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The imaging of HIV-related brain disease.


Many individuals infected with HIV eventually present with evidence of neurological involvement, including cognitive deterioration. Autopsy studies of patients with HIV-associated dementia (HAD) demonstrate damage to the deep white matter areas involved in sub-cortical dementia (including the caudate nucleus and basal ganglia). (8) This finding is complemented by results of both computed tomography (CT) and structural magnetic resonance imaging (sMRI), with association between HAD and both diffuse atrophy with ventricular dilatation (9) and deep white matter lesions. Furthermore, a correlation between declining cognitive function and the loss of volume in certain brain structures, including the basal ganglia and caudate nucleus, has also been reported. (10)

Dynamic contrast-enhanced MRI has identified subcortical grey and frontal white matter as the principal sites of early metabolic abnormalities in HIV disease. (11) Both increased regional cerebral blood volume and post-contrast enhancement have been reported in the basal ganglia in moderate and advanced HAD, reflecting increased vascularity and blood-brain barrier (BBB) permeability. These findings are consistent with the characteristics of the early neurological deficits, and the known predilection of HIV for the basal ganglia. (12) The degree of neurocognitive impairment in HIV is correlated both with the degree of BBB breakdown in the basal ganglia and with viral load. (13)


Diffusion tensor imaging (DTI), a recent advance in MRI methods, is uniquely suited to the study of subtle white matter abnormalities that are not detected by traditional MRI. DTI can be used to quantify the magnitude and directionality of tissue water mobility (i.e. self-diffusion). Barriers such as myelin sheaths, membranes, or white matter tracts result in greater self-diffusion along the axis of the barrier and reduced diffusion out of the tract. This type of restricted self-diffusion is termed 'anisotropic'. Fractional anisotropy (FA) is a measure derived from the diffusion tensor imaging that assesses the degree of anisotropic self-diffusion, i.e. the integrity of the white matter tract. (14) The higher the FA the healthier the tract; lower FA indicates damage to its integrity. DTI provides us with information about the large-scale networks that are made up of long tracts connecting distant relay stations in the brain (Fig. 1). (15) These networks are important for the development of higher brain functions such as language, praxis, social behaviour and emotion. Lesions affecting white matter connections lead to dysfunction, and cognitive disorders are sometimes better explained by a disconnection mechanism between distant cerebral regions than by primary damage of those regions themselves. (16)


DTI studies have revealed central nervous system abnormalities in asymptomatic HIV-positive patients with no cognitive impairment and normal structural MR studies. Diffuse damage to cerebral white matter, as evidenced by pallor on DTI, is one of the most frequent neuropathological features of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. (17) The white matter pallor has been found to be more prevalent and severe in patients with HAD. (17)



DTI abnormalities have been reported in the frontal white matter of cognitively asymptomatic patients infected with HIV, (18) and MR spectroscopy studies indicate that this region may be subject to early injury in patients infected with HIV. (19)

Studies utilising DTI have identified sub-cortical white matter and corpus callosum abnormalities in patients with HIV, despite normal-appearing white matter on MR and non-focal neurological examinations (20) (Fig. 2). Patients with the largest anisotropy decreases had the most advanced HIV disease. Interestingly, patients with the lowest viral loads and normal anisotropy were receiving HAART. This has led some to suggest that DTI could be used as a potential biomarker of brain injury in patients infected with HIV. (21)


DTI and other emerging neuro-imaging technologies may provide markers for early CNS disease in HIV-positive patients, allowing for the earliest possible detection of cognitive impairment. This in turn may facilitate early preventive antiretroviral treatment to reduce long-term damage. Novel imaging techniques such as DTI applied in individuals with mild forms of neurocognitive disorder may be a good place to start. Studies examining response to HAART in patients infected with HIV will be important to determine whether DTI abnormalities reflect reversible or more advanced, irreversible injury. Correlates of white matter damage and neurocognitive decline need to be sought, including whether measures of white matter damage in the central nervous system correlate with viral load, illness duration, age, treatment exposure and treatment adherence. These factors are almost certainly critical in determining the overall impact of HIV on brain function, and in particular on white matter integrity.


(1.) Grant I, Sacktor N, McArthur J. HIV and neurocognitive disorders. In: Gendelman H, Grant I, Everall I, Lipton S, Swindells S, eds. The Neurology of AIDS. Oxford: Oxford University Press, 2005.

(2.) Chang L, Ernst T, Leonido-Yee M, et al. Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 1999; 53: 782-789.

(3.) Ernst T, Chang L, Jovicich J, Ames N, Arnold S, Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology 2002, 59: 1343-1349.

(4.) Tozzi V, Balestra P, Galgani S, et al. Positive and sustained effects of highly active antiretroviral therapy on HIV-1-associated neurocognitive impairment. AIDS 1999; 13(14): 1889-1897.

(5.) Ferrando S, van GW, McElhiney M, Goggin K, Sewell M, Rabkin J. Highly active antiretroviral treatment in HIV infection: benefits for neuropsychological function. AIDS 1998; 12(8): F65-F70.

(6.) Langford TD, Letendre SL, Larrea GJ, Masliah E. Changing patterns in the neuropathogenesis of HIV during the HAART era. Brain Pathol 2003; 13: 195-210.

(7.) Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J. Evolution of HIV Dementia with HIV Infection. Baltimore, Md: Department of Neurology, Johns Hopkins University, 2007.

(8.) Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology 2004; 45: 549-559.

(9.) Stout JC, Ellis RJ, Jernigan TL, et al. Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group. Arch Neurol 1998; 55: 161-168.

(10.) Tucker KA, Robertson KR, Lin W, et al. Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 2004; 157: 153-162.

(11.) Berger JR, Nath A, Greenberg RN, et al. Cerebrovascular changes in the basal ganglia with HIV dementia. Neurology 2000; 54: 921-926.

(12.) Brew BJ, Rosenblum M, Cronin K, Price RW. AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations. Ann Neurol 1995; 38: 563-570.

(13.) Avison MJ, Nath A, Greene-Avison R, Schmitt FA, Greenberg RN, Berger JR. Neuroimaging correlates of HIV-associated BBB compromise. J Immunol 2004; 157: 140-146.

(14.) Basser PJ. Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR in Biomedicine 1995; 8(7/8): 333-344.

(15.) Musulam M-M. Imaging connectivity in the human cerebral cortex: the next frontier? Ann Neurol 2005; 57: 5-8.

(16.) Catani M. Diffusion tensor magnetic resonance imaging tractography in cognitive disorders. Curr Opin Neurol 2006; 9(6): 599-606.

(17.) Gray F, Scaravilli F, Everall I, et al. Neuropathology of early HIV-1 infection. Brain Pathol 1996; 6(1): 1-15.

(18.) Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO. White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study, Psychiatry Res Neuroimaging 2001; 106: 15-24.

(19.) Chang L, Lee PL, Yiannoutsos CT, et al. A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 2004; 23: 1336-1347.

(20.) Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W. Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. AJNR Am J Neuroradiol 2001; 22: 277-283.

(21.) Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB. Diffusion alterations in corpus callosum of patients with HIV. Am J Neuroradiol 2006; 27: 656-660.

Jackie Hoare, MB ChB, MRCPsych, FCPsych (SA)

Division of Neuropsychiatry, Department of Psychiatry and Mental Health, University of Cape Town
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Title Annotation:CLINICAL: IMAGING; human immunodeficiency virus
Author:Hoare, Jackie
Publication:Southern African Journal of HIV Medicine
Article Type:Clinical report
Geographic Code:6SOUT
Date:Oct 1, 2009
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