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Kaposi's sarcoma and central nervous system disease: a real association or an artifact of the control group? Terry Beirn Community Programs for Clinical Research on AIDS.

OBJECTIVES: To test the hypothesis that Kaposi's sarcoma (KS) protects against four central nervous system (CNS) diseases in HIV-1-infected individuals. STUDY POPULATION AND DESIGN: The study population of 9404 subjects included participants in Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) protocols who were enrolled between September 1990 and September 1998. This was an observational study. METHODS: Proportional hazards regression was used to estimate adjusted relative risks for predictors of four central nervous system diseases. Covariates included occurrence of Kaposi's sarcoma, occurrence of other opportunistic infections or malignancies, baseline CD4+ count, and other baseline characteristics. RESULTS: Among the 5944 participants without progression to AIDS at entry, 451 developed a CNS disease. The adjusted relative risk of any CNS disease for those who developed Kaposi's sarcoma versus those who did not develop any AIDS-defining event was 1.41 [95% confidence interval (CI), 0.98-2.03; P = 0.06]. In contrast, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.37 (95% CI, 0.24-0.57; P < 0.0001). Among the 3460 participants with progression to AIDS at entry, the adjusted relative risk of any CNS disease for those with Kaposi's sarcoma versus those with some other non-Kaposi's sarcoma AIDS-defining event was 0.71 (95% CI, 0.40-1.25; P = 0.23). CONCLUSIONS: Our analyses indicate that the risk of CNS disease associated with Kaposi's sarcoma depends strongly on the reference or control group chosen. When compared to individuals with other non-Kaposi's sarcoma AIDS-defining diseases, Kaposi's sarcoma is associated with a lower risk of CNS disease in HIV-1 positive individuals. However, when compared to individuals with no AIDS-defining disease or with a similarly mild AIDS-defining disease such as invasive candidiasis, Kaposi's sarcoma is associated with an equivalent risk of CNS disease.

AIDS Dementia Complex↗

Soluble CD30 levels in plasma and cerebrospinal fluid in multiple sclerosis, HIV infection and other nervous system diseases.

The CD30 molecule, a member of tumor necrosis factor superfamily, has been suggested to be preferentially expressed and released in soluble form by activated T cells that produce T helper 2 type (Th2) cytokines. To evaluate whether determination of soluble CD30 (sCD30) levels could have a diagnostic value in diseases associated with Th1 and Th2 cytokine involvement, we investigated sCD30 in plasma and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), HIV infection and other nervous system diseases. There was no statistically significant difference for plasma sCD30 levels in these clinical groups. However, patients with HIV infection had higher levels of sCD30 in CSF than MS patients. The mean sCD30 values were 3 to 6 folds higher in plasma than in CSF in all patient groups. No relationships were found between sCD30 levels and different clinical variables of MS and HIV infection, except that higher plasma sCD30 levels in HIV-infected patients were found in those with higher CD4+ T cell counts (> 200 x 10(6)) compared to the group with lower cell counts. The findings indicate that determinations of plasma and CSF sCD30 levels in MS and HIV infection have limited or no value as diagnostic or prognostic indicator.

Adult↗

Central nervous system disease associated with Langerhans' cell histiocytosis.

PURPOSE: To study the pathogenesis of central nervous system (CNS) lesions in Langerhans' cell histiocytosis (LCH), discuss their differential diagnosis and suggest guidelines for their management. PATIENTS AND METHODS: Central nervous system (CNS) disease with Langerhans' cell histiocytosis (LCH) is a poorly understood disorder. Most commonly, the hypothalamic-pituitary region is involved, leading to diabetes insipidus (DI) or other endocrinopathies. We report four patients in whom lesions in the pons, cerebellum, basal ganglia, cerebral white matter, or optic nerve and tract were demonstrated by magnetic resonance imaging (MRI). RESULTS: Three developed a progressive neurological disorder with cerebellar and pontine symptoms leading to severe disability--in one patient to blindness and death--in spite of various treatment approaches. In the fourth patient, who had MRI examinations to evaluate long-standing DI, CNS lesions were detected in the absence of neurological symptoms. There was no correlation between activity of LCH, severity and course of the CNS disease, or morphology of the lesions on MRI. Brain biopsy was performed in the three symptomatic patients and revealed cerebellar atrophy in one. Normal brain tissue was obtained from two patients. In none of the patients could autoantibodies to nervous system tissue be detected in serum or cerebrospinal fluid. CONCLUSION: Based on clinical, pathological, and MRI findings in our four patients and on information in the literature, we conclude that the CNS disease associated with LCH, although insufficiently understood, is likely to be a manifestation of histiocytosis in the brain, and we propose guidelines for the management of patients with this disorder.

