Journal of Neural Engineering

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 Journal of Neural Engineering

J. Neural Eng. 13 (2016) 031001 (16pp) doi:10.1088/1741-2560/13/3/031001

Topical Review

Powered exoskeletons for bipedal

locomotion after spinal cord injury
Jose L Contreras-Vidal1, Nikunj A Bhagat1, Justin Brantley1,
Jesus G Cruz-Garza1, Yongtian He1, Quinn Manley1, Sho Nakagome1,
Kevin Nathan1, Su H Tan1, Fangshi Zhu1 and Jose L Pons2
1
Laboratory for Non-invasive Brain-Machine Interface Systems, Department of Electrical Engineering,
University of Houston, Houston, TX 77204, USA
2
Neural Rehabilitation Group, Cajal Institute, Spanish Research Council, Av. Doctor Arce 37, Madrid
E-28002, Spain

E-mail: jlcontreras-vidal@uh.edu

Received 3 August 2015, revised 2 March 2016

Accepted for publication 3 March 2016
Published 11 April 2016

Abstract
Objective. Powered exoskeletons promise to increase the quality of life of people with lower-
body paralysis or weakened legs by assisting or restoring legged mobility while providing health
benefits across multiple physiological systems. Here, a systematic review of the literature on
powered exoskeletons addressed critical questions: What is the current evidence of clinical
efficacy for lower-limb powered exoskeletons? What are the benefits and risks for individuals
with spinal cord injury (SCI)? What are the levels of injury considered in such studies? What are
their outcome measures? What are the opportunities for the next generation exoskeletons?
Approach. A systematic search of online databases was performed to identify clinical trials and
safety or efficacy studies with lower-limb powered exoskeletons for individuals with SCI.
Twenty-two studies with eight powered exoskeletons thus selected, were analyzed based on the
protocol design, subject demographics, study duration, and primary/secondary outcome
measures for assessing exoskeleton's performance in SCI subjects. Main results. Findings show
that the level of injury varies across studies, with T10 injuries being represented in 45.4% of the
studies. A categorical breakdown of outcome measures revealed 63% of these measures were
gait and ambulation related, followed by energy expenditure (16%), physiological improvements
(13%), and usability and comfort (8%). Moreover, outcome measures varied across studies, and
none had measures spanning every category, making comparisons difficult. Significance. This
review of the literature shows that a majority of current studies focus on thoracic level injury as
well as there is an emphasis on ambulatory-related primary outcome measures. Future research
should: 1) develop criteria for optimal selection and training of patients most likely to benefit
from this technology, 2) design multimodal gait intention detection systems that engage and
empower the user, 3) develop real-time monitoring and diagnostic capabilities, and 4) adopt
comprehensive metrics for assessing safety, benefits, and usability.

S Online supplementary data available from stacks.iop.org/JNE/13/031001/mmedia

Keywords: Paraplegia, tetraplegia, spinal cord injury, orthoses, exoskeletons, over-ground
walking, gait intention

(Some figures may appear in colour only in the online journal)

1741-2560/16/031001+16$33.00 1 © 2016 IOP Publishing Ltd Printed in the UK

J. Neural Eng. 13 (2016) 031001
1. Introduction
In 2014, spinal cord injuries (SCI) were reported to affect
approximately 276 000 persons in the United States, with
approximately 12 500 new SCI cases each year
(NSCISC 2015). According to the University of Alabama
National Spinal Cord Injury Statistical Center and the Centers
for Disease Control and Prevention (CDC), the costs of living
with SCI can be considerable, and vary greatly due to the
severity, age of injury and loss of income. The lifetime costs
for an individual that can be directly linked to high tetraplegia
can reach $4.7 million (NSCISC 2015). SCI has a significant
impact on a person’s quality of life (QOL) and health status
(Behrman and Harkema 2000). Decreased mobility is likely
related to higher blood pressure, shorter life expectancy,
social stigma and increased rates of depression (Parent
et al 2011). Thus, walking is usually cited as one of the
primary goals of rehabilitation due to the physiological and
social implications (Ditunno et al 2008, Calhoun et al 2013).
Gait therapy is a rehabilitation method used to improve
general health and walking ability of individuals with lower
limb dysfunction. Even in the case of complete SCI subjects
with no voluntary control below the level of the lesion,
manually-assisted or robot assisted locomotor training can
result in beneficial effects in cardiovascular and muscu-
loskeletal systems (Hesse 2001, Hubli and Dietz 2013).
Robotic gait assistance allows increased training duration,
reproducible gait patterns as well as close monitoring of
patient progress during therapy (Hidler and Sainburg 2011).
Both the manual method, in which physical therapists
articulate the individual’s lower limbs by hand to maintain a
correct walking gait (Hesse 2001), and robotic gait method
have shown improved patient outcomes but there has not been
enough statistical evidence to definitively demonstrate the
advantages of robotic training (Yang and Musselman 2012).
More recently, research has focused on engaging the indivi-
dual and adjusting limb actuation based on the need and input
from the user. Thus, impedance-controlled robotic gait allows
for an assist-as-needed approach and is meant to keep the user
actively engaged in the walking process with the expectation
that rehabilitation will have a greater impact if the individual
is more focused on the task. The effectiveness of impedance
control has been demonstrated, but no comparison has yet
been done to show any statistically significant advantage over
other methods (Fleerkotte et al 2014).
With recent developments in robotic technologies, pow-
ered exoskeletons have emerged as practical devices for
assisting individuals with lower limb paralysis or weakened
limbs and as devices to assist and support the work of phy-
sical therapists. The US Food and Drug Administration
(FDA) have recently approved a de novo product classifica-
tion for powered exoskeletons (product code PHL, a Class II
device with special controls) (Food and Drug Administration,
HHS 2015). Unfortunately, while exoskeleton technology
continues to advance and psychological as well as physiolo-
gical benefits of legged mobility are likely, the anticipated
benefits across multiple physiological systems remain largely
2
Topical Review
unproven. Moreover, studies are required to evaluate the
potential risks of deploying this technology outside the clinic,
including falls, changes in blood pressure (diastolic hyper-
tension and hypotension) and heart rate, skin abrasions,
bruising, pressure sores, increased spasticity, lightheadedness,
and soft tissue injury.
This systematic review of powered exoskeletons for
bipedal locomotion in SCI patients was undertaken to address
five specific questions: (1) What is current evidence of clin-
ical efficacy for lower-limb powered exoskeleton? (2) What
are the benefits and risks for individuals with spinal cord
injury? (3) What are the levels of injury considered in such
studies? (4) What are their outcome measures? (5) What are
the opportunities for the next generation exoskeletons?
2. What constitutes a powered exoskeleton?
According to the FDA’s definition, a powered exoskeleton is
‘a prescription device that is composed of an external, pow-
ered, motorized orthosis used for medical purposes that is
placed over a person’s paralyzed or weakened limbs for the
purpose of providing ambulation’ (Food and Drug Adminis-
tration, HHS 2015). This definition differs from the termi-
nology proposed by (Herr 2009), which restricts the term
exoskeleton to a device that enhances the physical capabilities
of an able-bodied user, but is consistent with the view of an
orthosis as a device used to assist a person with an impair-
ment of the limbs.
For the purpose of this review, the NIH revised definition
of a clinical trial was used as inclusion criteria for the selection
of clinical studies of powered exoskeletons. The NIH defines a
clinical trial as ‘a research study in which one or more human
subjects are prospectively assigned to one or more interven-
tions (which may include placebo or other control) to evaluate
the effects of those interventions on health-related biomedical
or behavioral outcomes’ (http://grants.nih.gov/grants/guide/
notice-files/NOT-OD-15-015.html). Thus, a clinical study
included in this review is a research study in which one or more
human subjects are prospectively and necessarily assigned to a
powered exoskeleton for over-ground legged mobility to
evaluate the effects of the intervention(s) on functional, phy-
siological, behavioral, or psychological outcomes. Addition-
ally, to create a more comprehensive review of current
literature, a powered exoskeleton study was selected for
inclusion in this review if the purpose of the study was to
determine whether the powered exoskeleton intervention was
safe, efficacious, and/or effective, and the target population
was SCI. Moreover, only peer-reviewed journal and conference
papers were included in this review. However, studies that only
applied the exoskeleton for purposes of evaluating the feasi-
bility or performance of the device, absent of any monitoring of
the individual for physiological changes, were excluded from
review. Likewise, review papers or book chapters or non-
English articles were also excluded.
We also excluded passive orthoses such as ankle-foot
orthoses (AFOs) and reciprocating gait orthoses unless they
were part of a powered exoskeleton. For this information, the
J. Neural Eng. 13 (2016) 031001
reader is directed to several published reviews surveying the
state-of-the-art for lower-extremity powered exoskeletons (Ferris
et al 2007, Dollar and Herr 2008, Pons 2008, Yang et al 2008,
Bogue 2009, Herr 2009). While there are several studies
reviewing the overall design and control strategy of different
types of exoskeletons from an engineering perspective (Jimenez-
Fabian and Verlinden 2012, Tucker et al 2015), including gait
speed (Louie et al 2015), few have analyzed the rehabilitation
efficacy with these devices (Mehrholz and Pohl 2012, Federici
et al 2015, Lajeunesse et al 2015). However, to our knowledge,
no study has examined in detail the primary and secondary
outcomes of the published studies and clinical trials with pow-
ered exoskeletons for the SCI community.
2.1. Search strategy
We searched four online databases until 8th December, 2015
and retrieved 430 publications: 43 belonging to PubMed, 134
in Web of Science, 80 in ProQuest, and 123 in Scopus. The
following search terms were used in all fields: (robotic OR
power* OR over-ground OR walk* OR gait) AND (exoskele-
ton OR exoskeletal OR orthos*) AND (spinal cord injury OR
SCI OR paraplegia OR tetraplegia) AND (leg OR lower AND
(limb OR extremity)) AND (rehabilitation* OR clinical*).
After removing duplicate references, 327 references were
retained. These references were divided into three groups and
each group was independently reviewed by two authors. Each
author screened the title and abstracts of the assigned studies
and determined their eligibility for the review. Disagreements
between authors were resolved by mutual discussion. Studies
selected by each group were then pooled together to yield 11
studies. A separate literature search on Google Scholar was
conducted to find recent articles published since 2012, which
may have been missed by other databases. This search
resulted in 2100 results (excluding patents), which were fur-
ther filtered by adding the exoskeleton device names, pre-
viously identified to the search terms that had been used in the
initial search using the PubMed, Web of Science, ProQuest
and Scopus databases. Since Google Scholar restricts search
terms to 256 characters (Boeker et al 2013), we added the
exoskeleton names to the search terms one at a time, i.e.
(ORIGINAL_SEARCH_TERMS) AND (EXOSKELE-
TON_NAME). Hand searches of reference lists from
retrieved articles were completed. After screening for elig-
ibility, 11 additional articles were selected and combined with
the previously selected studies. Thus, in the end 22 studies
were selected that met our inclusion criteria and were inclu-
ded in this review. We also searched ClinicalTrials.gov for
registered studies with exoskeletons identified from the
selected studies (see table 1).
3. Wearable robots or powered exoskeleton
technologies
While there are numerous wearable robots or powered exos-
keletons for legged mobility under development, under clin-
ical trials with human subjects, or already marketed; we
3
Topical Review
identified studies with eight3 exoskeleton devices that fit the
inclusion criteria. These exoskeletons are described below.
3.1. Bionic Leg (AlterG Inc. Fremont, CA, USA, http://alterg.
com/products/bionic-leg/professional-physical-therapy/)
The AlterG Bionic Leg (formerly Tibion Bionic Leg) is a
unilateral robotic knee orthoses (RKO) for individuals with
asymmetric lower-limb motor impairments, for example the
Brown-Sequared syndrome (Bishop et al 2012). The device is
designed to assist the user during sit-to-stand transitions,
over-ground walking and stair climbing/descent. It uses four
force sensors mounted on a foot plate which detect the
amount and time of weight-bearing through the foot. Addi-
tional sensors which measure the knee angle and the exten-
sion force provided by the actuators are also incorporated.
The user interface allows a trained therapist to adjust the
amount of assistance and/or resistance provided by the
device, device range-of-motion as well as minimum force
required to activate the device. When the device is inactive, it
is back-drivable which functions as a safety feature and
allows therapist to position the lower extremity in weight-
bearing exercise mode. The device is untethered from any
cords and contains its own battery power that can lasts up to
2–3 h. For ensuring patient stability and safety, it is operated
with a walker (Bishop et al 2012).
3.2. Ekso exoskeleton (Eksobionics Ltd, Richmond, CA, USA;
http://eksobionics.com/)
Ekso is a wearable lower extremity robotic exoskeleton with
two legs connected to a torso structure containing the
computer and batteries. The torso is aligned to the user’s
lower back, and the exoskeleton legs are fastened to the user’s
legs by hook-and-loop fastener straps that align the user’s
lower back and joints with those of the device. Two additional
straps are tightened over the user’s shoulders to help support
the torso structure. The device has powered (bilaterally) hip
and knee joints in the sagittal plane and other movement
directions are restricted. The ankle joints of the exoskeleton
allow passive (spring) movement limited to the sagittal plane.
Currently, Ekso has four walk modes: in the first two walk
modes, either a physical therapist or the user actuates sit-to-
stand and steps with a button push; whereas in the other two
walk modes, gait intent detection to command the exoskele-
ton is accomplished by detecting the forward and lateral
movement of the user’s hips (to accomplish weight shift); or
by the user’s weight shift and the initiation of forward leg
movement. Ekso requires walking aids using provided crut-
ches to ensure stability and safety of the user; the bottoms of
the crutches are fitted with force sensors to ensure firm pla-
cement on the ground and at least partial weight-bearing. A
3
During online search on ClinicalTrial.gov we did find a clinical trial
(NCT02417532) registered for REX exoskeleton (Rex Bionics, New
Zealand). As compared to other exoskeleton reviewed in this study, REX’s
unique self-balancing feature is noteworthy. However, since this study does
not have any published results at this time, we exclude it from this systematic
review.
 J. Neural Eng. 13 (2016) 031001
Table 1. Summary of powered exoskeletons for individuals with SCI.

