Review
The next revolution in stroke care Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Expert Rev. Neurother. 14(11), 1307–1314 (2014)
Robert Teasell*1–3, Danielle Rice1, Marina Richardson1, Nerissa Campbell1, Mona Madady1, Norhayati Hussein4, Manuel MurieFernandez5 and Stephen Page6 1 Lawson Health Research Institute, St. Joseph’s Health Care, 801 Commissioners Road East London, Ontario, N6C 5J1, Canada 2 Parkwood Hospital, St. Joseph’s Health Care, 801 Commissioners Road East London, Ontario, N6C 5J1, Canada 3 Department of Physical Medicine and Rehabilitation, Western University, 1151 Richmond St, London, Ontario, N6A 3K6, Canada 4 Department of Rehabilitation Medicine, Cheras Rehabilitation Hospital, Jalan Yaacob Latif, 56000, Kuala Lumpur, Malaysia 5 Department of Neurology, Clinica Universidad de Navarra, Pamplona, Navarra, Spain 6 The Ohio State University Medical Center, 453 W Tenth Avenue, Suite 406, Columbus, OH 43210, USA *Author for correspondence: Tel.: +1 519 685 4292; extn. 44559 Fax: +1 519 685 4023 [email protected]
informahealthcare.com
Stroke is the second leading cause of death and disability worldwide. Initiatives to decrease the burden of stroke have largely focused on prevention and acute care strategies. Despite considerable resources and attention, the focus on prevention and acute care has not been successful in changing the clinical trajectory for the majority of stroke patients. While efforts to prevent strokes will continue to have an impact, the total burden of stroke will increase due to the aging population and decreased mortality rates. There is strong evidence for the effectiveness of rehabilitation in better managing stroke and its related disabilities. The time has come to shift the attention in stroke care and research from prevention and cure to a greater focus and investment in the rehabilitation and quality of life of stroke survivors. The rebalancing of stroke care and research initiatives requires a reinvestment in rehabilitation and community reintegration of stroke survivors. KEYWORDS: acute care • prevention • rehabilitation • stroke
Globally, stroke is the second leading cause of death and is one of the costliest and most burdensome diseases [1–3]. In 2010, The Global Burden of Disease Study estimated that there were 16.9 million people who experienced a first ever stroke, 5.9 million stroke-related deaths, 33 million stroke survivors and 102 million disability-adjusted life-years lost [4]. Since 1990, there has been continued growth in the overall incidence, mortality, prevalence and disability of stroke [4]. In Canada alone, more than 50,000 people per year suffer a stroke [5] and more than 300,000 are living with the complications of stroke [6]. When taking into account both the direct and indirect costs (physician services, hospital costs, decreased productivity and lost wages), it is estimated that stroke costs the Canadian economy $3.6 billion annually [7]. Stroke is a life-altering event that often has a dramatic effect on stroke survivors, their families, health care resources and society at large. The effects are seen well beyond the initial acute and sub-acute phases of care. It is estimated that 36% of stroke survivors are left with a discernible disability 5 years post stroke [8], with as many as 42% of survivors still dependent for performing basic activities of daily living 6 years post stroke [9]. Caregivers of stroke survivors experience an increase
10.1586/14737175.2014.968130
in their physical demands [10] along with a decrease in health-related quality of life [11,12]. Furthermore, caregivers have a 2.5 times greater risk of experiencing psychological distress [13,14], with as many as 50% of chronic stroke patients reporting long-term symptoms of depression [15,16]. The impact of stroke on stroke survivors and their families is a critical topic in stroke management [17], whose impact over the long term is well recognized [18], but often underestimated. The overall burden and impact of stroke imposed on both individuals and society has proven to be the impetus for governments around the world to increasingly invest in stroke care. Organized stroke care is now the accepted ‘gold standard’ [19] and can be divided into the management of vascular pathology and the recovery from the consequences of neurological injury [18]. While both of these elements are important components of modern stroke care, there has been a greater focus on acute management of the vascular pathology (i.e., stroke prevention and thrombolysis) than on the rehabilitation and recovery of neurological deficits. Our objective is to argue for a rebalancing of stroke care where the primary focus is not on prevention and cure but places a greater emphasis on rehabilitation and community reintegration.
