John F. Ditunno

International standards for neurological and functional classification of spinal cord injury

International Standards for Neurological and Functional Classification of Spinal Cord Injury

The International Standards Booklet for Neurological and Functional Classification of Spinal Cord Injury

The International Standards Booklet for Neurological and Functional Classification of Spinal Cord Injury

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 to18 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.

Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI

Objective: To compare the efficacy of step training with body weight support on a treadmill (BWSTT) with over-ground practice to the efficacy of a defined over-ground mobility therapy (CONT) in patients with incomplete spinal cord injury (SCI) admitted for inpatient rehabilitation. Methods: A total of 146 subjects from six regional centers within 8 weeks of SCI were entered in a single-blinded, multicenter, randomized clinical trial (MRCT). Subjects were graded on the American Spinal Injury Association Impairment Scale (ASIA) as B, C, or D with levels from C5 to L3 and had a Functional Independence Measure for locomotion (FIM-L) score <4. They received 12 weeks of equal time of BWSTT or CONT. Primary outcomes were FIM-L for ASIA B and C subjects and walking speed for ASIA C and D subjects 6 months after SCI. Results: No significant differences were found at entry between treatment groups or at 6 months for FIM-L (n = 108) or walking speed and distance (n = 72). In the upper motor neuron (UMN) subjects, 35% of ASIA B, 92% of ASIA C, and all ASIA D subjects walked independently. Velocities for UMN ASIA C and D subjects were not significantly different for BWSTT (1.1 ± 0.6 m/s, n = 30) and CONT (1.1 ± 0.7, n = 25) groups. Conclusions: The physical therapy strategies of body weight support on a treadmill and defined overground mobility therapy did not produce different outcomes. This finding was partly due to the unexpectedly high percentage of American Spinal Injury Association C subjects who achieved functional walking speeds, irrespective of treatment. The results provide new insight into disability after incomplete spinal cord injury and affirm the importance of the multicenter, randomized clinical trial to test rehabilitation strategies.

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 subjects functional ability to engage in activities of daily living, and (3) those that measure an individuals 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 individuals 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.

Neurologic recovery after traumatic spinal cord injury: data from the model spinal cord injury systems

OBJECTIVE To present data on neurologic recovery gathered by the Model Spinal Cord Injury (SCI) Systems over a 10-year period. DESIGN Case series. SETTING Twenty-one Model SCI Systems. PATIENTS A total of 3,585 individuals with traumatic SCI admitted between January 1, 1988 and December 31, 1997. MAIN OUTCOME MEASURES Neurologic impairment category; Frankel grade; American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade; motor score. RESULTS SCI caused by violence is more likely than SCI from nonviolent etiologies to result in a complete injury. Changes in severity of injury were similar using the older Frankel scale and the newer ASIA Impairment Scale. Individuals who were motor-complete with extended zones of sensory preservation but without sacral sparing were less likely to convert to motor-incomplete status than those with sacral sparing (13.3% vs 53.6%; p < .001). Motor score improvements at 1 year were related to severity of injury, with greater increases for better AIS grades except grade D, because of ceiling effects. Individuals with AIS grade B injuries have a mixed prognosis. CONCLUSION Neurologic recovery after SCI is influenced by etiology and severity of injury. Multicenter studies on prognostic features such as preserved pin sensation in grade B injuries may identify subgroups with similar recovery patterns. Identification of such groups would facilitate clinical trials for neurologic recovery in acute SCI.

Spinal shock revisited: a four-phase model

Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel four-phase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.

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 persons 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 persons 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.

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.

Recovery of ambulation in motor-incomplete tetraplegia.

OBJECTIVE To determine the effect of age and initial neurologic status on recovery of ambulation in patients with motor-incomplete tetraplegia. STUDY DESIGN Inception cohort study. SETTING Urban, tertiary care hospital with Regional Spinal Cord Injury Center. PATIENTS One hundred five patients with American Spinal Injury Association (ASIA) C or D tetraplegia at admission or within 72 hours of injury. MAIN OUTCOME MEASURE Ambulatory status at time of discharge from inpatient rehabilitation. RESULTS Ninety-one percent (30/33) of ASIA C patients younger than 50 years of age became ambulatory by discharge, versus 42% (13/31) ASIA C patients age 50 or older (p < .0001). All (41/41) patients initially classified as ASIA D became ambulatory by discharge. CONCLUSION For patients with ASIA D tetraplegia, prognosis for recovery of independent ambulation is excellent. For patients with ASIA C tetraplegia, recovery of ambulation is significantly less likely if age is 50 years or older.