Please refer to the attached document with the instructions

R E V I E W

Mirror Therapy in Stroke Rehabilitation: Current

Perspectives This article was published in the following Dove Press journal:

Therapeutics and Clinical Risk Management

Dorcas BC Gandhi 1,2

Albert Sterba 3

Himani Khatter 2

Jeyaraj D Pandian 2

1College of Physiotherapy, Christian

Medical College & Hospital Ludhiana,

Ludhiana, Punjab, India; 2Faculty of

Medicine, Masaryk University, Stroke

Brno, International Clinical Research

Center, St. Anne´s University Hospital,

Brno, Czech Republic; 3Department of

Neurology, Christian Medical College &

Hospital Ludhiana, Ludhiana, Punjab, India

Abstract: In contrast to varied therapy approaches, mirror therapy (MT) can be used even in

completely plegic stroke survivors, as it uses visual stimuli for producing a desired response

in the affected limb. MT has been studied to have effects not just on motor impairments but

also on sensations, visuospatial neglect, and pain after stroke. This paper attempts to system-

atically review and present the current perspectives on mirror therapy and its application in

stroke rehabilitation, and dosage, feasibility and acceptability in stroke rehabilitation. An

electronic database search across Google, PubMed, Web of Science, etc., generated 3871

results. After screening them based on the inclusion and exclusion criteria, we included 28

studies in this review. The data collected were divided on the basis of application in stroke

rehabilitation, modes of intervention delivery, and types of control and outcome assessment.

We found that most studies intervened for upper limb motor impairments post stroke. Studies

were equally distributed between intervention in chronic and acute phases post stroke with

therapy durations lasting between 1 and 8 weeks. MT showed definitive motor and sensory

improvements although the extent of improvements in sensory impairments and hemineglect

is limited. MT proves to be an effective and feasible approach to rehabilitate post-stroke

survivors in the acute, sub-acute, and chronic phases of stroke, although its long-term effects

and impact on activities of daily living need to be analysed extensively.

Keywords: mirror therapy, stroke, rehabilitation, motor, sensory, hemineglect, unilateral

neglect, pain

Introduction Stroke is the 3rd leading cause of years of life lost (YLL) across the world: age-

standardised YLL increased by 12.9% (10.6–15.2) from 1990 to 2007 and by

12.1% (9.9–14.1) from 2007 to 2017. Deaths from stroke increased from 5.-

29 million (5.22–5.40) to 6.17 million (6.04–6.33) across the globe between 2007

and 2017.1 The rise of multi-morbidity and effects of longevity reported by the

GBD (global burden of disease) thus increased DALYs (disability-adjusted life

years) due to stroke from 3.54% to 9.66% from 1990 to 2013 and there were

approximately 25.7 million stroke survivors in 2013, globally.2 HIC (high-income

countries) showed a 42% decrease in stroke while LMIC (low and middle-income

countries) showed a 100% increase in the past four decades.3 There are approxi-

mately 62 million stroke survivors across the world and one-third of them live with

severe disabilities.4 More than 80% of DALY occur in LMIC.5,6

In the post-stroke acute phase, approximately 60–80% of survivors present with

upper or lower limb motor impairments.7–10 Only 20% of severely paretic survivors

achieve full upper limb function as compared to 80% of mildly paretic stroke

Correspondence: Jeyaraj D Pandian Department of Neurology, Christian Medical College & Hospital, Ludhiana, Punjab 141008, India Tel +91 9915784750 Email [email protected]

Therapeutics and Clinical Risk Management Dovepress open access to scientific and medical research

Open Access Full Text Article

submit your manuscript | www.dovepress.com Therapeutics and Clinical Risk Management 2020:16 75–85 75

http://doi.org/10.2147/TCRM.S206883

DovePress © 2020 Gandhi et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the

work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

survivors.10 Fifty per cent of stroke survivors with an

initial presentation of plegic upper and lower

limbs regain partial motor function.7,9 Painful upper limb

(especially around the shoulders) and complex regional

pain syndrome-type I (CRPS-type I) are experienced in

approximately 50% of stroke survivors in the first year

post stroke, affecting their activities of daily living

(ADL).11–14 Around 40% with an acute right hemispheric

stroke and 20% of people with a left hemispheric stroke

present with hemineglect, especially visuospatial neglect,

which reduces to 15% and 5% respectively at the 3rd

month.15 Spatial neglect has proven to be detrimental for

functional recovery16,17 and is associated with reduced

quality of life.18 Long-term functional recovery is also

directly dependent on the initial severity of paresis.19

Rehabilitation strategies are required to be repetitive,

intensive, and task-specific for neuroplasticity to produce

recovery.20–22 It is reported that when therapy begins within

16 hrs to 6 months post stroke, there is significant improve-

ment in ADL performance with augmented exercise

therapy.23 In contrast to varied therapy approaches which

require some degree of voluntary movement, mirror therapy

(MT) can be used even in completely plegic, severely

paretic stroke survivors, as MT uses visual rather than

somatosensory stimuli for producing a desired response in

the affected limb.24 Mirror therapy is a type of rehabilitation

approach where the reflection (visual input) of a moving

non-affected limb gives the illusion of movement in the

affected limb. This is achieved by placing a mirror between

the arms or legs. MT has been studied to have effects not

just on motor impairments but also on sensations, visuos-

patial neglect, and pain after stroke.25

This paper attempts to systematically review and pre-

sent the current perspectives on mirror therapy with

respect to its:

1. Application in stroke rehabilitation

2. Dosage, feasibility, and acceptability in stroke

rehabilitation

Methods Inclusion criteria are as follows:

1. Study on mirror therapy for motor, sensory, and

perceptual impairments after stroke

2. Rehabilitation in the acute, sub-acute, and chronic

phases after stroke

3. Only randomised controlled trials

4. Articles published from January 2010 till June 2019

Exclusion criteria are as follows:

1. Studies written in languages other than English

2. Studies studying synergistic effects of mirror ther-

apy with other forms of therapies

3. Studies on other forms of therapy targeting the

mirror neuron system

Search Strategy We conducted this review using PRISMA guidelines. An

electronic database search was performed using the follow-

ing databases: PubMed, Web of Science. The search strategy

includes keywords combined with Boolean operators: mirror

AND (therapy OR rehabilitation) AND (stroke OR post-

stroke OR post-stroke). The selection strategy of the studies

is shown in the PRISMA flow chart (Figure 1).26

Review Process The studies were screened by two independent reviewers

based on their titles and abstracts. RCTs were identified and

full articles were obtained for the selected RCTs. All of the full

articles were then assessed in order to check the fulfilment of

the inclusion criteria. In case of a disagreement between the

reviewers, the decision was made by a third reviewer.