Ó 2014 Informa UK Ltd
ISSN 1473-7175
1307
Review
Teasell, Rice, Richardson et al.
Vascular care: prevention & acute care
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Stroke care has tended to focus on prevention & acute care
A stroke is often described as a ‘brain attack’, implying the need for urgent treatment much like a myocardial infarction. The increasing attention given to intravenous or endovascular ‘clot-busting’ drugs is built upon the concept of stroke as a catastrophic but potentially reversible event. A stroke strategy focused on prevention and cure implies that strokes are largely the result of inadequate risk factor management, poor lifestyle choices and/or failure to access ‘clot-busting’ drugs in a timely manner. In response, the majority of national stroke strategies have frontloaded stroke care with an emphasis on vascular care first and foremost through primary and secondary prevention strategies and thrombolysis. This strategy is based on the assumption that prevention efforts, and the use of thrombolytics acutely, will have the greatest potential for impact. Prevention
It is often reported that the majority of strokes are preventable [20], and that if all potential preventive strategies were maximized, the incident rate of heart attacks and strokes combined could be reduced by as much as 80% [21]. Hypertension is described as the single-most modifiable risk factor for stroke [22]. Other modifiable risk factors include medical conditions such as high cholesterol and Type 2 diabetes, as well as lifestyle factors such as smoking, alcohol consumption, physical activity and diet [20]. The promise of primary and secondary prevention activities has several challenges, such as behavioral compliance and conflicting evidence. Furthermore, even for well-established stroke risk factors, the evidence may not always be definitive. For example, while high cholesterol is frequently reported as a risk factor, epidemiological studies suggest there is no direct relationship between cholesterol blood levels and risk for stroke [23–25]. Nonetheless, there is evidence that lowering cholesterol with statins reduces the risk of stroke in high-risk patients, including those who have suffered a transient ischemic attack or stroke [23,26–28]. However, only 43% of adults with a history of cardiovascular disease take statins [29]. Likewise, diabetes has been found to increase the risk of stroke; however, intensive blood glucose management was not found to reduce the incidence of stroke [30–32]. These examples suggest that the relationship between risk factor management and prevention is complex, even when compliance is high. Despite the evidence for modifiable risk factor management, primary and secondary prevention activities face several challenges particularly regarding adherence to a healthy lifestyle. Obesity, for example, has been found to be associated with an increased risk of stroke [33]. Conceptually, weight loss or maintaining a healthy body mass index should reduce the risk for stroke; however, evidence is limited due to poor adherence to treatment regimens and weight-loss strategies, with only 5% adults participating in the recommended amount of physical activity to obtain health benefits [34]. It is also estimated that 1308
86% of stroke survivors’ time is spent being sedentary [35], with the majority of stroke survivors failing to meet the recommended exercise prescription or daily step counts for people living with a chronic illness or disability [36–38]. Acute care Thrombolysis
A promising development in the acute treatment for ischemic stroke has been tissue plasminogen activator (tPA) which acts to restore blood flow to the area of cerebral ischemia to prevent further neurological damage. tPA has been found to decrease mortality, shorten length of stay in hospital and improve disability status and discharge destination post stroke [39,40]. Up to 87% of strokes are ischemic; nevertheless, the restrictive inclusion criteria and short therapeutic window limit the use of tPA. There is strong evidence for tPA being effective when administrated between three and four and a half hours of stroke onset; however, the limit of the time frame is a contested issue [41,42]. It is believed that improvements in acute stroke services in order to optimize the use of tPA leads to improved patient outcomes and additional cost savings [43]. Currently, less than 10% of patients with stroke are treated within the allotted time frame [43] and, of these approximately 20–30% will benefit with improved outcomes [44]. These factors highlight that thrombolytics currently improve the outcomes of up to 2% of all strokes based on the percentage of patients who benefit (demonstrate little to no disability at 3 months), despite extensive resources spent on research and clinical delivery. Neuroprotectants
