Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol

Abstract

Introduction

Upper limb motor impairment after a stroke is an important sequela. Constraint-induced movement therapy is a rehabilitation approach that has strong evidence. The incorporation of transcranial direct-current stimulation has been proposed; however, there is a lack of studies that confirm its benefits. The principal aim is to compare the effectiveness of 7 days of active versus sham bi-hemispheric transcranial direct-current stimulation, combined with modified constraint-induced movement therapy, for motor and functional recovery of the hemiparetic upper limb in subacute stroke patients.

Method/design

Randomized, double blind, sham-controlled, parallel group clinical trial in two stroke units. Participants: adults over 18 years, at least 2 days post unihemispheric stroke event, with hemiparesis, and without severe pain, aphasia or cognitive impairment. Intervention: Patients will receive 7 days of continuous therapy and be assigned to one of the treatment groups: active bi-hemispheric transcranial direct-current stimulation or sham bi-hemispheric transcranial direct-current stimulation. Measurement: Evaluations will take place at days 0, 5, 7 and 10, and at 3rd months. The Fugl-Meyer Assessment – Upper Extremity, Wolf Motor Function Test, Functional Independence Measure and Stroke Impact Scale are considered.

Discussion

Modified constraint-induced movement therapy plus transcranial direct-current stimulation in subacute stroke patients with hemiparesis could maximize motor and functional recovery.

Trial registration: ClinicalTrials.gov identifier NCT03452254.

Keywords

Stroke non-invasive brain stimulation upper limb constraint-induced movement therapy occupational therapy early rehabilitation

Introduction

Stroke is one of the leading causes of serious long-term impairment. According to the estimates, 12,500 people annually suffer a new or recurrent ischemic stroke in Chile (MINSAL, 2013), which shows the magnitude of the problem. Motor impairment of the upper limb (UL) stands out as the main sequela after a stroke (80% of patients experience it) (Faria-Fortini et al., 2011). Constraint-induced movement therapy (CIMT) is a rehabilitation approach that has demonstrated strong evidence (Lin et al., 2019; Liu et al., 2017; Wattchow et al., 2018). Even though patients reach certain levels of recuperation through this approach, results are insufficient as 55–75% of patients continue to experience UL motor impairment (American Heart Association, n.d.). Because of this, it is pertinent to conduct research in order to explore new rehabilitation strategies.

Recent studies on functional neuroimaging suggest that there is an abnormal balance in motor cortex excitability after a stroke: relative under-excitability in the affected hemisphere and over-excitability in the unaffected hemisphere in patients with subacute/chronic stroke and moderate motor impairment (Cramer, 2008; Rehme and Grefkes, 2013). This imbalance would limit the possibilities of a greater recovery.

Non-invasive brain stimulation (NIBS), a series of techniques applied to the brain, have the ability to modulate cortical excitability (increasing or decreasing it) and optimize its plasticity (Wagner et al., 2007). One of these techniques is the transcranial direct-current stimulation (tDCS) technique, which applies a direct low-intensity current (0.5–2 mA) through a battery connected to two electrodes that are located in the scalp. Studies in tDCS and stroke have been conducted in aphasia, hemineglect, swallowing disorders and in the function of UL. It has been suggested that, in association with neurorehabilitation treatment, it can improve motor recovery (Biou et al., 2019; Elsner et al., 2016; Kandel et al., 2012). The application in motor recovery has been based on two fundamental principles: the reduction of interhemispheric imbalance and the improvement of brain plasticity. Therefore, it has been used either to directly increase activity within the ipsilesional motor cortex or to decrease activity within the contralesional M1 cortex. In recent studies it has been included in earlier stages of evolution (acute and subacute) and it has begun to incorporate motor training specific to the UL in occupational therapy and physical therapy (Butler et al., 2013; Hsu et al., 2012); however, there is little evidence available.

In order to re-establish brain balance, we proposed that the early introduction of NIBS, such as tDCS, to the motor rehabilitation training could promote improvement of UL function in patients with stroke. Nevertheless, there are not enough studies yet that confirm the benefits of using these techniques, define the most appropriate protocols and determine what patients in which evolving stage would be the best candidates for treatment.

