Critical West Nile Neuroinvasive Disease.

BACKGROUND: Data to guide neurointensivists seeing patients with West Nile Neuroinvasive disease (WNND) are lacking. We present a comparatively large series of patients with WNND admitted to the intensive care unit (ICU) and provide data on their early diagnosis, triage to the ICU and predictors of short-term outcomes. METHODS: We retrospectively identified patients aged ≥ 18 years old with WNND from January 1999 to November 2016. Demographic and clinical data, the modified Rankin Scale at discharge and disposition were collected. Univariate analysis was performed to find predictors of ICU admission and to assess the impact of ICU admission on the short-term outcomes. P values < 0.05 were considered significant. RESULTS: Among 26 patients, 16 were admitted to the ICU. Age < 60 years and the presentation with encephalitis and acute flaccid paralysis predicted ICU admission (P = 0.044 and 0.0007). Among patients requiring ICU admission, four died and no one was discharged home. ICU admission predicted longer hospital stay (P = 0.021), inhospital death (P = 0.034), survival with inability to walk independently (P = 0.0094), and discharge disposition other than home (P = 0.007). In the ICU group, older age was associated with longer hospital stay (P = 0.0001) and inhospital death (P = 0.035). CONCLUSION: WNND requiring ICU care has a high morbidity and mortality, especially among older patients. Survivors are highly disabled at discharge, but many improve over time. Therefore, more data on the long-term prognosis of survivors are needed to guide the goals of care in the acute setting.

Chikungunya infection presenting as mild encephalitis with a reversible lesion in the splenium: a case report.

Chikungunya fever is an Aedes mosquito-transmitted infection caused by chikungunya virus, an RNA virus in the family Togaviridae. The disease is characteristically manifested as fever, arthralgia, and/or rash. Various neurological manifestations like meningoencephalitis, myelitis, and myeloneuropathy have been mentioned in various reports. We present a rare case of chikungunya fever presenting with mild encephalitis with a reversible lesion of the splenium (MERS), which showed complete clinical and radiological recovery.

Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis.

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuVJL5) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuVJL5 associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuVJL5 isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

Intravenous immunoglobulin for the treatment of childhood encephalitis.

