To biopsy or not to biopsy in suspected herpes simplex encephalitis: a quantitative analysis

The authors performed a decision analysis to determine whether a patient suspected to have herpes simplex encephalitis (HSE) should undergo a brain biopsy or be treated empirically with medical therapy. In most cases, empiric treatment with acyclovir would be slightly favored; brain biopsy was not essential in management. However, brain biopsy was found useful for patients who had low CSF glucose at the time of initial lumbar puncture; such patients may have a very high risk to have other treatable conditions such as tuberculosis, brain abscess, toxoplasmosis, or cryptococcosis. The results of the analysis suggest that even with the advent of safe antiviral drug therapy such as acyclovir, brain biopsy is useful in a well-defined subset of patients with possible HSE. The rationale, however, is not to confirm HSE but rather to detect other treatable conditions.     

The immune response to herpes simplex virus encephalitis in mice is modulated by dietary vitamin E

Herpes simplex virus encephalitis (HSE) is the most common fatal sporadic encephalitis in humans. HSE is primarily caused by herpes simplex virus (HSV)-1 infection of the brain. HSE results in increased levels of oxidative stress, including the production of reactive oxygen species, free radicals, and neuroinflammation. The most biologically active form of vitamin E (VE) is alpha-tocopherol (alpha-TOC). In cellular membranes, alpha-TOC prevents lipid peroxidation by scavenging free radicals and functioning as an antioxidant. Supplementation with VE has been shown to decrease immunosenescence, improve immune function, and may be neuroprotective. To determine how VE deficiency and VE supplementation would alter the pathogenesis of HSE, we placed weanling male BALB/cByJ mice on VE-deficient (VE-D), VE-adequate (VE-A), or 10x VE-supplemented diets for 4 wk, and then infected the mice intranasally with HSV-1. VE-D mice had more severe symptoms of encephalitis than VE-A mice, including weight loss, keratitis, hunched posture, and morbidity. VE-D mice had increased cytokine and chemokine expression in the brain and increased viral titers. In contrast, VE supplementation failed to decrease cytokine production and had no effect on viral titer. We demonstrated that adequate levels of VE are important in limiting HSE pathology and that 10x supplementation does not enhance protection.     

阿昔洛韦联合奥卡西平治疗单纯性疱疹病毒性脑炎伴癫痫患儿的临床效果及对其炎性因子水平的影响

目的 探讨阿昔洛韦联合奥卡西平治疗单纯性疱疹病毒性脑炎（HSE）伴癫痫患儿的临床效果及对其炎性因子水平的影响。方法 64例HSE伴癫痫患儿随机分为两组各32例,对照组给予阿昔洛韦联合丙戊酸钠治疗,研究组给予阿昔洛韦联合奥卡西平治疗,比较两组的治疗效果及治疗前后的炎性因子水平。结果 研究组的治疗总有效率为93.75%,显著高于对照组的71.88%(P <0.05)。治疗后,两组的IL-1β、 IL-6、 TNF-α水平均较治疗前降低,且研究组的IL-1β、 IL-6、 TNF-α水平显著低于对照组（P <0.05）。结论 阿昔洛韦联合奥卡西平治疗HSE伴癫痫患儿临床效果显著,可有效改善炎性因子水平。     

Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers

BACKGROUND: The patient who complains of vague mental status changes requires extra vigilance in that the underlying condition might itself affect the patient's ability to communicate well and relate a medical history. The differential diagnosis of delirium is broad, ranging from the benign to the potentially fatal. The diagnostic uncertainty inherent in primary care is compounded when language and cultural differences interfere with physician-patient communication. METHODS: We undertook a MEDLINE-assisted review of the medical literature concerning herpes simplex encephalitis. Additionally, we performed an Internet search of several government Web sites to find current legal and federal guidelines concerning the use of medical interpreters. RESULTS AND CONCLUSIONS: We recount the case of a young Eastern European immigrant who complained initially of vague mental status changes and was found to have herpes simplex encephalitis. Diagnosis could have been made sooner had the physician been familiar with the patient's baseline mental status or had cultural and language barriers not stood between the physician and the patient and his mother. Herpes simplex encephalitis is a rare, but specific, cause of delirium for which prompt diagnosis and treatment with intravenous acyclovir can prevent death or serious sequelae.     

