AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Stroke rehabilitation is a combined and coordinated use of medical, social, educational, and vocational measures for retraining a person to his/her maximal physical, psychological, social, and vocational potential, consistent with physiologic and environmental limitations.

Many studies show that stroke rehabilitation is effective and can improve functional ability, even in patients who are elderly or medically ill and who have severe neurologic and functional deficits. Experts in stroke rehabilitation abound, but none have proven anything about rehabilitation to the satisfaction of anyone else.

Evidence from clinical trials supports the premise that early initiation of therapy favorably influences the outcome. When the initiation of therapy is delayed, patients may in the interim develop avoidable secondary complications, such as contractures and deconditioning.

The course of motor recovery reaches a plateau after an early phase of progressive improvement. Most recovery takes place in the first 3 months, and only minor additional measurable improvement occurs after the 6 months following onset; however, recovery may continue over a longer period of time in some patients who have significant partial return of voluntary movement. (See also the Medscape CME article Stroke Management Update: Research Highlights of 2006 and the eMedicine articles Stroke, Hemorrhagic and Stroke, Ischemic, as well as the Stroke/Cerebrovascular Disease resource center on Medscape.)

Pathophysiology

In the early phase following stroke, there is prompt initial improvement in function as the pathologic processes associated with the penumbra-ischemic metabolic injury, edema hemorrhage, and blood pressure (BP) resolve. The time frame for recovery of function in these reversibly injured neurons is relatively short, accounting for improvement in the first several weeks. The later ongoing improvement in neurologic function occurs by a different set of mechanisms that allow structural and functional reorganization within the brain. The processes involved in this reorganization represent neuroplasticity and may continue for many months. Restitution of partially damaged pathways and expansion of representational brain maps occur, implying recruitment of neurons that are not ordinarily involved in an activity.

A key aspect of neuroplasticity that has important implications for rehabilitation is the fact that the modifications in neuronal networks are use-dependent. Animal experimental studies and clinical trials in humans have shown that forced use and functional training contribute to improved function. On the other hand, techniques that promote nonuse may inhibit recovery.

In the past, the conventional wisdom was that benefits from rehabilitation are achieved primarily through training patients in new techniques that compensate for impairments (for example, using the uninvolved hand to achieve self-care independence). This approach avoided intense therapy on the weak upper limb. Currently, it is recognized that repeated participation by patients in active physical therapeutic programs probably provides direct influence on the process of functional reorganization in the brain and enhances neurologic recovery.

Theories of recovery

• Collateral sprouting from intact cells to the denervated region after some or all input has been destroyed
• Unmasking of neural pathways and synapses that are not normally used but that can be called upon when the dominant system fails (excitability to capture effects of remaining input)

Mechanisms of recovery of neurologic function

• The first mechanism is resolution of harmful local factors, which generally accounts for early spontaneous improvement after stroke (usually within the first 3-6 mo). These processes include resolution of local edema, resorption of local toxins, improvement of local circulation, and recovery of partially damaged ischemic neurons.
• The second recovery mechanism is neuroplasticity, which can take place early or late. Brain plasticity is the ability of the nervous system to modify its structural and functional organization. The 2 most plausible forms of plasticity are collateral sprouting of new synaptic connections and unmasking of previously latent functional pathways.
• Other mechanisms of plasticity include assumption of function by undamaged redundant neural pathways, reversibility from diaschisis, denervation supersensitivity, and regenerative proximal sprouting of transected neuronal axons. Experimental evidence indicates that plasticity can be altered by several external factors, including pharmacologic agents, electrical stimulation, and environmental stimulation.

Natural spontaneous neurologic recovery

• Patients recover after stroke in 2 different, but related, ways.
• • A reduction in the extent of neurologic impairment can result from spontaneous natural neurologic recovery (via the effects of treatments that limit the extent of the stroke) or from other interventions that enhance neurologic functioning. A patient demonstrating this form of recovery presents with improvements in motor control, language ability, or other primary neurologic functions.
  • The second type of recovery demonstrated by stroke patients is the improved ability to perform daily functions within the limitations of their physical impairments. A patient who has sensorimotor, cognitive, or behavioral deficits resulting from stroke may regain the capacity to carry out activities of daily living (ADL), such as feeding himself/herself, dressing, bathing, and toileting, even if some degree of residual physical impairment remains. The ability to perform these tasks can improve through adaptation and training in the presence or absence of natural neurologic recovery, which is thought to be the element of recovery on which rehabilitation exerts the greatest effect.

Frequency

United States

Stroke is the most common serious neurologic disorder in the United States, comprising 50% of all patients admitted to a hospital for a neurologic disease. In the 1960s, 500,000 new cases of stroke were reported per year. A decline in the overall incidence was noted late in the 1970s, but this decline flattened out in the 1980s. Since then, a small rise in incidence may be noted.

International

In most European countries, stroke is of great importance because of the tremendous expenditures arising from cost-intensive treatment and the large demand for continued nursing care. In Japan and other Asian countries, stroke is the second most frequent cause of death in patients aged 65 years or more. For Chinese stroke patients, disability at admission is the most important predictor of disability at discharge because of a lack of subacute care and rehabilitation facilities.¹

Mortality/Morbidity

Stroke is the third leading cause of death, exceeded only by cardiovascular disease and cancer. The mortality rate for stroke has nonetheless decreased, mainly because of advances in emergency and preventive medicine.

• Mortality rates in the general stroke survivor population are difficult to predict.
• • At 3 weeks to 1 month - 22-37%
  • At 1 year - 25-50%
  • At 5 years - 68-72%
  • At 6 years - 55%
  • At 10 years - 65%
• Individuals who survive the initial insult have good life expectancy.
• • Fifty percent remain alive after 5 years, and those surviving for longer than 18 months lived for periods comparable to those for general age-matched and sex-matched populations.
  • The average life expectancy is 7 years following rehabilitation; 30% survive for 11 years.
• Intracerebral hemorrhage carries the highest mortality rate of all types of strokes.
• • A reduction in mortality of 28% has been noted after 4 and 12 months if patients are treated for stroke on a stroke unit.²
  • The mortality rate is 24.6% on a stroke unit and 32.7% on a medical unit.

