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Introduction Current electroencephalography (EEG) practice relies on interpretation by expert neurologists, which introduces diagnostic and therapeutic delays that can impact patients’ clinical outcomes. As EEG practice expands, these experts are becoming increasingly limited resources. A highly sensitive and specific automated seizure detection system would streamline practice and expedite appropriate management for patients with possible nonconvulsive seizures. We aimed to test the performance of a recently FDA-cleared machine learning method (Claritγ, Ceribell Inc.) that measures the burden of seizure activity in real time and generates bedside alerts for possible status epilepticus (SE). Methods We retrospectively identified adult patients ( n  = 353) who underwent evaluation of possible seizures with Rapid Response EEG system (Rapid-EEG, Ceribell Inc.). Automated detection of seizure activity and seizure burden throughout a recording (calculated as the percentage of ten-second epochs with seizure activity in any 5-min EEG segment) was performed with Claritγ, and various thresholds of seizure burden were tested (≥ 10% indicating ≥ 30 s of seizure activity in the last 5 min, ≥ 50% indicating ≥ 2.5 min of seizure activity, and ≥ 90% indicating ≥ 4.5 min of seizure activity and triggering a SE alert). The sensitivity and specificity of Claritγ’s real-time seizure burden measurements and SE alerts were compared to the majority consensus of at least two expert neurologists. Results Majority consensus of neurologists labeled the 353 EEGs as normal or slow activity ( n  = 249), highly epileptiform patterns (HEP, n  = 87), or seizures [ n  = 17, nine longer than 5 min (e.g., SE), and eight shorter than 5 min]. The algorithm generated a SE alert (≥ 90% seizure burden) with 100% sensitivity and 93% specificity. The sensitivity and specificity of various thresholds for seizure burden during EEG recordings for detecting patients with seizures were 100% and 82% for ≥ 50% seizure burden and 88% and 60% for ≥ 10% seizure burden. Of the 179 EEG recordings in which the algorithm detected no seizures, seizures were identified by the expert reviewers in only two cases, indicating a negative predictive value of 99%. Discussion Claritγ detected SE events with high sensitivity and specificity, and it demonstrated a high negative predictive value for distinguishing nonepileptiform activity from seizure and highly epileptiform activity. Conclusions Ruling out seizures accurately in a large proportion of cases can help prevent unnecessary or aggressive over-treatment in critical care settings, where empiric treatment with antiseizure medications is currently prevalent. Claritγ’s high sensitivity for SE and high negative predictive value for cases without epileptiform activity make it a useful tool for triaging treatment and the need for urgent neurological consultation.

Background The use of processed electroencephalography (pEEG) for depth of sedation (DOS) monitoring is increasing in anesthesia; however, how to use of this type of monitoring for critical care adult patients within the intensive care unit (ICU) remains unclear. Methods A multidisciplinary panel of international experts consisting of 21 clinicians involved in monitoring DOS in ICU patients was carefully selected on the basis of their expertise in neurocritical care and neuroanesthesiology. Panelists were assigned four domains (techniques for electroencephalography [EEG] monitoring, patient selection, use of the EEG monitors, competency, and training the principles of pEEG monitoring) from which a list of questions and statements was created to be addressed. A Delphi method based on iterative approach was used to produce the final statements. Statements were classified as highly appropriate or highly inappropriate (median rating ≥ 8), appropriate (median rating ≥ 7 but < 8), or uncertain (median rating < 7) and with a strong disagreement index (DI) (DI < 0.5) or weak DI (DI ≥ 0.5 but < 1) consensus. Results According to the statements evaluated by the panel, frontal pEEG (which includes a continuous colored density spectrogram) has been considered adequate to monitor the level of sedation (strong consensus), and it is recommended by the panel that all sedated patients (paralyzed or nonparalyzed) unfit for clinical evaluation would benefit from DOS monitoring (strong consensus) after a specific training program has been performed by the ICU staff. To cover the gap between knowledge/rational and routine application, some barriers must be broken, including lack of knowledge, validation for prolonged sedation, standardization between monitors based on different EEG analysis algorithms, and economic issues. Conclusions Evidence on using DOS monitors in ICU is still scarce, and further research is required to better define the benefits of using pEEG. This consensus highlights that some critically ill patients may benefit from this type of neuromonitoring.

