Effect of transcranial Direct Current Stimulation on Severely Affected Arm-hand Motor Function in patients after an acute ischemic stroke. A Pilot Randomized Control Trial

Abstract

Objective:

To determine whether cathodal transcranial direct current stimulation (c-tDCS) to unaffected primary motor cortex (PMC) plus conventional occupational therapy (OT) improves functional motor recovery of the affected arm-hand in patients after an acute ischemic stroke compared to sham transcranial direct current stimulation (s-tDCS) plus conventional OT.

Design:

In this prospective, randomized, double-blind, sham-controlled, trial of 16 severe, acute ischemic stroke patients with severe arm-hand weakness were randomly assigned to either experimental (c-tDCS plus OT; n=8) or control (s-tDCS plus OT; n=8). All patients received standard 3 hours in-patient rehabilitation therapy, plus an additional ten 30-minute sessions of tDCS. During each session 1 mA of cathodal stimulation to the unaffected PMC followed by patient’s scheduled OT. The primary outcome measure was change in Action Research Arm Test (ARAT) total and sub-scores on discharge.

Result:

Application of c-tDCS to unaffected PMC resulted in a clinically relevant 10-point improvement in the affected arm-hand function based on ARAT total score compared to a 2 point improvement in the control group.

Conclusion:

Application of 30-minutes of c-tDCS stimulation to the unaffected PMC showed 10 point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistical significant this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

Introduction

Stroke is the leading cause of long-term disability, ¹ with arm-hand involvement in 70-80% of patients, and is persistent in 40% of patient. ^{2, 3} Persistence of upper extremity (UE) weakness after stroke has led to the development of novel rehabilitation techniques such as constraint induced therapy (CIT) ^{4, 5}, robotic ⁶ training and other intensive activity tasks such as bilateral arm training with rhythmic cueing ⁷ to improve functional motor recovery. These interventions, in general, force the use of the paretic arm and have registered positive improvement in motor function of the arm. ^4-7 Most of the interventional studies have been in chronic stroke patients (> 3-months post-event) as they are presumed not amendable to further recovery, as change in performance can be attributed to the intervention, and as they constitute a substantial percentage of stroke patient population with impairment and disability. ³

Activation of the primary motor cortex (PMC), which contributes to the pyramidal tract fibers, ⁸ generates fine distal movements that are fundamental to functional motor recovery. ⁹ Strokes affecting the PMC ¹⁰ with reduced sensorimotor cortex activation during finger movement have been associated with poor functional outcome. ¹¹ Cortical excitability is decreased in the affected PMC after a stroke relative to the unaffected motor cortex, due to increased transcallosal inhibition from the unaffected to the affected motor cortex. ^{12, 13} A great deal of interest has lately been focused on the ability to induce change in interhemispheric interactions following stroke. ¹⁴ Desirable effects can be induced by either inhibiting activity of the unaffected hemisphere or increasing excitability in the perilesional cortex of the damaged hemisphere to promote restoration of activity across bi-hemispheric neural networks and induce a more-adaptive plasticity. ¹⁵ The study by Hummel et al. found transcranial direct current stimulation of the affected hemisphere led to transient improvement in skilled motor functions mimicking activities of daily living in patients with chronic stroke. ¹⁶

