Spectrum of cognitive impairment in neurocysticercosis: differences according to disease phase.

OBJECTIVES: Cognitive decline related to neurocysticercosis (NC) remains poorly characterized and underdiagnosed. In a cross-sectional study with a prospective phase, we evaluated cognitive decline in patients with strictly calcified form (C-NC), the epidemiologically largest subgroup of NC, and investigated whether there is a spectrum of cognitive abnormalities in the disease. METHODS: Forty treatment-naive patients with C-NC aged 37.6 ± 11.3 years and fulfilling criteria for definitive C-NC were submitted to a comprehensive cognitive and functional evaluation and were compared with 40 patients with active NC (A-NC) and 40 healthy controls (HC) matched for age and education. Patients with dementia were reassessed after 24 months. RESULTS: Patients with C-NC presented 9.4 ± 3.1 altered test scores out of the 30 from the cognitive battery when compared to HC. No patient with C-NC had dementia and 10 patients (25%) presented cognitive impairment-no dementia (CIND). The A-NC group had 5 patients (12.5%) with dementia and 11 patients (27.5%) with CIND. On follow-up, 3 out of 5 patients with A-NC with dementia previously still presented cystic lesions with scolex on MRI and still had dementia. One patient died and the remaining patient no longer fulfilled criteria for either dementia or CIND, presenting exclusively calcified lesions on neuroimaging. CONCLUSIONS: Independently of its phase, NC leads to a spectrum of cognitive abnormalities, ranging from impairment in a single domain, to CIND and, occasionally, to dementia. These findings are more conspicuous during active vesicular phase and less prominent in calcified stages.

Cognitive impairment and dementia in neurocysticercosis: a cross-sectional controlled study.

OBJECTIVES: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). METHODS: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. RESULTS: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. CONCLUSIONS: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.

14-3-3 protein in the CSF of patients with rapidly progressive dementia.

BACKGROUND: The presence of 14-3-3 protein in the CSF has been described to have high sensitivity and specificity for Creutzfeldt-Jakob disease (CJD). OBJECTIVE: To relate 14-3-3 protein in the CSF with the clinical diagnoses of diseases causing rapidly progressive dementia. METHODS: The authors studied 46 patients with rapidly progressive dementia that was classified into three diagnostic groups: definitive or probable CJD, possible CJD, and other diagnoses. The definitive or probable CJD group comprised 17 patients (3 definitive sporadic, 1 probable iatrogenic, 3 familial, and 10 probable sporadic CJD cases), the possible CJD group was composed of 7 patients, and the group with other diagnoses had 22 patients. Detection of the 14-3-3 protein was done by the immunoblotting method. RESULTS: In the definitive or probable CJD group, the test for 14-3-3 protein in CSF was positive in 14 (82%) cases, whereas 3 patients (1 probable sporadic and 2 familial cases) had negative results. CSF was positive for 14-3-3 protein in three of seven cases with possible CJD (42%). In the group with other diagnoses, three individuals had false-positive results (13%). Their diagnoses were definitive Alzheimer's disease, hypercalcemia, and multiple intracerebral hemorrhages. CONCLUSIONS: The detection of 14-3-3 protein in CSF is a useful in vivo diagnostic test for CJD and, when used in the appropriate clinical context, shows a good correlation to CJD. The presence of the 14-3-3 protein in the CSF reinforces the CJD clinical diagnosis but may not be able to differentiate CJD from other causes of rapidly progressive dementia in everyday clinical practice.

Dosage of lactate in the cerebrospinal fluid in infectious diseases of the central nervous system.

This paper analyzes the diagnosis aid of the dosage of lactate in the cerebrospinal fluid (CSF) in infectious diseases of the central nervous system (CNS). We analyzed prospectively 130 samples of CSF of 116 patients with diagnoses of infectious processes in the CNS. The 130 samples of CSF were divided into five groups: 28 samples of the control group, 40 of bacterial meningitis, 22 of viral meningitis, 16 of fungal meningitis and 24 of patients presenting acquired immune deficiency syndrome (AIDS). The concentration of lactate in the CSF was elevated in the group of patients with bacterial meningitis (average = 46.2 mg/dL), fungal meningitis (average = 27.3 mg/dL) and in the AIDS group (average = 23.5 mg/dL). In the control group and viral meningitis group the lactate content in the CSF presented the reference rates according to the employed method. The lactate dosage in the CSF presented a negative correlation with glycorrhachia and positive correlation with the cellularity and total proteins of the CSF. We conclude that the lactate dosage in the CSF, although unspecific, helps to distinguish the infectious processes of the CNS.

Antigen-specific suppression of cultured lymphocytes from patients with neurocysticercosis.

