Annals of Biomedical Engineering ( 2014) DOI: 10.1007/s10439-014-1148-8

Therapeutic Effects of Functional Electrical Stimulation on Gait in Individuals Post-Stroke MICHAL KAFRI and YOCHEVED LAUFER Department of Physical Therapy Faculty of Social Welfare & Health Sciences, University of Haifa, Mount Carmel, Haifa 3498838, Israel (Received 3 June 2014; accepted 30 September 2014) Associate Editor Amet Gefen oversaw the review of this article.

Abstract—Functional electrical stimulation (FES) to lower extremity (LE) muscles is used by individuals post-stroke as an alternative to mechanical orthotic devices during gait or as a training modality during rehabilitation. Technological developments which improve the feasibility, accessibility and effectiveness of FES systems as orthotic and training devices, highlight the potential of FES for rehabilitating LE function in individuals post-stroke. This study presents a systematic review of the carryover effects of LE FES to motor performance when stimulation is not applied (therapeutic effects) in subjects post-stroke. A description of advances in FES technologies, with an emphasis on systems designed to promote LE function is included, and mechanisms that may be associated with the observed therapeutic effects are discussed. Eligible studies were reviewed for methodological quality, population, intervention and outcome characteristics. Therapeutic effects of FES were consistently demonstrated at the body function and activity levels when it was used as a training modality. Compared to matched treatments that did not incorporate FES, no definite conclusions can be drawn regarding the superiority of FES. When FES was used as an alternative to an orthotic device, it had no superior therapeutic effects at the activity level, yet patients still seemed to prefer it. Keywords—Functional electrical stimulation, Stroke, Hemiparesis, Gait, Therapeutic effect, Plasticity.

INTRODUCTION Stroke is defined as rapidly developing clinical signs of focal (or global) disturbances of cerebral function due to vascular origin, with symptoms lasting 24 h or longer.71 It is the principal cause of serious, long-term Address correspondence to Michal Kafri, Department of Physical Therapy Faculty of Social Welfare & Health Sciences, University of Haifa, Mount Carmel, Haifa 3498838, Israel. Electronic mail: [email protected]

disability among the elderly in the western world and the third most common cause of mortality worldwide.49,71 The most common impairment following stroke, affecting approximately 90% of stroke survivors is hemiparesis. Approximately 75% of individuals regain the ability to walk after a stroke to some extent, but often require an assistive device for functional ambulation.17 Technological advances provide opportunities to facilitate motor recovery and function following stroke. One such technology gaining recognition in stroke rehabilitation is functional electrical stimulation (FES). It entails the use of electrical stimulation that elicits muscle contractions designed to achieve specific activities. FES devices compensate for reduced motor control and are routinely used to promote functions such as walking or grasping.5,48 The effects of FES may also carryover to motor performance when the stimulation is not applied. This carry over effect is frequently termed therapeutic effect. However, these therapeutic effects at the body function and activity levels have not yet been systematically examined. The primary aim of this work was to systematically present and to critically review reported therapeutic benefits in regard to body function (e.g., muscle strength and tone), and mobility-related activities (e.g., gait speed) associated with lower extremity (LE) FES in individuals post-stroke. Knowledge about the therapeutic effects of FES is important to guide clinical decisions and to guide the bioengineering community in the development of appropriate technologies. A brief description of advances in FES technologies, with specific emphasis on systems designed to promote LE functions is included. Finally, we discuss possible mechanisms that may be associated with the observed therapeutic effects. Liberson et al.40 were the first to apply an FES system to overcome ineffective ankle dorsiflexion (drop  2014 Biomedical Engineering Society

M. KAFRI

foot) during the swing phase of gait, which is present in approximately 20% of individuals with stroke-related hemiparesis.12,69 Using a pressure sensor within the shoe to identify the swing and stance phases of the gait cycle, they introduced a single channel stimulator to activate the common peroneal nerve, allowing foot clearance during the swing phase of gait. Since then, particularly with advancements in microprocessing technology and the development of wireless systems,65 FES devices for the correction of foot drop have become commercially available and are used daily as an alternative to an ankle–foot orthosis (AFO) (a mechanical device used to prevent drop foot by limiting ankle motion throughout the gait cycle).4,5,59 The effectiveness of single channel FES in increasing gait velocity, reducing energy costs and improving social participation have been demonstrated repeatedly.37,38,45,64 Since then, dual and multi-channel FES systems have been developed to assist ambulatory subjects with hemiparesis by providing stimulation to additional muscle groups, to enhance push off at the terminal stance phase,29 or to improve knee62 or hip control.32 Multi-channel FES devices which stimulate a variety of lower extremity muscle groups are presently used in gait14 and cycling training.1,20 However, individuals post-stroke have limited access to these applications. While the technology of the various FES systems used for gait enhancement varies greatly, they all include a stimulation unit and a gait event detection device. The stimulation unit enables the clinician/user to set the pulse parameters and current intensity, with most units programmed to deliver biphasic pulses ranging from 300 ls to 600 ls duration and 20 Hz to 50 Hz frequency.16 Since a major limitation of electrical stimulation is rapid muscle fatigue, pulse parameter settings and in particular, optimal frequency patterns are sought to decrease this inadvertent side effect, while minimizing the discomfort associated with stimulation.23,41 Transcutaneous electrodes placed over the muscle belly or motor points of the target muscles are the most common mode of applying the stimuli, particularly for superficial muscles such as the ankle dorsiflexors.57,60 While surface electrodes are the least invasive, they are inappropriate for deeper muscle groups due to skin discomfort and to reduced selectivity associated with the stronger current intensities needed to reach deep muscles. To overcome these difficulties, both percutaneous, hair-thin electrodes13 connected to an external stimulator and completely implanted systems have7,15 been introduced. Although these applications are currently time limited, it is expected that with further technological advancements they may be used for extended periods, as well.

