Modifiable risk factors in asymptomatic patients

Hypertension is the most important risk factor . Subjects with blood pressure less than 120/80 mm Hg have approximately half the lifetime risk of stroke compared with subjects with hypertension . The degree of risk increases with higher levels of pressure and becomes particularly strong with levels higher than 160/95 mm Hg . The choice of antihypertensive agent should be individualized to each patient’s characteristics and comorbidities . There is a high risk of stroke in hypertensive patients with carotid stenosis . Based on Joint National Commission 7 guidelines, patients who have hypertension at baseline in most cases should be treated; a goal of less than 130/80 mm Hg is targeted as reasonable for most patients.

Heart disease is another important risk factor for stroke. The risk of stroke doubles in individuals who have coronary artery disease . Coronary artery disease accounts for the majority of subsequent deaths among stroke survivors. In patients with chronic, stable atrial fibrillation, the risk of stroke increases fivefold . When atrial fibrillation is a manifestation of rheumatic heart disease, the risk of embolic stroke becomes 17-fold greater than normal. Prevention of embolic stroke in these patients is best achieved with long-term anticoagulation. Treatment does carry the danger of intracranial hemorrhage, especially in elderly individuals and persons with impaired balance who are more likely to fall. When the risk of hemorrhage seems to be high; 325 mg of aspirin may be used as an alternative to warfarin. Overall, aspirin is much less effective than warfarin in preventing embolism .

Diabetes as an independent risk factor doubles the risk of stroke. Unfortunately, strict glycemic control reduces the risk of microvascular complications such as retinopathy, nephropathy, and neuropathy but does not seem to slow the progression of cerebral vascular disease. The recommended goal for hemoglobin A1c is less than 7%. Rigorous control of blood pressure and lipids is particularly important for patients with diabetes . Smoking has been shown to increase the risk for all stroke subtypes. The relative risk of stroke in heavy smokers (>40 cigarettes per day) is twice that of light smokers (<10 cigarettes per day). There are no randomized controlled trials of smoking cessation for stroke prevention. The risk for stroke associated with smoking decreases significantly 2 years after cigarette cessation and is at the level of nonsmokers by 5 years .

Hyperlipidemia is a risk factor for coronary artery disease. The relationship between serum cholesterol in stroke incidence seems to be more complex, however, because cholesterol is an established risk factor in atherosclerosis but seems to be only a weak risk factor for ischemic stroke . For patients with transient ischemic attack (TIA), ischemic stroke of atherosclerotic origin, or asymptomatic atherosclerotic cerebral vascular disease who have a baseline low density lipoprotein (LDL) more than 100 mg/dL, statin therapy is recommended . Lipid lowering by other means, such as fibrates, resins, and diets, does not have an impact on stroke incidence .

Elevated serum levels of homocystine are associated with premature atherosclerosis, which causes stroke, myocardial infarction, and peripheral vascular disease earlier in life . Homocystinemia can be treated with daily high-dose vitamin therapy, including vitamin B6 (pyridoxine) and folic acid. There is no guarantee this treatment reduces the risk of a recurrent stroke, however . Elevated fibrinogen levels correlate with higher risk of stroke, and fibrinogen levels are higher in individuals who smoke and have a high cholesterol diet .

Risk factors in symptomatic patients

Patients admitted to rehabilitation are at risk for a recurrent stroke. The probability of stroke recurrence is highest in the postacute period. For survivors of the initial stroke, the annual risk of a second stroke is approximately 5%, with a 5-year accumulative rate for recurrence at approximately 25% . Risk factors for initial stroke also increase the risk for a recurrent stroke . TIAs and minor stroke are important warning signals of impending completed stroke. Four percent to 8% of patients with TIAs develop a completed stroke, and the risk is 30% within the next 5 years . Patients with a TIA should receive prophylaxis against a completed stroke. The most widely accepted intervention is an antiplatelet drug, such as aspirin. Several trials have reported a reduced incidence of 20% to 25% using low- to high-dose daily aspirin. Currently, low-dose or regular strength aspirin should be recommended .

