Childhood Epilepsy

Introduction

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting millions of people worldwide. This research paper delves into the intricate realm of epilepsy, aiming to provide a comprehensive understanding of the underlying mechanisms, genetic factors, environmental contributions, and current research. Through an exploration of the latest scientific findings, this paper will shed light on this enigmatic condition and contribute to our understanding of epilepsy and seizures. In terms of definitions, a seizure is defined as “a burst of uncontrolled electrical activity between brain cells that causes temporary abnormalities in muscle tone or movements (stiffness, twitching or limpness), behaviors, sensations, or states of awareness” (Hopkins Medicine). Typically, the brain emits electrical impulses in an orderly pattern [see figure 1] of spikes and waves.

These spikes and sharp waves refer to Epileptiform Transits, which are the marker of patients with seizures or epilepsy.

Childhood absence epilepsy (CAE)

is a type of epilepsy characterized by brief, absence seizures that affects approximately 6.3 to 8.0 children per 100,000 per year (Kentab, A.Y., Bulayhi, S.A, Hamad, M.A., Al Wadei, A., and Bashiri, FA, 2022). This is the most common type of pediatric epilepsy. These seizures can be challenging to detect as they are mistakenly taken for daydreaming or inattentiveness. EEG (electroencephalogram) plays a crucial role in diagnosing and understanding CAE. The EEG records the brain's electrical activity, helping doctors identify specific patterns associated with absence seizures. In CAE, the EEG typically shows patterns called generalized 3 Hz spike-and-wave discharges. These patterns, characterized by regular 3-per-second spike-and-wave complexes, are a sign in diagnosing absence seizures. The EEG not only helps with diagnosis but also in determining the effectiveness of treatment and assessing the frequency and patterns of absence seizures in individuals with CAE.

Types of Seizures

CAS/CAE

They are two examples of many different types of seizures. For instance Generalized Seizures (or Grand Mal Seizures) are seizures that affect both sides of the brain. They involve tonic-clonic activity and loss of consciousness (LoC). Tonic Clonic activity involves moments consisting of muscle rigidity and relaxation. This is the activity most people think of when they think of seizures. LoC refers to an altered state of awareness in which the individual is unresponsive to their environment. A LoC can be brief or longer, lasting a few seconds or several minutes. The period immediately following a LoC and once seizure activity has ceased is called a postictal state. The postictal state is characterized by a period of confusion that includes alterations in orientation (trouble recalling personal information: one’s birthday, age, name, etc), headache, and fatigue. Individuals with epilepsy may be able to identify when a seizure may occur because of something called an aura. An epileptic aura involves sensory experiences that range from visual changes (e.g., their vision going dark as if the lights have been turned off), auditory (e.g, ringing in the ears, fuzzy hearing), tactile (e.g., bugs crawling on their skin or pinpricks), or perceptual (e.g., a nagging feeling or a sense that something is not right). A common aura cited in the literature is the smell of burnt toast.

Focal Seizures

Also known as partial seizures, occur when nerve cells in a specific part of the brain generate electrical signals. Because electrical activity is localized (occurring in a particular region of the brain), one's actions during a focal seizure are determined by the affected brain region. For example, if a seizure occurs on the right side of the brain, the left side of the body is affected, and vice versa. This is because nerve fibers in the brainstem cross over to the opposite side of the body.

Although there are many types of focal seizures, a common type often portrayed in movies and television shows is called a simple partial seizure. It involves involuntary movements (jerking of arms or legs) on one side of the body, the patient turning their head or eyes to one side, a pained expression on their face, and a tingling or unusual feeling on one side of the body.

