American Epilepsy Society Meeting: Seattle, Washington

At the 68th annual meeting of the American Epilepsy Society (AES) in Seattle, Washington, researchers Brian Litt, MD, Eugen Trinka, MD, MSc, and Kristen Park, MD, discussed important innovations and therapeutic considerations in epilepsy.

Predicting Seizures Before They Happen, Using Novel Sensors, Biomarkers, and Big Data

Brian Litt, MD, of the Penn Epilepsy Center and the Center for Neuroengineering and Therapeutics at the University of Pennsylvania, discussed how prize-based research saves money and stimulates innovation in epilepsy.

Litt and colleagues, in an initiative funded by the National Institutes of Health (NIH), used the novel method of conducting an online competition to predict the onset of epileptic seizures using sophisticated computer algorithms applied to a large set of human and animal electroencephalogram (EEG) data. By sharing information using an online portal at IEEG.org, and competing in a massive, prize-driven worldwide effort, the AES has stimulated innovation in the area of seizure prediction.

A total of 504 teams from over 30 countries entered the prediction contest, and teams analyzed data collected from animal and human EEG recordings to create computer algorithms that can predict when seizures will occur and detect EEG patterns indicating seizure activity.

Ultimately, the contest resulted in a 97% detection accuracy for seizures, achieved by Michael Hills of Melbourne, Australia, and an 84% accuracy in seizures prediction, by a collaboration of epilepsy researchers, programmers, and machine learning experts in Australia and California.

The use of prizes to drive innovation will cut down dramatically on the cost of research. An NIH and EU collaboration, with $40 million over 15 years, attempted to develop a seizure prediction algorithm, and achieved better than random results. In the challenge described here, in 3 months, with a $25,000 prize, researchers achieved 84% predictive accuracy and 97% detection accuracy.

Understanding Common Adverse Events Associated with Antiepileptic Medications

According to Eugen Trinka, MD, MSc, of the department of neurology at the Christian Doppler Medical Centre at Paracelsus Medical University in Salzburg, Austria, 5 main types of adverse effects are associated with the use of antiepileptic drugs (AEDs): (1) dose-related adverse events, (2) bizarre or idiosyncratic adverse events, (3) chronic, long-term toxicities, (4) teratogenic or carcinogenic effects, and (5) drug interactions with AEDs.

Common dose-related adverse events of AEDs include disturbances in cognition, mood, or coordination, as well as somatic adverse events, such as ataxia, diplopia, tremor, gastrointestinal symptoms, paraesthesia, and nausea. Methods of managing dose-related side effects associated with AEDs include up-titrating the dose slowly, targeting the lowest effective maintenance dose, changing the AED formulation, or using a prodrug (eg, eslicarbazepine instead of oxcarbazepine).

Bizarre or idiosyncratic adverse events may include skin rashes, blood dyscrasias, liver damage, angle closure glaucoma, aseptic meningitis, or pancreatitis. AEDs that contain aromatic rings, including carbamazepine, phenytoin, oxcarbazepine, and phenobarbital are most commonly associated with skin reactions. Lamotrigine is also associated with a higher rate of hypersensitivity reactions than other AEDs, but the risk may be minimized by raising the dose gradually.

Chronic toxicities of AEDs include weight loss, hormonal changes, weight gain, decreased bone mineral density, folate deficiency, sexual dysfunction, hirsutism, gingival hypertrophy, and visual loss. In these cases, discontinuation of the AED may be required.

The fourth type of toxic effect with AEDs, teratogenicity, is most strongly associated with valproic acid and phenobarbital, which are associated with birth defects and neurodevelopmental delays.

Finally, drug interactions are an important consideration with AEDs. Evaluating the potential drug—drug interactions associated with the effects of medications on the cytochrome P450 system is an important component of drug selection.

Because AEDs comprise a large group of drugs with unpredictable side effects, it is important to remember that careful observation is required. Pharmacists fill an important role in helping patients, caregivers, and physicians recognize and manage the potential adverse effects of AED therapy.

Considering Alternative Treatments for Epilepsy

Kristen Park, MD, assistant professor of pediatrics and neurology at the University of Colorado, discussed an important topic in the treatment of epilepsy: the use of alternative therapies.

A popular and controversial alternative treatment for epilepsy is medical marijuana, which contains cannabinoids. The side effect profile of cannabinoids is primarily gleaned from information gathered among long-term recreational users of marijuana. However, some animal studies have also been conducted.

According to Park, cannabinoids have been associated with pregnancy complications in animals when administered in the third trimester of gestation, and have led to permanently altered behavior in the resulting offspring. Similar effects have been observed in humans: the mothers of children who were exposed to cannabinoids during pregnancy have a higher incidence of psychiatric issues than the general population.

Other central nervous system toxicities have been documented with marijuana use, including a higher incidence of schizophrenia and depression in exposed adolescents, disturbed sleep quality, and impairment of learning, memory, and cognition, with concurrent reductions in the volume of the hippocampus as well as gray and white matter.

With medical marijuana, as with other herbal remedies, Park stated, “There is a lot of unknown risk, unknown benefit, and a lot of toxicity.”

For patients with epilepsy, alternative therapies are commonly used. More than half of all children with epilepsy have received some form of complementary treatment, often without the advice of the child’s neurologist. Openly discussing all treatments is an important component of care that may help patients and caregivers make a more informed decision about unapproved alternative treatments.

Michael R. Page earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.