Role of IL-4 in an experimental model of encephalitis induced by intracranial inoculation of herpes simplex virus-1 (HSV-1) / Papel da IL-4 em modelo experimental de encefalite induzida pela inoculação intracraniana do herpes simplex vírus-1 (HSV-1)

Herpes simplex virus-1 (HSV-1) is a pathogen that may cause severe encephalitis in humans. In this study, we aimed to investigate the role of interleukin-4 (IL-4) in a model of HSV-1 brain infection. IL-4 knockout (IL-4-/-) and wild type (WT) C57BL/6 mice were inoculated with 10(4) plaque-forming units of HSV-1 by the intracranial route. Histopathologic analysis revealed a distinct profile of infiltrating cells at 3 days post-infection (dpi). Infected WT mice presented mononuclear inflammatory cells while IL-4-/- mice developed meningoencephalitis with predominance of neutrophils. IL-4-/- mice had diminished leukocyte adhesion at 3 dpi when compared to infected WT animals in intravital microscopy study. Conversely no differences were found in cerebral levels of CXCL1, CXCL9, CCL3, CCL5 and TNF-α between WT and IL-4-/- infected mice. IL-4 may play a role in the recruitment of cells into central nervous system in this acute model of severe encephalitis caused by HSV-1.

O vírus herpes simplex-1 (HSV-1) é um patógeno que pode causar encefalite grave em humanos. Neste estudo, buscamos investigar o papel da interleucina-4 (IL-4) no modelo de infecção intracerebral por HSV-1. Camundongos C57BL/6 selvagens (WT) e deficientes no gene IL-4 (IL-4-/-) foram inoculados com 10(4) unidades formadoras de placas de HSV-1 por via intracraniana. A análise histopatológica revelou um padrão distinto de infiltrado leucocitário. Camundongos WT infectados apresentaram infiltrado de células mononucleares, enquanto camundongos IL-4-/- desenvolveram meningoencefalite com predomínio de neutrófilos 3 dias pós-infecção (dpi). Animais IL-4-/- tiveram menor adesão de leucócitos 3 dpi quando comparados aos animais WT infectados à microscopia intravital. Em contrapartida, não foram encontradas diferenças nos níveis cerebrais de CXCL1, CXCL9, CCL3, CCL5 e TNF-α entre camundongos WT e IL-4-/- infectados. Esses resultados sugerem que IL-4 pode desempenhar um papel no recrutamento de células no sistema nervoso central neste modelo agudo de encefalite grave causada pelo HSV-1.

Incidencia del virus herpes simplex en pacientes con infecciones agudas del sistema nervioso central / Incidence of herpes simplex virus infection in patients with acute central nervous system infections

Los Virus Herpes Simple son responsables de una variedad de infecciones a nivel de mucosas bucal y genital, son neurotrópicos, capaces de alojarse en células nerviosas y permanecer latentes con subsecuentes reactivaciones, en algunos casos pueden provocar meningitis y encefalitis. tienen una morbilidad significativa y una mortalidad elevada. El presente estudio tiene como objetivo determinar la incidencia de VHS en la etiología de los síndromes agudos del SNC mediante la detección en suero y LCR de anticuerpos específicos. Se estudiaron 93 muestras pareadas de pacientes con afecciones neurológicas que mostraron resultados negativos en el estudio bacteriológico de LCR y cuya relación Alb-LCR/Alb-suero fue <0,0075. Los anticuerpos fueron detectados por el método de inmunoensayo enzimático Elisa: Enzygnost® anti virus VHS/IgM-IgG (Behring, 1994), donde 1,2% (1/93) de las muestras de suero resultaron positivas para IgM; 89,24% (83/93)de los sueros resultaron positivos para IgG; y 27,39% (20/93) de las muestras de LCR presentaron anti-IgG positivo. La presencia de IgG en LCR sugiere la producción intratecal de estos anticuerpos en el SNC, lo que muestra una participación importante de este agente viral en las infecciones y enfermedades asociadas al SNC

