Bulbar Muscles Research Articles

Reliability of MScanFit Motor Unit Number Estimation in the Trapezius Muscle.

MScanFit motor unit number estimation (MUNE) is the most recent MUNE method which has shown promising results in extremity muscles, but it has not been applied to bulbar muscles. Bulbar muscles are particularly important in the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the feasibility and reliability of MScanFit MUNE in the accessory nerve and trapezius muscles. A total of twenty healthy participants were examined twice within 1-2 weeks. We extracted the MScanFit MUNE and size parameter, and compound muscle action potential (CMAP) amplitude values. The reliability of these parameters was assessed using the intra-rater coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland-Altman plots. We also correlated MUNE values with CMAP amplitudes using correlation coefficients. Mean MUNE values (Day 1 = 132.1 and Day 2 = 137.4), CMAP amplitudes (Day 1 = 9.71 mV and Day 2 = 10.10 mV) and size parameters did not differ between the two sessions (p > 0.05). CoV showed excellent reliability for MUNE values, size parameters, and CMAP amplitudes (CoV < 7%) whereas ICCs showed moderate reliability for MUNE values (ICC = 0.619), poor to moderate reliability for size parameters (between 0.393 and 0.689), and good reliability for CMAP amplitude (ICC = 0.864) There was no correlation between MUNE values and CMAP amplitudes. MScanFit MUNE is applicable and mostly reliable in the trapezius muscle. Further studies in patients are needed to investigate the sensitivity of MScanFit in this muscle in detecting motor unit loss, particularly in ALS.

Optimal time for the addition of non-corticosteroid immunosuppressants in myasthenia gravis: a single-center retrospective study in China.

Patients with myasthenia gravis (MG) display strong treatment heterogeneity. Recent studies have indicated that low-dose steroids or immunosuppressants are effective. However, factors affecting the add-on of non-corticosteroid immunosuppressants to corticosteroids remain unknown. Consecutive patients with MG were retrospectively reviewed from May 15, 2015, to December 29, 2020. We included one group of patients with steroid treatment alone and another group who transitioned to non-steroid immunosuppressant therapy. Clinical features of the included patients were analyzed. Univariate and multivariate Cox regression models were used to identify potential influential factors. A total of 107 patients with MG were analyzed, including 66 receiving corticosteroid treatment alone and 41 who subsequently also received non-corticosteroid immunosuppressant therapy. Eight potential factors were primarily selected in univariate analysis (Ps < 0.1). Achieving minimal symptom expression (MSE) within 6 months (HR: 4.424, 95%CI: 2.102-11.865), body mass index (BMI) (HR: 0.385, 95% CI: 0.186-0.797), quantitative MG (QMG) bulbar muscle score (HR: 1.553, 95% CI: 1.140-2.118), disease duration (HR: 0.987, 95% CI: 0.977-0.997) and relapse (HR: 2.638, 95% CI: 1.031-6.750) were finally identified as potential influencing factors. We found multifactorial clinical factors were highly associated with the add-on of non-steroid immunosuppressants after steroid treatment in patients with MG. Achieving MSE within 6 months, BMI, QMG bulbar muscle score at baseline before steroid treatment, disease duration, and disease relapse may represent crucial influencing factors, which should be considered to improve the long-term prognosis for patients with MG in future studies and practice.

A Dual Diagnosis of Myasthenia Gravis and Sjogren’s Syndrome in a Hispanic Patient: A Case-based Discussion of Clinical Findings, Therapeutic Implications, and Culturally Competent Care

The co-occurrence of myasthenia gravis (MG) and Sjogren's syndrome (SS) in a young, Hispanic, female patient underscores the diagnostic and therapeutic complexities inherent in autoimmune disorders. MG, a rare neuromuscular disorder characterized by autoantibodies impairing neuromuscular transmission, leads to variable muscle weakness and fatigue, notably affecting ocular and bulbar muscles. SS, an autoimmune condition with systemic manifestations, primarily affects secretory glands, resulting in symptoms such as xerostomia and xerophthalmia. Both conditions have higher prevalence rates in females, with MG particularly affecting young women under 40. Herein we present a case report and case-based discussion on diagnostic and management challenges of these two autoimmune conditions while highlighting issues specific to the Hispanic and underrepresented populations. Our goal is to highlight the intricate interplay between these two autoimmune pathologies to allow for more rapid recognition and reduce delay in diagnosis.

