Amantadine penetration into cerebrospinal fluid of a child with influenza A encephalitis

The use of amantadine has been advocated as treatment for influenza A encephalitis despite limited information regarding cerebrospinal fluid concentrations and the pathogenesis of encephalitis associated with influenza virus infections. We report a 2-year-old child with influenza A encephalitis treated with amantadine who achieved a potentially therapeutic concentration in cerebrospinal fluid. Despite this the child developed significant neurologic impairment.     

Varicella-zoster virus acquired at 4 months of age reactivates at 24 months and causes encephalitis

Varicella-zoster virus (VZV) reactivation in the brain caused encephalitis in a 2-year-old immunocompetent child who had chickenpox 20 months before. Radiologic findings were consistent with large to medium-vessel-vasculitis. VZV-DNA was detected in cerebrospinal fluid. Early acquisition of VZV may predispose to major neurologic complications that can occur years after the primary infection.     

Focal encephalitis with enterovirus infections

We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.     

儿童自身免疫性脑炎

儿童自身免疫性脑炎是由作用于神经元蛋白并影响神经递质传递及兴奋性的自身免疫性抗体所致。临床以抗N-甲基-D-天门冬氨酸 （N-methyl-D-aspartate,NMDA）受体脑炎和自身免疫性边缘叶脑炎最常见。儿童自身免疫性脑炎临床诊断主要依据临床表现、影像学检查、血液和（或）脑脊液抗体检测。糖皮质激素、丙种球蛋白和血浆置换是目前的一线治疗手段。重在早期诊断和早期免疫治疗,部分患儿预后良好。     

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??Abstracts?? Child autoimmune encephalitis is characterized by autoimmune antibodies specifically against neuronal proteins and affecting neurotransmitters and excitability. Clinically the most common autoimmune encephalitides are anti-NMDA receptor encephalitis and autoimmune limbic encephalitis. Diagnosis of child autoimmune encephalitis is mainly based on clinical manifestations?? imaging examination?? detection of autoimmune antibodies in blood and/or cerebrospinal fluid. Corticosteroids and gamma globulin and plasma exchange are the first-line treatment. Early diagnosis and early start of immunotherapy will lead to a good prognosis in some children with autoimmune encephalitis.     

Brainstem and striatal encephalitis complicating Mycoplasma pneumoniae pneumonia: possible benefit of intravenous immunoglobulin

Encephalitides of the brainstem and the striatum associated with Mycoplasma pneumoniae infection are believed to be mediated by an autoimmune process triggered by the organism, a toxin or direct invasion by the organism itself. Inability to identify M. pneumoniae from cerebrospinal fluid by culture or polymerase chain reaction suggested a possible immunologic process. A trial of intravenous immunoglobulin in a critically ill patient with encephalitis that developed in parallel to M. pneumoniae pneumonia was associated with neurologic improvement within 48 h of treatment.     

Encephalitis. Recent clinical, diagnostic and therapeutic aspects]

The subjects of this paper are mainly the encephalitis of viral origin and in addition 3 types of non-viral encephalitis of practical importance. A review is given on the current diagnostic possibilities including; clinical criteria; examination of the cerebrospinal fluid; neuroradiology and; etiological investigation by means of direct identification of the microbes in the cerebrospinal fluid or by measuring intrathecally produced antibodies. After some general statements concerning treatment the specifically treatable encephalitis caused by Herpes simplex virus, Mycoplasma pneumoniae, Borrelia burgdorferi and Toxoplasma gondii are discussed in more detail.     