Adult↗

Central nervous system disease in patients with systemic lupus erythematosus.

Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups.

Behavior↗

Analysis of cognitive and psychological deficits in systemic lupus erythematosus patients without overt central nervous system disease.

OBJECTIVE: To examine cognitive and psychological functioning in relation to antiribosomal P protein autoantibodies in patients with systemic lupus erythematosus (SLE) who had no previous history of central nervous system disease (non-CNS SLE). METHODS: Comprehensive neuropsychological and psychological tests were administered to 51 non-CNS SLE patients, 29 rheumatoid arthritis (RA) patients, and 27 healthy controls. RESULTS: Twenty-nine percent of the non-CNS SLE patients, 31% of the RA patients, and 11% of the control subjects were classified as cognitively impaired. Similar reductions in intelligence, attention, and fluency were detected in the non-CNS SLE and RA patients compared with controls. The non-CNS SLE patients showed a distinct deficit in learning compared with the RA and control groups. Forty-two percent of the non-CNS SLE patients demonstrated psychological distress, compared with 7% of the RA patients and 6% of the controls. In the patient groups, neither cognitive dysfunction nor psychological distress was associated with disease activity or prednisone dosage. Elevated serum levels of autoantibodies to ribosomal P protein were not associated with either psychological or cognitive abnormalities. CONCLUSION: These results suggest that certain cognitive deficits in non-CNS SLE patients may not be specific to the immunopathology of SLE. In contrast, it is possible that deficits in learning, as well as psychological distress without major psychiatric pathology, may be subtle manifestations of CNS lupus.

Adult↗

[Death from inflammatory central nervous system diseases during 1950-1984 at the Pavlov Medical Institute].

The inflammatory diseases of the central nervous system (cns) are characterized by dramatic clinical picture and the outcome depends on early diagnosis and early treatment as well. In the report the dynamics of the lethality after inflammatory diseases is studied retrospectively for 35 years (according to five-year-plans). Cases with inflammatory diseases of cns are within the ranges of 2.3% (1980-1984), 8.86 (1950-1954) or 3.58% on the average for the period out of 24,014 cases. The material is divided into two groups: 1. deceased with specific (tbc) meningitis and/or meningoencephalitis. 2. Deceased with nonspecific inflammatory diseases. Such grouping is justified by the difference, which is required in the therapy of these two groups of diseases. Deceased with specific inflammatory diseases--5.42% against 3.44% (with nonspecific) predominate during the first-year-plan (1950-1954). The deceased from the first group reduce sharply reaching 0.12% during the third and the following five-year-plans. The percentage of deceased from the second group show greater stability--2.82--2.14%. In this group there is a tendency to a reduction of purulent inflammatory diseases and an increase of serous (nonspecific) diseases. The relative number of secondary nonspecific inflammatory diseases, among which dominate otogenic, increase--47.1% due to a reduction in the number of deceased with primary nonspecific inflammatory diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of cerebrospinal fluid cells by flow cytometry and immunocytochemistry in inflammatory central nervous system diseases: comparison of low- and high-density cell surface antigen expression.