Transcranial direct current stimulation (tDCS) is a non-invasive and painless technique to modulate cortical excitability. tDCS has been found to be a safe procedure in human and animal studies based on no evidence of serious adverse effects or irreversible injury. ¹⁷ In tDCS, low-amplitude direct current is applied via two gel-sponge scalp electrodes (that have been embedded in a saline-soaked solution). These currents penetrate the skull to enter the brain. Despite substantial shunting of the current in the scalp, two recent modeling studies have shown that sufficient current penetrates the brain to modify neuronal transmembrane potentials, thereby influencing the threshold of excitability and the firing rate of individual neurons. ¹⁸ This direct neuronal stimulation by tDCS contrasts with the transcranial magnetic stimulation (rTMS), which excites the corticospinal neuron transynaptically. ¹⁹ When tDCS is applied for a sufficient time-period, cortical function is altered beyond the stimulation period. ^{16, 20} Anodal stimulation facilitates while cathodal stimulation inhibits motor-evoked potentials, this effect has been found to help improve implicit motor learning. ²⁰ Cathodal stimulation aims to inhibit unaffected hemisphere to restore inter-hemispheric competition after a stroke where the unaffected hemisphere overrides the affected hemisphere. The inter-hemispheric interaction between the two PMC is mainly inhibitory. ²¹ tDCS has the advantages of ease of application of stimulation while undergoing therapy, less bulky to carry, and is cheaper than rTMS. Brain stimulation techniques have the theoretical appeal of being able to selectively enhance adaptive patterns and suppress maladaptive patterns of activity, hence restoring equilibrium in imbalanced neural networks. Most of the tDCS motor recovery studies have assessed the speed of movement or change in muscle strength, with no information regarding how it translates into functional motor outcome. Furthermore, most of these studies have been in the sub-acute or chronic phases of the disease. Finally, the effects of tDCS brain stimulation studies have been undertaken without coupling it with any specific behavioral, physical or occupational therapy (OT). A recent review and meta-analysis of studies on the effect of tDCS on UE recovery post-stroke found it had a small non-significant effect on UE impairments and performance of activities. ²²

The recent decreasing length of acute in-patient rehabilitation hospitalization as a cost containment measure motivated us to evaluate techniques that complement the present conventional therapies to enhance potential post-stroke motor recovery. Therefore, we hypothesized whether ten 30-minute sessions of c-tDCS to PMC coupled with OT will augment improvement of arm-hand function compared to sham tDCS plus OT in patients with acute ischemic stroke. A further objective was to provide a sample size estimate from this pilot study that could guide design of a larger randomized controlled trial.

Methods

Patients and Procedures

A sample of 16 consecutive patients with unilateral, first severe, acute ischemic stroke who presented to the in-patient rehabilitation unit were randomly assigned (1:1) by computer generated randomization to either experimental or control group in blocks of 4. Neither the patient nor the therapist were aware of which group the patient was randomized too. The Inclusion criteria were:

1. Unilateral, first, acute stroke event within 7 to 10 days of admission to our in-patient rehabilitation facility,

2. Ischemic stroke documented clinically and by neuroimaging,

3. Severe arm-hand weakness (Medical Research Council (MRC) grade of 2 or less),

4. Medically stable from a cardio-respiratory stand point to participate in daily therapies,

5. Able to provide informed written consent (cognitively intact patients with admission Mini Mental Scale Examination [MMSE] greater than or equal to 21). In cognitively impaired patients with MMSE ≤ 20, proxy written consent was obtained from the legal authorized representative according to institutional IRB standards. Written informed consent was obtained by the admitting physicians.

The Exclusion criteria were:

1. Hemorrhagic stroke,

2. Prior stroke or history of epilepsy,

3. Medically unstable, demented, or terminally ill (e.g., patients with stroke as a complication of a terminal cancer),

4. Botulinum toxin injection for spasticity or other medications known to enhance motor recovery such as d-amphetamine, L-dopa,

5. Implanted pacemakers or defibrillators,

6. Refusal to provide written informed consent.

Patients with depression were not excluded from the study. Referral to a psychiatrist was made if deemed necessary. This study was approved and monitored by the University, and registered at ClinicalTrials.gov, #NCT 01201629. This study conforms to all CONSORT guidelines and reports the required information accordingly (see Supplementary Checklist).

