Case 12.2 – Afebrile Seizures (Epilepsy)

Seizures can be classified into:

• Focal seizures: arising within networks of one hemisphere. Focal seizures may remain localised and give rise to localised features such as twitching of one hand or it may spread to other parts of the hemisphere or both hemispheres giving rise to different symptoms.
• Generalised seizures: arising within and rapidly engaging networks of both hemispheres i.e. involvement on both sides of the brain.
• Unknown onset: those which are unable to classify.

Focal seizures can further be subdivided into:

• Focal aware: consciousness preserved; onset focal with motor or non-motor features.
• Focal impaired awareness: impaired level of consciousness; onset focal with motor or non-motor features.
• Focal to bilateral tonic-clonic: begin as focal seizure and spreads to bilateral tonic-clonic.

Generalised seizures can be further subdivided into:

• Motor onset: tonic-clonic, absence, myoclonic, clonic, tonic and atonic.
• Non-motor onset: typical, atypical, myoclonic and eyelid myoclonia.

Commonly encountered types of epilepsy in children include:

• Tonic-clonic seizures: the classic generalised convulsions (also known as grand mal seizures) with a tonic phase characterised by generalised stiffening with loss of consciousness followed by a clonic phase of rhythmic jerking of the limbs and the child is often incontinent of faeces or urine. In the postictal phase, the child remains unconscious and may sleep heavily for several hours. The seizure usually lasts no longer than a few minutes. In some children, the tonic-clonic seizure may be associated with facial cyanosis (central and/or peripheral).
• Absence seizures: common in childhood and adolescence (also known as petit mal). The child ceases activity and stares vacantly and may flutter the eyelids and exhibit some automatisms. If activity is ongoing, it can be interrupted to ask a question or give a command to confirm that there is loss of consciousness. Usually lasts only seconds, and recovery is rapid. The child will have no memory of events which occur during the seizure. The seizure will be associated with generalised 3 hertz spike and wave discharges on the electroencephalogram. May occur hundreds of times a day and schooling can be significantly affected, as can participation in sport and other activities. The episode can be easily missed and therefore the diagnosis delayed.
• Myoclonic seizures: characterised by brief, shock-like muscle contractions, they may be generalised or focal and often occur singly or in clusters shortly after awakening or before sleep. They commonly occur in teenagers. Often described as dropping things or an episode described as clumsiness. They may be precursors to a more generalised seizure disorder – the myoclonic seizures precede or follow the development of tonic-clonic seizures but may occur as the only seizure type. They may also be associated with a very severe form of epilepsy in infancy – termed infantile spasms – these can be difficult to diagnose and treat and are associated with serious developmental problems. Their presence is a medical emergency and requires immediate assessment by a paediatrician. EEG shows chaotic pattern called hypsarrhythmia.
• Atonic and tonic seizures: characterised by sudden loss of muscle tone, causing the child to fall to the ground; in contrast, a tonic seizure is characterised by a sudden increase in muscle tone. An atonic seizure lasts from 1-2 seconds and recovery is rapid with no postictal features.
• Focal seizures: those in which the electrical activity and symptoms are originating from one part of the brain. As seizures can arise from many different areas of the brain they can have many different symptoms such as an unusual smell or taste, facial twitching, finger twitching or a sensation spreading up one limb or over the body. Some focal seizures are associated with very odd sensations such as a feeling of being detached from events, déjà vu and hallucinations. Some focal seizures are associated with retention of consciousness while others may be associated with altered consciousness. Automatisms may be seen such as lip-smacking, plucking at clothing.

Juvenile myoclonic epilepsy (JME). This is one of the most common types of epilepsy seen in adolescence. Myoclonic jerks are experienced, especially shortly after awakening. Often these myoclonic jerks are well established before the patient seeks medical attention and, on occasions, patients may not have recognised them as seizures. In approximately one third of patients absence seizures will also occur which may predate the myoclonic jerks by months to years. The majority of patients with juvenile myoclonic epilepsy will eventually develop generalised tonic-clonic seizures which usually occur on awakening – this is the seizure type that usually brings the patient to medical attention.

The characteristic EEG findings are polyspike and wave discharges. However, it is often the history rather than the EEG that gives the diagnosis. JME is a syndrome that exhibits a clear genetic predisposition with a positive family history in 40-50% of patients. The patients, once diagnosed, need to be aware that there may be triggering factors such as sleep deprivation, photic stimulation or, occasionally, drugs such as amphetamines.

Absence seizures have been alluded to above. These are common in childhood and adolescence and are characterised by brief periods of loss of consciousness usually only lasting seconds. The child ceases what they are doing and stares vacantly and may flutter their eyelids.

