Posts Tagged biomarker

[ARTICLE] Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable – Full Text

In practical terms, biomarkers should improve our ability to predict long-term outcomes after stroke across multiple domains. This is beneficial for: (a) patients, caregivers and clinicians; (b) planning subsequent clinical pathways and goal setting; and (c) identifying whom and when to target, and in some instances at which dose, with interventions for promoting stroke recovery.2 This last point is particularly important as methods for accurate prediction of long-term outcome would allow clinical trials of restorative and rehabilitation interventions to be stratified based on the potential for neurobiological recovery in a way that is currently not possible when trials are performed in the absence of valid biomarkers. Unpredictable outcomes after stroke, particularly in those who present with the most severe impairment3 mean that clinical trials of rehabilitation interventions need hundreds of patients to be appropriately powered. Use of biomarkers would allow incorporation of accurate information about the underlying impairment, and thus the size of these intervention trials could be considerably reduced,4 with obvious benefits. These principles are no different in the context of stroke recovery as compared to general medical research.5

Interventions fall into two broad mechanistic categories: (1) behavioural interventions that take advantage of experience and learning-dependent plasticity (e.g. motor, sensory, cognitive, and speech and language therapy), and (2) treatments that enhance the potential for experience and learning-dependent plasticity to maximise the effects of behavioural interventions (e.g. pharmacotherapy or non-invasive brain stimulation).6 To identify in whom and when to intervene, we need biomarkers that reflect the underlying biological mechanisms being targeted therapeutically.

Our goal is to provide a consensus statement regarding the evidence for SRBs that are helpful in outcome prediction and therefore identifying subgroups for stratification to be used in trials.7 We focused on SRBs that can investigate the structure or function of the brain (Table 1). Four functional domains (motor, somatosensation, cognition, and language (Table 2)) were considered according to recovery phase post stroke (hyperacute: <24 h; acute: 1 to 7 days; early subacute: 1 week to 3 months; late subacute: 3 months to 6 months; chronic: > 6 months8). For each functional domain, we provide recommendations for biomarkers that either are: (1) ready to guide stratification of subgroups of patients for clinical trials and/or to predict outcome, or (2) are a developmental priority (Table 3). Finally, we provide an example of how inclusion of a clinical trial-ready biomarker might have benefitted a recent phase III trial. As there is generally limited evidence at this time for blood or genetic biomarkers, we do not discuss these, but recommend they are a developmental priority.912 We also recognize that many other functional domains exist, but focus here on the four that have the most developed science. […]

Continue —> Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation RoundtableInternational Journal of Stroke – Lara A Boyd, Kathryn S Hayward, Nick S Ward, Cathy M Stinear, Charlotte Rosso, Rebecca J Fisher, Alexandre R Carter, Alex P Leff, David A Copland, Leeanne M Carey, Leonardo G Cohen, D Michele Basso, Jane M Maguire, Steven C Cramer, 2017

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[ARTICLE] Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function – Full Text

What determines motor recovery in stroke is still unknown and finding markers that could predict and improve stroke recovery is a challenge. In this study, we aimed at understanding the neural mechanisms of motor function recovery after stroke using neurophysiological markers by means of cortical excitability (Transcranial Magnetic Stimulation – TMS) and brain oscillations (electroencephalography – EEG). In this cross-sectional study, fifty-five subjects with chronic stroke (62±14 yo, 17 women, 32±42 months post-stroke) were recruited in two sites. We analyzed TMS measures (i.e. motor threshold – MT – of the affected and unaffected sides) and EEG variables (i.e. power spectrum in different frequency bands and different brain regions of the affected and unaffected hemispheres) and their correlation with motor impairment as measured by Fugl-Meyer. Multiple univariate and multivariate linear regression analyses were performed to identify the predictors of good motor function. A significant interaction effect of MT in the affected hemisphere and power in beta bandwidth over the central region for both affected and unaffected hemispheres was found. We identified that motor function positively correlates with beta rhythm over the central region of the unaffected hemisphere, while it negatively correlates with beta rhythm in the affected hemisphere. Our results suggest that cortical activity in the affected and unaffected hemisphere measured by EEG provides new insights on the association between high frequency rhythms and motor impairment, highlighting the role of excess of beta in the affected central cortical region in poor motor function in stroke recovery.

Introduction

Stroke is a leading cause of morbidity, mortality, and disability worldwide (12). Among the sequels of stroke, motor impairment is one of the most relevant, since it conditions the quality of life of patients, it reduces their capability to perform their daily activities and it impairs their autonomy (3). Despite the advancements of the acute stroke therapy, patients require an intensive rehabilitation program that will partially determine the extent of their recovery (4). These rehabilitation programs aim at stimulating cortical plasticity to improve motor performance and functional recovery (5). However, what determines motor improvement is still unknown. Indeed, finding markers that could predict and enhance stroke recovery is still a challenge (6). Different types of biomarkers exist: diagnostic, prognostic, surrogate outcome, and predictive biomarkers (7). The identification of these biomarkers is critical in the management of stroke patients. In the field of stroke research, great attention has been put to biomarkers found in the serum, especially in acute care. However, research on biomarkers of stroke recovery is still limited, especially using neurophysiological tools.

A critical research area in stroke is to understand the neural mechanisms underlying motor recovery. In this context, neurophysiological techniques such as transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are useful tools that could be used to identify potential biomarkers of stroke recovery. However, there is still limited data to draw further conclusions on neural reorganization in human trials using these techniques. A few studies have shown that, in acute and sub-acute stage, stroke patients present increased power in low frequency bands (i.e., delta and theta bandwidths) in both affected and unaffected sides, as well as increased delta/alpha ratio in the affected brain area; these patterns being also correlated to functional outcome (811). Recently, we have identified that, besides TMS-indexed motor threshold (MT), an increased excitability in the unaffected hemisphere, coupled with a decreased excitability in the affected hemisphere, was associated with poor motor function (12), as measured by Fugl-Meyer (FM) [assessing symptoms severity and motor recovery in post-stroke patients with hemiplegia—Fugl-Meyer et al. (13); Gladstone et al. (14)]. However, MT measurement is associated with a poor resolution as it indexes global corticospinal excitability. Therefore, combining this information with direct cortical measures such as cortical oscillations, as measured by EEG, can help us to understand further neural mechanisms of stroke recovery.

To date, there are very few studies looking into EEG and motor recovery. For that reason, we aimed, in the present study, to investigate the relationship between motor impairment, EEG, and TMS variables. To do so, we conducted a prospective multicenter study of patients who had suffered from a stroke, in which we measured functional outcome using FM and performed TMS and EEG recordings. Based on our preliminary work, we expected to identify changes in interhemispheric imbalances on EEG power, especially in frequency bands associated with learning, such as alpha and beta bandwidths. […]

Continue —> Frontiers | Using Brain Oscillations and Corticospinal Excitability to Understand and Predict Post-Stroke Motor Function | Neurology

Figure 1. Topoplots showing the topographic distribution of high-beta bandwidth (25 Hz) for every individual. Red areas represent higher high-beta activity, while blue areas represent lower high-beta activity. Central region (C3 or C4) in red stands for the affected side. For patients with poor motor function, a higher beta activity of the affected central region as compared to the affected side is observed in 16 out of 28 individuals. For patients with good motor function, a similar activity over central regions bilaterally, or higher activity over the unaffected central area can be identified in 21 out of 27 individuals. FM = Fugl-Meyer.

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