Data Extraction After the selection of studies, the data were extracted for

information on the title, inclusion and exclusion criteria, type

of intervention, sample size, study methodology, primary and

secondary outcomes, study limitations, feasibility, and adher-

ence. The data collected weremainly divided on the basis of

application in stroke rehabilitation, modes of intervention

delivery, and types of control and outcome assessment.

Risk of bias evaluation and methodological quality: the

COCHRANE risk of bias tool was used to perform the risk

of bias assessment. The methodological quality of each

study was performed using the PEDro scale.27

Results Application in Stroke Rehabilitation Motor — Upper Limb

Out of the 28 studies included (Table 1) in this review, 78.6%

of them studied the effects of MTon motor functions of upper

extremities, in addition to sensory function in 6 studies28–33

and ADL/QOL in 9 studies. We noted a reduction in

Gandhi et al Dovepress

submit your manuscript | www.dovepress.com

DovePress Therapeutics and Clinical Risk Management 2020:1676

impairment as recorded by FMA in almost all except for 5

studies. Improvement in upper limb motor function was

reported in terms of either improved dexterity, gross and fine

motor movements, grip force, decreased movement time, or

proximal motor control in 10 studies.28,29,32,34–40 Two other

studiesreported no significantdifferencewith MT, in outcomes

measuring motor, sensory, and ADL components.41,42 Only 4

studied the effects of MTon spasticity, out of which 3 reported

no improvement as recorded on the Modified Ashworth

scale28,37,43 and one showed improvement on the Ashworth

scale,44 with 6 weeks of MT along with conventional rehabi-

litation. Sensory impairments were measured in 6 studies, and

4 report improved response to either noxious, tactile, or tem-

perature stimuli.28–31 Twelve of the studies28–32,36,38–40,45–47

intervened in the chronic phase of upper limb deficits after

stroke (ie after 6 months) while the rest intervened within the

acute and sub-acute phases. Duration of intervention ranged

between 3 and 8 weeks with MT sessions lasting between 20

and 45 min; 4 studies provided no additional conventional

rehabilitation.32,40,45,47

Motor — Lower Limb/Gait/Balance

Six studies reported on effects of MT on lower extre-

mity impairment/function, gait, and balance.33,39,43,48–50

Records identified through database searching (n =3871)

S cr

ee n

in g

In cl

u d

ed E

li gi

b il

it y

noitacifit ne

dI

Records after duplicates removed (n =635)

Records screened (n =635)

Records excluded (n =573)

Full-text articles assessed for eligibility

(n =62)

Full-text articles excluded, with reasons

(n =34)

Studies included in qualitative synthesis

(n =28)

Figure 1 PRISMA flow chart.

Dovepress Gandhi et al

Therapeutics and Clinical Risk Management 2020:16 submit your manuscript | www.dovepress.com

DovePress 77

These studies showed improved motor recovery as

recorded on Brunnstrom stages and improved lower

extremity function through improved walking speed,

single limb stance, step and stride lengths, static and

dynamic balance, and decreased mediolateral and ante-

roposterior sway in standing. Two studies also reported

a reduction in lower extremity impairment. Improved

forward reach in standing and coordination was also

reported but no improvement in cadence or stance or

swing phase velocity was seen.

Activities of Daily Living and Quality of Life

Eight of the 22 studies28,34,36,41,47,51–53 reported on the

effects of MTon ADLs and one on the quality of life through

the Euro-QOL-5 Domain (EQ5D) scale.32 ADLs showed no

improvement with MT in 3 studies, and neither did quality of

life. The rest of the studies did show improved performance

in ADLs through mainly the Functional Independence

Measure (FIM), otherwise through the Barthel Index and

Repty’s Functional Index. All of these studies did not report

on the long-term effects of MT on ADLS or QOL.

Sensory

We report paucity in the number of studies treating and

recording change in sensory impairments after stroke. Six

studies record changes in sensory impairments like pain,

tactile discrimination, response to touch, temperature, etc.

Only 1 study30 intervened for sensory issues by providing

varied texture stimulus during MT sessions to the affected

upper limbs. There was improved response to temperature

Table 1 Summary of Included Studies

First Author/Year Phase Intervention Target Duration of

Therapy (Weeks)

