Managing first-time seizures and epilepsy in children

A first seizure is a relatively common problem in paediatric general practice.

SALLY ACKERMANN, MB ChB, DCH, FCPaed

Senior Registrar in Paediatric Neurology, School of Child and Adolescent Health, University of Cape Town and Red Cross Children’s Hospital, Cape Town

Sally Ackermann is a senior registrar in paediatric neurology. She has an interest in the epidemiology of children with epilepsy.

RONALD VAN TOORN, MB ChB, MRCP, FCPaed

Senior Specialist in Paediatric Neurology, Stellenbosch University and Tygerberg Children’s Hospital, Cape Town

Ronald van Toorn has worked in the paediatric neurology department at Tygerberg Children’s Hospital since 2003. His field of interest includes epilepsy, especially its management in resource-poor countries.

Correspondence to: Sally Ackermann (sally.ackermann@yahoo.com)

An estimated 8% of the population will have a seizure at some point in their lifetime.1 Half of these occur during childhood, making a first-time seizure a commonly encountered problem in general paediatric practice.2 It is estimated that 1 in every 100 South Africans suffer from epilepsy; a small rural study in the Northern Province demonstrated an active prevalence of 6.7/1 000 children.3 The true burden of epilepsy in South African children is unknown but likely to be large. It is one of the most common chronic disorders managed by general practitioners, paediatricians and paediatric neurologists.

A stepwise approach to a suspected first-time seizure ensures a correct diagnosis and minimises unnecessary investigations and treatment.1 Epilepsy is defined as 2 or more unprovoked seizures and also requires a logical approach to management.

Stepwise approach to a child with a suspected first-time seizure

• Is this a true seizure?

• If so, what type of seizure is it?

• Is this the first seizure?

• Was the seizure provoked or unprovoked?

• What investigations are necessary?

• Is drug treatment necessary?

First-time seizures

Is this a true seizure?

A detailed eye witness account is essential but often not available. An incomplete history is the principal reason for misdiagnosis of epilepsy.4 There are many seizure mimics and paradoxically some subtle seizure types are easy to miss. Parents should be encouraged to capture the event on their cell phone or via video camera when there is doubt about true epileptic seizures. A few of the more common seizure mimics are detailed in Table I.

What type of seizure is it?

The International League Against Epilepsy (ILAE) has recently revised its classification of seizures.8 However, the most practical classification remains:

• generalised seizures including tonic, clonic, tonic-clonic, absence, myoclonic and atonic seizures and infantile spasms

• focal/partial seizures including simple partial seizures (during which awareness is retained), complex partial and secondary generalised seizures.

A seizure which cannot be categorised should remain unclassified until further witnessed events provide more information in order to avoid inappropriate investigations or therapy choices.

Is this the first seizure?

Directed questioning is essential to reveal unreported or unrecognised seizures such as myoclonic jerks and absences. It is important to ask leading questions about these features and to remember that seizures such as infantile spasms may be as subtle as a head nod followed by a cry. The mother will often not volunteer this information, particularly if she has previously been falsely reassured that her baby has colic.

Was the seizure provoked or unprovoked?

This is an important distinction to make. In many children, a thorough history and careful neurological examination will allow a diagnosis without the need for further evaluation.

• Provoked seizures are those occurring in temporal relation to an acute systemic or central nervous system (CNS) event, e.g. hypoglycaemia, fever, acute ischaemic stroke, CNS infections and toxins.

• Unprovoked seizures occur spontaneously without any known proximate precipitant or relation to an antecedent event.

• ‘Remote symptomatic’ seizures are sequelae of a static or progressive CNS disorder, e.g. congenital brain malformation, previous stroke or sequelae of perinatal asphyxia but without any apparent immediate precipitant.

The distinction has implications for future prognosis and management dealt with below.

What investigations are necessary?

Laboratory tests

Investigations should be performed based on the individual clinical history and examination findings.

• Blood pressure and fundoscopy are an essential part of the clinical examination in any child with a seizure.

• Routine blood tests, apart from serum glucose, are not recommended in children older than 6 months with a first unprovoked seizure provided there is cause no apparent, no neurological abnormality and the child returns to baseline alertness and functioning.5 Serum urea and electrolytes are important in children with a history of diarrhoea or vomiting.

• A toxicology screen should be performed if there is any question of drug or substance exposure evident from the history.

• Recommendations for lumbar puncture (LP) in the child with an unprovoked seizure are not based on strong evidence but include the child below 6 months of age and those with meningeal signs or persistently altered mental state without obvious cause.7

• In the child with fever an LP is indicated whenever meningeal signs are present or in young children (under 18 months) in whom signs of meningeal irritation may be absent, provided there are no contraindications.