MANAGEMENT OF EPILEPSY

The principles of management of epilepsy in childhood are as follows:

• The diagnosis of a seizure and then subsequent epilepsy syndrome must be made clearly and documented. Sometimes neuroimaging is required to rule out an underlying cause for an epileptic seizure. This is usually ordered by a paediatrician or neurologist and involves an MRI of the brain. It is not usually necessary unless focal features in the history are revealed or the clinical examination reveals neurological abnormalities or developmental problems.
• The type of seizure occurring determines which medication is best to control the seizures. In some particular epilepsy syndromes there are certain drug classes which are contra-indicated, such as the use of carbamazepine in juvenile myoclonic epilepsy and in other epilepsy syndromes, the use of sodium valproate (valproate should not be started in women of childbearing age unless there is no suitable alternative).
• The child and family need to be fully apprised of the benefits and side effects of the medication and any contraindications the patient may have to it. Different medications have different monitoring requirements.
• A single drug should be selected and titrated upwards until seizure control is achieved or side effects occur. The chosen anticonvulsant should be appropriate for the particular type of epileptic syndrome diagnosed. Often treatment is continued for at least two years after seizure freedom is achieved.
• If seizure control is not achieved with a single drug, the child should be referred to a paediatrician and/or neurologist for ongoing review. The assessment of seizure control and causes of failure is complex and often requires expertise beyond the capacity of a general practitioner. This is especially important in those whose epilepsy is refractory to treatment. In those with continuing frequent seizures there needs to be consideration as to whether there is a structural brain lesion, whether it is actually epilepsy or non-epileptic in nature and whether there have been medication compliance issues. These patients require specialist review.
• There needs to be particular consideration about drug interactions for those taking other medications – this is especially important in adolescents who are taking hormonal contraceptive therapy – some of the anticonvulsant therapies can reduce the efficacy of the hormonal therapy and cause it to fail. Conversely, the hormonal therapy can reduce the efficacy of the anticonvulsant therapy. The decision to commence combined hormonal therapy should always be discussed with a neurologist or paediatrician first if the patient has epilepsy and is taking an anticonvulsant.
• Counselling and education are important and include advice regarding the need for adequate sleep, compliance with medication and the avoidance of triggering factors such as alcohol excess and binge drinking. There needs to be safety measures advised regarding activities such as swimming and bicycle or horse-riding.
• Advice regarding driving rules and regulations and the responsibilities of the patient to advise the appropriate licensing authorities of their epilepsy, is important for adolescents.

Epilepsy may be categorised as symptomatic (structural/metabolic) or idiopathic (genetic) or unknown/cryptogenic.

Structural/metabolic causes include:

• Structural abnormalities such as cortical dysgenesis or dysplasia
• Brain damage: prenatal (e.g. intrauterine infections, toxins and vascular occlusion), perinatal (e.g. hypoxic-ischaemic encephalopathy) or postnatal (e.g. meningitis, encephalitis, head injury and vascular occlusion)
• Neurocutaneous syndromes: tuberose sclerosis, neurofibromatosis and Sturge–Weber syndrome
• Metabolic: hypoglycaemia, hypocalcaemia, hypomagnesaemia, hypernatraemia, hyponatraemia. Inborn errors of metabolism are rare causes and may be associated with developmental delay.

Genetic causes:

Many, e.g. JME, childhood absence epilepsy, benign neonatal convulsions.

Unknown/cryptogenic

A proportion of children have epilepsy where no cause is found and no epilepsy syndrome can be identified.

Electroencephalogram (EEG): although patients with seizures will often have normal EEGs. The EEG is used to support the clinical diagnosis and may help identify epilepsy syndromes. However, on occasions the EEG may reveal epileptiform discharges that support the diagnosis of epilepsy. The use of sleep, hyperventilation and photic stimulation during an EEG may increase the chances of identifying epileptiform abnormalities. A resting 12 lead ECG should also be ordered to exclude prolonged QT intervals or evidence of Wolff-Parkinson-White (WPW) syndrome which may suggest a cardiac cause for the collapse.

MRI scan: in those who have a focal onset to their seizure and those children with neurological signs or developmental problems to rule out structural problems such as a brain tumour.

Measurement of blood glucose at the time of the seizure. Other metabolic studies are of little value unless features of a metabolic disorder are present.

Hepatotoxicity from the valproate. Sodium valproate has a number of serious side effects that need to be monitored, one of which is hepatotoxicity. This side effect is more likely to occur in children less than three years of age and those who have an underlying metabolic disorder. Other side effects include weight gain, hair thinning, tremor and pancreatitis. It is important in childhood to monitor liver function when the patient is on valproate as hepatotoxicity may be a serious and at times a fatal complication. It is also a teratogenic medication and should not be commenced in women of childbearing age unless there is no suitable alternative. It is associated with major congenital malformations, most commonly spina bifida. An underlying metabolic disorder especially a mitochondrial cytopathy may be suggested by an increased lactate. This may make the child more susceptible to hepatotoxicity associated with valproate treatment.

Recent evidence shows that there is also a risk of developmental disorders in the fetus if a pregnant woman is exposed to sodium valproate, including a dose related decrease in IQ. A form needs to be completed between the treating physician and the patient if valproate is to be used in a woman of childbearing potential.

A full blood count should be taken along with assessment of liver and pancreatic function (LFT's, amylase and lipase). Some practitioners also get a baseline ammonia. If hepatotoxicity, pancreatitis or a significant haematological abnormality has occurred the valproate should be stopped immediately and the child should be commenced on another anticonvulsant appropriate for the control of his type of seizure disorder. The child may need admission to hospital for further work up especially if the hepatitis is severe or there is clinical dehydration due to the vomiting or abdominal pain is uncontrolled. In view of the diagnosis of juvenile myoclonic epilepsy it may be pertinent to consider the use of levetiracetam as an anticonvulsant in this patient, so that he can continue to have seizure control.