[Lymphocyte shift in a patient with herpetic encephalitis. Report of one case]. / Viraje linfocitario en un caso de encefalitis herpética: La importancia del análisis del líquido cefalorraquídeo. Caso clínico.

Central nervous system infections are a medical emergency, due to their high fatality and sequelae. Timely treatment is essential, and should be initially indicated empirically by clinical guidance, without microbiological certainty. Hence the importance of cerebrospinal fluid (CSF) analysis as an etiological and therapeutic guide in the crucial initial hours of management. We report a 57-year-old woman consulting for fever and altered mental status. A brain CAT scan was normal. A lumbar puncture disclosed a CSF with predominance of neutrophils. Suspecting a bacterial meningitis, antimicrobial treatment was started but 48 hours after, the patient did not improve. A new lumbar puncture disclosed a CSF with predominance of lymphocytes. The lymphocyte shift prompted a PCR that was positive for herpes virus. The patient was treated with acyclovir with a good evolution.

Viraje linfocitario en un caso de encefalitis herpética: La importancia del análisis del líquido cefalorraquídeo. Caso clínico / Lymphocyte shift in a patient with herpetic encephalitis. Report of one case

Central nervous system infections are a medical emergency, due to their high fatality and sequelae. Timely treatment is essential, and should be initially indicated empirically by clinical guidance, without microbiological certainty. Hence the importance of cerebrospinal fluid (CSF) analysis as an etiological and therapeutic guide in the crucial initial hours of management. We report a 57-year-old woman consulting for fever and altered mental status. A brain CAT scan was normal. A lumbar puncture disclosed a CSF with predominance of neutrophils. Suspecting a bacterial meningitis, antimicrobial treatment was started but 48 hours after, the patient did not improve. A new lumbar puncture disclosed a CSF with predominance of lymphocytes. The lymphocyte shift prompted a PCR that was positive for herpes virus. The patient was treated with acyclovir with a good evolution.

Epidemiological surveillance of herpes viral encephalitis in Cordoba, Colombia.

Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.

[Clinical characteristics of adult patients with herpetic meningoencephalitis: a nested case control study]. / Variables clínicas asociadas al diagnóstico de meningo-encefalitis herpética en pacientes adultos: un estudio anidado de casos y controles.

INTRODUCTION: Herpes simplex virus (HSV) is the most common etiology of sporadic encephalitis and presents with an estimated mortality of 50-70%. OBJECTIVE: To describe baseline characteristics of patients with herpetic encephalitis admitted to a tertiary teaching hospital and their difference with patients with non herpetic encephalitis. MATERIALS AND METHODS: Nested case control study using a retrospective cohort of patients with suspected encephalitis admitted to the Hospital Italiano de Buenos Aires (2006-2013). Adult patients included had a lumbar puncture with a positive or negative polimerase reaction for HSV. A case of herpetic encephalitis was defined as a positive polimerase reaction in spinal fluid. For each case, 5 controls were randomly selected. RESULTS: There were no baseline differences present between cases and controls. The only covariate associated with herpetic encephalitis was an abnormal brain magnetic resonance imaging (MRI) (OR: 5.37, IC 95% 1.42-20.38, p < 0.01). The most frecuent alterations in the MRI were extratemporal lesions or temporal ones with or without haemorrhage. DISCUSSION: There are no apparent baseline clinical differences between patients with or without herpetic encephalitis. A positive finding in a brain MRI should be taken into account during clinical workup.

Variables clínicas asociadas al diagnóstico de meningo-encefalitis herpética en pacientes adultos: un estudio anidado de casos y controles / Clinical characteristics of adult patients with herpetic meningoencephalitis: a nested case control study

Introduction: Herpes simplex virus (HSV) is the most common etiology of sporadic encephalitis and presents with an estimated mortality of 50-70%. Objective: To describe baseline characteristics of patients with herpetic encephalitis admitted to a tertiary teaching hospital and their difference with patients with non herpetic encephalitis. Materials and Methods: Nested case control study using a retrospective cohort of patients with suspected encephalitis admitted to the Hospital Italiano de Buenos Aires (2006-2013). Adult patients included had a lumbar puncture with a positive or negative polimerase reaction for HSV. A case of herpetic encephalitis was defined as a positive polimerase reaction in spinal fluid. For each case, 5 controls were randomly selected. Results: There were no baseline differences present between cases and controls. The only covariate associated with herpetic encephalitis was an abnormal brain magnetic resonance imaging (MRI) (OR: 5.37, IC 95% 1.42-20.38, p < 0.01). The most frecuent alterations in the MRI were extratemporal lesions or temporal ones with or without haemorrhage. Discussion: There are no apparent baseline clinical differences between patients with or without herpetic encephalitis. A positive finding in a brain MRI should be taken into account during clinical workup.

