Unraveling pathology in juvenile Alexander disease: serial quantitative MR imaging and spectroscopy of white matter.
BACKGROUND
Alexander disease is a rare disorder of the central nervous system with characteristic symmetric white matter abnormalities with frontal predominance on magnetic resonance (MR) images. Histopathology shows a lack of myelin in the affected white matter, variably interpreted as hypomyelination or demyelination. To increase our insight into the nature of the pathology leading to the MR imaging findings in Alexander disease, we applied serial MR imaging, spectroscopy, magnetization transfer (MT) imaging (MTI), and diffusion tensor imaging (DTI) in six patients with juvenile Alexander disease.


METHODS
The MR imaging protocol comprised T1- and T2-weighted spin echo images and fluid-attenuated inversion recovery images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and MT ratio (MTR) maps were generated, and MR spectroscopy concentrations were quantified for several metabolites.


RESULTS
MR imaging showed similar cerebral white matter abnormalities in all patients, with only minor increase on prolonged follow-up, despite sometimes serious clinical progression. MR spectroscopy showed highly elevated levels of myo-inositol, lactate, and choline-containing compounds and decreased total N-acetyl-aspartate and N-acetyl-aspartyl-glutamate levels in the abnormal white matter. High values of ADC were observed, and both FA and MTR were attenuated.


CONCLUSIONS
The sequential MR imaging findings in Alexander disease provide strong evidence against active demyelination as sole explanation for the underlying pathology. An alternative explanation for our spectroscopic, DTI, and MTI findings-which would suggest demyelination-could be hyperplasia and hypertrophy of astrocytes, as seen in low grade gliomas.
van der Voorn
J Patrick
JP
Department of Child Neurology, VU University Medical Center, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands. jp.vandervoorn@vumc.nl
Pouwels
Petra J W
PJ
Salomons
Gajja S
GS
Barkhof
Frederik
F
van der Knaap
Marjo S
MS
D000293:Adolescent; D000328:Adult; D038261:Alexander Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016880:Anisotropy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult