Skip to main content
Log in

Increased rates of sequelae post-encephalitis in individuals attending primary care practices in the United Kingdom: a population-based retrospective cohort study

  • Neurological Update
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The true extent of sequelae in encephalitis survivors relative to rates within the general population is not known. This study aimed to quantify increased risks of epilepsy, depressive disorders, anxiety disorders, psychotic disorders, bipolar disorder, cognitive problems, dementia, headache, and alcohol abuse among encephalitis cases. 2460 exposed individuals diagnosed with incident encephalitis in the Clinical Practice Research Datalink and 47,914 unexposed individuals without a history of encephalitis were included. Multivariable Poisson regression was used to estimate adjusted rate ratios in individuals with encephalitis compared to the general population and to estimate whether the effect of these outcomes varied over time. Individuals with encephalitis had an increased risk of all investigated outcomes. The highest RR was seen for epilepsy (adjusted RR 31.9; 95 % confidence interval 25.38–40.08), whereas the lowest was seen for anxiety disorders (1.46, 1.27–1.68). The second highest RRs were for particular psychiatric illnesses, including bipolar disorder (6.34, 3.34–12.04) and psychotic disorders (3.48, 2.18–5.57). The RR was highest in the first year of follow-up for all outcomes except headache; this was particularly true for epilepsy (adjusted RR in first year of follow-up 139.6, 90.62–215.03). This study shows that sequelae are common in survivors of encephalitis. We confirm the presence of outcomes more commonly linked to encephalitis and describe those less commonly identified as being associated with encephalitis. The results of this study have important implications for the management of encephalitis patients and for the design of tertiary prevention strategies, as many of these sequelae are treatable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Granerod J, Tam CC, Crowcroft NS, Davies NWS, Borchert M, Thomas SL (2010) Challenge of the unknown: a systematic review of acute encephalitis in non-outbreak situations. Neurology 75(10):924–932

    Article  CAS  PubMed  Google Scholar 

  2. Irani SR, Alexander S, Waters P et al (2010) Antibodies to Kv1 potassium channel-complex proteins leucine-rich, glioma inactivated 1 protein and contactin-associated protein-2 in limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. Brain 133(9):2734–2748

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R (2011) Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 10(1):63–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Granerod J, Cousens S, Davies NWS, Crowcroft NS, Thomas SL (2013) New estimates of incidence of encephalitis in England. Emerg Infect Dis. doi:10.3201/eid1909.130064

    PubMed  PubMed Central  Google Scholar 

  5. Easton A, Atkin K, Dowell E (2006) Encephalitis, a service orphan: the need for more research and access to neuropsychology. Br J Neurosci Nurs 2:488–492

    Article  Google Scholar 

  6. Granerod J, Ambrose HE, Davies NW et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10(12):835–844

    Article  PubMed  Google Scholar 

  7. Easton A (2016) Life after encephalitis: a narrative approach. Routledge, Oxford

    Google Scholar 

  8. Hjalmarsson A, Blomqvist P, Skoldenberg B (2007) Herpes simplex encephalitis in Sweden, 1990–2001: incidence, morbidity, and mortality. Clin Infect Dis 45:875–880

    Article  PubMed  Google Scholar 

  9. Fazekas C, Enzinger C, Wallner M et al (2006) Depressive symptoms following herpes simplex encephalitis–an underestimated phenomenon? Gen Hosp Psychiatry 28:403–407

    Article  PubMed  Google Scholar 

  10. Mailles A, De Broucker T, Costanzo P, Martinez-Almoyna L, Vaillant V, Stahl JP, Steering Committee and Investigators Group (2012) Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis 54(10):1455–1464

    Article  PubMed  Google Scholar 

  11. Herrett E, Gallagher AM, Bhaskaran K, Forbes H, Mathur R, van Staa T et al (2015) Data Resource Profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol. doi:10.1093/ije/dyv098

    PubMed  PubMed Central  Google Scholar 

  12. CPRD website. https://www.cprd.com/intro.asp

  13. Herrett E, Thomas SL, Schoonen WM et al (2010) Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 69:4–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lewis JD, Bilker WB, Weinstein RB, Strom BL (2005) The relationship between time since registration and measured incidence rates in the General Practice Research Database. Pharmacoepidemiol Drug Saf 14(7):443–451. doi:10.1002/pds.1115

    Article  PubMed  Google Scholar 

  15. Baumeister H (2012) Inappropriate prescriptions of antidepressant drugs in patients with subthreshold to mild depression: time for the evidence to become practice. J Affect Dis 139:240–243

    Article  PubMed  Google Scholar 

  16. CG90 (2009) Depression in adults: recognition and management. National Institute for Health and Care Excellence

  17. Pillai SC, Mohammad SS, Hacohen Y, Tantsis E, Prelog K, Barnes EH, Gill D, Lim MJ, Brilot F, Vincent A, Dale RC (2016) Postencephalitic epilepsy and drug-resistant epilepsy after infectious and antibody-associated encephalitis in childhood: clinical and etiologic risk factors. Epilepsia 57(1):e7–e11

