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Background: Identifying covert consciousness in intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC) is crucial for treatment decisions, but sensitive low-cost bedside markers are missing. We investigated whether automated pupillometry combined with passive and active cognitive paradigms can detect residual consciousness in ICU patients with DoC., Methods: We prospectively enrolled clinically low-response or unresponsive patients with traumatic or nontraumatic DoC from ICUs of a tertiary referral center. Age-matched and sex-matched healthy volunteers served as controls. Patients were categorized into clinically unresponsive (coma or unresponsive wakefulness syndrome) or clinically low-responsive (minimally conscious state or better). Using automated pupillometry, we recorded pupillary dilation to passive (visual and auditory stimuli) and active (mental arithmetic) cognitive paradigms, with task-specific success criteria (e.g., ≥ 3 of 5 pupillary dilations on five consecutive mental arithmetic tasks)., Results: We obtained 699 pupillometry recordings at 178 time points from 91 ICU patients with brain injury (mean age 60 ± 13.8 years, 31% women, and 49.5% nontraumatic brain injuries). Recordings were also obtained from 26 matched controls (59 ± 14.8 years, 38% women). Passive paradigms yielded limited distinctions between patients and controls. However, active paradigms enabled discrimination between different states of consciousness. With mental arithmetic of moderate complexity, ≥ 3 pupillary dilations were seen in 17.8% of clinically unresponsive patients and 50.0% of clinically low-responsive patients (odds ratio 4.56, 95% confidence interval 2.09-10.10; p < 0.001). In comparison, 76.9% healthy controls responded with ≥ 3 pupillary dilations (p = 0.028). Results remained consistent across sensitivity analyses using different thresholds for success. Spearman's rank analysis underscored the robust association between pupillary dilations during mental arithmetic and consciousness levels (rho = 1, p = 0.017). Notably, one behaviorally unresponsive patient demonstrated persistent command-following behavior 2 weeks before overt signs of awareness, suggesting prolonged cognitive motor dissociation., Conclusions: Automated pupillometry combined with mental arithmetic can identify cognitive efforts, and hence covert consciousness, in ICU patients with acute DoC., (© 2024. The Author(s).)

