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BACKGROUND: Arteritis is a complication of neurocysticercosis (NCC), which is not well known and could trigger strokes. The transcranial Doppler ultrasound (TCD) is a noninvasive method for detecting, staging, and monitoring cerebrovascular diseases. Nonetheless, the utility of TCD to evaluate cerebral hemodynamic changes, suggesting vasculitis associated with NCC remains uncertain. OBJECTIVE: To evaluate cerebral hemodynamic changes using TCD in patients with subarachnoid and parenchymal NCC. METHODS: There were 53 patients with NCC evaluated at a reference hospital for neurological diseases included (29 with subarachnoid and 24 with parenchymal). Participants underwent a clinical interview and serology for cysticercosis and underwent TCD performed within 2 weeks of enrollment. Mean flow velocity, peak systolic velocity, end diastolic velocity, and pulsatility index were recorded. RESULTS: Among the participants, there were 23 (43.4%) women, with a median age of 37 years (IQR: 29-48). Cerebral hemodynamic changes suggesting vasculitis were detected in 12 patients (22.64%); the most compromised vessel was the middle cerebral artery in 11 (91.67%) patients. There were more females in the group with sonographic signs of vasculitis (10/12, 83.33% vs. 13/41, 31.71%; p = 0.002), and this was more frequent in the subarachnoid NCC group (9/29, 31.03% vs. 3/24, 12.5%; p = 0.187), although this difference did not reach statistical significance. CONCLUSION: Cerebral hemodynamic changes suggestive of vasculitis are frequent in patients with NCC and can be evaluated using TCD.
ANTECEDENTES: La arteritis es una complicación de la neurocisticercosis (NCC), que no siempre se conoce y podría desencadenar enfermedad cerebrovascular. La ultrasonografía Doppler transcraneal (DTC) es un método no invasivo que sirve para detectar y monitorizar enfermedades cerebrovasculares. No obstante, la utilidad de la DTC para evaluar los cambios hemodinámicos cerebrales que sugieren vasculitis asociada a NCC sigue siendo incierta. OBJETIVO: Evaluar los cambios hemodinámicos cerebrales utilizando DTC en pacientes con NCC subaracnoidea y parenquimal. MéTODOS: Se incluyeron 53 pacientes con NCC (29 con subaracnoidea y 24 con parenquimal) evaluados en un hospital de referencia para enfermedades neurológicas. Los participantes se sometieron a una entrevista clínica y serología para cisticercosis y a una DTC realizada dentro de las 2 semanas posteriores a la inscripción. Se registraron la velocidad media del flujo, la velocidad sistólica máxima, la velocidad diastólica final y el índice de pulsatilidad. RESULTADOS: Los participantes incluyeron 23 (43,4%) mujeres con una mediana de edad de 37 años (rango intercuartílico [RIC]: 2948). Se detectaron cambios hemodinámicos cerebrales sugestivos de vasculitis en 12 pacientes (22,64%); el vaso más comprometido fue la arteria cerebral media, en 11 (91,67%) pacientes. Hubo más mujeres en el grupo con signos ecográficos de vasculitis (10/12, 83,33% versus 13/41, 31,71%; p = 0,002), y esto fue más frecuente en el grupo de NCC subaracnoidea (9/29, 31,03% versus 3/24, 12,5%; p = 0,187), aunque esta diferencia no alcanzó significancia estadística. CONCLUSIóN: Los cambios hemodinámicos cerebrales sugestivos de vasculitis son frecuentes en pacientes con NCC y pueden evaluarse mediante DTC.
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Circulação Cerebrovascular , Hemodinâmica , Neurocisticercose , Ultrassonografia Doppler Transcraniana , Humanos , Ultrassonografia Doppler Transcraniana/métodos , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/fisiopatologia , Neurocisticercose/complicações , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Hemodinâmica/fisiologia , Circulação Cerebrovascular/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Valores de ReferênciaRESUMO
We explored the association between serological status for hepatitis E and neurocysticercosis (NCC) in neurologic patients attending a national neurological referral center in Lima, Perú, between the years 2008 and 2012. Anti-hepatitis E antibodies were evaluated in patients with and without NCC, and a control group of rural general population. Anti-hepatitis E IgG was found in 23.8% of patients with NCC, compared with 14.3% in subjects without NCC from a general rural population (P = 0.023) and 14.4% in subjects with neurological complaints without NCC (P = 0.027). Seropositive patients had a median age of 44 years compared with 30 years in seronegative patients (P <0.001). No significant differences in sex, region of residence, or liver enzyme values were found. Seropositivity to hepatitis E was frequent in this Peruvian population and higher in patients with NCC, suggesting shared common routes of infection.
