病毒性脑炎早期诊断及病原学探讨(附175例报道)

目的探讨病毒性脑炎的早期诊断方法及病原学诊断的临床价值。方法对我院2005年临床诊断病毒性脑炎的175份病例就其临床资料进行回顾性分析,并对部分患者的脑脊液标本应用ELISA方法检测脑脊液中单纯疱疹病毒,呼吸道合胞病毒,柯萨奇B组病毒的IgM。结果脑电图检查160例,异常136例(85.00%);头CT检查90例,异常15例(16.67%);头MRI检查65例,异常42例(64.62%);脑脊液细胞学检测175例,异常166例(94.86%);血清特异性病毒抗体IgM检测74例,阳性26例,其中单纯疱疹病毒IgM阳性的13例,柯萨奇B组病毒IgM阳性的6例,呼吸道合胞病毒IgM阳性4例,巨细胞病毒IgM阳性3例;脑脊液特异性病毒抗体IgM检测70例,结果均为阴性。结论脑脊液细胞学在病毒性脑炎早期诊断及鉴别诊断中具有重要的价值,病原学诊断是病毒性脑炎诊断研究的发展方向,但其方法学有待于进一步完善。     

病毒性脑炎患者76例病原学分析

目的：探讨病毒性脑炎患者的临床表现及脑脊液病原学特点。方法采用胶体金法对2010-02-2012-02在我院诊治的76例病毒性脑炎患者的脑脊液进行巨细胞病毒、柯萨奇病毒、风疹病毒、EB病毒、人单纯疱疹病毒、呼吸道合胞病毒、腺病毒的特异性抗体检测,并对结果及临床表现进行归纳总结。结果76例患者脑脊液病毒检测阳性者71例,阳性率93.4％。结论头痛、呕吐、精神异常、抽搐等是病毒性脑炎常见的临床表现,腺病毒、巨细胞病毒、人单纯疱疹病毒是近年来中枢神经系统病毒感染的主要病毒。     

用逆转录聚集合酶链反应诊断柯萨奇病毒性脑膜炎

本研究应用逆转录聚合酶链反应技术（ＲＴ－ＰＣＲ）检测脑脊液及血清中柯萨奇病毒的ＲＮＡ。４３例临床确诊的病毒性脑膜炎患者中有１７例脑脊液ＲＴ－ＰＣＲ检查阳性，血清有１３例阳性；而对照组２１例其它中枢神经系统疾病的脑脊液及血清均为阴性。用柯萨奇病毒引物扩增其它病毒，结果也为阴性。因此，很适于进行柯萨奇病毒的早期、快速诊断。     

柯萨奇病毒性B5型脑炎

本组三例病毒性脑炎患者的脑脊液中分离出柯萨奇病毒Ｂ５型，就其临床特点，化验与特检作一介绍，治疗时，无环鸟苷，大剂量丙种球蛋白，在综合措施的基础上可取得一定效果。     

儿童病毒性脑炎198例临床分析

病毒性脑炎(Viral encephalitis)是由各种病毒所致的原发性脑炎,也称病毒性脑膜脑炎。随着病原学诊断方法的不断发展,一般采用病毒学命名,如单纯疱诊病毒(HSV-1 HSV-2)脑炎、柯萨奇病毒(COXBV)脑炎、流行性腮腺炎病毒(PPMV)脑炎等[1]。现将我院1998-08-2003-08收治的198例病毒性脑炎患儿的诊治分析如下。     

儿童病毒性脑炎198例临床分析

病毒性脑炎（Viral encephalitis)是由各种病毒所致的原发性脑炎，也称病素性脑膜脑炎。随着病原学诊断方法是不断发展，一般采用病毒学命名，如单纯疱诊病毒（HSV-1 HSV-2）脑炎、柯萨奇病素（COXBV）脑炎、流行性腮腺炎病毒（PPMV）脑炎等。现将我院1998-08—2003-08收治的198例病毒性脑炎患儿的诊治分析如下。     

