New guidelines for the diagnosis and treatment of neurocysticercosis: a difficult proposal for patients in endemic countries.

INTRODUCTION: Recent guidelines for the diagnosis and treatment for neurocysticercosis (NC) from the Infectious Disease Society of America/American Society of Tropical Medicine and Hygiene were developed to be used in the United States and Canada, where only a small fraction of NC cases occur. Areas covered: The paper discusses the strengths and weakness of the proposed guidelines. Expert commentary: Although these new guidelines bring much needed attention to a neglected parasitic disease, some of the recommendations made are based on insufficient and/or inadequate evidence. The authors only recommend one specific immunological assay for use in the diagnosis of NC, when evidence clearly supports other options. The authors strongly recommend dual-anthelminthic for patients with multiple active parenchymal cysts on the basis of one clinical trial that was stopped early. The authors recommend surgical removal of cysts in the fourth ventricle and long-term treatment for subarachnoid NC despite their own admission that there is little evidence to support these recommendations. We propose that clinicians should approach some of the recommendations in the new guidelines with caution and call for the establishment of gold-standard guidelines that can be used and adapted for the diagnosis and treatment of patients with NC worldwide.

Neurocysticercosis: the good, the bad, and the missing.

INTRODUCTION: Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management. The role of inflammation, which is required for parasite death and reabsorption, but may lead to severe complications, must be better understood. Valid screening tools including immunological and molecular tests need to be developed to reduce the reliance on neuroimaging which is not usually accessible in endemic areas. Prognosis for people with parenchymal NC is generally good after treatment, but there are no sufficiently powered randomized trials evaluating antiparasitic treatment for extraparenchymal NC. Most people with seizures do not develop epilepsy. Overemphasizing NC as the main cause of epilepsy could increase stigmatization with potential medico/social implications. Several tools for prevention and control of taeniasis/cysticercosis are available, but strategies to eradicate NC must be created with the involvement of all stakeholders.

New diagnostic criteria for neurocysticercosis: Reliability and validity.

OBJECTIVE: The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. METHODS: A group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity. RESULTS: Inter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specificity of 94.9%. INTERPRETATION: These criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis. Ann Neurol 2016;80:434-442.

Steroids in neuroinfection.

The consequences of inflammatory response are primarily responsible for morbimortality in bacterial meningitis. Early use of steroids in these cases can reduce mortality and hearing loss and improve functional outcome without causing significant side effects. The formal recommendation towards pneumoccocal meningitis is being extended to other forms of Bacterial Meningitis. The same thought can be applied to tuberculous meningitis. In neurocysticercosis and neuroschistosomiasis steroids are more useful than parasiticides in most cases. Despite the evidence favoring the use of steroids in herpes simplex encephalitis, it is not sufficient to definitely support such indication. Among the opportunistic infections that affect AIDS patients, neurotoxoplasmosis and progressive multifocal leukoencephalopaty are those most often considered for the use of steroids; steroids are safe to use, but no definite benefit could be demonstrated in both conditions.

Steroids in neuroinfection / Esteroides em neuroinfeccao

The consequences of inflammatory response are primarily responsible for morbimortality in bacterial meningitis. Early use of steroids in these cases can reduce mortality and hearing loss and improve functional outcome without causing significant side effects. The formal recommendation towards pneumoccocal meningitis is being extended to other forms of Bacterial Meningitis. The same thought can be applied to tuberculous meningitis. In neurocysticercosis and neuroschistosomiasis steroids are more useful than parasiticides in most cases. Despite the evidence favoring the use of steroids in herpes simplex encephalitis, it is not sufficient to definitely support such indication. Among the opportunistic infections that affect AIDS patients, neurotoxoplasmosis and progressive multifocal leukoencephalopaty are those most often considered for the use of steroids; steroids are safe to use, but no definite benefit could be demonstrated in both conditions.

