Encephalitis Explained

Encephalitis
Field:Neurology, infectious disease
Symptoms:Headache, fever, confusion, stiff neck, vomiting
Complications:Seizures, trouble speaking, memory problems, problems hearing
Duration:Weeks to months for recovery
Causes:Infection, autoimmune, certain medication, unknown
Types:Herpes simplex, West Nile, rabies, Eastern equine, others
Diagnosis:Based on symptoms, supported by blood tests, medical imaging, analysis of cerebrospinal fluid
Treatment:Antiviral medication, anticonvulsants, corticosteroids, artificial respiration
Prognosis:Variable
Frequency:4.3 million (2015)
Deaths:150,000 (2015)

Encephalitis is inflammation of the brain.[1] The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting.[2] Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.[3]

Causes of encephalitis include viruses such as herpes simplex virus and rabies virus as well as bacteria, fungi, or parasites.[3] Other causes include autoimmune diseases and certain medications.[4] In many cases the cause remains unknown.[4] Risk factors include a weak immune system.[4] Diagnosis is typically based on symptoms and supported by blood tests, medical imaging, and analysis of cerebrospinal fluid.[4]

Certain types are preventable with vaccines.[1] Treatment may include antiviral medications (such as acyclovir), anticonvulsants, and corticosteroids.[3] Treatment generally takes place in hospital.[3] Some people require artificial respiration.[3] Once the immediate problem is under control, rehabilitation may be required.[4] In 2015, encephalitis was estimated to have affected 4.3 million people and resulted in 150,000 deaths worldwide.[5] [6]

Signs and symptoms

Adults with encephalitis present with acute onset of fever, headache, confusion, and sometimes seizures. Younger children or infants may present with irritability, poor appetite and fever.[7] Neurological examinations usually reveal a drowsy or confused person. Stiff neck, due to the irritation of the meninges covering the brain, indicates that the patient has either meningitis or meningoencephalitis.[8]

Cause

In 30%-40% of encephalitis cases, the etiology remains unknown.[9]

Viral

See main article: Viral encephalitis and Herpesviral encephalitis. Viral infections are the usual cause of infectious encephalitis. Viral encephalitis can occur either as a direct effect of an acute infection, or as one of the sequelae of a latent infection. The majority of viral cases of encephalitis have an unknown cause; however, the most common identifiable cause of viral encephalitis is from herpes simplex infection.[10] Other causes of acute viral encephalitis are rabies virus, poliovirus, and measles virus.[11]

Additional possible viral causes are arboviral flavivirus (St. Louis encephalitis, West Nile virus), bunyavirus (La Crosse strain), arenavirus (lymphocytic choriomeningitis virus), reovirus (Colorado tick virus), and henipavirus infections.[12] [13] The Powassan virus is a rare cause of encephalitis.[14]

Bacterial and other

It can be caused by a bacterial infection, such as bacterial meningitis,[15] or may be a complication of a current infectious disease such as syphilis (secondary encephalitis).[16]

Certain parasitic or protozoal infestations, such as toxoplasmosis, malaria, or primary amoebic meningoencephalitis, can also cause encephalitis in people with compromised immune systems. Lyme disease or Bartonella henselae may also cause encephalitis.

Other bacterial pathogens, like Mycoplasma and those causing rickettsial disease, cause inflammation of the meninges and consequently encephalitis. A non-infectious cause includes acute disseminated encephalitis which is demyelinated.[17]

Limbic encephalitis

See main article: Limbic encephalitis.

Limbic encephalitis refers to inflammatory disease confined to the limbic system of the brain. The clinical presentation often includes disorientation, disinhibition, memory loss, seizures, and behavioral anomalies. MRI imaging reveals T2 hyperintensity in the structures of the medial temporal lobes, and in some cases, other limbic structures. Some cases of limbic encephalitis are of autoimmune origin.[18]

Autoimmune encephalitis

See main article: Autoimmune encephalitis.

Autoimmune encephalitis signs can include catatonia, psychosis, abnormal movements, and autonomic dysregulation. Antibody-mediated anti-N-methyl-D-aspartate-receptor encephalitis and Rasmussen encephalitis are examples of autoimmune encephalitis.[19] Anti-NMDA receptor encephalitis is the most common autoimmune form, and is accompanied by ovarian teratoma in 58 percent of affected women 18–45 years of age.[20]

Encephalitis lethargica

See main article: Encephalitis lethargica.

Encephalitis lethargica is identified by high fever, headache, delayed physical response, and lethargy. Individuals can exhibit upper body weakness, muscular pains, and tremors, though the cause of encephalitis lethargica is not currently known. From 1917 to 1928, an epidemic of encephalitis lethargica occurred worldwide.

