At least 10 million people sustain head trauma every year [2,3], making traumatic brain injury (TBI) one of the leading global causes of death and disease burden [1]. One of TBI’s major complications but poorly understood sequelae is post-traumatic epilepsy (PTE) [4–6]. PTE is a significant form of symptomatic epilepsies resulting from various brain insults [6]. In the general population, it causes 10–20% of symptomatic epilepsy and 5% of all epilepsy [7].

PTE poses significant health and socio-economic problem worldwide [8]. People with epilepsy are three times more likely to die prematurely than the general population, with the absolute number of deaths increasing by 39% [1]. Post-traumatic epileptic seizures are distinguished from non-epileptic post-traumatic seizures (PTS) by their etiology and timing after the trauma. Late seizures, occurring more than a week after the initial event, characterise PTE. [9]. The time between a TBI and the onset of the first seizure varies greatly [10]. In about 80% of cases, the first seizure following PTE occurs within the first year, and more than 90% of cases occur by the end of the second year [11]. Eighty-two percent of patients who experienced a late-onset seizure (more than a week after injury) also experienced a second seizure within the following two years [8]. Although a seizure during the first week after injury (early PTS) is linked to a higher incidence of late PTS (after the first week of injury), having a late PTS is correlated with an even higher risk of seizure recurrence [12–14]. The likelihood of seizures following a TBI has been predicted mathematically by several authors, but their clinical applicability for the majority of brain-injured people has not been tested [13]. Researchers have tried to pin down the true prevalence of PTE for decades, and their findings have yielded a wide range of reported numbers, from 1.3% to 53.3% [15–17]. This variation may be attributable to differences in the severity of the initial TBI. The cumulative incidence of PTE was reported to be 4.4 per 100 people with mild TBI, 7.6% per 100 people with moderate TBI, and 13.6 per 100 people with severe TBI in a three-year population-based study conducted in the United States [4].

In most TBI cases, cognitive difficulties are the most prominent impairments [18]. However, little is known about how PTE can exaggerate neuropsychological deficits. Preclinical TBI studies provided scientific proof that PTE may further deteriorate cognitive performance. This comorbidity is also reported in other secondary epilepsies, such as post-stroke epilepsy [19]. Cognitive performance includes motor function, memory, intelligence, attention or concentration, processing speed, language, and visual-spatial abilities [20]. Researchers found that mice induced with TBI followed by electroconvulsive shock seizures performed worse in the Barnes maze than mice who underwent TBI alone [21]. These findings on the “double hit” mice were related to increased glial activation.

Meanwhile, in a study by Shultz and colleagues [22] comparing rats that did or did not develop PTE at six months post-injury, no significant differences between the groups were observed in Morris water maze (MWM) performance. The few preclinical studies that evaluated the impacts of PTE on cognitive functions have yielded inconclusive results. In some studies, temporal complexities may contribute to the failure to distinguish between PTE versus non-PTE groups of post-TBI rats. One previous study found an alarming statistic: half of the people with epilepsy exhibit cognitive dysfunctions in multiple domains, including learning, memory, attention, and executive functioning [23]. Memory loss, however, is far more common [24]. As a result, it is prudent to postulate that epilepsy resulting from TBI adds deficits to an individual with TBI, thereby worsening neuropsychological performance.

This study involves two parts. Part I of the study is to determine the etiology of PTE in TBI individuals to quantify the incidence rate and stratify risks for developing PTE. Part II of the study examines the cognitive comorbidity of PTE in a diverse multi-ethnic population. Previously, several authors [5,6,13,25,26] had analysed predictors for PTE in a large sample of TBI people. Unfortunately, the geographical limitation prevents the broad generalisation of the results of these investigations. To the best of our knowledge, this study represents the first investigation in Malaysia with multi-ethnicity and various demographical backgrounds who were retrospectively reviewed for up to 2 years after brain injury. The results of this study are intended to add to the emerging body of knowledge for both professionals and the general public. Individuals with TBI and PTE face unique challenges that healthcare providers will consider. Due to this, better services and strategies to enhance these people’s lives could be created. Additionally, people with PTE and their families may be better prepared to deal with upcoming issues such as memory deficit, driving limits, intelligence, and the effect on caregivers, family members, and significant others. Furthermore, reducing the burden of comorbidities linked with decreased cognitive abilities and PTE would substantially impact the individual, society, and the economy.