Muscle & Nerve最新文献

Muscle injury resulting in markedly elevated creatine kinase levels is termed rhabdomyolysis. The muscle damage can occur because of direct or indirect trauma, or it can be related to the use of certain medications, toxins, illicit drugs, or the presence of underlying inflammatory, metabolic, or genetic disorders with a predisposition for rhabdomyolysis. A detailed review of history can help in identifying the underlying etiology. Identification and removal of the triggering/inciting factor and noxious stimuli should be attempted as soon as possible. Careful evaluation for any complications and initiation of appropriate treatment are recommended. Aggressive fluid therapy, correction of metabolic derangement, and, when warranted, renal replacement therapy, form the mainstays of treatment.

Introduction/aims: Health literacy (HL) can influence self-management and outcomes in chronic diseases, but it remains poorly characterized in the context of rare diseases, including myasthenia gravis (MG). This study aimed to explore general HL levels and specific HL domains and competencies in adults with MG and their associations with sociodemographic, clinical, and organizational factors.

Methods: A multicentre, observational, cross-sectional study was conducted between April and October 2024 in 22 neurology centres located in 11 regions of northern, central, and southern Italy. Eligible participants were adult patients (≥ 18 years) with a confirmed diagnosis of MG. Comparisons across patient groups were explored with non-parametric tests; multivariable linear models were used to estimate adjusted associations.

Results: A total of 113 participants were enrolled. The median HLS₁₉-Q12 total score was 58.3 (IQR: 41.7-75.0), indicating problematic HL. In adjusted models, higher education was significantly associated with lower appraisal competence (β = -11.1, 95% CI: -20.2, -2.0). Not meeting the Patient Acceptable Symptom State (PASS) was significantly associated with lower scores across multiple domains and competencies, while follow-up in centres with nurses specialized in MG was significantly associated with higher scores in access (β = 8.2, 95% CI: 0.9, 15.6), understanding (β = 10.8, 95% CI: 2.1, 19.4), application (β = 10.6, 95% CI: 2.6, 18.7), health care (β = 11.5, 95% CI: 2.9, 20.0), and health promotion (β = 11.9, 95% CI: 3.5, 20.2).

Discussion: Symptom-burdened patients and centres without specialized nursing support appear to be priority targets for HL-oriented interventions and organizational redesign.

Introduction/aims: Hypokalemic periodic paralysis (HypoKPP) is an ion channelopathy causing episodic skeletal muscle weakness triggered by hypokalemia. Reduced inward rectifier K⁺ (Kir) channel activity contributes to membrane depolarization and paralysis, suggesting that pharmacologic activation of muscle K⁺ channels may restore excitability. The Kv7 channel agonist retigabine previously mitigated low-K⁺ weakness in HypoKPP models. Here, we tested whether this effect persists under conditions producing sustained, severe weakness.

Methods: Extensor digitorum longus (EDL) muscles from mice homozygous for the SCN4A R669H mutation were studied by isometric twitch force recording at 34°C, with or without 20 U/L insulin. Weakness was induced by reducing extracellular K⁺ to 1.0 mM. Retigabine (10 μM) was applied to the bath, and twitch force was analyzed by paired or unpaired t tests (n = 4-7 per group).

Results: Baseline twitch force in 4.75 mM K⁺ was ~50% lower in HypoKPP than wild-type muscle (p = 0.01). Force declined further after 1 h in 4.75 mM K⁺ (p = 0.016) and was completely lost at 1.0 mM K⁺ with insulin. Retigabine significantly reduced loss of force at both 4.75 and 1.0 mM K⁺ (p = 0.047 and p = 0.007, respectively).

Discussion: Kv7 channel activation by retigabine preserved contractile force even during sustained depolarization from severe hypokalemia. These findings extend prior work and support development of K⁺ channel agonists as a therapeutic approach for HypoKPP.

Introduction/aims: Sex-specific differences in myasthenia gravis (MG) are widely acknowledged, yet data on sex-based outcomes of MG treatment are scarce. In accordance with Sex and Gender Equity in Research guidelines, this post hoc analysis assessed potential sex-specific differences in treatment outcomes in acetylcholine receptor antibody-positive (AChR-Ab+) generalized (g)MG participants in the Phase 3 ADAPT trial (NCT03669588).

