Multisensory stimulation to promote upper extremity motor recovery in stroke: A pilot study

Abstract

Introduction

Occupational therapists have been using various preparatory methods as part of the treatment sessions to prepare clients for occupational performance and participation in occupation. Studies have shown sensory stimulation both activates brain areas inducing cortical reorganization and modulates motor cortical excitability for the stimulated afferents, hence re-establishing the disrupted sensorimotor loop due to stroke. This pilot investigates the potential effects of using multisensory stimulation as a preparatory method prior to conventional training (CT) on upper-extremity motor recovery and self-care function in stroke patients.

Method

This was a quasi-randomized controlled pilot. Twelve participants (age in years = 67.17 + /−11.29) with upper extremity motor deficits were randomly allocated to multisensory therapy (n = 6) or conventional (n = 6) groups for 12-week training. Assessments were conducted at baseline and post-intervention using Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA), Manual Muscle Testing (MMT), Functional Test for the Hemiplegic Upper Extremity (Hong Kong version FTHUE-HK) and Modified Barthel Index (MBI).

Results

Significant between-group differences were shown in FMA (p = 0.003), FTHUE-HK (p = 0.028) and MMT (p = 0.034).

Conclusion

Multisensory stimulation could be used as a preparatory method prior to CT in improving upper extremity motor recovery in stroke rehabilitation. Further well-designed larger scale studies are needed to validate the potential benefits of this application.

Keywords

Multisensory motor recovery stroke upper extremity

Introduction

Stroke is a leading cause of long-term disability worldwide (Feigin et al., 2014). More than three-quarters of stroke survivors have an initial upper extremity (UE) motor deficit (Hatem et al., 2016; Lawrence et al., 2001). About 50% of them still cannot incorporate their paretic hand into daily activities at 6-months post stroke (Pollock et al., 2014). Despite the advances in stroke rehabilitation, post-stroke UE impairment is still a major challenge impacting on stroke survivors' functional participation and subjective wellbeing (Coupar et al., 2012). A recent Cochrane systematic review on reviews of randomized controlled trials of patients with stroke comparing interventions provided to improve upper limb function has reported no high-quality evidence can be found for any currently used interventions in routine practice. (Pollock et al., 2014). Developing effective strategies to maximize post-stroke UE recovery and enhance functional hand-use remains a major focus in stroke rehabilitation and research.

Stimulation of the afferent receptor has been found to enhance neuroplasticity in the brain and heighten excitation of the anterior horn cell via the reflex circuit (Kaelin-Lang et al., 2002). Studies examining thermal (Chen et al., 2005), tactile stimuli (Laaksonen et al., 2012) and vibration (Liepert and Binder, 2010) have reported encouraging results. Controlled sensory input is used to influence the reflexive motor response and enhance the excitability in motor cortex with the purpose of facilitating controlled motor functions and activity performance by the higher brain centers. Sensory stimulation can both activate brain areas inducing cortical reorganization and modulate motor cortical excitability for the stimulated afferents (Cramer et al., 2011; Gelnar et al., 1999). Specifically, Gelnar et al. (1999) compared the cortical representations for thermal, vibrotactile and motor performance tasks and found thermal stimuli could activate multiple cortical regions which were greater than those induced by other stimulations. Positive effects of thermal stimulation on UE motor recovery have been demonstrated in interventions for acute and chronic stroke survivors (Chen et al., 2005; Wu et al., 2010). Chen et al. (2005) used a cold pack (<0℃) and a hot pack (∼75 ℃) as thermal agents and detected uncomfortable signs at a mean time of 15 and 10 seconds, respectively, on paretic upper limbs. These provided references for sufficient stimulation to elicit noxious responses in the brain as well as for ceiling durations of heating and cooling stimulation on the paretic hand to avoid potential tissue damage. The researchers used a protocol of alternate heat/cold stimuli for 20–30 minutes daily plus standard therapy for 6 weeks and found significant improvements in sensory and motor functions of hemiplegic stroke patients. More recently, Hsu et al. (2013) reported a combination of thermal stimulation and a traditional stroke rehabilitation program could improve the lower extremity (LE) movement and function in people recovering from stroke.

