Epilepsy From Past to Present
Epilepsy is a neurological disease in which numerous electrical discharges occur in the brain and is a progressive disorder with recurrent seizures. The first sources in which it is mentioned are around 2000 BC. It was first mentioned in a Mesopotamian text as "his neck turning left, hands and feet are tense, and his eyes wide open, and from his mouth froth is flowing without him having any consciousness" (Kaculini et al., 2021). However, despite the 4000 years that have passed since the first report, epilepsy remains a mystery in many aspects.
This mystery, which could not be understood at the time it was defined, was attributed to some spiritual powers because of the approach of human beings to the subjects that they could not make sense of and define throughout the ages and its treatment was sought with spiritual rituals such as exorcism. Therefore, in addition to psychosocial and health problems, individuals with epilepsy have also been subjected to stigmatization and exclusion due to this stigma throughout history.
What is epilepsy?
Today, the International League Against Epilepsy (ILAE) defines epilepsy as a disorder or a family of disorders rather than a disease. The term disorder refers to a functional impairment that is not necessarily permanent, whereas the term disease usually refers to a more permanent impairment of normal function. Many heterogeneous health problems, for example, cancer or diabetes, contain numerous sub-disorders and are still recognized as diseases. The term "disorder" is still poorly understood and fails to account for the serious nature of epilepsy. The ILAE and the International Bureau of Epilepsy (IBE) have recently reached a consensus that epilepsy should be recognized as a disease (Fisher et al., 2014).
The ILAE, which is a serious health authority in the field of epilepsy, has defined three clinical possibilities for the diagnosis of epilepsy; the first of these is the presence of 2 unprovoked or reflex seizures at least 24 hours apart. Another possibility is an unprovoked (or reflex) seizure (normally reflex seizures are not a sufficient diagnostic criterion for epilepsy) and a probability (at least 60%) of another similar seizure occurring within 10 years after the two unprovoked seizures. The last possibility or a sufficient condition for diagnosis is the presence of a diagnosis of epilepsy syndrome (Fisher et al., 2014).
Prevalence
Epilepsy is a major global health problem affecting millions of people worldwide and can result in significant morbidity and mortality (Banerjee et al., 2009). Recognizing its prevalence and understanding the epidemiology of epilepsy is crucial for developing effective strategies to manage epilepsy and improve living conditions for individuals living with this neurological disorder. The number of epilepsy cases worldwide is estimated to be 0.7% (Asadi-Pooya and Farazdaghi, 2022). However, the incidence of epilepsy may vary between various regions in the world (Li et al., 2022). However, epilepsy can be seen at a higher rate in cities compared to rural areas, for example in China (Li et al., 2022).
Epilepsy in Turkey
Epilepsy has been the subject of many studies in Turkey and these studies have shown the number of cases of this neurological disease in our country. Studies conducted in various regions of Turkey have reported different prevalence rates and provided valuable information about the distribution of epilepsy in the population. Studies conducted in rural areas such as Silivri provided limited data on the disease (Karaağaç et al., 1999). In addition, studies conducted in urban settings such as Bursa city center have contributed to the understanding of the prevalence of epilepsy in more densely populated areas (Çalişir et al., 2006). The prevalence of epilepsy in Turkey is estimated to range from 6.1 to 10.2 per 1000 population, indicating the serious burden of the disease in the community (Dayapoğlu and Tan, 2016). Furthermore, studies focusing on specific demographic groups, such as schoolchildren in Kayseri City Centre, have noted varying prevalence rates by age and gender, with higher values generally observed in males (Canpolat et al., 2014). Overall, the fact that the prevalence of epilepsy in Turkey varies across regions and demographic groups emphasizes the importance of tailored approaches to address the needs of individuals living with epilepsy in the country.
Types of epilepsies and symptoms
ILAE has developed a comprehensive classification system that classifies epilepsy types according to various criteria. According to this classification, epilepsies are classified into three types: focal, which means occurring in a specific focus, generalized, which means occurring synchronously in multiple foci involving both brain hemispheres, and seizures of unknown origin. Within these frameworks, epilepsy syndromes that usually include more than one type of seizure are also defined (Aaberg et al., 2017).
Epilepsy types also present with different symptoms. For example, childhood occipital epilepsy, also known as the "Gastaut type", is characterized firstly by short seizures with visual symptoms such as basic visual hallucinations, illusions, or transient vision loss, followed by unilateral clonic seizures involving rapid contractions and relaxations of muscles (Caraballo et al., 2005). Temporal lobe epilepsy, on the other hand, can sometimes show a wide range of symptoms such as Deja-vu feeling, amnesia, anxiety, depression, nausea, auditory or olfactory hallucinations, fixed gaze, dilated pupils, and automatism (Anugwom et al., 2021). In addition, occipital lobe epilepsies may often be associated with autonomic signs and symptoms (Piccioli et al., 2009). In summary, the clinical manifestations of different types of epilepsy may overlap, which may lead to individualized management and specific symptoms exhibited by the individual.
