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 pres ented 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 t he dysmyelinative/inflammatory demyelinative lesions also are presented. Th e 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 d ominant participating cells in the noninflammatory myelopathy. Abnormalitie s 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 mou se model has developed axonal degeneration, particularly in spinal cord, an d is therefore more reminiscent of AMN than ALD. We continue to postulate t hat the fundamental defect in the myeloneuropathy of AMN is an axonal or ne uronal membrane abnormality perhaps due to the incorporation of VLCFA-gangl iosides, which perturbs the membrane's microenvironment and leads to dysfun ction and atrophy.