Predominately Subcortical White Matter (early involvement of U-fibers)

Macrocephalic

Normocephalic

Canavan Disease: Ashkenazi Jews, hypotonia (head lag), seizures, spasticity WM: NEAR-COMPLETE, subcortical/deep GM: thalami, globi pallidi MRS: NAA peak

Alexander Disease: Seizures, developmental delay, spasticity WM: ANTERIOR-PREDOMINANT, subcortical/deep/periventricular GM: basal ganglia ENHANCEMENT

Van der Knaap Disease (Megaloencephalic Leukoencephalopathy with Cysts): Macrocephaly, seizures, ataxia, spasticity WM: Subcortical with central sparing DWI: Increased proton movement ANTERIOR & FRONTOPARIETAL SUBCORTICAL CYSTS

Vanishing White Matter Disease: Initially normal motor function with relapsing/remitting but progressive ataxia/spasticity WM: subcortical, deep, & periventricular; ISOINTENSE TO CSF

Zellweger (Cerebrohepatorenal) Syndrome: Facial dysmorphism, mental retardation, hypotonia, hepatic dysfunction/jaundice, small renal cortical cysts WM: subcortical/deep (internal capsule) GM: globi pallidi MRS: lipid peak POLYMICROGYRIA/PACHYGYRIA, SUBEPENDYMAL GERMINOLYTIC CYSTS IN CAUDOTHALAMIC GROOVE

Galactosemia: Vomiting, intracranial pressure, hepatic dysfunction, hepatomegaly WM: diffuse subcortical/periventricular ASSOCIATED LIVER DISEASE

Kearns-Sayre Disease: MITOCHONDRIAL INHERITANCE OPHTHALMOPLEGIA WM: subcortical with deep sparing GM: globi pallidi/thalami/dorsal medulla DWI: restricted diffusion MRS: Lactate peak/NAA peak BASAL GANGLIA/THALAMIC CA++

Homocystinuria: Marfanoid body habitus, osteoporosis, mental retardation WM: Subcortical & deep (anterior limb internal capslule GM: basal ganglia spared BILATERAL INFERIOR (vs superior in Marfans) LENS DISLOCATION (ECTOPIA LENTIS); INFARCTS

Pelizaeus-Merzbacher disease:

Spasticity, abnormal eye/extrapyramidal movements, mental retardation

WM: NEAR-COMPLETE subcortical & deep with TIGROID or LEOPARD appearance due to sparing of perivascular spaces

Predominately

Deep White Matter

(early sparing of U-fibers)

Thalamic (Gray Matter) Involvement

No Thalamic Involvement

Krabbes Disease: 3-6 months, hypertonia, irritability WM: deep cerebral & cerebellar GM: thalami, basal ganglia, cerebellar dentate nuclei HYPERDENSE THALAMI

Gangliosidosis GM1 & GM2 (Tay-Sachs & Sandhoff): Cherry-red macula, hypotonia, mental retardation, seizures, spasticity WM: periventricular HYPERDENSE THALAMI Brainstem (Corticospinal Tract) Involvement No Brainstem (Corticospinal Tract) Involvement

X-linked Adrenoleukodystrophy: Adolescent , learning difficulty (ADHD), skin hyperpigmentation, adrenal failure, ataxia, seizures WM: POSTERIOR PERITRIGONAL WITH LEADING EDGE OF ENHANCEMENT, SYMMETRIC, pons/medulla involved

Maple Syrup Urine Disease: Neonate (< 1 wk) with vomiting, dystonia, & seizures

Metachromatic Leukodystrophy: 1-1.5 yrs, motor/mentation WM: symmetric deep/periventricular with TIGROID or LEOPARD appearance due to sparing of perivascular spaces; POSTERIOR PREDOMINANCE; NO ENHANCEMENT

Mucopolysaccharidoses (Hurlers, Hunters, Morquios): Macrocephalic, thick meninges WM: RADIATING PERIVENTRICULAR & CORPUS CALLOSAL CYSTIC AREAS (dilated perivascular spaces)

Other: Lowe (Oculocerebrorenal) Disease Phenylketonuria

WM: deep cerebellar, cerebral peduncle, globi pallidi, & dorsal pons
GM: globi pallidi DWI: RESTRICTION OF DIFFUSION

Merosin-deficient m. dystrophy

Predominately Gray Matter

Deep Gray Matter

Cortical Gray Matter

Leukodystrophy Mimics

Leigh Disease: MITOCHONDRIAL Respiratory failure, ataxia, visual/auditory problems, weakness BILATERAL SYMMETRIC T2/FLAIR HYPERINTENSITY & RESTRICTION OF DIFFUSION IN PUTAMINA

MELAS: MITOCHONDRIAL Myopathy, Encephalopathy, Lactic Acidosis, Strokes

Other: Organic Acidopathies Amino acid metabolic disorders

Neuronal ceroid lipofuscinoses: Vision failure, progressive dementia, seizures Cerebral/cerebellar atrophy, thalami/globi pallidi involvement Mucolipidosis type I: Neonatal (< 1 wk) presentation Inflammatory Processes White Matter Injury

WM: subcortical, brainstem, deep cerebellum

GM: basal ganglia MIGRATING INFARCTS MC IN PARIETOOCCIPITAL CORTEX

Subacute Sclerosing Panencephalitis: MEASLES INFECTION Progressive Multifocal Leukoencephalopathy: JC PAPOVAVIRUS INFECTION

Acute Disseminated Encephalomyelitis: Multifocal punctate to large flocculent T2/FLAIR hyperintesnse WM/basal ganglia lesions, which may enhance 10-14 DAYS FOLLOWING VIRAL ILLNESS OR IMMUNIZATION

Lyme Disease: Imaging findings simulate multiple sclerosis in a patient with skin rash, flu-like symptoms, &/or joint pain TORCH: Microcephaly, variable (typically asymmetric) WM demyelination &/or gliosis, periventricular Ca++, subependymal cysts

Radiation Injury: WM: sparing of subcortical Ufibers; scalloped margins DISTRIBUTION RELATES TO XRT FIELD (unless whole-brain XRT) 6-8 MONTHS FOLLOWING XRT

Periventricular Leukomalacia (WM Injury of Prematurity): Spastic diplegia, visual/cognitive impairment, associated with PROM/TORCH Mechanism: ischemic injury to watershed area WM: deep/periventricular with cystic change & volume loss Thin corpus callosum, undulating ventricular margin, enlarged ventricles

Axial T2WI in a child with Canavan disease shows periventricular, deep, and subcortical WM involvement, plus thalami (white arrow) and globi pallidi (white curved) involvement; very characteristic.

X-linked adrenoleukodystrophy with preferential involvement of descending pyramidal tract A-C. T2-weighted image shows demyelination of internal capsule, descending pyramidal tract (arrows, A) and cerebellar deep white matter (arrows, B). The peritrigonal white matter is relatively spared(C). D. On gadolinium-enhanced T1-weighted image, enhancing bilateral descending pyramidal tracts (arrows) are shown.

Coronal T2WI MR in another case of metachromatic leukodystrophy shows characteristic diffuse deep and periventricular white matter involvement, with sparing of the cerebellar white matter (white arrow).

Coronal FLAIR MR shows bilateral and symmetric periventricular and deep white matter signal abnormality but sparing of sub-cortical U-fibers (white arrow) in child with metachromatic leukodystrophy.

Axial T2WI shows diffuse high signal in the centrum semiovale with sparing of the subcortical Ufibers, typical of treatment related leukoencephalopathy. Patient is s/p whole brain XRT.