Yi Li1, Sarah Tymchuk2, John Barry3, Srikanth Muppidi4, Scheherazade Le1. 1. Stanford Comprehensive Epilepsy Center, Stanford University, Palo Alto, CA, USA. 2. Department of Psychiatry, University of Alberta Hospital, Alberta, Canada. 3. Stanford Department of Psychiatry, Stanford University, Palo Alto, CA, USA. 4. Stanford Department of Neurology, Stanford University, Palo Alto, CA, USA.
Abstract
OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. METHODS: We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.
OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. METHODS: We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.