Acute Viral Encephalitis Research Articles

Thrombocytopenia as a Prognostic Marker in Patients with Acute Encephalitis at a Tertiary Care Center in Northern India.

Acute encephalitis (AE) is associated with a high burden of mortality and permanent disability and has a spectrum of underlying etiologies. The prognosis of encephalitis is difficult and almost all the patients seem to be at a high risk of poor outcomes. A number of physiological changes take place during encephalitis and have been evaluated for their prognostic value. Platelet count, which has been recognized as a surrogate prognostic marker in various viral illnesses, has recently been recognized to have a prognostic value in AE too. In the present study, we attempted to study the role of thrombocytopenia in the prognosis of AE. Total of 98 cases based on clinical, cerebrospinal fluid, and radiological profiles consistent with the diagnosis of AE were enrolled in the study. A clinical profile was noted, and platelet count was assessed. Thrombocytopenia was defined as platelet count <150,000/mm3. Platelet count 100,000-150,000, 50,000-99,999, and <50,000/mm3 were considered mild, moderate, and severe thrombocytopenia. The underlying etiology was explored, and patients were followed till discharge/outcome. The outcome was noted in terms of the Modified Rankin score (MRS). MRS 0-2 was considered good, 3-4 fair, and 5-6 as poor outcome. The mean age of patients was 34.06 ± 18.76 years. Majority of patients were women (54.1%). Prevalence of thrombocytopenia was 75.5%. A total of 34 (45.9%) had mild, 30 (40.5%) had moderate, and 10 (13.5%) had severe thrombocytopenia. Acute viral encephalitis (unclassified) was the most common etiology (33.7%), followed by scrub meningoencephalitis (24.5%) and Japanese encephalitis (12.2%), respectively. Good, fair, and poor outcomes were noted in 48 (49%), 21 (21.4%), and 29 (29.6%) cases. On univariate analysis, no significant association of poor outcome was seen with age, sex, duration of fever, and mechanical ventilation need (P > 0.05). Low Glasgow Coma Scale (GCS), splenomegaly, low platelet count, and Japanese encephalitis virus/scrub typhus etiologies were found to be significantly associated with poor outcomes (P < 0.05). Thrombocytopenia compared to normal platelet count and severe thrombocytopenia compared to mild and moderate thrombocytopenia were significantly associated with poor outcomes (P < 0.05). On multivariate analysis, GCS <8 (odds ratio [OR] =4.52; 95% confidence interval [CI] =1.56-13.20) and thrombocytopenia (OR = 11.92; 95% CI = 1.38-103.32) emerged as independent predictors of poor outcome. The findings of the study showed that low GCS and thrombocytopenia could be used as predictors of poor outcomes in AE cases.

Prevalence & clinical outcome of autoimmune encephalitis versus viral encephalitis in children with acute encephalitis syndrome: A prospective observational study.

Background & objectives Acute encephalitic syndrome (AES), encompasses a wide spectrum of potential causes, clinical presentations, and outcomes. While infectious encephalitis is generally considered more prevalent, autoimmune encephalitis is emerging as a significant aetiology. Neuronal autoantibodies have been identified independently or in association with acute viral encephalitis. The primary objective of this study was to ascertain the prevalence and clinical manifestation of autoimmune encephalitis as well as of coexisting viral markers in children with AES. Methods This study was a prospective observational investigation conducted in a hospital setting. It involved enrolling children with AES who were admitted to specific tertiary hospitals. Children were subjected to examinations to detect the presence of viral markers and neuronal autoantibodies in both their blood and cerebrospinal fluid (CSF). All the participants received treatment based on established guidelines and was followed for six months for outcome assessment. Results During the study period, 867 children with AES were examined. Among these cases, 37 children (4.2%) were diagnosed with autoimmune encephalitis, and all of them tested positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibodies. Evidence of viral infection was seen in 409 (47.1%) of cases, out of which nearly 254 (29.2%) children had detectable HSV IgM antibodies. Among the 37 children with autoimmune encephalitis, 25 (67.5%) had evidence of a viral trigger, with eight of them tested positive for HSV IgM antibodies. The clinical presentation of autoimmune-associated AES was similar to those with viral aetiology. Interpretation & conclusions Autoimmune encephalitis triggered by neurotropic (HSV) viral infection was more prevalent in this study than in the earlier reports. Typically, these children show positive responses to immunosuppressive treatments if administered promptly. It is hence advisable to assess children who exhibit behavioural issues and movement disorders for possible autoimmune encephalitis.

