Metabolic Encephalopathy Stroke – Clinical Features

  • Svetlana Pundik
  • Jose I. Suarez


Stroke research has been the subject of increased attention in recent years. As a result, significant progress has been made in the understanding of the mechanisms of ischemic injury and development of potential methods of treatment. Unfortunately, only one therapy has been shown to be of benefit for acute ischemic stroke patients in a randomized controlled clinical trial: intravenous administration of recombinant tissue plasminogen activator (rt-PA) (The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (NINDS), 1995). Clinical and basic scientists have been contemplating the reasons for the failure to translate a large number of potential treatments into clinical practice. There are a number of possible explanations that include heterogeneity of human disease, and inherent species-related differences. In contrast to animal models where subjects have similar genetic material and undergo identical procedures, human stroke patients vary in their co-morbidities, age, risk factors, type and location of stroke, duration and severity of ischemia, among other things. Interestingly, the factors that contribute to the heterogeneity of human stroke play a significant role in the reversibility of ischemic injury (Table 5.1). We will discuss in this chapter some of the aspects that are associated with the ability of the brain tissue to improve its function following ischemia as it is seen in clinical practice.


Cerebral Blood Flow Acute Stroke Thrombolytic Therapy Hemorrhagic Transformation Recombinant Tissue Plasminogen Activator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. H.P., Adams, Jr., del Zoppo, G., M.J., Alberts, D.L., Bhatt, L., Brass, A., Furlan, R.L., Grubb, R.T., Higashida, E.C., Jauch, C., Kidwell, P.D., Lyden, L.B., Morgenstern, A.I., Qureshi, R.H., Rosenwasser, P.A., and Scott, E.F. Wijdicks, (2007): Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke, 38:1655–1711.PubMedCrossRefGoogle Scholar
  2. G.W., Albers, V.N., Thijs, L., Wechsler, S., Kemp, G., Schlaug, E., Skalabrin, R., Bammer, W., Kakuda, M.G., Lansberg, A., Shuaib, W., Coplin, S., Hamilton, M., and Moseley, M.P. Marks, (2006): Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann. Neurol., 60:508–517.PubMedCrossRefGoogle Scholar
  3. A.V., Alexandrov, S.E., Black, L.E., Ehrlich, C.B., and Caldwell, J.W. Norris, (1997): Predictors of hemorrhagic transformation occurring spontaneously and on anticoagulants in patients with acute ischemic stroke. Stroke, 28:1198–1202.PubMedCrossRefGoogle Scholar
  4. A.V., Alexandrov, W.S., Burgin, A.M., Demchuk, A., and El Mitwalli, J.C. Grotta, (2001): Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy: sonographic classification and short-term improvement. Circulation, 103:2897–2902.PubMedCrossRefGoogle Scholar
  5. J., Alvarez-Sabin, C.A., Molina, J., Montaner, J.F., Arenillas, R., Huertas, M., Ribo, A., and Codina, M. Quintana, (2003): Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator—treated patients. Stroke, 34:1235–1241.PubMedCrossRefGoogle Scholar
  6. G., Azzimondi, L., Bassein, F., Nonino, L., Fiorani, L., Vignatelli, G., and Re, R. D’Alessandro, (1995): Fever in acute stroke worsens prognosis. A prospective study. Stroke, 26:2040–2043.PubMedCrossRefGoogle Scholar
  7. E., Bandera, M., Botteri, C., Minelli, A., Sutton, K.R., and Abrams, N. Latronico, (2006): Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke, 37:1334–1339.PubMedCrossRefGoogle Scholar
  8. E., Beghi, G., Bogliun, G., Cavaletti, I., Sanguineti, M., Tagliabue, F., and Agostoni, I. Macchi, (1989): Hemorrhagic infarction: risk factors, clinical and tomographic features, and outcome. A case-control study. Acta Neurol. Scand., 80:226–231.PubMedCrossRefGoogle Scholar
