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.

Low Frequency-Repetitive Nerve Stimulation and Factors Affecting Decremental Response in Amyotrophic Lateral Sclerosis: A Retrospective Study of 449 Cases

A number of studies have demonstrated that decremental response to low frequency repetitive nerve stimulation (LF-RNS) is frequently observed in amyotrophic lateral sclerosis (ALS). However, due to the small sample size involved in previous studies, large discrepancies exist about the positivity rates of LF-RNS tests and factors affecting decremental response. This retrospective study of 449 cases, the largest sample size ever reported, shows that the overall positivity rate of LF-RNS is 49.9%. 3Hz RNS delivered to the accessory nerve has the best sensitivity and highest positivity rate. It obviously increases in response to upper limb onset, disease progression rate < 0.5 score/month, definite ALS and electromyography positive(EMG(+)) in sternocleidomastoid muscle. There is a linear increase in the decrement percentage of CMAP amplitude at 3Hz RNS delivered to the accessory nerve in response to longer disease duration, longer MUP duration and greater MUP duration increment percentage. These findings substantially advance the understanding of RNS results in ALS patients and effectively instruct clinical application.

Case Report: The Neuromusclar Triad of Immune Checkpoint Inhibitors: A Case Report of Myositis, Myocarditis, and Myasthenia Gravis Overlap Following Toripalimab Treatment

The neuromuscular adverse events of immune checkpoint inhibitor (ICI) treatment include myositis, polymyalgia rheumatica, myocarditis, and myasthenia syndrome. We report a 47-year old female presenting with external ophthalmoplegia, generalized muscle weakness, and third-degree atrioventricular block 4 weeks after toripalimab treatment for metastatic thymoma. Creatine kinase was elevated to 25,200 U/l and cardiac troponin I to 2.796 ng/ml. Autoantibody profiling shows positive anti-ryanodine receptor and anti-acetylcholine receptor antibodies and negative myositis specific antibodies. Repetitive nerve stimulation did not reveal decrement of compound muscle action potentials. Pulse methylprednisolone and immunoglobulin infusion, together with temporary pacemaker insertion normalized her muscle enzyme levels and cardiac rhythm. This is the first report of overlaping neuromuscular adverse event of toripalimab.

Persistent neuromuscular junction transmission defects in adults with spinal muscular atrophy treated with nusinersen

ObjectiveSpinal muscular atrophy (SMA) is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. Prior work in models and patients has demonstrated electrophysiological and morphological defects at the neuromuscular junction (NMJ). Therapeutic development has resulted in clinically available therapies to increase SMN protein levels in patients and improve muscle function. Here we aimed to investigate the effect of SMN restoration (via nusinersen) on NMJ transmission in adults with SMA.MethodsParticipants undergoing nusinersen treatment underwent 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve to assess compound muscle action potential amplitude decrement. Maximum voluntary isometric contraction (MVICT), Revised Upper Limb Module (RULM), and 6 min walk test (6MWT) were assessed for correlations with decrement.ResultsData from 13 ambulatory (7 men/6 women, mean age 40±11 years) and 11 non-ambulatory (3 men/8 women, mean age 38±12 years) participants were analysed. Cross-sectional analyses of RNS decrement were similar at 14 months of nusinersen (−14.2%±11.5%, n=17) vs baseline (−11.9%±8.3%, n=15) (unpaired t-test, p=0.5202). Longitudinal comparison of decrement in eight participants showed no change at 14 months (−13.9%±6.7%) vs baseline (−16.9%±13.4%) (paired t-test, p=0.5863). Decrement showed strong correlations with measures of MVICT, RULM and 6MWT but not age or disease duration.ConclusionAdults with SMA had significant NMJ transmission defects that were not corrected with 14 months of nusinersen treatment. NMJ defects were negatively associated with physical function, and thus may represent a promising target for additive or combinatorial treatments.

Lambert-Eaton Myasthenic Syndrome Presenting as Cerebellar Symptoms

A 79-year-old man visited neurology clinic due to gait ataxia and vertigo for 10 months. Neurologic examination revealed saccadic pursuit, mild dysmetria, impaired tandem gait, and areflexia that recovers after exercise. The amplitude of compound muscle action potentials recorded on the abductor digiti minimi increased up to 6,639.4% during repetitive nerve stimulation at 50 Hz stimulation. This case demonstrates that clinicians should consider Lambert-Eaton myasthenic syndrome as a differential diagnosis when a patient complains of gait ataxia and vertigo.