The effect of mirror therapy in stroke

The effect of mirror therapy compared to usual care on upper limb function in stroke patients

A systematic review

By: Yannick Breeschooten

Keywords: Mirror therapy; stroke; upper limb; motor impairment; rehabilitation.

Stroke is the second largest cause of death and disability worldwide with over 13 million new cases annually.1,2 Stroke causes damage to the brain which can affect movement and sensation of the arm.3,4 In the acute phase the prevalence of upper limb (i.e. arm, hand, and/or fingers) impairment is 50-80%, in the chronic phase this is 4050%.5 The most frequently observed impairments of the upper limb after stroke are paresis, abnormal muscle tone, a decrease in sensation, and coordination.5,6 Motor impairments of the upper limb are disabling, individuals with a stroke can experience a decrease in the ability to perform activities of daily living (ADLs). Performing ADLs largely depends on arm function, in particular activities such as feeding, dressing, self-care, and bathing.3,4,7 Between 55% and 75% of stroke survivors suffer long-term limitations in upper limb function.8 Only 5% to 20% achieve full functional recovery of the affected upper limb. Long-term motor impairment of the upper limb is associated with anxiety, a decrease in health-related quality of life, and well-being.3,4 For these reasons improving upper limb function during rehabilitation after stroke is a key element to maximize recovery.3,4 Usual care for the improvement of upper limb function can consist of several therapeutic interventions. These include robotic training, electrical stimulation, biofeedback, bilateral arm training, repetitive task training, task-specific training, and ‘hands-on’ therapy.2,4,6 Over the past several

Abstract

Background and purpose Motor impairment of the upper limb is common in the sub-acute (<6 months) and chronic phase (> 6 months) after stroke. These motor impairments are disabling and individuals experience a decrease in the ability to perform activities of daily living. Mirror therapy (MT) can be beneficial in improving motor impairment after stroke and is easy to use in addition to usual care (UC) (e.g. bilateral arm training) At present no review exists that describes the effect of MT combined with UC on motor impairment of the upper limb. The aim of this study is to investigate the effect of MT in combination with UC, compared to UC alone for improving upper limb motor function after stroke.

Methods A systematic search was performed in the electronic databases CINAHL, Pubmed/Medline, and Embase. Quality appraisal was done using the PEDro-scale. After data extraction, a best-evidence synthesis was conducted using the criteria set out by van Peppen et al.

Results Six studies were included in this review. Based on these studies there is limited evidence for the use of MT combined with UC. A sub-synthesis was preformed comparing MT combined with UC in the sub-acute and chronic phase. The sub-synthesis showed strong evidence for the use of MT in the chronic phase.

Conclusions There is limited evidence that MT in addition to UC is more effective in improving upper limb motor function. Sub-synthesis showed that MT combined with UC may be more beneficial in the chronic phase after stroke.

years mirror therapy (MT) has been proposed to be beneficial in improving motor impairment of the upper limb after stroke.6,7,9–11 MT was first described by Ramachandran in 1996 and was used for the treatment of phantom limb pain.3,12 The concept of using MT in stroke rehabilitation was derived from the work of Ramachandran.3,9 During MT stroke patients perform movements with the unimpaired limb while watching its reflection in a 2x2 meter mirror placed in the individual’s sagittal plane.9 This creates a visual illusion of enhanced movement ability in the impaired limb.13 Different hypotheses have been raised explaining the mechanisms that underlie the effect of MT. At first, it was suggested that paralysis after stroke might have a ‘learned’ component that MT could help ‘unlearn’.9 Secondly it is hypothesized that MT is a form of visually oriented motor imagery. Motor imagery itself is effective in rehabilitation protocols for hemiparesis, and the visual feedback of the imagined movement induced by the mirror can further enhance this effect.3,6,8 Thirdly it is hypothesized that MT activates the bilateral cortex which causes reorganization in other areas around the affected brain site, thus allowing for replacement of function and therefore affecting recovery of motor function.9,13,14 Two recent systematic reviews show that MT can be a promising intervention for improving upper limb function.7,9 Both in the sub-acute (< 6 months) and chronic phase after a stroke (> 6 months).7,9 The randomized controlled trial (RCT) of Yavuzer et al., reported beneficial outcomes in motor recovery of the upper limb when MT was followed in addition to usual care (UC).15 MT is a technique that is easy-to-apply is low-cost and it is proposed that MT can be used in conjunction with UC.8,9 At present no review exists that describes the effect of MT combined with UC. Therefore, the aim of this study is to investigate the effect of MT combined with UC, compared to only UC in improving upper limb motor function after stroke.