Clinical and neurophysiological characterization of p.Gly59Ser mutation in DCTN1: a study in a Thai family and a brief review.

Mutations in the Dynactin 1 (DCTN1) gene lead to various neurodegenerative disorders. The p.Gly59Ser mutation, the first pathogenic mutation identified in DCTN1, was initially reported in a family with distal hereditary motor neuropathy and early vocal cord paralysis. Since its discovery in 2003, this mutation has been documented in only three families worldwide, to the best of our knowledge. This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review. Five of the patients were female. The mean age of onset was 32.6 ± 1.9 years. Thai patients showed early involvement of intrinsic hand, facial, and bulbar muscles, with vocal cord impairment manifesting later in the disease course. Tongue fasciculations, not previously reported with this mutation, were observed in most Thai patients. Bilateral split-hands were consistently noted. Arytenoidectomy and cordotomy have proven beneficial in relieving upper airway obstruction and preventing life-threatening upper airway complications from vocal cord paralysis. The p.Gly59Ser mutation in DCTN1 presents with autosomal-dominant, adult-onset, lower motor neuronopathy/neuropathy. Compared to earlier reports, Thai patients exhibited more widespread involvement, including facial, bulbar, tongue, vocal cord, and limb muscles. In addition to vocal cord paralysis, the split-hand phenomenon emerges as another clinical hallmark of this condition.

Periodic Paralysis in a Child With Thermosensitive Mitochondrial Trifunctional Protein Deficiency.

Mitochondrial trifunctional protein (MTP) deficiency is a fatty acid oxidation disorder associated with a spectrum of phenotypes. Patients with high residual enzyme activity tend to have milder phenotypes, and recently, fever-induced episodic myopathy was reported in association with a thermosensitive form of MTP deficiency. We report a 10-year-old male with recurrent episodes of acute flaccid paralysis involving upper and lower extremities in association with bulbar muscle weakness in the context of febrile illness, a phenotype reminiscent of recurrent periodic paralysis. The episodes started at the age of 3 years and have always been followed by full recovery within 1-2 weeks with no residual weakness. Whole exome sequencing revealed a homozygous c.2132C > T, p.(Pro711Leu) variant in HADHA. The variant leads to mildly reduced long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain ketoacyl-CoA thiolase (LCKAT) enzyme activities and reduced MTP protein expression in patient's fibroblasts when cultured at 37°C. Enzyme activities and MTP protein expression diminished when fibroblasts were cultured at 40°C. This is the first published report of confirmed recurrent periodic paralysis as a manifestation of a thermosensitive form of MTP deficiency, and it calls for this condition to be considered when evaluating patients with recurrent periodic paralysis given therapeutic implications.

Risk Stratification and Management of Acute Respiratory Failure in Patients With Neuromuscular Disease.

Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) are the most common causes of acute neuromuscular respiratory failure resulting in ICU admission. This synthetic narrative review summarizes the evidence for the prediction and management of acute neuromuscular respiratory failure due to GBS and MG. We searched PubMed for relevant literature and reviewed bibliographies of included articles for additional relevant studies. English-language publications were reviewed. Data regarding study methodology, patient population, evaluation metrics, respiratory interventions, and clinical outcomes were qualitatively assessed. No single tool has sufficient sensitivity and specificity for the prediction of acute neuromuscular respiratory failure requiring mechanical ventilation. Multimodal assessment, integrating history, examination maneuvers (single breath count, neck flexion strength, bulbar weakness, and paradoxical breathing) and pulmonary function testing are ideal for risk stratification. The Erasmus GBS Respiratory Insufficiency Score is a validated tool useful for GBS. Noninvasive ventilation can be effective in MG but may not be safe in early GBS. Airway management considerations are similar across both conditions, but dysautonomia in GBS requires specific attention. Extubation failure is common in MG, and early tracheostomy may be beneficial for MG. Prolonged ventilatory support is common, and good functional outcomes may occur even when prolonged ventilation is required. Multimodal assessments integrating several bedside indicators of bulbar and respiratory muscle function can aid in evidence-based risk stratification for respiratory failure among those with neuromuscular disease. Serial evaluations may help establish a patient's trajectory and to determine timing of respiratory intervention.

