HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

1H-MRS alterations in the cerebellum of patients with familial hemiplegic migraine type 1.

AbstractBACKGROUND:
About 20% of patients with familial hemiplegic migraine (FHM) develop progressive cerebellar signs. Genetic studies have established an association with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar involvement are largely unknown.
OBJECTIVE:
To use proton MR spectroscopy (1H-MRS) to investigate metabolic alterations in the cerebellum as well as cortical regions known to be involved in the propagation of migraine aura.
METHODS:
Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy control subjects were studied. Eleven patients had clinical signs of cerebellar involvement. LCModel fits were used to estimate absolute concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing compounds, total creatine, and lactate in the superior cerebellar vermis (SCV), parietal cortex, and occipital cortex. To control for atrophy effects, automated image segmentation was performed using SPM99. The brain parenchyma fraction (BPF) was determined for all three regions.
RESULTS:
Compared with controls, the brain parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was significantly elevated in the SCV of patients with FHM. In contrast, no metabolite alterations were found in supratentorial regions. BPF and NAA in the SCV significantly correlated with cerebellar scores, in particular, gait ataxia.
CONCLUSIONS:
The findings suggest that there is a regionally distinct neuronal impairment in the superior cerebellar vermis that exceeds macroscopic tissue loss. Correlations with clinical scores emphasize the functional relevance of localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels. These measures may be useful to monitor disease progression. The observed reduction in glutamate may in part reflect impaired glutamatergic neurotransmission.
AuthorsM Dichgans, J Herzog, T Freilinger, M Wilke, D P Auer
JournalNeurology (Neurology) Vol. 64 Issue 4 Pg. 608-13 (Feb 22 2005) ISSN: 1526-632X [Electronic] United States
PMID15728280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CACNA1A protein, human
  • Calcium Channels
  • Lactates
  • Aspartic Acid
  • Glutamic Acid
  • Inositol
  • N-acetylaspartate
  • Creatine
  • Choline
Topics
  • Adolescent
  • Adult
  • Aspartic Acid (analogs & derivatives, analysis)
  • Brain Chemistry
  • Calcium Channels (genetics, physiology)
  • Cerebellum (chemistry)
  • Choline (analysis)
  • Creatine (analysis)
  • Dysarthria (etiology, metabolism)
  • Essential Tremor (etiology, metabolism)
  • Female
  • Gait Ataxia (etiology, metabolism)
  • Glutamic Acid (analysis)
  • Hemiplegia (etiology, genetics, metabolism, physiopathology)
  • Humans
  • Inositol (analysis)
  • Lactates (analysis)
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Migraine with Aura (etiology, genetics, metabolism, physiopathology)
  • Mutation
  • Parietal Lobe (chemistry)
  • Visual Cortex (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: