intraarterial pharmaceutical or mechanical thrombolysis presents an excellent opportunity for such a treatment. The MERCI retrieval device (Concentric Medical, Inc.) may be too traumatic to drag through the smaller delicate collateral arteries of the circle of Willis, but simultaneous pharmaceutical thrombolysis and mechanical clot retrieval through the less traumatic Penumbra microcatheter (Penumbra, Inc.) would be safer. 8 Here, we report our experience with the trans-ACoA approach, using the Penumbra microcatheter, for rapid revascularization of tandem MCA and cervical
David J. Padalino and Eric M. Deshaies
Toshikazu Nishioka, Hiroyuki Nakase, Mitsutoshi Nakamura, Noboru Konishi, and Toshisuke Sakaki
infarction, this condition has been frequently misdiagnosed. The term “ischemic penumbra” has been used to define regions in which CBF reduction passes the threshold that leads to the failure of electrical but not membrane function. The penumbra is thus a potentially treatable zone and a spatially dynamic brain region with limited viability, which is characterized by complex pathophysiological changes. A large amount of evidence suggests that ischemic penumbra occurs in animals and humans after focal brain ischemia. 8 In experimental animals, the pathophysiological
Kazuki Takahira, Taketo Kataoka, Tatsuya Ogino, Hideki Endo, and Hirohiko Nakamura
F or patients with acute stroke due to major intracranial vessel occlusion, a direct aspiration first pass technique (ADAPT) with a large-bore reperfusion catheter of the Penumbra system (Penumbra, Inc.) is an efficient management strategy and does not increase the incidence of symptomatic intracranial hemorrhage. 3 However, when we used the 3MAX reperfusion catheter as an inner catheter in cases of severe tortuosity of the vasculature, it could be impossible or hazardous to advance the large-bore reperfusion catheter of the Penumbra system to an embolus
Neil Haranhalli, Nnenna Mbabuike, Sanjeet S. Grewal, Tasneem F. Hasan, Michael G. Heckman, William D. Freeman, Vivek Gupta, Prasanna Vibhute, Benjamin L. Brown, David A. Miller, Babak S. Jahromi, and Rabih G. Tawk
area of infarct and penumbra, or salvageable brain tissue, with reasonable accuracy. 10 , 17 , 26 Traditionally, intravenous thrombolytic therapy has been the mainstay of treatment for patients with AIS, and the need for an individualized approach to treating these patients is becoming prominent. Recent randomized trials have demonstrated improved outcomes when endovascular therapy is used to treat patients with AIS with specific selection criteria; importantly, the majority of trials utilized some form of perfusion-weighted imaging (CTP, MR perfusion, multiphase CTA
Peter Frykholm, Lars Hillered, Bengt Långström, Lennart Persson, Johann Valtysson, and Per Enblad
relation to rCBF and CMRO 2 by using two approaches. In the first approach, two 2-hour periods in the experiments were analyzed: the MCAO period and the early post-MCAO period (denoted the “reperfusion phase”). In the second approach, the microdialysis probe regions were classified during MCAO according to the metabolic threshold level of the reversible/irreversible ischemia demonstrated earlier: 14, 15 severe ischemia, CMRO 2 less than 60% of that in the corresponding contralateral region; and penumbra, CMRO 2 decreased but greater than or equal to 60% and OER
Bo K. Siesjö
gross energy failure. 128, 129 Furthermore, edema develops at CBF values exceeding those causing overt disruption of ion homeostasis. 52, 140 Finally, the ischemic threshold for protein synthesis is even higher, suggesting that this function is extraordinarily sensitive to a reduction in CBF. 84, 159 The Concept of an Ischemic Penumbra The finding of separate thresholds for cessation of electrical signals and for loss of ion homeostasis led to the concept of an ischemic penumbra, that is, of perifocal tissues containing electrically inexcitable but
Hideo Okada, Yoshikazu Matsuda, Joonho Chung, R. Webster Crowley, and Demetrius K. Lopes