Methods: Participants received four once-weekly efgartigimod infusions (10 mg/kg) or placebo per cycle. Endpoints (primary: proportion of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders (Cycle 1); secondary: proportion of Quantitative Myasthenia Gravis (QMG) and early (Cycle 1) MG-ADL responders, and time with clinically meaningful improvements in MG-ADL score; additional: quality of life outcomes, pharmacodynamics) were assessed according to sex.

Results: Females were younger (mean age: 42.9 vs. 54.8 years), more likely to have undergone thymectomy (65.1% [56/86] vs. 44.2% [19/43]), and had higher baseline QMG scores (16.3 vs. 14.3) compared with males. Efgartigimod demonstrated homogeneous effects between sexes, with no significant difference in proportions of MG-ADL (p = 0.7014), early (Cycle 1) MG-ADL (p = 1.00), or QMG responders (p = 0.1595). Improvements in quality-of-life assessments, rates of minimal symptom expression, and mean total immunoglobulin G reductions (Cycle 1) were greater with efgartigimod verso placebo in females and males. Efgartigimod was well tolerated, with similar safety profiles across sexes.

Discussion: In ADAPT, efgartigimod-treated female and male AChR-Ab+ gMG patients had similar efficacy and safety outcomes. These data provide valuable insight for clinicians, given the established sex differences in MG disease course and treatment responses.

Trial registration: The ADAPT trial is registered on ClinicalTrials.gov (NCT03669588).

Introduction/aims: Direct involvement of the neuromuscular junction (NMJ) in the inflammatory process of Guillain-Barré syndrome (GBS) has been described. Despite this, the NMJ very rarely serves as a target for direct medical intervention in GBS. Here, we report the use of an acetylcholinesterase inhibitor, pyridostigmine, in four pediatric patients with axonal GBS.

Methods: All patients received standard immune therapy. Pyridostigmine treatment was started 7 weeks to 5 months after disease onset, and 5-11 weeks from reaching the plateau phase. Treatment efficacy was monitored by the 6-min walk, quadriceps femoris and hamstring strength (manual muscle testing), the pediatric evaluation of disability inventory-functional skills, and the GBS disability score. All tests were performed before and during drug intervention.

Results: All treated patients showed marked improvement in their motor and functional abilities. After 1 month of treatment, quadriceps femoris and hamstring strength increased by at least two points, and walking distance increased by 10-272 m. The pediatric evaluation of disability inventory functional skills mobility test increased by 22.3-34.7 points. No serious side effects were documented.

Discussion: Pyridostigmine may be a safe and effective add-on treatment in pediatric patients with axonal GBS who show insufficient response to immune therapy, and may be effectively used even at a late stage. Additional, larger studies are needed.

Introduction/aims: Dropped head syndrome (DHS) is common in advanced stages of amyotrophic lateral sclerosis (ALS), but infrequently reported among the early symptoms. We explored the frequency of DHS in a genetic ALS cohort harboring pathogenic variants to determine whether DHS is a prognostic factor for survival, particularly when appearing at an early stage.

Methods: We collected the following variables to investigate a phenotype/genotype correlation: pathogenic variant (PV), sex, age at clinical ALS onset, time between ALS onset and DHS onset, and between DHS onset and death. DHS appearing within 12 months of clinical onset was classified as early DHS (EDHS); otherwise, as late DHS (LDHS).

Results: We observed DHS in 62 of 93 patients with genetic ALS, with a median of 26.5 months between ALS clinical onset and identification of DHS. DHS was present in 72.1% of the 43 patients with C9orf72 expansions, 52.9% of the 34 with SOD1 , 100% of the 10 with FUS/TLS, and 50% of the 6 with other ALS gene PVs. EDHS appeared in 16 patients. Ten EDHS patients were C9orf72, and six were FUS/TLS . DHS was a significant factor for survival in the age-adjusted Cox regression model. The hazard ratio was 11.63 times higher for patients with DHS, with age as a concomitant variable.

Discussion: Our results suggest that DHS is more prevalent in patients with C9orf72 and FUS/TLS than in those with SOD1 and other ALS-linked genes, and a risk factor for short survival, especially when appearing within 12 months of ALS onset.

Introduction/aims: Amyotrophic lateral sclerosis (ALS) affects military veterans at a higher rate than the general civilian population. The aim of the present study is to assess symptom burden and satisfaction with care among persons with ALS care enrolled in the US Veterans Health Administration (VA).