Race

Many common risk factors for stroke are found in higher frequency among African Americans, including hypertension, diabetes mellitus (DM), heart disease, smoking, excessive alcohol use, and sickle cell disease. The incidence of stroke mortality among black men and women is double that seen in whites. Moreover, stroke mortality is 3- to 4-fold higher among blacks younger than 65 years than it is among whites.

Sex

The incidence of stroke is 19% higher among men than women of all races.

Age

Stroke is primarily a disease of older individuals, although 28% of strokes occur in persons younger than 65 years. Incidence is age-related. Stroke is uncommon in persons younger than 50 years, but incidence doubles each decade after age 55 years. After age 80 years, the incidence may be as high as 2.5 cases per 1000 population.

The effect of age on outcome may be related in part to more frequent co-impairments. If elderly patients have lost function before sustaining a stroke, less favorable outcomes following a stroke would be expected. Furthermore, elderly patients often do not receive as intensive a therapy as that provided to younger patients, perhaps because of a greater intolerance to activity. Older patients may be discharged sooner from a rehabilitation program.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Hemiparesis and motor recovery have been the most studied of all stroke impairments. As many as 88% of patients with acute stroke have hemiparesis. In a classic report, Twitchell described in detail the pattern of motor recovery following stroke.³ At onset, the upper extremity (UE) is more involved than the lower extremity (LE), and eventual motor recovery in the UE is less than in the LE. The severity of UE weakness at onset and the timing of the return of movement in the hand are both important predictors of eventual motor recovery in the UE. The prognosis for return of useful hand function is unfavorable when UE paralysis is complete at onset or grasp strength is not measurable by 4 weeks. However, as many as 9% of patients with severe UE weakness at onset may gain good recovery of hand function. As many as 70% of patients showing some motor recovery in the hand by 4 weeks make a full or good recovery. Full recovery, when it occurs, usually is complete within 3 months of onset.

Bard and Hirshberg claim that if no initial motion is noticed during the first 3 weeks or if motion in one segment is not followed within a week by the appearance of motion in a second segment, the prognosis for recovery of full motion is not favorable.

Movement typically returns 43-60 days (but no later than 3 months) poststroke. Almost all spontaneous recovery occurs within 6 months, but gains continue to occur 6-12 months following the stroke. Recovery occurs for months or years. Indeed, cessation of recovery after 6 months may be a self-fulfilling prophecy.

Physical

The initial clinical examination of a patient with an acute stroke includes a thorough, detailed neurologic examination. The neurologic findings are used by the rehabilitation team for prognostication, development of the specific details of the rehabilitation plan, and selection of the appropriate setting for rehabilitation. Reassessment of the patient's condition during rehabilitation provides a means of monitoring progress and subsequently evaluating outcome. The initial rehabilitation assessment should begin immediately following onset, within 2-7 days, and then subsequently at repeated intervals.

After stroke occurs, total loss of voluntary movement may be noted in involved extremities, with loss or decrease in muscle stretch reflexes (MSRs). Within 48 hours, MSRs and finger jerks are more active on the involved side, although they may require 3-29 days to develop. Within a short period, tone appears in the wrist and finger flexors, as well as in the ankle plantar flexors. As a result, the UE is prone to demonstrate the adductor/flexor pattern and the LE, the adductor/extensor pattern.

In 1-30 days, spasticity appears, resulting in resting posture, as follows:

• Upper extremity
• • Shoulder is in adduction and internal rotation.
  • Elbow is in flexion.
  • Forearm is in pronation/supination.
  • Wrist and fingers are in flexion.
• Lower extremity
• • Hip is in adduction and extension.
  • Knee is in extension
  • Ankle is in plantar flexion
  • Foot is in inversion
  • Within 1-38 days after stroke, clonus appears in ankle plantar flexors.
  • Onset of clasp-knife phenomenon occurs within 3-31 days.
  • Spasticity decreases with increased volitional movement, but MSRs always remain increased, despite total recovery.
• Recovery of movement
• • UE flexor synergy
  • • Shoulder flexion (6-33 days) ® elbow flexion (1-6 days later) ® finger and wrist flexion (1-13 days later) ® shoulder adduction/internal rotation
    • Clinically, flexor synergy can also present as scapula retraction/elevation, shoulder abduction (90°)/external rotation, elbow flexion (acute angle), and forearm supination (full range).
  • UE extensor synergy
  • • Shoulder ® elbow ® wrist/finger extension
    • Clinically, extensor synergy presents as scapula protraction, humerus flexion/internal rotation, elbow extension, and forearm pronation.
  • LE flexor synergy - Hip flexion/adduction (1-31 days) ® knee flexion (1-2 days later) ® ankle/toe dorsiflexion (25-90 days)
  • LE extensor synergy - Hip/knee extension ® ankle plantar flexion

Causes

• Causes of stroke in children and young adults include the following:
• • Cerebral embolism
  • Trauma to extracranial arteries
  • Subarachnoid hemorrhage
  • Sickle cell anemia
  • Vasculopathy
  • Coagulopathy
  • Cardiogenic emboli
  • Homocystinuria
  • Oral contraceptives
  • Childbirth
  • Drug use (cocaine)
  • HIV-associated disease
• Risk factors for stroke in asymptomatic patients include the following:
• • Hypertension
  • Heart disease (atrial fibrillation)
  • Smoking
  • Diabetes mellitus
  • Elevated fibrinogen
  • Erythrocytosis
  • Hyperlipidemia
• Risk factors for stroke in symptomatic patients include transient ischemic attacks (TIAs).
• Risk factors for recurrent stroke include the following:
• • Previous stroke
  • Hypertension
  • Heart disease
  • Heavy alcohol consumption
  • Diabetes mellitus
• Early death following a stroke usually is related to the underlying pathology and to the severity of the lesion. The 30-day survival rate for patients with cerebral infarction is 85%, but for patients with intracerebral hemorrhage, survival is reported to be only 20-52%.
• Better management of cardiac and respiratory disorders has reduced early mortality. However, hypertension, heart disease, and DM remain risk factors for recurrence of stroke.
• Coma following stroke onset indicates an unfavorable prognosis, presumably because coma occurs frequently in cerebral hemorrhage. When coma occurs in association with cerebral infarction, it reflects a large lesion with cerebral edema.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to Be Considered

TIA is an event in which neurologic symptoms develop and disappear over several minutes and, by definition, completely resolve within 24 hours.