Intervention:

Patients enrolled in the study received standard occupational and physical therapy by their assigned therapist for three hours per day. The “standard” occupational therapy at this institution is comprised of positioning and safe-handling of the paretic arm, passive and active range of movements, and techniques incorporating motor learning, neurodevelopment and propioceptive neuromuscular facilitative approaches. An additional ten sessions of 30 minutes/day, 5 days/week was provided consisting of cathodal tDCS (c-tDCS) or sham tDCS (s-tDCS) plus an additional hour of OT. Patients were seated either in a reclining chair or in an upright position in their hospital bed. Anodal and cathodal tDCS of 1 mA were delivered via two gel-sponge scalp electrodes (35 cm²) embedded in a saline-soaked solution. Unaffected PMC (hand area) was stimulated by a cathodal tDCS electrode positioned on the scalp over C3/4 (International 10/20 electroencephalogram system), while an anodal tDCS electrode was placed over the contralateral supra-orbital area. In the c-tDCS group stimulation was delivered continuously for 30 min. In the s-tDCS (“sham”) group, the electrodes were placed in the same positions as in active group, but stimulation was switched off after the initial 30 seconds, out of the field of view of the patient. ²³ Both group of patients initially mentioned a tingling sensation with the onset of the stimulation, which usually faded away in a few (< 30) seconds. ²³ Sham intervention was essential to blind the subject and the therapist to obtain an unbiased assessment of intervention effects. Twenty minutes of stimulation has been found to be safe. ²⁴ We provided 30 minutes of stimulation (which the device can provide at any one time) to see if long-term benefits of tDCs in motor learning in stroke patients could be further enhanced and/or maintained.

The DC-Stimulator manufactured by neuroConn Gmbh Germany was used. It has in-built safety features, including a microprocessor that maintains constant current flow and can be applied for up to 30 minutes at any one time.

Assessment:

The primary outcome measure was the Action Research Arm Test (ARAT), a standardized ordinal scale that measures UE function. ²⁵ ARAT is based on the assumption that complex UE movements used in daily life can be explained and assessed by 4 basic movements: grasp, grip, pinch and gross movements of extension and flexion at the elbow and shoulder (Appendix 1). The ARAT is graded on a 4-point scale (0-57 points). ARAT has high reliability and validity, ^{26, 27} The clinician initially demonstrated to the patient how each of the 4 basic movements was to be carried out, before asking the patient to perform these movements. Each UE is evaluated individually. ²⁶ The clinician placed the ARAT test items in the patient’s intact visual field. ARAT scoring was undertaken as per instructions. A change in the ARAT score of 5.7 points is a clinically relevant change. ²⁸

The secondary outcomes measures were the total Functional Independence Measure (TFIM^™), FIM-ADL sub-scores recorded at baseline, on discharge from the facility, and at 3-months follow-up, and discharge disposition. TFIM^™ was used to measure how the patient coped with the degree of disability as well as the progress patients make throughout their medical rehabilitation programs. ²⁹ The FIM scale is a reliable ³⁰ and valid ³¹ functional assessment measure widely used in rehabilitation settings. ³² The FIM has 18 items and each item is scored on an ordinal scale ranging from 1 to 7. The total FIM score (TFIM) quantifies level of independence and ranges from 18 (total dependence) to 126 (total independence) (Appendix 2). A change in TFIM score of 22 points is a clinically relevant change. ³³

Primary and secondary outcome measures were assessed at baseline on entry into the study and prior to discharge from the facility. Secondary outcome measure was also measured 3-months after their initial stroke.

Statistical Analysis

The data were analyzed by a professional bio-statistician involved from the inception of this study. The two groups were compared on relevant demographic variables to assess for any group differences using Students t-test and chi-square test for continuous and categorical data, respectively; mean ± standard deviation (SD) for continuous data and percentages for categorical data are shown in Table 1 Mean ± SD changes are reported for the primary and secondary outcome measures for admission to discharge (Table 2A) and admission to 3 months (Table 2B).

