Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis / La ausencia de hallazgos de inflamación en líquido cefalorraquídeo retrasa el inicio de inmunoterapia en la encefalitis anti-NMDAR

ABSTRACT Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

RESUMEN La encefalitis por receptor anti-N-metil-D-aspartato (anti-NMDAR) es una encefalopatía autoinmune con una amplia variedad de síntomas, incluyendo manifestaciones neuropsiquiátricas. Nuestro objetivo en este estudio fue analizar los resultados paraclínicos de pacientes diagnosticados con encefalitis anti-NMDAR y la asociación entre inicio de sintomatología, el diagnóstico y el inicio de inmunoterapia. Encontramos un EEG anormal en 27 pacientes (93.1%), así como IRM anormal en 19 de ellos (65.5%). En contraste, el análisis de LCR mostró un patrón inflamatorio en tan solo 13 pacientes (44.8%). La ausencia de pleocitosis o proteínas incrementadas en el LCR se asoció con un mayor tiempo desde el inicio de la sintomatología hasta el inicio del tratamiento (p=0.003). Concluimos que el LCR no inflamatorio puede retrasar el diagnóstico correcto y el inicio de tratamiento en encefalitis anti-NMDAR, por lo que se recomienda la realización de estudios exhaustivos, incluyendo EEG, ante la presencia de indicadores clínicos sugerentes del padecimiento.

Neurologic Manifestations of Enterovirus 71 Infection in Korea

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.

MENINGOENCEPHALITIS DUE TO VARICELLA ZOSTER VIRUS IN AIDS PATIENTS. REPORT OF ELEVEN CASES AND REVIEW OF THE LITERATURE / Meningoencefalite pelo vírus varicela-zoster em pacientes com AIDS. Relato de onze casos e revisão da literatura

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

As complicações neurológicas do vírus varicela-zoster (VVZ) são pouco frequentes e incluem vários quadros clínicos. A reativação do VVZ em pacientes com AIDS é geralmente associada com meningoencefalite aguda e grave. Nós relatamos os dados epidemiológicos, clínicos e virológicos de onze pacientes consecutivos com diagnóstico de HIV/AIDS e comprometimento do sistema nervoso central (SNC) devido ao VVZ. Todos os pacientes eram do sexo masculino e soropositivos para HIV. O principal fator de risco para a infecção pelo HIV foi o contato sexual sem proteção. A mediana da contagem de células CD4 T foi de 142 cel/µL. Todos apresentavam sinais e sintomas devido à meningoencefalite. Seis pacientes (54,5%) apresentaram pleiocitose; todos apresentaram hiperproteinorraquia com mediana de 2,1 g/dL. A reação em cadeia da polimerase de amostra do líquido cefalorraquidiano foi positiva para VVZ em todos eles. Todos os pacientes foram tratados com aciclovir por via intravenosa em doses de 30 mg/kg/dia durante 21 dias. A sobrevida global foi de 63% (sete de 11 pacientes). Os quatro pacientes mortos tiveram uma escassa resposta celular no LCR abaixo da mediana para este parâmetro. O VVZ deve ser incluído entre os patógenos oportunistas que podem comprometer o SNC com meningoencefalite difusa e grave em pacientes com doença avançada por HIV/SIDA.

Analysis of cerebrospinal fluid in racemose form of neurocysticercosis / Análise do líquido cefalorraquidiano na forma racemosa da neurocisticercose

The present work aimed to evaluate the pattern of CSF alterations in patients diagnosed with neurocysticercosis (NCC) in racemose form.Method This is a retrospective cohort study of patients with diagnosis of NCC in racemose form. CSF samples from 26 patients were analyzed. After patient-chart analysis was performed descriptive analysis of case studies and comparison between sexes in relation to variables were obtained with CSF by Mann-Whitney and Student’s t-tests.Results The sexes did not differ statistically when compared to pleocytosis in CSF. Eosinophils were present in 31% in samples while the ELISA test presented 80% sensitivity in this case series. Of the patient total, 24 presented a meningitis pattern with lymphocytic predominance.Conclusion There was no difference in inflammatory pattern between the sexes, with predominance of lymphocytic meningitis and 80% sensitivity by ELISA test of CSF patients with racemose form of NCC.

