lunedì 1 marzo 2010

Pelizaeus-Merzbacher disease


There is diffuse T2 prolongation within subcortical, deep, and periventricular cerebral and cerebellar white matter with involvement of internal capsules and corpus callosum. There is also involvement of cerebellar peduncles. No enhancement or diffusion restriction.

Differential diagnosis:
- Pelizaeus-Merzbacher
- Metachromatic leukodystrophy
- Adrenoleukodystrophy
- van der Knaap leukoencephalopathy
- Canavan disease

Diagnosis: Pelizaeus-Merzbacher

Pelizaeus-Merzbacher is a rare leukodystrophy which results in abnormal myelin production. The disease is related to the proteolipid protein 1 (PLP1) gene on the X chromosome. The products of this gene constitute about 50% of the mass of CNS white matter and are believed to serve an important structural function in compact myelin. The defect is most commonly a duplication of genetic material which is deleterious to oligodendrocytes.

The frequency is not certain but is conservatively thought to be more than 1 in 500,000. Clinical signs usually include some combination of nystagmus, stridor, spastic quadriparesis, hypotonia, cognitive impairment, ataxia, and tremor. Patients tend to be normocephalic. Nerve conduction tests typically normal (as opposed to most other leukodystrophies). Diagnosis involves clinical history and physical examination, MRI of the brain, and molecular diagnostic tests. Because of the heterogeneity of genetic defects and since females tend to be heterozygous, there is varying severity and clinical course.

No specific cure or treatment for Pelizaeus-Merzbacher disease is known. Medical care is currently limited to supportive care and includes tracheostomy, physical therapy, orthotics, and antispasticity agents, including intrathecal baclofen.


There is lack of myelin maturation on T2WI (i.e. white matter is brighter than it should be) and there is minimal myelin maturation on T1WI (i.e. white matter is darker than it should be). Changes may be difficult to identify under 1 year of age due to the normal lack of myelination. There is diffuse involvement without predilection for a specific distribution or sparing of sub cortical U-fibers. There is no enhancement (in contrast to Alexander or X-linked adrenoleukodystrophy). There is no telltale spectroscopy finding (in contrast to Canavan disease which has elevated NAA). There is no diffusion restriction (in contrast to adrenoleukodystrophy). There is no volume expansion of the white matter (in contrast to van der Knaap leukoencephalopathies).

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