ALS and myasthenia: An unusual association in a patient treated with riluzole

Treatment with riluzole has been proposed in both sporadic and familial amyotrophic lateral sclerosis (ALS). We report a patient with familial ALS who developed myasthenia gravis (MG) during treatment with riluzole. A 53-year-old man, with a positive family history spanning three generations of autosomal dominant ALS, presented with weakness and atrophy in his right hand, cramping pain in the muscles of both legs, and diffuse fasciculations. The patient complained also of difficulty in walking for long distances and in arising from a chair. Clinical examination revealed hyperreflexia, muscular atrophy, fasciculations, and weakness in the arms and legs. Sensory abnormalities were not present. Needle electromyography showed fibrillation potentials, positive sharp waves, fasciculations, and increased number of polyphasic and long-duration motor unit potentials in right tibialis anterior and vastus medialis muscles. Recruitment showed a poor interference pattern, with motor unit potentials firing rapidly. Motor conduction studies in the right and left median, ulnar, radial, and peroneal nerves were normal, as were sensory studies of the right and left median, ulnar, and sural nerves. Somatosensory evoked potentials elicited from the right and left median and posterior tibial nerves and recorded over the scalp also were normal. Motor evoked potentials had prolonged central motor conduction time (23 ms and 24 ms in right and left extensor digitorum brevis, respectively; normal value, 19 ms). Cerebrospinal fluid protein and glucose concentration and the cell count were normal. Treatment with riluzole was started, with an initial dose of 100 mg per day. After 3 months, the patient complained of unusual muscle fatigability which was promptly reversed by rest. On examination, the patient showed ptosis and diplopia. Repetitive nerve stimulation (RNS) at 3 Hz showed a decrement exceeding 40% in deltoid and orbicularis oculi muscle. Single-fiber electromyography (SFEMG) showed increased jitter in arms and cranial muscles (in five of 20 pairs of potentials recorded from extensor digitorum communis, biceps, and frontalis muscle, respectively) and blocks (in one of three and in three of five pairs of potentials from extensor digitorum communis and orbicularis oculi, respectively.) Following the intravenous injection of 5 mg edrophonium (Tensilon), ptosis and diplopia improved, and RNS showed a complete (biceps and deltoid) or partial (orbicularis oculi) reversal of decrement. The serum concentration of acetylcholine receptor (AChR) antibodies was increased (22.5 pmol/L in August 1996; normal values, <0.4 pmol/L). Computed tomographic scan of the thorax was normal. Pyridostigmine bromide (Mestinon) was started at the same time riluzole was stopped, with clinical improvement, chiefly in the cranial muscles. A second SFEMG showed shortening of abnormal jitter and a decreased incidence of blocking. The serum concentration of AChR antibodies gradually decreased (4 pmol/mL in February 1997; 2.2 pmol/mL in July 1998). In patients with ALS, electrophysiological studies often show signs of defective neuromuscular transmission (decrementing response to RNS, abnormal jitter, and an increased incidence of blocking), and a Tensilon test may be positive. However, in our patient, the clinical (particularly ocular muscle involvement) and neurophysiological findings as well as the clear improvement after treatment with anticholinesterase drugs suggest a diagnosis of MG in addition to the presence of established ALS. To our knowledge, a possible association between ALS and MG is very unusual. Noseworthy et al. described a patient whose presentation suggested MG but who subsequently developed tongue fasciculations and whose lack of response to treatment led to a diagnosis of ALS. Recently, Okuyama et al. described an ALS patient with increased AChR antibody (0.50 nmol/L), but clinical features of MG were not present and the presence of the AChR antibody may simply have been a coincidental finding without any pathoCCC 0148-639X/00/020294-03 © 2000 John Wiley & Sons, Inc.