Background Although the placement of an intraventricular catheter remains the gold standard technique for measuring intracranial pressure (ICP), the method has several limitations. Therefore, noninvasive alternatives to ICP (ICPni) measurement are of great interest. The main objective of this study was to compare the correlation and agreement of wave morphology between ICP (standard intraventricular ICP monitoring) and a new ICPni monitor in patients admitted with stroke. The second objective was to estimate the discrimination of the noninvasive method to detect intracranial hypertension. Methods We prospectively collected data of adults admitted to an intensive care unit with subarachnoid hemorrhage, intracerebral hemorrhage, or ischemic stroke in whom an invasive ICP monitor was placed. Measurements were simultaneously collected from two parameters [time-to-peak (TTP) and the ratio regarding the second and first peak of the ICP wave ( P 2/ P 1 ratio)] of ICP and ICPni wave morphology monitors (Brain4care). Intracranial hypertension was defined as an invasively measured sustained ICP > 20 mm Hg for at least 5 min. Results We studied 18 patients (subarachnoid hemorrhage = 14; intracerebral hemorrhage = 3; ischemic stroke = 1) on 60 occasions with a median age of 52 ± 14.3 years. A total of 197,400 waves (2495 min) from both ICP (standard ICP monitoring) and the ICPni monitor were sliced into 1-min-long segments, and we determined TTP and the P 2/ P 1 ratio from the mean pulse. The median invasively measured ICP was 13 (9.8–16.2) mm Hg, and intracranial hypertension was present on 18 occasions (30%). The correlation and agreement between invasive and noninvasive methods for wave morphology were strong for the P 2/ P 1 ratio and moderate for TTP using categoric ( κ agreement 88.1% and 71.3%, respectively) and continuous (intraclass correlation coefficient 0.831 and 0.584, respectively) measures. There was a moderate but significant correlation with the mean ICP value ( P 2/ P 1 ratio r  = 0.427; TTP r  = 0.353; p  < 0.001 for all) between noninvasive and invasive techniques. The areas under the curve to estimate intracranial hypertension were 0.786 [95% confidence interval (CI) 0.72–0.93] for the P 2/ P 1 ratio and 0.694 (95% CI 0.60–0.74) for TTP. Conclusions The new ICPni wave morphology monitor showed a good agreement with the standard invasive method and an acceptable discriminatory power to detect intracranial hypertension. Clinical trial registration Trial registration: NCT05121155.

Background Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis. Methods As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents. Results The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians ( n  = 213, 83%), were from the United States ( n  = 141, 55%), and represented academic centers ( n  = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ  = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ  = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ  = 0.552); and inability to follow commands (58%, κ  = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%). Conclusions There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.