Primary and secondary objectives

This aims of this study are to compare the effectiveness of 7 continuous days of bi-hemispheric tDCS, both active and sham, combined with modified constraint-induced movement therapy (mCIMT) for motor and functional recovery of the hemiparetic UL in hospitalized subacute stroke patients at Hospital Clínico de la Universidad de Chile and Hospital Clínico San José.

The secondary aims are to compare the results of combined bi-hemispheric tDCS (active or sham) with mCIMT, in:

Independence in basic activities of daily living after treatment and at 3 days and 3 months follow-up.

Percentage of upper limb motor recovery after treatment and at 3 days and 3 months follow-up.

Percentage of functional upper limb motor recovery after treatment and 3 days follow-up.

Score of quality of life at 3^rd month.

This comparison responds to the hypothesis that patients who receive bi-hemispheric and active tDCS combined with mCIMT (experimental group) obtain at least 30% more recovery of the paretic UL compared to the control group, who receive sham bi-hemispheric tDCS plus mCIMT after a protocol of 7 days of treatment.

Trial design

We propose to carry out a multicenter randomized clinical trial, double blind, sham-controlled, parallel group in two hospital centers. The trial is based in accordance with Consolidated Standards of Reporting Trials (CONSORT) and registered in ClinicalTrials.gov identifier NCT03452254 (Figure 1).

Figure 1.

Flow diagram of the randomized controlled trial.

Method

Participants and study setting

The study includes adults with a subacute unihemispheric stroke with deficit in UL motor control admitted to the Hospital Clínico Universidad de Chile and Hospital Clínico San José between June 2018 and July 2020. We will recruit 70 patients. Inclusion and exclusion criteria are described in Table 1.

Table 1.

Admission criteria.

Inclusion criteria	Exclusion criteria
Unihemispheric stroke event, ischemic or hemorrhagic, cortical or subcortical. Hemiparesis with unilateral brachial compromise. Evolution time ≥2 days (equal to or more than 2 days after stroke onset). Patient must be 18 years old or older. Proven ability to perform some movement with the upper limb: at least 20° active extension of the wrist and 10° extension in fingers and/or 20° abduction angle in the shoulder. Informed consent signed by the patient.	Previous central injury with motor sequelae. Severe aphasia with a score ≥2 in the language item of the National Institutes of Health Stroke Scale (NIHSS) assessment. Severe cognitive impairment with a score ≤15 points in the Mini-Mental State Examination (MMSE). Shoulder subluxation and/or pain > 4 points in the Numerical Rating Scale for Pain (NRS). Non-controlled epilepsy or epileptic seizures in the last 3 months. Metal implants or pacemaker. Pregnancy. Any other condition that, in the responsible physician’s opinion, could prevent the correct development of the treatment.

Inclusion criteria

Exclusion criteria

Unihemispheric stroke event, ischemic or hemorrhagic, cortical or subcortical.

Hemiparesis with unilateral brachial compromise.

Evolution time ≥2 days (equal to or more than 2 days after stroke onset).

Patient must be 18 years old or older.

Proven ability to perform some movement with the upper limb: at least 20° active extension of the wrist and 10° extension in fingers and/or 20° abduction angle in the shoulder.

Informed consent signed by the patient.

Previous central injury with motor sequelae.

Severe aphasia with a score ≥2 in the language item of the National Institutes of Health Stroke Scale (NIHSS) assessment.

Severe cognitive impairment with a score ≤15 points in the Mini-Mental State Examination (MMSE).

Shoulder subluxation and/or pain > 4 points in the Numerical Rating Scale for Pain (NRS).

Non-controlled epilepsy or epileptic seizures in the last 3 months.

Metal implants or pacemaker.

Pregnancy.

Any other condition that, in the responsible physician’s opinion, could prevent the correct development of the treatment.

Interventions

Patients will be randomized to one of the following treatment groups: (a) control group: sham bi-hemispheric tDCS combined with mCIMT; or (b) experimental group: active bi-hemispheric tDCS combined with mCIMT. Procedures for each technique are described as follows.