Herpes simplex viruses are agents responsible for a variety of infections on buccal and genital mucosa; they are neurotropic, capable of lodging in the nerve cells and remaining latent with subsequent reactivations; in some cases, they can provoke meningitis and encephalitis; and they have a significant morbidity and are associated with a high mortality. The present project aims to determine HSV’s effect on the etiology of acute central nervous system (CNS) syndromes using the detection of specific antibodies in serum and cerebrospinal fluid. The 93 paired samples from patients with neurological affectations studied demonstrated negative results in the LCR bacteriological study and their Alb-LCR/Alb-serum relation was < 0.0075. Antibodies were detected by the enzymatic immunoassay ELISA method, where 1.2% (1/93) of the serum samples turned out positive for IgM; 89.24% (83/93) of the serum samples resulted positive for IgG; and 27.39% (20/93) of LCR samples were positive for anti-IgG. IgG presence in LCR suggested the intrathecal production of these antibodies inside the CNS, which demonstrates a significant participation by this viral agent in infections and diseases associated with the CNS

[Herpes simplex virus encephalitis during immunosuppressive treatment of ulcerative colitis]

Today, with the advent of new medications, treatment of Ulcerative colitis [UC] has been markedly improved. Immunosuppressive drugs used in therapy predispose patients to opportunistic infections. A 22-year-old woman was admitted to emergency department due to acute exacerbation of UC and decreased level of consciousness. She was under treatment with 5-aminosalicylate, prednisolone and azathioprine. In neurological evaluation, patient had cerebral herniation. Non-contrast CT scan revealed multiple hemorrhagic areas in both frontal lobes. Right frontal craniotomy was performed emergently. Histopathologic evaluation of brain tissue was reported as "Herpes simplex encephalitis". Polymerase chain reaction [PCR] assay was also positive for HSV DNA. Immunosuppressive drugs such as azathioprine have a pivotal role in the treatment of resistant and/or severe cases of UC. Prevalence of infectious complications was reported to be 7.4%, 1.8% of which were severe [including herpes zoster encephalitis] .Our review of literature indicates that no case of herpes simplex encephalitis following immunosuppressive therapy for UC has been reported

Herpes simplex encephalitis: some interesting presentations.

Herpes Simplex Encephalitis (HSE) is the most common cause of fatal viral encephalitis. A high index of suspicion is mandatory for early diagnosis and successful therapy to restrict morbidity and mortality. We report 4 patients of HSE, with interesting presentations, viz. brainstem involvement in an immunosuppressed patient, Kluver-Bucy Syndrome-a consequence of untreated HSE, HSE in the postpartum period mistaken as cortical venous thrombosis, and response to inadequate treatment. They demonstrate the wide spectrum of clinical features, pitfalls in diagnosis, and a variable response to therapy in HSE.

Clinical, radiological and neurophysiological spectrum of JEV encephalitis and other non-specific encephalitis during post-monsoon period in India.

AIMS: To study the spectrum of encephalitis during the post-monsoon period in a tertiary care centre of India. METHODS: Clinical, neurophysiological and radiological features of patients with encephalitis are reported in this communication. The patients were subjected to clinical examination, CT or MRI scan, EEG, motor and somatosensory evoked potentials in both upper and lower limbs bilaterally and concentric needle electromyography. The laboratory studies for Japanese encephalitis (JE) comprised virus isolated, IgM capture ELISA, mercaptoethanol test and hemagglutination inhibition titre in paired sera against JE virus. Patients were classified into JEV encephalitis and non-specific encephalitis. On the basis of radiological features, they were classified into group I (thalamic or basal ganglia involvement), group II (brainstem involvement only) and group III (normal MRI). The outcome was defined into poor (bedridden), partial (dependent for daily activities) and complete (independent) recovery at the end of 3 months. RESULTS: Out of 26 patients (Age 7-70 years, mean 24.8 years), laboratory evidences of JEV infection was present in 14 patients and one patient had herpes simplex encephalitis. The patients with JEV encephalitis had more severe illness as evidenced by lower GCS score, higher frequency of anterior horn cell involvement, movement disorders and more extensive MRI changes. The EEG and MEP changes were also more frequently abnormal in the JEV group. On radiology, 15 patients had thalamic or basal ganglia involvement (group I), 3 isolated midbrain involvement (group II) and 8 had normal MRI (group III). Laboratory evidence consistent with JE were present in 11 out of 12 patients in group I and 3 out of 8 in group III, however, there was no laboratory evidence of JE virus infection in patients with isolated brainstem involvement. There was overlap in the neurologic and systemic manifestations in all the 3 radiological groups as well as in the groups with and without laboratory evidences of JEV infection. CONCLUSION: The observed overlap in neurological and systemic involvement in different subgroups of encephalitis may be due to JE or JE-like viral infection. The possibility of strain variation, change in virulence of organism or immunity of host needs further studies.