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In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study.

ObjectiveRecognition of potential for neurological recovery in patients who remain comatose after cardiac arrest is challenging and strains clinical decision making. Here, we utilize an approach that is based on physiological principles underlying recovery of consciousness and show correlation with clinical recovery after acute anoxic brain injury.MethodsA cohort study of 54 patients admitted to an Intensive Care Unit after cardiac arrest who underwent standardized bedside behavioral testing (Coma Recovery Scale – Revised [CRS‐R]) during EEG monitoring. Blinded to all clinical variables, artifact‐free EEG segments were selected around maximally aroused states and analyzed using a multi‐taper method to assess frequency spectral content. EEG spectral features were assessed based on pre‐defined categories that are linked to anterior forebrain corticothalamic integrity. Clinical outcomes were determined at the time of hospital discharge, using Cerebral Performance Categories (CPC).ResultsTen patients with ongoing seizures, myogenic artifacts or technical limitations obscuring recognition of underlying cortical dynamic activity were excluded from primary analysis. Of the 44 remaining patients with distinct EEG spectral features, 39 (88%) fit into our predefined categories. In these patients, spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness and favorable clinical outcome at the time of hospital discharge (P = 0.014).InterpretationPredicted transitions of neocortical dynamics that indicate functional integrity of anterior forebrain corticothalamic circuitry correlate with clinical outcomes in postcardiac‐arrest patients. Our results support a new biologically driven approach toward better understanding of neurological recovery after cardiac arrest.

IMPORTANCE Periodic discharges (PDs) that do not meet seizure criteria, also termed the ictal interictal continuum, are pervasive on electroencephalographic (EEG) recordings after acute brain injury. However, their association with brain homeostasis and the need for clinical intervention remain unknown.OBJECTIVE To determine whether distinct PD patterns can be identified that, similar to electrographic seizures, cause brain tissue hypoxia, a measure of ongoing brain injury. DESIGN, SETTING, AND PARTICIPANTSThis prospective cohort study included 90 comatose patients with high-grade spontaneous subarachnoid hemorrhage who underwent continuous surface (scalp) EEG (sEEG) recording and multimodality monitoring, including invasive measurements of intracortical (depth) EEG (dEEG), partial pressure of oxygen in interstitial brain tissue (PbtO 2 ), and regional cerebral blood flow (CBF). Patient data were collected from June 1, 2006, to September 1, 2014, at a single tertiary care center. The retrospective analysis was performed from September 1, 2014, to May 1, 2016, with a hypothesis that the effect on brain tissue oxygenation was primarily dependent on the discharge frequency.MAIN OUTCOMES AND MEASURES Electroencephalographic recordings were visually classified based on PD frequency and spatial distribution of discharges. Correlations between mean multimodality monitoring data and change-point analyses were performed to characterize electrophysiological changes by applying bootstrapping. RESULTSOf the 90 patients included in the study (26 men and 64 women; mean [SD] age, 55 [15] years), 32 (36%) had PDs on sEEG and dEEG recordings and 21 (23%) on dEEG recordings only. Frequencies of PDs ranged from 0.5 to 2.5 Hz. Median PbtO 2 was 23 mm Hg without PDs compared with 16 mm Hg at 2.0 Hz and 14 mm Hg at 2.5 Hz (differences were significant for 0 vs 2.5 Hz based on bootstrapping). Change-point analysis confirmed a temporal association of high-frequency PD onset (Ն2.0 Hz) and PbtO 2 reduction (median normalized PbtO 2 decreased by 25% 5-10 minutes after onset). Increased regional CBF of 21.0 mL/100 g/min for 0 Hz, 25.9 mL/100 g/min for 1.0 Hz, 27.5 mL/100 g/min for 1.5 Hz, and 34.7 mL/100 g/min for 2.0 Hz and increased global cerebral perfusion pressure of 91 mm Hg for 0 Hz, 100.5 mm Hg for 0.5 Hz, 95.5 mm Hg for 1.0 Hz, 97.0 mm Hg for 2.0 Hz, 98.0 mm Hg for 2.5 Hz, 95.0 mm Hg for 2.5 Hz, and 67.8 mm Hg for 3.0 Hz were seen for higher PD frequencies.CONCLUSIONS AND RELEVANCE These data give some support to consider redefining the continuum between seizures and PDs, suggesting that additional damage after acute brain injury may be reflected by frequency changes in electrocerebral recordings. Similar to seizures, cerebral blood flow increases in patients with PDs to compensate for the increased metabolic demand but higher-frequency PDs (>2 per second) may be inadequately compensated without an additional rise in CBF and associated with brain tissue hypoxia, or higher-frequency PDs may reflect inadequacies in brain compensatory...

