Continuous Electroencephalography Research Articles

Safety and Efficacy of Levetiracetam for Prevention of Epileptic Seizures in Acute Phase of Intracerebral Bleeding

Background: Epilepsy, characterized by recurrent, unprovoked seizures due to anomalous brain activity, is a significant complication for patients with intracerebral hemorrhage (ICH). The onset of epileptic convulsions during the acute phase of ICH can worsen the patient's prognosis and survival chances, making it crucial to identify a safe and effective method to prevent these seizures. Levetiracetam, a pyrrolidone derivative, is noted for its unique mechanism of action, exceptional tolerability, and advantageous pharmacokinetics, making it efficacious against various types of seizures. Objective: This study aims to evaluate the safety and efficacy of levetiracetam in preventing epileptic seizures during the acute phase of ICH and to determine its impact on neurological outcomes in this patient population. Methods: A cross-sectional investigation was conducted between October 2022 and June 2023 at Pak Emirates Military Hospital in Rawalpindi, Pakistan, involving 85 patients with spontaneous ICH confirmed by CT or MRI within 24 hours of symptom onset. Inclusion criteria included adult patients aged 18 or older, with various forms of ICH, excluding isolated subarachnoid hemorrhage, penetrating wound injury, depressed skull fracture, or early posttraumatic seizure. Patients with a Glasgow Coma Scale (GCS) score of less than 6, serum creatinine level >1.7 mg/dL, history of psychosis, unprovoked seizures, cerebrovascular accidents, traumatic brain injuries, or encephalitis within the previous three years were excluded. Patients were administered an initial loading dose of levetiracetam (1,000 to 1,500 mg), followed by a maintenance dose (500 to 1,500 mg every 12 hours) based on renal function. Continuous electroencephalography (cEEG) monitoring was used to detect seizures for at least the first 72 hours of hospital admission. The primary outcome was the incidence of epileptic seizures during hospitalization, while the secondary outcome was the patient's neurological status at discharge, assessed using the Modified Rankin Scale (mRS). Data were analyzed using descriptive statistics and the Chi-square test, with a p-value of ≤0.05 considered statistically significant. Analyses were conducted using SPSS version 25. Results: The mean age of the patients was 47.89 years (SD=7.46), with 62.35% male and 37.65% female. The mean GCS score at admission was 10.52 (SD=2.13), and the mean volume of ICH was 17.5 ml (SD=3.4). At baseline, 2.35% of patients had GCS scores of 3-5, which improved to 0% after treatment. The percentage of patients with GCS scores of 13-15 increased from 65.88% to 83.52% (p=0.3730). Seizures within the first 7 days occurred in 10.58% of patients, and the overall seizure incidence during hospitalization was 20%. At discharge, 9.41% of patients had an mRS score of 0, and the percentage of patients with an mRS score of 2 increased significantly from 18.18% to 37.64% (p=0.4086*). The percentage of patients with severe disability (mRS score of 5) significantly decreased from 22.72% to 5.68% (p=0.0094*). Conclusion: Levetiracetam is effective in improving neurological outcomes and reducing the incidence of seizures in patients with acute intracerebral hemorrhage, with a manageable safety profile. These findings suggest that levetiracetam can be a valuable addition to therapeutic strategies for managing ICH-related seizures, potentially enhancing patient care and improving health outcomes.

Pitfalls and possibilities of using Root SedLine for continuous assessment of EEG waveforms-based metrics in intensive care research.

