G.P.98 Dysfunction of the neuromuscular junction in patients with spinal muscular atrophy type 2 and 3

Abstract

Abstract Degeneration of the alpha motor neurons in the spinal cord is the pathological hallmark of SMA. Recent pathological studies in mouse models of SMA have uncovered significant additional abnormalities in the morphology of the neuromuscular junction (NMJ). It is not known whether these anatomical abnormalities of the NMJ result in NMJ dysfunction. Repetitive nerve stimulation (RNS) is a specific and relatively sensitive tool for detecting NMJ dysfunction. RNS was performed in four nerves from 35 patients, aged 8 years upwards, with SMA types 2, 3 and 4, 20 healthy controls, and 5 patients with motor neuron disease (MND). Pathological decremental responses (> 10%) during 3 Hz repetitive nerve stimulation were observed in 17 out of 35 (49%) patients with spinal muscular atrophy types 2 and 3, but not in healthy controls or patients with motor neuron disease. Amplitude changes during RNS in patients with SMA ranged from −32.4% to +16.1%, in healthy controls from −7.4% to +7.9% and in patients with MND from −10% to +2.7% (p 60%. Abnormal decremental responses were more often observed in patients with SMA type 2 than 3 (ns). Two out of four patients who tried pyridostigmine reported increased stamina. Anatomical changes of the NMJ in patients with SMA probably cause postsynaptic dysfunction of the neuromuscular junction. The finding that NMJ function is impaired in patients with SMA may offer new opportunities for treatment.