Recovery and prediction of hand motor function after stroke : a longitudinal study using novel methods to quantify hand function and connectivity in brain networks

Sammanfattning: Background: Stroke is a heterogeneous disease and a leading cause of physical disability among adults, severely affecting people’s health and life worldwide. According to current figures, one in four people risk suffering a stroke during their lifetime. One of the most common and enduring symptoms of stroke is unilateral weakness of the upper extremity. A key challenge in post stroke rehabilitation and research is the highly variable degree of recovery in patients and a remaining incomplete understanding of which factors contribute to this variability. This problem contributes to less effective interventions. Today’s prediction models lack precision on the individual level. Improved prediction models could assist clinicians in giving information on an individual’s expected outcome and recovery potential, and guide selection of interventions matching the specific impairment profile of the patient. Aim: The overall aim of this longitudinal prospective study was to identify key determinants for recovery of hand function after stroke by combining fine-grained measures of sensorimotor impairment and activity together with commonly used clinical scales and a multimodal neuroimaging protocol. Method and materials: Patients admitted to a regional in-patient rehabilitation department in Stockholm, Sweden, within 2-6 weeks of onset of a first time ischemic or haemorrhagic stroke and with upper extremity hemiparesis were eligible for inclusion. Exclusion criteria were inability to understand or follow instructions, disorders other than stroke affecting hand function, a cerebellar lesion, or contraindications for Magnetic Resonance Imaging (MRI) examination. Written informed consent was obtained from all participants. The study was approved by the Regional Ethical Review Board. The four Studies of this thesis were based on data collected in a prospective observational study of one study cohort, who underwent repeated assessments at three time points: ~3 weeks, 3 months and 6 months after stroke onset. Novel sensorimotor methods applied were as follows: Study I) the NeuroFlexor© for quantification of hand spasticity, Study II) the strength dexterity test for quantification of precision grip force control, Study III) the Adult Assisting Hand Assessment Stroke (Ad-AHA Stroke) for detailed characterization of bimanual activity performance and Study IV) a visuomotor grip force task for quantification of grip force modulation and force release. All studies incorporated the common comprehensive clinical assessment protocol and structural MRI, yielding a measure of corticospinal tract (CST) lesion load (wCST-LL) and Voxel based Lesion Symptom Mapping (VLSM). Resting-state functional MRI was included in studies III and IV. Results: In total n = 89 individuals with stroke were included, of whom n = 61 participated in Study I, n = 80 in Study II and all n = 89 in studies III and IV. In Study II, n = 23 healthy control subjects were included. Specific and nuanced assessments allowed delineation and understanding of the heterogeneous impairment and recovery profiles among stroke survivors, across multiple ICF levels. In Study I, subgroups of patients with divergent spasticity severity were identified. Severity of spasticity was predictive of poor hand motor recovery and development of secondary complications. In studies II and IV, evidence was found of persisting deficits in the ability to grasp and control finger and power-grip forces after stroke. In particular, force release explained unique variance in recovery of dexterous hand use over time. In studies II-IV, wCST-LL was confirmed to be a strong predictor of voluntary movement function over time, and was found to be a strong predictor of more severe hand spasticity and poorer bimanual activity performance. In Study III, a derived measure of shoulder abduction and finger extension (FMA-SAFE score) was found a strong was found to be a strong clinical marker of bimanual activity performance over time. Additional predictive factors were sensory and cognitive impairment. Resting state functional connectivity explained some additional variance in distal unimanual hand function and bimanual activity performance. Conclusions: As a whole, this thesis generated an improved understanding regarding force generation and force control functions of the hand, their interrelationship over time and relation to clinically assessed outcome and recovery after stroke. Moreover, this thesis advances our knowledge regarding longitudinal recovery and prediction of grasp and release capability. Further, this thesis provides the first detailed comparison of unimanual and bimanual recovery and their predictors after stroke. Increased understanding of factors contributing to variability in stroke recovery could contribute to development of new treatment paradigms with more specific targets for evaluation in clinical trials. This cohort represents a younger stroke population and the findings need further external validation in other age groups and in larger cohorts.