Reversible ischemic neurologic deficit is a transient neurologic event that lasts longer than 24 hours, resulting in only temporary impairment.

The degree of recovery of independent functioning during rehabilitation has been found to be greater than that which might have been expected by a reduction in neural impairments alone, suggesting that rehabilitation interventions play an important role in the patient's recovery of function. The 2 types of improvement are related in subtle and complex ways. Alternative compensatory functional strategies, such as one-handed dressing techniques for the hemiplegic patient, assume a major role in the performance of functional tasks when neurologic improvement is minimal or absent.

The degree of natural recovery of neurologic function varies, but figures on the relative frequencies of neurologic deficits during the early and later poststroke stages offer some insight into the degree of recovery that might be seen. The number of these deficits generally declines by approximately 33-50%. For example, the following reductions in prevalence from initial presentation have been found at 1-year follow-up:

• Hemiparesis - From 73% at presentation to 37%
• Aphasia - From 36% at presentation to 20%
• Dysarthria - From 48% at presentation to 16%
• Dysphagia - From 13% at presentation to 4%
• Incontinence - From 29% at presentation to 9%

The time required for recovery also varies. Although most improvements in physical functioning occur within the first 3-6 months, later recovery also is observed commonly. Although it is tempting to specify a definitive prognosis in a stroke patient, it is important to recognize that a multiplicity of variables determine ultimate outcome, which is why expectations for recovery often are inaccurate.

Sexual behavior changes

Following stroke, no significant changes occur in sexual interest or desire, but marked decline has been noted in the sexual behavior in both sexes.

• Thirty-six percent of patients remained sexually active poststroke.
• Thirty-three percent of men resumed unaltered intercourse.
• Forty-three percent of women resumed unaltered intercourse.
• Decreased frequency of intercourse resulting from altered sensation and custodial attitudes taken by the patient's spouse was reported.
• Thirty-eight percent of men reported slow normal erections following stroke.
• Twenty-nine percent of women reported slow normal vaginal lubrication poststroke.
• Eleven percent of men had no coital activity prestroke, and 64% had none poststroke.
• Thirty-five percent of women with no coital activity prestroke, and 54% had none poststroke
• Ejaculation was normal in 73% of men prestroke and in 22% of men poststroke.
• Orgasm was normal in 43% prestroke and in 11% normal poststroke.
• Enjoyment of sex
• • Men - 84% prestroke and 30% poststroke
  • Women - 65% prestroke and 31% poststroke
• The most common fears were of increased BP and of having another stroke.
• Sixty percent of men and 70% of women were found to have decreased sexual contact with their spouse.
• Thirty percent of patients reported having less than 1 sexual contact per month.
• Twenty percent of patients reported having no sexual contact.
• Spouses reported an overall feeling of psychological changes in their partner and changes in their sexual life poststroke.

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The goal of the initial laboratory evaluation of a patient with acute stroke is to establish an accurate diagnosis of the stroke and to determine the presence of any other intercurrent illness.
• Initial laboratory tests include the following:
• • Electrolytes, glucose, and cholesterol levels
  • Complete blood cell (CBC) count
  • Prothrombin time and activated partial thromboplastin time
  • Erythrocyte sedimentation rate
  • Urinalysis

Imaging Studies

• Computed tomography (CT) scanning of the head reveals acute hemorrhage, but it often is negative for the first 1-2 days in patients with cerebral infarction.⁴
• Magnetic resonance imaging (MRI) shows changes of cerebral infarction as early as a few hours postonset, but a CT scan usually is performed early because it is less expensive and reveals those structural lesions (eg, hemorrhage, tumor, abscess) that may require surgical management. Because of its greater resolution, MRI is more sensitive than CT scanning in detecting small lacunar strokes. MRI is also more sensitive than CT scanning in detecting lesions in the brainstem and cerebellum.
• Magnetic resonance angiography (MRA) is a technique for displaying details of cerebrovascular anatomy and pathology without the risks of conventional angiography.
• Nuclear medicine scanning techniques, such as positron emission tomography (PET) scanning and single-photon emission computed tomography (SPECT) scanning, detect the uptake of radiolabeled materials with signal intensity dependent on blood flow to the soft-tissue region. Changes can immediately be detected within the ischemic zone during acute cerebral infarct and hemorrhage.

Other Tests

• Lumbar puncture to reveal red blood cells in subarachnoid hemorrhage
• Electrocardiography to assess for valvular lesions and thrombi
• Transthoracic echocardiography or transesophageal echocardiography after suggested cerebral embolism
• Swallowing video fluoroscopy if there is any doubt about aspiration

Procedures

• Carotid endarterectomy is recommended for patients with symptomatic extracranial carotid artery disease with at least 70% stenosis in the internal carotid artery.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Rehabilitation Program

Physical Therapy

Rehabilitation should include therapy that is directed at specific training of skills and at functional training. Therapy should be given with sufficient intensity to promote skill acquisition. Major theories of rehabilitation training include the following:

• Traditional therapy - Range of motion (ROM), strengthening, mobilization, and compensatory techniques
• Bobath - Neurodevelopmental training
• • Muscle patterns, not isolated movements, used for motion.
  • Inability to direct nervous impulses to muscle in different combinations used by persons with intact central nervous system (CNS).
  • Abnormal muscle patterns suppressed before normal patterns are introduced.
  • Associated reactions - Mass synergies avoided because may strengthen weak, unresponsive muscles (reinforces abnormally increased tone reflexes and spasticity).
  • Reflex-inhibiting patterns used to inhibit abnormal postural reactions; facilitates automatic voluntary movements.
  • Abnormal patterns modified at proximal key points of control (eg, neck, spine, shoulder, pelvis).
• Knott, Voss - Proprioceptive neuromuscular facilitation⁵
• • Stimulation of nerve/muscle/sensory receptors to evoke response through manual stimuli to increase ease of movement and promote function
  • Normal neuromuscular mechanism capable of wide range of motor activities within limits of anatomical structure, developmental level, and previously learned neuromuscular responses; integrated and efficient without awareness of individual muscle action, reflex activity, and other reactions
  • Deficient neuromuscular mechanism inadequate to meet demands of life because of weakness, incoordination, adaptive joint shortening/immobility, muscle spasm, or spasticity
  • Specific demands placed by physical and occupational therapists have facilitating effects of neuromuscular mechanism and reverse limitations of patient.
  • Mass-movement patterns are in keeping with Beevor axiom (ie, the brain knows nothing of individual muscle action but only movement).
• Brunnstrom - Central facilitation using Twitchell's recovery; enhances specific synergies through the use of cutaneous/proprioceptive stimuli.