Exoskeleton

Degrees of freedom K HKA HKA HK KA HKA HaHKA HKA

Weight-bearing devices W C W/C/S W/C W/C C S W/B
Sensor measurements JA, JT, FF AJA, ACF, FF, EMG, JA, JA, Acc, Ori JA, FF, JA, FF, Ori IT, JA JA, JT
Acc/Ori (arm) FF, Acc IT, Ori
Device weight (kg) 3.6 20 15 12 9.2 23 ? 13
User height (cm) limit 153–182 158–188 145–185 155–191 <1.85 160–190 ? 145–180
User weight (kg) limit 136 100 80 113 90 100 ? 80
Gait initiation mode Foot sensors 1. Body tilt Knee EMG Body tilt Button push Body tilt ? Button push
and knee activation
extension
2. Button push
Unique features Unilateral — — — Hybrid (FES) — Hybrid (FES), Frame fits
4

active bodyweight between legs,

support easy to don
suspension harness within wheerchair
moves with
exoskeleton
ClinicalTrials.gov registra- NCT01701388 — NCT02202538 — NCT02322125 —
tion ID
NCT02324322 NCT01943669
NCT02132702 NCT02118194
NCT02065830 NCT02104622
NCT01251549
NCT00627107
NCT01454570

Note: Degrees of freedom: (Bilateral) Ha-hip ab/adduction, Hr-hip medial/lateral rotation, H-hip (sagittal), K-knee (sagittal), A-ankle (sagittal), Av-ankle in/eversion, underline-passive.
Weight-bearing devices: C-crutches, W-walker, B-parallel safety bars, S-suspension harness.
Sensor measurements: EMG-electromyography, JA-joint angle, AJA-arm joint angle, ACF-arm crutches force, IT-interaction torque, JT-joint torque, FF-foot contacting force/pressure, Acc-acceleration, Ori-orientation.

Topical Review
J. Neural Eng. 13 (2016) 031001
step will not be triggered unless both crutches are firmly on
the ground. Additionally, the controller uses a hierarchical
finite state machine to transition between the different
movements without forcing the user into unsafe positions
(Strausser and Kazerooni 2011). According to the manu-
facturer, newer versions of Ekso are capable of providing
variable assist or assist-as-needed power to the user. Thus,
therapists have the option to assign a specific amount of
power contribution to augment their patients’ efforts, or to
allow the exoskeleton to dynamically adjust to their needs in
real-time. Ekso has not currently been approved by the FDA
as a Class II device as a powered exoskeleton, but the com-
pany has submitted a 510(k) application and has been allowed
to continue device marketing during the review process.
3.3. Hybrid assisted limb (HAL; Cyberdyne Inc., Tsukuba,
Japan; http://cyberdyne.jp/english/)
HAL is a bilateral lower-limb exoskeleton with three active
degrees of freedom for actuating the hip, knee and ankle joints.
The HAL system comes in different models, allowing single
joint or full body support during walking, standing and sitting
(Suzuki et al 2007). It consists of six main parts: controller,
battery, power unit, electromyography (EMG) sensors, angu-
lar/acceleration sensors, and floor reaction force sensors
(Sankai 2011). The control system receives data from EMG,
angle/acceleration, and force sensors and computes the
necessary forces to complement the user’s actions. The use of
EMG to determine user’s intention, instead of a joystick or
other manual controller is beneficial, since it allows the user to
operate the device by simply attempting to initiate a movement.
Currently, the battery life allows 2 h 40 min operation time. For
patient safety and stability during walking, HAL is used with a
walker or cane (Kubota et al 2013). The HAL exoskeleton is
commercially marketed in Japan and Europe as a medical
prescription device developed for people who have lower-limb
disorders and people whose legs are weakening. The device
has been certified (ISO13485) under the European Medical
Device Directive (CE 0197). The manufacturer has applied for
marketing authorization of HAL for medical use as a new
medical device for orphan neural-muscular diseases, such as
muscular dystrophy, amyotrophic lateral sclerosis (ALS) under
Japan’s Pharmaceutical and Medical Device Law.
3.4. Indego (Parker Hannifin Corp., Macedonia, OH, USA;
http://indego.com/indego/en/home)
The Indego modular exoskeleton is comprised of powered
bilateral hip and knee joints, and it incorporates built-in AFOs
that provide ankle stability and exoskeleton weight transfer to
the ground (Hartigan et al 2015). The exoskeleton’s hip,
upper and lower leg modules assemble via quick-connects to
enable easy donning, doffing, and transportation as well as
compact storage of the device. Its slim profile is compatible
with standard mobility aids and can be worn while seated in a
wheelchair. The exoskeleton enables sitting, walking, stand-
ing, sit-to-stand, stand-to-walk, walk-to-stand, and stand-to-
sit transitions. Intent detection for locomotive and non-
5
Topical Review
locomotive tasks is based on the user’s ability to affect his
center of pressure (CoP) via the use of the upper body in
combination with a stability aid such as a walker. The con-
troller uses the distance between the CoP and the location of
the forward ankle joint as the primary command input to the
device. This requires the user to tilt the body forward or
backward such that the CoP moves in an anterior or posterior
direction, which commands the controller to transition to a
different movement mode. As a safety measure there are
brakes at the knee joints to prevent knee buckling in case of
power failure (Quintero et al 2011). On 8 March 2016, the
FDA released its summary of the 510(k) premarket notifica-
tion for the Indego exoskeleton (http://www.accessdata.fda.
gov/cdrh_docs/pdf15/k152416.pdf). The FDA reviewed the
Section 510(k) premarket notification of intent to market the
Indego device and has determined the Indego, as designed
and manufactured, meets the Special Controls specified in 21
CFR 890.3480, and is determined to be substantially
equivalent to the referenced predicate device (ReWalk exos-
keleton from Argo Medical Technologies), thus allowing
Parker Hannifin Corporation to market the Indego device,
subject to the general controls provisions of the Federal Food,
Drug, and Cosmetic Act.
3.5. Kinesis (Technaid, Madrid, Spain; http://technaid.com/en/
products/exoskeleton)
Kinesis is a lower limb rehabilitation robot designed for pro-
viding hybrid therapy of walking to patients with incomplete
spinal cord injury. The target population is patients with a
prognosis for functional recovery of walking, i.e. patients who
can walk short distances but depend on the wheelchair for
community ambulation, usually with some preservation of hip
flexor function. Kinesis is a knee-ankle-foot exoskeleton,
equipped with an active actuator in the knee, a passive elastic
actuator at the ankle for plantar and dorsal flexion, and is
equipped with force-sensitive resistors to detect foot-ground
contact, potentiometers to monitor joint angular position, and
embedded strain gauge-based Wheatstone bridge to measure
user-robot interaction torques (del-Ama et al 2012). A biolo-
gically inspired mechanism for the knee joint allows the joint
axis to follow the translational motion of the physiological
knee joint axis, improving kinematic compatibility between the
orthosis and the subject with respect to a single-axis joint. As a
hybrid-therapy system, Kinesis can provide functional elec-
trical stimulation (FES) to the knee extensor (rectus femoris
and vastus lateralis) and flexor (semitendinosus and biceps
femoris) muscles through surface electrodes. The main con-
troller for Kinesis consists of four components: a robotic or
joint controller, an FES controller, a muscle fatigue estimator,
and a finite state machine to coordinate the FES and joint
controllers. Kinesis uses shared control to operate the robot
actuators and FES of knee joint muscles while managing
muscle fatigue. The FES controller is only active during swing
phases of gait, while a PID controller for knee extensor mus-
cles is active across the full gait cycle. The Kinesis hybrid
controller works to minimize the interaction forces between the
user’s body and the exoskeleton (del-Ama et al 2014, 2015).
J. Neural Eng. 13 (2016) 031001
The Kinesis has several built-in safety measures including:
mechanical stops in the physiological limits of motion at the
robotic joints; software limits for maximum and minimum
positions in the admittance controller for the knee joint, max-
imum output torques, and FES pulse width and amplitude
modulation; and a mechanical safety button to physically dis-
connect power from the entire hardware (del-Ama et al 2014).
3.6. ReWalk (Argo Medical Technologies Ltd, Yokneam Ilit,
Israel; http://rewalk.com/)
The ReWalk is an end-effector-based robot with footplates
placed on a double crank and rocker gear system. The device
is comprised of a powered exoskeleton that bilaterally con-
trols the movements at the hip and knee joints (ankles are
articulated with spring-assisted dorsiflexion), a battery unit,
and a computer-based controller contained in a backpack, a
wireless mode selector, and sensors that measure upper-body
tilt angle, joint angles, and ground contact. The exoskeleton is
articulated to footplates distally and to a sacral band proxi-
mally. The device senses the patient’s movements to control
externally powered gait using closed-loop control algorithms
(Zeilig et al 2012). Thus, for example in the ‘walk’ mode,
forward flexion of the upper body is detected by the tilt
sensor, which triggers a step. The gait is a three-point pattern,
advancing one step at a time. Additional modes include sit-to-
stand, stand-to-sit, up steps, and down steps. The maximal
walking velocity in the latest model (ReWalk 6.0) is
2.6 km h−1 (Yang et al 2015). Undesirable rapid hip and knee
flexion, as may occur in a fall, is prevented by software,
which also provides a controlled speed during stand-to-sit
movements. The device requires walking aids (crutches or a
walker) to ensure stability and safety of the user. The FDA
has recently approved a version of the ReWalk for use in the
United States as a Class II (product class: powered exoske-
leton) prescription device with special controls under 21 CFR
Part 801.109 regulations. In December 2015, the US Dept. of
Veterans Affairs issued a national coverage policy for the
evaluation, training, and procurement of ReWalk Personal
exoskeleton systems for eligible veterans with SCI4.
3.7. WalkTrainer (SWORTEC, Switzerland, http://swortec.ch/
index.php/products/walktrainer)
The WalkTrainer is equipped with bilateral and pelvic orthoses,
active bodyweight support, closed-loop muscle stimulator and
a mobile frame. The leg orthoses are comprised of a light-
weight exoskeleton that is customized for each patient and is
attached posteriorly by a powered mechanical leg via bar lin-
kages (Stauffer et al 2009). The powered leg houses motors
and mechanisms for actuating the hip, knee and ankle joints in
parallel with the sagittal plane. The powered leg carries the
entire actuator mechanism, cables, battery pack, etc making the
4
Memorandum from Department of Veterans Affairs (VA) can be found
online at http://sci.va.gov/docs/VHAReWalkStatement_cleared.pdf. The
VA has recently listed a national, multi-center study utilizing the ReWalk
Personal 6.0 exoskeleton system (www.clinicaltrials.gov Identifier:
NCT02658656).
6
Topical Review
patient’s exoskeleton less bulky and thus enables the patient to
freely move their arms during walking. The patient’s feet are
attached to the powered leg using foot plates that are embedded
in the soles of specially modified shoes. The pelvic orthoses
has six degrees of freedom which are actuated in co-ordination
with the leg orthoses using foot switches to detect heel strike
and toe off. Force sensors and potentiometers mounted on each
axis of the exoskeleton help monitor the user’s interaction with
the orthoses and are used for implementing a selective com-
pliant control algorithm. Additionally, a 20-channel real-time
controlled muscle stimulator is used to augment the motion
generated by the user and further, minimize the interaction
forces between the user and the exoskeleton. The active body
weight support ensures safety of patient during walking by
precisely controlling the unloading force applied to the patient.
3.8. Wearable power-assist locomotor exoskeleton (WPAL;
Fujita Health University, Japan)
WPAL has six degrees of freedom for bilateral flexion-
extension at the hip, knee, and ankle joints. The level of the
robotic hip joint is under the perineum, and it has an anterior-
posterior curving slide mechanism that moves the virtual
rotation center of the robotic hip joint closer to the center of
the physical joint (Tanabe et al 2013b). Orthotic and robotic
components are modular to allow orthotic components to be
personalized whereas robotic components can be standardized
for mass production. WPAL has one standing/sitting mode
and three gait modes. Users can switch from simple gait mode
to another optional mode (curve mode and slow mode) while
walking by pulling a trigger or pressing a button. The curve
mode allows the user to turn smoothly. In the slow mode, the
step lengths of both feet are shortened. This mode is used for
uneven surfaces. For patient safety, WPAL is used with a
custom walker that provides stability during standing, walk-
ing and sitting. The walker also houses batteries, motor dri-
vers and computer for controlling the exoskeleton via a wired
interface (Tanabe et al 2013a).
A summary of the mechanical and controller character-
istics of these powered exoskeletons is provided in table 1.
Though marked differences exists across the different exos-
keletons reviewed above, some common features for the
exoskeletons can be drawn from these designs: currently, the
mainstream exoskeleton design provides 1–6 degrees of free-
dom in the sagittal plane to drive the user’s hip, knee, and
sometimes ankle joints to follow desired gait trajectories during
locomotion. Six of the systems integrate passive or active
actuators at the ankle joint to facilitate dorsiflexion and plantar
flexion. Generally, the user will partially depend on crutches,
or a walker to support their weight and maintain balance, and
joint angles and foot contact forces are often recorded to
monitor basic gait performance. Based on the available infor-
mation, all devices weigh less than 25 kg, and are operated
with an auxiliary weight-supporting device such as forearm
crutches or walker or body-weight support. The systems can be
adjusted to the user’s anthropometry to accommodate heights
between 145–191 cm and a mass less than 136 kg.
 J. Neural Eng. 13 (2016) 031001
Table 2. Selected studies of powered exoskeletons for SCI with outcomes measures.