Diagnostic Methods
Diagnosing epilepsy involves a range of methods including clinical assessments, neuroimaging, genetic testing, and advanced technological approaches. Electroencephalography (EEG) is becoming increasingly important in epilepsy diagnosis, with studies emphasizing the utility of wavelet-based EEG processing and deep learning algorithms for automatic seizure detection and epilepsy diagnosis. In addition, neuroimaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) are also essential to identify structural changes in the brain associated with epilepsy (Dakaj et al., 2016). Genetic testing is crucial in cases where a genetic disorder is suspected as the cause of epilepsy; it helps targeted treatment and increases diagnostic accuracy (Ream and Patel, 2015). In addition, dynamic video-EEG monitoring is also used to provide insight into seizure patterns and prognosis. These various methods collectively contribute to a comprehensive approach to epilepsy diagnosis, allowing healthcare professionals to tailor treatment strategies and improve patient outcomes.
Drug Therapy
Pharmacotherapy for epilepsy is critical to manage seizures effectively. The choice of drugs that are effective against seizures is crucial and can vary according to various factors, including seizure type and individual patient characteristics. Older anti-seizure drugs such as phenobarbital, phenytoin, primidone, carbamazepine, and valproate have been the classical options for epilepsy treatment (Crumrine, 2002). In some cases, combination therapies using more than one drug may be necessary to achieve optimal seizure control, but polytherapy may increase the risk of side effects (Gupta et al., 2023). Therapeutic drug monitoring, i.e. frequent blood measurements of some drugs such as carbamazepine, is critical to ensure the optimum blood level of the drug to control the seizure in the patient. In addition, advances in anti-seizure drug development have led to increased patient comfort, with drugs such as brivaracetam, gabapentin, and levetiracetam being better tolerated than other anti-seizure drugs (Zaccara et al., 2017). Overall, the pharmacotherapy of epilepsy continues to evolve with a focus on personalized treatment approaches to improve efficacy and minimize adverse effects. Here the physician decides according to the patient's specific situation.
Other treatments
Non-pharmacological therapies are important in the treatment of epilepsy, especially in cases of drug-resistant seizures. These interventions encompass a variety of approaches that can complement or serve as an alternative to conventional pharmacotherapy. The main non-pharmacological treatments for epilepsy include brain stimulation therapy, ketogenic diet, vagus nerve stimulation (VNS), and epilepsy surgery (Martin et al., 2016). These interventions offer a variety of strategies to help control seizures, improve quality of life, and address the challenges associated with drug-resistant epilepsy. Non-pharmacological treatments offer valuable options for individuals with epilepsy, providing personalized approaches that can improve overall management and outcomes for patients.
Causes and risk factors
Extensive research has examined maternal infections during pregnancy, genetic, and metabolic effects on epilepsy (McDermott et al., 2009, Oja et al., 2023). In addition to genetic factors, studies have also investigated the roles of sex hormones and gut microbiota in epilepsy risk and pointed to complex interactions between genetic predisposition and environmental factors in the etiology (causes) of the disease (Zeng et al., 2023, Ke et al., 2023). In addition, genitourinary system infections suffered by the mother during pregnancy have been associated with an increased risk of epilepsy in her baby (McDermott et al., 2009). However, the strongest basic risk factors can be summarized as brain infections such as meningitis, encephalitis, head traumas, brain damage caused by prenatal or perinatal causes (e.g. loss of oxygen or trauma during birth, low birth weight), congenital abnormalities or genetic conditions associated with brain malformations, strokes that restrict the amount of oxygen to the brain, genetic syndromes and brain tumors.
Living with epilepsy
Beyond the physical consequences of epilepsy, it also has significant effects on mental and social well-being (Goldman et al., 2016). People living with epilepsy may deal with a variety of comorbidities or conditions other than epilepsy. For example, epilepsy can often be accompanied by sleep disorders, neurobehavioral problems, and difficulties with transition from pediatric to adult care, underlining the need for comprehensive support and care (Weerd et al., 2004). Sleep disorders including excessive daytime sleepiness are pervasive in individuals with epilepsy and negatively affect their quality of life (Weerd et al., 2004). In addition, neurobehavioral comorbidities such as attention deficit and hyperactivity disorder, autism spectrum disorder, and cognitive disorders can be seen more commonly in this population (Kind et al., 2017).
