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PubMed1994

An unusual neurological feature of HIV-1 encephalopathy: Gerstmann's syndrome.

The authors describe the first case in literature of Gerstmann's syndrome (agraphia, acalculia, finger agnosia) occurred in HIV correlated encephalopathy developed as the first severe manifestation of HIV infection in a patient with prevalent white matter neuroradiologic alterations. The PDL rapidly extended from the left subcortical parietal-occipital regions to the pre-rolandic one, with subsequent involvement of the corpus calosum splenium and the bilateral temporal lobes white matter. The authors indicate the extent of the lesions and the involvement of the interhemispheric connection fibres as the pathogenetic mechanism of the "Gerstmann syndrome", that until today has not been reported in the literature of the wide variety of AIDS dementia complex. The administration of 1 g of zidovudine for about 9 months did not avoid the establishing of the neurologic damage, but the sudden suspension of the drug could have enhanced the exacerbation of inflammation and the involvement of areas whose lesion is classically believed responsible for cognitive impairment.

AIDS Dementia Complex↗
PubMed1990

Electroencephalogram and HIV infection: a prospective study in 100 patients.

In order to study the correlation between central nervous system (CNS) involvement and EEG abnormalities in HIV infection we studied 100 consecutive HIV patients. Patients were divided into 4 groups; Group I: 42 neurologically asymptomatic subjects; Group II: 6 patients with peripheral neuropathies; Group III: 28 patients with AIDS Dementia Complex; Group IV: 24 patients with secondary CNS involvement. The results of this study emphasize that abnormal EEGs are correlated with CNS involvement. Neurologically asymptomatic patients showed no abnormal tracings, but the presence of borderline EEGs (33%) in asymptomatic patients should be evaluated prospectively.

AIDS Dementia Complex↗
PubMed2002

Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients.

BACKGROUND AND PURPOSE: This study was designed to determine whether neuropsychological function in HIV-infected persons is correlated with loss of brain volume (as measured by percentage of brain parenchymal volume [PBV]). We hypothesized that whole-brain parenchymal volume might correlate with neuropsychologic performance, even before overt clinical dysfunction is apparent. METHODS: A computer-assisted segmentation technique with thin section MR imaging was used for 15 patients with HIV infection (seven symptomatic, eight asymptomatic) and for five HIV-negative control participants to quantify whole brain and CSF volumes. To determine the degree of brain atrophy, the PBV relative to that of intracranial content was calculated. Neuropsychological performance was assessed by using a standard battery of eight tests (NPZ-8 test battery). RESULTS: HIV-infected patients had significantly lower NPZ-8 scores (t[18] = 2.26, P <.05) and lower PBV (t[18] = 1.79, P <.01) than those of healthy control participants. With the Spearman rank order correlation coefficients, data analyzed for all 20 study participants (15 HIV-infected patients and five noninfected control participants) showed a significant (r = -0.50, P <.05) negative correlation between PBV and NPZ-8 test battery score. In addition, there was a significant negative correlation between subtest score of motor impairment and PBV (r = -0.69, P <.01) and between AIDS dementia complex score (r = -0.64) and PBV (P <.01). CONCLUSION: These correlations suggest that quantitation of PBV may offer an objective, easily acquired surrogate predictor of neuropsychological impairment and clinically apparent cognitive/motor dysfunction among HIV-infected persons.

AIDS Dementia Complex↗
PubMed1994

Lilliputian hallucinations and medical illness.

Lilliputian hallucinations have been described in patients with delirium, schizophrenia, seizure disorders, visual disturbances, and brain tumors. The authors report two cases of patients with lilliputian hallucinations, one with AIDS-dementia complex and the other with dementia following head trauma. This is the first time that lilliputian hallucinations have been described in association with such medical conditions.

AIDS Dementia Complex↗
PubMed1993

Human immunodeficiency virus-related headache.

We retrospectively assessed the frequency and clinical characteristics of headache occurring in human immunodeficiency virus (HIV)-infected patients in whom we had excluded all other causes, and determined the frequency of a similar headache in an HIV-negative group. Over a 1-year period, the HIV-related headache occurred in 2.8% of total admissions to the HIV service as opposed to 0.2% of admissions to the neurology service. The affected patients had advanced HIV infection (CD4+ cell count = 58.9 +/- 80.3; normal, > 500 x 10(-6)/l). The headache had features similar to those ascribed to HIV aseptic meningitis and was not related to the presence of AIDS dementia complex or its subsequent development over a 6-month follow-up. We propose that this is a distinct clinical entity related to HIV infection that is similar, if not identical, to HIV aseptic meningitis except for the lack of a CSF pleocytosis, probably reflecting the lymphocyte depletion that is characteristic of the more advanced state of HIV infection.