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Vírus da Hepatite E , Hepatite E , Neurocisticercose , Humanos , Neurocisticercose/epidemiologia , Neurocisticercose/imunologia , Neurocisticercose/complicações , Masculino , Adulto , Feminino , Hepatite E/epidemiologia , Hepatite E/imunologia , Vírus da Hepatite E/imunologia , Pessoa de Meia-Idade , Peru/epidemiologia , Adulto Jovem , Prevalência , Imunoglobulina G/sangue , Anticorpos Anti-Hepatite/sangue , Estudos Soroepidemiológicos , Adolescente , IdosoRESUMO
Patients with subarachnoid neurocysticercosis (NCC) are usually older than those with parenchymal disease. Whether this difference reflects a prolonged presymptomatic period or a delay in diagnosis is not clear. From 408 eligible patients, we retrospectively compared the age at symptom onset in 140 patients diagnosed with parenchymal (pure viable or pure calcified) and subarachnoid NCC who had a confirmatory image available not more than 2 years after the beginning of symptoms. Patients with mixed (parenchymal and subarachnoid) NCC or those with parenchymal cysts at different stages (viable and/or degenerating and/or calcified) were not included. After controlling by sex and residence in rural endemic regions, the mean age at symptom onset in patients with subarachnoid disease was 13.69 years older than those with viable parenchymal disease. A long incubation period is a major contributing factor to older age at presentation in subarachnoid NCC, independent of delayed diagnosis or access to care.
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Cistos , Neurocisticercose , Humanos , Idoso , Adolescente , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/epidemiologia , Estudos Retrospectivos , Espaço Subaracnóideo , População RuralRESUMO
We hypothesized that fetal exposure to the oxidative stress induced by the combined challenge of preeclampsia (PE) and high altitude would induce a significant impairment in the development of pulmonary circulation. We conducted a prospective study in La Paz (Bolivia, mean altitude 3625 m) in which newborns from singleton pregnancies with and without PE were compared (PE group n = 69, control n = 70). We conducted an echocardiographic study in these infants at the median age of two days. The percentage of cesarean deliveries and small for gestational age (SGA) infants was significantly higher in the PE group. Heart rate, respiratory rate, and oxygen saturation did not vary significantly between groups. Estimated pulmonary arterial pressure and pulmonary vascular resistance were 30% higher in newborns exposed to PE and high altitude compared with those exposed only to high altitude. We also detected signs of right ventricular hypertrophy in infants subjected to both exposures. In conclusion, this study provides evidence that the combination of PE and pregnancy at high altitude induces subclinical alterations in the pulmonary circulation of the newborn. Follow-up of this cohort may provide us with valuable information on the potential increased susceptibility to developing pulmonary hypertension or other pulmonary and cardiovascular disorders.
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Neurocysticercosis (NCC), the infection of the central nervous system caused by Taenia solium larvae (cysticerci), is a major cause of acquired epilepsy worldwide. Calcification in NCC is the most common neuroimaging finding among individuals with epilepsy in T. solium-endemic areas. We describe the demographic, clinical, and radiological profiles of a large hospital cohort of patients with calcified NCC in Peru (during the period 2012-2022) and compared profiles between patients with and without a previous known diagnosis of viable infection. A total of 524 patients were enrolled (mean age at enrollment: 40.2 ± 15.2 years, mean age at symptom onset: 29.1 ± 16.1 years, 56.3% women). Of those, 415 patients (79.2%) had previous seizures (median time with seizures: 5 years, interquartile range (IQR): 2-13 years; median number of seizures: 7 (IQR: 3-32)), of which 333 (80.2%) had predominantly focal to bilateral tonic-clonic seizures; and 358 (68.3%) used antiseizure medication). Patients had a median number of three calcifications (IQR: 1-7), mostly located in the frontal lobes (79%). In 282 patients (53.8%) there was a previous diagnosis of viable infection, while 242 only had evidence of calcified NCC since their initial neuroimaging. Most patients previously diagnosed with viable infection were male, had previous seizures, had seizures for a longer time, had more calcifications, and had a history of taeniasis more frequently than patients without previously diagnosed viable infection (all p < 0.05). Patients with calcified NCC were heterogeneous regarding burden of infection and clinical manifestations, and individuals who were diagnosed after parasites calcified presented with milder disease manifestations.