See also the Medscape CME entry EXCITE: Beneficial Effects of Constraint Therapy After Stroke Retained Long Term.

Occupational Therapy

Most patients with significant neurologic impairment who survive a stroke are dependent on others for performance of basic ADL (ie, bathing, dressing, feeding, toileting, grooming, transfers). The capacity of individuals to perform these activities usually is scored on disability rating scales, such as the Functional Independence Measure. Almost all patients show improved performance of ADL as recovery occurs.

Most improvement is noted in the first 6 months, although as many as 5% of patients show continued measurable improvement up to 12 months postonset. Other patients may show some functional improvement beyond 6 months, even though the disability scales usually fail to detect further improvement because of their limited sensitivity at the upper end of the functional range. (See also the Medscape CME entry Occupational Therapy Improves Personal Activities of Daily Living After Stroke.)

Reports of the levels of functional independence eventually reached by stroke patients after recovery vary from one author to another. This variability probably reflects differences between study populations, methods of treatment, follow-up, and data reporting. In most reports, 47-76% of patients achieve partial or total independence in performance of ADL. Most authors who have attempted to determine which factors predict ultimate ADL functional outcome have used multivariate analysis. Of the many independent variables tested, those listed below were reported to have the most influence on outcome. However, not all of these factors were shown to predict outcome status statistically in every study. Factors predicting poor ADL outcome include the following:

• Advanced age
• Comorbidities
• Myocardial infarction
• Diabetes mellitus
• Severe stroke
• Severe weakness
• Poor sitting balance
• Visuospatial deficits
• Mental changes
• Incontinence
• Low initial ADL scores
• Delay in initiating rehabilitation following onset

Speech Therapy

Approximately one third of patients with acute stroke have clinical features of aphasia. Language function in many of these patients improves, and, at 6 months or more after stroke, only 12-18% of patients have identifiable aphasia. Skilbeck and colleagues reported that patients with aphasia continue to show some late improvement in language function even more than 1 year after onset.

Patients who are classified initially as having Broca aphasia have variable outcomes. In patients with large hemisphere lesions, Broca aphasia persists with little recovery. Patients with smaller lesions confined to the posterior frontal lobe often show early progressive improvement, but the impairment may evolve into a milder form of aphasia with anomia and difficulty finding words. Patients with global aphasia tend to progress slowly, with comprehension often improving more than expressive ability does. The communicative ability of patients who initially have global aphasia improves over a longer period of time, up to a year or more postonset. Patients with global aphasia associated with large lesions may show only minor recovery, but recovery may be quite good in patients with smaller lesions. The extent of language recovery associated with Wernicke aphasia is variable.

Medical Issues/Complications

• Most patients with stroke who undergo rehabilitation have many other associated medical conditions that require professional attention. These problems might be preexisting medical illnesses that necessitate ongoing care (eg, hypertension, DM), secondary poststroke complications (eg, deep venous thrombosis, pneumonia), or acute poststroke exacerbations of preexisting chronic diseases (such as angina in a patient with ischemic heart disease). Management of these conditions can constitute major portions of the rehabilitation effort. Some patients may be more disabled by certain associated comorbid diseases than by the stroke itself.
• The occurrence of these associated conditions has several implications for management of stroke cases during and after rehabilitation. First, these problems can detract from the benefits of rehabilitation. Some medical problems, such as heart disease, have been found to affect the course and outcome of rehabilitation adversely following a stroke. Intercurrent medical complications can limit the patient's ability to participate in therapeutic exercise programs, inhibit functional skill performance, and reduce the likelihood of achieving favorable outcomes from rehabilitation. The rehabilitation interventions also might affect the medical condition adversely, causing an exacerbation of the disease or necessitating an adjustment in the treatment program. Patients who are treated in a stroke unit have better outcomes at discharge than do patients who are not.⁶

Surgical Intervention

• Tendon release - This can be performed in cases of severe spasticity or contractures.
• Carotid endarterectomy - The surgery can be carried out for patients with stenosis of 70% or greater.
• Carotid artery bypass to prevent a stroke or in patients who have had a TIA - There is no longer any clear indication for this; no benefit has been demonstrated from the surgery.
• Surgical bypass or endarterectomy involving the posterior circulation - Although there are reports of successful cases, these procedures remain largely experimental.

Consultations

• Psychologists
• • Psychosocial issues obviously are very important.
  • Numerous studies have reported on the influence of the psychological adjustment and coping mechanisms of the patient, as well as of his/her spouse and other family members, in determining the ultimate outcome.
• Neurologists
• Physiatrists

Other Treatment

• Biofeedback attempts to modify autonomic functions, pain, and motor disturbances through acquired volitional control, using auditory, visual, and sensory clues.⁷
• Functional electrical stimulation commonly is employed in UEs and LEs to improve strength, encourage and augment early active ROM, assist in the management of dependent peripheral edema through forceful isotonic muscle contraction, and establish early proprioceptive joint sense in the sensory-compromised patient.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Considerable effort has been invested in developing effective therapeutic agents that can arrest, delay, or reverse cerebral ischemia and neural injury. Current research has focused mainly on the following 4 pharmacologic treatments:

• Heparin
• Calcium channel blockers
• Thrombolytic agents
• Neuroprotective medications

Heparin

Intravenous heparin frequently is administered in the acute care setting to arrest stroke progression or to prevent its recurrence. Current available research has neither supported nor discredited the efficacy of heparin for acute stroke management, and clear guidelines for its use are lacking. The prevailing evidence supports the use of antiplatelet agents for the treatment of thrombotic stroke, but heparin may be appropriate for arresting an evolving stroke in some clinical situations. Because the risk of recurrent cardioembolic stroke is 12% within the first 3 weeks without anticoagulation therapy, the use of heparin and warfarin seem warranted if the risk of bleeding is otherwise low. (See also the eMedicine article Stroke Anticoagulation and Prophylaxis.)