Use of disease-modifying therapies in spinal muscular atrophy 5q in Mexico

5q Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease that causes weakness in the limbs, trunk, diaphragm, and bulbar muscles; without treatment it can lead to severe motor disability and even death. The Food and Drug administration (FDA) and COFEPRIS (Mexico's Federal Committee for Protection against Sanitary Risks) have approved 3 therapies to increase the production of survival motor neuron (SMN) protein and improve muscle strength and quality of life in patients: nusinersen, onasemnogene abeparvovec xioi, and risdiplam. Despite the fact that these therapies have shown efficacy, at the moment it is not possible to establish which of them is superior compared to the others. The most important thing is to establish the diagnosis of the disease and start any of the available treatments to avoid further functional disability and prevent death. The 3 treatments have different mechanisms of action and different adverse effects, and the use of each of them must be individualized according to the patient's profile.

Bulbar muscle impairment in patients with late onset Pompe disease: Insight from the French Pompe registry.

Late onset Pompe disease (LOPD) is a rare neuromuscular disorder caused by a deficit in acid alpha-glucosidase. Macroglossia and swallowing disorders have already been reported, but no study has focused yet on its frequency and functional impact on patients' daily life. We reviewed 100 adult LOPD patients followed in 17 hospitals in France included in the French national Pompe disease registry. The Swallowing Quality of Life Questionnaire and the Sydney Swallow Questionnaire were completed by patients, and a specialist carried out a medical examination focused on swallowing and assigned a Salassa score to each patient. Respiratory and motor functions were also recorded. Subgroup analysis compared patients with and without swallowing difficulties based on Salassa score. Thirty-two percent of patients presented with swallowing difficulties, often mild but sometimes severe enough to require percutaneous endoscopic gastrostomy (1%). Daily dysphagia was reported for 20% of our patients and aspirations for 18%; 9.5% were unable to eat away from home. Macroglossia was described in 18% of our patients, and 11% had lingual atrophy. Only 15% of patients presenting with swallowing disorders were followed by a speech therapist. Swallowing difficulties were significantly associated with macroglossia (p = 0.015), longer duration of illness (p = 0.032), and a lower body mass index (p = 0.047). Swallowing difficulties in LOPD are common and have significant functional impact. Increased awareness by physicians of these symptoms with systematic examination of the tongue and questions about swallowing can lead to appropriate multidisciplinary care with a speech therapist and dietitian if needed.

MYASTHENIA GRAVIS WITH FEATURES OF ACUTE PONS INFARCTION: A RARE CASE REPORT

Background: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease at neuromuscular synaptic transmission. The clinical sign of a myasthenia gravis is the presence of weakness that affects vision (ocular), bulbar and proximal skeletal muscles and also myasthenia gravis can resemble vascular disorders or any infectious diseases. Case: A 48-year-old Balinese male patient came to the emergency department of Prof I.G.N.G Ngoerah Central General Hospital complaining of shortness of breath. Shortness of breath is said to have occurred since one month ago. Shortness of breath improves slightly when the patient rests. Another complaint felt by the patient is that the right eyelid drops, especially during the daytime, will improve in the afternoon. The patient denied any weight loss or a history of malignancy. The patient about three months ago had fallen from a motorcycle and felt numbness in his right cheek until now. The patient has been undergoing treatment at the District General Hospital and he was diagnosed with myasthenia gravis and took Mestinon. CT scan of the head showed an acute infarction of the left pons accompanied by a suspicion of acute meningoencephalitis. Discussion: From the results of the RNS (Repetitive nerve stimulation) in this patient, it was found that the neuromuscular junction lesion was supportive of the description of the myasthenia gravis case. Conclusion: Myasthenia gravis is a disease of the nervous system with various manifestations. Good clinical examination and supporting examination are very necessary to confirm the diagnosis.

