In the current study, the prevalence of DRE was 21.3% of the study population. The percentage was similar to that reported by previous cohort studies conducted in referral centers by Kong and colleagues and by Espinosa and colleagues (both used ILAE DRE definition) in which the prevalence was 21.5% and 27.1%, respectively [12, 13].

It was also congruent to the rate of intractable seizures in a Glasgow study (25%) and a French study (prevalence ranged from 15.6% to 22.5%) [14, 15].

However, it was significantly higher than that reported in a previous community-based study in Egypt by Farghaly and colleagues, in which the prevalence of definite intractable patients was 11.4% [16]. This discrepancy can be explained by the difference in the study setting (clinic-based versus population/community-based) with a strong selection bias in clinic-based studies resulting in higher prevalence rates, especially that patients with more severe and poorly controlled epilepsy are more likely to be followed in specialized centers [17].

Previous studies have reported a slight predominance of epilepsy in males compared to females [18]. In our study, there was slight female predominance; however, male gender was found to be a risk factor for DRE in the univariate analysis but did not remain significant in the multivariate analysis. This result was similar to the findings of Farghaly and colleagues and Chentouf and colleagues [19].

In our study, older age was less associated with DRE, and it remained a significant protective factor in the multivariate analysis. This finding comes in agreement with the existing evidence showing that elderly patients have a lower risk for DRE compared to younger patients and seizure control can often be achieved with lower doses of AEDs in this age group [20, 21].

It is known that the duration of epilepsy has an impact on disease severity. In our study, patients with DRE had 4 years more of evolution in average compared to those without DRE. Similar findings were reported by a study of drug-resistant focal epilepsy (DRE group had 6 years more of evolution) [22] and in another study on patients with generalized epilepsy, where patients with DRE had more years of evolution (24.1 versus 14.7) [23].

Age of epilepsy onset has been suggested to be a major predictor of pharmacoresistance. Multiple studies showed that DRE was associated with younger age at the onset especially in the first year of life [24,25,26]. In our study, age at onset of epilepsy was significantly associated with DRE only in the univariate analysis with marginally negative influence (odds ratio = 0.94).

In this study, the etiology of epilepsy was a significant factor affecting the prognosis. Structural/metabolic etiology was identified in 52% of the intractable group compared to 23% of the controlled group. Moreover, this study demonstrated that the presence of neurological deficit and abnormal imaging findings were associated with DRE. These findings coincide with the results of a systemic review by Sultana and colleagues which found that the most frequent reported correlates and predictors of DRE included symptomatic epilepsy and having a neurological deficit [17].

On the other hand, presumed idiopathic/genetic etiology is classically considered as a relatively benign condition and has been previously reported as a protective factor that decreases the risk for DRE [27]. Furthermore, according to a retrospective study by Jiyang and colleagues, idiopathic etiology was not associated with poor outcome on both short-term and long-term prognosis in newly diagnosed patients [28]; similarly, in the current work, idiopathic/genetic etiology was a protective factor against intractability (OR: 0.322, CI 0.117–0.888, p 0.028).

The relation between seizure type and intractability has been inconsistent in previous studies, some showing an increased risk in patients with focal epilepsy [17], whereas others have found a relation between DRE and multiple seizure types [29]. In our study, 89% of the intractable group had generalized seizures and this was significantly associated with DRE, as demonstrated by both univariate and logistic regression analysis.

In the current study, intractable cases had higher initial seizure frequencies (10.7% had daily seizures and 34.7% had weekly seizures), and in the univariate analysis, this was significantly associated with drug resistance. These findings come in agreement with Tripathy et.al and Farghaly et.al who found a similar significant association between initial seizure frequency and intractability [29, 30].

Several studies found a relationship between status epilepticus and intractability. These results were consistent for both adults and children [30]. It could be explained in a bidirectional effect as on one hand, intractability leads to more seizures, SE, therefore, more brain damage and on the other hand, SE especially if prolonged leads to neuronal death, epileptogensis and further intractability. However, in the current study, SE was not a predictive factor for DRE. This finding comes in agreement with Tellez-Zenteno and colleagues who found no association [31].

In a systemic review by Xue ping and colleagues in 2019, EEG abnormality (including slow wave and epileptiform discharge) was reported to be a predictor for intractability [17, 29].

In the current study, there was an association between abnormal EEG findings and DRE in the univariate analysis and when EEG abnormalities were analyzed separately, only focal epileptic activity was a predictive factor for DRE and this comes in line with the aforementioned risk factors and points toward the idea that a structural/metabolic etiology of epilepsy especially when it results in neurological or electrophysiological abnormities is predictive of a more severe course of epilepsy [17].

In the current study, the diagnosis of epilepsy and start of treatment were delayed in a minority of cases and this delay was not associated with increased risk of DRE. This comes in concordance with a study by Parviainen and colleagues, who assessed the diagnostic delay in a cohort of newly diagnosed patients with focal epilepsy, and found no statistically significant association between the diagnostic delay and poor prognosis [32].

Failure of response to the first AED is a powerful prognostic factors influencing subsequent evolution and appearance of pharmacoresistance [33]. Kwan and Brodie reported that among patients who failed to respond to the first drug; only 11% of such patients subsequently became seizure-free compared to 40–55% of those who fail due to side effects. Furthermore, only 13% responded to the second AED and only 3% became seizure-free with two drugs [8].

In the current work, 60% of the intractable group failed to respond to the first AED and about 43% did not achieve lower seizures frequency with subsequent drugs. Both factors were predictors of DRE in the univariate analysis; however, no change in seizures frequency with add-on treatment remained statistically significant in the multivariate analysis.

Prescence of developmental delay is one of the most reported predictive factors for DRE in the pediatric population [34]. Some studies have shown that developmental delay is a common co-morbidity in patients with epilepsy compared to the general population [7, 35]. Similar to previous studies in adult patients, developmental delay has been significantly associated with DRE in the current work [23, 36].

Several other clinical variables have been associated with pharmacoresistance in the literature, such as family history of epilepsy, febrile seizures in infancy and psychiatric comorbidities [22]. The current work did not identify a statistically significant association between these factors and DRE.