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A. Sudbakhsh,M. Mashayekh,S. Ghazvinian B. Omidzohur
Acta Medica Iranica , 2007,
Abstract: Herpes simplex virus accounts for 10 to 25% of sporadic viral encephalitis throughout the world among people of different age with two peaks, one at 5 to 30 and the other at > 50 years of age. Pathologic process includes focal brain tissue inflammation and necrosis (predominantly temporal lobe). Therefore local neurological signs and symptoms will ensue. Although CSF pressure rising due to inflammation is expected, papilledema which is defined as a noninflammatory congestion of optic disk due to raised intracranial pressure has not yet been mentioned as a sign of focal encephalitis. In this article we report a 24 year-old patient with headache, fever and some degree of cognitive disorder who was definitely diagnosed (with MRI and PCR technique) and treated for herpes encephalitis. Unexpectedly he had papilledema which led to more investigation. Most signs and symptoms disappeared during two weeks of intravenous acyclovir therapy as did papilledema to some extent. In this case, positive CSF PCR test for HSV confirmed the diagnosis. However it seems that along with starting acyclovir therapy, performing other supplementary studies (e.g. CT scan, MRI with and without I.V. contrast, CSF cytology and serologic tests for HIV) to rule out other conditions that may be associated with papilledema and focal neurological signs (like malignancies), is mandatory.
Clinical signs as a guide for performing HSV-PCR in correct diagnosis of herpes simplex virus encephalitis
Abbas B,Abdolvahab A,Gholamali Y,Roshanak B
Neurology India , 2003,
Abstract: Background: Clinical criteria (symptoms) are not reliable enough to differentiate between different causes of encephalitis. The clinical presentation of herpes simplex virus encephalitis (HSVE) is not classically constant and in such a patient, therefore, it is vital to make early diagnosis. Aims: To investigate satisfactory and crucial clinical signs as guide to perform HSV-PCR in a rapid diagnosis of herpes simplex virus encephalitis. Material and Methods: A total of 156 CSF specimens from 70 patients with clinically suspected HSVE or meningoencephalitis were tested. The criteria for cases suspected of HSVE were fever >380C, altered mental status and other critical manifestations. CSF features, irregularity in brain CT scan and MRI findings were also assessed. All the specimens were collected before and after Acyclovir treatment. Polymerase chain reaction was performed using primers, which amplified DNA sequences for both HSV-1 and HSV-2. Statistical Analysis: To analyze data, two-tailed Fisher's exact test and the X2-test with Yates' correction were used as appropriate. The odds ratio was used to express the strength of association between the clinical factors and the PCR results. Results: HSV-DNA was detected in 18% of the specimens, belonging to 25.7% of the patients. Results indicate that the majority of the clinical symptoms are not specific to definitive clinical diagnosis of HSVE, except alteration in the level of consciousness odds ratio [0.27 (0.07-0.96) (P=0.033)]; and lateralization sign odds ratio [4.7 (0.98-22.6) (P=0.023)]. However, laboratory data, including total white blood cell count, especially the number of lymphocytes, and MRI findings could be suggested for HSV-PCR examination. Conclusion: At the first admission, a preliminary finding of at least two important clinical features mentioned above along with the pattern of CSF cell and differential counts could be sufficient to perform HSV-PCR which could ultimately result in a rapid and correct diagnosis of herpes simplex encephalitis.
Diagnosis and quantitative detection of HSV DNA in samples from patients with suspected herpes simplex encephalitis
Ziyaeyan, Mazyar;Alborzi, Abdolvahab;Haghighi, Afshin Borhani;Jamalidoust, Marziyeh;Moeini, Mahsa;Pourabbas, Bahman;
Brazilian Journal of Infectious Diseases , 2011, DOI: 10.1590/S1413-86702011000300005
Abstract: 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%) came from males and 99 (42%) from females. the hsv genome was detected in 22 (9.3%) 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 × 106 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.