Mode of MT Sample

Harmsen, 2015 40

Chronic UL motor 1 session Action-observation, u/l 37

Lin, 2014 39

Chronic UL motor, ambulation,

ADL

4 MB, b/l 29

Amasyalı, 201638 Chronic Hand motor 3 MF, u/l 17

Gurbuz, 2016 53

Sub-acute UL motor 4 MF, u/l 31

Mohan, 2013 50

Acute LL motor, balance 2 MF 22

Xu, 2017 43

Sub-acute LL, ambulation, spasticity 4 MF 46

Vural, 2015 28

Chronic CRPS, UL motor, ADL,

spasticity

4 MR, b/l 30

Wu, 2013 29

Chronic UL motor and sensory 4 MF, b/l 23

Rodrigues, 2015 45

Chronic UL motor 4 MB, b/l 16

Arya, 2018 46

Chronic UL sensory 6 MF, b/l 31

Samuelkamaleshkumar, 2014 37

Sub-acute Wrist and hand motor 3 MB, b/l 20

Cristina, 2015 44

Sub-acute UL motor 6 MF, b/l 15

Thieme, 2012 52

Sub-acute UL motor, ADLS, QOL,

visuospatial neglect

5 MF, b/l 60

Colomer, 2016 31

Chronic UL motor and sensory 8 MB, b/l 31

Michielsen, 2011 32

Chronic UL motor, pain, QOL 6 MF, b/l 40

Pandian, 2014 54

Acute Unilateral neglect 4 MB, b/l 47

Antoniotti, 2019 41

Acute UL motor 4 MF, u/l 35

Tyson, 2015 33

Acute UL and LL, motor and

sensory

1 MF 85

Chan, 2018 42

Acute UL motor 4 MF, b/l 35

Arya, 2015 46

Chronic UL motor 8 MB, u/l 33

Park, 2015 47

Chronic UL motor, ADL 4 MF, u/l 30

Radajewska, 2013 51

Sub-acute UL and hand motor, ADL 3 MF, b/l 60

Ji, 2015 49

Sub-acute Gait 4 MF, u/l 34

Park, 2015 36

Chronic UL motor, ADL 6 MF, u/l 30

Lee, 2012 35

Acute and sub-acute UL motor 4 MB, b/l 26

Invernizzi, 2013 34

Sub-acute UL motor, ADL 4 MF, u/l 26

In, 2016 48

Chronic Balance, gait 4 MB, VRRT 25

Yang, 2015 55

Sub-acute Pusher’s syndrome 3 MF 12

Abbreviations: UL, Upper Limb; u/l, Unilateral; ADL, Activities of Daily Living, MB, Mirror Box; b/l, bilateral; MF, Mirror Frame; LL, Lower Limb; CRPS, Complex Regional Pain Syndrome; QOL, Quality of Life; VRRT, Virtual Reality Reflection Therapy.

Gandhi et al Dovepress

submit your manuscript | www.dovepress.com

DovePress Therapeutics and Clinical Risk Management 2020:1678

and tactile sensation.28 reported decrease in pain experienced

post stroke. Another study intervening through task-based

MT46 reported that some of their patients experienced “cer-

tain perceptions“ in the affected upper limb like tingling,

movement flicker, mild pain, pinprick, and associated move-

ments after 6–8 weeks of MT, although this study did not

actively intervene for sensory issues.

Unilateral Neglect

Studies by Pandian et al and Thieme et al52,54 reported

recovery in visuospatial neglect in post-stroke patients with

MT for 4 and 5 weeks respectively. The patients showed

improvement in neglect in the near extrapersonal space and

representational neglect. It is important to note that both of

these studies intervened during the acute–sub-acute phases

post stroke. The study by Thieme et al52 studied effects of

MT in visuospatial neglect only in a small percentage of their

sample and the outcome was not blindly assessed. The

MUST trial by Pandian et al54 reports improved mean scores

for star cancellation, line bisection, and picture identification

tests at the 6th-month follow-up. This article also reports

a 2-study meta-analysis concluding that MT was effective

in treating unilateral neglect after stroke.

Yang et al55 intervened in the sub-acute phase for Pusher

syndrome post stroke. These patients showed improvement

by decreased severity of the syndrome and lower extremity

motor function improved on FMA. Another study reported

the positive effects of MT in reducing pain and improving

motor function in patients with complex regional pain syn-

drome after stroke. It is noteworthy that the intervention was

in the chronic phase of stroke. One of the studies by

Michielsen et al32 describes improved activation within the

affected motor cortex as an outcome measure with 6 weeks of

MT training which included home-based sessions as well.

Intervention Details Stage of Intervention

Thirteen of the studies studied the effects of MT in the

chronic phase of stroke, ie after 6 months of the onset

(those mentioned above and in 201648). The rest of the

studies either intervened in the acute or sub-acute phase of

stroke. The longest duration of intervention of 8 weeks

was seen in chronic stroke in two studies, both intervening

for upper extremity impairments.

Modes of Intervention Delivery

A majority of the studies (92.8%) used either mirror boxes or

mirror frames to deliver MT training. A mirror box is

a 3-D structure with the facility to place the affected limb

within it to avoid direct viewing of it by the patient, whereas

a 2-D mirror frame is placed between the 2 arms either

vertically or inclined in such a way so that the patient is

able to view the reflection of the normal arm in the mirror

without viewing the affected arm. The dimensions varied

based on which part of the body was being treated: upper

or lower extremity. Among the studies using the above-

mentioned mode of MT, 13 studies included bilateral sym-

metrical movements of the limbs28–30,32,35,37,39,42,44,45,51,52,54

as opposed to the remaining 13 studies which intervened with

unilateral movement of the unaffected limb. The study by

Harmsen et al40 delivered a modified form of therapy using

the participant-specific videos with reaching movements

from the unaffected arm that were videotaped and mirrored,

creating maximal postural familiarity and the illusion that the

affected arm performed the reaching movements in a normal

movement pattern. This form of action-observation mode

showed improved speed of upper limb movements, although

the long-term effect was not measured. A study by In et al

used Virtual Reality Reflection Therapy (VRRT) in treating

balance and gait after stroke. This is a technically enhanced

version of MT training where the patients in a high sitting

position placed their affected lower extremity into the VRRT

box and observed the projected movement of the unaffected

limb without visual asymmetry otherwise causing tilting of

the head and trunk. The movements of the unaffected limb

were captured through the camera and displayed over the

affected limb as the virtual reality reflection. This study

reported improved balance scores both in static and dynamic

tests, decreased anteroposterior sway with eyes open, and

decreased mediolateral sway with eyes open and closed, as

well as improved walking speed on a 10-metre walk test.

Four studies used task-based activities during MT

sessions30,33,46,47 while the rest used reaching activities

or simple graded movements of the limbs for therapy.

Two studies also included home-based sessions of mirror

therapy. It is important to note that no form of conven-

tional therapy was provided to the intervention group in 4

studies. Out of these, 2 studies (Rodrigues LC 2015, Park

Y 2015) showed definitive improvement in motor scores

for the upper limb and functional activities. Although, 1

study for chronic stroke reported that these gains did not

persist at the 6th-month follow-up.32

Intensity

The total duration of intervention varied from 1 week to 8

weeks. Fifty per cent of the studies had an intervention

Dovepress Gandhi et al

Therapeutics and Clinical Risk Management 2020:16 submit your manuscript | www.dovepress.com

DovePress 79

period of 4 weeks with the frequency ranging from 3 to 5

sessions per week. Each session’s duration varied from 20

to 90 min; in some cases excluding 20–30 min of control/

conventional therapy. One study reported the effects of 1

session of action-observation-based MT which was quite

intensive with 70 repetitions within a 10 trial set of MT.40

This study showed improvement in speed in upper limb

movements.