Introducción: El virus herpes simplex (VHS) es la causa reportada más común de encefalitis esporádica con una mortalidad estimada de 50 a 70%. Objetivo: Describir las características de los pacientes con encefalitis herpética (EH) en nuestro medio y sus variables clínicas asociadas. Materiales y Métodos: Estudio anidado de casos y controles sobre una cohorte retrospectiva en el Hospital Italiano de Buenos Aires (2006-2013). Se incluyeron pacientes adultos con sospecha de encefalitis a quienes se les realizó una punción lumbar con posterior reacción de polimerasa en cadena para VHS en líquido cefalorraquídeo. Por cada caso (reacción positiva para VHS) se tomaron cinco controles aleatoriamente seleccionados. Resultados: No se observaron diferencias significativas en las características demográficas y clínicas entre los casos de EH y los controles. La única variable clínica asociada al diagnóstico de EH fue la alteración en la resonancia magnética (RM) de cerebro (OR: 5,37, IC 95% 1,4220,38; p < 0,01). Los patrones más comunes de alteración en la RM fueron las lesiones extra-temporales o lesiones temporales con o sin hemorragia. Discusión: Este hallazgo nos hace jerarquizar el hallazgo de un resultado positivo en la RM durante la valoración inicial de un paciente con clínica compatible de EH.

[Neonatal herpes simplex encephalitis: clinical profile versus molecular biology]. / Encefalitis herpética neonatal: valor de la clínica versusla biología molecular.

Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

Encefalitis herpética neonatal: valor de la clínica versusla biología molecular / Neonatal herpes simplex encephalitis: clinical profile versus molecular biology

Herpes simplex encephalitis is a diagnostic challenge and causes high morbidity and mortality in children. Early suspicion of the disease and a rapid, safe and useful diagnostic test are relevant because up to 70% of the cases may die. We report the case of a newborn girl aged 25 days, who presented with a clinical picture that was compatible with herpes simplex encephalitis where the confirmation of the etiological diagnosis was delayed. Only by repeated real-time polymerase chain reaction it was possible to confirm the presence of herpes simplex virus type 1 in the cerebrospinal fluid.

La encefalitis herpética genera un desafío diagnóstico y es causa de alta morbi-mortalidad en niños. Se requiere de una sospecha clínica precoz y una prueba diagnóstica útil, rápida y segura, ya que sin tratamiento oportuno y adecuado, hasta 70% de los casos puede fallecer. Comunicamos el caso de una recién nacida de 25 días de vida, que presenta un cuadro clínico compatible con encefalitis herpética, donde el diagnóstico etiológico tardó en ser confirmado y sólo la técnica de reacción de la polimerasa en cadena en tiempo real (RPC-TR) aplicada de forma repetida permitió certificar la presencia de virus herpes simplex tipo 1 en el LCR.

Meningomielitis asociadas a infección por herpes virus humano 7: Comunicación de dos casos / Meningomyelitis associated with infection by human herpes virus 7: Report of two cases

Human herpesvirus 7 (HHV-7) may cause encephalomyelitis in immune competent adults. We report two patients infected by the virus. A 34-year-old male presenting with paraparesis and a sensitive deficiency located in D6 dermatome. Cerebrospinal fluid had 35 white blood cells per mm³ and 75 mg protein per dl. A PCR-microarray examination was positive for HHV-7. The patient was treated with prednisolone and ganciclovir with full recovery. A 27-year-old male presenting with headache, fever and diarrhea. Cerebrospinal fluid analysis showed 160 cells per mm³ and 75 mg protein per dl. Viral RNA detection was positive for HHV-7. The patient was managed with analgesia and rest and was discharged with the diagnosis of viral meningitis. Our communication supports the notion that HHV-7 may be considered as pathogen factor in humans, even in immune competent ones.

[Meningomyelitis associated with infection by human herpes virus 7: report of two cases]. / Meningomielitis asociadas a infección por herpes virus humano 7: Comunicación de dos casos.

Human herpesvirus 7 (HHV-7) may cause encephalomyelitis in immune competent adults. We report two patients infected by the virus. A 34-year-old male presenting with paraparesis and a sensitive deficiency located in D6 dermatome. Cerebrospinal fluid had 35 white blood cells per mm³ and 75 mg protein per dl. A PCR-microarray examination was positive for HHV-7. The patient was treated with prednisolone and ganciclovir with full recovery. A 27-year-old male presenting with headache, fever and diarrhea. Cerebrospinal fluid analysis showed 160 cells per mm³ and 75 mg protein per dl. Viral RNA detection was positive for HHV-7. The patient was managed with analgesia and rest and was discharged with the diagnosis of viral meningitis. Our communication supports the notion that HHV-7 may be considered as pathogen factor in humans, even in immune competent ones.