Neuronal apoptosis in herpes simplex virus - 1 Encephalitis (HSE)  [cached]
Athmanathan S,Vydehi B,Sundaram C,Vemuganti G
Indian Journal of Medical Microbiology , 2001,
Abstract: Herpes simplex virus infections are encountered often due to their ubiquitous nature. Common sites involved include skin, mucous membrane, genitalia, eye and the nervous system. HSV infection of the central nervous system can be life threatening. Little is known about the pathogenesis of this cataclysmic disease, at the cellular level. Virus induced apoptosis may play a role in the molecular pathogenesis of encephalitis. This study aims to detect the presence of apoptosis: a) In the brain tissue obtained at autopsy from a patient who succumbed to Herpes simplex virus - 1 encephalitis (HSE) and b) In a human glioblastoma cell line (SNB 19). Wedge tissue samples were obtained from the inferior surface of the frontal lobe and fixed in buffered formalin. Tissue sections were stained with haematoxylin and eosin for histopathological analysis. An indirect immunoperoxidase assay was performed for the detection of HSV -1 antigen in the tissue sections. Apoptosis in the brain tissue was detected employing the TUNEL assay (Terminal deoxynucleotidyl Transferase (TdT) mediated deoxy Uridine Triphosphate Nick End Labeling) using a commerically available kit (TdT Fragel DNA fragmentation detection kit, Oncogene Research Products, CA). HSV-1 induced apoptosis of SNB 19 cells were detected in-vitro by: a) Membrane blebbing assay and b) Hoechst 33258 staining. Classical features of viral encephalitis including the presence of intranuclear inclusions, neuronal loss and perivascular cuffing were seen in the tissue sections. The immunoperoxidase assay revealed the presence of abundant viral antigen in the neurons, microglial and satellite cells. TUNEL assay revealed many apoptotic neurons, microglial and satellite cells. In-vitro assays showed evidence of HSV-1 induced apoptosis in the SNB 19 cell line. These results suggest that virus induced apoptosis may play a role in the molecular pathogenesis of HSE. Further studies are warranted to elucidate the role of HSV-1 induced apoptosis, especially employing cell lines of neuronal origin.
Herpes simplex 1 encephalitis presenting as a brain haemorrhage with normal cerebrospinal fluid analysis: a case report
Effrossyni Gkrania-Klotsas, Andrew ML Lever
Journal of Medical Case Reports , 2008, DOI: 10.1186/1752-1947-2-387
Abstract: We present a patient who had a suggestive history but a totally normal lumbar puncture and only evidence of intracerebral haemorrhage in the brain magnetic resonance imaging. Diagnosis was made by using the cerebrospinal fluid polymerase chain reaction for herpes simplex virus.Herpes simplex encephalitis is being increasingly diagnosed with the availability of new diagnostic techniques. Herpes simplex encephalitis can present with the combination of haemorrhage and normal cerebrospinal fluid. Awareness of this common but, if left untreated, devastating condition should increase.The rapid diagnosis of central nervous system infection with herpes simplex virus (HSV) is important because of the potential morbidity and mortality associated with the disease as well as the wide availability of acyclovir which has been proven to ameliorate the symptoms. Left untreated, more than 70% of cases of HSV encephalitis (HSVE) are fatal and only approximately 11% of patients recover normal premorbid function [1,2]. Treatment with acyclovir has been proven to reduce mortality to approximately 20% [3,4]. So far, the diagnosis of HSVE has relied on the combination of a compatible clinical scenario, a suggestive brain computed tomography (CT) scan or brain magnetic resonance imaging (MRI) and the examination of the cerebrospinal fluid (CSF) by microscopy, biochemical analysis and polymerase chain reaction (PCR) for the presence of HSV DNA. HSVE has been left undiagnosed in the past, resulting in the patient's demise because of the lack of CSF pleocytosis, a normal CT and the absence of focal features on neurological examination [5].We present a case that illustrates the importance of the clinical scenario in a patient with atypical findings in imaging studies and a normal CSF examination.A 46-year-old man presented to our institution, during the summer months, following referral by another hospital. The patient was in good health until 1 week before admission to our hospital, when he s
An Unusual Presentation of Herpes Simplex Virus Encephalitis
Ray Boyapati,George Papadopoulos,James Olver,Michael Geluk,Paul D. R. Johnson
Case Reports in Medicine , 2012, DOI: 10.1155/2012/241710
Abstract: We present a case of a 65-year-old man with an acute alteration in mental state that was initially diagnosed as a functional psychiatric condition. After extensive workup, herpes simplex virus type 1 (HSV-1) was detected in the patient’s cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and he responded rapidly to treatment with acyclovir. The case illustrates the importance of actively excluding organic causes in such patients, the need to have a low threshold of suspicion for HSV encephalitis, and the central role of CSF PCR testing for the diagnosis of HSV encephalitis, even in the absence of CSF biochemical abnormalities.