AND

Y. LAUFER

A portable gait event detection device is essential for ensuring appropriate timing of the stimulation. This is particularly challenging because the input for activating stimulation must be provided in real time under a variety of conditions. These include different directions of gait progression (e.g., side or back stepping and stair negotiation) and different terrains (e.g., grass vs. tile). Furthermore, as individuals with hemiparesis present a variety of abnormal gait patterns (e.g., toe contact instead of heel contact at the initial stance phase), the effectiveness of any particular detection device may depend on the predominant gait deviation presented by an individual. A variety of sensors, such as goniometers, gyroscopes, accelerometers, inclinometers or force sensitive resistors and various sensor combinations have been developed to overcome these demands.24,51,52 Thus, for example, using an inclinometer can overcome missed detection of stance time due to variability of initial contact. Currently available systems have limitations, leading to missed steps and require further optimization. With this in mind, the commercially available systems that provide satisfactory results for individuals with hemiparesis utilize either a pressure sensor placed in the shoe of the affected limb, or a tilt sensor encased in a shank cuff attached to the affected limb.5

METHODS FES has both orthotic (i.e., the effect while the system is on) and therapeutic effects. Therapeutic effects resulting from LE FES are evaluated when it is not applied. The therapeutic effects may be observed following the application of LE FES during a predetermined training period or after prolonged use as an alternative to an orthotic device. These effects may include changes in gait characteristics or body function variables.

Literature Search Online searches of PubMed, CINAHL, PEDro, and Scopus databases were performed by the authors, with the last full search conducted in July 2014. The electronic search was completed by a hand search of bibliographic references of the included studies. The search terms used were [functional electrical stimulation OR neuromuscular electrical stimulation] AND [stroke OR hemiparesis OR cerebrovascular accident] AND [gait OR walking OR locomotion]. The search was restricted to clinical trials and the English language. The titles and abstracts of all identified articles were reviewed, with the full article read whenever deemed necessary to finalize a decision about its inclusion.

Therapeutic Effects of FES Post-Stroke

Inclusion and Exclusion Criteria Inclusion 1. Clinical trials that evaluated the therapeutic effects of FES to the LE of patients following a stroke by assessing at least one activity measure before and after treatment when FES was not applied; 2. At least one experimental and one control (or placebo) group were evaluated. Cross over design studies were included only if subjects were divided into two groups and crossed over for experimental and control interventions; 3. If FES was applied with an additional treatment and the control group received the same treatment.

Methodological Level of the Chosen Articles The methodological quality of the included papers according to the PEDro classification scale is presented in Table 7. The mean PEDro score of studies in which FES was applied as a rehabilitation tool in the acute and chronic phase was 6.6 (SD1.1) and 5.6 (SD1.3), respectively, and the mean score of studies in which FES was applied as an alternative to and orthotic device was 5.5 (SD 0.5). Nine studies received a PEDro score in the ‘good’ range and six in the ‘fair’ range, with only the study by Ambrosini et al.1 rated as excellent. Characteristics of Studies

Exclusion

Mode of Application

1. PEDro score of Con Others outcomes: not reported Within the FES group: All measures except balance: › Between groups: Walking speed, EMS: FES + GT vs. Con1-GT- NS., FES + GT/Con1GT > Con-ground. FAC: FES + GT > Con1-GT/Con2ground All other measures: NS Within the FES group: MI, EMS, FAC, walking speed: › FIM, BBT, BI: NS Between groups: All measures:FES + GT vs. Con1-GT: NS MI, Walking speed, EMS, FAC: FES + GT/Con1-GT > Con2-ground FIM, BBT, BI- NS Within the FES group: Spasticity PF, MVC DF :› Walking ability: TUG: not reported Between groups: Spasticity PF-FES Con Grs Walking ability-FES >Con Grs TUG-NS

Main therapeutic results

AND

FES + GT: n = 15; 61.8 ± 10.8 Con1-GT: n = 15; 66.1 ± 9.9 Con2-Ground: n = 20; 71.4 ± 14.0

FES + GT: n = 16; 62 ± 10 Con1-GT: n = 17; 66.6 ± 11.3 Con2-ground: n = 16; 73.4 ± 11.5

FES: n = 10; 51 ± 12 Con: n = 10; 56 ± 9.2

FES: n = 15; 59 ± 10 Con-placebo: n = 15; 56 ± 14

Groups: number of subjects; age (years)

TABLE 1. Characteristics and main results of studies of FES training for subjects in the acute/sub-acute, post-stroke phases.