Calcium channel blockers

Calcium channel blocking agents, such as nimodipine, are effective in the prevention of death from vasospastic complications of subarachnoid hemorrhage (SAH) and are recommended for routine use during the first 21 days after hemorrhage. Several trials testing nimodipine for acute ischemic stroke treatment have had disappointing results. The vasodilating effect of calcium channel blockers can hamper stroke recovery by increasing intracranial pressure.

Thrombolytic agents

In studies that have enrolled subjects within the first 2-6 hours after onset of infarction, thrombolytic agents have achieved recanalization of occluded cranial arteries in acute stroke. Although the employment of agents such as tissue plasminogen activator seems promising, acute hemorrhagic complications have limited their use.^{8, 9} Medications such as ancrod, an agent that binds to and inactivates fibrinogen, have subsequently come under study in an effort to find a safer thrombolytic treatment for acute stroke. (See also the eMedicine article Thrombolytic Therapy in Stroke and the Medscape CME entry New Guidelines for Treatment of Acute Ischemic Stroke.)

Several new oral anticoagulant medications are in the final stages of clinical trials for use in the prophylaxis of ischemic thromboembolic stroke. Once approved for use, the potential of such drugs in the arena of stroke treatment is significant.

Management of spasticity requires careful evaluation, goal setting, and selection of appropriate therapies. Dantrolene has been used for many years for pharmacologic treatment of hemiplegic spasticity caused by stroke, but early use of dantrolene did not improve function in a double-blind study.

A small number of patients are bothered by spontaneous spasms, occurring mostly in bed at night. These spasms usually can be adequately controlled with small doses of diazepam before bedtime. For localized spasticity, such as in the forearm flexors or calf muscles, intramuscular neurolysis with phenol or chemodenervation with intramuscular botulinum toxin injections can be very effective.

Neuroprotective medications

Another class of medications for the treatment of acute stroke is the neuroprotective agents. In particular, the N-methyl-D-aspartate (NMDA) receptor antagonists have shown the potential ability to delay neuronal injury. During ischemic injury, excitatory neurotransmitters, such as glutamate and aspartate, are released extracellularly. In high concentrations, these amino acids act on NMDA membrane receptors, causing an influx of cations that results in rapid neuronal death. Controlled studies testing the ability of NMDA antagonists to prevent cytotoxic injury during acute stroke are underway. (See also the eMedicine article Neuroprotective Agents in Stroke.)

Other agents have been used to treat stroke, including antioxidants, barbiturates, beta-adrenergic blockers, corticosteroids, dextran, hyperventilation drugs, naloxone, and vasodilators. Various opinions exist concerning the usefulness of these agents, but their effectiveness has not been demonstrated.

Drug Category: Antiplatelet agents

These agents inhibit platelet function by blocking cyclooxygenase and subsequent platelet aggregation. Antiplatelet therapy has been shown to reduce mortality by reducing the risk of fatal strokes, fatal myocardial infarctions, and vascular death in patients with a history of TIAs.

Drug Category: Calcium channel blockers

The vasodilating effect of this medication can hamper stroke recovery by increasing intracranial pressure.

Drug Category: Thrombolytic agents

The use of thrombolytic agents in acute stroke has been successful in achieving recanalization of occluded cranial arteries within the first 2-6 hours after onset of infarction. Treatment should be initiated only within 3 h after onset of stroke symptoms and after exclusion of intercranial hemorrhage by a CT scan or other diagnostic imaging method sensitive for the presence of hemorrhage.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Medical stability traditionally has been required for admission of a patient to a specialized rehabilitation unit; however, hospitals increasingly are transferring patients from acute wards to rehabilitation units at earlier stages, often when the patients still have unresolved medical problems. This practice has forced rehabilitation centers to expand their resources to care for these more complex cases and to provide closer medical and nursing monitoring. Local institutional referral patterns and practices usually determine the timing of transfer, but if earlier transfer to rehabilitation can be accomplished safely, patient care may be enhanced by earlier active participation of the patient in the rehabilitation program.¹⁰
• Planning for discharge from the inpatient rehabilitation program should begin on admission.
• • Discharge functional status, destination of discharge, and length of hospital stay are comparable in patients with a good prognosis.
  • Discharge functional status is comparable in patients with an unfavorable prognosis, but mortality is higher and the hospital stay is longer in medical wards.
• Discharge from the hospital often is thought of as the end of rehabilitation, with the assumption that a good program prepares the patient for reintegration into home and community; however, hospital discharge instead should be looked at as the end of the beginning of a new life in which the patient faces the challenge of adapting to different roles and relationships and of searching for new meaning in life. This adaptation involves resuming former roles in the family and with friends as much as possible and finding ways to live a meaningful life in the community.