FRESH is the first clinical tool to prognosticate long-term outcome after spontaneous SAH in a multidimensional manner. Ann Neurol 2016;80:46-58.

Objective:To test ketamine infusion efficacy in the treatment of super-refractory status epilepticus (SRSE), we studied retrospectively SRSE patients who were treated with ketamine. Additionally, we studied the effect of high doses of ketamine on brain physiology as reflected by invasive multimodality monitoring (MMM).Methods:We studied a consecutive series of 68 SRSE patients who were admitted between 2009 and 2018, were treated with ketamine and monitored with scalp EEG. Eleven of these patients underwent MMM at the time of ketamine administration. We compared patients who had seizure cessation after ketamine initiation to those who did not.Results:Mean age was 53+/-18 years old, 46% of patients were female. Seizure burden decreased by at least 50% within 24 hours of starting ketamine in 55 (81%) patients, with complete cessation in 43 (63%). Average dose of ketamine infusion was 2.2+/-1.8 mg/kg/h, with median duration of 2 (1; 4) days. Average dose of midazolam was 1.0+/-0.8 mg/kg/h at the time of ketamine initiation and was started at a median of 0.4 (0.1; 1.0) days before ketamine. Using a generalized linear mixed effect model, ketamine was associated with stable mean arterial pressure (OR 1.39, 95% CI 1.38-1.40), and with decreased in vasopressor requirements over time. We found no effect on intracranial pressure, cerebral blood flow, and cerebral perfusion pressure.Conclusion:Ketamine treatment was associated with a decrease in seizure burden in patients with SRSE. Our data support the notion that high dose ketamine infusions are associated with decreased vasopressor requirements without increased intracranial pressure.Classification of Evidence:This study provides Class IV evidence that ketamine decreases seizures in patients with SRSE.

Objective: To evaluate whether delayed appearance of intraventricular hemorrhage (dIVH) represents an independent entity from intraventricular hemorrhage (IVH) present on admission CT or is primarily related to the time interval between symptom onset and admission CT.Methods: A total of 282 spontaneous intracerebral hemorrhage (ICH) patients, admitted February 2009-March 2014 to the neurological intensive care unit of a tertiary care university hospital, were prospectively enrolled in the ICH Outcomes Project. Multivariate logistic regression was used to determine associations with acute mortality and functional long-term outcome (modified Rankin Scale).Results: A cohort of 282 ICH patients was retrospectively studied: 151 (53.5%) had intraventricular hemorrhage on initial CT scan (iIVH). Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (dIVH). The median times from symptom onset to admission CT were 1.1, 6.0, and 7.4 hours for the dIVH, iIVH, and no IVH groups (Mann-Whitney U test, dIVH vs iIVH, p , 0.001) and median time from onset to dIVH detection was 7.2 hours. The increase in ICH volume following hospital admission was larger in dIVH than in iIVH and no IVH patients (mean 17.6, 0.2, and 0.4 mL). After controlling for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but dIVH was not associated with any of the outcome measures. Conclusions:In ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome. In contrast, dIVH on subsequent scans is far less common and does not appear to portend worse outcome. Neurology ® 2015;84:989-994 GLOSSARY CI 5 confidence interval; CUMC 5 Columbia University Medical Center; dIVH 5 delayed intraventricular hemorrhage; GCS 5 Glasgow Coma Scale; ICH 5 intracerebral hemorrhage; ICHOP 5 ICH Outcomes Project; iIVH 5 initial IVH; IQR 5 interquartile range; IVH 5 intraventricular hemorrhage; mRS 5 modified Rankin Scale; OR 5 odds ratio.Intracerebral hemorrhage (ICH) is associated with high mortality and unfavorable outcome.1 In order to improve clinical outcomes, research efforts have primarily been directed towards understanding modifiable factors that worsen outcome, e.g., hematoma expansion after hospital admission.2,3 One recent study showed that delayed intraventricular hemorrhage (dIVH; intraventricular hemorrhage [IVH] that is not present on the initial admission CT but happens during hospitalization) occurs in up to every fifth ICH patient without IVH on initial CT and is independently associated with in-hospital mortality. 4 These results from one single-center study suggest that this subgroup of ICH patients is both at increased risk of unfavorable outcome and a promising target group, in which unfavorable outcome might potentially be prevented by frequent follow-up CTs and aggressive intervention. Before embarking on costly clinical trials to test this hypothe...

Objective Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain-injured patients. We evaluated whether EEG and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage. Methods A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into three groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending towards a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression. Results We identified 389 artifact-free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta-delta oscillations differentiated patients that were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (e.g., pupillary light reflex) contributed heavily to a linear model predicting behavioral state while brain physiology measures (e.g., brain oxygenation), structural injury, and clinical course added less. Interpretation EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness.