The RNS System neurostimulator and leads were implanted by a neurosurgeon. The neurostimulator was programmed to detect and, in those subjects assigned to receive stimulation, to stimulate in response to those detections. Evaluation for efficacy began 28 days after implantation, over three 28-day periods. Subjects were followed for 24 months postimplant. After two years, patients could transition to a long-term treatment trial for an additional five years.
The responder rate (≥ 50% seizure reduction) for the initial three 28-day periods, compared with baseline, was 24% for all disabling seizures, 27% for complex partial seizures, and 65% for generalized tonic clonic seizures. Seizure response appeared to be durable, as the responder rate for all disabling seizures was 48% at 18 months and 50% at 36 months. An analysis by seizure onset location revealed that the responder rate for hippocampal seizures (68%) was higher than the rate for neocortical seizures (38%).
Device-related serious adverse events included focal status epilepticus, an increase in seizure frequency, erosion, tissue infection, cranial reconstruction, fall injury, and wound infection, all of which were resolved.
A multicenter, double-blind, controlled pivotal trial is now under way at 29 sites across the United States.
Ambulatory Device Detects Sleep Apnea
A wearable sleep-monitoring device demonstrated high sensitivity and specificity for detecting apnea, according to data presented by John Duncan, MD, and colleagues. The research team has tested several prototypes of the device, with the current version consisting of a microphone, sensor dome, and adhesive that affixes to skin over the trachea.
According to Dr. Duncan, current ambulatory respiratory monitoring devices have several drawbacks: They tend to be too bulky to be comfortable, the sensor picks up too many movement artifacts, and they may require a large power source. The new system fits in the suprasternal notch and is designed to trigger an alarm in the event of more than 25 seconds of apnea. “We tried respiratory bands, electromyography, and axillary and chest wall placement, but the trachea is the best. The respiratory signal is very strong, it’s comfortable, you can get the cardiac signal at the same time, and it doesn’t come off when you roll over,” commented Dr. Duncan, Head of the Department of Clinical and Experimental Epilepsy at the Institute of Neurology at University College London.
Initial testing from 13 subjects (11 male; ages 18 to 33; weight, 50 to 100 kg) included 630 minutes of breathing data and 182 minutes of “voluntary apnea,” which were recorded by a computer and processed by an apnea detection algorithm. Despite ambient music and continuous head movement, the sensitivity and specificity were 99.2% and 99.92%, respectively. This translated into one false alarm for every 13.5 hours of monitoring and three missed apnea events from a total of 363 voluntary 30-second apnea episodes.
“Testing so far has been in volunteers. The next phase of trials will include overnight recordings in the sleep laboratory, using the sleep lab apnea data as the gold standard for comparison,” said Dr. Duncan.
Omega-3 Fatty Acids Improve Risk Factors for SUDEP
High-dose omega-3 fatty acids may improve cardiac risk factors and heart rate variability (HRV), a marker for the risk of sudden unexpected death in epilepsy (SUDEP), according to results of a randomized crossover pilot study reported by Christopher DeGiorgio, MD, Vice Chair and Professor in Residence of Neurology at the University of California, Los Angeles, and colleagues.
After a four-week baseline period, 11 subjects received high-dose omega-3 fatty acids, in the form of fish oil (9,600 mg/day), or placebo (soybean oil) for 12 weeks. A six-week washout period ensued, during which no drug was taken, followed by a crossover period. HRV was measured as SDNN (standard deviation of all normal R-R intervals for one hour) and SDANN (standard deviation of all R-R intervals in each successive five-minute epoch) and determined after one-hour ambulatory EKG monitoring at both the initial and last visits.
Overall, treatment with fish oil did not significantly affect seizure frequency or increase HRV. However, in four of five subjects with below-average HRV prior to treatment, the mean SDNN improved from 38.8 to 46.6 ms. Similarly, in the same subgroup, the SDANN improved from 17.5 to 21.2 ms. The researchers also found that the lower the baseline HRV, the better the improvement with fish oil.
In addition, the median HDL cholesterol level increased from 52 to 60 mg/dL, and the median triglyceride level decreased from 91 to 68 mg/dL.
“The results are preliminary, but this study provides the first evidence that risk factors for SUDEP, specifically low HRV, can be modified and improved,” Dr. DeGiorgio concluded. “We have begun a larger randomized trial of low- and high-dose omega-3 fatty acids versus corn oil placebo to test the hypothesis that omega-3 fatty acids improve risk factors associated with SUDEP.