  9. C., Brekenfeld, L., Remonda, K., Nedeltchev, F., Bredow, C., Ozdoba, R., Wiest, M., Arnold, H.P., and Mattle, G. Schroth, (2005): Endovascular neuroradiological treatment of acute ischemic stroke: techniques and results in 350 patients. Neurol.Res., 27 Suppl 1:S29–S35PubMedCrossRefGoogle Scholar
  10. J.P., Broderick, T., Hagen, T. Brott, T., and Tomsick, (1995): Hyperglycemia and hemorrhagic transformation of cerebral infarcts. Stroke, 26:484–487.PubMedCrossRefGoogle Scholar
  11. J., Castillo, R., Leira, M.M., Garcia, J., Serena, M., and Blanco, A. Davalos, (2004): Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke, 35:520–526.PubMedCrossRefGoogle Scholar
  12. I., Christou, A.V., Alexandrov, W.S., Burgin, A.W., Wojner, R.A., Felberg, M., and Malkoff, J.C. Grotta, (2000): Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke. Stroke, 31:1812–1816.PubMedCrossRefGoogle Scholar
  13. W.M., Clark, S., Wissman, G.W., Albers, J.H., Jhamandas, K.P., and Madden, S. Hamilton, (1999): Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA, 282:2019–2026.PubMedCrossRefGoogle Scholar
  14. P.A., Clavien, M., Selzner, H.A., Rudiger, R., Graf, Z., Kadry, V., and Rousson, W. Jochum, (2003): A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann. Surg., 238:843–850.PubMedCrossRefGoogle Scholar
  15. B., Eckert, C., Koch, G., Thomalla, T., Kucinski, U., Grzyska, J., Roether, K., Alfke, O., and Jansen, H. Zeumer, (2005): Aggressive therapy with intravenous abciximab and intra-arterial rtPA and additional PTA/stenting improves clinical outcome in acute vertebrobasilar occlusion: combined local fibrinolysis and intravenous abciximab in acute vertebrobasilar stroke treatment (FAST): results of a multicenter study. Stroke, 36:1160–1165.PubMedCrossRefGoogle Scholar
  16. H., Ehrenreich, M., Hasselblatt, C., Dembowski, L., Cepek, P., Lewczuk, M., Stiefel, H.H., Rustenbeck, N., Breiter, S., Jacob, F., Knerlich, M., Bohn, W., Poser, E., Ruther, M., Kochen, O., Gefeller, C., Gleiter, T.C., Wessel, M., De Ryck, L., Itri, H., Prange, A., Cerami, M., and Brines, A.L. Siren, (2002): Erythropoietin therapy for acute stroke is both safe and beneficial. Mol. Med., 8:495–505.PubMedGoogle Scholar
  17. S.T., Engelter, L.H., and Bonati, P.A. Lyrer, (2006): Intravenous thrombolysis in stroke patients of > or = 80 versus <80 years of age — A systematic review across cohort studies. Age Ageing, 35:572–580.PubMedCrossRefGoogle Scholar
  18. S. and Ghosh, M. Galinanes, (2003): Protection of the human heart with ischemic preconditioning during cardiac surgery: role of cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg., 126:133–142.PubMedCrossRefGoogle Scholar
  19. J.M. Gidday, (2006): Cerebral preconditioning and ischaemic tolerance. Nat. Rev. Neurosci., 7:437–448.PubMedCrossRefGoogle Scholar
  20. L., Gisselsson, M.L., and Smith, B.K. Siesjo, (1999): Hyperglycemia and focal brain ischemia. J. Cereb. Blood Flow Metab., 19:288–297.PubMedCrossRefGoogle Scholar
  21. W., Hacke, M., Kaste, C., Fieschi, von Kummer, R., A., Davalos, D., Meier, V., Larrue, E., Bluhmki, S., Davis, G., Donnan, D., Schneider, E., and Diez-Tejedor, P. Trouillas, (1998): Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet, 352:1245–1251.PubMedCrossRefGoogle Scholar
  22. S.I. and Harik, J.C. LaManna, (1988): Vascular perfusion and blood-brain glucose transport in acute and chronic hyperglycemia. J. Neurochem., 51:1924–1929.PubMedCrossRefGoogle Scholar
  23. Hypothermia after Cardiac Arrest Study Group (2002): Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N. Engl. J. Med., 346:549–556.Google Scholar
