Neuropsychiatric sequelae of Nipah virus encephalitis

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome. Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.     

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.     

晚发型抗N-甲基-D-天冬氨酸受体脑炎临床特征分析

目的分析晚发型抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特征。方法收集2010-01-01—2019-05-01于郑州大学第一附属医院住院确诊为抗NMDAR脑炎的患者临床资料,分析晚发型(≥50岁)患者数据,并与早发型(18~49岁)患者进行对比。结果18例晚发型患者中,男11例(61%),发病年龄50~84岁。晚发型患者中,9例(50%)患者出现前驱症状,精神行为异常是最常见的首发症状(44%)和临床表现(78%);头颅磁共振提示脑实质炎性病变9例(9/17,53%);脑脊液检验结果异常17例(94%);合并肿瘤4例(22%),均非畸胎瘤。相比于早发组患者,晚发组患者有更高的自主神经功能障碍比例(72%vs 45%,P=0.032),更高的岛叶病变比例(67%vs 27%,P=0.047),更高的脑脊液蛋白升高比例(56%vs 28%,P=0.023),以及更高的脑脊液鞘内IgG合成率升高比例(73%vs 44%,P=0.041)。晚发组合并肿瘤均非畸胎瘤,早发组合并肿瘤均为畸胎瘤(P=0.001)。结论相比早发型抗NMDAR脑炎患者,晚发型患者更易出现岛叶病变,更易出现脑脊液炎症反应,其发病机制可能与畸胎瘤不相关。     

Nipah virus: An emergent paramyxovirus causing severe encephalitis in humans

Nipah virus is a recently emergent paramyxovirus that is capable of causing severe disease in both humans and animals. The first outbreak of Nipah virus occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with respiratory syndrome that has a high mortality rate. The reservoir for Nipah virus is believed to be fruit bats, and humans are infected by contact with infected bats or by contact with an intermediate animal host such as pigs. Person to person spread of the virus has also been described. Nipah virus retains many of the genetic and biologic properties found in other paramyxoviruses, though it also has several unique characteristics. However, the virologic characteristics that allow the virus to cause severe disease over a broad host range, and the epidemiologic, environmental and virologic features that favor transmission to humans are unknown. This review summarizes what is known about the virology, epidemiology, pathology, diagnosis and control of this novel pathogen.     

Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response

Nipah virus is a newly discovered paramyxovirus transmitted directly from pigs to humans. During a large encephalitis outbreak in Malaysia and Singapore in 1998-9, most patients presented acutely. A 12 year old child is described who developed encephalitis 4 months after exposure to the virus. She was diagnosed by a new indirect IgG enzyme linked immunosorbent assay (ELISA), which is also described. The late presentation and IgG subclass responses had similarities to subacute sclerosing panencephalitis. Nipah virus should be considered in patients with encephalitis even months after their possible exposure.     

The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus.

A novel Hendra-like paramyxovirus named Nipah virus (NiV) was the cause of an outbreak among workers from one abattoir who had contact with pigs. Two patients had only respiratory symptoms, while 9 patients had encephalitis, 7 of whom are described in this report. Neurological involvement was diverse and multifocal, including aseptic meningitis, diffuse encephalitis, and focal brainstem involvement. Cerebellar signs were relatively common. Magnetic resonance imaging scans of the brain showed scattered lesions. IgM antibodies against Hendra virus (HeV) were present in the serum of all patients. Two patients recovered completely. Five had residual deficits 8 weeks later.     

Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic epileptic spasms

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].     

High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid

During the outbreak of Nipah virus encephalitis in Malaysia, stored cerebrospinal fluid (CSF) samples from 84 patients (27 fatal and 57 nonfatal cases) were cultured for the virus. The virus was isolated from 17 fatal cases and 1 nonfatal case. There were significant associations between CSF virus isolation and mortality as well as clinical features associated with poor prognosis. In addition, there was a positive linear correlation of CSF virus isolation with age. There was no significant association between CSF virus isolation and the character of the CSF, presence of Nipah-specific antibody in the serum or CSF, duration of illness before collection of samples, or sex or ethnicity of the patients. This study suggests that high viral replication in the central nervous system may be an important factor for high mortality.     

Electrical status epilepticus "invisible" to surface EEG in late-onset Rasmussen encephalitis

Rasmussen's encephalitis (RE) is a chronic, progressive disease that typically occurs in childhood, rarely in adulthood. When it does occur in adulthood, it may be associated with atypical electro-clinical features, and neuroimaging alterations usually help diagnosis. Unlike childhood forms, in which epilepsia partialis continua is usually observed, the EEG pattern in adult variants may be aspecific. We describe a highly interesting case of late-onset RE in which an electrical status epilepticus was not detected by the surface EEG, but by a recording with subdural electrodes.     

Dystonia, athetosis, and epilepsia partialis continua in a patient with late-onset Rasmussen's encephalitis.

