The Cutting Edge: Research in Deep Brain Stimulation for Epilepsy
What is Deep Brain Stimulation?
Deep brain stimulation (DBS) is a medical therapy in which an implanted device delivers electrical stimulation to regions deep in the brain. Some uses of DBS to treat movement disorders such as tremor and Parkinson's disease are currently approved by the U.S. Food and Drug Administration, while other uses are considered investigational. The use of DBS to treat epilepsy is in the early stages of research.
The device consists of three major components:
- A lead, composed of a thin wire with electrode contacts on it, implanted surgically into the brain
- A pacemaker-like generator, which is placed under the skin in the chest region and is programmed to deliver the electrical stimulation to the brain lead
- A connecting cable, tunneled under the scalp and neck, which links the brain lead to the generator.
A programming computer allows the doctor to adjust the stimulation intensity and rate, along with other settings, from outside the body. Settings are adjusted to maximize benefit and minimize any side effects related to the stimulation.
To treat movement disorders, doctors use any of three different brain targetsthe thalamus, the globus pallidus, and the subthalamic nucleusdepending on the disorder that is being treated. Sometimes only one side of the brain is treated, and other times two brain leads are implanted, one on the right side and one on the left.
How might deep brain stimulation treat epilepsy?
During seizures, the brain's normal electrical activity becomes overactive. Evidence from animal studies shows that the delivery of electrical stimulation to certain brain targets can sometimes stop this electrical hyperactivity, ending seizure symptoms that are underway. The target areas for stimulation involve a number of brain regions, all of which have been investigated in animals and some of which have been studied in humans. These include the cerebellum, caudate, thalamus, mamillary nuclei, anterior nucleus of the thalamus, and subthalamic nucleus.
Studies have been conducted on various species of animals with different types of epilepsy. One study in rats that experienced chemically induced seizures showed that stimulation in the anterior nucleus of the thalamus made it more difficult for seizures to occur. Another study in rats with a genetic epilepsy found that stimulation of the subthalamic nucleus at the beginning of a seizure was able to stop the seizure from continuing.
At the present time, it is not clear which brain region, when stimulated, will be most effective for preventing or stopping seizures. Also unknown is which types of seizures are most likely to respond to DBS. The mechanism by which electrical stimulation might suppress seizures also remains to be understood. One theory is that electrical stimulation blocks areas of the brain that can contribute to the generation or spread of seizure activity.
What do studies in humans show?
Most of the evidence supporting the notion that DBS might be helpful to treat epilepsy is derived from uncontrolled studies, in which patients and their doctors are aware that the electrical stimulation is being used. These studies provide important preliminary information and are guiding the development of more definitive research efforts. Controlled studies, which are more rigorous, have been conducted only in small groups of patients thus far.
Research on DBS in humans with epilepsy that has targeted the centromedian nucleus of the thalamus, the anterior nucleus of the thalamus, and the subthalamic nucleus has shown that some patients seem to have a reduction in the severity or frequency of their seizures. Further work is needed, however.
What is the focus of ongoing research in deep brain stimulation?
Current and future research is focused on addressing a number of important questions related to the use of DBS in epilepsy:
- What brain targets for DBS are the most effective for controlling seizures, and how effective is DBS for epilepsy?
- Can DBS reliably suppress the start of seizures, rapidly terminate seizures, or both?
- Are all epilepsy syndromes and seizure types equally responsive to DBS?
- What stimulation parameters are best for controlling seizures?
- Is there a way to detect when seizures start in the brain and deliver the stimulation only when needed?
- Can medication doses be reduced in patients receiving DBS therapy?
References
The following articles were used in preparing this piece. Look for more information at PubMed, a service of the National Library of Medicine:
Fisher RS, Uematsu S, Krauss GL, et al. Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. Epilepsia 1992; 33: 841-851.
[PMID 1396427]
Mirski MA, Rossell LA, Terry JB, Fisher RS. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Research 28: 89-100, 1997.
[PMID 9267773]
Starr PA, Vitek JL, Bakay RA. Deep brain stimulation for movement disorders. Neurosurgery Clinics of North America 9: 381-402, 1998. [PMID 9495900]
Velasco F, Velasco M, Velasco AL, Jimenez F, Marquez I, Rise M. Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies. Epilepsia 36: 63-71, 1995. [PMID 8001511]
Vercueil L, Benazzous A, Deransart C, et al.High-frequency stimulation of the sub-thalamic nucleus suppresses absence seizures in the rat: comparison with neurotoxic lesions. Epilepsy Research 31: 39-46, 1998. [PMID 9696299]