Changing Clinical Profile and Predictors of Mortality in Patients of Acute Febrile Encephalopathy from North India.

Introduction: Acute encephalitis syndrome (AES) or acute febrile encephalopathy is a clinical condition characterized by altered mental status occurring after or along with a short febrile illness. In developing countries, infections are the predominant cause of AES. Prominent infections known to cause AES include viruses (such as herpes simplex virus [HSV], Japanese Encephalitis [JE] virus, dengue, enteroviruses [EVs]), bacteria, fungus, and parasites. In the present study, we aim to analyze the etiology, clinical features, and predictors of mortality in patients presenting with acute febrile encephalopathy or acute encephalitic syndrome. The present study was a prospective observational study conducted at Post Graduate Institute of Medical Education and Research a tertiary care center in Chandigarh, India. Methods: A total of 105 patients with ≥18 years of age with fever (body temperature >101° F for duration ≤14 days) and altered sensorium (Glasgow coma scale [GCS] score ≤10) lasting for more than 24 h, either accompanying the fever or following it were enrolled. Demographic and clinical details were recorded on pro forma. Cerebrospinal fluid (CSF) analysis was performed for all the enrolled patients at admission for cytology, CSF glucose to blood glucose ratio, protein levels, gram stain and culture sensitivity, adenosine deaminase levels, polymerase chain reaction for HSV/EV/mycobacterium tuberculosis (TB) and immunoglobulin M Enzyme-linked immune assay for JE. Computed tomography of the brain was done in all patients while magnetic resonance imaging (MRI) of the brain was carried out in 75 patients. Results: Among the 105 patients, tubercular meningitis was seen in 27 (25.7%) patients followed by acute pyogenic meningitis in 18 (17.1%) patients. Probable viral encephalitis was present in 12 (11.4%) cases. Septic encephalopathy (n = 10) and scrub typhus encephalitis (n = 8), HSV encephalitis (n = 6), dengue encephalitis (n = 4), leptospirosis (n = 3) were the other infections causing acute febrile encephalitis in our study. In addition to fever and altered sensorium common symptoms observed were headache (52.4%), vomiting (35.2%), and seizures (29.5%). The factors predicting increased mortality were female gender, fever of more than 38°C at admission, GCS <7, MRI showing disease-related findings like altered signal intensity bilateral medial temporal and insular area in herpes simplex encephalitis, etc., changes, and the group of patients where a definite diagnosis could not be established during the hospital stay. Conclusions: Tubercular meningitis/central nervous system TB is the predominant cause of acute febrile encephalopathy in developing countries. Scrub and dengue encephalitis are emerging as an important cause of acute febrile encephalopathy and occur predominantly in postmonsoon seasons. Acute febrile encephalopathy remains an important cause of mortality in patients presenting to Emergency Department (ER). The strongest predictors of mortality are low GCS and undiagnosed cases of AES.

Association of Scrub Typhus in Children with Acute Encephalitis Syndrome and Meningoencephalitis, Southern India.

Scrub typhus is an established cause of acute encephalitis syndrome (AES) in northern states of India. We systematically investigated 376 children with AES in southern India, using a stepwise diagnostic strategy for the causative agent of scrub typhus, Orientia tsutsugamushi, including IgM and PCR testing of blood and cerebrospinal fluid (CSF) to grade its association with AES. We diagnosed scrub typhus in 87 (23%) children; of those, association with AES was confirmed in 16 (18%) cases, probable in 55 (63%), and possible in 16 (18%). IgM detection in CSF had a sensitivity of 93% and specificity of 82% compared with PCR. Our findings suggest scrub typhus as an emerging common treatable cause of AES in children in southern India and highlight the importance of routine testing for scrub typhus in diagnostic algorithms. Our results also suggest the potential promise of IgM screening of CSF for diagnosis of AES resulting from scrub typhus.

Viral aetiology in paediatric age group patients admitted with acute febrile encephalopathy in Western Rajasthan.