M. KAFRI Y. LAUFER

Alternate Gr FES: assignment; n = 27; 49.1 Con: 2 Gr; Pre, post n = 24; 50.1 RCT; FES: 2 Gr; n = 54; 52.8 Pre, post, FU (6 Con: months) n = 56; 53.2

Sabut54

Sheffler61

Alternate assignment; 2 Gr; Pre, post

Sabut55

± 10.1

± 12.2

± 10.4

± 8.8

FES + GT: n = 15; 53.3 ± 8.9 Con1-GT: n = 15; 51.2 ± 7.9 Con2-ground: n = 15; 52.3 ± 6.8 Gr FES: n = 16; 49.5 ± 8.9 Con: n = 14; 47.1 ± 12.4

FES: 17.3 ± Con: 18.2 ± FES: 44.7 ± Con: 44.9 ± 79.2 months

97.5 months

11.8 months

18.8 months

FES +GT: 2.6 ± 2.4 years Con1-GT: 2.4 ± 2.6 years Con2-ground: 4.0 ± 5.8 years FES: 20 months Con: 15 months

FES: 2.8 ± 3.3 years Con: 2.6 ± 3 years

Peurala47 RCT; 3 Gr; Pre, mid, post, FU (6 months)

FES: n = 20; 59 Con: n = 24; 62

FES: 3.6 ± 3.8 years Con: 3.3 ± 2.1 years

Time post-stroke

FES 1st period: 4.3 ± 3.4 years FES 2nd period: 5.6 ± 4.4 years

RCT; 2 Gr; Pre, mid, post, FU

Daly14

FES: n = 14; 57.7 ± 11.9 Con: n = 15; 63.6 ± 10.4

Groups: number of subjects; age (years)

Embrey18 RCT, Crossover; FES 1st period: 1 Gr; n = 16; 62.1 ± 11.6 Pre, post FES 2nd period: n = 13; 57.5 ± 10.0

RCT; 2 Gr; Pre, post

Daly13

Study design; No. of Gr; Time Publication of evaluations

Not provided

Not provided

FES: 0.36 ± 0.21 Con: 0.36 ± 0.16

FES + GT: 0.23 ± 0.28 Con1-GT: 0.26 ± 0.28 Con2-ground: 0.26 ± 0.4

Not provided

FES: 0.45 ± 0.22 Con: 0.35 ± 0.26

Not provided

Walking speed at pre-test (m/s) Main therapeutic results

Body Function: Spasticity TA; EMG static output; PROM & AROM; LE FM; PCI Activity: Walking speed (10 m); cadence; step length; Body functions: Spasticity PF; DF PROM & AROM; DF strength; LE FM; Body functions: LE FM Activity: mEFAP Participation: SSQOL

Within the FES group: All outcome measures: › Between groups: All outcome measures: FES > Con Within the FES group: All measures: ›, (mEAFP& SSQOL Maintained at FU, LE FM did not). Between groups: All measures: NS

Within the FES group: Walking measures: › Between groups: Walking measures: NS Other measures: not reported

Within the FES group: Tinetti Gait, LE FM knee flexion: › Between groups: Tinetti gait, LE FM knee flexion: FES > Con LE FM, 6 MW, Tinetti balance: NS Body function: Within groups: All outcome measures except FIM: › LE MMT; LE FM; FIM: NS Between groups: Activity: Walking speed; G.A.I.T; G.A.I.T-FES > Con Other outcome measures: not reported 6 MW;FIM; Tinetti balance Within the FES group: Body functions: Spasticity-DF & PF; muscle strength- Measures of activity and participation:› Spasticity-DF & PF: NS DF & PF Activity: PF strength: NS 6 MW; EFAP, SIS DF strength: › Participation: Between groups: At 1st period: SIS; 6 MW, SIS: FES > Con All other measures: NS Body functions: Within the FES group: Spasticity; LE MMT All measures except FIM: ›, FIM: NS Activity: Between groups: walking speed (10 m); 6 MW; MMAS; All measures: NS balance (postural sway); FIM

Body Function: LE FM Activity: Tinetti Gait & balance; 6 MW

Outcome measures

TABLE 2. Characteristics and main results of studies of FES training for subjects in the chronic, post-stroke phase.

Therapeutic Effects of FES Post-Stroke

RCT; 2 Gr; Pre, FU (30 weeks.)