AIDS Dementia Complex↗
PubMed2006

The neuropsychological profile of symptomatic AIDS and ADC patients in the pre-HAART era: a meta-analysis.

It remains essential to document the neuropsychological profile of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) and minor forms human immunodeficiency virus (HIV)-associated neurocognitive impairment by quantifying the magnitude of impairment across eras of treatment. Indeed, with the introduction of the highly active antiretroviral therapy (HAART), there is evidence of changes in aspects of ADC. To allow quantitative and qualitative comparisons with the HAART era studies, we developed a summary of neuropsychological performance acquired in pre-HAART era studies in advanced HIV infection and ADC. Using a meta-analytical procedure and a test nomenclature that accounts for task complexity, we found that individuals with symptomatic infection (but no AIDS) demonstrated a global mild level of cognitive impairment, except for the domains complex attention/psychomotor speed, motor coordination, and learning, which showed moderate impairment. Individuals with AIDS demonstrated a global moderate level of cognitive impairment with a predominance of deficits in attention, complex attention/psychomotor speed, learning, motor coordination, with additional deficits in verbal memory and reasoning. Individuals with ADC demonstrated the most severe cognitive disturbances in domains of learning, motor coordination, with additional deficits in veibal fluency and verbal memory. Moderate impairment was evidenced in domains of complex attention/psychomotor speed, whereas naming and visuospatial functions were relatively preserved. The profile of deficits in ADC suggests that it may not be only interpreted as a worsening form of the impairment that is seen in the AIDS and symptomatic stages of HIV disease but that there are also additional deficits suggestive of an alternate pathogenetic process(es).

AIDS Dementia Complex↗
PubMed1989

[Neuropathology of AIDS: Montefiore experience].

From September 1982 to December 1988 113 cases of AIDS have been autopsied and the brains examined at Montefiore Medical Center. Findings in four areas were presented; 1. Opportunistic infections In approximately one third of cases there were opportunistic infections which were often the cause of death. Cryptococcus, cytomegalovirus and toxoplasma were the three most common infections followed by papovavirus (progressive multifocal leukoencephalopathy) and herpes zoster. Tuberculosis, aspergillosis, histoplasmosis and infection with mycobacterium avium-intracellulare infection were found in only one case each. 2. Malignant lymphoma Both primary and metastatic lymphomas were seen in almost 10% of the cases. 3. HIV encephalitis This conclusion is regarded as the pathological substrate of "AIDS dementia complex" described by the neurologists. In general, it was characterized by cerebral atrophy and diffuse pallor of the white matter with gliosis. The basal ganglia and other areas of the CNS were also often involved. Histologically, there was perivascular infiltration of lymphocytes, macrophages and multinucleated giant cells. Microglial nodules were commonly seen. Electron microscopic and other techniques demonstrates the HIV virus within macrophages and multinucleated cells. 4. Cerebrovascular lesions These lesions are known in AIDS but their high frequency is not generally appreciated unless a careful search for microinfarcts is made. Microinfarcts were found in approximately 1/3 of our cases.

AIDS Dementia Complex↗
PubMed1999

Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia.

OBJECTIVE: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). BACKGROUND: Patients with HIV-cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. METHODS: Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). RESULTS: In 14 of 16 patients who tolerated HAART, CD4 count increased by 133+/-101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8+/-2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54+/-0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (-8.0%; p = 0.02) and in the basal ganglia (-14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased (MI/CR: -14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = -0.67, p = 0.03) and with the change in ADC stage (p = 0.04). CONCLUSIONS: HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].

AIDS Dementia Complex↗
PubMed2002

Regulation of indoleamine 2,3-dioxygenase expression in simian immunodeficiency virus-infected monkey brains.

The human immunodeficiency virus type 1-associated cognitive-motor disorder, including the AIDS dementia complex, is characterized by brain functional abnormalities that are associated with injury initiated by viral infection of the brain. Indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme in tryptophan catabolism in extrahepatic tissues, can lead to neurotoxicity through the generation of quinolinic acid and immunosuppression and can alter brain chemistry via depletion of tryptophan. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we demonstrate that cells of the macrophage lineage are the main source for expression of IDO in the SIV-infected monkey brain. Animals with SIV encephalitis have the highest levels of IDO mRNA, and the level of IDO correlates with gamma interferon (IFN-gamma) and viral load levels. In vitro studies on mouse microglia reveal that IFN-gamma is the primary inducer of IDO expression. These findings demonstrate the link between IDO expression, IFN-gamma levels, and brain pathology signs observed in neuro-AIDS.