N4-Hydroxycytidine/molnupiravir inhibits RNA virus-induced encephalitis by producing less fit mutated viruses.

A diverse group of RNA viruses have the ability to gain access to the central nervous system (CNS) and cause severe neurological disease. Current treatment for people with this type of infection is generally limited to supportive care. To address the need for reliable antivirals, we utilized a strategy of lethal mutagenesis to limit virus replication. We evaluated ribavirin (RBV), favipiravir (FAV) and N4-hydroxycytidine (NHC) against La Crosse virus (LACV), which is one of the most common causes of pediatric arboviral encephalitis cases in North America and serves as a model for viral CNS invasion during acute infection. NHC was approximately 3 to 170 times more potent than RBV or FAV in neuronal cells. Oral administration of molnupiravir (MOV), the prodrug of NHC, decreased neurological disease development (assessed as limb paralysis, ataxia and weakness, repeated seizures, or death) by 31% (4 mice survived out of 13) when treatment was started on the day of infection. MOV also reduced disease by 23% when virus was administered intranasally (IN). NHC and MOV produced less fit viruses by incorporating predominantly G to A or C to U mutations. Furthermore, NHC also inhibited virus production of two other orthobunyaviruses, Jamestown Canyon virus and Cache Valley virus. Collectively, these studies indicate that NHC/MOV has therapeutic potential to inhibit viral replication and subsequent neurological disease caused by orthobunyaviruses and potentially as a generalizable strategy for treating acute viral encephalitis.

Clinical and Etiological Profile of Children With Acute Viral Encephalitis in a Tertiary Care Hospital: A Cross-Sectional Study.

Acute encephalitis refers to the clinical diagnosis of children who have a sudden onset of symptoms and show evidence of inflammatory lesions in the brain. Timely diagnosis is crucial for both lifesaving measures and the preservation of brain functions. The objective of the study was to determine the clinical and etiological profile of acute viral encephalitis in children within a tertiary care hospital. This hospital-based cross-sectional study was conducted in the Pediatric Intensive Care Unit (PICU) at Dr. D. Y. Patil Medical College, Hospital, and Research Centre in Pune. The study included children aged one month to 12 years diagnosed with suspected viral encephalitis. Over 22 months, from August 2022 to June 2024, 35 children who met the inclusion criteria were enrolled. Data collection involved clinical examinations, laboratory investigations, and imaging studies, following informed consent from the parents or guardians. The study examined 35 patients with suspected acute encephalitis syndrome (AES) and found a male-to-female ratio of 3.4:1. Among the patients, 22 (62.85%) had a confirmed viral etiology, while 13 (37.17%) had an unknown etiology. The most common virus isolated was mumps, with school-age children most affected. The cases were concentrated in the Chikhali, Bhosari, Nigdi, and Chinchwad regions. Symptoms included fever, seizures, vomiting, and altered mental status. Low vaccination rates were observed, and the Glasgow Coma Scale (GCS) scores, shock incidence, and ventilation showed an association with mortality. Most patients required intensive care, antiedema measures, antibiotics, and antivirals. The mortality rate was 11.4%, with 17% of patients discharged with neurological sequelae. Causative agents such as mumps, herpes simplex virus (HSV), dengue, and many other viruses are now more prevalent than the Japanese encephalitis (JE) virus. Bad clinical course and fatal outcomes are observed in patients affected with rabies, HSV, and H1N1 influenza virus. Factors such as GCS scores, shock, and need for ventilation play a significant role in determining patient prognosis. Early detection and prompt treatment may aid in betteroutcomes for patients.

