Abstract
Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impaired. The effectiveness of the glutamate antagonist riluzole (Rilutek®, Rhône-Poulenc Rorer) in ALS has been shown in clinical studies. In healthy subjects it modifies intracortical excitability in a frequently used double-stimulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not always significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and potentially rebalances impaired intracortical excitability in ALS. We, therefore, enrolled 13 patients with clinically and electromyographically confirmed ALS into this study. Five patients had to be excluded because motor thresholds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9±11.9 years (± standard deviation) and mean symptom duration 9.6±2.5 months. Intracortical excitability was assessed before and 1.5 hours after the first intake of a loading dose of 100 mg of riluzole using a conventional paired-pulse TMS paradigm with interstimulus intervals (ISI) ranging from 1–30 ms and intensities adjusted to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshold for conditioning pulses. Patients’ baseline results were compared to those of 9 age-matched, healthy control subjects. Before drug intake, motor thresholds did not differ between groups, but there was significantly less intracortical inhibition in the ALS patient group. Riluzole intake did not significantly alter motor thresholds or intacortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracortical excitability in ALS. Our results are in contrast to the findings of Stefan et al (1998) [14] where a partial normalization of intracortical inhibition in ALS was observed after at least 5 days of drug intake. The difference between that study and our result may indicate a delayed onset of riluzole’s influence on intracortical excitability.
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References
Bajaj NP, Irving NG, Leigh PN, et al (1998) Alzheimer’s disease, amyotrophic lateral sclerosis, and transgenic mice. J Neurol Neurosurg Psychiatry 64:711–715
Benavides J, Camelin JC, Mitrani N, et al (1985) 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission-II. Biochemical properties. Neuropharmacology 24:1085–1092
Bensimon G, Lacomblez L, Meininger V (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/ Riluzole Study Group. N Engl J Med 330:585–591
Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial ‘Clinical limits of amyotrophic lateral sclerosis’ workshop contributors. J Neurol Sci 124:96–107
Enterzari-Taher M, Eisen A, Stewart H, et al (1997) Abnormalities of cortical inhibitory neurons in amyotrophic lateral sclerosis. Muscle Nerve 20:65–71
Herbert T, Drapeau P, Pradier L, et al (1994) Block of the rat brain IIA sodium channel subunit by the neuroprotective drug riluzole. Mol Pharmacol 45:1055–1060
Hillel AD, Miller RM, Yorkstone K, et al (1989) Amyotrophic lateral sclerosis severity scale. Neuroepidemiology 8: 142–150
Kujirai T, Caramia MD, Rothwell JC, et al (1993) Corticocortical inhibition in human motor cortex. J Physiol (Lond) 471:501–519
Lacomblez L, Bensimon G, Leigh PN, et al (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 347:1425–1431
Liepert J, Schwenkreis P, Tegenthoff M, et al (1997) The glutamate antagonist riluzole suppresses intracortical facilitation. J Neural Transm 104:1207–1214
Liepert J, Schwenkreis P, Witscher K, et al (1998) Modulation of intracortical facilitation and intracortical inhibition during 7 days of Riluzole ingestion. Electroencephalogr Clin Neurophysiol 107:83P
Martin D, Thompson MA, Nadler JV (1993) The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol 250:473–476
Plaitakis A (1990) Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis: a hypothesis. Ann Neurol 28:3–8
Stefan K, Kunesch E, Benecke R, et al (1998) Riluzole restores impaired intracortical inhibition in patients with ALS. J Neurol 245:401
Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464–1468
Rothstein JD, Tsai G, Kuncl RW, et al (1990) Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 28:18–25
Yokota T, Yoshino A, Inaba A, et al (1996) Double cortical stimulation in amyotrophic lateral sclerosis. J Neurol neurosurg Psychiatry 61:596–600
Ziemann U, Lonnecker S, Steinhoff BJ, et al (1996) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol 40:367–378
Ziemann U, Winter M, Reimers CD, et al (1997) Impaired motor cortex inhibition in patients with amyotrophic lateral sclerosis. Evidence from paired transcranial magnetic stimulation. Neurology 49:1292–1298
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Sommer, M., Tergau, F., Wischer, S. et al. Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis. J Neurol 246 (Suppl 3), III22–III26 (1999). https://doi.org/10.1007/BF03161086
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DOI: https://doi.org/10.1007/BF03161086