Review of the Longitudinal Management of Autoimmune Encephalitis, Potential Biomarkers, and Novel Therapeutics

Overview

Journal Neurol Clin Pract

Date 2024 Jun 4

PMID 38831758

Authors

Ahmad Z Mahadeen

Alise K Carlson

Jeffrey A Cohen

Rachel Galioto

Justin R Abbatemarco

Amy Kunchok

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: Increasing awareness and earlier diagnosis of autoimmune encephalitis (AE) have led to a greater number of patients being cared for longitudinally by neurologists. Although many neurologists are now familiar with the general approach to diagnosis and acute immunosuppression, this review aims to provide neurologists with guidance related to management beyond the acute phase of disease, including long-term immunosuppression, monitoring, potential biomarkers of disease activity, outcome measures, and symptom management.

Recent Findings: Observational studies in AE have demonstrated that early diagnosis and treatment is associated with improved neurologic outcomes, particularly in AE with antibodies targeting neuronal cell surface/synaptic proteins. The literature regarding long-term management is evolving. In addition to traditional immunosuppressive approaches, there is emerging use of novel immunosuppressive therapies (ISTs) in case series, and several randomized controlled trials are planned. Novel biomarkers of disease activity and methods to measure outcomes and response to treatment are being explored. Furthermore, it is increasingly recognized that many individuals have chronic symptoms affecting quality of life including seizures, cognitive impairment, fatigue, sleep disorders, and mood disorders, and there are emerging data supporting the use of patient centered outcome measures and multidisciplinary symptom-based care.

Summary: This review aims to summarize recent literature and offer a practical approach to long-term management of adult patients with AE through a multidisciplinary approach. We summarize current knowledge on ISTs, potential biomarkers of disease activity, outcome measures, and long-term sequelae. Further research is needed to answer questions regarding optimal IST, biomarker validity, and sequelae of disease.

Citing Articles

Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes with Progressive Supranuclear Palsy-like Manifestations.

Yamahara N, Takekoshi A, Kimura A, Shimohata T Brain Sci. 2024; 14(10).

PMID: 39452025 PMC: 11506429. DOI: 10.3390/brainsci14101012.

References

Wickel J, Chung H, Platzer S, Lehmann T, Pruss H, Leypoldt F . Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis. Trials. 2020; 21(1):625. PMC: 7346383. DOI: 10.1186/s13063-020-04516-7. View

Vernino S, Tuite P, Adler C, Meschia J, Boeve B, Boasberg P . Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol. 2002; 51(5):625-30. DOI: 10.1002/ana.10178. View

Lee W, Lee S, Shin Y, Lee H, Shin H, Kim D . Teratoma Removal, Steroid, IVIG, Rituximab and Tocilizumab (T-SIRT) in Anti-NMDAR Encephalitis. Neurotherapeutics. 2020; 18(1):474-487. PMC: 8116457. DOI: 10.1007/s13311-020-00921-7. View

Calabrese C, Kirchner E, Husni E, Moss B, Fernandez A, Jin Y . Breakthrough SARS-CoV-2 Infections in Patients With Immune-Mediated Disease Undergoing B Cell-Depleting Therapy: A Retrospective Cohort Analysis. Arthritis Rheumatol. 2022; 74(12):1906-1915. PMC: 9349969. DOI: 10.1002/art.42287. View

Suppiej A, Nosadini M, Zuliani L, Pelizza M, Toldo I, Bertossi C . Plasma exchange in pediatric anti-NMDAR encephalitis: A systematic review. Brain Dev. 2016; 38(7):613-22. DOI: 10.1016/j.braindev.2016.01.009. View

Randell R, Adams A, Van Mater H . Tocilizumab in Refractory Autoimmune Encephalitis: A Series of Pediatric Cases. Pediatr Neurol. 2018; 86:66-68. DOI: 10.1016/j.pediatrneurol.2018.07.016. View

Lunemann J, Nimmerjahn F, Dalakas M . Intravenous immunoglobulin in neurology--mode of action and clinical efficacy. Nat Rev Neurol. 2015; 11(2):80-9. DOI: 10.1038/nrneurol.2014.253. View

Dalmau J, Tuzun E, Wu H, Masjuan J, Rossi J, Voloschin A . Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol. 2007; 61(1):25-36. PMC: 2430743. DOI: 10.1002/ana.21050. View

Dinoto A, Cheli M, Bratina A, Sartori A, Manganotti P . Bortezomib in anti-N-Methyl-d-Aspartate-Receptor (NMDA-R) encephalitis: A systematic review. J Neuroimmunol. 2021; 356:577586. DOI: 10.1016/j.jneuroim.2021.577586. View

10.

Zhang Y, Huang H, Chen W, Liu G, Liu F, Su Y . Clinical efficacy of plasma exchange in patients with autoimmune encephalitis. Ann Clin Transl Neurol. 2021; 8(4):763-773. PMC: 8045938. DOI: 10.1002/acn3.51313. View

11.

Graus F, Titulaer M, Balu R, Benseler S, Bien C, Cellucci T . A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016; 15(4):391-404. PMC: 5066574. DOI: 10.1016/S1474-4422(15)00401-9. View

12.

Ratuszny D, Skripuletz T, Wegner F, Gross M, Falk C, Jacobs R . Case Report: Daratumumab in a Patient With Severe Refractory Anti-NMDA Receptor Encephalitis. Front Neurol. 2021; 11:602102. PMC: 7782967. DOI: 10.3389/fneur.2020.602102. View

13.

Dalmau J, Graus F, Villarejo A, Posner J, Blumenthal D, Thiessen B . Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004; 127(Pt 8):1831-44. DOI: 10.1093/brain/awh203. View

14.

Thompson J, Bi M, Murchison A, Makuch M, Bien C, Chu K . The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2017; 141(2):348-356. PMC: 5837230. DOI: 10.1093/brain/awx323. View

15.

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

16.

Abboud H, Briggs F, Buerki R, Elkasaby M, BacaVaca G, Fotedar N . Residual symptoms and long-term outcomes after all-cause autoimmune encephalitis in adults. J Neurol Sci. 2022; 434:120124. DOI: 10.1016/j.jns.2021.120124. View

17.

Emadi A, Jones R, Brodsky R . Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol. 2009; 6(11):638-47. DOI: 10.1038/nrclinonc.2009.146. View

18.

Lee W, Lee S, Moon J, Sunwoo J, Byun J, Lim J . Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study. Neurotherapeutics. 2016; 13(4):824-832. PMC: 5081109. DOI: 10.1007/s13311-016-0442-6. View

19.

Barmettler S, Ong M, Farmer J, Choi H, Walter J . Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA Netw Open. 2019; 1(7):e184169. PMC: 6324375. DOI: 10.1001/jamanetworkopen.2018.4169. View

20.

Thaler F, Zimmermann L, Kammermeier S, Strippel C, Ringelstein M, Kraft A . Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis: Real-world Evidence From the GENERATE Registry. Neurol Neuroimmunol Neuroinflamm. 2021; 8(6). PMC: 8488759. DOI: 10.1212/NXI.0000000000001088. View