Studies on upper extremities report positive effects

with treatment sessions lasting between 20 and 60 min

per day for 5 days a week, except for 2 studies that

reported no difference in motor scores between the inter-

vention and control groups. For the lower extremity, the

treatment sessions lasted between 15 min and 1 h, for 5–6

days a week.

Types of Control We found 2 broad categories of control arms, one provid-

ing sham mirror therapy/placebo (53.57% of studies) and

the other providing conventional therapy (46.43%) to the

control arm. Sham MT was provided either by using

a non-reflecting surface placed between the limbs or by

covering the mirror with a cloth or by displaying static

images/interactive visual feedback or by placing no mirror

between limbs. Conventional therapy varied from passive

movements/strengthening of the affected limb to compre-

hensive treatment combining physical and occupational

therapy along with speech and language therapy whenever

needed. Functional and task-based activities were included

in few of the studies as part of the control programme. All

conventional rehabilitation sessions were tailor-made to

patient needs and the duration lasted between 45 min and

5 hrs per day.

Types of Outcome Measures The included studies present a varied range of outcomes

measuring motor, sensory, and perceptual impairments along

with balance/gait, ADLs, and QOL. We have categorised these

scales based on the ICIDH, ie International Classification of

Impairment, Disability (activity limitation) and Handicap (par-

ticipation restriction), as presented in Table 2.

Feasibility and Acceptability/Adherence Fourteen studies did not contain any information about fea-

sibility or adherence at all.28–31,36,38,40–43,46–48,51,53 Apart

from several occasional and short-lived episodes of fatigue,

soreness, or swelling in the paretic limb,33,42 the MT was

generally well tolerated and no serious adverse effects were

reported.33,34,37,39,42,44,50,54,55 Overall, adherence to the MT

is assumed to be high, regarding that the majority of trials

employ directly supervised intervention;33 two studies even

Table 2 Types of Outcome Measures

Category Scales Used

Impairment Activity

Limitation

Participation

Restriction

Motor:

upper and

lower

extremity

FMA

Myoton 3

myometer

PROM

MCSI

MAS

Movement

time

Grip force

Wrist

extension

Bhakta test

Tardieu scale

Motricity

index

Brunnstrom

stages

MSS

WMFT

BBT

10-metre walk

test

MFT

Upper extremity

performance test

for the elderly

ARAT

Stroke-ULAM

BI

FIM

Sensory FMA

RNSA

RASP

TDT

VAS

NA NA

Unilateral

neglect

SCT

LBT

PIT

NA NA

Balance Postural sway BBS

BBA

FRT

TUG

Others Scale for

Contraversive

Pushing

Motion analysis

device

FAC

FAT

SIS

ABILHAND

mRS

EQ 5D

RFI

Abbreviations: FMA, Fugl Meyer Assessment; PROM, Passive Range Of Motion; MCSI, Modified Composite Spasticity Index; MSS, Motor Status Score; MFT, Manual

Function Test; ULAM, Upper Limb Activity Monitor; BI, Barthel Index; FIM,

Functional Independence Measure; RNSA, Revised Nottingham Sensory

Assessment; NSA, Nottingham Sensory Assessment; RASP, Rivermead

Assessment Of Sensory Perception; TDT, Tactile Discrimination Test; SMT,

Semmes-Weinstein Monofilament Test; VAS, Visual Analog Scale; SCT, Star

Cancellation Test; LBT, Line Bisection Test; PIT, Picture Identification Task; BBS,

Berg Balance Scale; BBA, Brunel Balance Assessment; FRT, Functional Reach Test;

TUG, Timed Up and Go Test; FAC, Functional Ambulation Categories; FAT,

Frenchay Arm Test; MAL, Motor Activity Log; mRS, Modified Rankin Score; EQ-

5D, EuroQOL-5 Domains; RFI, Repty Functional Index.

Gandhi et al Dovepress

submit your manuscript | www.dovepress.com

DovePress Therapeutics and Clinical Risk Management 2020:1680

explicitly stated a 100% participation rate.32,49 The highest

drop-out rate of 18.6% was recorded in a study comparing

effectiveness of MT in a group vs individual setting; this

study, however, concluded that the compliance and retention

rates in the group intervention are comparable to the indivi-

dual approach, and thus the MT group seems to be possible

even for severely disabled stroke patients.52

A study comparing two patient-led therapies (MT vs

lower limb exercises) reported that both interventions

were feasible, with 90% adherence. Nevertheless, both

groups did less therapy than recommended; and participants

receiving MT inclined to do less practice than those under-

going lower limb exercises. Furthermore, those with neglect

performed 69% less MT than those without, which was not

observed in the exercise group.33 In another study on add-

ing object-related bilateral symmetrical training to MT in

chronic stroke, the physiotherapist conducted the rehabilita-

tion programme at the patient's home in order to increase

participation. Despite 16% of sessions not being performed,

all subjects obtained an identical number of sessions and

finished the treatment.45 A 14.6% drop-out rate was calcu-

lated in stroke patients with a severely impaired arm.42 At

last, patients experiencing MT demonstrated higher levels

of motivation compared to those receiving sham therapy.35

Limitations A small sample size was the prevailing limitation

among the included studies.29,31,33,37,38,40,41,43,45,46,49,52,53,55

Additionally, the absence of follow-up did not allow assess-

ment of long-term retention of functional improvement in

patients after rehabilitation.28,31,34–37,41,43,44,46,47,49,53,55

A number of studies reported difficulties with generalisation

of the outcomes due to specific pre-selection

criteria32,36,38,47,48,51 or because they included patients with

a distinct level of functional impairment and time post

ictus.29,31,32,39,41,52 Another complication to the interpretation

of the MT effectiveness was that three studies observed

a difference in baseline measurements between the experimen-

tal and control groups.37,50,54 The impact of MTon changes in

cortical reorganisation and neural activation pre and post ther-

apy could not be examined as only one study implemented

fMRI in its protocol.32

Besides the aforementioned, there were some other

limitations declared by individual research teams which

may be pertaining to the remainder of studies as well.

