Clinical relevance of gait research applied to clinical trials in spinal cord injury

Brain Research Bulletin 78 (2009) 35–42

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Review

Clinical relevance of gait research applied to clinical trials in spinal cord injury John Ditunno a,∗ , Giorgio Scivoletto b a Jefferson Medical College, Regional Spinal Cord Injury Center of the Delaware Valley, Thomas Jefferson University, Regional Spinal Cord Injury Center of the Delaware Valley, 132 South 10th Street, Suite 375, Main Building, Philadelphia, PA 19107, United States b Spinal Cord Unit, IRCCS Fondazione Santa Lucia, Rome, Italy

a r t i c l e

i n f o

Article history: Received 29 November 2007 Received in revised form 10 August 2008 Accepted 11 September 2008 Available online 9 October 2008 Keywords: Spinal cord injury Gait Functional electrical stimulation Evaluation

a b s t r a c t The restoration of walking function following SCI is extremely important to consumers and has stimulated a response of new treatments by scientists, the pharmaceutical industry and clinical entrepreneurs. Several of the proposed interventions: (1) the use of functional electrical stimulation (FES) and (2) locomotor training have been examined in clinical trials and recent reviews of the scientific literature. Each of these interventions is based on research of human locomotion. Therefore, the systematic study of walking function and gait in normal individuals and those with injury to the spinal cord has contributed to the identification of the impairments of walking, the development of new treatments and how they will be measured to determine effectiveness. In this context gait research applied to interventions to improve walking function is of high clinical relevance. This research helps identify walking impairments to be corrected and measures of walking function to be utilized as endpoints for clinical trials. The most common impairments following SCI diagnosed by observational gait analysis include inadequate hip extension during stance, persistent plantar flexion and hip/knee flexion during swing and foot placement at heel strike. FES has been employed as one strategy for correcting these impairments based on analysis that range from simple measures of speed, cadence and stride length to more sophisticated systems of threedimensional video motion analysis and multichannel EMG tracings of integrated walking. A recent review of the entire FES literature identified 36 studies that merit comment and the full range of outcome measures for walking function were used from simple velocity to the video analysis of motion. In addition to measures of walking function developed for FES interventions, the first randomized multicenter clinical trial on locomotor training in subacute SCI was recently published with an extensive review of these measures. In this study outcome measures of motor strength (impairment), balance, Walking Index for SCI (WISCI), speed, 5 min walk (walking capacities) and locomotor functional independence measure (L-FIM), a disability measure all showed improvement in walking function based on the strategy of the response of activity based plasticity to step training. Although the scientific basis for this intervention will be covered in other articles in this series, the evolution of clinical outcome measures of walking function continues to be important for the determination of effectiveness in clinical trials. © 2008 Elsevier Inc. All rights reserved.

Contents 1. 2.

3. 4. 5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gait analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Observational gait analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Motion analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Functional electrical stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Locomotor clinical trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author. Tel.: +1 215 955 6579; fax: +1 215 955 5152. E-mail address: [email protected] (J. Ditunno). 0361-9230/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2008.09.003

