Epilepsy in Children

Essentials

• Early diagnosis of childhood epilepsy is important. In particular, epilepsy starting in infancy or at preschool age may delay the normal development of the child, and early diagnosis may improve the prognosis.
• All children in whom epilepsy is suspected should always be referred urgently to specialist care for further investigations.
• Diagnosis of epilepsy is based on the description and history of seizures, supplemented by EEG recordings and imaging studies.
• Pharmacological treatment should be chosen according to the type of epilepsy or syndrome. Medication that is inappropriate may lead to the aggravation of seizures or other neurological manifestations.
• Monitoring of the child's neurocognitive development and the provision of appropriate support are important in the treatment of childhood epilepsies.
• Some childhood epilepsies are self-limited and need only short-term medication.
• A child with drug-refractory epilepsy should be referred for consultation to a paediatric neurology unit with expertise in the treatment of severe epilepsy in order to confirm the aetiology and syndrome diagnosis and to assess the treatment possibilities.

Childhood epilepsy

• Epilepsy is a brain disease in which the patient has a chronic tendency to epileptic seizures, possibly involving other problems with neurological, cognitive, mental or social performance.
• Childhood epilepsies vary as regards aetiology, age of onset, symptoms and prognosis.
• Severe epilepsy is a state where, despite appropriate medication, there are significant epileptic symptoms affecting daily life, such as repeated seizures, cognitive or behavioural problems, delayed development or adverse treatment effects. About 20% of all affected children have severe epilepsy, and approximately one third of the children will have associated neurological signs and symptoms (developmental disability, locomotor disability, learning difficulties etc.).
• The incidence of epilepsy is about 0.35/1 000/year. It is highest during the first year of life (1.24/1 000). Its prevalence is about 0.4%.
• The classification of epilepsy is based on the character of the seizure symptoms, EEG findings and aetiology.
  • In focal epilepsy, the seizure symptoms and EEG changes associated with the seizures are limited to one hemisphere at the beginning of the seizure but may become generalised at a later stage.
  • In generalised epilepsy, the seizures and associated disturbance of the electrical activity of the brain occur in both hemispheres from the beginning.
• Common features of an epileptic seizure are
  • partial or complete disturbance of consciousness
  • involuntary motor activity, such as jerky rhythmic movements, stiffening, individual muscle jerks, muscle limpness
  • automatic movements, such as swallowing or picking at clothes or objects
  • spontaneous affective phenomena (e.g. fear) or sensory experiences (often at the beginning of a seizure, previously known as aura).
• The most common seizure in infancy is a cluster of infantile spasms during which extensor or flexor spasms lasting less than a second are observed. The spasms occur repeatedly every 5-10 seconds for several minutes.
• The cause of epilepsy may be structural, genetic, infectious, metabolic or immunological. Despite investigations, the cause may remain unknown.
  • The most common structural causes include developmental disorders and damage affecting the cerebral cortex.
  • Some epileptic diseases caused by a defect in a single gene are self-limiting and not associated with other problems, whereas others are difficult to treat and feature multiple associated problems.
  • In genetic multifactorial (earlier referred to as "idiopathic") epileptic syndromes, the child's development is usually normal, and investigations other than EEG will not reveal anything abnormal.
• An epileptic syndrome is a certain combination of signs and symptoms, types of seizures, and EEG or imaging findings. Such syndromes often have typical features including age at onset, prognosis, factors triggering seizures and diurnal variation of seizures.

Investigations

• The diagnosis of epilepsy is based on the history. It is very important to obtain a detailed description of seizures, the chronological order of the symptoms as well as the child's functional capacity during and after a seizure. Video recordings, taken either at home or in hospital, often yield additional information.
  • The first symptom of epilepsy may be just a decline or slowing noted in cognitive development. In infants, the most common signs are a decline in the ability to follow moving objects with their eyes and grasp objects, as well as loss of spirits. In toddlers, speech regression may be evident.
• During a neurological examination, diagnostic clues, such as local findings or skin changes, should be sought and the developmental stage of the child assessed.
• An EEG recording is always indicated when epilepsy is suspected.
  • Since in many forms of epilepsy abnormalities are slightly more likely to become evident during sleep, a sleep EEG recording is always preferred in children.
  • An EEG is indicated in infants whose cognitive development is delayed for an unexplained reason, even when no seizure activity has been noted.
  • A normal EEG does not rule out epilepsy, and an abnormal EEG is not sufficient to confirm the diagnosis of epilepsy with some rare exceptions (e.g. hypsarrhythmia associated with infantile spasm syndrome).
• Magnetic resonance imaging (MRI) is the most important aetiological investigation. An MRI is always indicated in a child who has been diagnosed with epilepsy, except in cases where, based on the clinical picture and EEG, a genetic multifactorial epileptic syndrome can reliably be identified.
• Other aetiological investigations may be considered should there be reason to suspect an underlying genetic, immunological, infectious or metabolic disease, for example.

