Patient Selection for Clinical Trials: The Reliability of the Early Spinal Cord Injury Examination

Abstract

Patients with incomplete spinal cord injuries can spontaneously recover motor function. Because of this, phase I and II trials of invasive interventions for acute spinal cord injury will likely involve neurologically complete injuries. It is therefore important to reliably identify complete injuries as early as possible. We examined the reliability of the early examination in motor complete spinal cord injuries by retrospectively analyzing the stability of baseline neurological status determined within 2 days of injury in 103 subjects. Baseline neurological status was compared to neurological status at follow-up, preferably within one week (101 of 103 subjects). When available (n = 68), neurological status at 1 year or later was also compared. Overall, 6.2% (5/81) of motor complete, sensory complete (ASIA A) subjects converted to motor complete, sensory incomplete status (ASIA B) between the initial and follow-up assessments; however, none exhibited motor recovery (ASIA C or D). At initial follow-up, 9.3% (4/43) of ASIA A subjects with factors affecting examination reliability were reclassified as ASIA B injuries compared to 2.6% (1/38) of ASIA A subjects without such factors. At year 1 or later, 6.7% (2/30) of ASIA A subjects without factors affecting exam reliability, converted to ASIA B status. None developed volitional motor function below the zone of injury. For subjects with factors affecting exam reliability, 17.4% (4/23) of ASIA A subjects converted to incomplete status and 13.0% (3/23) regained some motor function by one year or later (ASIA C or D). These data suggest that it is possible to identify within 48 h of injury, a subset of patients with a negligible chance for motor recovery who would be suitable candidates for future clinical trials of invasive treatments.

Abductor hallucis for monitoring lower-limb recovery after spinal cord injury in man

“…[19][20][21][22][23] Success in such trials will necessitate optimal subject selection and the utilization of outcome measures both sensitive to and specific for the treatment effects. 24 Detailed neurologic testing will almost certainly be a cornerstone of these outcome measures, as it has been for pharmacological clinical trials after acute SCI. 6,17,18,25 At this time, such neurologic testing does not include the AbH muscle, or any of the intrinsic foot muscles.…”

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 reliability of the initial and second examination in motor complete patients was also examined by Burns et al 20 Patients were examined initially within 48 h of SCI, again within a week before discharge and then 1 year after SCI. The early examination was classified as unreliable if there were factors affecting cognition (eg, traumatic brain injury, drug effects, psychological disorders), communication (patient on ventilator, language barriers) or other considerations that would undermine confidence in the examination.…”

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects

“…7 Before the 72 h post-injury mark, several factors such as spinal shock, medical instability or concomitant injuries affect the reliability of the neurological examination. 8 Furthermore, even with a reliable baseline neurologic examination performed acutely after injury, the extent of spontaneous recovery among SCI patients with the same AIS grade is extremely variable. 4 This variability in natural recovery forces investigators to enroll large numbers of patients into clinical trials of acute SCI therapies.…”