Experimental protocol Subjects Outcome variables

Time since
Number of Duration in Frequency Duration in injury in
ID Reference Device sessions hours per week weeks Number Age Injury level years 10 mWT 6 minWT TUG
1 (Bishop et al 2012) Bionic 7 1 — 2 1 22 C5/C6 4 $ ! $
Leg
2 (Kozlowski et al 2015) Ekso 8–24 2 1–2 — 7 21–49 T8,C8,C4,L1, 0.4–7.4 — — —
T9,T9,T10
3 (Kolakowsky-Hayner Ekso 6 0.33–1.0 1 6 7 19–40 T11,T10,T11, 0.2–1.5 — — —
et al 2013) T7,T12,T4,T8
4 (Kressler et al 2014) Ekso 18 1 3 6 3 26–38 T1/T2,T7, >1 — — —
T9/T10
5 (Cruciger et al 2014) HAL 24–36 0.5–0.75 2–3 12 1 34 T10 — — — —
6 (Kubota et al 2013) HAL 16 1.5 2 8 8 31–69 — 1.1–6.3 ! — $
7 (Tsukahara et al 2015) HAL 6 — — 3 months 1 39 T7/T8 — ! — —
8 (Aach et al 2014) HAL 51.75 — 5 3 months 8 36–63 T8,L1,T12,L1, 1–19 ! ! !
± 5.6 L1,L2,T11,T12
9 (Farris et al 2014) Indego 1 — — — 1 42 T10 10 ! ! !
10 (Evans et al 2015) Indego 2 — — — 5 28–51 T7,T8,T10, 1–20 — X —
T12,T6
7

11 (Hartigan et al 2015) Indego 5 1.5 — — 16 18–51 C5,C6,C6,T5, — X X —

T7,T5,T6,
T7,T12, T10,
T10,T11,T9,
T12,L1,T12
12 (del-Ama et al 2014) Kinesis 3 — — 2 3 35–43 L1,L2,L5 — ! ! —
13 (del-Ama et al 2015) Kinesis 3 — — — 3 35–43 L1,L2,L5 — X X —
14 (Esquenazi et al 2012) ReWalk 13–26 1–1.5 3 8 12 18–55 T8,T3,T8,T11, 1–24.3 X X —
T10,T10,T4,
T6,T10,T12,
T7,T4
15 (Fineberg et al 2013) ReWalk 11–45 1–2.0 3 5–6 months 6 24–62 T4,T1,T4,T8, 1.5–14 — — —
T11,T5
16 (Asselin et al 2015) ReWalk 12–54 1–1.5 — — 8 24–61 T4,T8,T11,T5, 1.5–14 — X —
[NCT01454570] T1,T9,T7,T2
17 (Zeilig et al 2012) ReWalk 7–24 0.83 — 3 months 6 21–48 T5,T7,T7,T9, 3–7 X X X
T10,T12
18 (Benson et al 2015) ReWalk 20 2 2 10 5 23–41 L1,T12,C7, 1.4–7.25 ! ! !
[NCT01943669] C8/T2,T9

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 J. Neural Eng. 13 (2016) 031001
Table 2. (Continued.)

Experimental protocol Subjects Outcome variables

Time since
Number of Duration in Frequency Duration in injury in
ID Reference Device sessions hours per week weeks Number Age Injury level years 10 mWT 6 minWT TUG

19 (Yang et al 2015) ReWalk 12–120 1–2.0 1 12 12 24–64 T4,T10,T4, 1–16 X X —

[NCT02118194] C8/T8,T11,
T5,T1,T9,T7,
T2,T2,C8
8

20 (Stauffer et al 2009) Walk- 12 1 1 12 6 — — — — — —

Trainer
21 (Tanabe et al 2013a) WPAL 2–11 1 — — 7 32–61 T12,T12,T11, 6–20 X — —
T9,T6,T6,T6
22 (Tanabe et al 2013b) WPAL 6–39 1 2–3 times/ 3–13 4 30–59 T12,T11, 4–20 — X —
month months T6,T12

Note: Outcome variable symbols: !: positive change; $: negative change; X: no comparison; —: data not available;
ClinicalTrials.gov registered study identifier shown in parenthesis [ ]; shaded rows indicate clinical studies; Unshaded rows indicate feasibility or preliminary evaluation studies.

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J. Neural Eng. 13 (2016) 031001
4. Analysis of powered exoskeletons studies for SCI
population
In this section, the 22 powered exoskeletons studies selected
above are analyzed based on the protocol design, subject
demographics, study duration, and primary/secondary out-
come measures for assessing exoskeleton’s performance in SCI
patients. These factors are summarized in table 2 for each of
the selected studies and discussed in detail below. The shaded
rows in table 2 distinguish clinical studies (based on NIH’s
revised definition in section 2) from feasibility or preliminary
evaluation studies that were included here for completeness.
4.1. Protocol designs varied across studies
Inspection of the session protocol across studies revealed large
differences in the number of sessions and overall duration of
experiments. The maximum number of sessions across all
studies was 120, yet a fraction of these were used for training
the subject in operating the exoskeleton (Yang et al 2015). A
single session study among the twenty-two studies is also
present (Farris et al 2014). Typically, the number of sessions
per week was two to three, with only one study conducting
experiments five days per week (Aach et al 2014). The dura-
tion of individual sessions ranged between one to two hours,
with no studies reported exceeding two hours per session.
4.2. Distribution of SCI subjects by level of injury differed
across studies
Table 2 also shows the distribution of subject demographics,
including number of subjects, their ages, injury level and time
since injury. One of the biggest sources of discrepancy among
these studies is in the number of participants enrolled. The
average number of subjects was six with a standard deviation
of four subjects, ranging between one and sixteen study par-
ticipants. Among the 22 studies, four reported findings based
on single subject data, with one of those being a single session
experiment. Interestingly, table 2 shows a wide range of SCI
injury levels included in these studies. This is also evident in
figure 1, which shows the distribution of level of injury across
all the studies. Figure 1 reveals that a majority of studies
included patients with thoracic level injuries, amongst which
patients with T10 injury were present in 45.4% of studies. Five
of the studies reported include patients with cervical level
injuries, whereas none of studies recruited patients with sacral
level injury. The time since injury reveals, that most of the
studies recruited chronic (…6 months) SCI subjects with the
exception of (Kolakowsky-Hayner et al 2013, Kozlowski
et al 2015) which also recruited acute SCI subjects.
4.3. Outcome measures focused on assessing mobility
Seven primary measures associated with functional ambula-
tion in SCI patients were identified by a recent survey (Lam
et al 2011): 10 meter walk test (10 mWT), 6 minute walk test
(6 mWT), timed up and go (TUG), spinal-cord injury func-
tional ambulation inventory (SCI-FAI), functional indepen-
dence measure, Spinal cord independence measure, and
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walking index for spinal cord injury (WISCI-II). Of these, the
first three are timed measures, and the latter three are cate-
gorical assessments of ambulation, with the SCI-FAI having
components of both. The experimental design of the studies
presented in this review host a variety of outcome metrics
including these seven measures, as well as other metrics
aimed to assess physiological and psychological changes, and
usability. Since the 10 mWT, 6 mWT, and TUG tests were
administered by a majority of the studies (as seen in figure 2),
we additionally report these tests in table 2 and compare their
outcomes. Further, we split the primary and secondary out-
comes of all studies into five categories: quantitative func-
tional ambulation assessments covers timing-based measures
related to functional walking; balance and level of assistance/
independence considers functional ambulatory measures
incorporating the categorical assessments and balance tests;
physiological improvements include measures studying
effects related to muscle, spasticity and bowel/bladder
function; energy expenditure during use covers metrics
looking at the energy required when using the exoskeleton;
and usability and comfort address the device ergonomics.
Figure 2 shows the categorical breakdown of all the
outcome measures used in the selected studies, as well as the
distribution of each category. It can be noted that 63% of the
outcome measures selected are gait and ambulation related,
with researchers emphasizing quantitative measures (45%)
over outcome measures evaluating balance, level of assistance
and independence (18%). This is followed by outcome
measures measuring energy expenditure (16%), physiological
improvements (13%), and usability and comfort (8%).
Overall, studies with the largest number of outcome measures
were based on ReWalk (20 measures across six studies),
followed by Indego (13 measures across three studies), HAL
(12 across four studies), and Kinesis (10 across two studies).
4.4. Overall comparison between studies
When comparing experimental designs, there is a general
consistency across all studies in the number of sessions per
week (1–3/week) during which the exoskeleton-based inter-
vention was provided. The treatment frequency is also con-
sistent with traditional locomotor training (e.g. robot-assisted
gait training) frequency of 2–5 sessions per week (Wirz
et al 2005, Schwartz et al 2011). Interestingly, (Aach
et al 2014) implemented their exoskeleton therapy for five
sessions per week and observed a positive change in the three
most commonly used outcome measures (10 mWT,
6 minWT, TUG). Five out of seven studies that compared
metrics pre- and post-intervention, report improvement from
baseline, whereas two studies reported negative change (see
table 2). Unfortunately, due to wide variation in metrics,
number of subjects, level of injury and training protocols, the
information available is not sufficient to make specific com-
parisons between these studies. For example, there is no
consensus on the duration for which the exoskeleton therapy
must be applied. Training duration varied from single trial
evaluations (Farris et al 2014) to longitudinal studies with
many subjects training over many sessions for more than two
J. Neural Eng. 13 (2016) 031001
Figure 1. Distribution of SCI injury level in participants of studies with powered exoskeletons.
months (e.g. Esquenazi et al 2012, Fineberg et al 2013, Yang
et al 2015). Future studies should be designed to be consistent
in the duration of intervention (total number of sessions,
sessions per week, and session duration), in order to allow
more meaningful comparisons. Moreover, based on published
results that reported positive changes in outcome variables
(see entries in table 2), a recommended dosage of 2 h per
session, for at least 20 sessions is recommended as it has been
noted that increases in gait speed using powered exoskeletons
are correlated with training time (Louie et al 2015).
5. Discussion
5.1. Level of injury of the SCI population should be better
represented in future studies
According to the National Spinal Cord Injury Statistical
Center, more than a half of SCI patients have cervical injuries,
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with C5 as the largest category, followed by thoracic level
injury (T1-T12) (NSCISC 2015). However, as pointed out in
this review, a majority of the studies focus on thoracic level
SCI and future studies focusing on wider levels of injury
including C1-C8, L2-L5, and S1-S5 are required. Yet, little is
known about how the level of injury affects the usage of
exoskeletons and it is likely that for safety reasons specialized
designs (e.g., devices with alternative human–device inter-
faces, automatic gait intent detection mechanisms, upper body
support, self-balancing designs, etc) will be needed for
C-level patients with tetraplegia with poor upper-body con-
trol. Of note is that pediatric SCI patients were not included in
this review as there were no studies that included SCI patients
younger than 16 years old. The pediatric SCI population may
have a greater potential for neurological recovery compared to
adults and thus should be investigated as a potential group for
training with these devices (Parent et al 2011). Thus, pedia-
tric-centered designs of powered exoskeletons for over-
ground walking should be considered in the near future.
J. Neural Eng. 13 (2016) 031001
Figure 2. Categorical distribution of outcome measures used in studies.
5.2. Outcome measures should be comprehensive and
consistent across studies of powered exoskeletons
Among the outcome measures evaluated in the selected stu-
dies, there was a general inconsistency in the metrics used.
While some studies relied on standardized tests and timed
measures to assess functional, physiological, or psychological
improvements in their subjects, others relied on custom
metrics and questionnaires or subjective observation-based
assessments. This posed a significant impediment in objec-
tively comparing devices and tracking their clinical efficacy
and benefit to patients. The categorical classification of
metrics (section 4.3) revealed that none of the studies had
outcome measures spanning every category. Only two studies
involving Kinesis (ID 12) and ReWalk (ID 17) had outcome
measures that spanned four categories. It appears that the
choice of outcome metrics used may be motivated by the
preference of the researchers that conduct these studies. Farris
et al (2014) mentioned this in their discussion, describing the
lack of standardized metrics used by researchers in char-
acterizing mobility and level of exertion in the use of assistive
devices.
The review of the literature shows that there is an
emphasis on ambulatory-related primary outcome measures,
where both quantitative and qualitative measures focusing on
gait and balance account for 63% of all measures in these
studies. Indeed, the 10 mWT, 6 minWT, and TUG are known
to be reliable, validated, and responsive (Lam et al 2011), and
thus they should be considered in future studies that assess
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potential benefits of balance and walking ability using pow-
ered exoskeletons. In addition, a recent study suggests an
adequate gait speed for community ambulation (e.g., to allow
safe street crossings) to be 0.49 m s−1 and this should be
taken into account as one of the measures for assessing
mobility benefits in real-world scenarios (Andrews
et al 2010). Improvements in bowel/bladder function, stabi-
lity and strength were only alluded to in a few of these studies
(Strausser and Kazerooni 2011, Zeilig et al 2012). A previous
review of the outcomes of SCI research found similar pitfalls
widely present across all areas of SCI research (Ham-
mell 2010). The author in (Hammell 2010) observed that the
SCI population felt that researchers may be overlooking many
of the desired outcomes of the populations and replacing them
with far-reaching goals, or worse, secondary or tertiary goals
beyond their direct vision of improvement. Furthermore, the
SCI population reported feeling that they were only part of a
study that evaluated differences in outcome metrics and not in
improvements in the QOL of the individual. Thus, it is dis-
couraging to see that the target population, which the
researchers are attempting to help, does not feel that they are
being adequately represented in these studies. This is also a
limitation of many of the studies presented in this review,
which do not specifically address the improvements in QOL,
but rather focus on changes within particular metrics related
mostly to walking mobility. Thus, for a simple paradigm shift
in future exoskeleton research for the SCI population, studies
should broaden their scope, including metrics across multiple
J. Neural Eng. 13 (2016) 031001
physiological systems as well as improvements in areas
related to QOL and usability.
5.3. Perception of benefits of using exoskeletons by individuals
with SCI
Although SCI patients generally consider it very important to
walk again, it is unclear if the mobility benefits of powered
exoskeletons (i.e., ability to stand up and walk) align well with
the desired outcomes or expectations of the diverse SCI
population (Benson et al 2015). In one study, 437 SCI survi-
vors were asked to rate their difficulty in dealing with 10
consequences of SCI, on a scale ranging from 0 (not hard at all)
to 10 (extremely hard). The highest rated five consequences
were decreased ability to walk or move, decreased control of
bowel, decreased control of bladder, decreased sexual function,
and pain (means ranged from 8.2 to 6.2); moreover, high rat-
ings of feeling sad were associated with high ratings of most
other consequences (Widerstrom-Noga et al 1999). A poll
(N=681; 51% quadriplegic and 49% paraplegic; 25% female,
65% male) by Anderson in 2004 assessed the priorities in
physical recovery after SCI directly from the patient population
(Anderson 2004). The study concluded that sexual function,
bladder and bowel function, walking movements, and trunk
stability are priorities in the recovery process of SCI patients,
but that the ranking of these priorities depended on whether the
patient had paraplegia or tetraplegia. In particular, walking
movements were prioritized by 15.9% of individuals with
paraplegia compared to 7.8% of individuals with tetraplegia.
Therefore, in addition to mobility, future studies should include
metrics that evaluate the devices in a manner that directly
complies with the desired outcomes of the SCI population. For
example, none of the studies measured changes in sexual
function, which is one of the most desired improvements of the
SCI population (Anderson 2004).
Individuals with SCI often face challenges with social
interactions, which may be overcome by use of an over-
ground exoskeleton that allows legged locomotion, facilitates
social interaction at eye level, and basic sitting and standing.
In a survey of wheelchair users and healthcare professionals
(Anderson 2004), 75% of the participants reported increased
social interaction as a rationale for using an exoskeleton. The
ability to carry out normal social interactions may provide
enormous psychological benefit to individuals who may
otherwise be limited in social environments. This possibility
is however rarely assessed in current studies of exoskeletons.
Although use of exoskeletons is focused on ambulation
and lower limb motor improvement, there may be secondary
benefits across multiple physiological systems, such as
improved bowel/bladder function, decreased chronic pain,
reduced spasticity, and increased bone marrow density
(BMD). Some of the clinical trials in this review (Zeilig
et al 2012) found that users of the device reported an
improvement in bladder and bowel function after training
with the ReWalk, although none of these studies provide
conclusive evidence. Additionally, it is believed that using
these devices can lead to a reduction in chronic pain and
spasticity (Esquenazi et al 2012, Zeilig et al 2012), but this
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Topical Review
needs to be confirmed. Decreased BMD is a common
symptom in SCI patients (Dolbow et al 2011) and degrada-
tion becomes rapidly evident within the first year of sustain-
ing the injury (Coupaud et al 2015). Dolbow and colleagues
report that passive loading of the lower limbs alone (such as
during standing) does not result in increased BMD and thus
additional methods of stimulation may be required to induce
bone growth (Dolbow et al 2011). Stressing the bone through
muscle contractions, such as natural muscle contractions
induced through walking or artificial contractions by FES,
shows potential for increasing BMD in non-weight bearing
individuals (Dolbow et al 2011, Bryce et al 2015). The use of
an over-ground powered exoskeleton does not specifically
activate muscle contractions in users (although residual EMG
can be detected in some SCI patients during exoskeleton use);
however, it is possible that active stimulation through
ambulation in an exoskeleton can result in increased BMD, or
at least attenuate any further loss after extended use. Thus,
hybrid exoskeletons (e.g. Kinesis and WalkTrainer) that
combine mobility with FES may provide these benefits.
Moreover, future powered exoskeletons could be explicitly
designed to target benefits across multiple physiological
systems, which may lead to wide spread adoption of this
technology by patients, physicians and insurance providers.
5.4. Medical device regulation of powered exoskeletons
Careful consideration of outcome measures is not only
important to evaluate the impact of exoskeleton intervention
on patients, but also required for obtaining marketing clear-
ance from appropriate regulatory authorities. In United States,
powered exoskeletons are classified as Class II devices and
require premarket notification 510(k) clearance from the FDA
before they can be marketed (Food and Drug Administration,
HHS 2015). Currently, ReWalk is the only over-ground
walking exoskeleton to receive FDA approval (http://
accessdata.fda.gov/cdrh_docs/reviews/den130034.pdf) for
home use for people with paraplegia due to SCI at levels T7-
L5 when accompanied by a specially trained caregiver. In
addition, it can also be used in rehabilitation institutions for
ambulation of SCI patients with T4-T6 injury. However, the
device is not approved for sporting activities or climbing
stairs. Additionally, patients and their caregivers are required
to undergo extensive training developed by the manufacturer
to learn and demonstrate proper use of the device. The new
FDA regulation implies that it will regulate all powered
exoskeletons as Class II (moderate to high risk) devices,
meaning that they are subject to general and special controls
prior to FDA approval, rather than Class I (low to moderate
risk) devices that are subject only to general controls.
The approval of ReWalk by the FDA can be considered
pivotal in many ways. First, it can increase the acceptance of
and confidence in powered exoskeletons among the health
care industry as well as users. Second, it will simplify to a
certain extent the path to commercializing exoskeletons, since
any new device, which can demonstrate to be ‘substantially
equivalent’ to ReWalk, can be readily approved by the FDA.
According to a recent press release (http://ir.eksobionics.
J. Neural Eng. 13 (2016) 031001
com/press-releases/detail/444/ekso-bionics-to-submit-
510k-notification-in-december), Ekso Bionics submitted a
510(k) application to the FDA in December 2014 and the
company has been allowed to continue to market the device
while the 510(k) submission is under review. Quite recently
(8 March 2016), the FDA also released 510(k) premarket
notification for the Indego exoskeleton, thus allowing Parker
Hannifin Corporation to market the device, subject to the
general controls provisions of the Federal Food, Drug, and
Cosmetic Act. Nonetheless, all exoskeletons reviewed here
(except ReWalk) have yet to demonstrate their safety and
efficacy and satisfy special controls as required by the FDA.
As clinical trials are completed and longer interventions are
performed, probable benefits and probable risks will be con-
firmed or disconfirmed.
5.5. Outlook
It is becoming clearer that worldwide markets are likely to
achieve significant growth as powered exoskeletons are used
inside rehabilitation centers and are deployed in homes and
outdoors. According to a recent market study by WinterGreen
Research, the rehabilitation robot market size is expected to
reach $1.1 billion by 2021, with the specialized exoskeleton
market to be considered as separate and additive to this market
(WinterGreen 2015). Although an increasing number of com-
panies are conducting clinical trials to obtain regulatory approval
in the US, Europe and Asia, there is no clear dominance of the
exoskeleton market. The most advanced systems that are cur-
rently being marketed are still emerging as commercial devices,
and specialized market applications are still being evaluated.
It is generally agreed that locomotor training using robot-
assisted therapies depends on patient engagement (Venka-
takrishnan et al 2014), reward (Goodman et al 2014) and the
desire of the patient to conquer the disability. Thus, wearable
robots that engage the patient with gait intent detection can
help motivate the patient, provide short-term reward via
immediate feedback of movement, and empower the patient
with direct control of his/her own health and QOL (Krebs
et al 2003, Blank et al 2014). Towards this extent, gait
intention detection systems for exoskeleton control, such as
by monitoring shifts in the center of mass (e.g. tilting the
trunk) (Zeilig et al 2012), may improve the efficacy of
rehabilitation by encouraging the user to actively participate
rather than relying solely on the assistance provided by the
exoskeleton. Other gait intent detection systems based on eye
gaze (Duvinage et al 2011) and hand movements (Hasegawa
et al 2009), have also been developed. More recently,
development of peripheral or brain neural interfaces for
automated gait intent detection and closed-loop control
involving both of these systems (Suzuki et al 2007, Fitz-
simmons et al 2009, Wieser et al 2010, Presacco
et al 2011, 2012, Wagner et al 2012, Kilicarslan et al 2013,
Bulea et al 2014, He et al 2014, Kwak et al 2015), are also
being explored. These emergent human–robot interfaces may
be critical in augmenting the range of users of such devices,
including subjects with tetraplegia.
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In addition, it is critical that new exoskeleton designs
scrutinize the metabolic and biomechanical cost of human
walking assisted by powered exoskeletons. Extended use of
these systems can lead to overuse injuries of the upper-body,
and physical and mental fatigue. These aspects were however,
rarely assessed in the studies reviewed here. Two recent
studies have shown in able body subjects that exoskeleton
designs can significantly reduce the metabolic cost of walking
(∼8%) relative to not wearing an exoskeleton (Mooney
et al 2014); even in the case of passive exoskeletons (Collins
et al 2015). Secondary outcome measures should also be
considered in future exoskeleton design. Although different
assessments were conducted to evaluate the impact of exos-
keleton intervention on patients’ pain, fatigue, and comfort
levels before and after the robot intervention, the systems
themselves reviewed here did not have sensors integrated into
the system that could directly monitor these dynamics in real
time. Recently, (Tamez-Duque et al 2015) presented a system
to monitor the pressure exerted on the user by the leg straps of
the exoskeleton. This is important as recent studies have
reported grade I/II skin aberrations in five out of ten enrolled
subjects (Benson et al 2015), and bruising and grade-1 skin
redness in two patients during exoskeleton use (Hartigan
et al 2015). Additionally, usability metrics such as the train-
ing period, i.e. time required by patients to learn to use a
powered exoskeleton, can help in the design of future inter-
ventions (Bryce et al 2015). For example, in (Kozlowski
et al 2015), the authors quantified the training period in terms
of number of sessions required to use the exoskeleton to stand
up, walk for at least 30 min, and sit down with little or no
assistance. The authors concluded that up to eight (median,
95% CI=5.4–10.6) sessions were required by six partici-
pants with cervical and thoracic level injuries to learn to use
the exoskeleton with minimal assistance, which may be cor-
related with age and time since injury (Kozlowski et al 2015).
Safety considerations are yet another important aspect in
the design of powered exoskeletons. Risks of falling, tripping
and slipping not only endanger the safety of patients using the
exoskeleton but also have social, emotional, and psycholo-
gical consequences (Tucker et al 2015). These incidents can
arise due to internal factors (e.g. controller failure) or external
factors (e.g. uneven terrain, moving objects or persons).
Current approaches to prevent such risks include mechanical
stops/limit switches (e.g. Kinesis) or use of walkers and
crutches (e.g. Bionic Leg, Ekso, ReWalk, HAL, Indego,
WPAL). WalkTrainer uses an active body-weight support. In
the reviewed studies, except for a single report of near-serious
adverse event (Benson et al 2015), none of the studies
reported any adverse events as a result of falling or slipping.
This suggests that the current approaches to prevent falls
during training with current devices may be effective and
should be continued in future studies. Furthermore, five stu-
dies (IDs: 1, 2, 11, 18, 19) reported in this review were
conducted with subjects with cervical lesions, out of which
four where clinical studies (IDs: 1, 2, 18, 19). This suggests
that it is feasible to include cervical level subjects and despite
their injury they may retain the ability to use crutches and
other body support systems. Moreover, subjects completely
J. Neural Eng. 13 (2016) 031001
lacking this ability could benefit from self-balancing exos-
keletons such as Rehab REX (from Rex Bionics; see http://
rexbionics.com/) and advanced human–machine interface
systems for detecting gait intention as discussed above.
Overall, a user-centered design of powered exoskeletons is
needed, which involves the development of innovative science
and technologies that minimize the mismatch between the
sensorimotor capabilities of the user and the exoskeleton,
leading to their intuitive integration and confluent interaction.
To gain adoption by end users, exoskeletons should be effec-
tive, reliable, safe and engaging and support the user in per-
forming intended actions with minimal effort and errors with
adequate interaction time (Contreras-Vidal et al 2015).
Although significant advances in the design of powered exos-
keletons have been achieved in the last decade, current systems
have not yet reached the level of performance required to
function in complex dynamic environments, usually require
extensive training and/or a trained staff to set-up or operate,
put insufficient emphasis on understanding long-term system-
level plasticity, and do not readily adapt to changing effects of
the patient’s neurological status, biomechanical condition,
attention, and fatigue. Moreover, the long-term reliability of
powered exoskeleton is currently unknown, and the lack of
standard metrics to quantify their effectiveness and reliability
impede fast translation to the end-user.
6. Conclusions
This systematic review focused on published literature of
powered exoskeletons for bipedal locomotion in individuals
with spinal cord injury. A total of twenty two studies with eight
powered exoskeleton systems met the inclusion criteria for
review. As depicted in table 1, many of these systems are rather
similar in design, focusing on lightweight frames with actively
powered hip and/or knee joints. Seven of the eight of the
exoskeletons reviewed in this study, are bilateral systems with
active actuators at the hip and knee joints in the sagittal plane
(except for Kinesis, which does not actuate the hip), whereas
Bionic Leg is a unilateral RKO. The current technology for
over-ground exoskeletons is relatively new and specific benefits
of long-term use of exoskeleton in gait training still remains to
be elusive. Several of the studies reviewed here are still in
feasibility and development stages. For a more holistic
assessment on how exoskeletons can be applied alone or
together with conventional rehabilitation therapies for effective
recovery, outcome measures for future studies should expand
their assessment metrics to account for more physiological and
usability measures as well as maintain consistency by using
standardized metrics for assessing safety, benefits, and usabil-
ity. Studies should also develop criteria for optimal selection
and training of patients most likely to benefit from a particular
device and make use of the array of sensors embedded in
exoskeletons to develop real-time monitoring and diagnostic
capabilities that can inform the physician while allowing
adjustment of the device according to the needs of the user.
14
Topical Review
Acknowledgments
This work was supported in part by NINDS Awards
R01NS075889, Mission Connect—TIRR Foundation.
References
Aach M, Cruciger O, Sczesny-Kaiser M, Höffken O, Meindl R C,
Tegenthoff M, Schwenkreis P, Sankai Y and Schildhauer T A
2014 Voluntary driven exoskeleton as a new tool for
rehabilitation in chronic spinal cord injury: a pilot study Spine
J. 14 2847–53
Anderson K D 2004 Targeting recovery: priorities of the spinal cord-
injured population J. Neurotrauma 21 1371–83
Andrews A W, Chinworth S A, Bourassa M, Garvin M,
Benton D and Tanner S 2010 Update on distance and velocity
requirements for community ambulation J. Geriatr. Phys.
Ther. 33 128–34
Asselin P, Knezevic S, Kornfeld S, Cirnigliaro C,
Agranova-Breyter I, Bauman W A and Spungen A M 2015
Heart rate and oxygen demand of powered exoskeleton-
assisted walking in persons with paraplegia J. Rehabil. Res.
Dev. 52 147–58
Behrman A L and Harkema S J 2000 Locomotor training after
human spinal cord injury: a series of case studies Phys. Ther.
80 688–700
Benson I, Hart K, Tussler D and Van Middendorp J J 2015 Lower-
limb exoskeletons for individuals with chronic spinal cord
injury: findings from a feasibility study Clin. Rehabil. 30
73–84
Bishop L, Stein J and Wong C K 2012 Robot-aided gait training in
an individual with chronic spinal cord injury: a case study
J. Neurol. Phys. Ther. 36 138–43
Blank A A, French J A, Pehlivan A U and O’Malley M K 2014
current trends in robot-assisted upper-limb stroke
rehabilitation: promoting patient engagement in therapy Curr.
Phys. Med. Rehabil. Rep. 2 184–95
Boeker M, Vach W and Motschall E 2013 Google Scholar as
replacement for systematic literature searches: good relative
recall and precision are not enough BMC Med. Res. Methodol.
13 131
Bogue R 2009 Exoskeletons and robotic prosthetics: a review of
recent developments Ind. Robot: Int. J. 36 421–7
Bryce T N, Dijkers M P and Kozlowski A J 2015 Framework for
assessment of the usability of lower-extremity robotic
exoskeletal orthoses Am. J. Phys. Med. Rehabil. 94 1
Bulea T C, Prasad S, Kilicarslan A and Contreras-Vidal J L 2014
Sitting and standing intention can be decoded from scalp EEG
recorded prior to movement execution Front. Neurosci. 8 376
Calhoun C L, Schottler J and Vogel L C 2013 Recommendations for
mobility in children with spinal cord injury Top. Spinal Cord
Injury Rehabil. 19 142–51
Collins S H, Wiggin M B and Sawicki G S 2015 Reducing the
energy cost of human walking using an unpowered
exoskeleton Nature 522 212–5
Contreras-Vidal J L, Kilicarslan A, Huang H and Grossman R G
2015 Human-centered design of wearable neuroprostheses and
exoskeletons AI Mag. 36 12–22
Coupaud S, Mclean A N, Purcell M, Fraser M H and Allan D B
2015 Decreases in bone mineral density at cortical and
trabecular sites in the tibia and femur during the first year of
spinal cord injury Bone 74 69–75
Cruciger O, Schildhauer T A, Meindl R C, Tegenthoff M,
Schwenkreis P, Citak M and Aach M 2014 Impact of
locomotion training with a neurologic controlled hybrid
J. Neural Eng. 13 (2016) 031001
assistive limb (HAL) exoskeleton on neuropathic pain and
health related quality of life (HRQoL) in chronic SCI: a case
study Disability Rehabil.: Assist. Technol. 1–6
del-Ama A J, Gil-Agudo Á, Bravo-Esteban E, Pérez-Nombela S,
Pons J L and Moreno J C 2015 Hybrid therapy of walking with
Kinesis overground robot for persons with incomplete spinal
cord injury: a feasibility study Robot. Auton. Syst. 73 44–58
del-Ama A J, Gil-Agudo Á, Pons J L and Moreno J C 2014 Hybrid
gait training with an overground robot for people with
incomplete spinal cord injury: a pilot study Front.Hum.
Neurosci. 8 298
del-Ama A J, Moreno J C, Gil-Agudo A, de-Los-Reyes A and
Pons J L 2012 Online assessment of human–robot interaction
for hybrid control of walking Sensors 12 215–25
Ditunno P L, Patrick M, Stineman M and Ditunno J F 2008 Who
wants to walk? Preferences for recovery after SCI: a
longitudinal and cross-sectional study Spinal Cord: Official J.
Int. Med. Soc. Paraplegia 46 500–6
Dolbow D, Gorgey A, Daniels J, Adler R, Moore J and Gater J D R
2011 The effects of spinal cord injury and exercise on bone
mass: a literature review NeuroRehabilitation 29 261–9
Dollar A M and Herr H 2008 Lower extremity exoskeletons and
active orthoses: challenges and state-of-the-art IEEE Trans.
Robot. 24 144–58
Duvinage M, Castermans T and Dutoit T 2011 Control of a lower
limb active prosthesis with eye movement sequences 2011
IEEE Symp. on Computational Intelligence, Cognitive
Algorithms, Mind, and Brain (CCMB) (11–15 April 2011)
pp 1–7
Esquenazi A, Talaty M, Packel A and Saulino M 2012 The ReWalk
powered exoskeleton to restore ambulatory function to
individuals with thoracic-level motor-complete spinal cord