Ticlopidine is an antiplatelet drug with a different action from aspirin. The Ticlopidine-Aspirin Study confirmed that ticlopidine has a more beneficial effect on stroke risk reduction over aspirin . It is expensive, however, and has side effects of diarrhea and neutropenia, which may diminish its value when compared with aspirin. Clopidogrel is another antiplatelet agent similar to ticlopidine. In clinical trials (CAPRIE), clopidogrel’s efficacy in preventing stroke is slightly 7% better than aspirin alone and it has fewer side effects . Another agent, dipyridamole, is approximately as effective as aspirin when taken alone, but it has an added benefit for prophylaxis when taken with aspirin . In a large clinical European trial (ESPS-2), anticoagulation was not recommended in the treatment of TIAs unless a patient had a major cardiac source of potential embolism .

Carotid endarterectomy has reduced the risk of stroke in patients with single or multiple TIAs and 70% or more stenosis of the ipsilateral internal carotid artery . Patients with stenosis of 50% to 70% do not have a hemodynamically significant lesion but may be considered for surgery if symptomatic. Carotid endarterectomy has not been proved superior to medical treatment in asymptomatic patients, but mortality rates between the two groups were similar .

Women and risk for stroke

The risk of ischemic stroke or intracerebral hemorrhage stroke during pregnancy in the first 6 weeks postpartum was 2.4 times greater than for nonpregnant women of similar age and race according to the Baltimore-Washington cooperative stroke study . Clinical trial data indicated that estrogen plus progesterone and estrogen alone increased stroke risks in postmenopausal women, including generally healthy women, and do not provide protection for women with established heart disease .

Physical activity and stroke prevention

Physical activity reduces stroke risk. The Harvard Alumni Study showed a decrease in total stroke risk in men who were highly physically active . Physical activity from sports, during leisure time, or at work was related to a reduced risk of ischemic stroke . The Northern Manhattan Study, which included white, African American, and Hispanic men and women in an urban setting, showed a decrease in ischemic stroke risk associated with physical activity levels across all racial, ethnic, gender, and age groups .

Rehabilitation strategies

The importance of activity after neurologic injury having therapeutic properties is an essential component of rehabilitation. Most activity in the rehabilitation gym focuses on teaching compensatory skills to foster independence in activities of daily living (ADLs). Several methods are currently used to facilitate movement in the affected extremity and teach compensatory techniques to perform ADLs. Rehabilitation principles center on improving range of motion, increasing strength in the affected extremity, and teaching compensatory strategies and mobility for ADLs. Some theories involve the facilitation of mass movements. They emphasize the use and training of the affected side rather than compensatory strategies. Neurodevelopmental training inhibits abnormal muscle patterns and encourages normal patterns to facilitate automatic, volitional movements . Proprioceptive neuromuscular facilitation evokes responses through manual stimuli to increase the ease of movement promoting function. Abnormal movement is not discouraged . The Brunnstrom theory enhances specific synergy patterns through the use of cutaneous or proprioceptive stimuli that ultimately translate into volitional movement outside of synergy patterns . Other theories involve the facilitation of isolated movement. Muscle tone and voluntary motor activity sometimes can be modified using sensory stimulation. Biofeedback is used to modify autonomic function, pain, and motor disturbances using volitional control auditory, visual, and sensory cues .

When compared, there is no superior solitary treatment method . Other applications of motor learning theory stress structured practice of goal-oriented tasks with specific feedback patterns for the successful transfer and retention of a new skill . Because of impairments in motor or sensory systems, transfers, ADLs, and ambulation become new skills that must be taught and performed in different ways. Another application of motor learning therapy is partial weight support treadmill training. A patient is able to ambulate in a harness system that decreases the amount of weight bearing required to ambulate. After 6 weeks of training in a randomized, controlled trial, the body weight support subjects scored higher in functional balance, motor recovering, over-ground walking speed, and endurance. At 3 months’ follow-up, however, the body weight support subjects continued to have higher scores in motor recovery and over-ground walking speed but not in over-ground walking endurance . It is not clear if partial weight-supported ambulation is able to decrease the length of stay for inpatient rehabilitation.