Procedures for mCIMT

Both groups will perform the mCIMT during a period of 7 consecutive days. This protocol consists of two main elements:

Restriction of the movements of the non-affected hand by wearing a mitt for 6 hours a day: we will use a mitt that limits movement of the fingers but allows free movements of the wrist, elbow and shoulder. Rehabilitation activities, including the ones proposed in the protocol, are performed within the 6 hours and the mitt can be removed for hygiene, bathing, feeding and all actions in which the mitt may pose a risk to the patient’s safety.

Two hours per day of intensive and individualized training of the affected arm, guided by an occupational therapist: the 2 hour training will be divided into two sessions of 1 hour each, with a lapse of at least 2 hours in between, which results in a total of 14 hours of intervention. During one of the daily sessions, the patient will receive 20 minutes of either the active or sham tDCS.

The sessions are based on the design used for task-oriented approaches. Eighteen functional activities were raised, which were classified according to complexity into basic, medium and advanced motor level activity (Table 2). Each functional activity is described in detail and includes 10 “shaping tasks,” which consisted of the movements or tasks necessary for the correct execution of the functional activity. Each shaping task is repeated 5–10 times depending on the motor level of the patient. The patient and the occupational therapist select a functional activity to work on until that activity can be executed efficiently, and then move on to a more complex one (for more detail see supplementary online material).

Table 2.

Functional activities classified by motor level.

Basic level	Intermediate level	Advanced level
Raise and lower arm from a table.	Wash your face.	Drink liquid from a glass.
Clean the table.	Cut a banana with a knife.	Brush your teeth.
Apply lotion on your arm.	Raise and lower your pants.	Eat with a fork.
Maintain a bottle of water upright.	Brush or comb your hair.	Separate legumes.
Put on and take off a sock.	Put large objects away in a basket or night table.	Open a lock.
Eat bread.	Classify large nuts and bolts.	Write your name.

At the same time, sessions will be organized in three blocks: preparation, activation and function (Table 3). In the third block, aimed at function, the patient has to choose one activity of daily living that can be performed in a hospital context. This activity will be performed during the protocol and adjusted according to the progress made. The content of the occupational therapy sessions will be based on the following techniques or concepts: tone modulation and body awareness; sensory-motor stimulation; activation of motor sequences in different postures (supine, seated, bipedal); motor facilitation techniques for functional activities in different ranges of movement. The activity will be tailored according to the patient’s condition; during the intervention, verbal and visual feedback will be given by the therapist.

Table 3.

Program of mCIMT session.

Block 1		Block 2		Block 3
Preparation15 minutes		Activation30 minutes		Function15 minutes
Objective: Encourage awareness of body posture and prepare the body and limb (structure) for the activity.	Therapist actions: Give the patient an idea of body posture during the exercise. The correct relation of each body segment for the activities should be emphasized: feet, hips, trunk, head, shoulder, arms and hands (proprioceptive and attentional information).	Objective: Train the motor functions of the upper limb involved in the activities of daily living chosen by the patient.	Therapist actions: The occupational therapist will work on activities for the coordination of movements and manual dexterity (reach/hold/handle objects and fine motor skills) with different objects according to the synergy sequence. Activities will work on different ranges of movements and body postures, adapted to the motor and cognitive level of the patient.	Objective: Train the patient in the activity of daily living of their choice.	Therapist actions: Work with the patient on the chosen activity of daily living by means of facilitation, activity graduation and cognitive demand, following the aforementioned guidelines. The mitt will be removed in this block in case the activity includes a bimanual process.

mCIMT: modified constraint-induced movement therapyFor more information, see supplementary material.

tDCS procedures

The application of the tDCS will be bi-hemispheric, and this technique and the first daily session of upper limb motor training will be applied simultaneously. This will result in seven sessions of tDCS stimulation for 7 consecutive days. The session will start with the application of the bi-hemispheric tDCS with a couple of surface sponge electrodes (25 cm²) soaked in saline solution and connected to a constant current generated by a battery. The device will have been previously set to provide either active or sham stimulation so as to keep both the patient and therapist blind. The device used will be a NE STARSTIM tCS® (Barcelona, Spain).The treatment modality will be as follows:

Active tDCS: The anodic electrode will be put on the affected M1 (C3/C4, according to the EEG 10/20 System). The cathodic electrode will be put on contralateral M1 (non-affected). We will apply a constant current of 2mA intensity for 20 minutes, with a 30-second ramp up and ramp down, while the patient performs the mCIMT session, which will last 1 hour.