Further Outpatient Care

• During postacute rehabilitation, all patients should be monitored carefully for evidence of cardiac disease. The classic features of coronary artery disease and congestive heart failure may be present, but often they are not. Ischemia may be silent. The clinical clues to significant coexisting heart disease may be subtle (eg, slower than expected progress, excessive fatigue, lethargy, mental changes). These cardiac complications can be treated successfully and are not contraindications for rehabilitation. The patient should undergo appropriate cardiac investigation with electrocardiography, Holter monitoring, and echocardiography and also should receive optimal therapy. 
• Rehabilitation program
• • Early initiation of therapies is desirable. Beginning rehabilitation early minimizes secondary complications, such as contractures and deconditioning, and helps to motivate the patient. Whether more intense therapy as an independent variable improves ultimate functional recovery is not known.¹¹
  • Evaluation of neurologic impairments should be made repeatedly during the course of the rehabilitation program. Ideally, evaluation should be made weekly in the early phases of rehabilitation to allow monitoring of the recovery process and to guide the therapeutic intervention. A clear need for committed medical direction is evident in patients who have sustained strokes. The role of the physician includes provision of medical care. Many patients have ongoing associated medical problems that require appropriate monitoring and therapy. The physician must act as a medical counselor, offering reasonable prognostication to patient and family, along with guidance in reduction of stroke risk factors and ongoing medical care. The physician also must give leadership to the team and assist in developing treatment protocols and setting treatment expectations.
  • The multiple problems that a patient can have following stroke require the active participation of a team of professionals. The treatment activities of the team members must be coordinated so that detailed evaluations are shared and agreements made regarding goals and treatment interventions.
  • Each of the professional therapists on the team should be knowledgeable about the appropriate interventions within his or her discipline for treating the disabilities of patients following stroke. The interventions should be directed at achieving specific therapeutic goals, which may be for the short term (for example, weekly goals) or longer term (for instance, goals to be reached by discharge). Having achieved those goals, the patient moves on to the next phase of rehabilitation or is discharged home to continue treatment as an outpatient.
  • Rehabilitation requires a functional approach. When impairments cannot be altered, every effort should be made to assist patients in compensating for deficits and adapting to alternative methods so that they can achieve optimal functional independence.

In/Out Patient Meds

• The rehabilitation program may be offered in different settings, such as an acute inpatient rehabilitation unit, a subacute inpatient rehabilitation unit, a home care environment, or an outpatient center. The acute rehabilitation setting is appropriate for patients who meet the admission criteria and are able to tolerate 3 hours or more of active therapy per day. An acute rehabilitation setting is preferred if the patient requires close monitoring of his/her medical status by medical and nursing professionals. If the patient's medical status is stable but the patient is unable to tolerate more than 1 hour of therapy a day, a subacute rehabilitation or skilled nursing setting is more appropriate. Patients who are independent or require only minimal assistance in self-care tasks and mobility are suited for outpatient therapy or a home care program.

Transfer

• Risks for suboptimal home care (72.6% prediction/validation rate) include the following:
• • A depressed caregiver
  • Inadequate knowledge of how to care for a family member following a stroke
  • A dysfunctional family
• A study by Young and Forster found home care to be cheaper than day hospital services (£385 vs £620 [approximately $546 vs $880]).¹²
• Outcome measurements have indicated a modest advantage in favor of home care.
• No difference in outcome was found between home care and hospital-based rehabilitation following acute care.
• Hospital-based services are 27% more expensive than home care services.
• Geriatric ward patients are 2.4 times less likely to die or to become institutionalized by 6 months if placed in day hospital service.
• Stroke unit patients demonstrate superior ADL performance at 6 months with home care (2.6 times more expensive) than they do with outpatient therapy.
• General medical ward patients had similar outcomes, although outpatient services cost 56% of home care.

Deterrence

• A useful set of cardiac precautions in patients undergoing rehabilitation was developed by Fletcher and colleagues. Activity should be terminated if any of the following symptoms develop:
• • New onset of cardiopulmonary symptoms
  • Heart rate decreases to less than 20% of baseline
  • Heart rate increases to greater than 50% of baseline
  • Systolic blood pressure increases to 240 mm Hg
  • Systolic BP decreases 30 mm Hg from baseline or to less than 90 mm Hg
  • Diastolic shortening fraction increases to 120 mm Hg

Complications

• Medical complications frequently occur during the postacute phase of rehabilitation, affecting up to 60% of patients and up to 94% of patients with severe lesions. Common medical and neurologic complications include the following:
• • Medical
    • Pulmonary aspiration, pneumonia - 40%
    • Urinary tract infection - 40%
    • Depression - 30%
    • Musculoskeletal pain, reflux sympathetic dystrophy - 30%
    • Falls - 25%
    • Malnutrition - 16%
    • Venous thromboembolism - 6%
    • Pressure ulcer - 3%
  • Neurologic
  • • Toxic or metabolic encephalopathy - 10%
    • Stroke progression - 5%
    • Seizures - 4%

• Seizures - Ischemic stroke patients were followed over the course of 2-4 years.
• • Seizures developed in 6-9% of patients.
  • Seizures developed in 26% of patients with cortical lesions.
  • Seizures developed in 2% of patients with subcortical lesions.
• Risk factors include the following:
• • Lobar hemorrhage (acute)
  • Cortical lesions (chronic)
  • Persistent paresis (50%)
• Other risk factors include the following:
• • Language function deficit, dysarthria
  • Visual field defect (20%), hemianopia
  • Posture and balance deficit
  • Sensory, cognitive, and perceptual function deficits
  • Bowel and bladder incontinence
  • Deconditioning
  • Congestive heart failure
  • Hypertension
  • Diabetes mellitus
  • Dysphasia
  • Spasticity
  • Contractures
  • Heterotopic calcification