Background: Intrahospital transportation (IHT) of patients with traumatic brain injury (TBI) is common and may have adverse consequences, incurring inherent risks. The data on the frequency and severity of clinical complications linked with IHT are contradictory, and there is no agreement on whether it is safe or potentially challenging for neurocritical care unit patients. Continuous intracranial pressure (ICP) monitoring is essential in neurointensive care. The role of ICP monitoring and management of cerebral autoregulation impairments in IHT of patients with severe TBI is underinvestigated. The purpose of this nonrandomized retrospective single-center study was to assess the dynamics of ICP and an improved pressure reactivity index (iPRx) as a measure of autoregulation during IHT., Methods: Seventy-seven men and fourteen women with severe TBI admitted in 2012-2022 with a mean age of 33.2 ± 5.2 years were studied. ICP and arterial pressure were invasively monitored, and cerebral perfusion pressure and iPRx were calculated from the measured parameters. All patients were subjected to dynamic helical computed tomography angiography using a 64-slice scanner Philips Ingenuity computed tomography scan 1-2 days after TBI. Statistical analysis of all results was done using a paired t-test, and p was preset at < 0.05. The logistic regression analysis was performed for cerebral ischemia development dependent on intracranial hypertension and cerebrovascular reactivity., Results: IHT led to an increase in ICP in all the patients, especially during vertical movement in an elevator (maximum 75.2 mm Hg). During the horizontal transportation on the floor, ICP remained increased (p < 0.05). The mean ICP during IHT was significantly higher (26.1 ± 13.5 mm Hg, p < 0.001) than that before the IHT (19.9 ± 5.3 mm Hg). The mean iPRx after and before IHT was 0.52 ± 0.04 and 0.23 ± 0.14, respectively (p < 0.001)., Conclusions: Both horizontal and vertical transportation causes a significant increase in ICP and iPRx in patients with severe TBI, potentially leading to the outcome worsening., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: According to international guidelines, neuroprognostication in comatose patients after cardiac arrest (CA) is performed using a multimodal approach. However, patients undergoing extracorporeal membrane oxygenation (ECMO) may have longer pharmacological sedation and show alteration in biological markers, potentially challenging prognostication. Here, we aimed to assess whether routinely used predictors of poor neurological outcome also exert an acceptable performance in patients undergoing ECMO after CA., Methods: This observational retrospective study of our registry includes consecutive comatose adults after CA. Patients deceased within 36 h and not undergoing prognostic tests were excluded. Veno-arterial ECMO was initiated in patients < 80 years old presenting a refractory CA, with a no flow < 5 min and a low flow ≤ 60 min on admission. Neuroprognostication test performance (including pupillary reflex, electroencephalogram, somatosensory-evoked potentials, neuron-specific enolase) toward mortality and poor functional outcome (Cerebral Performance Categories [CPC] score 3-5) was compared between patients undergoing ECMO and those without ECMO., Results: We analyzed 397 patients without ECMO and 50 undergoing ECMO. The median age was 65 (interquartile range 54-74), and 69.8% of patients were men. Most had a cardiac etiology (67.6%); 52% of the patients had a shockable rhythm, and the median time to return of an effective circulation was 20 (interquartile range 10-28) minutes. Compared with those without ECMO, patients receiving ECMO had worse functional outcome (74% with CPC scores 3-5 vs. 59%, p = 0.040) and a nonsignificant higher mortality (60% vs. 47%, p = 0.080). Apart from the neuron-specific enolase level (higher in patients with ECMO, p < 0.001), the presence of prognostic items (pupillary reflex, electroencephalogram background and reactivity, somatosensory-evoked potentials, and myoclonus) related to unfavorable outcome (CPC score 3-5) in both groups was similar, as was the prevalence of at least any two such items concomitantly. The specificity of each these variables toward poor outcome was between 92 and 100% in both groups, and of the combination of at least two items, it was 99.3% in patients without ECMO and 100% in those with ECMO. The predictive performance (receiver operating characteristic curve) of their combination toward poor outcome was 0.822 (patients without ECMO) and 0.681 (patients with ECMO) (p = 0.134)., Conclusions: Pending a prospective assessment on a larger cohort, in comatose patients after CA, the performance of prognostic factors seems comparable in patients with ECMO and those without ECMO. In particular, the combination of at least two poor outcome criteria appears valid across these two groups., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Improved understanding of post-cardiac arrest syndrome and clinical practices such as targeted temperature management have led to improved mortality in this cohort. Attention has now been placed on development of tools to aid in predicting functional outcome in comatose cardiac arrest survivors. Current practice uses a multimodal approach including physical examination, neuroimaging, and electrophysiologic data, with a primary utility in predicting poor functional outcome. These modalities remain confounded by self-fulfilling prophecy and the withdrawal of life-sustaining therapies. To date, a reliable measure to predict good functional outcome has not been established or validated, but the use of quantitative somatosensory evoked potential (SSEP) shows potential for this use. MEDLINE and EMBASE search using words "Cardiac Arrest" and "SSEP," "Somato sensory evoked potentials," "qSSEP," "quantitative SSEP," "targeted temperature management in cardiac arrest" was conducted. Relevant recent studies on targeted temperature management in cardiac arrest, plus studies on SSEP in cardiac arrest in the setting of hypothermia and without hypothermia, were included. In addition, animal studies evaluating the role of different components of SSEP in cardiac arrest were reviewed. SSEP is a specific indicator of poor outcomes in post-cardiac arrest patients but lacks sensitivity and has not clinically been established to foresee good outcomes. Novel methods of analyzing quantitative SSEP (qSSEP) signals have shown potential to predict good outcomes in animal and human studies. In addition, qSSEP has potential to track cerebral recovery and guide treatment strategy in post-cardiac arrest patients. Lying beyond the current clinical practice of dichotomized absent/present N20 peaks, qSSEP has the potential to emerge as one of the earliest predictors of good outcome in comatose post-cardiac arrest patients. Validation of qSSEP markers in prospective studies to predict good and poor outcomes in the cardiac arrest population in the setting of hypothermia could advance care in cardiac arrest. It has the prospect to guide allocation of health care resources and reduce self-fulfilling prophecy.

