HONOLULU—What if you could scan your patients for stroke-susceptibility loci or implant a device in their brains to repair stroke-damaged pathways?
Such forward-thinking concepts may be achievable, according to some leading researchers in the field of stroke medicine, who presented their ideas at the 2013 International Stroke Conference.
Two decades after investigators demonstrated the plasticity of the brain after stroke, the restorative processes that occur after the acute phase of stroke continue to be explored, opening up potential targets for new drugs. At the same time, neurotechnology is maturing.
“We’re quickly entering a brave new world of neuroengineering in the brain after stroke,” said Randolph J. Nudo, PhD, Director of the Center on Aging at the University of Kansas Medical Center, Kansas City.
In the emerging field of robotics, a neural interface system implanted in two humans with long-standing tetraplegia recorded neural signals from the brain as input commands to control a robotic arm. A miniaturized, closed-loop system implanted in the cerebral cortex of brain-injured rats has been shown to improve recovery. Dr. Nudo sees the potential of these advances for neurotransmitter sensing, open- and closed-loop drug delivery, and control of stem cell integration. Joel Stein, MD, Chair of Rehabilitative and Regeneration Medicine at Columbia University in New York City, said robotics are being used to deliver rehabilitation therapy. Exoskeletal workstations incorporate engaging games or virtual reality experiences to provide many repetitions for the patient without therapist fatigue. Wearable “bionic legs” provide external force to supplement muscle strength and improve motor skills through practice.
Not all robotic strategies have panned out, however. In a study of veterans, robot-assisted therapy provided only modest effects on poststroke upper-limb impairment. The robotic therapy also was somewhat more expensive than intensive human therapy ($9,977 vs $8,269).
Robotics may not always be better. But when they are as good as traditional approaches, they provide new efficiencies in terms of delivery, said Dr. Stein. “The bottom line is that robots are coming. We should prepare for them and expect them to become a key piece of clinical practice in this field in the future.”
The search for genetic susceptibility loci for stroke is in its infancy, but researchers are getting closer to their goal, said Ralph Sacco, MD, Professor and Chair of Neurology at the Miller School of Medicine, University of Miami. The collaborative METASTROKE study offered some findings, and the big push now, as the cost of these studies declines, is moving from common variants to rare variants using next-generation sequencing and whole-genome studies.
Large family studies that use next-generation sequencing, such as the NIH-supported Life After Linkage study, should also help in smaller, more homogeneous groups.
“We really have to refine our phenotypes using extreme phenotypes, subgroups, and subclinical traits and make sure we get the phenotype right, so all this next-generation sequencing will make sense,” Dr. Sacco said.
The ability to identify rare variants may suggest novel pathways that could serve as targets for drug therapy. Someday, clinicians could use genetic testing to identify at-risk patients for ultra-early stroke prevention therapies. Pharmacogenomic profiles will be used to personalize stroke prevention treatments.
A Global Pre-Emptive Strike
Several speakers looked to a prevention model to reverse the increasing global burden of stroke. Valery Feigin, MD, PhD, Director of the National Institute for Stroke and Applied Neurosciences, AUT University, in Auckland, New Zealand, said that priority should be given to a population-based approach that includes legislative measures aimed at environmental risk factors, such as European countries’ attempts to reduce citizens’ salt intake.
“A small shift in the distribution of risk factors across the population will result in a major drop in stroke incidence,” he said, noting, for example, that smoking cessation alone can reduce stroke risk by 12% to 19%.
The suggestion elicited comments during the discussion period, including concerns about creating a “nanny state” and a reminder of the situation involving New York City Mayor Michael Bloomberg’s effort to reduce the size of soft drinks. Still others suggested that such measures need to be positively reinforced and that governments have a civil obligation to act, given the massive costs of poor public health.
Lewis Morgenstern, MD, an epidemiologist and Director of the Stroke Program at the University of Michigan, Ann Arbor, observed that even in the West, where stroke incidence and mortality are declining, “Stroke is becoming more and more a disease of the poor and underserved.”
He called on clinicians to address these disparities through global research agendas and advocacy, and to reach out locally to poor and underserved populations with stroke prevention and preparedness messages. As for what they should emphasize, he highlighted a recent estimate that the cost of an endovascular procedure is at least $10,000, whereas a one-month supply of the blood pressure–lowering diuretic hydrochlorothiazide 25 mg costs $4.