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Eva Ratai, PhD; Trina Kok, BEng; Christopher Wiggins, PhD; Graham Wiggins, PhD; Ellen Grant, MD; Borjan Gagoski, MS; Gilmore O’Neill, MD; Elfar Adalsteinsson, PhD; Florian Eichler, MD

Arch Neurol. 2008;65(11):1488-1494.

Background  Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging.

Objective  To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms.

Patients and Methods  Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adrenomyeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included.

Results  Among adult X-ALD phenotypes, the myo-inositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P < .05). Both N-acetylaspartate to creatine (P = .03) and glutamate to creatine (P = .04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P = .02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman  = 0.66, P = .04).

Conclusions  Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD.

Author Affiliations: Departments of Radiology (Drs Ratai, C. Wiggins, G. Wiggins, and Grant) and Neurology (Drs O’Neill and Eichler), Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Charlestown; Harvard Medical School, Boston, Massachusetts (Drs Ratai, C. Wiggins, G. Wiggins, Grant, O’Neill, and Eichler); Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge (Ms Kok, Mr Gagoski, and Dr Adalsteinsson); and Harvard–Massachusetts Institute of Technology Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge (Dr Adalsteinsson).

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