Ironically, the belief that more intensive therapy is always better may not hold true. The possibility of too much activity too soon after injury could increase brain pathology . Some researchers have raised concerns about mass practice in the first few days after stroke after an experimental finding in rats demonstrated that more neurons may be damaged or the size of the infarct may increase by early overuse of a paretic limb . The level of exercise of a rat running on a rotating wheel is much greater than what a patient could possibly experience during therapy, however. Could the wrong type of activity be deleterious ? We actually may foster a “learned nonuse” by teaching compensatory rather than restorative techniques. There is merit to forced use of the impaired arm and it reinforces long-term use of the upper extremity in ADLs. The constraint-induced (CI) therapy experiment directly supports this concept of “learned nonuse.” Primates whose unaffected arm was restrained until intrinsic recovery occurred showed full use of the now-recovered limb once restraint was removed .

In addition to timing, there is concern about therapy intensity. Current treatment practices focus on the goals of returning a patient to independence as soon as possible and mitigating the effects of injury and its sequelae, such as spasticity. The current paradigm may need to be challenged. We deliver certain amounts of therapy based on time allotted. Maybe inpatient rehabilitation should offer 4 or 5 hours of therapy per day as a patient gets closer to discharge. Little rigorous evidence supports many of the traditional therapy approach models . Fortunately, many of the newer “restorative” treatments are more rigorous in their study design and may answer tough questions on best practice. For example, studies have compared different therapy protocols for CI therapies and skilled versus unskilled task practice. A new large, retrospective study supports the conclusion that conventional therapy has a significant dosage effect that may influence the current paradigm of acute rehabilitation. For example, in a study of outcomes at 70 skilled nursing facilities, an increased intensity of physical therapy and occupational therapy resulted in increased ADL ability and decreased length of stay . In two retrospective studies of high- and low-intensity rehabilitation settings, functional gains were significantly related to therapy intensity in rehabilitation duration, but effects were considered small . Exercise type also may play a role in rehabilitation. A program of progressive resistance training 1 year after stroke may improve strength of the affected limbs and motor function and balance .

Strength training

Strength training (eg, maximal effort, resistance exercise) has benefits at the muscular and neuromuscular levels. Improved recruitment is responsible for torque output within the first 6 weeks of strength training in deconditioned limbs. Muscle hypertrophy eventually follows. Neuroadaptation has been reported after strength training in patients with all types of muscular disorders After approximately 4 to 6 weeks of strength training, muscular adaptations produce additional gains in peak torque. The belief that excessive effort exacerbates hypertonia has prevented widespread use of strength training in persons with poststroke hemiparesis . This belief has not been confirmed in studies. Although it is clear that some muscle groups respond to strengthening programs, research has not documented clearly that they improve functional outcomes .

Fitness training

Fitness often declines in disabled persons, but trials show gains with progressive aerobic exercises (eg, walking on a treadmill 3 days a week) that are tailored to each patient’s tolerance. Benefits are seen even when the exercise is initiated years after a stroke . Despite consensus that stroke leads to profound cardiovascular deconditioning, the underlying principle has not been concluded. The disability of stroke is widely attributed to brain injury alone, and the diminished cardiovascular fitness is speculated to be caused by reduced central neural drive. There are, however, several major peripheral changes in skeletal muscle that could propagate disability and contribute to low fitness levels, including gross muscular atrophy and associated insulin resistance . One study detailed a home-based exercise intervention model to improve fitness. The program consisted of 36 sessions of 90 minutes’ duration over 12 to 14 weeks. Subjects in the usual-care group had services as prescribed by their physicians. All sessions for the exercise group were supervised by a physical or occupational therapist at home. Components of the program were range of motion and flexibility, strengthening, balance, upper-extremity functional use, and endurance training (eg, riding a stationary bike for 30 minutes). The intervention and usual-care groups improved in strength, balance, upper- and lower-extremity motor control, upper-extremity function, and gait velocity. Gains for the intervention group exceeded those in the usual-care group in balance, endurance, peak aerobic capacity, and mobility. The study demonstrated the practical used of home-based interventions compared with the more frequently applied hospital-based intervention programs for improving fitness and function after stroke . Another study looked at water-based exercise that lasted 12 weeks. Individuals in the experimental group exercised in a swimming pool for 1 hour, three times per week. The patients progressed to 30 minutes of water aerobics at 80% heart rate reserve, with the remainder of the time devoted to stretching, warm-up, and cooling down. The study size was limited but showed promising results, with the greatest relative gains in peak aerobic capacity (23% in the experimental group), perhaps arguing for strong consideration of this form of intervention for stroke survivors .

