California Pacific Currents 2002
At the Crossroads of Radiology, Technology Advances the Management of Epilepsy
An Interview with Kenneth D. Laxer, M.D.
With immense reserves of innovation and enthusiasm, Dr. Kenneth Laxer applies the science of magnetic resonance imaging (MRI) to epilepsy, advancing the diagnosis and treatment of this mysterious, dangerous, and disabling disorder. By marrying this area of radiology with epilepsy — a condition thus far overlooked by this technology —more surgical interventions are possible and improved outcomes are realized.
Q: This past spring, you were recruited to California Pacific Medical Center Research Institute from the University of California at San Francisco. Why the move from such a prestigious institution?
A: There is much to be done to advance the management of epilepsy. The environment at California Pacific is highly conducive to investigation. I am so impressed with the level of enthusiasm, flexibility, and support for my efforts to apply MRI technology to the treatment of epilepsy. California Pacific’s reputation of innovation and cooperation wins pharmaceutical industry support as well. Once it was known that I was moving to the Research Institute, two pharmaceutical companies promptly approached me to participate in clinical trials of promising experimental treatments.
Q: Dr. Laxer, you brought to the Medical Center a completely new approach to epilepsy treatment. How does it differ from traditional methods?
A: In the past, we relied upon electroencephalograms to understand the root of a patient’s epilepsy. Electroencephalograms are brain wave recordings from the surface of the head. My work adapts and applies neuroimaging techniques to this evaluation, allowing us to get a picture of metabolic abnormalities from inside the brain. This information complements that from outside the brain.
Q: High-tech instrumentation is used throughout medical care. These technologies, however, often arise from research conducted in very different areas than that to which they are eventually applied. Marrying the two must require a special kind of knowledge base. Did you come to this field from biophysical sciences or the laboratory bench?
A: Neither, really. I have an engineering background, which helps in grasping the physical science foundation behind imaging technologies. The leap really came, however, when I recognized the gap that existed in evaluation tools. With the great strides that MRI has made in other areas of medicine, I wondered, why were we not using it to learn more about epilepsy.
Q: What was involved in tailoring MRI to the challenges of managing epilepsy?
A: The radiologists and I really had to start from ground zero. We literally sat around the table with an anatomy textbook in front of us. The next step was to combine the logistics of imaging brain waves with the objective of resolving the region of the brain associated with the epileptic seizures. In patients with epilepsy, there are low-level, tell-tale brain waves in the area of the disturbance, even when the patient is not experiencing a seizure. Hence, we had to hone the technology to detect this pathologic activity.
The techniques that we are using now — and strive to improve continuously — are ultimately the result of a collaborative effort that reflects the contribution of a number of great people. To advance the technology to image brain waves required a team that was both dedicated and diverse in their respective areas of expertise; and that is where the Research Institute’s commitment really came into play. I was very excited about the team already assembled. There is Dr. David King-Stephens’s neurological background in epilepsy, Dr. Stephen Bunker’s knowledge of nuclear medicine, Dr. Peter Weber’s success in epileptic neurosurgery, Dr. Jerry Barancas on neuroradiology, and, Dr. Luis Bello-Espanosa on pediatric epilepsy. They each bring a huge amount of excitement to the project.
Q: To help us understand how it is treated, can you please briefly describe epilepsy?
A: With 180,000 new cases diagnosed annually, epilepsy is a condition that afflicts about 1% of the population. Epilepsy does not discriminate by age and strikes newborns as well as the aged. Although the origins of the disease are still somewhat a mystery, we do know that the characteristic seizures of epilepsy can be an outcome of any abnormality of the brain. While most seizures can be controlled through medication, 20–40% of cases are refractory to our best efforts. These are the people that we seek to help through our program.