  24. IMS Study Investigators (2004): Combined intravenous and intra-arterial recanalization for acute ischemic stroke: The Interventional Management of Stroke Study. Stroke, 35:904–911.Google Scholar
  25. K.C., Johnston, A.F., Connors, Jr., D.P., Wagner, W.A., Knaus, X., and Wang, E.C., Haley, Jr. (2000): A predictive risk model for outcomes of ischemic stroke. Stroke, 31:448–455.PubMedCrossRefGoogle Scholar
  26. K.C., Johnston, D.P., Wagner, E.C., Haley, Jr., andA.F., Connors, Jr. (2002): Combined clinical and imaging information as an early stroke outcome measure. Stroke, 33:466–472.PubMedCrossRefGoogle Scholar
  27. S.C. Johnston, (2004): Ischemic preconditioning from transient ischemic attacks? Data from the Northern California TIA Study. Stroke, 35:2680–2682.PubMedCrossRefGoogle Scholar
  28. T.H., Jones, R.B., Morawetz, R.M., Crowell, F.W., Marcoux, S.J., FitzGibbon, U., and DeGirolami, R.G. Ojemann, (1981): Thresholds of focal cerebral ischemia in awake monkeys. J. Neurosurg., 54:773–782.PubMedCrossRefGoogle Scholar
  29. H., Kamada, F., Yu, C., and Nito, P.H. Chan, (2007): Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood-brain barrier dysfunction. Stroke, 38:1044–1049.PubMedCrossRefGoogle Scholar
  30. L.P., Kammersgaard, H.S., Jorgensen, J., Reith, H., Nakayama, P.M., and Pedersen, T.S. Olsen, (2004): Short- and long-term prognosis for very old stroke patients. The Copenhagen Stroke Study. Age Ageing, 33:149–154.PubMedCrossRefGoogle Scholar
  31. R.K., Kharbanda, U.M., Mortensen, P.A., White, S.B., Kristiansen, M.R., Schmidt, J.A., Hoschtitzky, M., Vogel, K., Sorensen, A.N., and Redington, R. MacAllister, (2002): Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation, 106:2881–2883.PubMedCrossRefGoogle Scholar
  32. C.S., Kidwell, J.L., Saver, J., Carneado, J., Sayre, S., Starkman, G., Duckwiler, Y.P., Gobin, R., Jahan, P., Vespa, J.P., Villablanca, D.S., and Liebeskind, F. Vinuela, (2002): Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke, 33:717–724.PubMedCrossRefGoogle Scholar
  33. T. Kirino, (2002): Ischemic tolerance. J. Cereb. Blood Flow Metab., 22:1283–1296.PubMedCrossRefGoogle Scholar
  34. T., Kucinski, C., Koch, B., Eckert, V., Becker, H., Kromer, C., Heesen, U., Grzyska, H.J., Freitag, J., and Rother, H. Zeumer, (2003): Collateral circulation is an independent radiological predictor of outcome after thrombolysis in acute ischaemic stroke. Neuroradiology, 45:11–18.PubMedGoogle Scholar
  35. D.H., Lee, K.D., Jo, H.G., Kim, S.J., Choi, S.M., Jung, D.S., and Ryu, M.S. Park, (2002): Local intraarterial urokinase thrombolysis of acute ischemic stroke with or without intravenous abciximab: a pilot study. J. Vasc. Interv. Radiol., 13:769–774.PubMedCrossRefGoogle Scholar
  36. R., Leigh, O.O., Zaidat, M.F., Suri, G., Lynch, S., Sundararajan, J.L., Sunshine, R., Tarr, W., Selman, D.M., and Landis, J.I. Suarez, (2004): Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy. Stroke, 35:1903–1907.PubMedCrossRefGoogle Scholar
  37. D.S. Liebeskind, (2005): Collaterals in acute stroke: beyond the clot. Neuroimaging Clin. N. Am., 15:553–573, x.PubMedCrossRefGoogle Scholar
  38. P., Lyden, T., Brott, B., Tilley, K.M., Welch, E.J., Mascha, S., Levine, E.C., Haley, J., and Grotta, J. Marler, (1994): Improved reliability of the NIH stroke scale using video training. NINDS TPA Stroke Study Group. Stroke, 25:2220–2226.PubMedCrossRefGoogle Scholar
  39. S.N., Macciocchi, P.T., Diamond, W.M., and Alves, T. Mertz, (1998): Ischemic stroke: relation of age, lesion location, and initial neurologic deficit to functional outcome. Arch.Phys.Med.Rehabil., 79:1255–1257.PubMedCrossRefGoogle Scholar
