Clinical and Diagnostic Features of Autoimmune Encephalitis in Pediatric Practice

Justification. Autoimmune encephalitis (AE) is a group of immune-mediated diseases based on autoconfl ict to cells of the central nervous system caused by paraneoplastic, postinfectious, iatrogenic or idiopathic processes. Clinical manifestations are represented by general systemic, neurological, psychiatric symptom complexes. The diagnosis is based on clinical, laboratory and instrumental methods: regularity of clinical picture formation, laboratory tests (autoantibody determination), use of neuroimaging methods. Treatment approaches have common medication steps, which vary depending on the type of AE.

Purpose of the work. To study the data of scientifi c publications with subsequent structuring of information and to provide clinical and diagnostic characteristics of diff erential diagnosis of AE.

Methods. We have analyzed 35 scientifi c publications in MEDLINE, PubMed, Google Scholar, eLIBRARY database: clinical trials, randomized controlled trials, systematic reviews, clinical cases from 2001 to 2025.

Results. The results of the analysis provide information on AEs: age of debut; clinical manifestations of each type, which occur in pediatrics; features of laboratory (antibody detection) and instrumental (electroencephalogram, neuroimaging) diagnosis; association with cancer processes; therapy and prognosis.

Pediatric patients with suspected AE should undergo the diagnostic minimum (cerebrospinal puncture for autoantibody determination, magnetic resonance examination of the brain), target therapy (use of fi rst-line drugs) with further evaluation of the results (ex juvantibus therapy if necessary). Post-therapeutic follow-up with further exclusion of paraneoplastic syndrome for 5 years (if idiopathic AE is suspected) is also an important aspect.

Conclusion. In pediatric practice, the course of autoimmune encephalitis (AE) has several clinical and diagnostic features: in most cases, encephalitis is accompanied by a seizure syndrome; the neuroimaging pattern is variable; therapy in all cases begins with glucocorticosteroids and intravenous immunoglobulin with the addition of plasmapheresis; in the absence of positive dynamics, there is a transition to cytostatic and/or antitumor drugs; pediatric patients have a favorable prognosis and high survival rates in most types of AE.

1. Shalkevich L.V., Stashkov A.K. Modern approaches of diagnostics and treatment patients with autoimmune encephalitis. Modern perinatal medical technologies in solving the problems of demographic security (Sovremennye perinatalnye medicinskie tehnologii v reshenii problem demografi cheskoj bezopasnosti: sbornik nauchnyh trudov). 2023;16:475–486. https://medcenter.by/wp-content/uploads/2024/01/sbornik-2023-blokoblozhka-jel-versija_.pdf

2. Olivé-Cirera G., Fonseca E., Chen L.-W., Fetta A., Martínez-Hernández E., Guasp M., González-Álvarez V., Delgadillo V., Cantarín-Extremera V., Jiménez-Legido M., Monge-Galindo L., Felipe A., Beseler B., Turón-Viñas E., Fernández-Ramos J., Martínez-González M. J., Vázquez-López M., Arrabal Fernandez L., Alvarez-Molinero M., Muñoz-Cabello B., Camacho A., Nuñez-Enamorado N., Spatola M., Sabater L., Blanco Y., Saiz A., Graus F., Dalmau J., Armangué T. Differential diagnosis and comparison of diagnostic algorithms in children and adolescent with autoimmune encephalitis in Spain: a prospective cohort study and retrospective analysis. Lancet Neurol. 2025;24(1):54–64. doi: 10.1016/S1474-4422(24)00443-5

3. Abboud H., Probasco J. C., Irani S., Ances B., Benavides D. R., Bradshaw M., Pereira Christo P., Dale R. C., Fernandez-Fournier M., Flanagan E. P., Gadoth A., George P., Grebenciucova E., Jammoul A., Lee S.-T., Li Y., Matiello M., Morse A. M., Rae-Grant A., Rojas G., Rossman I., Schmitt S., Venkatesa A., Vernino S., Pittock S.J., Titulaer M.J. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J. Neurol. Neurosurg. Psychiatry. 2021;92:757–768. doi: 10.1136/jnnp-2020-325300

4. Yamakawa M., Mukaino A., Kimura A., Nagasako Y., Kitazaki Y., Maeda Y., Higuchi O., Takamatsu K., Watari M., Yoshikura N., Ikawa M., Sugimoto I., Sakurai Y., Matsuo H., Ando Y., Shimohata T., Nakane S. Antibodies to the α3 subunit of the ganglionic-type nicotinic acetylcholine receptors in patients with autoimmune encephalitis. J. Neuroimmunol. 2020;349:577399. doi: 10.1016/j.jneuroim.2020.577399.