Background Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. Aim To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. Methods A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. Results Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. Conclusion The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Background Intravenous (IV) milrinone, in combination with induced hypertension, has been proposed as a treatment option for cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, data on its safety and efficacy are scarce. Methods This was a controlled observational study conducted in an academic hospital with prospectively and retrospectively collected data. Consecutive patients with cerebral vasospasm following aSAH and treated with both IV milrinone (0.5 µg/kg/min −1 , as part of a strict protocol) and induced hypertension were compared with a historical control group receiving hypertension alone. Multivariable analyses aimed at minimizing potential biases. We assessed (1) 6-month functional disability (defined as a score between 2 and 6 on the modified Rankin Scale) and vasospasm-related brain infarction, (2) the rate of first-line or rescue endovascular angioplasty for vasospasm, and (3) immediate tolerance to IV milrinone. Results Ninety-four patients were included (41 and 53 in the IV milrinone and the control group, respectively). IV milrinone infusion was independently associated with a lower likelihood of 6-month functional disability (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI] = 0.10–0.77]) and vasospasm-related brain infarction (aOR = 0.19, 95% CI 0.04–0.94). Endovascular angioplasty was less frequent in the IV milrinone group (6 [15%] vs. 28 [53%] patients, p  = 0.0001, aOR = 0.12, 95% CI 0.04–0.38). IV milrinone (median duration of infusion, 5 [2–8] days) was prematurely discontinued owing to poor tolerance in 12 patients, mostly ( n  = 10) for “non/hardly-attained induced hypertension” (mean arterial blood pressure < 100 mmHg despite 1.5 µg/kg/min −1 of norepinephrine). However, this event was similarly observed in IV milrinone and control patients ( n  = 10 [24%] vs. n  = 11 [21%], respectively, p  = 0.68). IV milrinone was associated with a higher incidence of polyuria (IV milrinone patients had creatinine clearance of 191 [153–238] ml/min −1 ) and hyponatremia or hypokalemia, whereas arrhythmia, myocardial ischemia, and thrombocytopenia were infrequent. Conclusions Despite its premature discontinuation in 29% of patients as a result of its poor tolerance, IV milrinone was associated with a lower rate of endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes. These preliminary findings encourage the conduction of confirmatory randomized trials.

Background/Objective There are limited data on the risks and benefits of using andexanet alfa (AA) in comparison with four-factor prothrombin complex concentrate (4F-PCC) to reverse factor Xa inhibitors (FXi) associated intracranial hemorrhage (ICH). We sought to describe our experience with AA or 4F-PCC in patients with oral FXi-related traumatic and spontaneous ICH. Methods We conducted a retrospective review of consecutive adult patients with FXi-related ICH who received AA or 4F-PCC. FXi-related ICH cases included traumatic and spontaneous intracranial hemorrhages. Our primary analysis evaluated ICH stability on head computed tomography scan (CT), defined as a similar amount of blood from the initial scan at the onset of ICH to subsequent scans, at 6-h and 24-h post-administration of AA or 4F-PCC. For the subset of spontaneous intraparenchymal hemorrhages, volume was measured at 6-h and 24-h post-reversal. In secondary analyses, we evaluated good functional outcome at discharge, defined as a Modified Rankin Score of less than 3, and the incidence of thrombotic events after AA or 4F-PCC adminstration, during hospitalization. Results A total of 44 patients (16 traumatic and 28 spontaneous ICH) with median age of 79 years [72–86], 36% females, with a FXi-related ICH, were included in this study. The majority of spontaneous ICHs were intraparenchymal 19 (68%). Twenty-eight patients (64%) received AA and 16 patients (36%) received 4F-PCC. There was no difference between AA and 4F-PCC in terms of CT stability at 6 h (21 [78%] vs 10 [71%], p  = 0.71) and 24 h (15 [88%] vs 6 [60%], p  = 0.15). In a subgroup of patients with spontaneous intraparenchymal hemorrhage, there was no difference in the degree of achieved hemostasis based on hematoma volume between AA and 4F-PCC at 6 h (9.3 mL [6.9–26.4] vs 10 mL [9.4–22.1], adjusted p  = 0. 997) and 24-h (9.2 mL [6.1–18.8] vs 9.9 [9.4–21.1], adjusted p  = 1). The number of patients with good outcome based on mRS on discharge were 10 (36%) and 6 (38%) in the AA and 4F-PCC groups, respectively (adjusted p  = 0.81). The incidence of thromboembolic events was similar in the AA and 4F-PCC groups (2 [7%] vs 0, p  = 0.53). Conclusion In this limited sample of patients, we found no difference in neuroimaging stability, functional outcome and thrombotic events when comparing AA and 4F-PCC in patients with FXi-related ICH. Since our analysis is likely underpowered, a multi-center collaborative network devoted to this question is warranted.

