Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids.
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.


CONCLUSIONS
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. Neuroaxonal spheroids.
van der Knaap
M S
MS
Department of Child Neurology, Free University Hospital, Amsterdam, The Netherlands. ms.vanderknaap@azvu.nl
Naidu
S
S
Kleinschmidt-Demasters
B K
BK
Kamphorst
W
W
Weinstein
H C
HC
D000328:Adult; D001284:Atrophy; D001369:Axons / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D005192:Family Health; D017809:Fatal Outcome; D005220:Fathers; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011712:Pyramidal Tracts / Q000473:pathology; D013346:Subarachnoid Space / Q000473:pathology