Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids

M. S. Van Der Knaap, Sakkubai Naidu, B. K. Kleinschmidt-DeMasters, W. Kamphorst, H. C. Weinstein

Research output: Contribution to journalArticle

Abstract

Objective: To provide clinical, MRI, and histopathologic findings in a rare white matter disorder with autosomal dominant inheritance, so-called hereditary diffuse leukoencephalopathy with spheroids (HDLS). Background: Progressive leukoencephalopathies often constitute a diagnostic dilemma in both children and adults. In some cases, histopathologic examination of brain tissue is required for a classifying diagnosis. Methods: Clinical history, MRI, and autopsy findings were reviewed in three patients with HDLS: a father, his daughter, and an unrelated patient. Results: Clinical history consisted of an adult-onset neurologic deterioration with signs of frontal lobe dysfunction, epilepsy, spasticity, ataxia, and mild extrapyramidal disturbances. MRI findings included cerebral atrophy and patchy white matter changes, most pronounced in the frontal and frontoparietal area with extension through the posterior limb of the internal capsule into the pyramidal tracts of the brainstem. Autopsy in two patients revealed a leukoencephalopathy with frontoparietal and frontal preponderance and numerous neuroaxonal spheroids in the abnormal white matter. The pyramidal tracts were affected throughout the brainstem. Conclusion: Similar clinical and histopathologic findings have been reported in members of a Swedish pedigree. The homogeneity of the findings strongly suggests that HDLS is a distinct disease entity. In the absence of a biochemical or genetic marker, a definitive diagnosis requires histopathologic confirmation in one of the affected family members.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalNeurology
Volume54
Issue number2
StatePublished - Jan 25 2000

Fingerprint

Leukoencephalopathies
Pyramidal Tracts
Brain Stem
Autopsy
Frontal Lobe Epilepsy
Internal Capsule
Ataxia
Pedigree
Nuclear Family
Genetic Markers
Fathers
Nervous System
Atrophy
Molecular Biology
Extremities
Biomarkers
Brain
Hereditary Diffuse Leukoencephalopathy with Spheroids
White Matter

Keywords

  • Autosomal dominant
  • Leukoencephalopathy
  • Neuroaxonal spheroids

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Van Der Knaap, M. S., Naidu, S., Kleinschmidt-DeMasters, B. K., Kamphorst, W., & Weinstein, H. C. (2000). Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. Neurology, 54(2), 463-468.

Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. / Van Der Knaap, M. S.; Naidu, Sakkubai; Kleinschmidt-DeMasters, B. K.; Kamphorst, W.; Weinstein, H. C.

In: Neurology, Vol. 54, No. 2, 25.01.2000, p. 463-468.

Research output: Contribution to journalArticle

Van Der Knaap, MS, Naidu, S, Kleinschmidt-DeMasters, BK, Kamphorst, W & Weinstein, HC 2000, 'Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids', Neurology, vol. 54, no. 2, pp. 463-468.
Van Der Knaap MS, Naidu S, Kleinschmidt-DeMasters BK, Kamphorst W, Weinstein HC. Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. Neurology. 2000 Jan 25;54(2):463-468.
Van Der Knaap, M. S. ; Naidu, Sakkubai ; Kleinschmidt-DeMasters, B. K. ; Kamphorst, W. ; Weinstein, H. C. / Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. In: Neurology. 2000 ; Vol. 54, No. 2. pp. 463-468.
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