An improved functional neurological examination for use in nonhuman primate studies of focal reperfused cerebral ischemia

There is renewed interest in primate models of acute stroke for the evaluation of potential therapeutic agents prior to clinical trials. The development of more precise functional outcome measures would improve the pre-clinical assessment of neuroprotective strategies. We have constructed a grading scale that utilizes an increased number of goal-oriented tasks to assess both behavior and motor function. The new scoring system is designed to enhance precision and accuracy when compared to existing scales. Twenty-seven male baboons were subjected to 1 h of middle cerebral artery territory occlusion followed by reperfusion. Outcome was evaluated using both a standard neurological function scale and a new task-oriented scale. Each scoring system was assessed for reproducibility (inter-observer reliability) and for association with radiographic infarct volume. The task-oriented grading system was significantly less variable than the standard outcome measure (p <0.0001). The task-oriented neurological scale demonstrated stronger correlation with radiographic infarct volume (p < 0.0001) than the standard scale (p < 0.01) and more accurately reflected infarct size in animals with small strokes. Compared to the accepted system for grading neurological function, the task-oriented scale demonstrates improved inter- observer variability and a better association with radiographic outcome measures. Incorporating this refined neurological evaluation into a baboon model of stroke may serve to increase the functional predictive value of pre-clinical studies.