Diagnosis

People should only be diagnosed with encephalitis if they have a decreased or altered level of consciousness, lethargy, or personality change for at least twenty-four hours without any other explainable cause.[21] Diagnosing encephalitis is done via a variety of tests:[22] [23]

Prevention

Vaccination is available against tick-borne[24] and Japanese encephalitis[25] and should be considered for at-risk individuals. Post-infectious encephalomyelitis complicating smallpox vaccination is avoidable, for all intents and purposes, as smallpox is nearly eradicated.[26] Contraindication to Pertussis immunization should be observed in patients with encephalitis.[27]

Treatment

An ideal drug to treat brain infection should be small, moderately lipophilic at pH of 7.4, low level of plasma protein binding, volume of distribution of litre per kg, does not have strong affinity towards binding with P-glycoprotein, or other efflux pumps on the surface of blood–brain barrier. Some drugs such as isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones have good penetration to blood brain barrier.[28] Treatment (which is based on supportive care) is as follows:

Pyrimethamine-based maintenance therapy is often used to treat toxoplasmic encephalitis (TE), which is caused by Toxoplasma gondii and can be life-threatening for people with weak immune systems.[29] The use of highly active antiretroviral therapy (HAART), in conjunction with the established pyrimethamine-based maintenance therapy, decreases the chance of relapse in patients with HIV and TE from approximately 18% to 11%. This is a significant difference as relapse may impact the severity and prognosis of disease and result in an increase in healthcare expenditure.

The effectiveness of intravenous immunoglobulin for the management of childhood encephalitis is unclear. Systematic reviews have been unable to draw firm conclusions because of a lack of randomised double-blind studies with sufficient numbers of patients and sufficient follow-up.[30] There is the possibility of a benefit of intravenous immunoglobulin for some forms of childhood encephalitis on some indicators such as length of hospital stay, time to stop spasms, time to regain consciousness, and time to resolution of neuropathic symptoms and fever. Intravenous immunoglobulin for Japanese encephalitis appeared to have no benefit when compared with placebo (pretend) treatment.

Prognosis

Identification of poor prognostic factors include cerebral edema, status epilepticus, and thrombocytopenia.[31] In contrast, a normal encephalogram at the early stages of diagnosis is associated with high rates of survival.

Epidemiology

The number of new cases a year of acute encephalitis in Western countries is 7.4 cases per 100,000 people per year. In tropical countries, the incidence is 6.34 per 100,000 people per year.[32] The number of cases of encephalitis has not changed much over time, with about 250,000 cases a year from 2005 to 2015 in the US. Approximately seven per 100,000 people were hospitalized for encephalitis in the US during this time. In 2015, encephalitis was estimated to have affected 4.3 million people and resulted in 150,000 deaths worldwide.[6] [5] Herpes simplex encephalitis has an incidence of 2–4 per million of the population per year.[33]

Terminology

Encephalitis with meningitis is known as meningoencephalitis, while encephalitis with involvement of the spinal cord is known as encephalomyelitis.[4]

The word is from Ancient Greek, 'brain',[34] composed of,, 'in' and,, 'head', and the medical suffix -itis 'inflammation'.[35]