Background: Decompressive craniectomy (DC) has been shown to be an effective treatment for malignant cerebral infarction (MCI). There are limited nationwide studies evaluating outcome after craniectomy for MCI., Objective: To describe the evolution in DC practices for MCI, long-term survival, and associated prognostic factors., Methods: We searched the French medico-administrative national database to retrieve patients who underwent DC between 2008 and 2017., Results: A total of 1841 cases of DC were performed over 10 years in 51 centers. Mean age at procedure was 50.9 years, 18% were above 60 years, and 64.4% were male. There was a significant increase in DC for MCI over the 10 years (p < 0.001), and the annual volume of procedures more than doubled (95/year vs. 243/year). Early survival at one week and one month was 86%, 95% CI (84.5, 87.6) and 79.7%, 95% CI (77.8, 81.5), respectively. Long-term survival at 1 and 5 years were 73.6%, 95% CI (71.6, 75.7) and 68.9%, 95% CI (66.5, 71.4), respectively. Patients below 60 years at the time of DC (HR = 0.5; 95% CI [0.4, 0.7], p < 0.001), DC being performed in a center with a high surgical activity (HR = 0.8; 95% CI [0.6, 0.9], p = 0.002), and the patients having unimpaired consciousness (HR = 0.6; 95% CI [0.5, 0.8], p < 0.001) were associated with increased survival in both univariate and adjusted Cox regressions. 18.7% of the survivors had a cranioplasty inserted within 3 months and 57.8% within 6 months. The probability of having a cranioplasty at one year was 75.6%, 95% CI (77.9, 73.1)., Conclusion: Over the past 10 years in France, DC has been increasingly performed for MCI regardless of age. However, in-hospital mortality remains considerable, as about one quarter of patients died within the first weeks. For those who survive beyond 6 months, the risk of death significantly decreases. Early mortality is especially high for comatose patients above 60 years operated in inexperienced centers. Most of those who remain in good functional status tend to undergo a cranioplasty within the year following DC.

Background: Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure., Methods: In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method., Results: Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients., Conclusions: Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.

Background: Predicting neurological outcome in comatose survivors of cardiac arrest relies on clinical findings, radiological and neurophysiological test results. To evaluate the predictive accuracy of brain computed tomography (CT) and magnetic resonance imaging (MRI) for prognostication of neurological outcomes after cardiac arrest., Methods: We searched MEDLINE (database inception to August 2018) and included all observational cohort studies or randomized controlled trials including adult (16 years or older) survivors of cardiac arrest which evaluated the diagnostic accuracy of CT or MRI for predicting neurologic outcome or mortality. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All review stages were conducted independently by 2 reviewers, and where possible data were pooled using bivariate meta-analysis. The main outcome was to evaluate the of accuracy of CT and MRI in neuroprognostication of patients after cardiac arrest., Results: We included 44 studies that examined brain CT (n = 24) or MRI (n = 21) in 4008 (n per study, 9-398) patients. Decreased grey to white matter ratio on CT (20 studies) was useful for predicting poor neurological outcome (sensitivity 0.44, 95% CI 0.29-0.60; specificity 0.97, 95% CI 0.93-0.99; positive likelihood ratio [LR+] 13.8, 95% CI 6.9-27.7). Similarly, diffusion-weighted imaging (DWI) on MRI (16 studies; sensitivity 0.77, 95% CI 0.65-0.85; specificity 0.92, 95% CI 0.85-0.96; LR+ 9.2, 95% CI 5.2-16.4) and DWI and fluid-attenuated inversion recovery (FLAIR) MRI (4 studies, sensitivity 0.70, 95% CI 0.43-0.88; specificity 0.95, 95% CI 0.79-0.99; LR+ 13.4, 95% CI 3.5-51.2) were useful for predicting poor neurological outcomes. We found marked heterogeneity in timing of radiological examinations and neurological assessments relative to the cardiac arrest., Conclusion: Decreased grey to white matter ratio on CT and DWI or DWI and FLAIR on MRI are useful adjuncts for predicting poor early neurological outcome after cardiac arrest.

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO 2 ) monitors., Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8 h of daily monitoring. Brain PbO 2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO 2 below 19 mmHg for more than 6 min from baseline (PbO 2  > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21 mmHg) and "low" (< 19 mmHg) PbO 2 . Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension., Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO 2 , we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO 2 epochs (AUC 0.876)., Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

Background: Forty to sixty-six percent of patients resuscitated from cardiac arrest remain comatose, and historic outcome predictors are unreliable. Quantitative spectral analysis of continuous electroencephalography (cEEG) may differ between patients with good and poor outcomes., Methods: Consecutive patients with post-cardiac arrest hypoxic-ischemic coma undergoing cEEG were enrolled. Spectral analysis was conducted on artifact-free contiguous 5-min cEEG epochs from each hour. Whole band (1-30 Hz), delta (δ, 1-4 Hz), theta (θ, 4-8 Hz), alpha (α, 8-13 Hz), beta (β, 13-30 Hz), α/δ power ratio, percent suppression, and variability were calculated and correlated with outcome. Graphical patterns of quantitative EEG (qEEG) were described and categorized as correlating with outcome. Clinical outcome was dichotomized, with good neurologic outcome being consciousness recovery., Results: Ten subjects with a mean age = 50 yrs (range = 18-65) were analyzed. There were significant differences in total power (3.50 [3.30-4.06] vs. 0.68 [0.52-1.02], p = 0.01), alpha power (1.39 [0.66-1.79] vs 0.27 [0.17-0.48], p < 0.05), delta power (2.78 [2.21-3.01] vs 0.55 [0.38-0.83], p = 0.01), percent suppression (0.66 [0.02-2.42] vs 73.4 [48.0-97.5], p = 0.01), and multiple measures of variability between good and poor outcome patients (all values median [IQR], good vs. poor). qEEG patterns with high or increasing power or large power variability were associated with good outcome (n = 6). Patterns with consistently low or decreasing power or minimal power variability were associated with poor outcome (n = 4)., Conclusions: These preliminary results suggest qEEG metrics correlate with outcome. In some patients, qEEG patterns change over the first three days post-arrest.

