AIDS-associated vacuolar myelopathy. A morphometric study.

Abstract

The post-mortem pathology in 20 spinal cords of human immunodeficiency virus (HIV) infected patients with vacuolar myelopathy was quantified by evaluating (i) the intensity of myelin change, vacuolation and macrophage density; and (ii) the areas of white matter covered by each feature. Severity scores were constructed for (i) the anterior, lateral, and posterior white matter columns; (ii) each level of spinal cord; and (iii) the whole spinal cord [Cord Total and Cord Average Severity Scores (CTSS, CASS)]. Astroglial activation was scored separately. In 14 cords with mild-moderate vacuolar myelopathy (CASS = 23-259), macrophages were the most prominent pathological feature, and level severity scores were higher at mid-thoracic than cervical levels (P = 0.009). In six cords with severe vacuolar myelopathy (CASS = 396-614), vacuolation, demyelination and macrophages were equally evident and thoracic and cervical level severity scores were similar. The most severe lesions showed evidence of clearing of macrophages from the collapsed centres. A clinical lower limb score correlated with the anterior (P = 0.03) and lateral (P = 0.04) column total scores and with the CTSS (P = 0.04) in the nine patients who had had both myelopathy related disability and all cord levels available. There was no significant longitudinal gradient in score severity in the posterior, lateral or anterior columns and no evidence of a dying-back phenomenon. There was no evidence of Wallerian degeneration occurring as a primary process. Astroglial activation did not correlate with the severity or duration of the vacuolar myelopathy. Detection of HIV p24 antigen in the spinal cord related to the local presence of multinucleated giant cells and to antigen expression in the brain but not with the severity of vacuolar myelopathy. The pathology in vacuolar myelopathy appeared to start in the mid-low thoracic cord, with increasing rostral involvement as the disease became more severe. The relative prominence of macrophages in mild-moderate lesions suggests they may be involved early in the pathogenesis of vacuolar myelopathy.