PredominatelySubcortical White Matter

(early involvement of U-fibers)

Macrocephalic

Canavan Disease:Ashkenazi Jews, hypotonia (head lag), seizures, spasticityWM: NEAR-COMPLETE, subcortical/deepGM: thalami, globi pallidiMRS: ↑NAA peak

Alexander Disease:Seizures, developmental delay, spasticityWM: ANTERIOR-PREDOMINANT, subcortical/deep/periventricularGM: basal ganglia ENHANCEMENT

Van der Knaap Disease (Megaloencephalic Leukoencephalopathy with Cysts):Macrocephaly, seizures, ataxia, spasticity

WM: Subcortical with central sparingDWI: Increased proton movementANTERIOR & FRONTOPARIETAL SUBCORTICAL CYSTS

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

Normocephalic

Zellweger (Cerebrohepatorenal) Syndrome:Facial dysmorphism, mental retardation, hypotonia, hepatic dysfunction/jaundice, small renal cortical cystsWM: subcortical/deep (internal capsule)GM: globi pallidiMRS: ↑lipid peakPOLYMICROGYRIA/PACHYGYRIA, SUBEPENDYMAL GERMINOLYTIC CYSTS IN CAUDOTHALAMIC GROOVE

Galactosemia:Vomiting, ↑intracranial pressure, hepatic dysfunction, hepatomegalyWM: diffuse subcortical/periventricularASSOCIATED LIVER DISEASE

Kearns-Sayre Disease:MITOCHONDRIAL INHERITANCEOPHTHALMOPLEGIAWM: subcortical with deep sparingGM: globi pallidi/thalami/dorsal medullaDWI: restricted diffusionMRS: ↑Lactate peak/↓NAA peakBASAL GANGLIA/THALAMIC CA++

Homocystinuria:Marfanoid body habitus, osteoporosis, mental retardationWM: Subcortical & deep (anterior limb internal capsluleGM: basal ganglia sparedBILATERAL INFERIOR (vs superior in Marfan’s) LENS DISLOCATION (ECTOPIA LENTIS); INFARCTS

Pelizaeus-Merzbacher disease:Spasticity, abnormal eye/extrapyramidal movements, mental retardationWM: NEAR-COMPLETE subcortical & deep with “TIGROID or LEOPARD” appearance due to sparing of perivascular spaces

PredominatelyDeep White Matter

(early sparing of U-fibers)

Thalamic (Gray Matter) Involvement

Krabbe’s Disease:3-6 months, hypertonia, irritabilityWM: deep cerebral & cerebellarGM: thalami, basal ganglia, cerebellar dentate nucleiHYPERDENSE THALAMI

Gangliosidosis GM1 & GM2 (Tay-Sachs & Sandhoff):Cherry-red macula, hypotonia, mental retardation, seizures, spasticityWM: periventricularHYPERDENSE THALAMI

No Thalamic Involvement

Brainstem (Corticospinal Tract) Involvement

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

Maple Syrup Urine Disease:Neonate (< 1 wk) with vomiting, dystonia, & seizuresWM: deep cerebellar, cerebral peduncle, globi pallidi, & dorsal ponsGM: globi pallidiDWI: RESTRICTION OF DIFFUSION

No Brainstem (Corticospinal Tract) Involvement

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

Mucopolysaccharidoses (Hurler’s, Hunter’s, Morquio’s):Macrocephalic, thick meningesWM: RADIATING PERIVENTRICULAR & CORPUS CALLOSAL CYSTIC AREAS (dilated perivascular spaces)

Other:Lowe (Oculocerebrorenal) DiseasePhenylketonuriaMerosin-deficient m. dystrophy

PredominatelyGray Matter

Deep Gray Matter

Leigh Disease:MITOCHONDRIALRespiratory failure, ataxia, visual/auditory problems, weaknessBILATERAL SYMMETRIC T2/FLAIR HYPERINTENSITY & RESTRICTION OF DIFFUSION IN PUTAMINA

MELAS:MITOCHONDRIALMyopathy, Encephalopathy, Lactic Acidosis, Strokes WM: subcortical, brainstem, deep cerebellumGM: basal gangliaMIGRATING INFARCTS MC IN PARIETOOCCIPITAL CORTEX

Other:Organic AcidopathiesAmino acid metabolic disorders

Cortical Gray Matter

Neuronal ceroid lipofuscinoses:Vision failure, progressive dementia, seizuresCerebral/cerebellar atrophy, thalami/globi pallidi involvement

Mucolipidosis type I:Neonatal (< 1 wk) presentation

Leukodystrophy Mimics

Inflammatory Processes

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 enhance10-14 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

White Matter Injury

Radiation Injury:WM: sparing of subcortical U-fibers; scalloped marginsDISTRIBUTION 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/TORCHMechanism: ischemic injury to watershed areaWM: deep/periventricular with cystic change & volume lossThin 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 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.

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).

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