Background: Neurological complications in liver failure are common. Often under-recognized neurological complications are seizures and status epilepticus. These may go unrecognized without continuous electroencephalography (CEEG). We highlight the observed electro-radiological changes in patients with grade III/IV hepatic encephalopathy (HE) found to have seizures and/or status epilepticus on CEEG and the associated neuroimaging., Methods: This study was a retrospective review of patients with West Haven grade III/IV HE and seizures/status epilepticus on CEEG., Results: Eleven patients were included. Alcohol was the most common cause of HE (54.5%). All patients were either stuporous/comatose. The most common CEEG pattern was diffuse slowing (100%) followed by generalized periodic discharges (GPDs; 36.4%) and lateralized periodic discharges (LPDs, 36.4%). The subtype of GPDs with triphasic morphology was only seen in 27.3%. All seizures and/or status epilepticus were without clinical signs. Magnetic resonance imaging (MRI) was available in six patients. Cortical hyperintensities on diffusion weighted imaging sequence were seen in all six patients. One patient had CEEG seizure concomitantly with the MRI. Seven patients died prior to discharge., Conclusion: Seizures or status epilepticus in the setting of HE were without clinical findings and could go unrecognized without CEEG. The finding of cortical hyperintensity on MRI should lead to further evaluation for unrecognized seizure or status epilepticus.

Background: Existing studies of quantitative electroencephalography (qEEG) as a prognostic tool after cardiac arrest (CA) use methods that ignore the longitudinal pattern of qEEG data, resulting in significant information loss and precluding analysis of clinically important temporal trends. We tested the utility of group-based trajectory modeling (GBTM) for qEEG classification, focusing on the specific example of suppression ratio (SR)., Methods: We included comatose CA patients hospitalized from April 2010 to October 2014, excluding CA from trauma or neurological catastrophe. We used Persyst ® v12 to generate SR trends and used semi-quantitative methods to choose appropriate sampling and averaging strategies. We used GBTM to partition SR data into different trajectories and regression associate trajectories with outcome. We derived a multivariate logistic model using clinical variables without qEEG to predict survival, then added trajectories and/or non-longitudinal SR estimates, and assessed changes in model performance., Results: Overall, 289 CA patients had ≥36 h of EEG yielding 10,404 h of data (mean age 57 years, 81 % arrested out-of-hospital, 33 % shockable rhythms, 31 % overall survival, 17 % discharged to home or acute rehabilitation). We identified 4 distinct SR trajectories associated with survival (62, 26, 12, and 0 %, P < 0.0001 across groups) and CPC (35, 10, 4, and 0 %, P < 0.0001 across groups). Adding trajectories significantly improved model performance compared to adding non-longitudinal data., Conclusions: Longitudinal analysis of continuous qEEG data using GBTM provides more predictive information than analysis of qEEG at single time-points after CA., Competing Interests: The authors have no additional funding or conflicts of interest to report.

Background: The aim of this study was to evaluate the prognostic value of continuous electroencephalogram (cEEG) during the first 48 h following cardiac arrest (CA) in patients treated with targeted temperature management (TTM)., Methods: We reviewed data from 92 comatose post-CA patients over a 6 year-period; cEEG recordings were performed during TTM and restoration of normothermia. EEG findings were divided into four time-periods: 0-8, 8-16, 16-24, and 24-48 h after CA. Background EEG findings were defined as moderate encephalopathy (diffuse slowing with reactivity/variability), severe encephalopathy (diffuse slowing without reactivity/variability), burst suppression or suppression, and dichotomized as malignant (suppression/burst suppression/severe encephalopathy) or benign (moderate encephalopathy). Epileptiform activity was defined as the presence of seizures, sporadic epileptiform discharges, or periodic discharges. Neurological outcome was assessed at 3 months using the cerebral performance categories (CPC) score (good outcome: CPC 1-2)., Results: 26/92 (28%) patients had a good outcome. Malignant patterns were associated with a poor outcome at all time-points, with a high positive predictive value (94-97%) but a poor negative predictive value (44-56%). Epileptiform activity did not influence the prognostic value of EEG patterns. All patients with moderate encephalopathy and seizures or generalized periodic discharges had a poor outcome., Conclusions: cEEG can identify patients with poor outcome from the first hours following CA, with limited predictive value for good outcome. Epileptiform activity did not improve the prognostic accuracy of EEG, but seizures and generalized periodic discharges were associated with poor outcome even when developing on a benign EEG pattern.