Clinical meaningfulness and psychometric robustness of the MG Symptoms PRO scales in clinical trials in adults with myasthenia gravis.

The objective of this research was to generate psychometric evidence supporting the myasthenia gravis (MG) symptoms patient-reported outcome (PRO) scales as a fit-for-purpose measure of severity of core symptoms of MG and provide information allowing their meaningful interpretation using data from a phase 3 study in MG. Data from the MycarinG study, a phase 3 study of rozanolixizumab in patients with generalized MG who experience moderate to severe symptoms (ClinicalTrials.gov Identifier: NCT03971422) were analyzed with both classical test theory (CTT) and Rasch measurement theory (RMT). Meaningful within-individual change and group-level meaningful change were estimated for three MG Symptoms PRO scales using anchor- and distribution-based methods. Anchor-based methods used patient global impression of severity (PGIS) and change (PGIC) in MG symptoms as anchors. Good measurement properties of the MG Symptoms PRO scales were shown in the sample of 200 participants: good to excellent reliability (test-retest and internal consistency reliability) and validity (associations between items and scores within the MG Symptoms PRO scales and between the MG Symptoms PRO scores and other clinical outcomes-MG ADL, QMG score, MGC score, and MGFA classes-were as expected); and the items showed good coverage of the continuum and fit to the Rasch model. Triangulation of the anchor- and distribution-based method results led to the definition of clinically meaningful within-patient improvement in scores for Muscle Weakness Fatigability (-16.67), Physical Fatigue (-20.00), and Bulbar Muscle Weakness (-20.00), with associated ranges. Benchmarks are also proposed for the interpretation of group-level results. The strong psychometric performance of the MG Symptoms PRO scales and the information generated to guide its interpretation supports its use in clinical trials for demonstrating the clinical benefits of new treatments targeting core symptoms of MG (muscle weakness fatigability, physical fatigue, bulbar muscle weakness, respiratory muscle weakness, and ocular muscle weakness).

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.

Chest Dynamic MRI as Early Biomarker of Respiratory Impairment in Amyotrophic Lateral Sclerosis Patients: A Pilot Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. Methods: We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. Results: We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Conclusions: Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.

Advances in Understanding and Managing Myasthenia Gravis: Current Trends and Future Directions.

Myasthenia gravis (MG) is an autoimmune illness characterized by autoantibodies against the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), and an increasing number of extra postsynaptic proteins. Pathogenic autoantibodies reduce the number of functional AChRs in the neuromuscular junction's (NMJ)muscle end plate. The cause of the autoimmune response is unknown, but thymic abnormalities and immune regulatory deficiencies are significant. The disease's incidence is likely influenced by genetic predisposition, with sex hormones and exercise playing a role. MGcan affect any age, race, or gender and can be caused by any stressor, with infections being the most frequent cause. Treatment focuses on airway support and the triggering incident. MG is a rare autoimmune disease causing fatigue-inducing weakness in the axial, respiratory, leg, and bulbar muscles. Initially affecting the eyes, most MGpatients experience at least one worsening symptom during their illness. The disease is mainly caused by antibodies against the AChR, dependence on the immune system within cells, and engagement of the complement system. The complement system plays a significant role in MG, and complement inhibition can both prevent the onset and slow its development. Ocular MG affects around 15% of people, with most patients having blocking antibodies against the cholinergic receptor. There may be correlations between thymoma and other autoimmune conditions, especially thyroid illness. Treatment and management for MGinvolve removing autoantibodies from circulation or blocking effector mechanisms using techniques such as complement inhibition, plasmapheresis, and B-cell elimination.

Change of voltage-gated sodium channel repertoire in skeletal muscle of a MuSK myasthenia gravis mouse model.