See also

Further reading

External links

Notes and References

  1. Web site: Encephalitis. NHS Choices. 29 October 2017. en. 2016. live. https://web.archive.org/web/20170922022223/http://www.nhs.uk/Conditions/Encephalitis/Pages/Introduction.aspx. 22 September 2017.
  2. Ellul M, Solomon T . Acute encephalitis - diagnosis and management . Clinical Medicine . 18 . 2 . 155–159 . March 2018 . 29626021 . 6303463 . 10.7861/clinmedicine.18-2-155 .
  3. Web site: Meningitis and Encephalitis Information Page. NINDS. 29 October 2017. live. https://web.archive.org/web/20171029065744/https://www.ninds.nih.gov/Disorders/All-Disorders/Meningitis-and-Encephalitis-Information-Page. 29 October 2017.
  4. Web site: Meningitis and Encephalitis Fact Sheet. National Institute of Neurological Disorders and Stroke. 29 October 2017. live. https://web.archive.org/web/20171029065418/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Meningitis-and-Encephalitis-Fact-Sheet. 29 October 2017.
  5. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ, Coggeshall M, etal . GBD 2015 Disease and Injury Incidence and Prevalence Collaborators . Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 . Lancet . 388 . 10053 . 1545–1602 . October 2016 . 27733282 . 5055577 . 10.1016/S0140-6736(16)31678-6 .
  6. Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, Casey DC, Charlson FJ, Chen AZ, Coates MM, Coggeshall M, etal . GBD 2015 Mortality and Causes of Death Collaborators . Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 . Lancet . 388 . 10053 . 1459–1544 . October 2016 . 27733281 . 5388903 . 10.1016/S0140-6736(16)31012-1 .
  7. Web site: Symptoms of encephalitis. NHS. 5 January 2015. live. https://web.archive.org/web/20150105142821/http://www.nhs.uk/Conditions/Encephalitis/Pages/Symptoms.aspx. 5 January 2015.
  8. Book: Meningitis. Infobase Publishing. 2010-01-01. 978-1-4381-3216-7. Shmaefsky B, Babcock H . live. https://web.archive.org/web/20151030224553/https://books.google.com/books?id=KI5p3pADvSsC&pg=PA90&dq=meningoencephalitis+symptoms+stiff+neck&hl=en&sa=X&ved=0CCsQ6AEwAGoVChMIk7_kzqCSxwIVQYsNCh2nzwvd#v=onepage&q=meningoencephalitis%2520symptoms%2520stiff%2520neck&f=false. 2015-10-30.
  9. Web site: 2021-08-08 . Encephalitis . 2024-01-09 . www.hopkinsmedicine.org . en.
  10. Book: Roos KL, Tyler KL . Harrison's Principles of Internal Medicine. 2015. McGraw-Hill Education. New York, NY. 978-0-07-180215-4. 19. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&sectionid=79734335. Meningitis, Encephalitis, Brain Abscess, and Empyema. 2017-11-17. 2017-11-17. https://web.archive.org/web/20171117122546/http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&sectionid=79734335. live.
  11. Fisher DL, Defres S, Solomon T . Measles-induced encephalitis . QJM . 108 . 3 . 177–182 . March 2015 . 24865261 . 10.1093/qjmed/hcu113 . free .
  12. Kennedy PG . Viral encephalitis: causes, differential diagnosis, and management . Journal of Neurology, Neurosurgery, and Psychiatry . 75 . Suppl 1 . i10–i15 . March 2004 . 14978145 . 1765650 . 10.1136/jnnp.2003.034280 . live . https://web.archive.org/web/20151002151809/http://jnnp.bmj.com/content/75/suppl_1/i10 . 2015-10-02 .
  13. Book: Broder CC, Geisbert TW, Xu K, Nikolov DB, Wang LF, Middleton D, Pallister J, Bossart KN . Henipavirus . Immunization strategies against henipaviruses . Current Topics in Microbiology and Immunology . 359 . 197–223 . 2012 . 22481140 . 4465348 . 10.1007/82_2012_213 . 978-3-642-29818-9 .
  14. Web site: Symptoms & Treatment Powassan CDC . www.cdc.gov . 26 June 2019 . en-us . 4 December 2018 . 26 June 2019 . https://web.archive.org/web/20190626032132/https://www.cdc.gov/powassan/symptoms.html . live .
  15. Book: Johns Hopkins Internal Medicine Board Review: Certification and Recertification. Elsevier Health Sciences. 2012-01-01. 978-1-4557-0692-1. Ashar BH, Miller RG, Sisson SD . live. https://web.archive.org/web/20151129111640/https://books.google.com/books?id=KLBZ85zbTeYC&pg=PA113&dq=bacterial+meningitis+inflmation+of+encepha+definition&hl=en&sa=X&ved=0CGAQ6AEwCGoVChMI8PLmjZqSxwIVS6KACh03_QJ_#v=onepage&q=bacterial%2520meningitis%2520inflmation%2520of%2520encepha%2520definition&f=false. 2015-11-29.
  16. Hama K, Ishiguchi H, Tuji T, Miwa H, Kondo T . Neurosyphilis with mesiotemporal magnetic resonance imaging abnormalities . Internal Medicine . 47 . 20 . 1813–1817 . 2008-01-01 . 18854635 . 10.2169/internalmedicine.47.0983 . free .
  17. Web site: Howes DS, Lazoff M, Conrad SA, Hemphill RR, Huff JS, Pritz T, Talavera F . Brenner BE . Encephalitis: Practice Essentials, Background, Pathophysiology. live. https://web.archive.org/web/20150803144051/http://emedicine.medscape.com/article/791896-overview#a4. 2015-08-03. 2018-08-07 . MedScape .