Sham tDCS: We will use the same place and parameters of stimulation applied for the active group, but the stimulator will deactivate after 30 seconds of stimulation, with 30 seconds of ramp down. This will ensure that the patient will feel the initial tingling sensation at the beginning of the tDCS, which is a requisite for blinding.

The mCIMT session is the same for both groups.

General procedures

During the 7 consecutive protocol days, all patients should continue taking part in the usual interdisciplinary rehabilitation programs in their hospitals.

If the patient is discharged before the conclusion of the 7 days of protocol, the treatment will continue under an outpatient modality in the hospital until the protocol is completed. In addition, the patient will be asked to record their compliance with the use of the mitt, as well as the activities performed.

Outcome measures

We will collect relevant clinical and sociodemographic information. For the assessment of primary and secondary outcomes, the following evaluations will be used:

Fugl-Meyer Assessment – Upper Extremity (FMA-UE): evaluates motor recovery after a stroke. The four domains assessed include: motor function: 0–66 points (reflex activity, volitional movement within synergies, volitional movement mixing synergies, volitional movement with little or no synergy, wrist, hand, coordination/speed); sensation: 0–12 points (light touch, position); passive joint motion: 0–24 points; and joint pain: 0–24 points. Higher scores indicate a better performance (Fugl-Meyer et al., 1975).

Wolf Motor Function Test (WMFT): evaluates upper limb motor capacity by means of timed and functional tasks. It consists of 17 items, two strength tasks and 15 tasks that consider quality and time performance (scale from 0: “does not attempt with upper limb being tested” to 5: “uses the limb being tested, movement appears to be normal”) (Wolf et al., 2001).

Functional Independence Measure (FIM): evaluates the independence level in 18 activities of daily living (ADL) using a seven-level scale (1–7 from lower to higher independence) with total possible scores that range from 18 to 126 points (Young et al., 2009).

Stroke Impact Scale (SIS): assesses health-related quality of life with self-report assessment of stroke. The SIS has eight domains: strength, hand function, mobility, physical and instrumental activities of daily living (ADL and IADL), memory and thinking, communication, emotion and social participation. Scores for each domain range from 0–100, and higher scores indicate a better health-related quality of life (Carod-Artal et al., 2008).

Satisfaction questionnaire: at the end of the intervention, participants will complete a questionnaire containing 21 questions about their satisfaction with the protocol and the progress obtained, two questions on collateral effects and a blinding check question.

The assessments will be done in five stages: before the intervention starts (A0), on the 5th day of treatment (A1), once the intervention ends (A2), a 3-day follow-up (FU1) and 3-month follow-up after the end of the intervention to evaluate if the changes persist (FU2).

Sample size

The size of the sample was calculated based on the motor recovery of the UL (primary endpoint), evaluated through FMA-UE. We considered the results obtained from two randomized clinical trials that assessed motor recovery in patients with subacute stroke after a protocol of mCIMT (Singh and Pradhan, 2013; Wu et al., 2007). Usually, patients treated in Hospital Clínico Unversidad de Chile show initial motor performance scores of 32±13 points on the FMA-UE, similar to figures reported by Singh et al. However, the standard deviation is closer to Wu et al.’s (2007) article; therefore, we estimated that the experimental group could show a 30% increase after 7 days under the protocol (10 points in the FMA-UE), while the control group would not exhibit clinical changes, or at most only those that are minimally relevant according to the FMA-UE.

