Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury.

STUDY DESIGN: Two randomized, double-blind, placebo-controlled trials. OBJECTIVE: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI). SETTING: United States and Canada. METHODS: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors and extensors) and a 7-point Subject Global Impression of treatment (SGI; 1, terrible; 7, delighted). Secondary end points were: Penn Spasm Frequency Scale; the motor/sensory score from the International Standards for Neurological Classification of SCI; Clinician's Global Impression of Change of neurological status; and the International Index of Erectile Function (men) or the Female Sexual Function Index (women). RESULTS: The populations were 212 and 203 patients in the two studies, respectively. Changes from baseline in Ashworth score were -0.15 (placebo) and -0.19 (fampridine-SR) in the first study, and -0.16 (placebo) and -0.28 (fampridine-SR) in the second study. The between-treatment difference was not significant for either the Ashworth score or the SGI and, with few exceptions, neither were the secondary end points. Fampridine-SR was generally well tolerated; treatment-emergent adverse events (TEAEs) and serious TEAEs were reported with similar frequency between treatments. CONCLUSION: Fampridine-SR was well tolerated. No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI.

Walking Index for Spinal Cord Injury version II in acute spinal cord injury: reliability and reproducibility.

STUDY DESIGN: Administration of the walking index for SCI (WISCI) II is recommended to assess walking in spinal cord injury (SCI) patients. Determining the reliability and reproducibility of the WISCI II in acute SCI would be invaluable. OBJECTIVES: The objective of this study is to assess the reliability and reproducibility of the WISCI II in patients with traumatic, acute SCI. DESIGN: Test-retest analysis and calculation of reliability and smallest real difference (SRD). SETTING: SCI unit of a rehabilitation hospital. METHODS: Thirty-three patients, median age 44 years, median time since onset of SCI 40 days. Level: 20 cervical, 8 thoracic, 5 lumbar; ASIA (American Spinal Injury Association) impairment scale (AIS) grade: 32 D/1 C. Assessment of maximum WISCI II levels by two trained, blinded raters to evaluate interrater (IRR) and intrarater reliability. RESULTS: The intrarater reliability was 0.999 for therapists A and 0.979 for therapists B, for the maximum WISCI II level. The IRR for the maximum WISCI II score was 0.996 on day 1 and 0.975 on day 2. The SRD for the maximum WISCI II score was 1.147 for tetraplegics and 1.682 for paraplegics. These results suggest that a change of two WISCI II levels could be considered real. CONCLUSIONS: The WISCI II has high IRR and intrarater reliability and good reproducibility in the acute and subacute phase when administered by trained raters.

The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse.

STUDY DESIGN: Literature review. OBJECTIVE: To critically review all publications/internet sites that have described/used the Walking Index for Spinal Cord Injury (WISCI II), as a measure of impairment of walking function after spinal cord injury (SCI), in order to identify its psychometric properties, clarify its nature, specify misuse and incorporate the findings in an updated guide. METHOD: A systematic literature search was done of Ovid MEDLINE, CINAHL, PsychINFO, Cochrane Central Register of Controlled Trials, Scopus and electronic sites using key words: WISCI or WISCI II, SCI, paraplegia/ tetraplegia/ quadriplegia and ambulation/gait/walking. Among 1235 citations retrieved, 154 relevant articles/sites were identified, classified and examined by the authors; recommendations were made based on findings. RESULTS AND DISCUSSION: The validity (face/concurrent/content/construct/convergent/criterion) and reliability of the WISCI II has been documented in clinical trials and clinical series, and considered adequate by systematic reviewers. In chronic SCI subjects, reliable determination of the maximum (as opposed to self-selected) WISCI II level requires more time and experience by the assessor. The correct use of WISCI II is clarified for testing acute/chronic phases of recovery after SCI, age of subjects, devices and settings. The WISCI II and walking speed measures may be performed simultaneously. CONCLUSION: The increased use of the WISCI II is attributed to its unique characteristics as a capacity measure of walking function and its strong metric properties. Appropriate use of the WISCI II was clarified and incorporated into a new guide for its use. Combining it with a walking speed measure needs further study.