Given that strokes still occur, there has been a great deal of interest and research into neuroprotectants. Similar to thrombolytics, neuroprotectants are heavily time dependent, requiring the existence of a salvageable penumbra [45]. They are designed to restore neurological function in the brain and have been cited as a potential acute care intervention that reduces morbidity and mortality of individuals experiencing a stroke. Despite promising outcomes in animal trials, between 100 [46] and 200 [45] human clinical trials involving neuroprotectants have failed to report a benefit in clinical outcomes. In response to these unfavorable results, it has been suggested that research of neuroprotectants has not being conducted in a way that has allowed for a true evaluation of their usefulness [47]. In an effort to improve the translation of research from pre-clinical to clinical testing, a set of recommendations/guidelines was created by the Stair Therapy Academic Round Table (STAIR). Compliance with these guidelines has not been found to improve clinical outcomes [48]; however, this remains an active area of research. The growing burden of stroke
Developing countries have experienced a 100% increase in the incidence of stroke attributed to rapidly changing lifestyles [20,49]. Despite a recently reported 40% reduction in age-adjusted stroke incidence in developed countries, the overall burden of Expert Rev. Neurother. 14(11), (2014)
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
The next revolution in stroke care
stroke is expected to continue to rise with an aging population and a global rise in obesity, diabetes and smoking rates [50,51]. The limitations of prevention efforts and reversal type drugs in the acute phase are well known, yet it is frequently argued that a successful stroke system is one that is geared toward treating stroke as a ‘brain attack’. Given that patients who are seen early after stroke onset (including those not treated within the tPA window) are more likely to survive their strokes, there may be some truth to this assertion. For example, in 2000 the Ontario Stroke System was established, focusing primarily on thrombolysis and secondary prevention of stroke. In-hospital mortality in Ontario decreased from 14.4 to 11.4% between the years 2003 and 2010 [52]. As a result, based on 2003 rates, by 2010, 465 more patients survived their stroke than would have been expected. While this more aggressive approach to prevention and cure has led to an overall reduction in mortality following a stroke, there were more stroke survivors, many of whom had neurological disabilities. As stated earlier, these stroke survivors with disabilities tend to experience significant personal hardships and often become a lifelong, substantial burden on the health care system, long after the 3 to 7 days spent in acute care. Preventive measures and thrombolysis have not been enough to counter the effects of aging on the prevalence of stroke in developed countries, let alone in developing countries where stroke is becoming a serious public health concern. The harsh reality is that focusing on stroke as a consequence of inadequate risk factor management, poor lifestyle choices or failure to access clot-busting drugs quickly enough will not change the clinical trajectory for the majority of stroke victims who are faced with the prospect of having to live with often significant physical and cognitive disabilities. Recovery from neurological damage
Therapeutic efforts to facilitate recovery from neurological damage consist largely of stroke rehabilitation. Selective serotonin reuptake inhibitors (SSRIs) and monaminergic drugs are other therapies that have been found to improve neurological outcomes as a secondary finding to the traditional use of the drugs; however, evidence is limited and a more widely researched approach to neurological recovery has been stem cell therapy. Stem cells
Stem cells are a relatively untested but intriguing therapy envisioned to alter stroke sequelae at the neurological level by promoting regeneration of damaged areas of the brain [53]. There has been a tremendous growth in stem cell research since 2010; [54]; however, the mechanisms of action remain poorly understood [55] and study quality may be a concern [56]. Stem cell therapies may yet prove to be a viable treatment option, but even then it will likely be decades before they can be applied clinically [55], to improve patient outcomes and the adjunctive therapies needed to optimize stem cell efficacy still need to be identified. Most notably, it is becoming apparent informahealthcare.com
Review
that stem cell therapies would require a concurrent rehabilitation program for potential benefits to be fully realized. Stroke rehabilitation The growing evidence for stroke rehabilitation
