ELSEVIER Electroencephalography and clinical Neurophysiology 101 (1996) 32-41 Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation N. Kohara a,*, R. Kaji a, y. Kojima a, K.R. Mills c, H. Fujii a, T. Hamano a, j. Kimura a, N. Takamatsu b, T. Uchiyama b a Departmentof Neurology, Kyoto UniversityHospital, Shogoin, Sakyo-Ku, Kyoto 606, Japan b NEC-Sanei, Kyoto, Japan ¢ UniversityDepartment of Clinical Neurology, The Radcliffe Infirmary, Oxford, UK Accepted for publication: 19 July 1995 Abstract The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The motor units were recorded from the first dorsal interosseus muscles of 12 patients with ALS, 14 healthy subjects, 12 patients with upper motor neuron lesions and 9 with pure lower motor neuron diseases. More than 100 magnetic stimuli were delivered over the scalp during minimal muscle contraction. The occurrence of motor unit discharges was plotted in a peristimulus time histogram. An increase in discharge probability at latencies of 20-30 msec, that represents monosynaptic activation (primary peak) was found in normal units. Motor units from ALS patients with short disease durations had significantly increased discharge probabilities in the primary peak (P < 0.01). Motor units from 4 ALS patients with upper motor neuron signs showed double primary peaks: an initial synchronized peak followed by a dispersed peak. The latter was ascribed to a slow corticospinal pathway, which remains undetected or is functionally insignificant in healthy subjects. We conclude that the excitabilities of the surviving corticospinal tract pathways are abnormally increased in ALS, especially in the early stage. Keywords: Peristimulus time histogram (PSTH); Amyotrophic lateral sclerosis (ALS); Single motor unit; Excitability; Corticospinal tract 1. Introduction Amyotrophic lateral sclerosis (ALS) is a fatal disease of unknown etiology. It involves both the upper and lower motoneurons, of which those comprising the direct corti- cospinal system seem to be selectively involved (Hudson and Kiernan, 1988; Eisen et al., 1992; Kaji and Kimura, 1993). Mounting clinical, pathological and physiological evi- dence points to the progressive loss of motoneurons, but little is known about the interaction of the upper and lower motoneurons in the disease process. The advent of trans- cranial magnetic or electrical stimulation of the motor * Corresponding author. Tel.: + 81 75 7513772; Fax: + 81 75 7619780. cortex has made possible functional assessments of the corticospinal tract system. Previous studies that used sur- face recordings of compound muscle action potentials after cortical stimulation have shown prolonged conduction times from the cortex to the spinal level and decreased amplitude or complete lack of evoked muscle responses in ALS (Ingram and Swash, 1987; Schriefer et al., 1989; Eisen et al., 1990; Berardelli et al., 1991). These findings are not, however, specific to ALS. They have been re- ported in such diseases that affect upper motoneurons as multiple sclerosis (MS) (Hess et al., 1987; Berardelli et al., 1988; Ingram et al., 1988) and cerebrovascular disease (CVD) (Bridgers, 1990; Berardelli et al,, 1991). Characteristic findings of ALS, such as fasciculations and muscle cramps, sometimes antedate development of muscle weakness and atrophy (Tyler and Shefner, 1991). 0924-980X/96/$15.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved SSDI 0013-4694(95)00 1 66- 2 EEM 95065