Constraint-induced therapy

Behavioral research with deafferented primates led to the development of CI therapy for humans with impaired upper limbs after stroke. The CI therapy protocol involves promoting use of the more affected upper extremity for a target of 90% of the waking hours by constraining the less affected extremity with a padded mitt for 2 to 3 consecutive weeks to prevent use of the hand for compensation during ADLs. The patients received a type of task practice from therapists—termed “shaping”—for many hours per day. CI therapy was effective for improving movement ability in chronic stroke subjects who met minimal motor criteria of at least 20° extension at the wrist and at least 10° extension at the finger joint. A patient cannot be at a risk for falls because the more functional arm is restrained .

A recent placebo-controlled study showed that the gains from CI therapy are not associated with the amount of therapist attention and so must be the result of the activity of the training . The automated delivery of CI was just as effective as one-on-one therapist training . Skeptics argue that traditional training methods currently used by therapists may be just as effective if delivered at the higher doses that match CI therapy . That argument may be flawed because a comprehensive study that involved 66 chronic stroke subjects reported that the CI therapy group performed statistically better than a group of subjects who received an equal dose of neurodevelopmental technique with the arm movement scale . They found that the CI therapy group outperformed a traditional therapy group during acute rehabilitation on an arm impairment scale, with the largest difference in the pinch subscale . Another study also found advantages in a modified form of CI therapy than traditional therapy in patients who have chronic stroke . Elderly patients found similar benefits with modified CI therapy, and the study demonstrated substantial improvement in the abnormal movement patterns and reversed impairments rather than simply helping patients to adapt to residual impairments .

The results are attractive for acute and chronic stroke patients for gains with CI therapy; however, not every patient is eager to start. Compliance with the mitt restriction schedule has been reported at 32% . An opinion survey for therapists and patients reported that many stroke patients would not want to participate in CI therapy but would prefer a therapy protocol that lasted for more weeks, had shorter activity sessions, and involved fewer hours of wearing the restrictive devices . More than 60% of responding therapists also speculated that patients were unlikely to adhere to CI therapy . Some compromises may be needed for safety. Ambulation with a cane and a hemiparetic arm may place a patient at higher risk for balance instability and falls. Reimbursement for CI therapy also may be a limiting factor.

Rehabilitation strategies

The importance of activity after neurologic injury having therapeutic properties is an essential component of rehabilitation. Most activity in the rehabilitation gym focuses on teaching compensatory skills to foster independence in activities of daily living (ADLs). Several methods are currently used to facilitate movement in the affected extremity and teach compensatory techniques to perform ADLs. Rehabilitation principles center on improving range of motion, increasing strength in the affected extremity, and teaching compensatory strategies and mobility for ADLs. Some theories involve the facilitation of mass movements. They emphasize the use and training of the affected side rather than compensatory strategies. Neurodevelopmental training inhibits abnormal muscle patterns and encourages normal patterns to facilitate automatic, volitional movements . Proprioceptive neuromuscular facilitation evokes responses through manual stimuli to increase the ease of movement promoting function. Abnormal movement is not discouraged . The Brunnstrom theory enhances specific synergy patterns through the use of cutaneous or proprioceptive stimuli that ultimately translate into volitional movement outside of synergy patterns . Other theories involve the facilitation of isolated movement. Muscle tone and voluntary motor activity sometimes can be modified using sensory stimulation. Biofeedback is used to modify autonomic function, pain, and motor disturbances using volitional control auditory, visual, and sensory cues .