RCT, 2 Gr; Pre, FU (4, 8, 12, 26 weeks)

Kluding34

Kottink35 FES: n = 14; 55.2 ± 11.4 Con: n = 15; 52.9 ± 9.9

FES: n = 99; 60.7 ± 12.2 Con: n = 98; 61.6 ± 11

FES: n = 16; 52.2 ± 14.2 Con: n = 16; 61.2 ± 8.5 FES: n = 69 (divided into 2 Gr; with alternate order of FES/AFO use) Con: n = 93 (all FES subj + con with no FES period) Overall: n = 93; 57 ± 11.8

Groups: number of subjects; age (years)

FES: 9.07 ± 9.3 years Con: 5.67 ± 4.6 years

FES: 4.8 ± 5.3 years Con: 4.3 ± 4.1 years

FES: 3.6 years Con: 4.9 years Overall: 6.4 ± 3.6 months

Time post-stroke

Not provided

FES: 0.42 ± 0.21 Con: 0.42 ± 0.19

FES: 0.64 ± 0.46 Con: 0.48 ± 0.25 Overall: 0.42 ± 0.25

Walking speed at pre-test (m/s)

Body functions: MVC (TA, PL, GS, SL) TA activity during swing Activity: Walking speed (10 m)

Activity: Walking speed (10 m);Functional reach; 6 MW;TUG

Body function: PCI Activity: Walking speed (10 m) Body function: PCI Activity: Walking speed (10 m., figure of eight); Modified Rivermead mobility index

Outcome measures

Within the FES group: All measures: NS Between groups: All measures: NS Within the FES group: Walking speed (10 m. and figure of 8), and PCI: › Between groups: All measures: NS Sign. more preferred to continue walking with AFO (compared with AFO) Within the FES group: All measures, except functional reach : › Functional reach: NS Between groups: All measures: NS Within the FES group: Not reported Between groups: MVC of GS in knee flexion: FES > Con MVC of PL, TA, SL in knee flexion : NS MVC of TA, GS in knee extension: FES > Con SL MVC of PL, in knee extension: NS TA activity during swing: NS Walking speed: NS

Main therapeutic results

AND

›—significant improvement; 2 MW—2 min walk; 6 MW—6 min walk; AFO—ankle foot orthosis; AROM—active range of motion; BBT—Berg Balance Test, BI—Barthal Index; Con—control; CSS—Composite Spasticity Scale; DF—dorsi flexors; EFAP—Emory functional ambulatory profile; EMS—Elderly Mobility Scale; EMG—electromyography; FAC—Functional Ambulation Category; FES—functional electrical stimulation; FIM—functional independent measurement; FU—follow-up; FM—Fugl Meyer test; G.A.I.T—gait assessment and intervention tool; Gr—group; GS—gastrocnemius, GT—gait trainer; LE—lower extremity; mEAFP—Emory functional ambulatory profile; MI—Motricity Index; MMAS—modified motor assessment scale; MMT—manual muscle testing; MVC—maximal voluntary contraction; NS—not significant; PCI—physiologic cost index; PF—plantar flexors; PL—peroneus longus; PROM—passive range of motion; RCT—randomized controlled trial; RMA—Rivermead motor assessment; RMI—Rivermead mobility index; SIS—Stroke Impact Scale; SL—soleus; SSQOL—stroke specific quality of life; STS—sit to stand; TA—tibialis anterior; TCT—trunk control test, TUG—timed up and go; UMC—upright motor control test.

RCT, Crossover; 3 Gr.; Pre, FU (3,6,9,12 weeks)

RCT; 2 Gr. Pre, FU (4, 12 weeks)

Everaert19

Burridge

7

Publication

Study design; No. of Gr; Time of evaluations

TABLE 3. Characteristics and main results of studies with FES used as an alternative to an assistive device in subjects post-stroke.

M. KAFRI Y. LAUFER

8 channels; quad, hams, Gmax, TA; Bi-lateral

8 channels; quad, hams, GMax, TA; Bi-lateral

2 channels; Peroneal n., quad.

2 channels; Peroneal n., quad.

4 channels; quad; hams; medial GC; TA

Ferrante20

Ng44

Tong66

Yan73

Channels;site of stimulation

Ambrosini1

Publication

FES Parameters

300 ls; 20 Hz; To tolerance Surface –; –; –; Surface 400 ls; – Comfort threshold; Surface 400 ls; – 50–85 mA Surface 300 ls; 30 Hz; 20–30 mA Surface

Duration; frequency; intensity; electrodes

FES/Con1-placebo: Side-lying (leg sling supported) Con2: none

FES + GT/Con1 + GT: GT Con2-ground: Over ground walking

FES + GT/Con1 + GT: GT Con2-ground: Over ground walking

FES: Cycling Con: None

FES/Con-Placebo FES: Cycling

Mode of training

5 9 3 weeks; 30 min (FES) 60 min (placebo)

5 9 4 weeks; 20 min

5 9 4 weeks; 20 min

Daily 9 4 weeks; 35 min

5 9 4 weeks; 25 min

Rx. per week 9 # of weeks;session duration

FES and control treatments

PT & OT; 5 9 3 weeks; 2h

PT; 5 9 4 weeks; 40 min

PT; 5 9 4 weeks; 40 min

PT; Daily 9 4 weeks; 3h

PT; Daily 9 4 weeks; 3h

Other treatments (both groups)

TABLE 4. Characteristics of FES and control treatments in studies of FES training for subjects in the acute/sub-acute, post-stroke phases.

Therapeutic Effects of FES Post-Stroke

8 channels; TA, PL,GC, BF, STend, SMemb, VL, GMed

2 channels; Ankle dorsi & planter flexors

2 channels; Selected weakest muscle (hip ext, knee flex/ext, ankle pronators) 1 channel; Peroneal n.

