Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.241380
Source of Support: None, Conflict of Interest: None
Exercise is a very valuable but underutilized component of post stroke care. The evidence strongly supports the benefit of physical activity and exercise for stroke survivors. With education, encouragement, and spreading of awareness regarding the benefits and safety of exercise after stroke, and with the development of appropriate programs in hospitals and in communities, the ability to recruit patients to these programs will increase. These programs developed by trained exercise professionals should be offered early after stroke, when there is a probability of highest impact, and should continue to be monitored throughout the chronic stages to influence life-style changing behaviour and optimal overall health.
Post stroke neurorestoration is achieved by enhancing neurogenesis, angiogenesis, and oligodendrogenesis, which in concert promote neurological recovery.
Over the years, we have understood that the uni-model targeting of key events in stroke pathophysiology has not been effective in providing long-term benefits, leading to negative results in previous clinical neuroprotective stroke trials. A successful future stroke therapy needs to approach multiple pathophysiological mechanisms besides revascularization/reperfusion, including the addressal of thrombolytic-related adverse side-effects, the prevention of apoptosis (programmed cell death), as well as the stimulation of neuro-regeneration and neuronal plasticity.,
The exercise regimes under the ambit of comprehensive physiotherapy have evolved with experience over several decades; and, increasing scientific evidence now exists illustrating the mechanisms of how they may work to enhance the plasticity and aid in recovery of lost neurological abilities. The history is replete with examples of anecdotal reports and serendipitous discoveries which have essentially paved the way for a more solid understanding based on sound science.
Now we know that angiogenesis is the key feature responsible for post stroke neuronal reorganization and stroke recovery. Brain ischemia itself induces angiogenesis through the hypoxia inducible factor 1, a transcription factor that responds to the changing intracellular O2 concentration and induces erythropoietin expression. Angiogenesis is activated through the release of polypeptide growth factors and cytokines; and, the specific up-regulation of the angiogenic factors involves transforming growth factor beta, platelet derived growth factor, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor 2 in response to ischemia. VEGF is the most potent hypoxia inducible angiogenic factor amongst all these listed factors and is secreted by the endothelial cells and pericytes.
Exercise induces neurogenesis and angiogenesis through the growth factor cascade. Endurance exercises, that are exemplified by running up, regulate the brain derived neurotopic factor (BDNF) and synapsin 1 messenger ribose nucleic acid (mRNA), which help to facilitate better outcome in patients with stroke. Exercise also strengthens the micro- vascular integrity after cerebral ischemia and upregulates endothelial nitric oxide (NO) synthesis, which improve endothelium function, again up regulating the VEGF expression.
Motor weakness and the ability to walk have been the primary targets for testing interventions that may improve after stroke. Physical therapeutic interventions enhance recovery after stroke; however, the timing, duration and type of intervention require clarification and further trials. Pharmacotherapy, in particular with dopaminergic and selective serotonin-reuptake inhibitors, shows promise in enhancing motor recovery after stroke; however, further large scale trials are required.
Exploring the cost-effectiveness of different models of exercise participation for stroke survivors across a range of settings (institution, community and home, including the integration of family members as care givers), as well as of individuals into community programs, is being done, as is evidenced by the recently published Family-led Rehabilitation after Stroke in India (ATTEND) trial.
Establishing effective strategies to facilitate long-term adherence to regular exercise and physical activity following the onset of stroke is of paramount importance.
Continued research into different modalities of physical training (i.e., aerobics, resistance, and combined aerobics and resistance, etc) on the cardiovascular health and functional outcomes post stroke is being done and is encouraged.
The current study published by Pradhan et al., is a valiant attempt at securing clinical improvement utilizing an exercise regime in the presence of post stroke deficits. In this study, they describe the novel technique of amalgamating intelligently, the existing regimes into a more user-friendly and effective way to enhance post stroke neurological recovery with special emphasis on motor and tone improvement. The objective assessment was purely clinical and not assisted by neuroimaging or biochemical biomarkers of functional improvement.
We do have some concerns on the methodology employed in terms of the title of it being a “cluster randomized” trial. In a cluster randomized trial, clusters are randomly assigned the intervention or control arm, and all patients getting admitted/enrolled in that cluster, which could be a particular ward or out patients service etc., will get that intervention. In a cluster randomized trial, randomization does not happen at an individual patient level. There are also some concerns with regard to the procedures employed for “blinding”. The authors claim that each group along with the allotted physiotherapist was completely blinded to the other group. We wonder if it is possible to blind patients on the type of physiotherapy to be administered after explaining the two possible interventions in the consent form! The only reasonable option would be to have a blinded assessor. We are not sure we had one in this study.
The current study emphasizes on the conduction of high frequency, periodic physiotherapy for 2.5 hours. They claim that it is the first ever study utilizing this protocol. However, we have come across a paper by Wang et al., published in the year 2013 on 360 patients post stoke, wherein physiotherapy performed in patients for >3 hours every day had significantly better functional gains when compared to those receiving therapy <3 hours each day. A similar exercise regime has also been described in the Stroke Recovery Guide by the National Stroke Association in the year 2010.
Despite these concerns, the study reads well, and typifies what is required for optimizing the stroke outcome. The study also is in tune with the advancements taking place in this field, as regards optimizing different exercise regimes in concert with other interventional techniques for stroke recovery programs.
Constraint induced movement therapy (CIMT), an another variety of the interventional program, is now being combined with non-invasive brain stimulation techniques such as recurrent transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (TCDCS) for an enhanced benefit.
As demonstrated by two recently published clinical trials, the key to improving rehabilitation outcomes might be found in new assistive technologies such as robotic exoskeletons and brain-machine interfaces.,
The first study published by Verena et al., describes how the ARM in exoskeleton can facilitate the rehabilitation of hemiparesis caused by stroke. Therapy robotics have the potential to enhance recovery of a paralyzed arm or leg beyond what seems to be possible with conventional therapies. Myoelectric computer interface (MCI) is another technique being developed.,
Machines assisting recovery from stroke (MARS) is a rehabilitation engineering research center in USA, which is also developing several assistive devices that have the potential to enhance recovery with different exercise regimes.
Neurorestoration is a concept that has been proven emphatically in several experimental models of stroke. The lack of proof in the clinical settings will continue to be discouraging until the reasons for failure related to this endeavour are examined. The trials of the past cannot be termed as ‘failures' as they definitely have contributed to our understanding of the complex biology of brain injury. This knowledge must provide an impetus for the development of superior candidate molecules and methodological interventions that will enhance drug development and novel interventional regimes for the clinical testing.
Establishing effective exercise interventions that take place in both health care and home settings to optimize outcomes, maximizing adherence to these protocols and facilitating involvement of caregivers is the best way forward.