Specific Imaging Findings

The hallmark of MSUD on both CT and MRI is diffuse brain edema and dysmyelination; this results in swelling of the brain with diffuse white matter hypodensity on CT, T1 hypointensity, and hyperintensity on T2-weighted images. Diffusion imaging discriminates between two distinct appearances, depending on the state of myelination of the various brain structures. Abnormalities within myelinated areas show up as low diffusivity (bright on DWI and dark on ADC maps), corresponding to myelin edema – these typically include the dorsal brainstem, deep cerebellar white matter, posterior limbs of the internal capsules, and corticospinal tracts within the cerebral hemispheres. Conversely, the affected nonmyelinated areas appear as increased diffusion (dark on DWI and bright on ADC maps), reflecting vasogenic edema. Proton MR spectroscopy may show an abnormal peak at 0.9–1.0 ppm on both short and long echo-time spectra, produced by the methyl groups of branched-chain amino acids (BCAAs) and branched-chain alpha-keto acids (BCKAs); lactate may be present during metabolic crises. Ultrasound may show echogenic changes at the dorsal part of the pons and medulla, providing a noninvasive imaging method in critically ill newborns.

Pertinent Clinical Information

MSUD presents with four possible variants (classical, intermediate, intermittent, and thiamine-responsive), of which the classical form is the most common and severe. In this variant, typically a few days after an uneventful birth, the affected neonates present with a severe compromise of vital functions, ranging from difficult feeding and vomiting to lethargy and coma. Patients may die from brain edema if untreated. On the other hand, early diagnosis, lifelong dietary restriction, and monitoring of BCAAs may improve the prognosis. However, long-term outcome is usually characterized by some degree of neurological impairment, and episodes of metabolic decompensation in the context of catabolic stress, often associated with intercurrent non-specific illness, commonly recur. Other clinical variants are more uncommon and difficult to diagnose owing to a more insidious presentation and course.