Influenza surveillance system of Japan and acute encephalitis and encephalopathy in the influenza season

AIM: To understand the situation of influenza epidemics and neurologic complications during the influenza season in Japan. METHODS: The influenza surveillance system in Japan was reviewed and the data on influenza/influenza-like illness and neurologic complications, such as acute encephalitis/encephalopathy, were evaluated. RESULTS: From the data of the National Epidemiological Surveillance of Infectious Diseases (NESID), an increase in clinically diagnosed encephalitis/encephalopathy was clearly noted recently. Most cases reported were acute encephalitis/encephalitis. The number of cases of Reye's syndrome reported was stable and low in number, since the time of the recommendation of not using aspirin for pediatric febrile disease, particularly for influenza-like illness, in Japan. These acute encephalitis/encephalopathy cases were not correlated clearly with clinically diagnosed influenza patients before the 1997/98 influenza season from the surveillance data, although several case reports have shown a relationship. CONCLUSIONS: It is clarified from the NESID that neurologic complications such as acute encephalitis/encephalopathy, apart from Reye's syndrome, have occurred associated with influenza virus infection, especially among young children. Further investigation should be necessary to find the pathogenesis of this serious complication of influenza virus infection and whether this is unique in Japan, due to unclarified factor/factors, or whether it has not been recognized in other countries.     

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目的分析22例流行性乙型脑炎(乙脑)患者临床资料,总结乙脑的临床及影像学特征,丰富乙脑诊治经验。方法收集2011年1月至2011年12月广州市妇女儿童医疗中心神经康复科住院的22例乙脑患儿临床资料,分析发病特征、临床体征、影像学特征。对病例资料采用描述性分析的统计学方法。结果临床特征方面:22例乙脑患者除均表现出高热、意识障碍、惊厥、肢体瘫痪外,其中4例还表现出帕金森综合征的症状及体征。影像学方面:22例中21例表现出双侧丘脑受损,具有帕金森综合征表现的4例除双侧丘脑受累外,还有中脑大脑脚受损的影像学证据。结论乙脑除病毒性脑炎常见临床表现外,部分病例表现出帕金森综合征症状及体征,丘脑及中脑受累是乙脑的特征性影像学改变。     

Anti-NMDAR encephalitis misdiagnosed as Hashimoto's encephalopathy

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-defined autoimmune disorder. Hashimoto's encephalopathy (HE) is a still controversial entity, lacking definite diagnostic criteria.We described a 14-year-old-girl presenting with a clinical picture consistent with the diagnosis of anti-NMDAR encephalitis, confirmed by NMDAR antibody testing. Four years earlier, she had presented a similar episode of acute encephalopathy diagnosed as HE.Anti-NMDAR encephalitis and HE share similar clinical features so that the differential diagnosis can be difficult if specific antibodies are not tested. The correct diagnosis of anti-NMDAR encephalitis is crucial to plan the appropriate management and follow-up, namely in term of oncological screening, since it can be paraneoplastic in origin. We suggest to re-evaluate the clinical history of all subjects with previous HE diagnosis in order to evaluate the possible diagnosis of anti-NMDAR encephalitis and plan the appropriate management of these patients.     

儿童轻微脑炎/脑病伴可逆性胼胝体压部病变综合征的临床特点

目的探讨儿童轻微脑炎/脑病伴可逆性胼胝体压部病变综合征(MERS)的临床特点。方法对8例MERS患儿的临床资料进行回顾性分析。结果患儿发病年龄10个月至12岁,平均5岁2个月。主要临床特点为:有前驱感染史,其中包括发热5例,呕吐4例。临床表现为惊厥6例,意识障碍、阵发性视觉异常各3例。颅脑MRI弥散加权成像表现为胼胝体压部高信号,其中1例同时伴有双侧半卵圆中心、部分颞叶白质对称多发长T1、长T2信号。全部病例5~30 d后复查MRI,异常信号消失。随访3个月至2年,8例患儿神经发育均无异常。结论儿童MERS发病多与感染有关;颅脑MRI弥散加权成像示胼胝体压部高信号为其特征;多数患儿预后良好。     

Reye syndrome or side-effects of anti-emetics?

