Muscle & Nerve最新文献

Introduction/aims: Randomized controlled trials show that repeat intravenous immunoglobulin (IVIG) dosing and plasma exchange (PLEX) followed by IVIG (combination therapy) have no additional therapeutic benefit in Guillain-Barre Syndrome (GBS) non-responders. Furthermore, the delineation between GBS and Acute Onset CIDP (A-CIDP) can be particularly challenging and carries therapeutic implications. We aimed to evaluate the presence of repeat IVIG, combination therapy, and diagnostic reclassification from GBS to CIDP.

Methods: We performed a retrospective study of a large healthcare database for patients with GBS in the US from 2001 to 2018. We identified individuals initially diagnosed with GBS and later re-classified as CIDP. Multivariable logistic regression models were developed to determine associations between patient factors and repeat IVIG dosing, combination therapy, and diagnostic re-classification from GBS to CIDP.

Results: We identified 2325 patients with GBS. A total of 39.7% received repeat IVIG and 6.1% received combination therapy. The proportion of individuals initially diagnosed with GBS and then re-classified as CIDP was 32.0%. Repeat IVIG, combination therapy, and diagnostic reclassification remained stable over time. Female sex (OR 0.79, 95% CI 0.65-0.96) and medium-high net worth (OR 0.64, 95% CI 0.45-0.90) associated with repeat IVIG therapy, while Asian ethnicity associated with diagnostic re-classification from GBS to CIDP (OR 1.77, 95% CI 1.09-2.86).

Discussion: Repeat IVIG dosing was quite common in GBS before newer trials suggesting harm in non-responders, and IVIG/PLEX combination therapy continues to persist despite strong evidence against use in non-responders. Further, nearly one in three patients initially diagnosed with GBS is subsequently diagnosed with CIDP, but the reasons are unclear.

Peripheral nerve injury is common and can have devastating consequences. In severe cases, functional recovery is often poor despite surgery. This is primarily due to the exceedingly slow rate of nerve regeneration at only 1-3 mm/day. The local environment in the distal nerve stump supportive of nerve regrowth deteriorates over time and the target end organs become atrophic. To overcome these challenges, investigations into treatments capable of accelerating nerve regrowth are of great clinical relevance and are an active area of research. One intervention that has shown great promise is perioperative electrical stimulation. Postoperative stimulation helps to expedite the Wallerian degeneration process and reduces delays caused by staggered regeneration at the site of nerve injury. By contrast, preoperative "conditioning" stimulation increases the rate of nerve regrowth along the nerve trunk. Over the past two decades, a rich body of literature has emerged that provides molecular insights into the mechanism by which electrical stimulation impacts nerve regeneration. The end result is upregulation of regeneration-associated genes in the neuronal body and accelerated transport to the axon front for regrowth. The efficacy of brief electrical stimulation on patients with peripheral nerve injuries was demonstrated in a number of randomized controlled trials on compressive, transection and traction injuries. As approved equipment to deliver this treatment is becoming available, it may be feasible to deploy this novel treatment in a wide range of clinical settings.

Introduction/aims: Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are progressive neuromuscular disorders characterized by severe muscle weakness and functional decline (Pillen et al., Muscle Nerve 2008; 37(6):679-693). With new therapeutics, objective methods with increased sensitivity are needed to assess muscle function. Ultrasound imaging is a promising approach for assessing muscle fat and fibrosis in neuromuscular disorders. This study builds on prior work by combining ultrasound-based measurements of muscle size, shape, and quality, relating these measures to muscle strength, and proposing a multivariable image-based estimate of muscle function.

Methods: Maximum voluntary elbow flexion torque of 36 participants (SMA, DMD, and healthy controls) was measured by hand-held dynamometry and elbow flexor muscles were imaged using ultrasound. Muscle size (cross-sectional area, maximum Feret diameter or width, and thickness), quality (echogenicity, texture anisotropy index), and cross-sectional shape (diameter ratio) were measured. Multivariable regression was used to select ultrasound measurements that predict elbow flexion torque.