Prognosis

• Significant improvement in UE function usually is seen only in the first 3 months poststroke. If no return of motor function is noted after more than 6 months, prognosis for useful function is unfavorable. If no return of voluntary motor function is noted after more than 1 week, it is unlikely that full use of the affected UE will return.
• • Poor prognostic indicators
  • • Proprioceptive facilitation (tapping) response for more than 9 days
    • Traction response (shoulder flexors/adductors) in more than 13 days
    • Prolonged flaccid period
    • Onset of motion at longer than 2-4 weeks
    • Severe proximal spasticity
    • Absence of voluntary hand movement for more than 4-6 weeks
  • Predictors of outcome
  • • Type, distribution, pattern, and severity of physical impairment
    • Cognitive, language, and communication abilities
    • Number, types, and severity of comorbid conditions
    • Level of motivation or determination
    • Coping ability and coping style
    • Nature and degree of family and social supports
    • Type and quality of the specific training and adaptation program provided
• Stroke rehabilitation outcome
  • Starting rehabilitation early correlates with better outcome but may be confounded by case severity. Stroke rehabilitation improves functional ability even in patients who are elderly or medically ill, as well as in those who have severe neurologic/functional deficits. Significant gains that are achieved are not attributable only to spontaneous recovery.
  • Of patients who survive stroke by more than 30 days, 10% demonstrate complete spontaneous recovery, 10% show no benefit from any treatment, and 80% may benefit from treatment. Stroke survivors who do not undergo rehabilitation are more likely to be institutionalized.
  • Eighty-five percent of patients went home after 3 months of participation in a stroke rehabilitation program. After 43 days, 80% of patients returned home, 85% were ambulatory, and 50-62% were independent in performance of ADL. Functional state improved in the stroke unit from 6-52 weeks.
  • Patients in outpatient and nonoutpatient therapy groups showed statistical improvement between stroke onset, discharge to home, and 1-year follow-up. The outpatient therapy group required a longer rehabilitation stay, was more impaired at onset, and did not perform as well as the nonoutpatient group. The outpatient therapy group was associated with complete UE/LE hemiplegia, unilateral neglect, impaired proprioception, and urinary incontinence.
  • Sphincter function, level of neurologic impairment, and capacity to perform ADL related to outcome is assessed, but these measures are not useful to anticipate the outcome of each patient.
  • Patients unable to walk 3 months poststroke received therapy up to 2 years after the stroke. Seventy-four percent of patients walked without assistance. Seventy-nine percent of patients had a modified Barthel score below 70.
  • Rehabilitation should include therapy directed at specific training of skills and functional training. Therapy should be given with sufficient intensity to promote skill acquisition.

Patient Education

• Stroke is a common clinical problem with a significant impact on its survivors and on society. Stroke often presents as a disabling illness that not only involves many aspects of a patient's life but also places a substantial burden on family members and others. The aims of rehabilitation are to minimize the impact of the disability resulting from the stroke and to optimize the quality of life for both the patient and his/her personal caregiver.
• Emphasis on patient and family education regarding stroke, risk factor reduction, and strategies to maximize functional independence is important.
• Family involvement and support during the rehabilitation process can affect outcome.
• Remarkable recoveries have been reported in 3-6 years. (Patients have returned to work 3 years poststroke).
• The patient should be encouraged to resume intimate contact with his/her spouse or partner when appropriate.
• No special diet is required to improve the patient's motor recovery after stroke; however, the patient should avoid excessive weight gain and remain on the regular diet for conditions such as DM, hypertension, or hyperlipidemia.
• Every patient should avoid strenuous exercise after stroke, but it is a good idea to participate in an individualized exercise program. Reports in the literature state that for young stroke survivors who participated in an aerobic fitness program, improvement in fitness levels, ambulatory speed, and life satisfaction was statistically significant.
• For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• The rehabilitation management of patients with identified cardiac complications should include formal clinical monitoring of pulse and blood pressure during physical activities. Brief electrocardiac monitoring during exercise can add more specific information. Note that in deconditioned patients, the resting heart rate may be high, and, in an elderly patient, the estimated limit for heart rate based on 50% above resting may be too high. For patients on beta blockers, a reasonable limit might be a heart rate of around 20 beats above the resting level.

Special Concerns

• Criteria for admission to a comprehensive rehabilitation program may include the following:
• • Stable neurologic status
  • Significant persisting neurologic deficit
  • Identified disability affecting at least 2 of the following:
  • • Mobility
    • Self-care activities
    • Communication
    • Bowel or bladder control
    • Swallowing
  • Sufficient cognitive function to learn
  • Sufficient communicative ability to engage with the therapists
  • Physical ability to tolerate the active program
  • Achievable therapeutic goals