The Root SedLine Device is used for continuous electroencephalography (cEEG) based sedation monitoring in intensive care patients. The cEEG traces can be collected for further processing and calculation of relevant metrics not already provided. Depending on the device settings during acquisition, the acquired traces may be distorted by max/min values cropping or high digitization error. We aimed to systematically assess the impact of those distortions on metrics used for clinical research in the field of neuromonitoring.
Approach: A 16h cEEG acquired using the Root SedLine Device at the optimal screen settings was analyzed. Cropping and digitization error effects were simulated by consecutive reduction of the maximum cEEG amplitude by 2µV or by reducing the vertical resolution. Metrics were calculated within ICM+ using minute-by-minute data including total power, alpha delta ratio, and 95% spectral edge frequency. Data were analyzed by creating violin-plots or box-plots.
Main Results: Cropping led to a continuous reduction in total and band power leading to corresponding changes in variability thereof. Relative power and alpha delta ratio were less affected. Changes in resolution led to relevant changes. While total power and power of low frequencies were rather stable, power of higher frequencies increased with reducing resolution. 
Significance: Care must be taken when acquiring and analyzing cEEG waveforms from Root SedLine for clinical research. In order to retrieve good quality metrics, the screen settings must be kept within the central vertical scale while pre-processing techniques must be applied to exclude unacceptable periods.
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Evaluation of prognostic scores for status epilepticus in the neurology ICU: A retrospective study

ObjectiveStatus epilepticus (SE) in the neurology intensive care unit (ICU) is associated with significant morbidity. We aimed to evaluate the utility of existing prognostic scores, namely the Status Epilepticus Severity Score (STESS), Epidemiology Based Mortality Score in Status Epilepticus (EMSE)-EACE and Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT), among SE patients in the neurology ICU. MethodsNeurology ICU patients with SE requiring continuous electroencephalography (cEEG) monitoring over a 10 year period were included. The STESS, EMSE-EACE and END-IT scores were applied retrospectively. Receiver operating characteristic (ROC) analysis was performed to assess the discriminatory value of the scores for inpatient mortality and functional decline, as measured by increase in the modified Rankin Scale (mRS) on discharge. ResultsEighty-five patients were included in the study, of which 71 (83.5%) had refractory SE. Inpatient mortality was 36.5%. Sixty – seven (78.8%) of patients suffered functional decline, with a median mRS of 5 upon hospital discharge.The AUCs of the STESS, EMSE-EACE and END-IT scores associated with inpatient mortality were 0.723 (95% CI 0.613–0.833), 0.722 (95% CI 0.609–0.834) and 0.560 (95% CI 0.436–0.684) respectively. The AUCs of the STESS, EMSE-EACE and END-IT scores associated with functional decline were 0.604 (95% CI 0.468–0.741), 0.596 (95% CI 0.439–0.754) and 0.477 (95% CI 0.331–0.623). SignificanceSE was associated with high mortality and morbidity in this cohort of neurology ICU patients requiring cEEG monitoring. The STESS and EMSE-EACE scores had acceptable AUCs for prediction of inpatient mortality. However, the STESS, EMSE-EACE and END-IT were poorly-correlated with discharge functional outcomes. Further refinements of the scores may be necessary among neurology ICU patients for predicting discharge functional outcomes.

Prevalence of Electrographic Seizures in Hospitalized Patients With Altered Mental Status With No Significant Seizure Risk Factors Who Underwent Continuous EEG Monitoring: A Retrospective Study.

The objective of this study is to evaluate the prevalence of electrographic seizures in hospitalized patients with altered mental status and no significant risk factors for seizures. We retrospectively reviewed over a six-year period (2013-2019) the medical records of all adults admitted at Ohio State University Wexner Medical Center (OSUWMC), who underwent continuous electroencephalography (cEEG) monitoring for > 48 hours. Our primary objective was to identify the prevalence of electrographic seizures in patients with altered mental status and no significant acute or remote risk factors for seizures. A total of 1966 patients were screened for the study, 1892 were excluded (96.2%) and 74 patients met inclusion criteria. Electrographic seizures were identified in seven of 74 patients (9.45%). We found a significant correlation between electrographic seizures and a history of hepatic cirrhosis, n= 4 (57%), (p=0.035), acute chronic hepatic failure during admission, 71% (n=5), (p=0.027), and hyperammonemia (p =0.009). In this retrospective study of patients with altered mental status and no significant acute or remote risk factors for seizures who underwent cEEG monitoring for > 48 hours, electrographic seizures were identified in 9.45%. Electrographic seizures were associated with hepatic dysfunction and hyperammonemia. Based on our results, cEEG monitoring should be considered in patients with altered mental status and hepatic dysfunction even in the absence of other seizure risk factors.

