Autoimmune Encephalitis As Differential Diagnosis of Infectious Encephalitis

Overview

Journal Curr Opin Neurol

Specialty Neurology

Date 2014 May 6

PMID 24792345

Citations 62

Authors

Thais Armangue

Frank Leypoldt

Josep Dalmau

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: This review describes the main types of autoimmune encephalitis with special emphasis on those associated with antibodies against neuronal cell surface or synaptic proteins, and the differential diagnosis with infectious encephalitis.

Recent Findings: There is a continuous expansion of the number of cell surface or synaptic proteins that are targets of autoimmunity. The most recently identified include the metabotropic glutamate receptor 5 (mGluR5), dipeptidyl-peptidase-like protein-6 (DPPX), and γ-aminobutyric acid-A receptor (GABAAR). In these and previously known types of autoimmune encephalitis [N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2)], the prodromal symptoms or types of presentations often suggest a viral encephalitis. We review here clues that help in the differential diagnosis with infectious encephalitis. Moreover, recent investigations indicate that viral encephalitis (e.g., herpes simplex) can trigger synaptic autoimmunity. In all these disorders, immunotherapy is usually effective.

Summary: Autoimmune encephalitis comprises an expanding group of potentially treatable disorders that should be included in the differential diagnosis of any type of encephalitis.

Video Abstract: http://links.lww.com/CONR/A25,

Citing Articles

Anti-metabotropic glutamate receptor 5 coexistent anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

Gu Y, Xuan T, Li P, Zhou J, Wang Z Front Immunol. 2025; 16:1436246.

PMID: 40028323 PMC: 11867952. DOI: 10.3389/fimmu.2025.1436246.

Psychiatric manifestations of encephalitis.

Bean P, Heck A, Habis R, Sowmitran S, Cartaina Z, Gupta R Ann Clin Transl Neurol. 2025; 12(2):405-414.

PMID: 39776337 PMC: 11822797. DOI: 10.1002/acn3.52260.

Canine idiopathic generalized tremor syndrome, immune-mediated?.

Kajin F, Meyerhoff N, Meller S, Carlson R, Tipold A, Gutierrez-Quintana R Front Vet Sci. 2024; 11:1453698.

PMID: 39372900 PMC: 11449864. DOI: 10.3389/fvets.2024.1453698.

F-DPA714 PET/MRI as a potential imaging tool for detecting possible antibody-negative autoimmune encephalitis: a prospective study.

Meng H, He L, Chunyu H, Zhou Q, Wang J, Qu Q J Neurol. 2024; 271(12):7592-7604.

PMID: 39294471 DOI: 10.1007/s00415-024-12690-w.

Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis Presenting as Refractory Seizures.

Balaji N, Ignatowicz A, Kalra A, Mansour R, Jadhav V Cureus. 2024; 16(7):e64317.

PMID: 39131008 PMC: 11316415. DOI: 10.7759/cureus.64317.

References

Titulaer M, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T . Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013; 12(2):157-65. PMC: 3563251. DOI: 10.1016/S1474-4422(12)70310-1. View

Graus F, Delattre J, Antoine J, Dalmau J, Giometto B, Grisold W . Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004; 75(8):1135-40. PMC: 1739186. DOI: 10.1136/jnnp.2003.034447. View

Andrade D, Tai P, Dalmau J, Wennberg R . Tonic seizures: a diagnostic clue of anti-LGI1 encephalitis?. Neurology. 2011; 76(15):1355-7. PMC: 3090064. DOI: 10.1212/WNL.0b013e3182152808. View

Irani S, Michell A, Lang B, Pettingill P, Waters P, Johnson M . Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. Ann Neurol. 2011; 69(5):892-900. DOI: 10.1002/ana.22307. View

Mat A, Adler H, Merwick A, Chadwick G, Gullo G, Dalmau J . Ophelia syndrome with metabotropic glutamate receptor 5 antibodies in CSF. Neurology. 2013; 80(14):1349-50. PMC: 3656459. DOI: 10.1212/WNL.0b013e31828ab325. View