Effect of Timing of Rehabilitation Nursing Intervention on Children with Acute Viral Encephalitis

Background: Viral encephalitis (VE) refers to an acute intracranial inflammation mainly caused by various viral infections. Objectives: Viral encephalitis (VE) refers to an acute inflammation of the brain primarily caused by various viral infections. Methods: Data from 60 children with acute viral encephalitis (VE) who received 4 weeks of rehabilitation nursing from July 2019 to July 2020 were collected for retrospective analysis. These children were divided into two groups: An early intervention group (n = 30), where rehabilitation nursing started in the second week after admission, and a late intervention group (n = 30), where rehabilitation nursing began in the fourth week after admission. Motor function, daily living abilities, and limb spasticity were compared before and four weeks after nursing. Additionally, the outcomes of rehabilitation nursing—including recovery times from convulsions, cranial nerve disorders, and consciousness disorders—were also compared. Results: The scores for motor function and daily living ability were significantly higher, while the score for limb spasticity was lower in the early intervention group compared to the late intervention group (P &lt; 0.05). Additionally, the early intervention group experienced a significantly shorter recovery time from convulsions, cranial nerve disorders, and consciousness disorders than the late intervention group (P &lt; 0.05). Conclusions: Early rehabilitation nursing is effective in enhancing motor function, relieving limb spasticity, and improving the nursing outcomes for children with acute viral encephalitis (VE).

Transcranial Doppler Sonography in Acute Viral Encephalitis with Special Reference to Dengue Encephalitis

Abstract Introduction: Acute viral encephalitis syndrome including dengue encephalitis (DE) is an important tropical illness with a guarded prognosis. The cerebral blood flow may be affected in acute viral encephalitis. Transcranial Doppler (TCD) sonography can quantitatively determine intracranial vascular flow dynamics in acute viral encephalitis. Aim: We aimed to investigate the intracranial blood flow characteristics in patients with DE and compare with nondengue acute viral encephalitis patients. Materials and Methods: In this prospective study, all the cases of acute viral encephalitis including dengue were enrolled over 18 months and followed up at 3 months. TCD was performed to determine the mean velocity pulsatility index (PI) and resistive index (RI) across the middle cerebral artery, anterior cerebral artery, posterior cerebral artery (PCA), vertebral artery, and basilar artery and compared it among dengue versus nondengue group as well as outcome at 3 months. Results: Out of 39 patients, 19 were diagnosed with DE, whereas 20 patients suffered from the nondengue group. The elevated PI and RI in the left PCA were found to statistically significant (P = 0.001 and 0.008, respectively) in the DE group. There was no significant difference in any other TCD indices in any other vessel among both the groups. In addition, an initial low Glasgow Outcome Scale (GOS) and higher brain imaging abnormality were significantly associated with poor GOS of &lt;5 in both the groups. Conclusion: An elevated PI and RI of PCA could be an important initial TCD parameter in DE. TCD parameters did not affect the outcome of acute viral encephalitis.

Post-encephalitic movement disorders - The natural course

Post-encephalitis syndrome can present with a multitude of movement disorders. Dystonia and parkinsonism are frequently observed during the course of acute viral encephalitis. The proper elucidation of genesis of such movements is yet to be determined. The advent of such abnormal movements and response to treatment needs further illustration. In this case series, we present the course of illness of three such patients over a long follow-up duration.

Retracted: Detection and Diagnostic Value of Cytokines in Serum of Children with Acute Viral Encephalitis.

[This retracts the article DOI: 10.1155/2022/9997531.].

