Substantia nigra hyperechogenicity and CSF dopamine depletion in HIV

Abstract

Dopaminergic dysfunction is thought to play a pivotal role in human immunodeficiency virus (HIV)-related dementia. Decreased dopamine (DA) levels in the cerebrospinal fluid (CSF) and neuronal loss in the substantia nigra (SN) have been reported in HIV-infected patients, suggesting nigrostriatal damage. Structural changes detectable as hyperechogenicity in transcranial ultrasound (TCS) scans of the SN have been reported in patients with Parkinson's disease (PD) and other neurological conditions. In this study, we assessed the echomorphology of the SN in 40 HIV-positive patients compared to 40 age- and sex-matched healthy controls and correlated these findings with CSF levels of DA and the metabolites homovanillic acid (HVA) and 3,4-dihydroxy phenylacetic acid (DOPAC) and with neuropsychologic performance. We observed that the SN of HIV-infected patients was hyperechogenic relative to that of controls (0.07 +/- 0.05 vs. 0.04 +/- 0.07 cm(2); mean +/- SEM; P < 0.001) and that this SN hyperechogenicity was correlated with decreased DA levels in the CSF, decreased CD4 cell count, and an impaired performance in the psychopathology assessment scale (AMDP) subtest for drive and psychomobility. An association to CDC stage, duration of HIV infection, or presence of HIV dementia was not observed. Our results indicate changes in the nigrostriatal system in HIV-infected patients that are detectable as hyperechogenic SN precede prominent extrapyramidal symptoms and cognitive dysfunction.

Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity

“…However, these same regions have an additional unique feature that may explain observed results. One possible explanation for our findings of reduced connectivity in the striatum can be related to the high amounts of dopaminergic (D2) receptors that are diminished in HIV+ individuals [81–83]. In chronically infected HIV+ subjects, fronto-striatal motor functions are impaired by losses of dopamine activity in the striatum [81].…”

Drugs of Abuse, Dopamine, and HIV-Associated Neurocognitive Disorders/HIV-Associated Dementia

“…Importantly, Larsson et al [33] observed the decrease only during the AIDS stage. Obermann at al [35] went further using transcranial sonographic (TCS) examination to assess the morphology of the substantia nigra, a region rich in dopaminergic cell bodies, and its relationship to dopamine levels in the CSF, and with neuropsychological performance in different stages of HIV infection. This group concluded that early nigrostriatal damage is mediated through HIV neurotoxicity, which can be detected using TCS and that this change is correlated with dopamine depletion in the CSF in therapy-naive asymptomatic HIV-infected patients.…”

HIV-1-assoziierte neurokognitive Störung

“…Unter den modernen MR-basierten Verfahren konnten mit der MR-Spektroskopie und den Parametern apparenter Diffusionskoeffizient (ADC), Magnetisierungs-Transfer-Ratio (MTR), "diffusion tensor imaging" (DTI) und der voxelbasierten Morphometrie (VBM) Zusammenhänge zwischen der Störung des Gewebsaufbaus und klinischen Parametern gezeigt werden [16,47,54,87]. Weiterhin kann eine Hyperechogenität der Substantia nigra in der transkraniellen Sonographie beobachtet werden, die als Ausdruck einer dopaminergen Dysfunktion interpretiert wird [79]. Diese Verfahren eignen sich aber nicht für den Routineeinsatz.…”