Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression.

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3-5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9-22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis.

Active, passive and resting state paradigms using functional MRI (fMRI) or EEG may reveal consciousness in the vegetative (VS) and the minimal conscious state (MCS). A meta-analysis was performed to assess the prevalence of preserved consciousness in VS and MCS as revealed by fMRI and EEG, including command following (active paradigms), cortical functional connectivity elicited by external stimuli (passive paradigms) and default mode networks (resting state). Studies were selected from multiple indexing databases until February 2015 and evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. 37 studies were identified, including 1041 patients (mean age 43 years, range 16-89; male/female 2.1:1; 39.5% traumatic brain injuries). MCS patients were more likely than VS patients to follow commands during active paradigms (32% vs 14%; OR 2.85 (95% CI 1.90 to 4.27; p<0.0001)) and to show preserved functional cortical connectivity during passive paradigms (55% vs 26%; OR 3.53 (95% CI 2.49 to 4.99; p<0.0001)). Passive paradigms suggested preserved consciousness more often than active paradigms (38% vs 24%; OR 1.98 (95% CI 1.54 to 2.54; p<0.0001)). Data on resting state paradigms were insufficient for statistical evaluation. In conclusion, active paradigms may underestimate the degree of consciousness as compared to passive paradigms. While MCS patients show signs of preserved consciousness more frequently in both paradigms, roughly 15% of patients with a clinical diagnosis of VS are able to follow commands by modifying their brain activity. However, there remain important limitations at the single-subject level; for example, patients from both categories may show command following despite negative passive paradigms.

Continuous EEG monitoring in aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND: Continuous EEG (cEEG) may allow monitoring of patients with aneurysmal subarachnoid hemorrhage (SAH) for delayed cerebral ischemia (DCI) and seizures, including non-convulsive seizures (NCSz), and non-convulsive status epilepticus (NCSE). We aimed to evaluate: (a) the diagnostic accuracy of cEEG as a confirmatory test, (b) the prognostic value of EEG patterns suggestive of seizures and DCI, and (c) the effectiveness of intensified neuromonitoring using cEEG in terms of improved clinical outcome following SAH. METHODS: A systematic review was performed with eligible studies selected from multiple indexing databases through June 2014. The methodological quality of these studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Eighteen studies were identified, including cEEG data from 481 patients with aneurysmal SAH. NCSz were diagnosed in 7-18 % of patients; NCSE in 3-13 %. NCSE was associated with increased age (mean age 68 years) and mortality (82-100 %) compared to the entire patient population (53.9 years; mortality 13 %; p values <0.05). DCI was diagnosed in 20-46 % of patients. Quantitative EEG patterns suggestive of DCI included decreased alpha/delta ratio, relative alpha variability, and total power. All studies were subject to a high risk of bias concerning patient selection and cEEG methodology. CONCLUSIONS: cEEG monitoring following SAH detects an increased number of subclinical seizures and may predict DCI many hours in advance. NCSE is associated with high mortality and morbidity, whereas for DCI identified by cEEG this association is less clear. Prospective randomized controlled multicenter trials are needed to evaluate the benefits (or risks) of intensified treatment of seizures and DCI following SAH.