Stroke: Deep brain stimulation could help treat motor issues
- More people are surviving strokes, but many experience disabilities, sometimes for years afterward.
- Deep brain stimulation is an emerging form of treatment for various neurological conditions.
- A research team has now tested a deep brain stimulation device — previously tested on rodents — on human stroke survivors in a first-of-its-kind phase 1 clinical trial.
- The researchers discovered that this is a safe intervention, and that upper limb movement in affected stroke survivors improved after a regime combining deep brain stimulation with physiotherapy.
Stroke is increasingly survivable thanks to advances in treatment and public health campaigns targeted at early diagnosis, but up to 50% of survivors experience chronic disability, with many needing assistance with daily activities.
When something blocks the blood supply to part of the brain, the event is known as an ischemic stroke. When a blood vessel in the brain bursts, this is known as a hemorrhagic stroke.
The majority of strokes are ischemic strokes, and they occur when blood clots or other particles block the blood vessels in the brain. Fatty deposits can cause blockages by building up in the blood vessels, according to the Centers of Disease Control and Prevention (CDC).
Dr. Clare Jonas, research communications manager at the Stroke Association explained for Medical News Today:
“Ischemic stroke is a blockage in one of the brain’s blood vessels which causes neurons to start to die. The effects of stroke are dependent on where the blockage in the brain is. Stroke is a recoverable condition because the brain can ‘rewire’ itself around this damage to relearn skills like motor function. For [treating the] effects of stroke — like arm weakness — this traditionally means a lot of physiotherapy.”
Deep brain stimulation as stroke treatment
One option for the treatment of stroke patients currently being explored is deep brain stimulation. This is a surgical procedure in which a device is implanted under a patient’s skin and sends out electrical impulses into specific parts of the brain.
The pulses can disrupt existing brain signals in a way that can influence more normal brain activity to be restored.
Deep brain stimulation has been explored as a possible treatment for a number of conditions, including Parkinson’s disease, and treatment-resistant depression.
Devices providing deep brain stimulation have been developed and approved for treating epilepsy.
A group of scientists from the Lerner Research Institute, Cleveland Clinic, OH, led by Dr. Andre G. Machado, professor of neurosurgery at the Cleveland Clinic Lerner College of Medicine, developed a device to allow them to determine whether deep brain stimulation could help to restore movement in rodent models of stroke back in 2014.
The researchers surgically implanted deep brain stimulation devices into rats, then split the rodents into three groups. One group received regular brain stimulation for 5 weeks, one had occasional bursts of stimulation for 5 weeks, and the final group had no stimulation.
The researchers found that deep brain stimulation, particularly occasional bursts of stimulation, improved the number of nerve cells that had grown compared with rats that had received no electrical impulses.
They also showed that proteins associated with the plasticity of nerve cells, or their ability to regrow, increased, following deep brain stimulation. These findings were published in the Journal of Neuroscience.
Does this approach work in humans?
Now, over a decade since that team started preclinical work on deep brain stimulation therapy for stroke patients, they have published the results of their first phase 1 clinical safety trial in humans in Nature Medicine.
In this trial, the researchers surgically implanted a deep brain stimulation device connected to a part of the brain called the cerebellum into 12 individuals with moderate-to-severe upper-extremity impairment that had already lasted 1–3 years.
Stimulation was applied over a period of 4 to 8 months and then gradually decreased weekly over a period of 1 month. The participants also received physiotherapy before and during the period in which they were receiving deep brain stimulation, as well as during the 1 month of decreasing stimulation and for a further 1 month after the stimulation had ceased.
The researchers measured the change in the participants’ ability to move their upper limbs across this time period, and found that the most significant change was during the period patients were receiving deep brain stimulation and physiotherapy.
While no serious adverse events were reported during the trial, which suggests that the process is safe for patients, the study authors point out that they cannot determine at this stage if the improvements observed in upper limb movement were due to deep brain stimulation or physiotherapy.
Dr. Jean-Philippe Langevin, neurosurgeon, and director of the Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the research, told MNT he felt the results supported the progression to a multi-center phase 2 trial.
However, he also pointed to potential cost and impracticality as potential barriers to the adoption of this treatment:
“I believe that the results of this trial are exciting, and I would definitely expect further work to expand on the current outcomes. The surgery of deep brain stimulation placement and the neurostimulation were both found to be safe. The subjects also demonstrated meaningful functional improvement with the therapy. This improvement was also associated with evidence of metabolic cortical reorganization as seen on PET scan[s]. Overall, the design of the study was robust and it specifically made an effort to exclude the possibility that the improvements were related to the rehabilitation alone.”
Why deep brain stimulation for stroke?
Dr. Machado holds a patent for the use of this deep brain stimulation method in stroke recovery. The study was co-funded by Enspire DBS Therapy, established in 2010 and owned by Cleveland Clinic Innovations, in which Dr. Machado holds stock options and equity ownership rights and serves as the Chief Scientific Officer.
When asked why a less invasive procedure for deep brain stimulation was not considered for the phase 1 safety trial, Dr. Machado told MNT that “[t]here are many ways to provide brain stimulation — but not deep brain stimulation — less invasively.“
“One such technology is called transcranial magnetic stimulation,“ he noted. “There are thousands of studies in the literature examining the effects of transcranial magnetic stimulation on stroke recovery but, to date, no real proof that it works. That is one of the reasons why we tested the more invasive choice of deep brain stimulation.“
“We are investigating, still in the laboratory model, whether our novel [deep brain stimulation] approach can work for traumatic brain injury. We have not yet begun testing in humans,” added Dr. Machado.
Dr. Jonas, who was not involved in the research, commented: “There have been a few studies in recent years on deep brain stimulation as a treatment for the effects of stroke. For example, the authors of this study have previously trialed [deep brain stimulation] to treat post-stroke pain.
“It’s exciting to see research addressing ways to make physiotherapy more effective for stroke survivors. However, [deep brain stimulation] requires brain surgery, so it is unlikely to be a suitable treatment for most stroke survivors,“ said Dr. Jonas.
“Fortunately, there are potential alternatives — like noninvasive vagus nerve stimulation — which are likely to be suitable for a broader range of stroke survivors. See Dr. Sheharyar Baig’s work, which we’re funding,” she added.
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