Use of the newer antiepileptic drugs in pediatric epilepsies

Abstract

Children with epilepsy, particularly infants, differ from adults not only in the clinical manifestations of their seizures but also in the presence of unique electroencephalographic patterns, etiologies, and response to antiepileptic drugs (AEDs). There is a growing list of newer AEDs and nonpharmacologic therapies available to manage childhood epilepsy. These newer AEDs may not be overall more efficacious than the older drugs, but they do appear to be safer, better tolerated, and to have fewer drug-drug interactions. Selection of the AED for initial therapy must be based upon clinical judgment and patient-specific circumstances, such as the specific epilepsy syndrome being treated, anticipated duration of treatment, presence of comorbidities, ability to use certain formulations, and overall cost effectiveness. In some cases, seizures may be aggravated by the use of certain AEDs. Overall, oxcarbazepine is the first-line treatment for localization-related epilepsy with partial-onset seizures. For generalized epilepsies, the AED choice is highly dependent upon which specific syndrome is being treated. For generalized epilepsies with primarily absence seizures, lamotrigine is the AED of first choice. For mixed generalized epilepsies such as Lennox-Gastaut syndrome or juvenile myoclonic epilepsy, zonisamide or topiramate are the first-line agents. For infants with West syndrome, treatment is based upon the underlying etiology: vigabatrin for tuberous sclerosis; adrenocorticotropic hormone for children with no specific etiology uncovered (cryptogenic); and zonisamide for those with a severe symptomatic etiology other than tuberous sclerosis. Single drug therapy (monotherapy) is the goal of epilepsy treatment because this is associated with better compliance, fewer adverse effects, and lower cost. If the seizures prove intractable or adverse effects are encountered with the first AED, then a second monotherapy trial is undertaken. Once three appropriate medications at therapeutic doses have failed, other modalities should be considered, including epilepsy surgery, vagus nerve stimulation, and the ketogenic diet.

Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy

“…The most frequent ones are excessive weight gain, hyperphagia, water retention with edema, Cushingoid appearance, hypertension, behavioral disturbances, increased infection susceptibility, leukopenia, electrolyte disturbances, hyperglycemia, glycosuria, impaired glucose tolerance, frank diabetes and sleep disorders. Furthermore, long-term side effects such as hypothalamus-pituitary axis suppression, psychosis, osteoporosis, nephrocalcinosis, brain atrophy, cataracts and, in children, growth retardation, have also been reported (Gupta and Appleton, 2005;Malphrus and Wilfong, 2007). Since methylprednisolone treatment did not cause significant or persistent adverse effects in our case series [1/11 patient (9.1%) showed a modest transient hyperglycemia in the 24 hours after infusions; 1/11 patient (9.1%) a modest weight gain], methylprednisolone treatment, administered according to the regimen herein described, seems to be safe.…”

Epilepsy: recent advances

“…No case of hyponatraemia was reported. Though a good reflection of the experience within one busy paediatric centre, and with results in line with previous literature [20], the small number of patients in this study limits the statistical power and weakens any subgroup conclusions. What a study of this nature, of course, does not provide is any comparative data with other monotherapy options in this patient group, which ultimately is what would be most informative for clinical practice.…”

An overview on antiepileptic drugs

“…GNX has been shown to be well tolerated in adults and children and the commonly observed adverse events in children were agitation and somnolence. It is currently undergoing further development against newly diagnosed infantile spasms (90), in adults with refractory partial-onset seizures (91) and in women with catamenial epilepsy (92).…”