Table 1:

Demographics of the study population

Variables	Total (n=16)	Experimental + OT group (n=8)	Sham + OT group (n=8)	p-value
Age, years	62 ± 9	62 ± 11	63 ± 6	0.91
Sex (%male)	100	100	100	-
Race (%white)	75	88	63	0.25
Handed, (%right)	94	100	88	0.30
Onset to admission, days	6.4 ± 3.2	6.9 ± 3.7 [3-13]	5.9 ± 2.8 [1-9]	0.55
Length of stay, days	23.0 ± 8.8	24.5 ± 10.3 [14-44]	21.5 ± 7.4 [9-32]	0.52
Hemiplegia (Right/Left sided)	6/10	4/4	2/6	0.30
Cortical/Subcortical/Mixed	0/9/7	0/6/2	0/3/5	0.13
Vascular Risk factors (%yes)
Hypertension	69	63	75	0.59
Diabetes mellitus	31	25	38	0.59
Hyperlipidemia	44	50	38	0.61
Coronary artery disease	6	13	0	0.30
Atrial fibrillation	6	13	0	0.30
Current smokers	50	50	55	0.99
# modifiable risk factors	2.1 ± 1.1	2.1 ± 1.1	2.0 ± 1.2	0.83
Depression, BDI scores	8.9 ± 7.1	8.8 ± 7.0	9.1 ± 7.6	0.92
Admission MMSE	24.8 ± 3.5	24.1 ± 3.4	25.5 ± 3.7	0.46
Admission upper limb strength (MRC grade)	0.6 ± 1.1	0.6 ± 1.2	0.6 ± 1.2	0.99
Admission lower limb strength (MRC grade)	2.7 ± 1.4	2.3 ± 1.6	3.1 ± 1.0	0.21
Admission NIHSS	10.3 ± 3.6	10.0 ± 4.3	10.6 ± 3.0	0.74
Admission TFIM	60 ± 14	61 ± 17	59 ± 12	0.77
Admission FIM-ADL sub-scores	21.2 ± 7.5	21.0 ± 8.6	21.4 ± 6.8	0.92
Admission ARAT	2.9 ± 8.1	4.0 ± 10.9	1.9 ± 4.2	0.62
Admission ARAT-Grasp sub-scores	1.2 ± 3.6	1.9 ± 4.9	0.5 ± 1.4	0.46
Admission ARAT-Grip sub-scores	0.8 ± 2.2	1.0 ± 2.8	0.5 ± 1.4	0.66
Admission ARAT-Pinch sub-scores	0.3 ± 1.0	0.5 ± 1.4	0.0 ± 0.0	0.33
Admission ARAT-Gross sub-scores	0.8 ± 1.7	0.6 ± 1.8	0.9 ± 1.6	0.77

BDI=Beck Depression Inventory

MRC=Medical Research Council

ARAT=Action Research Arm Test

TFIM= Total Function Independence Measure

ADL=Activities of Daily Living

MMSE=Mini-Mental State Examination

NIHSS=National Institute of Health Stroke Scale

Table 2A:

Primary and secondary Outcome measures change scores (Admission to Discharge) adjusted for baseline scores.

Outcome measures	Experimental + OT group (n=8)	Sham + OT group (n=8)	Cohen’s d	p-value
ARAT	10.1 ± 13.5	1.7 ± 4.4	0.84	0.14
ARAT-Grasp sub-scores	2.7 ± 4.8	0.9 ± 2.3	0.48	0.37
ARAT-Grip sub-scores	3.7 ± 4.7	0.7 ± 1.9	0.84	0.14
ARAT-Pinch sub-scores	1.0 ± 1.7	0.0 ± 0.0	0.83	0.15
ARAT-Gross sub-scores	2.7 ± 3.3	0.1 ± 1.6	1.00	0.084
ARAT change > 5	4	1		0.094
TFIM	22.4 ± 15.7	25.3 ± 9.1	0.23	0.66
FIM-ADL sub-scores	12.9 ± 11.5	11.9 ± 5.3	0.11	0.83
Discharge disposition				0.61
Home	4	3
Subacute facility	4	5

ARAT=Action Research Arm Test

TFIM= Total Function Independence Measure

ADL=Activities of Daily Living

MMSE=Mini-Mental State Examination

NIHSS=National Institute of Health Stroke Scale

Table 2B:

Secondary Outcome measures change scores (Admission to 3 months) adjusted for baseline scores.

