The Evolution of Stroke Rehabilitation: Advances in Recovery and Neuromodulation

The Journey of Stroke Rehabilitation

In research, remarkable breakthroughs have been made over the last 3 decades in acute stroke care. From the revolutionary 1995 NINDS study showing that tissue-type plasminogen activator, or “clot busters”, can significantly improve a person’s chance of recovery, to recent studies expanding candidacy for those who can receive mechanical thrombectomy to include those with larger core infarcts on CT heads, and expanding the thrombolysis treatment beyond 4.5 hours.^1,2 However, even if a person receives reperfusion treatment, half of all survivors have residual disabilities. The vast majority of stroke survivors are in the chronic stroke recovery stage and treatment options have been limited in the past. Recently, there has been a shift in research focus and new hope to dedicate more resources to chronic stroke recovery.

Stroke Prevention Advancements

The core of stroke recovery is to promote rehabilitation from stroke deficits and prevent repeat strokes that can set back a person’s progress. Medication options have expanded in recent years to help prevent second strokes, as well as prevent first strokes. PCSK-9 inhibitors have revolutionized management of atherosclerotic risk and GLP-1 agonists can improve management of type 2 diabetes and lower the risk of cardiovascular disease and stroke.³ A new factor Xia inhibitor, asundexian, may become as commonly prescribed as aspirin in the future in secondary stroke prevention.⁴

Post Stroke Recovery Environment

Stroke rehabilitation has changed and has become more individualized, meeting the specific needs of patients and their caregivers. It is typically multidisciplinary, requiring different types of medical expertise at different points in a person’s recovery. Hospital providers such as ICU doctors, neurologists, and nurses help stabilize patients immediately after a stroke. Physical therapists, occupational therapists, and speech therapists initiate rehabilitation while the patient is still in the hospital and help determine the best environment to continue a patient’s recovery. Research shows that if patients can tolerate intense physical therapy early, they can have a better chance of improving their stroke symptoms and promoting neuroplasticity. Regardless of the newer technological advancements in stroke recovery, the core of recovery relies on the patient, their rehabilitation therapists, and their caregivers.

Previous Stroke Rehabilitation Investigations

Many different techniques have been tried in the past to improve a person’s residual stroke symptoms. Mirror therapy showed moderate improvement in motor function in an affected limb, but there were mixed results in reducing pain and having lasting effects beyond 6 months.⁵ Some therapists have incorporated mirror therapy successfully into their toolbox and have found it to benefit patient outcomes. Hyperbaric oxygen therapy, while safe, is not recommended for acute stroke therapy due to its limited feasibility to obtain when it is most beneficial (in hyperacute period 30-60 min).^6,7 In chronic stroke recovery, there are conflicting opinions whether it is beneficial and its effects are durable, especially in cognitive improvement. Constraint therapy showed some improvements in motor recovery, but unfortunately did not reduce disability.⁸ Previous investigations into medications (such as SSRI’s, dopamine agents, D-amphetamines, niacin, etc) have shown limited ability to improve functional recovery.

New Hope for Therapeutic Treatments With Neuromodulation

As technology advances, neuromodulation has shown great promise for chronic stroke recovery. Neuromodulation is the use of biomedical technology to deliver electrical or chemical treatment directly to a targeted area of the nervous system. It has many applications in other fields of neurology and psychiatry, and now is being adopted into stroke recovery to promote neuroplasticity.

VNS-REHAB was a paradigm shifting trial that showed vagal nerve stimulation paired with intensive rehabilitation improves arm motor recovery, even many years after a stroke⁹. This led to the FDA approval of the device. Rather than directly stimulating a focal spot in the brain, vagal nerve stimulation projects to many cortical neurons throughout the brain, promoting memory consolidation and goal-directed behavioral change. Motor improvements appear to persist after therapy, leading to improvement in quality of life and activities of daily living. Rehabilitation facilities throughout the country are adopting the protocol to give hope for many chronic stroke survivors with residual arm weakness.

While not a universal standard of care, repetitive transcranial magnetic stimulation as an adjunctive therapy has been shown to be helpful in arm recovery, by stimulating the injured side of the brain or suppressing the non-injured side’s maladaptive inhibition. Direct current stimulation is another neuromodulation technique that has variable benefit, but is likely helpful in specialized rehabilitation settings.¹⁰

Future Directions

New surgical approaches are also being investigated to improve neuroplasticity in stroke survivors. Currently, a pivotal study called the RESTORE trial (NCT05701280) is investigating if deep brain stimulation with intensive therapy can improve a patient’s moderate to severe arm weakness.

With advances in neuromodulation, stroke rehabilitation is still reliant on working closely and intensively with a trained therapist. Transportation is often a barrier to people being able to receive the appropriate intense level of therapy. By bringing the therapy to patient’s homes, telemedicine can hopefully improve access to specialized stroke therapists. Currently there is a clinical trial called TELEREHAB-2 (NCT06682429) that is actively enrolling at centers throughout the country to test if intensive daily tele-rehabilitation is superior to usual care in stroke patients.

Throughout the country, there are many centers looking into other advanced technologies for stroke rehabilitation, such as low intensity focused ultrasound stimulation, brain computer interfaces, robotics, understanding neural networks, and fitness-based cardiovascular conditioning.

Lastly, hopefully future research will also include hemorrhagic stroke recovery, post-stroke fatigue, cognitive impairments, visual recovery, and emotional wellbeing.

REFERENCES
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8. Corbetta D, Sirtori V, Castellini G, Moja L, Gatti R. Constraint-induced movement therapy for upper extremities in people with stroke. Cochrane Database Syst Rev. 2015;2015(10):CD004433. Published 2015 Oct 8. doi:10.1002/14651858.CD004433.pub3
9. Dawson J, Liu CY, Francisco GE, et al. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. 2021;397(10284):1545-1553. doi:10.1016/S0140-6736(21)00475-X
10. Keser Z, Ikramuddin S, Shekhar S, Feng W. Neuromodulation for Post-Stroke Motor Recovery: a Narrative Review of Invasive and Non‑Invasive Tools. Curr Neurol Neurosci Rep. 2023;23(12):893-906. doi:10.1007/s11910-023-01319-6