Viral Encephalitis


Article Author:
Saema Said


Article Editor:
Michael Kang


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
11/15/2018 11:32:37 PM

Introduction

Viral encephalitis is an inflammation of the brain parenchyma caused by a virus. It is the most common type of encephalitis and often coexists with viral meningitis. Viruses invade the host outside the central nervous system (CNS) and then reach the spinal cord and brain hematogenously or in a retrograde manner from nerve endings.[1][2][3]

Etiology

Infectious encephalitis can be viral, bacterial, fungal, protozoal, or helminthic in etiology. The etiology of many cases of encephalitis remains unknown despite extensive workup. Viruses are the most prevalent identified cause, accounting for about 70% of confirmed cases of encephalitis. In the United States, the most common causes of viral encephalitis are herpes simplex virus (HSV), West Nile virus, and the enteroviruses. Some of the other viral etiologic agents include varicella-zoster virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus type 6 and 7, measles virus, mumps virus, rubella virus, St. Louis virus, eastern equine virus, western equine virus, dengue virus, and rabies virus.[4][5][6]

Epidemiology

The incidence of viral encephalitis is 3.5 to 7.5 per 100,000 people, with the highest incidence in the young and elderly. The epidemiology of certain viral causes of encephalitis has changed through time. For example, vaccination has led to a decrease in the incidence of encephalitis due to mumps and measles. On the other hand, EBV and CMV encephalitis are seen more frequently now because they occur in immunocompromised individuals, such as AIDS, transplant, and chemotherapy patients. Other important epidemiologic factors include time of the year, geography, and animal or insect exposure. For instance, arboviruses (i.e., eastern equine, western equine, St. Louis, Venezuelan equine, Zika, and West Nile) cause disease during the summer months when mosquitos are active. St. Louis encephalitis is primarily seen in the Midwest and South, whereas tick-borne encephalitis occurs mainly in the north central and Northeastern United States.[7][8][9]

Pathophysiology

Viruses invade the host at a site outside the CNS and replicate. Most then reach the spinal cord and brain hematogenously. HSV, rabies, and herpes zoster virus are important exceptions to this. They travel to the CNS from nerve endings in a retrograde manner. Once in the brain, the virus and the host’s inflammatory response disrupt neural cell function.

Histopathology

Brain histology of individuals with viral encephalitis shows dead neurons with nuclear dissolution and hypereosinophilia within the cytoplasm on light microscopy. Because encephalitis is an inflammatory process, perivascular inflammatory cells such as microglia, macrophages, and lymphocytes are also seen. Virions within neurons can be visualized with electron microscopy, which allows for much greater magnification than light microscopy.

History and Physical

As mentioned above, the cause of many cases of encephalitis remains unknown despite extensive testing. Thus, history and physical exam play a vital role in making the diagnosis of viral encephalitis. Important elements of history include immune status, exposure to insects or animals, travel history, vaccination history, geography, and time of year. The most common sign and symptoms are fever, headache, seizures, and altered mental status. Neuropsychiatric features such as behavioral changes, hallucinations, and/or cognitive decline are often seen. Patients may also have other symptoms or exam findings that are more specific to a given virus. For example, rash and skin vesicles are seen with herpes zoster encephalitis, whereas lymphadenopathy and splenomegaly are usually associated with EBV. HSV encephalitis involves the temporal and frontal lobes, so it is often characterized by psychiatric features, memory deficits, and aphasia. On the other hand, motor symptoms such as choreoathetosis and parkinsonian movements are seen with some arboviruses because they predominately affect the basal ganglia.

Evaluation

Neuroimaging and lumbar puncture (LP) are essential initial diagnostic studies for evaluating patients with viral encephalitis. Computed tomography (CT) or magnetic resonance imaging (MRI) help exclude increased intracranial pressure and the risk of uncal herniation prior to performing an LP. MRI is also the most sensitive imaging modality for showing findings consistent with HSV encephalitis, such as temporal and frontal lobe involvement. Cerebrospinal fluid (CSF) should be analyzed for opening pressure, cell counts, glucose, and protein. CSF evaluation should also include polymerase chain reaction (PCR) testing for HSV-1, HSV-2, and enteroviruses. Additional testing, such as serology for arboviruses and HIV testing, may also be done based on history and clinical presentation. Brain biopsy and body fluid specimen cultures and PCR may also be helpful in establishing the etiology in some cases.[2][10][11]

Treatment / Management

The treatment of viral encephalitis is primarily supportive as there is no specific medical therapy for most central nervous system viral infections. A very important exception to this is HSV encephalitis. When started early, acyclovir has been shown to significantly decrease mortality and morbidity and limit the severity of long-term behavioral and cognitive impairment of HSV encephalitis. Therefore, empirically, it is recommended that physicians start all patients with suspected encephalitis on acyclovir. The recommended dose is 10 mg/kg intravenously (IV) every 8 hours for 14 to 21 days. Although not as effective as it is with HSV, nucleoside analogues are used for other herpesviruses as well. Acyclovir 10 to 15 mg/kg IV every 8 hours for 10 to 14 days, with possible adjunctive corticosteroids in immunocompetent patients, is recommended for varicella zoster virus. The recommended treatment for CMV encephalitis is a combination of ganciclovir 5 mg/kg IV every 12 hours and foscarnet 60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours for 21 days.

Another important component of the management of patients with viral encephalitis is serial intracranial pressure (ICP) monitoring. Elevated ICP is associated with a poor prognosis. Although there is limited data on their efficacy in viral encephalitis, steroids and mannitol can be given to relieve increased ICP.[12][13][14]

Differential Diagnosis

A broad differential diagnosis, both infectious and noninfectious, should be considered for encephalitis. These alternatives include malignancy, autoimmune or paraneoplastic diseases (e.g., anti-NMDA receptor encephalitis), brain abscess, tuberculosis or drug-induced delirium, neurosyphilis, or bacterial, fungal, protozoal, or helminthic encephalitis.

Prognosis

Most patients with viral encephalitis recover without sequelae. Those who remain symptomatic have difficulties in concentration, behavioral and speech disorders, and/or memory loss. In rare cases, patients may remain in a vegetative state.

Complications

  • Impairment in intelligence
  • Mood and behavior changes
  • Residual neurological deficits
  • Extrapyramidal symptoms (JE)
  • Hyponatremia (esp St. Louis encephalitis)
  • Encephalopathy
  • Mononeuropathy
  • Flaccid paralysis

Pearls and Other Issues

Patients with viral encephalitis should be admitted to the hospital for supportive care and IV antiviral therapy. They may require intensive care for frequent neurologic exams and/or respiratory support. Early initiation of medical therapy is essential for HSV, the most common cause of viral encephalitis, so all patients with suspected encephalitis should be started empirically on acyclovir as soon as possible.

Enhancing Healthcare Team Outcomes

Viral encephalitis is a serious disorder, and the morbidity and mortality depend on the type of virus and the severity of the infection. Viral encephalitis may primarily involve the brain but has repercussions in many other organs; hence a multidisciplinary approach in management is key. It has been estimated that a single bout of viral encephalitis can cost upwards of $2 million to the healthcare system. For patients who are untreated, mortality rates can be high. Mortality after herpes encephalitis can range more than 50%, and after western equine encephalitis, children may develop marked behavior changes and seizures. The eastern equine encephalitis can also have crippling effects on children including paralysis, seizures and mental retardation. The recent Zika virus epidemic has resulted in microcephaly in newborn infants. However, mortality is low with the La Crosse and the Venezuelan equine virus. Recent data reveal that the tick-borne encephalitis from the Orient is far more dangerous than the central European tick-borne encephalitis. Patients who acquire the Asian tick-borne encephalitis often have residual seizures for a long time.[15][16][17]

The key to the viral encephalitis is prevention. Surveillance of mosquitoes must be done to assess the risk of infectivity. Travelers should wear protective garments to prevent mosquito bite and sleep under a mosquito net. One should also avoid outdoor activities where the risk of tick-borne infections is high. The public has to remove containers of stagnant water from the home surroundings, and insecticide spraying may help. Vaccines are available against the EEE, WEE and VEE. However, their effectiveness is not 100%.[18][19][15]

 

 


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Viral Encephalitis - Questions

Take a quiz of the questions on this article.