1 channel; Peroneal n

1 channel; Peroneal n

Daly14

Embrey18

Peurala47

Sabut54

Sheffler61

5–150 ls; 30 Hz; 15–50 mA Implantable, Intra-muscle 1–150 ls; 15–50 Hz; 4–20 mA; Implantable, Intra-muscle – 35–50 Hz; To tolerance Surface 300 ls; 25 Hz; – Surface 300 ls; 40 Hz; 20–60 mA Surface 0.28 ms; 35 Hz Tolerance level Surface –; –; –; Surface

Duration; frequency; intensity; electrodes

FES/Con-AFO: PT + independent use of FES or AFO at home

FES: Over ground walking Con: None

FES: Over ground walking Con: None

FES + GT/Con1 + GT: GT Con2-ground:Over ground walking

FES/Con: Over ground walking

FES/Con: Ground level walking, BWSTT, home ex

FES/Con: Coordination ex., ground level walking, BWSTT, home ex

Mode of training

2 + daily use at home 9 12 weeks; 1 h + up to 8 h of FES or AFO use at the community

5X12 Weeks; 20–30 min

5 9 12 weeks; 30 min

5 9 3 weeks; 20 min

6 9 12 weeks; 1h

4 + daily home exercise X12 weeks; 1.5 h (clinic), 1 h (home)

4 + daily home practice 9 12 weeks; 1.5 h (clinic), 1 h (home)

Rx. per wk 9 # of weeks; session duration

FES and control treatments

None

PT & OT; 5X12 weeks; 1h

PT & OT; 5 9 12; 1h

PT; 5 9 3 weeks; 55 min

Evaluation and education; 1 9 12 weeks 30 min

None

None

Other treatments (both groups)

AND

Sabut55

8 channels; TA, PL, GC, BF, STend, SMemb, VL, GMed

Channels; site of stimulation

Daly13

Publication

FES Parameters

TABLE 5. Characteristics of FES and control treatments in studies of FES training for subjects in the chronic, post-stroke phase.

M. KAFRI Y. LAUFER

1 channel; Peroneal n

2 channels; Deep + superficial Peroneal n

Kluding34

Kottink35 –; 30 Hz; –; Implantable

400 ls; 50 Hz; 12–38 mA Surface –; –; –; Surface –; –; –; Surface

Duration;frequency; intensity;electrodes

FES Con: AFO

FES (NESS L300) Con: AFO

FES (WalkAide) Con: AFO

FES (Odstock) Con: not reported

Walking device

26 weeks; Daily use

30 weeks; Daily use

6 weeks (each phase); Daily use;

12–13 weeks; Daily use

Duration of device use

FES and control interventions

PT (FES group), PT + sensory TENS (Con group); 8 sessions during 1st 6 weeks (sensory TENS was given at the 1st 2 weeks only for the con Gr); PT (4 subjects from the FES Gr and 3 subjects from the Con Gr); 1 or 2 sessions per week

None

PT; 10 sessions during 1st 4 weeks; 1h

Other treatments (both groups)

AFO—ankle foot orthosis; BF—biceps femoris; BWSTT—body weight support treadmill training; Con—control; DF—dorsi flexion; ex—exercises; ext—extension; FES—functional electrical stimulation; flex—flexion; GMax—gluteus maximus; GMed—gluteus medius; Gr—group; GS—gastrocnemius, GT—gait trainer; hams—hamstrings; LE—lower extremity; n—nerve; OT—occupational therapy; PF—plantar flexion; PL—peroneus longus; PT—physical therapy; quad—quadriceps; Rx—treatment; SL—soleus; SMemb—semimembranosus; STend—semitendinosus, stim—stimulator; TA—tibialis anterior; TENS—transcutaneous electrical nerve stimulation; VL—vastus lateralis.

1 channel; Peroneal n

1 channel; Peroneal n

Channels; site of stimulation

Everaert19

Burridge

7

Publication

FES parameters

TABLE 6. Characteristics of FES and control treatments in studies with FES used as an alternative to an assistive device in subjects post-stroke.

Therapeutic Effects of FES Post-Stroke

Over-all

Eligibility criteriab

Rated by authors,

b

Yes Yes No Yes No No Yes 4/7 Yes Yes No No 2/4

Yes Yes Yes Yes No No Yes 5/7 Yes Yes Yes Yes 4/4

Eligibility criteria not included in total score.

