Prognostic factors in childhood epilepsy

About two-thirds of children with epilepsy will ultimately achieve seizure freedom. Many of them will be able to stop taking medication and remain seizure-free. Within this fairly positive broad view, the challenge for neurologists is defining the prognosis for an individual patient.

"If you're the parent of a child with epilepsy, you really want to know which third your child falls into," says Elaine C. Wirrell, M.D., a pediatric neurologist specializing in epilepsy at Mayo Clinic's campus in Rochester, Minnesota.

Population-based, longitudinal research at Mayo Clinic is uncovering prognostic factors for children with epilepsy. The retrospective studies involve the records of 467 children in Olmsted County, Minnesota, ages 1 month through 17 years who were newly diagnosed with epilepsy from 1980 to 2009.

"Because the research is population-based, we're getting a good sampling of difficult as well as relatively easily controlled epilepsies," Dr. Wirrell says. "We are recognizing that there are certain predictors for the likelihood of remission or lack of it."

Neuroimaging abnormalities

About 20 percent of children with epilepsy are deemed medically intractable, having failed to improve after trials of multiple medications. In children, uncontrolled seizures result in considerable comorbidity, including intellectual disability, physical injury, depression and anxiety, and failure to achieve independence.

Surgery offers the benefit of quicker seizure control. "But surgery is irreversible and not without risk. There's often a tendency to wait and try more medications," Dr. Wirrell says.

Accurate and early prediction of medical intractability is crucial for the choice between drug-based therapy and surgery. Yet factors associated with medically intractable epilepsy have been characterized less well in children than in adults.

The Mayo studies have pinpointed abnormal neuroimaging as a strong prognostic factor in childhood epilepsy. In a study published in the June 2013 issue of Epilepsia, the Mayo researchers identified 381 children in the study cohort who were followed for at least three years after diagnosis. Seventy-five of the children, or nearly 20 percent, were deemed medically intractable within two years of diagnosis.

After a median follow-up of 11.7 years, 49 percent of those children remained medically intractable. The researchers then analyzed the children's records for neuroimaging abnormalities, neurological examinations at diagnosis, and mode of epilepsy onset (focal, generalized or unknown).

"We found that the only predictive factor for medical intractability — and it was a very significant factor — was neuroimaging abnormality," Dr. Wirrell says. "If a child appears medically intractable early on and the MRI is abnormal, the epilepsy is unlikely to go away. In that situation, early surgery is extremely important to minimize the risk of prolonged seizures and other comorbidities."

Similarly, in a study published in the May 2013 issue of Epilepsia, the Mayo researchers found that neuroimaging abnormality is also the most significant predictor of pharmacoresistance in childhood epilepsy. About one-third of children with epilepsy who initially appear pharmacoresistant ultimately achieve seizure freedom without surgery. But only 8.6 percent of pharmacoresistant children with an abnormal MRI do so.

"In those children, early surgical intervention should be strongly considered to limit comorbidities," Dr. Wirrell says. "Conversely, a more cautious approach may be appropriate for children with normal imaging, as many remit with time."

Mortality risks

Mortality rates in children with epilepsy are four to five times higher than in the general pediatric population. However, the specific causes of seizure-related deaths in children haven't been elucidated. To do so, the Mayo researchers pooled their data with colleagues from Connecticut, Canada and the Netherlands.

In a study published in the July 2013 issue of Pediatrics, the researchers found that among the 2,229 subjects followed for more than 30,000 person-years, only 69 deaths occurred. Ten of those were attributed to sudden unexpected death in epilepsy, and three to other seizure-related causes. Among the remaining deaths, 48 were due to other natural causes.

Most of the deaths occurred in children with neurodisability or an underlying brain condition, and were secondary to infections and other complications. The death rate among children with "uncomplicated" epilepsy was not much greater than expected for the general population.

"The risk of death in an otherwise healthy, intellectually normal child with epilepsy is low," Dr. Wirrell says. "That information is very reassuring and helps us to provide better counseling to families."

For more information

Wirrell EC, et al. What predicts enduring intractability in children who appear medically intractable in the first 2 years after diagnosis? Epilepsia. 2013;54:1056.

Wirrell EC. Predicting pharmacoresistance in pediatric epilepsy. Epilepsia. 2013;54:19.

Berg AT, et al. Mortality risks in new-onset childhood epilepsy. Pediatrics. 2013;132:124.