As consequências da resposta inflamatória são as grandes responsáveis pela morbimortalidade das meningites bacterianas. O uso precoce de esteróides nestes casos pode reduzir a mortalidade e a perda auditiva, além de atenuar as consequências a longo prazo deste grupo de doenças, sem causar efeitos colaterais importantes. A recomendação formal de seu uso na meningite pneumocócica tem sido ampliada para outras formas de meningite bacteriana. O mesmo raciocínio pode ser aplicado para a Meningite tuberculosa. Na neurocisticercose e na neuroesquistossomose, os esteróides são mais úteis que as drogas parasiticidas na maior parte dos casos. Apesar de evidências a favor do seu uso na Encefalite Herpética, não existe ainda suporte definitivo para esta recomendação. Entre as infecções oportunísticas que ocorrem nos pacientes com AIDS, a Neurotoxoplasmose e a leucoencefalopatia multifocal progressiva são as mais frequentemente relacionadas com o uso dos esteróides; seu uso tem se mostrado seguro, mas seus benefícios não parecem bem estabelecidos em ambas as condições.

Season of birth as a risk factor for multiple sclerosis in Brazil.

Risk factors for development of multiple sclerosis (MS) are still a matter of debate. Latitude gradient, vitamin D deficiency and season of birth are among the most investigated environmental factors associated with the disease. Several international studies suggest that birth in spring is a substantial risk factor for MS. We investigated the season of birth as a potential risk for MS in different geographical regions of Brazil. We conducted a cross-sectional retrospective study with 2257 clinically definite MS patients enrolled in 13 Brazilian MS clinics in the south, southeast, and northeast regions of Brazil. Demographic and clinical data relating to date of birth and clinical features of the disease were collected and analysed, and subsequently compared with birth date among the general Brazilian population. The distribution of date of birth of MS patients showed an increase in spring and a decrease in autumn, with no difference being observed in the other seasons. In conclusion, season of birth is a probable risk factor for MS in most parts of Brazil. These findings may be related to the role that vitamin D plays in MS pathogenesis.

Neurocysticercosis: relationship between Taenia antigen levels in CSF and MRI.

OBJECTIVE: To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings in patients with definite diagnosis of neurocysticercosis (NC). METHOD: Sixty-three patients with definite diagnosis of NC were submitted to a MRI of the brain, and to a CSF examination, with a meticulous search for TA by ELISA. RESULTS: TA detection was positive in 36 patients (57.1%). A total of 836 lesions were analyzed, greatly within the cerebral parenchyma (98.7 of the lesions). Intact or non-degenerating cysts were the most common evolutive phase observed (50.4% of all lesions), 22.1% were degenerating cysts and 19.5% calcified cysts. We observed a significant relationship between TA levels detected and the total number of lesions and the number of non-degenerating cysts, but not with calcified lesions. CONCLUSION: According to our results, we propose at least four important types of contribution: (1) TA detection may allow etiologic diagnosis in transitional phases of NC, with non-characteristic images; (2) in final stages of evolution of cysticercoids in the CNS, lesions may not appear on CT or MRI, and TA detection may contribute to a definite etiologic diagnosis; (3) TA detection may permit diagnosis of NC in some patients with previous negative tests for antibody detection in CSF; (4) TA detection may represent an accurate marker of disease activity in the epileptic form of NC.

Neurocysticercosis: relationship between Taenia antigen levels in CSF and MRI / Neurocisticercose: relação entre antígeno da Taenia no líquido cefalorraquidiano e ressonância magnética

