Due to the varied etiology, survivors of the critical phases of the illness are a heterogeneous group. Mortality and morbidity vary depending on the underlying etiology, the immune status of the host, the extent and location of anatomic lesions, the development of complications, and the time to initiate treatment. Mortality as an outcome occurs in 6% to 9% in the US, and in 12% in England in infectious encephalitis.[3]Granerod J, Tam CC, Crowcroft NS, et al. Challenge of the unknown: a systematic review of acute encephalitis in non-outbreak situations. Neurology. 2010 Sep 7;75(10):924-32.
http://www.ncbi.nlm.nih.gov/pubmed/20820004?tool=bestpractice.com
[6]Vora NM, Holman RC, Mehal JM, et al. Burden of encephalitis-associated hospitalizations in the United States, 1998-2010. Neurology. 2014 Feb 4;82(5):443-51.
http://www.ncbi.nlm.nih.gov/pubmed/24384647?tool=bestpractice.com
[7]George BP, Schneider EB, Venkatesan A. Encephalitis hospitalization rates and inpatient mortality in the United States, 2000-2010. PloS One. 2014 Sep 5;9(9):e104169.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104169
http://www.ncbi.nlm.nih.gov/pubmed/25192177?tool=bestpractice.com
[124]Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015 Jan 27;84(4):359-66.
http://www.ncbi.nlm.nih.gov/pubmed/25540320?tool=bestpractice.com
Age >65 years old, immunocompromised (HIV or immunosuppressive medication-induced), mechanical ventilation, coma, acute thrombocytopenia, elevated cerebrospinal fluid polymorphonuclear count, cerebral edema, and status epilepticus are associated with poor outcomes.[124]Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology. 2015 Jan 27;84(4):359-66.
http://www.ncbi.nlm.nih.gov/pubmed/25540320?tool=bestpractice.com
[125]Thakur KT, Motta M, Asemota AO, et al. Predictors of outcome in acute encephalitis. Neurology. 2013 Aug 27;81(9):793-800.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908458
http://www.ncbi.nlm.nih.gov/pubmed/23892708?tool=bestpractice.com
The development of the late sequelae depends on age, etiology of the encephalitis, and severity of the clinical episode.[75]Chaudhuri A, Kennedy PG. Diagnosis and treatment of viral encephalitis. Postgrad Med J. 2002 Oct;78(924):575-83.
http://pmj.bmj.com/content/78/924/575.long
http://www.ncbi.nlm.nih.gov/pubmed/12415078?tool=bestpractice.com
Severe disability occurs in more than half of survivors. In children, long-term morbidity occurs in up to two-thirds of patients. This includes fatigue, cognitive impairment, attention and deficit disorders, dysphasia, motor impairment, ataxia, epilepsy, and personality changes.[126]Michaeli O, Kassis I, Shachor-Meyouhas Y, et al. Long-term motor and cognitive outcome of acute encephalitis. Pediatrics. 2014 Mar;133(3):e546-52.
http://www.ncbi.nlm.nih.gov/pubmed/24534397?tool=bestpractice.com
[127]McJunkin JE, Khan R, de los Reyes EC, et al. Treatment of severe La Crosse encephalitis with intravenous ribavirin following diagnosis by brain biopsy. Pediatrics. 1997 Feb;99(2):261-7.
http://www.ncbi.nlm.nih.gov/pubmed/9024460?tool=bestpractice.com
[128]Fowler A, Stödberg T, Eriksson M, et al. Childhood encephalitis in Sweden: etiology, clinical presentation and outcome. Eur J Paediatr Neurol. 2008 Nov;12(6):484-90.
http://www.ncbi.nlm.nih.gov/pubmed/18313340?tool=bestpractice.com
[129]Elbers JM, Bitnun A, Richardson SE, et al. A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease? Pediatrics. 2007 Feb;119(2):e399-407.
http://www.ncbi.nlm.nih.gov/pubmed/17272602?tool=bestpractice.com
Children with isolated cerebellar involvement or respiratory syncytial virus encephalitis tend to have a good prognosis.