Consumer preference in ranking walking function utilizing the walking index for spinal cord injury II.

STUDY DESIGN: Blinded rank ordering. OBJECTIVE: To determine consumer preference in walking function utilizing the walking Index for spinal cord injury II (WISCI II) in individuals with spinal cord injury (SCI)from the Canada, the Italy and the United States of America. METHOD: In all, 42 consumers with incomplete SCI (25 cervical, 12 thoracic, 5 lumbar) from Canada (12/42), Italy (14/42) and the United States of America (16/42) ranked the 20 levels of the WISCI II scale by their individual preference for walking. Subjects were blinded to the original ranking of the WISCI II scale by clinical scientists. Photographs of each WISCI II level used in a previous pilot study were randomly shuffled and rank ordered. Percentile, conjoint/cluster and graphic analyses were performed. RESULTS: All three analyses illustrated consumer ranking followed a bimodal distribution. Ranking for two levels with physical assistance and two levels with a walker were bimodal with a difference of five to six ranks between consumer subgroups (quartile analysis). The larger cluster (N=20) showed preference for walking with assistance over the smaller cluster (N=12), whose preference was walking without assistance and more devices. In all, 64% (27/42) of consumers ranked WISCI II level with no devices or braces and 1 person assistance higher than multiple levels of the WISCI II requiring no assistance. These results were unexpected, as the hypothesis was that consumers would rank independent walking higher than walking with assistance. CONCLUSION: Consumer preference for walking function should be considered in addition to objective measures in designing SCI trials that use significant improvement in walking function as an outcome measure.

Validity and reliability of the 10-m walk test and the 6-min walk test in spinal cord injury patients.

STUDY DESIGN: The 10-m walk test (10MWT) and the 6-min walk test (6MWT) have been recommended for assessment of walking in spinal cord injury (SCI) patients. The study was designed on test-retest analysis of the 10MWT and 6MWT. OBJECTIVES: The objective of this study was to assess validity/reliability of different methods of performing the tests. SETTING: The study was set at an SCI unit of a rehabilitation hospital. PATIENTS AND METHODS: A total of 37 patients; whose median age was 58.5 years (interquartile range 40-66, full range 19-77); median time since onset of SCI was 24 months (interquartile range 16.25-70.5, full range 6-109). Non-traumatic etiology in 20 out of 37 patients; level: 12C, 14T and 11L; American Spinal Injury Association Impairment Scale grade: 35D/2C. Assessment with the 10MWT (with or without dynamic start) and the 6MWT (short or long track) by two blinded raters to evaluate inter/intra-rater reliabilities. RESULTS: The 10MWT was performed in a median of 19 s (25th-75th interquartile range 13-28) with the dynamic start and of 18.4 s (25th-75th interquartile range 12.6-29.9) with the static start (P=0.092). The correlation between the results of the two methods was between 0.98 and 0.99. The inter- and intra-rater reliabilities were between 0.95 and 0.99 for both the methods. The 6MWT showed significant differences according to the track length: patients walked a median of 226.7 m (25th-75th interquartile range 123.2-319) on the longer track and of 187.6 m (25th-75th interquartile range 69.7-240.6) on the short one (P<0.001). The correlation between the results of the two methods was between 0.91 and 0.93. The inter- and intra-rater reliabilities were between 0.98 and 0.99. CONCLUSION: The 10MWT shows high inter/intra-rater reliability and shows comparable results with both dynamic and static start. The different testing conditions of the 6MWT (track/turns) results in significant differences that need standardization for use in future trials.

Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury.