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1. Introduction The restoration of walking function following severe paralysis due to spinal cord injury (SCI) is of major importance to clinicians and consumers [17–19,47,65]. In a study of subjects [19] with SCI, which employed a constrained consensus building process, nine consumer panels and three rehabilitation professionals panels, ranked walking as a high priority, irrespective of the severity of the spinal cord injury, the time of injury or age at the time of injury. All consumer panels and two of three professional staff panels ranked walking high, except for the inpatient rehabilitation professionals in the USA, who placed wheelchair as their preference due to early discharge that precluded inpatient training. Survey by questionnaire [2] and focus groups [39] also rank recovery of walking function as important to quality of life issues. This mandate by consumers has resulted in a response by the scientific community, drug industry and clinical entrepreneurs. So called scientific “miracles” of new treatments for regeneration of the spinal cord often appear in the lay press, which feed the optimism of those seeking the “cure”. New interventions, however, are emerging, which may offer the potential to restore neurological function and walking capacity [59]. In an effort to educate the lay public as to the current state of evidence based on animal research, clinical trials and validated/approved treatments 29 different treatments are reviewed in late stage preclinical or early clinical trials. The majority of studies deal with neuroprotection and repair/regeneration (19/29), while only several deal with approaches to rehabilitation interventions. The first rehabilitation intervention employs Functional electrical stimulation (FES) based on a strategy that corrects impairments identified by observational gait analysis and the second rehabilitation intervention is locomotor retraining based on a strategy of the use of step training to stimulate activity dependent plasticity. Both interventions require an understanding of the fundamental components of human locomotion in normal and pathological states, and how they can be modified by training and/or restoration of upright mobility. Several authors have advocated quantitative gait analysis as a clinical laboratory tool, while others have recommended observational gait analysis as an important component of outcome measures in clinical trials. Patrick [51] has suggested that gait analysis laboratories should be utilized as part of the standard assessment of walking to supplement routine clinical examination/judgment and functional capacity measures of walking, while Field-Fote et al. [26] have recommended that observational gait analysis is an essential domain in order to assess walking function in subjects with incomplete SCI. It appears, therefore, that systematic analysis of gait and walking function is necessary to develop measures, which may be utilized to determine the effectiveness of interventions [14]. Although the gait impairments identified by observational gait analysis and more sophisticated methods of motion analysis require continued study, we shall review the current approaches which provide the basis for FES strategies. FES and the use of neuroprostheses [46] to reduce these impairment of gait [65] and restore walking provide an important example of the relevance of gait analysis as a tool to assess the effectiveness of interventions. A recent review [49] of the literature revealed 36 articles worthy of comment. Most of the reports claim that the speed of walking and other components of gait may be improved by the synchronous electrical stimulation of muscles weakened by damage to the spinal cord. Although, the use of neuroprosthesis have not been incorporated routinely into clinical practice [62], we will examine the results of these studies to date. Finally, we shall examine the current outcome measures used in a large clinical trial of locomotor training to determine the effectiveness of improved walking function. Much of the scientific basis for

this clinical intervention had been developed over years of study of animal and human locomotion. The investigation of walking function in animals and humans [3–6,11,20,22,24,25,32,33,35,56,57], since the early 1990s has resulted in the stimulation of clinical investigation such as body weight support training trials. Since the scientific rationale will be covered in other articles in this series, we will focus on the clinical trial. Recently, a study of locomotor training for individuals with incomplete SCI has shown improved walking function as determined by increases in lower extremity strength and balance, increased walking speed and less need for physical assistance, walking aids and braces [16,22]. Although the superiority of body weight supported training over more conventional training with the same intensity and duration was not demonstrated, the importance of the intensity of locomotor training for subacute subjects with incomplete spinal cord has been demonstrated [22,23]. This study was important, in addition, because of the demonstration of the high correlation of impairment, walking function and disability measures for the first time in a randomized clinical trial. The need to develop valid and practical outcome measures for future large clinical trials is recognized.

2. Gait analysis 2.1. Observational gait analysis The physiologic assessment of walking for individuals with SCI has been of interest to clinicians and clinical investigators for over 50 years [31]. The characteristics of the abnormal gait was described in detail by Perry [52] in 1984 with the Rancho Los Amigos method of dividing gait into its component parts of stance and swing phase [34] (see Fig. 1). In a group of 14 chronic subjects with incomplete SCI, she [53] identified hip flexors limitation during swing phase due to weakness of the iliacus, rectus femoris and sartorius muscles. In addition, knee flexion was limited during swing phase due to antagonistic action of the rectus femoris and vastus lateralis. Such analysis offered practical strategies for muscle strengthening or other adaptations by treating clinicians to improve walking function. Similar analysis of gait was undertaken by individuals, who employed functional electrical stimulation to facilitate walking. For many years a technique of FES of the peroneal nerve introduced by Lieberson in 1961 [44] was utilized to compensate for the plantar flexed foot due to neurological weakness of the ankle dorsiflexors and evertor muscles. In an excellent study and review by van der Salm et al. [65], the specific impairments of gait in subjects with incomplete SCI were studied by direct observation of subjects from three centers in the Netherlands and Scotland and by questionnaire. The questionnaire responded to by SCI clinicians ranked the frequency of the gait deviations and their importance to walking function. They classified the impairment of gait into 4 categories: (1) stance phase stability; (2) swing phase foot clearance; (3) foot positioning and (4) step length and then ranked them based on the clinician’s judgment of the clinical importance (safe walking and training time). This method of classification was based on the Rancho Los Amigos observation list (Fig. 1), which was also the method used for the observation of gait impairments in the 21 subjects studied. As indicated by the authors [65], velocity and cadence were not included, in which the former has been viewed as an important endpoint in clinical trials [21]. Although the questionnaire samples the experience of SCI clinicians over a broad group of subjects, the observational analysis is limited to 21 subjects, who are community walkers and differ from the questionnaire group based on clinical experience, who were not community walkers. Since it is important to the analysis, to understand the clinical population, we will briefly summarize the neurological impairment. The subjects

