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

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

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

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 Ufibers, typical of treatment
related leukoencephalopathy.
Patient is s/p whole brain XRT.