PURPOSE: In this study, we are trying to find out viral aetiology in paediatric age group patients from 1 month to 15 years of age in Western Rajasthan region. METHODS: A total of 105 patients from 1 month to 15 years were recruited into this study. CSF samples were collected and were processed by multiplex real-time PCR for detection of various predefined panels of viral agents. ELISA was also done for all samples for detection of dengue, JE, measles and mumps. RESULTS: A total of 32 samples out of 105 were tested positive for viral agents. Viral aetiology detected in this study were Adenovirus (n â€‹= â€‹2), EBV (n â€‹= â€‹1), HHV-1 (n â€‹= â€‹10), HHV-6 (N â€‹= â€‹5), Parechovirus (n â€‹= â€‹1), Parvovirus B19 (n â€‹= â€‹7), Dengue (n â€‹= â€‹2) and Measles (n â€‹= â€‹1). Mixed infections were also detected, HHV-1 and HHV-6 (n â€‹= â€‹2), HHV-1 and Parvovirus B19 (n â€‹= â€‹1). In 73 patients no viral aetiology could be detected. CONCLUSIONS: Parvovirus B19 is sporadically prevalent in this geographical region. In this study, HHV-6 was also found which has not been reported earlier from India.

Intensive care management of patients with viral encephalitis.

Viral encephalitis is a severe syndrome that can lead to encephalopathy, seizures, focal deficits, and neurological sequelae and death. It is mainly caused by neurotropic herpes viruses (i.e., HSV and VZV), although other pathogens may be observed in specific geographic regions or conditions. Recent advances in neuroimaging and molecular biology (PCR, metagenomics) allow for faster and more accurate etiological diagnoses, although their benefits need to be confirmed to provide guidelines for their use and interpretation. Despite intravenous acyclovir therapy and supportive care, outcomes remain poor in about two-thirds of herpes encephalitis patients requiring ICU admission. Randomized clinical trials focusing on symptomatic measures (i.e. early ICU admission, fever control, and treatment of seizures/status epilepticus) or adjunctive immunomodulatory therapies (i.e. steroids, intravenous immunoglobulins) to improve neurologic outcomes have not been conducted in the ICU setting. Large prospective multicenter studies combining clinical, electrophysiological, and neuroimaging data are needed to improve current knowledge on care pathways, long-term outcomes, and prognostication.

Evaluating cognitive outcomes in adult patients with acute encephalitis syndrome: a prospective study from a tertiary care center in Nepal.

Purpose: Although cognitive impairment is a known complication of acute encephalitis syndrome (AES), few studies have evaluated cognitive outcomes in patients with encephalitis. The primary objective of this study was to assess the cognitive profiles of patients diagnosed with AES, which is pivotal for improving rehabilitation strategies and prognostic measures. Methods: This study was conducted at the Tribhuvan University Teaching Hospital. Adult patients with AES who met inclusion criteria were enrolled. The Montreal Cognitive Assessment (MoCA) tool was used to assess cognitive function at admission, discharge, and 3-month follow-up. Results: Thirty-six patients were enrolled in our study. The mean age of the participants was 43 ± 18 years. Fourteen patients (38.9%) were female, and 22 (61.1%) were male. Tuberculous (TB) meningoencephalitis was present in 14 cases (38.9%), with herpes simplex virus (HSV) encephalitis in 14 (38.9%), bacterial meningoencephalitis in 4 (11.1%), autoimmune encephalitis in 2 (5.6%), and Japanese encephalitis in 2 (5.6%). Patients with bacterial meningoencephalitis had the highest MoCA scores at admission, whereas those with HSV encephalitis had the highest scores at discharge and follow-up. Compared with the scores at admission, the scores at discharge and follow-up increased significantly in patients with TB meningoencephalitis and HSV encephalitis. The MoCA score at discharge was established as a significant predictor of cognitive function at follow-up. Conclusion: We found that active treatment can improve the outcomes of AES patients with cognitive impairment. Although infectious etiologies are most common in low-income countries such as Nepal, autoimmune etiologies should not be overlooked.

Eco-epidemiological risk factors for Japanese encephalitis in the endemic region of North East India: a hospital-based case-control study.

