Electrocorticographic (ECoG) activity was recorded for up to 129 h from 12 acutely brain-injured human patients using six platinum electrodes placed near foci of damaged cortical tissue. The method probes ECoG activity in the immediate vicinity of the injured cortex and in adjacent supposedly healthy tissue. Six out of twelve patients displayed a total of 73 spontaneous episodes of spreading depression of the ECoG. Of the remaining 6 patients 1 displayed an episode of synchronous depression of ECoG during surgery. Using the same electrodes we also measured the slow potential changes (SPC) (0.005-0.05 Hz) to test the hypothesis that the ECoG depressions were identical to Leao's cortical spreading depression (CSD), and to be able to record peri-infarct depolarisations (PIDs) in electrically 'silent' cortical tissue. Changes in the SPC indicate depolarization of brain tissue. For the analysis, the SPCs were enhanced by calculating the time integral of the ECoG signal. Spreading ECoG depressions were accompanied at every single recording site by stereotyped SPCs, which spread across the cortical mantle at 3.3 (0.41-10) mm/min (median, range), i.e. at the same speed of spread as the depression of the ECoG activity. The amplitude of the SPCs was 0.06-3 mV. In 4 out of 6 patients the ECoG recovered spontaneously. In 2 patients we subsequently recorded recurrent SPCs, but without recovery of the initial ECoG background activity until 2-5 h later. This represents the first direct recording of PIDs in acutely injured human brain. Evidence from this and our previous study of 14 brain-injured patients suggests that CSDs in acute brain disorders occur at higher incidence in patients <30 years (83%) than above (33%). CSD was recorded in 4 out of 5 traumatic brain injury patients, and in 2 out of 7 patients with spontaneous haemorrhages. We conclude that the spreading ECoG depressions recorded in patients are identical to CSDs recorded in animal experiments. We furthermore provide direct electrophysiological evidence for the existence of PIDs and hence a penumbra in the human brain. We hypothesize that the depolarization events might contribute to tissue damage in acute disorders in the human brain.

Objective-To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) -including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage.Methods-63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days.Results-32 of 63 patients exhibited CSDs (5 to 75 episodes), and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test).Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In two patients ongoing repeated seizures were interrupted each time CSD occurred.Conclusions-Seizure activity occurs in association with CSD in the injured human brain. No conflicts of interestPublisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Significance-ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms that is not accessible by scalp EEG recordings. NIH Public Access

Cortical spreading depolarizations (SD) have been shown to occur frequently in patients with aneurysmal subarachnoid hemorrhage (SAH) and are associated with delayed ischemic brain damage. In animal models the link between SD and cell damage is the microvascular spasm coupled to the passage of SDs, resulting in spreading ischemia. Here we compared the hemodynamic changes induced by SD between human and rat cerebral cortex. Specifically, we addressed the question, whether the full spectrum of regional cerebral blood flow (rCBF) responses to SD is found in the human brain in a similar fashion to animal models. SDs were identified by slow potential changes in electrocorticographic recordings and the rCBF response profiles and magnitudes were analyzed. We found a large variability of rCBF changes concomitant to SDs in rat and in human recordings. The spectrum ranged from normal hyperemic responses to prolonged cortical spreading ischemia with intermediate forms characterized by biphasic (hypoemic-hyperemic) responses. The bandwidths of rCBF responses were comparable and the relative response magnitudes of hypo- and hyperperfusion phases did not differ significantly between rats and humans. The correspondence of the rCBF response spectrum to SD between human and animal brain underscores the importance of animal models to learn more about the mechanisms underlying the early and delayed pathological sequelae of SAH.

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