Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Nabil Seery; Robb Wesselingh; Paul Beech; Laurie M. McLaughlin; Tiffany Rushen; Amy J. Halliday; Liora Ter Horst; Sarah P. Griffith; Mirasol Forcadela; Tracie H. Tan; Christina Kazzi; Cassie Nesbitt; James Broadley; Katherine Buzzard; Andrew J. Duncan; Wendyl Jude D'Souza; Yang David Tran; Anneke Van Der Walt; Genevieve Skinner; Bruce V. Taylor; Andrew Swayne; Amy Brodtmann; David Gillis; Ernest Gerard Butler; Tomas Kalincik; Udaya K. Seneviratne; Richard A. MacDonell; Stefan Blum; Sudarshini Ramanathan; Charles B. Malpas; Stephen William Reddel; Todd A. Hardy; Terence J. O'Brien; Paul G. Sanfilippo; Helmut Butzkueven; Mastura Monif; for the Australian Autoimmune Encephalitis Consortium

doi:10.1212/NXI.0000000000200412

Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Nabil Seery
, Robb Wesselingh
, Paul Beech
, Laurie M. McLaughlin
, Tiffany Rushen
, Amy J. Halliday
, Liora Ter Horst
, Sarah P. Griffith
, Mirasol Forcadela
, Tracie H. Tan
, Christina Kazzi
, Cassie Nesbitt
, James Broadley
, Katherine Buzzard
, Andrew J. Duncan
, Wendyl Jude D'Souza
, Yang David Tran
, Anneke Van Der Walt
, Genevieve Skinner
, Bruce V. Taylor

Andrew Swayne, Amy Brodtmann, David Gillis, Ernest Gerard Butler, Tomas Kalincik, Udaya K. Seneviratne, Richard A. MacDonell, Stefan Blum, Sudarshini Ramanathan, Charles B. Malpas, Stephen William Reddel, Todd A. Hardy, Terence J. O'Brien, Paul G. Sanfilippo, Helmut Butzkueven, Mastura Monif, for the Australian Autoimmune Encephalitis Consortium

Research output: Contribution to journal › Article › Research › peer-review

18 Citations (Scopus)

Abstract

Background and ObjectivesFew studies have evaluated acute immunotherapy and relapse prevention strategies in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (Ab)-mediated encephalitis. The objective of this study was to analyze the outcomes of acute and long-term immunotherapy strategies in this population.MethodsWe undertook a multicenter cohort study of 55 patients with anti-LGI1 Ab-mediated encephalitis, either recruited prospectively or identified retrospectively from 10 Australian hospitals as part of the Australian Autoimmune Encephalitis Consortium. Clinical data were collected, including treatment durations of all relevant immunotherapies. Clinical outcomes that we examined included (1) time to first clinical relapse, (2) improvement on modified Rankin Scale (mRS), and (3) favorable binary composite clinical-functional outcome at 12 months. A favorable outcome was defined as fulfilling all three of mRS less than 3, a score of 1 or less in the memory dysfunction component of the Clinical Assessment Scale in Autoimmune Encephalitis, and absence of drug-resistant epilepsy.ResultsRituximab, adjusted for concomitant use of other immunotherapies, was associated with increased time to first relapse (hazard ratio 0.10; 95% CI 0.001-0.85; p = 0.03). Intravenous pulsed methylprednisolone was associated with an improvement in mRS (OR 4.48; 95% CI 1.03-21.3; p = 0.048) and a favorable composite clinical-functional outcome (OR 4.96; 95% CI 1.07-27.2; p = 0.049) at 12 months. DiscussionRituximab may be effective at preventing relapses in patients with anti-LGI1 Ab-mediated encephalitis. Acute methylprednisolone treatment may be associated with favorable outcomes at 12 months.Classification of EvidenceThis study provides Class IV evidence that for patients with anti-LGI1 Ab-mediated encephalitis, rituximab prevents relapses and acute methylprednisolone is associated with favorable outcomes at 12 months.

Original language	English
Article number	e200412
Number of pages	12
Journal	Neurology: Neuroimmunology and NeuroInflammation
Volume	12
Issue number	4
DOIs	https://doi.org/10.1212/NXI.0000000000200412
Publication status	Published - 19 Jun 2025

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10.1212/NXI.0000000000200412Licence: CC BY-NC-ND

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Seery, N., Wesselingh, R., Beech, P., McLaughlin, L. M., Rushen, T., Halliday, A. J., Horst, L. T., Griffith, S. P., Forcadela, M., Tan, T. H., Kazzi, C., Nesbitt, C., Broadley, J., Buzzard, K., Duncan, A. J., D'Souza, W. J., Tran, Y. D., Van Der Walt, A., Skinner, G., ... for the Australian Autoimmune Encephalitis Consortium (2025). Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study. Neurology: Neuroimmunology and NeuroInflammation, 12(4), Article e200412. https://doi.org/10.1212/NXI.0000000000200412

