Overview of acute encephalitis and encephalopathy

Acute encephalitis/encephalopathy includes a wide variety of diseases and syndromes. Marked advances have recently been made with regard to their classification, pathophysiology, diagnosis and treatment. Clinical and pathologic features of acute encephalitis are determined by pathogens (mostly viruses), humoral immunity and cellular immunity, and those of acute encephalopathy by cytokine storm, metabolic disorder (mitochondrial, in particular)and excitotoxicity.     

Epidemiology of acute encephalitis or encephalopathy in Japan

Epidemiological situation on acute encephalitis in Japan from 2004 to 2009 are described. Acute encephalopathy suspected infectious disease origin such as influenza encephalopathy are involved. Data are based on the National Epidemiological Surveillance of Infectious Diseases (NESID) under Infectious Disease Control Law. During these 6 years, 1467 cases are reported. More than 50% of them are less than 10 year old, and top age group is 1 yo and the second group is 0 yo. In 2004, acute encephalopathy outbreak(cause unknown although mushroom poisoning was suspected) occurred in northern part of Japan, and this event was detected under this reporting system. Major cause of acute encephalitis/encephalopathy are influenza virus infection (acute influenza encephalopathy: AIE) and many AIE cases were reported during influenza A/H1N1 2009 outbreak. Eight cases of measles encephalitis among adolescence and young adult age were reported in 2007, however, no report since 2008.     

Clinical variability in viral infection related acute encephalitis or encephalopathy

Children with acute encephalopathy (AEP) or acute encephalitis(AE) show variable findings in the clinical manifestations and on the neuroimaging. Patients with AE present variable symptoms: disturbance of consciousness, seizure, ataxia, dystonia, abnormal behavior, apnea, and others. This variability depends on the location of lesions including basal ganglia, brain stem, cerebellum, or cerebral gray/white matter. In AEP, MRI findings can be categorized into (1) severe brain edema, (2) acute necrotizing encephalopathy, (3) cortical necrosis that appears 4-5 days after the onset, and (4) others. Serum AST elevates in approximately 50% of AEP patients, and among them around 60% develops DIC. The high AST group includes Reye syndrome(RS), mimic RS and AEP with shock syndrome.     

Differential diagnosis for diseases similar to acute encephalitis/encephalopathy

Acute encephalitis/encephalopathy is a life-threatening disease, and early diagnosis is important. The acute encephalitis/encephalopathy is characterized by impaired consciousness, delirium, convulsion, pyrexia, vomiting, headache, paralysis and so on. We need to distinguish various diseases with similar symptoms, such as febrile seizure, bacterial meningitis, acute disseminated encephalomyelitis, cerebrovascular disease, non-convulsive status epilepticus, benign convulsion with gastroenteritis, hypoglycemia, inherited metabolic disease, toxicosis, heat attack, somatoform disorder and so on, from acute encephalitis/encephalopathy. We describe the features of these diseases in point of view with difference from acute encephalitis/encephalopathy. A synthetic and prompt evaluation including medical interview, neurological sign, blood examination, computed tomography, magnetic resonance imaging, spinal fluid examination, electroencephalogram, is necessary to diagnose as acute encephalitis/encephalopathy.     

儿童急性脑炎/脑病的不良预后因素分析

目的 探究影响急性脑炎/脑病(acute encephalitis/encephalopathy, AE)患儿预后的因素。方法 回顾性分析2018年6月1日至2021年5月30日于福建省妇幼保健院儿科临床确诊为AE患儿的临床资料及不良预后(出院时有以下情况：院内死亡、气管切开、胃肠内管饲、需要康复治疗及难治性癫痫)。采用多因素Logistic回归分析影响AE不良预后的因素。结果 研究纳入AE患儿105例,出现不良结局34例(32.4%),其中发生院内死亡5例(4.8%)。多因素Logistic回归分析结果显示,发热持续时间长(>5天)、惊厥发作≥3次、呼吸衰竭、合并脏器功能损伤是AE不良预后的危险因素。结论 发热持续时间长(>5天)、惊厥发作≥3次、呼吸衰竭、合并脏器功能损伤与AE不良预后密切相关,临床早期发现高风险患儿并及时给予针对性干预措施可改善患儿预后。     

