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Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course
M S van der Knaap1, P G Barth, G F Vrensen
1Department of Child Neurology, Free University Hospital, Amsterdam, The Netherlands.
Abstract:
Recently, we described an as yet unidentified white matter disorder in eight patients which probably has an autosomal recessive mode of inheritance. The disease was characterized by megalencephaly and leukoencephalopathy with onset during the 1st year of life and a delayed onset of slowly progressive neurological dysfunction. No basic biochemical defect could be identified. Brain biopsy was performed in one of the patients and the histopathological findings are described in the present report. A spongiform leukoencephalopathy was revealed, without cortical involvement. Most vacuoles were covered by single five-layered membranes, representing single myelin lamellae. Some vacuoles were partially covered by multi-lamellar myelin sheaths or oligodendroglial cell extensions. The vacuoles were never found in the middle or inner parts of myelin sheaths, but involved the outermost lamellae of myelin sheaths only, whereas the remainder of the myelin sheaths remained undisturbed. The histopathological findings place the disease among the vacuolating myelinopathies, although it is distinct from the well-known forms. Possible pathophysiological mechanisms are splitting of the outermost myelin lamellae at the intraperiod line or a disturbance of compaction of the outermost myelin lamellae at the intraperiod line.
Insights
This study details a rare white matter disorder with megalencephaly and leukoencephalopathy. Histopathology reveals spongiform changes affecting only the outermost myelin layers, distinct from known vacuolating myelinopathies.
Area of Science:
- Neurology
- Pathology
- Genetics
Background:
- Describes a newly identified autosomal recessive white matter disorder.
- Characterized by megalencephaly, leukoencephalopathy, and progressive neurological decline starting in infancy.
Observation:
- Presents histopathological findings from a brain biopsy of one affected patient.
- Revealed a spongiform leukoencephalopathy without cortical involvement.
Findings:
- Vacuoles were observed within the outermost myelin lamellae, specifically at the intraperiod line.
- These vacuoles were membrane-bound and did not affect the inner myelin sheath structure.
- The observed pathology distinguishes this disorder from other known vacuolating myelinopathies.
Implications:
- Suggests potential pathophysiological mechanisms involving myelin lamellar splitting or compaction defects.
- Highlights the need for further research to identify the underlying biochemical defect and genetic basis.
- Contributes to the classification and understanding of rare white matter disorders.