Results: Significant differences were observed in muscle size (decreased), shape (thinned), and quality (decreased) with increased disease severity and compared to healthy participants. CSA (brachioradialis R² = 0.51), maximum Feret diameter (biceps R² = 0.49, brachioradialis R² = 0.58) and echogenicity (brachioradialis R² = 0.61) were most correlated with torque production. Multivariable regression models identified that muscle size (CSA, maximum Feret diameter) and quality (echogenicity) were both essential to predict elbow flexion torque (R² = 0.65).

Discussion: A multivariable approach combining muscle size and quality improves strength predictions over single variable approaches. These methods present a promising avenue for the development of sensitive and functionally relevant biomarkers of neuromuscular disease.

Introduction/aims: While amyotrophic lateral sclerosis (ALS) is primarily characterized as a motor system disorder, there is a growing body of evidence indicating sensory involvement. This study aimed to examine the hypothesis that somatosensory processing is impaired in ALS.

Methods: Study participants were ALS patients followed at the Neuromuscular Outpatient Unit, as well as healthy volunteers, from March 2021 to July 2023. The Medical Research Council (MRC) sum score was calculated for nine muscle groups bilaterally. The clinical status of patients was evaluated with the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Penn Upper Motor Neuron core. Somatosensory temporal discrimination thresholds (STDTs) were recorded on the medial and lateral parts of both hands. Somatosensory cortex excitability was investigated with the paired somatosensory evoked potentials (SEP) paradigm in a subgroup.

Results: Increased STD values were detected in ALS patients compared to controls in both medial (107.66 ± 35 ms vs. 82.7 ± 32.5 ms, p = .001) and lateral (106.5 ± 34.5 ms vs. 82.9 ± 31.3 ms, p = .002) hands. There were no significant differences in STDTs among ALS patients across four regions (medial and lateral parts of the right and left hands). Amplitude ratios obtained from the paired-pulse SEP paradigm were approximately 1 for all interstimulus intervals (ISIs). STDTs did not show any correlations with motor findings or scales.

Discussion: Somatosensory processing appears to be compromised among ALS patients. The lack of correlation between impaired STDT and motor findings implies that it is a purely sensory deficit in ALS.

Introduction/aims: In vasculitic neuropathy (VN), it is not known whether nerve conduction studies (NCSs) showing low amplitude sensory nerve action potentials (SNAPs) or those with absent responses have a higher yield in detecting appropriate nerves for pathological confirmation. Our goal was to describe NCS findings of nerves prior to biopsy in patients with VN.

Methods: We performed a retrospective study between January 2000 and April 2021 in patients with VN who either met pathological definite criteria for VN or criteria for clinically probable VN and had NCS of the sural or superficial radial sensory nerves prior to biopsy of the same nerve.

Results: We included 61 patients with VN. The pathological findings showed 37 (60.7%) definite, 14 (23%) probable, and 2 (3.3%) possible VN; eight (13%) samples did not meet Peripheral Nerve Society pathological criteria. Most patients who met definite (20 out of 37, 54%) and probable (9 out of 14, 64%) VN pathological criteria had absent SNAPs. Only three out of eight (37.5%) patients without VN pathological findings had absent SNAPs. There was no statistically significant correlation between pathological diagnosis and SNAP amplitude (χ² = 1.98, p = .58). Additionally, no association was found between VN pathological criteria and use of immunomodulatory treatment (p = .67) or corticosteroids (p = .52).

Discussion: Most nerves with pathological VN findings showed no response on NCS. In patients with suspected VN, sural or superficial radial sensory nerves with absent responses on NCS are adequate biopsy targets as compared to nerves in which SNAPs can be recorded.

