Explaining Plasticity after Stroke?

Abstract

Stroke is the leading cause of disability. However, patients may show excellent functional recovery despite severe initial impairment in the first days post stroke. In the past few years there has been an upsurge of studies across neurological disorders that have tried to find indications of beneficial neuronal plasticity, i.e. changes in brain function related to improved neurological functioning, in an attempt to identify new therapeutic targets. Unfortunately, the functional significance of many of the brain changes observed on MRI remains unclear; it has been difficult to relate some of those changes to functional preservation and recovery. The overall aim of this thesis was to investigate changes in brain function related to motor impairment as well as functional recovery in stroke patients (measured with clinical measures and kinematics). In the first chapter we systematically review the current state of longitudinal imaging in stroke until 2008 and assess all studies according to their methodology. In the second chapter we review literature on stroke recovery and plasticity from preclinical studies in rats to RCTs in humans. The focus lied specifically on the defining what upper limb recovery entails as well as exploring what is meant in literature when neural plasticity is referred to. In the 3 experimental papers that follow upper-limb function and brain activity patterns are investigated. In general the brain seems to be quite invariant in response to initial damage beyond 5 weeks after stroke and is nicely able to substitute for residual damage either by a different use of end effector or by more subtle compensation (top down control, using more feedback, more attention). However the massive reduction in function that is seen hours after stroke is more likely not to be a result of actual neuronal damage but to be a result of functional deafferentation of all connected areas to the infarcted area. The goal of future imaging studies should be indeed clearly oriented towards understanding the difference between adaptive processes due to residual damage in the brain as well understanding spontaneous neurological recovery how much of this is alleviation of diaschisis, or some form of repair of neuronal function. What factors define what patients show recovery and what patients will not.