Muscle vibration is also a powerful stimulus which can induce widespread cortical activation and reorganization (Münte et al., 1996). Findings have been reported that muscle vibration promotes motor recovery and function in stroke through remodeling the sensorimotor organization in the brain and change the excitability of the vibrated muscles (Marconi et al., 2011; Paoloni et al., 2014).

It has been proposed that multisensory feedback could promote motor learning by re-establishing the disrupted sensorimotor loop due to stroke (Johansson, 2011). Studies have demonstrated that multisensory stimulation strategies activate both unimodal sensory areas and the association areas in the brain which may lead to activation of the increased connection of the associated motor cortex, and enhance neuroplasticity (Johansson, 2012; Takeuchi and Izumi, 2015). A combination of multisensory stimulation with neurorehabilitation therapies may produce synergistic effects in cortical reorganization and maximize functional gains in stroke patients (Takeuchi and Izumi, 2015).

Occupational therapists have been using different preparatory methods to prepare clients for occupational performance which may include sensory stimulation, or selected physical modalities, such as application of hot/cold packs at the beginning of a treatment session to prepare soft tissue for movement (Walter and Winston, 2018).

“Preparatory methods” is one of the general categories of occupational therapy interventions and refers to any “modalities, devices, and techniques to prepare the client for occupational performance” (American Occupational Therapy Association (AOTA), 2014).

Typically, preparatory methods “do not require the client's active participation but are done by the therapist to support the client's participation or engagement in the intervention process” (Walter and Winston, 2018). Thus, preparatory methods are done by occupational therapy practitioners to affect specific body structures and body functions, and to support the client's participation in interventions, with an ultimate goal of promoting engagement and performance in occupation.

The objective of this study was to initially investigate the potential effects of using multisensory stimulation (thermal and vibration) as preparatory method prior to conventional training (CT) on UE motor recovery in stroke patients. It is hypothesized that a combined protocol using multisensory stimulation and CT can synergistically facilitate and better promote motor recovery after stroke than using CT alone.

Method

Study design

This was a quasi-randomized-controlled pre-post pilot. All outcome measures were conducted at baseline (pretest) and post-intervention (post-test) by an independent assessor. After baseline assessment, participants were randomly allocated according to admission sequence to a multisensory therapy (MT) group or a CT group, conducted by two occupational therapists, one for each group. Ethics approval for this study was obtained from the Hospital Authority Ethics Committee in accordance with the Declaration of Helsinki. Written informed consent was obtained from all the participants.

Participants

This initial pilot was conducted at a local Geriatric Day Hospital. Inclusion criteria for the adult stroke survivors (age 50+) included: (1) first-time ischemic or hemorrhagic stroke; (2) stroke onset >3 weeks and <6 months; (3) motor deficit ranging from 0 to 4 on the Medical Research Council Scale for muscle strength; (4) able to follow verbal instructions. The exclusion criteria were: (1) skin conditions/ injuries over the stimulation application areas; (2) contraindication for ice or vibration application (e.g. acute inflammation, venous problems, thrombosis, or Raynaud disease); (3) musculoskeletal (e.g. UE fracture) or cardiac disorders (e.g. unstable heart disease); (4) other neurological conditions (e.g. Parkinson's disease); and (5) history of diabetes or sensory impairment attributable to peripheral vascular disease or neuropathy.

Outcome measurements

Assessments were conducted at baseline and post-intervention, using the Fugl-Meyer Assessment (FMA) of Motor Recovery after Stroke, Manual Muscle Testing (MMT), Functional Test for the Hemiplegic Upper Extremity (Hong Kong version) and Modified Barthel Index (MBI).