Purpose: Japanese encephalitis (JE) has emerged as a major public health concern in North East India due to its complex eco-epidemiological risk factors. The objective of this study was to understand the various risk factors associated with JE infection in the endemic study location. Methods: A hospital-based case-control study was conducted at Jorhat Medical College and Hospital from August 2017 to September 2018. The study participants included 49 confirmed JE cases with two control arms, one consisting of non-JE acute encephalitis syndrome (AES) patients (n = 91) and the other of non-JE non-AES patients (n = 140), admitted at the same time in the pediatric and medicine wards. A predesigned, pretested, structured questionnaire was used for data collection. Results: Univariate analysis revealed the following to be risk factors: age at onset, sex, religion, immunization status, proximity to pigs, proximity to paddy fields (<100 m), use of a mosquito net, impregnated mosquito net, mosquito repellent, and outdoor activities. Multiple logistic regression analysis identified age at onset (adjusted odds ratio [AOR], 20.900; 95% confidence interval [CI], 2.210-31.815) and proximity to pigs (AOR, 4.190; 95% CI, 1.592-11.040) as risk factors for the first control arm and proximity to paddy fields (<100 m) (AOR, 8.470; 95% CI, 2.0251-35.438) was the only risk factor found for second control arm, whereas impregnated mosquito nets (AOR, 0.082; 95% CI, 0.009-0.725) and mosquito repellent (AOR, 0.173; 95% CI, 0.052-0.575) were found to be associated with the second control arm. Conclusion: Age at onset, proximity to pigs, proximity to paddy fields (<100 m), impregnated mosquito nets, and mosquito repellent were the most significant risk factors for JE in the NE region to warrant public health actions.

Encefalitis aguda necrotizante, diagnóstico retador en una niña con deterioro neurológico súbito

La encefalopatía aguda necrotizante (EAN) es una entidad muy poco frecuente, con compromiso neurológico importante, en la cual los hallazgos radiológicos de lesiones en sistema nervioso central necróticas, simétricas y multifocales son esenciales para diagnosticarla. Se asocia a una respuesta inmune exagerada. Se reporta el caso de una niña de 1 año y 3 meses, previamente sana y con un deterioro neurológico súbito posterior a un cuadro febril de un día y convulsiones, con necesidad de reanimación y ventilación. La neuroimagen demostró las lesiones características de EAN y se manejó con tratamiento inmunomodulador así como antibiótico y antiviral. Se aisló únicamente un adenovirus y rinovirus en muestra respiratoria. La paciente sobrevivió con morbilidad importante como secuelas neurológicas, traqueostomía y gastrostomía. Este es el primer de EAN caso publicado en Costa Rica.

Acute necroziting encephalopathy (ANE) is a rare and serious entity, with significant neurological involvement, in which the radiological findings of symmetric and multifocal necroziting lesions in central nervous system are characteristic. It is an immune-mediated disease with incompletely recognized pathogenesis. We present the case of a 1 year old child, previously healthy, that presented with acute neurological deterioration after a day of fever and seizures. She required reanimation and ventilation. Typical findings of ANE were found in neuroimaging and she was treated with inmunomodulating therapy, antibiotics and antivirals. Only rhinovirus and adenovirus were isolated in respiratory sample. The patient survived with significant neurological sequelae. This is the first case of ANE published in Costa Rica.

[A clinical and pathological report of delayed encephalopathy after heat stroke].

Objective: To explore the clinical manifestations, dynamic neuroimaging changes and brain histopathologic characteristics of a patient with delayed encephalopathy after heat stroke. Methods: In October 2019, the clinical manifestations, electroencephalogram, cerebrospinal fluid, imaging changes and brain histopathological characteristics of a patient with brain damage caused by heat stroke were retrospectively analyzed. Results: The patient was a 40-year-old male who suddenly appeared dizziness, unconscious, high fever when working in the high temperature environment. The EEG showed diffuse slow wave activity. Early CT was normal, and abnormal signals gradually appeared in the basal ganglia region of the thalamus after a few days. In the late, the MRI found a large area of abnormal signals under the cerebral cortex, and white matter was involved. Pathological examination of brain biopsy showed that cortical neuron loss, loose white matter changes, and significant demyelination changes, while no inflammatory cell infiltration was observed in subarachnoid space, meninges, and dermal white matter. Conclusion: Imaging examination dynamic changes of the delayed encephalopathy is important in the heat stroke, and the main pathological manifestation is demyelination.

