Adrenomyeloneuropathy: A Neuropathologic Review Featuring Its Noninflammatory Myelopathy

The neuropathologic features of adrenomyeloneuropathy (AMN) are reviewed by supplementing those few previously published cases with 5 additional cases collected over the years. The endocrine involvement in AMN is briefly presented to serve as a pathogenetic backdrop and to emphasize that most of the...

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Bibliographic Details
Published in:Journal of neuropathology and experimental neurology 2000-02, Vol.59 (2), p.89-102
Main Authors: POWERS, JAMES M, DECIERO, DAVID P, ITO, MASUMI, MOSER, ANN B, MOSER, HUGO W
Format: Article
Language:English
Subjects:
Adrenoleukodystrophy - pathology
Animals
Biological and medical sciences
Errors of metabolism
Fatty acids
Humans
Ligases
Lipids (lysosomal enzyme disorders, storage diseases)
Medical sciences
Metabolic diseases
Nervous System Diseases - pathology
Spinal Cord Diseases - pathology
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Summary:The neuropathologic features of adrenomyeloneuropathy (AMN) are reviewed by supplementing those few previously published cases with 5 additional cases collected over the years. The endocrine involvement in AMN is briefly presented to serve as a pathogenetic backdrop and to emphasize that most of the lesions in AMN, as in adreno-leukodystrophy (ALD), are noninflammatory in the traditional sense of the word. The myeloneuropathy is emphasized, but the dysmyelinative/inflammatory demyelinative lesions also are presented. The preponderance of available data indicates that the myeloneuropathy of AMN is a central-peripheral distal (dying-back) axonopathy, as was originally proposed. The severity of the myeloneuropathy does not appear to correlate with the duration or severity of endocrine dysfunction. Microglia are the dominant participating cells in the noninflammatory myelopathy. Abnormalities in the ALD gene, which encodes a peroxisomal ABC half-transporter, do not correlate with clinical phenotypes. The relationship of the gene product, ALDP, to the peroxisomal very long chain fatty acid (VLCFA) synthetase, the activity of which is deficient in ALD/AMN, is unclear. An ALD-knockout mouse model has developed axonal degeneration, particularly in spinal cord, and is therefore more reminiscent of AMN than ALD. We continue to postulate that the fundamental defect in the myeloneuropathy of AMN is an axonal or neuronal membrane abnormality perhaps due to the incorporation of VLCFA-gangliosides, which perturbs the membraneʼs microenvironment and leads to dysfunction and atrophy.
ISSN:0022-3069
1554-6578
DOI:10.1093/jnen/59.2.89