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Neurological Sciences

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02-11-2023 | Autoimmune Encephalitis | Original Article

Predictive value of persistent antibodies at 6 months for relapse in neuronal surface antibody-associated autoimmune encephalitis

Authors: Fang Zhang, Yingshi Guo, Miaomiao Liu, Huijun Shen, Hong Zhou, Yujie Yi, Jie Wang

Published in: Neurological Sciences | Issue 4/2024

Abstract

Background

For patients with neuronal surface antibody-associated autoimmune encephalitis (NSAE) whose clinical symptoms gradually improve, the recommended course of immunotherapy in China is about 6 months. We aim to explore the relationship between persistent antibody positivity when immunotherapy is discontinued at 6 months and subsequent relapse.

Methods

Prospective inclusion of NSAE patients with clinical remission after 6-month immunotherapy. Their antibody titers and other clinical data were collected at onset and 6 months later. Based on the antibody test results at 6 months, patients were divided into an antibody-persistent group and an antibody-negative conversion group, and then the rate of relapse between the two groups were compared.

Results

The study included 28 NSAE patients who were antibody-positive at diagnosis. After 6-month immunotherapy, there were 16 (57.1%) cases with persistent antibodies and 12 (42.9%) cases with antibody-negative conversion. In the acute phase of onset, seizures were more common in patients with persistent antibodies (87.5% vs. 50.0%, p = 0.044). During a mean follow-up period of 22 months, patients with persistent antibodies were more likely to experience relapse than those with antibody-negative conversion (37.5% vs. 0.0%, p = 0.024). There were no significant differences in antibody types, CSF findings, results of MRI and EEG, tumor combination, immunotherapy, and long-term outcome between the two groups (p > 0.05).

Conclusions

For patients with persistent antibodies when immunotherapy is discontinued at 6 months, persistent antibody positivity was associated with a higher relapse rate.

Graus F, Titulaer MJ, Balu R et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15(4):391–404. https://doi.org/10.1016/S1474-4422(15)00401-9CrossRefPubMedPubMedCentral

Chinese Society of Neuroinfectious Diseases and Cerebrospinal Fluid Cytology (2022) Expert consensus on diagnosis and treatment of autoimmune encephalitis in China. Chin J Neurol 55(9):931–949. https://doi.org/10.3760/cma.j.cn113694-20220219-00118CrossRef

Lai QL, Cai MT, Zheng Y et al (2022) Evaluation of csf albumin quotient in neuronal surface antibody-associated autoimmune encephalitis. Fluids Barriers Cns 19(1):93. https://doi.org/10.1186/s12987-022-00392-2CrossRefPubMedPubMedCentral

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. https://doi.org/10.1016/S1474-4422(12)70310-1CrossRefPubMedPubMedCentral

Rodriguez A, Klein CJ, Sechi E et al (2022) Lgi1 antibody encephalitis: acute treatment comparisons and outcome. J Neurol Neurosurg Psychiatry 93(3):309–315. https://doi.org/10.1136/jnnp-2021-327302CrossRefPubMed

Varley JA, Strippel C, Handel A, Irani SR (2023) Autoimmune encephalitis: recent clinical and biological advances. J Neurol. https://doi.org/10.1007/s00415-023-11685-3CrossRefPubMedPubMedCentral

Zhong R, Chen Q, Zhang X, Zhang H, Lin W (2022) Relapses of anti-nmdar, anti-gababr and anti-lgi1 encephalitis: a retrospective cohort study. Front Immunol 13:918396. https://doi.org/10.3389/fimmu.2022.918396CrossRefPubMedPubMedCentral

Gresa-Arribas N, Titulaer MJ, Torrents A et al (2014) Antibody titres at diagnosis and during follow-up of anti-nmda receptor encephalitis: a retrospective study. Lancet Neurol 13(2):167–177. https://doi.org/10.1016/S1474-4422(13)70282-5CrossRefPubMed

Ariño H, Armangué T, Petit-Pedrol M et al (2016) Anti-lgi1-associated cognitive impairment: presentation and long-term outcome. Neurology 87(8):759–765. https://doi.org/10.1212/WNL.0000000000003009CrossRefPubMedPubMedCentral

10.

