Neural Mechanisms of Exercise: Anti-Depression, Neurogenesis, and Serotonin Signaling

Depression is associated with decreased serotonin metabolism and functioning in the central nervous system, evidenced by both animal models of depression and clinical patient studies. Depression is also accompanied by decreased hippocampal neurogenesis in diverse animal models. Neurogenesis is mainly defined in dentate gyrus of hippocampus as well as subventricular zone. Moreover, hypothalamus, amygdala, olfactory tubercle, and piriform cortex are reported with evidences of adult neurogenesis. Physical exercise is found to modulate adult neurogenesis significantly, and results in mood improvement. The cellular mechanism such as adult neurogenesis upregulation was considered as one major mood regulator following exercise. The recent advances in molecular mechanisms underlying exercise-regulated neurogenesis have widen our understanding in brain plasticity in physiological and pathological conditions, and therefore better management of different psychiatric disorders.

Antigenic and genetic characterization of the first rabies virus isolated from the bat Eumops perotis in Brazil

Although the main transmitters of rabies in Brazil are dogs and vampire bats, the role of other species such as insectivorous and frugivorous bats deserves special attention, as the rabies virus has been isolated from 36 bat species. This study describes the first isolation of the rabies virus from the insectivorous bat Eumops perotis. The infected animal was found in the city of Ribeirão Preto, São Paulo. The virus was identified by immunofluorescence antibody test (FAT) in central nervous system (CNS) samples, and the isolation was carried out in N2A cell culture and adult mice. The sample was submitted to antigenic typing using a panel of monoclonal antibodies (CDC/Atlanta/USA). The DNA sequence of the nucleoprotein gene located between nucleotides 102 and 1385 was aligned with homologous sequences from GenBank using the CLUSTAL/W method, and the alignment was used to build a neighbor-joining distance-based phylogenetic tree with the K-2-P model. CNS was negative by FAT, and only one mouse died after inoculation with a suspension from the bat's CNS. Antigenic typing gave a result that was not compatible with the patterns defined by the panel. Phylogenetic analysis showed that the virus isolated segregated into the same cluster related to other viruses isolated from insectivorous bats belonging to genus Nyctinomops ssp. (98.8% nucleotide identity with each other).

Aids-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil

Few data are available about progressive multifocal leukoencephalopathy (PML) in patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The objectives of this study were to describe the main features of patients with PML and estimate its frequency among AIDS patients with central nervous system (CNS) opportunistic diseases admitted to the Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive study was performed. Twelve (6%) cases of PML were identified among 219 patients with neurological diseases. The median age of patients with PML was 36 years and nine (75%) were men. Nine (75%) patients were not on antiretroviral therapy at admission. The most common clinical manifestations were: focal weakness (75%), speech disturbances (58%), visual disturbances (42%), cognitive dysfunction (42%), and impaired coordination (42%). The median CD4+ T-cell count was 45 cells/µL. Eight (67%) of 12 patients were laboratory-confirmed with PML and four (33%) were possible cases. Eleven (92%) presented classic PML and only one case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four (33%) patients, PML was the first AIDS-defining illness. During hospitalization, three patients (25%) died as a result of nosocomial pneumonia and nine (75%) were discharged to home. Cases of PML were only exceeded by cases of cerebral toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three more frequent neurologic opportunistic infections in Brazil. The results of this study suggest that PML is not an uncommon HIV-related neurologic disorder in a referral center in Brazil.

Astrocytic and microglial response and histopathological changes in the brain of horses with experimental chronic Trypanosoma evansi infection

This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.

Clinical and epidemiological analysis of patients with HIV/AIDS admitted to a reference hospital in the northeast region of Brazil

The AIDS epidemic has become a worldwide phenomenon of enormous magnitude and extension, deeply transforming medical practices and public health initiatives. This retrospective survey aimed to analyze clinical and epidemiological characteristics of patients with HIV/AIDS admitted to the Institute of Tropical Diseases Natan Portella, Teresina, Piauí, Brazil, from January, 2001 through December, 2004. Of the 828 patients, 43% were from other states and 71.3% were men. Average patient age was 35.4 ± 11.5 years-old and 85.5% were illiterate or had primary education. The main form of exposure to HIV was heterosexual behavior (54.1%), while injectable drug use was confirmed by only 2.7% of registered cases. The most frequent infectious complications were candidiasis (42.4%) and pneumocystosis (22.2%). Sixty-eight cases (8.2%) of visceral leishmaniasis were registered. Using multivariate analysis, individuals aged over 40 years-old, patients with active tuberculosis, Pneumocystis carinii pneumonia and central nervous system cryptococcosis showed increased risk of death. In this study, young male adults with low educational levels predominated and the most frequent opportunistic infections were candidiasis and pneumocystosis.

