Proton magnetic resonance spectroscopy in Huntington's disease: evidence in favour of the glutamate excitotoxic theory

Mov Disord. 1996 Mar;11(2):167-73. doi: 10.1002/mds.870110209.

Abstract

The gene responsible for Huntington's disease (HD) has been located, but its action and the pathophysiology of HD remain unclear. Glutamate excitotoxicity may contribute to the striatal neurodegeneration seen in HD. We used localised proton magnetic resonance spectroscopy (MRS) of the brain to investigate five patients with early HD, one symptom-free gene carrier, and 14 healthy volunteers. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx), and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr), were calculated. Spectra were analysed from the striatum and the occipital and the temporal cortex. The HD patients all had an elevated Glx/Cr in spectra localised to the striatum, compared with healthy controls, and one patient also had an elevated thalamic Glx/Cr. The mean Glx/Cr was unaltered in the cortical spectra of HD patients. The asymptomatic gene carrier displayed no spectral abnormalities. Our findings suggest disordered striatal glutamate metabolism and may support the theory of glutamate excitotoxicity in HD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / physiology
  • Cerebral Cortex / physiopathology
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Genetic Carrier Screening
  • Glutamic Acid / physiology*
  • Glutamine / physiology
  • Humans
  • Huntington Disease / diagnosis
  • Huntington Disease / genetics
  • Huntington Disease / physiopathology*
  • Magnetic Resonance Imaging*
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiology
  • Reference Values
  • Synaptic Transmission / physiology*

Substances

  • Glutamine
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate