title: A comprehensive analysis of metabolic changes in the salvaged penumbra.
abstract: BACKGROUND
  We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery.
  
  
  METHODS
  One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5 h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24 h after stroke onset, including single-voxel, short-echo-time (30 ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area.
  
  
  RESULTS
  The concentrations of total creatine (5.39 vs 5.85 mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13 mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24 h (r (2) = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24 h (r (2) = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001).
  
  
  CONCLUSIONS
  Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24 h and greater disability at 3 months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia. andrew.bivard@newcastle.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bivard
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Nawaf
authors.initials: N
authors.lastname: Yassi
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnamurthy
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Longting
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Spratt
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Ferdi
authors.initials: F
authors.lastname: Mittef
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Neurology, John Hunter Hospital, University of Newcastle, 1/Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Parsons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D018698:Glutamic Acid; D003401:Creatine
keywords: Clinical outcome; Glutamate; Ischemic stroke; Penumbra; Spectroscopy