Methods: A custom online survey was created with questions about symptom prevalence and management as well as care satisfaction. A survey link was sent by email to all veterans with an ICD-10 diagnosis of ALS in the VA for whom an email address was available in the electronic health record.

Results: Responses were received from 413 individuals (16% response rate). Respondents reported high care satisfaction and higher prevalence of treatment of symptoms compared to prior surveys of persons with ALS in the United States. Self-reported outcomes, including treatment, education, and satisfaction, were better for Veterans receiving care exclusively within the VA compared to those receiving care at both VA and non-VA facilities or receiving care exclusively at non-VA facilities. Areas for further improvement identified in the survey include education on genetic testing and research and management of non-motor symptoms.

Discussion: This survey indicates that, overall, veterans with ALS receive comprehensive symptom-based care within the nationalized VA care system and report high levels of satisfaction. Furthermore, this study provides baseline data and findings that may be used for quality improvement efforts across a large healthcare system and may serve as a model for similar efforts in other health systems.

Introduction/aims: Durable medical equipment (DME)-wheelchairs, non-invasive ventilation, gastrostomy tubes, and communication devices-provides vital support for individuals with amyotrophic lateral sclerosis (ALS). Here, we describe DME use in COURAGE-ALS evaluating reldesemtiv's efficacy and safety in ALS, to evaluate if DME use can be considered an endpoint of interest in ALS trials.

Methods: COURAGE-ALS, a multicentre, double-blind, randomized, placebo-controlled clinical trial was conducted at 83 sites in the United States, Canada, Europe, and Australia. Participants were randomized 2:1 to receive reldesemtiv or placebo for 24 weeks, followed by 24 weeks of active drug treatment. Exploratory outcomes included reasons for prescribing, extent of use, DME types, and regional differences.

Results: Among 482 participants, 166 (34.4%) were using at least one DME item at baseline. Among 276 participants completing study visits through Week 24, 130 (47.1%) initiated use of a total of 188 new DME items post-baseline through 24 weeks. Manual wheelchairs were most used at baseline (89 items) and initiated (47 items) during the trial. Both baseline DME use and initiating a new item were associated with lower ALS Functional Rating Scale-Revised scores and worse quality of life. The trial was terminated early due to futility. Treatment assignment did not impact DME use. Regional disparities were noted.

Discussion: This study shows that DME is commonly prescribed to ALS trial participants. Further understanding of geographic differences in DME access and their impact on clinical outcomes is warranted prior to including DME use as an endpoint in ALS trials.

Trial registration: ClinicalTrials.gov identifier: (NCT04944784).

Introduction/aim: Anti-neurofascin (Nf) -associated neuropathies represent a distinct subset of immune neuropathies. While literature on this entity is evolving, there is currently no published data on these disorders from India. The study aims to characterize Indian patients presenting with anti-Nf-associated neuropathies.

Methods: A retrospective chart review (January 2019-April 2024) of patients who had tested positive for one or more anti-Nf antibodies in a tertiary university teaching hospital was carried out. Their clinical, investigative, and therapeutic data were documented and analyzed.

Results: 38 patients with varied clinical presentations were studied. Acute and chronic forms were equally common. Sensorimotor weakness, sensory ataxia, tremors, and fluctuating course were common in the chronic group. Acute presentations were typically motor predominant, severe at onset, with rapid progression to nadir. Four patients with recurrent acute presentations were noted. A demyelinating predominant pattern was seen in 19, axonal predominant pattern in 16, and features of chronic immune radiculopathy in 3 patients. Nodal antibodies were more frequent than paranodal antibodies. About two-thirds of patients required more than two immunotherapeutic agents. A favorable response to rituximab was observed in 16/21 patients. Patients with both nodal and paranodal antibodies (Pan Nf neuropathies) were more severe and resistant to therapy.

Discussion: Anti-Nf-associated neuropathies in this Indian cohort were clinically heterogeneous, spanning acute, chronic, and recurrent phenotypes. Tremors, sensory ataxia, pain, and fulminant onset are valuable diagnostic clues. Pan-Nf-associated neuropathies were consistently severe and treatment-resistant. Rituximab demonstrated significant benefit in most cases, supporting its use in refractory and relapsing disease.