title: Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids.
abstract: The pathologic features of adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids (ALAS) are variable, and this has led to different hypotheses as to whether primarily demyelination or axonopathy may underlie this disorder. Typical ALAS pathology is rarely accompanied by focal multiple sclerosis (MS)-like plaques. In ALAS pathology accompanied by focal multiple sclerosis (MS)-like plaques cases, the pathologic features cannot be distinguished from those of progressive MS with diffusely abnormal white matter. To clarify these issues, we examined neuropathologic features in 159 representative samples from 5 ALAS cases (3 men and 2 women aged 39-61 years) and in 95 representative samples from 3 chronic MS cases (1 man and 2 women aged 50-73 years). The white matter abnormalities in ALAS cases were characterized by 3 evolving stages: 1) white matter with numerous spheroids in a background of well-myelinated fibers; 2) moderate loss of myelinated fibers with sparse to moderate number of spheroids; and 3) leukodystrophy-like pattern of confluent axonal and myelin loss. The application of this staging system suggests that myelin loss in ALAS is preceded by axonopathy. In progressive MS cases, the diffusely abnormal white matter pathology could be attributed to both primary demyelination and axonopathy. Some cases with predominant axonopathy are difficult to distinguish from cases with ALAS.
authors: From the London Health Sciences Center (MA, L-CA) and Western University (MA, L-CA), London; and Sunnybrook Health Sciences Center, University of Toronto (JK), and Tanz Center for Research in Neurodegenerative Diseases (L-NH), Toronto, Ontario, Canada; Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida (RR); and Department of Pathology, King Abdulaziz University and Hospital, Jeddah, Saudi Arabia (MA).
authors: Murad
authors: M
authors: Alturkustani
authors: Julia
authors: J
authors: Keith
authors: Lili-Naz
authors: LN
authors: Hazrati
authors: Rosa
authors: R
authors: Rademakers
authors: Lee-Cyn
authors: LC
authors: Ang
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000473:pathology*