Antiedema Therapy in Ischemic Stroke

Bardutzky, Juergen; Schwab, Stefan

doi:10.1161/strokeaha.107.490193

Cited by 174 publications

(118 citation statements)

References 91 publications

(112 reference statements)

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“…Medical treatment strategies for increased ICP are in accordance with those used in the management of supratentorial stroke and may include osmotic therapy, artificial coma, hyperventilation, barbiturates, buffers, and steroids. 8,55 However, none of these treatments is supported by adequate evidence of efficacy from experimental studies or randomized clinical trials. 1,25 In fact, several reports suggest that these measures are ineffective or even detrimental, at least in supratentorial infarction.…”

Section: Conservative Treatmentmentioning

confidence: 99%

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Space-occupying cerebellar infarction: complications, treatment, and outcome

Neugebauer

Witsch

Zweckberger

et al. 2013

FOC

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Space-occupying brain edema is a frequent and one of the most dreaded complications in ischemic cerebellar stroke. Because the tight posterior fossa provides little compensating space, any space-occupying lesion can lead to life-threatening complications through brainstem compression or compression of the fourth ventricle and subsequent hydrocephalus, both of which may portend transtentorial/transforaminal herniation. Patients with large cerebellar infarcts should be treated and monitored very early on in an experienced stroke unit or (neuro)intensive care unit. The general treatment of ischemic cerebellar infarction does not differ from that of supratentorial ischemic strokes. Treatment strategies for space-occupying edema include pharmacological antiedema and intracranial pressure–lowering therapies, ventricular drainage by means of an extraventricular drain, and suboccipital decompressive surgery, with or without resection of necrotic tissue. Timely escalation of treatment is crucial and should be guided by clinical and neuroradiological rationales. Patients in a coma after hydrocephalus and/or local brainstem compression may also benefit from more aggressive surgical treatment, as long as the conditions are reversible. Contrary to the general belief that outcome in survivors of space-occupying cerebellar stroke is usually good, recent studies suggest that for many of these patients, the long-term outcome is not good. In particular, advanced age and additional brainstem infarction seem to be predictors for poor outcome. Further trials are necessary to investigate these findings systematically and provide better selection criteria to help guide decisions about surgical therapies, which should always be carried out in close cooperation among neurointensive care physicians, neurologists, and neurosurgeons.

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Section: Conservative Treatmentmentioning

confidence: 99%

“…1,25 In fact, several reports suggest that these measures are ineffective or even detrimental, at least in supratentorial infarction. 8,55 No valid data are available in infratentorial stroke.…”

Section: Conservative Treatmentmentioning

confidence: 99%

Space-occupying cerebellar infarction: complications, treatment, and outcome

Neugebauer

Witsch

Zweckberger

et al. 2013

FOC

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“…Pharmacologic strategies to combat inflammation or edema formation in acute ischemic stroke are currently not available. 8 Interestingly, however, there is increasing evidence of a tightly regulated interplay between thrombotic and inflammatory mechanisms during stroke development and this "thromboinflammation" might be accessible to specific therapeutic interventions. 9 High-molecular-weight kininogen (KNG) is an important constituent of the plasma contact-kinin system which represents a network of serially connected serine proteases.…”

Section: Introductionmentioning

confidence: 99%

Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation

Langhauser¹,

Göb²,

Kraft³

et al. 2012

Blood

121

123

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Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. Highmolecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng Ϫ/Ϫ mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng Ϫ/Ϫ mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases. (Blood. 2012;120(19): 4082-4092) IntroductionThe pathology of ischemic stroke is complex and involves a myriad of distinct molecular pathways and cellular interactions. Among these, progressive thrombus formation in the cerebral microvasculature is a key process that can cause secondary infarct growth despite successful recanalization of larger proximal brain vessels both under experimental conditions as well as in humans. 1,2 We recently identified the intrinsic coagulation cascade as a novel and safe antithrombotic target for the prevention and treatment of acute ischemic stroke. 3 Genetic depletion or pharmacologic blockade of coagulation factor XII (FXII), the origin of the intrinsic pathway, markedly reduced intracerebral thrombus formation and infarct growth in mice without increasing the risk of bleeding complications. 4,5 Clot formation was also significantly reduced in several in vitro models of thrombosis after FXII inhibition. 5 Current pathophysiologic concepts also emphasize the importance of inflammatory mechanisms in stroke. 6 The cerebral endothelium is activated early during the course of an ischemic event, leading to the up-regulation of cell adhesion molecules and successive trafficking of inflammatory cells (neutrophils, macrophages, T cells) from the blood stream into the brain parenchyma. Those cells attracted from the periphery in concert with resident cell populations (endothelial cells, microglia) secrete an array of soluble immune mediators such as cytokines and chemokines that perpetuate the inflammatory response to cause direct or indirect ti...

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“…In terms of therapeutic window, this will vary depending on the type of ischemia (focal vs global) and severity, but could be up to 6 hours following stroke (focal ischemia; Ohta et al, 2007) and up to 12 hours following global ischemia (Colbourne et al, 1999b;Coimbra & Walsh, 1994). With respect to rewarming it is becoming increasingly accepted that slow rewarming at the rate of 0.2 -0.3°C/hour is most desirable (Bardutzky & Schwab, 2007;.…”

Section: Timing and Duration Of Hypothermiamentioning

confidence: 99%