病毒性脑炎患者Borna病病毒P24基因片段的检测

目的探讨Borna病病毒(BDV)感染与人类病毒性脑炎的关系。方法采用荧光定量套式逆转录酶聚合酶链反应(FQ nRT PCR)检测了59例临床诊断的原因未明的病毒性脑炎及112名健康人外周血单个核细胞(PBMC)中BDVP24基因片段。结果59例原因未明的病毒性脑炎患者中有3例PBMC中检出BDVP24基因片段,而112名健康对照均未检出。病毒性脑炎患者BDV阳性率(5.08%)高于健康对照,差异有统计学意义(P<0.05),且BDVP24基因片段检测阳性病例的脑脊液中其他常见致脑炎病毒(单纯疱疹病毒、带状疱疹病毒、腮腺炎病毒、柯萨奇病毒和巨细胞病毒)检查均为阴性。结论中国的部分病毒性脑炎患者中存在BDV感染,BDV感染与病毒性脑炎的发病可能有关。     

PCR快速检测病毒性脑炎患者脑脊液中HSV、CXV和CMV

本文应用聚合酶链反应(PCR)和逆转录PCR(RT-PCR)技术检测了27例临床诊断为病毒性脑炎患者和25例其他神经疾病(OND)对照组患者脑脊液(CSF)中单纯疱疹病毒(HSV)、柯萨奇病毒(CXV)和巨细胞病毒(CMV)。27例患者组检出HSV13例、CXV2例、CMV1例，总阳性率为59．3％，而OND对照组皆为阴性。随着检测技术的完善及对更多种类病毒采用PCR早期快速诊断方法的建立，将有效地指导特异性抗病毒药物的选择应用，从而提高治愈率，降低病死率和改进预后。     

散发性和病毒性脑炎的脑电图

本文探讨脑电图（ＥＦＧ）辅助诊断散发性和病毒性脑炎的临床价值。临床资料和结果散发性和病毒性脑炎２６８例来自１９８７年１月～１９９７年１２月。ＥＥＧ随访２次以上。按年龄分甲组４～６岁、乙组７～１２岁、丙组１３～１８岁和丁组１９～６０岁。＜１３岁２０５例;＞１３岁６３例。均有病毒感染史,根据临床表现诊断,为散发性病毒性脑炎１０２例,病毒性脑炎１６６例。主要临床表现见表１。辅助检查：３０例查脑脊液常规：白细胞升高８例,其中潘氏试验弱阳性３例。正常２２例。从血清中检测病毒抗体系列３２例：柯萨奇病毒阳性１…     

2014-2015年石家庄地区儿童病毒性脑炎临床流行病学及临床表现

目的研究石家庄地区儿童病毒性脑炎的临床特点、临床流行病学及病原学特征,为临床诊治提供依据。方法选取2014-2015年于河北省儿童医院住院治疗、出院诊断为病毒性脑炎的1091例石家庄地区患儿,随机抽取200例进行分析,入选病例急性期脑脊液(CSF)检测病毒Ig M抗体,标本选择检测的病毒抗体种类由临床医生根据临床症状及特点选择相应的病毒抗体检测。结果 200例患儿年龄为1.5岁~12岁,平均年龄4.91±0.06岁,以学龄前儿童多见(72.6%);散居儿童(64.5%)多于托幼儿童及学生(35.5%);男性116例,女性82例(男女比例为1.4:1);发病地区以正定(38.0%)、藁城(30.0%)为主,乡村111例,城市89例(比例为1.2:1);发病至入院平均时间3.21±0.89d;所有患儿均出现发热,症状依次为恶心、呕吐(84.5%);头痛、头晕(81.5%);腹痛(58.0%);嗜睡(51.5%);腹泻(12.0%);皮疹(1.6%),病理征阳性(1.4%)。病原学检查均为肠道病毒,分别为埃可病毒176例(88.0%)及柯萨奇病毒24例(12.0%),全年均有发病,流行高峰为夏秋季节。结论肠道病毒是2014-2015年石家庄地区病毒性脑炎流行的主要病原,且在时间和地区分布上有明显集中趋势,应加强对病毒性脑炎的预警和防范。     