Rapid deterioration of a case of anti–N-methyl-D-aspartate receptor encephalitis with an ovarian teratoma, mimicking viral encephalitis

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis has recently emerged as an autoimmune encephalitis syndrome. Younger females are more likely to develop this condition which usually presents as a multistage illness with predominant neuropsychiatric manifestations. It is associated with the neuroglial surface antibodies developing against NMDAR. The association of ovarian teratoma has been well recognised in this condition and tumour resection will intensify the recovery of the illness along with immunotherapy. We present a case of 19-year-old female who presented with acute onset of fever, encephalopathy and facial myorhythmia mimicking acute viral encephalitis. Her clinical status deteriorated within a short period. Later, her CSF became positive for NMDAR antibody and a right ovarian teratoma was detected. Her clinical status markedly improved with immunotherapy and excision of the teratoma following a diagnosis of Anti-NMDAR encephalitis. As a potentially treatable neurological condition, clinicians should be aware of this autoimmune encephalitis syndrome causing encephalitis.

Ifit2 restricts murine coronavirus spread to the spinal cord white matter and its associated myelin pathology.

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-β-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 post-infection (chronic phase). Our study demonstrates that Ifit2 deficiency causes extensive RSA59 spread throughout the spinal cord gray and white matter, associated with impaired CD4+ T and CD8+ T cell infiltration. Further, the cervical lymph nodes of RSA59 infected Ifit2-/- mice showed reduced activation of CD4+ T cells and impaired IFNγ expression during acute encephalomyelitis. Interestingly, BBB integrity was better preserved in Ifit2-/- mice, as evidenced by tight junction protein Claudin-5 and adapter protein ZO-1 expression surrounding the meninges and blood vessels and decreased Texas red dye uptake, which may be responsible for reduced leukocyte infiltration. In contrast to sparse myelin loss in WT mice, the chronic disease phase in Ifit2-/- mice was associated with severe demyelination and persistent viral load, even at low inoculation doses. Overall, our study highlights that Ifit2 provides antiviral functions by promoting acute neuroinflammation and thereby aiding virus control and limiting severe chronic demyelination. IMPORTANCE Interferons execute their function by inducing specific genes collectively termed as interferon-stimulated genes (ISGs), among which interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is known for restricting neurotropic viral replication and spread. However, little is known about its role in viral spread to the spinal cord and its associated myelin pathology. Toward this, our study using a neurotropic murine β-coronavirus and Ifit2-deficient mice demonstrates that Ifit2 deficiency causes extensive viral spread throughout the gray and white matter of the spinal cord accompanied by impaired microglial activation and T cell infiltration. Furthermore, infected Ifit2-deficient mice showed impaired activation of T cells in the cervical lymph node and relatively intact blood-brain barrier integrity. Overall, Ifit2 plays a crucial role in mounting host immunity against neurotropic murine coronavirus in the acute phase while preventing mice from developing viral-induced severe chronic neuroinflammatory demyelination, the characteristic feature of human neurological disease multiple sclerosis (MS).

Etiological aspects of viral encephalitis explored using PCR-based cerebrospinal fluid analysis, considering patients’ HIV status

This study examined 124 patients suffering from acute viral encephalitis who were admitted to the Center for the Development of Professional Skills of Medical Personnel between 2014 and 2019. The research focused on the outcomes of cerebrospinal fluid PCR diagnostics in viral encephalitis cases, taking into account patients' HIV status. Findings revealed that PCR testing offers a more reliable diagnosis and, when lab resources permit, should be employed for CSF analysis to more accurately identify the etiological agent responsible for SVE. It is advised to repeat real-time PCR diagnostics of CSF in cases where the cause of SVE remains undetermined to improve detection rates of SVE's causative factors and enhance targeted therapy effectiveness, shifting from empirical and symptomatic to etiotropic approaches.

