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Phenotypic variation in leukoencephalopathy with vanishing white matter
M S van der Knaap1, W Kamphorst, P G Barth
1Department of Child Neurology, Free University Hospital, Amsterdam, The Netherlands.
Objective:
The objective of this study is to describe milder and later onset variants of a recently described leukoencephalopathy with vanishing white matter.
Background:
The diagnostic criteria used currently for this disease include an early-childhood onset of neurologic deterioration.
Methods:
Clinical, MRI, and spectroscopic findings of five patients were reviewed who fulfilled all inclusion criteria for the disease of vanishing white matter, apart from the age at onset. In one patient histopathologic findings were documented.
Results:
Onset of the disease was in late childhood or adolescence in four patients, and one patient was still presymptomatic in his early twenties. The course of the disease tended to be milder than in the patients with early-childhood onset. MRI revealed a diffuse cerebral hemispheric leukoencephalopathy with evidence of white matter rarefaction. MRS of the abnormal white matter showed a serious decrease but not complete disappearance of all "normal" signals and, in some patients, the presence of extra signals from lactate and glucose. Changes in relative spectral peak heights were compatible with axonal damage or loss, but not with active demyelination or substantial gliosis. Autopsy in one patient confirmed the extensive rarefaction of the cerebral white matter. There was a commensurate loss of axons and myelin sheaths. Within the brainstem, pontine lesions were present, also involving the central tegmental tracts--a phenomenon previously described in early-onset patients.
Conclusion:
Later onset does occur in the disease of vanishing white matter, and both MRS and histopathology are compatible with a primary axonopathy rather than primary demyelination.
Insights
Milder forms of vanishing white matter (VWM) disease present later in childhood or adolescence. Histopathology and MRI suggest VWM is a primary axonopathy, not demyelination.
Area of Science:
- Neurology
- Neuroimaging
- Pathology
Background:
- Vanishing white matter (VWM) disease is typically diagnosed based on early-childhood onset of neurological decline.
- This study investigates variants of VWM with later onset and milder symptoms.
Observation:
- Five patients with VWM, excluding age of onset, were analyzed for clinical, MRI, and spectroscopic data.
- One patient underwent histopathological examination.
Findings:
- Four patients experienced disease onset in late childhood or adolescence; one remained presymptomatic into their twenties.
- MRI revealed diffuse cerebral hemispheric leukoencephalopathy with white matter rarefaction.
- Magnetic Resonance Spectroscopy (MRS) indicated reduced but not absent white matter signals, with some lactate and glucose presence, suggesting axonal damage rather than active demyelination or gliosis.
- Histopathology confirmed extensive white matter rarefaction with commensurate axonal and myelin sheath loss, including brainstem pontine lesions.
Implications:
- Vanishing white matter disease can manifest with later onset and a milder clinical course.
- MRS and histopathological findings support VWM as a primary axonopathy, challenging the traditional view of it being a primary demyelinating disease.