    Article  CAS  PubMed  Google Scholar 

  18. Rismanchi N, Gold JJ, Sattar S, Glaser CA, Sheriff H, Proudfoot J, Mower A, Crawford JR, Nespeca M, Wang SG (2015) Epilepsy after resolution of presumed childhood encephalitis. Pediatr Neurol 53(1):65–72

    Article  PubMed  Google Scholar 

  19. Depression after Traumatic Brain Injury was developed by J Fann and T Hart in collaboration with the Model Systems Knowledge Translation Center. http://www.msktc.org/tbi/factsheets/Depression-After-Traumatic-Brain-Injury#sthash.HlR0e0MJ.dpuf

  20. Blomström Å, Karlsson H, Svensson A, Frisell T, Lee BK, Dal H, Magnusson C, Dalman C (2014) Hospital admission with infection during childhood and risk for psychotic illness—a population-based cohort study. Schizophr Bull 40(6):1518–1525

    Article  PubMed  Google Scholar 

  21. Avramopoulos D, Pearce BD, McGrath J, Wolyniec P, Wang R, Eckart N, Hatzimanolis A, Goes FS, Nestadt G, Mulle J, Coneely K, Hopkins M, Ruczinski I, Yolken R, Pulver AE (2015) Infection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation. PLoS One 10(3):e0116696

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hokkanen L, Launes J (1997) Cognitive recovery instead of decline after acute encephalitis: a prospective follow up study. J Neurol Neurosurg Psychiatry 63:222–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gatson JW, Stebbins C, Mathews D, Harris TS, Madden C, Batjer H, Diaz-Arrastia R, Minei JP (2015) Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases. J Neurosurg 1–8

  24. Lucas S (2015) Posttraumatic headache: clinical characterization and management. Curr Pain Headache Rep 19(10):48

    Article  PubMed  Google Scholar 

  25. Russo A, D’Onofrio F, Conte F, Petretta V, Tedeschi G, Tessitore A (2014) Post-traumatic headaches: a clinical overview. Neurol Sci 35(1):153–156

    Article  PubMed  Google Scholar 

  26. Neligan A, Sander JW (2009) The incidence and prevalence of epilepsy. In: Sander JW, Rugg-Gunn, FJ, Smalls JE (eds) Epilepsy 2009: from benchside to bedside. A practical guide to epilepsy. Lecture notes from the Twelfth Epilepsy Teaching Weekend, 18–20 September 2009, St. Anne’s College, Oxford. International League Against Epilepsy (UK Chapter) and National Society for Epilepsy: Chalfont St Peter, Bucks, pp 15–21

  27. Rait G, Walters K, Griffin M, Buszewicz M, Petersen I, Nazareth I (2009) Recent trends in the incidence of recorded depression in primary care. Br J Psychiatry 195(6):520–524

    Article  PubMed  Google Scholar 

  28. Frisher M, Collins J, Millson D, Crome I, Croft P (2004) Prevalence of comorbid psychiatric illness and substance misuse in primary care in England and Wales. J Epidemiol Community Health 58(12):1036–1041

    Article  PubMed  PubMed Central  Google Scholar 

  29. Beghi E, Nicolosi A, Kurland LT et al (1984) Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950–1981: I. Epidemiology. Ann Neurol 16:283–294

    Article  CAS  PubMed  Google Scholar 

  30. Cizman M, Jazbec J (1993) Aetiology of acute encephalitis in childhood in Slovenia. Pediatr Infect Dis J 12:903–908

    Article  CAS  PubMed  Google Scholar 

  31. Lee T, Tsai C, Yuan C, Wei C, Tsao W, Lee R, Cheih S, Huang I, Chen K (2003) Encephalitis in Taiwan: a prospective hospital-based study. Jpn J Infect Dis 56:193–199

    PubMed  Google Scholar 

  32. Studahl M, Bergstrom T, Hagberg L (1998) Acute viral encephalitis in adults: a prospective study. Scand J Infect Dis 30:215–220

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Harriet Forbes for extraction of the data.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julia Granerod.

Ethics declarations

Funding

This report is independent research commissioned and funded by the Department of Health’s Policy Research Programme (Enhanced Diagnostic and Management Strategies to Improve the Identification and Outcome of Individuals with Encephalitis, 047/1084). The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health.

Ethics

This study was approved by the Independent Scientific Advisory Committee of the Medicines and Healthcare Products Regulatory Authority (ISAC_09_061RA2) and the Ethics Committee of the London School of Hygiene and Tropical Medicine.

Conflicts of interest

The authors declare that they have no conflict of interest.

Data sharing

No additional data available.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Granerod, J., Davies, N.W.S., Ramanuj, P.P. et al. Increased rates of sequelae post-encephalitis in individuals attending primary care practices in the United Kingdom: a population-based retrospective cohort study. J Neurol 264, 407–415 (2017). https://doi.org/10.1007/s00415-016-8316-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-016-8316-8

Keywords

Navigation