[Herpetic encephalitis: case series of 15 patients confirmed by polymerase chain reaction]. / Encefalitis herpética: serie clínica de 15 casos confirmados por reacción de polimerasa en cadena.

Encephalitis by herpes simplex virus (HSV) is an sporadic and the most important cause of encephalitis in the western world. The aim of this study was to describe the main clinical features and response to therapy in a representative series of cases. Fifteen cases confirmed by polymerase chain reaction were identified in two university hospitals in Santiago. Average age was 41 years (range 5-78) being 80% over 30 years old. Most cases presented with fever and sensorial involvement (80%) or headache (67%) and only a minority with seizures or focal signs (< or =15%). Extracerebral herpetic lesions were present in two patients (13%). Average length of symptoms was 3. 8 days and most cases were associated to type 1 HSV (86.7%). Changes were detected in 91.7% of those evaluated with electroencephalogram, in 81.8% of those evaluated with nuclear magnetic resonance and in only 13.3% of those evaluated with a cerebral CT-scan. All patients were treated with acyclovir and case-fatality ratio was 13.3%, although one death in a patient with AIDS and CNS lymphoma could not be related to HSV. Six patients (40%) showed neurological deficit at discharge. Death or neurological deficit at discharge was associated with a delay > 3 days before acyclovir therapy. (p = 0.01, two-tailed Fisher test).

Encefalitis herpética: Serie clínica de 15 casos confirmados por reacción de polimerasa en cadena / Herpetic encephalitis: Case series of 15 patients confirmed by polymerase chain reaction

La encefalitis herpética es la causa más frecuente de encefalitis esporádica en el mundo occidental. Para conocer las principales características clínicas de esta enfermedad en nuestro medio, se efectuó un análisis de casos confirmados por reacción de polimerasa en cadena en dos hospitales universitarios de Santiago. Un total de 15 casos pudo ser identificado con un promedio de edad de 41 años (5-78 años) y 80% ³ 30 años, el primero de ellos el año 1998. La mayor parte se presentó con fiebre y compromiso de conciencia (80% cada uno) o cefalea (67%). Las convulsiones y la focalización fueron infrecuentes (£ 15%) y sólo 2 casos (13%) tuvieron además una manifestación herpética extracerebral. La duración promedio de los síntomas fue de 3,8 días. La mayor parte estuvo asociada al serotipo 1 (86,7%). El 91,7% de los casos evaluados presentó alteraciones electroencefalográficas, 81,8% alteraciones en la resonancia magnética y sólo 13,3% en la tomografía axial computarizada. La totalidad de los pacientes fue tratada con aciclovir y la letalidad fue de 13,3%, aunque el deceso en un paciente con SIDA y linfoma del SNC no pudo ser atribuido a la infección herpética. Seis pacientes (40%) presentaban secuelas neurológicas al momento del egreso. La muerte o alteraciones neurológicas al alta estuvieron asociadas significativamente a un inicio del tratamiento > 3 días desde el inicio de los síntomas. (p = 0,01 prueba bilateral de Fisher).

Encefalitis: ¿cuáles y cómo tratar? / Encephalitis: which are and how to treat?

La causa más frecuente de encefalitis es la infección viral que invade el SNC por vía sanguínea (p ej.: enterovirus) , nervios periféricos (p ej.: rabia) y menos frecuentemente, vía nervio olfatorio (p ej.: amebas de vida libre). El compromiso focal de las células nerviosas explica las variaciones sintomáticas. En nuestro medio ningún virus predomina ostensiblemente y las características epidemiológicas y clínicas pueden crear confusión inicial. La encefalitis herpética es una emergencia neurológica por la necesidad de un diagnóstico precoz, para instalar el tratamiento específico. El VHS-1 es importante en niños y los adultos; VHS-2 en el neonato. El rendimiento del aislamiento viral en el LCR es bajo, la RPC tiene una sensibilidad aproximada de 91 por ciento y alta especificidad permaneciendo positiva hasta cinco a siete días después de iniciada la sintomatología y/o el tratamiento. El EEG es sensible pero poco especifico. La RM es el examen imagenológico indicado en etapa aguda; la TAC permite controlar la evolución. La biopsia cerebral se reserva para casos con falta de respuesta objetiva al tratamiento. El aciclovir reduce la letalidad y las secuelas de la encefalitis herpética, dosis de 60 mg/kg/d en recién nacidos han elevado su sobrevida. Valaciclovir y famciclovir, con similar actividad antiviral, podrían emplearse para prolongar el efecto antiviral más allá de 21 días. En la encefalitis por enterovirus las manifestaciones cutáneas o la miocarditis pueden orientar el diagnóstico etiológico inicialmente. Se debate la capacidad de Mycoplasma pneumoniae para producir trastornos del SNC, si bien invade el LCR, no se ha logrado definir su rol patógeno. Menos importantes son VHH-6, virus de Epstein-Barr, adenovirus, Bartonella henselae, Cryptococcus neoformans, Leptospira sp. y otros. Es posible que nuevos tratamientos específicos estimulen el desarrollo de tecnologías que nos permitan conocer mejor los reales agentes de encefalitis aguda en nuestro país.