BACKGROUND: Encephalitis is a syndrome of neurological dysfunction due to inflammation of the brain parenchyma, caused by an infection or an exaggerated host immune response, or both. Attenuation of brain inflammation through modulation of the immune response could improve patient outcomes. Biological agents such as immunoglobulin that have both anti-inflammatory and immunomodulatory properties may therefore be useful as adjunctive therapies for people with encephalitis. OBJECTIVES: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) as add-on treatment for children with encephalitis. SEARCH METHODS: The Cochrane Multiple Sclerosis and Rare Diseases of the CNS group's Information Specialist searched the following databases up to 30 September 2016: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and the WHO ICTRP Search Portal. In addition, two review authors searched Science Citation Index Expanded (SCI-EXPANDED) & Conference Proceedings Citation Index - Science (CPCI-S) (Web of Science Core Collection, Thomson Reuters) (1945 to January 2016), Global Health Library (Virtual Health Library), and Database of Abstracts of Reviews of Effects (DARE). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IVIG in addition to standard care versus standard care alone or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected articles for inclusion, extracted relevant data, and assessed quality of trials. We resolved disagreements by discussion among the review authors. Where possible, we contacted authors of included studies for additional information. We presented results as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). MAIN RESULTS: The search identified three RCTs with 138 participants. All three trials included only children with viral encephalitis, one of these included only children with Japanese encephalitis, a specific form of viral encephalitis. Only the trial of Japanese encephalitis (22 children) contributed to the primary outcome of this review and follow-up in that study was for three to six months after hospital discharge. There was no follow-up of participants in the other two studies. We identified one ongoing trial.For the primary outcomes, the results showed no significant difference between IVIG and placebo when used in the treatment of children with Japanese encephalitis: significant disability (RR 0.75, 95% CI 0.22 to 2.60; P = 0.65) and serious adverse events (RR 1.00, 95% CI 0.07 to 14.05; P = 1.00).For the secondary outcomes, the study of Japanese encephalitis showed no significant difference between IVIG and placebo when assessing significant disability at hospital discharge (RR 1.00, 95% CI 0.60 to 1.67). There was no significant difference (P = 0.53) in Glasgow Coma Score at discharge between IVIG (median score 14; range 3 to 15) and placebo (median 14 score; range 7 to 15) in the Japanese encephalitis study. The median length of hospital stay in the Japanese encephalitis study was similar for IVIG-treated (median 13 days; range 9 to 21) and placebo-treated (median 12 days; range 6 to 18) children (P = 0.59).Pooled analysis of the results of the other two studies resulted in a significantly lower mean length of hospital stay (MD -4.54 days, 95% CI -7.47 to -1.61; P = 0.002), time to resolution of fever (MD -0.97 days, 95% CI -1.25 to -0.69; P < 0.00001), time to stop spasms (MD -1.49 days, 95% CI -1.97 to -1.01; P < 0.00001), time to regain consciousness (MD -1.10 days, 95% CI -1.48 to -0.72; P < 0.00001), and time to resolution of neuropathic symptoms (MD -3.20 days, 95% CI -3.34 to -3.06; P < 0.00001) in favour of IVIG when compared with standard care.None of the included studies reported other outcomes of interest in this review including need for invasive ventilation, duration of invasive ventilation, cognitive impairment, poor adaptive functioning, quality of life, number of seizures, and new diagnosis of epilepsy.The quality of evidence was very low for all outcomes of this review. AUTHORS' CONCLUSIONS: The findings suggest a clinical benefit of adjunctive IVIG treatment for children with viral encephalitis for some clinical measures (i.e. mean length of hospital stay, time (days) to stop spasms, time to regain consciousness, and time to resolution of neuropathic symptoms and fever. For children with Japanese encephalitis, IVIG had a similar effect to placebo when assessing significant disability and serious adverse events.Despite these findings, the risk of bias in the included studies and quality of the evidence make it impossible to reach any firm conclusions on the efficacy and safety of IVIG as add-on treatment for children with encephalitis. Furthermore, the included studies involved only children with viral encephalitis, therefore findings of this review cannot be generalised to all forms of encephalitis. Future well-designed RCTs are needed to assess the efficacy and safety of IVIG in the management of children with all forms of encephalitis. There is a need for internationally agreed core outcome measures for clinical trials in childhood encephalitis.

MicroRNA-125b in peripheral blood: a potential biomarker for severity and prognosis of children with viral encephalitis.

This study aims to evaluate the effect of peripheral blood miR-125b expression on severity and prognosis in children with viral encephalitis (VE). Children with VE (severe and mild groups) were grouped into VE group, and 40 healthy children as control group. Plasma RNA was extracted, and real-time quantitative PCR was conducted to detect miR-125b relative expression. Associations of miR-125b expression with clinical characteristics and prognosis of VE children were analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of the prognostic value of miR-125b. Univariate analysis and logistic regression analysis were performed to analyze risk factors of the prognoses of VE children. The plasma miR-125b expression was higher in the VE group than in the control group and higher in the severe group than the mild group. MiR-125b expression was associated with status convulsion, hemiplegia, multiple organ injuries, and stress hyperglycemia in VE children. Patients with poor prognosis exhibited higher miR-125b expression than those with good prognosis, and the rate of high miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR-125b expression to predict prognosis of VE children was 0.833. When the cutoff value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and miR-125b were considered as risk factors for poor prognosis in VE children. Peripheral blood miR-125b expression may be correlated with the severity and prognosis of VE in children.

MRI signal intensity differentiation of brainstem encephalitis induced by Enterovirus 71: a classification approach for acute and convalescence stages.

