Autoimmune Encephalitis epidemiology and demographics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Julinka Auta Fernandes
|
Autoimmune Encephalitis Microchapters |
|
Differentiating Autoimmune Encephalitis from Other Conditions |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Autoimmune Encephalitis On the Web |
Overview
Autoimmune encephalitis is an uncommon group of immune-mediated brain disorders affecting children and adults. Epidemiological estimates depend on the antibody subtype, diagnostic criteria, population, and access to testing. Antibody-negative disease and differences in case ascertainment complicate comparisons between studies.[1] Population-based rates should be distinguished from the proportion of patients diagnosed in a referral hospital or antibody-testing cohort.
Epidemiology and Demographics
Prevalence
Autoimmune encephalitis had an age- and sex-adjusted point prevalence of 13.7 per 100,000 people in Olmsted County, Minnesota, on January 1, 2014, based on 21 prevalent cases. The study used a broad definition that included acute disseminated encephalomyelitis and myelin oligodendrocyte glycoprotein (MOG)-associated presentations; this estimate is not a worldwide prevalence.[2]
Incidence
Autoimmune encephalitis incidence must be interpreted according to the study population, observation period, and case definition. The following estimates describe different disease spectra and should not be pooled or treated as interchangeable national or global rates.
| Setting | Observation period | Case definition and ascertainment | Incidence per 100,000 person-years |
|---|---|---|---|
| Olmsted County, Minnesota, United States | 1995–2015 | Broad autoimmune encephalitis definition, including antibody-positive, antibody-negative, and selected demyelinating syndromes; 24 incident cases. | 0.8, age- and sex-adjusted.[2] |
| France | 2018 | Antibody-positive autoimmune encephalitis subgroup identified through the national reference center. | Approximately 0.2; originally reported as 2.1 per million person-years.[3] |
| The Netherlands | 2016–2021 | Nationwide antibody-associated autoimmune encephalitis and paraneoplastic neurologic syndromes combined; not an encephalitis-only population. | Approximately 0.6; originally reported as approximately 5.6 per million person-years.[4] |
| Denmark | 2019–2023 | Nationwide antibody-based ascertainment of neuronal cell-surface, glutamic acid decarboxylase 65 (GAD65), and glial fibrillary acidic protein (GFAP)-associated disease; antibody-negative disease was not captured. | Approximately 0.3; reported autoimmune encephalitis rate 2.8 per million person-years.[5] |
Rates converted from a denominator of one million are approximate and rounded. The Danish study also examined related nonencephalitic antibody-associated syndromes; its authors reported a higher rate when these were included.[5]
Recorded incidence in Olmsted County increased from 0.4 in 1995–2005 to 1.2 per 100,000 person-years in 2006–2015, attributed to increased detection of antibody-positive cases.[2] Increasing diagnosed incidence does not, by itself, demonstrate an equivalent increase in the underlying biological occurrence of disease.
Case Fatality Rate
Autoimmune encephalitis case fatality varies with the subtype, patient characteristics, associated neoplasm, severity, and follow-up duration. A single annual or worldwide case-fatality percentage should not be inferred from heterogeneous clinical cohorts.[1]
| Subtype and cohort | Follow-up context | Reported finding |
|---|---|---|
| N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis: large international observational cohort | Outcomes were assessable in 501 patients; deaths were reported during the first 24 months. | 30 deaths among 501 patients, approximately 6.0%.[6] |
| Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis: Dutch cohort of 38 patients | Two-year case-fatality estimate. | 19.0% in this small cohort.[7] |
These findings describe deaths within particular patient cohorts, rather than deaths per total population. Differences between the cohorts do not establish a direct comparison of subtype-specific lethality.
Age
Autoimmune encephalitis can occur throughout life, including childhood and older adulthood. The age distribution differs substantially between antibody-associated syndromes. Pediatric assessment must account for developmental stage and a different distribution of antibody syndromes.[8]
The following are illustrative cohort demographics, rather than population incidence estimates or age restrictions.
| Antibody-associated syndrome | Cohort size | Reported age | Reported sex distribution |
|---|---|---|---|
| NMDAR-antibody encephalitis | 577 patients | Median 21 years; range 8 months to 85 years. There were 211 patients younger than 18 years. | 468 patients, approximately 81%, were female.[6] |
| Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis: Chinese multicenter cohort | 117 patients | Median onset age 57 years. | 81 patients, 69.2%, were male.[9] |
| Contactin-associated protein-like 2 (CASPR2)-antibody disease, including encephalitis and Morvan syndrome | 38 patients | Median onset age 66 years. | 34 patients, approximately 89.5%, were male.[10] |
| α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-antibody encephalitis | 22 patients | Median 62 years; range 23–81 years. | 14 patients, approximately 63.6%, were female.[11] |
| Gamma-aminobutyric acid type B receptor (GABABR) encephalitis: initial case series | 15 patients | Median 62 years; range 24–75 years. | Eight patients were male. This small series does not establish a population sex ratio.[12] |
Gender
Autoimmune encephalitis does not have a uniform male-to-female distribution. Published studies generally report sex, and the observed proportions depend on the antibody subtype and cohort.