Persistent preceding focal neurologic deficits in children with chronic Epstein-Barr virus encephalitis

Epstein-Barr virus encephalitis is a self-limiting disease with few sequelae. Persistence of neurologic deficits prior to and after the acute illness has yet to be described in children. We describe five children with persistent cognitive and focal neurologic deficits due to chronic Epstein-Barr virus encephalitis with various T2-weighted magnetic resonance imaging abnormalities. Clinical features were a 9-year-old boy with aphasia and apraxia, an 11-year-old girl with impulsivity and inappropriate behavior, a 17-year-old boy with deterioration of cognitive skills and judgment, a 5-year-old boy with complex-partial seizures, and a 6-year-old girl with obsessive-compulsive behavior. All patients had elevated serum Epstein-Barr virus titers for acute infection, with cerebrospinal fluid polymerase chain reaction positive for Epstein-Barr virus in four patients. Three children were treated with methylprednisolone with minimal improvement without changes on magnetic resonance imaging. Epstein-Barr virus encephalitis can present with chronic and insidious neurologic symptoms and should be considered in the differential diagnosis of children with acute or chronic neurologic illness of unknown etiology.     

抗GABA(B)R脑炎临床、脑电图及随访研究

目的分析抗GABA(B)R脑炎临床,影像学及脑电图(EEG)特征。方法 5例血清和脑脊液(CSF)抗GABA(B)R抗体阳性的抗GABA(B)R脑炎,分析CSF白细胞数、头颅磁共振(MRI)、24h长程视频脑电图(VEEG)和预后特点。结果 5例抗GABA(B)R脑炎中,精神行为异常2例,意识障碍2例,CSF白细胞数增高4例,癫痫发作5例,其中癫痫持续状态4例(80%)。24h VEEG监测3例各导可见多量阵发性长程持续5~30s、4~6Hzθ节律,并前额、额、前颞可见尖波或复合性慢波。未见异常2例。头颅MRI异常1例,累及海马、额叶皮质。呼吸衰竭1例,行气管插管,未用呼吸机辅助呼吸。1例合并血和CSF抗Hu抗体阳性并发肺癌。随访半年死亡3例(60%),完全正常2例(40%)。结论抗GABA(B)R脑炎是以癫痫发作为特点的疾病,本组5例患者均早期出现严重的癫痫发作。预后与癫痫的严重程度和是否合并肿瘤有关。     

乙脑患儿血清和脑脊液中NSE含量变化与临床的关系

目的研究乙脑患儿血清和脑脊液中NSE含量变化的临床意义。方法检测46例乙脑患儿极期、恢复期血清和脑脊液中NSE含量,检测23例对照组儿童血清和脑脊液中NSE含量。结果乙脑患儿极期血清和脑脊液中NSE含量在普通型、重型、对照组三组之间两两比较差异均有显著统计学意义;恢复期普通型乙脑患儿血清和脑脊液中NSE含量与对照组比较差异无统计学意义;恢复期重型乙脑患儿血清和脑脊液中NSE含量与普通型、对照组比较差异均有统计学意义;各型乙脑患儿血清和脑脊液中NSE含量极期与恢复期比较差异有显著统计学意义;极期乙脑患儿血清和脑脊液中NSE含量变化呈正相关。结论乙脑患儿血清和脑脊液中NSE含量随乙脑的发生发展缓解而变化,其增高程度与病情的严重程度呈正相关。检测NSE水平对判定乙脑患儿脑损伤程度及预后有重要参考价值。     