Rasmussen's encephalitis is a rare autoimmune disorder characterized by intractable epilepsy and progressive hemispheric dysfunction. The disorder usually affects children, although cases have been reported with symptom onset in late adolescence or adulthood. Myoclonus is common in Rasmussen patients, usually occurring as part of epilepsia partialis continua (EPC); however, other hyperkinetic movements are rare. This report documents a 19-year-old woman with Rasmussen's encephalitis whose clinical presentation was dominated by foot dystonia, arm athetosis, and EPC. Intravenous immunoglobulin improved both hyperkinetic movements and EPC, but benefit was transient. The clinical significance and implications of these findings are discussed.     

晚发与非晚发精神分裂症对照研究

对４个医疗单位精神科住院病人中的晚发性精神分裂症２４７例进行观察，以非晚发性精神分裂症病人２６４例为对照。结果发现，晚发组女性显著较多，病前性格内向者显著较少，家族精神病遗传史显著较少。发病诱因以晚发组显著较多，起病急或亚急者亦然。两组文化程度相仿，近期疗效以晚发组显著较好。作者认为，不仅有年龄的不同，晚发组病例在其他方面也有不少特点，精神分裂症应有晚发型为独立的亚型。     

A case of paraneoplastic limbic encephalitis associated with malignant lymphoma presenting with a late-onset bilateral thalamic lesion

A 63-year-old man presented with cognitive impairment including disturbance of memory functions and character change. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging revealed signal hyperintensities in the bilateral medial temporal lobes. Cerebrospinal fluid analysis revealed high protein concentrations, positive results for the oligoclonal band, and a slightly positive result for glutamate receptor ε2 (GluRε2) antibody. Voltage-gated potassium channel (VGKC) antibody was slightly positive in serum. Computed tomography showed enlargement of the left supraclavicular, left axillary, and renal hilar lymph nodes, and 18 F-fluoro-2-deoxy-D-glucose positron emission tomography revealed increased uptake at the same sites. Lymph node biopsy findings were consistent with diffuse large B-cell lymphoma. Based on these findings, the patient was diagnosed with paraneoplastic limbic encephalitis (PLE) associated with malignant lymphoma. The patient received intravenous injection of immunoglobulin and R-CHOP chemotherapy, but his neurological condition deteriorated. MR imaging showed atrophic changes in the medial temporal lobes during immunotherapy and chemotherapy. FLAIR/T2-weighted imaging revealed signal hyperintensities in the bilateral thalami after the first course of R-CHOP chemotherapy. This is the first report of PLE associated with diffuse large B-cell lymphoma presenting with late-onset bilateral thalamic lesions.     

Herpes encephalitis and paraneoplastic limbic encephalitis

Pathological examination of four autopsy cases of herpes simplex virus encephalitis reconfirmed that the inflammatory necrotizing lesions occurred predominantly in the limbic system. This site predilection can be explained by the viral spread via the olfactory pathway, or along the meningeal branches of the trigeminal nerves and by the localization of specific herpes virus receptors. Case studies of non-herpetic paraneoplastic limbic encephalitis were briefly introduced and the results suggest that a specific protein recognized by antibody exists in the limbic system. Thus, both virological and immunological evidence suggests that the human limbic system has specific proteins which are unique in the human brain.     

Long-term neurological and functional outcome in Nipah virus infection

OBJECTIVE: Nipah virus (NiV) is an emerging zoonosis. Central nervous system disease frequently results in high case-fatality. Long-term neurological assessments of survivors are limited. We assessed long-term neurologic and functional outcomes of 22 patients surviving NiV illness in Bangladesh. METHODS: During August 2005 and May 2006, we administered a questionnaire on persistent symptoms and functional difficulties to 22 previously identified NiV infection survivors. We performed neurologic evaluations and brain magnetic resonance imaging (MRI). RESULTS: Twelve (55%) subjects were male; median age was 14.5 years (range 6-50). Seventeen (77%) survived encephalitis, and 5 survived febrile illness. All but 1 subject had disabling fatigue, with a median duration of 5 months (range, 8 days-8 months). Seven encephalitis patients (32% overall), but none with febrile illness had persistent neurologic dysfunction, including static encephalopathy (n = 4), ocular motor palsies (2), cervical dystonia (2), focal weakness (2), and facial paralysis (1). Four cases had delayed-onset neurologic abnormalities months after acute illness. Behavioral abnormalities were reported by caregivers of over 50% of subjects under age 16. MRI abnormalities were present in 15, and included multifocal hyperintensities, cerebral atrophy, and confluent cortical and subcortical signal changes. INTERPRETATION: Although delayed progression to neurologic illness following Nipah fever was not observed, persistent fatigue and functional impairment was frequent. Neurologic sequelae were frequent following Nipah encephalitis. Neurologic dysfunction may persist for years after acute infection, and new neurologic dysfunction may develop after acute illness. Survivors of NiV infection may experience substantial long-term neurologic and functional morbidity.