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Neuroradiology Case of the Week

Case 133

Loris F. Cedeno, MD, Jeevak Almast, MD,
and Per-Lennart Westesson, MD, PhD, DDS

Clinical Presentation: A nine-day-old male with a history of ornithine transcarbamylase deficiency presented with hyperammonemia and diffuse change on EEG. This study was performed for clinical suspicion for intracranial abnormality.

Radiological Findings: There are symmetric multiple areas of hyperintensity on diffusion-weighted images in bilateral cerebral peduncles, basal ganglia, internal capsule, and white matter adjacent to the perirolandic cortex. Some of these areas are also hyperintense on FLAIR images (Figs 1-4).

Discussion: The urea cycle requires proper functioning of five different types of enzymes to convert excessive ammonium into urea, which is excreted in the urine. Our patient had ornithine transcarbamylase deficiency which is the most common form of urea cycle enzyme defect. This defect results in failure of condensation of ornithine with carbamyl phosphate which leads to high levels of plasma ammonium and high urine orotic acid levels. Full-term neonates appear healthy for the first 24-48 hours of life and then develop progressive lethargy, hypothermia and apnea. The presence of high levels of ammonia results in the conversion of large amounts of glutamate to glutamine by glutamine synthetase; this occurs mainly in the astrocytes. It is thought that the accumulation of large quantities of glutamine cause changes in intracellular osmolality and result in subsequent astrocyte swelling, brain edema, intracranial hypertension, and cerebral hypoperfusion. Images reveal abnormal signal in bilateral lentiform nuclei as well as in the perirolandic and insular cortices. Our case demonstrates similar findings as those reported previously in the literature. In addition, MR spectroscopy will demonstrate markedly increased peaks at 2.05-2.55 and 3.68-3.85 ppm which are assigned to glutamate/glutamine complex.
     In general most metabolically active and mature regions of the neonatal brain are the regions that are damaged first in the setting of hypoperfusion or cessation of perfusion all together. In neonates, brain injury from a urea cycle disorder can be differentiated from that due to profound hypotension by the absence of thalamic injury and by normal neurologic status within the first days of life. Early detection will aid in earlier treatment (liver transplant) and help prevent chronic impairment.

References:

1. Takanashi J, Barkovich AJ, Cheng SF, Weisiger K, Zlatunich CO, Mudge C, Rosenthal P, Tuchman M, Packman S. Brain MR imaging in neonatal hyperammonemic encephalopathy resulting from proximal urea cycle disorders. AJNR Am J Neuroradiol. 2003 Jun-Jul;24(6):1184-7. [Medline]
2. Majoie CB, Mourmans JM, Akkerman EM, Duran M, Poll-The BT. Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings. AJNR Am J Neuroradiol. 2004 Jan;25(1):32-5. [Medline]
3. Choi CG, Yoo HW. Localized proton MR spectroscopy in infants with urea cycle defect. AJNR Am J Neuroradiol. 2001 May;22(5):834-7. [Medline]