Ciano-Petersen NL, Robert M, Muñiz-Castrillo Set al (2023) Prognostic value of persistent csf antibodies at 12 months in anti-nmdar encephalitis. Neurol Neuroimmunol Neuroinflamm 10(4). https://doi.org/10.1212/NXI.0000000000200108

11.

Gong X, Chen C, Liu X et al (2021) Long-term functional outcomes and relapse of anti-nmda receptor encephalitis. Neurology - Neuroimmunol Neuroinflammation 8(2):e958. https://doi.org/10.1212/NXI.0000000000000958CrossRef

12.

Yu Y, Wu Y, Cao X et al (2021) The clinical features and prognosis of anti-nmdar encephalitis depends on blood brain barrier integrity. Mult Scler Relat Disord 47:102604. https://doi.org/10.1016/j.msard.2020.102604CrossRefPubMed

13.

Nosadini M, Granata T, Matricardi S et al (2019) Relapse risk factors in anti-n-methyl-d-aspartate receptor encephalitis. Dev Med Child Neurol 61(9):1101–1107. https://doi.org/10.1111/dmcn.14267CrossRefPubMed

14.

Wu CY, Wu JD, Chen CC (2021) The association of ovarian teratoma and anti-n-methyl-d-aspartate receptor encephalitis: an updated integrative review. Int J Mol Sci 22(20). https://doi.org/10.3390/ijms222010911

15.

Dalmau J, Gleichman AJ, Hughes EG et al (2008) Anti-nmda-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 7(12):1091–1098. https://doi.org/10.1016/S1474-4422(08)70224-2CrossRefPubMedPubMedCentral

16.

Hughes EG, Peng X, Gleichman AJ et al (2010) Cellular and synaptic mechanisms of anti-nmda receptor encephalitis. J Neurosci 30(17):5866–5875. https://doi.org/10.1523/JNEUROSCI.0167-10.2010CrossRefPubMedPubMedCentral

17.

Lancaster E, Dalmau J (2012) Neuronal autoantigens–pathogenesis, associated disorders and antibody testing. Nat Rev Neurol 8(7):380–390. https://doi.org/10.1038/nrneurol.2012.99CrossRefPubMedPubMedCentral

18.

Gabilondo I, Saiz A, Galán L et al (2011) Analysis of relapses in anti-nmdar encephalitis. Neurology 77(10):996–999. https://doi.org/10.1212/WNL.0b013e31822cfc6bCrossRefPubMed

19.

Dai Y, Zhang J, Ren H et al (2019) Surgical outcomes in patients with anti-n-methyl d-aspartate receptor encephalitis with ovarian teratoma. Am J Obstet Gynecol 221(5):481–485. https://doi.org/10.1016/j.ajog.2019.05.026CrossRef

20.

Leypoldt F, Höftberger R, Titulaer MJ et al (2015) Investigations on cxcl13 in anti-n-methyl-d-aspartate receptor encephalitis: a potential biomarker of treatment response. Jama Neurol 72(2):180–186. https://doi.org/10.1001/jamaneurol.2014.2956CrossRefPubMedPubMedCentral

21.

Ciano-Petersen NL, Cabezudo-García P, Muñiz-Castrillo S, Honnorat J, Serrano-Castro PJ, Oliver-Martos B (2021) Current status of biomarkers in anti-n-methyl-d-aspartate receptor encephalitis. Int J Mol Sci 22(23). https://doi.org/10.3390/ijms222313127

22.

Zeng C, Chen L, Chen B et al (2018) Th17 cells were recruited and accumulated in the cerebrospinal fluid and correlated with the poor prognosis of anti-nmdar encephalitis. Acta Biochim Biophys Sin (Shanghai) 50(12):1266–1273. https://doi.org/10.1093/abbs/gmy137CrossRefPubMed

23.

