Paulo Pereira Christo

Neurological disease in HIV-infected patients in the era of highly active antiretroviral treatment: a Brazilian experience

To study characteristics of neurological disorders in HIV/AIDS patients and their relationship to highly active antiretroviral treatment, a cross-sectional study was conducted in an infectious disease public hospital in Belo Horizonte, Brazil, between February 1999 and March 2000. Of the 417 patients enrolled, neurological disease was observed in 194 (46.5%) and a new AIDS-defining neurological event developed in 23.7% of individuals. Toxoplasmosis (42.3%), cryptococcosis meningitis (12.9%) and tuberculosis (10.8%) were the most common causes of neurological complications. The majority (79.3%) of patients were on highly active antiretroviral treatment and these individuals using HAART showed higher CD4 cell counts (p = 0.014) and presented stable neurological disease (p = 0.0001), although no difference was found with respect to the profile of neurological complications. The neurological diseases continue to be a frequent complication of HIV/AIDS and infections are still its main causes in Brazil, even in the highly active antiretroviral treatment era.

Plasma levels of soluble tumor necrosis factor receptors are associated with cognitive performance in Parkinson's disease.

Inflammatory mechanisms have been implicated in a series of neuropsychiatric conditions, including behavioral disturbances, cognitive dysfunction, and affective disorders. Accumulating evidence also strongly suggests their involvement in the pathophysiology of Parkinsons disease (PD). This study aimed to evaluate plasma levels of inflammatory biomarkers, and their association with cognitive performance and other non‐motor symptoms of PD. PD patients and control individuals were subjected to various psychometric tests, including the Mini‐Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Becks Depression Inventory (BDI). Biomarker plasma levels were measured by enzyme‐linked immunosorbent assay (ELISA). PD patients exhibited worse performance on MMSE and the programming task of FAB, and presented higher soluble tumor necrosis factor receptor (sTNFR) plasma levels than control individuals. Among PD patients, increased sTNFR1 and sTNFR2 concentrations were associated with poorer cognitive test scores. After multiple linear regression, sTNFR1 and education remained a significant predictor for FAB scores. Our data suggest that PD is associated with a proinflammatory profile, and sTNFRs are putative biomarkers of cognitive performance, with elevated sTNFR1 levels predicting poorer executive functioning in PD patients.

Alterações cognitivas na infecção pelo HIV e Aids

Primary neurological complications of AIDS include cognitive deficits such as HIV-associated dementia and milder forms such as cognitive/motor disorders, which cause changes in daily activities and reduce the quality of life of patients. Infection with HIV-1 is the most common, predictable and treatable cause of cognitive deficits in individuals with less than 50 years of age. . Despite advances in the understanding of clinical characteristics, pathogenesis and neurobiological aspects and widespread use of highly active antiretroviral therapy (HAART), neurological complications and cognitive deficits still persist with serious personal and socioeconomic consequences, thus representing a great therapeutic challenge. In the pre-HAART era dementia was a common complication of infection whose incidence declined during the HAART era. However, prevalence of dementia has increased, especially that of milder forms due to the increased number of infected individuals and increased life expectancy. Cognitive alterations associated with HIV are typically sub cortical and can be associated with behavioral and motor disorders. These syndromes are clinically diagnosed by neuropsychological tests, while neuroimaging and analysis of cerebrospinal fluid contribute to diagnosis. This review is an update on current epidemiological status, clinical characteristics and diagnosis of cognitive complications observed during the course of HIV infection.

Cerebrospinal fluid levels of chemokines in HIV infected patients with and without opportunistic infection of the central nervous system

Chemokines are chemoattractant cytokines involved in the immune response of a wide variety of diseases. There are few studies assessing their role in opportunistic infections in HIV-infected patients. In this study, we measured CC and CXC chemokines in cerebrospinal fluid (CSF) samples obtained from 40 HIV-infected patients with or without opportunistic infections of the central nervous system (CNS). CSF samples were also analyzed for quantification of total protein, cell count and HIV-1 RNA. HIV+ patients with cryptococcal meningitis had higher levels of CCL2, CCL3, CCL5, CXCL9 and CXCL10 when compared to patients without opportunistic neurological infections. Furthermore, HIV+ patients with associated cryptococcal meningitis had higher levels of CCL3, CXCL9 and CXCL10 when compared to HIV+ patients with associated toxoplasmic encephalitis. CCL3 and CXCL9 levels were positively correlated with CSF HIV-1 RNA levels, CSF protein concentration, and CSF cell count. CXCL10 level was correlated with the CSF viral load and the CSF cell count and CCL5 level was correlated with the CSF cell count. In conclusion, the profile of chemokines in CSF of HIV patients may differ according to the modality of the presented opportunistic infection and according to other biological markers, such as viral load in CSF. These differences are probably related to different patterns of neuroinflammatory responses displayed by patients with different opportunistic neurological infections.