Yes No Yes No No 2/5

Concealed allocation

Yes Yes Yes Yes Yes 5/5

Random allocation

No Yes No Yes 2/2

Yes Yes No Yes Yes Yes Yes 6/7

Yes Yes Yes Yes Yes 5/5

Baseline comparable

No No No No 0/4

No No No No No No No 0/7

Yes No No No No 1/5

Blind subject

No No No No 0/4

No No No No No No No 0/7

No No No No No 0/5

Blind therapist

No No Yes No 1/4

Yes Yes No No Yes No No 3/7

Yes No No Yes Yes 3/5

Blind assessor

Yes Yes No Yes 3/4

Yes No Yes Yes Yes Yes Yes 6/7

Yes Yes Yes Yes Yes 5/5

Adequate Follow-up

No No Yes Yes 2/4

No No No No No No Yes 1/7

No No Yes Yes No 2/5

Intention to-treat

Yes Yes Yes Yes 4/4

Yes Yes Yes Yes Yes Yes Yes 7/7

Yes Yes Yes Yes Yes 5/5

Between-group comparison

Yes Yes Yes Yes 4/4

Yes Yes Yes Yes Yes Yes Yes 7/7

Yes Yes Yes Yes Yes 55

Point estimates and variability

AND

a

Training-acute/sub-acute phases Ambrosini1 8 Yes 5 Yes Ferrantea20 Nga44 7 Yes Tong66 7 Yes 6 No Yan73 Summary 4/5 Training-chronic phase Daly13 7 Yes Daly14 6 No 4 Yes Embrey18 Peurala47 6 Yes 5 Yes Sabut55 Sabut54 4 Yes 7 Yes Sheffler61 Summary 6/7 Alternative for assistive device Burridge7 5 Yes Everaert19 6 Yes Kluding34 5 Yes Kottink35 6 Yes Summary 4/4

Study

TABLE 7. Summary of methodological quality based on the PEDro classification.

M. KAFRI Y. LAUFER

Therapeutic Effects of FES Post-Stroke

assistive device). For example, inclusion criteria in the study by Embery et al.18 were the ability to walk continuously at least 15 min 4 times a day, and in the study by Sheffler et al.,61 the ability to walk independently without an AFO for approximately 10 m. In contrast, independent gait was not expected at the acute stage, as for example, individuals were only expected to stand supported or unsupported for 1 min.44 Characteristics of FES Parameters All included studies reported the type of electrodes used, indicating that with the exception of three studies which employed implanted electrodes,13,14,35 the majority of the studies used surface electrodes. In contrast, FES pulse parameters were not consistently reported, with some studies not reporting any parameters, while others varying in the amount of detail provided. Generally, pulse frequency ranged between 15– 50, and pulse duration with surface electrodes ranged between 280–400 ls, and up to 150 ls with implanted electrodes. Current amplitude was specified only in 7 studies and ranged between 4 mA (with implanted electrodes) to a maximum of 85 mA. The studies did not provide any details regarding the guidelines used to determine the choice of pulse parameters. Therapeutic Effects of Lower Extremity FES Mobility-Related Therapeutic Effects Increased walking speed is the most common effect reported, as measured by a range of assessment tools.1,8,14,19,20,34,35,44,47,55,66 Overall, findings indicate clinically important increases in gait speed. For example, a prospective study that involved 99 subjects with chronic hemiparesis, reported significant gait speed improvements following 30 weeks of habitual use of peroneal FES, with an effect size of 0.75 and with 29% of the participants increasing their speed beyond the minimal clinically important difference.34,45 Positive therapeutic effects of FES were also reported for other mobility-related variables including walking independence,44,66 walking distance14,18,34 physiologic cost index (PCI),8,19,55 and other variables such as stair negotiation, which were rated in a variety of mobility scales.44,66 The therapeutic effect of FES on balance using an array of clinical scales including the Berg balance scale,44,66 timed up and go73 and Tinetti balance assessment,13,14 did not demonstrate any clear patterns. Body Function-Related Therapeutic Effect FES effects on muscle strength and voluntary range of motion were reported in 10 studies.1,14,18,20,34,44,47,54,55,61All but one had a positive

outcome.34 Only 4 studies examined the effect of FES on spasticity, with all indicating a positive effect in the sub-acute73 and chronic phases.18,47,54 Are the Therapeutic Effects Specific to FES Intervention? As demonstrated in the previous section, FES has therapeutic effects on a wide array of mobility-related variables and on some body functions. However, the question arises whether these effects are due primarily to the electrical stimulation delivered by the FES, which entails the actual activation of weakened muscles and sensory input, or whether they can be achieved by any means that enable functional movement. The training studies presented contradictory findings regarding the superiority of training with FES relative to control training without FES. For example, Yan et al.73 compared individuals at the sub-acute post-stroke phase who received FES training in the side-lying position, mimicking gait movements with comparable control groups. They found better outcomes in the FES group in terms of spasticity, muscle voluntary contraction and walking ability. Similarly, superior positive effects were reported following cycling training.1 In contrast, Ng et al.44 reported similar therapeutic effects for FES and control interventions. When FES was used as an alternative for assistive device, no superior therapeutic effects were reported with the FES compared to the AFO,8,19,34,35 For example, in a study that compared the orthotic and therapeutic effects of FES and AFO using a cross-over design, individuals in the chronic post-stroke phase were assigned to an FES-first group or to an AFO-first group.19 Both the FES and the AFO interventions resulted in significant therapeutic improvements in gait speed and PCI, with no significant differences in gains between groups. However, it should be noted, that when given the choice, most participants preferred FES over AFO, and perceived that FES had greater therapeutic benefits on walking safely. In a different study,34,45 subjects in the chronic phase post-stroke were randomly assigned to use either an AFO or FES daily. The therapeutic effects assessed after 30 weeks indicated gains in gait speed, which were not significantly different between groups. Similar findings were reported for all other outcome variables including, 6 min walk distance,34 timed up and go,34 and PCI.8,19 The only exception was the study by Kottink et al.35 that measured, in addition to walking speed, muscle force. They reported stronger therapeutic effects on the maximal voluntary contraction of the gastrocnemius and tibialis anterior muscles in a group that regularly used two-channel, implanted FES, compared with a group that used standard assistive devices. Other

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muscle force variables, as well as walking speed, did not differ between groups in this study as well.

