In the human brain, ≈30% of the energy is spent on synaptic transmission. Disappearance of synaptic activity is the earliest consequence of cerebral ischemia. The changes of synaptic function are generally assumed to be reversible and persistent damage is associated with membrane failure and neuronal death. However, there is overwhelming experimental evidence of isolated, but persistent, synaptic failure resulting from mild or moderate cerebral ischemia. Early failure results from presynaptic damage with impaired transmitter release. Proposed mechanisms include dysfunction of adenosine triphosphate-dependent calcium channels and a disturbed docking of glutamate-containing vesicles resulting from impaired phosphorylation. We review energy distribution among neuronal functions, focusing on energy usage of synaptic transmission. We summarize the effect of ischemia on neurotransmission and the evidence of long-lasting synaptic failure as a cause of persistent symptoms in patients with cerebral ischemia. Finally, we discuss the implications of synaptic failure in the diagnosis of cerebral ischemia, including the limited sensitivity of diffusion-weighted MRI in those cases in which damage is presumably limited to the synapses.

To evaluate the value of continuous electroencephalography in early prognostication in patients treated with hypothermia after cardiac arrest. Prospective cohort study. Medical intensive care unit. Sixty patients admitted to the intensive care unit for therapeutic hypothermia after cardiac arrest. None. In all patients, continuous electroencephalogram and daily somatosensory evoked potentials were recorded during the first 5 days of admission or until intensive care unit discharge. Neurological outcomes were based on each patient’s best achieved Cerebral Performance Category score within 6 months. Twenty-seven of 56 patients (48%) achieved good neurological outcome (Cerebral Performance Category score 1–2). At 12 hrs after resuscitation, 43% of the patients with good neurological outcome showed continuous, diffuse slow electroencephalogram rhythms, whereas this was never observed in patients with poor outcome. The sensitivity for predicting poor neurological outcome of low-voltage and isoelectric electroencephalogram patterns 24 hrs after resuscitation was 40% (95% confidence interval 19%–64%) with a 100% specificity (confidence interval 86%–100%), whereas the sensitivity and specificity of absent somatosensory evoked potential responses during the first 24 hrs were 24% (confidence interval 10%–44%) and 100% (confidence interval: 87%–100%), respectively. The negative predictive value for poor outcome of low-voltage and isoelectric electroencephalogram patterns was 68% (confidence interval 50%–81%) compared to 55% (confidence interval 40%–60%) for bilateral somatosensory evoked potential absence, both with a positive predictive value of 100% (confidence interval 63%–100% and 59%–100% respectively). Burst-suppression patterns after 24 hrs were also associated with poor neurological outcome, but not inevitably so. In patients treated with hypothermia, electroencephalogram monitoring during the first 24 hrs after resuscitation can contribute to the prediction of both good and poor neurological outcome. Continuous patterns within 12 hrs predicted good outcome. Isoelectric or low-voltage electroencephalograms after 24 hrs predicted poor outcome with a sensitivity almost two times larger than bilateral absent somatosensory evoked potential responses.

Objectives: Early identification of potential recovery of postanoxic coma is a major challenge. We studied the additional predictive value of EEG. Methods: 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. Results: 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. Conclusions: EEG within 24 hours is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest.