UCSF Pediatric Focus

Rare Pediatric Epilepsies Demand Rare Expertise

A new UCSF center offers children with rare pediatric epilepsies timely diagnosis and treatment to prevent delays, which can lead to lasting neurological damage and a lifetime of seizures.

Genetic epilepsies, especially in newborns, are underdiagnosed and may require different, more targeted treatments than most neonatal seizures – treatments that are generally not well understood, according to pediatric and neonatal epileptologist Maria Roberta Cilio, MD, PhD, a world-renowned expert in assessing and treating these epilepsies.

The newly created UCSF Center of Excellence for Rare Pediatric Epilepsies will offer families rapid diagnosis and treatment of such epilepsies with the hope of preventing lasting neurological damage and, in some cases, a lifetime of seizures. “Delays can make it more difficult to restore patients to baseline, so the first step in precision medicine has to be early treatment,” says Cilio.

She leads the center, which is part of the UCSF Pediatric Epilepsy Center and Neuro-Intensive Care Nursery. Most days, she is available around the clock for any neonate with suspected neonatal-onset epilepsy. Her rare expertise – as well as the training she offers fellow UCSF neurologists and epileptologists – enables the center to make initial diagnoses by accurately analyzing the clinical and electroencephalographic (EEG) features of the patient, the so-called phenotype, and evaluating imaging from advanced techniques that include video electroencephalography and MRI spectroscopy. This results in more timely, personalized treatment while awaiting the results of genetic testing.

Changing the Course of Familial Neonatal Epilepsy

Cilio recently authored publications in Neurology and Epilepsia, the latter of which was highlighted in NeurologyAdvisor, that document cases where the diagnosis of rare, genetic-based epilepsies led to nonstandard treatments for neonatal seizures and positive patient outcomes.

“Typically, when newborns seize, we automatically treat them with high-dose phenobarbital, but this is not a good option, for example, for benign familial neonatal epilepsy, which is associated with the genetic mutation KCNQ2,” says Cilio.

She describes a recent case in which she treated an intubated infant who was transferred to UCSF on high-dose phenobarbital. Cilio ordered video-EEG monitoring, examined the infant and recognized benign familial neonatal epilepsy, prompting her to halt the phenobarbital and replace it with oral carbamazepine, an older drug rarely used in the neonatal intensive care unit. By the next day, the child had stopped seizing and was able to breastfeed and go home; genetic testing confirmed the KCNQ2 mutation.

These are not easy diagnoses, but her experience allows Cilio to quickly recognize clinical and EEG features that characterize the disorders, and to make a clinical diagnosis with a high degree of confidence.

Prioritizing Personalized Care

Once she’s made the diagnosis, Cilio can quickly turn to more appropriate alternative treatments. In another recent case, for example, a patient arrived at UCSF with seizures and a pronounced movement disorder. Cilio recognized a disorder associated with the SCN2A mutation. “We used L-dopa/carbidopa, which is not often used in young children, to successfully treat the movement disorder and carbamazepine to treat the seizures,” says Cilio.

Cilio expects the new center will also advance understanding of these mutations and how they contribute to seizure disorders, but her first priority is precision, patient-centered care.

“Lab testing takes time, so the ability to quickly apply informed clinical judgment in these cases is extremely important,” says Cilio.