By analysing two patients initially diagnosed as Reye syndrome evidence is given that in some patients considered as having Reye syndrome, the syndrome is an escalation of symptoms due to viral disease and to unrecognized drug-induced encephalopathy, mainly by anti-emetics. A detailed drug history, considering all medication — not exclusively aspirin — taken during the full course of the illness is essential to differentiate between Reye syndrome and drug-induced symptoms. In addition, a critical analysis is presented of the four main case-control surveys that have lead to the proposal that salicylates are primary causative agents of Reye syndrome. In these surveys, medications given during the prodromal illness were adequately recorded, but other drugs given after the onset of vomiting have been overlooked or deliberately excluded. New epidemiological studies are needed, recording all drugs given to the patients throughout the full course of their illness until the moment of admission, in order to elucidate the mystery of Reye syndrome.     

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??Objective To compare the etiology and clinical characteristics of clinically mild encephalitis/encephalopathy with a reversible splenial lesion of corpus callosum in Chinese children with those cases from different countries. Methods The clinical and imaging features of two children with the diagnosis of MERS were analyzed and pediatric MERS cases were screened from “China National Knowledge Infrastructure”??“China Biology Medicine”??“PubMed ” and “Web of Science” databases for analysis between January??2000 and February??2015. Results A total of 115 cases were collected and the male to female ratio was 1.1 to 1?? with onset age of 6 months to 14 years old. There was usually a certain infection before the onset. About 58.3% of infectious pathogens were detected?? and influenza virus and rotavirus infection were very common pathogens?? followed by bacterial infections and mycoplasma pneumoniae infection. The neurological symptoms manifested as mental and behavioral disorders ??42.6%???? seizures ??37.4%???? decreased consciousness ??5.2%?? or consciousness??25.2%?? and dysarthria ??6.9%??. The MR imaging ??MRI?? findings exhibited lesions in an isolated splenial or the white matter and entire corpus callosum?? and completely disappeared at follow-up MRI. With anti-infection and symptomatic treatments??the clinical symptoms of most patients were relieved without leaving any serious neurological sequelae. Conclusion Infection is a prevalent predisposing factor of MERS in children?? with nonspecific clinical characteristics. The MRI examination plays a role of implication for diagnosis. And all clinical symptoms of patients will disappear within a few days and the prognosis of patients is good.     

Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapy

BACKGROUND: To establish a treatment strategy for acute encephalopathy and encephalitis associated with influenza virus infection, the pathophysiology of the disease was investigated through manifestations and laboratory findings of patients. PATIENTS AND METHODS: A child with central nervous system (CNS) complications during the course of influenza virus infection was analyzed in view of immunologic abnormalities. In addition, four children with acute encephalopathy and encephalitis were enrolled in the hypothermia treatment for the purpose of stabilizing the cytokine storm in the CNS. RESULTS: The CNS symptoms preceded the systemic progression to the failure of multiple organs (MOF) and disseminated intravascular coagulopathy (DIC). The mild hypothermia suppressed the brain edema on computed tomography (CT) scanning and protected the brain from the subsequent irreversible neural cell damage. CONCLUSION: The replicated viruses at the nasopharyngeal epithelium may disrupt the olfactory mucosa and gain access to the brain via the olfactory nerve system. The direct virus-glial cell interaction or viral stimulation of the glial cells induces the production and accumulation of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-alpha, in the CNS. The cytokine storm results in neural cell damage as well as the apoptosis of astrocytes, due to the TNF-alpha-induced mitochondrial respiratory failure. The disruption of the blood-brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF. Mild hypothermia appears promising in stabilizing the immune activation and the brain edema to protect the brain from ongoing functional, apoptotic neural and glial damage and the systemic expansion of the cytokine storm.     

Influenza-associated encephalopathy in Japan: Pathogenesis and treatment

It is estimated that more than 100 children die of influenza-associated encephalopathy (influenza encephalopathy) every year in Japan. Influenza encephalopathy is distinct from Reye's syndrome. Specifically, 20% of influenza encephalopathy patients exhibit bilateral thalamic necrosis on neuroimaging, a lesion referred to as acute necrotizing encephalopathy (ANE). Influenza encephalopathy may develop by the same pathogenetic mechanisms as ANE, possibly via vasoactive substances or a process leading to vasoconstriction in the central nervous system (CNS). A novel substitution at the receptor-binding site (Tyr 137 to Phe) was reported to be found exclusively in influenza type A (H3N2) viruses isolated from patients with influenza encephalopathy, suggesting that encephalopathy may be caused by a variant influenza type A (H3N2) virus. Recently, it has been reported that cytokines may mediate the disease and that a high plasma concentration of interleukin-6 could be an indicator of progression to encephalopathy. Although it is unknown whether influenza virus invades the CNS, amantadine therapy for influenza encephalopathy has been tried in Japan, in patients in whom influenza type A infection has been demonstrated by rapid antigen detection tests.     