Recent Population Dynamics of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV) causes acute viral encephalitis in humans and reproductive disorders in pigs. JEV emerged during the 1870s in Japan, and since that time, JEV has been transmitted exclusively throughout Asia, according to known reporting and sequencing records. A recent JEV outbreak occurred in Australia, affecting commercial piggeries across different temperate southern Australian states, and causing confirmed infections in humans. A total of 47 human cases and 7 deaths were reported. The recent evolving situation of JEV needs to be reported due to its continuous circulation in endemic regions and spread to non-endemics areas. Here, we reconstructed the phylogeny and population dynamics of JEV using recent JEV isolates for the future perception of disease spread. Phylogenetic analysis shows the most recent common ancestor occurred about 2993 years ago (YA) (95% Highest posterior density (HPD), 2433 to 3569). Our results of the Bayesian skyline plot (BSP) demonstrates that JEV demography lacks fluctuations for the last two decades, but it shows that JEV genetic diversity has increased during the last ten years. This indicates the potential JEV replication in the reservoir host, which is helping it to maintain its genetic diversity and to continue its dispersal into non-endemic areas. The continuous spread in Asia and recent detection from Australia further support these findings. Therefore, an enhanced surveillance system is needed along with precautionary measures such as regular vaccination and mosquito control to avoid future JEV outbreaks.

Structured Imaging Approach for Viral Encephalitis.

MR imaging is essential in diagnosing viral encephalitis. Clinical features, cerebrospinal fluid analysis and pathogen confirmation by polymerase chain reaction can be supported by assessing imaging features. MR imaging patterns with typical locations can identify pathogens such as temporal lobe for herpes simplex virus type 1; bilateral thalami for Japanese encephalitis and influenza virus ; and brainstem for enterovirus and rabies. In this article, we have reviewed representative viral encephalitis and its MR imaging patterns. In addition, we also presented acute viral encephalitis without typical MR imaging patterns, such as dengue and varicella-zoster virus encephalitis.

Neurological sequelae after encephalitis associated with herpes simplex virus in children: systematic review and meta-analysis

BackgroundEncephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection.ObjectiveTo assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV.MethodsThis systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used.ResultsOf the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2–62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30–55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2–14.6). The included studies presented regular quality and substantial heterogeneity.ConclusionEven with antiviral therapy, half of patients will develop some type of disability.

Neurological Consequences of Arvi

This work includes consideration of neurological consequences of acute respiratory viral infection (ARVI), such as meningitis, encephalitis, headache, sleep disorders and mental disorders. The authors are based on existing studies showing that ARVI can cause inflammatory processes in the nervous system and lead to long-term health consequences. The article also discusses methods of diagnosis and treatment of neurological manifestations of ARVI. The research results may be useful for doctors treating patients with acute respiratory viral infections, as well as for people who want to understand the possible consequences of this disease. In addition, the authors note that the neurological consequences of ARVI can be especially dangerous for certain groups of patients, such as children, the elderly and people with concomitant diseases. Therefore, it is important to pay attention to the neurological symptoms of ARVI and to carry out timely diagnosis and treatment. The paper also notes that possible causes of neurological manifestations of ARVI may be not only viruses, but also immune mechanisms, as well as other factors such as stress and lack of physical activity during the disease. In general, the article provides an overview of the neurological consequences of ARVI, indicating their severity and the need for additional research in this area. This information can be useful both for doctors and for the general public, helping to understand the importance of prevention and timely treatment of acute respiratory viral infections.

Acute Viral Encephalitis in Adults

Acute Viral Encephalitis in Adults

B cells going viral in the CNS: Dynamics, complexities, and functions of B cells responding to viral encephalitis.