单纯疱疹病毒性脑炎20例临床诊治分析

目的探讨单纯疱疹病毒性脑炎的临床早期诊断与治疗方法。方法回顾性分析20例单纯疱疹病毒性脑炎的临床资料。结果（1）20例均为急性或亚急性起病;（2）临床多以头痛、发热、记忆减退、精神异常、癫痫发作伴或不伴意识障碍为首发症状;（3）头颅MRI检查比CT敏感,早期可见单侧或双侧颞叶、额叶、顶叶或岛叶呈异常高信号;（4）脑电图出现中度异常脑波,多呈颞额部偏胜、周期性棘-慢波;（5）脑脊液细胞学以淋巴细胞反应为主,部分病例可见大量红细胞;（6）更昔洛韦及高压氧疗的应用疗效显著。结论根据早期临床表现、影像学特征、脑电图、脑脊液检查可以拟诊单纯疱疹病毒性脑炎,早期应用更昔洛韦,结合高压氧治疗可显著改善其预后。     

Atypical computed tomographic appearance of herpes simplex encephalitis

In cases of herpes simplex encephalitis, a low density lesion in the temporal lobe is a common CT finding, whereas hemorrhagic lesion is rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. Two cases of hemorrhagic lesion observed on CT in herpes simplex encephalitis are reported, and atypical CT findings of herpes simplex encephalitis is discussed.     

口服阿昔洛韦治疗深层单纯疱疹病毒性角膜炎的临床观察

目的 观察抗病毒药物阿昔洛韦治疗深层单纯疱疹病毒性角膜炎的疗效.方法 将59例病例(59眼)深层单纯疱疹病毒性角膜炎随机分为2组,A组(28眼)采用阿昔洛韦局部及静脉给药,B组(31眼)采用阿昔洛韦口服.结果 两组的治愈率差异无统计学意义(P>0.05),复发率两组差异有统计学意义(P<0.05).结论 口服阿昔洛韦能有效预防深层单纯疱疹病毒性角膜炎的复发.     

The Nixon Budget Crisis—One Medical School's ‘Share’

A 25-year-old Hispanic woman presented with painful oral ulcers, a sore throat, and dysphagia of two weeks' duration. She was treated empirically with acyclovir for presumed herpes simplex stomatitis and esophagitis and sent home. A week later, she returned with complaints of worsening sore throat, fever (as high as 38.9°C), and cough producing yellow-green sputum. She had not had chills, shortness of breath, burning on urination, or a change in bowel habits.     

Another case of West Nile fever in the Netherlands: a man with encephalitis following a trip to Canada

Shortly after his return to the Netherlands from a trip to Ontario, a part of Canada where infection with West-Nile virus has been reported, a 69-year-old man became increasingly confused and generally unwell, accompanied by fever. The clinical picture was compatible with viral encephalitis and this was supported by EEG findings and the results of the cerebrospinal-fluid examination. MRI of the brain did not contribute to the diagnosis. The patient was treated with aciclovir because herpes simplex encephalitis was suspected, and he recovered from his illness within a few days. The EEG normalised as well. The most important remaining symptom was diminished short-term memory function. After the patient was discharged, rising antibody titres against West-Nile virus were found in two consecutive sera; there were no antibodies to other encephalitis-causing viruses (such as Q fever virus and St. Louis encephalitis virus). This case report concerns the second imported case of West-Nile fever in the Netherlands and the first one with encephalitis.     

Infectious encephalitis in France from 2000 to 2002: the hospital database is a valuable but limited source of information for epidemiological studies

Many virus and bacteria can cause encephalitis but are rarely identified as the aetiological agent by individual diagnosis. In France, the only continuous source of information about encephalitis is the national hospital medical database (NHMD). Data from the VIH-negative patients recorded in mainland France between 2000 and 2002 with a diagnosis of encephalitis were extracted and analysed according to demographic, geographical and temporal distribution. Hospitalisation details were described. An average of 1200 patients was recorded each year. They were residents of all French districts and equally hospitalized in university hospitals and non university hospitals. Their mean age was 38, and most were men. The aetiological diagnosis was unknown for 80%. The most frequent aetiological diagnosis was herpes simplex virus in adults, and VZV virus in children. These results give us some clues to design a national study on encephalitis. The study will be implemented in mainland France in 2007 and will last one year. We invite all voluntary hospitals to include their encephalitic patients in our study.     

Etiology of Encephalitis in Australia, 1990�C2007

Encephalitis is a clinical syndrome commonly caused by emerging pathogens, which are not under surveillance in Australia. We reviewed rates of hospitalization for patients with encephalitis in Australia’s most populous state, New South Wales, from January 1990 through December 2007. Encephalitis was the primary discharge diagnosis for 5,926 hospital admissions; average annual hospitalization rate was 5.2/100,000 population. The most commonly identified pathogen was herpes simplex virus (n = 763, 12.9%). Toxoplasma encephalitis and subacute sclerosing panencephalitis showed notable declines. The average annual encephalitis case-fatality rate (4.6%) and the proportion of patients hospitalized with encephalitis with no identified pathogen (69.8%, range 61.5%–78.7%) were stable during the study period. The nonnotifiable status of encephalitis in Australia and the high proportion of this disease with no known etiology may conceal emergence of novel pathogens. Unexplained encephalitis should be investigated, and encephalitis hospitalizations should be subject to statutory notification in Australia.     

