182 patients have been monitored by electrocorticography from subdural platinum strips.
New information recently analysed suggests for the first time that longer periods of depolarisation may be associated with poorer recovery from injury when this is assessed 6 months later.
table with breakdown of included patients - to be added
Current data suggest that depolarisations occur
(a) in essentially all patients with major progressive stroke following occlusion of the middle cerebral artery (Dohmen et al: Ann Neurol 2008;63:720 –728),
(b) in 55-60% of those who have suffered a focal contusion with major head injury or (Strong et al: Stroke 2002 Dec;33(12):2738-43; Hartings et al: J Neurotrauma 2009 Nov; 26:1857-66) or
(c) a spontaneous intracerebral haemorrhage near the brain surface (Fabricius et al: Brain 2006 Mar;129(Pt 3):778-90),
(d) and in 70-90% of patients after major subarachnoid haemorrhage from intracranial aneurysm (Dreier et al: Brain 2006 Dec;129(Pt 12):3224-37).
Methods for postprocessing electrocorticography data monitored in patients receiving intensive care have been reported (Hartings et al: J Neurophysiol 2009; 102:2563-75), together with criteria for identifying PIDs in patients (Fabricius et al: Brain. 2006 Mar;129(Pt 3):778-90).
Following serious subarachnoid haemorrhage, clusters of depolarisations are associated with neurological deterioration, and in some patients at around 6-9 days, with imaging appearances of freshly developing cortical ischaemia (Dreier et al, Brain. 2006 Dec;129(Pt 12):3224-37). Depolarisations are also shown to cause cortical spreading ischemia in humans (Dreier et al: Brain 2009 Jul; 132:1866-81), which limits oxygen availability and may contribute to imaging changes (Bosche et al: Ann Neurol 2010; 67:607-617).
Spreading depolarizations have been shown to be associated with other mechanisms of secondary injury in patients, including sub-clinical seizures (Fabricius et al: Clin Neurophysiol 2008 Sep; 119:1973-84), fever, and hypotension (Hartings et al: J Neurotrauma 2009 Nov; 26:1857-66).
Considering patients with all 4 conditions together, the first evidence is now emerging to suggest that longer periods of depolarisation are associated with worse outcome, but it is not yet known whether this predicts adverse outcome independent of factors already known to affect outcome. To answer this question is COSBID’s principal goal – since treatment methods are available that might control or minimize depolarisations (Dohmen et al: Ann Neurol 2008 Jun; 63:720-8).
Dreier,J.P., Ebert,N., Priller,J., Megow,D., Lindauer,U., Klee,R., Reuter,U., Imai,Y., Einhaupl,K.M., Victorov,I. et al 2000. Products of hemolysis in the subarachnoid space 34 inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage? J Neurosurg 93:658-666.
Higuchi,T., Takeda,Y., Hashimoto,M., Nagano,O., and Hirakawa,M. 2002. Dynamic changes in cortical NADH fluorescence and direct current potential in rat focal ischemia: relationship between propagation of recurrent depolarization and growth of the ischemic core. Journal of Cerebral Blood Flow & Metabolism 22:71-79.
Hartings, J. A., Rolli, M. L., Lu, X. C., Tortella, F. C. 2003. Delayed secondary phase of peri-infarct depolarizations after focal cerebral ischemia: relation to infarct growth and neuroprotection. J Neurosci 23:11602-10.
Richter,F., Rupprecht,S., Lehmenkuhler,A., and Schaible,H.G. 2003. Spreading depression can be elicited in brain stem of immature but not adult rats. J Neurophysiol. 90:2163-2170.
Gursoy-Ozdemir,Y., Qiu,J., Matsuoka,N., Bolay,H., Bermpohl,D., Jin,H., Wang,X., Rosenberg,G.A., Lo,E.H., and Moskowitz,M.A. 2004. Cortical spreading depression activates and upregulates MMP-9. J Clin. Invest. 113:1447-1455.
Yanamoto,H., Miyamoto,S., Tohnai,N., Nagata,I., Xue,J.H., Nakano,Y., Nakajo,Y., and Kikuchi,H. 2005. Induced spreading depression activates persistent neurogenesis in the subventricular zone, generating cells with markers for divided and early committed neurons in the caudate putamen and cortex. Stroke. 36:1544-1550.
Umegaki,M., Sanada,Y., Waerzeggers,Y., Rosner,G., Yoshimine,T., Heiss,W.D., and Graf,R. 2005. Peri-infarct depolarizations reveal penumbra-like conditions in striatum. Journal of Neuroscience 25:1387-1394.
Shin,H.K., Dunn,A.K., Jones,P.B., Boas,D.A., Moskowitz,M.A., and Ayata,C. 2006. Vasoconstrictive neurovascular coupling during focal ischemic depolarizations. J Cereb. Blood Flow. Metab. 26:1018-1030.
Strong AJ, Anderson PJ, Watts HR, et al: Peri-infarct depolarizations lead to loss of perfu-sion in ischaemic gyrencephalic cerebral cortex. Brain 2007;130:995-1008.
Farkas E, Pratt R, Sengpiel F, Obrenovitch TP (2007) Direct, live imaging of cortical spreading depression and anoxic depolarisation using a fluorescent, voltage-sensitive dye. J Cereb Blood Flow Metab 28:251–62
Hashemi,P., Bhatia,R., Nakamura,H., Dreier,J.P., Graf,R., Strong,A.J., and Boutelle,M.G. 2008. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leao's spreading depression. J Cereb Blood Flow Metab In press. Advance online publication: doi 10.1038/jcbfm.2008.108.
Sukhotinsky,I., Dilekoz,E., Moskowitz,M.A., and Ayata,C. 2008 Hypoxia and hypotension transform the blood flow response to cortical spreading depression from hyperemia into hypoperfusion in the rat. J Cereb Blood Flow Metab In press. Advance online publication: doi 10.1038/jcbfm.2008.35.