Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

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.

Encefalite herpética associada a mieloma múltiplo: desafio diagnóstico / Herpetic encephalitis associated with multiple myeloma: a diagnostic challenge

O mieloma múltiplo é a segunda neoplasia onco-hematológica mais comum, correspondendo a 1% das neoplasias malignas. Trata-se de uma condição subdiagnosticada, assim como a encefalite herpética. Entretanto, é comum a relação do mieloma com infecções, em decorrência do acometimento da imunidade humoral. A encefalite viral herpética tem como principal agente o vírus do herpes simples 1. O caso foi descrito baseado em um raciocínio clínico, visando contribuir para uma melhor caracterização do quadro clínico e do diagnóstico de duas entidades clínicas que possuem baixa suspeição diagnóstica e elevada morbimortalidade. Durante o curso da investigação, foram propostas variadas etiologias como responsáveis pelo rebaixamento do nível de consciência, levando a uma pesquisa de um espectro mais amplo de hipóteses diagnósticas, as quais precederam a confirmação do diagnóstico final. O quadro clínico atípico descrito apresentou obstáculos à suspeição diagnóstica correta, pois a ausência dos sinais e sintomas característicos de ambas as doenças levaram à pesquisa de um arsenal mais amplo de diagnósticos diferenciais. Assim, o atraso no diagnóstico e o início tardio do tratamento foram fatores que contribuíram para o prognóstico reservado do paciente. A associação dessas doenças é pouco descrita na literatura, de modo que mais estudos acerca do assunto se fazem necessários. (AU)

Multiple myeloma is the second most common onco-hematologic neoplasm, accounting for 1% of malignant neoplasms. As herpetic encephalitis, it is an underdiagnosed condition. However, the relation of myeloma with infections is common, due to the involvement of humoral immunity. Herpetic encephalitis has as its main etiological agent the herpes simplex virus 1. The case was described based on a clinical reasoning, aiming to contribute to a better characterization of the clinical picture and diagnosis of two entities that have low rates of diagnostic suspicion and high rates of morbidity and mortality. During the course of investigation, several etiologies were proposed as responsible for the decreased level of consciousness, leading to a search for a broader range of diagnostic hypotheses, which preceded confirmation of the final diagnosis. The atypical clinical picture described presented obstacles to the correct diagnostic suspicion, as the absence of symptoms and signs characteristic of both diseases led to the search for a broader arsenal of differential diagnoses. Thus, delayed diagnosis and late treatment were factors that contributed to the patient's reserved prognosis. The association of these diseases is poorly described in the literature, so further studies on that subject are required. (AU)

Meningoencefalitis herpética: ¿cuándo sospecharla? / Herpetic meningoencephalitis: a review

La encefalitis herpética (EH) secundaria a la infección por el virus de herpes simple 1 (VHS1) es la causa conocida más frecuente a nivel mundial de infección viral fatal del sistema nervioso central (SNC). La agresividad de su curso clínico y la morbilidad asociada a su desarrollo obligan a todo médico generalista a mantener una alta sospecha clínica para lograr su diagnóstico. Ciertas manifestaciones clínicas como la fiebre asociada a alteraciones en el sensorio o a alteraciones en el comportamiento de un paciente o a ambas posibilidades se presentan en un porcentaje superior al 90% de los casos confirmados. La solicitud en el líquido cefalorraquídeo (LCR) de la reacción en cadena de la polimerasa (PCR) para el VHS1 es el estudio complementario de laboratorio que posee la mayor sensibilidad y especificidad para confirmar el diagnóstico de EH. A su vez, la resonancia nuclear magnética (RNM) es el estudio de imagen que posee mayor sensibilidad y especificidad para el diagnóstico de la enfermedad. La EH secundaria al VHS1 es, de las infecciones virales que afectan el SNC, la única que posee tratamiento específico. La instauración temprana de tratamiento con aciclovir disminuye la mortalidad asociada al desarrollo de la enfermedad de un 70% y sin tratamiento, hasta un 10-20%. El objetivo principal de esta revisión es señalar las diversas situaciones clínicas en las cuales se debe sospechar la EH así como guiar la correcta utilización de los estudios complementarios e instaurar de manera temprana el tratamiento para reducir al máximo la morbimortalidad. (AU)