Stroke rehabilitation is designed to maximize the stroke survivor’s functional independence through careful coordination of the efforts of a specialized interdisciplinary rehabilitation team or program. There are over 1200 randomized controlled trials (RCTs) examining interventions utilized in rehabilitation of stroke patients, excluding secondary prevention interventions [57]. The extent of this evidence and the concepts of neuroplasticity and brain reorganization have largely erased notions that rehabilitation gains are due to spontaneous recovery alone. Whereas some recovery of stroke deficits takes place naturally in the first few months following stroke, evidence has established rehabilitation therapy enhances and extends recovery. Stroke rehabilitation is, by its very nature, complex and multidisciplinary; an individualized series of interventions delivered to a population with widely differing premorbid conditions, stroke causes, impairments, levels of disability and goals. Some interventions have stronger evidence and appear to be more efficacious at addressing specific types of impairments and disabilities. Stroke units
The Stroke Unit Trialist Collaboration (SUTC) characterizes a stroke unit as the presence of a hospital-based, multidisciplinary, stroke-specific, management team [58]. In their updated 2013 Cochrane review, the authors confirmed previous findings regarding the effectiveness of stroke units in improving patient outcomes and decreasing mortality [58]. Interestingly, it has long been accepted that these improved patient outcomes are a result of a more timely, intense and coordinated rehabilitation program [56]. Stroke rehabilitation units, where an interdisciplinary rehabilitation team conducts specialized stroke care, has been widely studied [59]. In contrast to more general rehabilitation units, these specialized units have been shown to reduce disability by as much as 48% for moderate-to-severe strokes [60]. It is not entirely clear what factors contribute to the effectiveness of stroke units; however, it has been suggested that the presence of an interdisciplinary team, stroke-specialized clinicians and the availability of diagnostic procedures are important [61]. It has been noted that medically stable individuals following a stroke should be transferred to a rehabilitation facility offering rehabilitation clinicians and pathways dedicated solely to stroke [62]. Early, intensive, task-specific therapy
There is no clear consensus on the optimal time to start rehabilitation following a stroke, as the majority of rehabilitation research has taken place in the post-acute phase of care. Research based on animal models shows that early on following a stroke (2 to 5 weeks post), the brain demonstrates a heightened sensitivity, or is ‘primed’, for maximal response to 1309
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Review
Teasell, Rice, Richardson et al.
rehabilitation therapies; such that delays getting into rehabilitation are detrimental to recovery [63]. A number of studies conducted in acute care patient populations have demonstrated clinical associations between early admission to rehabilitation (75 years of age. Stroke 2003;34(10):2440-4 Hurford R, Charidimou A, Fox Z, et al. Domain-specific trends in cognitive impairment after acute ischaemic stroke. J Neurol 2013;260(1):237-41 Brady MC, Kelly H, Godwin J, Enderby P. Speech and language therapy for aphasia following stroke. Cochrane Database Syst Rev 2012;5:Cd000425
84.
Diamond PT, Holroyd S, Macciocchi SN, Felsenthal G. Prevalence of depression and outcome on the geriatric rehabilitation unit. Am J Phys Med Rehabil 1995;74(3):214-17
85.
Van De Weg FB, Kuik DJ, Lankhorst GJ. Post-stroke depression and functional outcome: a cohort study investigating the influence of depression on functional recovery from stroke. Clin Rehabil 1999; 13(3):268-72
86.
87.
Gainotti G, Antonucci G, Marra C, Paolucci S. Relation between depression after stroke, antidepressant therapy, and functional recovery. J Neurol Neurosurg Psychiatry 2001;71(2):258-61 Mead GE, Hsieh CF, Lee R, et al. Selective serotonin reuptake inhibitors for stroke recovery: a systematic review and meta-analysis. Stroke 2013;44(3):844-50
88.
Teasell R, et al. Stroke: more than a ‘brain attack’. Int J Stroke 2014;9(2):188-90
89.
Korner-Bitensky N. When does stroke rehabilitation end? Int J Stroke 2013;8(1): 8-10
••
This opinion piece provides a background of the evidence relating to stroke rehabilitation and suggestions of how to move forward with providing rehabilitation to both patients and their families.
90.
Page SJ, Sisto S, Levine P, McGrath RE. Efficacy of modified constraint-induced movement therapy in chronic stroke: a single-blinded randomized controlled trial. Arch Phys Med Rehabil 2004;85(1):14-18
91.
Lee MJ, Kilbreath SL, Singh MF. Comparison of effect of aerobic cycle training and progressive resistance training on walking ability after stroke: a randomized sham exercise-controlled study. J Am Geriatr Soc 2008;56(6):976-85
92.
