title: Are we armed with the right data? Pooled individual data review of biomarkers in people with severe upper limb impairment after stroke.
abstract: To build an understanding of the neurobiology underpinning arm recovery in people with severe arm impairment due to stroke, we conducted a pooled individual data systematic review to: 1) characterize brain biomarkers; 2) determine relationship(s) between biomarkers and motor outcome; and 3) establish relationship(s) between biomarkers and motor recovery. Three electronic databases were searched up to October 2, 2015. Eligible studies included adults with severe arm impairment after stroke. Descriptive statistics were calculated to characterize brain biomarkers, and pooling of individual patient data was performed using mixed-effects linear regression to examine relationships between brain biomarkers and motor outcome and recovery. Thirty-eight articles including individual data from 372 people with severe arm impairment were analysed. The majority of individuals were in the chronic (> 6 months) phase post stroke (51%) and had a subcortical stroke (49%). The presence of a motor evoked potential (indexed by transcranial magnetic stimulation) was the only biomarker related to better motor outcome (p= 0.02). There was no relationship between motor outcome and stroke volume (cm3), location (cortical, subcortical, mixed) or side (left vs. right), and corticospinal tract asymmetry index (extracted from diffusion weighted imaging). Only one study had longitudinal data, thus no data pooling was possible to address change over time (preventing our third objective). Based on the available evidence, motor evoked potentials at rest were the only biomarker that predicted motor outcome in individuals with severe arm impairment following stroke. Given that few biomarkers emerged, this review highlights the need to move beyond currently known biomarkers and identify new indices with sufficient variability and sensitivity to guide recovery models in individuals with severe motor impairments following stroke.
  
  
  
  CRD42015026107.
authors.affiliation: Department of Physical Therapy, University of British Columbia, Vancouver, Canada; Stroke Division, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; NHMRC Center of Research Excellence in Stroke Rehabilitation and Brain Recovery, Australia.
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Hayward
authors.affiliation: Department of Physical Therapy, University of British Columbia, Vancouver, Canada; College of Science Health and Engineering, La Trobe University, Melbourne, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: School of Kinesiology, Auburn University, Auburn, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Lohse
authors.affiliation: Department of Physical Therapy, University of British Columbia, Vancouver, Canada.
authors.forename: Sue
authors.initials: S
authors.lastname: Peters
authors.affiliation: Stroke Division, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia; NHMRC Center of Research Excellence in Stroke Rehabilitation and Brain Recovery, Australia; College of Science Health and Engineering, La Trobe University, Melbourne, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Bernhardt
authors.affiliation: College of Science Health and Engineering, La Trobe University, Melbourne, Australia; Occupational Therapy Department, Alfred Health, Melbourne, Australia.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Lannin
authors.affiliation: Department of Physical Therapy, University of British Columbia, Vancouver, Canada; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Boyd
mesh_terms: D015415:Biomarkers; D019054:Evoked Potentials, Motor / Q000502:physiology*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D020521:Stroke / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000706:statistics & numerical data*; D034941:Upper Extremity / Q000503:physiopathology*
chemical_list: D015415:Biomarkers
keywords: Biomarker; Neuroimaging; Neurophysiology; Stroke; Upper extremity