Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients With Parenchymal Neurocysticercosis.

BACKGROUND: The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.

Zika Virus Meningoencephalitis in an Immunocompromised Patient.

The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.

Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates.

Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics.

Comparative Study of Paired Serum and Cerebrospinal Fluid Samples from Neurocysticercosis Patients for the Detection of Specific Antibody to Taenia solium Immunodiagnostic Antigen.

Neurocysticercosis (NCC) is an important disease of the central nervous system caused by infection with Taenia solium metacestodes. In addition to the clinical findings and the imaging analysis, the results of immunological tests are informative for the diagnosis of NCC. To compare the usefulness of serum and cerebrospinal fluid (CSF) samples for antibody detection, paired serum and CSF samples from patients with NCC and other neurological diseases were examined by an enzyme-linked immunosorbent assay with low-molecular-weight antigens purified from T. solium cyst fluid in a blinded fashion. The sensitivity of both serum and CSF samples was 25.0% in inactive NCC cases (n = 4) and 90.9% in active NCC cases (n = 33), and the specificity of serum and CSF was 100% and 95.8%, respectively. When the serum and CSF samples were combined, the sensitivity in active NCC cases became 100%. There was no difference in test performance between serum and CSF samples. Based on these results, we recommend the detection of specific antibodies in serum for the diagnosis of active NCC because of the ease of collection. When the antibody test is negative, however, CSF should be used to confirm NCC and to rule out other medical disorders of the central nervous system. Antibody detection test using only serum or CSF has a limited diagnostic value and cannot be recommended for the diagnosis of suspected inactive NCC cases.

Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. METHODS: A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. RESULTS: Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. CONCLUSIONS: This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE-HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS.

Cross-cultural adaptation and validation of the episodic autobiographic memory interview for Brazilian Portuguese / Validação e adaptação transcultural da entrevista para avaliação da memória episódica autobiográfica para o português brasileiro

Episodic memory enables the storage of personal events with specific temporal and spatial details, and their retrieval through a sensory experience, usually visual, which is called autonoetic consciousness. While, in Brazil, several scales for the evaluation of anterograde episodic memory have been validated, there is not yet an instrument to assess the episodic autobiographical memory. The aim of this study is thus to make a cross-cultural adaptation and validation of the Episodic Autobiographic Memory Interview (EAMI) for Brazilian Portuguese. Altogether, 11 patients with Alzheimer’s disease (AD) and 10 healthy controls (CTs) were evaluated. EAMI scores for AD patients were lower than those of CTs, and these scores also correlated positively with the Remember-Know coefficient. The intraclass correlation coefficient indicated a good inter-rater reliability. The Portuguese version of EAMI showed a good reliability and validity, which suggests that it is a useful tool for evaluation of autobiographical memory in Brazilian patients.

A memória episódica possibilita o arquivamento de eventos pessoais, com seus detalhes temporais e espaciais, e sua recuperação através de uma experiência sensorial, geralmente visual, chamada de consciência autonoética. No Brasil, foram validados vários instrumentos para avaliação da memória episódica anterógrada, porém não há ainda uma escala para avaliar a memória episódica autobiográfica. O objetivo deste estudo é realizar uma validação e adaptação transcultural da Entrevista para avaliação da Memória Episódica Autobiográfica (EMEA) para o português brasileiro. Onze pacientes com doença de Alzheimer (DA) e 10 controles normais foram avaliados. Os escores dos pacientes com DA na EMEA foram menores do que nos controles saudáveis. Estes escores se correlacionaram positivamente com o coeficiente Lembrar-Saber. O coeficiente de correlação intraclasse indicou uma confiabilidade inter-examinadores adequada. A EMEA demonstrou uma boa validade e confiabilidade, sugerindo que ela é um instrumento útil para a avaliação da memória autobiográfica em pacientes brasileiros.

Cross-cultural adaptation and validation of the episodic autobiographic memory interview for Brazilian Portuguese.