Postencephalitic epilepsy occurs in 10% by 5 years and 20% by 20 years.[130]Annegers JF, Hauser WA, Beghi E, et al. The risk of unprovoked seizures after encephalitis and meningitis. Neurology. 1988 Sep;38(9):1407-10.
http://www.ncbi.nlm.nih.gov/pubmed/3412588?tool=bestpractice.com
The presence of seizures during hospitalization and an abnormal brain magnetic resonance imaging are the strongest predictors of development of postencephalitic epilepsy. The etiology of encephalitis, presence of focal neurologic deficits, and interictal electroencephalographic abnormalities do not influence development of postencephalitic epilepsy.[131]Singh TD, Fugate JE, Hocker SE, et al. Postencephalitic epilepsy: clinical characteristics and predictors. Epilepsia. 2015 Jan;56(1):133-8.
http://onlinelibrary.wiley.com/doi/10.1111/epi.12879/full
http://www.ncbi.nlm.nih.gov/pubmed/25523929?tool=bestpractice.com
For herpes simplex virus encephalitis, older age, decreased level of consciousness, and delay or lack of treatment with acyclovir are associated with high mortality rates. Diffuse cerebral edema and intractable seizures are additional poor prognostic indicators. Survivors frequently have disabling neurologic sequelae such as (short-term) memory impairment, personality and behavioral changes, psychiatric issues, and anosmia.[132]McGrath N, Anderson NE, Croxson MC, et al. Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. J Neurol Neurosurg Psychiatry. 1997 Sep;63(3):321-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169720/pdf/v063p00321.pdf
http://www.ncbi.nlm.nih.gov/pubmed/9328248?tool=bestpractice.com
Some have observed associations of anti-NMDAR encephalitis after HSV encephalitis.[133]Armangue T, Spatola M, Vlagea A, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol. 2018 Sep;17(9):760-72.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128696
http://www.ncbi.nlm.nih.gov/pubmed/30049614?tool=bestpractice.com
Severe behavioral and personality changes including Kluver-Bucy syndrome, seen before acyclovir became widely available, are no longer common.
Mortality rates in autoimmune encephalitis are generally lower than in infectious cases; however, prolonged recovery and potential for relapse make longer-term management challenging.[1]Venkatesan A, Michael BD, Probasco JC, et al. Acute encephalitis in immunocompetent adults. Lancet. 2019 Feb 16;393(10172):702-16.
http://www.ncbi.nlm.nih.gov/pubmed/30782344?tool=bestpractice.com
Mortality rates for anti-N-methyl-D-aspartate (NMDA) receptor encephalitis are up to 6%, and relapse occurs in 12% to 25% of patients.[31]Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563251
http://www.ncbi.nlm.nih.gov/pubmed/23290630?tool=bestpractice.com
[134]Gabilondo I, Saiz A, Galán L, et al. Analysis of relapses in anti-NMDAR encephalitis. Neurology. 2011 Sep 6;77(10):996-9.
http://www.ncbi.nlm.nih.gov/pubmed/21865579?tool=bestpractice.com
[135]Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010 Jun;133(pt 6):1655-67.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877907
http://www.ncbi.nlm.nih.gov/pubmed/20511282?tool=bestpractice.com
Earlier immune treatment has been associated with better outcomes but cognitive and behavioral changes may persist.[31]Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563251
http://www.ncbi.nlm.nih.gov/pubmed/23290630?tool=bestpractice.com
[135]Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010 Jun;133(pt 6):1655-67.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877907
http://www.ncbi.nlm.nih.gov/pubmed/20511282?tool=bestpractice.com
[136]Yeshokumar AK, Gordon-Lipkin E, Arenivas A, et al. Neurobehavioral outcomes in autoimmune encephalitis. J Neuroimmunol. 2017 Nov 15;312:8-14.
http://www.ncbi.nlm.nih.gov/pubmed/28889962?tool=bestpractice.com
Mortality rates may be lower for anti-leucine-rich glioma-inactivated 1 encephalitis than anti-NMDA encephalitis, but longer-term relapse rates might be higher.[1]Venkatesan A, Michael BD, Probasco JC, et al. Acute encephalitis in immunocompetent adults. Lancet. 2019 Feb 16;393(10172):702-16.
http://www.ncbi.nlm.nih.gov/pubmed/30782344?tool=bestpractice.com
[137]Ariño H, Armangué T, Petit-Pedrol M, et al. Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome. Neurology. 2016 Aug 23;87(8):759-65.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999321
http://www.ncbi.nlm.nih.gov/pubmed/27466467?tool=bestpractice.com
[138]van Sonderen A, Thijs RD, Coenders EC, et al. Anti-LGI1 encephalitis: clinical syndrome and long-term follow-up. Neurology. 2016 Oct 4;87(14):1449-56.
http://www.ncbi.nlm.nih.gov/pubmed/27590293?tool=bestpractice.com