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Fig. 1. Rancho Los Amigos Gait List (published with the permission of Dr. Robert Waters). Rancho Los Amigos observation list. The gait is divided into several phases: IC, initial contact; LR, loading response; MSt, mid-stance; TSt, terminal stance; PSw, pre-swing; Isw, initial swing; MSw, mid-swing; TSw, terminal-swing. The body is also divided into trunk, pelvis, hip, knee, ankle, and toes. For every body part several impairments can be scored (shown for only a few impairments). Only white boxes can be ticked for impairments at a certain stage in the gait.

were almost equally divided between paraplegia (10/22, T4–T12) and quadriplegia (11/22, C4–C7), but 19 (19/21) were classified as ASIA Impairment Scale (AIS) D and only 2 as ASIA C. All but 1 subject used walking aids (20/21) and/or braces (7/21). Both subjects with ASIA C were classified as “physiologic walking”, while the remainder were community (13/21) or household walkers (4/21). ASIA D subjects, typically are community walkers as reported in other studies [9,45]. They found that inadequate hip extension during the stance phase and persistent plantar flexion of the foot during swing phase were the most common and important impairments. In addition, impaired foot contact at heel strike to mid stance and limited hip and knee flexion during the swing phase followed in this ranking. 2.2. Motion analysis Motion analysis is a commonly employed method for diagnosis and documenting clinical improvement, which has been used in a number of small studies [1,36], but recently has been suggested as a “conceptual basis for application of real-time movement feedback” and a strategy for the design of new interventions [10,28,58]. In a larger study of 27 subjects, kinematic gait analysis (motion analysis) was found to be important in determining the pattern of abnormality in the gait of subjects with incomplete SCI. The rationale for the study was to demonstrate that the pattern of walking of subjects with SCI was due not only to weakness of the muscles but also spasticity and that it differed in subjects with thoracic lesions compared to lumbar [42]. It was shown that he angular velocity of the knee was slower in thoracic lesions due to knee flexor spasms and in the ankle of lumbar lesions. This is an important example of the use of study of cadence, forward velocity of the knee and ankle

and stride length in reaching quantified observations to support clinical observations of altered walking due to spasticity. Similar methods were used in small trials [29,50,61,67] of the effect of drugs such as clonidine and cyproheptadine on walking of individuals with significant spasticity with measures of the kinematic pattern and electromyographic activity. In a larger study [55] of 9 subjects, intrathecal clonidine was used and velocity, stride amplitude, cycle duration and electromyographic patterns were used as end points. 3. Functional electrical stimulation FES to improve walking is one of the earliest interventions [44] utilized to improve gait and continues to be studied in small trials. Current interventions range from the use of surface electrodes to implanted devices to activate the muscles of locomotion. The better papers relevant to our review are summarized in the following section and those elements of gait research relevant to clinical interventions are stated. Unfortunately, the complexity of the instrumentation, which is still evolving [62], and the difficulties encountered in planning large trials led the reviewers to state that “the quality of these studies are low with no RCT (randomized clinical trials) having been conducted, and single case studies a common research design”. This does not negate the important contributions of gait research in the development of clinical interventions, but we must encourage the support by agencies and investigators to pursue high quality trials in the future. Three different strategies regarding FES were discussed as specific treatment strategies based on the prerequisites developed by Perry [52]. They included: (1) inadequate hip extension dur-