Episodic memory enables the storage of personal events with specific temporal and spatial details, and their retrieval through a sensory experience, usually visual, which is called autonoetic consciousness. While, in Brazil, several scales for the evaluation of anterograde episodic memory have been validated, there is not yet an instrument to assess the episodic autobiographical memory. The aim of this study is thus to make a cross-cultural adaptation and validation of the Episodic Autobiographic Memory Interview (EAMI) for Brazilian Portuguese. Altogether, 11 patients with Alzheimer's disease (AD) and 10 healthy controls (CTs) were evaluated. EAMI scores for AD patients were lower than those of CTs, and these scores also correlated positively with the Remember-Know coefficient. The intraclass correlation coefficient indicated a good inter-rater reliability. The Portuguese version of EAMI showed a good reliability and validity, which suggests that it is a useful tool for evaluation of autobiographical memory in Brazilian patients.

Neurocysticercosis: A natural human model of epileptogenesis.

OBJECTIVE: To develop a better understanding of mechanisms of seizures and long-term epileptogenesis using neurocysticercosis. METHODS: A workshop was held bringing together experts in epilepsy and epileptogenesis and neurocysticercosis. RESULTS: Human neurocysticercosis and parallel animal models offer a unique opportunity to understand basic mechanisms of seizures. Inflammatory responses to degenerating forms and later-stage calcified parasite granulomas are associated with seizures and epilepsy. Other mechanisms may also be involved in epileptogenesis. SIGNIFICANCE: Naturally occurring brain infections with neurocysticercosis offer a unique opportunity to develop treatments for one of the world's most common causes of epilepsy and for the development of more general antiepileptogenic treatments. Key advantages stem from the time course in which an acute seizure heralds a start of the epileptogenic process, and radiographic changes of calcification and perilesional edema provide biomarkers of a chronic epileptic state.

Characteristics of mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis.

Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.

Neurocysticercosis.

Cysticercosis is one of the most common parasitic diseases of the nervous system in humans, and constitutes a major public health problem for most of the developing world. The clinical manifestations of neurocysticercosis (NCC) largely depend on the the host immune response against the parasite. NCC diagnosis is based upon neuroimaging studies (computerized tomography, magnetic resonance imaging) and antibody/antigen detection in the serum and the cerebrospinal fluid. Anticysticercal therapy has been marked by an intense controversy. Randomized controlled trials evaluating the clinical benefit of treatment have yield conflicting data with some studies indicating a benefit and others failing to show a difference. Prevention strategies must rely on multiple approaches, tailoring each to the special features of the particular endemic area.

Neurocysticercosis / Neurocisticercose

Cysticercosis is one of the most common parasitic diseases of the nervous system in humans, and constitutes a major public health problem for most of the developing world. The clinical manifestations of neurocysticercosis (NCC) largely depend on the the host immune response against the parasite. NCC diagnosis is based upon neuroimaging studies (computerized tomography, magnetic resonance imaging) and antibody/antigen detection in the serum and the cerebrospinal fluid. Anticysticercal therapy has been marked by an intense controversy. Randomized controlled trials evaluating the clinical benefit of treatment have yield conflicting data with some studies indicating a benefit and others failing to show a difference. Prevention strategies must rely on multiple approaches, tailoring each to the special features of the particular endemic area.

A cisticercose é uma das doenças parasitárias mais frequentes do sistema nervoso humano e constitui grave problema de saúde pública na maioria dos países em desenvolvimento. As manifestações clínicas da neurocisticercose (NCC) estão na dependência do número, tipo, localização e estágio de desenvolvimento dos cisticercos, assim como da resposta imunológica do hospedeiro contra o parasita. O diagnóstico da NCC é baseado nos exames de neuroimagem (tomografia computadorizada, ressonância magnética) e na detecção de antígenos/anticorpos no soro e no líquido cefalorraquiano. O tratamento antiparasitário tem sido marcado por uma intensa controvérsia. Os ensaios controlados e randomizados avaliando os benefícios clínicos da terapêutica têm revelado dados conflitantes em que alguns estudos indicam um benefício e outros não. As estratégias de prevenção devem ser fundamentadas na adoção simultânea de múltiplas medidas, adaptadas às características específicas de uma determinada região endêmica.

