Demographics, Clinical Characteristics, and Management Strategies of Epilepsy in Saudi Arabia: A Systematic Review

Epilepsy accounts for a large part of the global burden of neurological disorders. This review aimed to assess the demographics, clinical characteristics, and management of patients with epilepsy in Saudi Arabia based on studies published from 2018 to 2023. A systematic review was carried out using PubMed, Medline, Embase, and Cochrane Library from January 2018 to January 2023, where key terms related to the epidemiology, clinical characteristics, treatment, and management strategy of epilepsy in Saudi Arabia were used to search for related studies. All relevant articles published in this period in the English language were included, and data about authors, year of the study, sample size, study design, demographic characteristics, clinical characteristics, and treatment strategy were collected. A male preponderance, a 6-24.9% family history of epilepsy, an equal distribution of focal and tonic-clonic epilepsy, EEG abnormalities of 19.7-70%, and a higher prevalence of monotherapy regimens were the main findings of this review.


Introduction And Background
Epilepsy is a neurological illness characterized by a persistent predisposition to epileptic seizures and by the associated neurological, cognitive, psychological, and social effects [1].It represents around 9.9% of the worldwide burden of neurological illnesses and is the most common non-infectious neurological ailment [2].
Around 50 million people worldwide suffer from epilepsy, according to estimates from the World Health Organization [3], with 4.7 million living in the Eastern Mediterranean region at the moment [4].These high numbers highlight the serious health risks associated with epilepsy and the necessity of receiving the right care.The higher risk of early death among epileptic patients relative to the general population is a concerning feature of epilepsy [5].
All age groups are impacted by epilepsy, which has detrimental effects on the patients, their families, and the healthcare system [6].Additionally, epilepsy patients experience social, emotional, mental, and physical effects [7].Even when their epilepsy is under control, individuals with epilepsy nevertheless face higher rates of early death and disability than the general population, and many of them also report a lower quality of life [8].Furthermore, among all the neurological illnesses, epilepsy has been linked to the greatest rates of disability-adjusted life years in both sexes [9].About 60% of instances of epilepsy have an unidentified primary cause [10].Epilepsy can be caused by hereditary or genetic disorders, as well as severe brain injury, stroke, and sequelae from previous illnesses; in many cases, both triggers are involved [11].The 2010 International League against Epilepsy (ILAE) study classified the etiology of epilepsy as systemic, inherited, and unknown [12].
For epilepsy, antiseizure medication (ASM) (formerly referred to as anti-epileptic drug) therapy is regarded as the accepted standard of care.There are currently over 20 ASMs on the market, the majority of them have been created and put to good use for a long time.The chemical makeup and modes of action of these ASMs vary [13].When patients with epilepsy take their ASMs as prescribed, their seizures are usually wellcontrolled and benign, but the psychological and social problems that arise after receiving an epilepsy diagnosis can be far more damaging than the actual seizures [14].To address the psychological and social problems associated with epilepsy, physical management should be paired with educational intervention [15].

Data Extraction
One investigator extracted data regarding the authors, year of the study, sample size, study design, demographic characteristics, clinical characteristics, and treatment strategy.Another investigator independently reviewed the accuracy of the extracted data.

Assessment of the Studys' Risk of Bias
Two investigators independently evaluated the methodological quality of the selected studies.Pre-specified questions for each study design were used to measure the risk of bias, and studies with a high risk of bias were not included [20].
Only six studies assessed the educational level of the participants; of these, four showed a predominance of high-school educational level [24,26,29,31].While the predominance was for bachelor's degrees of education in two studies [27,30].Information is not available.

