In the Field
The Dreifuss-Penry Epilepsy Award: Tobias Loddenkemper, MD: On Detecting Diurnal and Nocturnal Patterns for Seizures
When Tobias Loddenkemper, MD, was a child growing up in Germany, he would often accompany his father to work. A professor of educational sciences, the senior Loddenkemper specialized in memory and learning — and his lessons sunk in.
“It had a huge impact,” said Dr. Loddenkemper. “I learned a lot about university research and it opened my eyes to neurology.”
Those early classes had long-term results. This year, Dr. Loddenkemper, 39, is the 2012 winner of the Dreifuss-Penry Epilepsy Award for his work in connecting diurnal rhythms to seizure patterns.
By increasing the medication dose to the onset time of seizures, Dr. Loddenkemper, a physician at Children's Hospital in Boston and assistant professor of neurology at Harvard Medical School, was able to reduce the number of seizures in previously intractable patients.
The introduction of diurnal and nocturnal seizure pattern detection, and adjustment of treatment according to times of greatest seizure susceptibility led to a paradigm shift in clinical epileptology. Instead of a simple ‘one-size-fits-all’ two or three times per day medication dosing, patients received individualized monitoring of seizure frequency and spike patterns and adjusted, patient-oriented treatment regimens.
By changing the medication to an individualized program, 64.7 percent of patients became seizure free, and 88.2 percent experienced more than a 50 percent reduction in seizures with fewer side effects and at no additional cost.
“When I attended medical school in Müenster, I read an article about circadian rhythms that was fascinating,” said Dr. Loddenkemper, explaining his interest in diurnal rhythms. “In the study volunteers spent time in containers without sunlight and no outside ‘zeitgebers’ — no wristwatches, television or scheduled mealtimes,” he said.
“They were allowed to spend the days as they liked, and slept when they wanted. It taught me a lot about the internal clock, that even when there's no sunlight out, there's a clock inside the brain that keeps ticking.”
At the same time, Dr. Loddenkemper decided to focus on epilepsy. During an elective, he had met a 24-year-old patient with Lennox Gastaut syndrome. The patient, who wore a helmet constantly to protect his head from injury during seizures, was severely mentally delayed and had a cluster of seizures during the office visit.
“It was devastating to think that, despite three medications, we were unable to do much for this patient,” Dr. Loddenkemper recalled.
When he moved to the Cleveland Clinic in 2000 for a fellowship in clinical neurophysiology, he was exposed to a much larger patient population. Going from a local university to an expert center, he said, was a huge change — both in the volume of patients and the amount of expertise available.
Dr. Loddenkemper was drawn to working with children and completed his residency in pediatric epilepsy at the Cleveland Clinic before moving to Children's Hospital in Boston in 2008.
“If you treat seizures in children early you can interfere with the developmental side effects and you can really make a tremendous difference for each child,” he said. “Despite hemispherectomy, children learned to walk and talk and were seizure free.
“To see such amazing results in kids with previously intractable epilepsy was very inspiring. In pediatrics, ongoing seizures are an emergency — seizures beget seizures and can interfere with development. At an age when the brain should be learning to walk, talk or read, instead it's learning how to seize. So if you can stop seizures early, you are helping with a lifetime of developmental progress.”
As part of his research at Harvard, Dr. Loddenkemper looked at the timing of different seizures using video EEG recordings in the Epilepsy Monitoring Unit. His team is now looking into other ways of characterizing seizures and epileptogenicity at different day and night times using clinical findings and EEG parameters.
Most recently, they started using wristband sensors, developed in conjunction with Massachusetts Institute of Technology, that track movement and electrodermal skin response.
“Patients have always kept seizure diaries, but with the development of the portable sensors or wristbands, we may be able to track seizures more accurately over time,” he said.
Linking patterns between circadian rhythms and epilepsy involves looking into spike patterns and EEG changes, he said. The investigators also analyze brain tissue samples and MRI images to find out more about the receptors and brain circuits that are involved.
In the future, they plan on analyzing markers in the blood and urine, such as melatonin or cortisol levels, to see if additional patterns appear.
“Although we are only at the beginning, we were able to reduce seizures and spikes by using individualized medication treatment programs that consider individual seizure and spiking peaks,” he said.
So far, the results look promising. It's been “very successful” in helping patients with intractable seizures, with fewer side effects and without additional medication cost. If the paradigm applies to other treatment markers, he said, the goal is to be able to counsel patients better and develop individualized medication programs.
In addition to his team at Children's Hospital, Dr. Loddenkemper said he was particularly grateful that he had — and continues to have — strong mentors in his field, specifically his Boston colleagues Drs. Blaise Bourgeois, Sanjeev Kothare and Alan Leviton. He also pointed out Cleveland Clinic doctors Elaine Wyllie and Hans Lüders, who taught him how to read EEGs.
Pediatric epilepsy is also part of his home life — and a family affair — as he met his wife, Karen Stannard, MD, at an epilepsy conference.