When to perform an electroencephalogram (EEG)(Fig. 1)

An EEG should be requested after 2 or more seizures but may be performed after the first event if it will specifically alter management. Examples include children with a suspected benign focal seizure disorder and unusual syncopal events. A EEG can be performed on an outpatient basis. The clinician should be aware that an EEG abnormality alone is not sufficient to make a diagnosis of seizures and the absence of an abnormality does not exclude seizures.6 An estimated 5 - 8% of healthy children will have interictal EEG abnormalities.6

The EEG technologist should be informed about which seizure type is suspected as this may influence the way in which the study is performed. Sleep enhances the yield of a positive test by 30%, especially in certain seizure types, e.g. temporal lobe epilepsy. It is worth considering a drowsy or a sleep study in the child with a normal awake EEG but a convincing history of seizures.6 Sleep deprivation prior to the test is useful in the older child. Younger children may require sedation. Children with suspected infantile spasms should have an initial awake EEG as the pathognomonic finding of hypsarrhythmia may be attenuated in the sleeping infant. Infantile spasms are a medical emergency and an EEG should not be delayed as these children need urgent intervention.

Neuroimaging

If neuroimaging is indicated, MRI is the preferred modality but a CT scan is usually sufficient. Urgent neuroimaging should be performed in the following settings:

• status epilepticus without obvious cause7

• postictal focal neurological deficit which does not quickly resolve7

• a child who does not return to neurological baseline within a few hours after the seizure – the effects of emergency medication used to terminate the seizure should be taken into consideration7

• the child with suspected raised intracranial pressure.

Routine imaging should be performed in the following settings:

• a child who is stable and has had a focal seizure of unknown cause7

• a child with other unexplained abnormal neurological findings7

• a child with significant developmental delay of unknown cause7

• children under 1 year of age with an unprovoked seizure.7

There is no evidence to support routine imaging after an unprovoked first-time generalised seizure as the sole indication.4 , 7

Is seizure prophylaxis necessary?

The majority of first-time seizures do not need drug treatment. The indiscriminate use of drug therapy may lead to unnecessary side-effects and loss of parental trust. Watchful waiting is usually the most sensible option in the case of an unprovoked first-time seizure, provided the risks of another seizure do not outweigh the risks of treatment. These include cognitive, behavioural, pharmacological and psychosocial risks of long-term therapy to the child. Certain provoked seizures may warrant short-term prophylaxis (approximately 3 months), e.g. neurocysticercosis with multiple lesions and a prolonged first seizure.

Recurrence risks of first-time seizures

The cumulative risk of having a second seizure increases to 42% after 8 years’ follow-up. However, data suggest that the majority of recurrences occur within the first 1 - 2 years with only 3% occurring after 5 years.6

According to ILAE criteria a ‘first seizure’ includes multiple seizures within 24 hours but with recovery of consciousness between seizures. Approximately 10% of first-time, unprovoked seizures will present with status epilepticus.5 Potential risks resulting from a second seizure are a concern but data from studies in children indicate that even prolonged seizures rarely cause discernable brain damage provided there is no underlying neurological insult.5 Sudden unexpected death in children with epilepsy is uncommon. Sudden unexpected death in children is often related to an underlying neurological handicap rather than epilepsy itself.5

Factors increasing the likelihood of a second seizure include a remote symptomatic cause, younger age at presentation (under 2 years) and focal seizures or focal neurological findings on examination. This correlates with a higher incidence of symptomatic epilepsy. Recurrence rates are lowest in children with no clear aetiology or suspected genetic aetiology (approximately 30%). The overall recurrence risk following a first prolonged seizure appears to be no different to that following a brief seizure; however, any recurrence is also likely to be prolonged.5

Early anti-epileptic drug (AED) treatment, i.e. after the first seizure, may reduce the risk of seizure recurrence but has not been shown to improve the prognosis for long-term remission and does not prevent epilepsy.2 , 5

Epilepsy

Diagnosis of epilepsy
• Differentiation of seizures from seizure mimics and classification of seizure types as detailed above
• Determination of the underlying aetiology
• Classification of the epilepsy syndrome
• Selection of anti-epileptic agent if treatment warranted

Determination of the underlying aetiology

Instead of the aetiological terms idiopathic, symptomatic and cryptogenic, the following three categories have been recommended by the ILAE:8

• Genetic: epilepsy in which no underlying structural brain lesion or other neurological symptoms or signs are present. The epilepsy is due to a presumed or known genetic defect in which seizures are the core symptom of the disorder and are usually age dependent, e.g. childhood absence epilepsy.

• Structural-metabolic: the presence of a distinct structural or metabolic condition that has been demonstrated to be associated with a substantially increased risk of epilepsy. Structural lesions may be acquired, e.g. stroke or trauma; or genetic, e.g. tuberous sclerosis or malformations of cortical development.

• Unknown cause: the nature of the underlying cause is unknown; the cause is believed to be symptomatic but no aetiology is as yet identified.

Classification of the epilepsy syndrome

Up to two-thirds of cases can be assigned to specific syndromes at initial diagnosis. Of those remaining about a third will be assigned to more specific categories within the following 2 years.6 Common or important syndromes that should be recognised early are highlighted in Table II.