Influenza-associated encephalitis/encephalopathy in childhood

Influenza-associated acute encephalitis/encephalopathy in childhood was reviewed. Annual incidence of this disease condition is estimated as 100-500 cases in Japanese children. Mortality rate of this disease would be as high as 40% died with a rapid fulminant course. Coagulopathies, hepatic dysfunctions and brain CT abnormalities were risk factors for the poor prognosis. The destruction of the vascular endothelial cells via the activation of inflammatory cytokines by influenzavirus would presumably be the pathomechanism of the neurological dysfunction.     

新生儿胆红素脑病发病机制与防治

黄疸是新生儿时期常见临床现象,胆红素脑病是其严重并发症,重者可致死,幸存者常留下“核黄疸四联症”和智力低下等后遗症。因此,正确认识胆红素脑病的发病机制,对合理干预新生儿黄疸,预防胆红素脑病及其后遗症的发生有着重要意义。本文从胆红素的神经毒性作用、胆红素毒性作用的影响因素及胆红素脑病的防治措施3方面进行综述。     

Genetic susceptibility to virus associated encephalitis or encephalopathy

There has been rapid progress in the understanding of the protective mechanism against infection during the past decade. We reviewed the genetic susceptibility in familial or recurrent encephalitis/encephalopathy and subacute sclerosing panencephalitis (SSPE). Recessive mutation of UNC-93B1 and dominant mutation of TLR3 were associated with herpes simplex encephalitis (HSE). Those mutations impair the dsRNA-induced IFN-alpha/beta and IFN-lambda production and predispose to HSE. Dominant mutation of RANBP2 (encoding a nuclear pore protein) was detected in familial or recurrent patients with acute necrotizing encephalopathy. Polymorphisms of MxA, IL-4, IRF1, TLR3, PD1 and TLR3 are probably associated with the development of SSPE. Identification of causing or predisposing genes would enable the early diagnosis and the establishment of effective protection or treatment.     

Prognosis of acute encephalopathy

The prognosis in children with acute encephalopathy who were achieved rehabilitation in our rehabilitation center was presented. Main sequelae was motor disturbance 25%, mental deterioration 90%, higher cortical dysfunction 80% and epilepsy 70%. The patients were divided into 5 groups according to the clinical courses at the onset: cases with metabolic disorders, cases with cytokine storms, cases with status convultics, cases with severe refractory status epilepticus, and cases with the main symptom of decreased consciousness. Typical cases of each group were showed with their brain MRI and single photon emission cerebral tomography (SPECT). In cases with metabolic disorders and cytokine storms, the sequelae were generally severe. In cases with status convulticus, main sequelae was mental deterioration. In cases with severe refractory status epileptics, most contraversial problem was epilepsy. In cases with the main symptom of decreased consciousness, higher cortical dysfunction was the main problem.     

Pathogenesis of acute pneumonia

The patients with acute pneumonias demonstrated interdependent changes in lipid peroxidation (LPO), antioxidant system (AOS), immune system (IS), and in the pituitary-adrenocortical system (PAS), related to the character of the disease course. The most pronounced changes were seen in the patients with acute pneumonias eventuating in pneumofibrosis. The high level of LPO was combined with AOS depletion, immunodeficiency formation, and with dysfunction of the PAS. Antibacterial treatment did not exert any appreciable effect on the characteristics under study. Thus, the level of LPO and AOS status are important components in the pathogenesis of acute pneumonias, determining the character of the disease course and outcome. It is advisable that research work aimed at the design of the principles of antioxidant therapy may be intensified.     

Pathogenesis of acute porphyria

The pathogenesis of the clinical manifestations of acute porphyria has been considered in the light of their pathological changes and their aberrations of the haem biosynthetic pathway. These manifestations may be explained almost entirely upon a neurogenic basis. A number of hypotheses have been considered to explain the clinical, pathological and biochemical features. Of these hypotheses two seem more impressive: (i) the neurological manifestations may be explained by a deficiency of haem in neural tissues; (ii) the porphyrin precursor 5-aminolaevulinic acid (ALA) may have in addition specific pharmacological activity.     

