Introduction/Aims: We aimed to describe the clinical phenotype, histopathological findings and overall survival (OS) of the immune-mediated neuromuscular complications of graft-versus-host disease (GVHD).Methods: We conducted a retrospective chart review of adult patients presenting with immune-mediated neuromuscular complications of GVHD to Mayo Clinic, between April 2013 and July 2018.We collected clinical and laboratory characteristics, histopathological findings, response to treatment and survival data.Results: We identified 20 patients with a mean age at presentation of 55 y. Mean time from transplant to neurological presentation was 14 mo. Myositis was the most common complication seen in 17 patients, manifesting with predominantly axial and/or proximal weakness. Eleven patients had a muscle biopsy showing diffuse perimysial, predominantly macrophagic infiltration in 10, 3 of them with perimysial perivascular lymphocytic collections, and endomysial and perimysial lymphocytic infiltration in 1. Only two patients had a neuropathic complication: one each with acute inflammatory demyelinating polyradiculoneuropathy and neuralgic amyotrophy. A single patient had a myasthenic syndrome presenting with fluctuating foot drop.Nineteen patients were treated and all responded to immunosuppressive agents; however, 11 had further GVHD flares requiring escalation of therapy. After a median follow-up of 83 mo, seven (35%) patients died: five from progressive GVHD and two from infections. The 5-y OS from time of transplant was 68%.Discussion: Myositis is the most common immune-mediated neuromuscular complication of GVHD while peripheral neuropathy and myasthenic syndromes appear less common. The macrophage-predominant infiltration on muscle biopsy deserves further study to better clarify the role of macrophages in GVHD pathogenesis.
A 30-year-old woman with congenital vocal cord paralysis presented for evaluation of fatigable proximal upper limb weakness and difficulty maintaining the neck erect. Neurologic examination showed bilateral asymmetric eyelid ptosis, mild weakness (MRC 4/5), and atrophy of neck extensors and shoulder girdle muscles, whereas lower limb muscle strength was normal. Repetitive nerve stimulation revealed decremental responses in orbicularis oculis and trapezius. Needle electromyography demonstrated myopathic changes in proximal and paraspinal muscles. Acetylcholine receptor and muscle skeletal receptor tyrosine kinase (MuSK) antibodies, creatine kinase (CK), and lactate were negative or normal. Next-generation sequencing detected two heterozygous variants in the MUSK gene. One variant, c.79+2T>G, is a known pathogenic variant, and the other, c.2165T>C (p.V722A), is a novel missense variant, predicted to be pathogenic by in silico analysis. The two variants were proven to be in trans. This case expands the clinical and molecular spectrum of MuSK congenital myasthenic syndromes.
Outcomes similar to randomized controlled trials are attainable in 'real-world' settings. Workflow time metrics were independent predictors of clinical outcome, and differed between the two hospitals owing to site-specific organizational differences.
Introduction/Aims: The full spectrum of the clinical phenotype of facioscapulohumeral muscular dystrophy (FSHD), beyond skeletal muscle weakness, remains poorly characterized. In this study, we describe systemic manifestations and symptom burden in a large series of FSHD patients.Methods: We performed a retrospective chart review of FSHD patients seen at our institution between 2000 and 2017. We reviewed patients' responses to a comprehensive review of symptoms and the results of diagnostic testing for sensorineural hearing loss, cardiac disease, dysphagia, ocular abnormalities, and respiratory insufficiency. We assessed the association between disease manifestations and age of onset, genetic profile, and disease duration.
Results:We identified 87 patients with FSHD. The most common reported symptoms included pain (71%), difficulty sleeping (41%), headaches (27%), and altered mood (24%). When tested, 7 of 16 (44%) patients had sensorineural hearing loss, 20 of 60 (33%) had cardiac arrhythmias or conduction defects, 17 of 45 (38%) had echocardiogram abnormalities, 12 of 25 (48%) had reduced forced vital capacity, and 4 of 10 (40%) had oropharyngeal dysphagia. However, patients with these abnormalities represented 8%, 23%, 20%, 14%, and 5% of total number of patients, respectively, as uniform screening was lacking. Ocular pathology attributable to FSHD was not detected.Discussion: FSHD demonstrates a broad clinical phenotype. Increased vigilance among neurologists to screen for systemic manifestations of the disease is warranted.More uniform screening and future population-based studies are needed to compare findings in FSHD patients with the general population.
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