The biological parasite-host interactions involved in neurocysticercosis (NC) are of a complex nature. A lymphoproliferation assay was performed using mononuclear cells from 11 patients with NC, who were classified according to the alterations obtained by imaging examinations. Antigen extracts from the membrane and/or scolex of Taenia solium and from the vesicular fluid of Taenia crassiceps were used. Mononuclear cells from patients with NC showed antigen-specific suppression when compared with a control group. The patients presenting calcified cysts showed higher suppression when compared with patients in the active phase of disease. The antigen in the vesicular fluid of T. crassiceps seems to play a suppressor role in vitro, completely inhibiting cell proliferation induced by the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen.

Cysticercus antigens in cerebrospinal fluid samples from patients with neurocysticercosis.

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n = 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra, and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular-weight peptides were only detected in CSF samples from patients with NC by immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the diagnosis and prognosis of cysticercosis, the detection of antigens may contribute as an additional marker to the study and clarification of the parasite-host relationship.

Diffusion-weighted MRI in two cases of familial Creutzfeldt--Jakob disease.

Diffusion-weighted magnetic resonance imaging (DWI) has been described as a useful tool for the diagnosis of sporadic Creutzfeldt--Jakob disease (CJD). To our knowledge, DWI abnormalities have not previously been reported in familial CJD. In two patients with familial CJD associated with distinct mutations at codon 183 and at codon 210 of the prion protein gene, DWI showed a high signal in the basal ganglia and in the cerebral cortex. These abnormalities are similar to those described in sporadic CJD. This observation expands the value of DWI for the diagnosis of some forms of familial CJD. It remains to be investigated whether this finding also holds for CJD associated with other mutations of the prion protein gene.

Total IgE detection in paired cerebrospinal fluid and serum samples from patients with neurocysticercosis.

Neurocysticercosis (NC), the presence of Taenia solium metacestodes in tissues, is the most frequent and severe parasitic infection of the central nervous system. We investigated the presence of total IgE by an automated chemiluminescence assay in 53 paired cerebrospinal fluid (CSF) and serum samples from patients with NC (P) and in 40 CSF samples from individuals with other neurological disorders as the control group (C). Total IgE concentration ranged from 1.2 to 6.6 IU/ml (mean = 1.4 IU/ml, standard deviation-sd = 1.1 IU/ml) in 28.3% of CSF samples from the P group, a value significantly higher than for the C group ( pound1.0 IU/ml). The serum samples from the P group showed concentrations ranging from 1. 0 to 2330.0 IU/ml (mean = 224.1 IU/ml, sd = 452.1 IU/ml), which were higher than the normal value cited by the manufacturer (<100.0 IU/ml) in 32.1% of the samples. A significant difference was observed in CSF samples from the P and C groups (p = 0.005) and in serum samples from the P group compared to the normal value (p = 0. 005), with sera showing more frequent abnormal results.

Neurocysticercosis: detection of IgG, IgA and IgE antibodies in cerebrospinal fluid, serum and saliva samples by ELISA with Taenia solium and Taenia crassiceps antigens.

We assayed samples of cerebrospinal fluid (CSF), serum and saliva from patients with neurocysticercoses, control group and individuals with other parasitoses, by ELISA with Taenia crassiceps vesicular fluid antigen (Tcra) and Taenia solium total antigen (Tso) for the detection of antibodies. The sensitivity for IgG-Tcra was 100% for CSF and serum, and 32.0% for saliva; and for IgG-Tso 100% for CSF, 80.0% for serum and 24.% for saliva. Specificity was 100% for CSF and 80.0% for serum with both antigens, and 100% for saliva with Tcra and 87.5% with Tso. The sensitivity and specificity for IgA-Tcra was, respectively, 40.0% and 100% for CSF, 36.0% and 97.1% for serum, and 4.0% and 90.0% for saliva. IgE detection showed 24.0% sensitivity and 97.1% specificity for serum, with no detection in CSF samples. The search for antibodies revealed the presence of IgG > IgA > IgE in CSF, serum and saliva samples, with IgG being present in all phases of the disease, while IgA/IgE were more frequent in the inactive form.

Specific Taenia crassiceps and Taenia solium antigenic peptides for neurocysticercosis immunodiagnosis using serum samples.

Neurocysticercosis (NC), i.e., the presence of the larval form of Taenia solium in tissues, is the most frequent and severe infection involving the central nervous system. Paired serum and cerebrospinal fluid (CSF) samples from patients with NC, CSF and serum samples from a control group, and serum samples from patients with other parasitoses were studied by enzyme-linked immunosorbent assay (ELISA) and by immunoblotting with Taenia crassiceps vesicular fluid antigen (Tcra) and Taenia solium total saline antigen (Tso) for the detection of immunoglobulin G antibodies. ELISAs carried out with the Tso and Tcra antigens showed 94.1 and 95.6% sensitivities, respectively, for the detection of antibodies in CSF and 70.6% and 91.2% sensitivities, respectively, for the detection of antibodies in serum, with 100% specificity for the detection of antibodies in CSF and 80% specificity for the detection of antibodies in serum for both antigens. On the basis of the reactivities of the peptides in the samples analyzed, the peptides of

Analysis of cells in cerebrospinal fluid from patients with neurocysticercosis by means of flow cytometry.