Mild brain hypothermia for influenza encephalitis/encephalopathy and its significance

During the Winter or Influenza season in Japan, there has been an increase in the number of patients presenting with Central Nervous System complaints or symptoms. One of the causes is reported be Influenza encephalitis/encephalopathy. Some of these patients undergo a course of Reye's Syndrome, Acute Necrotizing Encephalopathy (ANE), or Hemorrhagic Shock and Encephalopathy(HSE), of which the pathologic features are still unknown. It is likely that the major underlying feature is cerebral edema, caused by impairments in the blood-brain barrier, which is mediated by inflammatory cytokines. Mild brain hypothermia may be an effective treatment in preventing cerebral edema by preventing the cytokine activation and elevations in brain temperature. A combination of mild brain hypothermia and high-dose corticosteroid therapy is thought to be effective in the treatment of influenza encephalitis/encephalopathy.     

Pathogenesis of hepatic encephalopathy: the tumour necrosis factor-alpha theory

Hepatic encephalopathy (HE) is a major complication for acute and chronic liver failure. Despite several decades of intensive clinical and basic research, the pathogenesis of HE is still incompletely understood, and the precise mechanisms causing brain dysfunction in liver failure are still not fully established. Several theories concerning the pathogenesis of HE have been previously suggested, including the ammonia theory, which received the most attention. These theories are not mutually exclusive and the validity of none of them has been definitely proved experimentally. In this review article, an attractive theory concerning the pathogenesis of HE, the tumour necrosis factor-alpha (TNF) theory, is presented and comprehensively discussed after accumulation of sufficient data which indicate that the pro-inflammatory cytokine, TNF, is strongly involved in the pathogenesis of HE associated with both acute and chronic liver failure. This theory seems to be superior to all other previous theories in the pathogenesis of HE, and may induce development of other beneficial therapeutical modalities for HE directed towards inhibition of TNF production and/or action, and towards enhancement of its degradation.     

急性中毒性脑病的CT诊断

目的:探讨急性中毒性脑病的CT表现,提高对本病的认识。材料与方法:搜集急性中毒性脑病18例,回顾性分析其脑部CT表现特点,其中原发病为重症肺炎5例,毒鼠强中毒4例,腹泻3例,有机磷农药中毒2例,CO中毒2例,不明原因2例。结果:CT表现:脑水肿18例,脑实质密度减低,脑室及脑池受压变小,严重者全脑密度呈均一性减低;蛛网膜下腔出血14例,表现为后纵裂池及天幕等处条片状高密度影;脑内出血2例,呈斑片状高密度影。结论:CT能够反映中毒性脑病的病变范围、严重程度和预后情况,对临床及时正确诊治,减少后遗症具有重要意义。     

Autoimmune encephalitis with posterior reversible encephalopathy syndrome: A case report

BACKGROUNDPosterior reversible encephalopathy syndrome (PRES) is a neuroimaging-based syndrome and is associated with multifocal vasogenic cerebral edema. Patients with PRES frequently demonstrate headache, seizure, encephalopathy, altered mental function, visual loss and so on. We here report a patient who showed persistent neurologic deficits after PRES and was ultimately diagnosed with autoimmune encephalitis (AE). CASE SUMMARYThis case exhibits a rare imaging manifestation of anti-casper 2 encephalitis which was initially well-matched with PRES and associated vasogenic edema. CONCLUSIONAE should be further considered when the etiology, clinical manifestations, and course of PRES are atypical.     

A rare etiology of mild encephalitis/encephalopathy with reversible splenial lesion

Legionella is a rare cause of mild encephalitis/encephalopathy with reversible splenial lesion, which should be considered in patients with risk factors. Brain magnetic resonance imaging (MRI) and legionella urinary antigen test can help the diagnosis since cerebrospinal fluid (CSF) can be normal.