5. Lin K.-L., Lin J.-J. Neurocritical care for Anti-NMDA receptor encephalitis. Biomedical Journal. 2020;43:251–258. doi: 10.1016/j.bj.2020.04.002

6. Nguyen L., Wang C. Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies. Int. J. Gen. Med. 2023;16:7–21. doi: 10.2147/IJGM.S397429

7. Höltje M., Mertens R., Schou M. B., Saether S. G., Kochova E., Jarius S., Prüss H., Komorowski L., Probst C., Paul F., Bellmann-Strobl J., Gitler D., Benfenati F., Piepgras J., AhnertHilger G., Ruprecht K. Synapsin-antibodies in psychiatric and neurological disorders: prevalence and clinical fi ndings. Brain Behav. Immun. 2017;66:125–134. doi: 10.1016/j.bbi.2017.07.011

8. Zhang T.-Y., Cai M.-T., Zheng Y., Lai Q.-L., Shen C.-H., Qiao S., Zhang Y.-X. Anti-Alpha-Amino-3-Hydroxy5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review. Front. Immunol. 2021;12:652820. doi: 10.3389/fimmu.2021.652820

9. Ancona C., Masenello V., Tinnirello M., Toscano L. M., Leo A., La Piana C., Toldo I., Nosadini M., Sartori S. Autoimmune Encephalitis and Other Neurological Syndromes With Rare Neuronal Surface Antibodies in Children: A Systematic Literature Review. Front. Pediatr. 2022;10:866074. doi: 10.3389/fped.2022.866074

10. Guo C.-Y., Gelfand J.M., Geschwind M.D. Anti-gammaaminobutyric acid receptor type A encephalitis: a review. Curr. Opin. Neurol. 2020;33(3):372–380. doi: 10.1097/WCO.0000000000000814

11. Dade M., Berzero G., Izquierdo C., Giry M., Benazra M., Delattre J.-Y., Psimaras D., Alentorn A. Neurological Syndromes Associated with Anti-GAD Antibodies. Int. J. Mol. Sci. 2020;21(10):3701. doi: 10.3390/ijms21103701

12. Jarius S., Wildemann B. ‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/ DNER, other antibodies, diagnostic pitfalls, summary and outlook. J. Neuroinfl ammation. 2015;12:168. doi: 10.1186/s12974-015-0358-9

13. Venkatraman A., Opal P. Paraneoplastic cerebellar degeneration with anti-Yo antibodies — a review. Ann. Clin. Transl. Neurol. 2016;3(8):655–663. doi: 10.1002/acn3.328

14. Shams'ili S., Grefkens J., De Leeuw B., Van den Bent M., Hooijkaas H., Van der Holt B., Vecht C., Smitt P.S. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain. 2003;126(6):1409–1418. doi: 10.1093/brain/awg133

15. Lubarski K., Mania A., Michalak S., Osztynowicz K., Mazur-Melewska K., Figlerowicz M. The Clinical Spectrum of Autoimmune-Mediated Neurological Diseases in Paediatric Population. Brain Sci. 2022;12(5):584. doi: 10.3390/brainsci12050584

16. Segal Y., Bukstein F., Raz M., Aizenstein O., Alcalay Y., Gadoth A. PD-1-inhibitor-induced PCA-2 (MAP1B) Autoimmunity in a Patient with Renal Cell Carcinoma. Cerebellum. 2022;21(2):328–331. doi: 10.1007/s12311-021-01298-9

17. Moragas M., Martínez-Yélamos S., Majós C., FernándezViladrich P., Rubio F., Arbizu T. Rhombencephalitis: a series of 97 patients. Medicine. 2011;90(4):256–261. doi: 10.1097/MD.0b013e318224b5af

18. Jarius S., Bräuninger S., Chung H.-Y., Geis C., Haas J., Komorowski L., Wildemann B., Roth C. Inositol 1,4,5-trisphosphate receptor type 1 autoantibody (ITPR1-IgG/anti-Sj)associated autoimmune cerebellar ataxia, encephalitis and peripheral neuropathy: review of the literature. J. Neuroinfl ammation. 2022;19(1):196. doi: 10.1186/s12974-022-02545-4

19. Kuang Z., Baizabal-Carvallo J. F., Mofatteh M., Xie S., Wang Z., Chen Y. Anti-homer-3 Antibody Encephalitis in a 10-Year-Old Child: Case Report and Review of the Literature. Front. Neurol. 2022;13:929778. doi: 10.3389/fneur.2022.929778