Primary aspergilloma and subacute invasive aspergillosis in two AIDS patients

Although uncommon, invasive aspergillosis in the setting of AIDS is important because of its peculiar clinical presentation and high lethality. This report examines two AIDS patients with a history of severe cellular immunosuppression and previous neutropenia, who developed subacute invasive aspergillosis. One female patient developed primary lung aspergilloma, with dissemination to the mediastinum, vertebrae, and spine, which was fatal despite antifungal treatment. The second patient, who had multiple cavitary brain lesions, and eye and lung involvement, recovered following voriconazole and itraconazole, and drugs for increasing neutrophil and CD4+ lymphocyte levels. These cases demonstrate the importance of Aspergillus infections following neutropenia in AIDS patients, and emphasize the need for early and effective antifungal therapy.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.

Analysis of correlation between cerebrospinal fluid and plasma HIV-1 RNA levels in patients with neurological opportunistic diseases

The question of whether HIV-1 RNA in cerebrospinal fluid (CSF) is derived from viral replication in the central nervous system or simply reflects the transit of infected lymphocytes from the blood compartment has long been a matter of debate. Some studies found no correlation between CSF and plasma viral load, whereas others did. The lack of a correlation between the two compartments suggests that the presence of HIV-1 RNA is not simply due to the passive passage of the virus from blood to CSF but rather due to intrathecal replication. To evaluate the correlation between plasma and CSF HIV-1 RNA levels and to identify situations in which there is no correlation between the two compartments, seventy patients were prospectively studied. The association between CSF and plasma viral load was evaluated in the total population and in subgroups of patients with similar characteristics. A correlation between the CSF and plasma compartments was observed for patients undergoing highly active antiretroviral therapy (HAART), those with a CD4 T lymphocyte count lower than 200 cells/mm³, and those with increased CSF protein content. On the other hand, no correlation was observed for patients without adequate virological control, who had a CD4 count higher than 200 cells/mm³ and who did not use HAART. The correlation between the two compartments observed in some patients suggests that CSF HIV-1 RNA levels may reflect plasma levels in these subjects. In contrast, the lack of a correlation between the two compartments in patients who were not on HAART and who had normal CSF proteins and a poor virological control possibly indicates compartmentalization of the virus in CSF and, consequently, plasma-independent intrathecal viral replication.

Spectrum of Neurologic Complications in Chronic Lymphocytic Leukemia

Neurologic disease is believed to be an unusual complication during the course of chronic lymphocytic leukemia. Nevertheless, it has already been proven in autopsy series that the incidence of occult nervous system infiltration is much higher than was previously expected. The advent of more potent drugs to treat this lymphoproliferative disorder has brought a new hope for a possible cure in the future. However, an appropriate systemic treatment for central nervous system infiltration of this disease is still lacking. Also, due to the potent immunosuppressive properties of the agents used in the up-front treatment, for example, the purine nucleoside analogues, we have witnessed an increase in the incidence of opportunistic infections, with progressive multifocal leukoencephalopathy being one of the most serious. The goal of this review is to summarize the spectrum of neurologic derangements linked to chronic lymphocytic leukemia and to raise clinicians’ awareness to recognize the possibility of such associations.

Atypical Phenotype in Two Patients with LAMA2 Mutations

Congenital muscular dystrophy type 1A is caused by mutations in the LAMA2 gene, which encodes the a2-chain of laminin. We report two patients with partial laminin-a2 deficiency and atypical phenotypes, one with almost exclusive central nervous system involvement (cognitive impairment and refractory epilepsy) and the second with marked cardiac dysfunction, rigid spine syndrome and limb-girdle weakness. Patients underwent clinical, histopathological, imaging and genetic studies. Both cases have two heterozygous LAMA2 variants sharing a potentially pathogenic missense mutation c.2461A>C (p.Thr821Pro) located in exon 18. Brain MRI was instrumental for the diagnosis, since muscular examination and motor achievements were normal in the first patient and there was a severe cardiac involvement in the second. The clinical phenotype of the patients is markedly different which could in part be explained by the different combination of mutations types (two missense versus a missense and a truncating mutation).