BACKGROUND: The objective of this study is to assess standardized histograms of signal intensities of T1 signal and T2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with Enterovirus 71 related brainstem encephalitis (BE), and with respect to (3) healthy normal. METHODS: Our subjects were hospitalized between March 2010 and October 2012, and underwent pre- and post-contrast MRI studies. The research question to be answered is whether the comparison of the MRI image intensity histograms and relevant statistical quantification can add new knowledge to the diagnosis of BE patients. So, both 25 cases in acute stage with prolonged T1 and T2 signal, without enhancement, and 13 cases in convalescence stage were introduced. In additional, a healthy group with 25 cases was recruited for comparison. RESULTS: MRI signal intensity histogram changes of the lesions were compared at the acute and convalescence stages of the disease. Our preliminary results suggest that standardized histograms of signal intensities and their statistical properties are able to provide diagnostic information for the clinical assessment of the disease. Different stages pertaining to the histogram plots comparison showed that overall T1 signal intensity values increase as we traverse from the acute stage to the convalescence stage. And then for the healthy subjects, the T2 signal intensity values changed their magnitudes in a reverse direction. However, exceptions of this can happen in four cases where the primary lesions occurred in the brainstem that developed encephalomalacia resulting in a lower signal in T1WI and higher signal in T2WI. Statistical analysis revealed there was significant difference of T1 signal intensity among the three groups; and also, the T2 signal intensity was lower than other two groups. CONCLUSIONS: Standardized histogram of T1 and T2 intensity provide valuable and useful information for disease diagnosis and evaluation, which can potentially help medical doctors to save the lives of children.

Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned.

The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.

[Clinical features of viral encephalitis with bilateral acute retinal necrosis syndrome].

OBJECTIVE: To explore the clinical features of viral encephalitis with acute retinal necrosis syndrome.
 Methods: Clinical symptoms, laboratory tests, treatment and prognosis for 6 patients with viral encephalitis and acute retinal necrosis syndrome, who admitted to Xiangya Hospital from October 2013 to March 2015, were retrospectively analyzed.
 Results: Clinical features of the six cases are similar. Anti-virus treatment and anti-inflammation therapy can improve the prognosis. 
 Conclusion: Viral encephalitis with acute retinal necrosis syndrome is common and the neurological physicians need to strengthen the understanding of this disease.

Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.

Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes.

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

OBJECTIVE: The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. METHODS: Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. RESULTS: Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. SIGNIFICANCE: We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain network.

Clinical characteristics and outcome of clinically diagnosed viral encephalitis in southwest China.

Patients with viral encephalitis have a high incidence of morbidity and mortality. We analyze the clinical characteristics and outcome of patients with clinically diagnosed viral encephalitis to investigate possible predictors of prognosis. We retrospectively evaluated 1107 patients diagnosed with viral encephalitis in southwest China from 2009 to 2012 by evaluating their outcomes using the Glasgow Outcome Scale. We compared patient outcome at hospital discharge with long-term follow-up visits, and evaluated the prognostic indicators of the outcome. At hospital discharge, 375 (33.9 %) of the 1107 patients who survived made a full recovery, while 399 (36.0 %), 160 (14.5 %), and 145 (13.1 %) had mild, moderate or severe neurologic sequelae, respectively. Twenty-eight (2.5 %) of the patients died prior to discharge from the hospital. Of the 1027 patients who had follow-up assessments, 658 (64.1 %) made a full recovery, while 213 (20.7 %), 103 (10.0 %), and 19 (1.8 %) had mild, moderate or severe neurologic sequelae, respectively. Six (0.6 %) of the patients died after discharge from the hospital. Use of mechanical ventilation, lower Glasgow coma score, and concurrent seizures are predictors for a poor outcome in patients both at hospital discharge and at long-term follow-up visits.

[Viral encephalitis in children]. / Encefalitis virales en la infancia.

Viral encephalitis is a severe illness that produces inflammation of the brain. CNS viral infections frequently occur as a complication of systemic viral infections. Over 100 viruses are implicated as causative agents, including herpes simplex virus type I which is the most common agent implied in non-epidemic encephalitis in all population groups in the world, and is responsible for the most severe cases in all ages. Many viruses, for which there are vaccines, may also cause encephalitis: measles, mumps, polio, rabies, rubella, and chickenpox. The virus causes an inflammation of the brain tissue, which may progress to destruction of nerve cells, cause bleeding and brain damage, leading to severe encephalitis, such as hemorrhagic or necrotizing encephalitis, with a worse prognosis, producing serious sequelae or death. The clinical evolution includes the presence of headache, fever and altered consciousness rapidly progressive. The outcome of viral encephalitis is variable, some cases are mild, with full recovery, but there are serious cases that can cause severe sequel in the brain. To diagnose this illness as soon as possible is essential, through laboratory tests (biochemistry, virus PCR, culture) and neuroimaging (CT, MRI) and above all, the establishment of early treatment to prevent the development of the process and possible complications. The prognosis worsens if the initiation of treatment is delayed.

