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Neurology 2000;54:58
© 2000 American Academy of Neurology


Articles

Pharmacologic reversal of cortical hyperexcitability in patients with ALS

M. Donatella Caramia, MD, M. Giuseppina Palmieri, MD, M. T. Desiato, MD, C. Iani, MD, A. Scalise, MD, S. Telera, MD and G. Bernardi, MD

From the Clinica Neurologica, Department of Neuroscience (Drs. Caramia, Palmieri, Desiato, Iani, Scalise, Telera, and Bernardi), Università di Roma Tor Vergata; and the IRCCS (Drs. Caramia, Palmieri, Scalise, Telera, and Bernardi), S. Lucia, Rome, Italy.

Address correspondence and reprint requests to Dr. M. Donatella Caramia, Dipartimento di Neuroscienze, Clinica Neurologica c/o Ospedale S. Eugenio, Piazzale dell’Umanesimo 10, 00144 Roma-Italia; e-mail: mwjones{at}ats.it

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission.

BACKGROUND: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness.

METHODS: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the "drug-free" profile of paired TMS; (2) paired TMS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks’ treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day).

RESULTS: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p < 0.01) after diazepam and GBP.

CONCLUSIONS: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.

Key words: ALS—Paired transcranial magnetic stimulation—Intracortical inhibition—Motor evoked potential—GABAergic drugs




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