Fugl-Meyer Assessment (FMA)

The FMA is one of the most widely used quantitative measures of motor impairment in post-stroke hemiplegic patients (Fugl-Meyer et al., 1975) with high test–retest reliability (ICC = 0.97), inter-rater reliability (r = 0.98–0.99) and responsiveness (SRM = 1.42; Gladstone et al., 2002; Hsieh et al., 2009). This measure assesses the synergistic and voluntary movement using a scale of 0–2 (0 = unable; 1 = partial; 2 = performs fully) after stroke in five domains (motor function, sensory function, balance, joint range of motion, joint pain). The motor domain includes UE and LE tests (UE maximum score = 66; LE maximum score = 34). In this study, we used the UE text of the motor domain for the analyses.

Manual muscle testing

MMT was used for the evaluation of the motor recovery and strength of shoulder flexion after stroke. The biceps brachii, one of the stimulated target muscles, is one of the three muscles (with coracobrachialis and anterior deltoid) that flex the shoulder and plays an important role in stabilizing the upper limb for functional reaching tasks (Landin et al., 2017). MMT has been shown to be a clinically useful tool with excellent inter-rater reliability (ICC = 0.98) in trained examiners for the use in patients with stroke (Gregson et al., 2000).

Functional Test for the Hemiplegic Upper Extremity (Hong Kong version)

The Hong Kong version of Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) was modified from the original version developed by Wilson et al. (1984) to evaluate the recovery of the hemiplegic UE after stroke from non-use to full hand function in a hierarchy of seven functional levels, based on Brunnstrom's developmental stages of stroke recovery (BSMR). The test consists of 13 activities which are sequenced in a hierarchy of seven functional levels by degree of difficulty from level 1 (no active movement) to level 7 (isolated control with good coordination, e.g. key turning).

The FTHUE-HK has been validated showing good inter-rater reliability (r = 0.93, p < 0.01), test–retest reliability (r = 0.90, p < 0.01). High correlations were found between the FTHUE–HK functional levels and the FMA UE sub-score (r = 0.88, p < 0.01) and the FMA hand sub-score (r = 0.88, p < 0.01). The FTHUE–HK also has moderate correlation with the self-care score of the Functional Independence Measure (r = 0.46, p < 0.01; Fong et al., 2004).

Modified Barthel index

The MBI was used to measure functional performance in basic activities of daily living (ADL). The test has been shown to have good validity and sensitivity as well as very good inter-rater reliability (ICC = 0.979) in stroke patients (Fricke and Unsworth, 1997).

Interventions

Multisensory therapy group

The MT group received a 12-week intervention (two sessions/ week; 90 minutes/session) conducted by an occupational therapist. Each session began with 15 minutes of sensory stimulation (cold and vibration), 45 minutes of motor training and 30 minutes of self-care training.

Thermal stimulation (cold) was applied with an ice cube (15 seconds) over the dorsum of the hand and skin over forearm extensor for ten times (Chen et al., 2005; Floeter et al., 1998). Muscle vibration was applied using a handheld vibrator (91 Hz; model Thrive, Osaka Japan) on the wrist flexors (flexor carpi radialis and ulnaris); biceps brachii and wrist extensor (extensor carpi radialis) muscles for 10 minutes (Paoloni et al., 2014; Rosenkranz and Rothwell, 2004). Patients were encouraged to attend to the vibrated muscles when they were receiving the vibration and actively move the paretic arms and hands to promote a voluntary or reflex movement (Rosenkranz and Rothwell, 2004).

The UE motor training session included active or active-assistive UE motor practice of reaching, grasping–releasing and muscle strengthening.

The self-care training included UE focused self-care task practice, in which the participants were encouraged to attempt to use the paretic arm and/or hand to aid or perform the tasks, as well as basic self-care training with whole body involvement.

Conventional training group

The CT group included 12 weeks (two sessions/ week; 90 minutes/session) training conducted by an occupational therapist. Each session included 60 minutes of UE motor practice (same as in MT group) and 30 minutes of self-care training (same as in MT group).