Background: Lack of electroencephalography (EEG) background reactivity during therapeutic hypothermia (TH) has been associated with poor outcome in post-anoxic comatose patients. However, decision on intensive care withdrawal is based on normothermic (NT) evaluations. This study aims at exploring whether patients showing recovery of EEG reactivity in NT after a non-reactive EEG in TH differ from those remaining non-reactive., Methods: Patients with non-reactive EEG during TH were identified from our prospective registry of consecutive comatose adults admitted after successful resuscitation from CA between April 2009 and June 2014. Variables including neurological examination, serum neuron-specific enolase (NSE), procalcitonin, and EEG features were compared regarding impact on functional outcome at 3 months., Results: Seventy-two of 197 patients (37 %) had a non-reactive EEG background during TH with thirteen (18 %) evolving towards reactivity in NT. Compared to those remaining non-reactive (n = 59), they showed significantly better recovery of brainstem reflexes (p < 0.001), better motor responses (p < 0.001), transitory consciousness improvement (p = 0.008), and a tendency toward lower NSE (p = 0.067). One patient recovering EEG reactivity survived with good functional outcome at 3 months., Conclusions: Recovery of EEG reactivity from TH to NT seems to distinguish two patients' subgroups regarding early neurological assessment and transitory consciousness improvement, corroborating the role of EEG in providing information about cerebral functions. Understanding these dynamic changes encourages maintenance of intensive support in selected patients even after a non-reactive EEG background in TH, as a small subgroup may indeed recover with good functional outcome.

Background: The bilateral absence of the cortical N20 median-nerve somatosensory evoked potential (SSEP) is a strong predictor of poor outcome from coma. However, when N20s are present, accurate prognostication is challenging. Here, we investigated the potential for later SSEP components to help disambiguate outcome in these cases., Methods: In a retrospective review of data from two intensive care units, the amplitudes and latencies of the N20, P25, and N35 components of 28 patients in coma were quantified and related to outcome at discharge from primary care (average 1-month post-injury). Only patients who had survived primary care were included in order to avoid self-fulfilling prophecies, and to focus outcome prediction on those patients with relatively present SSEPs., Results: The amplitudes of the N20 and N35 components (averaged across hemispheres) significantly predicted the range of outcomes beyond death. Abnormal amplitudes of the N20 and N35--as derived from a healthy control group--were significantly associated with poor outcome. The relative latencies of the cortical components were not related to outcome., Conclusions: While it is well documented that absent SSEPs are highly predictive of poor outcome, the current data indicate that the relative preservation (absolute amplitude) of "present" N20 and N35 SSEP components can also provide predictive value and thereby inform clinicians and families with decision-making in coma. Further prospective study will elucidate the relative contributions of etiology to the predictive power of these SSEP measures.

Background: We hypothesized that the degree of preserved functional connectivity within the DMN during the first week after cardiopulmonary arrest (CPA) would be associated with functional outcome at hospital discharge., Methods: Initially comatose CPA survivors with indeterminate prognosis at 72 h were enrolled. Seventeen CPA subjects between 4 and 7 days after CPA and 17 matched controls were studied with task-free fMRI. Independent component analysis was performed to delineate the DMN. Connectivity strength in the DMN was compared between CPA subjects and controls, as well as between CPA subjects with good outcome (discharge Cerebral Performance Category or CPC 1-2) and those with bad outcome (CPC 3-5). The relationship between connectivity strength in the posterior cingulate cortex (PCC) and precuneus (PC) within the DMN with discharge CPC was evaluated using linear regression., Results: Compared to controls, CPA subjects had significantly lower connectivity strength in subregions of the DMN, the PCC and PC (p < 0.0001). Furthermore, connectivity strength in the PCC and PC was greater in CPA subjects with good outcome (n = 8) than those with bad outcome (n = 9) (p < 0.003). Among CPA subjects, the connectivity strength in the PCC and PC showed strong linear correlations with the discharge CPC (p < 0.005)., Conclusions: Among initially comatose CPA survivors with indeterminate prognosis, task-free fMRI demonstrated graded disruption of DMN connectivity, especially in those with bad outcomes. If confirmed, connectivity strength in the PC/PCC may provide a clinically useful prognostic marker for functional recovery after CPA.

