The first patient to ever undergo deep brain stimulation (DBS) to restore motor function following hemiparesis after ischemic stroke is exceeding researchers’ expectations for her functional improvements in the first four months of management pairing DBS with rehabilitative therapy.
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That’s the word from Cleveland Clinic neurosurgeon Andre Machado, MD, PhD, who is overseeing the patient’s care after surgically implanting DBS electrodes in her cerebellum in a milestone operation at Cleveland Clinic in December 2016, as detailed here.
“Within a few weeks of when the DBS device was turned on earlier this year, the patient reported she could move her affected arm in ways she had not been able to since her stroke,” says Dr. Machado, Chairman of Cleveland Clinic’s Neurological Institute. “And her progress has been steady — week after week, month after month, her function continues to improve. The improvement has been more than we expected.”
Part of an NIH-funded first-in-human trial
The patient is the first in an FDA-approved, first-in-human clinical trial of DBS for stroke recovery being conducted at Cleveland Clinic with funding support from the National Institutes of Health’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.
The researchers, led by Dr. Machado and neuroscientist Kenneth Baker, PhD, plan to ultimately enroll 12 patients in the study. A second enrollee has undergone surgery for DBS electrode implantation but has not yet completed initial physical training with stimulation turned on.
Candidates for the trial are patients who have severe residual hemiparesis from an ischemic stroke 12 to 24 months earlier in spite of rehabilitative therapy. “These are patients with chronic stroke who have failed to improve significantly after training with physical and occupational therapy,” says Dr. Machado. “So if we see a significant effect after the DBS surgery, we have reason to believe it’s the effect of the DBS plus rehabilitative therapy rather than of therapy alone. That’s the hypothesis of our trial — that DBS targeting the dentate nucleus of the cerebellum can allow these patients to regain more function from therapy than they could with therapy alone.”
Treatment protocol at a glance
The first patient has now completed the trial’s initial protocol, as follows (“therapy” below refers to two 90-minute sessions of combined physical and occupation therapy each week):
- One month of therapy following enrollment to establish baseline function
- Surgery to implant the DBS electrodes and battery
- Four-week resting period at home to recover from surgery
- Eight weeks of therapy without the DBS device turned on, to establish a new functional baseline
- Four weeks of programming the DBS device with the assistance of transcranial magnetic stimulation to assess response. “This involved many days of assessing the patient’s response to DBS settings to help us determine those that were most effective for her without causing side effects,” Dr. Machado explains.
- Four months of therapy with the DBS device turned on continuously
The protocol also calls for one month of slowly weaning off the DBS device, which the first patient has not yet done.
The therapy regimen used focuses on repetitive task practice and is the gold standard for upper extremity rehabilitation, says Anson Rosenfeldt, PT, DPT, one of two therapists working with patients in the trial. “Our protocol calls for patients to repeat an activity 70 to 100 times in one session,” she notes. “We’re really pushing the number of repetitions and challenging patients to move their arm and hand in different ways.”
The biggest difference from therapy regimens used for other patients with hemiplegia from stroke is that compensation from the unaffected side is strictly discouraged. “We want to challenge the patient’s brain in new ways to promote lasting change,” says Rosenfeldt, who is shown with the patient in the photo at the top of this post.
Here the patient performs one of the many tasks she was unable to do with her affected arm prior to DBS and physical training.
Continuing improvements prompt protocol revision
For the trial’s first patient, those efforts are paying off. In addition to progressive improvements in her scores on a multitude of objective tests of arm and hand function, the patient reports that she is now able to use her affected hand while cooking and to play games with her grandchildren. She also performs a host of daily tasks more efficiently, such as folding laundry.
“After four months of DBS plus therapy, this patient’s function has not plateaued,” says Dr. Machado. “We haven’t yet found the limits of how much she can improve. This makes us hopeful that this strategy will help other patients too.”
As a result of this continuing progress, the team is revising its study design to allow patients an opportunity to continue concurrent stimulation and therapy longer than the initially planned four-month window.
“Many questions remain,” Dr. Machado notes, including whether ongoing stimulation is needed to preserve functional improvements or if patients may maintain improvements gained after a limited period of stimulation and physical training. “We look forward to learning much more as this trial continues.”
One thing that’s certain is that more options are needed for this population. “About half of chronic stroke patients have a residual neurological deficit severe enough to require assistance with their ADLs, even after weeks of physical and occupational therapy,” Dr. Machado observes. “We need a tool that enhances the effects of therapy alone. This first patient gives us hope that help may be on the way.”