All the participants continued with their usual routine medical care.

Statistical analysis

All analyses were performed using SPSS 23 (SPSS, Inc., Chicago, IL, USA). Group differences in demographics and all outcome measures at baseline were compared using independent samples t-test and Fisher's exact test when appropriate. Paired-samples t-tests were performed to evaluate the within-group differences. Gain scores (post-test score – pre-test score) were calculated for all outcome measures and comparisons of gain scores between groups were performed with independent samples t-tests. The statistical significant level was set at p < 0.05 (two-tailed). The Shapiro-Wilk test was used to assess the normality of data to justify the use of t-test for a small sample size.

Results

A total of 148 stroke clients were screened for eligibility and 12 upper-extremity paretic stroke patients (mean age = 67.17 + /−11.29) were recruited and randomly assigned by admission sequence to a MT (n = 6) or a CT (n = 6) group. All the recruited participants completed the 12 weeks training and post-intervention assessment. Figure 1 shows the flow of participant. Time from stroke at enrollment ranged from 4 weeks to 6 weeks. Baseline characteristics are tabulated in Table 1. No significant baseline differences were found for demographic characteristics or outcome assessment results between the two groups.

Figure 1.

Study flow chart.

Table 1.

Participants' baseline characteristics.

Characteristics	Multisensory Therapy Group (n = 6)	Conventional Training Group (n = 6)	P – value (2-tailed)
Age,^a years, [range/mean (SD)]	48–76/ 65.5 (10.45)	51–86/ 68.83 (12.83)	0.633
Gender,^b n (%), (female/male)	3 (50)/ 3 (50)	2 (33.3)/ 4 (66.7)	1.00
Paretic limb,^b n (%), (right/left)	5 (83.3)/ 1 (16.7)	4 (66.7)/ 2 (33.3)	1.00
MMSE,^a score [range/ mean (SD)]	16–30/ 27.33 (5.61)	13–28/ 22.5 (5.65)	0.168
BSMR,^a score [range/mean (SD)]	1–5/ 2.83 (1.47)	1–5/ 3.17 (1.83)	0.736
FMA,^a score [range/mean (SD)]	0–54/ 26 (22.16)	2–56/ 33.17 (23.70)	0.600
MMT,^a score [range/mean (SD)]	0–4/ 2.42 (1.43)	0–4/ 2.83 (1.60)	0.645
FTHUE-HK,^a score [range/mean (SD)]	1–4/ 2.17 (1.47)	1–4/ 2.67 (1.37)	0.556
MBI,^a score [range/mean (SD)]	60–88/ 74.67 (11.47)	48–85/ 63.50 (13.62)	0.156

MMSE, Mini Mental State Examination; BSMR, Brunnstrom Stages of Motor Recovery;

FMA, Fugl-Meyer Assessment of Motor Recovery after Stroke; MMT, Manual Muscle Testing;

FTHUE-HK, Hong Kong version of Functional Test for the Hemiplegic Upper Extremity;

MBI, Modified Barthel Index.

Independent sample t-test.

Fisher's exact test.

Table 2 illustrates the performance of the two groups for all outcome measures. The results of paired-samples t-test revealed significant within-group improvements for the MT group in all outcomes. CT group also showed significant improvements in different outcomes but not in FTHUE-HK.

Table 2.

Outcomes at baseline and post-intervention.

