Pharmacologic reversal of cortical hyperexcitability in patients with ALS.
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.
Caramia
M D
MD
Clinica Neurologica, Department of Neuroscience, Università di Roma Tor Vergata, and the IRCCS, S. Lucia, Rome, Italy. mwjones@ats.it
Palmieri
M G
MG
Desiato
M T
MT
Iani
C
C
Scalise
A
A
Telera
S
S
Bernardi
G
G
D000085:Acetates / Q000627:therapeutic use; D000588:Amines; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology*; D003509:Cyclohexanecarboxylic Acids; D003975:Diazepam / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D019054:Evoked Potentials, Motor; D005260:Female; D018755:GABA Agonists / Q000627:therapeutic use; D018757:GABA Modulators / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D008280:Magnetics; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010812:Physical Stimulation / Q000379:methods; D019782:Riluzole / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018755:GABA Agonists; D018757:GABA Modulators; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D019782:Riluzole; D003975:Diazepam