Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies targeting the leucine-rich glioma-inactivated protein 1

Anteneh Feyissa, Christopher Lamb, Sean J Pittock, Avi Gadoth, Andrew McKeon, Christopher Jon Klein, Jeffrey W. Britton

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 (LGI1-Ab) autoimmune epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures. Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic–clonic (GTCs) (n = 28, 50%), and focal non-motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.

Original languageEnglish (US)
Pages (from-to)348-356
Number of pages9
JournalEpilepsia Open
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2018

Fingerprint

Leucine
Glioma
Anticonvulsants
Epilepsy
Seizures
Drug Therapy
Antibodies
Proteins
Immunotherapy
etiracetam
Voltage-Gated Potassium Channels
Sodium Channels
Valproic Acid
Age of Onset

Keywords

  • Autoimmune encephalitis
  • Drug-resistant epilepsy
  • Faciobrachial dystonic seizures
  • Sodium channel blockers
  • Voltage-gated potassium channel complex

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies targeting the leucine-rich glioma-inactivated protein 1. / Feyissa, Anteneh; Lamb, Christopher; Pittock, Sean J; Gadoth, Avi; McKeon, Andrew; Klein, Christopher Jon; Britton, Jeffrey W.

In: Epilepsia Open, Vol. 3, No. 3, 01.09.2018, p. 348-356.

Research output: Contribution to journalArticle

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abstract = "Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 (LGI1-Ab) autoimmune epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures. Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66{\%} (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63{\%}), followed by focal with impaired awareness (FIA) (n = 29, 52{\%}), generalized tonic–clonic (GTCs) (n = 28, 50{\%}), and focal non-motor seizures with preserved awareness (n = 28, 50{\%}). The majority had more than one seizure type (n = 49, 88{\%}; median = 2.5). Thirty-eight patients (68{\%}) became seizure free: 29 (76{\%}) with immunotherapy, 3 (5{\%}) with AEDs alone, 2 (3{\%}) with AEDs before any immunotherapy, and 4 (7{\%}) with AEDs after immunotherapy. Levetiracetam (n = 47, 84{\%}) and valproic acid (n = 21, 38{\%}) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9{\%}). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.",
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AU - Feyissa, Anteneh

AU - Lamb, Christopher

AU - Pittock, Sean J

AU - Gadoth, Avi

AU - McKeon, Andrew

AU - Klein, Christopher Jon

AU - Britton, Jeffrey W.

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N2 - Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 (LGI1-Ab) autoimmune epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures. Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic–clonic (GTCs) (n = 28, 50%), and focal non-motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.

AB - Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 (LGI1-Ab) autoimmune epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures. Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic–clonic (GTCs) (n = 28, 50%), and focal non-motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.

KW - Autoimmune encephalitis

KW - Drug-resistant epilepsy

KW - Faciobrachial dystonic seizures

KW - Sodium channel blockers

KW - Voltage-gated potassium channel complex

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