Chu KS, Eng JJ, Dawson AS, et al. Water-based exercise for cardiovascular fitness in people with chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil 2004;85(6):870-4
93.
Pang MY, Eng JJ, Dawson AS, et al. A community-based fitness and mobility exercise program for older adults with chronic stroke: a randomized, controlled trial. J Am Geriatr Soc 2005;53(10):1667-74
94.
Wolf SL, Thompson PA, Winstein CJ, et al. The EXCITE stroke trial: comparing early and delayed constraint-induced movement therapy. Stroke 2010;41(10):2309-15
95.
Wu CY, Chuang LL, Lin KC, et al. Randomized trial of distributed constraint-induced therapy versus bilateral arm training for the rehabilitation of upper-limb motor control and function after stroke. Neurorehabil Neural Repair 2011; 25(2):130-9
96.
Meinzer M, Streiftau S, Rockstroh B. Intensive language training in the rehabilitation of chronic aphasia: efficient training by laypersons. J Int Neuropsychol Soc 2007;13(5):846-53
97.
Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science 1996;272(5269):1791-4
98.
Dobkin BH, Dorsch A. New evidence for therapies in stroke rehabilitation. Curr Atheroscler Rep 2013;15(6):331
99.
Canadian Stroke Network. The quality of stroke care in Canada. 2011
100.
Gilligan AK, Thrift AG, Sturm JW, et al. Stroke units, tissue plasminogen activator, aspirin and neuroprotection: which stroke intervention could provide the greatest community benefit? Cerebrovascular Diseases 2005;20(4):239-44
101.
Donnan GA, Howells DW, Markus R, et al. Can the time window for administration of thrombolytics in stroke be increased? CNS Drugs 2003;17(14):995-1011
102.
Saposnik G, Johnston SC, Raptis S, et al. Stroke journal: what is being published to advance the field? Stroke 2013;44(9):2644-9
Expert Rev. Neurother. 14(11), (2014)
The next revolution in stroke care Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Expert Rev. Neurother. 14(11), 1307–1314 (2014)
Robert Teasell*1–3, Danielle Rice1, Marina Richardson1, Nerissa Campbell1, Mona Madady1, Norhayati Hussein4, Manuel MurieFernandez5 and Stephen Page6 1 Lawson Health Research Institute, St. Joseph’s Health Care, 801 Commissioners Road East London, Ontario, N6C 5J1, Canada 2 Parkwood Hospital, St. Joseph’s Health Care, 801 Commissioners Road East London, Ontario, N6C 5J1, Canada 3 Department of Physical Medicine and Rehabilitation, Western University, 1151 Richmond St, London, Ontario, N6A 3K6, Canada 4 Department of Rehabilitation Medicine, Cheras Rehabilitation Hospital, Jalan Yaacob Latif, 56000, Kuala Lumpur, Malaysia 5 Department of Neurology, Clinica Universidad de Navarra, Pamplona, Navarra, Spain 6 The Ohio State University Medical Center, 453 W Tenth Avenue, Suite 406, Columbus, OH 43210, USA *Author for correspondence: Tel.: +1 519 685 4292; extn. 44559 Fax: +1 519 685 4023 [email protected]
informahealthcare.com
Stroke is the second leading cause of death and disability worldwide. Initiatives to decrease the burden of stroke have largely focused on prevention and acute care strategies. Despite considerable resources and attention, the focus on prevention and acute care has not been successful in changing the clinical trajectory for the majority of stroke patients. While efforts to prevent strokes will continue to have an impact, the total burden of stroke will increase due to the aging population and decreased mortality rates. There is strong evidence for the effectiveness of rehabilitation in better managing stroke and its related disabilities. The time has come to shift the attention in stroke care and research from prevention and cure to a greater focus and investment in the rehabilitation and quality of life of stroke survivors. The rebalancing of stroke care and research initiatives requires a reinvestment in rehabilitation and community reintegration of stroke survivors. KEYWORDS: acute care • prevention • rehabilitation • stroke
Globally, stroke is the second leading cause of death and is one of the costliest and most burdensome diseases [1–3]. In 2010, The Global Burden of Disease Study estimated that there were 16.9 million people who experienced a first ever stroke, 5.9 million stroke-related deaths, 33 million stroke survivors and 102 million disability-adjusted life-years lost [4]. Since 1990, there has been continued growth in the overall incidence, mortality, prevalence and disability of stroke [4]. In Canada alone, more than 50,000 people per year suffer a stroke [5] and more than 300,000 are living with the complications of stroke [6]. When taking into account both the direct and indirect costs (physician services, hospital costs, decreased productivity and lost wages), it is estimated that stroke costs the Canadian economy $3.6 billion annually [7]. Stroke is a life-altering event that often has a dramatic effect on stroke survivors, their families, health care resources and society at large. The effects are seen well beyond the initial acute and sub-acute phases of care. It is estimated that 36% of stroke survivors are left with a discernible disability 5 years post stroke [8], with as many as 42% of survivors still dependent for performing basic activities of daily living 6 years post stroke [9]. Caregivers of stroke survivors experience an increase
