Table of Contents  

Pinter: Rehabilitation in stroke patients – focusing on the future


Stroke is a common disease worldwide, with an estimated incidence of 150 per 100 000 in developed countries.1 A great number of patients have activity limitations caused by sensorimotor and cognitive impairments.

Therefore, stroke is a leading cause of disability and the burden of stroke is borne disproportionately by older people, among whom the incidence and prevalence of ischaemic stroke are higher than in younger individuals.2,3 For each successive 10 years after 55 years of age, the stroke rate more than doubles in both men and women; 65% of all strokes occur in individuals older than 65 years.2,4 Over time, performance measure-based treatment rates for ischaemic stroke patients in all age groups have improved substantially, resulting in smaller age-related treatment gaps.5 Functional outcomes are also worse in older patients who experience ischaemic stroke than in younger patients, and these differences remain despite adjustment for baseline differences in stroke risk factors and other comorbidities.68

Improved understanding of age-related differences in stroke presentation, quality of care and outcomes will become even more important as the number of stroke-related events in older people increases dramatically over forthcoming decades as a result of the ageing population.3,9,10 Worldwide, annually, about 15 million people have a stroke. Five million survivors are left permanently disabled, with complications including motor (50–83%), cognitive (50%) and language impairments (23–36%) and psychological disturbances (20%). Estimates indicate that 33–42% of patients still require assistance with activities of daily living (ADLs) 6 years post stroke, and 36% of patients remain disabled after 5 years.9,11

Recovery after stroke is complex. Many interventions have been developed to support motor and cognitive recovery (recovery of impairment and associated function), and many randomized controlled trials and systematic reviews have been carried out.12,13 However, most of these interventions do not explicitly target a specific age group and have been tested using a variety of patient groups and outcome measures.

Search strategy

This review focuses mainly on the evidence underlying stroke rehabilitation, including the principles of rehabilitation practice and specific, particularly neurophysiological, interventions. References for this review were identified through searches using MEDLINE, EMBASE and the Cochrane Library, with the search terms ‘stroke’ and ‘ischaemia’ in combination with ‘rehabilitation’, ‘motor function’, ‘walking ability’, ‘cognitive function’, ‘aphasia’ ‘participation’ and ’functional outcome’.

Preference was given to papers published between 2000 and 2014. Only papers published in English were reviewed in detail, selecting studies for evaluating the evidence of therapeutic options and the effectiveness of functional outcome in older stroke patients. Since spontaneous recovery is an important confounder of rehabilitation interventions in observational studies in the first 3 months after stroke, emphasis on randomized trials and systematic reviews is crucial in stroke.14

The aims of this review are to summarize the available evidence from systematic reviews of randomized controlled trials and Cochrane reviews, and to identify randomized clinical trials in which interventions show promising efficacy.

Motor impairment

The most common and widely recognized impairment caused by stroke is motor impairment, characterized as a limitation or loss of function in motor control or a limitation in mobility. Therefore, much of the focus of stroke rehabilitation is on the recovery of impaired movement and the associated functions based on the paradigm of motor relearning.15 Task- and context-specific training are accepted principles in motor learning, which suggests that training should target the goals that are relevant for the needs of patients.

Apart from occupational therapy, strategies focus on the practice of personal ADLs.16,17 Several interventions have a potential effect on arm function, at least within the selected populations that have been studied. These interventions include constraint-induced movement therapy (CIMT), electromyographic (EMG) biofeedback, mental practice with motor imagery and robotics. In addition, simultaneous bilateral training, repetitive task training and electrostimulation showed a borderline effect.18

The most promising intervention for upper limb (arm) function seems to be CIMT, on which there have been a substantial number of trials, including a multicentre study.19 Patients who benefit from CIMT are those with active wrist and finger extension on the affected limb who are neglecting this movement in daily life. Although CIMT appears to have moderately positive effects on disability and motor function improvement, it is not clear whether it maintains efficacy in the long run.20 A meta-analysis published in 2011 found a trend towards positive effects of high-intensity and low-intensity CIMT in acute or subacute stroke, but also suggests that low-intensity CIMT might be more beneficial during this period than high-intensity CIMT.21

In recent years, new electromechanical-assisted training therapies have been developed to improve arm function in stroke patients.2226 Robotic devices can provide high-intensity, repetitive task-specific, interactive treatment of the impaired limb (passive and/or active-assisted exercises) and allow patients’ motor recovery to be monitored, measuring changes in forces and movement kinematics.27

