Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection.

Interleukin-18 (IL-18) and interferon-gamma (IFN-γ) exert important functions in both innate and adaptive immune responses against intracellular pathogens and viruses. Previous studies suggested that host genetic factors, including cytokines gene polymorphisms, could be involved in the pathogenesis of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Thus, we analyzed -137C/G and -607A/C of the IL-18 promoter and +874T/A of the IFN-γ in DNA samples from 98 HTLV-1-infected individuals exhibiting or not clinical symptoms and 150 healthy control individuals. The IL-18 promoter -607CC genotype was significantly lower in HTLV-1 asymptomatic carriers (HAC) and HTLV-1-infected individuals (HAC + HAM/TSP) than healthy control group. In contrast, the -607AC genotype was significantly higher in HAC and HTLV-1-infected individuals group compared to the healthy control group. The -137G/-607A IL-18 haplotype was higher in infected group than healthy control group, and the -137C/-607C IL-18 haplotype was increased in the healthy control group compared to the others. Finally, the IFN-γ polymorphism analysis showed that the HTLV-1-infected individuals with +874AT genotype presented higher proviral load than +874AA genotype. These data indicate that the IL-18-607AC genotype and -137G/-607A haplotype could be a risk factor for HTLV-1 infection, whereas the protective effect could be conferred by -607CC genotype and -137C/-607C haplotype. Also, the IFN-γ could be implicated on the proviral load levels.

Using the National Institute of Health Stroke Scale to predict dysphagia in acute ischemic stroke.

BACKGROUND AND PURPOSE: Oropharyngeal dysphagia is a common manifestation in acute stroke. Aspiration resulting from difficulties in swallowing is a symptom that should be considered due to the frequent occurrence of aspiration pneumonia that could influence the patient's recovery as it causes clinical complications and could even lead to the patient's death. The early clinical evaluation of swallowing disorders can help define approaches and avoid oral feeding, which may be detrimental to the patient. This study aimed to create an algorithm to identify patients at risk of developing dysphagia following acute ischemic stroke in order to be able to decide on the safest way of feeding and minimize the complications of stroke using the National Institutes of Health Stroke Scale (NHISS). METHODS: Clinical assessment of swallowing was performed in 50 patients admitted to the emergency unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, with a diagnosis of ischemic stroke, within 48 h after the beginning of symptoms. Patients, 25 females and 25 males with a mean age of 64.90 years (range 26-91 years), were evaluated consecutively. An anamnesis was taken before the patient's participation in the study in order to exclude a prior history of deglutition difficulties. For the functional assessment of swallowing, three food consistencies were used, i.e. pasty, liquid and solid. After clinical evaluation, we concluded whether there was dysphagia. For statistical analysis we used the Fisher exact test, verifying the association between the variables. To assess whether the NIHSS score characterizes a risk factor for dysphagia, a receiver operational characteristics curve was constructed to obtain characteristics for sensitivity and specificity. RESULTS: Dysphagia was present in 32% of the patients. The clinical evaluation is a reliable method of detection of swallowing difficulties. However, the predictors of risk for the swallowing function must be balanced, and the level of consciousness and the presence of preexisting comorbidities should be considered. Gender, age and cerebral hemisphere involved were not significantly associated with the presence of dysphagia. NIHSS, Glasgow Coma Scale, and speech and language changes had a statistically significant predictive value for the presence of dysphagia. CONCLUSIONS: The NIHSS is highly sensitive (88%) and specific (85%) in detecting dysphagia; a score of 12 may be considered as the cutoff value. The creation of an algorithm to detect dysphagia in acute ischemic stroke appears to be useful in selecting the optimal feeding route while awaiting a specialized evaluation.

Noninvasive intracranial pressure monitoring for HIV-associated cryptococcal meningitis.

Mortality and adverse neurologic sequelae from HIV-associated cryptococcal meningitis (HIV-CM) remains high due to raised intracranial pressure (ICP) complications. Cerebrospinal fluid (CSF) high opening pressure occurs in more than 50% of HIV-CM patients. Repeated lumbar puncture with CSF drainage and external lumbar drainage might be required in the management of these patients. Usually, there is a high grade of uncertainty and the basis for clinical decisions regarding ICP hypertension tends to be from clinical findings (headache, nausea and vomiting), a low Glasgow coma scale score, and/or fundoscopic papilledema. Significant neurological decline can occur if elevated CSF pressures are inadequately managed. Various treatment strategies to address intracranial hypertension in this setting have been described, including: medical management, serial lumbar punctures, external lumbar and ventricular drain placement, and either ventricular or lumbar shunting. This study aims to evaluate the role of a non-invasive intracranial pressure (ICP-NI) monitoring in a critically ill HIV-CM patient.