  40. J. and Maher, V. Hachinski, (1993): Hypothermia as a potential treatment for cerebral ischemia. Cerebrovasc. Brain Metab. Rev., 5:277–300.PubMedGoogle Scholar
  41. S.R. and Martini, T.A. Kent, (2007): Hyperglycemia in acute ischemic stroke: a vascular perspective. J. Cereb. Blood Flow Metab., 27:435–451.PubMedCrossRefGoogle Scholar
  42. N.M., Menezes, H., Ay, Z.M., Wang, C.J., Lopez, A.B., Singhal, J.O., Karonen, H.J., Aronen, Y., Liu, J., Nuutinen, W.J., and Koroshetz, A.G. Sorensen, (2007): The real estate factor: quantifying the impact of infarct location on stroke severity. Stroke, 38:194–197.PubMedCrossRefGoogle Scholar
  43. J., Moncayo, de Freitas, G.R., J., Bogousslavsky, M., and Altieri, van Melle, G. (2000): Do transient ischemic attacks have a neuroprotective effect? Neurology, 54:2089–2094.PubMedCrossRefGoogle Scholar
  44. M. Nedergaard, (1987): Transient focal ischemia in hyperglycemic rats is associated with increased cerebral infarction. Brain Res., 408:79–85.PubMedCrossRefGoogle Scholar
  45. J.P., Nolan, P.T., Morley, Vanden Hoek, T.L., R.W., Hickey, W.G., Kloeck, J., Billi, B.W., Bottiger, P.T., Morley, J.P., Nolan, K., Okada, C., Reyes, M., Shuster, P.A., Steen, M.H., Weil, V., Wenzel, R.W., Hickey, P., Carli, Vanden Hoek, T.L., and D. Atkins, (2003): Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation, 108:118–121.PubMedCrossRefGoogle Scholar
  46. R., Noor, C.X., and Wang, A. Shuaib, (2003): Effects of hyperthermia on infarct volume in focal embolic model of cerebral ischemia in rats. Neurosci. Lett., 349:130–132.PubMedCrossRefGoogle Scholar
  47. T.K., Nordt, K.J., Klassen, D.J., and Schneider, B.E. Sobel, (1993): Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. Arterioscler. Thromb., 13:1822–1828.PubMedCrossRefGoogle Scholar
  48. T.K., Nordt, K., Peter, C., and Bode, B.E. Sobel, (2000): Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells. J. Clin. Endocrinol. Metab., 85:1563–1568.PubMedCrossRefGoogle Scholar
  49. T.S., Olsen, U.J., and Weber, L.P. Kammersgaard, (2003): Therapeutic hypothermia for acute stroke. Lancet Neurol., 2:410–416.PubMedCrossRefGoogle Scholar
  50. S.T., Onesti, C.J., Baker, P.P., and Sun, R.A. Solomon, (1991): Transient hypothermia reduces focal ischemic brain injury in the rat. Neurosurgery, 29:369–373.PubMedCrossRefGoogle Scholar
  51. S. and Oppenheimer, V. Hachinski, (1992): Complications of acute stroke. Lancet, 339:721–724.PubMedCrossRefGoogle Scholar
  52. N.G., Pabello, S.J., Tracy, A., and Snyder-Keller, R.W., Keller, Jr. (2005): Regional expression of constitutive and inducible transcription factors following transient focal ischemia in the neonatal rat: influence of hypothermia. Brain Res., 1038:11–21.PubMedCrossRefGoogle Scholar
  53. A., Pandolfi, A., Giaccari, C., Cilli, M.M., Alberta, L., Morviducci, De Filippis, E.A., A., Buongiorno, G., Pellegrini, F., and Capani, A. Consoli, (2001): Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat. Acta Diabetol., 38:71–76.PubMedCrossRefGoogle Scholar
  54. M.W., Parsons, P.A., Barber, P.M., Desmond, T.A., Baird, D.G., Darby, G., Byrnes, B.M., and Tress, S.M. Davis, (2002): Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann. Neurol., 52:20–28.PubMedCrossRefGoogle Scholar
  55. S.J. Phillips, (1994): Pathophysiology and management of hypertension in acute ischemic stroke. Hypertension, 23:131–136.PubMedCrossRefGoogle Scholar
  56. W.J. Powers, (1993): Acute hypertension after stroke: the scientific basis for treatment decisions. Neurology, 43:461–467.PubMedCrossRefGoogle Scholar