Objective: To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings in patients with definite diagnosis of neurocysticercosis (NC). Method: Sixty-three patients with definite diagnosis of NC were submitted to a MRI of the brain, and to a CSF examination, with a meticulous search for TA by ELISA. Results: TA detection was positive in 36 patients (57.1 percent). A total of 836 lesions were analyzed, greatly within the cerebral parenchyma (98.7 of the lesions). Intact or non-degenerating cysts were the most common evolutive phase observed (50.4 percent of all lesions), 22.1 percent were degenerating cysts and 19.5 percent calcified cysts. We observed a significant relationship between TA levels detected and the total number of lesions and the number of non-degenerating cysts, but not with calcified lesions. Conclusion: According to our results, we propose at least four important types of contribution: (1) TA detection may allow etiologic diagnosis in transitional phases of NC, with non-characteristic images; (2) in final stages of evolution of cysticercoids in the CNS, lesions may not appear on CT or MRI, and TA detection may contribute to a definite etiologic diagnosis; (3) TA detection may permit diagnosis of NC in some patients with previous negative tests for antibody detection in CSF; (4) TA detection may represent an accurate marker of disease activity in the epileptic form of NC.

Objetivo: Determinar a relação entre a detecção de antígeno de Taenia (TA) no líquido cefalorraquidiano (LCR) e achados de ressonância magnética (RM) em pacientes com diagnóstico definitivo de neurocisticersose. Método: Sessenta e três pacientes com diagnóstico de NC foram submetidos a exame de RM e exame de LCR com pesquisa de antígeno de Taenia por método imunoenzimático. Resultados: A detecção de TA foi positiva em 36 pacientes (57,1 por cento). Um total de 836 lesões foram analizadas sendo 98,7 por cento intraparemquimatosas, 50,4 por cento dos cistos encontravam-se íntegros, 22,1 por cento degenerados e 19,5 por cento calcificados. Foi observada relação significativa entre a presença dos níveis de TA detectados com o número total dos cistos e também com o número de cistos íntegros. Não foi observada relação com cistos calcificados. Conclusão: (1) a detecção de TA permite o diagnóstico etiológico em formas transicionais na NC com imagem pouco característica; (2) em estágio evolutivo final de um cisticerco no sistema nervoso, este pode não aparecer na tomografia computadorizada ou RM sendo a presença do antígeno importante para confirmação diagnóstica; (3) a detecção do TA permite também o diagnóstico de NC nos casos em que as reações inumológicas são negativas; (4) a detecção do TA representa um marcador de atividade da doença nas formas epiléticas da NC.

Taenia solium DNA is present in the cerebrospinal fluid of neurocysticercosis patients and can be used for diagnosis.

Neurocysticercosis is the most frequent parasitic infection of the CNS and the main cause of acquired epilepsy worldwide. Seizures are the most common symptoms of the disease, together with headache, involuntary movements, psychosis and a global mental deterioration. Absolute diagnostic criteria include the identification of cysticerci, with scolex, in the brain by MRI imaging. We demonstrate here, for the first time, that T. solium DNA is present in the cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis of parasite DNA in the CSF may be a strong support for the diagnosis of neurocysticercosis.

Neurocisticercose: relação entre dosagem de antígenos de taenia no líquido cefalorraquidiano e imagem através de ressonância magnética / Neurocysticercosis: relationship between taenia antigen detection in the cerebrospinal fluid and magnetic resonance imaging