AIDS Dementia Complex↗
PubMed1994

gp120-mediated alterations in astrocyte ion transport.

The pathogenesis of the acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) is unknown. However, recent work indicates that neurons and astrocytes are functionally compromised by exposure to viral components or cellular factors released from HIV-1-infected macrophages/microglia. We show that exposure of primary cultured rat astrocytes to the major HIV envelope glycoprotein gp120 results in alterations of ion and solute transport that may contribute to neuronal cell injury.

AIDS Dementia Complex↗
PubMed2001

Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in cerebrospinal fluid of AIDS patients with neuronal destruction.

BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

14-3-3 Proteins↗
PubMed1992

Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients with acute bacterial or viral meningitis and in AIDS patients with various cerebral disorders. Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis. On the contrary, most of the samples from patients with viral meningitis (predominantly caused by mumps virus) had no detectable IL-6 activity in CSF. A moderate increase of IL-6 levels was detected in the CSF of AIDS patients with AIDS dementia complex (ADC), progressive multifocal leukoencephalopathy and cerebral toxoplasmosis. Moreover, higher levels of IL-6 were detected in the CSF of patients with cryptococcal meningitis. We conclude that the initial events of CSF inflammation in patients with acute viral meningitis are different from those in patients with acute bacterial meningitis, and the role of IL-6 is less critical to the process.

AIDS Dementia Complex↗
PubMedDate not supplied

[Neurological syndromes in HIV patients. Part III -- HIV-related diffuse diseases of the central nervous system].

The last part of the review of the neurological syndromes observed among people who are HIV-infected deals with AIDS Dementia Complex, viral (CMV, HSV, VZV) encephalitides and cryptococcal meningitis and other less frequent diseases. Clinical presentation, neuropathology, diagnostic procedures and treatments are described. Diagnostic algorithm for central nervous system diseases in people with HIV is included. The main purpose of the present reviews is to pursue the common ground regarding treatment and diagnostic procedures with consulting neurologists and neurosurgeons for future cooperation in a growing area of HIV related neurology.

AIDS Dementia Complex↗
PubMed1998

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

AIDS Dementia Complex↗
PubMed1990

An update on selected organic mental syndromes.

The authors review recent literature on four medical conditions that constitute important examples of organic mental disorders: AIDS dementia complex, cocaine abuse, cerebrovascular accident, and traumatic brain injury. These disorders are of particular interest because they are frequently the result of high-risk behaviors and the patients are often young adults. Progress in classification and diagnosis, along with greater understanding of pathophysiological mechanisms, has facilitated therapies to ameliorate some symptoms. More specific classification of organic mental disorders should facilitate the examination of biological factors believed responsible for functional psychiatric disturbances.

AIDS Dementia Complex↗
PubMed1992

Interleukin-6 and granulocyte macrophage-CSF in the cerebrospinal fluid from HIV infected subjects with involvement of the central nervous system.

We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM-CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC.

AIDS Dementia Complex↗
PubMedDate not supplied

[Neuropsychiatric aspects of HIV infection and AIDS].

Neurotropism of H.I.V. has recently been recognized. More than one third of Aids patients have neurological complications (infections, tumors, multifocal progressive leuko-encephalopathy...) attributed to immunological failure. Necropsy reveals more frequent neuropathology (75%). "AIDS Dementia Complex" (A.D.C.) has been described. Neuropsychological impairment (and personality alteration) is frequent (20-40%) even in asymptomatic patients. H.I.V. infects the C.N.S. early in the course of viral infection and prior to the development of classical associated neurological abnormalities. Mental disorders are frequent: anxiety, depression, suicidal behavior, etc. They can be psychological reactions, although they are often already present before H.I.V. infection in "high risk groups". The signification of psychosis is discussed. Overview of literature.

AIDS Dementia Complex↗
PubMed1992

[Use of 99mTc-HMPAO SPECT in the study of AIDS-correlated dementia].

AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, grey and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc 99m HMPAO has proved to be an useful tool in studying Alzheimer and multi-infarct dementia, and its use has been recently proposed in AIDS-dementia. We studied with Tc 99m HMPAO 57 Pts (11 HIV+, 26 ARC, 17 AIDS) and control group of 7 drug-addicted seronegative Pts. We found positive results in 45% SPECT, 18% CT, 0% neurological tests of dementia in HIV+ phase, versus 52%, 41, 20% in ARC phase and 94%, 88% and 76% in AIDS phase, while all control Pts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99 mTc HMPAO has an important role in assessing CBF changes in earlier stages of AIDS disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease.

AIDS Dementia Complex↗