Herpesvirus resistance to antiviral drugs: a review of the mechanisms, clinical importance and therapeutic options

During the past decade, potent agents against herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), and cytomegalovirus (CMV) have become available. The increasing clinical use of acyclovir, ganciclovir, and foscarnet has been associated with the emergence of drug-resistant herpesvirus strains. Resistance to acyclovir or ganciclovir most frequently results from deficient intracellular phosphorylation of these agents which is required for drug activation. Resistance to foscarnet is due to viral DNA polymerase mutants that permit viral replication despite the presence of the drug. In immunocompetent patients, herpesvirus resistance is rare and generally does not correlate with clinical outcome. In contrast, in immunocompromised hosts, resistance of HSV, VZV, and CMV is increasingly detected, and may be associated with disease refractory to antiviral therapy. Foscarnet treatment has been used with some clinical benefit in patients with acyclovir-resistant HSV or VZV, or ganciclovir-resistant CMV. For therapy of resistant mucocutaneous HSV disease, topical trifluorothymidine, and topical or intravenous cidofovir (HPMPC) have yielded encouraging results that warrant further investigation. Improved methods for detection of herpesvirus resistance, and validation of alternative therapy for patients with documented resistance are required to reduce the clinical impact of drug-resistant herpesviruses.     

Neonatal herpes simplex virus infection in the British Isles

Summary. This study was set up to estimate the incidence of neonatal herpes simplex virus (HSV) infection in the British Isles, and to document the outcome of neonatal infection. Paediatricians reported cases of neonatal HSV through the active reporting scheme of the British Paediatric Association Surveillance Unit. Over a 5half year period (1986-91) 76 infants with neonatal HSV infection were reported, an incidence of recognised infection in the British Isles of 1.65/100000 livebirths. Twenty-five infants had HSV-1 infection, 24 HSV-2 and in 27 virus type was unknown. Twenty-seven had disseminated infection, 23 herpes encephalitis and 26 localised infection. Nineteen infants (25%) died in the neonatal period, and a further 25 (33%) have subsequently died or have long-term sequelae. At least half of the infants had been discharged home before symptoms became apparent. For 21 women there was evidence of a maternal genital herpes infection at some time, but this was reported or diagnosed retrospectively after neonatal HSV was suspected in 19 cases, and ante-natally in only two. Neonatal HSV is rare in the British Isles and routine antenatal screening for genital herpes infection during pregnancy is not justified. A high proportion of infected infants present with non-specific signs and symptoms and without mucocutaneous involvement; furthermore, there is rarely a history of maternal infection. As early diagnosis and prompt treatment is essential, there must be a high level of awareness of the serious nature of neonatal HSV infection.     

2006-2008年广东省病毒性脑炎监测情况分析

目的了解广东省病毒性脑炎的病原学特征和流行病学特点。方法分别选择位于广东省中部、西部和东部的各1家三甲医院为监测点,以临床诊断为病毒性脑炎的病例为监测对象,于2006年9月至2008年9月收集有关病例信息,并采集病例的血清和脑脊液,分别采用ELISA和RT-PCR(或PCR)的方法进行病原学检测,ELISA法检测单纯疱疹病毒(HSV)、乙脑病毒(JEV)、腺病毒(ADV)、埃可病毒(ECOH)、柯萨奇病毒(COX)、巨细胞病毒(CMV)IgM抗体;RT-PCR(或PCR)法检测黄病毒(包括乙脑病毒和西尼罗病毒WNV)、肠道病毒(包括埃可病毒和柯萨奇病毒)、单纯疱疹病毒I和II型、腺病毒、巨细胞病毒和Colti病毒的病毒核酸。同时收集同期广东省报告乙脑病例资料进行比较分析。结果2006年9月至2008年9月3家监测医院共收治病毒性脑炎病例195例,男女性别比为1.6∶1(120/75),各年龄段均有发病,但以10岁及以下儿童为多,占26.67%;同期广东省共报告乙脑发病例数296例,其中以10岁及以下和11~14岁儿童为主,分别占70.27%、26.01%。对3家监测医院收集的152例病毒性脑炎病例的血清进行病...     

