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A comparative morphologic analysis of adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia – a role for oxidative damage
Author(s) -
Ali Zarina Sultana,
Van Der Voorn J. Patrick,
Powers James M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a401
Subject(s) - lipofuscin , pathology , oxidative stress , leukodystrophy , luxol fast blue stain , ferritin , myelin , medicine , biology , disease , endocrinology , central nervous system
We compare, in a blinded protocol, five cases of hereditary diffuse leukoencephalopathy with spheroids (HDLS) and ten cases of the pigmentary type of orthochromatic leukodystrophy (POLD), four of which have a family history of neurological illness. Patients presented in the third to sixth decade (mean 41 yrs) with behavioral, cognitive, and motor symptoms. All cases display widespread myelin loss, predominantly fronto‐temporal with relative sparing of subcortical U‐fibers, and variable numbers of both neuroaxonal spheroids and pigmented glia. Microscopically, spheroids contain amyloid precursor/neurofilament proteins and ubiquitin. Glia and numerous pigmented macrophages stain consistently with diastase‐PAS, Sudan black, prolonged Ziehl‐ Nielsen, and cresyl violet, but variably for iron and ferritin. Ultrastructurally, autofluorescent glial lipopigments consist of lobulated masses of predominantly finely‐granular, electron‐dense material, consistent with ceroid, an end product of oxidative damage. Glial immunoreactivity to markers of oxidative stress (HO‐1, SOD2) and damage (HNE, MAL, NT) is noted, particularly in cases with increased iron and ferritin. These data support the hypothesis that the similar clinico‐pathologic features of HDLS and POLD represent a common disease possibly due to an oxidative insult, but further pathogenetic mechanisms should be explored.