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目的探讨神经元特异性烯醇化酶(NSE)、S-100β对肠道病毒71型(EV71)脑炎的早期诊断及脑损伤程度的评估价值。方法选取2008年5月至2010年12月山东大学齐鲁儿童医院重症监护室(PICU)收治的EV71脑炎患儿(EV71脑炎组)100例,同期住院的其他病毒性脑炎患儿89例为其他病毒性脑炎组,非神经系统感染患儿22例为阴性对照组。采用ELISA法检测所有EV71脑炎组及其他病毒性脑炎组患儿急性期及恢复期脑脊液与血清NSE及S-100β蛋白含量,检测阴性对照组患儿急性期及恢复期血清NSE及S-100β蛋白含量及急性期脑脊液NSE及S-100β蛋白含量,并分别进行比较。结果 EV71脑炎组急性期脑脊液、血清及恢复期血清中NSE与S-100β高于阴性对照组,差异均有统计学意义(P均<0.01)。EV71脑炎组急性期脑脊液中NSE低于其他病毒性脑炎组,差异有统计学意义(P<0.05)。EV71脑炎组急性期血清与恢复期脑脊液、血清中S-100β蛋白低于其他病毒性脑炎组,差异有统计学意义(P<0.05)。EV71脑干脑炎组急性期与恢复期脑脊液、血清中NSE显著高于普通脑炎组,差异有统计学意义(P<0.05或P<0.01);EV71脑干脑炎组急性期与恢复期脑脊液、血清中S-100β蛋白显著高于EV71普通脑炎组,差异有统计学意义(P<0.01)。血清与脑脊液中NSE与S-100β有明显相关性(r=0.782、0.734,P均<0.01)。结论监测手足口病患儿脑脊液与血清NSE、S-100β可早期诊断是否合并中枢神经感染,并可评估脑损伤程度及预后。     

抗N-甲基-D-天门冬氨酸受体脑炎与病毒性脑炎的关系

抗N-甲基-D-天门冬氨酸受体(anti-N-methyl-d-aspartate receptor,NMDAR)脑炎是一种常见的自身免疫性脑炎,近年来逐渐被神经医学领域所认识.该病具有相对一致的临床表现,脑脊液具有特异性的抗NMDAR抗体,免疫治疗有较好的临床效果.抗NMDAR脑炎与病毒性脑炎关系密切,在认识该病之前,其常常被误诊为病毒性脑炎.近来大量研究发现病毒感染是抗NMDAR脑炎的重要诱发因素,而部分病毒性脑炎尤其是单纯疱疹病毒脑炎的复发,是由病毒感染继发中枢神经系统免疫性炎性反应所致,需要进行免疫治疗.因此认识抗NMDAR脑炎及其与病毒性脑炎的关系,对患者的诊治与预后有重要影响.     

A patient with rubella encephalitis and status epilepticus

Rubella is an important childhood disease that was historically widespread but is now very infrequent. It is an acute viral infection ordinarily characterized by mild constitutional symptoms. Complications are relatively uncommon in childhood. Encephalitis similar to that seen with measles occurs in about 1 in 6,000 cases. The severity is highly variable, and there is an overall mortality rate of 20%. Symptoms in survivors usually resolve within 1-3 week without neurologic sequelae. An 8.5-year-old boy presented with rubella encephalitis and status epilepticus. Five days before admission the patient had erythematous maculopapular rash on the face, spreading to the trunk and extremities. On the admission day, he had a generalized tonic-clonic seizure with loss of consciousness. Microscopic and cytologic examinations of cerebrospinal fluid showed nonspecific. Electro-encephalography (EEG) showed diffuse slowing. An enzyme linked immunosorbent assay (ELISA) revealed that rubella IgM antibody titer was positive in serum and in cerebrospinal fluid. One day later, the patient became conscious with normal physical condition. As a conclusion, it is possible to prevent the complications of rubella infection, especially the congenital rubella syndrome and encephalitis with a rapid and efficient vaccination program.     