Cognitive and surgical outcome in mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis: a cohort study.

BACKGROUND: Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC. METHODS: Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC. FINDINGS: cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05-2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69-1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27-3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20-5.32; p = 0.012). INTERPRETATION: cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.

Modulation of angiogenic factor VEGF by DNA-hsp65 vaccination in a murine CNS tuberculosis model.

Tuberculosis (TB) is a serious public health problem. Development of experimental models and vaccines are essential to elucidate physiopathological mechanisms and to control the disease. Vascular endothelial growth factor (VEGF) is a potent activator of vascular permeability and angiogenesis. VEGF seems to participate in breakdown of the blood brain-barrier (BBB) in tuberculous meningitis (TBM), contributing to worsening of disease. Therefore, the objective here was to extent the characterization of our previously described murine model of central nervous system TB (CNS-TB) by describing the VEGF participation in the CNS disease, and suggesting a vaccination plan in mice. Plasmid encoding DNA protein antigen DNA-hsp65 has been described as a protector against TB infection and was used here to test its effectiveness in the prevention of VEGF production and TB disease. Vaccinated mice and its controls were injected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) in cerebellum. Four weeks after BCG injection, mice were perfused and brains were paraffin-embedded for VEGF expression analysis. We observed VEGF immunohistochemical expression in TBM and granulomas in non-vaccinated mice. The DNA-hsp65 treatment blocked the expression of VEGF in mice TBM. Therefore, our murine model indicated the VEGF participation in the physiopathology of CNS-TB and the potential prevention of the DNA-hsp65 in the disease progression.

Altered expression of degranulation-related genes in CD8+ T cells in human T lymphotropic virus type I infection.

Human T lymphotropic virus type I (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE methodology to screen for differentially expressed genes in CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients to identify genes involved in HAM/TSP development. SAGE analysis was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between HAC and HAM/TSP libraries identified 285 differentially expressed tags. We focus on cytotoxicity and cytokine-related genes due to their potential biological role in HTLV-1 infection. Our results showed that patients with HAM/TSP have high expression levels of degranulation-related genes, namely GZMH and PRF1, and of the cytoskeletal adaptor PXN. We found that GZMB and ZAP70 were overexpressed in HTLV-infected patients compared to the noninfected group. We also detected that CCL5 was higher in the HAM/TSP group compared to the HAC and CT groups. Our findings showed that CD8+ T cells of HAM/TSP patients have an inflammatory and active profile. PXN and ZAP70 overexpression in HTLV-1-infected patients was described for the first time here and reinforces this concept. However, although active and abundant, CD8+ T cells are not able to completely eliminate infected cells and prevent the development of HAM/TSP and, moreover, these cells might contribute to the pathogenesis of the disease by migrating to the central nervous system (CNS). These results should be further tested with biological functional assays to increase our understanding on the role of these molecules in the development of HTLV-1-related diseases.

The contribution of a murine CNS-TB model for the understanding of the host-pathogen interactions in the formation of granulomas.

Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB, characterized morphologically by brain granulomas and tuberculous meningitis (TBM). Experimental strategies for the study of the host-pathogen interaction through the analysis of granulomas and its intrinsic molecular mechanisms could provide new insights into the neuropathology of TB. To verify whether cerebellar mycobacterial infection induces the main features of the disease in human CNS and better understand the physiological mechanisms underlying the disease, we injected bacillus Calmette-Guerin (BCG) into the mouse cerebellum. BCG-induced CNS-TB is characterized by the formation of granulomas and TBM, a build up of bacterial loads in these lesions, and microglial recruitment into the lesion sites. In addition, there is an enhanced expression of signaling molecules such as nuclear factor-κB (NF-κB) and there is a presence of inducible nitric oxide synthase (iNOS) in the lesions and surrounding areas. This murine model of cerebellar CNS-TB was characterized by cellular and biochemical immune responses typically found in the human disease. This model could expand our knowledge about granulomas in TB infection of the cerebellum, and help characterize the physiological mechanisms involved with the progression of this serious illness that is responsible for killing millions people every year.