Complex Focal Seizures

These involve changes in consciousness, where the individual is not aware of their surroundings and is unaware of what is happening. A child with a complex focal seizure may stare into space, make chewing motions, wander rooms without a purpose, try to grab objects out of the air, say words that don’t make sense, and be generally unresponsive to their environment (e.g., not responding to calling). Focal seizures generally follow an aura. Partial seizures occur when nerve cells in a specific part of the brain generate electrical signals. Because electrical activity is localized (occurs in a particular region of the brain), the way one acts during a focal seizure is determined by the region of the brain affected. If, for example, a seizure occurs on the right side of the brain, the left side of the body is affected. Likewise, when the left side of the brain seizes, the right side of the body is affected. This is because nerve fibers in the brainstem cross over to the opposite of the body. Although there are many types of focal seizure, a common type often portrayed in movies and television shows is called a simple partial seizure. They involve involuntary movements (jerking of arms or legs) on one side of the body, the patient turning his/her head or eyes to one side, a pained expression on their face, and a tingling or unusual feeling on one side of the body.

Complex focal seizures involve changes in consciousness, where the individual is not aware of their surroundings and is unaware of what is happening. A child with a complex focal seizure will stare into space, make chewing motions, wander rooms without a purpose, try to grab objects out of the air, say words that don’t make sense, and be generally unresponsive to their environment (e.g., not responding to calling). Focal seizures generally follow an aura.

Absence Seizures

They are brief episodes during which the patient is unresponsive, lacking any motor components. They most commonly affect children between four and twelve years old and are associated with several generalized epilepsies, including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), and juvenile myoclonic epilepsy (JME). These seizures exhibit a classic EEG finding of 3-Hz spike-and-wave discharges, forming the basis of an electroclinical diagnosis. Regarding location, absence seizures primarily occur in the frontal and temporal lobes, associated with attention, planning, organization, processing speed, and memory. However, research into the effects of absence seizures on executive functioning, memory, and learning is limited. This paper aims to contribute to this area of study.

Historically, in 1951, William G. Lennox and Henri Gastaut reported a 66% concordance for the EEG pattern of 3-Hertz spike-and-wave in monozygotic twins. Further studies, such as the one by Doose et al in 1970, supported this pattern and implicated multifactorial inheritance. Genetics of CAS : The involvement of genes like the voltage-gated T-type calcium channel gene, GABA-A receptor subunits GABRG2 and GABRG3, and the CACNA1A gene was observed.

In CAE, the SLC2A1 gene, responsible for the GLUT1 protein, was identified. Mutations in SLC2A1 were found in up to 10-12% of children with refractory absences, suggesting a link to abnormal brain imaging. Individuals without SLC2A1 mutations exhibited normal background EEG activity, neurodevelopmental examination, and brain imaging despite a documented generalized 3 to 4 Hz spike-wave EEG pattern.

Effect of CAS on Attention

Seizures and epilepsy can significantly impact attention and cognitive function. The effects vary based on seizure type, frequency, and individual differences, leading children with epilepsy to resemble those with Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD is a neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity affecting functioning in multiple areas.

Inattention may manifest as difficulty sustaining focus, making careless mistakes, forgetfulness, distractibility, and avoidance of mentally challenging work. Hyperactivity involves excess motor movement like fidgeting and moving around when expected to be seated. Impulsivity entails acting before considering consequences, leading to careless mistakes, interrupting others, not waiting their turn, and difficulty following rules.

A diagnosis of ADHD relies on specific DSM-5-TR criteria and involves comprehensive assessment through interviews, cognitive testing, observations, and rating scales. ADHD is associated with frontal lobe dysfunction, particularly in attention, organization, planning, and problem-solving.

Epilepsy is characterized by recurrent, unprovoked seizures resulting from abnormal brain electrical activity. Its causes include genetic factors, brain injury, infection, or structural abnormalities. While seizures are the hallmark symptom, individuals with epilepsy may also experience cognitive and attentional difficulties related to underlying brain abnormalities, the effects of seizures, and/or prescribed medications. A diagnosis involves a history of recurrent seizures, EEG results, and imaging studies.

Effect of CAS on Memory

After an absence seizure, some individuals may enter a postictal state, characterized by altered consciousness. This period varies in duration and may involve confusion or memory deficits. Memory impairments (occurring shortly before, during, or after the seizure) during the postictal state are typically temporary, with most individuals recovering cognitive functions asthe postictal period resolves.

