Specific Imaging Findings

MRI shows a diffuse leukoencephalopathy with swelling of the white matter, involving both the supratentorial and the infratentorial compartments. There is a centripetal pattern of involvement, with relative sparing of the internal capsules and corpus callosum until later stages of the disease. The affected white matter appears T1 hypointense and hyperintense on T2-weighted images, with signal approaching that of the CSF, due to diffuse spongy degeneration. The same regions are bright on DWI and dark on ADC maps, consistent with reduced diffusivity of water, compatible with intramyelinic edema. The gray matter of the thalami and globi pallidi is also involved, whereas the caudate nuclei, putamina, and claustra are spared. There is no pathological enhancement of affected structures following contrast administration. Canavan disease has a pathognomonic appearance on proton MR spectroscopy with a marked increase of the NAA peak, as a result of its accumulation within the brain tissue. Other possible and nonspecific MR spectroscopy findings include decrease of choline and creatine, increased myo-inositol levels, and presence of lactate.

Pertinent Clinical Information

There are three clinical variants of Canavan disease: neonatal, infantile, and juvenile, of which the infantile (presenting by age 3–6 months) is by far the most common. Patients present with macrocrania, hypotonia, lethargy, seizures, spasticity, optic atrophy, and developmental delay. The clinical phenotype is variably severe depending on the degree of enzyme activity in individual cases.