  18. Book: Larner, A. J.. Neuropsychological Neurology: The Neurocognitive Impairments of Neurological Disorders. Cambridge University Press. 2013-05-02. 978-1-107-60760-6. live. https://web.archive.org/web/20151030055159/https://books.google.com/books?id=hO_lWEDsJYMC&pg=PA156&dq=limbic+encephalitis+definition&hl=en&sa=X&ved=0CCIQ6AEwAWoVChMIxouQj-2RxwIVBaKACh1J3w-x#v=onepage&q=limbic%2520encephalitis%2520definition&f=false. 2015-10-30.
  19. Armangue T, Petit-Pedrol M, Dalmau J . Autoimmune encephalitis in children . Journal of Child Neurology . 27 . 11 . 1460–1469 . November 2012 . 22935553 . 3705178 . 10.1177/0883073812448838 .
  20. Dalmau J, Graus F . Antibody-Mediated Encephalitis . The New England Journal of Medicine . 378 . 9 . 840–851 . March 2018 . 29490181 . 10.1056/NEJMra1708712 . free . 3623281 . 2445/147222 .
  21. Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA . Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium . Clinical Infectious Diseases . 57 . 8 . 1114–1128 . October 2013 . 23861361 . 3783060 . 10.1093/cid/cit458 .
  22. Web site: Encephalitis: Diagnosis. NHS Choices. 2015-08-05. live. https://web.archive.org/web/20150716081924/http://www.nhs.uk/Conditions/Encephalitis/Pages/Diagnosis.aspx. 2015-07-16.
  23. Kneen R, Michael BD, Menson E, Mehta B, Easton A, Hemingway C, Klapper PE, Vincent A, Lim M, Carrol E, Solomon T . Management of suspected viral encephalitis in children - Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group national guidelines . The Journal of Infection . 64 . 5 . 449–477 . May 2012 . 22120594 . 10.1016/j.jinf.2011.11.013 .
  24. Web site: Tick-borne Encephalitis: Vaccine . International travel and health . World Health Organization . 2 April 2013 . dead . https://web.archive.org/web/20131203053717/http://www.who.int/ith/vaccines/tbe/en/ . 3 December 2013 .
  25. Web site: Japanese encephalitis . Immunization, Vaccines and Biologicals . World Health Organization . 2 April 2013 . dead . https://web.archive.org/web/20131203031151/http://www.who.int/immunization/topics/japanese_encephalitis/en/ . 3 December 2013 .
  26. Web site: CDC Media Statement on Newly Discovered Smallpox Specimens. www.cdc.gov. 2016-05-19. live. https://web.archive.org/web/20160520220838/http://www.cdc.gov/media/releases/2014/s0708-NIH.html. 2016-05-20. January 2016.
  27. Web site: Vaccines . Contraindications and Precautions to Commonly Used Vaccines in Adults . 2015-08-05 . Center for Disease Control . dead . https://web.archive.org/web/20150823024025/http://www.cdc.gov/vaccines/schedules/hcp/imz/adult-contraindications.html . 2015-08-23 .
  28. Nau R, Sörgel F, Eiffert H . Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections . Clinical Microbiology Reviews . 23 . 4 . 858–883 . October 2010 . 20930076 . 2952976 . 10.1128/CMR.00007-10 .
  29. Connolly MP, Goodwin E, Schey C, Zummo J . Toxoplasmic encephalitis relapse rates with pyrimethamine-based therapy: systematic review and meta-analysis . Pathogens and Global Health . 111 . 1 . 31–44 . February 2017 . 28090819 . 5375610 . 10.1080/20477724.2016.1273597 .
  30. Iro MA, Martin NG, Absoud M, Pollard AJ . Intravenous immunoglobulin for the treatment of childhood encephalitis . The Cochrane Database of Systematic Reviews . 2017 . CD011367 . October 2017 . 10 . 28967695 . 6485509 . 10.1002/14651858.CD011367.pub2 .
  31. Venkatesan A . Epidemiology and outcomes of acute encephalitis . . 28 . 3 . 277–282 . June 2015 . 25887770 . 10.1097/WCO.0000000000000199 . 21041693 .
  32. Jmor F, Emsley HC, Fischer M, Solomon T, Lewthwaite P . The incidence of acute encephalitis syndrome in Western industrialised and tropical countries . Virology Journal . 5 . 134 . 134 . October 2008 . 18973679 . 2583971 . 10.1186/1743-422X-5-134 . free .
  33. Rozenberg F, Deback C, Agut H . Herpes simplex encephalitis : from virus to therapy . Infectious Disorders Drug Targets . 11 . 3 . 235–250 . June 2011 . 21488834 . 10.2174/187152611795768088 .
  34. Web site: The University of Chicago Library . Woodhouse's English-Greek Dictionary . 2013-01-10 . de . 2017-03-05 . https://web.archive.org/web/20170305002545/http://artflx.uchicago.edu/cgi-bin/efts/dicos/woodhouse_test.pl?keyword=%5EBrain%2C%20subs. . dead .
  35. The word seems to have had a meaning of “lithic imitation of the human brain” at first, according to the Trésor de la langue française informatisé (cf. the article on “encéphalite”). The first use in the medical sense is attested from the early 19th century in French (J. Capuron, Nouveau dictionnaire de médecine, chirurgie…, 1806), and from 1843 in English respectively (cf. the article “encephalitis” in the Online Etymology Dictionary). Retrieved 11 March 2017.

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