Delivering electrical impulses to the dorsal columns of the spinal cord in rats alleviated the symptoms of Parkinson’s disease in a recent study. If the finding proves true in people, such a treatment, already used to alleviate intractable pain, would offer an alternative to the more invasive deep brain stimulation (DBS).
The main side effect of stimulating the dorsal columns of the spinal cord, the ridges through the spine where spinal nerves attach, is a tingling sensation, says Miguel Nicolelis of the Duke University Medical Center, the leader of a group developing this technique. “There are no major side effects, and the risks of stimulating the spinal cord are much lower than stimulating deep in the brain,” he says. “This will be a much safer procedure, much easier to perform, and much cheaper.
“Most Parkinson patients could be eligible for this type of procedure,” he adds, instead of the very carefully chosen few deemed eligible for DBS surgery.
The brain of a person with Parkinson’s disease lacks dopamine, a neurotransmitter vital for controlling voluntary movement. In DBS, pulses of electricity are delivered via electrodes implanted deep within the brain and attached to a battery implanted under the skin below the clavicle, relieving tremors. But implanting the electrodes requires difficult brain surgery.
Nicolelis got the idea of stimulating the spinal cord instead from experiments he did a decade ago in which attempted to control seizures in rats. He found he could disrupt and prevent seizures in the rats by delivering electrical stimulation to the trigeminal nerve, a large nerve in the face. Later, he observed that the pattern of electrical activity produced by the brains of mice bred to have symptoms of Parkinson’s disease looked very similar to seizure activity.
“I thought, if it looks like epilepsy, maybe we can treat it like epilepsy, so we started to stimulate the trigeminal nerve in the face,” Nicolelis says. “Then I thought, if we go to the dorsal column in the spinal cord, we may reach the entire motor system, and that’s what happened. If I had not done that study 10 years ago about epilepsy, I never would have thought of this.”
When the electrical stimulator is implanted into the dorsal column of mice and rats that display the tremors characteristic of Parkinson’s disease, their movement improves within 4 seconds. The treatment also reduces low-frequency seizures in the animals—a problem also experienced by some people with Parkinson’s disease. The research was reported in the March 20 issue of Science. [see the lab's video of the rat on and off stimulation, an mpg file]
Nicolelis has already traveled to Brazil to set up primate research on the effectiveness of the technique. “If we get same findings in primates, then next year we can envision starting some clinical work on humans,” Nicolelis says. And since the technology used to deliver the impulses to the spinal cord already has been used for decades to treat chronic pain, “we’re talking about the possibility of a very quick translation to the clinic,” he says. “These days you can buy the equipment right off the shelf.”
Meanwhile, researchers at Stanford led by Karl Deisseroth have found that stimulating the axons, or neural “wires” that travel from the surface of the brain to the subthalamic nucleus near the top of the spinal cord, relieves tremors in rodents just as effectively as deep brain stimulation of the subthalamic nucleus itself.
This suggests that stimulating a part of the brain closer to the surface, possibly through noninvasive techniques, might provide relief to Parkinson’s patients without the need for deep-brain surgery. The research was published April 17, also in Science.
Deisseroth sees links between his research and the spinal cord stimulation the Nicolelis team conducted.
“They’re putting their electrodes in the spinal cord, but they’re stimulating the fibers that likely arise from the cortex,” Deisseroth says. “I think it fits well with what we’ve found. There are definitely fibers in the rat that arise from the motor cortex—the area we implicated in our experiments—and that run to the dorsal part of the spinal cord.”
“The stimulation could be external,” he adds. “Transcranial magnetic stimulation, for example, doesn’t penetrate deep into the brain, but it certainly reaches the motor cortex, which means it’s a completely noninvasive treatment. If targeted more precisely, it might turn out to be helpful in movement disorders.”