Neurocisticercose (NC) é a doença parasitária mais comum do SNC, representando grave problema de saúde pública em nosso país. O diagnóstico da NC é baseado em dados clínicos e epidemiológicos, reações sorológicas no soro e LCR, além de exames de neuroimagem. A detecção de antígenos de Taenia através de teste de ELISA, mediante a utilização de anticorpos altamente purificados, constitui metodologia recente capaz de informar sobre a vigência de atividade clínica da doença. O objetivo deste estudo foi determinar a relação entre a dosagem de antígenos de Taenia mo LCR com as imagens obtidas através da RM, em pacientes com o diagnóstico definido de NC segundo os critérios diagnósticos atuais. Sessenta e três pacientes foram submetidos a exame detalhado do LCR, além de pesquisa de antígeno de Taenia através de teste de ELISA, utilizando anticorpos de soro de coelhos imunizados com líquido vesicular de Taenia crassiceps. Uma amostra de sangue foi colhida simultaneamente à coleta do LCR, e um exame de RM encefálica foi realizado em todos os pacientes. Observamos relação significativa entre a detecção de antígenos de Taenia e o número total de lesões e do número de cistos íntegros detectados pela RM. Quando comparados dois ou mais cistos em degeneração com apenas um cisto, observamos detecção significativamente mais alta no primeiro grupo. Encontramos também detecção de antígenos significativamente mais alta quando as lesões se localizavam na profundidade dos hemisférios cerebrais, mas não na presença de cistos calcificados. Os resultados demonstram que a detecção de antígenos de Taenia se mostra congruente com os achados de neuroimagem. Algumas outras variáveis estudadas no LCR, como número de células, teor de globulinas gama e teste de ELISA, também se mostraram concordantes, demonstrando que a resposta inflamatória na NC mobiliza tanto a imunidade celular quanto a imunidade humoral.

Neurocysticercosis (NC) is the most common parasitic infection of the nervous system, remaining a serious public health in our country. NC diagnosis is supported by clinical and epidemiological data, specific serological reactions in the blood and CSF, and neuroimaging findings. Detection of anti-Taenia antigens using ELISA techniques is a recent methodology that provides information about clinical activity of the disease. The objective of the study was to determine relationship between Taenia antigen detection in the CSF and MRI in patients with definite diagnosis of NC according to current diagnostic criteria. Sixty-three patients were submitted to a thorough CSF examination and Taenia antigen research. Antigens were detected in CSF samples by ELISA assay obtained from rabbit sera antibodies immunized with Taenia crassiceps cysticerci vesicular fluid. A blood sample was simultaneously collected and a MRI was performed in every patient. We observed a significant relationship between Taenia antigen detection and the total number of lesions and intact cysts detected by MRI. When comparing two or more degenerating cysts with only one we observed a significant higher antigen detection in the first group. We also found a significant higher antigen detection when cysts were deeply located in the cerebral hemispheres, but not in the presence of calcified cysts. Results demonstrate that Taenia antigen detection is congruent with neuroimaging findings. Some CSF characteristics, like number of cells, gamma globulin concentration and ELISA assay were also concordant with Taenia antigen detection, indicating that inflammatory reaction in NC comprise cellular and humoral immunological factors.

Taenia antigens detection in the cerebrospinal fluid of patients with neurocysticercosis and its relationship with clinical activity of the disease.

OBJECTIVE: (1) To determine the concentration of Taenia antigens in the cerebrospinal fluid (CSF) of patients with neurocysticercosis (NC); (2) to establish its relationship with clinical activity of the disease and with classical variables of CSF. METHOD: A CSF examination was performed in one sample from 36 patients with definitive diagnosis of NC, including: quantitative and cytomorphological study, biochemical tests, immunological reactions for cysticercosis and Taenia antigens. The antibodies for antigens detection were obtained from the larval form of Taenia crassiceps, ORF strain. After intraperitoneal passage through female mice, a group of rabbits was immunized with vesicular fluid antigens. RESULTS: The Taenia antigen was detected in CSF from 17 patients (47.2%), especially in those patients with epileptic symptoms in the last 12 months. CONCLUSION: Taenia antigens presence in CSF have significant relationship with clinically active forms of NC, being a more sensitive marker than the classic eosinophil presence.

