Neurocognitive functioning in acute or early HIV infection

We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIV?) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIV? participants. All AEH participants were HIV infected for less than 1 year. Average domain deficit scores were calculated in seven neurocognitive domains. HIV?, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16 weeks [interquartile range, IQR: 10.3–40.7] as compared to 4.9 years [2.8–11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIV? group (mean rank?=?1.43), intermediate neurocognitive functioning in the AEH group (mean rank?=?1.71), and the worst in the chronically HIV infected (mean rank?=?2.86; L statistic?=?94, p?相似文献   

Neurocognitive impairment with hepatitis C and HIV co-infection in Southern Brazil

Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n?=?20), HIV mono-infected (n?=?48), HIV/HCV co-infected (n?=?12), and HIV?/HCV-uninfected controls (n?=?48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three infection groups compared with the uninfected control group, but no statistically significant differences among mono- and co-infected groups were found. HCV infection was associated with cognitive deficits, independently of liver dysfunction. HCV infection did not show an additive effect on neurocognitive function among HIV+. NCI was independent of HCV RNA on peripheral blood, CSF, and hepatic injury. While we did not find additive global effect, in the present study, there was some evidence of additive HIV/HCV co-infection effects in speed of information processing, executive function, and verbal fluency domains when comparing the co-infected group with the other three groups. NP impairment was not dependent on HCV subtypes.     

Neurocognitive symptoms and impairment in an HIV community clinic

BACKGROUND: Neurocognitive impairment is a frequent complication of HIV infection and heralds a poor survival prognosis. With the availability of highly active antiretroviral therapy (HAART), survival times for HIV-infected patients have markedly increased although the effects of HAART on the prevalence of neurocognitive impairment remain uncertain. OBJECTIVE: To determine the relationship between self-reported neurocognitive symptoms and neuropsychological (NP) performance together with the impact of HAART among HIV-infected patients. METHODS: A cross-sectional study was performed in which patients without previously documented neurocognitive impairment attending an HIV community clinic were questioned about neurocognitive symptoms and a NP test battery was administered. RESULTS: Of the eighty-three patients examined, neurocognitive symptoms were reported by 34% of patients and were associated with a shorter duration of HAART and higher viral loads. Patients reporting neurocognitive symptoms were also more likely to exhibit impaired NP performance (p<0.005) with NP impairment being detected in 46% of all patients examined (12% with HIV-associated dementia). Neuropsychological impairment was directly correlated with age (p<0.001), plasma viral load (p<0.005) and inversely correlated with the number of prescribed antiretroviral drugs (p<0.01). CONCLUSIONS: These results suggest that neurocognitive symptoms are predictive of impaired NP performance and that NP impairment remains a frequent finding among older patients with higher viral loads. An increased number of antiretroviral drugs may be neuroprotective.     

Neurocognitive impairment is worse in HIV/HCV-coinfected individuals with liver dysfunction

Journal of NeuroVirology - Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons...     

Neurocognitive disturbances in HIV

HIV infection is associated with disturbances in brain function which reflect themselves in HIV associated neurocognitive disorder (HAND). Neurocognitive examination is a sensitive and relevant approach to detecting and monitoring HAND. The approaches to evaluating the various neurocognitive disturbances are reviewed, along with consideration of cofactors that may influence expression of these disorders.     

Selective attention deficits associated with mild cognitive impairment and early stage Alzheimer's disease in adults with Down syndrome

Adults with Down syndrome and early stage Alzheimer's disease showed decline in their ability to selectively attend to stimuli in a multitrial cancellation task. They also showed variability in their performance over the test trials, whereas healthy participants showed stability. These changes in performance were observed approximately 2 years prior to a physician's diagnosis of possible Alzheimer's disease, which was made when they were exhibiting declines in episodic memory suggestive of mild cognitive impairment. Performance on this task varied with the evolution of dementia, showed modestly good sensitivity and specificity, and was relatively easy to administer. Given these qualities this task could be a valuable addition to a neuropsychological battery intended for the assessment of mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.     

