The importance of early immunotherapy in patients with faciobrachial dystonic seizures

Julia Thompson, Mian Bi, Andrew G Murchison, Mateusz Makuch, Christian G Bien, Kon Chu, Pue Farooque, Jeffrey M Gelfand, Michael D Geschwind, Lawrence J Hirsch, Ernest Somerville, Bethan Lang, Angela Vincent, Maria I Leite, Patrick Waters, Sarosh R Irani, Faciobrachial Dystonic Seizures Study Group, Zsolt Illés (Member of author group)

Research output: Contribution to journalJournal articleResearchpeer-review

39 Downloads (Pure)

Abstract

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

Original languageEnglish
JournalBrain
Volume141
Issue number2
Pages (from-to)348-356
ISSN0006-8950
DOIs
Publication statusPublished - 1. Feb 2018

Fingerprint

Leucine
Glioma
Limbic Encephalitis
Cognitive Dysfunction
Cognition
Electroencephalography
Serum

Keywords

  • cognitive impairment
  • faciobrachial dystonic seizures
  • immunotherapy
  • leucine-rich glioma-inactivated 1
  • seizures

Cite this

Thompson, J., Bi, M., Murchison, A. G., Makuch, M., Bien, C. G., Chu, K., ... Illés, Z. (2018). The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain, 141(2), 348-356. https://doi.org/10.1093/brain/awx323
Thompson, Julia ; Bi, Mian ; Murchison, Andrew G ; Makuch, Mateusz ; Bien, Christian G ; Chu, Kon ; Farooque, Pue ; Gelfand, Jeffrey M ; Geschwind, Michael D ; Hirsch, Lawrence J ; Somerville, Ernest ; Lang, Bethan ; Vincent, Angela ; Leite, Maria I ; Waters, Patrick ; Irani, Sarosh R ; Faciobrachial Dystonic Seizures Study Group ; Illés, Zsolt. / The importance of early immunotherapy in patients with faciobrachial dystonic seizures. In: Brain. 2018 ; Vol. 141, No. 2. pp. 348-356.
@article{45bfe5742ff5424886a7bb8b177a81b5,
title = "The importance of early immunotherapy in patients with faciobrachial dystonic seizures",
abstract = "Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10{\%}) patients. By contrast, 51{\%} showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56{\%} developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.",
keywords = "cognitive impairment, faciobrachial dystonic seizures, immunotherapy, leucine-rich glioma-inactivated 1, seizures",
author = "Julia Thompson and Mian Bi and Murchison, {Andrew G} and Mateusz Makuch and Bien, {Christian G} and Kon Chu and Pue Farooque and Gelfand, {Jeffrey M} and Geschwind, {Michael D} and Hirsch, {Lawrence J} and Ernest Somerville and Bethan Lang and Angela Vincent and Leite, {Maria I} and Patrick Waters and Irani, {Sarosh R} and {Faciobrachial Dystonic Seizures Study Group} and Zsolt Ill{\'e}s",
note = "{\circledC} The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.",
year = "2018",
month = "2",
day = "1",
doi = "10.1093/brain/awx323",
language = "English",
volume = "141",
pages = "348--356",
journal = "Brain",
issn = "0006-8950",
publisher = "Heinemann",
number = "2",

}

Thompson, J, Bi, M, Murchison, AG, Makuch, M, Bien, CG, Chu, K, Farooque, P, Gelfand, JM, Geschwind, MD, Hirsch, LJ, Somerville, E, Lang, B, Vincent, A, Leite, MI, Waters, P, Irani, SR, Faciobrachial Dystonic Seizures Study Group & Illés, Z 2018, 'The importance of early immunotherapy in patients with faciobrachial dystonic seizures', Brain, vol. 141, no. 2, pp. 348-356. https://doi.org/10.1093/brain/awx323

The importance of early immunotherapy in patients with faciobrachial dystonic seizures. / Thompson, Julia; Bi, Mian; Murchison, Andrew G; Makuch, Mateusz; Bien, Christian G; Chu, Kon; Farooque, Pue; Gelfand, Jeffrey M; Geschwind, Michael D; Hirsch, Lawrence J; Somerville, Ernest; Lang, Bethan; Vincent, Angela; Leite, Maria I; Waters, Patrick; Irani, Sarosh R; Faciobrachial Dystonic Seizures Study Group ; Illés, Zsolt (Member of author group).

In: Brain, Vol. 141, No. 2, 01.02.2018, p. 348-356.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The importance of early immunotherapy in patients with faciobrachial dystonic seizures

AU - Thompson, Julia

AU - Bi, Mian

AU - Murchison, Andrew G

AU - Makuch, Mateusz

AU - Bien, Christian G

AU - Chu, Kon

AU - Farooque, Pue

AU - Gelfand, Jeffrey M

AU - Geschwind, Michael D

AU - Hirsch, Lawrence J

AU - Somerville, Ernest

AU - Lang, Bethan

AU - Vincent, Angela

AU - Leite, Maria I

AU - Waters, Patrick

AU - Irani, Sarosh R

AU - Faciobrachial Dystonic Seizures Study Group

A2 - Illés, Zsolt

N1 - © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

AB - Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

KW - cognitive impairment

KW - faciobrachial dystonic seizures

KW - immunotherapy

KW - leucine-rich glioma-inactivated 1

KW - seizures

U2 - 10.1093/brain/awx323

DO - 10.1093/brain/awx323

M3 - Journal article

C2 - 29272336

VL - 141

SP - 348

EP - 356

JO - Brain

JF - Brain

SN - 0006-8950

IS - 2

ER -

Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain. 2018 Feb 1;141(2):348-356. https://doi.org/10.1093/brain/awx323