Predicting Functional Gains in a Stroke Trial

Abstract

Background and Purpose-A number of therapies in development for patients with central nervous system injury aim to reduce disability by improving function of surviving brain elements rather than by salvaging tissue. The current study tested the hypothesis that, after adjusting for a number of clinical assessments, a measure of brain function at baseline would improve prediction of behavioral gains after treatment. Methods-Twenty-four patients with chronic stroke underwent baseline clinical and functional MRI assessments, received 6 weeks of rehabilitation therapy with or without investigational motor cortex stimulation, and then had repeat assessments. Thirteen baseline clinical/radiological measures were evaluated for ability to predict subsequent trial-related gains. Results-Across all patients, bivariate analyses found that greater trial-related functional gains were predicted by (1) smaller infarct volume, (2) greater baseline clinical status, and (3) lower degree of activation in stroke-affected motor cortex on baseline functional MRI. When these 3 variables were further assessed using multivariate linear regression modeling, only lower motor cortex activation and greater clinical status at baseline remained significant predictors. Note that lower baseline motor cortex activation was also associated with larger increases in motor cortex activation after treatment. Conclusions-Lower motor cortex activity at baseline predicted greater behavioral gains after therapy, even after controlling for a number of clinical assessments. The boosts in cortical activity that paralleled behavioral gains suggest that in some patients, low baseline cortical activity represents underuse of surviving cortical resources. A measure of brain function might be important for optimal clinical decision-making in the context of a restorative intervention.

Mesencephalic Corticospinal Atrophy Predicts Baseline Deficit but Not Response to Unilateral or Bilateral Arm Training in Chronic Stroke

“…Some reports, including ours in chronic stroke however, have not found this relationship [39,40]. Certainly, lesion location influences the size-deficit relationship.…”

Functional MRI Correlates of Lower Limb Function in Stroke Victims With Gait Impairment

“…7,8 However, fundamental differences in the neural control of hand and leg movement have to be expected, eg, considering the role of spinal interneurons in central pattern generation for gait 9 versus the almost exclusively cerebralcerebellar control of fine hand movements. 10,11 Patterns of brain activation associated with recovery, specifically of lower limb function, after stroke therefore may be different from those for hand movements. 5,10,12,13 Brain responses to ankle movements in healthy subjects have been characterized using fMRI, 7,8,14,15 but studies in patients with gait impairment have been limited to multiple sclerosis 16 and patients with stroke with heterogenous lesion types (subcortical, cortical, brainstem).…”

Stratifying Patients With Stroke in Trials That Target Brain Repair

“…In patients with chronic stroke, a smaller degree of ipsilesional primary motor cortex activation during an fMRI scan obtained at study baseline predicted gains from motor-related therapy, and did so more strongly than many other clinical or imaging metrics did. 17 Furthermore, patients who showed the highest gains from therapy also showed the largest boosts in motor cortex activation. The model suggests that patients who have intact but underused motor cortex resource can be trained to increase motor cortex activity, and that fMRI at baseline is providing a useful measure of the therapy's biological target.…”

“…A wide range of candidate tests exists for such patient stratification (Table). Initial studies [17][18][19][20] suggest the potential use of this approach, though these require independent verification and validation. Further study of the many factors that influence stroke recovery, both spontaneous and treatment-induced, will provide a means to best stratify patients seeking therapies that target brain repair.…”