What are the characteristics of childhood epilepsy? - Chapter 10

Epilepsy is a symptom, not a cause, of brain dysfunction. Epilepsy may result from a range of disorders, including traumatic injury, cerebral infection, and metabolic disorders. Epilepsy is the most common neurological condition in childhood. Its prevalence is around 5 in every 1,000 children with the highest incidence in infancy, in particular the first year. These numbers are higher in developing countries. In fact, approximately 80% of people with epilepsy live in the developing world. The prevalence rate of childhood epilepsy is so high because the developing brain is more prone to seizures, in particular during infancy, reflecting immaturity of both signalling systems and the morphological and structural organisation of neuronal networks. 

Over the past decade, our understanding of epilepsy has changed drastically. To date, epilepsy is conceptualised as a brain network disease, which has particular implications for the assessment of children with epilepsy. In fact, if epilepsy is a disease of brain networks, and cognition and behaviour are primary functions of those brain networks, then epilepsy is as much a disorder of cognition and behaviour as it is of seizures. The diagnosis of epilepsy is made on clinical grounds with examinations used to confirm the diagnosis, characterise the seizure disorder, and determine the underlying cause. In doing so, an EEG can aid in the diagnosis of specific epilepsy syndromes and distinguish focal from generalised seizures. Video-EEG may be needed when the diagnosis remains uncertain. Brain imaging, such as MRI, is used when an underlying abnormality is suspected. Typically, the first treatment option is anti-epileptic drugs (AED). A second treatment option (occurring in approximately 30% of children) is formed by surgery. Epilepsy has a high rate of comorbidity, including comorbid developmental delay (22%), speech and language deficits and learning difficulties (23%), and intellectual disability (68%). 

How to define and classify epilepsy?

A common language for defining and classifying epilepsy, which will be used in this chapter, is provided by the Commission on Classification and Terminology (CCT). An epileptic seizure refers to a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Seizures can be provoked (if associated with precipitating factors such as illness or an acute brain insult) or unprovoked (without identification of a specific precipitating factor). Commonly, seizures in childhood are provoked by fever, also called febrile seizures, and do not result in a diagnosis of epilepsy. Epilepsy is defined as a disorder of the brain characterised by an enduring predisposition of the brain to generate seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. The following operational clinical definition is used to guide diagnosis of epilepsy:

1. At least two unprovoked or reflex seizures occurring more than 24 hours apart.
2. One unprovoked or reflex seizure and a probability of more seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures occurring over the next ten years.
3. Diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who had age-dependent epilepsy syndrome, but are not past the applicable age or those who have remained seizure free for the last ten years and without medication for the last five years. 

The inclusion of diagnosis of an epilepsy syndrome (point 3) enables the clinical definition to extend to children with rare forms of epilepsy, such as Landau-Kleffner syndrome (LKS) who may not have overt seizures, but demonstrate changes in function as a result of underlying epileptic activity. Epileptic encephalopathy (EE) refers to a condition in which the epileptic activity itself may contribute to severe cognitive and behavioural impairments above and beyond what is expected from the underlying pathology alone and may worsen over time. 

Besides a clinical classification, the ILAE has adopted an operational (practical) classification of seizure type which starts with the determination of seizure onset as focal (originate within networks limited to one hemisphere) or generalised (originate within and rapidly engage bilaterally distributed networks). A third category is provided for seizures with unknown onset. Next, within both focal, generalised, and unknown onset, seizures are further classified as either motor onset or non-motor onset and then into a number of further subtypes. Epileptic spasms can be of focal, generalised or unknown onset and are characterised by sudden and brief contractions of axial (neck and trunk) and proximal limb muscles. They usually occur in clusters of varying intensity in which the intensity depends on severity of muscle contraction and the number of muscle groups that is involved. 

Grouping seizures by specific characteristics as was done before is clinical useful, but has limited relevance for the treatment and management of epilepsy. Children with the same seizure type may vary greatly in prognosis and response to treatment. In fact, it is well-established that certain individuals share common characteristics beyond seizure type and that these grouping can be identified as distinct epilepsy syndromes. The definition of what constitutes a epilepsy syndrome refers to a group of clinical entities identified by a cluster of electroclinical characteristics. These electroclinical syndromes can be identified on the basis of:

1. Age of onset.
2. Specific EEG characteristics.
3. Seizures types.
4. Cognitive and developmental antecedents and consequences.
5. Motor and sensory examination.
6. Provoking or triggering factors.
7. Patterns of seizure occurrence with regard to sleep.

Diagnosis of such a specific epilepsy syndrome has important implications for treatment and prognosis. 

The ILAE proposed a new classification system. The new framework for classification is a multilevel classification which adopts a more flexible approach to the classification of epilepsy. The first level classifies seizure type (focal, generalised, or unknown). The second level classifies epilepsy types (focal, generalised, combined generalised, unknown). The third level classifies epilepsy syndromes, in which a specific syndromic diagnosis can be made. In addition, consideration of associated comorbidities and aetiologies is included in the framework.

What are the causes of seizures and epilepsy?

Seizures are the result of abnormal firing of neurons. Aetiology forms a key concept guiding the treatment and management of children with epilepsy. In doing so, six aetiologic subgroups have been proposed:

1. Genetic.
2. Structural.
3. Metabolic.
4. Immune.
5. Infectious.
6. Unknown (cryptogenetic / presumed symptomatic).

Over the past decades, our understanding of the causes of epilepsy has improved greatly. In 1975, the majority of epilepsy were characterised as 'idiopathic' (genetic). Nowadays, epilepsy of unknown cause comprises a much smaller proportion due to the discovery of autoimmune epilepsies, epilepsies with lesions that are only identifiable with MRI and, most importantly, the reclassification of many epilepsies that were previously considered idiopathic as having a genetic cause. 

