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Primary generalized epilepsies of adolescence
This encompasses several distinct syndromes with significant overlap the Juvenile Myoclonic Epilepsy (JME), Juvenile Absence Epilepsy (JAE), the early morning GTC seizures on awakening and others. Often patients have components of all three. VPA is the drug of choice and using the other drugs like CBZ, PHT & PB leads to intractability. Acetozolamide (AZ) and LTG are other
choices. Treatment is usually needed for prolonged duration.Many less common syndromes are beyond the scope of this discussion.

Only 50% of cases or less can be classified into such specific syndromes. In the remaining the prominent seizure type helps decide the appropriate therapy.

Seizure type

The two broad calssifications of seizures are:

Partial seizures
These are also known as localization-related and are divided into simple, complex partial and secondarily generalized seizures.

CBZ, PHT, PB & Primidone (PM) have been shown to be equally effective in newly diagnosed adults. However the percentage of adults dropping out because of side effects was more in the PB and PM groups thereby suggesting that CBZ and PHT should be first choice due to their more favorable side-effect profile. VPA was compared to CBZ in another study in adults and though both were equally effective in controlling generalized seizures, CBZ was superior in controlling purely partial seizures. In young children our experience has been slightly different, in that seizures with a prominent motor component, either generalized or partial, respond better to VPA; purely complex or simple partial seizures, especially in older children and adolescents, appear to respond well to CBZ. The new AEDs with a strong anti-epileptic effect in partial seizures are CLB and VGB. These have been tried even as first line monotherapy with efficacy equivalent to CBZ. LTG and GBP have a weaker effect. Topiramate (TPM) and Tiagabine (TGB), (still not available in India) are fairly effective drugs, though their use is mainly as adjunctive therapy in refractory seizures.

Generalized seizures
These include GTC, myoclonic, absence and atonic seizures occuring either alone or in combination as part of the primary idiopathic or secondary cryptogenic or symptomatic epilepsies. VPA being a broad spectrum drug has become the mainstay of therapy in this group. Though high dose VPA therapy had become fashionable in difficult to control seizures most authorities do not recommend going too high, because of the risk of a dose related encephalopathy-parkinsonism syndrome associated with brain atrophy. ESM is still a preferred drug in pure absence epilepsies though there is a risk of precipitating GTC seizures.

The BZDs are also broad-spectrum agents with fairly rapid response rates in many of the generalized and partial epilepsies. However CLP is limited by a high degree of tolerance within a few months and also by its myriad side effects especially on cognition and behavior. CLB being a slightly different BZD has however become a major drug, as side effects and tolerance rates are acceptably low. LTG is another drug with a high therapeutic index in the generalized epilepsies with a strong effect on all types. It is especially effective in combination with VPA.

Age and gender considerations

We do not use CBZ in infants as far as possible. There is a risk of inducing generalized seizures in this age group especially when there are multiple seizure types. An attractive hypothesis to explain this phenomenon may be the tendency of CBZ to induce generalized spike and wave discharges in young children who have profuse synaptic connections, making secondary bilateral synchrony that much easier. This might lead to language and cognitive deterioration in some children. PB is very useful in young infants with partial and secondarily generalized seizures, and the adverse effects in this age group are much less than in the toddler and school going child. Though PHT has excellent efficacy, the formulations available in India i.e. suspensions and capsules make this a difficult drug to use in young children. Also absorption and drug clearance is fairly variable and hence drug levels fluctuate widely leading to erratic seizure control. VPA was not preferred in infants because of the risk of fatal liver disease. However this appears to have been overstated and is really a problem only if the child has a metabolic disorder like a mitochondrial cytopathy or a Beta-oxidation defect. VGB is a good drug even in infants; however recent reports of field defects in those using high doses chronically is a cause for concern because of the difficulty of doing perimetry in this group. CLB and LTG are well tolerated.

In the school-age child, where learning is a priority, PB, PM, BZDs GBP and even VGB can cause significant neurobehavioral side effects which can interfere with academic performance. CBZ and VPA are the mainstays of first line therapy. Adolescents tend to medicate themselves and therefore it is preferable to use once or twice a day dosing as they often forget the afternoon dose and do not like to take this dose in front of their peers. Sustained release CBZ, PHT & CLB are good choices. In the primary generalized epilepsies where VPA is needed there are sustained release preparations, available only abroad. In most however, twice daily dosing is adequate.

We try and avoid PHT in girls-especially adolescents because of the cosmetic side effects, which may become irreversible. Coarsening of the facies, gum hyperplasia and hirsutism are commonplace with long term phenytoin.

Premorbid disorders/diseases

This is an important consideration when choosing an appropriate drug in an effort to minimize adverse effects. Children who are already retarded and who have behavior and school problems, are more prone to aggression and hyperactivity, as compared to those who are normal in neurobehavior at baseline. PB, VGB , BZDs and GBP are all drugs with an adverse effect on behavior and hence must be used cautiously in this group. The BZDs may adversely effect children with in-coordination and problems in motor skills. Those with tremors and fine motor problems may be worsened by high doses of VPA. BZDs may worsen the problem of drooling in-patients with cerebral palsy.

Obese children may gain significant weight with the use of VPA, VGB and more recently CLB, such that the weight gain may become the major problem rather than the seizures. Infants with GE reflux and recurrent vomiting are often made worse with the VPA in liquid form, as it may cause gastritis and more reflux. Those with sleep disorders, common in autistic children, are significantly worsened by the use of BZDs and PB.

Infants with diagnosed or suspected metabolic disorders are more prone to the liver toxicity of VPA and this is relatively contra- indicated.