The frequency and severity of absence seizures can impact their effect on memory. Individuals experiencing frequent or prolonged seizures may face a higher risk of memory-related difficulties compared to those with less frequent or shorter seizures. Seizures in the frontal lobe can weaken planning abilities, hindering the organization of thoughts or actions. For example, when creating a shopping list, one might think or write the same item multiple times.

Epilepsy, including absence seizures, is sometimes linked to cognitive comorbidities. Those with epilepsy may face an increased risk of cognitive challenges, such as memory deficits. It's crucial to recognize that the relationship between seizures and memory is complex and can vary among individuals, commonly resulting in difficulties acquiring and retaining new information, which can impact academic performance.

Effect of CAS on Learning

Seizures and epilepsy can significantly impact learning due to their effects on cognitive function, attention, and psychosocial well-being. These effects are particularly pronounced in academic settings, where reading, writing, and mathematics can be adversely affected. Concerning reading, CAE may cause difficulties in concentration and attention, hampering a child's ability to learn individual letter sounds and their combinations to form words. CAE can also disrupt the motor control and coordination necessary for handwriting. Children with epilepsy may struggle with maintaining a consistent writing pace, forming letters accurately, or organizing their thoughts coherently. Challenges in math may arise because seizures disrupt the functioning of the parietal-frontal networks involved in mathematical cognition. Additionally, medications used to treat epilepsy can contribute to difficulties in reading proficiency, comprehension, written expression, and math problem-solving.

Developmentally, epilepsy can interfere with milestones, causing delays in motor skills. Seizures can impact fine motor skills, crucial for tasks like tying shoelaces, buttoning clothes, or using utensils, as well as gross motor skills, including running, jumping, or riding a bike. This interference can contribute to slower progress in academic and social skill development.

Treatment for CAS

The treatment for CAS typically involves a combination of medications

A wide range of medications is available to manage seizures called Antiepileptic Drugs - AEDs. The choice of medication depends on the specific patient and the goal is to find the most effective medication with the fewest side effects. Antiepileptic medications, commonly prescribed to manage seizures, can have side effects that impact cognitive function and learning. Some individuals may experience difficulties with concentration, memory, processing speed (speed of information processing), mood (reduced frustration tolerance/aggression), and motor coordination (legible handwriting).

The most frequently prescribed medications for pediatric epilepsy are Keppra and Carbamazepine.

Keppra (or Levetiracetam) is an antiepileptic drug whose exact mechanism of action is not fully understood but is believed to involve the modulation of neurotransmitter release, including GABA (gamma-aminobutyric acid) and glutamate. It is commonly used to treat partial-onset seizures in adults and children who are at least one month old and can be used as adjunctive therapy for myoclonic seizures in juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures.

Carbamazepine (or Tegretol) is an antiepileptic drug (AED) and mood stabilizer that works by stabilizing sodium channels. This leads to decreased excitability and hyperactivity of neurons. Carbamazepine is used to treat numerous seizures, including focal seizures (partial seizures) and generalized tonic-clonic seizures. It is also prescribed for trigeminal neuralgia and bipolar disorder.

Side effects

Both Keppra and Carbamazepine can cause the following side effects: drowsiness/fatigue, muscle weakness, coordination difficulties, loss of appetite, irritability, headaches, dizziness, nausea, blurred vision, dry mouth, and difficulty sleeping. More serious but rare side effects of Keppra include hallucinations, severe skin reactions (Stevens-Johnson syndrome), and blood disorders (decreased blood cell counts). Serious side effects of Carbamazepine include serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), agranulocytosis (severe reduction in white blood cells), liver problems (monitoring liver function is important), hyponatremia (low sodium levels), and hypersensitivity reactions. Despite these potential side effects, effective management of absence seizures can positively impact memory.

Mental Health and Comprehensive Seizure Management

Living with epilepsy can also impact emotional well-being. Individuals may experience anxiety, depression, or social challenges. Stigma or misconceptions about epilepsy may affect social interactions, potentially impacting the development of social skills and relationships. This can lead to disruptions at school and in the learning process. It is important to note, however, that the impact of epilepsy on learning varies from person to person. Some individuals may have well-controlled seizures with minimal impact on their daily activities, while others may face more significant challenges.