Muscle-specific kinase myasthenia gravis (MuSK MG) is caused by autoantibodies against MuSK in the neuromuscular junction (NMJ). MuSK MG patients have fluctuating, fatigable skeletal muscle weakness, in particular of bulbar muscles. Severity differs greatly between patients, in spite of comparable autoantibody levels. One explanation for inter-patient and inter-muscle variability in sensitivity might be variations in compensatory muscle responses. Previously, we developed a passive transfer mouse model for MuSK MG. In preliminary ex vivo experiments, we observed that muscle contraction of some mice, in particular those with milder myasthenia, had become partially insensitive to inhibition by μ-Conotoxin-GIIIB, a blocker of skeletal muscle NaV1.4 voltage-gated sodium channels. We hypothesised that changes in NaV channel expression profile, possibly co-expression of (μ-Conotoxin-GIIIB insensitive) NaV1.5 type channels, might lower the muscle fibre's firing threshold and facilitate neuromuscular synaptic transmission. To test this hypothesis, we here performed passive transfer in immuno-compromised mice, using 'high', 'intermediate' and 'low' dosing regimens of purified MuSK MG patient IgG4. We compared myasthenia levels, μ-Conotoxin-GIIIB resistance and muscle fibre action potential characteristics and firing thresholds. High- and intermediate-dosed mice showed clear, progressive myasthenia, not seen in low-dosed animals. However, diaphragm NMJ electrophysiology demonstrated almost equal myasthenic severities amongst all regimens. Nonetheless, low-dosed mouse diaphragms showed a much higher degree of μ-Conotoxin-GIIIB resistance. This was not explained by upregulation of Scn5a (the NaV1.5 gene), lowered muscle fibre firing thresholds or histologically detectable upregulated NaV1.5 channels. It remains to be established which factors are responsible for the observed μ-Conotoxin-GIIIB insensitivity and whether the NaV repertoire change is compensatory beneficial or a bystander effect.

Neurofilament Light Chain in Spinal Bulbar Muscle Atrophy and Amyotrophic Lateral Sclerosis 4 (P2-11.010)

Neurofilament Light Chain in Spinal Bulbar Muscle Atrophy and Amyotrophic Lateral Sclerosis 4 (P2-11.010)

Myasthenic Crisis in a Child: Successful Recovery after Early Identification and Intervention

Background: Juvenile myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder and has a varied presentation in childhood making it a diagnostic challenge. Clinical Description: An 8-year-old girl presented to the pediatric emergency with multiple episodes of falling, drooling of saliva, dysphagia, and bilateral ptosis. Within a few hours of admission, she had acute deterioration, developed respiratory failure, and was put on ventilatory support. Management and Outcome: A myasthenic crisis was suspected and a neostigmine challenge test was done. She was managed in the emergency with atropine, neostigmine, intravenous immunoglobulin, and supportive care. Subsequently, she achieved complete remission with steroids, physostigmine, and oral mycophenolate mofetil over the next 6 weeks. Conclusion: Juvenile MG may rarely be the cause of generalized muscular weakness. A strong suspicion of myasthenic crisis must be kept in case of sudden deterioration involving bulbar and respiratory muscles, in a patient with neurologic weakness. Early intervention in this rare condition can be lifesaving.

Respiratory morbidity in patients with spinal muscular atrophy-a changing world in the light of disease-modifying therapies.

Respiratory complications are common in spinal muscular atrophy (SMA) and significantly contribute to morbidity and mortality in these patients. Generalized respiratory and bulbar muscle weakness translates into diverse and complex clinical consequences necessitating strict follow-up and specialized care. The natural history of SMA has evolved drastically in recent years as a result of the introduction of novel, disease-modifying therapies. While the impact of these therapies on motor function is well described in literature, its consequence for respiratory management has not been extensively studied. In this review we aim to provide a comprehensive overview of the respiratory morbidities, their follow-up, management, and the impact of novel therapies in SMA.