Classification and categorisation may assist one in predicting prognosis and response to treatment. In many cases, however, this is only possible in retrospect. See Tables III and IV.

Selection of anti-epileptic agent

Points to consider when deciding on initiation of therapy:

• The decision to treat should be tailored to the individual child.

• Treatment may not be needed in some of the ‘benign’ epilepsy syndromes such as benign rolandic epilepsy.

• Treatment goals vary according to the epilepsy syndrome; seizure control without adverse drug effects may not be achievable in all and inappropriate polytherapy may lead to unacceptable side-effects without added benefit.

• Approximately 60 - 70% of newly diagnosed epileptics will become seizure free with first or second choice monotherapy.10

• New drugs should be trialled for 3 - 6 months and then gradually discontinued if there is poor response. The likelihood of response to each new agent dramatically decreases with each drug failure. Intractability implies epilepsy that is uncontrolled despite the use of 2 appropriately chosen agents at therapeutic dosages.

• Parents should be warned of potentially life-threatening side-effects as well as the more common ones, e.g. Stevens-Johnson syndrome with use of carbamazepine and lamotrigine, both of which should be titrated slowly to lessen this risk.

• Certain drugs should be avoided with specific seizure types, e.g. carbamazepine may exacerbate myoclonus, absences and drops; lamotrigine may exacerbate myoclonus.

• Drug levels are only useful in certain situations, e.g. sodium valproate levels are useful only for determining non-adherence and drug toxicity and should not be used for dose titration.

Who to refer for tertiary opinion

• Children who have atypical features of the traditionally ‘benign’ epilepsy syndromes, e.g. absences which start before age 4 years

• Any epilepsy patient who does not achieve adequate control on monotherapy, provided the drug is trialled at an adequate dose and compliance is established

• Multiple seizure types

• Children with epilepsy and unexplained developmental delay or intellectual disability

Withdrawal of therapy

The belief that all children should be seizure free for at least 2 years has been challenged in recent years. There is evidence that in children with ‘benign epilepsies’ AEDs may be withdrawn if they have been free of seizures for a period of between 6 and 12 months.12 However, as a general rule a seizure-free period of 2 years should be attained before considering drug therapy withdrawal (exceptions include the child with a focal lesion such as neurocysticercosis who has been started on short-term prophylaxis, as discussed above).

The relapse rate after AED withdrawal is approximately 30% at 2 years overall, with 50% of these occurring during the period of drug withdrawal.12 Aetiology and syndromic diagnosis are the main predictive factors.9 Recurrence risk is lowest in children with childhood absence epilepsy and benign focal epilepsy of childhood and highest in those with symptomatic seizures or history of Todd’s paresis following seizures.12

If the child is on multiple AEDs, they should be withdrawn sequentially, i.e. one at a time. Withdrawal of medication should occur gently over a period of 6 weeks. If seizures recur during this period the dose of the AED being withdrawn should be stepped up to the dose prior to the current stepped-down dose.

References
1.   Seneviratne U. Management of the first seizure: an evidence-based approach. Postgrad Med J 2009;85:667-673.
2.   Wiebe S, Tellez-Zenteno J, Shapiro M. An evidence-based approach to the first seizure. Epilepsia 2008;49(Supp.1):50-57.
3.   Christianson AL, Zwane ME, Manga P, Rosen E, Venter A, Kromberg JGR. Epilepsy in rural South African children - prevalence, associated disability and management. S Afr Med J 2000;90(3):262-266.
4.   Smith D, Defalla BA, Chadwick DW. The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic. Q J Med 1999;92:15-23.
5.   Hirtz D, Berg A, Bettis D, et al. Practice parameter: Treatment of the child with a first unprovoked seizure. Neurology 2000;55:616-623.
6..   Guerrini R. Epilepsy in children. Lancet 2006;367:499-524.
7.   Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Camfield P. Practice parameter: Evaluating a first nonfebrile seizure in children. Neurology 2000;55:616-623.
8.   Berg AT, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia: Early View, date February 2010.
9.   Fenichel GM. Clinical Pediatric Neurology: A Signs and Symptoms Approach. 5th ed. Philadelphia: Elsevier Saunders, 2005.
10. Raspall-Chaure M, Neville BG, Scott RC. The medical management of the epilepsies in children: conceptual and practical considerations. Lancet Neurol 2008;7:57-69.
11. Ramos-Lizana J, Aguirre-Rodriguez J, Aguilera-Lopez P, Cassinello-Garcia E. Recurrence risk after withdrawal of antiepileptic drugs in children with epilepsy: A prospective study. Eur J Paediatr Neurol 2010;14:116-124.
12.Raymond AA. How to stop antiepileptic drugs. Neurology Asia 2007;12(Supp.1):27-29.

Fig. 1. EEG showing 3 per second (3Hz) spike and wave discharges typical of absence epilepsy.