Literature DB >> 19194883

Brain metabolism in Rett syndrome: age, clinical, and genotype correlations.

Alena Horská1, Luciano Farage, Genila Bibat, Lídia M Nagae, Walter E Kaufmann, Peter B Barker, SakkuBai Naidu.   

Abstract

OBJECTIVE: Brain metabolism, as studied by magnetic resonance spectroscopy (MRS), has been previously shown to be abnormal in Rett syndrome (RTT). This study reports the relation of MRS findings to age, disease severity, and genotype.
METHODS: Forty RTT girls (1-14 years old) and 12 age-matched control subjects were examined. Single-voxel proton MRS of left frontal white matter was performed.
RESULTS: NAA/Cr ratios decreased and myoinositol/Cr ratios increased with age in RTT patients (both p < 0.03), whereas these ratios were stable in control. The mean glutamate and glutamine/Cr ratio was 36% greater in RTT patients than in control (p = 0.043). The mean NAA/Cr ratio was 12.6% lower in RTT patients with seizures compared with those without seizures (p = 0.017). NAA/Cr ratios decreased with increasing clinical severity score (p = 0.031). Compared with patients with T158X, R255X, and R294X mutations, and C-terminal deletions, patients with the R168X mutation tended to have the greatest severity score (0.01 < or = p < or = 0.11) and the lowest NAA/Cr ratio (0.029 < or = p < 0.14).
INTERPRETATION: Decreasing NAA/Cr and increasing myoinositol/Cr with age are suggestive of progressive axonal damage and astrocytosis in RTT, respectively, whereas increased glutamate and glutamine/Cr ratio may be secondary to increasing glutamate/glutamine cycling at the synaptic level. The relations between NAA/Cr, presence or absence of seizures, and disease severity suggest that MRS provides a noninvasive measure of cerebral involvement in RTT.

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Year:  2009        PMID: 19194883      PMCID: PMC2676876          DOI: 10.1002/ana.21562

Source DB:  PubMed          Journal:  Ann Neurol        ISSN: 0364-5134            Impact factor:   10.422


  45 in total

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