Preservation of thalamocortical circuitry is essential for good recovery after cardiac arrest

Continuous electroencephalographam (EEG) monitoring contributes to prediction of neurological outcome in comatose cardiac arrest survivors. While the phenomenology of EEG abnormalities in postanoxic encephalopathy is well known, the pathophysiology, especially the presumed role of selective synaptic failure, is less understood. To further this understanding, we estimate biophysical model parameters from the EEG power spectra from individual patients with a good or poor recovery from a postanoxic encephalopathy. This biophysical model includes intracortical, intrathalamic, and corticothalamic synaptic strengths, as well as synaptic time constants and axonal conduction delays. We used continuous EEG measurements from hundred comatose patients recorded during the first 48 h postcardiac arrest, 50 with a poor neurological outcome [cerebral performance category (CPC = 5)] and 50 with a good neurological outcome (CPC = 1). We only included patients that developed (dis-)continuous EEG activity within 48 h postcardiac arrest. For patients with a good outcome, we observed an initial relative excitation in the corticothalamic loop and corticothalamic propagation that subsequently evolved towards values observed in healthy controls. For patients with a poor outcome, we observed an initial increase in the cortical excitation-inhibition ratio, increased relative inhibition in the corticothalamic loop, delayed corticothalamic propagation of neuronal activity, and severely prolonged synaptic time constants that did not return to physiological values. We conclude that the abnormal EEG evolution in patients with a poor neurological recovery after cardiac arrest may result from persistent and selective synaptic failure that includes corticothalamic circuitry and also delayed corticothalamic propagation.</p

Early EEG contributes to multimodal outcome prediction of postanoxic coma

Objectives:\ud Early identification of potential recovery of postanoxic coma is a major challenge. We studied the additional predictive value of EEG. \ud \ud Methods:\ud Two hundred seventy-seven consecutive comatose patients after cardiac arrest were included in a prospective cohort study on 2 intensive care units. Continuous EEG was measured during the first 3 days. EEGs were classified as unfavorable (isoelectric, low-voltage, burst-suppression with identical bursts), intermediate, or favorable (continuous patterns), at 12, 24, 48, and 72 hours. Outcome was dichotomized as good or poor. Resuscitation, demographic, clinical, somatosensory evoked potential, and EEG measures were related to outcome at 6 months using logistic regression analysis. Analyses of diagnostic accuracy included receiver operating characteristics and calculation of predictive values. \ud \ud Results:\ud Poor outcome occurred in 149 patients (54%). Single measures unequivocally predicting poor outcome were an unfavorable EEG pattern at 24 hours, absent pupillary light responses at 48 hours, and absent somatosensory evoked potentials at 72 hours. Together, these had a specificity of 100% and a sensitivity of 50%. For the remaining 203 patients, who were still in the “gray zone” at 72 hours, a predictive model including unfavorable EEG patterns at 12 hours, absent or extensor motor response to pain at 72 hours, and higher age had an area under the curve of 0.90 (95% confidence interval 0.84–0.96). Favorable EEG patterns at 12 hours were strongly associated with good outcome. EEG beyond 24 hours had no additional predictive value. \ud \ud Conclusions:\ud EEG within 24 hours is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest

Unstandardized Treatment of Electroencephalographic Status Epilepticus Does Not Improve Outcome of Comatose Patients after Cardiac Arrest

Objective: Electroencephalographic status epilepticus occurs in 9–35% of comatose patients after cardiac arrest. Mortality is 90–100%. It is unclear whether (some) seizure patterns represent a condition in which anti-epileptic treatment may improve outcome, or severe ischemic damage, in which treatment is futile. We explored current treatment practice and its effect on patients’ outcome. Methods: We retrospectively identified patients that were treated with anti-epileptic drugs from our prospective cohort study on the value of continuous electroencephalography (EEG) in comatose patients after cardiac arrest. Outcome at 6 months was dichotomized between “good” [cerebral performance category (CPC) 1 or 2] and “poor” (CPC 3, 4, or 5). EEG analyses were done at 24 h after cardiac arrest and during anti-epileptic treatment. Unequivocal seizures and generalized periodic discharges during more than 30 min were classified as status epilepticus. Results: Thirty-one (22%) out of 139 patients were treated with anti-epileptic drugs (phenytoin, levetiracetam, valproate, clonazepam, propofol, midazolam), of whom 24 had status epilepticus. Dosages were moderate, barbiturates were not used, medication induced burst-suppression not achieved, and treatment improved electroencephalographic status epilepticus patterns temporarily (<6 h). Twenty-three patients treated for status epilepticus (96%) died. In patients with status epilepticus at 24 h, there was no difference in outcome between those treated with and without anti-epileptic drugs. Conclusion: In comatose patients after cardiac arrest complicated by electroencephalographic status epilepticus, current practice includes unstandardized, moderate treatment with anti-epileptic drugs. Although widely used, this does probably not improve patients’ outcome. A randomized controlled trial to estimate the effect of standardized, aggressive treatment, directed at complete suppression of epileptiform activity during at least 24 h, is needed and in preparation

Postanoxic alpha, theta or alpha-theta coma: Clinical setting and neurological outcome

Aim The aim of this study was to determine the prognosis of 26 consecutive adults with alpha coma (AC), theta coma (TC) or alpha-theta coma (ATC) following CRA and to describe the clinical setting and EEG features of these patients. Methods We retrospective analyzed a prospectively collected cohort of adult patients diagnosed as having AC, TC or ATC after CRA between January 2008 and June 2016. None of patients included in this analysis underwent therapeutic hypothermia (TH). Neurological outcome was expressed as the best score 6 months after CRA using the five-point Glasgow-Pisttsburgh Cerebral Performance Categories (CPC) Results Twenty-six patients were identified with a diagnosis of postanoxic AC, TC or ATC coma. There were 20 (77%) men and 6 (23%) women. The mean age was 63?±?16?years. The most frequent EEG pattern was TC (21 patients, 80%), followed by AC (3 patients, 12%) and ATC (2 patients, 8%). The cardiac rhythm as primary origin of the CRA was ventricular fibrillation (VF) in 16 patients (61.5%), asystole in 8 patients (34.6%) and ventricular tachycardia (VT) in one patient (3.8%). The presence of EEG reactivity was present in 8 patients (30%). The mortality rate was 85%. Of the 4 surviving patients, two (3.8%) had moderate disability (CPC 2), one (3.8%) had severe disability (CPC 3) and one (3.8%) reached a good recovery. The age was significantly lower in survivors 46.2?±?10.8 versus nonsurvivors 63.3?±?15.5 (p?=?0.04). There was increased association of EEG reactivity with survival (p?=?0.07). Conclusion Hypoxic-ischemic AC, TC and ATC are associated with a poor prognosis and a high rate of mortality. In younger patients with AC, TC and ATC and incomplete forms showing reactivity on the EEG, there is a greater probability of clinical recovery