The herpes simplex virus type 1 (HSV1) encephalitis (EH) is the most common known cause of sporadic fatal encephalitis worldwide. The fatal consequences in the development of this disease and the morbidity related to it, should alert general practitioner to be always aware of its possible diagnosis. Clinical features such as fever associated with altered mental status or disturbances in the level of consciousness are present in more than 90% of confirmed cases. The analysis of the polymerase chain reaction (PCR) for HSV1 in central nervous system (CNS) fluid is the laboratory study of choice for establishing the diagnosis with the best sensitivity and specificity. Moreover, magnetic resonance image (MRI) is the most sensitive and specific imaging study for the detection of this entity. The VHS1 EH is one of the few treatable viral infection of the central nervous system to date. Hence, early administration of adequate antiviral therapy with Acyclovir remains paramount. The early administration of empiric therapy can decrease the mortality rate from 70% without treatment to 10-20% in confirmed cases. We sought to describe the disease's clinical features, and to further discuss the accurate use of diagnostic tools and treatment strategies in order to reduce the high related morbi-mortality. (AU)

Las encefalitis herpéticas: encefalitis producidas por la familia herpes / Herpetic encephalitis: encephalitis produced by the herpes family

La familia herpesviridae presenta seis virus neurotropos (herpes virus simpletipo 1 y 2, el varicela-zóster, citomegalovirus, herpes virus humano tipo 6 yel Epstein-Barr) que son conocidos por su capacidad de producir encefalitisen niños y adultos. La encefalitis producida por el herpes virus simple tipo 1es la mejor conocida, el resto guarda una serie de incógnitas relativas a susmanifestaciones clínicas, diagnósticas y terapéuticas no bien dilucidadashasta el momento. La aplicación de técnicas de biología molecular aplicadasal LCR han permitido una expansión del conocimiento en la materia. La actualrevisión pretende una puesta al día en la materia desde la literatura consultaday el pequeño aporte de nuestra experiencia, resaltando las similitudes ydiferencias entre estas encefalitis.

Diagnosis and quantitative detection of HSV DNA in samples from patients with suspected herpes simplex encephalitis

Diagnosis of herpes simplex encephalitis (HSE) is based on the detection of herpes simplex virus (HSV) DNA in patients' CSF samples. HSV DNA quantitation has the potential for estimating the effects of antiviral therapy. The aim of this study was to diagnose HSV DNA in HSE suspected patients and the quantitative analysis of its genome using real-time PCR to assess the value of the viral load in the course of antiviral treatment. The CSF samples were collected from 236 consecutive HSE suspected patients from November 2004 to May 2008. Upon DNA extraction, the samples were analyzed by Real-Time PCR assay. A set of primers amplified a common sequence of HSV glycoprotein B gene. The copy numbers of unknown samples were expressed via a standard curve drawn with a known amount of amplified cloned plasmid. Of the 236 samples, 137 (58 percent) came from males and 99 (42 percent) from females. The HSV genome was detected in 22 (9.3 percent) patients by PCR, 13 males/ 9 females. Serial CSF samples were available from 10 of the 22 patients. The range of the HSV DNA copy numbers in the clinical samples ranged from 2.5 × 10² to 1.7 × 10(6) copies/mL of CSF. Quantitative PCR results can be helpful in evaluating the efficacy of antiviral therapy in the above-mentioned patients. There is an association between the initial viral load and the duration of treatment course.

Clinical manifestations, laboratory findings and outcomes of children with herpetic encephalitis in Amirkola children hospital, Northern Iran

Herpes simplex encephalitis [HSE] is a fatal infection of the central nervous system. The early diagnosis of HSE is crucial because the early introduction of antiviral therapy can significantly decrease mortality and morbidity associated with this disease. This study was carried out to determine the clinical manifestations, laboratory findings and the outcome of the children admitted due to a presumptive diagnosis of HSE to Amirkola Children Hospital; a referral hospital in the north of Iran, during 2006-2007. This cross-sectional study was performed on patients with diagnosis of HSE in Amirkola Hospital, affiliated to the Babol University of Medial Sciences in the north of Iran. All of the children with a diagnosis of encephalitis were enrolled in this study. After admission, a special investigation including CSF analysis, electroencephalogram [EEG], Computerized tomography [CT scan] and/or magnetic resonance imaging [MRI] were performed. PCR [Polymerase Chain Reaction] analysis for herpes virus DNA was done on CSF sample in all patients. All the patients with a clinical diagnosis of herpetic encephalitis were treated with acyclovir at the time of admission but every patient with a positive PCR was assumed as a definite diagnosis of HSE. Clinical manifestations, laboratory findings and outcome of patients were collected. At the end of the study, frequency of HSE was reported according to the PCR for HSV DNA among the children admitted due to encephalitis. The mean age of the patients was 5.58 +/- 3.46 years. The most common clinical manifestations were fever [70%], nausea, vomiting [54%] and headache [44%]. Seizure was more common among girls, and was significantly more prevalent in younger patients. Abnormal EEG was presents in 42%, abnormal CT-scan in 38% and abnormal MRI in 48% of subjects. PCR was positive in 34% of our patients. All patients were discharged from the hospital after treatment with acyclovir. Herpetic encephalitis should be considered in each patient admitted with sudden change in the level of consciousness in a previously healthy child with fever and antecedent viral infection

