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viral encephalitis

Etiology: 1) common a) Herpes simplex virus (HSV)-1 (50-75%) [8] b) Varicella zoster virus c) arboviruses - encephalitis virus, between June & October [2] - West Nile virus - Powassan virus d) enteroviruses (< 34 years of age) between May & Nov [2] e) mumps virus 2) less common a) cytomegalovirus (CMV) b) Epstein-Barr virus (EBV) c) Human Immunodeficiency virus (HIV) - JC virus d) measles virus 3) rare - adenoviruses - influenza-A virus - parainfluenza virus - rabies virus - rubella - Colorado tick fever virus - lymphocytic choriomeningitis virus Epidemiology: 1) 48% of encephalitis is viral encephalitis 2) Herpes encephalitis most common viral encephalitis 3) 2/3 of cases > 40 years of age 4) 3000 cases in USA/year 2005; 7 per 100,000 [8] Pathology: - temporal lobe affected with Herpes simplex encephalitis Clinical manifestations: 1) herpes encephalitis a) fever b) hemicranial headache c) altered mental status [2] 1] disorder of arousal 2] language impairment 3] behavioral disorder 4] memory impairment d) focal cranial nerve palsy e) hemiparesis f) ataxia g) focal seizures h) fulminant symptoms evolve over days* 2) also see encephalitis virus (includes West Nile virus) * distinguishing feature from paraneoplastic limbic encephalitis * also see Herpes simplex encephalitis Laboratory: 1) lumbar puncture & cerebrospinal fluid analysis a) CSF cultures generally unrewarding b) PCR/ISH for herpes simplex virus DNA 1] 95% sensitivity, 98% specificity [2] 2] may be negative early during the course of HSV encephalitis 3] repeat testing indicated if initial result is negative & MRI neuroimaging shows temporal lobe inflammation [2] c) CSF serology d) bloody CSF suggests Herpes simplex encephalitis e) mild-moderately elevated CSF protein f) lymphocytic pleocytosis g) CSF glucose is generally normal h) CSF may be normal in 3-5% of patients i) Varicella zoster IgG or Varicella zoster DNA j) IgM antibodies by ELISA for flavivirus (arbovirus) - West Nile virus IgM in CSF - West Nile virus RNA 2) brain biopsy (gold standard) a) viral culture b) histopathology c) electron microscopy Special laboratory: - EEG: a) periodic focal spikes on a background of slow or low-amplitude activity b) temporal predominance of EEG Radiology: 1) magnetic resonance imaging (MRI) a) areas of increased signal intensity on T2-weighted spin-echo images 1] frontotemporal cortex 2] cingulate gyrus 3] insular regions 4] temporal lobe inflammation (Herpes simplex) 2) CT of head with contrast if MRI not available a) temporal-parietal areas of low absorption b) mass effect c) contrast enhancement Complications: - increased risk for Alzheimer's disease [9] Management: 1) neurosurgery consult 2) supportive therapy a) intensive care units support b) monitoring of intracranial pressure c) fluid restriction d) avoid hypotonic fluid e) suppression of fever f) prophylaxis for seizures with standard anticonvulsant therapy g) patients at risk for: - aspiration pneumonia, stasis ulcers, contractures, DVT, infections of lines & catheters 3) empiric acyclovir 10 mg/kg IV every 8 hours for 10 days a) do not wait for laboratory confimation [2] b) treatment of choice for Herpes simplex encephalitis [2] c) 14-21 days of treatment for confirmed HSV encephalitis [2] d) effective treatment for arbovirus encephalitis is not available [2] e) discontinue acyclovir if CSF herpes simplex virus DNA is negative [2] unless MRI neuroimaging shows temporal lobe inflammation f) oral acyclovir does not reach therapeutic levels [2] 4) neurologic sequellae vary with severity & etiology

Interactions

disease interactions

Related

encephalitis virus

Specific

AIDS dementia complex; AIDS encephalopathy; HIV-associated dementia (HAD) Herpes simplex encephalitis Powassan virus progressive multifocal leukoencephalopathy (PML) Rocio viral encephalitis; Rocio viral infection St. Louis encephalitis subacute sclerosing panencephalitis (Dawson disease, SSPE) viral meningoencephalitis

General

encephalitis viral infection

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 2312-14
  2. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2018, 2021.
  3. ARUP Consult: Encephalitis, Infectious The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/encephalitis-infectious
  4. Tunkel AR, Glaser CA, Bloch KC et al The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47(3):303-27 PMID: 18582201 (corresponding National Guideline Clearinghouse entry withdrawn Dec 2013)
  5. Singh TD et al. The spectrum of acute encephalitis: Causes, management, and predictors of outcome. Neurology 2015 Jan 27; 84:1 PMID: 25540320 http://www.neurology.org/content/early/2014/12/24/WNL.0000000000001190
  6. Armangue T, Leypoldt F, Malaga I et al Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol. 2014 Feb;75(2):317-23. PMID: 24318406 Free PMC Article
  7. Solomon T, Michael BD, Smith PE et al Management of suspected viral encephalitis in adults-- Association of British Neurologists and British Infection Association National Guidelines. J Infect. 2012 Apr;64(4):347-73. PMID: 22120595
  8. Rothaus C Viral Encephalitis. NEJM Resident 360. Aug 8, 2018. https://resident360.nejm.org/content_items/viral-encephalitis-2 - Rothaus C A Woman with Fever, Headache, and Progressive Encephalopathy NEJM Resident 360. Jan 23, 2019 https://resident360.nejm.org/content_items/a-woman-with-fever-headache-and-progressive-encephalopathy
  9. George J Viruses Tied to Subsequent Dementia, Other Neurodegenerative Diseases. Viral encephalitis and Alzheimer's disease showed strongest links. MedPage Today January 30, 2023 https://www.medpagetoday.com/neurology/generalneurology/102872 - Levine KS, Leonard HL, Blauwendraat C et al Virus exposure and neurodegenerative disease risk across national biobanks. Neuron. 2023. Jan 19 PMID: 36669485Free article https://www.cell.com/neuron/fulltext/S0896-6273(22)01147-3
  10. National Institute of Neurological Disorders and Stroke (NINDS) NINDS Encephalitis and Meningitis Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Meningitis-and-Encephalitis-Information-Page