Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy

AJNR Am J Neuroradiol. 2003 Mar;24(3):476-80.

Abstract

Background and purpose: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / adverse effects
  • Acetates / therapeutic use*
  • Aged
  • Amines*
  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Cell Survival / drug effects*
  • Cell Survival / physiology
  • Creatine / metabolism
  • Cyclohexanecarboxylic Acids*
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Female
  • Follow-Up Studies
  • Gabapentin
  • Humans
  • Magnetic Resonance Imaging*
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged
  • Motor Cortex / drug effects*
  • Motor Cortex / physiopathology
  • Parietal Lobe / drug effects
  • Parietal Lobe / physiopathology
  • Reference Values
  • Treatment Outcome
  • gamma-Aminobutyric Acid*

Substances

  • Acetates
  • Amines
  • Cyclohexanecarboxylic Acids
  • Excitatory Amino Acid Antagonists
  • Aspartic Acid
  • gamma-Aminobutyric Acid
  • Gabapentin
  • N-acetylaspartate
  • Creatine