Sufficient knowledge of gender differences in epilepsy is still lacking, and the consequences of epilepsy on both sexes are not adequately approached. To our knowledge, this is the first report exploring sex differences in psychosocial issues, seizure types, etiological features, and utilization patterns of AEDs in people with chronic epilepsy in Cairo, Egypt.
Patients’ demographic and social characteristics
The mean age of onset of epilepsy in our cohort was 26 ± 12.414; this was relatively higher than other studies [14] but may be explained by the presence of a specialized pediatric hospital in our vicinity.
Both illiteracy (29.2%) and unemployment (males 35.2%, females 64.71%) were higher in our cohort compared to the general population (illiteracy 20.9%; unemployment 9.4% in males and 24.2% in females) as reported by the Central Agency for Public Mobilization and Statistics (CAPMAS) of Egypt in 2015 [15]. When comparing both sexes, females were more illiterate and significantly higher numbers were unemployed.
Hazardous risks at workplaces were reported only by males (p ˂ 0.00) and included handling sharp objects or heavy machines, long-hour drivers, builders, and exposure to fire as bakers.
Our study showed that less epileptic patients had ever been married (66.1% male and 80.4% females) in comparison to the general statistics (80% male and 90% females) [16], with more single epileptic males than females.
This significant psychosocial impact and the diverse effect of epilepsy on both sexes was also reported by others [17] and may be related, in general, to the epilepsy stigma, in addition to the males’ higher social responsibilities [18] and the females’ sociocultural restrictions.
The rate of drug abuse in our cohort (13.8%) was higher than that found in a recent cross-sectional, community-based survey on almost all Egyptian governments [19], which reported that about 6.7% of the Egyptians were dealing regularly with substance(s). In concordance with our results, they found significantly higher numbers of male abusers (15.8% males versus 2.2% females). Similarly, Najafi and his colleagues [20], found drug abuse to be more frequent in epileptic patients compared to the general population, with the most frequent substance abused being tramadol.
Seizure types and epilepsy classification
The relative dominance of generalized epilepsies as seizure type is evident in several Egyptian [21], Arabian [22], and developing countries’ studies [23]. However, some epidemiological Egyptian [24] [25] and developed countries’ studies [26] reported the predominance of focal seizures. It is expected that in developing countries, in which more symptomatic epilepsy is found, a higher rate of focal seizures should be reported. However, in hospital-based studies, there is greater under-representation of focal epilepsy because of less frequent access for such patients to the hospital due to the less frightening aspect of these seizures, inferring a methodological rather than any real geographic difference.
Our results showed that more females complained of more than one seizure type and the same results were shown by Mullins and his colleagues [27]; however, they reported multi-seizure (> 2) type to be equal in both sexes, an observation that we recommend to be further studied. They also found that idiopathic generalized epilepsy (IGE) is more common in females; in our cohort, this was true for JME, IGTC, and TLE, but juvenile absence epilepsy (JAE) was more common in males (p = 0.02). However, due to the few numbers of subjects in this group, we suggest that our results would be interpreted with caution.
Seizures pattern and control
The overall reporting of precipitating factors was 20.3%; this is less than what was mentioned in previous studies [8]. We relate such differences to methodological issues as most of those studies used predesigned, close-ended questionnaires while we recorded what was mentioned in the patients’ files during their clinic interviews.
The higher reporting of precipitating factors by our female patients may be related to their having an additional factor related to hormonal changes during menstruation causing changes in seizure frequency in association with menstrual cycles [28]. It is also plausible that differences in both brain-derived and systemically derived estrogens between sexes may lead to differences in responses to the inciting event of the seizure [29].
Similarly, Maiwald and colleagues [30], also found that, out of 500 patients with epilepsy, 31 (6%) claimed to sense prodromal symptoms and most participants were females.
While differences in symptom reporting based upon sex are due to psychological, biological, or sociological factors remain unclear, the impact of one or all of these factors on epilepsy is points requiring further study [29].
Analysis of seizure timing revealed that males suffered from more diurnal seizures. In the context that males had a significantly higher number of GTCs, we find our results close to Fernández and his colleagues [31], who stated that evolution of GTCs peaks at 6–9 am; however, another study [32] found that tonic-clonic seizure distribution showed no difference between day and night. This disagreement can be related to methodological issues as we depended on self-reporting, while studies evaluating the relationship of sleep/awake and circadian patterns to seizures depended chiefly on EEG analysis [31, 32].
The control of seizures was much better in the female group; this may be attributed to better compliance to medication, idiopathic seizures, stability of social life, and lower rate of substance abuse compared to males. Similar results were reported by Obiako and his colleagues [33] when they investigated prognostic factors for epileptic seizure outcomes.
It is worth noting that the overall percentage of controlled patients (45.6%) was inferior to previous studies [34]. This may be related to being a hospital-based study carried out in the tertiary referral hospital, which is usually challenged with more cases of refractory epilepsy while easy-to-treat cases normally achieve good control after the first AED and do not require the assistance of an expert epileptologist; however, we do recommend further studies to investigate this issue.
Etiological causes of symptomatic epilepsy
A significantly higher number of females had idiopathic etiology, whereas more males had an underlying secondary etiology with trauma being the leading cause. Our results agree with previous reports indicating that head injuries [14] are the most common underlying etiological cause of chronic epilepsy, with males being at a greater exposure risk. When comparing our results with another Egyptian study, led by Farghaly and his colleagues [35], they found that cerebrovascular stroke, rather than trauma, was the most common cause of symptomatic epilepsy among adults and the elderly while perinatal insults were the most common among children (< 18 years). This difference regarding adult epileptic patients may be related to the geographic characteristics as the mentioned study was carried out in Al-kharga District (New Valley), at the southern part of Egypt, where the majority live in rural areas with a density of 0.58/km2, while the majority of our subjects came from Giza, the third-largest city in Egypt and the world’s seventh largest suburb, with a density of 2.300/km2, and the highest number of traffic accidents as reported by The Central Agency for Public Mobilization and Statistics [15].
It is noteworthy that the number of patients with unknown etiology (cryptogenic) is relatively high compared to previous studies [19, 33], in addition to low numbers of hippocampal sclerosis and cortical dysplasias detected in our study. This could be due to the limited access to 3Tesla Magnetic Resonance Imaging (MRI) and comprehensive epilepsy protocol imaging for economic reasons.
Diagnostic studies for epilepsy
Neither the EEG nor neuroimaging results showed gender differences between our cohorts. Although the percentage of patients who had undergone diagnostic tests is comparable to previous studies [14, 16, 17], it is still inadequate for such essential investigations. We attributed this deficiency to the lack of registration in the archived record and/or the reluctance in doing EEG studies either due to financial issues or good control of seizures with treatment.
AED utilization
Prescribers in our tertiary referral center generally followed treatment guidelines for epilepsy in terms of first-line drugs, with a tendency to shift towards the use of newer AEDs if indicated. Results showed that most patients were treated with first-generation AEDs, which are offered freely. Males were more likely to be prescribed VPA for generalized seizures, with a trend to shift to levetiracetam for females due to its better safety profile on females in the child-bearing period and in hepatic patients.
Since this study included patients attending a tertiary care hospital, it may bear certain selection biases. It did not include patients treated in other neurology clinics, at primary or secondary care centers, those treated privately, or undiagnosed patients. Also, being a retrospective study, some information was liable to recall bias and incompleteness as results of EEG or neuroimaging hindered the recognition of certain features and the diagnosis of epilepsy syndromes in some patients.