title: Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study.
abstract: BACKGROUND
  Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants.
  
  
  METHODS
  We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues.
  
  
  RESULTS
  While age correlated negatively with normalised penumbral volume (Kendall's τ b=-0.234, p=0.048) and lesion volume (Kendall's τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendall's τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort.
  
  
  CONCLUSIONS
  These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.
authors.affiliation: Clinical Neurosciences, University of Cambridge, Cambridge, UK. smriti.agarwal@cantab.net
authors.forename: Smriti
authors.initials: S
authors.lastname: Agarwal
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Scoffings
authors.forename: P Simon
authors.initials: PS
authors.lastname: Jones
authors.forename: S Tulasi
authors.initials: ST
authors.lastname: Marrapu
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Barry
authors.forename: Eoin W
authors.initials: EW
authors.lastname: O'Brien
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Warburton
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001810:Blood Volume; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D002533:Cerebral Angiography / Q000379:methods; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D003097:Collateral Circulation / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D008578:Meninges / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D010865:Pilot Projects; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed / Q000379:methods