HIV leucoencephalopathy and TNFalpha expression in neurones.
BACKGROUND
Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor alpha (TNFalpha), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine.


OBJECTIVE
To examine the clinical/neuroradiological features of HIVL and the expression of TNFalpha in HIVL.


METHODS
Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry.


RESULTS
Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNFalpha was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNFalpha expression in neurones of the frontal cortex and basal ganglia.


CONCLUSIONS
This study provides the first demonstration of staining for TNFalpha in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNFalpha.
Rostasy
K
K
Paediatric Neurology, University of Göttingen, Germany.
Monti
L
L
Lipton
S A
SA
Hedreen
J C
JC
Gonzalez
R G
RG
Navia
B A
BA
D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001479:Basal Ganglia / Q000473:pathology; D001706:Biopsy; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000473:pathology; D015700:HIV Envelope Protein gp41 / Q000032:analysis; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009460:Neurologic Examination; D009474:Neurons / Q000473:pathology; D009483:Neuropsychological Tests; D019258:Saquinavir / Q000008:administration & dosage; D018119:Stavudine / Q000008:administration & dosage; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D015215:Zidovudine / Q000008:administration & dosage
D044966:Anti-Retroviral Agents; D015700:HIV Envelope Protein gp41; D014409:Tumor Necrosis Factor-alpha; D015215:Zidovudine; D018119:Stavudine; D019258:Saquinavir