Epilepsy is one of the most frequent neurologic disorders affecting children. Although most children have relatively favorable long-term outcomes — achieving seizure freedom with or even without medication — epilepsy is a diverse disorder. Variations in severity and prognosis can make treatment decisions challenging and increase the uncertainty and anxiety experienced by patients and their families.
Research at Mayo Clinic in Rochester, Minn., is shedding new light on predictive factors and outcomes for children with epilepsy. Retrospective studies of patients over a 25-year period are yielding information about medical intractability, outcomes in cryptogenic epilepsy, lesions underlying seizures and mortality rates. The Mayo studies are among the few longitudinal studies of pediatric epilepsy and the first to use the new 2009 International League Against Epilepsy classifications.
"We wanted to study long term a cohort of patients who presented in the modern era of epilepsy treatment," says Elaine C. Wirrell, M.D., a pediatric neurologist specializing in epilepsy at Mayo Clinic in Minnesota. "There have been significant advances in the genetic and metabolic understanding of epilepsy. MRI also has been a huge advantage in understanding the pathogenesis and treatment of epilepsy."
The Mayo researchers started by identifying all children in Olmsted County, Minn., ages 1 month through 17 years with newly diagnosed epilepsy from 1980 to 2004. Diagnostic factors, treatment and outcomes from the medical records of the 467 patients identified were recorded and analyzed.
Previously, no population-based study of pediatric epilepsy focused on outcomes in very young children. The Mayo researchers reviewed the cases of 127 children who had a diagnosis of epilepsy before age 3 years. The study was published in the September 2012 issue of Epilepsia.
More than one-third of the children had medically intractable epilepsy. That categorization generally occurred early, with 61 percent of medically intractable cases classified by one year after diagnosis and 93 percent within five years. The study also identified four significant predictors of medical intractability:
Early identification of medical intractability can lead to more appropriate treatment and better outcomes. "Once children are classified as having medically intractable epilepsy, they need to be assessed for epilepsy surgery," Dr. Wirrell says. "Unfortunately, many will not be suitable candidates for surgery. But you don't want them to have five medications fail and have recurring daily seizures if surgery might improve their development and reduce mortality rate."
Symptomatic forms of epilepsy — those with a known cause — generally have poorer outcomes than idiopathic forms. The term "cryptogenic" has been used to describe epilepsy believed to be symptomatic but for which the cause is unknown. The prognosis for these cases is poorly understood.
The Mayo research team compared long-term outcomes for children with focal epilepsy classified as cryptogenic vs. symptomatic. The study was published in the April 2011 issue of Epilepsia.
Importantly, the patients with cryptogenic focal epilepsy had significantly higher likelihood of achieving seizure freedom than the patients with symptomatic type (81 vs. 55 percent) and much lower likelihood of medical intractability (7 vs. 40 percent).
"Instead of considering cryptogenic focal epilepsy to be 'probably' symptomatic, it should be considered a separate entity, with a relatively favorable long-term outcome," Dr. Wirrell says.
Factors predicting favorable outcome include absence of structural abnormality on MRI, normal neurologic examination and normal cognition. "If you can't find the underlying cause of seizures in focal epilepsy, even after imaging and careful analysis, and the child's neurologic exam is normal, the prognosis is very good," Dr. Wirrell says. "Most of those children will ultimately be able to come off medication and remain seizure-free long term."
Although focal or hemispheric lesions generally portend poorer outcomes for children with epilepsy, "the outcome is not always bleak," Dr. Wirrell says. The Mayo research team reviewed the records of 37 children with newly diagnosed epilepsy who had a focal lesion at initial diagnosis. The study was published in the August 2011 issue of Epilepsia.
At final follow-up, 24 of the patients (65 percent) were seizure-free. Twelve patients (32 percent of the cohort) achieved seizure freedom without surgery. Most of the seizure-free patients (58 percent) had encephalomalacia. The group's size limits the statistical significance of that etiologic finding, "but the study results are striking and deserve further investigation," Dr. Wirrell notes. "Every MRI abnormality is not created equal. Some of these children can have a pretty benign outcome."
Many parents who witness their child's first seizure, particularly a grand mal seizure, "think the child is dying. It's very scary," Dr. Wirrell says. "The possibility of their child dying of epilepsy is foremost in the parents' minds."
The Mayo research team conducted one of the few population-based studies of mortality rates and sudden unexplained death in epilepsy in children. The study was published in the December 2012 issue of Epilepsia.
Although the study found a higher mortality rate than would be expected in a general pediatric population, the overall rate was low: 3.4 percent, or 16 of 467 patients in the cohort. Two of the deaths were related to epilepsy and 14 were caused by complications, mostly respiratory, of underlying neurologic disease or unrelated disease.
The investigators found that death occurred significantly more in children with:
"Kids whose epilepsy is not medically intractable and who are otherwise neurologically normal have an exceedingly low risk of seizure-related death," Dr. Wirrell says. "We can't counsel families that the risk is zero, but we can tell them the risk is low."
Wirrell, et al.Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: A retrospective, population-based study. Epilepsia. 2012;53:1563.
Wirrell, et al. A population-based study of long-term outcomes of cryptogenic focal epilepsy in childhood: Cryptogenic epilepsy is probably not symptomatic epilepsy. Epilepsia. 2011;52:738.
Dhamija, et al. A population-based study of long-term outcome of epilepsy in childhood with a focal or hemispheric lesion on neuroimaging. Epilepsia. 2011;52:1522.
Nickels, et al. Epilepsy-related mortality is low in children: A 30-year population-based study in Olmsted County, MN. Epilepsia. 2012;53:2164.