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.

I

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

Adult.After puberty get personality and mental changes, cortical and cerebellar regression to frank dementia in third to fourth decade

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.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.

Niemann-Pick disease.

GM1 gangliosidoses.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.

GM2 gangliosidoses.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 individual names.

GM1 gangliosidosis.

GM2 gangliosidosis.

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).

Adrenoleukodystrophy.

Zellweger syndrome.

MELAS DISEASE WITH SPECTOSCOPY.

MELAS-related mutations.

Leigh disease.

Disorders of amino acid and organic acid metabolism.

Honeycomb appearance of the brain in a patient with Canavan disease.

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.

Alexander disease.

Alexander disease (2-year-old boy).

Pelizaeus-Merzbacher disease.

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, spasticity.Seizures.Optic atrophy and ocular impairmentsMRI: Reversal of gray-white signal due to diffuse demyelination

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.

HCC

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.

Thank You.