Research reportFactors affecting post-stroke motor recovery: Implications on neurotherapy after brain injury
Introduction
Stroke has declined to the fifth most common cause of death in the United States after devoting extensive efforts for controlling stroke risk factors and optimizing acute care of stroke patients [1]. However, stroke remains a leading cause of disability among adults in the United States and globally [1], [2], [3]. Of the estimated 800,000 strokes that occur in the US per year, the majority of stroke survivors develop long-term functional deficits [1]. The NINDS sponsored r-tPA trials have reported that the percentage of patients that still had mild to moderate functional deficits (Modified Rankin Scale of 2–5) at 3 and 12 months after a stroke were 44% and 35%, respectively, despite the fact that they received r-tPA in the acute phase [4], [5]. Although these functional deficits may include cognitive, speech, visual, sensory and motor deficits, the most commonly recognized deficit after stroke is motor impairment that have negative impact on subject’s mobility and quality of life [5].
Functional deficits after stroke are also associated with huge financial burden on the patient, family, and society. It is estimated the average lifetime cost of caring for one stroke patient (across all stroke sub-types) was about $103,576 in 1990 which included the cost of acute care, long-term ambulatory care, and nursing home care [6]. The overall financial cost of post-stroke management of patients as well as the demand on rehabilitation therapy has also increased with the increase in numbers of stroke survivors reaching an annual total of $3.4 billion in the US [1].
Post-stroke motor recovery is a complex, dynamic, and multifactorial process in which an interplay among genetic, pathophysiologic, sociodemographic and therapeutic factors determines the overall recovery trajectory. Therefore, rehabilitation strategies that aim to improve post-stroke recovery outcomes require a thorough understanding of those major determinants. In this paper, we review the major factors influencing post-stroke motor recovery and its implication for neurotherapy after brain injury. We categorized those factors into three groups socio-demographic factors (age, gender, race, socio-economic status and others), clinical factors (the initial injury, co-morbidities, post-stroke depression and rehabilitation therapeutics), and genetic factors (Fig. 1).
Section snippets
Age
Older age is commonly identified as a significant prognostic factor for poorer outcome after ischemic and hemorrhagic stroke where nearly half of older stroke survivors experience mild-to-severe disability [7], [8], [9], [10], [11], However, the proposed prognostic value of age have been challenged by studies on long-term recovery [12], [13]. Whereas age may be an independent predictor of early outcomes after stroke [14], [15], [16], the effect of age on long-term outcome measures is less
Stroke subtype
The two major subtypes of stroke, hemorrhagic and ischemic stroke, result in different patterns of acute and chronic recovery. In general, hemorrhagic stroke patients tend to have greater functional impairment at presentation. However, patients with ICH tend to have a more pronounced and faster recovery than those with ischemic stroke of comparable severity [39], [40], [41].
The initial injury
Although several reparatory and regenerative processes occur following stroke, the extent of initial injury is a major
Genetic factors
Several studies on genetic variations in stroke and cardiovascular risk have associated multiple single nucleotide polymorphisms (SNPs) with increased risk [75], [76] or severity of ischemic stroke [77]. Yet, investigating genetic variants that may influence chronic recovery and response to rehabilitation therapy is still in infancy. Such genetic polymorphism may account for some of the inter-individual variability seen in stroke recovery, and may have implication for individualized
Conclusion
The increased number of stroke survivors creates a high demand for effective and accessible neuro-rehabilitation therapies. A thorough understanding of the pathophysiology and pattern of stroke recovery will boost the existing therapeutics and develop new rehabilitational interventions in the pipeline. Equally important is the understanding of non-pathophysiological and modifiable factors that may negatively or positively impact recovery process. Therefore, significant areas for further
Acknowledgements
Dr. Feng acknowledges grant support from National Institute of Health (P20GM109040 and HD086844), from American Heart Association (14SDG1829003 and 15SFDRN26030003) and South Carolina Clinical & Translational Research Insitute (UL1 TR001450). Mr. Alawieh acknowledges grant support from the American Heart Association (15PRE25250009). Dr. Zhao acknowledge grant support from National Natural Science Foundation(81572232) and Shanghai Natural Science Foundation(13ZR1436600).
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Authors contributed equally to this work.