Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings.

OBJECTIVE: To study prospectively the clinical features and laboratorial characteristics of 24 patients with central nervous system (CNS) involvement with paracoccidioidomycosis (PCM). PCM is an infectious disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in subtropical areas of Central and South America. METHODS: From 173 cases of PCM, 24 (13.9%) had CNS involvement (NPCM) and were studied prospectively from 1993 to 1997. In all the patients, the diagnosis of systemic PCM was made by the demonstration of the P. brasiliensis organisms or positive serology, DID (double immunodiffusion). In seven cases the diagnosis was made by means of a CNS biopsy. CNS clinical manifestations, neuroimaging (CT or MRI) and CSF cytochemical characteristics were reported. RESULTS: The mean age was 44 years (range 25-72 years); 23 patients were male, only one was female. Neurological symptoms began before systemic symptoms in 21%; simultaneously in 33%, and after systemic symptoms in 46%. Epilepsy was the more frequent neurological presentation (44%). Twenty-three cases had parenchymatous involvement and in two of these cases there was an association with meningitis and one case had spinal cord involvement. Lesions were more frequent in the brain hemispheres (69%), in 65% there were multiple granuloma characterized by hypodense images with annular or nodular enhancing. All cases were treated with sulphamethoxazole-trimethoprin. Four patients died, while 20 patients showed a good therapeutic response. CONCLUSION: NPCM should always be considered in the differential diagnosis of expanding lesions of the CNS and meningoencephalitis. Being alert to this diagnosis depends on knowledge of epidemiology. There was good response to sulphamethoxazole-trimethoprin treatment.

IgG intrathecal synthesis and specific antibody index in patients with neurocysticercosis.

UNLABELLED: We analyzed cerebrospinal fluid (CSF) and blood serum from 55 patients with neurocysticercosis (NC) at different clinical stages. According to inflammatory activity in the CSF, three stages were identified: (1) reactive, when there was at least an increase in the number of cells; (2) weakly reactive, when significant alterations were found in the CSF, including an increase in gamma globulins, albeit without hypercytosis; (3) non-reactive, when there was neither hypercytosis nor increase in gamma globulins. Nineteen patients had the reactive form; 18 had the weakly reactive form; 18 displayed the non-reactive form. Local immunoproduction was intense in the reactive group, moderate in the weakly reactive group, and absent in the non-reactive group. The specific antibody index was raised in approximately 2/3 of patients with the reactive form, 2/3 in those with the weakly reactive form, and 1/3 in those with the non-reactive form. IN CONCLUSION: (1) the classical CSF syndrome in NC can present both in complete and partial modes; (2) local immunoproduction can occur in weakly reactive forms; (3) a raised specific antibody index can occur in the absence of an inflammatory reaction in the CSF.

Application of an improved biuret method to the determination of total protein in urine and cerebrospinal fluid without concentration step by use of Hitachi 7170 auto-analyzer.

A biuret automated colorimetric assay for total protein in urine and cerebrospinal fluids was established. The procedures were as follows. Acidify all urine sample before analysis. Add precipitant Na(2)WO(4) to urine samples. After 10 min, centrifuge, decant the supernatant fluid, drain the inverted tubes on absorbent tissue, dissolve the precipitation with 0.1 mol/L NaOH, and finally adapt the reconstituted urine to the Hitachi 7170 analyzer. A cell-free cerebrospinal fluid sample produced by centrifugation can be inserted in an auto-analyzer for protein measurement directly. The program: mix 35 microl sample (CSF or reconstituted urine) and standard with 0.2 mol/L NaOH; incurable at 37 degrees C for 5 min, and real A1. Add concentrated biuret reagent, and 10 min later measure absorbance A2 at 546 nm vs. reagent blank. Secondary wavelength was 700 nm. The test results were calculated against a one-point standard. This biuret colorimetric method was relatively simple, fast, and accurate for the determination of protein in urine and cerebrospinal fluid, with a wide linearity extending from 0.125 g/L up to 6 g/L, had a good correlation with Benzethonium chloride turbidimetry technique, and was a practical routine method.

[Progressive paralysis. A case report]. / Paralisi progressiva. Descrizione di un caso.