Outcomes	Multisensory Therapy Group				Conventional Training Group				P-value (Between group)
Outcomes	Baseline (Mean ± SEM)	Post- intervention (Mean ± SEM)	P-value (Within group)	Gain scores (Mean ± SEM)	Baseline (Mean ± SEM)	Post- intervention (Mean ± SEM)	P-value (Within group)	Gain scores (Mean ± SEM)	P-value (Between group)
FMA	26.0 ± 9.05	42.33 ± 7.14	0.003*	16.33 ± 3.03	33.17 ± 9.68	36.83 ± 10.51	0.026*	3.67 ± 1.17	0.003*
MMT	2.42 ± 0.58	4.17 ± 0.31	0.002*	1.75 ± 0.31	2.83 ± 0.65	3.67 ± 0.60	0.011*	0.83 ± 0.52	0.034*
FTHUE-HK	2.17 ± 0.60	4.50 ± 0.85	0.001*	2.33 ± 0.33	2.67 ± 0.56	3.50 ± 0.92	0.141	0.83 ± 0.48	0.028*
MBI	74.67 ± 4.68	91 ± 3.75	<0.001*	16.33 ± 1.82	63.50 ± 5.56	83.33 ± 3.49	0.002*	19.83 ± 3.35	0.380

FMA, Fugl-Meyer Assessment of Motor Recovery after Stroke;

FTHUE-HK, Hong Kong version of Functional Test for the Hemiplegic Upper Extremity;

MMT, Manual Muscle Testing; MBI, Modified Barthel Index;

SEM, standard error mean

P < 0.05

The results of independent samples t-test for gain scores demonstrated significant between-group differences in favor of the MT group in FMA; FTHUE-HK and MMT.

Discussion

The aim of this pilot study was to initially investigate the potential effects of combining multisensory stimulation and CT on UE motor recovery in stroke survivors. Both the MT and CT groups showed significant effects by time on motor recovery and basic ADL at completion of 12 weeks training.

The MT group had demonstrated significantly higher improvements in upper-extremity motor recovery and functional use as revealed from the FMA and FTHUE-HK results, compared to the CT group at post intervention. The higher improvement in the MT group can be explained by the multisensory stimulation given to the participants before their participation in UE remedial activities for the MT group. Hummelsheim et al. (1995) suggested cutaneous stimulation could produce facilitative effects and improve motor evoked potential of target muscles in stroke survivors with severe paresis of the arm and hand.

Recently, ‘priming’ has been proposed as a tool for inducing neuroplasticity and enhancing the effects in neurorehabilitation. Priming represents a type of implicit memory involving a nonconscious influence of past experiences of previous stimuli on current performance or behavior changes (Stoykov and Madhavan, 2015). For example, sensory stimulation such as icing over the hand applied prior to motor training may induce changes in the excitability of the cortical projections of hand muscles facilitating motor learning and therefore improve motor function of the hand. The brain, which is primed by a prior method of afferent activation (e.g. icing), will become more responsive to the accompanying training since the resting state of neurons have been modulated prior to the subsequent motor training and therefore enhancing the resulting synaptic plasticity.

The use of sensory stimuli can be regarded as a priming technique which may prepare the sensorimotor system for improved responses, in subsequent motor practice, by increasing the excitability of the stroke-affected motor system, resulting in the increased plastic reorganization responding to the practiced activity (Pomeroy et al., 2011). In our present study, the preparation of participants' paretic limbs with multisensory stimulation at the beginning of each training session in the MT group might have increased their responsiveness to subsequent training activities and therefore enhanced the resulting outcomes. Nevertheless, further studies with support of advanced neuroimaging techniques will be needed to clearly unveil the underlying mechanisms. The present findings support previous studies that additional afferent stimuli plus CT protocol improves UE motor recovery and with greater effects compared to CT alone (Marconi et al., 2011; Wu et al., 2010).

Our study differs from previous similar studies in that two different stimuli (cold and vibration) were used successively for a relatively short duration (15 minutes) instead of only a single stimulus, either thermal stimulus (with both heat and cold) or only vibration (Hsu et al., 2013; Paoloni et al., 2014). A functional magnetic resonance imaging (fMRI) study has reported there is no significant difference between the cortical changes induced by the noxious cold stimuli and the noxious heat stimuli (Davis et al., 1998). Therefore, the use of only cold stimulus alone as the thermal stimulation in our study was sufficient for inducing the expected cortical changes.