Methods Design In conducting and reporting this systematic review the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed.16

Information sources For the identification of eligible studies, a systematic search was performed in the electronic databases CINAHL, Pubmed/Medline, and Embase up to March 2022.

Search strategy The PICO framework was used to formulate the search queries. P: Patients who suffered a stroke aged 18 years or over with upper limb impairment I: Mirror therapy C: Usual care O: Upper limb motor function For all the PICO elements, the MesH terms and title/abstract terms were identified and added to the search. No limitations to the search were made. A complete overview of the search strategy can be found in Appendix 1 in the supplementary online material.

Inclusion criteria Studies were eligible for inclusion if they met the following criteria; Patients aged 18 years or over who suffered a stroke; mirror therapy combined with usual care;the outcome measured upper limb motor function; randomized controlled trials, and full-text available in Dutch or English. Studies were excluded if they were; pilot or feasibility studies or patients suffering from other neurological disorders.

Study selection Studies were first screened for eligibility based on title and abstract, this was done by two independent reviewers (AS, YB). Disagreement between reviewers was discussed until consensus was reached. After this full-text articles were read and screened. In addition, the reference lists of all relevant articles were screened manually.

Data extraction The reviewer (YB) extracted data relevant to the research question. The following data were extracted: authors; publication year; country of data collection; study design; population characteristics such as age and gender; type of stroke; time since stroke; paretic side; and the number of participants per study group; description of the intervention, and control; intervention period, and outcomes (Table 1). If data were missing attempts were made to contact the first two authors to acquire the missing information.

Methodological Quality Appraisal Two reviewers (AS, YB) independently assessed the methodological quality of the studies included. The quality appraisal was scored using a scale for quality assessment of RCT’s the PEDro scale.17 Disagreement between reviewers was discussed until consensus was reached. Depending on the score on the PEDro scale an article was placed in one of the following categories17 : ‘Poor’ quality <4 points ‘Fair’ quality 4 to 5 points ‘Good’ quality 6 to 8 points ‘Excellent’ quality 9 to 10 points A score of 8 is considered optimal for trials that evaluate complex interventions.17

Synthesis Heterogeneity due to differences in outcomes, intervention type, and patient characteristics was expected. For this reason, a best-evidence synthesis is most appropriate. A best-evidence synthesis was applied to all studies using the criteria set out by van Peppen et al., based on the score of the PEDro scale.18 Five levels of evidence were distinguished; strong evidence;moderate evidence ; limited evidence;indicative findings and; no or insufficient evidence.18 No evidence was classified if the number of studies that showed evidence was < 50%.18 If results show a difference in outcome of MT combined with UC in the

Identification of studies via databases and registers

Records identified from*:

Databases:

Pubmed (n = 48)

CINAHL (n= 80)

Embase (n= 184)

Total/combined (n=312) Records removed before screening:

Duplicate records removed (n = 88 )

Records marked as ineligible by automation tools (n = 0)

Records removed for other reasons (n = 0)

Records screened (n = 224 ) Records excluded** (n = 182) phase after stroke44–46,48 and two studies included patients in the chronic phase (> 6 months).43,47 One study included patients with severe motor function impairment of the upper limb (Motricity Index score less than 57 out of 100).46 In Table 2 an overview is given of the intervention, outcome parameters, and study results. Overall, both the MT group and CT group followed therapy sessions five days a week for three to six weeks.43–48 The duration of MT sessions varied from 15 minutes to 60 minutes per session and was followed in addition to CT in all studies.43–48 All studies had a baseline and final assessment but no follow-up.

Reports sought for retrieval (n = 42)

Reports assessed for eligibility (n = 30)

Included

Studies included in review (n = 6) Reports of included studies (n = 0) Reports not retrieved (n = 12)

Reports excluded:

Reason 1 wrong design (n = 1 )

Reason 2 wrong comparison (n = 5)

Reason 3 wrong intervention (n = 10)

Reason 4 wrong outcome (n= 5)

Reason 5 wrong population (n=2)

Reason 6 article not available in Dutch or English (n=1) Methodological quality The assessment of the methodological quality of the six included studies was done independently by two reviewers. The scores on the PEDro-scale ranged from four to eight, which indicated ‘fair’ to ‘good’ quality. Two studies had a score of four and one of five suggesting ‘fair’ quality of the studies. The weaknesses that were identified in these studies were lack of blinding, no description of allocation procedures, and limited description of statistical analyses.44,45,47 Three studies had ‘good’ quality but scores were lowered because of the inadequate description of the blinding procedure and one study did not mention the use of an intention to treat analysis.43,46,48 An overview of the quality assessment is found in Table 3.