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The diagnosis of neurocysticercosis (NCC) is principally based on neuroimaging (magnetic resonance imaging or computed tomography), instrumentation that is scarcely available in the rural regions where Taenia solium transmission, primarily occurs due to poor sanitation conditions. Immunological assays for antigen or antibody detection complement the neuroimaging approach. However, no field-applicable assays to diagnose viable NCC or to guide the referral of cases for neuroimaging or for appropriate management are available. We performed an exploratory study on urine and serum samples using 1H-nuclear magnetic resonance (NMR)-based metabolomics to discriminate NCC patients (n = 14) from healthy control subjects (n = 22). Metabolic profiles demonstrated a discrimination between the urines of NCC patients and noninfected control subjects with a moderate predictive accuracy (R2 = 0.999, Q2 = 0.434). NMR metabolomics analysis has been proven useful in depicting biomarkers linked to other infectious diseases, various types of cancer, and other disorders. Our results, albeit preliminary, open a door to the development of better methods for detecting NCC through the identification of biomarkers participating in disturbed metabolic pathways.
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BACKGROUND: Neurocysticercosis (NCC) is a common cause of late-onset epilepsy worldwide, but there is still minimal information regarding its impact on a patient's quality of life. This study evaluated quality of life in a series of patients with epilepsy secondary to NCC using the QOLIE (Quality of Life in Epilepsy)-31 questionnaire. METHODOLOGY: This cross-sectional study included 155 Peruvian patients between 16 and 70â¯years of age with epilepsy due to viable intraparenchymal NCC, who enrolled in two trials of anti-parasitic treatment during the period 2006-2011. The QOLIE-31 questionnaire was applied before the onset of anti-parasitic treatment. The associations between QOLIE-31 scores, sociodemographic characteristics, clinical, and neuroimaging data were analyzed with Kruskal-Wallis test and generalized linear models (GLM). RESULTS: The average QOLIE-31 score was 55.8 (SD⯱â¯7.6), with 119 individuals (76.8%) scoring in the poor quality-of-life category. Generalized tonic-clonic seizures and secondarily generalized epileptic seizures were associated with a lower QOLIE-31, as well as a low level of education with a value of pâ¯=â¯0.05. There were no associations between QOLIE-31 scores and other variables such as sex, age, antiepileptic medication, number of parasitic cysts, and number of compromised brain regions. On multivariate analysis, a greater number of generalized epileptic seizures maintained a statistically significant association with detrimental QOLIE-31 scores. CONCLUSION: Quality of life is affected in NCC, mainly in relation to the number of prior generalized epileptic seizures.
Assuntos
Epilepsia , Neurocisticercose , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Humanos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico por imagem , Qualidade de Vida , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Convulsões/etiologia , Inquéritos e QuestionáriosRESUMO
The diagnosis of neurocysticercosis (NCC) depends on neuroimaging and serological confirmation. While antibody detection by enzyme-linked immunoelectrotransfer blot (EITB) fails to predict viable NCC, EITB banding patterns provide information about the host's infection course. Adding antigen enzyme-linked immunosorbent assay (Ag-ELISA) results to EITB banding patterns may improve their ability to predict or rule out of viable NCC. We assessed whether combining EITB banding patterns with Ag-ELISA improves discrimination of viable infection in imaging-confirmed parenchymal NCC. EITB banding patterns were grouped into classes using latent class analysis. True-positive and false-negative Ag-ELISA results in each class were compared using Fisher's exact test. Four classes were identified: 1, EITB negative or positive to GP50 alone (GP50 antigen family); 2, positive to GP42-39 and GP24 (T24/42 family), with or without GP50; and 3 and 4, positive to GP50, GP42-39, and GP24 and reacting to bands in the 8-kDa family. Most cases in classes 3 and 4 had viable NCC (82% and 88%, respectively) compared to classes 2 and 1 (53% and 5%, respectively). Adding positive Ag-ELISA results to class 2 predicted all viable NCC cases (22/22 [100%]), whereas 11/40 patients (27.5%) Ag-ELISA negative had viable NCC (P < 0.001). Only 1/4 patients (25%) Ag-ELISA positive in class 1 had viable NCC, whereas 1/36 patients (2.8%) Ag-ELISA negative had viable NCC (P = 0.192). In classes 3 and 4, adding Ag-ELISA was not contributory. Combining Ag-ELISA with EITB banding patterns improves discrimination of viable from nonviable NCC, particularly for class 2 responses. Together, these complement neuroimaging more appropriately for the diagnosis of viable NCC.