The events of the cellular immune response in neurocysticercosis (NC) are not fully understood. Studies of the CD3, CD3/CD4, CD3/CD8, CD45/CD19, and CD45/CD56 molecules and activation-related CD69 molecule in cells from the cerebrospinal fluid (CSF) and peripheral blood (PB) of patients with NC may provide a better elucidation of the inflammatory and immunological events occurring in this disease. Seven patients with NC and 3 individuals with other disorders were evaluated by a three-color flow cytometric method. CD69 was detected in a higher percentage of cells in all CSF samples from patients, but not in PB or CSF from the control group. The percentage of CD3+ cells did not differ significantly in CSF and PB cells from patients and controls. The predominance of CD3+CD8+ cells was observed in CSF from one patient and in PB from 2 patients, who were in stage III of the disease (inflammatory process). The percentage of CD45+CD19+ cells was higher in CSF than in PB from patients who presented anti-cysticercus antibodies in CSF. The percentage of CD45+CD56+ cells in CSF was higher than in PB, but this rate was similar to reference values reported by other authors. Our data suggest that the cytometric method applied to a larger number of CSF samples may provide a better understanding of the cell-mediated immune response involved in NC.

[Neurologic evaluation of non-Hodgkin's lymphoma in adult patients: a prospective study]. / Avaliação neurológica de pacientes adultos com linfoma não-Hodgkin. Estudo prospectivo.

This prospective study included 67 adult patients with low, intermediate or high malignancy degrees of non-Hodgkin's lymphomas according to the Working Formulation. Patients with or without anti-HIV antibodies in the serum were considered. All patients were submitted to neurologic evaluation, and 63 of them to examination of the cerebrospinal fluid (CSF). Patients presenting neurologic signs and symptoms were 42 (62.7%). Neurologic findings and CSF changes were correlated. The association of localized thoraco-lumbar pain and CSF changes (presence of neoplastic cells, increased protein concentration and/or increased gamma globulin content) was statistically significant, as the association of abnormal muscle strength in the lower limbs and CSF changes in patients without HIV antibodies in the serum. Cranial nerve dysfunction (III, IV and VI cranial nerves) correlated with the finding of neoplastic cells in the cerebrospinal fluid.

[Non-Hodgkin lymphoma in adults. Protein profile of CSF and serum in 25 patients]. / Linfoma não-Hodgkin em adultos. Perfil proteico do lcr e do soro de 25 doentes.

Twenty-five non-Hodgkin's adult patients of a cohort studied for detection of neurologic involvement were evaluated on the cerebrospinal fluid (CSF) protein profile. CSF and serum were collected in the same occasion. Blood-brain barrier and local synthesis of IgG were studied. There was an incidence of neurologic signs and symptoms in 48% of all patients. Samples analysis showed: increase of total protein in CSF in 52%; local synthesis of IgG in one HIV seropositive patient; IgG concentration increase in the CSF in the absence of malignant cells in the CSF in two patients that clinically improved after chemotherapy; oligoclonal bands only in the CSF in one HTLV-I seropositive patient. These data show that the study of CSF protein profile can contribute in the characterization of CNS involvement in non-Hodgkin lymphoma.

Immunoblot with cerebrospinal fluid from patients with neurocysticercosis using antigen from cysticerci of Taenia solium and Taenia crassiceps.

A comparative study was conducted on membrane (M) and vesicular fluid (VF) from cysticerci of Taenia solium (Tso) obtained from naturally infected swine and the Taenia crassiceps ORF strain (Tc) maintained by experimental infection of female BALB/c mice. The study was carried out using immunoblotting to detect antibodies in cerebrospinal fluid (CSF) from patients with neurocysticercosis. No reactivity was observed in the 32 samples from a control group. Of the 23 CSF fluid samples from patients with neurocysticercosis, 22 (95.6%) were reactive in the M-Tso blot and 21 (91.3%) were reactive in the other three blots (VF-Tso, M-Tc, and VF-Tc). Immunodominant peptides in each antigen were 98-92 kD, 56-52 kD, and 72-68 kD in M-Tso; 72-68 kD, 120 kD, 155 kD, 98-94 kD, 76 kD, and 115-108 kD in VF-Tso: 72 kD, 62 kD, and 42 kD in M-Tc; and 72-68 kD and 95-92 kD in VF-Tc. The cross-reactivity observed in the immunoblots performed on CSF samples from patients with neurocysticercosis indicates that the parasites share important epitopes present at sufficient concentrations for use in immunologic tests.

