Connectivity-Based Predictions of Hand Motor Outcome for Patients at the Subacute Stage After Stroke

No clue if any of this has a truly objective basis for predictions. Lots of big words used though. I bet your doctor can't translate this into 8th grade English either.
http://journal.frontiersin.org/article/10.3389/fnhum.2016.00101/full?

Julia Lindow¹, Martin Domin¹, Matthias Grothe², Ulrike Horn¹, Simon B. Eickhoff^3,4 and Martin Lotze^1*

• ¹Functional Imaging Unit, Center for Diagnostic Radiology, University of Greifswald, Greifswald, Germany
• ²Institute of Neurology, University of Greifswald, Greifswald, Germany
• ³Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
• ⁴Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany

Background: Connectivity-based predictions of hand motor outcome have been proposed to be useful in stroke patients. We intended to assess the prognostic value of different imaging methods on short-term (3 months) and long-term (6 months) motor outcome after stroke.
Methods: We measured resting state functional connectivity (rsFC), diffusion weighted imaging (DWI) and grip strength in 19 stroke patients within the first days (5–9 days) after stroke. Outcome measurements for short-term (3 months) and long-term (6 months) motor function was assessed by the Motricity Index (MI) of the upper limb and the box and block test (BB). Patients were predominantly mildly affected since signed consent was necessary at inclusion. We performed a multiple stepwise regression analysis to compare the predictive value of rsFC, DWI and clinical measurements.
Results: Patients showed relevant improvement in both motor outcome tests. As expected grip strength at inclusion was a predictor for short- and long-term motor outcome as assessed by MI. Diffusion-based tract volume (DTV) of the tracts between ipsilesional primary motor cortex and contralesional anterior cerebellar hemisphere showed a strong trend (p = 0.05) for a predictive power for long-term motor outcome as measured by MI. DTV of the interhemispheric tracts between both primary motor cortices was predictive for both short- and long-term motor outcome in BB. rsFC was not associated with motor outcome.
Conclusions: Grip strength is a good predictor of hand motor outcome concerning strength-related measurements (MI) for mildly affected subacute patients. Therefore additional connectivity measurements seem to be redundant in this group. Using more complex movement recruiting bilateral motor areas as an outcome parameter, DTV and in particular interhemispheric pathways might enhance predictive value of hand motor outcome.

Introduction

Stroke is the leading cause of adult disability worldwide, leaving a majority of patients with lingering upper limb impairment (World Health Organization, 2012). Knowing more about motor outcome would be advantageous to achieve the best results in rehabilitation. For long-term motor outcome prediction, parameters are needed that can be assessed within the first days, when patients are in the acute care units.

Functional magnetic resonance imaging (fMRI) raised high expectations because functional representation of movements can be assessed longitudinally in vivo. However, activation fMRI protocols are demanding and patients’ compliance is difficult to control for. In contrast, resting state fMRI (rs-fMRI) requires little compliance and can therefore be conducted comparable to structural MRI in the acute (0–24 h after stroke onset) to subacute (24 h to 6 weeks after stroke) phase after stroke (Di Pino et al., 2014). Especially rs-fMRI functional connectivity (FC) between cortical motor areas has been described to be associated with motor impairment (Carter et al., 2010). Astonishingly, only a low number of studies examined the prognostic value of resting-state functional connectivity (rsFC) for motor outcome in acute stroke patients.

To date the best predictor of later hand motor outcome is the initially measured hand motor impairment. Especially the Fugl-Meyer test (Sanford et al., 1993) has been described as a valuable predictor of hand motor outcome for 2, 6 and 12 months after stroke for mildly to moderately impaired patients (Feys et al., 2000). Likewise the active motion range is known to be a good predictor of short-term (3 months; Beebe and Lang, 2009) and long-term (6 months; Smania et al., 2007) hand motor outcome.