STUDY OBJECTIVE: A fairly uncommon case of neurosyphilis is reported in a not immunocompromised patient. CASE REPORT: A case of general paresis in a 40 year-old male with the recent onset of mania is described. Psychiatric anamnesis was negative. Neurologic examination was negative. Laboratory tests were performed and serologic tests for syphilis were positive. Cerebrospinal fluid (CSF) examination showed 80 leukocytes/mm3, a reactive Venereal Disease Research Laboratory (VDRL) and normal protein concentration. CSF gamma globulin with an oligoclonal pattern and abnormal IgG index were found. A test for antibodies to Human Immunodeficiency Virus (HIV) was negative. The patient underwent a high dose intravenous penicillin G regimen for two weeks. A follow-up six months later showed a normal CSF even though the IgG index was still abnormal and the mental status was unchanged. CONCLUDING REMARKS: The authors suggest that patients with neurologic and/or psychiatric symptoms with a recent onset and a reactive VDRL should undergo a CSF examination to exclude a possible neurosyphilis.

HTLV-I associated tropical spastic paraparesis: cerebral spinal fluid evolutive aspects in 128 cases

Com o objetivo de verificar se existe mudanças na intensidade da resposta inflamatória do líquido cefalorraqueano (LCR) no curso da paraparesia espastica tropical (PET) associada ao HTLV-1 foram estudados retrospectivamente os exames de LCR de 128 pacientes com PET. Os resultados indicam que embora alteraçöes inflamatórias possam persistir por período superior a 10 anos, existe tendência a diminuiçäo de sua intensidade ou mesmo de normalizaçäo após o segundo ano de evoluçäo da doença

HTLV-I associated tropical spastic paraparesis. Cerebral spinal fluid evolutive aspects in 128 cases.

In order to evaluate if there is variation on the intensity of cerebral spinal fluid (CSF) response during HTLV-I associated tropical spastic paraparesis (TSP) evolution we retrospectively reviewed 128 cases. The results indicate that although CSF inflammatory alterations can persist over a 10-year period, they tend to become slight or even absent after the second year of TSP evolution.

[Neurocysticercosis: benign natural course]. / Wagrzyca mózgu: lagodny przebieg naturalny.

In a waiter aged 51 without clinical symptoms, but with a history of sporadic epileptic seizures in young age, radiological examination demonstrated multiple calcifications in the brain corresponding to calcified cysticerci. Similar lesions were found in the muscles of the thighs and left lower leg. After another 18 years without cerebral symptoms these calcifications were demonstrated in CT. The case indicates that the natural course of cerebral cysticercosis may be asymptomatic or oligosymptomatic, and that it is useful to distinguish between active and inactive cysticercosis.

Treatment of HTLV-I-associated myelopathy with high-dose intravenous gammaglobulin.

Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality.

Laboratory investigation of cerebrospinal fluid proteins.

Analysis of CSF proteins is useful in the diagnosis and management of neurological diseases in the following situations: 1. In inflammatory conditions when there is breakdown of blood-CSF barrier integrity. Meningitis is a medical emergency, with CSF total protein measurement being only a screening test. 2. In the detection of immune responses within the CNS. This is by far the most important application in a routine clinical setting, as it is now a firmly established criterion in the diagnosis of multiple sclerosis. Oligoclonal bands restricted to the CSF are the only reliable indicators of intrathecal immunoglobulin G synthesis and are practically always associated with inflammatory disease of the CNS. The method fo choice for detecting oligoclonal bands is isoelectric focusing with immunofixation. Quantitative measurement of IgG in the CSF is of no value in diagnostic pathology. 3. In destructive brain diseases when brain-specific proteins are released into the CSF, measurement of these proteins can give prognostic information.

[The significance of isoelectric focusing of unconcentrated cerebrospinal fluid in the detection of oligoclonal zones in multiple sclerosis]. / Význam izoelektrické fokusace nekoncentrovaného mozkomísního moku v detekci oligoklonálních pruhu u sclerosis multiplex.

In a group of 31 patients with a confirmed diagnosis of multiple sclerosis the authors assessed the presence of oligoclonal abnormality of gammaglobulins in cerebrospinal fluid. Specimens of non-concentrated cerebrospinal fluid were examined by two separating methods which use as a vehicle polycryamide gel: isoelectric focusing and a modified electrophoretic technique. By isoelectric focusing an oligoclonal state was proved in 71%, the finding was doubtful in 16.1% and negative in 12.9%. The applied electrophoretic separation revealed an oligoclonal state in 58.1%, the finding was doubtful in 25.8%, negative in 16.1%. In cerebrospinal fluid where isoelectric focusing did not prove an oligoclonal finding, the latter was not detected by electrophoresis either. The method of isoelectric focusing is obviously more sensitive than mere electrophoretic separation. In common practice, it is, however, better to use electrophoresis in vehicles which positively influence the separation process, best in a polyacrylamide gel. Only when the finding is negative or doubtful and there is urgentclinical suspicion, it is suitable to supplement the examination by isoelectric focusing.