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Neurocisticercose , Taenia solium , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Neurocisticercose/diagnóstico , Sensibilidade e EspecificidadeRESUMO
Magnetic resonance images from 197 patients with calcified neurocysticercosis (NCC), 38 with viable NCC and 197 NCC-free healthy rural villagers were evaluated to compare the frequency of hippocampal atrophy/sclerosis (HAS) across these populations. Scheltens' medial temporal atrophy scale was used for hippocampal rating. The median age of the 432 study participants was 46 years (interquartile range, 29-62 years), and 58% were women. Hippocampal atrophy/sclerosis was disclosed in 26.9% patients with calcified NCC, compared with 7.9% in patients with viable NCC and 8.1% in healthy rural villagers. After adjusting for age, gender, and history of epilepsy, hippocampal atrophy/sclerosis was more frequent in patients with calcified NCC than in those with viable cysts (RR, 3.60; 95% CI, 1.18- 0.99; P = 0.025) and healthy rural villagers (RR, 3.43; 95% CI, 1.94-6.06; P < 0.001), suggesting that hippocampal damage develops late in the course of this parasitic disease.
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Calcinose/complicações , Hipocampo/patologia , Neurocisticercose/complicações , Adulto , Atrofia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/parasitologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Negligenciadas/complicações , Doenças Negligenciadas/diagnóstico por imagem , Doenças Negligenciadas/patologia , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/patologia , EscleroseRESUMO
Neurocysticercosis (NCC) is endemic in many parts of the world, carrying significant neurological morbidity that varies according to whether lesions are located inside the cerebral parenchyma or in extraparenchymal spaces. The latter, in particular subarachnoid NCC, is assumed to be more severe, but no controlled studies comparing mortality between types of NCC exist. The aim of this study was to compare all-cause mortality between patients with intraparenchymal NCC and those with subarachnoid NCC. Vital status and sociodemographic characteristics were evaluated in patients with intraparenchymal viable, intraparenchymal calcified, and subarachnoid NCC attending a neurological referral hospital in Lima, Perú. Survival analyses using Kaplan-Meier curves and Cox proportional regression models were carried out to compare mortality rates between groups. From 840 NCC patients followed by a median time of 82.3 months, 42 (5.0%) died, six (1.8%) in the intraparenchymal viable group, four (1.3%) in the calcified group, and 32 (16.6%) in the subarachnoid group (P < 0.001). Older age and lower education were significantly associated with mortality. The age-adjusted hazard ratio for death in the subarachnoid group was 13.6 (95% CI: 5.6-33.0, P < 0.001) compared with the intraparenchymal viable group and 10.7 (95% CI: 3.7-30.8, P < 0.001) when compared with the calcified group. We concluded that subarachnoid disease is associated with a much higher mortality in NCC.
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Neurocisticercose/mortalidade , Neurocisticercose/patologia , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espaço Subaracnóideo , Taenia soliumRESUMO
BACKGROUND: Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. METHODS: Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. RESULTS: The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02-1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05-1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08-1.46), mild antibody response (RR, 1.14; 95% CI, 1.002-1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14-1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02-1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08-1.93), or complete cure (RR, 1.48; 95% CI, 1.29-1.71) were associated with a increased risk of calcification. CONCLUSIONS: Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.
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Neurocisticercose , Taenia solium , Albendazol/uso terapêutico , Animais , Antiparasitários/uso terapêutico , Encéfalo , Humanos , Neurocisticercose/complicações , Neurocisticercose/tratamento farmacológico , Neurocisticercose/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologiaRESUMO
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.