Acute neuromuscular disorders in critically ill children

Acute neuromuscular disorders are a group of neurological emergencies characterized by rapid onset of motor weakness commonly involving the respiratory and bulbar muscles. These can be acute or an exacerbation of the chronic neuromuscular disease. An accurate and timely diagnosis allows for the timely institution of specific therapies, improving long-term functional outcomes. Landry–Guillain–Barre syndrome (LGBS), acute transverse myelitis, compressive myelopathy, traumatic spinal lesions, and anterior horn cell myelitis (due to viral infections) are some of the common causes of acute motor weakness in children. LGBS is the most common among all. The diagnosis relies on clinical presentation, signs, cerebrospinal fluid analysis, electrophysiological studies, and neuroimaging of the spine. Once compressive or traumatic spinal lesions are suspected, immediate neuroimaging of the spine is essential to plan early neurosurgical intervention. Pediatric intensive care unit (PICU) admission is often required for supportive management and immunomodulation. Supportive management typically includes endotracheal intubation to protect the airway, mechanical ventilation (MV) to support breathing, monitoring, management of autonomic dysfunction, control of pain, physiotherapy, adequate nutrition, prevention of pressure sores, bladder–bowel care, psychological support, and planning of long-term care. Autonomic dysfunction can cause hemodynamic instability, arrhythmias, sudden cardiac arrest, and death, requiring close monitoring and management in PICU. Tracheostomy is often needed in children who continue to have respiratory paralysis and are predicted to require long-term term mechanical ventilation. The outcome generally depends on the primary disease and long-term care.

Clinical Features and Prognostic Analysis of MuSK-Antibody-Positive Myasthenia Gravis versus Double-Seropositive Myasthenia Gravis: A Single-Center Study from Central South China.

To decipher the discrepancies between muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) and double-seropositive myasthenia gravis (DSP-MG), and to determine prognostic factors for minimal manifestation status (MMS) achievement in MG patients with MuSK autoantibodies (MuSK-Ab). A total of 34 MG patients seropositive for MuSK-Ab were enrolled in this study. The demographic and clinical features were compared between MuSK-MG (n = 28) and DSP-MG (n = 6) patients, and factors affecting MMS induction in all patients with MuSK-Ab were identified using Cox regression analysis. Compared to MuSK-MG patients, those with DSP-MG had similar clinical characteristics, except that they had a lower frequency of bulbar muscle involvement at nadir (50% vs 92.9%; P = 0.029) and higher proportions of comorbidities with diabetes mellitus (33.3% vs 0%; P = 0.027) and thymic abnormalities (33.3% vs 0%; P = 0.027). Higher MG Activities of Daily Living (MG-ADL) scores (HR = 0.16, 95% CI: 0.037-0.7, P = 0.015) and axial muscle involvement at nadir (HR = 0.39, 95% CI: 0.16-0.94, P = 0.035) were negative prognostic factors for MMS achievement in patients with MuSK-Ab regardless of acetylcholine receptor antibody (AChR-Ab) positivity. Multivariable Cox regression analysis further established higher MG-ADL scores at the nadir (HR = 0.19, 95% CI: 0.04-0.94; P = 0.042) as an independent risk factor for MMS achievement. DSP-MG was comparable to MuSK-MG and could be considered a single entity in our cohort. In all MG patients with MuSK-Ab, a higher MG-ADL score at nadir may herald a lower chance of MMS achievement, with no observed potential effect of AChR-Ab presence.

Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment

Background5q-associated spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons with consecutive weakness and atrophy of the limb, respiratory, and bulbar muscles. While trunk and limb motor function improve or stabilize in adults with SMA under nusinersen and risdiplam treatment, the efficacy on bulbar function in this age group of patients remains uncertain. However, it is important to assess bulbar dysfunction, which frequently occurs in the disease course and is associated with increased morbidity and mortality.MethodsBulbar function was evaluated prospectively in 25 non-ambulatory adults with type 2 and 3 SMA before and 4 and 12 months after risdiplam treatment initiation using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R). Extremity function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM).ResultsSubjective swallowing quality, measured with the SSQ, improved after 12 months of therapy with risdiplam. For the b-ALSFRS-R, a non-significant trend towards improvement was observed. The RULM score improved after 12 months of risdiplam therapy, but not the HFMSE score. HFMSE and RULM scores did not correlate with the SSQ but the b-ALSFRS-R score at baseline.ConclusionsThe improvement in subjective swallowing quality under risdiplam treatment, despite an advanced disease stage with severe motor deficits, strengthens the importance of a standardized bulbar assessment in addition to established motor scores. This may reveal relevant treatment effects and help individualize treatment decisions in the future.