A Case with Herpes Simplex Virus Encephalitis  [PDF]
Mesut Ba?ak,Sibel Serin,Davut Dama,Ay?egül Dalbeler
Medical Journal of Bakirk?y , 2011,
Abstract: Sudden fever, headache, focal neurological findings together with various levels of unconsciousness or seizure disorders are the characteristic features for encephalitis. Herpes simplex virus type 1 is most common viral agent in etiology. Clinically, it’s difficult to diagnose the disease. Routine laboratory results are usually nonspecific. When symptoms and clinical findings confirm the diagnosis and the HSV antigen or antibody is seen in laboratory results with associated typical radiological lesions, it is life saving to start antiviral therapy immediately. In our case, provided with literature research we disscussed a 37 years old man who presented to our internal medicine department with headache, nausea, vomiting and fever, without neurological symptoms and findings, diagnosed as herpes simplex encephalitis and started asyclovir treatment.
Cortical Blindness As A Sequelae Of Horpes Simplex Encephalitis : A Case Report
Nalini A,Srinivasa R,Acharya P.T
Annals of Indian Academy of Neurology , 2000,
Abstract: A one year five month old girl had presented with fever, altered consciousness and seizures of five days duration. Diagnosis of Herpes simplex virus (HSV) encephalitis was made with the results of brain computed tomography (bilateral temporal hypodensities), magnetic resonance imaging showing bitemporal and extensive bilateral occipital hyperintensities and the detection of HSV antigen in the cerebrospinal fluid by indirect immunoflourescence technique. High titres of anti HSV antibodies were detected in the CSF by ELISA. During recovery the child developed cortical blindness which persisted at the end of one year follow up.
Influence of Perineurial Cells and Toll-Like Receptors 2 and 9 on Herpes simplex Type 1 Entry to the Central Nervous System in Rat Encephalitis  [PDF]
Biborka Bereczky-Veress,Nada Abdelmagid,Fredrik Piehl,Tomas Bergstr?m,Tomas Olsson,Birgit Sk?ldenberg,Margarita Diez
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012350
Abstract: Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers area of DA rats, whereas PVG rats remained completely asymptomatic. In the present study we investigated the early immunokinetics in these strains to address the underlying molecular mechanisms for the observed difference. The virus distribution and the immunological responses were compared in the whiskers area, trigeminal ganglia and brain stem after 12 hours and the first four days following infection using immunohistochemistry and qRT-PCR. A conspicuous immunopathological finding was a strain-dependent difference in the spread of the HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi. In the whiskers area infected perineurial cells were abundant in the susceptible DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was confined only to the epineurium. In both strains activation of Iba1+/ED1+ phagocytic cells followed the distribution pattern of HSV-1 staining, which was visible already at 12 hours after infection. Notably, in PVG rats higher mRNA expression of Toll-like receptors (Tlr) -2 and -9, together with increased staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other Tlr-pathway markers were expressed at higher levels in the susceptible DA rats. Our data demonstrate the novel observation that genetically encoded properties of the host nerve and perineurial cells, recruitment of phagocyting cells together with the low expression of Tlr2 and -9 in the periphery define the susceptibility to HSV-1 entry into the nervous system.
Effect of combinations of antiviral drugs on herpes simplex encephalitis  [cached]
Bryan M Gebhardt,Federico Focher,Richard Eberle,et al
Drug Design, Development and Therapy , 2009,
Abstract: Bryan M Gebhardt1, Federico Focher2, Richard Eberle3, Andrzej Manikowski4, George E Wright41LSU Eye Center, Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; 2Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy; 3Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA; 4GLSynthesis Inc., Worcester, MA, USAAbstract: 2-Phenylamino-6-oxo-9-(4-hydroxybutyl)purine (HBPG) is a thymidine kinase inhibitor that prevents encephalitic death in mice caused by herpes simplex virus (HSV) types 1 and 2, although its potency is somewhat less than that of acyclovir (ACV). The present study was undertaken to determine the effect of combinations of HBPG and either ACV, phosphonoformate (PFA), or cidofovir (CDF) against HSV encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and treated twice daily intraperitoneally for five days with HBPG, alone or in combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days, and the day of death of each was recorded. All of the combinations showed additivity, and the combination of HBPG + ACV appeared to be synergistic, ie, protected more mice against HSV-1 encephalitis compared with each drug given alone. Delay of treatment with HBPG for up to two days was still effective in preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor HBPG and the antiherpes drug ACV may have synergistic activity against HSV encephalitis. The development of a potent and safe combination therapy for the prevention and/or treatment of HSV infection of the central nervous system can improve the outcome of this infection in humans.Keywords: antivirals, herpetic encephalitis
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