Figure 1 Flow scheme of included studies

different phases of stroke (i.e. sub-acute or chronic) a sub-*Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). synthesis will be conducted. The goal of the sub-synthesis **If automation tools were used, indicate how many records were excluded by a human and how many were is to determine if there is a difference in effect of the use excluded by automation tools. of MT combined with UC in the different phases following a stroke.

Results Study selection of studies screened and assessed The primary search in CINAHL, Pubmed/Medline, and 1 Embase yielded 312 hits of which 88 were duplicates. Duplicates were removed and the remaining studies were screened on title and abstract. After screening the title and abstract 42 studies were considered to be possibly relevant. Of these studies, twelve studies were not available in full text, which left 30 possible relevant studies. After full-text screening 24 studies were excluded. One study did not meet inclusion criteria based on the study design.19 Five studies used MT in the control group.20–24 Ten studies did not meet the criteria for the intervention.25–34 Five studies focused solely on hand function or did not have the correct outcome.35–39 Two studies were excluded based on the population which did not meet the inclusion criteria.40,41 Lastly one article was excluded based on the language criterion since the study was written in Turkish.42 In total, six studies were included (Figure 1).43–47

Study characteristics In Table 1, an overview of study characteristics is shown. Two studies took place in an outpatient setting 43,47, and four studies in an in-patient setting.44–46,48, In total the studies included 218 participants (mean age range 54-66 years).43–48 The sample size of the studies ranged from n=25 to n=60.44,47 Four studies included patients in the sub-acute (< 6 months) Results of individual studies Chinnavan et al.47 and Wu et al.43 included participants in the chronic phase of stroke. Both studies showed a significant between-group difference in favor of the MT group. In the study of Wu et al, no analysis of within-group differences was mentioned.43,47 The within-group analysis in the study of Chinnavan et al.47 showed a significant improvement in Fugel Meyer Assessment (FMA) score in both the intervention group and control group. Four studies conducted their research in the sub-acute phase of stroke. 44–46,48 The study of Chan et al, showed significant within-group improvement in FMA, Wolf motor function test-time (WMFT- time), and Wolf motor function test-functional ability scores (WMFT-FAS). No significant between-group difference was found.46 Gurbuz et al showed significant within-group differences in both the Brunstromm score and the FMA score for both groups. The between-group difference only showed a significant improvement in FMA score in the MT group 48 Lee et al showed significant improvement in the FMA score, Motor function test (MFT) score, and Brunstromm score in both groups. The between-group difference showed significant improvement in the MT group on all outcomes.45 Radjweska et al. was the only study that had subgroups within the MT and CT group based on which side was affected. All subgroups showed significant improvement on both the Frenchay Arm test (FAT) score and Motor status score (MSS). Only the left arm group showed a significant betweengroup difference in the FAT in favor of the MT group. 44 Synthesis of results Mirror therapy combined with usual care vs. usual care All six studies compared MT combined with UC to UC

Citation/ location Study design

Chinnavan et al., (2020) Malaysia 47 Prospective RCT Stroke patients with a group between 45 to 65 years (over 6 months and above- chronic phase)

MT = 13 CT = 12 Outpatient N/A TG: 18/7 N/A N/A Lesion site: N/A Side of brain lesion: N/A Dominant side: N/A Paretic side: TG: 14/11

Sample N Treatment setting Type of stroke (I/H) Gender (M/F) Average age mean (SD) (years) Time since stroke mean (SD) Lesion site (C/S) /Side of brain lesion/ (L/R) Paretic side (L/R) / Dominant side (L/R)

Chan et al., (2018) China 46 Prospective, single blinded RCT Stroke patients with a severely impaired arm (within 1 month- subacute phase)

MT = 20 CT = 21 In-patient

Gurbuz et al., (2016) Turkey 48 Assessorblinded RCT Stroke patients (within the past 6 months- subacute phase) In-patient

MT = 16 CT = 15 MT: 10/5 CT: 17/3

MT: 15/1 CT: 10/5

Lee et al., (2012) Korea 45 RCT Stroke patients (previous six months – subacute phase) In-patient

MT = 14 CT = 14 N/A

Radajewska et al., (2013) Poland 44 RC Hemiparetic right-handed stroke patients (810 weeks after onset- subacute phase) In-patient