Ben-Pazi H, Stoner J, Cunningham M . Dopamine receptor autoantibodies correlate with symptoms in Sydenham's chorea. PLoS One. 2013; 8(9):e73516. PMC: 3779221. DOI: 10.1371/journal.pone.0073516. View

Lancaster E, Martinez-Hernandez E, Titulaer M, Boulos M, Weaver S, Antoine J . Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology. 2011; 77(18):1698-701. PMC: 3208954. DOI: 10.1212/WNL.0b013e3182364a44. View

Armangue T, Leypoldt F, Malaga I, Raspall-Chaure M, Marti I, Nichter C . Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Ann Neurol. 2013; 75(2):317-23. PMC: 3961499. DOI: 10.1002/ana.24083. View

Venkatesan A, Tunkel A, Bloch K, Lauring A, Sejvar J, Bitnun A . Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013; 57(8):1114-28. PMC: 3783060. DOI: 10.1093/cid/cit458. View

10.

Petit-Pedrol M, Armangue T, Peng X, Bataller L, Cellucci T, Davis R . Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol. 2014; 13(3):276-86. PMC: 4838043. DOI: 10.1016/S1474-4422(13)70299-0. View

11.

Panzer J, Gleichman A, Lynch D . Glutamatergic autoencephalitides: an emerging field. J Neural Transm (Vienna). 2014; 121(8):957-68. PMC: 4090301. DOI: 10.1007/s00702-013-1152-4. View

12.

Gultekin S, Rosenfeld M, Voltz R, Eichen J, Posner J, Dalmau J . Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000; 123 ( Pt 7):1481-94. DOI: 10.1093/brain/123.7.1481. View

13.

Titulaer M, Soffietti R, Dalmau J, Gilhus N, Giometto B, Graus F . Screening for tumours in paraneoplastic syndromes: report of an EFNS task force. Eur J Neurol. 2010; 18(1):19-e3. PMC: 3086523. DOI: 10.1111/j.1468-1331.2010.03220.x. View

14.

Glaser C, Honarmand S, Anderson L, Schnurr D, Forghani B, Cossen C . Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis. 2006; 43(12):1565-77. DOI: 10.1086/509330. View

15.

Thomas L, Mailles A, Desestret V, Ducray F, Mathias E, Rogemond V . Autoimmune N-methyl-D-aspartate receptor encephalitis is a differential diagnosis of infectious encephalitis. J Infect. 2013; 68(5):419-25. DOI: 10.1016/j.jinf.2013.12.001. View

16.

Florance N, Davis R, Lam C, Szperka C, Zhou L, Ahmad S . Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol. 2009; 66(1):11-8. PMC: 2826225. DOI: 10.1002/ana.21756. View

17.

Mailles A, Stahl J . Infectious encephalitis in france in 2007: a national prospective study. Clin Infect Dis. 2009; 49(12):1838-47. DOI: 10.1086/648419. View

18.

Armangue T, Titulaer M, Malaga I, Bataller L, Gabilondo I, Graus F . Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr. 2012; 162(4):850-856.e2. PMC: 3582718. DOI: 10.1016/j.jpeds.2012.10.011. View

19.

Lancaster E, Huijbers M, Bar V, Boronat A, Wong A, Martinez-Hernandez E . Investigations of caspr2, an autoantigen of encephalitis and neuromyotonia. Ann Neurol. 2011; 69(2):303-11. PMC: 3059252. DOI: 10.1002/ana.22297. View

20.

De Tiege X, Rozenberg F, Portes V, Lobut J, Lebon P, Ponsot G . Herpes simplex encephalitis relapses in children: differentiation of two neurologic entities. Neurology. 2003; 61(2):241-3. DOI: 10.1212/01.wnl.0000073985.71759.7c. View