Hypothetical vaccination of the Dutch population with a herpes simplex virus vaccine: estimation of the profitability using a demographic projection model

The apparently increasing evidence of herpes simplex virus infections of the genital tract has focused attention on preventing the infection by vaccination. Herpes genitalis is not, however, the most quantitatively important clinical manifestation of herpes simplex virus infections. Because 41% of the hospitalized patients are younger than 20 years, vaccination of birth cohorts would be more favourable. In this paper the financial benefits of a hypothetical herpes simplex virus vaccination were calculated with the use of a population projection model. For the Netherlands, if the price of the hypothetical herpes simplex virus vaccine equals the cost price of the mumps component of the combined mumps-measles-rubella vaccine, the herpes vaccine would be profitable within 8 years.     

Behaviour modification in retraining showering and dressing skills for a person with severe memory loss

Herpes simplex encephalitis (HSE) is often associated with severe memory deficits and decreased independence in activities of daily living. This paper presents a case study of a person with memory problems following HSE. Occupational therapy intervention was aimed at increasing independence in showering and dressing. Data were collected on three criteria: independent showering and dressing; sequenced showering and dressing; and verbal mediation. The subject increased his independence in showering and dressing, but there was little change in the sequencing of these tasks or in verbal mediation. Future research into these techniques using a more sophisticated single-subject design is recommended.     

Pharmacological treatment of Bell's palsy: favourable effects of prednisolone-based therapy now demonstrated

Bell's palsy accounts for two-thirds ofall acute facial palsies. Presumed reactivation of the herpes simplex virus and concurrent swelling of the facial nerve prompted the use of antivirals in combination with corticosteroids, although evidence supporting the effectiveness of this approach was weak. A recently published randomized placebo-controlled clinical trial assessed the effectiveness of adding valacyclovir to prednisolone; another larger primary-care-based study compared treatment with prednisolone, acyclovir or both with placebo. In patients with severe or complete facial palsy, the addition of valacyclovir improved the chance of complete recovery, but as this study was single-blinded, results should be interpreted with caution. Early treatment with prednisolone (25 mg twice daily for to days) significantly improved the chance of complete recovery at 3 and 9 months. Acyclovir, given alone or in addition to prednisolone, did not show any benefit.     

Acute encephalitis: report on 32 consecutive pediatric cases observed in one hospital

We report 32 cases of acute encephalitis consecutively hospitalized in one hospital, from January 1991 to December 2002. The causative agent was identified in 26 cases (81%). The main associated viruses were varicella-zoster (10 children; 31%), Herpes simplex (6 children; 19%), and enteroviruses (4 children; 13%). At the acute phase, the most relevant biological findings were electroencephalogram results and CSF analysis. The initial encephalic imaging was primarily helpful to exclude other acute neurological diseases whereas long-term imaging was a prognostic factor for necrotizing encephalitis. The microbiological diagnosis required several days or weeks to be determined. It did not influence the initial management. In addition to the 6 cases of herpetic encephalitis, 19 children (78% altogether) were then treated by acyclovir before a definitive diagnosis was made. Twenty-two children (69%) had a favorable outcome, 2 (6%) had moderate sequels, 2 (6%) had important ones, and 5 (16%) had major ones. One (3%) child died. The outcome was highly dependant on the causative agent and the mechanism of encephalitis. This series gives information on the epidemiology of encephalitis in children in our region over a period of 12 years.     

荧光PCR法检测2008年-2017年单纯疱疹病毒Ⅱ型感染的临床结果与分析

目的了解浙江地区疑似生殖器疱疹患者单纯疱疹病毒Ⅱ型(HSV-Ⅱ)感染情况,为临床诊断治疗提供依据。方法实时荧光PCR法对浙江省人民医院2008年-2017年2 230例疑似泌尿生殖道疱疹患者进行HSV-Ⅱ核酸检测。结果在2 230例疑似泌尿生殖道疱疹患者中,女性1 554例,男性676例,共检测出HSV-Ⅱ型阳性557例,阳性率为24.98%。557例HSV-Ⅱ感染患者中女性405例,阳性率为26.06%;男性152例,阳性率为22.49%,男、女感染率差异无统计学意义(P> 0.05)。557例HSV-Ⅱ型阳性患者分5个年龄段即<20岁、20岁~29岁、30岁~39岁、40岁~49岁、≥50岁分析,阳性率分别为3.05%、42.01%、29.80%、14.72%、10.23%。结论泌尿生殖道HSV-Ⅱ感染检出率较高,提示临床需重视对疑似生殖道疱疹病毒感染患者进行HSV-Ⅱ核酸检测;HSV-Ⅱ感染无性别差异,但感染主要集中在20岁~29岁患者。实时荧光PCR法在HSV-Ⅱ检测中具有快速、灵敏度高、简便等优点,适用于临床检测。