MT subgroup right arm paresis = 15 MT subgroup left arm paresis = 15 CT subgroup right arm paresis = 15 CT subgroup left arm paresis = 15 N/A

Wu et al., (2013) Taiwan 43 Single-blinded RCT Stroke patients (onset of more than 6 months- chronic phase)

MT = 16 CT = 17 Outpatient MT: 10/6 CT: 10/7 MT: 10/5 CT: 12/8

MT: 10/6 CT: 7/8

MT: 8/5 CT: 7/6

MT: 18/12 CT: 18/12

MT: 11/5 CT: 12/5 MT: 65.3 (11.8) CT: 64.1 (13.3) MT: 13.9 (6.7) CT: 12.7 (6.6) (days)

MT: 60.9 (10.9) CT: 60.8 (20.0) MT: 46.1 (43.3) CT: 42.4 (37.8) (days)

MT: 58.8 (12.1) CT: 55.4 (12.2) MT: 3.5 (1.5) CT: 3.6 (1.3) (months)

(L/R) MT: female: 61.2/60.8, male 60.2/57.3 (L/R) MT: 10/10 CT: 8/9 (weeks)

CT: female 66/60.1, male 57.7/63.1 Lesion site: MT: 4/11 CT: 3/17 Side of brain lesion: N/A Dominant side: N/A Paretic side: MT: 10/5 CT: 12/8

Lesion site: N/A Side of brain lesion: N/A Dominant side: MT: 1/15 CT: 0/15 Paretic side: MT: 8/8 CT: 6/9

Lesion site: N/A Side of brain lesion: N/A Dominant side: N/A Paretic side: MT: 5/8 CT: 6/7

Lesion site: N/A Side of brain lesion: N/A Dominant side: N/A

Paretic side: MT: 15/15 CT: 15/15

MT: 54.77 (11.66) CT: 53.59 (10.21) MT: 19.31 (12.57) CT: 21.88 (15.55) (months) Lesion site: N/A Side of brain lesion: MT: 8/8 CT: 7/10 Dominant side: N/A Paretic side: N/A

RCT = Randomized controlled trial; N = number of participants; MT = mirror therapy group; CT = conventional therapy group; TG = total group; I/H =Ischemic/Haemorrhagic; M/F = male/female; SD = standard deviation; C/S = Cotrical/Subcortical; L/R = Left/Right; N/A =not available.

alone. Three studies showed a significant improvement in upper limb motor function in favor of the intervention group.43,45,47 The other three studies did not find a statistically significant between-group difference.44,46,48 One of the studies is a high-quality RCT ( PEDro score > 4) that shows a significant improvement in motor function of the upper limb. Therefore, there is limited evidence for MT combined with UC to be superior to UC alone. Mirror therapy combined with usual care vs. usual care: Sub-acute or chronic phase after stroke Four studies were conducted in the sub-acute phase after stroke.44–46,48 One study showed no significant between-group difference.46 Two studies showed significant improvement in one outcome, but other outcomes showed no significant between-group difference 44,48 Lastly one study showed significant improvement in upper limb motor function in the MT group.45 Since < 50% of the studies show evidence, no evidence will be classified for MT in the sub-acute phase. Two of the included studies were conducted in the chronic phase after stroke. Both studies had a score of at least four on the PEDro scale and showed significant improvement in upper limb motor function in favor of the MT group.43,47 This shows strong evidence for the use of MT in addition to usual care in the chronic phase of stroke.