To obtain the sample size, we considered a statistical power of 80%, a one-tailed significance level of 5%, a base assessment measurement, and three follow-up assessments (repeated measurement design). As a result, we will have 56 patients enrolled, with 28 patients in each group and seven more patients for each group in case of possible drop-outs, which totals 70 patients, or 35 patients per group.

Randomization, blinding and allocation strategy

Patients will be assigned to the active tDCS plus mCIMT group or to the sham tDCS plus mCIMT group using randomized blocking to ensure the balance between the treatments. Once the person in charge of recruiting receives the patient’s informed consent, he will notify the person in charge of randomization, who will not have any relationship with the patient. He will not know the patient’s clinical record, and will not be influenced by head researchers, evaluators or therapists. This person will send a text message to the person responsible for programming and installing the tDCS, who will then proceed to set the tDCS as either active or simulated. The data analysis will be performed by a statistician who does not work in the participating hospitals and has no contact with the study participants.

Statistical analysis

Descriptive statistics

Regarding descriptive statistical analysis of continuous numeric variables, we will use the average and standard deviation in the case of normally distributed variables, and median and 25–75 percentile (for each time and group) in the case of non-normally distributed variables. For qualitative categorical and ordinal data, we will use absolute and relative frequency (number and percentage), which will be illustrated in a frequency table.

Analytic statistics

We will compare the two groups by means of mixed models to control variability between treatments and patients. All confidence intervals will be 95%, while the significance level will be 5%. If the drop-outs are higher than our estimates and the difference between the groups is significant, we will also calculate a post hoc statistical power. We will use STATA software, version 14.0.

Discussion

The present study is the first to use mCIMT with tDCS in patients with subacute stroke who are hospitalized. It has the potential to return brain balance early on in a patient with mild to moderate motor deficit after a stroke and maximize the chances of motor and functional recovery of the affected upper limb, allowing greater performance in basic ADL at discharge. This may then reflect a more effective socio-labor reintegration, and a lower use of or cost to the socio-sanitary services that these people require.

The intensity of proposed mCIMT (2 hours a day of training with 6 hours of restriction for 7 days) is related to the recommendation made by Dromerick et al. (2009). They suggest that low-intensity CIMT, such as the one proposed here, would be better than high-intensity CIMT in patients who have suffered an acute stroke. We intend to contribute to national clinical guidelines in order to reduce clinical variability in the treatment of motor and functional recovery of people after a stroke (through early rehabilitation strategies).

Moreover, a study of high methodological quality with a larger sample size than in similar studies is proposed, which accounts for the high impact it can generate. An early intervention protocol lasting 7 days is proposed for people who have suffered a stroke and who are hospitalized in two institutions in Chile with great demand for care: the Hospital Clínico Universidad de Chile and Hospital Clínico San José. The 7-day protocol adapts to the average hospitalization time that mild to moderate stroke patients with have in these institutions, which ensures their viability and future replicability in these and other tertiary level health care institutions.

This research is a contribution to occupational therapy and rehabilitation treatment in daily clinical practice, testing a standardized protocol for early rehabilitation, clearly detailing 18 functional activities and/or basic ADL, giving professionals a tool with evidence. Furthermore, to integrate occupational therapy technology in early stages of stroke could reduce costs in later stages, while also reducing the severity of the deficit and the burden generated by years lived with increasing disability. If we achieve a lower level of disability in patients who are of a productive age, they will have greater possibilities for labor reintegration and/or be less burdened by disease when they are elderly, thus preventing future dependence.

To date, there are no randomized clinical trials of mCIMT in acute and subacute stroke (Fleet et al., 2014). Liu et al.’s (2017) meta-analysis demonstrated that CIMT or mCIMT might be more beneficial than traditional rehabilitation therapy in acute and subacute stroke. However, large-scale, well-designed multicenter studies are needed to further confirm the impact that the degree of CIMT or mCIMT has on functional outcomes in acute and subacute stroke.

For the first time, the tDCS experience combined with restrictive therapy will be recorded in a very early approach context. In the case of positive results, the application of a protocolized rehabilitation strategy will be encouraged in the early care of people after a stroke.

Supplemental Material

BJO904339 Supplemental Material1 - Supplemental material for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol

Supplemental material, BJO904339 Supplemental Material1 for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol by Maricel A Garrido, Evelyn A Άlvarez, Fabrizio L Acevedo, Álvaro I Moyano, Natalia P Castillo and Gabriel A Cavada in British Journal of Occupational Therapy

Supplemental Material

BJO904339 Supplemental Material2 - Supplemental material for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol

Supplemental material, BJO904339 Supplemental Material2 for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol by Maricel A Garrido, Evelyn A Άlvarez, Fabrizio L Acevedo, Álvaro I Moyano, Natalia P Castillo and Gabriel A Cavada in British Journal of Occupational Therapy

Supplemental Material

BJO904339 Supplemental Material3 - Supplemental material for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol

Supplemental material, BJO904339 Supplemental Material3 for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol by Maricel A Garrido, Evelyn A Άlvarez, Fabrizio L Acevedo, Álvaro I Moyano, Natalia P Castillo and Gabriel A Cavada in British Journal of Occupational Therapy

Supplemental Material

BJO904339 Supplemental Material4 - Supplemental material for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol

Supplemental material, BJO904339 Supplemental Material4 for Early non-invasive brain stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in stroke patients: Study protocol by Maricel A Garrido, Evelyn A Άlvarez, Fabrizio L Acevedo, Álvaro I Moyano, Natalia P Castillo and Gabriel A Cavada in British Journal of Occupational Therapy

Footnotes

Acknowledgments

We appreciate the support of the research team of the Physical Medicine and Rehabilitation Service of Hospital Clínico Universidad de Chile. Special thanks to Elisabet Guzmán, Paulina Corona, Constanza Rojas, Valentina Provoste, Nicole Jara, Katherine Silva, Paula Ruz, Matías Acuña, Catalina Leyton, Tatiana Donoso, Atilio González and Joaquín Varas.

We appreciate the support of the research team of the Physical Medicine and Rehabilitation Service of Hospital Clínico San José. Special thanks to Javiera Sepúlveda, Paulina del Solar, Miguel Fuentes, Francisco Bustos and Bárbara Peralta.

We appreciate the support of Universidad Central de Chile and Universidad de Chile for its sponsorship.

We appreciate the support of the following occupational therapy students: Evelyn Jelvez, Romina Canales, Daniela Cofré, Geraldine Arrué, Paula Arce, Camila Contreras, Melissa Cortés and Natalia Díaz for their participation in the implementation phase of the study. Finally, we appreciate professors Pablo Burgos and Juan José Marimán for their technical support.

Research ethics

The Ethics Committee of the Hospital Clínico de la Universidad de Chile (OAIC 849/16) approved the project in December 2016. All participants will provide informed consent and their safety and respect will be protected.

Consent

All participants will provide written informed consent to be interviewed for the study, including authorization to use data, images and videos.

Declaration of conflicting interests

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The trial is funded by “Fondo Nacional para la Investigación y Desarrollo en Salud” (FONIS – National Fund for Health Research and Development), belonging to the “Comisión Nacional de Investigación Científica y Tecnológica de Chile” (CONICYT – National Commission for Scientific and Technological Investigation). The commission will not participate in any of the stages pertaining to the study.

Contributorship

Maricel Garrido and Evelyn Álvarez participated in the conception, literature review and design of the study protocol. Fabrizio Acevedo and Natalia Castillo participated in design of intervention activities, patient recruitment and data collection. Álvaro Moyano participated in patient recruitment and data collection. Gabriel Cavada participated in statistical design.

All authors contributed to the methodology of the project and the statistical analysis plan.

All authors reviewed and edited the manuscript and approved the final version.

ORCID iD

Maricel Garrido M

Supplemental material

Supplementary material is available at: DOI:10.1177/0308022620904339.

References

American Heart Association (n.d.) Available at: https://www.heart.org/ (accessed 14 August 2019).

Biou

Cassoudesalle

Cogné

, et al. (2019) Transcranial direct current stimulation in post-stroke aphasia rehabilitation: A systematic review. Annals of Physical and Rehabilitation Medicine 62(2): 104–121.