  57. A.I. Qureshi, (2004): Endovascular treatment of cerebrovascular diseases and intracranial neoplasms. Lancet, 363:804–813.PubMedCrossRefGoogle Scholar
  58. A.I., Qureshi, P., Harris-Lane, J.F., Kirmani, N., Janjua, A.A., Divani, Y.M., Mohammad, J.I., and Suarez, M.O. Montgomery, (2006): Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: an open-label, dose-ranging, phase I study. Neurosurgery, 59:789–796.PubMedCrossRefGoogle Scholar
  59. J., Reith, H.S., Jorgensen, P.M., Pedersen, H., Nakayama, H.O., Raaschou, L.L., and Jeppesen, T.S. Olsen, (1996): Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet, 347:422–425.PubMedCrossRefGoogle Scholar
  60. M., Ribo, C., Molina, J., Montaner, M., Rubiera, R., Delgado-Mederos, J.F., Arenillas, M., and Quintana, J. Alvarez-Sabin, (2005): Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke, 36:1705–1709.PubMedCrossRefGoogle Scholar
  61. J.C. and Rose, S.A. Mayer, (2004): Optimizing blood pressure in neurological emergencies. Neurocrit. Care, 1:287–299.PubMedCrossRefGoogle Scholar
  62. J.L., Saver, K.C., Johnston, D., Homer, R., Wityk, W., Koroshetz, L.L., and Truskowski, E.C. Haley, (1999): Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators. Stroke, 30:293–298.PubMedCrossRefGoogle Scholar
  63. B. Schaller, (2005): Ischemic preconditioning as induction of ischemic tolerance after transient ischemic attacks in human brain: its clinical relevance. Neurosci. Lett., 377:206–211.PubMedCrossRefGoogle Scholar
  64. W.R., Selman, R.C., Crumrine, C.C., Rosenstein, C., Jenkins, J.C., LaManna, R.A., and Ratcheson, W.D. Lust, (1991): Rapid metabolic failure in spontaneously hypertensive rats after middle cerebral artery ligation. Metab. Brain Dis., 6:57–64.PubMedCrossRefGoogle Scholar
  65. D.G., Sherman, R.P., Atkinson, T., Chippendale, K.A., Levin, K., Ng, N., Futrell, C.Y., and Hsu, D.E. Levy, (2000): Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. JAMA, 283:2395–2403.PubMedCrossRefGoogle Scholar
  66. M., Sitzer, C., Foerch, T., Neumann-Haefelin, H., Steinmetz, B., Misselwitz, C., and Kugler, T. Back, (2004): Transient ischaemic attack preceding anterior circulation infarction is independently associated with favourable outcome. J. Neurol. Neurosurg. Psychiatry, 75:659–660.PubMedCrossRefGoogle Scholar
  67. W.S., Smith, G., Sung, S., Starkman, J.L., Saver, C.S., Kidwell, Y.P., Gobin, H.L., Lutsep, G.M., Nesbit, T., Grobelny, M.M., Rymer, I.E., Silverman, R.T., Higashida, R.F., and Budzik, M.P. Marks, (2005): Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke, 36:1432–1438.PubMedCrossRefGoogle Scholar
  68. J.I., Suarez, O.O., Zaidat, J.L., Sunshine, R., Tarr, W.R., and Selman, D.M. Landis, (2002): Endovascular administration after intravenous infusion of thrombolytic agents for the treatment of patients with acute ischemic strokes. Neurosurgery, 50:251–259.PubMedGoogle Scholar
  69. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995): Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med., 333:1581–1587.Google Scholar
  70. E.C. Toescu, (2005): Normal brain ageing: models and mechanisms. Philos. Trans. R. Soc. Lond. B Biol. Sci., 360:2347–2354.PubMedCrossRefGoogle Scholar
  71. D., Toni, M., Fiorelli, S., Bastianello, A., Falcou, G., Sette, V., Ceschin, M.L., and Sacchetti, C. Argentino, (1997): Acute ischemic strokes improving during the first 48 hours of onset: predictability, outcome, and possible mechanisms. A comparison with early deteriorating strokes. Stroke, 28:10–14.PubMedCrossRefGoogle Scholar
  72. T., Toyoda, S., Suzuki, N.F., and Kassell, K.S. Lee, (1996): Intraischemic hypothermia attenuates neutrophil infiltration in the rat neocortex after focal ischemia-reperfusion injury. Neurosurgery, 39:1200–1205.PubMedCrossRefGoogle Scholar
