Thursday March 18 2010
Electrodes were implanted for 'deep brain stimulation'
“Deep brain stimulation is a promising therapy for epilepsy,” reported the BBC. The article said that patients who had resistant epilepsy (a type of epilepsy that does not respond to drug treatment) and who had regular seizures were selected for the new treatment.
Deep brain stimulation (DBS) is a surgical treatment in which electrodes are implanted into specific areas of the brain along with a device “like a pacemaker” that delivers small electrical impulses. Following the surgery, there was a 41% reduction in seizures for patients who received brain stimulation, compared with a 14.5% decline in seizures in the control group.
The study points to a promising new treatment for a potentially large number of people with resistant epilepsy. The implant was given to epileptics who had specific types of epileptic seizures starting with a “partial seizure”. As such, the treatment may not be effective in people with other forms of epilepsy. This is likely to be less than the one-third of all people with epilepsy that was implied in news reports.
The selection of patients suitable for treatment will need refining once long-term (defined as more than two years) complications are known, to ensure that each individual receives maximum benefit with minimal harm.
Where did the story come from?
This research was carried out by Dr Robert Fisher, director of the Epilepsy Centre at Stanford University, and colleagues from around the US, all members of the SANTE Study Group. The study was supported by Medtronic (the manufacturers of the device) and a National Institutes of Health grant. The paper was published in the peer-reviewed medical journal Epilepsia.
The BBC also quotes the author of the study, who cautioned, “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.”
What kind of research was this?
This was a double blind randomised trial of a new device implanted in the brain that is aimed at reducing the number of seizures in people with a specific form of epilepsy, in which attacks are set off by abnormal electrical disturbances in a limited region of the brain.
The devices were placed in an area of the brain where they could stimulate the anterior nuclei of the thalamus. This area lies deep within the centre of the brain, above the brain stem, and was chosen following several successful previous trials and animal studies in it. One of these randomised trials had shown a 50% reduction in the number of seizures in people with the implant. In this study, the researchers wanted to test the long-term effects and complications of the technique over a two-year period.
What did the research involve?
The carefully selected participants consisted of men and women aged 18 to 65 who were subject to “medically refractory partial seizures, including secondarily generalised seizures”. Partial seizures (also known as focal seizures) only affect a part of the brain when they first begin, without loss of consciousness. They can sometimes progress to a full generalised seizure in which consciousness is lost. To qualify, those recruited had to have at least six seizures a month, but no more than 10 a day, as recorded in a daily seizure diary for three months. The participants also had to have tried at least three anti-epileptic drugs that had not achieved adequate seizure control, and to be taking between one to four drugs at the start of the study.
After three months of observation, during which the participants took note of the number of seizures they had in a diary, all had the device inserted, usually under general anaesthetic. The device was implanted in 110 patients. One month after surgery, participants were randomly allocated to receiving either treatment of no treatment in a way that ensured neither the patient nor the operator knew whether treatment was being received. The blinded phase lasted three months, after which all patients received non-blinded stimulation for nine months.
Treatment involved the electrodes being stimulated with five-volt pulses, on for one minute and off for five minutes. This sequence ran continuously for the patients in the active treatment group for three months.
The participants recorded the number of seizures in diaries and the researchers monitored the severity of seizures using the Liverpool Seizure Severity Scale (LSSS), which is an accepted scale. They also used a Quality of Life in Epilepsy (QoLIE-31) score along with neuropsychological testing. Appropriate statistical tests were then used to analyse the results.
What were the basic results?
Out of 157 enrolled participants, 110 underwent bilateral electrode implantations. The 54 patients allocated to stimulation and 55 patients in the control groups were similar. One patient was excluded form the analysis as they had failed to complete enough diary entries.
The researchers say there were an average 19.5 seizures per month at the start of the study. In the last month of the blinded phase, the stimulated group had a 29% greater reduction in seizures compared with the control group.
At the end of the blinded phase, there was a 14.5% reduction in seizures in the control group compared with a 40.4% reduction in the stimulated group, before adjustments were made in the analysis. Complex partial and “most severe” seizures were significantly reduced by stimulation.
After two years, there was a 56% median (average) reduction in seizure frequency and 54% of patients had a seizure reduction of at least 50%. Fourteen patients were seizure-free for at least six months.
The researchers noted that five deaths occurred, none of which were related to the implantation or stimulation of the device. No participant had symptomatic bleed into the brain or brain infection. Two participants had temporary stimulation-associated seizures. There were 14 infections near the lead or stimulator, but none within the brain. There were significant differences between the groups through the three-month blinded phase, with participants in the stimulated group more likely to report depression and memory problems as adverse events than in the non-stimulated group.
How did the researchers interpret the results?
The researchers say that bilateral stimulation of the anterior nuclei of the thalamus reduced seizures and the benefit persisted for two years of study. Complication rates were reportedly modest and the benefit of DBS is shown for some epilepsy patients who were resistant to previous treatments.
This study provides reliable evidence of the effectiveness of this new treatment for drug-resistant epilepsy. However, the treatment will not be suitable for all patients with epilepsy.
The researchers say that epilepsy is relatively common with about 1% of the population having the condition. About a third of these people do not respond adequately to anti-epileptic drugs. Because the type of epilepsy studied in this trial was specifically “partial epilepsy”, it is not possible to say that one-third of people with resistant epilepsy could benefit from the treatment.
The long-term risks of this treatment are not yet fully understood, as the authors acknowledge. The device is surgically implanted in the brain, a procedure not without its risks, and permanently having an implant would expose an individual to the risk of infection. As one of the researchers points out, “DBS therapy is invasive and serious complications can occur. Additional clinical knowledge would help to determine the best candidates for DBS therapy.” The selection of patients suitable for treatment will need refining to ensure that each individual receives maximum benefit with minimal harm.