title: Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature.
abstract: We present a two-generation family consisting of a father and two daughters, who had an adult-onset leukodystrophy characterized by widespread destruction of cerebral white matter with neuroaxonal spheroids. The mode of inheritance appears to be autosomal dominant. All three patients presented with a variety of motor and cognitive symptoms, including frontal lobe signs, 4-7 years before death. Each followed a chronic course until death at ages 39, 46, and 51. At autopsy, the white matter loss was widespread but most prominent in the cerebrum with descending corticospinal tract degeneration and relative sparing of subcortical U-fibers. Pigmented glial cells were present, most of which appear to be macrophages, but inconstantly Prussian blue-positive. This disease is consistent with published reports of hereditary diffuse leukoencephalopathy with spheroids (HDLS). However, a review of the literature and a personal review of the neuropathology of the original case of the pigmentary type of orthochromatic leukodystrophy (POLD) reveal overlapping clinical and neuropathologic features between these two previously distinct entities, suggesting a common pathogenetic and perhaps etiological relationship between the two.
authors.affiliation: Department of Pathology, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marotti
authors.forename: Sharon
authors.initials: S
authors.lastname: Tobias
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fratkin
authors.forename: James M
authors.initials: JM
authors.lastname: Powers
authors.forename: C Harker
authors.initials: CH
authors.lastname: Rhodes
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D005192:Family Health; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D019150:Neuroaxonal Dystrophies / Q000150:complications / Q000235:genetics / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology*; D009679:Nuclear Family; D010858:Pigmentation / Q000502:physiology*; D012196:Review Literature as Topic; D013194:Staining and Labeling / Q000379:methods
chemical_list: D016900:Neurofilament Proteins