DISCUSSION To summarize, it should be noted that therapeutic benefits of FES were consistently demonstrated for most variables. These effects were also achieved when FES was used in training modes other than walking, such as cycling and leg movements in side-lying. This indicates the possibility of effectively implementing FES training in individuals who do not have yet the capacity to walk. However, when compared to matched treatments that did not incorporate FES, the results are inconsistent. Therefore, no definite conclusions can be drawn regarding the unique superiority of FES. In contrast, consistent findings indicate that when FES is used as an alternative to an assistive device it has no superior therapeutic effects than AFO. Furthermore, it must be stressed that the therapeutic effects achieved by habitual FES intervention were not generally of a magnitude that eliminated the need to use the FES as an assistive device during walking. It is difficult to determine optimal treatment protocols due to inconsistent and wide ranging outcome measures, varying exposures to FES, and the different FES parameters used. In addition, it is not clear which individuals will benefit from FES, and what baseline characteristics predict better therapeutic outcomes. While an early study by Merletti et al.43 indicated that time since lesion, spasticity, and intensity of treatment are important predictors of positive therapeutic results, further research is necessary to substantiate this. In the section below, we discuss rationale for therapeutic effects of LE FES. While functional changes in mobility performance may be attributed to the direct effects on muscle structure and function (i.e., muscle composition, muscle strength, and spasticity), two other important central mechanisms may be involved: the direct effects of electrical stimulation on brain plasticity53 and enhanced motor learning resulting from repetitive practice. FES Induced Brain Plasticity Cumulative evidence indicates that FES, neuromuscular electrical stimulation, and sensory level electrical stimulation, with or without voluntary movement, can modify cortical excitability and promote brain plasticity at different levels of the nervous system. FES as a Sensory Stimulation FES by its very nature induces not only motor stimulation but also results in the excitation of

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superficial and proprioceptive sensory fibers.3 Sensory stimulation has been shown to induce changes in the excitability of the motor cortex10,28,50 and is associated with reorganization of motor maps of the corresponding muscles.42 A systematic review regarding motor recovery of individuals post-stroke, concluded that delivery of sensory stimulation via transcutaneous electrical stimulation (TENS) at intensities that excluded motor nerve excitation, enhanced different aspects of motor recovery in both the upper and lower extremities, such as hand functions and walking endurance.36 Furthermore, it has been demonstrated by functional MRI (fMRI) that electrical stimulation, specifically of the peroneal nerve, was associated with increased activity in brain regions related to the motor network.21 The activity level in the secondary somatosensory and insula regions was higher for electrical stimulation as compared with active movement.21 This increase in activation might result from the proprioceptive input, or an increase in attention. In contrast to the common mode of sensory stimulation, where continuous input is provided, FESrelated sensory stimulation is rhythmic and coordinated with the targeted movement. These unique characteristics of FES have been shown to play a role in neural plasticity. For example, short-term neural plasticity was achieved when the common peroneal nerve was stimulated at a sensory level at a rate that mimicked afferent stimulation during slow speed walking.46 These plastic changes did not occur when stimulation was provided in a uniform pattern unrelated to gait pattern. FES Coupled with Voluntary Movement Findings in able-bodied individuals indicate that electrical stimulation (sensory, motor or FES) in conjunction with voluntary muscle contractions is superior to electrical stimulation alone in regard to cortical excitability and plasticity.11,30,31,72 Thus, for example, Yamaguchi et al.72 recently demonstrated that sensory stimulation coupled with voluntary contraction increased cortical excitability (as recorded by motor evoked potentials (MEP)), with the increases proportional to the force of the voluntary contraction. As in normal physiological responses during contractions, inhibition was obtained in the muscles antagonist to the contracting muscles. Similar findings were reported by Khaslavskaia et al.30 for the LE. They studied MEP in the tibialis anterior after repetitive electrical stimulation of the common peroneal nerve at rest and with voluntary ankle dorsi-flexion or plantar flexion. The pattern of the electrical stimulation delivery was similar to that used during peroneal FES. They found that relative to rest, MEP following 30 min of voluntary

