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Mayo Clinic in Rochester, Minn., conducts about 100 deep brain stimulation (DBS) procedures a year. The list of disorders treated includes:
Four years ago, the DBS practice expanded to include children, as well as adults.
As is true in adults, successful DBS treatment in children depends on careful patient selection; precise neural targeting; and extensive, individualized stimulator programming.
At Mayo, an interdisciplinary committee with membership from the departments of neurology, neurosurgery, psychiatry, neuropsychology, pain neurology, nurse programming, and speech pathology reviews every DBS candidate, weighs risk factors against potential benefits, and comes to consensus about disease management.
Kendall H. Lee, M.D., Ph.D., the neurosurgery director of the DBS program at Mayo Clinic, and his colleague, Squire M. (Matt) Stead, M.D., Ph.D., a pediatric neurologist, note that the three patients with Tourette syndrome whom they have treated have responded well. The symptoms in one of the patients, who was 19 years old at the time of surgery, all but disappeared after programming adjustments to the DBS stimulator.
DBS for dystonia in children can help eliminate some symptoms. As Dr. Stead explains, "It is the best treatment we have to offer for dystonia that is medically refractory. Patients differ in response, but, on average, both adults and children experience about a 50 percent improvement with DBS."
Asked about the outcomes for children with chorea, Dr. Stead notes that none have had complete symptom remission, but all have had improvement. As an example, he cites a 5-year-old child who was nonverbal before surgery and was able to begin speaking after DBS.
Mayo Clinic is one of the few institutions in the world to offer DBS for intractable epilepsy in children. The program's youngest patient, and the youngest in the world to undergo DBS, was a 3-year-old child with Lennox-Gastaut syndrome.
"The response was excellent, with marked seizure reduction," says Dr. Lee. Dr. Stead adds, "There is no treatment available for this very serious condition, so we were pleased to see how well DBS worked."
Dr. Lee is also the director of Mayo's neural engineering laboratory and a Mayo-based, multi-institutional DBS consortium investigating the mechanisms of neurostimulation across a spectrum of disorders.
WINCS circuit board
In research funded by the National Institutes of Health and benefactor grants, Dr. Lee, Kevin E. Bennet, chair of Mayo's Division of Engineering, and their colleagues developed the Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS), a device that can monitor neurochemical output of targeted brain sites in real time during DBS.
It appears likely that DBS evokes the release of neurochemicals. DBS uses a high-frequency stimulation device applying five to 100 stimulation pulses a second. Traditional chemical detection systems, such as mass spectrometry, are an impractical means of monitoring in vivo chemical changes in the brain during DBS stimulation. WINCS, however, is capable of electrochemical detection using fast-scan cyclic voltammetry and amperometry, sampling a subsecond at a time.
Electrochemical monitoring through WINCS during DBS surgery in animals suggests that the positive effects of DBS are based on changes in neural activity and neurochemical transmitters in interconnected structures within a given neural network.
Anterior-posterior skull radiograph showing DBS lead
Lateral skull radiograph showing DBS lead
The thalamus, for example, is known to be an effective DBS target for seizure suppression. Dr. Lee and his colleagues have applied high-frequency stimulation (HFS), which mimics DBS, to brain slices from ferrets, monitoring changes with WINCS. They found that HFS suppressed spindle wave oscillations in the nucleus reticularis thalami and in thalamocortical relay neurons in the lateral geniculate nucleus. It also caused elevation in extracellular glutamate levels for many seconds after stimulation.
Identification of the prolonged release of glutamate, which decreases neuronal input resistance and abolishes thalamic network oscillatory action in response to HFS, is a step forward in explaining how DBS inhibits seizures and tremor.
WINCS is not just a research tool. The goal is to use WINCS to monitor neurochemical changes during human DBS surgery, to improve target identification and placement precision. In the study cited above, for example, Dr. Lee and his colleagues found that HFS-mediated neurotransmitter release may begin in astrocytes, which may turn out to be an as yet unappreciated target for DBS stimulation.
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