Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis

Abstract

Background: Drug resistant epilepsy (DRE) is very common among children and adults and studies had found some related risk factors for DRE, while the results were not consistent. The aim of this study was to identify risk factors for drug-resistant epilepsy.

Methods: Three electronic databases (Medline, Embase and Cochrane library) were searched to identify studies with a cohort design reporting on epidemiologic evidence regarding risk factors for DRE.

Results: The pooled prevalence of DRE in newly diagnosed epilepsy patients was 25% (95% CI 17-32%). Abnormal electroencephalography (EEG) (both slow wave and epileptiform discharges) (RR 2.80; 95% CI 1.95-4.0), status epilepticus (SE) (RR 11.60; 95% CI 7.39-18.22), symptomatic etiology (RR 3.36; 95% CI 2.53-4.46), multiple seizure types (RR 3.66; 95% CI 2.37-5.64) and febrile seizures (RR 3.43; 95% CI 1.95-6.02) were identified as strong risk factors for DRE. In addition, firm conclusions cannot be drawn for poor short-term outcomes of therapy, neurodevelopment delay and high initial seizure frequency for the heterogeneity of study results. The predictive effect of focus onset seizure was not stable after removing one study and switching the effect model. Age of onset was not risk factors for DRE.

Conclusions: The current meta-analysis identified potential risk factors for DRE. The results may contribute to better prevention strategies and treatments for DRE.

Figure 1

Flowchart of the literature search performed. DRE = drug resistant epilepsy.

Figure 2

A. The pooled prevalence of DRE regardless of the number of AEDs. DRE = drug resistant epilepsy, AED = antiepileptic drug. B. The pooled prevalence of DRE by 2 AEDs. DRE = drug resistant epilepsy, AED = antiepileptic drug. C. The pooled prevalence of DRE by 3 AEDs. DRE = drug resistant epilepsy, AED = antiepileptic drug.

Figure 3

A. Pooled results of EEG abnormality for DRE, EEG = electroencephalogram. A-1. Pooled results of EEG slow wave for DRE, EEG = electroencephalogram. A-2. Pooled results of EEG epileptiform discharges for DRE, EEG = electroencephalogram. B. Pooled results of SE for DRE, SE = status epilepticus. C. Pooled results of focus onset seizure for DRE. D. Pooled results of multiple seizure type for DRE. E. Pooled results of symptomatic aetiology for DRE. F. Pooled results of febrile seizures for DRE. G. Pooled results of poor short-term outcome of therapy for DRE. H. Pooled results of neurodevelopment delay for DRE. I. Pooled results of high initial seizure frequency for DRE. I-1. Pooled results of daily seizures for DRE. I-2. Pooled results of seizures more frequent than 10 times for DRE. L. Pooled results of age of onset for DRE. DRE = drug resistant epilepsy.

Figure 3 (Continued)

A. Pooled results of EEG abnormality for DRE, EEG = electroencephalogram. A-1. Pooled results of EEG slow wave for DRE, EEG = electroencephalogram. A-2. Pooled results of EEG epileptiform discharges for DRE, EEG = electroencephalogram. B. Pooled results of SE for DRE, SE = status epilepticus. C. Pooled results of focus onset seizure for DRE. D. Pooled results of multiple seizure type for DRE. E. Pooled results of symptomatic aetiology for DRE. F. Pooled results of febrile seizures for DRE. G. Pooled results of poor short-term outcome of therapy for DRE. H. Pooled results of neurodevelopment delay for DRE. I. Pooled results of high initial seizure frequency for DRE. I-1. Pooled results of daily seizures for DRE. I-2. Pooled results of seizures more frequent than 10 times for DRE. L. Pooled results of age of onset for DRE. DRE = drug resistant epilepsy.

Figure 4

A. Publication bias test of overall prevalence of DRE. DRE = drug-resistant epilepsy. B. Publication bias test of overall prevalence of DRE defined by 2 AEDs. DRE = drug-resistant epilepsy, AED = antiepileptic drug.