STUDY DESIGN: Retrospective, longitudinal analysis of motor recovery data from individuals with cervical (C4-C7) sensorimotor complete spinal cord injury (SCI) according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). OBJECTIVES: To analyze the extent and patterns of spontaneous motor recovery over the first year after traumatic cervical sensorimotor complete SCI. METHODS: Datasets from the European multicenter study about SCI (EMSCI) and the Sygen randomized clinical trial were examined for conversion of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, change in upper extremity motor score (UEMS) or motor level, as well as relationships between these measures. RESULTS: There were no overall differences between the EMSCI and Sygen datasets in motor recovery patterns. After 1 year, up to 70% of subjects spontaneously recovered at least one motor level, but only 30% recovered two or more motor levels, with lesser values at intermediate time points. AIS grade conversion did not significantly influence motor level changes. At 1 year, the average spontaneous improvement in bilateral UEMS was 10-11 motor points. There was only moderate relationship between a change in UEMS and a change in cervical motor level (r(2)=0.30, P<0.05). Regardless of initial cervical motor level, most individuals recover a similar number of motor points or motor levels. CONCLUSION: Careful tracking of cervical motor recovery outcomes may provide the necessary sensitivity and accuracy to reliably detect a subtle, but meaningful treatment effect after sensorimotor complete cervical SCI. The distribution of the UEMS change may be more important functionally than the total UEMS recovered.

Outcome measures: evolution in clinical trials of neurological/functional recovery in spinal cord injury.

The need to determine the beneficial effect of the treatment of spinal cord injury (SCI) requires clearly defined standardized measures of the severity of injury and how well the function is restored. Improved neurological recovery should be linked to increased capacity to perform tasks such as walking, reaching and grasping, which results in meaningful gains in mobility and self-care. Measurements of recovery, capacity, mobility and self-care are the outcomes used to determine the benefits from the treatment and have evolved over the last century with contributions by the mentors and protégés of Sir Ludwig Guttmann, whom we honor today. Randomized clinical trials in the past 20 years have taught us many lessons as to which outcome measures have the greatest validity and reliability. The International Standards for Neurological Classification of SCI have become the clinical gold standard for measurement of severity, but would benefit from pathophysiological surrogates to better understand the mechanisms of recovery. Measurements of walking capacity have emerged as valid/reliable/responsive and upper extremity measures are in development, which help distinguish neurological improvement from rehabilitation adaptation. Performance of self-care and mobility has been linked to capacity and severity outcomes. In addition, new partnerships between clinical trial entities, professional societies, industry and federal agencies should facilitate identification of priorities and uniformity of measurement standards. Our ultimate goal is to improve the quality of life of those individuals with SCI whom we serve, but we must focus our investigative efforts carefully, systematically and rigorously as clinical scientists.

Outcome measures in spinal cord injury: recent assessments and recommendations for future directions.

STUDY DESIGN: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. OBJECTIVES: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. METHODS: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. RESULTS: Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. CONCLUSION: Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial.

International standards to document remaining autonomic function after spinal cord injury.

STUDY DESIGN: Experts opinions consensus. OBJECTIVE: To develop a common strategy to document remaining autonomic neurologic function following spinal cord injury (SCI). BACKGROUND AND RATIONALE: The impact of a specific SCI on a person's neurologic function is generally described through use of the International Standards for the Neurological Classification of SCI. These standards document the remaining motor and sensory function that a person may have; however, they do not provide information about the status of a person's autonomic function. METHODS: Based on this deficiency, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) commissioned a group of international experts to develop a common strategy to document the remaining autonomic neurologic function. RESULTS: Four subgroups were commissioned: bladder, bowel, sexual function and general autonomic function. On-line communication was followed by numerous face to face meetings. The information was then presented in a summary format at a course on Measurement in Spinal Cord Injury, held on June 24, 2006. Subsequent to this it was revised online by the committee members, posted on the websites of both ASIA and ISCoS for comment and re-revised through webcasts. Topics include an overview of autonomic anatomy, classification of cardiovascular, respiratory, sudomotor and thermoregulatory function, bladder, bowel and sexual function. CONCLUSION: This document describes a new system to document the impact of SCI on autonomic function. Based upon current knowledge of the neuroanatomy of autonomic function this paper provides a framework with which to communicate the effects of specific spinal cord injuries on cardiovascular, broncho-pulmonary, sudomotor, bladder, bowel and sexual function.