Butler

Shuster

O’Hara

, et al. (2013) A meta-analysis of the efficacy of anodal transcranial direct current stimulation for upper limb motor recovery in stroke survivors. Journal of Hand Therapy 26(2): 162–171.

Carod-Artal

Coral

Trizotto

, et al. (2008) The stroke impact scale 3.0: Evaluation of acceptability, reliability, and validity of the Brazilian version. Stroke 39(9): 2477–2484.

Cramer

(2008) Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery. Annals of Neurology 63(3): 272–287.

Dromerick

Lang

Birkenmeier

, et al. (2009) Very early constraint-induced movement during stroke rehabilitation (VECTORS): A single-center RCT. Neurology 73(3): 195–201.

Elsner

Kugler

Pohl

, et al. (2016) Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke. Cochrane Database of Systematic Reviews 3: CD009645.

Faria-Fortini

Michaelsen

Cassiano

, et al. (2011) Upper extremity function in stroke subjects: Relationships between the international classification of functioning, disability, and health domains. Journal of Hand Therapy 24(3): 257–265.

Fleet

Page

MacKay-Lyons

, et al. (2014) Modified constraint-induced movement therapy for upper extremity recovery post stroke: What is the evidence? Topics in Stroke Rehabilitation 21(4): 319–331.

10.

Fugl-Meyer

Jääskö

Leyman

, et al. (1975) The post-stroke hemiplegic patient. 1. A method for evaluation of physical performance. Scandinavian Journal of Rehabilitation Medicine 7(1): 13–31.

11.

Hsu

Cheng

Liao

, et al. (2012) Effects of repetitive transcranial magnetic stimulation on motor functions in patients with stroke. Stroke 43(7): 1849–1857.

12.

Kandel

Beis

Le Chapelain

, et al. (2012) Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: A review. Annals of Physical and Rehabilitation Medicine 55(9–10): 657–680.

13.

Lin

Tsai

Wang

, et al. (2019) Effectiveness and superiority of rehabilitative treatments in enhancing motor recovery within 6 months poststroke: A systemic review. Archives of Physical Medicine and Rehabilitation 100(2): 366–378.

14.

Liu

Huai

Gao

, et al. (2017) Constraint-induced movement therapy in treatment of acute and sub-acute stroke: A meta-analysis of 16 randomized controlled trials. Neural Regeneration Research 12(9): 1443–1450.

15.

MINSAL (2013) Accidente Cerebrovascular Isquémico en personas de 15 años y más – Orientación en Salud. Superintendencia de Salud, Gobierno de Chile. Available at: www.supersalud.gob.cl/difusion/665/w3-article-611.html (accessed 17 March 2019).

16.

Rehme

Grefkes

(2013) Cerebral network disorders after stroke: Evidence from imaging-based connectivity analyses of active and resting brain states in humans. The Journal of Physiology 591(1): 17–31.

17.

Singh

Pradhan

(2013) Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial. Annals of Indian Academy of Neurology 16(2): 180–184.

18.

Wagner

Valero-Cabre

Pascual-Leone

(2007) Noninvasive human brain stimulation. Annual Review of Biomedical Engineering 9(1): 527–565.

19.

Wattchow

McDonnell

Hillier

(2018) Rehabilitation interventions for upper limb function in the first four weeks following stroke: A systematic review and meta-analysis of the evidence. Archives of Physical Medicine and Rehabilitation 99(2): 367–382.

20.

Wolf

Catlin

Ellis

, et al. (2001) Assessing Wolf motor function test as outcome measure for research in patients after stroke. Stroke 32(7): 1635–1639.

21.

Chen

Tang

, et al. (2007) Kinematic and clinical analyses of upper-extremity movements after constraint-induced movement therapy in patients with stroke: A randomized controlled trial. Archives of Physical Medicine and Rehabilitation 88(8): 964–970.

22.

Young

Fan

Hebel

, et al. (2009) Concurrent validity of administering the Functional Independence Measure (FIM) instrument by interview. American Journal of Physical Medicine & Rehabilitation 88(9): 766–770.

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