Discussion The aim of this systematic review was to summarise current evidence on the effect of MT combined with UC, compared to UC alone in improving upper limb motor function after stroke. The studies that are included in this review show limited evidence for the superiority of MT in addition to UC versus CT alone. A sub-synthesis of MT combined with UC in the sub-acute or chronic phase after stroke showed strong evidence for the use of MT combined with UC in the chronic phase. It should be noted that this is based on only two studies, with one of them having limited internal validity.47 For this reason the results of the sub-synthesis should be interpreted with caution. The systematic review and meta-analysis of Gardenia et al. shows a small benefit for MT in comparison to UC in the improvement of upper limb function.9 Only this does not reach statistical significance. The studies included in their review had similar characteristics like mild-to-moderate impairment of the affected arm, and a diverse range of therapies used in the control groups, and most studies included patients in the sub-acute phase of stroke.9 The studies showed significant improvement within groups but not between groups. This could be because there are mostly patients included in the sub-acute phase of stroke. In this phase, spontaneous recovery after a stroke is still taking place.46 Which could explain the improvement in upper limb motor function in both groups. Also, most studies did not report significant improvement in the Brunstromm stage, in this systematic review the same was found. These results were found in studies where MT solely focused on the distal part of the upper limb. In the studies that focused on both the proximal and distal parts, a significant improvement was found in favor of the MT group.9 This could be because synergy patterns are evaluated with the Brunstromm stages and synergy patterns are mostly triggered when multi-joint movements are made.48 The review of Jafaar et al. showed similar improvements in upper limb motor function in the chronic phase of stroke.7 It is proposed that neuroplasticity is still enhanced during a long-lasting period post-stroke. This enables improvement in function even in the chronic phase of stroke.7 Some patients still show improvement 24 months after stroke.7 Therefore it seems that recovery is not limited to the 3-6 month period and MT can still be beneficial in the chronic phase.7 The strengths and limitations of this review should be considered in evaluating the findings. Not all articles that were possibly eligible were retrieved full-text. Authors were contacted to retrieve the full-text articles but unfortunately, there was no response. Due to this important findings might be missed. Another limitation is that this review focused solely on general upper limb motor impairment. By doing this, studies that focused only on the hand and wrist were excluded. If the review focused on more specific outcomes dived in specific regions (i.e. shoulder, elbow, wrist, and hand) this may have given a completer impression of the effect of MT. The strengths of the review are that this is the first review that focuses solely on the effect of MT combined with UC . Also, the risk of bias was reduced by having two independent reviewers do the study selection and quality appraisal. Four of the six articles showed an FMA score that was greater than the minimally clinically important difference (MCID).45–48 Three of these articles showed greater improvement in the FMA score in the intervention group compared to the control group.45,47,48 The MCID of WMFT-time was 19 sec and for WMFT-FAS this was 1.2 points.46 In the study of Chan et al. both groups showed an improvement in the WMFT-time and WMFT-FAS that was clinically meaning-

Table 3 Methodological quality of included studies using the Physiotherapy Evidence Database (PEDro) scale.

Random allocation Concealed allocation Groups similar at baseline Participant blinding Therapist blinding Assessor blinding < 15% dropouts Intention to treat analysis Between-group difference reported Point measures and measures of variability Total Quality

Chinnavan et al., (2020)

Chan et al., (2018)

Gurbuz et al., (2016)

Lee et al., (2012)

Radajewska et al., (2013)

Wu et al., (2013) x x

x

x x x

x

x

x

x

x x

x

x

x

x

x x

x

x x

x

x x 4/10

7/10

8/10

5/10

4/10

8/10 Fair

Good

Good

Fair

Fair

Good

ful.46 As the results of this review show MT combined with UC may not be more beneficial.44,46,48 But there seems to be a clinically meaningful improvement in both groups which suggests that MT does not have an unfavorable effect. Also MT is a technique that is easy-to-apply, low-cost, and can be used in conjunction with other treatments.8,9 For these reasons, it can still be a useful intervention in clinical practice.

The studies included in this review had different limitations, one of them being that no studies reported a longterm follow-up. Sample sizes were small, which can make the statistical power for rejecting the null hypothesis small, therefore proving the difference between the intervention and control group is limited. All control groups followed a different intervention and in addition frequency and duration of the intervention varied in all studies. Therefore it is not clear what the optimal frequency and duration of MT are. The studies are not robust enough to strongly support conclusions. Larger robust RCTs are needed to investigate the effectiveness of MT in stroke rehabilitation. Future studies should also try to determine the optimal frequency and duration of MT. It may be useful to evaluate the effectiveness of MT in different phases following a stroke to determine in which phase patients will benefit the most from MT.

Conclusions There is limited evidence for the superiority of MT combined with UC versus UC alone for improving upper limb motor function after stroke. Sub-synthesis of MT in the sub-acute and chronic phase after stroke showed strong evidence for the use of MT combined with UC in the chronic phase. The results of the sub-synthesis in the chronic phase after stroke are based on two studies with one study having limited internal validity. Therefore results of the sub-synthesis should be interpreted with caution. Future research should focus on determining the optimal frequency, duration and effectiveness of MT in different phases following a stroke.

Conflict of Interest Statement The author declares that there is no conflict of interest in relation to the work presented.

AUTHOR Yannick van Breeschooten, fysiotherapeut Topfit-Fysiotherapie, Lelystad yannickbreeschooten@outlook.com

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