Taenia antigens detection in the cerebrospinal fluid of patients with neurocysticercosis and its relationship with clinical activity of the disease

OBJETIVO: (1) Determinar a concentração de antígenos de Taenia no líquido cefalorraquidiano (LCR) em doentes com neurocisticercose; (2) estudar sua relação com a atividade clínica da doença e com as variáveis clássicas do LCR. MÉTODO: Em 36 pacientes com diagnóstico definido de neurocisticercose foi realizado exame do LCR, com estudo citológico e citomorfológico, exame bioquímico, reações imunológicas para cisticercose e detecção de antígenos de Taenia. Os anticorpos para detecção desses antígenos foram obtidos a partir da forma larvar da Taenia crassiceps, cepa ORF. Após a inoculação e proliferação intraperitoneal dessa forma larvária em ratas, foi imunizado um grupo de coelhos com seu líquido vesicular. RESULTADOS: Em 17 pacientes (47,2%) foi detectado antígeno de Taenia, especialmente naqueles com manifestação epiléptica nos últimos 12 meses. CONCLUSÃO: A detecção de antígeno de Taenia guarda relação significativa com a vigência de formas clinicamente ativas, sendo, nestas formas, marcador mais sensível que a eosinofilorraquia.

Cranioestenose da sutura metópica: efeito teratogênico do valproato de sódio. Relato de caso / Metopic suture craniosynostosis: sodium valproate teratogenic effect. Case report

OBJETIVO: alertar que o uso de valproato de sódio durante a gravidez pode determinar cranioestenose no recém-nascido, em especial a trigonocefalia. MÉTODO: relato de um caso de trigonocefalia em menina de 6 meses, filha de pais jovens, näo fumantes e cuja mäe fez uso de fenobarbital 100 mg/dia e valproato de sódio 500 mg duas vezes/dia durante toda a gravidez. Foi realizada revisäo bibliográfica sobre o assunto. RESULTADO: no ato cirúrgico pôde-se confirmar a presença de esclerose óssea sobre a sutura metópica. A revisäo bibliográfica permitiu o encontro de relatos prévios sobre a teratogenicidade do valproato de sódio, que determina principalmente cranioestenose da sutura metópica. CONCLUSÄO: o uso de valproato de sódio durante a gravidez pode determinar como açäo teratogênica a cranioestenose, especialmente a trigonocefalia (fechamento precoce da sutura metópica)

Doença encéfalo-vascular como primeira manifestaçäo de arterite temporal: relato de dois casos / Brain vascular disease presenting as first manifestation of temporal arteritis: report of two cases

É raro doença encéfalo-vascular como primeira manifestaçäo de arterite temporal. Relatamos dois casos, nos quais o diagnóstico emergiu da anamnese. Mulher de 55 anos havia apresentado enfarto em hemisfério cerebral esquerdo há 3 meses. Vinha com melhora progressiva quando teve perda visual completa e a família nos procurou para uma segunda opiniäo. A paciente havia tido hemiplegia direita, afasia e distúrbio visual à esquerda no primeiro episódio; o quadro atual era de perda visual completa bilateral. Com suspeita de arterite temporal a paciente foi internada; a VHS era de 97 mm e a fundoscopia mostrava intensa neurite óptica isquêmica. Homem de 75 anos apresentou síndrome de Wallemberg. Na revisäo da anamnese destacou-se cefaléia temporal e no exame, processo inflamatório na regiäo da artéria temporal; a VHS era de 70 mm e a biópsia confirmou diagnóstico. A "tecnolatria" tem contaminado o exercício da medicina; convém que relembremos a soberania dos dados clínicos.

Síndrome de Aicardi: relato de dois casos / Aicardi's syndrome: report of 2 cases

A síndrome de Aicardi é caracterizada por agenesia do corpo caloso, retardo mental severo, convulsöes (frequentemente espasmos em flexäo), alteraçöes caracteristicas do eletroencefalograma (padräo surto-depressäo), lacunas coriorretinianas típicas, ocorrência no sexo feminino. Outros achados associados säo displasias de costelas e de vértebras; heterotipias corticais säo encontradas frequentemente. A síndrome é de natureza hereditária, sendo no presente considerada devida a traço dominante ligado ao cromossoma X, com letalidade masculina. Descrevem-se dois casos da síndrome que mostram o quadro clínico completo da entidade