Take Quiz
A 33-year-old undergoes an emergent unenhanced brain CT which reveals diffuse brain swelling. The patient was found unconscious with nuchal rigidity and a positive Babinski. Which of the following is the patient's most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 35 year old previously healthy female has had headaches for a few days and her family reports behavior changes. She has been more talkative, outgoing, and flirtatious with strangers. When she was sexually inappropriate with a store clerk her family brought her to her doctor. The only finding was a low grade fever. MRI was ordered urgently and showed an inferomedial temporal lobe lesion. Which of the following diagnostic tests is indicated?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 35-year-old previously healthy female has had headaches for a few days and her family reports behavior changes. She has been more talkative, outgoing, and flirtatious with strangers. After she was sexually inappropriate with a store clerk her family brought her to her healthcare provider. The only finding was a low-grade fever. MRI was ordered urgently and showed an inferomedial temporal lobe lesion. Lumbar puncture is done. What treatment is indicated?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following statements about encephalitis is correct?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 44-year-old man returns from Dallas after a 1-week vacation where he spent a lot of time outside. He is now complaining of muscle aches, eye pain, rash, headache, nausea, anorexia, and generalized weakness. He says there were many mosquitoes in the area and he was bitten numerous times. Vital signs are notable for a fever of 102F. Physical exam shows a diffuse mild maculopapular erythematous rash. Given the clinical picture, which of the following would be expected on the initial workup?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 47-year-old male is brought to the emergency department for 2 days of fever, headache, and altered mental status. His wife reports that he has been confused and forgetful since yesterday. The patient is an accountant with no significant medical history. He has had no sick contacts and has not traveled recently. He does not use tobacco or illicit drugs but drinks alcohol occasionally. Temperature is 38C, blood pressure is 126/84 mmHg, and pulse is 72/minute. Mucous membranes are moist with no lesions. No lymphadenopathy is present. Lungs are clear to auscultation and heart sounds are normal with no murmur. The abdomen is soft and nontender with no hepatosplenomegaly. He has nuchal rigidity and is alert and oriented only to self. He has no motor or sensory deficits but can only follow simple commands. Cerebrospinal fluid analysis shows a white blood cell count of 150/mm3, red blood cell count of 8/mm3, protein concentration of 130 mg/dL, and glucose concentration of 40 mg/dL. Which of the following is best next step in management?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 42-year-old female is admitted to the intensive care unit for fever, altered mental status, and slurred speech. Her medical history is significant for diabetes mellitus and hypertension. She does not use tobacco or illicit drugs but drinks alcohol occasionally. Temperature is 38C, blood pressure is 126/84 mmHg, and pulse is 72/minute. Mucous membranes are moist with no lesions. No lymphadenopathy is present. Lungs are clear to auscultation and heart sounds are normal with no murmur. The abdomen is soft and nontender with no hepatosplenomegaly. She is alert and oriented only to self and can only follow simple commands. Her exam is also positive for nuchal rigidity and aphasia. MRI of the brain shows fluid-attenuated inversion recovery hyperintensity in the left temporal lobe. What is the most likely diagnosis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 32-year-old male is admitted to the intensive care unit for progressive change in mental status, delirium, and rapidly progressive cognitive impairment. His medical history is significant for advanced HIV disease. MRI of the brain shows evidence of periventricular inflammation and meningeal enhancement. What is the recommended treatment?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 25-year-old male presents with 2 days of fever, headache, altered mental status, and involuntary movements. His wife reports that he recently returned from a summer camp program, where he works as a camp counselor and was complaining of mosquito bites. He has no significant medical history. He does not use tobacco or illicit drugs but drinks alcohol occasionally. Temperature is 38C, blood pressure is 126/84 mmHg, and pulse is 72/minute. On exam, he has involuntary chorea and writhing movements of his extremities. Which of the following will most likely be revealed by serology testing?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
An 8-year-old male is brought to the emergency department for altered mental status. His parents report that he has had a fever and headache for the past 2 days and has become increasingly lethargic. He has no significant medical history, and his vaccinations are up to date. The provider suspects encephalitis. What is the most likely cause of his encephalitis?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 55-year-old female presents with 3 days of fever, headache, and progressive cognitive decline. She has no significant medical history. She has no sick contacts and no recent travel history. She does not use tobacco, or illicit drugs, but drinks alcohol occasionally. Temperature is 38 C, blood pressure is 126/84, and pulse is 72/min. Mucous membranes are moist with no lesions. No lymphadenopathy is present. Lungs are clear to auscultation and heart sounds are normal with no murmur. The abdomen is soft and nontender with no hepatosplenomegaly. She has nuchal rigidity and is alert and oriented only to self. She has no motor or sensory deficits but can only follow simple commands. Cerebrospinal fluid (CSF) analysis shows a white blood cell count of 150/mm3, red blood cell count of 3/mm3, protein concentration of 130 mg/dL, and glucose concentration of 40 mg/dL. CSF polymerase chain reaction (PCR) testing is positive for herpes simplex virus 1. Magnetic resonance imaging is most likely to show involvement of which part of the brain?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Viral Encephalitis - References

