Brain Advance Access published online on May 3, 2007
Brain, doi:10.1093/brain/awm058
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Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency
1Clinic for Special Children, Strasburg, PA, 2California Institute of Technology, Department of Biology, Pasadena, CA and 3University of California, San Francisco, Department of Radiology, Neuroradiology Section, San Francisco, CA, USA
Correspondence to:
Kevin A. Strauss, MD, Clinic for Special Children, 535 Bunker Hill Road, Strasburg, PA 17579, USA E-mail: kstrauss{at}clinicforspecialchildren.org
Despite early diagnosis, one-third of Amish infants with glutaryl-CoA dehydrogenase deficiency (GA1) develop striatal lesions that leave them permanently disabled. To better understand mechanisms of striatal degeneration, we retrospectively studied imaging results from 25 Amish GA1 patients homozygous for 1296C>T mutations in GCDH. Asymptomatic infants had reduced glucose tracer uptake and increased blood volume throughout gray matter, which may signify a predisposition to brain injury. Nine children (36%) developed striatal lesions: three had sudden motor regression during infancy whereas six had insidious motor delay associated with striatal lesions of undetermined onset. Acute striatal necrosis consisted of three stages: (1) an acute stage, within 24 h of motor regression, characterized by cytotoxic oedema within the basal ganglia, cerebral oligemia, and rapid transit of blood throughout gray matter; (2) a sub-acute stage, 4–5 days after the onset of clinical signs, characterized by reduced striatal perfusion and glucose uptake, and supervening vasogenic oedema; and (3) a chronic stage of striatal atrophy. Apparent diffusion coefficient maps revealed that at least two of the six patients with insidious motor delay suffered striatal injuries before or shortly after birth, followed by latent periods of several months before disability was apparent. Thus, acute and insidious presentations may occur by similar mechanisms, and differ only with regard to the timing of injury. Intravenous fluid and dextrose therapy for illnesses during the first 2 years of life was the only intervention that was clearly neuroprotective in this cohort (odds ratio for brain injury = 0.04, 95% confidence interval = 0.01–0.34; P < 0.001).
Key Words: glutaric aciduria type 1; striatal necrosis; diffusion; perfusion; cerebral metabolism
Abbreviations: ADC, apparent diffusion coefficient; CBF, cerebral blood flow; CBV, cerebral blood volume; CI, confidence interval; CSF, cerebrospinal fluid; FDG, 2-[18F]fluoro-2-deoxy-D-glucose; GA1, glutaric aciduria type 1; GCDH, glutaryl-CoA dehydrogenase; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; MTT, mean transit time; OR, odds ratio; PCT, perfusion computed tomography; PET, positron emission tomography; SUVbsa, standard uptake value corrected for body surface area
Received September 17, 2006. Revised February 12, 2007. Accepted March 2, 2007.