Explaining Plasticity after Stroke?

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

Investigating secondary white matter degeneration following ischemic stroke by modelling affected fiber tracts

Secondary white matter degeneration is a common occurrence after ischemic stroke, as identified by Diffusion Tensor Imaging (DTI). However, despite recent advances, the time course of the process is not completely understood. The primary aim of this study was to assess secondary degeneration using an approach whereby we create a patient-specific model of damaged fibers based on the volumetric characteristics of lesions. We also examined the effects of secondary degeneration along the modelled streamlines at different distances from the primary infarction using DTI. Eleven patients who presented with upper limb motor deficits at the time of a first-ever ischemic stroke were included. They underwent scanning at weeks 6 and 29 post-stroke. The fractional anisotropy (FA), mean diffusivity (MD), primary eigenvalue (λ1), and transverse eigenvalue (λ23) were measured. Using regions of interest based on the simulation output, the differences between the modelled fibers and matched contralateral areas were analyzed. The longitudinal change between the two time points and across five distances from the primary lesion was also assessed using the ratios of diffusion quantities (rFA, rMD, rλ1, and rλ23) between the ipsilesional and contralesional hemisphere. At week 6 post-stroke, significantly decreased λ1 was found along the ipsilesional corticospinal tract (CST) with a trend towards lower FA, reduced MD and λ23. At week 29 post-stroke, significantly decreased FA was shown relative to the non-lesioned side, with a trend towards lower λ1, unchanged MD, and higher λ23. Along the ipsilesional tract, the rFA diminished, whereas the rMD, rλ1, and rλ23 significantly increased over time. No significant variations in the time progressive effect with distance were demonstrated. The findings support previously described mechanisms of secondary degeneration and suggest that it spreads along the entire length of a damaged tract. Future investigations using higher-order tractography techniques can further explain the intravoxel alterations caused by ischemic injury

Mean results for Amplitude and Force tasks for the unaffected and affected hand for patients and controls.

<p>Bars show the mean beta per ROI (±1 SD) cerebellum, PM, SMA, postcentral gyrus, precentral gyrus and insula for the left (affected) and right (unaffected) hemisphere (LH, RH). Patients’ T-maps were flipped so affected hand was always the right hand.</p

Results ANOVA Differences in brain activation between and within groups.

<p>Abbreviations: F value for F-statistic, p p-value for f-statistic.</p><p>¹ = group * ROI * hemisphere interaction</p><p>² = group * ROI interaction</p><p>³ = condition * ROI * hemisphere interaction</p><p>⁴ = condition * ROI interaction</p><p>Results ANOVA Differences in brain activation between and within groups.</p

Group activation move vs. rest for 4 sessions, unaffected amplitude (UA), affected amplitude (AA), unaffected force (UF), and affected force (AF) between patients (P) and controls(C).

<p>For illustration purposes threshold was set at T>5 uncorrected.</p

Patient Characteristics.

<p>Abbreviations: TPS time post stroke, M Male, F Female, Hand Handedness (Dexterity was established by the Edinburgh Hand Inventory), R right, L left, R+ forced to write, A ambidextrous, Hem lesioned hemisphere, P pontine, C extending to cortex, SC subcortical.</p><p>*NHPT results are given as percentage of norm scores (corrected for age and handedness).</p><p>Patient Characteristics.</p

Results from analysis of data-glove data on task performance and mirror movements and scores on isometric contractions derived from EMG-data for controls.

<p>Abbreviations: EMG Electromyography, MM mirror movements, SD standard deviation, t-test student’s t test statistic, p p-value for student’s t test statistic, UA unaffected amplitude, AA affected amplitude, UF unaffected force, AF affected force, NA Data unavailable (due to malfunction of equipment), <math><mrow><mrow><mi>%</mi><mi>M</mi><mi>V</mi><mi>E</mi></mrow><mo stretchy="true">¯</mo></mrow></math> % of EMG signal during maximum voluntary contraction.</p><p>Results from analysis of data-glove data on task performance and mirror movements and scores on isometric contractions derived from EMG-data for controls.</p

Histogram of incidence of isometric contractions (MM) in the contralateral hand defined by a score consisting of the correlation of the electromyography (EMG) signal measured at the extensor muscles of the contralateral hand during the task with the task boxcar multiplied by the average % of maximal voluntary contraction (%MVE¯) (measured before the session in the scanner) of the muscle during the session.

<p>Patient-scores are depicted in black. Control-scores are depicted in grey.</p

Results from analysis of data-glove data on task performance and mirror movements and scores on isometric contractions derived from EMG-data for patients.

<p>Abbreviations: EMG Electromyography, MM mirror movements, SD standard deviation, t-test student’s t test statistic, p p-value for student’s t test statistic, UA unaffected amplitude, AA affected amplitude, UF unaffected force, AF affected force, NA Data unavailable (due to malfunction of equipment), <math><mrow><mrow><mi>%</mi><mi>M</mi><mi>V</mi><mi>E</mi></mrow><mo stretchy="true">¯</mo></mrow></math> percentage of EMG signal during maximum voluntary contraction.</p><p>Results from analysis of data-glove data on task performance and mirror movements and scores on isometric contractions derived from EMG-data for patients.</p