The efficacy of haemoperfusion combined with continuous venovenous haemodiafiltration in the treatment of severe viral encephalitis in children.

BACKGROUND: This study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis. METHODS: The records of children with viral encephalitis who received blood purification treatment in the authors' hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed. RESULTS: The experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P < 0.05). The extent of brain MRI lesions correlated positively with CSF NPT levels (P < 0.05). In the experimental group (14 cases), the serum NPT levels decreased after treatment, whereas the CSF NPT levels increased after treatment, and the differences were statistically significant (P < 0.05). Dysphagia and motor dysfunction correlated positively with CSF NPT levels (P < 0.05). CONCLUSION: Early HP combined with CVVHDF in the treatment of severe viral encephalitis in children may be a better approach than CVVHDF only for improving prognosis. Higher CSF NPT levels indicated the likelihood of a more severe brain injury and a greater possibility of residual neurological dysfunction.

Trend of hospital utilization for encephalitis.

Encephalitis generally results in a serious illness requiring hospitalization. The aim of this study was to describe the epidemiology of hospitalization for encephalitis in Italy, taking into account the geographical distribution, aetiology, seasonality and evolution of hospitalization rates over recent years. The mean hospitalization rate was 5·88/100 000. For most of these hospitalizations (n=13 119, 55·6%), no specific cause of encephalitis was reported. The most common aetiological category was 'viral', which accounted for 40·1% (n=4205) of such hospitalizations (rate 1·05/100 000). Within this category, herpes virus was the leading causative agent (n=1579, 0·39/100 000). This report highlights a significant increase of 'viral encephalitis not otherwise specified' (ICD-9 code 049·9) vs. a reduction of all other causes. A seasonal pattern was noted in people aged ≥65 years in this group. Specific surveillance of encephalitis without known origin should be reinforced in order to identify the potential role of emerging pathogens and to design preventive interventions.

Cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis.

Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

Fatal case of human rabies imported to Italy from India highlights the importance of adequate post-exposure prophylaxis, October 2011.

In October 2011, an Indian man resident in Italy was admitted to a hospital in Mantua, Italy with symptoms of acute encephalitis. Due to a recent history of bite by a suspected rabid dog in India, where he had received incomplete post-exposure treatment, rabies was suspected. The patient died after 22 days of intensive care treatment and rabies was confirmed post mortem. This report stresses the need of appropriate post-exposure prophylaxis in rabies-endemic countries.

Successful outcome of Epstein-Barr virus encephalitis managed with bilateral craniectomy, corticosteroids and aciclovir.

We present a 19-year-old woman with severe encephalitis and raised intracranial pressure requiring decompressive craniectomy. Her clinical features were consistent with encephalitis in the context of acute primary Epstein-Barr virus (EBV) infection (infectious mononucleosis). Serology, bone marrow aspirate and PCR of blood and cerebrospinal fluid confirmed the diagnosis. She was treated with corticosteroids and aciclovir. She was critically unwell for 3 weeks, requiring artificial ventilation but eventually made a good recovery. EBV encephalitis is uncommon, making the diagnosis and decisions about clinical management challenging.

Viral Encephalitis in Adults: A Narrative Review.

Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis of viral encephalitis involves both the direct action of invading pathogens and the damage generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by the patient depends on the severity and location of the ongoing inflammatory process. Most of the viral encephalitides are characterized by an acute development, fever, variable alterations in consciousness (confusion, lethargy, even coma), seizures (focal and generalized) and focal neurologic signs. The specific diagnosis of encephalitis is usually based on lumbar puncture. Cerebrospinal fluid examination should be performed in all patients unless absolutely contraindicated. Also, electroencephalogram and neuroimaging play a prominent role in diagnosis. Airway protection, ventilatory support, the management of raised intracranial pressure and correction of electrolyte disorders must be immediately considered in a patient with altered mental status. The only therapy strictly recommended is acyclovir in HSV encephalitis. The use of adjunctive glucocorticoids has poor-quality evidence in HSV, EBV, or VZV encephalitis. The role of antiviral therapy in other types of viral encephalitis is not well defined.