Myelopathies in human immunodeficiency virus (HIV) infection

The clinical and pathological features of 51 patients with myelopathy (one of whom had two presentations) drawn from a population of approximately 1900 HIV-seropositive patients were studied over 26 months. Vacuolar myelopathy (VM) (n=26, 50%) commonly presented subacutely. Clinical variants included pure spastic paraparesis and no sustained weakness throughout follow-up. Cognitive dysfunction, cerebral atrophy and peripheral neuropathy were common. Most progressed to wheelchair dependence and bladder incontinence. Other myelopathies (OTM) (n=26) divided into (i) those with immunosuppression as a predisposing factor (CMV, Herpes zoster, lymphoma), and (ii) those with myelopathy incidental to HIV disease (cervical spondylosis, cord contusion, etc.). CMV was the commonest cause. Post mortems in 10 VM and 4 OTM confirmed the clinical diagnosis in all. The annual incidence of all myelopathies was 1.1% in all HIV-seropositives, 3.5% in AIDS, 0.6% in symptomatic non-AIDS, and 0.1% in well seropositives. The incidence of vacuolar myelopathy was 0.6% of all HIV-seropositives, 2% in AIDS and 0.2% in symptomatic non-AIDS patients. HIV and nutritional parameters, serum B12 and folate were not different in VM, OTM, or sequential admission (n=51) and neurologically asymptomatic (n = 30) controls. Survival analysis of patients with myelopathy showed no significant difference with 49 AIDS controls. A pathogenetic role for TNFa; in VM was investigated by immunocytochemistry. The amount of staining in macrophages, microglia and endothelial cells was higher in 15 cords with VM than in 9 HIV-seropositive and HIV-seronegative controls. Its distribution corresponded to the areas of pathology. CSF and blood TNFa levels (ELISA) were no higher in 16 VM, than in 8 OTM and 47 HIV-seropositive and seronegative controls. A morphometric study of 20 cords with VM suggested a rostral progression in disease and early macrophage involvement in the pathogenesis of VM. The pathogenesis of VM may involve a combination of immune-mediated myelin and oligodendrocyte injury, impairment of repair mechanisms due to the depletion of S-adenosylmethionine, and HIV augmentation of macrophage activation