In a review by Mehrholz et al.,28 it was stressed that the use of robotic devices may not significantly improve ADLs, although evidence for improvement of motor function and strength of the upper limb was obtained. It is important to consider that robotic therapy uses robots simply as vehicles to apply many repetitions of arm training.29 Furthermore, it seems unlikely that therapy provided by robotic devices will give better results than therapy provided by humans under the premise that intensity, amount and frequency of therapy are exactly comparable.28 Moreover, beneficial effects on motor recovery of the arm have been recorded in trials of mental practice30 and EMG biofeedback,31,32 while repetitive task training and electrostimulation show a borderline effect.18,33 However, for none of these interventions is there sufficient evidence to come to a conclusion about their effectiveness in a routine clinical setting.18

Although simultaneous bilateral training involving the execution of identical activities with both arms simultaneously is well established,34 there is currently insufficient evidence about the relative effect of bilateral training compared with placebo, no intervention or usual care. Studies of varied methodological quality suggest that bilateral training may be no more effective than other upper limb interventions for performance in ADLs or motor functional outcome of the upper limb.35

Altogether, very limited evidence seems to be available for interventions to improve hand function. Nevertheless, this lack of evidence could be changed by a relatively small number of new trials.

Recovery of lower limb motor function, postural control and walking ability following stroke is crucial for enhancing independence in mobility, and there it is no doubt that physiotherapy is effective in the early phase after stroke.36 However, a recent meta-analysis supports the efficacy of physiotherapy interventions late after stroke.37 Impaired postural control and a high incidence of falls are commonly observed in stroke patients, particularly in the early phase.38 Therefore, restoration of postural stability is essential. Interventions to facilitate sitting and standing balance include neurophysiological and motor approaches, repetitive task training as well as biofeedback with a moving platform. Task-specific training seems to improve sit-to-stand function and standing balance,39 while biofeedback with a force plate or a moving platform has been found to improve stand symmetry alone but did not improve balance during active functional activities; nor did it improve overall independence.40,41 Nevertheless, despite a considerable number of intervention studies, at the moment no definitive conclusions can be drawn regarding the best approach to facilitate the recovery of balance following stroke.18,42

Since there is a direct relation between independence in walking and lower limb strength, the primary goal of therapy of lower limb motor impairment is to facilitate the recovery of movement and consequently to improve the function of walking. The outcome measurement for interventions targeted at walking ability predominantly include measures of gait speed, although often included are measures of stride length, gait endurance and functional ambulation.

Apparent improvements in walking speed are obtained for several interventions, including high-intensity physiotherapy, repetitive task training,43,44 cardiorespiratory physical fitness training39 and fitness training incorporating a mixture of cardiorespiratory training.45,46 Overall, the trials have tended to be small and their quality inadequate; thus, there are no techniques whose routine use in clinical practice can be recommended. Only the trials of cardiorespiratory physical fitness training provided robust evidence of a benefit in terms of walking ability.39

In recent years, in addition to overground gait training,47 treadmill training with and without partial body weight support enabling the repetitive practice of complex gait cycles has been introduced for the rehabilitation of stroke patients.48 A randomized controlled trial has provided evidence that treadmill walking with body weight support tends to result in more people walking independently and earlier after stroke.49 Since there is clear evidence from systematic reviews that more intensive intervention is associated with better outcome,50 it can be argued that the difference between the groups results not from the type of training but from the amount of training afforded by the interventions. However, one disadvantage of treadmill training is the effort required by therapists to set the paretic limbs and to control weight shift. For this reason, automated electromechanical gait machines were introduced. These consisting of either a robot-driven exoskeleton orthosis51 or an electromechanical solution with two driven foot plates simulating the phases of gait.52

The use of electromechanical-assisted gait training devices in combination with physiotherapy increases the chance of regaining independent walking ability after stroke, although no improvements in walking velocity or walking capacity can be expected. It appears that patients in the acute phase benefit more than chronic stroke patients.53

In up to 20% of stroke patients, a persisting weakness of the contralateral foot is a major cause of gait impairment, usually described as ‘drop foot’.54 Such patients are unable to actively dorsiflex the foot during the swing phase of gait, which results in compensatory movement patterns, decreased gait velocity, restricted functional mobility and an increased risk of falls.55,56

Functional electrical stimulation (FES) is a popular post-stroke gait rehabilitation intervention. Use of drop foot stimulation can be traced back almost 50 years57 and, although modern technology has improved functionality and reliability, the basic principles of application have changed very little.58 Surface or implanted electrodes are placed over the common peroneal nerve or its branches, delivering pulses of electricity to produce ankle dorsiflexion and eversion in order to lift the foot through the swing phase of walking and place it in a safe position for weight bearing at first contact, stabilizing the ankle. The stimulation is timed to the gait cycle, often using a pressure-sensitive foot switch placed inside the shoe, although tilt sensors have also been used.59 Stimulation begins when the heel lifts from the ground and continues until weight is returned to the foot switch.