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Albendazol/análogos & derivados , Anti-Helmínticos/sangue , Anti-Helmínticos/uso terapêutico , Neurocisticercose/sangue , Neurocisticercose/tratamento farmacológico , Praziquantel/sangue , Praziquantel/uso terapêutico , Adolescente , Adulto , Idoso , Albendazol/sangue , Albendazol/uso terapêutico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto JovemRESUMO
Neurocysticercosis (NCC), caused by Taenia solium larvae that reside in the central nervous system, results in serious public health and medical issues in many regions of the world. Current diagnosis of NCC is complex requiring both serology and costly neuroimaging of parasitic cysts in the brain. This diagnostic pipeline can be problematic in resource-constrained settings. There is an unmet need for a highly sensitive and clinically informative diagnostic test to complement the present diagnostic approaches. Here, we report that T. solium-derived cell-free DNA is readily detectable in the urine of patients with the subarachnoid and parenchymal forms of NCC, and discuss the potential utility of this approach in enhancing and refining T. solium diagnostics.
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Ácidos Nucleicos Livres/genética , Disfunção Cognitiva/parasitologia , DNA de Helmintos/genética , Neurocisticercose/parasitologia , Taenia solium/genética , Animais , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/urina , Sistema Nervoso Central/parasitologia , Sistema Nervoso Central/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , DNA de Helmintos/sangue , DNA de Helmintos/urina , Humanos , Larva/genética , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/fisiopatologia , Neuroimagem/métodos , Peru , Reação em Cadeia da Polimerase/métodos , Taenia solium/isolamento & purificaçãoRESUMO
OBJECTIVE: Discordances between imaging findings of parenchymal neurocysticercosis and seizure expression have been reported, and as such the possibility that neurocysticercosis and seizures may frequently coexist by chance has been raised. In this study, we evaluate the topographic relationship between seizure foci based on semiology and electroencephalography with the location of parenchymal neurocysticercotic lesions. METHODS: Seizure information, neuroimaging (computed tomography and magnetic resonance imaging [MRI]) and electroencephalographic data from three randomized clinical trials of individuals with parenchymal neurocysticercosis and focal seizures were analyzed. Blinded epileptologists defined a potential seizure onset zone and a symptomatogenic zone for each individual based on semiology. The topographic relationship between semiology, either lesion location or areas of perilesional edema on baseline MRI, and electroencephalographic abnormalities were assessed. RESULTS: Fifty-eight patients with one or two parenchymal neurocysticercotic lesions were included in this study. From them, 50 patients (86%; 95% CI, 75%-93%) showed a clinical-topography relationship with the potential seizure onset zone, and 44 (76%) also with the symptomatogenic zone. From the eight patients with no topographic relationship, five had focal seizures 30 days before or after the baseline MRI and showed perilesional edema. All of these five patients showed a clinical-topography relationship between such seizures and an area of perilesional edema, making a total of 55 patients (95%; 95% CI, 85%-99%) with clinical-topography relationship when perilesional edema is considered. Most patients with focal epileptiform discharges (7/8, 88%) had a topographic association between electroencephalographic focality, the potential seizure onset zone and a cysticercotic lesion. CONCLUSION: Seizure semiology and focal epileptiform discharges are topographically related to neurocysticercotic lesions in most patients. These data strongly support seizure origin in the cortex surrounding these lesions.
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Encéfalo/patologia , Neurocisticercose/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Adolescente , Adulto , Idoso , Antiparasitários/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurocisticercose/tratamento farmacológico , Neurocisticercose/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Convulsões/fisiopatologia , Tomógrafos Computadorizados , Adulto JovemRESUMO
OBJECTIVE: We conducted a retrospective, case-control study of neurocysticercosis patients to ascertain early markers that identify subjects likely to develop treatment-resistant seizures. METHODS: Clinical histories and imaging studies from 38 neurocysticercosis patients who had been followed for 18 months after treatment were evaluated. Both pairwise and multifactorial analyses were conducted to identify factors associated with continued seizures. RESULTS: Eleven of 38 patients continued to have seizures during the follow-up period. On univariate analysis, the number of neurocysticercosis lesions, number of bands on the baseline neurocysticercosis western blot, edema volumes on follow-up MRI scans, edema volume changes between baseline and follow-up images, and proportion of calcified lesions with perilesional edema were all significantly increased in subjects who had persistent seizures during the 18-month follow-up period. On multivariate analyses using recursive partition and random forest algorithms, variables associated with persistent seizures included: the number of total and calcified lesions, presence of perilesional edema, the rate of change in the lesion and edema volumes from baseline to follow-up, and the number of bands on the neurocysticercosis western blot. INTERPRETATION: Measures of both inflammation and disease burden are key risk factors for persistent seizures despite anticonvulsant treatments in patients with neurocysticercosis. Inflammation is therefore a potentially modifiable risk factor for the frequently seen severe seizure disorders in patients with neurocysticercosis.