Who wants to walk? Preferences for recovery after SCI: a longitudinal and cross-sectional study.

STUDY DESIGN: Cross-sectional and longitudinal direct observation of a constrained consensus-building process in nine consumer panels and three rehabilitation professional panels. OBJECTIVES: To illustrate differences among consumer and clinician preferences for the restoration of walking function based on severity of injury, time of injury and age of the individual. SETTING: Regional Spinal Cord Center in Philadelphia, USA. METHODS: Twelve panels (consumer and clinical) came to independent consensus using the features-resource trade-off game. The procedure involves trading imagined levels of independence (resources) across different functional items (features) at different stages of recovery. RESULTS: Walking is given priority early in the game by eight out of nine consumer panels and by two out of three professional panels. The exception consumer panel (ISCI<50) moved walking later in the game, whereas the exception professional panel (rehRx) moved wheelchair early but walking much delayed. Bowel and Bladder was given primary importance in all panels. CONCLUSIONS: Walking is a high priority for recovery among consumers with spinal cord injury irrespective of severity of injury, time of injury and age at time of injury. Among professional staff, walking is also of high priority except in rehabilitation professionals.

Validation of the walking index for spinal cord injury in a US and European clinical population.

OBJECTIVE: To demonstrate the prospective construct validity of the walking index for spinal cord injury (WISCI) in US/European clinical population. DESIGN: Prospective Cohort in Denmark, Germany, Italy and the USA. PARTICIPANTS/METHOD: Participants with acute complete/incomplete (ASIA Impairment Scale (AIS) A, B, C and D) traumatic spinal cord injuries were enrolled from four centers. Lower extremity motor scores (LEMS), WISCI level and Locomotor Functional Independence Measure (LFIM) levels were assessed with change in ambulatory status. WISCI progression was assessed for monotonic direction of improvement (MDI). LEMS were correlated to WISCI/LFIM. Use of walking aids/braces were analyzed. RESULTS: One hundred and seventy participants were enrolled and 20 excluded. Of the 150 participants (USA 112/150; Europe 38/150) (AIS A=59, B=19, C=32, D=40), LEMS and WISCI assessments were performed initially and at final assessment (3-12 months post injury) or until maximum WISCI score of 20. Eighty-five percent of motor complete (66/78) and 10% (7/72) of motor incomplete participants showed no progression (73/150). Of the remaining participants (77/150) who improved, 81% (62/77) showed MDI. However, the deviation from MDI occurred only at one time-point in 10/15 participants. LEMS correlated with WISCI at initial and final assessment (0.47 and 0.91 P<0.001). Parallel bar use differed between the US and Europe possibly due to patterns of care. Use of braces also differed. CONCLUSION: The results support the hierarchical ranking of the WISCI scale and the correlation of WISCI levels to impairment (LEMS) in a clinical setting of four nations. Differences in practice between the US and Europe need consideration in design of trials.

Comparison of speeds used for the 15.2-meter and 6-minute walks over the year after an incomplete spinal cord injury: the SCILT Trial.

BACKGROUND: Timed walking speed for 6 to 15 m and the distance walked in 2 to 12 minutes are frequently used outcome measures in rehabilitation trials, presumably reflecting different aspects of walking ability. The database from the Spinal Cord Injury Locomotor Trial (SCILT), which tested 2 interventions for mobility upon admission for initial rehabilitation of an incomplete traumatic spinal cord injury (SCI), was used to compare the walking speed employed for each test. METHODS: From 66 to 70 patients with upper motor neuron lesions from C-5 to T-10 performed a 15.2-m and a 6-minute walk as fast as the patient deemed safe at 3 months (end of the trial intervention) and 6 and 12 months after entry. The means, standard errors, and quartiles were calculated for the speed used for each task. RESULTS: The mean speed for the 15.2-m walk did not differ from that used for the 6-minute walk at 3 and 6 months but was significantly faster at 12 months. Differences became apparent at each assessment in patients in the highest quartiles (>1.0 m/s) for the 15.2-m walk. Their speed was from 14% to 24% higher than the speed used for the 6-minute walk. CONCLUSION: The speed of the 15.2-m walk as a measure of walking ability compared to the distance walked in 6 minutes may not represent separable domains of mobility. Differences were apparent only in the most highly functional patients, who could ambulate in the community. Any difference in the walking speed used for these 2 tasks does not make enough of a clinical distinction to encourage including both a 6-minute walk and a 15.2-m walk as outcome measures in clinical trials of locomotor interventions for SCI.

