Neurophysiological Characterization of Subacute Stroke Patients: A Longitudinal Study

Nowhere in here do they use objective brain scans to try to predict recovery. When will that occur?
http://journal.frontiersin.org/article/10.3389/fnhum.2016.00574/full?

Giuseppe Lamola¹, Chiara Fanciullacci^1,2, Giada Sgherri¹, Federica Bertolucci¹, Alessandro Panarese², Silvestro Micera^2,3, Bruno Rossi¹ and Carmelo Chisari^1*

• ¹Unit of Neurorehabilitation, Department of Neuroscience, University of Pisa, Pisa, Italy
• ²The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
• ³Translational Neural Engineering Lab, Center for Neuroprosthetics, Lausanne, Switzerland

Various degrees of neural reorganization may occur in affected and unaffected hemispheres in the early phase after stroke and several months later. Recent literature suggests to apply a stratification based on lesion location and to consider patients with cortico-subcortical and subcortical strokes separately: different lesion location may also influence therapeutic response. In this study we used a longitudinal approach to perform TMS assessment (Motor Evoked Potentials, MEP, and Silent Period, SP) and clinical evaluations (Barthel Index, Fugl-Meyer Assessment for upper limb motor function and Wolf Motor Function Test) in 10 cortical-subcortical and 10 subcortical ischemic stroke patients. Evaluations were performed in a window between 10 and 45 days (t0) and at 3 months after the acute event (t1). Our main finding is that 3 months after the acute event patients affected by subcortical stroke presented a reduction in contralateral SP duration in the unaffected hemisphere; this trend is related to clinical improvement of upper limb motor function. In conclusion, SP proved to be a valid parameter to characterize cortical reorganization patterns in stroke survivors and provided useful information about motor recovery within 3 months in subcortical patients.

Introduction

New frontiers in stroke rehabilitation aim to improve functional recovery taking advantage from the knowledge of mechanisms of cortical reorganization that occur after the acute event (Schaechter, 2004), the so-called “top-down” approach (Chisari, 2015). Literature findings have provided insight into the mechanisms of behavioral rehabilitation techniques, such as constraint-induced movement therapy (Liepert, 2006), and have led to the development of cortical stimulation protocols to improve upper limb recovery (Ward and Cohen, 2004; Nowak et al., 2008; Chisari et al., 2014). The main hypothesis is that an imbalanced inter-hemispheric inhibition occurs following stroke, so the purpose of various rehabilitation approaches is to increase excitability of perilesional intact regions of the affected hemisphere and/or to decrease excitability of the contralesional hemisphere (Hummel and Cohen, 2006; Nowak et al., 2009). Anyway, until now still no customized treatment has been proposed strictly based on the correlations between neurophysiological and functional evaluations.

Transcranial magnetic stimulation (TMS) is a valid tool to obtain data about cortical reorganization (Rossini et al., 2003). TMS is currently used to elicit motor evoked potential (MEP), recorded by surface electromyography (EMG). MEP presence, as a measure of cortical excitability changes and corticospinal tract integrity, offers useful prognostic information about functional outcome (Hendricks et al., 2002; Brouwer and Schryburt-Brown, 2006; Pizzi et al., 2009; Stinear et al., 2014). In pre-activated muscles, TMS may also induce a transient suppression of the EMG-activity after MEP, the so-called silent period (SP) (Kukowski and Haug, 1991; Uozumi et al., 1992), as an inhibitory effect. SP is reported to be abnormally increased in the paretic hand after a stroke (Haug and Kukowski, 1994; Braune and Fritz, 1996; Harris-Love et al., 2016) and tend to decrease with motor recovery. To date, studies on the role of the SP in predicting motor recovery after severe stroke showed rather inconsistent results (van Kuijk et al., 2005, 2014).

Starting from the study conducted by Liepert et al. (2005) the impact of lesion location on motor excitability and motor performance was investigated. The authors evaluated patients with pure motor strokes in four different brain areas (motor cortex lesions, striatocapsular lesions, lacunar lesions of the internal capsule and paramedian pontine lesions), concluding that lesion location determines a specific pattern of motor excitability changes. Recently Thickbroom et al. (2015) highlighted that both the anatomical level of the lesion and to the degree of paretic motor impairment are related cortical excitability and reorganization after stroke. These findings suggest that rehabilitative trials should stratify patients basing on lesion type.

Coupar et al. (2011) also suggest that integrating early clinical data with neurophysiological measurements could be useful to predict long-term recovery and outcome. A remarkable example is the study conducted by Di Lazzaro et al. (2010), which evaluated whether long-term potentiation (LTP)- and long-term depression (LTD)-like changes produced by intermittent theta burst stimulation (iTBS) in acute stroke correlate with outcome at 6 months. They recruited ischemic stroke patients (both with cortical and subcortical lesions) in the first 10 days after stroke, finding that functional recovery is directly correlated with LTP-like changes in affected hemisphere (AH) and LTD-like changes in unaffected hemisphere (UH) and inversely correlated with the baseline excitability of UH. Nevertheless, it is suitable to underline that neurophysiological data during early period post-stroke may suffer from wide inter-subject variability. In particular, Swayne et al. (2008) found that day-to-day variation in clinical performance was unrelated to physiological measures in the first days after the acute event.

Following these considerations our hypothesis was that different stroke lesion location may imply differences in the mechanisms of brain reorganization that lead motor recovery in subacute phase. Our aim was to identify neurophysiological parameters that can be used as markers to describe motor recovery and as factors to guide neurorehabilitation treatment in subacute stroke patients with different lesions.

For this reason we correlated neurophysiological and functional features in a cohort of stroke patients recruited in a specific time window from the acute event and subdivided in cortico-subcortical and subcortical strokes; evaluations were also performed at 3 months after stroke to monitor changes in brain reorganization and clinical behavior.