Massive unilateral hemispheric infarction often develops progressive postischemic edema that leads to a malignant course of stroke with mortality of up to 80% with conventional medical therapies. Hypothermia and decompressive hemicraniectomy have shown neuroprotective effects in several animal models of focal transient and permanent MCA occlusion by reducing infarct size and improving neurological outcome. Our aim in this paper was to review the possible mechanisms of both therapies as well as the optimal time window and duration of application of each treatment in animal model and in human malignant MCA infarction reported in the literature.

1.
Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R: ‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 1996;53:309–315.
2.
Marion DW: Moderate hypothermia in severe head injuries: the present and the future. Curr Opin Crit Care 2002;8:111–114.
3.
Colbourne F, Corbett D, Zhao Z, Yang J, Buchan AM: Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model. J Cereb Blood Flow Metab 2000;20:1702–1708.
4.
Kawai N, Okauchi M, Morisaki K, Nagao S: Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats. Stroke 2000;31:1982–1989.
5.
Kollmar R, Henninger N, Bardutzky J, Schellinger PD, Schabitz WR, Schwab S: Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke – an MRI study. Exp Neurol 2004;190:204–212.
6.
Maier CM, Ahern K, Cheng ML, Lee JE, Yenari MA, Steinberg GK: Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 1998;29:2171–2180.
7.
Morikawa E, Ginsberg MD, Dietrich WD, Duncan RC, Kraydieh S, Globus MY, Busto R: The significance of brain temperature in focal cerebral ischemia: histopathological consequences of middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 1992;12:380–389.
8.
Ridenour TR, Warner DS, Todd MM, McAllister AC: Mild hypothermia reduces infarct size resulting from temporary but not permanent focal ischemia in rats. Stroke 1992;23:733–738.
9.
Yanamoto H, Nagata I, Nakahara I, Tohnai N, Zhang Z, Kikuchi H: Combination of intraischemic and postischemic hypothermia provides potent and persistent neuroprotection against temporary focal ischemia in rats. Stroke 1999;30:2720–2726.
10.
Yanamoto H, Nagata I, Niitsu Y, Zhang Z, Xue JH, Sakai N, Kikuchi H: Prolonged mild hypothermia therapy protects the brain against permanent focal ischemia. Stroke 2001;32:232–239.
11.
Commission for Thermal Physiology of the International Union of Physiological Sciences: Glossary of Terms for Thermal Physiology, ed 3. IUPS Thermal Commission, 2001, vol 51, pp 245–280.
12.
Bernard SA, Buist M: Induced hypothermia in critical care medicine: a review. Crit Care Med 2003;31:2041–2051.
13.
Tisherman SA, Rodriguez A, Safar P: Therapeutic hypothermia in traumatology. Surg Clin North Am 1999;79:1269–1289.
14.
Inamasu J, Ichikizaki K: Mild hypothermia in neurologic emergency: an update. Ann Emerg Med 2002;40:220–230.
15.
Busto R, Dietrich WD, Globus MY, Valdes I, Scheinberg P, Ginsberg MD: Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab 1987;7:729–738.
16.
Wang Y, Lim LL, Levi C, Heller RF, Fisher J: Influence of admission body temperature on stroke mortality. Stroke 2000;31:404–409.
17.
Reith J, Jorgensen HS, Pedersen PM, Nakayama H, Raaschou HO, Jeppesen LL, Olsen TS: Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 1996;347:422–425.
18.
Castillo J, Davalos A, Marrugat J, Noya M: Timing for fever-related brain damage in acute ischemic stroke. Stroke 1998;29:2455–2460.
19.
Marion DW: Controlled normothermia in neurologic intensive care. Crit Care Med 2004;32:S43–S45.
20.
Sutton LN, Clark BJ, Norwood CR, Woodford EJ, Welsh FA: Global cerebral ischemia in piglets under conditions of mild and deep hypothermia. Stroke 1991;22:1567–1573.
21.
Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR Jr, Muizelaar JP, Wagner FC Jr, Marion DW, Luerssen TG, Chesnut RM, Schwartz M: Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med 2001;344:556–563.
22.
Kollmar R, Schabitz WR, Heiland S, Georgiadis D, Schellinger PD, Bardutzky J, Schwab S: Neuroprotective effect of delayed moderate hypothermia after focal cerebral ischemia: an MRI study. Stroke 2002;33:1899–1904.