Clinical spectrum, aetiology and predictors of acute febrile encephalopathy at a tertiary hospital in south India - A prospective observational study.

Acute febrile encephalopathy is a common syndrome in the tropics with high mortality encountered by emergency physicians. In order to study the aetiology of acute febrile encephalopathy and its mortality and functional outcome over one year, data on all patients >18 years of age with short duration of fever (<14 days) and altered mental status were collected and followed up until one month after discharge. Non-infectious aetiology, found in 29%, portends a poor outcome.

Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion Associated With Adenoviral Pneumonia.

Acute encephalopathy with biphasic seizures and late reduced diffusion is a subtype of acute encephalopathy described in a cohort of Japanese children. Few cases have been reported in countries other than Japan. It is characterized clinically by biphasic seizures and late reduced subcortical diffusion on magnetic resonance imaging (MRI). We report the case of a 3-year-old Korean girl with acute encephalopathy with biphasic seizures and late reduced diffusion who presented with status epilepticus associated with fever and pneumonia. Human adenovirus was detected from a respiratory specimen using multiplex real-time reverse transcriptase polymerase chain reaction. After 5 days, she developed a second cluster of seizures followed by altered consciousness, aphasia, stereotypic movement, and developmental regression. Her brain MRI showed symmetrical and extensive restricted diffusion in the subcortical white matter, which finally resulted in global brain atrophy, consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. Here, we report a case of acute encephalopathy with biphasic seizures and late reduced diffusion associated with preceding adenoviral pneumonia.

Diagnosis and treatment of 12 cases of febrile infection-related epilepsy syndrome / 中国医师杂志

Objective@#To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome (FIRES).@*Methods@#The clinical data of 12 children with FIRES admitted to Xiangya Hospital of Central South University from 2015 to 2018 were retrospectively analyzed. The basic information, clinical manifestations, electroencephalogram, imaging examination, treatment and prognosis were analyzed.@*Results@#Of the 12 patients, 7 were male and 5 were female. The age of onset was (7.0±3.7)years (1.3 year to 13 years). The average hospitalization time (34-86 days, median 52 days). Twelve patients were healthy before the disease, and had fever before convulsion. The interval between fever and seizure was (3.5±1.7)days (1-7 days). The status epilepticus and consciousness deficit were the main clinical manifestations. The electrogram of 8 patients showed status epilepticus when admitted. 12 patients had disturbance of consciousness; the acute episodes were focal seizures (100%, 12/12) and generalized tonic-clonic seizures (41.7%, 5/12). All patients used 3-5 antiepileptic drugs (median 4), all treated with hormones and gamma globulin. 4 patients with ketogenic diet (KD) were treated within 2 weeks of onset, and the average duration from onset to electroencephalogram (EEG) improvement was (19.2±5.0)days. In 8 patients who did not use KD within 2 weeks of onset, the average duration from onset to EEG improvement was (29.9±9.6)days.@*Conclusions@#FIRES is more common in normal children with school age. The main manifestation is refractory status epilepticus in the days after acute fever, focal episodes of seizures, anti-epileptic drug resistance. Early initiation of KD produces a favorable prognosis.

Diagnosis and treatment of 12 cases of febrile infection-related epilepsy syndrome / 中国医师杂志