Oligoclonal bands in cerebrospinal fluid detected by PhastSystem isoelectric focusing.

Pharmacia's "PhastSystem" for semi-automated isoelectric focusing (IEF) in thin precast polyacrylamide gels (PAGE) was found to be as sensitive as high-resolution protein electrophoresis (HRPE) in agarose gels and conventional PAGE-IEF for detection of oligoclonal banding (OB) in concentrated cerebrospinal fluid (CSF) samples. Both PhastSystem IEF and HRPE revealed OB in CSF from eight of nine multiple sclerosis patients and four of 10 patients with various types of infection of the central nervous system as opposed to only two of 70 patients with miscellaneous neuropsychiatric disorders. The PhastSystem also frequently detected OB in silver-stained, unconcentrated CSF from patients with multiple sclerosis.

Electrophoretic determination of albumin and gamma globulin concentrations in the cerebrospinal fluid of dogs with encephalomyelitis attributable to canine distemper virus infection: 13 cases (1980-1987).

Thirteen dogs with encephalomyelitis attributable to canine distemper virus infection were classified into 3 groups on the basis of histopathologic evidence of virus-induced lesions in CNS tissue. Analysis of data indicated a similarity within groups when arranged by age, clinical neurologic signs, and alterations in the CSF electrophoretic protein values. Comparison with results in dogs with experimentally induced canine distemper encephalomyelitis suggested that when grouped by age, CSF electrophoretic values are helpful in predicting the CNS histopathologic changes in dogs with naturally acquired canine distemper encephalomyelitis.

A micro-method for measuring total protein in cerebrospinal fluid by using benzethonium chloride in microtiter plate wells.

By using a benzethonium chloride concentration 12-fold that described originally (Clin Chem 1979;25:1317-9), we developed a reliable method suitable for routine measurement of total protein in cerebrospinal fluid. Only 10 microL of sample is required. Reactivity to immunoglobulin G (IgG) and to albumin (Alb) is similar, as is necessary for specimens that can have very varied IgG/Alb ratios. The assay, performed in a microtiter plate for ease of use, has a between-batch coefficient of variation of 3.4% for a protein concentration of 450 mg/L. This contrasts with a dye-binding technique with Ponceau S, for which the CV was 9% at the same concentration.

[Monoclonal gammopathy in HIV infection]. / Monoklonale Gammopathie bei HIV-Infektion.

A lambda-light chain-IgA plasmocytoma, accompanied by a changing clinical picture of fever, nocturnal perspirations and weight loss, developed in a 46-year-old homosexual male with AIDS, stage IV (classification according to the Centers for Disease Control). He had been suffering from recurrent Salmonella septicaemia. Serum protein electrophoresis demonstrated marked elevation of the beta- and gamma-fractions (44% and 24%, respectively). There were 15% plasma cells in the differential blood count and in the bone marrow smear. Immunoelectrophoresis demonstrated free lambda-light chains. The IgA concentration in cerebrospinal fluid was raised to 202 mg/l, and there was an IgA paraproteinaemia. The patient died during a recurrence of the Salmonella septicaemia from septic cardiovascular failure.

Cerebrospinal fluid immunoglobulins and multiple sclerosis. Correspondence with magnetic resonance imaging and visually evoked potential changes.

The clinical (disability) and paraclinical (visually evoked potential [VEP]/magnetic resonance imaging [MRI]) data of patients with definite or probable multiple sclerosis (MS) were compared with their cerebrospinal fluid (CSF) immunoglobulins taken within the same period of time. For patients with definite diagnosis by the Schumacher criteria (n = 61) we found significant correlations between CSF immunoglobulin content (absolute gamma-globulin value [aggv]) and quantified MRI factors (r = .47), between aggv and the sum of VEP latencies of both eyes (r = .53), and also between MRI and VEP changes (r = .62). This was not true for the patients with a probable MS diagnosis and for patients with first attacks. No correlations were evident between aggv and disability status or duration of the illness. The results give support to recent neuropathologic and experimental findings in animals indicating close pathogenic connections between CSF immunoglobulins and demyelination in MS.

Cytoproteic CSF findings in 33 MS patients: usefulness for diagnosis.