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目的探讨急性淋巴细胞白血病(ALL)儿童因使用甲氨蝶呤(MTX)出现的急性脑病的临床及影像学特点。方法 2005-07-01—2009-08-31首都医科大学附属北京儿童医院血液病中心收治的ALL患儿637例,回顾性分析应用MTX后发生急性脑病病例的临床和影像学资料。结果 7例患儿应用MTX后3～10 d发生急性脑病,主要表现为偏瘫、全身抽搐、言语不利、单侧肢体无力和面瘫,予对症治疗后3～5 d内缓解。急性脑病的发生与MTX剂量、患儿年龄和MTX代谢有关。4例患儿弥散加权成像(DWI)表现为深部白质的弥散受限,以半卵圆中心和放射冠区为著。结论 MTX诱发的急性脑病主要表现为一过性、局灶性运动功能损害,DWI的弥散受限是MTX诱发急性脑病诊断的敏感手段。     

急性淋巴细胞白血病患儿中可逆性脑病临床总结

目的探讨急性淋巴细胞白血病患儿化疗后可逆性脑病的临床和影像学特点。方法回顾分析2015年9月1日至2018年9月1日住院时发生脑病的急性淋巴细胞白血病患儿的临床资料。结果研究期间共收治新发急性淋巴细胞白血病582例,9例患儿发生10次可逆性脑病(1例患儿发生2次),其中男6例、女3例,脑病发生中位年龄6.55岁(3.9~12.5岁)。最常见的神经系统临床表现是抽搐,其次是肌无力和感觉异常。7例患儿曾接受培门冬治疗;5例患儿在脑病发生前有急性高血压病史;6例患儿在脑病发生时有低钠血症,部分有低纤维蛋白原血症。头颅磁共振成像检查均提示T1和T2信号异常,累及部位多见于顶枕叶。结论联合化疗、化疗药物鞘内注射和急性高血压是可逆性脑病发生的高危因素;监测血压、血钠、纤维蛋白原,以及头颅磁共振成像检查有助于早期发现可逆性脑病。     

Kleine–Levin syndrome elicited by encephalopathy with reversible splenial lesion

Kleine–Levin syndrome is a rare sleep disorder of unknown etiology characterized by repetitive episodes of hypersomnia between asymptomatic periods. We report the case of a 13‐year‐old girl who presented with drowsiness triggered by influenza A as the first episode. Magnetic resonance imaging (MRI) on day 6 showed transient reduction of diffusion in the corpus callosum splenium. The patient was diagnosed with encephalopathy with a reversible splenial lesion. The symptoms resolved after 10 days, but additional episodes of hypersomnia lasting 5–10 days occurred 1, 5, 6, 11, 13, and 25 months after the first episode. MRI during hypersomnia indicated no lesions, and sleep duration and cognition were normal between episodes. The patient was diagnosed with Kleine–Levin syndrome. Electroencephalographic and clinical findings during the first episode were similar to those during the other episodes. Encephalopathy with a splenial lesion and Kleine–Levin syndrome may have similar pathological mechanisms causing a disturbance in consciousness.     

