Wednesday, November 18, 2009

Presentations of adult onset leukodystrophy

Costello DJ et al. The Neurologist 2009;15:319-328
ALD kids get spastic paraparesis with detrusor instability. Defect is VLFA's ABCD1 mutation. MRI lesion is leukodystrophy starting posteriorly, may enhance partially and be confused with inflammatory disease. Adults may present with neuropsychiatric disease, followed by spasticity, ataxia, seizures, and death. Two thirds of female carriers also develop some sort of progressive myelopathic picture. They may have more pain and be misdiagnosed as having MS or fibromyalgia. Adult cerebral (AC-ALD) is more fulminant than X-ALD.

MLD is aut rec. Presentations in younger patients include disturbed gait, ataxia, quadriplegia, optic atrophy, and peripheral neuropathy, to decerebrate rigidity. In adults, presentation is often neuropsychiatric with misdiagnosis of schizophrenia, or even normal, with neuropscyh testing especially showing problems with visuospatial construction. There are dramatic elevated sulfatides due to arylsulfatase deficiency.

In Krabbe disease, beta galactocerberosidase occurs, is characterized by , in adult form, various motor presentations with progressive cognitive decline, seizures, cortical blindness with 20 % having uniform slowing of nerve conduction studies. Substrate (galactosylceramide) levels are increased but only mildly, but within oligodendrocyte, there are 100 fold increases in psychosine which is cytotoxic and selectively damages oligodendrocytes. Its been described up to age 84. Get posterior predominant involvement, no enhancement.

In Vanishing White matter disease, adult onset, there is cognitive involvement, pseudobulbar palsy, spastic paraparesis, with an important association with ovarian failure, "ovarioleukodystrophy." Its caused by mutations in e1f2b, affects ribosomes and proteins, causes cystic degeneration and rarefaction of the white matter. Clinical features not completely understood, probably is more common than thought.

Alexander disease-- due to mutation in GFAP, causes Rosenthal fibers. Get bulbar and pseudobulbar palsy with white matter abnormalities starting in front.

Canavan disease-- increased NAA in urine, Spectroscopy is good to diagnose this.

Hereditary diffuse leukoencephalopathy with spheroids is almost exclusively diagnosed in adults. Present with deteriorated behavior and personality and seizures. Diagnosis is by tissue.

Pelizaeus Merzbacher is X linked but like ALD carrier females have a forme of disease. Tremor, ataxia, dementia, and progressive spastic paraplegia occur. Mutation on PLP 1 on X q 22 occur. Classic hypomyelinated CNS disorder.

Recessive hypomyelinating leukoencephalopathy (RHL) =PM like disease is a hypomyelinating disease.

others see text, also for Rx

1 comment:

shashank said...

Here is a link to more information about the genetics of Leukoencephalopathy with Vanishing White Matter that was prepared by our genetic counselor and which has links to some useful resource for those dealing with this condition: There is also a number listed for anyone who wants to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA