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Clinical Applications for Deep Brain Stimulation Continue to Expand

http://www.medscape.com/viewarticle/444233

Nov 07, 2002
By Paula Moyer
Reuters Health
NEW YORK

Deep brain stimulation is on its way to FDA approval for several neurologic disorders, according to Dr. Mahlon DeLong, speaking in Orlando at the 32nd annual meeting of the Society for Neuroscience. He noted that it is already indicated for Parkinson's disease and tremor.

The technique involves the introduction of electrodes into the brain through which small electrical currents are delivered. Originally developed to replace surgical destruction of a portion of the thalamus, deep brain stimulation is also currently applied to the globus pallidus and the subthalamic nucleus.

"Deep-brain stimulation has moved forward rapidly in its clinical applications," Dr. DeLong told Reuters Health. "In addition to Parkinson's disease and tremor, this modality has applications in other forms of movement disorders as well as neuropsychiatric conditions such as obsessive-compulsive disorder, Tourette's syndrome, and eating disorders."

Dr. DeLong, the chair of neurology at Emory University School of Medicine in Atlanta, Georgia, commented on the implications of research presented at a symposium on deep brain stimulation. The chair of the symposium was Dr. Robert Gross, also of Emory.

At the same time that research confirming the clinical applications of deep brain stimulation has advanced quickly, understanding of the scientific underpinnings has lagged behind, he said. "Only recently has it come to be understood that the technique creates a reversible lesion," said Dr. DeLong.

Dr. Jonathan Dostrovsky and colleagues at the University of Toronto found that high-frequency electrical stimulation in the human brain inhibits the firing of brain cells near the stimulation electrode. They examined the effects of microstimulation through a recording microelectrode located within 1 mm of the stimulation site.

The investigators obtained recordings from 350 thalamic neurons in 31 awake patients who underwent functional stereotactic surgery during which the electrodes would be implanted. Single stimuli generally had no effect other than a short burst of firing.

However, high frequency trains of stimuli produced prolonged inhibition averaging 2.8 seconds in 40% of the cells after the train was terminated. This response occurred in more than 60% of cells firing in bursts due to low threshold calcium spikes. In most cases, the inhibition was preceded by several long bursts that occurred within a few hundred milliseconds after the train was terminated.

On the basis of these findings, the investigators reported that high frequency stimulation may cause many thalamic neurons to become hyperpolarized, and that hyperpolarization may be one of the mechanisms that mediates tremor reduction with deep brain stimulation.

In other work, Dr. Warren Grill, of the department of bioengineering at Case Western Reserve University developed a computer-based model of the electric fields generated in the brain by deep brain stimulation. He and his colleagues found that implanted electrodes are surrounded by diverse neural elements; yet these different neural elements respond at similar stimulation thresholds. This finding of non-selective neuronal effects both furthers the understanding of deep brain stimulation and complicates it, he reported.

"We now want to understand the full potential of deep brain stimulation and how to modify the technique to achieve more selective effects," said Dr. DeLong. "A fundamental lesson that we have learned is that diseases such as Parkinson's disease are circuit disorders involving localized, discrete circuits. In diseases such as Parkinson's disease, abnormal activity, such as synchronous discharge, begins to propagate through the circuits. In deep brain stimulation, the approach is to break up the abnormal activity and allow remaining intact portions of the brain to function more normally."
 

© 2002 Reuters Ltd