Nevertheless, different cortical areas in the brain are activated by different afferent stimuli and they are spatially distinct although some may overlap across different stimulation parameters (Davis et al., 1998; Gelnar et al., 1999). A variety of stimulation is suggested to activate various areas across the brain and better enhancing the induced neural plasticity (Johansson, 2000). Therefore, a combination of different stimulation may activate a wider range of cortical areas and therefore enhance greater cortical reorganization, which may further facilitate the effects of subsequent therapies to a greater extent and better improve the functional motor recovery in the MT group. Although encouraging results, using two different stimuli, were found in this pilot, further studies to compare the advantage of the multisensory intervention to single sensory interventions are still needed to allow a better understanding in this area.

Although the MT group demonstrated a much greater gain in FMA score than the CT group, this could be biased by the ceiling effect of the scale which may be most responsive to those clients with severe to moderated deficits (Gladstone et al., 2002). Furthermore, individual differences in spontaneous recovery may also confound the effects of interventions. Motor and functional improvements are time dependent at least during the first six months post stroke (Kwakkel et al., 2006). It is of particular importance to control the potential time-dependent changes in future well-designed randomized controlled studies to reveal more conclusive findings.

Surprisingly, although the MT group had demonstrated significantly higher improvements in upper-extremity motor recovery and muscle strength compared to the CT group at post intervention, no significant group differences were found in basic ADL outcome as revealed by MBI scores. Strong association has been found between muscle weakness and limitation in functions after stroke (Bohannon, 2007). However, stroke recovery is a heterogeneous process which depends on interplay of multiple factors such as area of lesion and patient characteristics. The MBI, despite its being widely used and well-validated psychometric properties, may not be adequate to detect the subtle changes in response to the dynamic process of motor recovery in stroke. Common ADL assessment tools may not be able to accurately reflect an individual's actual use of the paretic UE since most of the daily living tasks can be done or compensated by the non-paretic one. In addition, the overall functional outcome could also be influenced by different interventions or personal strategies including use of compensatory strategies, environment and/or task modifications, compensation mechanism adopted by patient. Self-reported tools specifically assessing performance of affected UE use in activities typically completed in daily life and with good reported psychometric properties, such as the Motor Activity Log, may be included in future studies (Uswatte et al., 2005). However, caution should be made regarding the potential impacts of cognitive impairment, which is common in person with stroke, on the reliability of self-reported measures.

Limitation

Although the results are encouraging, one needs to interpret the results with caution from a pilot with a small sample.

The present findings will need further validation in well-designed larger scale randomized controlled studies. Basing on the results of this study and using G*Power to conduct a power calculation and determine sample size (Faul et al., 2007), and taking into consideration an average dropout rate of 25% (French et al., 2007), a sample size of 24 will be needed to detect a large between-group effect size of d ≥ 1.0 at 80% power, alpha set at 0.05 (two-tailed) for future studies. The sample for this study was not representative of the whole population of adult stroke survivors and the small sample size also limited the feasibility of recruiting a homogeneous group of participants or stratification of data such as age, or stage of motor deficit which may have effects on the intervention responses and influence the outcomes. Last but not least, although an UE function test has been included in this study, the ADL assessment used did not sufficiently reflect the specific UE functional changes in response to ongoing UE motor recovery. Including the Assessment of Motor and Process Skills (AMPS) to measure ADL performance and supported by the use of accelerometers in future studies to measure the use of the paretic upper-limb in everyday activities may help provide more meaningful information on the upper-extremity motor performance.

Conclusion

This study demonstrated the beneficial effects of combining multisensory stimulation and CT on UE motor recovery and self-care function in stroke patients. Multisensory stimulation could be used as a preparatory method prior to CT for improving UE motor recovery in stroke rehabilitation. Further well-designed larger scale studies are needed to validate the potential benefits of employing multisensory stimulation and a combined protocol in stroke rehabilitation, particularly for population with severe UE paresis.

Key findings

• Adding multisensory stimulation (using ice and vibration) as a preparatory method prior to CT has initially demonstrated positive effects in promoting upper-extremity motor recovery in stroke patients.