The examination of cerebrospinal fluid (CSF) continues to play an important role in the diagnosis of inflammatory diseases of the central nervous system (CNS). Immunocytochemistry and flow cytometry are the most commonly used methods for analysis of surface markers on CSF cells. We here compared these methods in the examination of CSF cells from a total of 68 patients with acute and chronic inflammatory CNS diseases. Expression of costimulatory molecules CD80 (B7-1) and CD86 (B7-2) as activation markers that are present at low density on the cell surface was analyzed in comparison to CD22 (B-cells) and CD4 (T-cell subset), that show high staining intensities. For CD22 and CD4, the results obtained with both methods were similar and reliable. Using flow cytometry, CD80 expression was detected in 6% of CSF cells in patients with chronic inflammatory CNS disease, as compared to 2% using immunocytochemistry, where the reliability of the data was found to be higher. We conclude that for examination of low-density surface markers on CSF cells, particularly with low cell counts, immunocytochemistry may be more reliable.

Antigens, CD↗

The utility of clinical and radiographic features in the diagnosis of cytomegalovirus central nervous system disease in AIDS patients.

BACKGROUND: Polymerase chain reaction (PCR) assays of cerebrospinal fluid (CSF) for cytomegalovirus (CMV) DNA have facilitated the diagnosis of CMV-associated central nervous system disease in AIDS patients. We attempt to correlate clinical and radiographic features that are associated with CMV PCR- positivity in CSF from AIDS patients with neurologic disease. METHODS AND RESULTS: A retrospective case controlled comparison was made of CMV PCR-positive and PCR-negative patients. RESULTS: CMV PCR-positive patients were significantly more likely to have nystagmus, prior CMV retinitis, and CSF protein levels.90 mg/dL. Of patients with 0, 1, and $2 of these features, 5.6%, 55.2%, and 88.9%, respectively, were PCR-positive. Ependymal enhancement was present by magnetic resonance imaging in 9 of 12 PCR-positive, and in 8 of 30 PCR-negative patients. CONCLUSION: These clinical and radiographic features may serve as useful adjuncts toward the establishment of the diagnosis of CMV-associated neurologic disease in AIDS patients.

AIDS-Related Opportunistic Infections↗

Human herpes virus type 7 DNA in the cerebrospinal fluid of children with central nervous system diseases.

UNLABELLED: Human herpes virus type 7 (HHV-7) has been associated with unspecific febrile syndrome, exanthem subitum (ES), viral rashes and Epstein-Barr virus (EBV) like syndrome. Neurological complications such as hemiplegia or seizures have been described in a few children with ES. Whether HHV-7 may also affect the CNS in the absence of ES is unknown. In this study, we investigated CSF samples from children with different neurological diseases for the presence of HHV-7 specific DNA. A HHV-7 specific nested polymerase chain reaction (PCR) was established amplifying a 478 bp DNA sequence of the glycoprotein U23 of HHV-7 strain SB. 68 children with CNS diseases with inflammatory CSF findings (n = 24), CNS diseases without inflammatory CSF findings (n = 18) and febrile seizures (n = 26) were examined. A total of 26 children with infectious diseases in the absence of neurological disease and 11 children without signs of a peripheral infection and without neurological disease served as controls. The CSF samples of six children from the study groups were HHV-7 PCR positive, but none from the controls. These children were diagnosed with aseptic meningitis (n = 1), viral encephalitis/meningoencephalitis (n = 2), facial palsy (n = 1), vestibular neuritis (n = 1) and febrile seizure (n = 1). CONCLUSION: These results indicate that human herpes virus type 7 infection is associated with central nervous system disease in children and should be considered in children whether inflammation in the cerebrospinal fluid is present or not.

Adolescent↗

[Exposure to electromagnetic fields and risk of central nervous system diseases among employees at Danish electric companies].