[Alternative diagnoses among suspected herpes simplex encephalitis patients with negative polymerase chain reaction]. / Diagnósticos alternativos em pacientes com suspeita de encefalite por Herpes simplex e negativos à reação em cadeia por polimerase (PCR).

The aim of this study was to analyze the diagnosis found in a series of patients in which the diagnosis of Herpes simplex encephalitis (HSE) was ruled out by a negative polymerase chain reaction (PCR) result for HSV DNA in cerebrospinal fluid (CSF) samples. Forty three out of 61 HSE suspected patients had negative PCR. An alternative diagnosis was established in 41.9% of these patients. These patients were diagnosed as having viral (2 cases-11.1%) and non viral (5 cases-27.2%) CNS infections, vascular (4 cases-22.2%) and demyelinating diseases (3 cases-16.7%), metabolic disturbances (3 cases-16.7%), and CNS tumor (1 case-5.6%). The non specific clinical presentation of this disease and the availability of an efficient treatment for HSE explain why several patients with other diseases were initially treated with acyclovir. The early use of PCR in CSF was considered essential for the evaluation of the acute encephalitis cases in this study.

Diagnósticos alternativos em pacientes com suspeita de encefalite por Herpes simplex e negativos à reaçäo em cadeia por polimerase (PCR) / Alternative diagnoses among suspected Herpes simplex encephalitis patients with negative polymerase chain reaction (PCR)

O objetivo do presente estudo é analisar os diagnósticos encontrados em uma série de pacientes cuja suspeita clínica inicial era de encefalite herpética (HSE), mas que tiveram este diagnóstico afastado através de resultado negativo à reaçäo em cadeia por polimerase (PCR) para detecçäo do Herpes simples (HSV) em líquido cefalorraqueano (LCR). Em 43 dos 61 pacientes com suspeita de HSE estudados (70,5 por cento) o resultado à PCR foi negativo. O diagnóstico diferencial foi elucidado em 41,9 por cento dos 43 casos em que a PCR para HSV resultou negativa. Nestes, as patologias diagnosticadas foram infecçöes virais (2 casos-11,1 por cento) e näo virais (5 casos-27,2 por cento), doenças vasculares (4 casos-22,2 por cento), desmielinizantes (3 casos-16,7 por cento), distúrbios tóxico-metabólicos (3 casos-16,7 por cento) e tumor do sistema nervoso central (1 caso-5,6 por cento). A pouca especificidade do quadro clínico e a disponibilidade de tratamento eficaz e seguro para a HSE justificam a grande quantidade de casos tratados com aciclovir, mas cujo diagnóstico de encefalite pelo HSV näo foi confirmado. A utilizaçäo da PCR no LCR contribuiu para melhor avaliaçäo etiológica dos quadros de encefalite aguda aqui estudados

[Dynamics of intrathecal immunoglobulin synthesis]. / Dinámica de la síntesis intratecal de inmunoglobulinas.

INTRODUCTION: Dynamics of the immune response in Central Nervous System (CSN) is different from the well-known switch of IgM synthesis to IgG synthesis in blood. OBJECTIVE: Broadcast the behavior and the factors involved in the dynamics of the intrathecal immune response in infectious neurological disorders. DEVELOPMENT: The lack of a switch from IgM class response to IgG response could be more related to regulation-modulation mechanisms of the CNS immune response than differs from blood in a different cytokines composition, and the possibility of chemokines synthesis during the neuroinflammatory process, and the neuroimmune-endocrine mechanisms. The immune pattern can be stable like neuroborreliosis, and can be modify like in herpes simplex meningoencephalitis. It could have a typical pattern like in Neisseria meningitidis meningoencephalitis and neurotuberculosis. Also the pattern could be still detectable for many years after sufficient treatment and complete recovery of the symptom-free patients like in neurosyphilis or an advanced precocious response during the childhood. In HIV encephalopathy the pattern remains the same during the evolution but in other virus infections, like Echo 6 or Coxsackie B5, depends on the biological agent. CONCLUSIONS: In order to know the acuity of the disease, we have to know the physiopathologic characteristics of the biological agents, time courses, locations of the pathological processes, and the host age. The main signs in cerebrospinal fluid of an acute, active disease of CNS are the increased of cerebrospinal fluid cell count and the increased of albumin ratio.