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ing stance phase; (2) excess of plantar flexion during swing and impaired initial foot contact and (3) limited hip and knee flexion during swing. In the first category, poor hip extension during stance phase is usually due to weakness of the gluteal muscles and results in poor stability during stance with limitations of the step length of the opposite extremity. It also contributes to pelvic drop, a finding, which the SCI experts ranked as a high priority for correction. Using a combination of FES to the gluteus maximus and medius/minimus in stance phase, solves this problem [63] and is more efficient [48]. The authors recommend use of surface electrodes during training to be followed by implanted electrodes for more permanent use. In the second category, excessive plantar flexion results in problems with foot clearance during swing and poor foot placement at heel strike. FES to the peroneal nerve stimulates both the ankle dorsiflexors and evertor muscles, which can correct this problem and is used with implanted electrodes [38] Several strategies are offered for limited hip and knee flexion during swing, which is the third category in their classification. This gait impairment results in a stiff leg, often associated with increased spasticity, and results in problems with foot clearance. Direct stimulation to the hamstrings and hip flexors (although more difficult), stimulation to the calf muscle during push off or stimulation of the withdrawal reflex are offered as three different potential interventions. One of their important conclusions is that not only the ankle movements must be treated to restore gait, but also hip extension and hip and knee flexion, so they discuss the feasibility of a four channel system for each leg. This study, regardless of limitations, is an extremely important approach, because it examines the major impairments of walking and identifies their clinical relevancy in order to develop an intervention. Thus, it represents an example of gait research, in which there is an analysis of the most frequent and common impairments of walking during the phases of gait, observed by clinical investigators, who specialize in SCI and rank the impairments based on their clinical relevancy. This analysis then serves as a method to base treatment strategies for specific functional electrical stimulation interventions. In a more recent review of the benefits of FES-assisted gait for individuals with SCI, Nightingale et al. [49] categorized the studies into 3 groups: (1) clinical outcomes, (2) fitness and (3) functional walking. Although 496 papers were reviewed, most were either not adequately studied or lacked sufficient evidence, so that only 36 were included. In the clinical outcomes category that purported to show improvements in spasticity, bone density or muscle strength, gait parameters were not utilized and cardiovascular function was used as an indicator of improved fitness. For the purposes of our review, we will focus on studies based on functional walking and the measures of gait/walking utilized by the investigators (Table 1). In the analysis of improvement in gait function, gait velocity was utilized in the majority of the 14 studies [49]. In half of the studies, changes in stride length and/or cadence was measured. Only one study Johnston et al. [37] reported an improvement in pelvic stability and joint kinematics. This limited use of a more detailed analysis of improvement in specific gait impairments is unclear and emphasis appears to be on speed and stride length rather than on joint kinematics. The studies that examined improved functional outcomes such as increased standing, walking with less assistance and mobility scales, only one [54] reported on decreased gait deviations on an observed gait scale. Field-Fote et al. [26] has advocated that an observational gait scale be added to assessment of functional improvement in the SCI-FAI test. When FES-assisted gait is compared to alternative systems such as strength training, comparison to different training regimes such as BWST and use of orthoses, gait analysis including video analy-

sis is frequently used. Most studies of the effects on gait involve a small number of subjects and vary from 3 to 27. There appears to be justification to examine some of the larger studies and a few of the small studies to see where detailed analysis was performed. The largest recent study [27] of 27 subjects with chronic motor incomplete SCI employed 12 weeks of body weight support training with and without FES on the treadmill and during over ground walking. Parameters of walking speed, step length and step symmetry were measured before and after training and showed that those subjects with initial slower speed (<0.1 m/s, N = 15) increased their speed in 85% of cases, whereas those with initial fast speed showed only an increase in 9% of cases. The largest sample of 31 subjects with chronic incomplete SCI was studied in four centers and reported in 1999 [69]. Subjects served as their own controls and parameters of speed, cycle time and stride length were measured with and without FES. Similar to Field-Fote results, the greater gains in speed was seen in the slower walkers (<0.3 m/s). Since stride length was increased, the speed increase was attributed to this rather than more steps. Several subjects improved enough to switch from one aid to another such as walker to canes and others progressed from a wheel chair to walking which appears to be a clear indication of clinical improvement. Although these results of increased velocity are consistent with many of the smaller case series, the issue of clinical relevancy must be raised again. How much of an improvement in speed is of clinical importance [43]? This issue is not been thoroughly addressed. Another recent study [54] compared partial weight support training supplemented with FES to traditional physical therapy in a cross-over design of 14 subjects with acute SCI. The gait parameters used in the study were over ground walking endurance and speed, cadence, stride length and observational gait analysis plus speed, distance and percentage body weight support on the treadmill. While speed and endurance both improved in the FES treated group, the confidence intervals were large and the cross-over design presents some questions regarding continued training effects of one treatment followed by another. Finally, a very recent study [62] of only 5 subjects with chronic incomplete SCI were customized to a new neuroprosthesis, based on an approach of voluntary activation and an FES program. This FES program was designed to stimulate the gait cycle through open loop control which was defined and scaled to each subject. The subject voluntarily triggered the cycle just before toe off and a 2 min walk was measured. The sequence of the muscle stimulation was based “loosely” on muscle timing patterns for normal gait and modified to the recruitment produced by FES. This application illustrates the importance of gait studies for the design of the FES program. Again, an increase in velocity was reported, but step frequency also increased in addition to stride length. The measures of stride point up the need to examine other parameters than simply velocity, because there were improvements from step to step to step through (a full cycle of both legs), facilitated by the FES and accounting for the improved velocity. One subject improved sufficiently that he no longer felt the braces necessary reflecting a clinically significant change. It is important to appreciate that changes in the use of devices reported in two of these studies indicate an important clinical parameter of improvement even though one of the subjects walked slower. While the above studies did not represent Class 1 evidence based on well-designed randomized multicenter trials, they utilized parameters of gait, which have been developed from gait research and applied to clinical situations. Stride length, frequency and stride symmetry did provide more information regarding the increased velocity.

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Table 1 Listing of clinical studies related to FES [49] and Locomotor Training [16]. Clinical trials on functional electrical stimulation Braun Z, Mizrahi J, Najenson T, Graupe D.

Isakov E, Mizrahi J, Najenson T. Mizrahi J, Braun Z, Najenson T, Graupe D.

Klose KJ et al.

Granat MH, Ferguson AC, Andrews BJ, Delargy M.

Ladouceur M, Barbeau H

Ladouceur M, Barbeau H

Johnston TE, Finson RL, Smith BT, Bonaroti DM, Betz RR, Mulcahey MJ. Thrasher TA, Flett HM, PopovicMR.

Thrasher TA, PopovicMR.

Activation of paraplegic patients by functional electrical stimulation: training and biomechanical evaluation. Biomechanical and physiological evaluation of FES-activated paraplegic patients. Quantitative weightbearing and gait evaluation of paraplegics using functional electrical stimulation Evaluation of a training program for persons with SCI paraplegia using the Parastep 1 ambulation system: part 1. Ambulation performance and anthropometric measures. The role of functional electrical stimulation in the rehabilitation of patients with incomplete spinal cord injury – observed benefits during gait studies. Functional electrical stimulation-assisted walking for persons with incomplete spinal injuries: longitudinal changes in maximal overground walking speed. Functional electrical stimulation- assisted walking for persons with incomplete spinal injuries: changes in the kinematics and physiological cost of overground walking. Functional electrical stimulation for augmented walking in adolescents with incomplete spinal cord injury. Gait training regimen for incomplete spinal cord injury using functional electrical stimulation. FES-assisted walking for rehabilitation of incomplete spinal cord injury.

Clinical trials on functional electrical stimulation and body weight support Field-Fote EC. Combined use of body weight support, functional electric stimulation, and treadmill training to improve walking ability in individuals with chronic incomplete spinal cord injury. Field-Fote EC, Tepavac D. Improved intralimb coordination in people with incomplete spinal cord injury following training with body weight support and electrical stimulation. Hesse S, Werner C, Bardeleben A. Electromechanical gait training with functional electrical stimulation: case studies in spinal cord injury. Postans NJ, Hasler JP, Granat MH, Maxwell DJ. Functional electric stimulation to augment partial weight bearing supported treadmill training for patients with acute incomplete spinal cord injury: a pilot study. Clinical trials on body weight support Dobkin B, Apple D, Barbeau H, Basso M, Behrman A, Deforge D, Weight-supported treadmill vs overground Ditunno J, Dudley G, Elashoff R, Fugate L, Harkema S, . Saulino training for walking after acute incomplete SCI M, Scott M, and the Spinal Cord Injury Locomotor Trial (SCILT) Group Dobkin B, Barbeau H, Deforge D, Ditunno J, Elashoff R, Apple D, The evolution of walking-related outcomes Basso M, Behrman A, Fugate L, Harkema S, MSaulino M, Scott over the first 12 weeks of rehabilitation for M and the Spinal Cord Injury Locomotor Trial Group incomplete traumatic spinal cord injury: the multicenter randomized spinal cord injury locomotor trial Ditunno JF Jr, Barbeau H, Dobkin BH, Elashoff R, Harkema S, Validity of the walking scale for spinal cord Marino RJ, Hauck WW, Apple D, Basso DM, Behrman A, injury and other domains of function in a Deforge D, Fugate L, Saulino M, Scott M, Chung J; Spinal Cord multicenter clinical trial. Injury Locomotor Trial Group.

