Educationals

Choice of antiepileptic drug

Since the last few years there are new molecules being introduced every few months in the Indian market and the pediatrician is faced with a hitherto unavailable choice of which agent would be best suited for particular patient. This discussion is an attempt to rationalize this decision using both literature review and personal observations.

Important factors to consider in this decision include the
following :

• Epilepsy syndrome diagnosis if possible
• Type of seizure/seizures
• Age and gender of the patient
• Premorbid conditions/disorders
• Cost of therapy.
  

Epilepsy syndromes

Drug research and development has only recently targeted specific epileptic syndromes and diseases, providing us with invaluable data on which specific drugs help which syndromes. Felbamate (FBM) and Lamotrigine (LTG) have been shown in double blind randomized trials to be extremely effective in the Lennox-Gastaut syndrome of multiple seizure types. Similarly Vigabatrin (VGB) has been shown to be more than 90% effective in infantile spasms due to tuberous sclerosis (TS). A brief summary of the appropriate drugs in specific syndromes follows

Neonatal seizures

This is discussed elsewhere. It is important to emphasize that most are acute symptomatic seizures and will need specific management and only short term AEDs. Parenteral phenobarbital (PB) and phenytoin (PHT) either alone or sequentially control most seizures if appropriate doses are given; inadequate doses are the usual reason for failure. It must be also stressed that overdose may occur due to decreased hepatic and renal clearance in neonates with HIE or other systemic ailments.

Infantile spasms (IS)

ACTH is probably the drug of first choice being some-what more effective than prednisolone. They have been shown to stop the spasms, reduce or reverse the cognitive decline/epileptic encephalopathy and reduce possibly the risk of long-term epilepsy. Recently it has been demonstrated that low doses (20- 40 IU) are as effective as high doses. The problem in India is
availability, making prednisolone the drug of choice. Recently European data supports the use of oral hydrocortisone in refractory cases. VGB is a strong competitor for this condition and has established itself as the drug of choice in IS due to TS. The benzodiazepines (BZDs) are next with nitrazepam (NZP) being the most effective and tolerated. Side effects and the phenomenon of tolerance limit clonazepam (CLP). Though there were good reports of valproate (VPA) in IS our experience has been disappointing. Higher doses may be useful but the price of GI side effects limits it use.

Febrile seizures

This is discussed elsewhere in detail. Suffice it to emphasize that this rarely needs long-term treatment and should be managed with parental reassurance and/or intermittent BZD therapy with wither diazepam (DZ) or clobazam (CLB). Rectal DZ is probably more effective than oral; however ease of administration makes the oral preferable. If long term treatment is planned VPA and PB are effective. Carbamazepine (CBZ) and PHT do not help and in our experience at least, CBZ might worsen the seizures in a few children.

Lennox-Gastaut syndrome(LGS)

As mentioned earlier, LTG and FBM are most effective. The former has just been introduced and the latter has fallen out of favor because of bone marrow and liver toxicity. At present we start with VPA and add CLB in case the seizures do not get controlled.

LTG is the rational next step. Though CBZ and PHT may be useful for associated partial seizures there is a real risk of pushing these children into minor absence or myoclonic status and hence those should be avoided. BZDs may increase seizures as well because of their sedative effects. Many children are poorly controlled and alternative therapies like the ketogenic diet and epilepsy surgery (corpus callostomy) should be considered early.

Childhood absence epilepsy

Benign partial epilepsies of childhood

The most common of these are the BECTS and the BEOPS. The seizures are infrequent and remit easily especially in the former, despite significant EEG abnormalities. Often no treatment is needed. However in case treatment is given, CBZ and VPA are the drugs of choice according to the literature. Our experience is better with VPA because of the tendency of CBZ to increase the generalization of epileptiform discharges and possibly induce language and cognitive problems. This atypical evolution of benign partial epilepsy has been recently reported in six patients, five of whom were on CBZ, CLB and Gabapentin (GBP) are two new AEDs that are being tried in these conditions.

Landau Kleffner and Related Syndromes (LKS)

This syndrome of epilepsy and aphasia has been extensively studied. The language disturbance appears to be due to epileptic dysfunction of bilateral posterior temporal & parietal cortex and usually involves auditory comprehension first. Later the aphasia progresses to mutism. Initial expressive language disorders have been noted rearely when the epileptic abnormalities are more in the rolandic areas. Clinical seizures are not really much of a problem and in fact may never occur. Steroids are the mainstay of therapy and do lead to remission in some. Repeated courses may be needed. The remission is often associated with normalization of the EEG. The long-term course is variable; some children with persistent aphasia benefit form surgery. For seizures, CBZ should be avoided as the language disturbance might worsen. VPA or CLB are useful. A closely related disorder is the ESES syndrome (Electrical Status in Show Wave Sleep) where again the language, cognitive and behavioral regression is more prominent than the seizures. These are usually myoclonic in nature. Steroids are used with a poorer response rate and BZDs (not VPA) are the drug of choice for the myoclonias.