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exercise was increased the most when the electrical stimulation was coupled with the movement. In this study as well, the increase in cortical excitability was limited to the contracting muscle. Although both studies demonstrated similar results, it should be noted that the type of electrical stimulation differed, i.e., sensory72 vs. motor.30 Using a study protocol in which FES was used for an actual walk, Kido Thompson et al.31 measured the MEP of tibialis anterior and soleus muscles before and after 30 min of treadmill walking, with and without peroneal FES. Similarly, they found an increase in MEP in the tibialis anterior immediately after walking training with FES that lasted for 30 min. No significant increase was observed after walking without stimulation. The importance of coupling voluntary movement with FES was further demonstrated by Christensen et al.11 They used fMRI to explore the nature of the connection between the secondary somatosensory cortex and the primary motor cortex in FES-evoked movements vs. voluntary movements assisted by FES. While removing the effect of the sensory stimulation on brain activation by peripheral ischemic nerve block, they found that activation in the secondary somatosensory cortex was reduced when movement was evoked only by FES, but not for movement that was assisted by FES. Furthermore, Gandolla et al.22 explored the coupling between brain regions under conditions of voluntary or passive movements with or without FES to the peroneal nerve. They found that the proprioceptive input elicited by the FES increased the sensitivity of the primary somatosensory cortex selectively to primary motor cortex projections, and that this increase was higher when FES was coupled with voluntary dorsi-flexion, compared to passive dorsi-flexion.22 Generally, fMRI studies demonstrated that voluntary movement together with electrical stimulation was associated with increased brain activity in the primary motor cortex, the primary and secondary somatosensory cortices, the sensorimotor cortex, and the cerebellum, as well as with increased coupling between specific brain regions.11,21,22,26,27 Although discussion of mechanisms at the cellular level is beyond the scope of this work, it is worth mentioning that a plausible effect of coupling between FES and voluntary movement might be attributed to enhanced synchronization between preand post-synaptic activation, which is necessary for plastic changes.53 Implications for Individuals Post-stroke Overall, the above mentioned studies in able-bodied individuals support the potential of FES to promote brain plasticity and suggest that greater changes would occur if FES was combined with voluntary movement

of the corresponding muscles. Two distinctions are relevant when considering the implications for individuals post-stroke. First, the input delivered to the central nervous system by FES might be affected by stroke-related impairments (i.e., reduced contraction force and sensory input). Furthermore, the capacity of the nervous system to respond to this input might be altered by the cerebral lesion itself. Second, we speculate that the coupling between the FES stimulation and voluntary movement is limited due to hemiparesis. Moreover, because FES provides the assistance needed for walking, it is possible that FES encourages dependence on the system, thus reducing or eliminating voluntary activation of the muscles, even in individuals who have the capacity to do so. Such dependence is probably increased by the difficulty in recruiting the muscles at a rate necessary for the increased gait velocity achieved by FES-assisted walking. The development of FES systems in which the electrical stimulation is elicited when the electromyogram signal from the target muscle reaches a predetermined threshold, might provide a mechanism to promote involvement of voluntary movement when it is possible.2,39 Another point to consider is whether combining FES with stimuli other than voluntary movement, such as mental imagery or movement observation can effectively substitute for the effect of coupling FES with voluntary movement.

FES Enhances Motor Learning It is possible that neural plasticity occurs due to general changes in motor behavior that are promoted by FES, but can be similarly enhanced by other interventions that enable function. Motor learning is a process in which practice or experience leads to relatively permanent changes in the ability to perform skilled movements.56 Several training principles are expected to facilitate motor learning through neural plasticity. The main principles include goal-directed, task-specific training that is intensive in terms of number of repetitions, challenging, salient and motivating.25,33All of these principles are met by FES. The orthotic effects of peroneal FES enable the individual to walk more efficiently, as indicated by increases in gait speed and decreases in PCI, which in turn may encourage increased task-specific practice. O’Dell et al.45 recorded the number of steps taken 6 and 24 weeks after the beginning of their study, as a measure of compliance in individuals who used FES as an alternative to an orthotic device. Mean steps per day increased from 2092 to 2369. Although these numbers are lower than those of able-bodied individuals,67 they demonstrate that during a period of 5 months of FES

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use, individuals not only maintained, but even increased their activity level. For motor learning to occur, an individual must be motivated to actively engage in the rehabilitation process. Several studies have demonstrated that individuals post-stroke present with positive attitudes toward FES.6,19,68,70 High satisfaction was expressed regarding various aspects, including quality of gait pattern, effort of walking, and stability during walking.58,63 It has been shown that when given the opportunity, most individuals prefer peroneal FES over an AFO.6,19Additionally, from a psychological perspective, peroneal FES was described as providing a feeling of normality.6 Studies that showed similar therapeutic effects for AFO and FES support the speculation that the observed therapeutic effects are mediated by enhanced motor learning.

CONCLUSIONS FES technology has the potential to promote gait performance, as well as other aspects of LE motor recovery following a stroke. Yet, additional, wellcontrolled studies are warranted to substantiate these findings. Studies in able-bodied individuals demonstrating increased neural plasticity when electrical stimulation was coupled with voluntary contractions indicate the need to develop FES systems that enable voluntary movement whenever possible during the stimulation. Further technological advances are expected to increase the availability and usability of single and multi-channel FES systems, contributing significantly to gait and consequently, to the quality of life of individuals post-stroke.

CONFLICT OF INTEREST The authors have no conflicts of interest.

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