When compared, there is no superior solitary treatment method . Other applications of motor learning theory stress structured practice of goal-oriented tasks with specific feedback patterns for the successful transfer and retention of a new skill . Because of impairments in motor or sensory systems, transfers, ADLs, and ambulation become new skills that must be taught and performed in different ways. Another application of motor learning therapy is partial weight support treadmill training. A patient is able to ambulate in a harness system that decreases the amount of weight bearing required to ambulate. After 6 weeks of training in a randomized, controlled trial, the body weight support subjects scored higher in functional balance, motor recovering, over-ground walking speed, and endurance. At 3 months’ follow-up, however, the body weight support subjects continued to have higher scores in motor recovery and over-ground walking speed but not in over-ground walking endurance . It is not clear if partial weight-supported ambulation is able to decrease the length of stay for inpatient rehabilitation.

Ironically, the belief that more intensive therapy is always better may not hold true. The possibility of too much activity too soon after injury could increase brain pathology . Some researchers have raised concerns about mass practice in the first few days after stroke after an experimental finding in rats demonstrated that more neurons may be damaged or the size of the infarct may increase by early overuse of a paretic limb . The level of exercise of a rat running on a rotating wheel is much greater than what a patient could possibly experience during therapy, however. Could the wrong type of activity be deleterious ? We actually may foster a “learned nonuse” by teaching compensatory rather than restorative techniques. There is merit to forced use of the impaired arm and it reinforces long-term use of the upper extremity in ADLs. The constraint-induced (CI) therapy experiment directly supports this concept of “learned nonuse.” Primates whose unaffected arm was restrained until intrinsic recovery occurred showed full use of the now-recovered limb once restraint was removed .

In addition to timing, there is concern about therapy intensity. Current treatment practices focus on the goals of returning a patient to independence as soon as possible and mitigating the effects of injury and its sequelae, such as spasticity. The current paradigm may need to be challenged. We deliver certain amounts of therapy based on time allotted. Maybe inpatient rehabilitation should offer 4 or 5 hours of therapy per day as a patient gets closer to discharge. Little rigorous evidence supports many of the traditional therapy approach models . Fortunately, many of the newer “restorative” treatments are more rigorous in their study design and may answer tough questions on best practice. For example, studies have compared different therapy protocols for CI therapies and skilled versus unskilled task practice. A new large, retrospective study supports the conclusion that conventional therapy has a significant dosage effect that may influence the current paradigm of acute rehabilitation. For example, in a study of outcomes at 70 skilled nursing facilities, an increased intensity of physical therapy and occupational therapy resulted in increased ADL ability and decreased length of stay . In two retrospective studies of high- and low-intensity rehabilitation settings, functional gains were significantly related to therapy intensity in rehabilitation duration, but effects were considered small . Exercise type also may play a role in rehabilitation. A program of progressive resistance training 1 year after stroke may improve strength of the affected limbs and motor function and balance .

Strength training

Strength training (eg, maximal effort, resistance exercise) has benefits at the muscular and neuromuscular levels. Improved recruitment is responsible for torque output within the first 6 weeks of strength training in deconditioned limbs. Muscle hypertrophy eventually follows. Neuroadaptation has been reported after strength training in patients with all types of muscular disorders After approximately 4 to 6 weeks of strength training, muscular adaptations produce additional gains in peak torque. The belief that excessive effort exacerbates hypertonia has prevented widespread use of strength training in persons with poststroke hemiparesis . This belief has not been confirmed in studies. Although it is clear that some muscle groups respond to strengthening programs, research has not documented clearly that they improve functional outcomes .