抗N-甲基-D-天冬氨酸受体脑炎相关细胞因子的研究进展

抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎为一类中枢神经系统自身免疫炎症性疾病，目前对其免疫机制知之甚少。脑脊液中除抗NMDAR抗体检测外，缺乏与疾病相关标志物，导致部分患者延误诊治。为此，近年针对细胞因子的研究不断增加，旨在评价其是否可作为新型生物标志物对疾病进行评估并协助诊治。现有研究表明部分细胞因子与抗NMDAR脑炎疾病进程可能相关，故该文就抗NMDAR脑炎相关细胞因子研究进展进行综述。     

病毒性脑炎患儿脑脊液Caveolin-1、IL-1β、VEGF的变化与意义

目的 比较病毒性脑炎患儿不同时期脑脊液中Caveolin-1、IL-1β、VEGF水平的差异,探讨Caveolin-1、IL-1β、VEGF在病毒性脑炎的发病机制中的作用,以及评估其对病毒性脑炎的病情严重程度及预后判断的临床意义.方法 病例来自于2011年7月至2012年7月在湖南省儿童医院神经内2科住院的病毒性脑炎患儿65例,急性期54例,恢复期11例;按临床表现又分为轻度组40例及重度组25例,收集对照组10例,癫（癎）组10例.完善脑脊液、脑电图、头MRI等检查.应用双抗体夹心ELISA法检测以上患儿脑脊液中Caveolin-1、IL-1β、VEGF的水平.结果 Caveolin-1、IL-1β、VEGF水平在病毒性脑炎急性期分别为（49.209±22.320） pg/ml、（16.923±6.823） ng/ml、（44.342±19.264） ng/ml,在恢复期的表达分别为（33.253±20.349）pg/ml、（11.724±3.009） ng/ml、（30.312±18.147） ng/ml,显著高于对照组（P＜0.01）.急性期与恢复期相比,差异有统计学意义（P＜0.05）.病毒性脑炎急性期表达高于癫（癎）组,差异有统计学意义（P＜0.05）.病毒性脑炎组患儿脑脊液中蛋白含量在0.5 -1.0 g/L范围的脑脊液中Caveolin-1与IL-1β及VEGF表达水平高于≤0.5 g/L组,且其差异具有显著性（P＜0.01）.不同的脑炎严重程度、不同的抽搐频繁程度、不同的EEG改变严重程度患儿脑脊液中Caveolin-1、IL-1β、VEGF水平之间差异无统计学意义（P＞0.05）.但头MRI改变严重者,脑脊液中Caveolin-1、IL-1β、VEGF水平增高明显,且差异有统计学意义（P＜0.05）.结论 Caveolin-1、IL-1β、VEGF可能参与病毒性脑炎的发病机制,对病毒性脑炎的病情严重性评估及预后判断有一定意义.     

Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children

Reports of neurologic manifestations of human parvovirus B19(B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten(29%) were immunocompromised and 17(39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15(44.1%) patients, and focal neurologic signs in 12(35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid(CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 Ig M(82.6%) and CSF B19 DNA(90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen(57.6%) patients recovered completely, 11(33.3%) patients had some neurological sequelae and 3(8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1 protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed.     

The diagnostic value of cytology of the CSF (author's transl)]

Cytological examination of cerebrospinal fluid needs special techniques of cell collecting and staining. On condition of realizing the methodical requirements cytology of the cerebrospinal fluid brings more advancement in diagnostics than other laboratory examinations. The advantages of this procedure are: 1. Meningitis, meningoencephalitis, and subarachnoidal hemorrhage can be immediately diagnosed by cytological examination of the cerebrospinal fluid. In cases of encephalitis cytological findings depend on the extend of the inflammatory process and its distance from the cerebrospinal fluid compartement. Absence of tumor cells in preparations of cerebrospinal fluid cannot exclude primary or secundary brain tumors. 2. Cytological examination enables a better insight into the dynamics of cellular reactions proceeding in the cerebrospinal fluid as well as in its enlining tissues.     

急性播散性脑脊髓炎合并抗接触蛋白关联蛋白2抗体自身免疫性脑炎1例报告

目的 探讨急性播散性脑脊髓炎(ADEM)合并抗接触蛋白关联蛋白2(Caspr 2)抗体自身免疫性脑炎的临床特征.方法 回顾分析1例ADEM合并抗Caspr2抗体自身免疫性脑炎患儿的临床资料.结果 患儿,女性,7岁10月龄,因发热伴精神差入院,病程中相继出现癫痫发作、嗜睡、昏迷、认知功能损害、精神性格改变、失眠、神经性疼...     