20. Xiao J., Fu P.-C., Li Z.-J. Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy. BMC Neurol. 2022;22(1):129. doi: 10.1186/ s12883-022-02649-7

21. Irie K.-I., Tateishi T., Moritaka T., Sakurada N., Kikuchi S., Taniwaki T. Anti-glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus initially presenting with one-sided stiff face: A case report. Front. Neurol. 2022;13:1021437. doi: 10.3389/fneur.2022.1021437

22. Khojah O., Makkawi S., Alghamdi S. Anti-mGluR1 encephalitis: Case illustration and systematic review. Front. Neurol. 2023;14:1142160. doi: 10.3389/fneur.2023.1142160

23. Chen S., Ren H., Lin F., Fan S., Cao Y., Zhao W., Guan H. Anti-metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review. Brain Behav. 2023;13(5):e3003. doi: 10.1002/brb3.3003

24. Zhu B., Sun M., Yang T., Yu H., Wang L. Clinical, imaging features and outcomes of patients with anti-GFAP antibodies: a retrospective study. Front. Immunol. 2023;14:1106490. doi: 10.3389/fimmu.2023.1106490

25. Vitaliani R., Mason W., Ances B., Zwerdling T., Jiang Z., Dalmau J. Paraneoplastic Encephalitis, Psychiatric Symptoms, and Hypoventilation in Ovarian Teratoma. Ann. Neurol. 2005;58(4):594–604. doi: 10.1002/ana.20614

26. Smitt P. S., Grefkens J., De Leeuw B., Van den Bent M., Van Putten W., Hooijkaas H., Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J. Neurol. 2002;249(6):745–753. doi: 10.1007/s00415-002-0706-4

27. Sabater L., Gómez-Choco M., Saiz A., Graus F. BR serine/threonine kinase 2: A new autoantigen in paraneoplastic limbic encephalitis. J. Neuroimmunol. 2005;170(1–2):186–190. doi: 10.1016/j.jneuroim.2005.08.011

28. Chan K. H., Vernino S., Lennon V. A. ANNA-3 Anti-Neuronal Nuclear Antibody: Marker of Lung Cancer-Related Autoimmunity. Ann. Neurol. 2001;50(3):301–311. doi: 10.1002/ana.1127

29. Salama S., Khan M., Pardo S., Izbudak I., Levy M. MOG antibody associated encephalomyelitis. Mult. Scler. 2019;25(11):1427–1433. doi: 10.1177/1352458519837705

30. Zhang Y.-Z. H., Ni Y., Gao Y.-N., Shen D. D., He L., Yin D., Meng H.-Y., Zhou Q.-M., Hu J., Chen S. Anti-IgLON5 disease: a novel topic beyond neuroimmunology. Neural. Regen. Res. 2023;18(5):1017–1022. doi: 10.4103/1673-5374.355742

31. Jarius S., Wildemann B. ‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC. J. Neuroinfl ammation. 2015;12:167. doi: 10.1186/s12974-015-0357-x

32. Dai X., Kuang L., Feng L., Yi X., Tang W., Liao Q., Long X., Wang J., Li J., Yang H., Xiao B., Li G., Chen S. Anti-Dopamine Receptor 2 Antibody-Positive Encephalitis in Adolescent. Front. Neurol. 2020;11:471. doi: 10.3389/fneur.2020.00471

33. De Bruijn M.A.A.M., Bruijstens A.L., Bastiaansen A.E.M., Van Sonderen A., Schreurs M.W.J., Sillevis Smitt P.A.E., Hintzen R.Q., Neuteboom R.F., Titulaer M.J. Pediatric autoimmune encephalitis. Neurol. Neuroimmunol. Neuroinfl amm. 2020;7(3):e682. doi:10.1212/NXI.0000000000000682

34. Hardy D. Autoimmune Encephalitis in Children. Pediatr. Neurol. 2022;132:56–66. doi: 10.1016/j.pediatrneurol.2022.05.004

35. Kang Q., Liao H., Yang L., Fang H., Ning Z., Liao C., Gan S., Wu L. Clinical analysis of 173 pediatric patients with antibodymediated autoimmune diseases of the central nervous system: a single-center cohort study. Front. Immunol. 2023;14:1140872. doi: 10.3389/fimmu.2023.1140872

36. Tanaka K., Kawamura M., Sakimura K., Kato N. Significance of Autoantibodies in Autoimmune Encephalitis in Relation to Antigen Localization: An Outline of Frequently Reported Autoantibodies with a Non-Systematic Review. Int. J. Mol. Sci. 2020;21(14):4941. doi: 10.3390/ijms21144941