Although multiple sclerosis (MS) is mainly defined on clinical grounds, CSF parameters still remain important diagnostic and scoring tools. To demonstrate the usefulness of some easy laboratory techniques, a CSF cytomorphological and agarose gel electrophoresis (AGE) evaluation was undertaken in 33 MS patients: 79% presented a lymphoid cell profile and in 73% the gamma globulin fraction was abnormal. In the great majority of cases (97%) either or both cytological and electrophoretical abnormalities were found.

[Oligoclonal aspects of IgG of the cerebrospinal fluid. Methods of analysis and clinical correlations]. / L'oligoclonalité des IgG du liquide céphalo-rachidien. Méthodes d'analyse et corrélations cliniques.

Intrathecal synthesis of immunoglobulins is analyzed by two methods: quantitatively by immunoglobulin titration (IgG index) in cerebrospinal fluid (CSF) and qualitatively by demonstration of oligoclonal distribution of gammaglobulins. The authors report the results of a comparative study evaluating the IgG index and agarose electrophoresis versus electrofocusing. Sensitivity of electrofocusing was higher than the IgG index of standard agarose electrophoresis. Electrofocusing is the best method of proving intrathecal synthesis of immunoglobulins. Although oligoclonal bands are a useful aid in the diagnosis of multiple sclerosis, they indicate an immunological response but are not diagnostic for a particular disease.

[High-dose intravenous penicillin therapy in neurosyphilis: study of 62 cases. II. Evaluation of cerebrospinal fluid]. / Penicilinoterapia intravenosa em altas doses na neurossífilis: Estudo de 62 casos. II. Avaliação do líqüido cefalorraqueano.

Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Forty-one patients had pleocytosis in the CSF before treatment. Six months and twelve or more months later, abnormal cell count was observed in 4 (9.8%) and in 3 patients (7.3%), respectively. The CSF protein level and the titers of Wassermann reaction in the CSF decreased slowly after treatment. The gammaglobulin concentration of the CSF and the immunoglobulin production inside the blood-brain barrier were still increased beyond the first year after treatment. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with lesser doses of intramuscular penicillin that were reported in the literature.

[A cerebrospinal fluid syndrome in neurocysticercosis]. / Síndrome do líquido cefalorraqueano na neurocisticercose: estudo crítico sobre a evolução da imunidade humoral.

The study is based on 371 cerebrospinal fluid (CSF) samples and 324 serum samples from 40 patients with neurocysticercosis (NC) submitted to treatment with praziquantel. The aim of the study is a critical evaluation on humoral immunity in CSF NC syndrome. The analysis of NC patients at diagnosis and in the follow-up period was performed considering three connected criteria: the clinical one, the CSF examination and the computed tomography. For the study of CSF and serum samples a systematization of collection was scheduled in relation to: diagnosis; period of treatment; follow-up. A total of 13 samples for each case for a follow-up period of two years was scheduled. For the study of humoral immunity a semiquantitative methodology was employed to verify the intra blood-brain barrier (BBB) gamma globulins synthesis. It was based upon electrophoretic profile data on CSF and serum proteins, and relations and indexes. Normal values were previously characterized in a normal control group. This group was formed by 50 patients with chronic headache who presented normal neurological examination, as well as, CSF-examination and serum proteinogram under the safety limits of normality. To verify intra BBB gamma globulins synthesis it was considered the gamma globulin content of the CSF and serum, the gamma globulins/prealbumin + albumin relationship, the Link and Tibbling index, the intra BBB gamma globulins synthesis of Tourtellotte and col., and the appearance of oligoclonal bands in the CSF. Confirmation of the disease was performed by immunological reactions for cysticercosis: complement fixation test in CSF and serum; immunofluorescent test and enzyme-linked immunosorbent assay (ELISA) in CSF. Interference factors in the CSF NC syndrome were analysed at first such as those related to: clinical aspects, time of disease, previous dependence on corticotherapy, ventricular derivation shunts, tomographic findings. It was shown that all of them produce several degrees of interference in the intensity of the CSF NC syndrome. Data on intra BBB gamma globulins synthesis were verified in 37 patients (92.5%). It occurred in a persistent pattern in 18 cases (45%) during all the study phases, and not showed changes that might be related to treatment. On the other hand, it was shown that analysis of the results must always be performed case by case due to large dispersion of events observed and the differences of behavior of data related to humoral immunity, when critically analysed during diagnosis, treatment period and in the follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)