Bridging the Translational Gap in Stroke Recovery & Rehabilitation Research Workshop

The two-day agenda focused on knowledge gaps in aligning animal model and human stroke recovery, specifically focusing on how the models should distinguish spontaneous recovery from functional improvement through rehabilitation. Expanding on these topics, the discussions shifted toward identifying clearly defined research opportunities across several recurring themes for translational research in stroke recovery. These included: use of animal models to address clinical gaps; better understanding of the molecular mechanisms of recovery; exploiting potential new targets to enhance spontaneous recovery; identification of methods to align clinical and preclinical patient-relevant outcomes; use of translational models to inform and address dosing and timing of interventions; and discovery of biomarkers that cross the translational bridge. The meeting concluded with a round-table discussion of practical issues and transformative ideas for implementing large-scale stroke recovery and rehabilitation trials in StrokeNet.

Conclusions:

The workshop identified accessible, achievable, and aspirational opportunities for achieving major new insights into biology, translational biomarkers, and therapeutic advances in stroke recovery over the next 5-10 years. Accessible opportunities are those that can be achieved with current approaches by honing current practice, adapting present technologies, and establishing community guidelines. Achievable opportunities require further development of present approaches, including defining the difference between compensation and recovery in animal models. Finally, aspirational opportunities require at least one element of blue sky thinking or novel development. The steering committee of this workshop plans to publish a proceeding that will more fully describe what work is needed to achieve successful translation of restorative therapies from bench to clinic and establish effective guideposts for future stroke recovery and rehabilitation research.

Accessible

Accessible opportunities can be achieved with current approaches by honing current practice, adapting present technologies, and establishing community guidelines. This included combining preclinical and clinical teams, potentially through partially supported sabbaticals for cross-study with pre-clinical and clinical and rehab to acute exposure in stroke. Recovery researchers also need to better differentiate recovery and compensation in animal models as it pertains to human stroke and establish consistency in data collection across labs. In addition, standards and guidelines should be defined for how aged animals and comorbid conditions (e.g., diabetes and hypertension) are studied in translational models. Clinical opportunities to establish co-variates in the brain, such as dense array EEG, MEG, and resting state MRI., should be pursued. Kinematic analyses in rodent and humans to establish parallel patterns of recovery of motor control, as well as mapping differences in human vs rodent descending motor output, are accessible now as areas of study. Combination therapy was thought to be another viable opportunity to model. Animal models should include a basic level of activity or environmental stimulation/enrichment to mimic the clinical experience. Lastly, clinical recovery trials should further explore the use of wearable technology, include social determinants data (e.g., social isolation, social support, the area of deprivation index), and more closely examine the acute recovery period through the incorporation of imaging and outcome measures in acute stroke trials.

Achievable

Achievable opportunities require further development of present approaches, including defining the difference between compensation and recovery in animal models. Cognitive impairment modeling in animals and development of routine and validated cognitive outcome measures in human stroke were also seen as achievable opportunities. Pre-clinical modeling should adopt a standard set of criteria that include at a minimum: 1) identification of a plasticity mechanism, 2) association of such a mechanism with recovery, 3) replication in an outside lab, 4) association with training effect and prehensile function, and 5) potential testing in higher species, when warranted. Lastly, consistency in clinical trials would benefit from the development of a standard rehabilitation control group for which to compare to all recovery trials.

Aspirational

Aspirational opportunities require at least one element of blue sky thinking or novel development. They include computational modeling and analysis of patient differences and identification of fluid, structural, and electrophysiological biomarkers that can be measured in both animals and humans. When the field is more mature, investigators could partner together for iterative development of biomarkers and applications and the use of genetics to identify mutations that might associate with recovery and be a source for biomarkers. Research should also develop new outcome measures for proposed four functions in hemiparesis: dexterity, strength, synergies, and compensation. Finally, clinical researchers should work with colleagues in acute treatment and prevention and include community partners to identify pathways for new funding or approval (e.g., through The Centers for Medicare & Medicaid Services) for rehabilitation therapies.