Prioritizing the mental and emotional health of children with CAS is essential for comprehensive seizure management. A tailored approach involves age-appropriate counseling, educational support to combat stigma, involvement in support networks, and regular family engagement. Integrating stress-reducing activities, such as mindfulness, into the care plan contributes to emotional well-being. Collaborative medication management, consistent follow-ups, and open communication between healthcare providers, parents, and children enhance the overall effectiveness of CAS management. This holistic strategy recognizes the interconnectedness of physical, emotional, and social aspects, ensuring a well-rounded and supportive care environment for children with epilepsy.

Case Study of Absence Seizure

Case: The negative impact of absence seizures on attention can be illustrated using an 11-year-old male who will be referred to as “Bob”. Bob was a typically developing toddler who was able to identify the letters in his name at 12-months old. Bob developed first absence seizures at 21-months old and continued to have absence seizures until shortly after his fifth birthday. In total, Bob had six epileptic events that lasted around 20-30 seconds. These seizures occurred one after another and were present for five years. Additionally, Bob was in status for two minutes during his most severe seizures. His seizures began as absence seizures and were followed by tonic-clonic activity.

Effect of CAS on learning and development: Bob Following his first seizure, Bob began to show challenges with focus, motor activity (e.g., fidgeting, moving about when expected to be seated), and trouble recalling letters of the alphabet he could previously identify. They also involved postictal confusion. As he aged, trouble with focus, motor activity, and impulsivity (e.g., blurting out answers, acting before thinking about the consequences) became evident. These difficulties impacted his functioning at school, in the community, and at home. They made it harder for him to learn to read and follow multi step instruction.

Management: Bob’s pediatrition prescribed focalin, which is a mild stimulant to the central nervous system (CNS) that affects certain chemicals in the brain. These chemicals bring about hyperactivity and impulse control. Focalin is a prescription medicine that is used to treat ADHD.

Conclusion

Although there isn't much research on Childhood Absence Epilepsy (CAE), the goal of this paper is to examine the effects of absence seizures on attention, memory, and learning over time. During absence seizures, characterized by brief episodes of staring or subtle movements, there is a temporary loss of awareness. This results in a disruption in attention, as the frequent seizures throughout the day lead to a shortened attention span, reducing the child's ability to focus. This disruption can have consequences on academic performance, social interactions, mood, and overall cognitive functioning. Children with CAE may face challenges in learning new information, recalling information (especially during or around seizures), completing schoolwork quickly, making sense of information read, playing rule-based games, and managing their mood (experiencing sadness, anxiety, or stress). Given these challenges, it is crucial to increase research on CAE and track the short- and long-term effects of these seizures. As mentioned earlier, CAE symptoms may mimic ADHD, raising questions about the duration of ADHD-like symptoms in children with CAE, whether symptoms resolve over time, if they are worsened by breakthrough seizures, and if treatments for ADHD can address these difficulties. Finally, it's important to investigate whether antiepileptic drugs (AED) contribute to any cognitive changes.

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Impact Statement

This research paper aims to provide a comprehensive review of the genetic factors, environmental contributions, and current research on epilepsy. A case study is used to highlight the impact of seizures on daily functioning.The Extended Research Program (ERP) program prepared me to write formal research papers. It allowed me to work closely with a mentor to develop a research question and learn to use the scientific method to explore a topic. In regular meetings, we reviewed journal articles and discussed their strengths and weaknesses. Topics discussed included: hypothesis formulation, analysis, and conclusion drawing. This prepared me to be a better student, whether it’s by doing research and experiments in biology or writing essays and narratives in English. Over the course of this project, I learned about the extensive impact of epilepsy on adolescents and adults. Particularly on the impact of recurrent seizures on cognitive, emotional, and behavioral functioning.

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_By: Alianna Shehu_

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.