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA

The reactivation of Chagas disease in HIV infected patients presents high mortality and morbidity. We present the case of a female patient with confirmed Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+ lymphocyte cell count was 318 cells/mm3. After two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (HAART), the patient had good clinical, parasitological and radiological evolution. We used a qualitative polymerase chain reaction for the monitoring of T. cruzi parasitemia during and after the treatment. We emphasize the potential value of molecular techniques along with clinical and radiological parameters in the follow-up of patients with Chagas disease and HIV infection. Early introduction of HAART, prolonged induction and maintenance of antiparasitic therapy, and its discontinuation are feasible, in the current management of reactivation of Chagas disease.

EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

Medullary Schistosomiasis

BACKGROUND: Schistosomal infestation of the central nervous system is a rare cause of cord compression, although a predominant one in endemic areas. CASE DESCRIPTION: A 38-year-old male, native of Ivory Coast, with a history of 1 month of progressive paraparesis, neurogenic bladder, diminished deep tendon reflexes of the lower limbs, and sensory level. The magnetic resonance imaging (MRI) showed a medullary lesion at D4-D5 level, suggestive of an intramedullary tumor. Laminotomy of D3 to D5 and excision of a grayish white lesion according to a preliminary histopathologic review suggestive of a high grade glioma. Definitive histopathology review established the diagnosis of medullary schistosomiasis. CONCLUSION: Schistosomal myeloradiculopathy should be considered in patients presenting with cord compression or features of transverse myelitis, especially in patients from endemic areas or low social economic settlements.

Juvenile Systemic Lupus Erythematosus in Portugal: Clinical and Immunological Patterns of Disease Expression in a Cohort of 56 Patients

Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic, clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent. Objective: To define the pattern of disease expression and to gain better understanding in patients with juvenile onset systemic lupus erythematosus (SLE) in Portugal. Methods: The features of unselected patients with systemic lupus erythematosus who had disease onset before the age of 18 years were retrospectively analysed in three Portuguese centres with Pediatric Rheumatology Clinic over a 24-year period (1987-2011). Demographic,clinical and laboratory manifestations, therapy and outcome were assessed. Results: A cohort of 56 patients with a mean age at disease onset of 12.6±4.04 years (mean±1SD) (range, 1.0-17.0 years) and a mean period of follow-up of 5.5±5.4 years. Forty six (82.1%) patients were female. The most common disease manifestations were musculoskeletal (87.5%), mucocutaneous (80.3%) and haematological abnormalities (75%). Lupus nephritis was diagnosed in 46.4% of patients and consisted of glomerular ne - phritis in all cases. Neuropsychiatric manifestations occurred in 21.4% but severe central nervous system complications were uncommon, as brain infarcts and organic brain syndrome in 4 (7.1%) patients. Antinuclear antibodies and anti-double stranded DNA were positive in most patients in (98.2% and 71.4% respectively), as well as low C3 and/or C4 were observed frequently (85.7%). Generally, most patients had a good response to therapy as demonstrated by a significant decreasing of SLEDAI score from disease presentation to the last evaluation. The SLEDAI at diagnosis, the maximum SLEDAI and the incidence of complications were significantly higher in patients with neurolupus and/or lupus nephritis. Therapy included oral steroids (87.5%), hydroxychloroquine (85.7%), azathioprine (55.4%), IV cyclophosphamide (28.6%) along with other drugs. Six (10.7%) patients were treated with rituximab. Long-term remission was achieved in 32%, disease was active in 68%, adverse reactions to therapy occurred in 53.6% and complications/severe manifestations in 23.2%. Two patients died, being active disease and severe infection the causes of death. Conclusions: This study suggests that in our patients the clinical and laboratory features observed were similar to juvenile systemic lupus erythematosus patients from other series. Clinical outcome was favourable in the present study. Complications from therapy were frequent.