In more severely affected stroke patients, the intactness of the corticospinal tract (CST), as tested with diffusion weighted imaging (DWI) is useful for the prediction of hand motor outcome (Lindenberg et al., 2012; Stinear et al., 2012; Groisser et al., 2014; Byblow et al., 2015). TMS-measures such as the asymmetry index of hand muscle motor evoked potentials is a clinically well suited predictive method for describing motor outcome in patients after stroke (e.g., Stinear et al., 2012; Byblow et al., 2015). At the subacute phase, a positive association between fractional anisotropy (FA) measured at the height of the posterior limb of the internal capsule of the ipsilesional side and hand motor performance has been shown (Jang et al., 2005; Konishi et al., 2005; Nelles et al., 2008; Byblow et al., 2015). Most authors used FA as well as axial and radial diffusivity for quantification of intactness of the CST. When comparing the predictive value of these measurements, differences in axial diffusivity of the pyramidal tract from the ipsilesional to the contralesional hemisphere at the acute phase had the highest association with 3 and 6 months motor outcome of grip strength and nine hole peg test (NHPT) in a sample of 10 initially strongly impaired stroke patients (Groisser et al., 2014). Probabilistic tractography methods using the DWI data are capable of reconstructing diffusion pathways over long distances even when fibers are crossing (Lindenberg et al., 2010). We thought that the possibility to find alterations among long anatomical pathways might be advantageous for predicting motor outcome even in less severely impaired patients.

Carter et al. (2012a,b) assessed connectivity approaches as a promising method for understanding the impact of cerebral lesions on motor function and its restitution. Consequently, they combined DWI of the CST with FC measurements as assessed by rs-fMRI. For rs-fMRI positive associations with motor performance at the chronic phase after stroke (>6 weeks after stroke; Di Pino et al., 2014) have been described between homotopic motor areas of the affected and the unaffected side indicating that more “balanced” activity between hemispheres is associated with better upper-limb control (Urbin et al., 2014). For rs-fMRI two studies describe a positive association between homolog motor areas between both hemispheres and motor performance (Carter et al., 2010, 2012a). However, both did not measure future motor outcome using resting state connectivity but performed only correlative measurements assessed at about the same time. Overall, stroke patients with motor impairment show decreased interhemispheric M1-connectiviy and increased resting-state connectivity between ipsilesional M1 and secondary motor areas particularly in the ipsilesional hemisphere (Rehme et al., 2015). Over a period of 3 months the reduced interhemispheric M1 rsFC normalizes (Golestani et al., 2013). To date only one study has applied longitudinal motor outcome measurements to investigate the value of rsFC for predicting motor outcome. Park et al. (2011) investigated rs-fMRI in 12 subacute stroke patients and found a positive association between 6 months motor outcome measured with Fugl-Meyer-Score and rsFC of the ipsilesional M1 with the contralesional thalamus, supplementary motor area (SMA), and medial frontal gyrus.

The present study examined the prognostic value of motor (grip strength, NHPT), and clinical (NIH stroke scale; NIHSS) scores, DWI of long tracts and rs-FC for patients at the subacute stage with predominantly only mild unilateral brain damage. We used two different motor outcome scores: the motricity index (MI) for upper limb and the box and block test (BB) to examine separate aspects of upper limb function namely strength (MI), and hand grip transfer (BB). We hypothesized that intactness of long tracts, would be a predictor for both scores. However, hand strength is represented unilaterally, whereas grip transfer recruits bilateral resources from both hemispheres (Lotze et al., 2012). More bilateral activation might involve increased information transfer (inhibitory or excitatory) via the corpus callosum between both primary motor cortices (M1). Therefore we hypothesized that integrity of interhemispheric fibers would be better predictors for BB, whereas CST integrity might be a better predictor for MI. In addition, we expected lower rsFC between ipsilesional primary motor cortex and contralesional secondary motor areas (SMA, dorsal premotor cortex, dPMC) to be associated with better motor outcome (MI and BB; Wang et al., 2010).