In a very simplistic scheme, patients with epilepsy can be classified into 3 general etiologic categories, which is relevant in considering surgical candidacy (Berg et al 2000; 2001a; 2001b; 2001c). In pediatric patients, epidemiological studies indicate that epilepsy from presumed genetic etiologies (eg, absence seizures, Rolandic epilepsy) accounts for 32% of new-onset cases whereas those from structural brain lesions (eg, stroke, cortical dysplasia) occur in 18%. This was confirmed in an epidemiologic study demonstrating that 16% of pediatric epilepsy patients have MRI abnormalities potentially relevant to their disease (Berg et al 2009). The remaining 50% of new-onset pediatric epilepsy patients have unknown or as yet unidentified etiologies. The finding that 50% of new-onset epilepsy cases in children cannot properly be diagnosed in the current millennium using modern neuroimaging and EEG is rather sobering. That said, MRI and other forms of neuroimaging have proven critical in assisting clinicians in the diagnosis of children with therapy-resistant epilepsy (Salamon et al 2008). In children with new-onset epilepsy of non-idiopathic etiologies, 22% will have positive MRI scans, and 54% of those will become drug resistant (Berg et al 2009).
Seizure control with AEDs in the first 2 years of treatment differs depending on the epilepsy etiology category. Genetic (old idiopathic) pediatric epilepsy patients can expect a 95% chance of near seizure control with AEDs (fewer than 1 seizure per month), and the rate for unknown cases is 90%. By comparison, pediatric patients with epilepsy from structural lesions, who are the best potential surgical candidates, can expect near seizure control with 50% probability or less (Spooner et al 2006). Hence, in a general pediatric practice, the number of new-onset epilepsy patients whose seizures are not controlled with AEDs would be expected to be about 23% to 33%. About 10% to 15% of all children with epilepsy will be referred for a comprehensive epilepsy evaluation, and 4% to 6% will receive some sort of epilepsy neurosurgery (Berg et al 2009). Population studies with follow-up intervals of nearly 40 years indicate that children younger than 16 years of age with symptomatic epilepsy are the least likely to become seizure-free as adults (Sillanpaa et al 1998; Sillanpaa and Schmidt 2006). Hence, young children with epilepsy from structural brain lesions are at greatest risk for not being controlled with AEDs, and failure of seizure control during childhood adversely affects brain development.
We can predict when a child is “therapy resistant” and should be referred to a pediatric epilepsy center based on response to initial AED treatment and etiology category. Once a child has failed to eliminate seizures after 2 to 3 AEDs in mono- or polytherapy, the probability that other drugs will stop seizures is less than 5%, and even less if that child has a lesion on MRI scan (Kwan and Brodie 2000; 2002; Chapell et al 2003). This is especially true for younger patients (less than 2 years old) with catastrophic epilepsy syndromes (Berg et al 2006). Hence, therapy resistance does not mean failure of all AEDs, and it should not take years to decide that a child has intractable epilepsy. In the youngest child, this decision should be made within weeks in order to prevent epilepsy-induced encephalopathy, especially if that child has a known lesion on neuroimaging (Semah et al 1998; Stephen et al 2001).
It is also important to note that seizures in children do not always follow anticipated clinical rules, and pediatricians and parents should be aware of this variability so as not to miss a potentially surgically treatable child. For example, infants and young children with unilateral focal or hemispheric lesions often present with what appear to be generalized clinical seizures and bihemispheric EEG abnormalities (Chugani et al 1988; 1990). This may confuse the practicing physician into thinking they are dealing with a nonoperative process when, in fact, the child is a surgical candidate with a high chance of seizure control postsurgery. Children may present with focal epilepsy that rapidly (sometimes within days) progresses to generalized events, or they may initially present with infantile spasms. Children with infantile spasms are at high risk for epileptic encephalopathy and should be treated emergently (Devlin et al 2003). Similarly, children may present with focal EEG patterns and an apparent negative MRI (initially classified as unknown) but harbor focal surgically treatable pathologies (converted classification to structural). This is especially true for cortical dysplasia, which can be difficult to identify in the young, rapidly growing brain because of cerebral cortical development and white matter myelination. Another clinical presentation often unique to children is the presence of multiple lesions, with only 1 or 2 of them being epileptogenic, as is often the case in children with multiple tubers from tuberous sclerosis complex (Weiner et al 2006; Wu et al 2006). Hence, pediatric patients can present with generalized seizures with focal pathologies, with focal pathologies and EEG with an apparent negative initial MRI, and with multiples lesions where removing 1 or 2 of them will result in excellent seizure control. The evaluation of these more complex epilepsy cases is probably best performed at a pediatric epilepsy center where physicians are familiar with the typical and atypical presentations of children with surgically treatable epilepsy syndromes.