Fitness training

Fitness often declines in disabled persons, but trials show gains with progressive aerobic exercises (eg, walking on a treadmill 3 days a week) that are tailored to each patient’s tolerance. Benefits are seen even when the exercise is initiated years after a stroke . Despite consensus that stroke leads to profound cardiovascular deconditioning, the underlying principle has not been concluded. The disability of stroke is widely attributed to brain injury alone, and the diminished cardiovascular fitness is speculated to be caused by reduced central neural drive. There are, however, several major peripheral changes in skeletal muscle that could propagate disability and contribute to low fitness levels, including gross muscular atrophy and associated insulin resistance . One study detailed a home-based exercise intervention model to improve fitness. The program consisted of 36 sessions of 90 minutes’ duration over 12 to 14 weeks. Subjects in the usual-care group had services as prescribed by their physicians. All sessions for the exercise group were supervised by a physical or occupational therapist at home. Components of the program were range of motion and flexibility, strengthening, balance, upper-extremity functional use, and endurance training (eg, riding a stationary bike for 30 minutes). The intervention and usual-care groups improved in strength, balance, upper- and lower-extremity motor control, upper-extremity function, and gait velocity. Gains for the intervention group exceeded those in the usual-care group in balance, endurance, peak aerobic capacity, and mobility. The study demonstrated the practical used of home-based interventions compared with the more frequently applied hospital-based intervention programs for improving fitness and function after stroke . Another study looked at water-based exercise that lasted 12 weeks. Individuals in the experimental group exercised in a swimming pool for 1 hour, three times per week. The patients progressed to 30 minutes of water aerobics at 80% heart rate reserve, with the remainder of the time devoted to stretching, warm-up, and cooling down. The study size was limited but showed promising results, with the greatest relative gains in peak aerobic capacity (23% in the experimental group), perhaps arguing for strong consideration of this form of intervention for stroke survivors .

Constraint-induced therapy

Behavioral research with deafferented primates led to the development of CI therapy for humans with impaired upper limbs after stroke. The CI therapy protocol involves promoting use of the more affected upper extremity for a target of 90% of the waking hours by constraining the less affected extremity with a padded mitt for 2 to 3 consecutive weeks to prevent use of the hand for compensation during ADLs. The patients received a type of task practice from therapists—termed “shaping”—for many hours per day. CI therapy was effective for improving movement ability in chronic stroke subjects who met minimal motor criteria of at least 20° extension at the wrist and at least 10° extension at the finger joint. A patient cannot be at a risk for falls because the more functional arm is restrained .

A recent placebo-controlled study showed that the gains from CI therapy are not associated with the amount of therapist attention and so must be the result of the activity of the training . The automated delivery of CI was just as effective as one-on-one therapist training . Skeptics argue that traditional training methods currently used by therapists may be just as effective if delivered at the higher doses that match CI therapy . That argument may be flawed because a comprehensive study that involved 66 chronic stroke subjects reported that the CI therapy group performed statistically better than a group of subjects who received an equal dose of neurodevelopmental technique with the arm movement scale . They found that the CI therapy group outperformed a traditional therapy group during acute rehabilitation on an arm impairment scale, with the largest difference in the pinch subscale . Another study also found advantages in a modified form of CI therapy than traditional therapy in patients who have chronic stroke . Elderly patients found similar benefits with modified CI therapy, and the study demonstrated substantial improvement in the abnormal movement patterns and reversed impairments rather than simply helping patients to adapt to residual impairments .

The results are attractive for acute and chronic stroke patients for gains with CI therapy; however, not every patient is eager to start. Compliance with the mitt restriction schedule has been reported at 32% . An opinion survey for therapists and patients reported that many stroke patients would not want to participate in CI therapy but would prefer a therapy protocol that lasted for more weeks, had shorter activity sessions, and involved fewer hours of wearing the restrictive devices . More than 60% of responding therapists also speculated that patients were unlikely to adhere to CI therapy . Some compromises may be needed for safety. Ambulation with a cane and a hemiparetic arm may place a patient at higher risk for balance instability and falls. Reimbursement for CI therapy also may be a limiting factor.