Serum and cerebrospinal fluid S100B concentrations in patients with neurocysticercosis.

The clinical manifestations of neurocysticercosis (NC) are varied and depend on the number and location of cysts, as well as on the host immune response. Symptoms usually occur in NC when cysticerci enter a degenerative course associated with an inflammatory response. The expression of brain damage markers may be expected to increase during this phase. S100B is a calcium-binding protein produced and released predominantly by astrocytes that has been used as a marker of reactive gliosis and astrocytic death in many pathological conditions. The aim of the present study was to investigate the levels of S100B in patients in different phases of NC evolution. Cerebrospinal fluid and serum S100B concentrations were measured in 25 patients with NC: 14 patients with degenerative cysts (D), 8 patients with viable cysts (V) and 3 patients with inactive cysts. All NC patients, except 1, had five or less cysts. In most of them, symptoms had been present for at least 1 month before sample collection. Samples from 8 normal controls (C) were also assayed. The albumin quotient was used to estimate the blood-brain barrier permeability. There were no significant differences in serum (P = 0.5) or cerebrospinal fluid (P = 0.91) S100B levels among the V, D, and C groups. These findings suggest that parenchymal changes associated with a relatively small number of degenerating cysts probably have a negligible impact on glial tissue.

Therapy for neurocysticercosis. Comparison between albendazole and praziquantel.

Praziquantel and albendazole have been recently described as effective drugs for treatment of intraparenchymal brain cysticercosis. We performed a prospective study comparing the efficacy of these drugs. Twenty-two patients were treated with praziquantel and 21 with albendazole. In addition, 16 patients were treated with symptomatic drugs only and used as controls. Treatment was discontinued in two patients receiving praziquantel and one patient receiving albendazole owing to acute decompensation of the increased intracranial pressure, and one of them died. Albendazole and praziquantel were effective when compared with the control group. However, albendazole was significantly more effective than praziquantel in reducing the total number of cysts in the computed tomographic scans (88% vs 50%). Despite these results, however, analysis of clinical course showed a high frequency of neurologic sequelae. Considering the risks and fallibility of anticysticercal therapy, the real solution for this serious disease continues to be prophylaxis of infestation.

Detection of Strongyloides stercoralis in the cerebrospinal fluid of a patient with acquired immunodeficiency syndrome.

We report a case of Strongyloides stercoralis hyperinfection syndrome in a patient with acquired immunodeficiency syndrome with CNS involvement who died despite prompt institution of thiabendazole.

Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy.

BACKGROUND: Several studies suggest that neurocysticercosis is the main cause of symptomatic epilepsy in developing countries. In such areas, calcified cysticercotic lesions (CCL) are frequently found in patients with complex partial seizures associated with hippocampal sclerosis (HS). The authors studied whether there are clinical and pathologic differences between HS patients with and without CCL. METHODS: The authors determined the clinical and pathologic findings of 30 patients with HS and compared them with 32 patients with HS + CCL. Hippocampi from both groups were measured for fascia dentata Timm staining and cell density in hippocampal subfields. RESULTS: In the HS + CCL group, single or multiple CCL were found in all lobes with no lobar predominance. An initial precipitating event occurred in 83.3% of HS and in 62.5% of HS + CCL. First complex partial seizure occurred at 10.1 years in HS and at 11.9 years in HS + CCL. No significant differences were found for fascia dentata Timm staining and hippocampal cell densities. Good postsurgery outcome (Engel I classification) did not differ between groups, with this result occurring in 76.6% of patients with HS and 81.2% of patients with HS + CCL. CONCLUSIONS: The presence of CCL does not influence the clinical and pathologic profile of patients with hippocampal atrophy. Clinical histories and postsurgical outcomes were similar to those of patients with classic HS, suggesting that the CCL is probably, in this set of patients, a coincidental pathology and does not have a role in epileptogenesis.

Proposed diagnostic criteria for neurocysticercosis.

Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute--histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major--lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor--lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic--evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.

Disseminated muscular cysticercosis with myositis induced by praziquantel therapy.

Cysticercosis, the infestation with the encysted larval stage of Taenia solium, is increasingly recognized as a major problem in most countries in Latin America, Asia, and Africa, involving mainly the central nervous system. Muscle involvement is also common, although it usually remains asymptomatic. We describe a case of disseminated muscular cysticercosis followed by myositis (fever, diffuse myalgia, weakness of the lower limbs, and inflammatory reaction around dying cysticerci) induced by praziquantel therapy, an event not described previously.

