Pharmacologic reversal of cortical hyperexcitability in patients with ALS

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
Issue number1
Publication statusPublished - Jan 11 2000


  • ALS
  • GABAergic drugs
  • Intracortical inhibition
  • Motor evoked potential
  • Paired transcranial magnetic stimulation

ASJC Scopus subject areas

  • Neuroscience(all)


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