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  When the brain suffers an injury such as a stroke, neurons release glutamate onto nearby neurons, which become excited and overloaded with calcium, after which they die (left). Normal neurotransmission (above) is altered during injury, causing excess calcium to activate enzymes, eventually leading to destruction of the cell. Since this process occurs via glutamate receptors, including N-Methyl-D-aspartate (NMDA) receptors, scientists believe that damage can be stopped through the use of agents that block these receptors. Several such drugs are now in human clinical trials.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Sze KH, Wong E, Or KH. Factors predicting stroke disability at discharge: a study of 793 Chinese. Arch Phys Med Rehabil. Jul 2000;81(7):876-80. [Medline].
2. Langhorne P, Williams BO, Gilchrist W. Do stroke units save lives?. Lancet. Aug 14 1993;342(8868):395-8. [Medline].
3. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain. Dec 1951;74(4):443-80. [Medline].
4. Hankey GJ, Davis SJ, Stewart-Wynne EG. Cranial CT scan appearances that correlate with patient outcome in acute stroke. Clin Exp Neurol. 1987;23:71-4. [Medline].
5. Pomeroy VM, Cloud G, Tallis RC, et al. Transcranial magnetic stimulation and muscle contraction to enhance stroke recovery: a randomized proof-of-principle and feasibility investigation. Neurorehabil Neural Repair. Apr 4 2007;[Medline].
6. Kalra L, Dale P, Crome P. Improving stroke rehabilitation. A controlled study. Stroke. Oct 1993;24(10):1462-7. [Medline].
7. Woodford H, Price C. EMG biofeedback for the recovery of motor function after stroke. Cochrane Database Syst Rev. 2007;(2):CD004585. [Medline].
8. Albers GW, Bates VE, Clark WM. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA. Mar 1 2000;283(9):1145-50. [Medline]. [Full Text].
9. Gore JM, Sloan M, Price TR, et al. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial. Circulation. Feb 1991;83(2):448-59. [Medline].
10. Davidoff GN, Keren O, Ring H. Acute stroke patients: long-term effects of rehabilitation and maintenance of gains. Arch Phys Med Rehabil. Oct 1991;72(11):869-73. [Medline].
11. Paolucci S, Grasso MG, Antonucci G. Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors. Arch Phys Med Rehabil. Jan 2001;82(1):2-8. [Medline].
12. Young J, Forster A. Day hospital and home physiotherapy for stroke patients: a comparative cost-effectiveness study. J R Coll Physicians Lond. Jul 1993;27(3):252-8. [Medline].
13. Adams RD, Victor M. Principles of Neurology. 5^th ed. New York, NY: McGraw-Hill; 1993.
14. Allsup-Jackson G. Sexual dysfunction of stroke patients. Sexuality Dis. 1981;4(3):161-8.
15. Anderson TA. Rehabilitation of patients with completed stroke. In: Kottke FJ, Lehmann JS, eds. Krusen's Handbook of Physical Medicine and Rehabilitation. 4^th ed. Philadelphia, Pa: WB Saunders; 1990.
16. Averbuch M, Hibler J, Roth EJ. Effects of Aerobic Exercise on Young Persons Post-Stroke. Baltimore, Md: Department of Veterans Affairs; 1998. Rehabilitation R&D Progress Reports.
17. Bach y Rita P. Central nervous system lesions: sprouting and unmasking in rehabilitation. Arch Phys Med Rehabil. Sep 1981;62(9):413-7. [Medline].
18. Bach-y-Rita P. Brain plasticity as a basis of the development of rehabilitation procedures for hemiplegia. Scand J Rehabil Med. 1981;13(2-3):73-83. [Medline].
19. Blakemore CB, Falconer MA. Long-term effects of anterior temporal lobectomy on certain cognitive functions. J Neurol Neurosurg Psychiatry. Aug 1967;30(4):364-7. [Medline].
20. Boldrini P, Basaglia N, Calanca MC. Sexual changes in hemiparetic patients. Arch Phys Med Rehabil. Mar 1991;72(3):202-7. [Medline].
21. Brandstater ME. Stroke rehabilitation. In: DeLisa JA, ed. Rehabilitation Medicine: Principles and Practice. 3^rd ed. Philadelphia, Pa: Lippincott-Raven; 1998:1998.
22. Brandsteter ME, Basnajian JV. Stroke Rehabilitation. Philadelphia, Pa: Lippincott Williams & Wilkins; 1987.
23. Bray GP, DeFrank RS, Wolfe TL. Sexual functioning in stroke survivors. Arch Phys Med Rehabil. Jun 1981;62(6):286-8. [Medline].
24. Caillet R. The Shoulder in Hemiplegia. Philadelphia, Pa: FA Davis; 1980.
25. Carroll D. Hand function in hemiplegia. J Chronic Dis. May 1965;18:493-500. [Medline].
26. Cohen ME, Marino RJ. The tools of disability outcomes research functional status measures. Arch Phys Med Rehabil. Dec 2000;81(12 Suppl 2):S21-9. [Medline].
27. Coull BM, Brockschmidt JK, Howard G. Community hospital-based stroke programs in North Carolina, Oregon, and New York. IV. Stroke diagnosis and its relation to demographics, risk factors, and clinical status after stroke. Stroke. Jun 1990;21(6):867-73. [Medline].
28. Dam M, Tonin P, Casson S. The effects of long-term rehabilitation therapy on poststroke hemiplegic patients. Stroke. Aug 1993;24(8):1186-91. [Medline].
29. Delisa JA, Mikulic MA, Melnick RR. Stroke rehabilitation: Part II. Recovery and complications. Am Fam Physician. Dec 1982;26(6):143-51. [Medline].
30. Dombovy ML, Basford JR, Whisnant JP. Disability and use of rehabilitation services following stroke in Rochester, Minnesota, 1975-1979. Stroke. Sep-Oct 1987;18(5):830-6. [Medline].
31. Dombovy ML, Sandok BA, Basford JR. Rehabilitation for stroke: a review. Stroke. May-Jun 1986;17(3):363-9. [Medline].
32. Evans RL, Bishop DS, Haselkorn JK. Factors predicting satisfactory home care after stroke. Arch Phys Med Rehabil. Feb 1991;72(2):144-7. [Medline].
33. Feigenson JS. Stroke rehabilitation: effectiveness, benefits, and cost. Some practical considerations. Stroke. Jan-Feb 1979;10(1):1-4. [Medline].
34. Fugl-Meyer AR, Jaasko L. Post-stroke hemiplegia and sexual intercourse. Scand J Rehabil Med Suppl. 1980;7:158-66. [Medline].
35. Garraway WM, Whisnant JP, Drury I. The changing pattern of survival following stroke. Stroke. Sep-Oct 1983;14(5):699-703. [Medline].
36. Garrison SJ, Rolak LA, Dodaro RR, et al. Rehabilitation of the stroke patient. In: DeLisa JA, ed. Rehabilitation Medicine: Principles and Practice. 2^nd ed. Philadelphia, Pa: JB Lippincott; 1993.
37. Gladman J, Whynes D, Lincoln N. Cost comparison of domiciliary and hospital-based stroke rehabilitation. DOMINO Study Group. Age Ageing. May 1994;23(3):241-5. [Medline].
38. Gustafsson D, Elg M. The pharmacodynamics and pharmacokinetics of the oral direct thrombin inhibitor ximelagatran and its active metabolite melagatran: a mini-review. Thromb Res. Jul 15 2003;109 Suppl 1:S9-15. [Medline].
39. Hacke W, Kaste M, Fieschi C. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. Oct 4 1995;274(13):1017-25. [Medline].
40. Harlacher R, Pullen R, Pientka L. Costs of rehabilitation in elderly patients with stroke in a German geriatric clinic. Int J Rehabil Res. Sep 2000;23(3):169-71. [Medline].
41. Harlow HF. Higher functions of the nervous system. Annu Rev Physiol. 1953;15:493-514. [Medline].
42. Heinemann AW, Roth EJ, Cichowski K. Multivariate analysis of improvement and outcome following stroke rehabilitation. Arch Neurol. Nov 1987;44(11):1167-72. [Medline].
43. Indredavik B, Bakke F, Solberg R. Benefit of a stroke unit: a randomized controlled trial. Stroke. Aug 1991;22(8):1026-31. [Medline].
44. Johnston MV, Kirshblum S, Shiflett SC. Prediction of outcomes following rehabilitation of stroke patients. Neuro Rehabil. 1992;2(4):72-97.
45. Kauhanen ML, Korpelainen JT, Hiltunen P. Domains and determinants of quality of life after stroke caused by brain infarction. Arch Phys Me