First, the interactive character of the experimental condi-

tion excluded the blinding of both the therapists and the

participants.37,52 Second, the design of the mirror box

precludes movements such as shoulder overhead motion

and rotation, which might be the cause of less pronounced

improvement in the upper arm movement compared to the

wrist and hand in the intervention group.46 Third, several

authors expressed the lack of quality of movement46,49 or

the active range of motion43 assessment as one of their

limitations. When applying attention-dependent rehabilita-

tion techniques, a comprehensive cognition and depression

evaluation both before and during or after the treatment

would be of value.28,41,44 The role of MT in patients

presenting with an additional effect of the presence of

cognitive impairments (seen commonly in lacunar

strokes)56,57 needs to be analysed. Our study does not

evaluate the effect of MT in those with cognitive impair-

ments. Extending our results to such a group of patients

needs to be extensively researched.

Future studies should involve a larger sample size and more

homogeneous distribution in relation to sensory impairment or

motor paresis.38 Further on, new studies ought to be executed

on optimal duration, intensity, and content38 while also focus-

ing on ADL.53

Risk of bias and methodological quality: the average

PEDro score was 7±0.93 and no study showed a poor

score (score <4), 2 (7.1%) of the studies showed fair

quality (score 4–5), and most studies (89.3%) had a good

methodological quality. Only 1 study (3.6%) showed

excellent quality (score 9–10). The risk of bias scored on

the Cochrane tool is depicted in Figure 2.

Discussion Various hypotheses have been postulated on the neurophy-

siological basis of MT. The first hypothesis suggests the

presence of a mirror neuron system (MNS) in the frontotem-

poral region and superior temporal gyrus (STG)58,59 which

discharges with a goal-oriented hand action or through obser-

vation of a similar action by another person.60,61 This action-

observation facilitates the corticospinal pathway; in turn

improving motor function by eliciting mental imagery62

and inducing motor learning.63 Observation of biological

motion also is thought to aid in recovery from neglect by

activation of the STG.64,65 The second hypothesis suggests

potential mechanisms like increased self-awareness and spa-

tial attention by activation of the STG, precuneus, and poster-

ior cingulate cortex (PCC). MT increases activity in primary

and secondary visual and somatosensory areas, thus enhan-

cing attention, conscious awareness of sensory feedback, and

avoidance of learned non-use of the affected limb.66–69 The

third hypothesis describes the role of MT in activation and

Dovepress Gandhi et al

Therapeutics and Clinical Risk Management 2020:16 submit your manuscript | www.dovepress.com

DovePress 81

recruitment of the otherwise dormant, ipsilateral motor path-

ways originating in the unaffected hemisphere and projecting

ipsilaterally to the paretic side of the body.70–72 The role of

MT in promoting normalisation of balance within the hemi-

spheres post stroke by modulating the excitability of the

primary motor cortex (M1) has also been hypothesised.24,73

During MT, both the affected limb movement and the passive

observation of movement of the unaffected limb as reflected

in the mirror influence M1 excitability.24 Bhasin et al74

observed an increase in the activation of primary motor

area Brodmann area 4 post MT (restitution principle of

neuroplasticity).

Our review has reported effects of MT in rehabilitation

post stroke. More than half of the studies intervened and

recorded improvements in the acute phase of stroke. This

can potentially change clinical practice as MT can inter-

vene for a completely flaccid limb, unlike other rehabilita-

tion approaches (Constraint Induced Movement Therapy

(CIMT), therapy with computer games, virtual reality, etc.)

where a minimal amount of voluntary movement is a pre-

requisite for initiating therapy.

Few studies have previously reported that MT, when

combined with bilateral arm training, increases the visual

or mental imagery feedback, which in turn facilitates

upper limb motor function.75 Our review supports this

finding and additionally reports that bilateral arm training

shows positive results in both sub-acute and chronic motor

impairments of the upper limb and for hemineglect.

A future scope for MT would be to identify its relation

to the differing presentations of stroke among men and

women. The differing risk factors, stroke severity, and

neurological outcomes between men and women may

demand a modified application of MT for rehabilitation

in individual genders.76 Research is also needed into the

effect of MT in different subtypes of stroke, be it pure

motor strokes or those with sensory and other components.

The role of MT in rehabilitating acute and chronic lacunar

strokes (which show better functional prognosis), its long-

term effects, and associated improvement in quality of life

can be investigated to set the stage.77

Conclusion MT is a feasible method for training post-stroke impairments

(motor, sensory, perceptual deficits) in acute, sub-acute, and

chronic phases. Inclusion of bilateral arm training improves

patient response to MT. The required dosage of MT, long-term

effects, and impact on ADLs and QOL on various subtypes of

stroke need to be analysed extensively in larger populations.

Disclosure Dr Dorcas BC Gandhi reports grants from Wellcome Trust

Research Training Fellowship, outside the submitted work.

The authors report no other conflicts of interest in this work.

References 1. GBD 2017 Causes of Death Collaborators. Global, regional, and

national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736–1788.

2. Feigin VL, Krishnamurthi RV, Parmar P, et al. Update on the global burden of ischemic and haemorrhagic stroke in 1990–2013: the GBD 2013 study. Neuroepidemiology. 2015;45:161–176. doi:10.1159/000 441085

0 10 20 30 40 50 60 70 80 90 100

Randomization process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported result

Overall Bias

Low risk Medium risk High risk

Figure 2 The risk of bias scored on the Cochrane tool.