O objetivo deste trabalho foi avaliar o padrão de alterações do LCR de pacientes com diagnóstico de neurocisticercose (NCC) na forma racemosa.Método Trata-se de estudo de coorte retrospectiva, de pacientes com diagnóstico de forma racemosa da NCC. Foram analisadas amostras de LCR de 26 pacientes. Após análise de prontuário foi realizada análise descritiva da casuística e comparação entre sexos em relação às variáveis obtidas com o LCR por meio dos testes de Mann-Whitney e t-Student.Resultados Não houve diferença estatisticamente significante quando comparado à pleocitose no LCR entre os sexos. Houve presença de eosinofilorraquia em 31% das amostras e o teste ELISA apresentou sensibilidade de 80% nesta casuística. Do total de paciente, 24 apresentaram padrão de meningite com predomínio linfocítico.Conclusão Não houve diferença no padrão inflamatório entre os sexos, com predomínio de meningite linfocítica e sensibilidade de 80% ao teste ELISA do LCR de pacientes da forma racemosa de NCC.

Un modelo de predicción de meningitis bacteriana en recién nacidos con pleocitosis del líquido cefalorraquídeo / A bacterial meningitis predictive model for newborns with cerebrospinal fluid pleocytosis

Introducción: se han desarrollado herramientas de predicción de meningitis bacteriana (MB) en pacientes pediátricos, pero ellas no incluyen el período neonatal. Objetivo: diseñar y validar un modelo de predicción de MB en pacientes neonatales quienes presentan pleocitosis del líquido cefalorraquídeo (LCR) al ser evaluados por variables clínicas y de laboratorio. Pacientes y método: estudio retrospectivo y analítico, que incluyó 320 pacientes neonatales evaluados por probable infección, en quienes se hizo el diagnóstico de meningitis, 45 con MB y 275 con meningitis aséptica, e ingresados en el Servicio de Neonatología del Hospital Pediátrico Universitario Juan M. Márquez, entre Febrero de 1992 y Diciembre del 2009. Se creó un Modelo Predictivo de Meningitis Bacteriana, sobre la base de un conjunto de variables identificadas mediante procedimientos de análisis uni y multivariado. El modelo se diseñó a partir de una población de derivación y se contrastó en otro grupo, este de validación. Resultados: las variables seleccionadas para integrar el modelo predictivo fueron: 1) Apariencia de estado tóxico-infeccioso, 2) Convulsiones en el transcurso de la enfermedad, 3) Tinción de Gram del LCR positiva, 4) Proporción de leucocitos polimorfonucleares en el LCR >80 por ciento, y 5) Glucorraquia <1.0 mMol/l. Con estas variables se alcanzaron sensibilidad y valor predictivo negativo de 100.0 por ciento. Con el modelo propuesto, en el grupo de derivación no hubo ningún paciente malclasificado con predicción negativa de MB pero portador de este tipo de infección. En el grupo de validación, el modelo tuvo un desempeño similar, lo cual lo acredita como un modelo de predicción validado internamente. Conclusiones: el modelo de predicción diseñado descansa en variables de evaluación rutinarias, y permitió identificar inequívocamente la totalidad de los pacientes neonatales con MB. Su empleo podría ser una herramienta útil en la toma de decisiones clínicas

Introduction: there were developed a prediction tools for bacterial meningitis (BM) in pediatric patients, but those do not include the neonatal period. Objetive: to develop and validate a prediction model for BM in neonatal patients who present pleocytosis of the cerebrospinal fluid (CF) when they were evaluated by clinical and laboratory variables. Patients and method: retrospective and analytic study, which included 320 neonatal patients evaluated for probable infection, with the diagnosis of meningitis, 45 with BM and 275 with aseptic meningitis, and who were admitted in the Neonatology Ward at the Universitary Pediatric Hospital Juan M. Márquez, from february of 1992 up to december of 2009. There was developed a Predictive Model for BM, owing to some variables identified in uni and multivariate analysis. This model was developed from a derivation group and it was contrasted in the validation group. Results: the variables selected to be included at the predictive model were: 1) Toxic appearance, 2) Seizures in the course of the illness, 3) positive CF Gram stain, 4) Polymorphonuclear leukocytes proportion in CF >80 percent , and 5) CF glucose concentration <1.0 mMol/l. The values for the variables as a whole revealed to have 100.0 percent sensitivity and negative predictive values. With this proposed model there were not any patient misclassified with negative prediction for BM, who result bearer of this kind of infection, in the derivation group. In the validation group the model had a similar performance, which accredit it like an internally validate model. Conclusions: the prediction model developed rest on rutinary evaluation variables, and it allowed to identify without errors all neonatal patients with BM. The ejecution of this model would be an usefull tool in the clinical decisions making