Although stroke causes multijoint gait deficits, FES is commonly used for the correction of only the swing phase foot drop. Ankle plantarflexor muscles play an important role during gait. Surface stimulation of the peroneal nerve and an ankle–foot orthosis have been shown to improve gait and, as a result, social participation and quality of life.58,6062 A randomized single-blind trial of ankle–foot orthosis compared with surface stimulation in stroke patients with drop foot found no significant difference in gait speed. Nevertheless, user satisfaction was significantly higher in the drop foot stimulation group.60

Recently, an implantable four-channel drop foot stimulator (ActiGait®; Ottobock, Berlin, Germany) with independent electrode adjustment, enabling a more specific stimulation, resulted in improved walking speed and restoration of the physiological ankle movement in patients with stroke-related drop foot.63,64 The therapeutic effect was found to be improved compared with surface stimulation, combined with an easier handling of the stimulation device.65

Virtual reality is a relatively recent approach that may enable simulated practice of functional tasks at a higher dosage than traditional therapies.50,66 Virtual reality has been defined as the ‘use of interactive simulations created with computer hardware and software to present users with opportunities to engage in environments that appear and feel similar to real-world objects and events’.67 Although research into the value of virtual reality in rehabilitation is becoming more common,68,69 virtual reality is not yet commonplace in clinical rehabilitation settings. The findings of a recent review suggest that virtual reality is a promising new rehabilitation approach for stroke recovery. However, to date, the number of studies is too low and the sample size too small to draw conclusions.70

Swallowing problems are a frequent consequence of stroke and can affect up to 80% of stroke patients in the acute phase.71 Although the majority of stroke patients show some swallowing recovery within the first month after stroke, up to 40% of patients continue to experience dysphagic problems, to different degrees, a year later.72,73 Indeed, dysphagia confers an increased risk of pneumonia after stroke,74 and patients with dysphagia in the chronic phase require a gastrostomy tube for feeding.73 Current therapeutic modalities used to manage dysphagic stroke, apart from behavioural adaptations,75,76 include neuromuscular stimulation strategies.7781 Evidence that enteral feeding alters swallow physiology is lacking, and there are significant limitations in the clinical practice.75 Against this background, interest in utilizing the so-called ‘neuroplasticity’ of the central nervous system to adapt to the lesion, promoting functional recovery, has grown.

Observations of recovery of swallow function during the acute phase post stroke is associated with enlargement of the cortical representation of the pharyngeal region in the undamaged hemisphere,82 and led to a novel therapy strategy, pharyngeal electrical stimulation (PES). Consequently, it has been shown that PES – using swallowed intraluminal electrodes – can enhance the excitability and organization of the human pharyngeal motor cortex.83 Fraser80 established the precise parameters for PES necessary to induce short-term (1-hour) excitation of the swallowing motor system in stroke patients with dysphagia, suggesting that such treatment might also be effective in the longer term. Indeed, a randomized controlled study of stroke patients83 found that PES resulted in long-term improvement in dysphagia in comparison with a control group. Subsequently, this study confirmed consistency of treatment effect and proved that the treatment benefit in the target patient population was both substantial and statistically significant.83

It seems that PES is safe and well tolerated in stroke patients and study findings, although preliminary, suggest that it reduces aspiration and improves global feeding status.83 Nevertheless, a larger trial using PES will help establish the future clinical utility of this novel rehabilitative tool.

Cognitive and other impairments

Cognitive impairment is a frequent consequence of stroke, and it has been estimated that 50% of patients present cognitive impairment in the early phase after stroke and up to 32% of patients demonstrate persistent cognitive impairment up to 3 years after the onset of their first stroke.84

Typically, domains of cognition are attention and attention span, concentration, memory and executive functions, while visuospatial perception and apraxia are classified as disorders that are separate from cognitive impairment.