Gandhi et al Dovepress

submit your manuscript | www.dovepress.com

DovePress Therapeutics and Clinical Risk Management 2020:1682

3. Feigin VL, Norrving B. A new paradigm for primary prevention strategy in people with elevated risk of stroke. Int J Stroke. 2014;9:624–626. doi:10.1111/ijs.12300

4. Ferri CP, Schoenborn C, Kalra L, et al. Prevalence of stroke and related burden among older people living in Latin America, India and China. J Neurol Neurosurg Psychiatry. 2011;82:1074–1082. doi:10.1136/jnnp.2010.234153

5. Feigin VL, Roth GA, Naghavi M, et al. Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol. 2016;15:913–924. doi:10.1016/S1474-4422(16)30073-4

6. Hata J, Kiyohara Y. Epidemiology of stroke and coronary artery disease in Asia. Circ J. 2013;77:1923–1932. doi:10.1253/circj.CJ-13-0786

7. Kwakkel G, Boudewijn J, Jeroen V, et al. Probability of regaining dexterity in the flaccid upper limb impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34:2181–2186. doi:10.1161/01.STR.0000087172.16305.CD

8. Barker WH, Mullooly JP. Stroke in a defined elderly population, 1967-1985. A less lethal and disabling but no less common disease. Stroke. 1997;28(2):284–290. doi:10.1161/01.STR.28.2.284

9. Jorgensen HS, Nakayama H, Raaschou HO, et al. Recovery of walk- ing function in stroke patients: the copenhagen stroke study. Arch Phys Med Rehabil. 1995;76(1):27–32. doi:10.1016/S0003-9993(95) 80038-7

10. Nakayama H, Jorgensen HS, Raaschou HO, et al. Recovery of upper extremity function in stroke patients: the copenhagen stroke study. Arch Phys Med Rehabil. 1994;75(4):394–398. doi:10.1016/0003- 9993(94)90161-9

11. Jönsson AC, Lindgren I, Hallström B, et al. Prevalence and intensity of pain after stroke: a population based study focusing on patients’ perspectives. J Neurol Neurosurg Psychiatry. 2006;77(5):590–595. doi:10.1136/jnnp.2005.079145

12. Kocabas H, Levendoglu F, Ozerbil OM, et al. Complex regional pain syndrome in stroke patients. Int J Rehabil Res. 2007;30(1):33–38. doi:10.1097/MRR.0b013e3280146f57

13. Lundström E, Smits A, Terént A, et al. Risk factors for stroke-related pain 1 year after first-ever stroke. Eur J Neurol. 2009;16(2):188–193. doi:10.1111/ene.2009.16.issue-2

14. Sackley C, Brittle N, Patel S, et al. The prevalence of joint contrac- tures, pressure sores, painful shoulder, other pain, falls, and depres- sion in the year after a severely disabling stroke. Stroke. 2008;39 (12):3329–3334. doi:10.1161/STROKEAHA.108.518563

15. Ringman JM, Saver JL, Woolson RF, et al. Frequency, risk factors, anatomy, and course of unilateral neglect in an acute stroke cohort. Neurology. 2004;63(3):468–474. doi:10.1212/01.WNL.0000133011. 10689.CE

16. Buxbaum LJ, Ferraro MK, Veramonti T, et al. Hemispatial neglect subtypes, neuroanatomy, and disability. Neurol. 2004;62:749–756. doi:10.1212/01.WNL.0000113730.73031.F4

17. Farne` A, Buxbaum LJ, Ferraro M, et al. Patterns of spontaneous recovery of neglect and associated disorders in acute right brain-damaged patients. J Neurol Neurosurg Psychiatry. 2004;75:1401–1410. doi:10.1136/jnnp.2002.003095

18. Franceschini M, La Porta F, Agosti M, et al. Is health-related-quality of life of stroke patients influenced by neurological impairments at one year after stroke? Eur J Phys Rehabil Med. 2010;46(3):389–399.

19. Hendricks HT, Limbeek JV, Geurts AC, et al. Motor recovery after stroke: a systematic review of the literature. Arch Phys Med Rehabil. 2002;83:1629–1637. doi:10.1053/apmr.2002.35473

20. Barreca S, Wolf SL, Fasoli S, et al. Treatment interventions for the paretic upper limb of stroke survivors: a critical review neurorehabil neural repair. Neurorehabilitation Neural Repair. 2003;17 (4):220–226. doi:10.1177/0888439003259415

21. Kleim JA, Jones TA. Principles of experience-dependent neural plasti- city: implications for rehabilitation after brain damage. J Speech Lang Hear Res. 2008;51(1):225–239. doi:10.1044/1092-4388(2008/018)

22. Van Peppen RP, Kwakkel G, Wood-Dauphinee S, et al. The impact of physical therapy on functional outcomes after stroke: what’s the evidence? Clin Rehabil. 2004;18(8):833–862. doi:10.1191/02692 15504cr843oa

23. Kwakkel G, van PR, Wagenaar RC, et al. Effects of augmented exercise therapy time after stroke: a meta-analysis. Stroke. 2004;35 (11):2529–2539.

24. Garry MI, Loftus A, Summers JJ. Mirror, mirror on the wall: viewing a mirror reflection of unilateral hand movements facilitates ipsilateral M1 excitability. Exp Brain Res. 2005;163(1):118–122. doi:10.1007/ s00221-005-2226-9

25. Thieme H, Morkisch N, Mehrholz J, et al. Mirror therapy for improv- ing motor function after stroke (Review). Cochrane Database Syst Rev. 2018;7.

26. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that eval- uate health care interventions: explanation and elaboration. PLoS Med. 2009;6:7. doi:10.1371/journal.pmed.1000100

27. Foley NC, Teasell RW, Bhogal SK, et al. Stroke rehabilitation evidence-based review: methodology. Top Stroke Rehabil. 2003;10 (1):1–7.

28. Vural SP, Yuzer GFN, Ozcan DS, Ozbudak SD, Ozgirgin N. Effects of mirror therapy in stroke patients with complex regional pain syndrome type 1: a randomized controlled study. Arch Phys Med Rehabil. 2016;97(4):575–581. doi:10.1016/j.apmr.2015.12.008

29. Wu CY, Huang PC, Chen YT, Lin KC, Yang HW. Effects of mirror therapy on motor and sensory recovery in chronic stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2013;94 (6):1023–1030. doi:10.1016/j.apmr.2013.02.007

30. Arya KN, Pandian S, Puri V. Mirror illusion for sensori-motor training in stroke: a randomized controlled trial. J Stroke Cerebrovascular Dis. 2018;27(11):3236–3246. doi:10.1016/j.jstrokecerebrovasdis.2018.07.012

31. Colomer C, Noe E, Llorens Rodríguez R. Mirror therapy in chronic stroke survivors with severely impaired upper limb function: a randomized controlled trial. Eur J Phys Rehabil Med. 2016;52 (3):271–278.