Clinical Characteristics and Management Strategy
As for the clinical characteristics of patients with epilepsy included in this systemic review, five studies showed a higher prevalence of generalized tonic-clonic epilepsy type [11,17,23,26,31], five studies showed a predominance of focal epilepsy type [21,22,25,27,28], and three studies did not assess the epilepsy type [24,29,30].
Only five studies assessed the frequency of the seizures, where 68.7% of patients in the Alkoblan et al.
2023 study had seizures on a yearly basis [24], 33% had monthly seizures in the Asiri et al. 2022 study [26], and 61.4% had up to three seizures per year in the A. Alharbi et al. 2022 study [27].At the same time, 48.1% were seizure-free over the previous 3 months in the Alshamrani et al. 2020 study [30] and 57.7% had ≤5 seizures before treatment [22].
Of the 13 studies included in this review, only 5 studies assessed the EEG findings of the patients with epilepsy included.Nine studies assessed the management strategy of the studied patients.Of these studies, five studies showed a higher prevalence of monotherapy regimens [17,21,22,25,26], three studies showed a higher prevalence of polytherapy anti-epileptic medicine (AEM) regimens, while three studies did not assess the management strategy [27,28,31].[23] showed that 61% of patients with epilepsy had idiopathic/cryptogenic epilepsy, and Al Taho et al. ( 2018) [31] found that 90.6% had an idiopathic cause and 5.3% had cryptogenic epilepsy.

Shahid et al. (2018)
The study done by Alhaidari et al. (2022) [28] showed that 67% had structural epilepsy, and the study done by Alonazi et al. ( 2018) [11] showed that 43% of patients had structural/metabolic epilepsy and 44% had unknown epilepsy.MRI neuroimaging was done only in two studies [21,28], where 30% of patients with epilepsy had abnormal MRI findings in the first study as compared to 70% in the second study.