10.1586/14737175.2014.968130
in their physical demands [10] along with a decrease in health-related quality of life [11,12]. Furthermore, caregivers have a 2.5 times greater risk of experiencing psychological distress [13,14], with as many as 50% of chronic stroke patients reporting long-term symptoms of depression [15,16]. The impact of stroke on stroke survivors and their families is a critical topic in stroke management [17], whose impact over the long term is well recognized [18], but often underestimated. The overall burden and impact of stroke imposed on both individuals and society has proven to be the impetus for governments around the world to increasingly invest in stroke care. Organized stroke care is now the accepted ‘gold standard’ [19] and can be divided into the management of vascular pathology and the recovery from the consequences of neurological injury [18]. While both of these elements are important components of modern stroke care, there has been a greater focus on acute management of the vascular pathology (i.e., stroke prevention and thrombolysis) than on the rehabilitation and recovery of neurological deficits. Our objective is to argue for a rebalancing of stroke care where the primary focus is not on prevention and cure but places a greater emphasis on rehabilitation and community reintegration.
Ó 2014 Informa UK Ltd
ISSN 1473-7175
1307
Review
Teasell, Rice, Richardson et al.
Vascular care: prevention & acute care
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Stroke care has tended to focus on prevention & acute care
A stroke is often described as a ‘brain attack’, implying the need for urgent treatment much like a myocardial infarction. The increasing attention given to intravenous or endovascular ‘clot-busting’ drugs is built upon the concept of stroke as a catastrophic but potentially reversible event. A stroke strategy focused on prevention and cure implies that strokes are largely the result of inadequate risk factor management, poor lifestyle choices and/or failure to access ‘clot-busting’ drugs in a timely manner. In response, the majority of national stroke strategies have frontloaded stroke care with an emphasis on vascular care first and foremost through primary and secondary prevention strategies and thrombolysis. This strategy is based on the assumption that prevention efforts, and the use of thrombolytics acutely, will have the greatest potential for impact. Prevention
It is often reported that the majority of strokes are preventable [20], and that if all potential preventive strategies were maximized, the incident rate of heart attacks and strokes combined could be reduced by as much as 80% [21]. Hypertension is described as the single-most modifiable risk factor for stroke [22]. Other modifiable risk factors include medical conditions such as high cholesterol and Type 2 diabetes, as well as lifestyle factors such as smoking, alcohol consumption, physical activity and diet [20]. The promise of primary and secondary prevention activities has several challenges, such as behavioral compliance and conflicting evidence. Furthermore, even for well-established stroke risk factors, the evidence may not always be definitive. For example, while high cholesterol is frequently reported as a risk factor, epidemiological studies suggest there is no direct relationship between cholesterol blood levels and risk for stroke [23–25]. Nonetheless, there is evidence that lowering cholesterol with statins reduces the risk of stroke in high-risk patients, including those who have suffered a transient ischemic attack or stroke [23,26–28]. However, only 43% of adults with a history of cardiovascular disease take statins [29]. Likewise, diabetes has been found to increase the risk of stroke; however, intensive blood glucose management was not found to reduce the incidence of stroke [30–32]. These examples suggest that the relationship between risk factor management and prevention is complex, even when compliance is high. Despite the evidence for modifiable risk factor management, primary and secondary prevention activities face several challenges particularly regarding adherence to a healthy lifestyle. Obesity, for example, has been found to be associated with an increased risk of stroke [33]. Conceptually, weight loss or maintaining a healthy body mass index should reduce the risk for stroke; however, evidence is limited due to poor adherence to treatment regimens and weight-loss strategies, with only 5% adults participating in the recommended amount of physical activity to obtain health benefits [34]. It is also estimated that 1308
