title: Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.
abstract: BACKGROUND
  Recently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome.
  
  
  METHODS
  We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome.
  
  
  RESULTS
  Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome.
  
  
  CONCLUSIONS
  These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00472381.
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; CONAM, UPMC Paris 6, Inserm, U1127, CNRS, UMR 7225, Paris, France; APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle épinière, Centre de Neuro-Imagerie de Recherche (CENIR), Paris, France.
authors: Charlotte
authors: C
authors: Rosso
authors: APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Christine
authors: C
authors: Pires
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; INSERM, APHP, Centre d'Investigation Clinique CIC9503, Département des Maladies du Système Nerveux, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Jean-Christophe
authors: JC
authors: Corvol
authors: APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Flore
authors: F
authors: Baronnet
authors: APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Sophie
authors: S
authors: Crozier
authors: APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Anne
authors: A
authors: Leger
authors: APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Sandrine
authors: S
authors: Deltour
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; Institut du Cerveau et de la Moelle épinière, Centre de Neuro-Imagerie de Recherche (CENIR), Paris, France.
authors: Romain
authors: R
authors: Valabregue
authors: APHP, Service de Neuroradiologie, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Mélika
authors: M
authors: Amor-Sahli
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; CONAM, UPMC Paris 6, Inserm, U1127, CNRS, UMR 7225, Paris, France; Institut du Cerveau et de la Moelle épinière, Centre de Neuro-Imagerie de Recherche (CENIR), Paris, France; APHP, Service de Neuroradiologie, Hôpital Pitié-Salpêtrière, Paris, France.
authors: Stéphane
authors: S
authors: Lehéricy
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; APHP, Service de Neuroradiologie, Hôpital Pitié-Salpêtrière, Paris, France; COGIMAGE, UPMC Paris 6, Inserm, U1127, CNRS, UMR 7225, Paris, France.
authors: Didier
authors: D
authors: Dormont
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France; UPMC Paris 6, Inserm, U1127; CNRS, UMR 7225, Paris, France; APHP, Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Paris, France; COGIMAGE, UPMC Paris 6, Inserm, U1127, CNRS, UMR 7225, Paris, France.
authors: Yves
authors: Y
authors: Samson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000473:pathology*; D007328:Insulin / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020521:Stroke / Q000473:pathology*
chemical_list: D007328:Insulin