Objective To investigate the clinical features,diagnosis and treatment of febrile infection-related epilepsy syndrome (FIRES).Methods The clinical data of 12 children with FIRES admitted to Xiangya Hospital of Central South University from 2015 to 2018 were retrospectively analyzed.The basic information,clinical manifestations,electroencephalogram,imaging examination,treatment and prognosis were analyzed.Results Of the 12 patients,7 were male and 5 were female.The age of onset was (7.0 ± 3.7)years (1.3 year to 13 years).The average hospitalization time (34-86 days,median 52 days).Twelve patients were healthy before the disease,and had fever before convulsion.The interval between fever and seizure was (3.5 ± 1.7) days (1-7 days).The status epilepticus and consciousness deficit were the main clinical manifestations.The electrogram of 8 patients showed status epilepticus when admitted.12 patients had disturbance of consciousness;the acute episodes were focal seizures (100％,12/12) and generalized tonic-clonic seizures (41.7％,5/12).All patients used 3-5 antiepileptic drugs (median 4),all treated with hormones and gamma globulin.4 patients with ketogenic diet (KD) were treated within 2 weeks of onset,and the average duration from onset to electroencephalogram (EEG) improvement was (19.2 ± 5.0)days.In 8 patients who did not use KD within 2 weeks of onset,the average duration from onset to EEG improvement was (29.9 ± 9.6) days.Conclusions FIRES is more common in normal children with school age.The main manifestation is refractory status epilepticus in the days after acute fever,focal episodes of seizures,anti-epileptic drug resistance.Early initiation of KD produces a favorable prognosis.

Acute Childhood Encephalitis and Encephalopathy following Infectious Symptoms: a Single Center Study / 대한소아신경학회지

PURPOSE: Acute encephalitis and encephalopathy are preceded by respiratory or enteric infection, whose pathogens can be detected more easily with advanced tools. However, studies for pathogens in Korea remain scarce. We investigated the clinical characteristics and pathogens in childhood encephalitis and encephalopathy. METHODS: We retrospectively reviewed the records of children with acute encephalitis and encephalopathy admitted to our hospital between March 2013 and February 2017. RESULTS: The 51 included patients were aged 5.8±4.4 years (mean±standard deviation), comprising 36 with encephalitis (70.6%) and 15 with encephalopathy (29.4%). Respiratory symptoms (62.7%) were more common than enteric symptoms (45.1%). Brain MRI was abnormal in 54.9%, and leu-kocytosis in the cerebrospinal fluid was noted in 41.2%. The prevalence of diseases was highest in winter (29.4%). In encephalitis, eight patients had infective encephalitis (15.7%), comprising enterovirus (N=4), Epstein-Barr virus (N=3; one with HHV6 coinfection), and tsutsugamushi in-fection (N=1). The 11 patients with ADEM included 1each with adenovirus, influenza A, and mycoplasmal infection. One patient with Bickerstaff-brainstem encephalitis had mycoplasmal pneumonia. In the 15 patients with encephalitis of unknown etiology, rhinovirus (N=3), influenza A (N=2), adenovirus (N=1), and mycoplasmal infection (N=6) were found. In the encephalopa-thy group, three patients had abnormal brain MRI: ANE with influenza A, AESD with exanthem subitum, and norovirus-associated MERS. In the remaining 12 patients, influenza A (N=2), ade-novirus, rhinovirus, enterovirus, norovirus (N=1 for each virus), and mycoplasmal infection (N=4) were found. CONCLUSION: Acute childhood encephalitis and encephalopathy were the most prevalent in winter and were fre-quently associated with respiratory infections.

Acute febrile encephalopathy in children and predictors of mortality.

BACKGROUND: Incidence of acute febrile encephalopathy (AFE) is high in children and associated with high mortality and sequela. Limited data is available about predictors of mortality in children of AFE from central India. AIM: To study the predictors of mortality in children of AFE. METHODS: This is observational, prospective study, carried out in a tertiary care hospital of central India. Duration of the study was two years (2010 to 2012). One hundred and seventy six children in the age group of one month to 12 years, presented with fever ≤ 2wks duration and altered mental status lasting for more than 4h were enrolled in the study. Outcome was evaluated in the study subjects. Data was analysed by use of Chi-square test, Fisher's exact test and multivariate regression. P-value ≤ 0.05 was considered statistically significant. RESULTS: Maximum enrolled children were of viral encephalitis (46.59%) and rest, were of pyogenic meningitis, tuberculosis meningitis and cerebral malaria. Among independently significant variables, shock, severe anaemia, bradycardia, Glasgow coma scale (GCS) of less than eight and refractory seizures were found to be significant and other variables like respiratory failure, multiorgan dysfunction syndrome and abnormal coagulation profile were found insignificant on full model of multivariate regression analysis. CONCLUSION: Refractory seizures, GCS <8, bradycardia, shock and severe anaemia were independent predictors for mortality in children of AFE.