Congenital myasthenic syndrome in a cohort of patients with ‘double’ seronegative myasthenia gravis

ABSTRACT Background: Congenital myasthenic syndromes (CMS) have some phenotypic overlap with seronegative myasthenia gravis (SNMG). Objective: The aim of this single center study was to assess the minimum occurrence of CMS misdiagnosed as double SNMG in a Brazilian cohort. Methods: The genetic analysis of the most common mutations in CHRNE, RAPSN, and DOK7 genes was used as the main screening tool. Results: We performed genetic analysis in 22 patients with a previous diagnosis of ‘double’ SNMG. In this study, one CMS patient was confirmed due to the presence of compound heterozygous variants in the CHRNE gene (c.130insG/p.Cys210Phe). Conclusions: This study confirmed that CMS due to CHNRE mutations can be mistaken for SNMG. In addition, our study estimated the prevalence of misdiagnosed CMS to be 4.5% in ‘double’ SNMG patients of our center. Based on our findings, genetic screening could be helpful in the diagnostic workup of patients with ‘double’ SNMG in whom differential diagnosis is recommended.

Electrophysiological studies in patients with seropositive/seronegative myasthenia gravis

Background: Myasthenia gravis (MG) affects the neuromuscular transmission, causing fluctuating muscle weakness and fatigue. This study is carried out with the aim to study the electrophysiologic findings of different subtypes of MG referred to our center in Tehran, Iran. Methods: All patients with MG presenting to neurology department of Shariati Hospital, Tehran University of Medical Sciences were enrolled. Clinically, patients with MG were categorized as ocular vs. generalized. The acetylcholine receptor (Ach-R) and muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies were performed. Repetitive Nerve Stimulation (RNS) was performed using the standard method, with supramaximal stimulation of muscles at the 3 Hz frequency by surface electrode at rest. Abductor pollicis brevis (APB) (median nerve), anconeus (radial nerve), trapezius (accessory nerve), and nasalis (facial nerve) muscles were studied in all patients. Single fiber electromyography (SFEMG) was performed by standard method. Results: 196 seropositive patients with MG were included in the study. In electrophysiological studies, RNS was performed for 146 patients of Ach-R-Ab positive MG, with positive results in 110 patients. In addition, SFEMG was conducted for 8 patients with negative RNS, which resulted in 7 positive tests.

Late-onset double-seronegative myasthenia gravis syndrome and myasthenic crisis due to nivolumab use for Hodgkin’s lymphoma

Introduction Insofar, use of programmed cell death-1 (PD-1) immune checkpoint inhibitors in oncology has been linked with several immune-mediated neurologic effects. However, grade 3 to 4 adverse events such as myasthenic crisis have been vanishingly rare. Case presentation: We present herein a unique patient with Hodgkin lymphoma who developed late-onset double-seronegative myasthenia gravis syndrome followed by myasthenic crisis after 16 weeks of therapy with nivolumab. One day prior to this event, she developed ptosis, diplopia, bulbar symptoms of dysphagia, dysarthria, orthopnea as well as extremity weakness. She required intubation, mechanical ventilation, plasmapheresis and steroid therapy. Management and outcome: She gradually achieved a near-complete resolution of neurologic symptoms over the next several weeks. On a follow-up visit eight weeks later, she only has some residual diplopia. Restaging scans showed a continued decrease in size of the mediastinal mass, without abnormal uptake. She remains on prednisone 10 mg orally daily. Discussion Prompt recognition of this rare phenomenon, immediate discontinuation of checkpoint inhibitor therapy and subsequent management with immunosuppressive therapy are necessary steps in order to minimize the considerable rates of morbidity and mortality.