86% of stroke survivors’ time is spent being sedentary [35], with the majority of stroke survivors failing to meet the recommended exercise prescription or daily step counts for people living with a chronic illness or disability [36–38]. Acute care Thrombolysis
A promising development in the acute treatment for ischemic stroke has been tissue plasminogen activator (tPA) which acts to restore blood flow to the area of cerebral ischemia to prevent further neurological damage. tPA has been found to decrease mortality, shorten length of stay in hospital and improve disability status and discharge destination post stroke [39,40]. Up to 87% of strokes are ischemic; nevertheless, the restrictive inclusion criteria and short therapeutic window limit the use of tPA. There is strong evidence for tPA being effective when administrated between three and four and a half hours of stroke onset; however, the limit of the time frame is a contested issue [41,42]. It is believed that improvements in acute stroke services in order to optimize the use of tPA leads to improved patient outcomes and additional cost savings [43]. Currently, less than 10% of patients with stroke are treated within the allotted time frame [43] and, of these approximately 20–30% will benefit with improved outcomes [44]. These factors highlight that thrombolytics currently improve the outcomes of up to 2% of all strokes based on the percentage of patients who benefit (demonstrate little to no disability at 3 months), despite extensive resources spent on research and clinical delivery. Neuroprotectants
Given that strokes still occur, there has been a great deal of interest and research into neuroprotectants. Similar to thrombolytics, neuroprotectants are heavily time dependent, requiring the existence of a salvageable penumbra [45]. They are designed to restore neurological function in the brain and have been cited as a potential acute care intervention that reduces morbidity and mortality of individuals experiencing a stroke. Despite promising outcomes in animal trials, between 100 [46] and 200 [45] human clinical trials involving neuroprotectants have failed to report a benefit in clinical outcomes. In response to these unfavorable results, it has been suggested that research of neuroprotectants has not being conducted in a way that has allowed for a true evaluation of their usefulness [47]. In an effort to improve the translation of research from pre-clinical to clinical testing, a set of recommendations/guidelines was created by the Stair Therapy Academic Round Table (STAIR). Compliance with these guidelines has not been found to improve clinical outcomes [48]; however, this remains an active area of research. The growing burden of stroke
Developing countries have experienced a 100% increase in the incidence of stroke attributed to rapidly changing lifestyles [20,49]. Despite a recently reported 40% reduction in age-adjusted stroke incidence in developed countries, the overall burden of Expert Rev. Neurother. 14(11), (2014)
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
The next revolution in stroke care
stroke is expected to continue to rise with an aging population and a global rise in obesity, diabetes and smoking rates [50,51]. The limitations of prevention efforts and reversal type drugs in the acute phase are well known, yet it is frequently argued that a successful stroke system is one that is geared toward treating stroke as a ‘brain attack’. Given that patients who are seen early after stroke onset (including those not treated within the tPA window) are more likely to survive their strokes, there may be some truth to this assertion. For example, in 2000 the Ontario Stroke System was established, focusing primarily on thrombolysis and secondary prevention of stroke. In-hospital mortality in Ontario decreased from 14.4 to 11.4% between the years 2003 and 2010 [52]. As a result, based on 2003 rates, by 2010, 465 more patients survived their stroke than would have been expected. While this more aggressive approach to prevention and cure has led to an overall reduction in mortality following a stroke, there were more stroke survivors, many of whom had neurological disabilities. As stated earlier, these stroke survivors with disabilities tend to experience significant personal hardships and often become a lifelong, substantial burden on the health care system, long after the 3 to 7 days spent in acute care. Preventive measures and thrombolysis have not been enough to counter the effects of aging on the prevalence of stroke in developed countries, let alone in developing countries where stroke is becoming a serious public health concern. The harsh reality is that focusing on stroke as a consequence of inadequate risk factor management, poor lifestyle choices or failure to access clot-busting drugs quickly enough will not change the clinical trajectory for the majority of stroke victims who are faced with the prospect of having to live with often significant physical and cognitive disabilities. Recovery from neurological damage