Discussion
Thirteen publications that evaluated the clinical traits and approach to treating epilepsy in Saudi Arabia were included in this review.Patients with epilepsy in these trials ranged in age from 0 to 90 years.Ages ranged from 41 to 44 years old, according to other studies [32][33][34].
According to this review, men are more likely than women to have epilepsy [11,17,21,22,25,26,28,31]. Previous investigations [32,[35][36][37] revealed a similar male predominance.This discrepancy was ascribed to the fact that men are more likely than women to have head injuries and that women tend to hide their epilepsy diagnosis [35][36][37].This result, however, was at odds with earlier research on the Arab community that indicated an incidence of epilepsy that favored women.This distinction was also made clear by epidemiological research conducted on the Arab community, which suggested that the gender discrepancy may have its roots in community differences [38,39].Other worldwide research [40,41] also revealed the same female majority.There are hints that women may be more inclined to hide their illness since it would have resulted in social stigma and made marriage more difficult [40,41].
In the included studies, the percentage of people with a family history of epilepsy varied from 6% to 24.9% [22,30].This prevalence range is in line with national studies, such as the one carried out in Al Qassim in 2001 [42] as well as global research [43,44].
This review concluded that there was a similar predominance of focal epilepsy and generalized tonic-clonic epilepsy types.Five studies found that the prevalence of focal seizures was higher than that of generalized tonic-clonic seizures.It was also demonstrated by Khreisat et al. that the most prevalent kind of seizure in structural/metabolic epilepsy was generalized tonic-clonic seizures.Caregivers and doctors may occasionally fail to notice the onset of seizures, which may have begun as focal seizures before becoming generalized, which explains the high prevalence of generalized epilepsy [45].Banerjee et al. highlighted the higher prevalence of generalized onset seizures in underdeveloped nations by reporting focal onset seizures ranging from 20% to 66% in a review [41].These authors suggest that uncertainties in the application of the classification and a lesser level of diagnostic expertise may account for these variations [41].
Moreover, Garcia-Martin et al. found that focally onset epileptic seizures accounted for the majority of seizures (75.5%) as opposed to generalized seizures (17.5%) [46].In a study of adults with epilepsy (mean age, 31.5 years), Rezaeian et al. found that widespread crises (78%) were more common than focal crises (22%) [47].Similar to our data, tonic-clonic seizures were common among the generalized crises.This result was in line with prior research involving Asian and African studies [48,49].However, other studies observed a higher proportion of focal seizures [32,50,51].This discrepancy was ascribed to patients' and observers' inadequate detection of the early focal symptoms, which causes them to miss the onset and become aware of the patient's broad convulsion [52].Meanwhile, some of the reported generalized seizures may have been focal seizures that progressed to bilateral tonic-clonic seizures.Cultural concerns may have contributed to an underreporting of focal seizures [53].
According to Shahid et al. (2018) [23] and Al Taho et al. (2018) [31], 90.6% of patients with epilepsy had idiopathic causes of epilepsy and 5.3% had cryptogenic epilepsy.These findings are presented in this review.This predominance was also noted in earlier research, which reported a high frequency of idiopathic epilepsy [3,54].
Typically, organic brain lesions presenting with neurological abnormalities, developmental delay, and abnormal EEG cause this kind of epilepsy [56].The most frequent cause of structural/metabolic epilepsy, according to research by Kroczka et al. [55], was perinatal insults, primarily hypoxia ischemic encephalopathy.Metabolic disorders, infections, and trauma were the next most common causes.
Corresponding to this, earlier research [56] examined a variety of causes with varying frequency such as intracranial infection, cerebral deformity, degenerative brain illness, and brain damage sustained during neonatal life.
Based on the AEM utilized in this research, three studies demonstrated a greater incidence of polytherapy AEM regimen and five studies demonstrated a higher prevalence of monotherapy AEM regimen [17,21,22,25,26].Three studies did not evaluate the management strategy that was employed [27,28,31].A prior study found that monotherapy AEM regimens were more common and that the most often prescribed medications were carbamazepine, valproic acid, phenobarbital, and lamotrigine [32].This agrees with the present review where the most commonly reported drugs in studies involved in this review were levetiracetam, valproic acid, lamotrigine, valproate, and carbamazepine.
Studies have shown that 20% to 30% of patients with epilepsy had trouble controlling their epilepsy [57].Furthermore, in other investigations, the degree of control over epileptic seizures was not altered by the administration of novel ASMs [58,59].In earlier research, monotherapy was employed at a frequency of 48.6% to 60% [47,50,51].
According to the current analysis, there have only been two studies that used MRI neuroimaging [21,28], with the first study showing 30% of patients with epilepsy with aberrant MRI findings and the second study showing 70%.It was discovered that neuroimaging might investigate the connection between anomalies in brain activity and the anatomical locations of brain pathologies [60].Determining the cause of symptomatic epilepsy and the degree of related disease is also helpful.Nonetheless, certain anomalies, such as focal cortical dysplasia, became apparent with age and were not initially identified by neuroimaging.In a similar vein, a recent study conducted in Saudi Arabia revealed that children who experienced their first apparent seizure had a significant frequency of abnormalities (42.7%) on brain CT scans [61].This implies that when a youngster presents with their first seizure, emergency CT should be taken into consideration.The Arteaga-Rodríguez et al. investigation reported the utilization of at least one brain imaging test, with positive results between computed tomography and magnetic resonance imaging of the skull of 48.6% and 77.9%, respectively [32].It has been established that magnetic resonance imaging is the best imaging modality for treating epilepsy [62].
For most epileptic patients, electroencephalography (EEG) is a practical and economical investigative method [63].The classification of seizure types, the identification of a particular condition, and the subsequent long-term prognosis prediction can all be aided by EEG [60].The EEG results of the patients with epilepsy were evaluated in just five trials included in this analysis, with EEG abnormalities ranging from 19.7% to 70%.Furthermore, this review's spectrum of EEG abnormalities is consistent with that of earlier research [32,47].

Summary
In the 13 studies that were reviewed, there was a male preponderance in 9 studies, and between 6% and 24.9% of patients had a family history of epilepsy.Five studies suggested focal epilepsy was more common, and five suggested generalized tonic-clonic epilepsy was more common.EEGs showed abnormalities in the range of 19.7% to 70%.Five studies showed a higher prevalence of monotherapy regimens, and three showed a higher incidence of polytherapy.Only two investigations used MRIs, and the results revealed 30% and 70% of anomalies.The studies had various aims, and patient demographics and clinical and management data were included in most of the studies.However, several studies lack certain data, as this is related to some clinical and treatment regimens of epilepsy because gathering this information was not the main objective of the study.

FIGURE 1 :
FIGURE 1: PRISMA flow diagram for the inclusion and exclusion criteria of articles PRISMA: Preferred Reporting Items for Systematic Review and Meta-Analysis

Table 1
summarizes the demographic characteristics of each study included.

Table 2
summarizes the clinical characteristics and antiseizure medication regimen of each study included.