Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy.
OBJECTIVE
Proton MR spectroscopy has revealed impaired neuronal integrity in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). We hypothesized that the N-acetylaspartate (NAA)-creatine (Cr) ratios in the motor cortex and adjacent brain could reflect the therapeutic effectiveness of gabapentin (GBP) treatment in ALS.


METHODS
Eight patients with ALS underwent MR spectroscopy before and 26.5 days +/- 8.8 after starting GBP. In 10 patients with ALS who were not treated with GBP, paired spectra were obtained 21.4 days +/- 7.2 apart. Fourteen healthy subjects underwent a single MR spectroscopic examination. The NAA/Cr ratio was measured in the precentral gyrus, the postcentral gyrus, the superior parietal lobule, the supplementary motor area, and the premotor cortex.


RESULTS
The NAA/Cr ratio was decreased in the precentral and postcentral gyri of patients with ALS compared with healthy controls. In those with ALS, the change in the NAA/Cr ratio was not different between treated patients and untreated patients in any of the regions studied.


CONCLUSIONS
No improvement in neuronal integrity was detected in motor and nonmotor cerebral regions after GBP treatment. This result agrees with that of prior investigations showing the equivocal clinical effectiveness of GBP for ALS and supports the validity of the NAA/Cr ratio as a surrogate of therapeutic effectiveness.
Kalra
Sanjay
S
Department of Neurology and Neurosurgery, McGill University, Magnetic Resonance Spectroscopy Unit, Montreal Neurological Institute and Hospital, Quebec, Canada.
Cashman
Neil R
NR
Caramanos
Zografos
Z
Genge
Angela
A
Arnold
Douglas L
DL
D000085:Acetates / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000588:Amines; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D003401:Creatine / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D000077206:Gabapentin; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D012016:Reference Values; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C000179:N-acetylaspartate; D003401:Creatine