Genetics
The genetic basis of epilepsy is a multifactorial phenomenon involving various genetic determinants such as single gene mutations, polygenic inheritance, mitochondrial inheritance, and chromosomal mutations (Yang et al., 2022). Studies have shown that genetic factors play a role in both rare, highly penetrant Mendelian or de novo pathogenic variants and polygenic effects in more common epilepsies (Trujillo et al., 2023). Studies have used genetic risk factors through association studies and large patient cohorts to improve our understanding of the genetic architecture of epilepsy.
Summary
In summary, epilepsy is a complex disease that has been recognized since ancient times, however, there is still no complete cure for it yet even today. Fortunately, many people in society today achieve seizure control with anti-epileptic drugs. However, there is still a group of patients resistant to treatment with a rate as high as 30%. However, scientific research in the field continues in Turkey and worldwide, and today we are much closer to solving the mystery of epilepsy.
Aaberg, K.M.,et al. 2017. Seizures, Syndromes, and Etiologies in Childhood Epilepsy: The International League Against Epilepsy 1981, 1989, and 2017 Classifications Used in a Population‐based Cohort. (2017).
Anugwom, G., et al. 2021. Temporal Lobe Epilepsy Misdiagnosed as Schizophrenia: A Case Report.(2021).
Asadi‐Pooya, A.A. & Farazdaghi, M. 2022. Definition of Drug‐resistant Epilepsy: A Reappraisal Based on Epilepsy Types. (2022).
Banerjee, P.N., et al. 2009. The Descriptive Epidemiology of Epilepsy—A Review. (2009).
Canpolat, M., et al. Prevalence and Risk Factors of Epilepsy Among School Children in Kayseri City Center, an Urban Area in Central Anatolia, Turkey. (2014).
Caraballo, R.H., et al. Late‐onset, “Gastaut Type”, Childhood Occipital Epilepsy: An Unusual Evolution. (2005).
Crumrine, P.K. Antiepileptic Drug Selection in Pediatric Epilepsy. (2002).
Çalışır, N., et al. Prevalence of Epilepsy in Bursa City Center, an Urban Area of Turkey. (2006).
Dakaj, N., et al. 2016. Accuracy of Conventional Diagnostic Methods for Identifying Structural Changes in Patients With Focal Epilepsy. (2016).
Dayapoğlu, N. & Tan, M. Clinical Nurses' Knowledge and Attitudes Toward Patients With Epilepsy. (2016).
Fisher, R.S., et . ILAE Official Report: A practical clinical definition of epilepsy. (2014).
Goldman, A.M., et al. 2014 Epilepsy Benchmarks Area IV: Limit or Prevent Adverse Consequence of Seizures and Their Treatment Across the Lifespan. (2016).
Gupta, S., et al. A Prospective Observational Study on Changing Trends of Antiepileptics Prescription Amongst Physicians in India. (2023).
Helbig, I. & Lowenstein, D.H. Genetics of the Epilepsies. (2013).
Kaculini, C.M., et al. The History of Epilepsy: From Ancient Mystery to Modern Misconception. (2021).
Karaağaç, N., et al. Prevalence of Epilepsy in Silivri, a Rural Area of Turkey. (1999).
Ke, B., et al. Sex Hormones and Risk of Epilepsy: A Bidirectional Mendelian Randomization Study. (2023).
Kind, C., et al. Prevalence, Risk Factors, and Neurobehavioral Comorbidities of Epilepsy in Kenyan Children. (2017).
Li, W., et al. Is There an Epilepsy Belt of High Prevalence Rate in China? (2022).
Martin, K., et al. Ketogenic Diet and Other Dietary Treatments for Epilepsy. (2016).
Mcdermott, S., et al. Maternal Genitourinary Infection Appears to Synergistically Increase the Risk of Epilepsy in Children of Women With Epilepsy. (2009).
Oja, K.T., et al. Untargeted Metabolomics Profiling in Pediatric Patients and Adult Populations Indicates a Connection Between Lipid Imbalance and Epilepsy. (2023).
Piccioli, M., et al. Ictal Headache and Visual Sensitivity. (2009).
Ream, M.A. & Patel, A.D. Obtaining Genetic Testing in Pediatric Epilepsy. (2015).
Sheidley, B.R., et al. Genetic Testing for the Epilepsies: A Systematic Review. (2021).
Trujillo, S., et al. Knowledge and Beliefs About Epilepsy Genetics Among Hispanic and non‐Hispanic Patients. (2023).
Weerd, A.D., et al. Subjective Sleep Disturbance in Patients With Partial Epilepsy: A Questionnaire‐based Study on Prevalence and Impact on Quality of Life. (2004).
Yang, C., et al. Cadherins and the Pathogenesis of Epilepsy. (2022).
Zaccara, G., et al. Tolerability of New Antiepileptic Drugs: A Network Meta-Analysis. (2017).
Zeng, Y., et al. Roles of Gut Microbiome in Epilepsy Risk: A Mendelian Randomization Study. (2023).