Differential diagnosis

• Non-epileptic seizures are more common than epileptic seizures.
• Symptoms of non-epileptic seizures in infants and toddlers include simple febrile convulsions, symptoms originating from gastro-oesophageal reflux, tics, childhood masturbation and breath-holding spells.
• Syncope is possible in school-age children. Functional seizures are rarer than in adults.

Principles of pharmacological treatment Pharmacological Interventions for Epilepsy in People with Intellectual Disabilities, Immediate Antiepileptic Drug Treatment, Versus Placebo, Deferred, or No Treatment for First Unprovoked Seizure, Early Versus Late Antiepileptic Drug Withdrawal in Pediatric Epilepsy, Ethosuximide, Sodium Valproate or Lamotrigine for Absence Seizures in Children and Adolescents, Levetiracetam Add-on for Drug-Resistant Focal Epilepsy in Children, Ketogenic Diets for Epilepsy in Children

• The first aid management of prolonged seizures Acute Care of Seizures of Cerebral Origin in Children:
  • rectal diazepam (Stesolid^® ); 5 mg in children weighing up to 15 kg and 10 mg in children weighing more, or
  • buccal midazolam (Buccolam^® ); see Acute Care of Seizures of Cerebral Origin in Children for dosage.
• Long-term medication is usually introduced after a second epileptic seizure within one year or if the aetiology suggests that recurring seizures are highly probable. Pharmacological treatment is not always needed in genetic self-limiting epileptic syndromes.
• The treatment goal is freedom from seizures without adverse effects. If freedom from seizures cannot be achieved, the aim should be to achieve the best possible quality of life.
• The dose is usually increased gradually in order to avoid the emergence of adverse effects. Therapeutic levels are reached with most medication within approximately three weeks.
  • The dose should be calculated according to the weight of the child. The adult dose must not be exceeded.
  • Efficacy depends not only on the type of medication but also on the dose. If seizures are not controlled, a dose increase should therefore be attempted first. If the seizures continue despite the higher dose, another monotherapy should be tried.
  • Most antiepileptics are administered in the morning and in the evening. If the child vomits within half an hour from the administration of the drug, the dose may be repeated.
  • In some cases, two concomitant drugs are indicated. In such a case, drugs with a different mode of action should be used.
• Blood counts and ALT should be checked before starting the medication and at least once during the initial months of medication. If oxcarbazepine is started, plasma sodium levels should additionally be measured. ECG may be indicated depending on medication.
  • Thereafter, laboratory investigations (including drug concentrations) are only needed when adverse effects,drug interactions, absorption problems or nonadherence are suspected, or if seizures continue despite medication.
• An attempt should be made to withdraw medication after two seizure-free years.
  • However, in certain syndromes, such as juvenile myoclonic epilepsy, there is a significant risk of seizure recurrence even after several seizure-free years and medication is therefore usually continued even in adulthood.
  • In many childhood genetic self-limiting epilepsies, withdrawal of medication may be considered as soon as after one year.
  • If pharmacological management of seizures has been difficult or if the cause of epilepsy is structural, the need for treatment may be longer, even indefinite.
• First-line drugs
  • Focal epilepsy: oxcarbazepine, carbamazepine or levetiracetam
  • Childhood absence epilepsy: ethosuximide or valproate
  • Other genetic generalised epilepsies, e.g. juvenile absence epilepsy and myoclonic epilepsy: valproate except for girls of or approaching fertile age. Alternatives include lamotrigine and levetiracetam.
  • Infantile spasm syndrome: ACTH or vigabatrin
  • Severe generalised epilepsies, e.g. Lennox-Gastaut syndrome: valproate, but combination medication is usually necessary
  • Neonatal onset epilepsy:phenobarbital and levetiracetam. Carbamazepine is the first-line drug in certain types of genetic neonatal epilepsy.
• For severe epilepsy, dietary, surgical and stimulation therapies should be considered in addition to medication.

Referral to a paediatric neurologist and the chain of treatment

• Primary health care: responsible for identification of symptoms, first aid for seizures, referral to a paediatric neurologist, normal follow-up and vaccination at child welfare clinic and in school health care
• Paediatric neurology unit within specialized care: responsible for diagnosis and differential diagnosis of epilepsy and associated symptoms (such as learning difficulties or developmental disability), treatment, multidisciplinary rehabilitation and follow-up
• Multidisciplinary teams specialized in epilepsy within university/tertiary care hospitals: responsible for investigations and treatment consultations regarding severe epilepsy
• Centres specialized in epilepsy, epilepsy surgery teams: responsible for special diagnostics and surgical treatment of severe epilepsy (demanding specialist level treatment)

References

• Scheffer IE, Berkovic S, Capovilla G et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58(4):512-521. [PubMed]