What are the characteristics of common genetic epilepsies?

Childhood absence epilepsy (CAE)

Childhood absence epilepsy (CAE) is the most common of the genetic, generalised epilepsies and accounts for 8-15% of all childhood epilepsies. On average, it starts around age six. Absence seizures (a type of seizures involving staring spells which usually last less than fifteen seconds) are the only seizures that manifest themselves in CAE, yet they can occur frequently, sometimes in the hundreds each day. These absence seizures are enhanced by hyperventilation. CAE is probably caused via a complex inheritance with several gene mutations. Standard treatment is provided by anti-epileptic drugs (AEDs). CAE typically enables a good prognosis, although recent studies indicate an increased risk of cognitive, learning, and behavioural disorders. 

Benign epilepsy with centrotemporal spikes (BECTS)

Benign epilepsy with centrotemporal spikes (BECTS) is the most commonly occurring genetic focal epilepsy syndrome in childhood. BECTS typically has an onset between age four and ten with a peak around seven years. The tendency for remission by the onset of adolescence explains the label for this condition as being benign. Seizures are infrequent and manifest with motor and/or sensory signs involving the face, for example unilateral tonic or clonic contractions, and mouth, with speech arrest and hyper salivation also commonly observed. In AED, seizures often occur at night while the child is asleep and may occur so infrequently that AEDs are not prescribed. BECTS is associated with normal cognitive functioning and has an excellent prognosis, although there is a growing body of evidence suggesting poorer performance on a range of functional measures. 

Dravet syndrome

Dravet syndrome, also known as severe myoclonic epilepsy of infancy, is a rare yet severe form of genetic epilepsy. Seizures typically begin in the first year of life in a previously healthy baby with no known risk factors for epilepsy. Various types of seizures may occur over time. Seizures may triggered by heat, physical exertions, and variations in light (strobing, eye closure, visual patterns, and so forth). Typically, early developmental milestones are met, but development declines in the second year of life and continues to a global developmental delay in which the child may even lose previously established skills. Prognosis is typically poor. Most children remain fully dependent with a degree of intellectual disability. 

What are the characteristics of structural (focal) epilepsies?

Temporal lobe epilepsy (TLE)

Temporal lobe epilepsy (TLE) may occur at any range, as is typical for focal epilepsies, but onset in later childhood and adolescence is common. The seizures are characterised by motionless staring, fearful or bewildered facial expression, unresponsiveness, hand and mouth movements that resemble voluntary actions, and post-ictal confusion or sleepiness. 

Frontal lobe epilepsy

Frontal lobe epilepsy involves seizures that result from frontal lobe pathology and often occur from sleep. These seizures are brief in duration and typically manifest themselves with prominent motor features such as unilateral or bilateral stiffening or jerking, loud vocalisation, and hyperkinetic automatisms such as tapping, cycling, or running. Seizures may occur multiple times a night. Outcome and prognosis depends on the degree to which cognitive networks are disrupted by the underlying pathology.

What are the characteristics of combined structural - genetic epilepsies?

Tuberous slecorsis (TS)

Tuberous sclerosis (TS) refers to an inherited neurocutaneous disease of cell differentiation and proliferation, which affects multiple organs. The earlier the age of seizure onset, the worse the outcome. Seizures initially manifest as epileptic spams and are associated with developmental slowing and even regression. Early and effective treatment (possibly surgery if the tubers responsible for the seizures can be localised) may decrease the developmental impact of TS. 

Landau-Kleffner syndrome (LKS)

Lastly, Landau-Kleffner syndrome (LKS), also known as acquired epileptic aphasia, is part of a spectrum of epileptic encephalopathies (EE) characterised by a markedly abnormal EEG pattern during sleep, known as electrical status of slow wave sleep (ESES). LKS typically has its onset between age three and ten and is characterised by verbal auditory agnosia (the inability to make sense of speech sounds). Some children develop even a complete inability to interpret environmental sounds and are, for example, not able to interpret dogs barking. Other deficits that may develop are related to motor skills, behaviour and attention. 

How to treat epilepsy?

The first treatment option typically is anti-epileptic drugs (AED). Almost half of the patients will become seizure free after the first prescribed AED. Yet, it is important to note that the prognosis in terms of seizure control for people who do not respond to the first prescribed AED rapidly decreases with the failure of each subsequent AED to provide good control. When choosing to treat epilepsy with AEDs, the goal is to control seizures with a single medication and to avoid negative side effects. Initial choice of a particular AED depends on seizure type and epilepsy syndrome. Commonly reported side effects are related to learning and behavioural difficulties.

Another treatment option is surgery. Surgery may be considered when AED treatment fails to manage the epilepsy effectively or when it can offer the child a good chance of a life free of seizures and without the need for medication. Success of surgery depends on accurately locating the epileptogenic lesion, usually via neuroimaging, in which complete resection is the best predictor of postoperative seizure freedom. Surgery is typically preceded by pre-surgery assessment, in which video-EEG monitoring and anatomical MRI are core components. 

Other treatment options include dietary modifications, including the ketogenetic diet (high in fat, low in carbohydrate, and moderate in protein intake) as well as a range of psychological therapies, including relaxation therapy, cognitive behaviour therapy (CBT), and biofeedback. These psychological therapies may help in managing identified 'triggers' for seizures, such as stress, lifestyle factors, and comorbid psychological problems such as depression.