A diverse number of DNA and RNA viruses have the potential to invade the central nervous system (CNS), causing inflammation and injury to cells that have a limited capacity for repair and regeneration. While rare, viral encephalitis in humans is often fatal and survivors commonly suffer from permanent neurological sequelae including seizures. Established treatment options are extremely limited, predominantly relying on vaccines, antivirals, or supportive care. Many viral CNS infections are characterized by the presence of antiviral antibodies in the cerebral spinal fluid (CSF), indicating local maintenance of protective antibody secreting cells. However, the mechanisms maintaining these humoral responses are poorly characterized. Furthermore, while both viral and autoimmune encephalitis are associated with the recruitment of diverse B cell subsets to the CNS, their protective and pathogenic roles aside from antibody production are just beginning to be understood. This review will focus on the relevance of B cell responses to viral CNS infections, with an emphasis on the importance of intrathecal immunity and the potential contribution to autoimmunity. Specifically, it will summarize the newest data characterizing B cell activation, differentiation, migration, and localization in clinical samples as well as experimental models of acute and persistent viral encephalitis.

Risk factors for acute encephalitis and early seizure recurrence in complex febrile seizures.

The purpose of this study is to elucidate risk factors for central nervous system infection and early seizure recurrence in children with febrile seizures (FSs) and thus facilitate outpatient management of complex FS. This single-center, retrospective cohort study investigated 688 children (6-60months old) with FSs in Japan during 2011-2021. We investigated the incidence and clinical manifestations of children with acute encephalitis or bacterial meningitis. Logistic regression modeling was used to examine risk factors for seizure recurrence within 24h. Among children with recurrent FSs, the distribution of intervals between first and second FS was assessed. Among 145 children with complex FSs, 2 patients (1.4%) had acute viral encephalitis and none had bacterial meningitis. Acute encephalitis was found in 2 of 8 patients (25%) with FSs prolonged ≥30min and 2 of 3 patients (67%) requiring ≥2 intravenous anticonvulsants to stop seizures. Seizure recurrence within 24h was observed in 16% of participants and was independently associated with preceding use of diazepam and family history of FS. In 82% of patients with FS recurrence within 24h, early recurrences occurred within 8h of the first seizure. Conclusion: Patients with prolonged or refractory FSs are still indicated for hospital admission due to the risk of acute encephalitis. FS patients with a family history of FS may be managed safely by 8-h observation or single-dose rectal diazepam as prophylaxis against early recurrent seizure. What is Known: •Hospitalization has been recommended for children with complex febrile seizures due to the increased risk of central nervous infections. •Recent studies showed low incidences of bacterial meningitis (<1%) in children with complex febrile seizures in the presence of routine immunization. What is New: •Acute encephalitis was identified in 1.4% of children with complex febrile seizures, characterized by prolonged seizures ≥30 min and refractory seizures. •Early recurrent seizures may be safely managed by prophylactic diazepam or 8-h expectant observation.

A pediatric case of West Nile virus chorioretinitis associated with unilateral acute idiopathic maculopathy

We report a pediatric case of unilateral acute idiopathic maculopathy (UAIM) associated with West Nile virus (WNV) infection. A 10-year-old child with a 15-day history of presumed acute viral encephalitis, complained of blurred vision in the right eye. Clinical and multimodal imaging findings, including disruption of the foveal ellipsoid zone (EZ) with preservation of the external limiting membrane on Swept Source OCT (SS OCT), were consistent with UAIM. The finding of associated curvilinear chorioretinal lesions in the setting of encephalitis led a diagnosis of WNV infection to be considered and subsequently confirmed by serology. The EZ spontaneously restored over a few weeks with near complete visual recovery. This is a unique pediatric case of UAIM associated with serologically proven WNV infection.

Detection and Diagnostic Value of Cytokines in Serum of Children with Acute Viral Encephalitis.

Acute viral encephalitis is one of the serious infectious diseases. In order to analyze the diagnostic efficacy of serum procalcitonin (PCT), C-reactive protein (CRP), and S100B protein in acute viral encephalitis, a total of 100 children with acute viral encephalitis from July 2019 to December 2021 are selected and included in the viral encephalitis group. The results show that S100B protein model has high specificity and sensitivity and is simple to operate. It provides new ideas and directions for differential diagnosis, improvement, and optimization of relevant clinical diagnosis and treatment schemes and has high clinical value.