Wendel EM, Thonke HS, Bertolini A et al (2022) Temporal dynamics of mog antibodies in children with acquired demyelinating syndrome. Neurology - Neuroimmunol Neuroinflammation 9(6):e200035. https://doi.org/10.1212/NXI.0000000000200035CrossRef

24.

Waters P, Fadda G, Woodhall M et al (2020) Serial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. Jama Neurol 77(1):82–93. https://doi.org/10.1001/jamaneurol.2019.2940CrossRefPubMed

25.

López-Chiriboga AS, Majed M, Fryer J et al (2018) Association of mog-igg serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for mog-igg-associated disorders. Jama Neurol 75(11):1355–1363. https://doi.org/10.1001/jamaneurol.2018.1814CrossRefPubMedPubMedCentral

26.

Oliveira LM, Apóstolos-Pereira SL, Pitombeira MS, Bruel TP, Callegaro D, Sato DK (2019) Persistent mog-igg positivity is a predictor of recurrence in mog-igg-associated optic neuritis, encephalitis and myelitis. Mult Scler 25(14):1907–1914. https://doi.org/10.1177/1352458518811597CrossRefPubMed

27.

Alexopoulos H, Kosmidis ML, Dalmau J, Dalakas MC (2011) Paraneoplastic anti-nmdar encephalitis: long term follow-up reveals persistent serum antibodies. J Neurol 258(8):1568–1570. https://doi.org/10.1007/s00415-011-5982-4CrossRefPubMed

28.

Hansen HC, Klingbeil C, Dalmau J, Li W, Weissbrich B, Wandinger KP (2013) Persistent intrathecal antibody synthesis 15 years after recovering from anti-n-methyl-d-aspartate receptor encephalitis. Jama Neurol 70(1):117–119. https://doi.org/10.1001/jamaneurol.2013.585CrossRefPubMedPubMedCentral

29.

de Bruijn M, van Sonderen A, van Coevorden-Hameete MH et al (2019) Evaluation of seizure treatment in anti-lgi1, anti-nmdar, and anti-gaba(b)r encephalitis. Neurology 92(19):e2185–e2196. https://doi.org/10.1212/WNL.0000000000007475CrossRefPubMedPubMedCentral

30.

Liu X, Guo K, Lin J et al (2022) Long-term seizure outcomes in patients with autoimmune encephalitis: a prospective observational registry study update. Epilepsia 63(7):1812–1821. https://doi.org/10.1111/epi.17245CrossRefPubMed

31.

Zhong R, Zhang X, Chen Q, Li M, Guo X, Lin W (2022) Acute symptomatic seizures and risk of epilepsy in autoimmune encephalitis: a retrospective cohort study. Front Immunol 13:813174. https://doi.org/10.3389/fimmu.2022.813174CrossRefPubMedPubMedCentralADS

32.

Shen CH, Fang GL, Yang F et al (2020) Seizures and risk of epilepsy in anti-nmdar, anti-lgi1, and anti-gaba(b) r encephalitis. Ann Clin Transl Neurol 7(8):1392–1399. https://doi.org/10.1002/acn3.51137CrossRefPubMedPubMedCentral

33.

Rada A, Birnbacher R, Gobbi C et al (2021) Seizures associated with antibodies against cell surface antigens are acute symptomatic and not indicative of epilepsy: insights from long-term data. J Neurol 268(3):1059–1069. https://doi.org/10.1007/s00415-020-10250-6CrossRefPubMed

Title: Predictive value of persistent antibodies at 6 months for relapse in neuronal surface antibody-associated autoimmune encephalitis
Authors: Fang Zhang
Yingshi Guo
Miaomiao Liu
Huijun Shen
Hong Zhou
Yujie Yi
Jie Wang
Publication date: 02-11-2023
Publisher: Springer International Publishing
Keywords: Autoimmune Encephalitis
Encephalitis
Anti-NMDA Receptor Encephalitis
Published in: Neurological Sciences / Issue 4/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-023-07151-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Predictive value of persistent antibodies at 6 months for relapse in neuronal surface antibody-associated autoimmune encephalitis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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