- NMDAR-antibody encephalitis showed female predominance in the large international cohort above.[6] However, a Western Chinese cohort of 244 patients included 128 females, approximately 52.5%, demonstrating that a single female-to-male ratio should not be applied to every population.[13]
- LGI1- and CASPR2-associated cohorts frequently show male predominance, as illustrated above. These patterns do not exclude patients of either sex.[9][10]
Race
Autoimmune encephalitis has been reported across racial and ethnic groups. In the small Olmsted County study, incidence was 2.8 versus 0.7 per 100,000 person-years among Black and White residents, respectively. Small subgroup numbers limit generalization; the observation does not establish a biological explanation for the difference.[2]
Developed Countries
Autoimmune encephalitis estimates from high-resource health systems remain sensitive to diagnostic access and reporting. The French study found a lower observed national rate of combined autoimmune encephalitis and paraneoplastic neurologic syndromes than its modeled expected rate, suggesting underdiagnosis or underreporting.[3] Danish investigators also identified higher diagnosed incidence in the region hosting the national testing center, consistent with an influence of local expertise on case ascertainment.[5]
The Dutch nationwide study provides important antibody-associated disease data, but its combined autoimmune encephalitis/paraneoplastic syndrome rate should not be presented as an autoimmune encephalitis-only rate.[4]
Developing Countries
Autoimmune encephalitis is documented in published hospital cohorts from countries including India and China. A prospective Northwestern Indian study described 42 patients, with a mean onset age of 31 years and nearly equal numbers of males and females.[14] A Chinese prospective referral-center cohort included 220 patients with NMDAR-antibody encephalitis and described barriers involving referral access, timely diagnosis, and financial concerns.[15]
These referral cohorts demonstrate recognized disease but do not establish national population incidence or prevalence. Geographic comparisons must account for case definitions, referral patterns, and the availability of validated antibody testing rather than assuming that fewer reported cases indicate less disease.
References
- ↑ 1.0 1.1 Hahn C, Budhram A, Alikhani K, et al. (2024). "Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults". Can J Neurol Sci. 51 (6): 734–754. doi:10.1017/cjn.2024.16. PMID 38312020 Check
|pmid=value (help). - ↑ 2.0 2.1 2.2 2.3 Dubey D, Pittock SJ, Kelly CR, et al. (2018). "Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis". Ann Neurol. 83 (1): 166–177. doi:10.1002/ana.25131. PMID 29293273.
- ↑ 3.0 3.1 Hébert J, Riche B, Vogrig A, et al. (2020). "Epidemiology of paraneoplastic neurologic syndromes and autoimmune encephalitides in France". Neurol Neuroimmunol Neuroinflamm. 7 (6): e883. doi:10.1212/NXI.0000000000000883. PMID 32847939 Check
|pmid=value (help). - ↑ 4.0 4.1 Kerstens J, Schreurs M, de Vries JM, et al. (2024). "Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance". Neurol Neuroimmunol Neuroinflamm. 11 (6): e200318. doi:10.1212/NXI.0000000000200318. PMID 39467237 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 5.0 5.1 5.2 Gaist TA, Nissen MS, Funch S, et al. (2026). "Fifteen years of autoimmune encephalitis in Denmark: incidence, epidemiology, and trends in treatment". J Neurol. 273 (8): 488. doi:10.1007/s00415-026-13979-8. PMID 42493607 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ 6.0 6.1 6.2 Titulaer MJ, McCracken L, Gabilondo I, et al. (2013). "Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study". Lancet Neurol. 12 (2): 157–165. doi:10.1016/S1474-4422(12)70310-1. PMID 23290630.
- ↑ van Sonderen A, Thijs RD, Coenders EC, et al. (2016). "Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up". Neurology. 87 (14): 1449–1456. doi:10.1212/WNL.0000000000003173. PMID 27590293.
- ↑ Cellucci T, Van Mater H, Graus F, et al. (2020). "Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient". Neurol Neuroimmunol Neuroinflamm. 7 (2): e663. doi:10.1212/NXI.0000000000000663. PMID 31953309.
- ↑ 9.0 9.1 Qiao S, Wu HK, Liu LL, et al. (2021). "Clinical Features and Long-Term Outcomes of Anti-Leucine-Rich Glioma-Inactivated 1 Encephalitis: A Multi-Center Study". Neuropsychiatr Dis Treat. 17: 203–212. doi:10.2147/NDT.S292343.
- ↑ 10.0 10.1 van Sonderen A, Ariño H, Petit-Pedrol M, et al. (2016). "The clinical spectrum of Caspr2 antibody-associated disease". Neurology. 87 (5): 521–528. doi:10.1212/WNL.0000000000002917. PMID 27371488.
- ↑ Höftberger R, van Sonderen A, Leypoldt F, et al. (2015). "Encephalitis and AMPA receptor antibodies: Novel findings in a case series of 22 patients". Neurology. 84 (24): 2403–2412. doi:10.1212/WNL.0000000000001682. PMID 25979696.
- ↑ Lancaster E, Lai M, Peng X, et al. (2010). "Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen". Lancet Neurol. 9 (1): 67–76. doi:10.1016/S1474-4422(09)70324-2. PMID 19962348.
- ↑ Gong X, Chen C, Liu X, et al. (2021). "Long-term Functional Outcomes and Relapse of Anti-NMDA Receptor Encephalitis: A Cohort Study in Western China". Neurol Neuroimmunol Neuroinflamm. 8 (2): e958. doi:10.1212/NXI.0000000000000958. PMID 33589542 Check
|pmid=value (help). - ↑ Sharma B, Paul M, Bagaria AK (2023). "A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India". J Assoc Physicians India. 71 (9): 39–44. doi:10.59556/japi.71.0312. PMID 38700300 Check
|pmid=value (help). - ↑ Xu X, Lu Q, Huang Y, et al. (2020). "Anti-NMDAR encephalitis: A single-center, longitudinal study in China". Neurol Neuroimmunol Neuroinflamm. 7 (1): e633. doi:10.1212/NXI.0000000000000633. PMID 31619447.