Outcome measures	Experimental + OT group (n=8)	Sham + OT group (n=8)	Cohen’s d	p-value
TFIM	31.4 ± 18.1	42.7 ± 14.9	0.68	0.24
FIM-ADL sub-scores	21.0 ± 10.2	20.3 ± 8.5	0.07	0.90

TFIM= Total Function Independence Measure

ADL=Activities of Daily Living

Cohen’s d is interpreted as d ~ 0.2 is a small, d ~ 0.5 is a medium, d ~ 0.8 is a large effect size.

Group differences in the changes in outcome measures, admission to discharge and admission to 3 months, were analyzed using generalized linear models. Baseline outcome measures were included as independent variables in the linear model, as were potential confounders (e.g. age, stroke severity). Effect size for the group differences was estimated using Cohen’s d., with the interpretation: d ~ 0.2 is a small, d ~ 0.5 is a medium, d ~ 0.8 is a large effect size. ³⁴ Data analyses were conducted using IBM SPSS Statistics (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp). Results corresponding to p-values lower than 5% are described as significant and reported. Sample size estimation used PASS 14 Power Analysis and Sample Size Software (2015, NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass).

Results:

Seventy acute ischemic stroke patients were consecutively assessed for participation in the study (Figure for the study CONSORT flow diagram). Fifty-two patients were excluded for not meeting the inclusion criteria and two refused to participate in the tDCS citing risk. Table 1 presents the baseline characteristics/demographics of our study sample (n=16) on admission. There were no significant differences showing that the two groups were well matched for basic demographics and variables known to influence functional motor outcome such as age, sex, race, stroke severity (based on NIHSS and MRC grade), and presence of depression. Our sample comprised mainly non-hispanic white (75%) men (100%), aged 62 ± 9 years with severe stroke (NIHSS 10.3 ± 3.6, range 3 - 17). The mean scores for ARAT, TFIM and FIM-ADL were 2.9 ± 8.1, 60 ± 14, 21.2 ± 7.5. The mean time from onset to tDCS was 6.4 ± 3.2 days. No adverse effects were reported except for a tingling sensation at the site of scalp electrode at the beginning of the session. This was observed in both groups of patients and thus unable to distinguish c-tDCS from sham sessions. Four patients were lost to follow-up.

Figure 1:

COHORT flow diagram of the study

The baseline measurement of all outcome variables was similar across both groups. There was a 10 point improvement on the ARAT scale (a change of 5.7 points is considered clinically relevant) that was achieved by the time of discharge in the c-tDCS group compared to a 2 point improvement in the s-tDCS group. This showed a large effect size (Cohen’s d = 0.84), however; it did not reach significance (p=0.18). Similarly, changes in the ARAT sub-scores showed large effect sizes (d > 0.8, except for ARAT-Grasp, d = 0.48 “medium”) but did not reach significance (p > 0.05). Similar improvement of motor function was observed for secondary outcome measures for both groups in the change in the TFIM and FIM-ADL sub-scores, albeit not significant (p > 0.05) and with a small effect size. Post-hoc examination of the improvements in ARAT scores showed that patients with subcortical infarcts in the intervention group made the largest recovery compared to the sham group (Figure 2). Four patients in the experimental vs. three in the sham group went home (Table 2A).

Figure 2.

Average change in scores from Admission to Discharge for ARAT and FIM scales adjusted for baseline scores. Patients in the experimental c-tDC group are in the top graph; patients in the sham s-tDC groups are in the bottom graph. Patients with subcortical infarcts are shown in black bars; patients with mixed cortical and subcortical infarcts are shown in grey bars; error bars indicate standard deviation.

The power analyses determined that, based on the variation in measures seen in this pilot study, a total sample size of 50 (25/group) would be sufficient to detect a change of 5 points on the ARAT and a change of 7 on the FIM-ADL with 80% power at alpha=0.05. Therefore, the clinically relevant changes of 5.7 and 22 are detectable with this sample size.