@article{5d31d73b143747d8b3a04c750e8eb89c,

title = "Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study",

abstract = "Background and ObjectivesFew studies have evaluated acute immunotherapy and relapse prevention strategies in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (Ab)-mediated encephalitis. The objective of this study was to analyze the outcomes of acute and long-term immunotherapy strategies in this population.MethodsWe undertook a multicenter cohort study of 55 patients with anti-LGI1 Ab-mediated encephalitis, either recruited prospectively or identified retrospectively from 10 Australian hospitals as part of the Australian Autoimmune Encephalitis Consortium. Clinical data were collected, including treatment durations of all relevant immunotherapies. Clinical outcomes that we examined included (1) time to first clinical relapse, (2) improvement on modified Rankin Scale (mRS), and (3) favorable binary composite clinical-functional outcome at 12 months. A favorable outcome was defined as fulfilling all three of mRS less than 3, a score of 1 or less in the memory dysfunction component of the Clinical Assessment Scale in Autoimmune Encephalitis, and absence of drug-resistant epilepsy.ResultsRituximab, adjusted for concomitant use of other immunotherapies, was associated with increased time to first relapse (hazard ratio 0.10; 95\% CI 0.001-0.85; p = 0.03). Intravenous pulsed methylprednisolone was associated with an improvement in mRS (OR 4.48; 95\% CI 1.03-21.3; p = 0.048) and a favorable composite clinical-functional outcome (OR 4.96; 95\% CI 1.07-27.2; p = 0.049) at 12 months. DiscussionRituximab may be effective at preventing relapses in patients with anti-LGI1 Ab-mediated encephalitis. Acute methylprednisolone treatment may be associated with favorable outcomes at 12 months.Classification of EvidenceThis study provides Class IV evidence that for patients with anti-LGI1 Ab-mediated encephalitis, rituximab prevents relapses and acute methylprednisolone is associated with favorable outcomes at 12 months.",

author = "Nabil Seery and Robb Wesselingh and Paul Beech and McLaughlin, \{Laurie M.\} and Tiffany Rushen and Halliday, \{Amy J.\} and Horst, \{Liora Ter\} and Griffith, \{Sarah P.\} and Mirasol Forcadela and Tan, \{Tracie H.\} and Christina Kazzi and Cassie Nesbitt and James Broadley and Katherine Buzzard and Duncan, \{Andrew J.\} and D'Souza, \{Wendyl Jude\} and Tran, \{Yang David\} and \{Van Der Walt\}, Anneke and Genevieve Skinner and Taylor, \{Bruce V.\} and Andrew Swayne and Amy Brodtmann and David Gillis and Butler, \{Ernest Gerard\} and Tomas Kalincik and Seneviratne, \{Udaya K.\} and MacDonell, \{Richard A.\} and Stefan Blum and Sudarshini Ramanathan and Malpas, \{Charles B.\} and Reddel, \{Stephen William\} and Hardy, \{Todd A.\} and O'Brien, \{Terence J.\} and Sanfilippo, \{Paul G.\} and Helmut Butzkueven and Mastura Monif and \{for the Australian Autoimmune Encephalitis Consortium\}",

note = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2025",

month = jun,

day = "19",

doi = "10.1212/NXI.0000000000200412",

language = "English",

volume = "12",

journal = "Neurology: Neuroimmunology and NeuroInflammation",

issn = "2332-7812",

publisher = "Ovid Technologies (Wolters Kluwer) - American Academy of Neurology",

number = "4",

}

Seery, N , Wesselingh, R, Beech, P, McLaughlin, LM, Rushen, T, Halliday, AJ, Horst, LT, Griffith, SP, Forcadela, M, Tan, TH , Kazzi, C, Nesbitt, C, Broadley, J, Buzzard, K, Duncan, AJ, D'Souza, WJ, Tran, YD, Van Der Walt, A, Skinner, G, Taylor, BV, Swayne, A, Brodtmann, A, Gillis, D, Butler, EG, Kalincik, T, Seneviratne, UK, MacDonell, RA, Blum, S, Ramanathan, S, Malpas, CB, Reddel, SW, Hardy, TA, O'Brien, TJ, Sanfilippo, PG, Butzkueven, H , Monif, M & for the Australian Autoimmune Encephalitis Consortium 2025, 'Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study', Neurology: Neuroimmunology and NeuroInflammation, vol. 12, no. 4, e200412. https://doi.org/10.1212/NXI.0000000000200412

TY - JOUR

T1 - Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis

T2 - A Multicenter Cohort Study

AU - Seery, Nabil

AU - Wesselingh, Robb

AU - Beech, Paul

AU - McLaughlin, Laurie M.

AU - Rushen, Tiffany

AU - Halliday, Amy J.

AU - Horst, Liora Ter

AU - Griffith, Sarah P.

AU - Forcadela, Mirasol

AU - Tan, Tracie H.

AU - Kazzi, Christina

AU - Nesbitt, Cassie

AU - Broadley, James

AU - Buzzard, Katherine

AU - Duncan, Andrew J.

AU - D'Souza, Wendyl Jude

AU - Tran, Yang David

AU - Van Der Walt, Anneke

AU - Skinner, Genevieve

AU - Taylor, Bruce V.

AU - Swayne, Andrew

AU - Brodtmann, Amy

AU - Gillis, David

AU - Butler, Ernest Gerard

AU - Kalincik, Tomas

AU - Seneviratne, Udaya K.