Neurocognitive disturbances in HIV

HIV infection is associated with disturbances in brain function which reflect themselves in HIV associated neurocognitive disorder (HAND). Neurocognitive examination is a sensitive and relevant approach to detecting and monitoring HAND. The approaches to evaluating the various neurocognitive disturbances are reviewed, along with consideration of cofactors that may influence expression of these disorders.     

Mitochondrial cytopathies associated with HIV infection

The tremendous progress achieved during the last few years with the use of highly active antiretroviral therapy in suppressing HIV replication together with improvements in immunity have been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis due to didanosine, neuropathy due to zalcitabine, myopathy due to zidovudine, and lactic acidosis due to stavudine. These mitochondrial toxicities can affect several organs, presenting different patterns of symptoms: from asymptomatic to states with few symptoms despite huge metabolic abnormalities whose prognosis is immediately life-threatening. Beyond the inhibition of DNA polymerase gamma using nucleoside analogs, responsible for decreasing mitochondrial DNA in certain targeted organs, it appears that several physiopathologic mechanisms interact to explain this observed toxicity, HIV itself plays a role, and the underlying genetic pool needs to be better identified. Such cases mean that, it is imperative to avoid cumulated toxicities caused by associated treatments. With serious cases, or persistent symptoms despite discontinuing the nucleoside analogs responsible for such toxicity, one must propose vitamins, mitochondrial co-factors, or anti-oxidants. However, the future lies in the use of potent, less toxic nucleoside analogs, and in developing compounds belonging to other classes of antiretrovirals.     

New-onset seizures associated with HIV infection

The authors studied new-onset seizures in 60 heterosexual black South African HIV-infected patients who had not used IV drugs. An intracranial space-occupying lesion was identified in 53% of patients, meningitis in 22%, and no additional cause in 25%. Of the patients with an identifiable cause, 64% had probable tuberculosis (tuberculoma or tuberculous meningitis). The majority of patients had late-stage HIV infection (CD4 counts <200/mm(3)).     

Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck’s depression score, and years of education, there was 0.04 lower log₁₀ HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log₁₀ increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.     

Acute hemiplegia associated with HIV infection

An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.     

Intellectual impairment in patients with epilepsy in Ile-Ife, Nigeria

Introduction – Epilepsy is the most common non‐infectious neurologic disease in developing countries such as Africa, including Nigeria. This study was designed to assess the intellectual performance of patients with epilepsy (PWE) in Nigeria hoping that the result will serve as the basis for educational, vocational, and social counseling. Methods – Forty‐one PWE were studied along with 41 age‐, sex‐ and education‐matched healthy controls. A questionnaire was developed and applied to all subjects and history was taken from patients and eyewitness. The intellectual function of each subject was assessed with the aid of Wechsler Adult Intelligence Scale adapted for Nigerians. All patients subsequently had electroencephalography (EEG) performed and the EEG findings were noted. SPSS statistical package was used to analyze the data. Result – The PWE performed poorly on the verbal IQ, performance IQ, and full scale IQ scores when compared with controls (P < 0.05) and 20% of PWE had mental retardation. Long duration of epilepsy, long duration of antiepileptic drug therapy, younger age at onset of epilepsy, increased frequency of seizures, and low educational status were found to have negative impacts on intellectual performance in PWE (P < 0.05) while seizure types and type of antiepileptic drugs (carbamazepine or phenytoin) did not influence intellectual performance. Conclusion – This study shows that PWE had significant intellectual impairment when compared with controls. In addition, long duration of epilepsy, long duration of AED therapy, earlier age of onset, increased seizure frequency, and low educational status had a negative impact on intellectual functioning in PWE.     

Autistic disorder associated with congenital HIV infection

Although autistic disorder is rare, we identified three children with this syndrome in a sample of 286 children with congenital HIV infection. The prevalence of autistic disorder was thus greater than expected from epidemiological data. The present article describes the clinical manifestations and course of development of the three children. Etiologic heterogeneity in autism is assumed by most investigators because of the occurrence of autistic disorder in persons with a variety of other disorders (e. g. viral or genetic). We hypothesize that there is a complex relation between congenital HIV infection and austistic disorder and suggest the need for systematic investigations of larger series of HIV positive children.

