Brain MRI Findings in Poorly Controlled Homocystinuria

Posted By Charles Li
Brain MRI Findings in Poorly Controlled Homocystinuria

Case History: A two-year-old female with homocystinuria due to CBS deficiency was admitted to improve metabolic control after incidentally finding mild asymptomatic bilateral papilledema on routine ophthalmologic examination. Initial laboratory analyses revealed poorly controlled disease, presumably due to poor treatment compliance, characterized by elevated plasma homocysteine (203 μmol/L) and markedly elevated plasma methionine (1182 μmol/L) concentrations. Plasma methionine had also been markedly elevated (1007–1211 μmol/L) for six months preceding admission. Lumbar puncture revealed elevated ICP (28 cm H2O) and elevated CSF methionine (199 μmol/L). Ophthalmologic examination revealed edema of the optic nerve heads, greater on the left, without ectopia lentis, visual field or acuity deficits. Imaging Findings: Brain MRI on admission performed on a 1.5 T scanner (panels A, C, E, G, I) revealed signal abnormalities throughout white matter (†) and bilateral globi pallidi (*). Age-matched normal is shown for comparison (panels B, D, F, H). White matter was abnormally dark on T1-weighted images (A) and bright on T2-weighted images (C) due to prolonged T1 and T2 relaxation. Diffusion weighted images (E) and calculated apparent diffusion coefficient maps (G) revealed diffusion restriction throughout the white matter. High-resolution T2-weighted images of the orbits (I) showed papilledema (thick arrow) and dilated optic nerve sheaths (thin arrows). The white matter of the pons and cerebellum was also abnormally T2­bright (‡). MR spectroscopy (J) of the left frontal lobe white matter shows small NAA and large choline peaks without a lactate peak. No abnormal enhancement occurred after administration of intravenous gadolinium-based contrast. No venous filling defects were present on MR venography. Brief Discussion: The underpinning pathophysiologic mechanisms of these white matter changes are theorized to be multifactorial, possibly involving direct cellular injury from methionine (which is also elevated in CBS deficiency), cell swelling due to intracellular osmotic effects of betaine therapy, myelin vacuolization, and demyelination. These topics are explored in-depth in our case report manuscript. Significance: This case demonstrates not only severe and rare white matter signal changes in poorly controlled CBS deficiency, but also additional similar signal abnormalities in the basal ganglia not described in prior case reports, which have all been published outside of the radiology literature. In addition, papilledema, optic nerve sheath dilation and brain swelling provide specific imaging evidence of ICP elevation in this case, manifested only as reversible brain swelling in imaging studies from prior cases. These findings have been shown to resolve with improved disease control and reduction/cessation of betaine therapy, and therefore should not be mistaken for other vascular, toxic or metabolic disorders, such as hypoxic-ischemic injury,

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