Background: To investigate the effect of mild hypothermia on conduction times and amplitudes of median nerve somatosensory evoked potentials (SEP) in patients after cardiopulmonary resuscitation (CPR)., Methods: Patients treated with hypothermia after CPR who underwent SEP recording during hypothermia and after rewarming were selected from a prospectively collected database. Latencies and amplitudes of N9 (peripheral conduction time, PCT), N13, and N20 were measured. The central conduction time (CCT) was defined as peak-peak latency N13-N20. Recordings of 25 patients were assessed by a second observer to determine the intraclass correlation coefficient (ICC)., Results: A total of 115 patients were included. The mean body temperature at SEP during hypothermia was 33.1 °C (SD 0.8) and after rewarming 37.1 °C (SD 0.8). Mean latencies of N9, N13, and N20 and mean CCT were longer during hypothermia. There were no consistent differences in amplitudes. There was an almost perfect ICC for assessment of latencies and amplitudes., Conclusions: This study showed that PCT and CCT of median nerve SEP were prolonged during treatment with hypothermia after CPR compared with after rewarming. Amplitudes did not differ consistently.

Background: We report four patients who developed periodic eyelid opening following hypoxic ischemic injury. This manuscript reviews the clinical course of our patients as well as previously published cases and discusses the neuroanatomical basis of eyelid opening., Methods: Data were collected from the patients' electronic medical record and digital electroencephalography recordings., Results: In all patients, periodic eyelid opening was associated with a burst-suppression pattern on electroencephalography (EEG). Rapid eyelid opening appeared with the onset of bursts, while slow eyelid closure coincided with periods of suppression. Progressive rostrocaudal deterioration in brainstem function ensued, in each case culminating in brain death., Conclusions: Our experience and prior reports suggest that periodic eyelid opening following cardiac arrest is associated with a burst-suppression pattern on EEG. Since burst-suppression is highly (though not invariably) predictive of a poor outcome in this patient population, intensivists should be familiar with this neurological sign. Prospective studies are needed to define the neurophysiology of this phenomena and clarify its clinical significance.

The loss of the N20 component on testing median somatosensory evoked potentials (SSEP) has been established as the most reliable indicator of unfavorable prognosis in post-cardiopulmonary arrest patients. With the intervention of therapeutic hypothermia in the management of patients who remain comatose following cardiopulmonary arrest that association is now in dispute. Abandoning SSEP as a key prognostic indicator of neurologic outcome would be a serious loss and cannot be justified.

Background: Periodic epileptiform discharges (PEDs) are a frequent finding in comatose patients undergoing continuous EEG (cEEG) monitoring, but their clinical significance is unclear. PET and SPECT studies indicate that PEDs can be associated with focal hypermetabolism and hyperemia, suggesting that in some cases this pattern may be ictal and potentially harmful. We hypothesized that frequent PED activity in comatose patients is associated with reduced likelihood of recovery of consciousness., Methods: We identified all comatose patients treated in the Columbia neuro-ICU between June 2008 and August 2009 who underwent ten or more consecutive days of video cEEG monitoring (N = 67), and classified them into three groups: those with (1) prolonged PEDs (five or more consecutive days), (2) intermittent PEDs (at least one but fewer than five consecutive days), and (3) no PEDs. Outcome at discharge was assessed by the Glasgow Outcome Scale and classified as dead (GOS 1), vegetative (GOS 2), and command-following (GOS 3-5)., Results: Mean age was 56 years, mean admission Glasgow Coma Scale score was seven, and the median duration of cEEG monitoring was 18 (range 10-111) days. The most common diagnoses were hypoxic-ischemic encephalopathy (18%), subarachnoid hemorrhage (16%), epilepsy (15%), encephalitis (15%), metabolic encephalopathy (13%), and intracerebral hemorrhage (12%). 37% of patients (N = 25) had prolonged PEDs, 31% (N = 21) had intermittent PEDs, and 31% (N = 21) had no PEDs. Prolonged PEDs were associated with the presence of SIRPIDS (P = 0.009), electrographic seizures (P = 0.019), and number of AEDs administered (P < 0.0001). However, the presence of intermittent or prolonged PED activity had no impact on mortality (31% overall) or recovery of consciousness (command-following) at the time of discharge (36% overall)., Conclusion: Persistent spontaneous PED activity in comatose patients is associated with SIRPIDs and electrographic seizures, but has no impact on the likelihood of survival or recovery of consciousness.

We present the video of a patient who presented massive and ongoing rhythmic abdominal myoclonus in postanoxic coma.