Albendazole metabolism in patients with neurocysticercosis: antipyrine as a multifunctional marker drug of cytochrome P450.

The present study investigates the isoform(s) of cytochrome P450 (CYP) involved in the metabolism of albendazole sulfoxide (ASOX) to albendazole sulfone (ASON) in patients with neurocysticercosis using antipyrine as a multifunctional marker drug. The study was conducted on 11 patients with neurocysticercosis treated with a multiple dose regimen of albendazole for 8 days (5 mg/kg every 8 h). On the 5th day of albendazole treatment, 500 mg antipyrine was administered po. Blood and urine samples were collected up to 72 h after antipyrine administration. Plasma concentrations of (+)-ASOX, (-)-ASOX and ASON were determined by HPLC using a chiral phase column and detection by fluorescence. The apparent clearance (CL/f) of ASON and of the (+) and (-)-ASOX enantiomers were calculated and compared to total antipyrine clearance (CL(T)) and the clearance for the production of the three major antipyrine metabolites (CLm). A correlation (P

Use of neuron-specific enolase for assessing the severity and outcome in patients with neurological disorders.

Neuron-specific enolase (NSE) is a glycolytic enzyme present almost exclusively in neurons and neuroendocrine cells. NSE levels in cerebrospinal fluid (CSF) are assumed to be useful to estimate neuronal injury and clinical outcome of patients with serious clinical manifestations such as those observed in stroke, head injury, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. We compared levels of NSE in serum (sNSE) and in CSF (cNSE) among four groups: patients with meningitis (N=11), patients with encephalic injuries associated with impairment of consciousness (ENC, N=7), patients with neurocysticercosis (N=25), and normal subjects (N=8). Albumin was determined in serum and CSF samples, and the albumin quotient was used to estimate blood-brain barrier permeability. The Glasgow Coma Scale score was calculated at the time of lumbar puncture and the Glasgow Outcome Scale (GOS) score was calculated at the time of patient discharge or death. The ENC group had significantly higher cNSE (P=0.01) and albumin quotient (P=0.005), but not sNSE (P=0.14), levels than the other groups (Kruskal-Wallis test). Patients with lower GOS scores had higher cNSE levels (P=0.035) than patients with favorable outcomes. Our findings indicate that sNSE is not sensitive enough to detect neuronal damage, but cNSE seems to be reliable for assessing patients with considerable neurological insult and cases with adverse outcome. However, one should be cautious about estimating the severity of neurological status as well as outcome based exclusively on cNSE in a single patient.

Determination of albendazole metabolites in plasma by HPLC.

Albendazole is an antihelminthic agent belonging to the benzimidazole class and has been used successfully in the treatment of neurocysticercosis. We report here a method for the determination of the two major albendazole metabolites in plasma, albendazole sulfone and albendazole sulfoxide. The method consists of drug extraction from 500 microL of plasma previously acidified with chloroform-isopropanol (9:1, v/v) and extract purification with n-hexane immediately before chromatographic analysis. Separation of drugs and of the internal standard (mebendazole) was performed on an RP-18 column using acetonitrile-0.25N sodium acetate buffer (3:7, v/v), pH 5.0, as the mobile phase and using detection at 290 nm.

[Neurocysticercosis]. / Neurocisticercose.

It has been estimated that 50 million people are infected with the taeniasis/cysticercosis complex in the world today and that 50,000 die each year. It also appears that 350,000 individuals remain infected in Latin America. In Ribeirão Preto, Brazil, neurocysticercosis has been identified in 7.5% of the patients admitted to a ward specialized in the treatment of neurologic diseases. Its clinical manifestations comprise seizures, intracranial hypertension, cysticercotic meningitis, psychiatric symptoms, apoplectic or endarteritic form, and spinal cord syndrome. Lethality of neurocysticercosis varies from 16.4% to 25.9%. Diagnosis is dependent on the results of computed tomography of the brain and examination of the cerebrospinal fluid. Lately, albendazole in association with steroids has been elected the treatment of choice for neurocysticercosis. In the authors' opinion, compulsory notification of cases and preventive measures should be implemented. In Brazil, in the absence of a centralized program of control, regional initiatives should be stimulated, keeping in mind WHO's advice: "Think globally, act locally".