4. Locomotor clinical trial Investigation of the gait training of animals and subsequently humans as a result of paralysis due to spinal cord injury demonstrated improved patterns of walking without physical assistance on a treadmill. Analysis of EMG patterns during the gait cycle

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demonstrated a return toward normal patterns in animals [24] and in humans [35]. These studies and other observations from clinical case series [68] stimulated a clinical trial on locomotor training. Although specific gait analysis was not employed as an endpoint in this trial due to practical considerations, a new group of clinical outcome measures of walking function were reported for the

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first time in a randomized multicenter trial [7,21,22]. Most of these measures such as the locomotor functional independence measure (L-FIM), walking speed for 50 feet (50 FW), the Walking Index for Spinal Cord Injury (WISCI), the Berg balance scale (BBS) and the 6 min walk (6 MW) had not been used previously in a multicenter clinical trial and their response in the locomotor trial of subjects with incomplete SCI have been recently described [16]. They will be discussed briefly in the context of their clinical significance and how this relates to the clinical investigation of gait below. In order for walking measures to be used in a clinical trial they must be standardized (performed in a consistent environment with specified instructions related to distance, time and other appropriate dimensions), reliable and practical. Because individuals who are recovering from paralysis may not be able to initially stand and walk, baseline data such as speed of walking and walked distance may not be possible. More precise analysis of stride, cadence and other kinesiologic events, therefore would present similar problems. However, if we wish to determine the effect of different methods of locomotor or gait training during the recovery phase we must be able to study subjects as early as possible. For these reasons, other clinical correlates must be identified. For example, the recovery of muscle strength can be recorded at baseline and an increase in strength in the legs has shown to correlate with improved walking function [40]. The summation of strength scores has been used in previous clinical trials [8,22,30] and is a valid measure of neurological improvement. Stationary or static measures of

strength as performed by the International Standards, however, do not test the dynamic function of upright mobility and factors such as sensory input and muscle hyperactivity. It, therefore, appears desirable to measure walking by further quantitative and qualitative methods. Gait analysis certainly could provide more detailed quantitative/qualitative data. In the locomotor trial, which compared step training on a treadmill to a control group with more conventional training methods, baseline lower extremity strength was the best predictor of future walking function as measured by the Walking Index for Spinal Cord Injury [16,22]. The other walking measures of speed and distance likewise correlated well with improvement in strength of the legs. It was shown, however that all subjects improved and their improvement was better than anticipated by historical controls, which suggests that the intensity and duration of training may have played a role. Could gait research provide us with an improved understanding of how this improvement occurs as a result of intensity and duration of training? One of the outcome measures of walking capacity is the speed of walking and has been demonstrated to be valid and reliable for use in clinical trials for incomplete SCI subjects [16,23,60,66,70]. Gait analysis could provide more precise measures of cadence, stance/swing and double support parameters between subjects, who walk at similar speeds. As suggested by van der Salm et al. [65], many of the impairments of gait during swing and stance at the hip, knee and foot may be analyzed in subjects with incom-

Table 2 WISCI II scoring sheet [12]. Descriptors Gait: reciprocal

; swing through

Devices //bars < 10 m

Braces Long leg braces-uses 2 Uses 1 Short leg braces–uses 2 Uses 1 Locked at knee Unlocked at knee