Phase 2 trial of sustained-release fampridine in chronic spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group clinical trial. OBJECTIVE: Assess safety and efficacy of sustained-release fampridine in subjects with chronic spinal cord injury. SETTING: A total of 11 academic rehabilitation research centers in the United States. METHODS: A total of 91 subjects with motor-incomplete spinal cord injury (SCI), randomized to three arms: fampridine, sustained release, 25 mg b.i.d. (Group I), 40 mg b.i.d. (Group II), and placebo (Group III) for 8 weeks. OUTCOME MEASURES: Patient diary questionnaire, Ashworth score, American Spinal Cord Injury Association International Standards, International Index of Erectile Function, bladder and bowel management questionnaires, and Clinician and Subject Global Impressions (Clinician Global Impression of change, Subject Global Impression (SGI)). Safety was evaluated from adverse events, physical examinations, vital signs, electrocardiograms, and laboratory tests. RESULTS: In total, 78% of the subjects completed the study. More (13/30) discontinued from Group II than Group I (4/30) and Group III (3/31). The most frequent adverse events across groups were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in Group II experienced a seizure. SGI changed significantly in favor of Group I (P=0.02). Subgroup analysis of subjects with baseline Ashworth scores >1 showed significant improvement in spasticity in Group I versus III (P=0.02). CONCLUSIONS: Group I showed significant improvement in SGI, and potential benefit on spasticity. The drug was well tolerated. Group II showed more adverse events and discontinuations.

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design.

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community.

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics.

The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent.

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures.

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials.

The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.

The evolution of walking-related outcomes over the first 12 weeks of rehabilitation for incomplete traumatic spinal cord injury: the multicenter randomized Spinal Cord Injury Locomotor Trial.

BACKGROUND: The Spinal Cord Injury Locomotor Trial (SCILT) compared 12 weeks of step training with body weight support on a treadmill (BWSTT) that included overground practice to a defined but more conventional overground mobility intervention (CONT) in patients with incomplete traumatic SCI within 8 weeks of onset. No previous studies have reported walking-related outcomes during rehabilitation. METHODS: This single-blinded, randomized trial entered 107 American Spinal Injury Association (ASIA) C and D patients and 38 ASIA B patients with lesions between C5 and L3 who were unable to walk on admission for rehabilitation. The Functional Independence Measure (FIM-L) for walking, 15-m walking speed, and lower extremity motor score (LEMS) were collected every 2 weeks. RESULTS: No significant differences were found at entry and during the treatment phase (12-week mean FIM-L = 5, velocity = 0.8 m/s, LEMS = 35, distance walked in 6 min = 250 m). Combining the 2 arms, a FIM-L >or= 4 was achieved in < 10% of ASIA B patients, 92% of ASIA C patients, and all of ASIA D patients. Walking speed of >or= 0.6 m/s correlated with a LEMS near 40 or higher. CONCLUSIONS: Few ASIA B and most ASIA C and D patients achieved functional walking ability by the end of 12 weeks of BWSTT and CONT, consistent with the primary outcome data at 6 months. Walking-related measures assessed at 2-week intervals reveal that time after SCI is an important variable for entering patients into a trial with mobility outcomes. By about 6 weeks after entry, most patients who will recover have improved their FIM-L to >3 and are improving in walking speed. Future trials may reduce the number needed to treat by entering patients with FIM-L < 4 at > 8 weeks after onset if still graded ASIA B and at > 12 weeks if still ASIA C.