Hemagglutination test for the diagnosis of human neurocysticercosis: development of a stable reagent using homologous and heterologous antigens.

A hemagglutination (HA) test was standardized using formalin- and tannin-treated gander red blood cells sensitized with a total salt extract of C. cellulosae (HA-Cc) and an antigenic extract of Cysticercus longicollis (HA-Cl) vesicular fluid. A total of 61 cerebrospinal fluid (CSF) samples were assayed, 41 from patients with neurocysticercosis and 20 from a control group which were, respectively, reactive and non-reactive to ELISA using C. cellulosae. The CSF samples from the control group did not react and 35 (85.4%) and 34 (82.9%) CSF samples from patients were reactive to the HA-Cc and HA-Cl tests, respectively. The reagents ready for use were stable up to 6 months when stored at 4 degrees C in 50% glycerol. The present results confirm that the reagent using Cysticercus longicollis stabilized with glycerol can be used as an alternative in the immunological diagnosis of neurocysticercosis.

[Intrathecal immunoglobulin synthesis evaluation in bone marrow transplantation]. / Avaliação da síntese intratecal de immunoglobulinas no transplante de medula óssea.

The central nervous system involvement in chronic graft versus host disease (GVHD) has been suggested. Chronic GVHD resembles auto immune connective tissue disorders. In order to investigate the immunoglobulin intra blood brain barrier (BBB) synthesis during chronic GVHD, and contribute to understanding the pathophysiology of the disease, we studied 33 patients who underwent allogeneic bone marrow transplants (BMT) from HLA identical related donors. Immunoglobulin intra BBB synthesis was investigated quantitative and qualitatively. The samples were collected pre BMT, pos BMT and during chronic GVHD. There were no evidence of immunoglobulin intra BBB synthesis, and no oligoclonal bands were found. Only isolated cases suggested IgO and IgA intra BBB synthesis, and in one case IgM during GVHD.

[Blood-brain barrier evaluation in bone marrow transplantation]. / Avaliação da barreira hemato-encepfálica no transplante de medula óssea.

The blood-brain barrier (BBB) contributes to the central nervous system (CNS) immunological isolation. BBB has never been studied in patients who developed chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplants (BMT), from HLA identical related donors. BBB disruption was investigated through the cerebrospinal fluid (CSF) proteins, quantitative and graphically, in order to detect the incidence and possible pathophysiology of the CNS involvement in chronic GVHD. Thirty three CSF and matched serum samples from chronic myeloid leukemia patients were collected pre BMT pos BMT and during chronic GVHD. There was no evidence of BBB disruption in any patient studied.

[Adenosine deaminase in the cerebrospinal fluid of patients with acquired immunodeficiency syndrome]. / Adenosino-deaminase no líquido celalorraqueano de pacientes com a síndrome da imunodeficiência adquirida.

The adenosine-deaminase (ADA) activity was evaluated in CSF samples from 263 patients with AIDS. An elevated ADA activity in CSF was found in patients with: antibodies to toxoplasmosis, syphilis or cytomegalovirus; Cryptococcus neoformans or their antigens; tuberculous meningitis; lymphoma. There was no statistical difference among all these groups in respect to ADA activity. However, the ADA activity in CSF from AIDS patients without CSF changes other than HIV antibodies, even unspecific changes, was not elevated. This may suggest that ADA is related to AIDS associated pathologies activity rather than to HIV infection itself.

Polymerase chain reaction in the diagnosis of tuberculous meningitis. Preliminary report.

In this preliminary report the results of PCR for detection of DNA sequences (65 KDa antigen) of Mycobacterium tuberculosis in CSF samples from 20 patients are registered. In 10 patients there were clinical and laboratory findings suggesting the diagnosis of tuberculous meningitis (test group). In the other 10 patients, clinical and laboratory findings suggested meningitis or meningo-encephalitis from other etiologies (control group). In 7 patients from the test group antigenic DNA sequences of Mycobacterium tuberculosis were found in CSF by PCR; positive results were not registered in the control group.

Polymerase chain reaction in the diagnosis of tuberculous meningitis: preliminary report

Nesse relato preliminar säo registrados os resultados da pesquisa de PCR para detecçäo de sequências de DNA (antígeno 65 KDa) do Mycobacteruium tuberculosis no LCR. Foram estudadas amostras de LCR de 20 pacientes: em 10 havia suspeita clínica e laboratorial de neurotuberculose (grupo de teste); nos outros 10 havia suspeita diagnóstica de meningite ou menigoencefalite de outras etiologias ( grupo controle). Em 7 dos 10 pacientes do primeiro grupo a pesquisa de sequências antigênicas de DNA do Mycobacterium tuberculosis por PCR foi positiva; em nenhum dos pacientes do grupo controle a pesquisa foi positiva