Predictive models in the diagnosis and treatment of autoimmune epilepsy

Divyanshu Dubey, Jaysingh Singh, Jeffrey W. Britton, Sean J Pittock, Eoin Flanagan, Vanda A Lennon, Jan-Mendelt Tillema, Elaine C Wirrell, Cheolsu Shin, Elson So, Gregory D Cascino, Dean Marko Wingerchuk, Matthew T. Hoerth, Jerry J. Shih, Katherine C Nickels, Andrew McKeon

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28 Citations (Scopus)

Abstract

Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. Methods: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. Results: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. Significance: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Original languageEnglish (US)
JournalEpilepsia
DOIs
StateAccepted/In press - 2017

Fingerprint

Epilepsy
Immunotherapy
Antibodies
Seizures
Therapeutics
Movement Disorders
Autoantibodies
Cerebrospinal Fluid
Sensitivity and Specificity
Brain Diseases
Surface Antigens
Dementia
Blood Proteins
Membrane Proteins
Central Nervous System
Retrospective Studies
Magnetic Resonance Imaging
Cell Membrane

Keywords

  • Autoimmune limbic encephalitis
  • Diagnosis
  • Epilepsy
  • Immunotherapy
  • Paraneoplastic limbic encephalitis
  • Predictive model

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

@article{4e7d0cbccd664bd09a027d0cebd957dd,
title = "Predictive models in the diagnosis and treatment of autoimmune epilepsy",
abstract = "Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. Methods: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50{\%} reduction of seizure frequency at the first follow-up. Results: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7{\%} vs. 21.6{\%}, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7{\%} and 77.9{\%}, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5{\%} and 83.8{\%}, respectively. Significance: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.",
keywords = "Autoimmune limbic encephalitis, Diagnosis, Epilepsy, Immunotherapy, Paraneoplastic limbic encephalitis, Predictive model",
author = "Divyanshu Dubey and Jaysingh Singh and Britton, {Jeffrey W.} and Pittock, {Sean J} and Eoin Flanagan and Lennon, {Vanda A} and Jan-Mendelt Tillema and Wirrell, {Elaine C} and Cheolsu Shin and Elson So and Cascino, {Gregory D} and Wingerchuk, {Dean Marko} and Hoerth, {Matthew T.} and Shih, {Jerry J.} and Nickels, {Katherine C} and Andrew McKeon",
year = "2017",
doi = "10.1111/epi.13797",
language = "English (US)",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Predictive models in the diagnosis and treatment of autoimmune epilepsy

AU - Dubey, Divyanshu

AU - Singh, Jaysingh

AU - Britton, Jeffrey W.

AU - Pittock, Sean J

AU - Flanagan, Eoin

AU - Lennon, Vanda A

AU - Tillema, Jan-Mendelt

AU - Wirrell, Elaine C

AU - Shin, Cheolsu

AU - So, Elson

AU - Cascino, Gregory D

AU - Wingerchuk, Dean Marko

AU - Hoerth, Matthew T.

AU - Shih, Jerry J.

AU - Nickels, Katherine C

AU - McKeon, Andrew

PY - 2017

Y1 - 2017

N2 - Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. Methods: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. Results: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. Significance: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

AB - Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. Methods: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up. Results: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively. Significance: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

KW - Autoimmune limbic encephalitis

KW - Diagnosis

KW - Epilepsy

KW - Immunotherapy

KW - Paraneoplastic limbic encephalitis

KW - Predictive model

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U2 - 10.1111/epi.13797

DO - 10.1111/epi.13797

M3 - Article

C2 - 28555833

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JO - Epilepsia

JF - Epilepsia

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