Post Stroke Brain Plasticity François CHOLLET MD, PhD Neurology Department: Stroke Unit Toulouse University Hospital (CHU) Neurosciences Institute of Toulouse CNRS, INSERM, University, CHU Versailles le 20 Juin 2013
Presenter Disclosure Information François Chollet, MD, PhD Post Stroke Brain Plasticity Consultancy for Pierre Fabre Research Institute Versailles le 20 Juin 2013
Post Stroke Brain Plasticity
Post Stroke Brain Plasticity Complex molecular phenomenons and targets for therapeutic inteventions From U Dinargl et al Trends in Neurosciences 2003
Post Stroke Brain Plasticity From animal experiments Several mechanisms in a prolonged time course Adapted from a drawing by C. Stinear
Post Stroke Brain Plasticity Exploring Recovery from stroke: A spontaneous clinical phenomenon Partial but constant or nearly constant Difficult to predict at the very acute phase Magnitude Time course rtpa only validated treatment Stroke units Brain plasticity Rationale basis for recovery mechanisms
Post Stroke Brain Plasticity Observed phenomenons after a unique single lesion of the Brain : Recruitment of remote areas and alternative networks Adaptative changes of cortical maps Overactivation of remaining cortices Individual strategies
Post Stroke Brain Plasticity Brain Plasticity : Recruitment of remote areas and alternative networks Adaptative changes of cortical maps Overactivation of remaining cortices Individual strategies Spontaneous phenomenon Limited magnitude Identified with modern neuroimaging tools Capable to be modulated? Drugs Rehabilitaion rtms, TDCS
Post Stroke Brain Plasticity Brain Plasticity: Recruitment of remote areas and alternative networks Adaptative changes of cortical maps Overactivation of remaining cortices Individual strategies Non specific of a neurological function Non specific of Stroke disease Sometimes independant from recovery. CNS and Peripheral Nervous System
Ward et al, Brain 2006
Post Stroke Brain Plasticity Time Course
Post Stroke Brain Plasticity Correlation to Recovery and Controversies Brain Plasticity and functional recovery fmri signal statistically correlated to motor scores recorded several weeks after the stroke onset, in patients undergoing recovery. Liepert et al 1998, Musso et al 1999, Nelles et al 2001, Tombari et al 2004. Respective role of recruited areas: role of the contralesional «unlesioned» cortex: controversial area
Deleterious effect of contralesional activations: in patients recovering from ischaemic stroke (Calautti et 2007, Johansen-Berg 2002, Loubinoux et al 2003, Ward et al 2003, Saur et al 2006) N. Ward and L.Cohen Arch Neurol 2004
Exploring recovery from Stroke Brain Plasticity exists in stroke recovering patients Can it be modulated? What is the role of training? What can be the role of drugs? What about SSRIs and Fluoxetine?
42 Y old, Right Handed Ischemic stroke Conduction aphasia And apraxia of speech: CASE Report: RC
Speech Rehabilitation Visual training of images naming 6weeks, 6d/7 30 images Naming : Controls: 94.5% RC before: 20% RC after: 56.7%(*)
Neuro-imaging data: Naming Control Task Controls RC Before RC after
Post Stroke Brain Plasticity Post Stroke spontaneous intra cerebral reorganization exists Post Stroke task-induced intracerebral reorganization also exists What can be the effect of monoaminergic drugs?
Methylphenidate / Placebo - Active movement Anterior cingulum «healthy» side Lesioned side Face S1M1 hand S1M1 PMC hand S1M1 P < 0.05
fluoxetine significantly improved motor skills of the affected side A single dose of fluoxetine was enough to modulate cerebral sensorymotor activation
-acute ischaemic stroke causing hemiparesia or hemiplegia. -no depression -Fugl-Meyer Motor Scale (FMMS) score -randomized between day 5 and day 10 after stroke onset.
Exploring recovery from Stroke with fmri Post Stroke spontaneous intra cerebral reorganization exists Post Stroke task-induced intracerebral reorganization exists Monoaminergic drugs (NA, 5-HT) improve motor performance and modulate brain spontaneous plasticity. Post stroke drug-induced plasticity also exists
Exploring recovery from Stroke with fmri Difficulty to image a poorly recovered neurological function with fmri New challenge: brain connectivity and changes in brain connectivity
Post Stroke Brain Plasticity Difficulty to image a poorly recovered neurological function with fmri New challenge: brain connectivity and changes in brain connectivity: Resting State Sequence
Resting State
Post Stroke Brain Plasticity Difficulty to image a poorly recovered neurological function New challenge: brain connectivity and changes in brain connectivity: Resting State Sequence Diffusion Tensor Imaging
Diffusion tensor imaging myelin DT MRI permits the measurement of water self-diffusivity and gives information about the size, shape and orientation of brain structures in vivo. axon It is an index of tissue integrity and structural connectivity. The diffusion tensor encodes the principal direction fo diffusion in every voxel: this information can be used to reconstruc WM pathways in vivo From Sabatini U Seed voxel streamline
Diffusion tractography PROJECTION Corona radiata Fornix COMMISSURAL Corpus callosum Anterior commissure ASSOCIATION Cingulum Inferior longitudinal Arcuate Uncinate Inferior fronto-occipital
Post Stroke Brain Plasticity Difficulty to image a poorly recovered neurological function with fmri New challenge: brain connectivity and changes in brain connectivity: Resting State Sequence Diffusion Tensor Imaging
1 - New neurons are recruited (Cortical plasticity) fmri 2 - New nervous pathways are recruited (Subcortical plasticity) Tractography Identify WHICH nervous pathway is used BUT Tractography is based on DTI, which is a STRUCTURAL technique The COMBINATION between BOLD-activated areas (fmri) Tractography which circuits are used
fmri - Probabilistic Tractography from RECOVERED RIGHT HAND R L BOLD-activated areas are BILATERAL Cherubini et al, 2007
Post Stroke Brain Plasticity New challenge: brain connectivity and changes in brain connectivity MRI developments Resting State Sequence Diffusion Tensor Imaging Multi-modal approach