AU - MacDonell, Richard A.

AU - Blum, Stefan

AU - Ramanathan, Sudarshini

AU - Malpas, Charles B.

AU - Reddel, Stephen William

AU - Hardy, Todd A.

AU - O'Brien, Terence J.

AU - Sanfilippo, Paul G.

AU - Butzkueven, Helmut

AU - Monif, Mastura

AU - for the Australian Autoimmune Encephalitis Consortium

PY - 2025/6/19

Y1 - 2025/6/19

N2 - Background and ObjectivesFew studies have evaluated acute immunotherapy and relapse prevention strategies in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (Ab)-mediated encephalitis. The objective of this study was to analyze the outcomes of acute and long-term immunotherapy strategies in this population.MethodsWe undertook a multicenter cohort study of 55 patients with anti-LGI1 Ab-mediated encephalitis, either recruited prospectively or identified retrospectively from 10 Australian hospitals as part of the Australian Autoimmune Encephalitis Consortium. Clinical data were collected, including treatment durations of all relevant immunotherapies. Clinical outcomes that we examined included (1) time to first clinical relapse, (2) improvement on modified Rankin Scale (mRS), and (3) favorable binary composite clinical-functional outcome at 12 months. A favorable outcome was defined as fulfilling all three of mRS less than 3, a score of 1 or less in the memory dysfunction component of the Clinical Assessment Scale in Autoimmune Encephalitis, and absence of drug-resistant epilepsy.ResultsRituximab, adjusted for concomitant use of other immunotherapies, was associated with increased time to first relapse (hazard ratio 0.10; 95% CI 0.001-0.85; p = 0.03). Intravenous pulsed methylprednisolone was associated with an improvement in mRS (OR 4.48; 95% CI 1.03-21.3; p = 0.048) and a favorable composite clinical-functional outcome (OR 4.96; 95% CI 1.07-27.2; p = 0.049) at 12 months. DiscussionRituximab may be effective at preventing relapses in patients with anti-LGI1 Ab-mediated encephalitis. Acute methylprednisolone treatment may be associated with favorable outcomes at 12 months.Classification of EvidenceThis study provides Class IV evidence that for patients with anti-LGI1 Ab-mediated encephalitis, rituximab prevents relapses and acute methylprednisolone is associated with favorable outcomes at 12 months.

AB - Background and ObjectivesFew studies have evaluated acute immunotherapy and relapse prevention strategies in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody (Ab)-mediated encephalitis. The objective of this study was to analyze the outcomes of acute and long-term immunotherapy strategies in this population.MethodsWe undertook a multicenter cohort study of 55 patients with anti-LGI1 Ab-mediated encephalitis, either recruited prospectively or identified retrospectively from 10 Australian hospitals as part of the Australian Autoimmune Encephalitis Consortium. Clinical data were collected, including treatment durations of all relevant immunotherapies. Clinical outcomes that we examined included (1) time to first clinical relapse, (2) improvement on modified Rankin Scale (mRS), and (3) favorable binary composite clinical-functional outcome at 12 months. A favorable outcome was defined as fulfilling all three of mRS less than 3, a score of 1 or less in the memory dysfunction component of the Clinical Assessment Scale in Autoimmune Encephalitis, and absence of drug-resistant epilepsy.ResultsRituximab, adjusted for concomitant use of other immunotherapies, was associated with increased time to first relapse (hazard ratio 0.10; 95% CI 0.001-0.85; p = 0.03). Intravenous pulsed methylprednisolone was associated with an improvement in mRS (OR 4.48; 95% CI 1.03-21.3; p = 0.048) and a favorable composite clinical-functional outcome (OR 4.96; 95% CI 1.07-27.2; p = 0.049) at 12 months. DiscussionRituximab may be effective at preventing relapses in patients with anti-LGI1 Ab-mediated encephalitis. Acute methylprednisolone treatment may be associated with favorable outcomes at 12 months.Classification of EvidenceThis study provides Class IV evidence that for patients with anti-LGI1 Ab-mediated encephalitis, rituximab prevents relapses and acute methylprednisolone is associated with favorable outcomes at 12 months.

UR - https://www.scopus.com/pages/publications/105009275870

U2 - 10.1212/NXI.0000000000200412

DO - 10.1212/NXI.0000000000200412

M3 - Article

C2 - 40537079

AN - SCOPUS:105009275870

SN - 2332-7812

VL - 12

JO - Neurology: Neuroimmunology and NeuroInflammation

JF - Neurology: Neuroimmunology and NeuroInflammation

IS - 4

M1 - e200412

ER -

Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study

Abstract

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Autoimmune Encephalitis - a rare and debilitating neurological illness affecting the Australian population. A study of the Australian Autoimmune Encephalitis Consortium.

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Acute and Long-Term Immune-Treatment Strategies in Anti-LGI1 Antibody-Mediated Encephalitis: A Multicenter Cohort Study

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Autoimmune Encephalitis - a rare and debilitating neurological illness affecting the Australian population. A study of the Australian Autoimmune Encephalitis Consortium.

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