A study on viral CNS inflammation beyond herpes encephalitis

The early diagnosis of herpes simplex virus encephalitis (HSVE) enables induction of antiviral therapy in this potentially life-threatening disease. The study aimed to determine clinical findings including cerebrospinal fluid (CSF) data and MRI imaging in HSVE patients and to identify features distinguishing HSVE from encephalitis of other viral etiologies. We retrospectively reviewed consecutive patients who were diagnosed with viral encephalitis between 2000 and 2014 at the University Hospital Halle. Forty-nine patients with viral encephalitis were identified. A viral etiology could be confirmed by PCR or antibody testing in 22/49 (44.9 %) of patients (15 (30.6 %) HSV, 5 (10.2 %) VZV, 2 (4.1 %) EBV). In HSVE, typical findings were focal slowing in electroencephalophy (EEG) (80 %, p?=?0.021) and presence of cortical (86.7 %, p?=?0.030) lesions in MRI. Restricted diffusion was particularly helpful in detection of early signal abnormalities in HSVE (p?=?0.014). In 27/49 (55.1 %) of patients, no causative agent could be elucidated. In these patients, 15/27 (55.6 %) experienced a rather “benign” disease course with no MRI pathology despite initially HSVE mimicking clinical picture. However, CSF was significantly different showing a higher amount of granulocytes and activated lymphocytes. The remaining 12/27 (44.4 %) patients developed MRI changes consistent with encephalitis, in 4 of these patients, disease course was fatal. Beside PCR-based serology as standard procedure, MRI including diffusion-weighted images and EEG represent additional tools in early HSVE diagnosis. CSF cytology might be particularly supportive in differentiating likely benign forms of encephalitis.     

Chronic mumps virus encephalitis. Mumps antibody levels in cerebrospinal fluid

To study the outcome of mumps virus encephalitis 47 patients were contacted 1-15 years after the acute encephalitis associated with mumps virus infection. Twenty-three patients experienced clinical sequelae such as difficulties in memory and learning, focal motor or sensory signs, and loss of hearing and visual acuity. Lumbar puncture was performed on 8 patients. Antibodies to mumps virus were detected in 6 cerebrospinal fluid (CSF) specimens using enzyme immunoassay and in 3 patients an abnormal serum/CSF antibody ratio was observed 11, 26 and 58 (controls greater than 85); 14.3, 1.4 and 6.1 years after the acute encephalitis, respectively. Antibodies to other microbes were either undetectable in the CSF or the serum/CSF ratios were normal. The clinical sequelae in about half of the patients and the signs of intrathecal mumps antibody production are suggestive of a chronic process in the central nervous system after encephalitis associated with mumps virus infection.     

Granulomatous Herpes Simplex Encephalitis in an Infant With Multicystic Encephalopathy: A Distinct Clinicopathologic Entity?

BackgroundHerpes simplex virus encephalitis can manifest as a range of clinical presentations including classic adult, neonatal, and biphasic chronic-granulomatous herpes encephalitis.MethodWe report an infant with granulomatous herpes simplex virus type 2 encephalitis with a subacute course and multicystic encephalopathy.CaseA 2-month-old girl presented with lethargy and hypothermia. Computed tomography scan of the head showed multicystic encephalopathy and calcifications. Cerebrospinal fluid analysis by polymerase chain reaction testing for herpes simplex virus 1 and 2, enterovirus, and cytomegalovirus was negative. Normal cerebrospinal fluid interferon-α levels argued against Aicardi-Goutières syndrome. The patient died 2 weeks after presentation. At autopsy, multicystic encephalopathy was confirmed with bilateral gliosis, granulomatous inflammation with multinucleated giant cells, and calcifications. Bilateral healing necrotizing retinitis suggested a viral etiology, but retina and brain were free of viral inclusions and immunohistochemically negative for herpes simplex virus-2 and cytomegalovirus. However, polymerase chain reaction analysis showed herpes simplex virus-2 DNA in four cerebral paraffin blocks. Subsequent repeat testing of the initial cerebrospinal fluid sample using a different polymerase chain reaction assay was weakly positive for herpes simplex virus-2 DNA.ConclusionGranulomatous herpes simplex virus encephalitis in infants can present with subacute course and result in multicystic encephalopathy with mineralization and minimal cerebrospinal fluid herpes simplex virus DNA load. Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present.     

