This document provides information on various leukodystrophies and white matter diseases categorized based on their patterns of white matter and gray matter involvement on MRI. It describes diseases that predominantly involve subcortical white matter such as Canavan disease. It also describes diseases that involve deep white matter sparing U-fibers such as metachromatic leukodystrophy. Finally it describes diseases with predominant gray matter or combined white and gray matter involvement such as Leigh disease. Representative MRI images are provided to illustrate the characteristic patterns of involvement for some of the diseases.

2. Predominately
Subcortical White Matter
(early involvement of U-fibers)
Macrocephalic Normocephalic
Canavan Disease: Alexander Disease: Van der Knaap Disease (Megaloencephalic Vanishing White Matter Disease:
Ashkenazi Jews, hypotonia (head Seizures, developmental delay, spasticity Leukoencephalopathy with Cysts): Initially normal motor function with
lag), seizures, spasticity WM: ANTERIOR- Macrocephaly, seizures, ataxia, spasticity relapsing/remitting but progressive ataxia/spasticity
WM: NEAR-COMPLETE, subcortical/deep PREDOMINANT, subcortical/deep/periventricular WM: Subcortical with central sparing WM: subcortical, deep, & periventricular;
GM: thalami, globi pallidi GM: basal ganglia DWI: Increased proton movement ISOINTENSE TO CSF
ANTERIOR & FRONTOPARIETAL SUBCORTICAL CYSTS
MRS: ↑NAA peak ENHANCEMENT
Zellweger (Cerebrohepatorenal) Syndrome: Galactosemia: Kearns-Sayre Disease: Homocystinuria: Pelizaeus-Merzbacher disease:
Facial dysmorphism, mental Vomiting, ↑intracranial pressure, hepatic MITOCHONDRIAL INHERITANCE Marfanoid body habitus, osteoporosis, mental Spasticity, abnormal eye/extrapyramidal
retardation, hypotonia, hepatic dysfunction, hepatomegaly retardation movements, mental retardation
OPHTHALMOPLEGIA
dysfunction/jaundice, small renal cortical cysts WM: diffuse subcortical/periventricular WM: Subcortical & deep (anterior limb internal WM: NEAR-COMPLETE subcortical & deep with
WM: subcortical with deep sparing
WM: subcortical/deep (internal capsule) ASSOCIATED LIVER DISEASE capslule “TIGROID or LEOPARD” appearance due to sparing
GM: globi pallidi/thalami/dorsal medulla of perivascular spaces
GM: globi pallidi GM: basal ganglia spared
DWI: restricted diffusion
MRS: ↑lipid peak BILATERAL INFERIOR (vs superior in Marfan’s) LENS
MRS: ↑Lactate peak/↓NAA peak DISLOCATION (ECTOPIA LENTIS); INFARCTS
POLYMICROGYRIA/PACHYGYRIA, SUBEPENDYMAL
GERMINOLYTIC CYSTS IN CAUDOTHALAMIC BASAL GANGLIA/THALAMIC CA++
GROOVE

3. Predominately
Deep White Matter
(early sparing of U-fibers)
Thalamic (Gray Matter) Involvement No Thalamic Involvement
Krabbe’s Disease: Gangliosidosis GM1 & GM2 (Tay-Sachs &
3-6 months, hypertonia, irritability Sandhoff):
WM: deep cerebral & cerebellar Cherry-red macula, hypotonia, mental
retardation, seizures, spasticity
GM: thalami, basal ganglia, cerebellar No Brainstem (Corticospinal Tract)
WM: periventricular Brainstem (Corticospinal Tract) Involvement
dentate nuclei Involvement
HYPERDENSE THALAMI HYPERDENSE THALAMI
X-linked Adrenoleukodystrophy: Maple Syrup Urine Disease: Metachromatic Leukodystrophy: Mucopolysaccharidoses Other:
Adolescent , learning difficulty (ADHD), skin Neonate (< 1 wk) with vomiting, dystonia, & 1-1.5 yrs, ↓motor/mentation (Hurler’s, Hunter’s, Morquio’s): Lowe (Oculocerebrorenal) Disease
hyperpigmentation, adrenal seizures WM: symmetric deep/periventricular with Macrocephalic, thick meninges Phenylketonuria
failure, ataxia, seizures WM: deep cerebellar, cerebral “TIGROID or LEOPARD” appearance due to WM: RADIATING PERIVENTRICULAR & Merosin-deficient m. dystrophy
WM: POSTERIOR PERITRIGONAL WITH peduncle, globi pallidi, & dorsal pons sparing of perivascular spaces; POSTERIOR CORPUS CALLOSAL CYSTIC AREAS (dilated
LEADING EDGE OF GM: globi pallidi PREDOMINANCE; NO ENHANCEMENT perivascular spaces)
ENHANCEMENT, SYMMETRIC, pons/medulla
involved DWI: RESTRICTION OF DIFFUSION

4. Predominately
Gray Matter
Deep Gray Matter Cortical Gray Matter Leukodystrophy Mimics
Leigh Disease: MELAS: Other: Neuronal ceroid lipofuscinoses:
MITOCHONDRIAL MITOCHONDRIAL Organic Acidopathies Vision failure, progressive
Respiratory Myopathy, Encephalopathy, Lactic Amino acid metabolic disorders dementia, seizures
Inflammatory Processes White Matter Injury
failure, ataxia, visual/auditory Acidosis, Strokes Cerebral/cerebellar
problems, weakness WM: subcortical, brainstem, deep atrophy, thalami/globi pallidi
BILATERAL SYMMETRIC T2/FLAIR cerebellum involvement
HYPERINTENSITY & RESTRICTION OF GM: basal ganglia
DIFFUSION IN PUTAMINA Mucolipidosis type I:
MIGRATING INFARCTS MC IN
PARIETOOCCIPITAL CORTEX Neonatal (< 1 wk) presentation
Subacute Sclerosing Acute Disseminated Lyme Disease: Radiation Injury: Periventricular Leukomalacia
Panencephalitis: Encephalomyelitis: WM: sparing of subcortical U- (WM Injury of Prematurity):
Imaging findings simulate
MEASLES INFECTION Multifocal punctate to large multiple sclerosis in a patient fibers; scalloped margins Spastic diplegia, visual/cognitive
flocculent T2/FLAIR hyperintesnse with skin rash, flu-like DISTRIBUTION RELATES TO XRT impairment, associated with
WM/basal ganglia lesions, which symptoms, &/or joint pain FIELD (unless whole-brain XRT) PROM/TORCH
Progressive Multifocal may enhance
Leukoencephalopathy: 6-8 MONTHS FOLLOWING XRT Mechanism: ischemic injury to
10-14 DAYS FOLLOWING VIRAL watershed area
JC PAPOVAVIRUS INFECTION TORCH:
ILLNESS OR IMMUNIZATION WM: deep/periventricular with
Microcephaly, variable (typically
cystic change & volume loss
asymmetric) WM demyelination
&/or gliosis, periventricular Thin corpus callosum, undulating
Ca++, subependymal cysts ventricular margin, enlarged
ventricles

5. 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.

16. 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.

18. 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.

28. 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.