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Brain metabolism in rett syndrome: Age, clinical, and genotype correlations

Authors

  • Alena Horská PhD,

    Corresponding author
    1. Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD
    • The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 217 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205
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  • Luciano Farage MD,

    1. Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD
    2. Medical School, Brasilia University, Brasilia, DF, Brazil
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  • Genila Bibat MD,

    1. Kennedy Krieger Institute, Baltimore, MD
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  • Lídia M. Nagae MD,

    1. Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD
    2. Albert Einstein Hospital, São Paulo, Brazil
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  • Walter E. Kaufmann MD,

    1. Kennedy Krieger Institute, Baltimore, MD
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  • Peter B. Barker DPhil,

    1. Division of Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD
    2. Kennedy Krieger Institute, Baltimore, MD
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  • Sakkubai Naidu MD

    1. Kennedy Krieger Institute, Baltimore, MD
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  • Potential conflict of interest: Nothing to report.

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 ≤ p ≤ 0.11) and the lowest NAA/Cr ratio (0.029 ≤ 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. Ann Neurol 2009;65:90–97

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