Aseptic meningitis and encephalitis because of herpesviruses and enteroviruses in an immunocompetent adult population

Background and aim:  Human herpesviruses (HHVs) and enteroviruses (EVs) are the major causative agents of CNS viral infections. The aim of the study was to identify the etiology and determine the frequency of aseptic meningitis and encephalitis due to HHVs and EVs in an immunocompetent adult population.
Methods:  Eighty-one patients (ages ≥15) with aseptic meningitis or encephalitis treated in the Infectious Diseases Hospital of Thessaloniki, Greece, during 2003–2006, were included in the study. Polymerase chain reaction for detection of herpes- and enterovirus genome direct in cerebrospinal fluid samples was performed.
Results:  Based on clinical and laboratory data, 36/81 patients had meningitis and 45/81 had encephalitis. Etiology was defined in 11 patients (31%) with aseptic meningitis. EVs were the major causative agents (8/36, 22%), followed by varicella zoster virus (2/36, 5%) and herpes simplex virus-2 (HSV-2) (1/36, 3%). Etiology was identified in 8 of 45 (18%) patients with encephalitis, EV (4/45, 9%) and HSV-1 (4/45, 9%) being the most common pathogens.
Conclusion:  Enteroviruses are the most common cause of adult aseptic meningitis and together with HSV-1 the main causes of encephalitis.     

Dengue infection presenting with central nervous system manifestation

The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical manifestations of encephalitis-like illness who were admitted to the Department of Pediatrics, Siriraj Hospital were prospectively studied for any evidence of dengue virus infection. The diagnosis of dengue virus infection was based on mosquito viral isolation and serologic and polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection. All of these 8 patients were diagnosed by serology. In addition to the serologic diagnosis, four also had positive PCR, one had positive viral isolation, and one had both positive PCR and viral isolation. Only two patients were diagnosed by serologic evidence alone. All except one had clinical courses and laboratory findings compatible with typical dengue infection. All had obvious encephalitic clinical manifestations with normal cerebrospinal fluid findings except one patient, who had mildly increased cerebrospinal fluid protein. All of these patients recovered completely and had benign clinical courses except one patient, who developed leakage symptoms. None had liver failure. Dengue virus can cause acute encephalopathy with fever. It can masquerade as other types of acute viral encephalitis. However, its clinical course and prognosis are usually favorable.     

Isoelectric focusing herpes simplex virus-gB overlay study in brainstem encephalitis

We report a case of herpetic brainstem encephalitis (HBE) retrospectively diagnosed in adult patient. Conventional immunovirological studies failed to disclose the etiology of this patient's affection. An isoelectric focusing-antigen overlay (IEF-O) technique showed that the target of one of the four cerebrospinal fluid oligoclonal bands was herpes simplex virus (HSV)-1 glycoprotein B, indicating a specific anti-HSV immunoresponse restricted to the CNS. IEF-O may represent a useful support for in vivo diagnosis of HBE.     

Diagnosis of Epstein-Barr virus–induced central nervous system infections by DNA amplification from cerebrospinal fluid

A nested polymerase chain reaction was used for the detection of Epstein-Barr virus DNA in 1 patient with encephalitis, and in 1 patient with myelitis. Epstein-Barr virus DNA was detected in cerebrospinal fluid samples obtained at the onset of neurological symptoms in both patients, and serological findings indicated ongoing Epstein-Barr virus infection. In the patient with encephalitis, herpes simplex virus type 1 DNA was transiently detected in the cerebrospinal fluid, while Epstein-Barr virus DNA was still present on day 44 after admittance. Single-photon emission computed tomography in this patient indicated a frontal bilateral hypoperfusion. The diagnostic value of polymerase chain reaction on cerebrospinal fluid and serum samples for Epstein-Barr virus infections of the central nervous system is emphasized.