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Zusammenfassung Obwohl eine autistische Störung selten ist, haben wir drei Kinder mit diesem Syndrom in einer Stichprobe von 286 Kindern mit kongenitaler HIV-Infektion identifiziert. Die Prävalenz der autistischen Störung war infolgedessen größer, als aufgrund epidemiologischer Daten zu erwarten gewesen wäre. Der vorliegende Artikel beschreibt die klinischen Symptome und den Entwicklungsverlauf dieser drei Kinder. Eine ätiologische Heterogenität des Autismus wird von den meisten Untersuchern angenommen, weil die autistische Störung bei einer Reihe von verschiedenen Störungen (z.B. viral oder genetisch bedingt) vorkommt. Unserer Hypothese zufolge gibt es eine komplexe Beziehung zwischen kongenitaler HIV-Infektion und autistischer Störung. Hiernach gibt es einen Bedarf für systematische Untersuchungen größerer Kollektive von HIV-positiven Kindern.

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Résumé Bien que la pathologie autistique soit rare, nous avons identifié trois enfants avec le syndrome dans un échantillon de 286 enfants avec une infection HIV congénitale. La prévalence du trouble autistique était ainsi plus élevée que celle attendue par les données épidémiologiques. L'article décrit les manifestations cliniques et l'évolution de ces trois enfants. L'hétérogénéité étiologique de l'autisme est admise par la plupart des investigateurs du fait de la survenue de l'autisme chez des sujets présentant une grande variété d'autres troubles (viraux ou génétiques). Nous faisons l'hypothèse d'une relation complexe entre l'infection HIV congénitale et la pathologie autistique et nous suggérons le besoin d'investigatons systématiques de séries plus étendues d'enfants HIV positifs.

     

Cognitive function in early HIV infection

This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman’s correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.     

Cell-free mitochondrial DNA in CSF is associated with early viral rebound,inflammation, and severity of neurocognitive deficits in HIV infection

Cell-free mitochondiral DNA (mtDNA) is an immunogenic molecule associated with many inflammatory conditions. We evaluated the relationship between cell-free mtDNA in cerebrospinal fluid (CSF) and neurocognitive performance and inflammation during HIV infection. In a cross-sectional analysis, we evaluated the association of mtDNA levels with clinical assessments, inflammatory markers, and neurocognitive performance in 28 HIV-infected individuals. In CSF, we measured mtDNA levels by droplet digital PCR, and soluble CD14 and CD163, neurofilament light, and neopterin by ELISA. In blood and CSF, we measured soluble IP-10, MCP-1, TNF-α, and IL-6 by ELISA, and intracellular expression of IL-2, IFN-γ, and TNF-α in CD4⁺ and CD8⁺ T cells by flow cytometry. We also evaluated the relationship between CSF pleocytosis and mtDNA longitudinally in another set of five individuals participating in an antiretroviral treatment (ART) interruption study. Cell-free CSF mtDNA levels strongly correlated with neurocognitive performance among individuals with neurocognitive impairment (NCI) (r?=?0.77, p?=?0.001). CSF mtDNA also correlated with levels of IP-10 in CSF (r?=?0.70, p?=?0.007) and MCP-1 in blood plasma (r?=?0.66, p?=?0.01) in individuals with NCI. There were no significant associations between inflammatory markers and mtDNA in subjects without NCI, and levels of mtDNA did not differ between subjects with and without NCI. MtDNA levels preceded pleocytosis and HIV RNA following ART interruption. Cell-free mtDNA in CSF was strongly associated with the severity of neurocognitive dysfunction and inflammation only in individuals with NCI. Our findings suggest that within a subset of subjects cell-free CSF mtDNA is associated with inflammation and degree of NCI.     

Neurocognitive impairment and dementia in mood disorders

In a substantial percentage of patients, mood disorders are accompanied by persistent neurocognitive impairment. Elderly patients with dementia often suffer from depression. Neurocognitive tests and imaging are increasingly used to complement diagnostics. Tests assessing memory, attention, executive functions, and visuospatial abilities might help to distinguish mood disorder patients who can be expected to develop dementia from those who will not. This review presents a summary of knowledge on neurocognitive profiles differentiating impairment in mood disorders and dementia. Ideas on pathophysiological causation and progression are translated into recommendations for patient management.