A few years ago Harkema began testing epidural stimulation on a few patients who had not responded to locomotor training. She surgically implanted electrodes on the outermost layer of the cord and stimulated right below threshold level. Because the cord is used to receiving a lot of input from the brain, it doesn’t respond as strongly to sensory input. The purpose of this stimulation is to make the spinal cord more responsive to sensory cues so they can trigger its inherent motor programs. So far Harkema has only tried the technique on three patients. After about seven months of stimulation in combination with stand training (where harnesses support part of the patients’ weight and therapists manually position the limbs), they were able to stand and support their full weight for the first time in years. Harkema reports that one patient regained the ability to voluntarily move his toes and ankles and bend his knees 90 degrees while lying down—but only while receiving epidural stimulation. The voluntary movement was a surprise for Harkema and she concludes that “you don’t need much to execute these movements if you get the spinal cord in the right functional state.” But none of her patients have been able to take a step yet. She thinks that it may be possible to get stepping once her research team refines stimulation and the array of 16 electrodes used.
Harkema speculates that activating the spinal cord also amplifies the residual connections between it and the brain, allowing this tiny bit of brain input to be “heard” by the system.
Growing New Wires
Bulking up brain input by getting new axons—wirelike extensions of brain cells—to grow through the damaged part of the spinal cord is the holy grail of regeneration research. A set of elegant experiments in rats published last year in the journal Science show that even when only a minuscule fraction—2 percent—of connections between the brain and spinal cord are left, epidural stimulation combined with locomotor training can cajole new connections through the part of the spinal cord that was cut. Professor Grégoire Courtine and his colleagues at the Center for Neuroprosthetics and Brain Mind Institute at the Swiss Federal Institute of Technology, trained paralyzed rats with incomplete lesions using a miniature version of the locomotor training devices used for people. A harness held some of the animal’s body weight so that only the paralyzed hindlimbs made contact with the ground. Researchers gave the epidural stimulation while the rat was coaxed to walk toward a treat. After three weeks of training, the rats were able to take their first steps and after about five more weeks, they could climb stairs and maneuver around obstacles. Courtine found that after training, the lesion site became home to new axons. It recovered about 45 percent of the number of pre-lesion connections, a growth explosion considering the initial cut left so few axons.
Unlike Harkema’s patients, Courtine’s rats also got drugs that ramp up communication between neurons in the spinal cord. Both researchers agree that the next step would be to give patients this combination treatment but the drugs used in rats have yet to be approved by the FDA for people. Courtine suggests that until then, epidural stimulation in patients can be improved by targeting more than one area of the spinal cord. The idea has yet to be tested.
Locomotor training and epidural stimulation studies suggest that with some brain connections left, it is possible to regrow or enhance those connections and recover voluntary control. But there is an ongoing debate about whether a sensorimotor complete injury (the patient cannot move or feel) also means an anatomically complete injury (that there are absolutely no remaining connections between brain and cord). According to neurologist John W. McDonald, director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute, about two thirds of patients with complete injuries have some connections left. Dietz disagrees noting that the “five to ten centimeters of bleeding and crushed neurons” that result from a spinal cord injury make it very unlikely for axons to survive.