morphology and strength, suggesting that US is likely a good biomarker for strength. However, its use is not "one size fits all." Future investigations should continue to assess this relationship in different muscles and expand the generalizability to clinical populations.

Introduction/aims: The number of clinical trials in facioscapulohumeral muscular dystrophy (FSHD) is expected to increase in the near future. There is a need for clinical outcome assessments (COAs) that can capture disease progression over the relatively short time span of a clinical trial. In this study, we report the natural progression of FSHD and determine the feasibility of COAs for clinical trials.

Methods: Genetically confirmed FSHD patients underwent various COAs at baseline and after 5 years. COAs consisted of the Motor Function Measure (MFM), manual muscle testing using the Medical Research Council score, six-minute walk test, quantitative muscle strength assessment of the quadriceps muscle, clinical severity score, and FSHD evaluation score (FES). Statistical significance and the minimal clinically important difference (MCID) were calculated and power calculations were performed.

Results: One hundred fifty-four symptomatic FSHD patients were included, with a mean (SD) age of 51.4 (14.6) years old. All COAs showed a minimal, yet statistically significant progression after 5 years. MCID was reached for the MFM Domain 1, MFM total score, and FES. These three COAs showed the lowest sample size requirements for clinical trials (185, 156, and 201 participants per group, respectively, for a trial duration of 2 years).

Discussion: The captured FSHD disease progression rate in 5 years was generally minimal. The COAs in this study are not feasible for clinical trials with a duration of 2 years. Extended trial durations or novel outcome assessments might be necessary to improve trial feasibility in FSHD.

Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years have witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. The evolution of an extensive corticomotoneuronal system appears restricted to the human species, with ALS representing a uniquely human disease. While some, very select non-human primates have limited corticomotoneuronal projections, these tend to be absent in all other animals. From a general perspective, the early clinical features of ALS may be considered to reflect failure of the corticomotoneuronal system. The characteristic loss of skilled motor dexterity involving the limbs, and speech impairment through progressive bulbar dysfunction specifically involve those motor units having the strongest corticomotoneuronal projections. A similar explanation likely underlies the unique "split phenotypes" that have now been well characterized in ALS. Large Betz cells and other pyramidal corticomotoneuronal projecting neurons, with their extensive dendritic arborization, are particularly vulnerable to the elements of the ALS exposome such as aging, environmental stress and lifestyle changes. Progressive failure of the proteosome impairs nucleocytoplasmic shuffling and induces toxic but soluble TDP-43 to aggregate in corticomotoneurons. Betz cell failure is further accentuated through dysfunction of its profuse dendritic arborizations. Clarification of system specific genomes and neural networks will likely promote the initiation of precision medicine approaches directed to support the key structure that underlies the neurological manifestations of ALS, the corticomotoneuronal system.

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.

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.