a large-bore aspiration catheter (stentriever-aspiration, or Solumbra, technique), have been reported to improve the recanalization rate; 6 , 9 however, debate exists regarding how to achieve optimal recanalization safely and effectively in refractory cases. In this report, we describe the Y-configured stentriever technique combining 2 Trevo ProVue devices (Stryker Neurovascular) with an ACE64 catheter (Penumbra) for a strongly rooted thrombus on the middle cerebral artery (MCA) bifurcation, focusing on its feasibility, technical advantages and disadvantages, and
Fernando G. Diaz, James I. Ausman, Bharat Mehta, Manuel Dujovny, Raul A. de los Reyes, Jeffrey Pearce, and Suresh Patel
management of cerebral ischemia, three questions must first be answered: 1) Is any viable tissue left which may benefit from the restoration of blood flow? 2) How quickly must blood flow be reestablished to prevent or limit severe tissue damage? and 3) What are the potential surgical risks and complications which could develop after blood flow has been restored to an area of cerebral ischemia? The concept of improving blood flow to the ischemic penumbra, “a zone of nonfunctioning but still viable tissue that may recover its function if blood flow can be restored…,” 2 is
Bo K. Siesjö
✓ This article examines the pathophysiology of lesions caused by focal cerebral ischemia. Ischemia due to middle cerebral artery occlusion encompasses a densely ischemic focus and a less densely ischemic penumbral zone. Cells in the focus are usually doomed unless reperfusion is quickly instituted. In contrast, although the penumbra contains cells “at risk,” these may remain viable for at least 4 to 8 hours. Cells in the penumbra may be salvaged by reperfusion or by drugs that prevent an extension of the infarction into the penumbral zone. Factors responsible for such an extension probably include acidosis, edema, K+/Ca++ transients, and inhibition of protein synthesis.
Central to any discussion of the pathophysiology of ischemic lesions is energy depletion. This is because failure to maintain cellular adenosine triphosphate (ATP) levels leads to degradation of macromolecules of key importance to membrane and cytoskeletal integrity, to loss of ion homeostasis, involving cellular accumulation of Ca++, Na+, and Cl−, with osmotically obligated water, and to production of metabolic acids with a resulting decrease in intra- and extracellular pH.
In all probability, loss of cellular calcium homeostasis plays an important role in the pathogenesis of ischemic cell damage. The resulting rise in the free cytosolic intracellular calcium concentration (Ca++) depends on both the loss of calcium pump function (due to ATP depletion), and the rise in membrane permeability to calcium. In ischemia, calcium influx occurs via multiple pathways. Some of the most important routes depend on activation of receptors by glutamate and associated excitatory amino acids released from depolarized presynaptic endings. However, ischemia also interferes with the intracellular sequestration and binding of calcium, thereby contributing to the rise in intracellular Ca++.
A second key event in the ischemic tissue is activation of anaerobic glucolysis. The main reason for this activation is inhibition of mitochondrial metabolism by lack of oxygen; however, other factors probably contribute. For example, there is a complex interplay between loss of cellular calcium homeostasis and acidosis. On the one hand, a rise in intracellular Ca++ is apt to cause mitochondrial accumulation of calcium. This must interfere with ATP production and enhance anaerobic glucolysis. On the other hand, acidosis must interfere with calcium binding, thereby contributing to the rise in intracellular Ca++.
Part II: Mechanisms of damage and treatment
Bo K. Siesjö
(see above). Events in the penumbral zone are different since, at least initially, changes in energy state are less dramatic and ionic transients are absent or of short duration. However, the penumbra is at risk since, due to the reduced blood flow, energy metabolism is compromised in the sense that it cannot adequately cope with metabolic stress. It was observed by Harris, et al. , 76 that ischemic tissues that had not yet transgressed the threshold for gross membrane failure could show spontaneous ionic transients of the type seen in spreading depression. More