Introduction/aims: The paraspinal muscles are an important component of electrodiagnostic testing for radiculopathy. In the cervical region, a protocol for cervical paraspinal mapping assumes accurate placement of the electromyography (EMG) needle into the cervical multifidus. However, there is scant information regarding the accuracy of needle placement in that muscle. This study examines the accuracy of this protocol in sampling the intended multifidus muscle of cadavers.

Methods: An experienced electromyographer directed needles to multifidus at C5, C7, and T2 spinous processes of 19 embalmed cadavers, and injected color dyes. Separately another examiner dissected the cadavers, noting whether the dye was in the correct location and whether its trajectory approached any "danger zones" of nerve, artery, or joint.

Results: The dye was in the multifidus muscle 100% of the time and hit the intended bony target in 79%, 73%, and 79% of C5, C7, and T2 insertions. No insertion was found in a danger zone.

Discussion: The results indicate modest accuracy for EMG needle placement as proposed in the clinical protocol. Clinical utility of this method requires more work including the establishment of norms, sensitivities, specificities, and clinical impact.

Introduction/aims: While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management and outcomes of early-treated infants with SMA.

Methods: We analyzed retrospective data at 12 centers on infants with SMA treated at age ≤6 weeks from August 2018 to December 2023.

Results: Sixty-six patients, 35 with two SMN2 copies and 31 with ≥3 SMN2 copies, were included. Twenty-five (38%, 22 with two SMN2 copies), had SMA findings before initial treatment which was onasemnogene abeparvovec in 47 (71%) and nusinersen in 19 (29%). Thirty-two received sequential or combination treatments, including 16 adding nusinersen or risdiplam due to SMA findings following onasemnogene abeparvovec. All sat independently. Compared to children with ≥3 SMN2 copies, those with two SMN2 copies were less likely to walk (23/34 [68%] vs. 31/31 [100%], p < .001) and less likely to walk on time (9/34 [26%] vs. 29/31 [94%], p < .001); one non-ambulatory child was <18 months old and was excluded from this analysis. No patients required permanent ventilation or exclusively enteral nutrition; six required nocturnal non-invasive ventilation and four utilized supplemental enteral nutrition, all with two SMN2 copies.

Discussion: Early treatment of infants with SMA can improve outcomes as indicated by our cohort, all of whom sat independently and are without permanent ventilation. However, our study demonstrates ongoing disability in most children with two SMN2 copies despite early monotherapy and emphasizes the need for additional research, including earlier monotherapy, initial combination therapy, prenatal treatment, and non-SMN modifying treatments.

Introduction/aims: Persons with spinal muscular atrophy (pwSMA) report progressive muscle weakness but also reduced endurance when performing repetitive tasks in daily life, referred to as "performance fatigability" (PF). Data regarding the effects of the new disease-modifying drugs on PF are scarce. Thus, our main objective was to examine PF in adult ambulatory pwSMA treated long-term with nusinersen.

Methods: Six-minute walk test (6MWT) data from 14 adult pwSMA treated with nusinersen for up to 70 months were retrospectively analyzed to determine PF. Performance fatigability was defined as the percentage change in the distance covered between the last and first minute of the 6MWT. In addition, relationships between PF and other clinical features were assessed.

Results: Performance fatigability was found in 12/14 pwSMA (85.7%) prior to treatment. The mean distance walked in the sixth minute (71.1 m) was shorter than the distance covered in the first minute (81.8 m), corresponding to a mean PF of 13.1% (95% confidence interval (CI): 6.5-19.6, p = .0007). During treatment with nusinersen, there was a mean reduction in PF of 5.6% (95% CI: -10.0 to -1.3, p = .0148). We found no relationship between PF and fatigue as measured by the Fatigue Severity Scale.

Discussion: This study demonstrates the presence of PF as an independent component of motor impairment and as a potential therapeutic target in our cohort of adult ambulatory pwSMA. Furthermore, the observations in our cohort suggest that nusinersen may have a beneficial effect on PF.