23.
Nishio S, Yunoki M, Chen ZF, Anzivino MJ, Lee KS: Ischemic tolerance in the rat neocortex following hypothermic preconditioning. J Neurosurg 2000;93:845–851.
24.
Mancuso A, Derugin N, Hara K, Sharp FR, Weinstein PR: Mild hypothermia decreases the incidence of transient ADC reduction detected with diffusion MRI and expression of c-fos and hsp70 mRNA during acute focal ischemia in rats. Brain Res 2000;887:34–45.
25.
Yager JY, Asselin J: Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic-ischemic brain damage in the immature rat. Stroke 1996;27:919–925.
26.
Nakashima K, Todd MM: Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke 1996;27:913–918.
27.
Huang FP, Zhou LF, Yang GY: Effects of mild hypothermia on the release of regional glutamate and glycine during extended transient focal cerebral ischemia in rats. Neurochem Res 1998;23:991–996.
28.
Xu L, Yenari MA, Steinberg GK, Giffard RG: Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 2002;22:21–28.
29.
Deng H, Han HS, Cheng D, Sun GH, Yenari MA: Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke 2003;34:2495–2501.
30.
Wagner S, Nagel S, Kluge B, Schwab S, Heiland S, Koziol J, Gardner H, Hacke W: Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia. Brain Res 2003;984:63–75.
31.
Karibe H, Zarow GJ, Graham SH, Weinstein PR: Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1994;14:620–627.
32.
Thornhill J, Corbett D: Therapeutic implications of hypothermic and hyperthermic temperature conditions in stroke patients. Can J Physiol Pharmacol 2001;79:254–261.
33.
Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W: Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29:2461–2466.
34.
Schwab S, Georgiadis D, Berrouschot J, Schellinger PD, Graffagnino C, Mayer SA: Feasibility and safety of moderate hypothermia after massive hemispheric infarction. Stroke 2001;32:2033–2035.
35.
Georgiadis D, Schwarz S, Kollmar R, Schwab S: Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 2001;32:2550–2553.
36.
De Georgia MA, Krieger DW, Abou-Chebl A, Devlin TG, Jauss M, Davis SM, Koroshetz WJ, Rordorf G, Warach S: Cooling for acute ischemic brain damage (COOL AID): a feasibility trial of endovascular cooling. Neurology 2004;63:312–317.
37.
Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan IL, Mayberg MR, Furlan AJ: Cooling for acute ischemic brain damage (COOL AID): an open pilot study of induced hypothermia in acute ischemic stroke. Stroke 2001;32:1847–1854.
38.
Krieger DW, Demchuk AM, Kasner SE, Jauss M, Hantson L: Early clinical and radiological predictors of fatal brain swelling in ischemic stroke. Stroke 1999;30:287–292.
39.
Von Kummer R, Meyding-Lamade U, Forsting M, Rosin L, Rieke K, Hacke W, Sartor K: Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol 1994;15:9–15.
40.
Barber PA, Demchuk AM, Zhang J, Kasner SE, Hill MD, Berrouschot J, Schmutzhard E, Harms L, Verro P, Krieger D: Computed tomographic parameters predicting fatal outcome in large middle cerebral artery infarction. Cerebrovasc Dis 2003;16:230–235.
41.
Oppenheim C, Samson Y, Manai R, Lalam T, Vandamme X, Crozier S, Srour A, Cornu P, Dormont D, Rancurel G, Marsault C: Prediction of malignant middle cerebral artery infarction by diffusion-weighted imaging. Stroke 2000;31:2175–2181.
42.
Arenillas JF, Rovira A, Molina CA, Grive E, Montaner J, Alvarez-Sabin J: Prediction of early neurological deterioration using diffusion- and perfusion-weighted imaging in hyperacute middle cerebral artery ischemic stroke. Stroke 2002;33:2197–2203.
43.
Thomalla GJ, Kucinski T, Schoder V, Fiehler J, Knab R, Zeumer H, Weiller C, Rother J: Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging. Stroke 2003;34:1892–1899.
44.
Serena J, Blanco M, Castellanos M, Silva Y, Vivancos J, Moro MA, Leira R, Lizasoain I, Castillo J, Davalos A: The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke 2005;36:1921–1926.
45.