Background The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease. Case Presentations Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam. Discussion Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood–brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established. Conclusions Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood–brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.

Background High intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) may induce secondary brain injury following aneurysmal subarachnoid hemorrhage (aSAH). In the current study, we aimed to determine the temporal incidence of insults above/below certain ICP/CPP thresholds, the role of pressure autoregulation in CPP management (PRx and CPPopt), and the relation to clinical outcome. Methods In this retrospective study, 242 patients were included with aSAH, who were treated in the neurointensive care unit, Uppsala University Hospital, Sweden, 2008–2018, with ICP monitoring the first 10 days post-ictus. Data from ICP, pressure autoregulation (PRx), CPP, and CPPopt (the CPP with the lowest/optimal PRx) were analyzed the first 10 days. The percentage of good monitoring time (GMT) above/below various ICP and CPP thresholds was calculated, e.g., ICP > 20 mm Hg (%), CPP < 60 mm Hg (%), and ∆CPPopt (CPP–CPPopt) < − 10 mm Hg (%). Results Of the 242 patients, 63 (26%) had favorable (GOS-E 5–8) and 179 (74%) had unfavorable (GOS-E 1–4) outcome at 12 months. Higher proportion (GMT) of ICP insults above 20 mm Hg was most common the first 3 days post-ictus and was then independently associated with unfavorable outcome. CPP gradually increased throughout the 10 days post-ictus, and higher proportion of GMT with CPP < 90 mm Hg was independently associated with unfavorable outcome in the late vasospasm phase (days 6.5–10). PRx was above 0 throughout the 10 days and deteriorated in the late vasospasm phase. Higher values were then independently associated with unfavorable outcome. There was no difference in GMT of CPP deviations from CPPopt between the outcome groups. Conclusions Avoiding intracranial hypertension early and maintaining a high CPP in the vasospasm phase when the pressure autoregulation is most disturbed may improve clinical outcome after aSAH.

Background Lifestyle modifications and advances in surgical and endovascular techniques for treating unruptured intracranial aneurysm (UIA) have vastly evolved over the last few decades and may have reduced the incidence of aneurysmal subarachnoid hemorrhage (aSAH). However, the actual impact of these changes on the rates and outcomes of aSAH remain unexplored. Thus, we studied national aSAH admissions and outcome trends and changes of major risk factors over time. Methods We queried the National Inpatient Sample between 2006 and 2018 to identify adult patients admitted and treated for UIA or ruptured aneurysm with aSAH. The Cochran–Armitage test was conducted to assess the linear trend of proportion of prevalence, inpatient mortality, hypertension, and current smoking status among aSAH admissions. Multivariable logistic regression was conducted to assess the odds of presenting with aSAH versus UIA, in addition to the odds of inpatient mortality among patients with aSAH. Results A total of 159,913 patients presented with UIA and 133,567 presented with aSAH. Admissions for aSAH decreased by 0.97% ( p  < 0.001) per year. Current smoking and hypertension were associated with higher odds of being admitted for aSAH compared with the treatment for UIA (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.29–1.48; OR 1.15, 95% CI 1.08–1.22, respectively). Compared with White patients, Black patients (OR 1.32, 95% CI 1.21–1.43), Hispanic patients (OR 1.38, 95% CI 1.25–1.52), and patients of other races and/or ethnicities (OR 1.73, 95% CI 1.54–1.95) had a higher chance of presenting with aSAH. Rates of inpatient mortality among aSAH admissions showed no change over time ( p  = 0.21). Among patients admitted with aSAH, current smoking and hypertension showed an upward trend of 0.58% ( p  < 0.001) and 1.60% ( p  < 0.001) per year, respectively. Conclusions Despite a downward trend in the annual frequency of hospitalizations for aSAH, inpatient mortality rates for patients undergoing treatment of the ruptured aneurysm have remained unchanged in the United States. Smoking and hypertension are increasingly prevalent among patients with aSAH. Thus, efforts to control these modifiable risk factors must be further strengthened.