injury Am. J. Phys. Med. Rehabil. 91 911–21
Evans N, Hartigan C, Kandilakis C, Pharo E and Clesson I 2015
Acute cardiorespiratory and metabolic responses during
exoskeleton-assisted walking overground among persons with
chronic spinal cord injury Top. Spinal Cord Injury Rehabil. 21
122–32
Farris R J, Quintero H A, Murray S A, Ha K H, Hartigan C and
Goldfarb M 2014 A preliminary assessment of legged mobility
provided by a lower limb exoskeleton for persons with
paraplegia IEEE Trans. Neural. Syst. Rehabil. Eng. 22 482–90
Federici S, Meloni F, Bracalenti M and de Filippis M L 2015 The
effectiveness of powered, active lower limb exoskeletons in
neurorehabilitation: a systematic review NeuroRehabilitation
37 321–40
Ferris D P, Sawicki G S and Daley M A 2007 A physiologist’s
perspective on robotic exoskeletons for human locomotion Int.
J. HR 4 507–28
Fineberg D B, Asselin P, Harel N Y, Agranova-Breyter I,
Kornfeld S D, Bauman W A and Spungen A M 2013 Vertical
ground reaction force-based analysis of powered exoskeleton-
assisted walking in persons with motor-complete paraplegia
J. Spinal Cord Med. 36 313–21
Fitzsimmons N A, Lebedev M A, Peikon I D and Nicolelis M A
2009 Extracting kinematic parameters for monkey bipedal
walking from cortical neuronal ensemble activity Front. Integr.
Neurosci. 3 3
Fleerkotte B M, Koopman B, Buurke J H, van Asseldonk E H,
van der Kooij H and Rietman J S 2014 The effect of
impedance-controlled robotic gait training on walking ability
and quality in individuals with chronic incomplete spinal cord
injury: an explorative study J. Neuroeng. Rehabil. 11 26
Food and Drug Administration, HHS 2015 Medical devices;
physical medicine devices; classification of the powered lower
extremity exoskeleton; republication final order; republication
Fed. Regist. 80 25226–30
Goodman R N, Rietschel J C, Roy A, Jung B C, Diaz J,
Macko R F and Forrester L W 2014 Increased reward in ankle
15
Topical Review
robotics training enhances motor control and cortical efficiency
in stroke J. Rehabil. Res. Dev. 51 213–27
Hammell K R 2010 Spinal cord injury rehabilitation research: patient
priorities, current deficiencies and potential directions Disabil.
Rehabil. 32 1209–18
Hartigan C, Kandilakis C, Dalley S, Clausen M, Wilson E,
Morrison S, Etheridge S and Farris R 2015 Mobility outcomes
following five training sessions with a powered exoskeleton
Top. Spinal Cord Inj. Rehabil. 21 93–9
Hasegawa Y, Junho J and Sankai Y 2009 Cooperative walk control
of paraplegia patient and assistive system 2009 IEEE/RSJ Int.
Conf. on Intelligent Robots and Systems, 2009 IROS (10–15
October 2009) pp 4481–6
He Y, Nathan K, Venkatakrishnan A, Rovekamp R, Beck C,
Ozdemir R, Francisco G E and Contreras-Vidal J L 2014 An
integrated neuro-robotic interface for stroke rehabilitation using
the NASA X1 powered lower limb exoskeleton Conf. Proc. IEEE
Engineering Medicine and Biology Society pp 3985–8
Herr H 2009 Exoskeletons and orthoses: classification, design
challenges and future directions J. Neuroeng. Rehabil. 6 21
Hesse S 2001 Locomotor therapy in neurorehabilitation
NeuroRehabilitation 16 133–9
Hidler J and Sainburg R 2011 Role of robotics in neurorehabilitation
Top. Spinal Cord Injury Rehabil. 17 42–9
Hubli M and Dietz V 2013 The physiological basis of
neurorehabilitation—locomotor training after spinal cord
injury J. NeuroEngineering Rehabil. 10 1–8
Jimenez-Fabian R and Verlinden O 2012 Review of control
algorithms for robotic ankle systems in lower-limb orthoses,
prostheses, and exoskeletons Med. Eng. Phys. 34 397–408
Kilicarslan A, Prasad S, Grossman R G and Contreras-Vidal J L
2013 High accuracy decoding of user intentions using EEG to
control a lower-body exoskeleton Conf. Proc. IEEE
Engineering Medicine and Biology Society pp 5606–9
Kolakowsky-Hayner S A, Crew J, Moran S and Shah A 2013 Safety
and feasibility of using the Ekso™ bionic exoskeleton to aid
ambulation after spinal cord injury J. Spine S4 003
Kozlowski A, Bryce T and Dijkers M 2015 Time and effort required
by persons with spinal cord injury to learn to use a powered
exoskeleton for assisted walking Top. Spinal Cord Injury
Rehabil. 21 110–21
Krebs H I, Palazzolo J J, Dipietro L, Ferraro M, Krol J,
Rannekleiv K, Volpe B T and Hogan N 2003 Rehabilitation
robotics: performance-based progressive robot-assisted therapy
Auton. Robots 15 7–20
Kressler J, Thomas C K, Field-Fote E C, Sanchez J,
Widerström-Noga E, Cilien D C, Gant K, Ginnety K,
Gonzalez H and Martinez A 2014 Understanding therapeutic
benefits of overground bionic ambulation: exploratory case
series in persons with chronic, complete spinal cord injury
Arch. Phys. Med. Rehabil. 95 1878–87
Kubota S, Nakata Y, Eguchi K, Kawamoto H, Kamibayashi K,
Sakane M, Sankai Y and Ochiai N 2013 Feasibility of
rehabilitation training with a newly developed wearable robot
for patients with limited mobility Arch. Phys. Med. Rehabil. 94
1080–7
Kwak N S, Muller K R and Lee S W 2015 A lower limb exoskeleton
control system based on steady state visual evoked potentials
J. Neural. Eng. 12 056009
Lajeunesse V, Vincent C, Routhier F, Careau E and Michaud F 2015
Exoskeletons’ design and usefulness evidence according to a
systematic review of lower limb exoskeletons used for
functional mobility by people with spinal cord injury Disabil.
Rehabil. Assist. Technol. 1–13
Lam T, Noonan V K and Eng J J 2011 A systematic review of
functional ambulation outcome measures in spinal cord injury
Spinal Cord 46 246–54
Louie D R, Eng J J and Lam T 2015 Gait speed using powered
robotic exoskeletons after spinal cord injury: a systematic
J. Neural Eng. 13 (2016) 031001
review and correlational study J. NeuroEngineering Rehabil.
12 1–10
Mehrholz J and Pohl M 2012 Electromechanical-assisted gait
training after stroke: a systematic review comparing end-
effector and exoskeleton devices J. Rehabil. Med. 44 193–9
Mooney L M, Rouse E J and Herr H M 2014 Autonomous
exoskeleton reduces metabolic cost of human walking during
load carriage J. NeuroEngineering Rehabil. 11 1–11
NSCISC 2015 National Spinal Cord Injury Statistical Center 2015
Facts and Figures at a Glance (Birmingham, AL: University
of Alabama at Birmingham) Retrieved on 31 July 2015
(https://nscisc.uab.edu/PublicDocuments/fact_figures_docs/
Facts%202015.pdf)
Parent S, Mac-Thiong J M, Roy-Beaudry M, Sosa J F and Labelle H
2011 Spinal cord injury in the pediatric population: a
systematic review of the literature J. Neurotrauma 28 1515–24
Pons J L 2008 Wearable Robots: Biomechatronic Exoskeletons
(Hoboken, NJ: Wiley)
Presacco A, Forrester L W and Contreras-Vidal J L 2012 Decoding
intra-limb and inter-limb kinematics during treadmill walking
from scalp electroencephalographic (EEG) signals IEEE Trans.
Neural Syst. Rehabil. Eng. 20 212–9
Presacco A, Goodman R, Forrester L and Contreras-Vidal J L 2011
Neural decoding of treadmill walking from noninvasive
electroencephalographic signals J. Neurophysiol. 106 1875–87
Quintero H, Farris R, Hartigan C, Clesson I and Goldfarb M 2011 A
powered lower limb orthosis for providing legged mobility in
paraplegic individuals Top. Spinal Cord Injury Rehabil. 17 25–33
Sankai Y 2011 HAL: hybrid assistive limb based on cybernics
Robotics Research ed M Kaneko and Y Nakamura (Berlin:
Springer)
Schwartz I, Sajina A, Neeb M, Fisher I, Katz-Luerer M and
Meiner Z 2011 Locomotor training using a robotic device in
patients with subacute spinal cord injury Spinal Cord 49
1062–7
Stauffer Y, Allemand Y, Bouri M, Fournier J, Clavel R, Metrailler P,
Brodard R and Reynard F 2009 The walktrainer-a new
generation of walking reeducation device combining orthoses
and muscle stimulation IEEE Trans. Neural Syst. Rehabil. Eng.
17 38–45
Strausser K A and Kazerooni H 2011 The development and testing
of a human machine interface for a mobile medical
exoskeleton 2011 IEEE/RSJ Int. Conf. on Intelligent Robots
and Systems (IROS) (Piscataway, NJ: IEEE)
Suzuki T, Sonoda S, Saitoh E, Onogi K, Fujino H, Teranishi T,
Oyobe T, Katoh M and Ohtsuka K 2007 Prediction of gait
outcome with the knee-ankle-foot orthosis with medial hip
joint in patients with spinal cord injuries: a study using
recursive partitioning analysis Spinal Cord 45 57–63
Tamez-Duque J, Cobian-Ugalde R, Kilicarslan A,
Venkatakrishnan A, Soto R and Contreras-Vidal J L 2015
Real-time strap pressure sensor system for powered
exoskeletons Sensors 15 4550–63
16
Topical Review
Tanabe S, Hirano S and Saitoh E 2013a Wearable power-assist
locomotor (WPAL) for supporting upright walking in persons
with paraplegia NeuroRehabilitation 33 99–106
Tanabe S, Saitoh E, Hirano S, Katoh M, Takemitsu T, Uno A,
Shimizu Y, Muraoka Y and Suzuki T 2013b Design of the
wearable power-assist locomotor (WPAL) for paraplegic gait
reconstruction Disability Rehabil. Assistive Technol. 8 84–91
Tsukahara A, Hasegawa Y, Eguchi K and Sankai Y 2015
Restoration of gait for spinal cord injury patients using HAL
with intention estimator for preferable swing speed IEEE
Trans. Neural Syst. Rehabil. Eng. 23 308–18
Tucker M R, Olivier J, Pagel A, Bleuler H, Bouri M, Lambercy O,
Millán J D R, Riener R, Vallery H and Gassert R 2015 Control
strategies for active lower extremity prosthetics and orthotics: a
review J. Neuroeng. Rehabil. 12 1
Venkatakrishnan A, Francisco G E and Contreras-Vidal J L 2014
Applications of brain-machine interface systems in stroke
recovery and rehabilitation Curr. Phys. Med. Rehabil. Rep. 2
93–105
Wagner J, Solis-Escalante T, Grieshofer P, Neuper C,
Muller-Putz G and Scherer R 2012 Level of participation in
robotic-assisted treadmill walking modulates midline
sensorimotor EEG rhythms in able-bodied subjects
Neuroimage 63 1203–11
Widerstrom-Noga E G, Felipe-Cuervo E, Broton J G,
Duncan R C and Yezierski R P 1999 Perceived difficulty in
dealing with consequences of spinal cord injury Arch. Phys.
Med. Rehabil. 80 580–6
Wieser M, Haefeli J, Butler L, Jancke L, Riener R and Koeneke S
2010 Temporal and spatial patterns of cortical activation
during assisted lower limb movement Exp. Brain. Res. 203
181–91
WinterGreen 2015 Rehabilitation Robots: Market Shares, Strategy,
and Forecasts, Worldwide 2015 to 2021
Wirz M, Zemon D H, Rupp R, Scheel A, Colombo G, Dietz V and
Hornby T G 2005 Effectiveness of automated locomotor
training in patients with chronic incomplete spinal cord injury:
a multicenter trial Arch. Phys. Med. Rehabil. 86 672–80
Yang A, Asselin P, Knezevic S, Kornfeld S and Spungen A 2015
Assessment of in-hospital walking velocity and level of
assistance in a powered exoskeleton in persons with spinal
cord injury Top. Spinal Cord Inj. Rehabil. 21 100–9
Yang C-J, Zhang J-F, Chen Y, Dong Y-M and Zhang Y 2008 A
review of exoskeleton-type systems and their key technologies
Proc. Inst. Mech. Eng. C 222 1599–612
Yang J F and Musselman K E 2012 Training to achieve over ground
walking after spinal cord injury: a review of who, what, when,
and how J. Spinal Cord Med. 35 293–304
Zeilig G, Weingarden H, Zwecker M, Dudkiewicz I, Bloch A and
Esquenazi A 2012 Safety and tolerance of the ReWalk
exoskeleton suit for ambulation by people with complete
spinal cord injury: a pilot study J. Spinal Cord Med. 35
96–101