A lack of neuroinhibitory function may result in unopposed excitotoxic neuronal damage in
amyotrophic lateral sclerosis (ALS).
To determine whether there are reductions in γ-aminobutyric acid (GABA) levels and
elevations in glutamate-glutamine (Glx) levels in selected brain regions of patients with ALS by use
of proton magnetic resonance spectroscopy.
Case-control study using short echo time and GABA-edited proton magnetic resonance spectroscopy
at 3 T with regions of interest in the left motor cortex, left subcortical white matter, and pons;
data analyzed using logistic regression, t tests, and Pearson correlations; and
post hoc analyses performed to investigate differences between riluzole-naive and riluzole-treated
patients with ALS.
Tertiary referral center.
Twenty-nine patients with ALS and 30 age- and sex-matched healthy controls.
Fifteen patients were taking 50 mg of riluzole twice a day as part of their routine clinical care
Main Outcomes and Measures
Levels of GABA, Glx, choline (a marker of cell membrane turnover), creatine (a marker of energy
metabolism), myo-inositol (a marker of glial cells), and N-acetylaspartate (a
marker of neuronal integrity).
Patients with ALS had significantly lower levels of GABA in the motor cortex than did healthy
controls (P < .01). Patients with ALS also had significantly lower
levels of N-acetylaspartate in the motor cortex
(P < .01), subcortical white matter
(P < .05), and pons (P < .01) and
higher levels of myo-inositol in the motor cortex (P < .001) and
subcortical white matter (P < .01) than did healthy controls.
Riluzole-naive patients with ALS had higher levels of Glx than did riluzole-treated patients with
ALS (P < .05 for pons and motor cortex) and healthy controls
(P < .05 for pons and motor cortex). Riluzole-naive patients with
ALS had higher levels of creatine in the motor cortex (P < .001 for
both comparisons) and subcortical white matter (P ≤ .05 for both
comparisons) than did riluzole-treated patients with ALS and healthy controls. Riluzole-naive
patients with ALS had higher levels of N-acetylaspartate in the motor cortex than
did riluzole-treated patients with ALS (P < .01).
Conclusions and Relevance
There are reduced levels of GABA in the motor cortex of patients with ALS. There are elevated
levels of Glx in riluzole-naive patients with ALS compared with riluzole-treated patients with ALS
and healthy controls. These results point to an imbalance between excitatory and inhibitory
neurotransmitters as being important in the pathogenesis of ALS and an antiglutamatergic basis for
the effects of riluzole, although additional research efforts are needed.