Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: HIV/AIDS is a global epidemic that accounts for a large percentage of the mortality in South
Africa every year. Since the implementation of anti-retroviral treatment, HIV positive
individuals have been living longer, and the cognitive impairment associated with the disease
is becoming increasingly apparent. During the initial systemic infection of HIV, the virus
migrates through the blood-brain barrier and inflicts axonal injury by causing upregulation of
cytokines and neurotoxic proteins. HIV-associated dementia is a neuropsychological
classification of cognitive impairment in HIV and a variety of symptoms have been classified
as a part of the dementia complex. One of these is apathy, which is thought to be a precursor
for dementia in HIV patients. Three groups of individuals have been recruited and scanned
using magnetic resonance imaging (MRI) to examine changes in the brain. These are an HIV
non-apathetic cohort, an HIV apathetic cohort and a healthy control cohort. Diffusion tensor
imaging (DTI) is an MRI technique used to quantitatively assess white matter (WM) integrity
using metrics such as fractional anisotropy (FA). Voxel-based analysis, tract-based spatial
statistics (TBSS) and tractography are three established DTI analysis methods that have been
applied in numerous studies. However, there are certain methodological strengths and
limitations associated with each technique and therefore all three of these techniques were
used to compare WM differences across groups. The frontal-subcortical pathways are known
to be abnormal in apathy, and this has been demonstrated in a number of imaging studies.
Most of these studies have examined apathy in the context of neurodegenerative disorders
such as Alzheimer’s disease and Parkinson’s. However, to our knowledge this is the first DTI
study in HIV apathetic patients. With the tractography method, the anterior thalamic radiation
and the corpus callosum were reconstructed for each individual to determine whether there
were any global changes in these tracts. No significant changes were found. However, a
variety of regions in the WM were significantly abnormal in the HIV cohorts when comparing
the data at a voxel-based level and using TBSS. This included areas such as the genu and
splenium of the corpus callosum, the internal capsule and corona radiata. Changes in frontal
WM for the HIV apathy group are an indication of dysfunction in the frontal-striatal circuits,
and previous literature has implicated these circuits in the neuropathology of apathy in a
variety of central nervous system (CNS) disorders. / AFRIKAANSE OPSOMMING: MIV/VIGS is `n wêreldwye epidemie wat verantwoordelik is vir `n hoë sterftesyfer in Suid-
Afrika elke jaar. Sedert die inleiding van anti-retrovirale behandeling, het die MIV-positiewe
populasie se lewensduur verleng. Tesame met langer lewensduur, het die kognitiewe
verswakking wat geassosieer word met die siekte ook meer prominent na vore gekom.
Gedurende die beginstadium van sistemiese infeksie in MIV is daar `n migrasie van die virus
deur die bloed-breinskans. MIV kan indirek verantwoordelik wees vir aksonale beskadiging
deur verhoging van neurotoksiese proteine en sitokinien te induseer. MIV-geassosieerde
demensie is `n neurosielkundige klassifikasie van kognitiewe verswakking in MIV en
verskeie simptome is al geïdentifiseer as deel van die demensie kompleks. Een van die
simptome is apatie en daar word gespekuleer dat dit `n voorloper is vir demensie in MIV
pasiënte. Drie groepe individue was gewerf vir die studie en geskandeer deur magnetiese
resonansie beeldvorming (MRB) om sodoende veranderinge in die brein te ondersoek. Die
groepe was onderskeidelik `n HIV nie-apatiese kohort, `n HIV apatiese kohort en `n gesonde
kontrole kohort. Diffusie tensor beelding (DTB) is `n MRB tegniek wat toegepas word om
witstof integriteit te meet deur gebruik te maak van maatstawwe soos fraksionele anisotropie
(FA). “Voxel-based analysis”, “tract-based spatial statistics (TBSS)” en “tractography” is drie
gevestigde DTB analitiese metodes wat al in talle studies toegepas was. Daar is egter sekere
metodologiese voordele en beperkings verbonde aan elke tegniek en daarom is al drie
tegnieke gebruik om witstof verskille tussen groepe te vergelyk. Die frontale-subkortikale
roetes in die brein is bekend vir abnormaliteite in apatie en dit was ook al gedemonstreer in
verskeie studies. Die meeste van die studies het apatie ondersoek in die konteks van neurodegeneratiewe
siektes soos Alzheimer se siekte en Parkinson se siekte. Maar sover ons weet is
hierdie die eerste DTB studie in MIV pasiënte met apatie. Met die “tractography” metode was
die anterior thalamic radiation en corpus callosum herbou vir elke individu. Dit was om te
bepaal of daar enige globale veranderinge is in hierdie gebiede, maar geen beduidende
veranderinge is gevind nie.`n Verskeidenheid van gebiede in die witstof was beduidend
abnormaal in die MIV kohorte wanneer die data vergelyk was met “TBSS” en “voxel-based
analysis.” Dit het gebiede ingesluit soos die genu en splenium van die corpus callosum, die
internal capsule en die corona radiata. Veranderinge in die frontale witstof vir die MIVapatie
groep is `n aanduiding van disfunksie in die frontale-striatale bane. Vorige literatuur
impliseer dat hierdie bane betrokke is in die neuro-patologie van apatie in verskeie sentrale
senuweestelsel (SS) steurings.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/5146 |
| Date | 12 1900 |
| Creators | Fouche, Jean-Paul |
| Contributors | Strijdom, Hans, Carey, Paul Dermot, Spottiswoode, Bruce Shawn, University of Stellenbosch. Faculty of Health Sciences. Dept. of Biomedical Sciences. Medical Physiology. |
| Publisher | Stellenbosch : University of Stellenbosch |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | xii, 68 p. : ill. (some col.) |
| Rights | University of Stellenbosch |
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