Background: Low cerebrospinal fluid volume is typically diagnosed in patients presenting with positional headaches. However, severe intracranial hypotension and brain sagging may cause orthostatic coma. We present a case that illustrates this uncommon presentation., Method: Case report., Results: A 50-year-old man presented with orthostatic headaches and then developed bilateral subdural hematomas. Following unilateral subdural hematoma evacuation, the patient became gradually drowsier and more confused. Upon transfer to our hospital, he would become comatose each time he was placed in the upright position. Successful epidural patch at the level of a spontaneous cerebrospinal fluid leak documented by myelography resulted in complete resolution of his orthostatic symptoms despite reaccumulation of the subdural fluid collection., Conclusions: Evacuation of subdural fluid collections may be detrimental in patients with low CSF volume by exacerbating the intracranial hypotension. Extreme brain sagging may lead to anatomical distortion of the diencephalon and brainstem resulting in coma.

Introduction: It is unclear whether the rate of stimulation for somatosensory evoked potentials (SEPs) can influence the presence or absence of cortical responses to median nerve stimulation in comatose patients. If so, this could affect how SEPs are performed and interpreted for prognostication in coma. Our objective was to determine how frequently our comatose patients had absent median nerve SEP responses at 3 Hz stimulation, but present responses at 1 Hz stimulation, and to report outcomes of these patients., Methods: We reviewed SEP recordings in 639 comatose patients over a 9-year period. All had stimulation at 3 Hz and 1 Hz. This is a retrospective review., Results: There were seven patients who had absent median nerve SEP responses at 3 Hz stimulation bilaterally, but had present responses at 1 Hz on one or both sides. Six of the seven died. One 16-year-old patient with traumatic brain injury awoke, but had moderate disability., Conclusions: Stimulation rate is an important determinant of presence or absence of cortical responses in about 1% of comatose patients. It is unclear whether such patients have a different outcome that those with absent responses at both rates of stimulation.

Background: Diagnosing brain death in children is challenging. Guidelines recommend using confirmatory testing to provide ancillary information to support the diagnosis. Brain tissue oxygenation (PbtO(2)) is being increasingly used in the adult neurocritical care for continuous monitoring of the adequacy of brain oxygenation; however, data in pediatrics is limited. Evidence from adult studies suggests that persistent PbtO(2) of 0 mmHg is associated with brain death, but this relationship has not yet been demonstrated in children; therefore, we examined our experience with PbtO(2) monitoring and brain death in children with acute neurological pathology., Methods: We retrospectively reviewed patient records from a prospectively maintained database of 85 children who were ventilated for coma due to acute neurological injury and who received intracerebral monitoring., Results: We identified five children who had suffered brain death while being monitored. PbtO(2) had decreased to 0 mmHg in all five children at the time of brain death diagnosis. In contrast, PbtO(2) in patients, who did not develop brain death, never decreased to 0 mmHg. We review the benefits and drawbacks of using brain tissue oxygenation as ancillary information in diagnosing brain death in children., Conclusions: Preliminary data from this study suggest that PbtO(2) decreases to 0 mmHg when brain death occurs in children. Further study is needed to determine the limitations, and the sensitivity and specificity of this finding in a larger group of children.

Objective: Full Outline of Unresponsiveness (FOUR) score has previously been validated scale in the Neurosciences Intensive Care Unit. In this study, we sought to validate the use of FOUR score in the emergency department (ED) using non-neurology staff. We also compared its performance to the Glasgow Coma Scale (GCS) and correlated it to functional outcome at hospital discharge and overall survival., Methods: We prospectively rated 69 patients with initial neurologic symptoms presenting to the ED. Three types of examiners performed the FOUR score: ED physician, ED resident, and ED nurse. Patients were followed through hospital discharge; functional outcome was measured using modified Rankin Score (mRS)., Results: Interrater reliability for FOUR score and GCS was excellent (respectively, kappa(w) = 0.88 and 0.86). Both FOUR score and GCS predicted functional outcome, and overall survival with and without adjustment for age, sex, and alertness group., Conclusion: The FOUR score can be reliably used in the ED by non-neurology staff. Both FOUR score and GCS performed equally well, but the neurologic detail incorporated in the FOUR score makes it more useful in management and triage of patients.