Human cytomegalovirus DNA in cerebrospinal fluid

To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinal fluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal fluid is discussed. By applying the polymerase chain reaction to cerebrospinal fluid, the mode of brain invasion by CMV can be clarified further.     

A case of agammaglobulinaemia complicated by meningoencephalitis due to Echo virus 27

A boy with agammaglobulinaemia diagnosed and treated from the age of 3 years 2 months developed encephalitis at 4 years 3 months. The illness showed a remitting but deteriorating course until death aged 6 years 5 months. Echo virus type 27 was isolated from the cerebrospinal fluid during the terminal illness. The virus was not isolated from five earlier cerebrospinal fluid samples nor was virus detected in a temporal lobe biopsy.     

儿童抗N-甲基-D-天门冬氨酸受体脑炎的诊断与鉴别诊断

自身免疫性脑炎相对少见,且临床表现多种多样,很难在疾病早期给予确诊。因此,儿科临床医生应该熟悉自身免疫性脑炎的临床症状、体征、辅助检查特点、影像学改变、免疫学特征以及鉴别诊断要点。为正确诊断抗N-甲基-D-天门冬氨酸受体（NMDAR）脑炎,患儿应该进行包括寡克隆带检测的脑脊液检查、头颅磁共振扫描以及普通脑电图和/ 或24 h 视频脑电图检查。对于早期出现精神症状和癫癎发作的患儿尤其注意进行血液和脑脊液中抗NMDAR 抗体测定。脑电图出现“δ 刷”时对该病临床诊断有帮助。脑脊液NMDAR 抗体阳性是诊断该病的金标准。抗NMDAR 脑炎的鉴别诊断非常宽泛,儿童患者应该主要与单纯疱疹病毒性脑炎、其他自身免疫性脑炎及精神病相鉴别。     

Human cytomegalovirus DNA in cerebrospinal fluid.

To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinal fluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal fluid is discussed. By applying the polymerase chain reaction to cerebrospinal fluid, the mode of brain invasion by CMV can be clarified further.     

Ictal asystole and anti-N-methyl-D-aspartate receptor antibody encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is a recently identified autoimmune disorder that is increasingly recognized in children. Most cases occur in girls and women and may be paraneoplastic with an associated ovarian teratoma. Characteristic clinical features include neuropsychiatric symptoms, dyskinesias, decreased consciousness, and autonomic instability. We report the first case of asystole associated with temporal lobe seizures in this disorder and highlight the need for careful monitoring for this potentially fatal complication. A 15-year-old previously healthy girl presented with focal seizures and personality changes that progressed to periods of agitation and confusion alternating with catatonia. Anti-NMDAR antibodies were detected in the cerebrospinal fluid and serum. Twenty-six days after initial presentation, new seizures developed characterized by bradycardia and oxygen desaturation. Continuous video-electroencephalogram monitoring captured 3 seizures with left-temporal onset and associated asystole. An ovarian teratoma was diagnosed by pelvic ultrasound and computed tomography, and surgical resection was followed by gradual improvement in her neuropsychiatric symptoms. Treatment with phenobarbital beginning on day 26 lead to the cessation of seizures. However, asymptomatic bradycardia and pauses of 3 seconds continued. After insertion of a demand pacemaker on day 46, there were no further cardiac events. The patient was also treated with 2 courses of intravenous immunoglobulin. Outpatient follow-up at 4 months revealed near-complete neurologic recovery and no cardiac events. To our knowledge, ictal asystole has not previously been described as a complication of anti-NMDAR encephalitis; it is a preventable cause of death in this emerging pediatric disorder, which presents with protean symptoms and is easily misdiagnosed.