32. Michielsen ME, Selles RW, van der Geest JN, et al. Motor recovery and cortical reorganization after mirror therapy in chronic stroke patients: a Phase II randomized controlled trial. Neurorehabil Neural Repair. 2011;25(3):223–233. doi:10.1177/1545968310385127

33. Tyson S, Wilkinson J, Thomas N, et al. Phase II pragmatic rando- mized controlled trial of patient-led therapies (mirror therapy and lower-limb exercises) during inpatient stroke rehabilitation. Neurorehabil Neural Repair. 2015;29(9):818–826. doi:10.1177/ 1545968314565513

34. Invernizzi M, Negrini S, Carda S, Lanzotti L, Cisari C, Baricich A. The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: a randomized controlled trial. Eur J Phys Rehabil Med. 2013;49(3):311–317.

35. Lee MM, Cho HY, Song CH. The mirror therapy program enhances upper-limb motor recovery and motor function in acute stroke patients. Am j Phys Med Rehabil. 2012;91(8):689–700. doi:10.1097/ PHM.0b013e31824fa86d

36. Park JY, Chang M, Kim KM, Kim HJ. The effect of mirror therapy on upper-extremity function and activities of daily living in stroke patients. J Phys Ther Sci. 2015;27(6):1681–1683. doi:10.1589/jpts. 27.1681

37. Samuelkamaleshkumar S, Reethajanetsureka S, Pauljebaraj P, Benshamir B, Padankatti SM, David JA. Mirror therapy enhances motor performance in the paretic upper limb after stroke: a pilot randomized controlled trial. Arch Phys Med Rehabil. 2014;95 (11):2000–2005. doi:10.1016/j.apmr.2014.06.020

38. Amasyali SY, Yaliman A. Comparison of the effects of mirror ther- apy and electromyography-triggered neuromuscular stimulation on hand functions in stroke patients: a pilot study. Int J Rehabil Res. 2016;39(4):302–307. doi:10.1097/MRR.0000000000000186

Dovepress Gandhi et al

Therapeutics and Clinical Risk Management 2020:16 submit your manuscript | www.dovepress.com

DovePress 83

39. Lin KC, Huang PC, Chen YT, Wu CY, Huang WL. Combining afferent stimulation and mirror therapy for rehabilitating motor func- tion, motor control, ambulation, and daily functions after stroke. Neurorehabil Neural Repair. 2014;28(2):153–162. doi:10.1177/ 1545968313508468

40. Harmsen WJ, Bussmann JB, Selles RW, Hurkmans HL, Ribbers GM. A mirror therapy–based action observation protocol to improve motor learning after stroke. Neurorehabil Neural Repair. 2015;29 (6):509–516. doi:10.1177/1545968314558598

41. Antoniotti P, Veronelli L, Caronni A, et al. No evidence of effective- ness of mirror therapy early after stroke: an assessor-blinded rando- mized controlled trial. Clin Rehabil. 2019;33(5):885–893. doi:10.11 77/0269215518824737

42. Chan WC, Au-Yeung SS. Recovery in the severely impaired arm post-stroke after mirror therapy: a randomized controlled study. Am j Phys Med Rehabil. 2018;97(8):572–577. doi:10.1097/PHM.000 0000000000919

43. Xu Q, Guo F, Salem HM, Chen H, Huang X. Effects of mirror therapy combined with neuromuscular electrical stimulation on motor recovery of lower limbs and walking ability of patients with stroke: a randomized controlled study. Clin Rehabil. 2017;31 (12):1583–1591. doi:10.1177/0269215517705689

44. Cristina LM, Matei D, Ignat B, Popescu CD. Mirror therapy enhances upper extremity motor recovery in stroke patients. Acta Neurologicabelgica. 2015;115(4):597–603.

45. Rodrigues LC, Farias NC, Gomes RP, Michaelsen SM. Feasibility and effectiveness of adding object-related bilateral symmetrical train- ing to mirror therapy in chronic stroke: a randomized controlled pilot study. Physiother Theory Pract. 2016;32(2):83–91. doi:10.3109/ 09593985.2015.1091872

46. Arya KN, Pandian S, Kumar D, Puri V. Task-based mirror therapy augmenting motor recovery in poststroke hemiparesis: a randomized controlled trial. J Stroke Cerebrovascular Dis. 2015;24 (8):1738–1748. doi:10.1016/j.jstrokecerebrovasdis.2015.03.026

47. Park Y, Chang M, Kim KM, An DH. The effects of mirror therapy with tasks on upper extremity function and self-care in stroke patients. J Phys Ther Sci. 2015;27(5):1499–1501. doi:10.1589/jpts. 27.1499

48. In T, Lee K, Song C. Virtual reality reflection therapy improves balance and gait in patients with chronic stroke: randomized con- trolled trials. Med Sci Monitor. 2016;22:4046. doi:10.12659/ MSM.898157

49. Ji SG, Kim MK. The effects of mirror therapy on the gait of subacute stroke patients: a randomized controlled trial. Clin Rehabil. 2015;29 (4):348–354. doi:10.1177/0269215514542356

50. Mohan U. Effectiveness of mirror therapy on lower extremity motor recovery, balance and mobility in patients with acute stroke: a randomized sham-controlled pilot trial. Ann Indian Acad Neurol. 2013;16(4):634. doi:10.4103/0972-2327.120496

51. Radajewska A, Opara JA, Kucio C, Blaszczyszyn M, Mehlich K, Szczygiel J. The effects of mirror therapy on arm and hand function in subacute stroke in patients. Int J Rehabil Res. 2013;36(3):268–274. doi:10.1097/MRR.0b013e3283606218

52. Thieme H, Bayn M, Wurg M, Zange C, Pohl M, Behrens J. Mirror therapy for patients with severe arm paresis after stroke–a rando- mized controlled trial. Clin Rehabil. 2013;27(4):314–324. doi:10.11 77/0269215512455651

53. Gurbuz N, Afsar SI, Ayaş S, Cosar SN. Effect of mirror therapy on upper extremity motor function in stroke patients: a randomized controlled trial. J Phys Ther Sci. 2016;28(9):2501–2506. doi:10.15 89/jpts.28.2501

54. Pandian JD, Arora R, Kaur P, Sharma D, Vishwambaran DK, Arima H. Mirror therapy in unilateral neglect after stroke (MUST trial): a randomized controlled trial. Neurology. 2014;83(11):101 2–1017. doi:10.1212/WNL.0000000000000773