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OBJECTIVE: To evaluate the diagnostic performance of two commercially available ELISA kits, Novalisa® and Ridascreen® , for the detection of antibodies to Taenia solium, compared to serological diagnosis of neurocysticercosis (NCC) by LLGP-EITB (electro-immunotransfer blot assay using lentil-lectin purified glycoprotein antigens). METHODS: Archive serum samples from patients with viable NCC (n = 45) or resolved, calcified NCC (n = 45), as well as sera from patients with other cestode parasites (hymenolepiasis, n = 45 and cystic hydatid disease, n = 45), were evaluated for cysticercosis antibody detection using two ELISA kits, Novalisa® and Ridascreen® . All NCC samples had previously tested positive, and all samples from heterologous infections were negative on LLGP-EITB for cysticercosis. Positive rates were calculated by kit and sample group and compared between the two kits. RESULTS: Compared to LLGP-EITB, the sensitivity of both ELISA assays to detect specific antibodies in patients with viable NCC was low (44.4% and 22.2%), and for calcified NCC, it was only 6.7% and 4.5%. Sera from patients with cystic hydatid disease were highly cross-reactive in both ELISA assays (38/45, 84.4%; and 25/45, 55.6%). Sera from patients with hymenolepiasis cross-reacted in five cases in one of the assays (11.1%) and in only one sample with the second assay (2.2%). CONCLUSIONS: The performance of Novalisa® and Ridascreen® was poor. Antibody ELISA detection cannot be recommended for the diagnosis of neurocysticercosis.
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Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Separação Imunomagnética/métodos , Neurocisticercose/diagnóstico , Taenia solium/isolamento & purificação , Animais , Antígenos de Helmintos/sangue , Testes Imunológicos , Neurocisticercose/sangue , Neurocisticercose/parasitologia , Sensibilidade e Especificidade , Taenia solium/imunologiaRESUMO
Background: The enzyme-linked immunoelectrotransfer blot (EITB) assay is the reference serological test for neurocysticercosis (NCC). A positive result on EITB does not always correlate with the presence of active infections in the central nervous system (CNS), and patients with a single viable brain cyst may be EITB negative. Nonetheless, EITB antibody banding patterns appears to be related with the expression of 3 protein families of Taenia solium, and in turn with the characteristics of NCC in the CNS (type, stage, and burden of viable cysts). Methods: We evaluated EITB antibody banding patterns and brain imaging findings of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes using latent class analysis. The association between classes and brain imaging findings was assessed. Results: Four classes were identified. Class 1 (patients negative or only positive to the GP50 band, related to the protein family of the same name) was associated with nonviable or single viable parenchymal cysticerci; class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42 protein family, with or without anti-GP50 antibodies) was associated with intraparenchymal viable and nonviable infections; classes 3 and 4 (positive to GP50, GP42-39, and GP24 but also responding to low molecular weight bands GP21, GP18, GP14, and GP13, related to the 8 kDa protein family) were associated with extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions: EITB antibody banding patterns correlate with brain imaging findings and complement imaging information for the diagnosis of NCC and for staging NCC patients.
Assuntos
Anticorpos Anti-Helmínticos/análise , Encéfalo/patologia , Neurocisticercose/patologia , Taenia solium/imunologia , Adulto , Idoso , Animais , Encéfalo/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , NeuroimagemRESUMO
BACKGROUND: The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. METHODS: The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. RESULTS: Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZ-alone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). CONCLUSIONS: The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. CLINICAL TRIALS REGISTRATION: NCT00441285.
Assuntos
Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Encefalopatias/tratamento farmacológico , Neurocisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Taenia solium/efeitos dos fármacos , Adolescente , Adulto , Albendazol/farmacologia , Animais , Anticestoides/farmacologia , Encefalopatias/parasitologia , Feminino , Humanos , Masculino , Neurocisticercose/parasitologia , Praziquantel/farmacologia , Adulto JovemRESUMO
BACKGROUND: The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection. METHODOLOGY: Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg. PRINCIPAL FINDINGS: Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1ß/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-ß secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls. CONCLUSIONS/SIGNIFICANCE: T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.