B. Sweeney

Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study

OBJECTIVES To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, , and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychogical assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

Cortical and subcortical JC virus infection: two unusual cases of AIDS associated progressive multifocal leukoencephalopathy.

Two patients with AIDS and progressive neurological syndromes had necropsies that identified JC virus infection of the cerebral or cerebellar cortex. The unusual presentation of progressive multifocal leukoencephalopathy with grey matter involvement and normal cerebral imaging is discussed.

Proton spectroscopy in HIV infection: Relaxation times of cerebral metabolites

In vivo proton spectroscopy has demonstrated abnormalities in the cerebral metabolite ratios from subjects with acquired immunodeficiency syndrome (AIDS). Some of the sequences employed are subject to T1 or T2 weighting, which may affect spectroscopic interpretation. The relaxation times of choline (Cho), creatine (Cr), and N-acetyl (NA) resonances have been estimated at 1.5 T in 21 patients infected with the human immunodeficiency virus (HIV) and 8 controls using gradient localised, spin-echo spectroscopic sequences of varying echo and repetition times. A statistically significant increase in the T2 of NA was found in the HIV seropositive patients who had diffuse abnormalities on MR imaging consistent with HIV encephalopathy (493 +/- 199 ms) when compared to controls (292 +/- 118 ms; p < .05). No other statistically significant differences were found in the relaxation times between patients and control subjects. These results demonstrate that signals from the NA resonance obtained using long echo time sequences in subjects who are HIV seropositive are not solely indicative of metabolite concentration.

Optic neuritis and HIV-1 infection.

A patient is reported who developed acute optic neuritis in the context of severe immunodeficiency associated with HIV-1 infection. The clinical, laboratory, and radiological features are described and the possible associations with syphilis, multiple sclerosis, lymphoma, and HIV-1 infection are discussed.

Cerebral magnetic resonance relaxometry in HIV infection

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

Neurophysiological assessment of peripheral nerve and spinal cord function in asymptomatic HIV-1 infection: Results from the UCMSM/Medical Research Council neurology cohort

As part of the Medical Research Council prospective study of the neurological complications of HIV infection, neurophysiological tests of spinal cord and peripheral nerve function were recorded in a cohort of homosexual or bisexual men. The studies included motor and sensory nerve conduction studies, vibration perception thresholds, somatosensory evoked potentials and motor evoked potentials elicited by magnetic stimulation. The results were compared with markers of immune function. The findings from 114 volunteers were analysed in a cross-sectional study. Fifty-nine were HIV-seropositive but asymptomatic, 26 had progressed to the symptomatic stages of HIV disease and 29 were persistently HIV-seronegative. There was some evidence of a mild sensory axonopathy in the symptomatic HIV-seropositive group. No differences were detected between the asymptomatic HIV-seropositive group and the HIV-seronegative comparison group. There were no consistently significant correlations between the neurophysiological measurements and CD4 counts and β2-microglobulin levels. On repeated testing, there was no evidence of a trend towards deterioration over a mean period of approximately 3 years in 36 HIV-seropositive subjects who remained asymptomatic compared with 22 HIV-seronegatives. These findings have failed to demonstrate neurophysiological evidence of spinal cord or peripheral nerve dysfunction in the asymptomatic stages of HIV infection.