Therapeutic efforts to facilitate recovery from neurological damage consist largely of stroke rehabilitation. Selective serotonin reuptake inhibitors (SSRIs) and monaminergic drugs are other therapies that have been found to improve neurological outcomes as a secondary finding to the traditional use of the drugs; however, evidence is limited and a more widely researched approach to neurological recovery has been stem cell therapy. Stem cells
Stem cells are a relatively untested but intriguing therapy envisioned to alter stroke sequelae at the neurological level by promoting regeneration of damaged areas of the brain [53]. There has been a tremendous growth in stem cell research since 2010; [54]; however, the mechanisms of action remain poorly understood [55] and study quality may be a concern [56]. Stem cell therapies may yet prove to be a viable treatment option, but even then it will likely be decades before they can be applied clinically [55], to improve patient outcomes and the adjunctive therapies needed to optimize stem cell efficacy still need to be identified. Most notably, it is becoming apparent informahealthcare.com
Review
that stem cell therapies would require a concurrent rehabilitation program for potential benefits to be fully realized. Stroke rehabilitation The growing evidence for stroke rehabilitation
Stroke rehabilitation is designed to maximize the stroke survivor’s functional independence through careful coordination of the efforts of a specialized interdisciplinary rehabilitation team or program. There are over 1200 randomized controlled trials (RCTs) examining interventions utilized in rehabilitation of stroke patients, excluding secondary prevention interventions [57]. The extent of this evidence and the concepts of neuroplasticity and brain reorganization have largely erased notions that rehabilitation gains are due to spontaneous recovery alone. Whereas some recovery of stroke deficits takes place naturally in the first few months following stroke, evidence has established rehabilitation therapy enhances and extends recovery. Stroke rehabilitation is, by its very nature, complex and multidisciplinary; an individualized series of interventions delivered to a population with widely differing premorbid conditions, stroke causes, impairments, levels of disability and goals. Some interventions have stronger evidence and appear to be more efficacious at addressing specific types of impairments and disabilities. Stroke units
The Stroke Unit Trialist Collaboration (SUTC) characterizes a stroke unit as the presence of a hospital-based, multidisciplinary, stroke-specific, management team [58]. In their updated 2013 Cochrane review, the authors confirmed previous findings regarding the effectiveness of stroke units in improving patient outcomes and decreasing mortality [58]. Interestingly, it has long been accepted that these improved patient outcomes are a result of a more timely, intense and coordinated rehabilitation program [56]. Stroke rehabilitation units, where an interdisciplinary rehabilitation team conducts specialized stroke care, has been widely studied [59]. In contrast to more general rehabilitation units, these specialized units have been shown to reduce disability by as much as 48% for moderate-to-severe strokes [60]. It is not entirely clear what factors contribute to the effectiveness of stroke units; however, it has been suggested that the presence of an interdisciplinary team, stroke-specialized clinicians and the availability of diagnostic procedures are important [61]. It has been noted that medically stable individuals following a stroke should be transferred to a rehabilitation facility offering rehabilitation clinicians and pathways dedicated solely to stroke [62]. Early, intensive, task-specific therapy
There is no clear consensus on the optimal time to start rehabilitation following a stroke, as the majority of rehabilitation research has taken place in the post-acute phase of care. Research based on animal models shows that early on following a stroke (2 to 5 weeks post), the brain demonstrates a heightened sensitivity, or is ‘primed’, for maximal response to 1309
Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by Korea University on 12/27/14 For personal use only.
Review
Teasell, Rice, Richardson et al.
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This opinion piece provides a background of the evidence relating to stroke rehabilitation and suggestions of how to move forward with providing rehabilitation to both patients and their families.
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Expert Rev. Neurother. 14(11), (2014)