Cushing H: The establishment of cerebral hernia as a decompressive measure for inaccessible brain tumor: With the description of intramuscular methods of making the bone defect in temporal and occipital regions. Surg Gynecol Obstet 1905;1:297–314.
46.
Britt RH, Hamilton RD: Large decompressive craniotomy in the treatment of acute subdural hematoma. Neurosurgery 1978;2:195–200.
47.
Doerfler A, Forsting M, Reith W, Staff C, Heiland S, Schabitz WR, von Kummer R, Hacke W, Sartor K: Decompressive craniectomy in a rat model of ‘malignant’ cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach. J Neurosurg 1996;85:853–859.
48.
Forsting M, Reith W, Schabitz WR, Heiland S, von Kummer R, Hacke W, Sartor K: Decompressive craniectomy for cerebral infarction. An experimental study in rats. Stroke 1995;26:259–264.
49.
Engelhorn T, von Kummer R, Reith W, Forsting M, Doerfler A: What is effective in malignant middle cerebral artery infarction: reperfusion, craniectomy, or both? An experimental study in rats. Stroke 2002;33:617–622.
50.
Hofmeijer J, Schepers J, Veldhuis WB, Nicolay K, Kappelle LJ, Bar PR, van der Worp HB: Delayed decompressive surgery increases apparent diffusion coefficient and improves peri-infarct perfusion in rats with space-occupying cerebral infarction. Stroke 2004;35:1476–1481.
51.
Doerfler A, Engelhorn T, Heiland S, Benner T, Forsting M: Perfusion- and diffusion-weighted magnetic resonance imaging for monitoring decompressive craniectomy in animals with experimental hemispheric stroke. J Neurosurg 2002;96:933–940.
52.
Engelhorn T, Doerfler A, de Crespigny A, Beaulieu C, Forsting M, Moseley ME: Multilocal magnetic resonance perfusion mapping comparing the cerebral hemodynamic effects of decompressive craniectomy versus reperfusion in experimental acute hemispheric stroke in rats. Neurosci Lett 2003;344:127–131.
53.
Rieke K, Schwab S, Krieger D, von Kummer R, Aschoff A, Schuchardt V, Hacke W: Decompressive surgery in space-occupying hemispheric infarction: results of an open, prospective trial. Crit Care Med 1995;23:1576–1587.
54.
Schwab S, Steiner T, Aschoff A, Schwarz S, Steiner HH, Jansen O, Hacke W: Early hemicraniectomy in patients with complete middle cerebral artery infarction. Stroke 1998;29:1888–1893.
55.
Gupta R, Connolly ES, Mayer S, Elkind MS: Hemicraniectomy for massive middle cerebral artery territory infarction: a systematic review. Stroke 2004;35:539–543.
56.
Uhl E, Kreth FW, Elias B, Goldammer A, Hempelmann RG, Liefner M, Nowak G, Oertel M, Schmieder K, Schneider GH: Outcome and prognostic factors of hemicraniectomy for space occupying cerebral infarction. J Neurol Neurosurg Psychiatry 2004;75:270–274.
57.
Wagner S, Schnippering H, Aschoff A, Koziol JA, Schwab S, Steiner T: Suboptimum hemicraniectomy as a cause of additional cerebral lesions in patients with malignant infarction of the middle cerebral artery. J Neurosurg 2001;94:693–696.
58.
Walz B, Zimmermann C, Bottger S, Haberl RL: Prognosis of patients after hemicraniectomy in malignant middle cerebral artery infarction. J Neurol 2002;249:1183–1190.
59.
Vahedi K, Benoist L, Kurtz A, Mateo J, Blanquet A, Rossignol M, Amarenco P, Yelnik A, Vicaut E, Payen D, Bousser MG: Quality of life after decompressive craniectomy for malignant middle cerebral artery infarction. J Neurol Neurosurg Psychiatry 2005;76:1181–1182.
60.
Morley NC, Berge E, Cruz-Flores S, Whittle IR: Surgical decompression for cerebral oedema in acute ischaemic stroke. Cochrane Database Syst Rev 2002;CD003435.
61.
Georgiadis D, Schwarz S, Aschoff A, Schwab S: Hemicraniectomy and moderate hypothermia in patients with severe ischemic stroke. Stroke 2002;33:1584–1588.
62.
Doerfler A, Schwab S, Hoffmann TT, Engelhorn T, Forsting M: Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats. Stroke 2001;32:2675–2681.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.