A study of acute febrile encephalopathy with special reference to viral etiology

Objective  To study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis. Methods  A prospective hospital based study conducted on the consecutive patients admitted in a pediatric unit during the period of 1^st February 2004 to 31st January 2005 based on the following inclusion criteria: (1) Age more than 1 month and less than 18 years and (2) A diagnoses of acute febrile encephalopathy, based on the following criteria: (i) fever (ii) acute depression of consciousness or mental deterioration for more than 12 hours with or without motor or sensory deficit and (iii) Total duration of illness at the time of admission 1 week or less. Results  The final study group comprised of 151 patients with mean age of 3.21 ± 2.9 (range of mth-13 years) and male: female ratio of 1.71: 1. A diagnosis other than viral encephalitis was reached in 94 patients (62.3 %). Pyogenic meningitis was the most frequent diagnosis 51(33.8 %) followed by tubercular meningitis 12 (7.9 %), and cerebral malaria 8 (5.2 %) in the patient group of non-viral causes. Fifty-seven cases (37.3%) were suspected as viral encephalitis and mean age of the cases suspected as viral encephalitis was 2.8 ± 2.9 (Range 1 mth-10 yrs) with male: female ratio of 1.28: 1. Etiological diagnosis was reached or considered probable in 41 (72%) cases out of the suspected patients. The most common etiological agent identified was enterovirus 71 in 20 patients (35.1 %). The other viruses identified were mumps in 6 (10.5%), Japanese encephalitis in 5 (8.7%), and measles in 4 (7%) cases. MRI brain was done in 39 patients and was abnormal in 14 patients. Out of 57 cases of suspected viral encephalitis 10 patients expired within 48 hours, 2 > 48 hours and 19 atients had significant neurological sequels at discharge. Conclusion  The etiology of acute febrile encephalopathy varies from infectious etiologies to noninfectious metabolic disorders. There are no distinguishing clinical or radiological features to differentiate the various causes of viral encephalitis. The clinical and the radiological findings in encephalitis should be interpreted in the geographical and other epidemiological background.     

肠道感染相关性出血性休克与脑病综合征临床分析

目的探讨肠道感染相关的出血性休克与脑病综合征临床特点。方法分析12例与文献报道的出血性休克与脑病综合征相一致的患儿,均为突发昏迷和抽搐、高热、休克、水样腹泻、代谢性酸中毒、DIC、肝肾功能损害,前躯期为严重的水样便。结果大便检测3例轮状病毒阳性:高死亡率和严重的运动和语言障碍是其特点;极显著的肝酶学改变,血胆红素多正常。入院1～2d后肝转氨酶达高峰,多于1周内恢复正常;随着休克的纠正,肾功能于1～2d内转正常,病情缓解,但神经功能却发生进行性损害:发病后持续昏迷或频繁抽搐,肺出血,难以纠正的休克,持续无尿,出血不止,多于短期内死亡;本组死亡7例,4例留有严重的神经后遗症,1例神经功能正常。结论应提高对出血性休克与脑病综合征的临床认识。治疗关键是纠正休克,肠源性的全身炎症反应可能参与发病机制。     

Effect of mass immunization against influenza encephalopathy on mortality rates in children

BACKGROUND: Since the Japanese influenza vaccination program for school children was terminated in 1994, a steep rise has been noted in the number of young children reported with fulminant influenza and influenza associated with acute encephalopathy/encephalitis. The purpose of the present study was to interpret and clarify the effect of mass influenza vaccination on mortality of Japanese children, aged <19 years, with influenza and influenza-associated acute encephalopathy/encephalitis. METHODS: The authors examined the distribution of mortality rates of children in Japan aged <19 years with influenza during 1950-2000, influenza associated with central nervous system (CNS) signs in the period 1950-1978, and the estimated cases of influenza associated with acute encephalopathy/encephalitis in the period 1987-2000. RESULTS: Total influenza mortality among children aged <19 years has increased since 1990, with children aged <4 years after 1994 being the worst affected. The mean values of mortality rates of influenza associated with central nervous system signs during 1963-1978 and the estimated mortality of children aged <9 years during 1979-1994 were significantly lower than in some years before 1962, and after 1995 (P < 0.05). The annual mortality rates of influenza-associated acute encephalopathy/encephalitis during 1995-2000 were significantly higher than the expected mortality of influenza associated with central nervous system signs in children aged <14 years (P < 0.05). CONCLUSION: The results of the present study suggest that mass immunization of school-aged children reduced the mortality rate from influenza-associated acute encephalopathy/encephalitis in children less than 9 years of age.     

伴岛叶三层现象的急性坏死性脑病一家系临床及遗传学分析

目的探讨伴岛叶三层现象(TA)的急性坏死性脑病(ANE)临床及遗传学特征。方法回顾分析1个确诊为ANE家系的临床资料。结果先证者为男性,4.5岁时以惊厥、意识障碍起病,1岁时有热性惊厥史;头颅磁共振示对称性多灶性损害,岛叶存在TA。家系中有6例患者,起病年龄6月龄至50岁,主要以发热后惊厥或惊厥持续状态及意识障碍起病,3例因惊厥持续状态死亡;免疫治疗及能量支持可改善预后。基因检测发现家系RANBP2基因变异(NM_006267;c.1754 CT[p.T585M])。结论首次报道TA可出现于岛叶。