[Cryptococcus meningitis: clinical course, development and histopathologic aspects depending on the predisposing factors]. / Meningite criptocócica: aspectos clínicos, evolutivos e histopatológicos segundo a condição predisponente.

Seventeen consecutive cases of cryptococcal meningitis diagnosed at Hospital das Clínicas of Ribeirão Preto Medical School (São Paulo State Brazil) between 1969 and 1985 were reviewed. For analysis the patients were separated in 3 groups: I. three patients without immunodeficiency; II. six patients with associated disease: cancer (3), diabetes (2) and alcoholism (1); III. Eight renal transplant recipients that developed cryptococcosis after 18 to 67 months of immunosupression with steroids and azathioprine. The median interval between onset of symptoms and diagnosis of infection was greater in Group II (53 days) than in Groups I (25 days) or III (28 days). Neck stiffness, cranial nerve involvement and papilledema were more frequent in Group I than in Group II or III, but fever and focal neurological signs were observed only in patients of two last groups. Cerebrospinal fluid examination showed a mild lymphocytic pleocytosis in most patients, but transplant cases had polymorphonuclear cells more frequently. Late mortality was higher in patients with underlying disease and the prognosis was better for transplant patients that received effective antifungal therapy. Besides cryptococci, autopsy findings in 8 cases revealed granuloma formation in tissues, except in patients of Group II (2 cases). The differences between the groups suggest that clinical characteristics, evolution and postmortem findings of the cryptococcal meningitis are changed according to type of immunodeficiency presented by the patient.

[Monitoring of vegetables sold in Ribeirão Preto, SP, Brazil]. / Fiscalização de verduras comercializadas no município de Ribeirão Preto, SP.

The ingestion of raw vegetables represents an important means of transmission of several infectious diseases. The objective of the present study was to perform a microbiological and parasitological evaluation of the vegetables commercially sold in the municipality of Ribeirão Preto, SP, Brazil. Of a total of 172 commercial concerns analyzed, 115 (67%) presented irregularities in the vegetables they sold, such as elevated concentration of fecal coliforms in 63%, presence of Salmonella in 9%, and presence of enteroparasites in 33%. The commercial concerns with the highest frequencies of vegetables showing inadequate results were: grocery stores (92%), CEAGESP (75%), fruit and vegetables stores (71%), traveling vendors (71%), fairs (69%), supermarkets (52%), and vegetable gardens (18%). The type of contamination was uniformly distributed among these commercial concerns. Most of the contaminated vegetables (61%) were from gardens located in the municipality of Ribeirão Preto. Considering the high frequency of fecal contamination and the potential risk of disease transmitted by vegetables, we suggest greater enforcement in the sanitary surveillance of the food offered to the population.

[Monitoring of lettuce crops of Ribeirão Preto, SP, Brazil]. / Fiscalização de hortas produtoras de verduras do município de Ribeirão Preto, SP.

The ingesting of raw vegetables plays an important role in the transmission of several infectious diseases due to the high frequency of irrigation with wastewater. The objective of this study was to evaluate the sanitary conditions of all lettuce producing crops in Ribeirão Preto through microbiological and parasitological analysis of both irrigation water and lettuce together with the implantation of an effective crop monitoring. Laboratory analysis of 129 crops showed irregularities in 26 (20.1%) of these: high concentration of fecal coliforms in 17% of the lettuce, presence of Salmonella in 3.1% and several enteroparasites (Ascaris sp, Ancylostomidae, Strongyloides sp, Hymenolepis nana, and Giardia sp ) in 13.1%. Persistent irregularities determined the definitive closing down of one producer; all of the remaining 128 crops were eventually approved, thus demonstrating the efficacy of lettuce crop monitoring. Crops approved in the laboratory analysis were awarded a Sanitary Inspection Certificate - an unprecedented procedure in our Country - that resulted in a better acceptance of the monitoring.

[Neurocysticercosis. I. Clinical and laboratory course of 151 cases]. / Neurocisticercose. I. Evolução clínico-laboratorial de 151 casos.

