Imaging of pediatric
white matter disease.
Dr/ ABD ALLAH NAZEER. MD.
Pediatric white matter disorders can be distinguished
into well-defined leukoencephalopathies, and undefined
leukoencephalopathies. The first category may be subdivided into:
(a) hypomyelinating disorders; (b) dysmyelinating disorders; (c)
leukodystrophies; (d) disorders related to cystic degeneration of
myelin; and (e) disorders secondary to axonal damage. The second
category, representing up to 50% of leukoencephalopathies in
childhood, requires a multidisciplinar approach in order to define
novel homogeneous subgroups of patients, possibly representing
‘‘new genetic disorders’’ (such as megalencephalic
leukoencepahlopathy with subcortical cysts and vanishing white
matter disease that have recently been identified). In the majority of
cases, pediatric white matter disorders are inherited diseases. An
integrated description of the clinical, neuroimaging and
pathophysiological features is crucial for categorizing myelin
disorders and better understanding their genetic basis. A review of
the genetic disorders affecting white matter in the pediatric age,
including some novel entities, is provided.
Most common leukodystrophies.
Disorder that primarily that affect
white matter (Leukodystrophies).
The disease has 3 Presentations
Late infantile (18-24 months)
Gait disturbance, hypotonia to hypertonia, regression,
involuntary movements, neuropathy, cherry red spot
Juvenile (4-10 years)
Bradykinesia, poor school performance, ataxia, movement
disorder, neuropathy, slower progression
After puberty get personality and mental changes, cortical
and cerebellar regression to frank dementia in third to
Metachromatic leukodystrophy. (a) T2-weighted MR image demonstrates bilateral
confluent areas of high signal intensity in the periventricular white matter. Note
the classic sparing of the sub-cortical U fibers (arrowheads). (b) Contrast material–
enhanced MR image shows lack of enhancement in the demyelinated white
matter, a finding that is characteristic of metachromatic leukodystrophy.
Metachromatic leukodystrophy. (a) T2-weighted MR image shows numerous linear tubular
structures with low signal intensity in a radiating (“tigroid”) pattern within the demyelinated
deep white matter. (b) T2-weighted MR image shows a punctate (leopard skin) pat-tern in
the demyelinated centrum semiovale, a finding that suggests sparing of the white matter. (c)
On a contrast-enhanced T1-weighted MR image, the tigroid pattern seen in a appears as
numerous punctate foci of enhancement (arrows) within the demyelinated white matter,
which is unenhanced and has low signal intensity (leopard skin pattern).
Krabbe disease with abnormal signal within the thalami and capsular regions.
Niemann–Pick disease : refers to a group of inherited severe metabolic disorders that allow
sphingomyelin to accumulate in lysosomes, which are organelles in animal cells. The severe
form is fatal in toddlerhood; people with milder forms may live into their teens or young
adulthood. This disease involves dysfunctional metabolism of sphingolipids, which are fats
found in cell membranes, so it is a kind of sphingolipidosis. Sphingolipidoses, in turn, are
included in the larger family of lysosomal storage diseases (LSDs).
Niemann-Pick disease adult onset with psychosis.
The GM1 gangliosidoses are caused by a deficiency of beta-
galactosidase, with resulting abnormal storage of acidic lipid
materials in cells of the central and peripheral nervous systems,
but particularly in the nerve cells.
The GM2 gangliosidoses are a group of related genetic
disorders that result from a deficiency of the enzyme
beta-hexosaminidase. This enzyme catalyzes the
biodegradation of fatty acid derivatives known as
gangliosides. The diseases are better known by their
ALD in a 5-year-old boy. (a) T2-weighted MR image shows symmetric confluent demyelination
in the peritrigonal white matter and the corpus callosum. (b) On a T1-weighted MR image, the
peritrigonal lesions appear hypointense. (c) Gadolinium-enhanced T1-weighted MR image
reveals a characteristic enhancement pattern in the intermediate zone (arrows) representing
active demyelination and inflammation. (8) ALD involving the corpus callosum splenium. T2-
weighted MR image shows the corpus callosum splenium with diffuse high signal intensity
(arrows). No abnormality of the periventricular white matter is seen.
X-linked adrenoleukodystrophy (7-year-old boy).
MELAS DISEASE WITH SPECTOSCOPY.
Disorders of amino acid and organic acid metabolism.
Honeycomb appearance of the brain in a patient with Canavan disease.
Canavan disease in a 6-month-old boy with macrocephaly. (a) T2-weighted MR image shows
extensive high-signal-intensity areas throughout the white matter, resulting in gyral
expansion and cortical thinning. Striking demyelination of the subcortical U fibers is also
noted. (b) T1-weighted MR image shows demyelinated white matter with low signal intensity.
(c) Photomicrograph (original magnification, 200; hematoxylin-eosin stain) shows ballooning
of the myelin sheaths of oligodendrocytes due to massive intramyelinic edema.
Alexander disease (2-year-old boy).
Xq22 mutation in proteolipid protein 1 (PLP1)
Onset in first few months of life with rotary
head movements, rotary nystagmus, & motor
delay Then ataxia, tremor, choreoathetosis,
Optic atrophy and ocular impairments
MRI: Reversal of gray-white signal due to
Pelizaeus—Merzbacher (15-month-old boy).
PMD in a 7-month-old boy. T2-weighted MR image reveals almost no
myelination of the cerebral white matter. The sub-cortical white matter
is also involved, as are the internal and external capsules (arrow-heads).
Megalencephalic leukoencephalopathy with subcortical cysts (8-month-old boy).
Vanishing White Matter Disease.
Vanishing White Matter Disease (VWM) is inherited in an
autosomal recessive manner, meaning that it is a disease
that can run in the family. Symptoms generally appear in
young children who may have been appearing to develop
fairly normally. However, it has been shown recently that
it can begin at or shortly after birth, as well, or even in
adulthood. A striking feature of the disease is that the
symptoms get worse slowly for the most part, but there
are episodes of rapid deterioration that follow an
infection or head trauma. The patient may have a partial
recovery following these episodes, or the episode may
lead to coma and death.
Vanishing white matter disease.
A rare syndrome characterized mainly by childhood ataxia and reduced myelination
of the cerebral nerves. Motor and mental development in the first few years of life is
normal with progressive neurodegeneration occurring between 2 and 5 years of age.
Fever and trauma to the head can speed up disease progression.
Cerebellar hypomyelination syndrome.