References

Im JH,Baek J,Durey A,Kwon HY,Chung MH,Lee JS, Current Status of Tick-Borne Diseases in South Korea. Vector borne and zoonotic diseases (Larchmont, N.Y.). 2018 Oct 17     [PubMed]
Kadambari S,Harvala H,Simmonds P,Pollard AJ,Sadarangani M, Strategies to improve detection and management of human parechovirus infection in young infants. The Lancet. Infectious diseases. 2018 Oct 12     [PubMed]
Blom K,Cuapio A,Sandberg JT,Varnaite R,Michaëlsson J,Björkström NK,Sandberg JK,Klingström J,Lindquist L,Gredmark Russ S,Ljunggren HG, Cell-Mediated Immune Responses and Immunopathogenesis of Human Tick-Borne Encephalitis Virus-Infection. Frontiers in immunology. 2018     [PubMed]
Kumar B,Manuja A,Gulati BR,Virmani N,Tripathi BN, Zoonotic Viral Diseases of Equines and Their Impact on Human and Animal Health. The open virology journal. 2018     [PubMed]
Silva ASG,Diniz Matos AC,da Cunha MACR,Rehfeld IS,Galinari GCF,Marcelino SAC,Saraiva LHG,Martins NRDS,de Pino Albuquerque Maranhão R,Lobato ZIP,Pierezan F,Guedes MIMC,Costa EA, West Nile virus associated with equid encephalitis in Brazil, 2018. Transboundary and emerging diseases. 2018 Oct 14     [PubMed]
Soung A,Klein RS, Viral Encephalitis and Neurologic Diseases: Focus on Astrocytes. Trends in molecular medicine. 2018 Oct 9     [PubMed]
Baldwin KJ,Cummings CL, Herpesvirus Infections of the Nervous System. Continuum (Minneapolis, Minn.). 2018 Oct     [PubMed]
Phipps P,Johnson N,McElhinney LM,Roberts H, West Nile virus season in Europe. The Veterinary record. 2018 Aug 18     [PubMed]
Ben Abid F,Abukhattab M,Ghazouani H,Khalil O,Gohar A,Al Soub H,Al Maslamani M,Al Khal A,Al Masalamani E,Al Dhahry S,Hashim S,Howadi F,Butt AA, Epidemiology and clinical outcomes of viral central nervous system infections. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2018 Aug     [PubMed]
Leahy CB,Mathur S,Majeed T, The clinical approach to managing herpes simplex virus encephalitis. British journal of hospital medicine (London, England : 2005). 2018 Oct 2     [PubMed]
Jayaraman K,Rangasami R,Chandrasekharan A, Magnetic Resonance Imaging Findings in Viral Encephalitis: A Pictorial Essay. Journal of neurosciences in rural practice. 2018 Oct-Dec     [PubMed]
Reid S,Thompson H,Thakur KT, Nervous System Infections and the Global Traveler. Seminars in neurology. 2018 Apr     [PubMed]
Gaieski DF,O'Brien NF,Hernandez R, Emergency Neurologic Life Support: Meningitis and Encephalitis. Neurocritical care. 2017 Sep     [PubMed]
Taba P,Schmutzhard E,Forsberg P,Lutsar I,Ljøstad U,Mygland Å,Levchenko I,Strle F,Steiner I, EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis. European journal of neurology. 2017 Oct     [PubMed]
Beaman MH, Community-acquired acute meningitis and encephalitis: a narrative review. The Medical journal of Australia. 2018 Oct 15     [PubMed]
Lyons JL, Viral Meningitis and Encephalitis. Continuum (Minneapolis, Minn.). 2018 Oct     [PubMed]
Chen W,Su Y,Jiang M,Liu G,Tian F,Ren G, Status epilepticus associated with acute encephalitis: long-term follow-up of functional and cognitive outcomes in 72 patients. European journal of neurology. 2018 Oct     [PubMed]
Gyawali N,Taylor-Robinson AW, Confronting the Emerging Threat to Public Health in Northern Australia of Neglected Indigenous Arboviruses. Tropical medicine and infectious disease. 2017 Oct 17     [PubMed]
Charlier C,Beaudoin MC,Couderc T,Lortholary O,Lecuit M, Arboviruses and pregnancy: maternal, fetal, and neonatal effects. The Lancet. Child     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of PA-Hospital Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for PA-Hospital Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in PA-Hospital Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of PA-Hospital Medicine. When it is time for the PA-Hospital Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study PA-Hospital Medicine.