INTRODUCTION: Occupational exposure to electromagnetic fields has been associated with neurological diseases, such as amyotrophic lateral sclerosis, senile dementia, Parkinson's disease and Alzheimer's disease. MATERIAL AND METHOD: I studied the incidence of disease in the central nervous system in 30,631 persons employed at Danish electric companies between 1900 and 1993. I linked the cohort to the nationwide, population-based Danish National Register of Patients and compared the number of cases of these diseases found between 1978 and 1993 with the corresponding rates in the general population. In addition, I fit the data on utility workers to a multiplicative Poisson regression model in relation to estimated levels of exposure to 50 Hz electromagnetic fields. RESULTS: Overall, there was an increase in the risk of senile dementia and motor neuron diseases combined. The incidences of Parkinson's disease, Alzheimer's disease and other diseases of the central nervous system were essentially unrelated to exposure to electromagnetic fields. A decreased risk of epilepsy compared with the general population probably reflects a healthy worker effect; I observed an increased risk of epilepsy based on internal comparisons. DISCUSSION: The increased risk of senile dementia and motor neuron diseases may be associated with above average levels of exposure to electromagnetic fields.

Alzheimer Disease↗

Indications for differential diagnosis of nontumor central nervous system diseases from tumors. A positron emission tomography study.

To accurately differentiate nontumor central nervous system (CNS) diseases from brain tumors, we retrospectively evaluated the cerebral circulation and metabolism in patients with nontumor CNS diseases using positron emission tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen (rCMRO2), and of glucose (rCMRGI), and the uptake of 11C-methyl-L-methionine (11C-Met) were visually evaluated in lesions and compared with values for the contralateral white matter regions. PET findings were correlated with those of x-ray computed tomography (CT) and magnetic resonance imaging (MRI), and were analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were changeable from disease to disease or from stage to stage of disease progression. rOEF and rCMRO2 remained low in 5 and 6, respectively, of 9 nontumor CNS diseases examined, whereas these parameters were increased in CNS infections such as brain abscess. Overall, noteworthy was the locally increased rOEF and rCMRO2 in the patients with a brain abscess in contrast to the values for patients with gliomas. rCMRGI reflected biological characteristics of each disease, and correlated with cell density, whether reactive glial cells or inflammatory cells. 11C-Met was accumulated at a certain stage of nontumor CNS diseases, which implied uptake of the tracer as a result of disruption of the blood-brain barrier as well as metabolic incorporation.

Adolescent↗

Fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid of patients with central nervous system diseases.

Herpes simplex virus antibodies were studied in 73 patients with various diseases of the central nervous system. In 29 patients, there were rising titers of fluorescence and neutralizing antibodies to herpes simplex virus in the cerebrospinal fluid (CSF). The CSF antibodies were predominantly IgG. In one patient, IgM was found during the fourth, but not during the eighth week of illness. The CSF antibody titers did not correlate with the serum antibody titers or with the severity of the neurologic defect. No fluorescence antibodies were found in the CSF of 52 of 53 control patients. The presence of CSF fluorescence antibodies may be of considerable value in the diagnosis of herpes simplex encephalitis. However, the absence of these antibodies in the early stage of the disease does not exclude the possibility of infection with herpes simplex virus.

Adolescent↗

HIV-1 and its causal relationship to immunosuppression and nervous system disease in AIDS: a review.

Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency virus type 1 (HIV-1), has claimed more than 10 million lives over the past 15 years. There are approximately 30 million HIV-positive people worldwide, 89% of whom reside in sub-Saharan Africa and Asia. The intricate relationship between the virus and HIV-related human multisystem pathology prompted scientists to modify many previously established concepts about infectious diseases and immunology, and to test new ones. The results of this work helped resolve many, albeit not all, long-standing problems concerning HIV-1 immune escape, its cellular tropism, and pathogenesis of HIV-related immunosuppression and nervous system disease. The most impressive advances have been made in antiretroviral drug treatment of HIV infection, which has resulted in dramatically reducing AIDS-related mortality, morbidity, and perinatal transmission. However, considering the magnitude of the worldwide HIV-AIDS pandemic, prohibitive cost and unusually exacting nature of combination drug treatment, as well as the emergence of drug-resistant HIV mutants, the disease and virus remain formidable and unpredictable, particularly in the area of prevention and vaccine development. Here, we have reviewed the most pertinent recently published studies of various aspects of HIV/AIDS intended to answer the following questions: what have we learned and what remains to be determined regarding this unorthodox viral disorder?

AIDS Dementia Complex↗