Biomarkers of recovery after stroke

Abstract

Purpose of review: A better understanding of the molecular events underlying stroke recovery might be useful to optimize restorative therapies. Measurement of these events, however, is generally inaccessible in humans, at least at the molecular level. Substitute measures, or biomarkers, that are accessible might provide deeper insights into spontaneous recovery in humans. This review considers advances in use of biomarkers to understand recovery from stroke, and to serve as a surrogate measure of stroke recovery, including in a clinical trial context.

Recent findings: Among the key recent findings is that measures of brain function and injury are the strongest predictors of treatment effect, moreso than behavioral measures are, despite the reliance on behavioral measures as study entry criteria. Functional neuroimaging studies have provided insights into therapeutic mechanism of action. In addition, measures of central nervous system function have been used to estimate individual therapy needs, findings that suggest the potential to tailor restorative therapies to the specific needs of individual patients.

Summary: Many therapies are emerging as potentially useful to promote improved recovery after stroke. Continued advances in biomarkers are providing new insights into the neurobiology of both spontaneous and therapy-induced brain repair after stroke.

Figure 1

Specificity of fMRI measures in relation to post-stroke therapy. Ten patients with chronic left brain hemiparetic stroke underwent fMRI scanning during two tasks, received three weeks of robotic therapy, then underwent repeat fMRI scanning. The content of the robotic therapy emphasized grasp/release movements. Group fMRI maps are displayed for 9 (bottom row) to 10 (top row) patients in whom such data were available. The top row shows evolution of fMRI activation for the task that was extensively practiced as part of therapy, with a significant 20-fold increase in left primary sensorimotor cortex activation. The bottom row shows that this increase was absent for a control task, pronation-supination, that relied on similar muscles but that was not rehearsed as part of therapy. The results suggest specificity of therapy effects on an fMRI biomarker[17].

Figure 2

Potential of fMRI to provide an independent measure for predicting response to therapy in chronic stroke. Twenty four patients underwent baseline behavioral and fMRI testing received six weeks of therapy, and had repeat behavioral testing. Measures of (A) baseline motor status, the arm motor Fugl-Meyer (FM) score and of (B) baseline brain function, the degree of activation in ipsilesional primary motor cortex as measured from fMRI brain mapping each predicted behavioral gains from subsequent therapy, and survived as the only such predictors in a multivariate model. Note that variables not surviving in the model included the classic stroke outcome predictors of age, time post-stroke, and infarct volume. In this population, better baseline motor status predicted greater gains from therapy. Also, lesser baseline motor cortex function during distal upper extremity movements predicted greater gains, suggesting underuse of available motor cortex resource at baseline. The two variable model, while exciting in its emphasis that behavioral and fMRI measures can have independent and complementary value, nevertheless only explained 40% of the variance in response to therapy[57].