Early pathologic changes in hereditary diffuse leukoencephalopathy with spheroids.
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a familial neurodegenerative disease clinically characterized by progressive cognitive and motor dysfunction. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene have recently been identified in HDLS patients. The presence of diffuse axonal spheroids, myelin loss, and pigmented microglia in the white matter are pathologic hallmarks of HDLS; however, early pathologic findings have not been described in HDLS patients. We report a Japanese family with HDLS. A novel heterozygous c.653 C>Y mutation in the CSF1R gene was identified in the female proband who died at the age of 63 years; postmortem findings were compatible with HDLS. We also autopsied her sister who was considered to be neurologically asymptomatic and died of tuberculosis at the age of 44 years. Postmortem studies revealed patchy axonal degeneration and myelin loss, predominantly in the subcortical white matter. Pigmented microglia were distributed diffusely throughout the cerebral white matter and expressed CSF1R poorly. In conclusion, our observations suggest that the pathology of HDLS may initially be characterized by multifocal lesions in subcortical white matter regions. Moreover, pigmented microglia poorly express CSF1R and are distributed diffusely throughout the white matter at the early disease stage, preceding axonal damage and myelin loss.
From the Department of Neurology, Nagoya University Graduate School of Medicine (YR, GS), Aichi, Japan; and Department of Neurology, Nagoya Daiichi Red Cross Hospital (TA, YG, KM), Aichi, Japan; and Institute for Medical Science of Aging, Aichi Medical University (YI, MY), Aichi, Japan.
Yuichi
Y
Riku
Takashi
T
Ando
Yoji
Y
Goto
Kazuo
K
Mano
Yasushi
Y
Iwasaki
Gen
G
Sobue
Mari
M
Yoshida
D000328:Adult; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology; D008875:Middle Aged