HIV-1 RNA levels in cerebrospinal fluid and plasma and their correlation with opportunistic neurological diseases in a Brazilian AIDS reference hospital

BACKGROUND Plasma HIV RNA levels reflect systemic viral replication but in CNS it may occur relatively independent of systemic infection, yet clinical application of CSF HIV-1 RNA levels is less clear. OBJECTIVE To compare CSF and plasma HIV-1 RNA levels of patients with different opportunistic neurological diseases to those without neurological disease, as well as to correlate these levels with the outcome of the disease and use of HAART. METHOD 97 patients who had lumbar puncture for routine work up of suspected neurological diseases, were divided in 2 groups: without neurological disease (23) and with neurological disease (74). NASBA was used for plasma and CSF HIV RNA. RESULTS Median CSF viral load was higher in toxoplasmic encephalitis, cryptococcal meningitis, HIV dementia and neurological diseases without a defined etiology when compared to patients without neurological disease. There was no difference between plasma viral load in patients with and without neurological diseases. Median viral load was higher in plasma and CSF among patients who died when compared to those successfully treated. CSF and plasma viral load were lower in patients with opportunistic diseases on HAART than without HAART. CONCLUSION CSF viral load was higher in patients with any neurological disease, but this difference was not present in plasma viral load, suggesting that neurological disease influences more the CSF than plasma compartments. Notwithstanding different neurological diseases were not possible to be differentiated by the levels of CSF HIV-1.

Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease

Cognitive impairment and depressive symptoms are of great interest in Parkinsons disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD.

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients’ demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.

An unusual case of Fahr's disease.

Resident, Department of Neurosurgery, Santa Casa de Belo Horizonte, Belo Horizonte MG, Brazil; Assistant, Department of Neurosurgery, Santa Casa de Belo Horizonte and Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte MG, Brazil; Assistant, Department of Neurology, Santa Casa de Belo Horizonte, Belo Horizonte MG, Brazil; Assistent I, Department of Psycology, Universidade Federal de Minas Gerais, Belo Horizonte MG, Brazil.

IL-6 serum levels are elevated in Parkinson's disease patients with fatigue compared to patients without fatigue

To investigate the influence of interleukin-6 (IL-6) and soluble tumor necrosis factor receptors (sTNFR) in fatigued Parkinsons disease (PD) patients. Forty-four PD patients were evaluated, and fatigue was assessed with the Parkinson Fatigue Scale. Logistic regression analysis was used to evaluate the contribution of disease severity scores and cytokine levels on fatigue scores. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of IL-6 in fatigue. Fatigued PD patients had worse cognitive function and depressive symptoms. These patients had worse PD signs and symptoms, displayed more advanced stages of PD, and had greater functional dependence. There was a significant difference in IL-6 serum levels (p=0.026), but there was no difference in sTNFR levels. Total scores on the Unified Parkinson Disease Rating Scale (β=1.108; p=0.004) and IL-6 levels (β=12.843; p=0.020) were found to be significant predictors of fatigue scores. A ROC curve revealed that IL-6 concentrations of 1.18pg/ml represented the best cut-off value for detecting fatigue (sensitivity of 0.941 and specificity of 0.704). Fatigued PD patients have poor clinical outcomes and elevated IL-6 serum levels when compared with non-fatigued patients. These results suggest that IL-6 may play a role in the pathophysiology of fatigue in PD.

Syphilitic meningitis in HIV-patients with meningeal syndrome: report of two cases and review.

Few patients with symptomatic neurosyphilis present with signs and symptoms of acute meningitis. Here we report two cases of syphilitic meningitis diagnosed in HIV patients with meningeal syndrome. The first case, a 30-year-old black bisexual male, had concurrent meningeal and ocular syphilis with persistent unusually low CSF glucose levels. He responded well to 21 days of intravenous penicillin therapy. The second case was a 55-year-old female with epilepsy, depression, behavioral disorder and confusion. The diagnosis of HIV infection was made after onset of the syphilitic meningitis. She was treated with 21 days i.v. penicillin with improvement in her clinical condition. The clinical aspects of combined neurosyphilis and HIV infection, plus special features of diagnosis and treatment are discussed.