Neurological outcomes after cervical spinal cord injury

In addition to overcoming biological barriers that limit regeneration and repair in the central nervous system after spinal cord injury, clinicians and researchers are faced with the daunting task of assessing the safety and efficacy of therapeutics proposed to ameliorate neurological deficits in humans. While the selection of an appropriate clinical endpoint will depend on a number of factors, including the phase of study and the underlying biological activity, the estimated effect size based on preclinical studies in animal models of spinal cord injury of most therapeutics are expectedly small. A potential promising strategy to detect subtle but clinically meaningful changes in humans is to focus on individual spinal segments partially damaged adjacent to the level of injury. The primary aim of this thesis was to evaluate the validity of segmental sensorimotor outcomes for the purpose of devising clinical trial endpoints for spinal cord injury. In Chapters Two through Five, I focus this investigation on evaluating sensory outcomes. Chapter Two is chiefly intended to introduce clinical sensory testing methods (i.e. light touch and pinprick) and provide a better understanding of the relationship between the neuropathology of spinal cord injury and afferent anatomy and physiology. In order to address limitations of clinical sensory testing methods, the subsequent three chapters are focused on the application of segmental neurophysiological approaches. More specifically, this involves a series of studies in individuals with spinal cord injury aimed at objectively measuring conduction deficits in the dorsal column and spinothalamic tract based on outcomes from sensory evoked potentials. The thesis then shifts to the segmental assessment of motor function. In Chapter Six, changes in muscle strength are examined in the first year after cervical spinal cord injury, with a specific interest in documenting the relationship between improvements in motor scores in the upper extremities and the recovery of motor levels. This chapter concludes by linking functional independence and neurological outcomes. The discussion that follows is intended to provide an outline of how the knowledge acquired during the course of this doctoral thesis could be translated into phases of a clinical trial program.