//bars 10 m Walker–Standard Rolling Platform Crutches-uses 2 uses 1 Canes-quad Uses 2 Uses 1 No devices

Assistance Max assit × 2 people

Patient reported comfort level Very comfortable

Min/mod assist × 2 people

Slightly comfortable

Min/mod assist × 1 person

Neither comfortable nor uncomfortable

Other:

Slightly uncomfortable Very uncomfortable

No braces

No assistance

WISCI Levels Level 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Level assigned

Devices Parallel bars Parallel bars Parallel bars Parallel bars Parallel bars Walker Two crutches Walker Walker One cane/crutch Two crutches Two crutches Walker One cane/crutch One cane/crutch Two crutches No devices No devices One cane/crutch No devices .

Braces Braces Braces Braces No braces Braces Braces Braces No braces Braces Braces No braces Braces No braces No braces Braces No braces No braces Braces No braces No braces

Assistance

Distance

2 persons 2 persons 1 person 1 person No assistance 1 person 1 person 1 person No assistance 1 person 1 person No assistance No assistance 1 person No assistance No assistance 1 person No Assistance No assistance No assistance

Unable Less than 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m 10 m

J. Ditunno, G. Scivoletto / Brain Research Bulletin 78 (2009) 35–42

plete SCI and improved by treatment. Perhaps, clinically relevant impairments remain although speed has improved, particularly in the severely impaired subjects, thus greater attention to the quality of the gait is indicated. It has also been reported that the use of different devices can also alter speed in the same subjects [64] and the use crutches as compared to a walker can be more efficient and result is faster walking. In addition, testing the same patients for walking speed at different WISCI levels [41], likewise reveals differences in efficiency, which may be related to devices or physical assistance. A change in WISCI levels may alter both devices and physical assistance. The WISCI [12,13,15] integrates devices that include devices which stabilize the joints such as braces and devices which are walking aids such as walkers, crutches and canes which compensate for weakness and instability of the legs by support from the upper extremities (Table 2). When the devices are added or removed and/or physical assistance is changed the speed and efficiency of walking is altered. Since these alterations in speed and efficiency are not solely related to improvements in independence (less use of devices or physical assistance), it is obvious they need closer examination. More precise gait studies that examine the role of device/assistance substitution may provide clues for future treatment approaches. Perhaps maximizing speed or decreasing the use of less devices/physical assistance may not be the best indication of overall walking improvement and factors of balance, posture, distance and efficiency need to be addressed. 5. Conclusions Gait research provides SCI clinical investigators with a critical understanding of the altered mechanisms of walking after SCI and methods to better diagnose/describe pathological gait and walking impairments. Based on this improved classification, successful strategies to improve walking such as FES have been implemented in over 30 well-designed studies. Often these studies employ sophisticated methods of motion analysis with measurement of synchronized muscle activity, joint motion, forces, and other gait parameters of cadence, stride length and velocity. Such methods, however, are not currently practical for large multicenter randomized clinical trials (MRCT), because of expense and other limited resources. Less complicated measures of walking function such as walking speed, walking distance and the Walking Index for Spinal Cord Injury, which correlate with muscle weakness due to paralysis, have recently emerged and were used in a MRCT on locomotor training. These are valid and reliable tools recommended for use in clinical trials to determine effectiveness. The evolution of improved outcome measures of impaired walking function in SCI, based on continued gait research remains highly relevant to clinical investigation. Conflicts of interest None. References [1] R. Abel, M. Schablowski, R. Rupp, H.J. Gerner, Gait analysis on the treadmillmonitoring exercise in the treatment of paraplegia, Spinal Cord 40 (1) (2002) 17–22. [2] K.D. Anderson, Targeting recovery: priorities of the spinal cord-injured population, J. Neurotrauma 21 (10) (2004) 1371–1383. [3] H. Barbeau, K. Norman, J. Fung, M. Visintin, M. Ladouceur, Does neurorehabilitation play a role in the recovery of walking in neurological populations? Ann. N. Y. Acad. Sci. 860 (1998) 377–392. [4] H. Barbeau, M. Ladouceur, K.E. Norman, A. Pepin, A. Leroux, Walking after spinal cord injury: evaluation, treatment, and functional recovery, Arch. Phys. Med. Rehabil. 80 (2) (1999) 225–235.

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