Muscle & Nerve最新文献

Introduction/aims: Spinal muscular atrophy (SMA) manifests with progressive motor neuron degeneration, leading to muscle weakness. Onasemnogene abeparvovec is a US Food and Drug Administration-approved gene replacement therapy for SMA. This study aimed to present short-term data of children in the United Arab Emirates (UAE) treated with onasemnogene abeparvovec, particularly in the context of children requiring invasive ventilatory support via tracheostomy.

Methods: A retrospective analysis was performed on 60 children who received onasemnogene abeparvovec. All these children received corticosteroids. They were followed up for up to 3 months. Motor function assessments were performed before and after the gene therapy. Comprehensive clinical evaluations, including pulmonary functions, were performed at baseline and the 3-month mark.

Results: Forty-three percent were male, and the mean age at the time of infusion was 29.6 months (SD ± 17.2). The mean weight was 10.1 kg (SD 2.6). All children demonstrated marked improvements in motor function within 3 months of gene therapy administration. No adverse effects attributable to corticosteroid therapy were observed. Positive clinical outcomes, including increased ventilator-free intervals, reduced antibiotic dependency, and fewer hospital admissions, were reported among children with invasive ventilation via tracheostomy.

Discussion: This study demonstrates the favorable tolerability and promising responses to onasemnogene abeparvovec in invasively ventilated pediatric patients. Early improvements in motor function, as observed within 3 months post-treatment, suggest its potential as a viable therapeutic option for this vulnerable patient population.

The immune-mediated necrotizing myopathies (IMNM) are autoimmune myositides clinically characterized by proximal predominant weakness and elevated creatine kinase (CK). They may be associated with autoantibodies (anti-HMGCR, anti-SRP), triggered by statin use (e.g., anti-HMGCR myopathy), associated with cancer, or may be idiopathic. Immunotherapy is required to improve strength and decrease the CK level, but no therapies are currently approved by the U.S. Food and Drug Administration for the treatment of IMNM. The optimal treatment strategy for IMNM is currently unknown and wide practice variation exists in the management of this condition. However, observational studies and expert opinion suggest that certain therapies may be more effective for the different serological subtypes of IMNM. HMGCR IMNM often responds favorably to intravenous immunoglobulin (IVIG) even as monotherapy. Signal recognition peptide and seronegative IMNM typically require combination immunotherapy, most often consisting of an oral immunosuppressant, corticosteroids, and IVIG or rituximab. Patients often remain on immunotherapy for years and relapse is common during tapering of immunotherapy. Further studies are needed to guide the optimal management of these patients.

Introduction/aims: Spinal muscular atrophy (SMA) is a multisystem disorder. We assessed metabolic syndrome (MetS) prevalence in adults with SMA and its association with motor function, quality of life (QoL), fatigue, and depression.

Methods: MetS was diagnosed using 2009 consensus criteria. Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and 36-Item Short Form Health Survey (SF-36) were recorded and correlations between muscle function, depression, fatigue, QoL, and MetS were analyzed.

Results: We included 36 individuals (18 males; mean age: 38.7 ± 14.6 years). MetS was present in 25.0%. The most common component of MetS was central obesity (69.7%). Nearly half of the SMA individuals exhibited at least one abnormal lipid level result. Individuals with MetS more frequently were SMA type 3 (77.8% vs. 37.0%, p = .02) and had higher levels of fatigue (48.4 ± 6.7 vs. 39.5 ± 11.6, p = .03) than those without MetS. No associations of the presence of MetS with ambulatory status or HFMSE/RULM scores were observed. SMA individuals with MetS scored significantly lower in mental and social domains of QoL and total SF-36 score (p = .04). We observed weak to moderate correlations between the presence of MetS and SMA type, presence of comorbidities, QoL, and fatigue.

Discussion: The frequency of MetS was modestly higher among adults with SMA than in the general population, particularly in SMA type 3. MetS was associated with reduced QoL and increased fatigue. Larger studies are needed to fully understand the significance of MetS in adults with SMA.

Introduction/aims: F-wave testing frequently reveals after-discharges of varied morphologies in patients with primary peripheral nerve hyperexcitability syndrome (PNHS), although reports are scant. This study aimed to explore the morphological characteristics of the after-discharges during F-wave tests in PNHS, and to assess the association between after-discharges and the disease classification.

Methods: We conducted a retrospective analysis of patients diagnosed with PNHS between 2014 and 2022. The morphological characteristic and duration of after-discharges during F-wave tests were analyzed. After-discharges in the Morvan syndrome group were compared with those in non-Morvan group, and between groups with positive or negative voltage-gated potassium channel (VGKC) complex antibodies.

Results: Twenty-nine patients were included in the study, of which 25 exhibited after-discharges. All after-discharges in Morvan patients occurred following compound muscle action potential (CMAP). In non-Morvan patients, after-discharges occurred following F-wave (32%) and CMAP (47%). The durations of after-discharges following CMAP were significantly prolonged in Morvan (54.2 ± 18.8 ms) compared to non-Morvan patients (34.5 ± 15.0 ms). The majority of antibody-positive patients (18/20) exhibited after-discharges following CMAP, whereas 67% of antibody-negative patients (6/9) showed after-discharges following F-wave.

Discussion: The varying presentations of after-discharges, including their location (after CMAP or F-wave) and the duration of after-discharge can assist in clinically classifying PNHS.