  73. M.C. and Tseng, K.C. Chang, (2006): Stroke severity and early recovery after first-ever ischemic stroke: results of a hospital-based study in Taiwan. Health Policy, 79:73–78.PubMedCrossRefGoogle Scholar
  74. K.R., Turley, L.H., and Toledo-Pereyra, R.U. Kothari, (2005): Molecular mechanisms in the pathogenesis and treatment of acute ischemic stroke. J. Invest. Surg., 18:207–218.PubMedCrossRefGoogle Scholar
  75. B.G., van den, A., Wilmer, G., Hermans, W., Meersseman, P.J., Wouters, I., Milants, Van Wijngaerden, E., H., and Bobbaers, R. Bouillon, (2006): Intensive insulin therapy in the medical ICU. N. Engl. J. Med., 354:449–461.CrossRefGoogle Scholar
  76. B.G., van den, P., Wouters, F., Weekers, C., Verwaest, F., Bruyninckx, M., Schetz, D., Vlasselaers, P., Ferdinande, P., and Lauwers, R. Bouillon, (2001): Intensive insulin therapy in the critically ill patients. N. Engl. J. Med., 345:1359–1367.CrossRefGoogle Scholar
  77. Van Hemelrijck, A., S., Hachimi-Idrissi, S., Sarre, G., and Ebinger, Y. Michotte, (2005): Post-ischaemic mild hypothermia inhibits apoptosis in the penumbral region by reducing neuronal nitric oxide synthase activity and thereby preventing endothelin-1-induced hydroxyl radical formation. Eur. J. Neurosci., 22:1327–1337.PubMedCrossRefGoogle Scholar
  78. K.N., Vemmos, K., Spengos, G., Tsivgoulis, N., Zakopoulos, E., Manios, V., Kotsis, M., and Daffertshofer, D. Vassilopoulos, (2004): Factors influencing acute blood pressure values in stroke subtypes. J. Hum. Hypertens., 18:253–259.PubMedCrossRefGoogle Scholar
  79. S., Wegener, B., Gottschalk, V., Jovanovic, R., Knab, J.B., Fiebach, P.D., Schellinger, T., Kucinski, G.J., Jungehulsing, P., Brunecker, B., Muller, A., Banasik, N., Amberger, K.D., Wernecke, M., Siebler, J., Rother, A., and Villringer, M. Weih, (2004): Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke, 35:616–621.PubMedCrossRefGoogle Scholar
  80. M., Weih, K., Kallenberg, A., Bergk, U., Dirnagl, L., Harms, K.D., and Wernecke, K.M. Einhaupl, (1999): Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain? Stroke, 30:1851–1854.PubMedCrossRefGoogle Scholar
  81. C., Weimar, A., Ziegler, I.R., and Konig, H.C. Diener, (2002): Predicting functional outcome and survival after acute ischemic stroke. J. Neurol., 249:888–895.PubMedCrossRefGoogle Scholar
  82. J.M. Weinberger, (2006): Evolving therapeutic approaches to treating acute ischemic stroke. J. Neurol. Sci., 249:101–109.PubMedCrossRefGoogle Scholar
  83. J.P. Whisnant, (1996): Effectiveness versus efficacy of treatment of hypertension for stroke prevention. Neurology, 46:301–307.PubMedCrossRefGoogle Scholar
  84. Z.K., Wu, J., Laurikka, A., Saraste, V., Kyto, E.J., Pehkonen, T., and Savunen, M.R. Tarkka, (2003): Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations. Ann. Thorac. Surg., 76:528–534.PubMedCrossRefGoogle Scholar
  85. H., Yanamoto, S.C., Hong, S., Soleau, N.F., and Kassell, K.S. Lee, (1996): Mild postischemic hypothermia limits cerebral injury following transient focal ischemia in rat neocortex. Brain Res., 718:207–211.PubMedCrossRefGoogle Scholar
  86. M., Yong, H.C., Diener, M., and Kaste, J. Mau, (2005): Characteristics of blood pressure profiles as predictors of long-term outcome after acute ischemic stroke. Stroke, 36:2619–2625.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Svetlana Pundik
    • 1
  • Jose I. Suarez
    • 2
  1. 1.University Hospitals of ClevelandClevelandNorway
  2. 2.Department of Neurology and NeurosurgeryVascular Neurology and Neurocritical Care, Baylor College of MedicineHoustonUSA

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