What the study has added

This pilot study showed that the application of ice and vibration, which are easily accessible at low cost, for 15 minutes as preparation before CT can be effective in improving UE motor function in stroke patients.

Footnotes

Research ethics

Kowloon west cluster research ethics committee approved the study (Reference number: KW/EX-14-210(82-17); 2015).

Consent

All participants provided written informed consent to participate in the research study.

Declaration of conflicting interests

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

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

References

American Occupational Therapy Association (2014) Occupational therapy practice framework: Domain and process (3rd ed.). American Journal of Occupational Therapy 68(Suppl. 1): S1–S48. https://doi.org/10.5014/ajot.2014.682006 .

Bohannon

(2007) Muscle strength and muscle training after stroke. Journal of Rehabilitation Medicine 39: 14–20.

Chen

Liang

Shaw

(2005) Facilitation of sensory and motor recovery by thermal intervention for the hemiplegic upper limb in acute stroke patients: A single-blind randomized clinical trial. Stroke 36: 2665–2669.

Coupar

Pollock

Rowe

et al. (2012) Predictors of upper limb recovery after stroke: a systematic review and meta-analysis. Clinical Rehabilitation 26(4): 291–313.

Cramer

Sur

Dobkin

et al. (2011) Harnessing neuroplasticity for clinical applications. Brain 134(6): 1591–1609.

Davis KD, Kwan CL, Crawley AP, et al. (1998) Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. Journal of Neurophysiology 80(3): 1533–1546.

Faul F, Erdfelder E, Lang AG, et al. (2007) G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 39(2): 175–191.

Feigin

Forouzanfar

Krishnamurthi

et al. (2014) Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. The Lancet 383(9913): 245–255.

Floeter

Gerloff

Kouri

et al. (1998) Cutaneous withdrawal reflexes of the upper extremity. Muscle & Nerve 21(5): 591–598.

10.

Fong

Chan

et al. (2004) Development of the Hong Kong version of the functional test for the hemiplegic upper extremity (FTHUE-HK). Hong Kong Journal of Occupational Therapy 14(1): 21–29.

11.

French

Thomas

Leathley

et al. (2007) Repetitive task training for improving functional ability after stroke. Cochrane Database Systematic Review 4(4): CD006073.

12.

Fricke

Unsworth

(1997) Inter-rater reliability of the original and the modified Barthel Index, and a comparison with the Functional Independence Measure. Australian Occupational Therapy Journal 44(1): 22–29. .

13.

Fugl-Meyer

Jaasko

Leyman

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

14.

Gelnar

Krauss

Sheehe

et al. (1999) A comparative fMRI study of cortical representations for thermal painful, vibrotactile, and motor performance tasks. Neuroimage 10(4): 460–482.

15.

Gladstone

Danells

Black

(2002) The Fugl-Meyer assessment of motor recovery after stroke: a critical review of its measurement properties. Neurorehabilitation and Neural Repair 16(3): 232–240.

16.

Gregson

Leathley

Moore

et al. (2000) Reliability of measurements of muscle tone and muscle power in stroke patients. Age and Ageing 29(3): 223–228.

17.

Hatem

Saussez

della Faille

et al. (2016) Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery. Frontiers in Human Neuroscience 10(442): 1–22.

18.

Hsieh

Lin

et al. (2009) Responsiveness and validity of three outcome measures of motor function after stroke rehabilitation. Stroke 40(4): 1386–1391. .

19.

Hsu

Lee

Hsu

et al. (2013) Effects of noxious versus innocuous thermal stimulation on lower extremity motor recovery 3 months after stroke. Archives of Physical Medicine and Rehabilitation 94(4): 633–641.

20.

Hummelsheim

Hauptmann

Neumann

(1995) Influence of physiotherapeutic facilitation techniques on motor evoked potentials in centrally paretic hand extensor muscles. Electroencephalography and Clinical Neurophysiology 97(1): 18–28. .

21.

Johansson

(2000) Brain plasticity and stroke rehabilitation. The Willis lecture. Stroke 31(1): 223–230.

22.

Johansson

(2011) Current trends in stroke rehabilitation: A review with focus on brain plasticity. Acta Neurologica Scandinavica 123(3): 147–159.

23.

Johansson

(2012) Multisensory stimulation in stroke rehabilitation. Frontiers in Human Neuroscience 6(60): 1–11.

24.

Kaelin-Lang

Luft

Sawaki

et al. (2002) Modulation of human corticomotor excitability by somatosensory input. Journal of Physiology 540(2): 623–633. .

25.

Kwakkel

Kollen

Twisk

(2006) Impact of time on improvement of outcome after stroke. Stroke 37(9): 2348–2353. .

26.

Laaksonen

Kirveskari

Mäkelä

et al. (2012) Effect of afferent input on motor cortex excitability during stroke recovery. Clinical Neurophysiology 123(12): 2429–2436.

27.

Landin

Thompson

Jackson

(2017) Actions of the Biceps Brachii at the Shoulder: A Review. Journal of Clinical Medicine Research 9(8): 667–670. http://doi.org/10.14740/jocmr2901w .

28.

Lawrence

Coshall

Dundas

et al. (2001) Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke 32(6): 1279–1284.

29.

Liepert

Binder

(2010) Vibration-induced effects in stroke patients with spastic hemiparesis–a pilot study. Restorative Neurology and Neuroscience 28(6): 729–735.

30.

Marconi

Filippi

Koch

et al. (2011) Long-term effects on cortical excitability and motor recovery induced by repeated muscle vibration in chronic stroke patients. Neurorehabilitation and Neural Repair 25(1): 48–60.

31.

Münte

Jöbges

Wieringa

et al. (1996) Human evoked potentials to long duration vibratory stimuli: role of muscle afferents. Neuroscience Letters 216(3): 163–166.

32.

Paoloni

Tavernese

Fini

et al. (2014) Segmental muscle vibration modifies muscle activation during reaching in chronic stroke: A pilot study. NeuroRehabilitation 35(3): 405–414.

33.

Pollock

Farmer

Brady

et al. (2014) Interventions for improving upper limb function after stroke. Cochrane Database of Systematic Reviews 12(11): CD010820.

34.

Pomeroy

Aglioti

Mark

et al. (2011) Neurological principles and rehabilitation of action disorders: rehabilitation interventions. Neurorehabilitation and Neural Repair 25(5 Suppl): 33S–43S.

35.

Rosenkranz

Rothwell

(2004) The effect of sensory input and attention on the sensorimotor organization of the hand area of the human motor cortex. Journal of Physiology 561(1): 307–320.

36.

Stoykov

Madhavan

(2015) Motor priming in neurorehabilitation. Journal of Neurologic Physical Therapy 39(1): 33–42.

37.

Takeuchi

Izumi

(2015) Combinations of stroke neurorehabilitation to facilitate motor recovery: perspectives on Hebbian plasticity and homeostatic metaplasticity. Frontiers in Human Neuroscience 9(349): 1–15.

38.

Uswatte

Taub

Morris

et al. (2005) Reliability and validity of the upper-extremity Motor Activity Log-14 for measuring real-world arm use. Stroke 36(11): 2493–2496.

39.

Walter

Winston

(2018) Therapeutic occupations and modalities. In: Schultz-Krohn

Pendleton

(eds) Pedretti's Occupational Therapy: Practice Skills for Physical Dysfunction, 8th ed. St. Louis, MO: Elsevier, Inc.

40.

Wilson

Baker

Craddock

(1984) Functional test for the hemiplegic upper extremity. American Journal of Occupational Therapy 38(3): 159–164. .

41.

Lin

Hsu

et al. (2010) Effect of thermal stimulation on upper extremity motor recovery 3 months after stroke. Stroke 41(10): 2378–2380.