Laryngeal electromyography (LEMG) is a technique used to characterize neuropathic injuries to the recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN). The RLN and SLN innervate the laryngeal muscles to produce vocal fold (VF) motion and elongation, respectively. VF motion deficiencies can affect voice, swallowing, and breathing, which can greatly affect a patient's quality of life. Neuropathy-related VF motion deficiencies most often result from surgical interventions to the skull base, neck, or chest likely due to the circuitous route of the RLN. LEMG is ideally conducted by an electromyographer and an otolaryngologist using a team-approach. LEMG is a powerful diagnostic tool to better characterize the extent of neuropathic injury and thus clarify the prognosis for VF motion recovery. This updated review discusses current techniques to improve the positive and negative predictive values of LEMG using laryngeal synkinesis and quantitative LEMG. Synkinesis can be diagnosed by comparing motor unit potential amplitude during vocalization and sniff maneuvers when recording within adductor muscles. Quantitative turns analysis can measure motor unit recruitment to avoid subjective descriptions of reduced depolarization during vocalization, and normal values are >400 turns/s. By integrating qualitative, quantitative, and synkinetic data, a robust prognosis can help clinicians determine if VF weakness will recover. Based on LEMG interpretation, patient-centered treatment can be developed to include watchful waiting, temporary VF augmentation, or definitive medialization procedures and laryngeal reinnervation.

Introduction/aims: Given the importance of early diagnosis and treatment of myasthenia gravis (MG), it is critical to understand disparities in MG care. We aimed to determine if there are any differences in testing, treatment, and/or access to neurologists for patients of varying sex and race/ethnicity with MG.

Methods: We used a nationally representative healthcare claims database of privately insured individuals (2001-2018) to identify incident cases of MG using a validated definition. Diagnostic testing, steroid-sparing agents, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and thymectomy were defined using drug names or CPT codes. Steroid use was defined using AHFS class codes. We also determined whether an individual had a visit to a neurologist and the time between primary care and neurologist visits. Logistic regression determined associations between sex and race/ethnicity and testing, treatments, and access to neurologists.

Results: Female patients were less likely to get a computed tomography (CT) chest (odds ratio (OR) 0.73, 95% confidence interval (CI): 0.64-0.83), receive steroids (OR: 0.85, 95% CI: 0.75-0.97), steroid-sparing agents (OR: 0.84, 95% CI: 0.72-0.97), and IVIG or PLEX (OR: 0.80, 95% CI: 0.67-0.95). Black patients were less likely to receive steroids (OR: 0.78, 95% CI: 0.63-0.96). No significant disparities were seen in access to neurologists.

Discussion: We found healthcare disparities in MG treatment with female and Black patients receiving less treatment than men and those of other races/ethnicities. Further research and detailed assessments accounting for individual patient factors are needed to confirm these apparent disparities.

Introduction/aims: Multidisciplinary care for patients with amyotrophic lateral sclerosis (ALS) is recommended in international guidelines, but reaches its limits when immobility increases. This pilot project addresses this gap by delivering home-based, specialized, multiprofessional support to ALS patients who are not able to attend outpatient care. The study assessed the feasibility of this model of care and the satisfaction of both patients and caregivers.

Methods: This was a longitudinal cohort study of patients with ALS and their caregivers in the surroundings of Munich, Germany. Patients were regularly visited at home by a multiprofessional team (neurologists/palliative care physicians, nurse, social worker, chaplain).

Results: A total of 94 patients with ALS were included in the homecare project and 88 patients and 74 caregivers were enrolled in the accompanying study. The mean care duration was 221 days, enabling 61% of the 49 deceased patients to die at home. Notably, 20% of patients chose a way to hasten death. Patient satisfaction (ICECAP Supportive Care Measure [SCM]: 23.7/28, CollaboRATE: 10.6/12) and caregiver perception of the end-of-life phase (Caregiver Evaluation of the Quality of End-Of-Life Care [CEQUEL]: 24.9/26) were high.

Discussion: This pilot project successfully implemented specialized, home-based multidisciplinary care for ALS patients and caregivers, demonstrating both feasibility and high satisfaction. The program enabled a large proportion of patients to remain in their homes, reducing the need for hospital care. The multiprofessional approach, including neuropalliative, psychosocial and spiritual support provided comprehensive care that addressed needs of patients and caregivers. Further research is warranted to explore cost-effectiveness.

In 2016, MLOS (myasthenia gravis Lambert-Eaton overlap syndrome) was coined to represent an entity of overlap syndrome of myasthenia gravis and Lambert-Eaton myasthenic syndrome. Fifty-five MLOS patients have been identified. Modification of the diagnostic criteria for MG by adding MuSK positive antibody testing is recommended. Two MuSK positive MLOS patients were identified by the new diagnostic criteria.

Introduction/aims: Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.

Methods: Two individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES).

Results: The two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.

Discussion: Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.

Introduction/aims: Diagnostic criteria for multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensorimotor neuropathy (MADSAM) require the involvement of at least two peripheral nerves. However, many patients with very similar features have clinical involvement of only a single peripheral nerve, which may preclude their correct diagnosis and treatment. The present study aimed to present a cohort of such patients and discuss the role of ultrasonography (US) in their diagnosis.

Methods: Patients with nonvasculitic immune-mediated motor mononeuropathies (MM) and sensorimotor mononeuropathies (SMM) were recruited prospectively or identified from the electronic records. They were invited to comprehensive follow-up visits consisting of clinical examination, electrodiagnostic (EDx), and US studies.

Results: Twenty-four patients (13 men) were studied (11 with MM). The characteristics of MM and SMM patients were very similar to MMN and MADSAM, respectively. The US, in addition to a long-swollen segment (average length, 20 cm) in the clinically affected nerve, revealed nerve swelling in, on average, six additional sites in clinically unaffected nerves.

Discussion: In patients with clinical and EDx involvement of only a single nerve, an US demonstration of multifocal peripheral nerve swelling points to a more widespread, probably dysimmune mechanism. Further studies are needed to evaluate the value of US as a supplementary method for the diagnosis of MADSAM and MMN in patients with clinical involvement of a single nerve.