Neurocysticercosis is a serious public health problem in our midst, which accounted for 7.3% of the hospital admissions and 2.7% of all cases of the out patient clinic attendance of the Discipline of Neurology of the School of Medicine--Ribeirão Preto, São Paulo University, from 1979 to 1986. A total of 151 patients with a minimum follow-up of 6 months were selected for the present study including clinical and laboratory evolution, a topic which is rarely considered in the literature. The onset of the disease was characterized by: epileptic seizures in 82 patients (54.3%), increased intracranial pressure (ICP) in 40 (26.5%), meningitis in 21 (13.9%), headache in the absence of increased ICP or meningitic signs in 7 (4.6%), and spinal cord syndrome in 1 (0.6%). In the group with the epileptic form, 36.6% of the patients later developed other neurological syndromes, such as cysticercotic meningitis, mental disorders and increased ICP after a 6 to 7 years interval. In the group with the hypertensive form, 55% of the patients developed other manifestations during the period of evolution, especially meningitis and epileptic seizures, after a significantly shorter interval than for the epileptic form. In the meningitic form, 19% of the patients showed a recurrence of the syndrome after a mean interval of 10.7 weeks: an additional 66.6% developed a combination with other syndromes, especially increased ICP and epileptic seizures. The death rate was 7.9%, the main cause being increased ICP (83.3%). When the abnormalities of the complementary tests were investigated in the various forms of clinical presentation in terms of their predictive value it was concluded that, in the epileptic form, the presence of cysts in CT scan and/or abnormalities in CSF indicates a greater risk of developing other neurologic syndromes. No significant differences in the patterns of abnormalities of these investigations were detected in the remaining clinical forms. Most cystic lesions detected by CT scan (90.9%) were associated with CSF abnormalities, especially pleocytosis and positive complement fixation test. Conversely, this proportion was only 26% in patients with calcifications.

[Neurocysticercosis. II. Evaluation of treatment with praziquantel]. / Neurocisticercose. II. Avaliação da terapêutica com praziquantel.

The results of the use of praziquantel (PZQ) for the etiologic treatment of neurocysticercosis (NC) are presented. The drug was administered to 45 patients (24 women and 21 men) at increasing doses of 10 to 50 mg/kg/day during the first week and with maintenance on the last dose for two additional weeks, preferentially for patients that presented intraparenchymatous cystic lesions in the computed axial tomography. Follow-up ranged from 8 months to 4 years and a half (median, 2.7 years). During PZQ administration 27 patients (60%) presented side effects which required interruption of treatment in three cases. Decompensation of the increased ICP occurred in two cases (one of them fatal). Exacerbation of CSF pleocytosis occurred in 26 patients (57.7%). Evaluation of the results of PZQ treatment showed a lower clinical-laboratory rate of success than reported in the literature. The most appropriate indications for the use of PZQ are discussed on the basis of the present data and of reports by other investigators. In view of the risks and fallibility of treatment with PZQ, the solution of NC resides in the prevention of infestation.

[Chronic nervous form of Chagas disease: clinical course and anatomopathology of a case followed-up for 20 years]. / Forma nervosa crônica da doença de Chagas: estudo clínico evolutivo e anatomopatológico de um caso seguido durante vinte anos.

The chronic nervous forms of Chagas' disease involve both the central and peripheral nervous systems although they are not detected at the frequency indicated by Chagas in his initial observations. The present report concerns a patient with chronic Chagas' disease since childhood who progressively developed involvement of voluntary motility, muscle tone, coordination, and cranial nerves. The patient also had Chagas' heart and colon disease. The patient died after surgery for hemicolectomy and was autopsied. Histologic study of the central nervous system revealed demyelination of the spinocerebellar tracts and posterior columns, a great reduction in the Purkinje cells number, extensive cell loss of the substantia nigra and locus coeruleus, lacunar state in the basal nuclei, tissue infiltration by aberrant Herring bodies, porencephaly, and thickening of the meninges.

[Epilepsy and chronic Chagas disease]. / Epilepsia e donença de Chagas crônica.

The epileptic syndrome in chronic Chagas' disease is rarely reported in neurological literature. At the present time many papers have demonstrated that histopathological basis of Chagas' disease is a neuronal destruction. The authors studied 167 epileptic patients; 44 out of them had a chronic form of the disease. It was made a comparison of semiologic data between the two groups, and also the evaluation of the therapeutic results with anticonvulsant drugs. The chagasic patients had the onset of epileptic seizures later than the control group, with great predominance of partial seizures of autonomic type. The neurologic examination and cerebrospinal fluid test revealed moderate rates of disturbances, but not sufficient to characterize a neurologic syndrome. The EEG study was performed in 15 of the 44 cases and revealed a suggestive pattern of a diffuse cerebral damage in half of patients. Anticonvulsant therapy based on use of phenylhydantoin, barbituric acid derivates, primidone and benzodiazepines, showed that control of epileptic seizures in Chagas' diseases is more difficult and requires greater quantities of drugs than in the control group.