55. Yang YR, Chen YH, Chang HC, Chan RC, Wei SH, Wang RY. Effects of interactive visual feedback training on post-stroke pusher syndrome: a pilot randomized controlled study. Clin Rehabil. 2015;29 (10):987–993. doi:10.1177/0269215514564898

56. Jacova C, Pearce LA, Costello R, et al. Cognitive impairment in lacunar strokes: the SPS3 trial. Ann Neurol. 2012;72(3):351–362. doi:10.1002/ana.v72.3

57. Blanco-Rojas L, Arboix A, Canovas D, et al. Cognitive profile in patients with a first-ever lacunar infarct with and without silent lacunes: a comparative study. BMC Neurol. 2013;16(13):203. doi:10.1186/1471-2377-13-203

58. Lamont K, Chin M, Kogan M. Mirror box therapy: seeing is believing. Explore. 2011;7(6):369–372. doi:10.1016/j.explore.2011.08.002

59. Luigi C, Giacomo R. The mirror neuron system. Arch Neurol. 2009;66(5):557–560. doi:10.1001/archneurol.2009.41

60. Buccino G, Binkofski F, Riggio L. The mirror neuron system and action recognition. Brain Lang. 2004;89(2):370–376. doi:10.1016/ S0093-934X(03)00356-0

61. Giacomo R. Maddalena FD, Luigi C. Mirror neurons and their clinical relevance. Nature Clin Pract Neurol. 2009;5(1):24. doi:10. 1038/ncpneuro0990

62. Pomeroy VM, Clark CA, Miller JS, et al. The potential for utilizing the “mirror neurone system” to enhance recovery of the severely affected upper limb early after stroke: a review and hypothesis. Neurorehabil Neural Repair. 2005;19(1):4–13. doi:10.1177/1545 968304274351

63. Buccino G, Solodkin A, Small SL. Functions of the mirror neuron system: implications for neurorehabilitation. Cognit Behav Neurol. 2006;19(1):55–63. doi:10.1097/00146965-200603000-00007

64. Karnath HO. New insights into the functions of the superior temporal cortex. Nature Rev Neurosci. 2001;2(8):568. doi:10.1038/35086057

65. Allison T, Puce A, McCarthy G. Social perception from visual cues: role of the STS region. Trends Cogn Sci. 2000;4(7):267–278. doi:10.1016/S1364-6613(00)01501-1

66. Rothgangel A, de Bie RA, Bastiaenen CH, et al. The role of the mirror neuron system in rehabilitation with mirror therapy following middle cerebral artery infarction: a pilot fMRI study-51. Annual Meeting of the German Society of Medical Informatics, Biometry and Epidemiology (GMDS); 2006; 34; Leipzig.

67. Matthys K, Smits M, Van der Geest JN, et al. Mirror-induced visual illusion of hand movements: a functional magnetic resonance ima- ging study. Arch Phys Med Rehabil. 2009;90(4):675–681. doi:10.10 16/j.apmr.2008.09.571

68. Michielsen ME, Smits M, Ribbers GM, et al. The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke. J Neurol Neurosurg Psychiatry. 2011;82 (4):393–398. doi:10.1136/jnnp.2009.194134

69. Deconinck FJ, Smorenburg AR, Benham A, et al. Reflections on mirror therapy: a systematic review of the effect of mirror visual feedback on the brain. Neurorehabil Neural Repair. 2015;29 (4):349–361. doi:10.1177/1545968314546134

70. Ezendam D, Bongers R, Jannink M. Systematic review of the effec- tiveness of mirror therapy in upper extremity function. DisabilRehabil. 2009;31:2135–2149.

71. Staudt M, Grodd W, Gerloff C, et al. Two types of ipsilateral reorga- nization in congenital hemiparesis: a TMS and fMRI study. Brain. 2002;125(10):2222–2237. doi:10.1093/brain/awf227

72. Schwerin S, Dewald JPA, Hatzi M, et al. Ipsilateral versus contral- ateral cortical motor projections to a shoulder adductor in chronic hemiparetic stroke: implications for the expression of arm synergies. Exp Brain Res. 2008;185:509–519. doi:10.1007/s00221-007-1169-8

73. Dong Y, Winstein CJ, Albistegui-DuBois R, et al. Evolution of FMRI activation in the perilesional primary motor cortex and cerebellum with rehabilitation training-related motor gains after stroke: a pilot study. Neurorehabil Neural Repair. 2007;21(5):412–428. doi:10.117 7/1545968306298598

Gandhi et al Dovepress

submit your manuscript | www.dovepress.com

DovePress Therapeutics and Clinical Risk Management 2020:1684

74. Bhasin A, Srivastava PMV, Kumaran SS, et al. Neural interface of mirror therapy in chronic stroke patients: a functional magnetic resonance imaging study. Neurol India. 2012;60(6):570–576. doi:10.4103/0028-3886.105188

75. Yavuzer G, Selles R, Sezer N, et al. Mirror therapy improves hand function in subacute stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2008;89:393–398. doi:10.1016/j.apmr.2007. 08.162

76. Arboix A, Cartanyà A, Lowak M, et al. Gender differences and woman-specific trends in acute stroke: results from a hospital-based registry (1986–2009). Clin Neurol Neurosurg. 2014;127:19–24. doi:10.1016/j.clineuro.2014.09.024

77. Arboix A, Blanco-Rojas L, Martí-Vilalta JL. Advancements in under- standing the mechanisms of symptomatic lacunar ischemic stroke: translation of knowledge to prevention strategies. Expert Rev Neurother. 2014;14(3):261–276. doi:10.1586/14737175.2014.884926

Therapeutics and Clinical Risk Management Dovepress Publish your work in this journal Therapeutics and Clinical Risk Management is an international, peer- reviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines. This journal is indexed on PubMed Central, CAS,

EMBase, Scopus and the Elsevier Bibliographic databases. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors.

Submit your manuscript here: https://www.dovepress.com/therapeutics-and-clinical-risk-management-journal

Dovepress Gandhi et al

Therapeutics and Clinical Risk Management 2020:16 submit your manuscript | www.dovepress.com

DovePress 85