Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations

Abstract

Progressive ischaemic damage in animals is associated with spreading mass depolarizations of neurons and astrocytes, detected as spreading negative slow voltage variations. Speculation on whether spreading depolarizations occur in human ischaemic stroke has continued for the past 60 years. Therefore, we performed a prospective multicentre study assessing incidence and timing of spreading depolarizations and delayed ischaemic neurological deficit (DIND) in patients with major subarachnoid haemorrhage (SAH) requiring aneurysm surgery. Spreading depolarizations were recorded by electrocorticography with a subdural electrode strip placed on cerebral cortex for up to 10 days. A total of 2110 h recording time was analysed. The clinical state was monitored every 6 h. Delayed infarcts after SAH were verified by serial CT scans and/or MRI. Electrocorticography revealed 298 spreading depolarizations in 13 of the 18 patients (72%). A clinical DIND was observed in seven patients 7.8 days (7.3, 8.2) after SAH. DIND was time-locked to a sequence of recurrent spreading depolarizations in every single case (positive and negative predictive values: 86 and 100%, respectively). In four patients delayed infarcts developed in the recording area. As in the ischaemic penumbra of animals, delayed infarction was preceded by progressive prolongation of the electrocorticographic depression periods associated with spreading depolarizations to >60 min in each case. This study demonstrates that spreading depolarizations have a high incidence in major SAH and occur in ischaemic stroke. Repeated spreading depolarizations with prolonged depression periods are an early indicator of delayed ischaemic brain damage after SAH. In view of experimental evidence and the present clinical results, we suggest that spreading depolarizations with prolonged depressions are a promising target for treatment development in SAH and ischaemic stroke.

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

“…In SAH, CSD provided excellent detection of subsequent delayed ischemic neurological deficits (positive predictive value, 86%; negative predictive value, 100%). The events of neurological decline were closely time-linked to CSD, providing biologic plausibility for their role as more than an epiphenomenon [80]. Invasive measures of brain tissue oxygenation showed that waves of CSD following SAH resulted in significant stress on the balance of brain oxygen supply and demand, causing waves of brain tissue hypoxia followed by rebound hyperoxia.…”

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

“…An entirely different scenario may apply in the human brain acutely injured for example by ischemic stroke, brain trauma, or subarachnoid or intracerebral hemorrhage (ICH) (Hansen and Lauritzen, 1984;Strong et al, 2002;Fabricius et al, 2006;Dreier et al, 2006;Dohmen et al, 2008). This has been studied recently in patients who underwent neurosurgery including craniotomy because of their acute brain condition, by using cortical electrode strips similar to the technology applied in epilepsy surgery.…”

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization

“…7-9 Clusters of SD impose particularly severe energy demands on the injured brain. [15][16][17][18] Clinical microdialysis enables monitoring of the local metabolic status of brain tissue in patients with TBI. [18][19][20][21][22][23][24] Boutelle and coworkers developed a rapid sampling microdialysis (rsMD) system that monitors SD-associated glucose transients with 30-s temporal resolution.…”