Deep Brain Stimulation: a Therapy and Investigative Tool

by Guy McKhann, M.D.

October 02, 2013

In an article in The Wall Street Journal by Shirley Wang, the run-up to the use of deep brain stimulation for the treatment of dystonia in a 17-year-old girl is presented. The idea of using a neurosurgical procedure to modify a disorder of movement is at least 50 years old. Initially, surgeons made lesions deep in the brain to modify movement disorders such as tremor. The electrodes they implanted were used primarily to determine the site of the lesion.

The introduction of implantable electrodes that stimulated the brain (bypassing the lesioning) is relatively recent, thanks to the work of Alim Benabid and his colleagues in France. The use of this implantable technology followed the experience cardiologists had with implantable pacemakers going back to the 1960s. Benabid reported significant improvement for patients with tremor, establishing the field of deep brain stimulation (DBS) for neurological disorders. The primary use of DBS has been in Parkinson’s disease; at least 30,000 Parkinson’s patients have received this therapy.

With the success in Parkinson’s disease, it was a natural extension to consider the use of DBS in other conditions, including dystonia (the symptoms of which are described in Wang’s article). Search YouTube for “DBS dystonia” and you’ll see the effects it can have. DBS, as opposed to a lesion in the brain, can be turned off and on.

What can we expect to happen to Emily Cisar, the child in Wang’s article, who at the time of this writing had not been hooked up to her stimulator? There have been no long-term, large-scale studies of the efficacy of DBS in dystonia, but she has at least a 50 percent chance of significant improvement. Part of the problem is that not all dystonia, or DBS, is the same. A major factor is what target is chosen for stimulation.

For many people with Parkinson’s disease, the preferred target is the subthalamic nucleus, a small group of neurons involved in motor control. This target was identified by Mahlon DeLong and his colleagues at Emory based on elegant neurophysiolgical studies in the monkey that had developed Parkinson’s symptoms after exposure to a toxin, MPTP. These Parkinson’s monkeys showed marked improvement with stimulation of the subthalamic nucleus, leading to this target in the human. For Emily, however, a different target was chosen: a larger group of nerve cells called the globus pallidus. We have gradually recognized that the brain works in a series of circuits, some of which are excitatory and some inhibitory. DBS taps into these circuits, usually in an inhibitory way.

DBS is being tried in a variety of conditions, including depression, obsessive-compulsive disorder, pain, and epilepsy. To my mind, this is human experimentation, not to be done by amateurs but by experts who can handle not only the surgery but also the longer-term follow-up and, most importantly, who can learn from their experience. DBS is clearly here to stay, not only as a therapeutic tool, but also as a means to understanding neurologic and psychiatric disease.