Prediction of bacterial meningitis based on cerebrospinal fluid pleocytosis in children

Children with cerebrospinal fluid pleocytosis are frequently treated with parenteral antibiotics, but only a few have bacterial meningitis. Although some clinical prediction rules, such as bacterial meningitis score, are of well-known value, the cerebrospinal fluid white blood cells count can be the initial available information. Our aim was to establish a cutoff point of cerebrospinal fluid white blood cell count that could distinguish bacterial from viral and aseptic meningitis. A retrospective study of children aged 29 days to 17 years who were admitted between January 1st and December 31th, 2009, with cerebrospinal fluid pleocytosis (white blood cell > 7 µL-1) was conducted. The cases of traumatic lumbar puncture and of antibiotic treatment before lumbar puncture were excluded. There were 295 patients with cerebrospinal fluid pleocytosis, 60.3% females, medium age 5.0 ± 4.3 years distributed as: 12.2% 1-3 months; 10.5% 3-12 months; 29.8% 12 months to 5 years; 47.5% >5 years. Thirty one children (10.5%) were diagnosed with bacterial meningitis, 156 (52.9%) viral meningitis and 108 (36.6%) aseptic meningitis. Bacterial meningitis was caused by Neisseria meningi tidis (48.4%), Streptococcus pneumoniae (32.3%), other Streptococcus species (9.7%), and other agents (9.7%). cerebrospinal fluid white blood cell count was significantly higher in patients with bacterial meningitis (mean, 4839 cells/µL) compared to patients with aseptic meningitis (mean, 159 cells/µL, p < 0.001), with those with aseptic meningitis (mean, 577 cells/µL, p < 0.001) and with all non-bacterial meningitis cases together (p < 0.001). A cutoff value of 321 white blood cell/µL showed the best combination of sensitivity (80.6%) and specificity (81.4%) for the diagnosis of bacterial meningitis (area under receiver operating characteristic curve 0.837). Therefore, the value of cerebrospinal fluid white blood cell count was found to be a useful and rapid diagnostic test to distinguish between bacterial and nonbacterial meningitis in children.

A Case of Recurrent Neuro-Behcet's Disease after Tooth Extraction

We report a 39-yr-old man with neuro-Behcet's disease (NBD) in remission who developed left-sided ataxia with a sensory deficit about 10 days after tooth extraction. Several years ago, he experienced a similar episode of relapse after tooth extraction. Brain magnetic resonance imaging showed a newly developed right thalamic lesion. In cerebrospinal fluid, lymphocyte-dominant pleocytosis and mild elevation of IgG were found. Immunologic factors may be important in the pathogenesis of NBD because of the time delay between tooth extraction and relapse. Careful observation and prevention are needed before dental procedures in patients with NBD.

Pseudomigrânea com pleocitose liquórica: monitorizaçäo intermitente da pressäo intracraniana. Relato de caso / Pseudomigraine with CSF pleocytosis: intermittent measurement of the intracranial pressure. Case report

A pseudomigrânea com pleocitose é uma desordem benigna e auto limitada, caracterizada por sintomas recorrentes, sugestivos de migrânea associada a comprometimento neurológico focal e a alteraçöes no líquido cefalorraquidiano. Monitorizamos a pressäo intracraniana em um paciente com este diagnóstico durante os seus períodos sintomáticos e assintomáticos. O paciente foi submetido a três punçöes lombares com análise citoquímica demonstrando aumento de leucócitos, predominando monomorfonucleares, sem a identificaçäo de agente etiológico. Durante a primeira e a terceira punçäo lombar o paciente apresentava sintomas neurológicos e cefaléia com características de migrânea, sua pressäo intracraniana era de 400 e 440 mmH2O respectivamente. Em um momento assintomático realizamos nova punçäo lombar ao qual demonstrou pressäo intracraniana de 190 mmH20. Os mecanismos fisiopatológicos desta desordem permanecem ainda desconhecidos, existindo algumas evidências que ela esteja relacionada a fenômenos autoimunes, que durante os períodos sintomáticos produzem uma reduçäo no fluxo sangüíneo cerebral assemelhando-se a depressäo alastrante. Os achados neste relato de caso sugerem a possibilidade de influência das oscilaçöes da pressäo intracraniana nos possíveis mecanismos fisiopatológicos da pseudomigrânea com pleocitose