Prevalence, Causes and Management of Encephalitis

Encephalitis is a major cause of morbidity, mortality, and permanent neurological disability in both adults and children. The term "encephalitis" literally means inflammation of part or all of the "brain" or the brain parenchyma. Encephalitis affects people of all ages; however, the incidence is higher in the pediatric population. Although both genders are affected, most studies showed slight dominance in men. There are two main types with different causes: primary or infectious encephalitis can develop when a fungus, virus, or bacteria infects the brain and accounts for approximately 70% of confirmed cases of encephalitis, and secondary or post-infectious encephalitis when the immune system is active and reacts. to a previous infection and mistakenly attacks the brain. The clinical manifestations depend on whether the brain parenchyma or the meninges are predominantly involved and cause an encephalitic or meningitis syndrome. Diagnostic tests should include a lumbar puncture, an MRI of the brain, and an EEG for suspected encephalitis. In encephalitis, a broad differential diagnosis, both infectious and non-infectious, should be considered. These alternatives include malignancy, autoimmune or paraneoplastic diseases (eg, anti-NMDA receptor encephalitis), brain abscess, drug-induced tuberculosis or delirium, neurosyphilis, or bacterial, fungal, protozoal, or helminthic encephalitis. Antiviral medications, such as intravenous acyclovir, are often given at the initial diagnosis of encephalitis before the cause is known. Acyclovir is the best treatment for herpes simplex encephalitis. If medication can be started soon after symptoms appear, the chance of a full recovery is much higher.

Noncanonical Transmission of a Measles Virus Vaccine Strain from Neurons to Astrocytes

ABSTRACT Viruses, including members of the herpes-, entero-, and morbillivirus families, are the most common cause of infectious encephalitis in mammals worldwide. During most instances of acute viral encephalitis, neurons are typically the initial cell type that is infected. However, as replication and spread ensue, other parenchymal cells can become viral targets, especially in chronic infections. Consequently, to ascertain how neurotropic viruses trigger neuropathology, it is crucial to identify which central nervous system (CNS) cell populations are susceptible and permissive throughout the course of infection, and to define how viruses spread between distinct cell types. Using a measles virus (MV) transgenic mouse model that expresses human CD46 (hCD46), the MV vaccine strain receptor, under the control of a neuron-specific enolase promoter (NSE-hCD46+ mice), a novel mode of viral spread between neurons and astrocytes was identified. Although hCD46 is required for initial neuronal infection, it is dispensable for heterotypic spread to astrocytes, which instead depends on glutamate transporters and direct neuron-astrocyte contact. Moreover, in the presence of RNase A, astrocyte infection is reduced, suggesting that nonenveloped ribonucleoproteins (RNP) may cross the neuron-astrocyte synaptic cleft. The characterization of this novel mode of intercellular transport offers insights into the unique interaction of neurons and glia and may reveal therapeutic targets to mitigate the life-threatening consequences of measles encephalitis. IMPORTANCE Viruses are the most important cause of infectious encephalitis in mammals worldwide; several thousand people, primarily the very young and the elderly, are impacted annually, and few therapies are reliably successful once neuroinvasion has occurred. To understand how viruses contribute to neuropathology, and to develop tools to prevent or ameliorate such infections, it is crucial to define if and how viruses disseminate among the different cell populations within the highly complex central nervous system. This study defines a noncanonical mode of viral transmission between neurons and astrocytes within the brain.

Infantile hemiconvulsion-hemiplegia epilepsy syndrome associated with GRIN2A gene mutation

Introduction. Infantile hemiconvulsion-hemiplegia and epilepsy (IHHE) syndrome is defined as a specific syndrome in a patient < 2 years of age, presenting as a new onset refractory status epilepticus with unilateral motor seizures and acute imaging abnormalities, fever, hemiparesis >24 hours, and excluding infectious encephalitis. Case outline. We present results of follow-up in 11 year-old girl with IHHE, associated with GRIN2A mutation. The girl had normal development until the first febrile hemiconvulsive status epilepticus at the age of seven months. Neuroimaging initially showed right hemisphere edema, followed by progressive right side hemiatrophy. The patient has resistant epilepsy, left side hemiparesis, and good language and cognitive development. Conclusion. Despite IHHE described many years ago, some syndrome's features, including etiology have remained unexplained. The association of IHHE and GRIN2A mutation is described in current manuscript for the first time in scientific literature.

COVID-19 Post-Infectious Encephalitis Presenting With Delirium as an Initial Manifestation

We report the case of a 65-year-old man with COVID-19 (coronavirus disease-2019) post-infectious encephalitis who presented with delirium as an initial manifestation. He had severe COVID-19 pneumonia and recovered with dexamethasone and tocilizumab. One week after discharge, he developed abnormal behavior and delirium without fever and respiratory symptoms. Brain magnetic resonance imaging showed no abnormalities. Cerebrospinal fluid showed pleocytosis and elevated protein concentrations and was negative for severe acute respiratory syndrome-coronavirus-2 RNA. No anti-neuronal autoantibodies against intracellular and neuronal surface proteins were detected. The cerebrospinal fluid inflammatory changes compatible with post-infectious encephalitis, and the patient recovered with intravenous methylprednisolone and intravenous immunoglobulin therapy. Delirium could be an initial symptom of post-infectious encephalitis in older adults with COVID-19, and these patients may require immunosuppressive therapy.

Antibody Negative Autoimmune Encephalitis: A Case Report

Encephalitis is characterized by inflammation of the brain. Literature describes autoimmune as one of the most common aetiology of non-infectious encephalitis. Given the similarities in clinical, imagological and laboratory findings with viral encephalitis and due to the wide variety of clinical features, the diagnosis is rather challenging and therefore physicians need an increased clinical suspicion to make the correct diagnosis. We report a case of a 35-year-old male with no past medical history that presented with two episodes of autoimmune encephalitis in a 6-month period. Despite having the typical clinical presentation and imagological findings consistent with autoimmune encephalitis, this case had negative results for antibodies, which delayed the diagnosis. It is essential to highlight the importance of considering the hypothesis of autoimmune aetiology on the differential diagnosis of all patients presenting with clinical and magnetic resonance imaging results suggestive of probable encephalitis, regardless of the negative antibodies results. This case clearly depicts the difficulties of diagnosing and treating an autoimmune encephalitis. The main goal of this case report is to increase awareness towards early diagnosis to promptly implement a specific treatment that has proven to improve the outcome and prognosis.

Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment and Recent Patents

Background:: Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management and recent patents of acute childhood infectious encephalitis. Methods:: We used PubMed Clinical Queries and keywords of “encephalitis” AND “childhood” as a search engine, and patents were searched using the key term “encephalitis” in google.patents.com and patentsonline.com. Results:: Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next generation sequencing, improve diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, and cerebral perfusion pressure support and seizure control. Recent patents are related to diagnosis, treatment and prevention of acute infectious encephalitis. Conclusions:: Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. Specific antimicrobial agents and vaccines development is ongoing.