The use of a neck brace does not influence visual vertical perception.

UNLABELLED: Subjective visual vertical (SVV) evaluates the individual's capacity to determine the vertical orientation. Using a neck brace (NB) allow volunteers' heads fixation to reduce cephalic tilt during the exam, preventing compensatory ocular torsion and erroneous influence on SVV result. OBJECTIVE: To analyze the influence of somatosensory inputs caused by a NB on the SVV. METHOD: Thirty healthy volunteers performed static and dynamic SVV: six measures with and six without the NB. RESULTS: The mean values for static SVV were -0.075º±1.15º without NB and -0.372º±1.21º with NB. For dynamic SVV in clockwise direction were 1.73º±2.31º without NB and 1.53º±1.80º with NB. For dynamic SVV in counterclockwise direction was -1.50º±2.44º without NB and -1.11º±2.46º with NB. Differences between measurements with and without the NB were not statistically significant. CONCLUSION: Although the neck has many sensory receptors, the use of a NB does not provide sufficient afferent input to change healthy subjects' perception of visual verticality.

The use of a neck brace does not influence visual vertical perception / O uso do colar cervical não influência na percepção de verticalidade visual

Subjective visual vertical (SVV) evaluates the individual's capacity to determine the vertical orientation. Using a neck brace (NB) allow volunteers' heads fixation to reduce cephalic tilt during the exam, preventing compensatory ocular torsion and erroneous influence on SVV result. OBJECTIVE: To analyze the influence of somatosensory inputs caused by a NB on the SVV. METHOD: Thirty healthy volunteers performed static and dynamic SVV: six measures with and six without the NB. RESULTS: The mean values for static SVV were -0.075º±1.15º without NB and -0.372º±1.21º with NB. For dynamic SVV in clockwise direction were 1.73º±2.31º without NB and 1.53º±1.80º with NB. For dynamic SVV in counterclockwise direction was -1.50º±2.44º without NB and -1.11º±2.46º with NB. Differences between measurements with and without the NB were not statistically significant. CONCLUSION: Although the neck has many sensory receptors, the use of a NB does not provide sufficient afferent input to change healthy subjects' perception of visual verticality.

A subjetiva vertical visual (SVV) avalia a capacidade do indivíduo determinar a posição vertical. O uso do colar cervical (CC) fixa a cabeça do voluntário, reduzindo a inclicação cefálica durante o exame e prevenindo a torção ocular compensatória que influencia na SVV. OBJETIVO: Analisar a influência de informações sometossensoriais causadas pelo uso de um CC na SVV. MÉTODO: Trinta voluntários saudáveis realizaram a SVV estática e dinâmica: seis medidas com e seis medidas sem o CC. RESULTADOS: O valor médio da SVV estática foi -0,075º±1,15º sem CC e -0,372º±1,21º com. Na SVV dinâmica no sentido horário foi 1,73º±2,31º sem CC e 1,53º±1,80º com. Na SVV dinâmica no sentido anti-horário foi -1,50º±2,44º sem CC e -1,11º±2,46º com. As diferenças entre as medidas com e sem CC não foram estatisticamente significativas. CONCLUSÃO: Apesar de o pescoço possuir inumeros receptores sensoriais, o uso do CC não fornece aferências suficientes para alterar a percepção de visual de verticalidade de voluntários saudáveis.

Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis.

AIMS: Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS: A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS: Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS: Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

Unusual presentation of brain aspergillosis in chronic granulomatous disease.

Aspergillus is a frequently observed pathogen in patients with chronic granulomatous disease. We report on a patient with chronic granulomatous disease and severe brain aspergillosis with an unusual presentation and favorable course. We discuss the impact of this infection on morbidity and mortality, adequate therapeutic management, and the need to investigate a possible fungal infection, despite nonspecific signs.