Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids

Murad Alturkustani, Julia Keith, Lili Naz Hazrati, Rosa Rademakers, Lee Cyn Ang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume74
Issue number3
DOIs
StatePublished - Mar 28 2015

Keywords

  • Adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids
  • Axonal leukodystrophy
  • Hereditary diffuse leukoencephalopathy with spheroids
  • Progressive multiple sclerosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Pathologic staging of white matter lesions in adult-onset leukoencephalopathy/leukodystrophy with axonal spheroids'. Together they form a unique fingerprint.

Cite this