Attention deficits are the most prominent neuropsychological changes in stroke survivors, reducing cognitive productivity while leaving other cognitive functions intact.85 However, trials of various interventions aimed at cognitive rehabilitation have revealed that training might improve alertness and attention span in patients with attention deficit.86

In a review of interventions for spatial neglect, improvement was found in the patients’ ability to complete tests such as marking the midpoint of a line and finding visual targets. However, its effect on patients’ ability to carry out meaningful everyday tasks or to live independently was not clear.87

Although speech therapy significantly improves language and communication deficits,88,89 particularly during the very early stages of stroke recovery,90 residual aphasia has a multifactorial impact on quality of life and participation.91

Overall, information on the clinical effects of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce.12

Cognitive and psychosocial disorders are known to disrupt the daily activities of people with stroke.92 Often, stroke patients do not spontaneously find effective strategies to cope with affective and cognitive problems.93 However, after adjusting for the degree of physical disability, people with cognitive deficits remain more dependent, and this dependence has been found be increased 2 years post stroke.94,95

Cognitive impairment following stroke reduces independence in performing basic ADLs, such as eating, dressing and toileting, as well as instrumental ADLs, such as housework and social interactions.96 However, there are not enough high-quality trials to be able to make recommendations that support or refute the use of specific cognitive retraining interventions to improve functional outcomes following a stroke.97

In recent years, efforts have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies such as additional brain stimulation to enhance cognitive recovery.98

Repetitive transcranial magnetic stimulation (rTMS) was introduced as a therapeutic tool for improving the efficacy of rehabilitation for recovery after stroke.99 It is evident that disturbances of interhemispherical processes after stroke result in a pathological hyperactivity of the intact hemisphere.100

There is a growing body of research investigating the capacity of rTMS to facilitate recovery in stroke patients by modifying cortical and subcortical networks. Clinical trials applying rTMS have already shown promising effects on recovery of cognitive functions.101 In line with this finding, a few small studies have reported that reducing activity in the left (non-affected) parietal lobe by inhibitory low-frequency rTMS can improve hemineglect by reducing abnormally increased interhemispherical transcallosal inhibition from the non-affected to the affected cortex.102,103 Moreover, in a recent review it was concluded that rTMS is a promising approach to reduce the interhemispherical imbalance in neglect patients and to ameliorate symptoms.104

Aphasia is a frequent consequence of stroke with serious implications for patients’ autonomy. Although speech therapy significantly improves language and communication deficits, particularly in the very early stages of stroke recovery, residual aphasia has a multifactorial impact on quality of life and participation.

With reference to the theory of transcallosal disinhibition,105 recent studies in stroke patients with chronic aphasia suggest that restoring the left-hemispheric language network by inhibiting the overactive right homologue frontal speech areas using rTMS as a complementary treatment is linked to better recovery of language and communications deficits.106 Moreover, a recent functional imaging study proposed that inhibitory rTMS of the right-hemispheric Broca homologue together with subsequent speech therapy prevents the establishment of right-hemispheric lateralization and that this normalization of the activation pattern might be accompanied by enhanced clinical improvement.107

Overall, based on evidence that rTMS is able to non-invasively modulate cortical activity, this technique is growing in importance in the field of stroke recovery. The possibility of non-invasively interacting with the functioning of the brain and its plasticity mechanisms opens new scenarios in the neurorehabilitation field.


Stroke rehabilitation presents specific challenges for research and for the application of evidence-based practice, as well as neurophysiology-related novel strategies. Although relearning of skills and theories of motor control are crucial to many rehabilitation interventions, the neurophysiology underpinning stroke rehabilitation is often poorly established. Moreover, interventions tend to be complex, containing several interrelated components, and therapies target several different problems from relieving very specific impairments to improving activity and participation.

The substantial increase in the number of clinical trials investigating rehabilitation in the past 20 years shows the rising interest of rehabilitation clinicians in evidence-based care. There are still many gaps and shortcomings in the evidence base for interventions to promote motor and cognitive recovery after stroke. At present, the evidence base for clinical practice can provide only broad indicative guidance. The main general recommendations seem to be that the alleviation of cognitive impairment and restoration of motor function should focus on high-intensity, repetitive task-specific practice with feedback on performance. Nevertheless, we believe that neuroplasticity enhanced due to neuromodulation of different neuronal systems will play a major role in the field of neurorehabilitation in the future.



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