Basal ganglia involvement in herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) is a leading cause of sporadic, nonepidemic viral encephalitis in children and adults. We report a very rare case of HSE with involvement of bilateral thalamus, putamen, upper pons and midbrain, with development of extrapyramidal symptoms which responded to corticosteroid therapy. A 15-mth-old female baby admitted with complaint of fever for 5 days and generalised tonic clonic seizure 10 hours before admission. On clinical examination patient was drowsy, temperature was 39.4 oC and vitals were stable with signs of increased intracranial tension. There were no signs of meningeal irritation. Patient gradually become unconscious in the next few hours and pupils were constricted bilaterally with development of atonia in all four limbs and neck muscles. Doll’s eye phenomenon was absent.

Encefalite herpética em paciente do sexo feminino de 48 anos previamente hígida / Herpes simplex encephalitis in a forty-eight-year old female-patient

A encefalite herpética (EHS) é uma patologia grave, com alto índice de morbidade e letalidade. Esta doença se expressa por um quadro clínico agudo, tendo como principais manifestações:febre, cefaléia e alterações cognitivas e psíquicas. Desta forma, a suspeição clínica, associada a exames laboratoriaise de imagem são de fundamental importância para a detecção precoce e tratamento imediato desta patologia, a fim de impedir sua progressão rapidamente fatal. Neste relato, apresentamos um caso de EHS em uma paciente do sexo feminino, 48 anos, internada no Hospital dos Plantadores de Cana - Campos dos Goytacazes, RJ.(AU)

The herpes simplex encephalitis (HSE) is a serious pathology, with a high rate of morbidly and lethality. This diseasepresents a acute clinical condition, it had like principal symptons: fever, headache and cognitive and psychological alterations. In such a way, the clinical suspicion is associated to laboratorials examinations and of image. This are extremely important to early detect and fast treatment this pathology, on purpose to impede the quickly fatal progression of the illness. In this report, we present a case of Herpes Simplex Encephalitis in a forty-eight-years old female-patient, to taken into thePlantadores de Cana Hospital - Campos dos Goytacazes, RJ.(AU)

Encefalite herpética em lactente: relato de caso / Infant herpetic encephalitis in a suckling: case report

A encefalite herpética é defenida como um processo inflamatório agudo do parênquima encefálico em conseqüência da infecção pelo vírus herpes simples. O presente trabalho refere-se a um caso de encefalite herpética em lactente de um ano e oito meses de idade após quadro de infecção das vias aéreas superiores, que evolui com atraso no desenvolvimento neuropsicomotor. O objetivo do estudo é demonstrar a necessidade do diagnóstico precoce, em que o uso de drogas antivirais específicas contribui para o prognóstico do paciente.

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).

Herpes simplex encephalitis in North West India.

All patients admitted with provisional diagnosis of an encephalitic illness over a period of 30 months, were studied. Special investigations included CSF analysis, EEG, CT scan and MRI. Herpes simplex virus (HSV) antibody estimation in CSF and blood was done simultaneously using ELISA. Patients with diagnosis of cerebral venous thrombosis, cerebral malaria, tubercular meningitis etc, who resembled herpes simplex encephalitis (HSE), were excluded systematically with relevant investigations. 28 patients showed electroencephalographic, serologic and/or neuroradiological evidence of herpes simplex encephalitis. Males were affected more than females. Age ranged from 4 years to 65 years. Main clinical features included altered sensorium (100%) and seizures (89%). Serological test for HSV antibody in CSF and blood was positive in 14 patients. Fronto-temporal localisation was seen in EEG of 18 patients. CT and MRI were fairly characteristic with bilateral asymmetric fronto-temporal lesions. Patients with mild disease and who reported earlier responded well to treatment with acyclovir. Mortality was higher if treatment was delayed or if the disease was severe. Delayed treatment even in less severe cases produced neurological deficit in many survivors. Despite limitations of non-availability of CSF-PCR and serial estimation of HSV antibodies, the study is an attempt to highlight the value of high index of suspicion of HSE on clinical grounds, systematically excluding cases with different aetiologies resembling HSE and planning early antiviral therapy to reduce both mortality and morbidity associated with this fatal disease.