Introduction: Several studies have been performed to assess the prognostic value of early neurological and neurophysiological findings in patients with postanoxic coma, but they have not led to precise, generally accepted, prognostic rules. This study was performed to assess whether it is possible to create a prognostic outcome table, using a combination of clinical variables and the electroencephalogram (EEG)., Methods: Clinical variables and EEG were registered on admission, at day 1-5, day 6-14, and day 15-42, and were related to the Glasgow outcome scale (GOS) at 30 and 180 days. The EEG abnormalities were categorized using the EEG classification system proposed by Synek (J Clin Neurophysiol 5:161-174, 1988) and Young et al. (Can J Neurol Sci 24:320-325, 1997). These EEG classifications were then further divided into prognostic categories., Results: Age was a significant predictor of outcome. The early recorded clinical variables were the most predictive and the GCS showed a limited prognostic value. The first EEG registration proved to be the most predictive. The Synek-classification was divided into three prognostic categories: "benign," "malignant," and "fatal" and the Young-classification into four: "benign," "intermediate," "malignant," and "fatal." An outcome prediction table is proposed using the Young-classification stratified for age., Conclusion: Age is an important variable determining the prognostic value of the EEG and should always be taken into consideration. The prognostic categories, especially when derived from the Young-classification, showed a good prognostic value. Although this is a pilot study, we believe that the revised prognostic categories have a good prognostic value in predicting outcome and are worth further investigation and validation.

Much has been written about the neurologic basis and rationale for the coma examination, but little has been written about its ethical framework. In contrast to the neurologic framework, the ethical basis for the use of painful stimuli in the coma examination is context dependent and value driven, aimed at identifying the ethical justification for healthcare professionals to cause pain for patients in ways that would not be tolerated or justifiable in any other setting. Basic ethical principles can be used to justify the use of painful stimuli to examine patients, but they also impose limits on their use. To clarify the ethical issues that apply to the coma examination, we review its neurologic and ethical bases and propose a practical test by which to justify the use of painful stimuli.

We review the interest of cognitive event-related potentials (ERPs) in comatose, vegetative, or minimally conscious patients. Auditory cognitive ERPs are useful to investigate residual cognitive functions, such as echoic memory (MMN), acoustical and semantic discrimination (P300), and incongruent language detection (N400). While early ERPs (such as the absence of cortical responses on somatosensory-evoked potentials) predict bad outcome, cognitive ERPs (MMN and P300) are indicative of recovery of consciousness. In coma-survivors, cognitive potentials are more frequently obtained when using stimuli that are more ecologic or have an emotional content (such as the patient's own name) than when using classical sine tones.

Introduction: Prognostic determination of patients in coma after resuscitation from cardiac arrest is both common and difficult. We explored clinical and electrophysiological testing to determine their associations with favorable and poor outcomes., Methods: We studied 75 comatose patients resuscitated from cardiac arrest, excluding those who were brain dead or continuously sedated; none received hypothermia therapy. Clinical examinations were performed on day 1., Results: The following proportions recovered awareness: 2 of 18 patients with absent pupillary reflexes; 18 of 57 with preserved pupillary reflexes (p = 0.08); 2 of 32 with absent corneal reflexes; 16 of 43 with preserved corneal reflexes (p = 0.001); 0 of 15 with absent oculovestibular reflexes; and 8 of 29 with preserved oculovestibular reflexes (p < 0.037). Purposeful movements were associated with a high probability of recovery, whereas other categories were unfavorable. Other categories of motor response were associated with an increased proportion of those who died without recovering awareness, but each category had some survivors. Somatosensory evoked potentials (SSEPs) were recorded from 47 patients. One of 21 patients with loss of the N20 component survived, compared with survival of 11 of 26 patients in whom it was present (p = 0.003). All 5 patients with preserved N70 responses recovered awareness in a subgroup of 33 patients. Sixteen of 22 subjects with mild electroencephalogram (EEG) abnormalities recovered consciousness, compared with the survival of 3 of 50 patients with malignant EEG patterns (p = 0.0000001). Combining SSEP with EEG findings produced even greater predictive value., Conclusion: It seems unlikely that any single test will prove to have 100% predictive value for outcome; further studies combining clinical, EEG, and SSEP testing are warranted.

Introduction: It is unclear whether patients or subpopulations of patients might benefit from EEG monitoring., Methods: We conducted a prospective trial of continuous electroencephalogram monitoring (CEEG; 48 hours)., Results: Eleven of 55 (20%) patients who underwent CEEG monitoring recorded seizures. Of patients with acute structural brain lesions (ASBLs), 10 of 31 (32%) patients experiences recorded seizures, whereas only 24 (4%) patients with metabolic encephalopathies experienced recorded seizures (p < 0.01). Six patients with ASBLs (11%) and one patient with metabolic encephalopathy (4%) had spikes/interictal epileptiform discharges (p = 0.087)., Conclusion: Our study suggests that CEEG monitoring may be more valuable for detection of seizures in patients with ASBLs than in patients with metabolic encephalopathies.