Discussion

The results of this randomized double-blind sham controlled pilot study in acute stroke patients (1 to 13 days after stroke) shows that 10 30-minutes sessions of c-tDCS paired with OT shows some improvement in severely affected arm-hand function (~10 point improvement with a large effect size); however, it did not reach significance, which is likely a reflection of the small sample size given the large effect size observed. In our study factors known to influence functional motor outcomes such as age, sex, stroke severity and level of disability were equally matched for the two groups, so the influence of these factors on functional outcomes measured was minimal. Likewise none of these patients had depression, spasticity or shoulder pain to influence the results. There were more mixed lesions (cortical plus subcortical, 6/8) in the sham vs. 2/8 in the c-tDCS group. The larger recovery in ARAT scores in the subcortical group indicates an intact cortex may be essential for motor recovery as it indicates the preservation of the cortico-spinal tract. It has been shown in the animal model that motor recovery from a corticospinal lesion takes days compared to weeks for cortical infarcts. ^{35, 36} However, this difference had no impact on baseline clinical motor impairment and disability scores for the two groups, as they were matched.

The timing of the intervention, is as crucial as the intensity of therapy based on amount (minutes) and frequency (sessions per day). Intensive activity-based treatments in chronic stroke patients (≥ 6-8 months post-stroke) have demonstrated improvement in motor impairment and functional outcome measures, ^5-7 yet similar intensive activity-based studies in acute stroke patients (≤ 5 weeks post-stroke) have shown that they are no better than traditional /conventional therapies in several studies. ^37-39 In fact higher-doses of intensive training have been found to be inferior to lower-dose training during the acute time period. ^{37, 40} In the acute/subacute phase stroke patients make non-linear recovery often described as “spontaneous neurological improvement”. This is due to a number of underlying mechanisms including the resolution of underlying edema and diaschisis, and general toxic/metabolic effects of stroke. It has been shown in both animal ⁴¹ and human ⁴² based studies that most of the motor recovery occurs in the initial 2-10 weeks post-stroke. Thus it may be prudent to administer these therapies in moderation in this time window (10, 30-minute sessions as in this study) while a higher-dose of more intensive training may be more appropriate in the later phase (after 6-weeks) when the patient has a stable neurological state, and able to tolerate more intensive therapy.

For this trial we chose severe stroke patients as 40% of all stroke patients with UE impairment fail to regain arm and hand function at 6-months, ^{2, 3} and are left with severe disability, often ending up in long-term care facility with poor quality of life. ⁴³ We show that using this procedure during the initial acute rehabilitation period, when maximum post-stroke functional recovery is said to occur, ⁴⁴ would help decrease their impairment, improve disability, and enable them to be discharged home.

This study has several limitations. First, the small sample size and single center study limits the generalization of the study result, and limits the statistical analysis. Second, the patient population recruited was those who had severe ischemic strokes. Typically stroke studies have usually focused on strokes of mild-to-moderate severity. Third, evaluation of the intervention outcome was short term, and so is unable to comment on its longer term effect. Finally, this placement method may not provide accurate localization for the electrodes compared to one based on fMRI or TMS with CMAP recording from abductor digit minimi (which may not be discernible in a plegic arm-hand anyway). However, the ease of electrode placement by this system, and if tDCS is of proven benefit, would make it easier to incorporate this as a treatment modality in a rehabilitation setting. A further consideration is that the sample is all male, which limits the generalizability of the results. The strengths of this study are the large effect sizes (as measured by Cohen’s d) seen in ARAT scores and sub-scores, its homogenous sample of stroke patients with severe UE impairment, it being undertaken within the critical window of 4-weeks post-stroke, and with tDCS stimulation being immediately followed by therapy.

While no significant differences were shown in this study, the results in Figure 2 are encouraging for the intervention. For the ARAT measures and for the TFIM and ADL-FIM larger improvements are seen in the intervention group. Similar to our study, large improvements in Barthel Index scores were found in the initial 10-weeks post-stroke in a study of 101 stroke patients by Kwakkel et al. ³⁷ Power analysis based on the results of this pilot study showed that a sample size of 50 patients (25 patients in each group) would be needed to show significance for ARAT total, grip, pinch, and gross if the similar improvements continued to be seen.

Conclusions

This is the first randomized controlled trial to compare c-tDCS to s-tDCS in patients with severe, acute ischemic stroke study, suggests that 30-minutes of c-tDCS stimulation to the unaffected PMC showed a 10 point improvement in the ARAT score. This corresponds to a large effect size in improvement of affected arm-hand function in patients with severe, acute ischemic stroke. Although not statistical significant this suggests that larger studies, enrolling at least 25 patients in each group, and with a longer follow-up are warranted.

Appendix 1: Action Research Arm Test (ARAT)

Activity	Score
Grasp
1. Block, wood, 10 cm cube (If score = 3, total = 18 and to Grip)	_______
Pick up a 10 cm block
2. Block, wood, 2.5 cm cube (If score = 0, total = 0 and go to Grip)	_______
Pick up 2.5 cm block
3. Block, wood, 5 cm cube	_______
4. Block, wood, 7.5 cm cube	_______
5. Ball (Cricket), 7.5 cm diameter	_______
6. Stone 10 x 2.5 x 1 cm	_______
Coefficient of reproducibility = 0.98
Coefficient of scalability = 0.94
Grip
1. Pour water from glass to glass (If score = 3, total = 12, and go to Pinch)	_______
2. Tube 2.25 cm (If score = 0, total = 0 and go to Pinch)	_______
3. Tube 1 x 16 cm	_______
4. Washer (3.5 cm diameter) over bolt	_______
Coefficient of reproducibility = 0.99
Coefficient of scalability = 0.98
Pinch
1. Ball bearing, 6 mm, 3rd finger and thumb (If score = 3, total = 18 and go to Grossmt) _______
2. Marble, 1.5 cm, index finger and thumb (If score = 0, total = 0 and go to Grossmt) _______
3. Ball bearing 2nd finger and thumb	_______
4. Ball bearing 1st finger and thumb	_______
5. Marble 2nd finger and thumb	_______
6. Marble 1st finger and thumb	_______
Coefficient of reproducibility = 0.99
Coefficient of scalability = 0.98
Grossmt (Gross Movement)
1. Place hand behind head (If score = 3, total = 9 and finish)	_______
2. (If score = 0, total = 0 and finish	_______
3. Place hand on top of head	_______
4. Hand to mouth	_______
Coefficient of reproducibility = 0.98
Coefficient of scalability = 0.97

Instructions: There are four subtests: Grasp, Grip, Pinch, and Gross Movement. Items in each are ordered so that:

• If the subject passes the first, no more need to be administered and he scores top marks for that subtest

• If the subject fails the first and fails the second, he scores zero, and again no more tests need to be performed in that subtest

• Otherwise he needs to complete all tasks within the subtest

Appendix 2: Functional Independence Measure (FIM)

Activities	Score
Self-Care
A. Eating
B. Grooming
C. Bathing
D. Dressing - Upper Body
E. Dressing - Lower Body
F. Toileting
Sphincter Control
G. Bladder Management
H. Bowel Management
ADL Subtotal Score
Transfer
I. Bed, Chair, Wheelchair
J. Toilet
K. Tub, Shower
Locomotion
L. Walk/Wheelchair
M. Stairs
Motor Subtotal Score
Communication
N. Compréhension
O. Expression
Social Cognition
P. Social interaction
Q. Problem Solving
R. Memory
Cognitive Subtotal Score
TOTAL FIM

Levels:
	7 Complete Independence (Timely, Safely)	No Helper
	6 Modified Independence (Device)
	Modified Dependence
	5 Supervision
	4 Minimal Assist (Subject=75%+)
	3 Moderate Assist (Subject=50%+)	Helper
	Complete Dependence
	2 Maximal Assist (Subject=25%)
	1 Total Assist (Subject=0%+)