We have found that a certain number of those patients with epilepsy that is uncontrolled by drug therapies do benefit from surgical resection of the portion of the brain in which the problem originates. To date, however, deciding which patients will improve based on electroencephalogram readings has been an inexact science. Using these new, high resolution imaging techniques in combination with electroencephalogram recordings yields an excellent prediction rate: 90% of patients for whom the two techniques mapped the same area in the brain become free from seizures after surgery. Therefore, this imaging approach advances the precision of the procedure.
Q: Once you are in a patient’s brain during the surgery, what guides you?
A: I work with Dr. Peter Weber, who is an expert in epilepsy surgery. When the root of the problem lies in an area of the brain that does not control sensitive brain function, we have a good chance of being able to localize the source, resect it, and eliminate seizures for the individual. The surgery may even be performed with the patient under local anesthesia and awake. That way, we can check throughout the procedure to make sure that a brain function, such as speech, will not be compromised. The entire team is in the operating room with the patient during the procedure, monitoring his or her brain waves and making recommendations as we proceed.
Q: Can surgery be dangerous?
A: No, it is not terribly dangerous; postoperatively, 98% of patients have no diminishment of any sort of brain function. Therefore, the main objective is to avoid the ordeal of surgery if there is not a high likelihood that it will be successful. We counsel each patient, yet it is ultimately his or her choice to proceed or not. Given quality-of-life issues, some patients may wish to have surgery even if the chances of successful resolution of seizures are low. Others may wish to try nonsurgical approaches, given the predicted success rate, or just continue to deal with their seizures.
Q: Besides surgery, are there other applications of this imaging technique for epilepsy?
A: Absolutely. With better information on brain activity through imaging, we can also make estimates as to which drug therapies are likely to be effective in a given patient. This is important because some medications, given to the wrong patients, can actually exacerbate the condition. The information that we learn from neuroimaging also provides alternative options for nonoperable epilepsy and, where surgery might have been considered, avoid it altogether in favor of proper medications.
Q: Where do you see this technology taking the medical management of epilepsy 10 years in the future?
A: I think that neuroimaging will certainly, over the coming decade, continue to aid in the selection of patients who are — or are not — good candidates for surgery. It will also help clinicians communicate with patients and advise them regarding the predicted outcomes of surgery in their particular cases. And it will help identify patient populations that are ideal for new drug therapies.
We are still largely in the dark as to the underlying abnormalities of epilepsy. This technology also has the potential to help identify these disease origins. For example, neuroimaging has already identified genetic syndromes that lead to epilepsy. With this information, researchers were able to link the disorder within families and put it through genetic analysis. Older techniques could not have resolved the underlying problem, but, with neuroimaging, malformations related to epilepsy can be visualized. Through the scans and certain detective work, some of the genes at fault have been traced.
It has also been gratifying to start to see this technology spin off into other areas of neurology. Alzheimer’s Disease is just one condition where it holds promise. Multiple sclerosis and movement disorders are other areas in which this technology can potentially make some strides.
Q: What are your personal goals for your research?
A: There is one goal that is dear to me, though somewhat unrelated to disease evaluation. Not all of the problems associated with epilepsy are medical ones, at least not directly. With medications and now, more than ever, with surgery, we can help patients with uncontrolled epilepsy get their seizures under control. Equally serious considerations with this condition, however, are the social consequences. Many times we are able to finally get a patient’s seizures under control but have virtually no impact on the quality of their lives. Epilepsy strikes people without respect to their background. As a group, however, many people who suffer from epilepsy also suffer from under-education and underemployment. They may also be ostracized socially.
There is practical support that can improve the lives of people with epilepsy. This kind of “cure” involves teaching simple tasks to people who have been disabled by the disorder, such as how to write a resume, fill out a job application, and obtain a driver’s license. People with whom I share this goal are actively involved in outreach, gaining corporate commitments to employ some of these patients through work internship programs. Our goal for our patients is to get some training under their belts, as well as some personal victories.
Q: With these advancements and the strength of your team, do you think that people will start to hear about your successes at California Pacific?
A: Patients go where people do a good job caring for their medical needs. The people here at the Medical Center are already doing a great job; I just hope I can continue the tradition.