What Do You See? Signature Pedagogy in Continuous Electroencephalography Teaching.

Electroencephalography (EEG) is commonly used in neurology, but there is variability in how neurologists interpret EEGs, potentially from variability in EEG teaching. Little is known about how EEG teaching is done to prepare neurologists for professional practice. We interviewed a group of EEG experts to characterize their teaching practices around continuous EEG (cEEG). We used signature pedagogy as a framework to analyze and interpret the data. We identified pervasive and characteristic forms of cEEG teaching. Teaching is based on apprenticeship, relying on "learning by doing" in the context of real-life clinical practice. There are habitual steps that learners take to anchor teaching, which typically occurs during rounds. There is a common language and core knowledge that trainees need to master early in their training. There are pervasive characteristic forms of cEEG teaching. These findings can help facilitate instructional design and implementation of complementary or enhanced cEEG teaching practices.

Multimodal neuromonitoring in the pediatric intensive care unit

Neuromonitoring is used to assess the central nervous system in the intensive care unit. The purpose of neuromonitoring is to detect neurologic deterioration and intervene to prevent irreversible nervous system dysfunction. Neuromonitoring starts with the standard neurologic examination, which may lag behind the pathophysiologic changes. Additional modalities including continuous electroencephalography (CEEG), multiple physiologic parameters, and structural neuroimaging may detect changes earlier. Multimodal neuromonitoring now refers to an integrated combination and display of non-invasive and invasive modalities, permitting tailored treatment for the individual patient. This chapter reviews the non-invasive and invasive modalities used in pediatric neurocritical care.

Background EEG Suppression Ratio for Early Detection of Cerebral Injury in Pediatric Cardiac Arrest.

Our objective was to assess the utility of the 1-h suppression ratio (SR) as a biomarker of cerebral injury and neurologic prognosis after cardiac arrest (CA) in the pediatric hospital setting. Prospectively, we reviewed data from children presenting after CA and monitored by continuous electroencephalography (cEEG). Patients aged 1month to 21years were included. The SR, a quantitative measure of low-voltage cEEG (≤ 3µV) content, was dichotomized as present or absent if there was > 0% suppression for one continuous hour. A multivariate logistic regression analysis was performed including age, sex, type of CA (i.e., in-hospital or out-of-hospital), and the presence of SR as a predictor of global anoxic cerebral injury as confirmed by magnetic resonance imaging(MRI). We included 84 patients with a median age of 4years (interquartile range 0.9-13), 64% were male, and 49% (41/84) had in-hospital CA. Cerebral injury was seen in 50% of patients, of whom 65% had global injury. One-hour SR presence, independent of amount, predicted cerebral injury with 81% sensitivity (95% confidence interval (CI) (66-91%) and 98% specificity (95% CI 88-100%). Multivariate logistic regression analyses indicated that SR was a significant predictor of both cerebral injury (β = 6.28, p < 0.001) and mortality (β = 3.56, p < 0.001). The SR a sensitive and specific marker of anoxic brain injury and post-CA mortality in the pediatric population. Once detected in the post-CA setting, the 1-h SR may be a useful threshold finding for deployment of early neuroprotective strategies prior or for prompting diagnostic neuroimaging.

Acute seizure activity in neonatal inflammation-sensitized hypoxia-ischemia in mice.

To examine acute seizure activity and neuronal damage in a neonatal mouse model of inflammation-sensitized hypoxic-ischemic (IS-HI) brain injury utilizing continuous electroencephalography (cEEG) and neurohistology. Neonatal mice were exposed to either IS-HI with Escherichia coli lipopolysaccharide (LPS) or HI alone on postnatal (p) day 10 using unilateral carotid artery ligation followed by global hypoxia (n = 10 [5 female, 5 male] for IS-HI, n = 12 [5 female, 7 male] for HI alone). Video cEEG was recorded for the duration of the experiment and analyzed for acute seizure activity and behavior. Brain tissue was stained and scored based on the degree of neuronal injury in the hippocampus, cortex, and thalamus. There was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI with regards to seizure duration (mean = 63 ± 6 seconds for HI vs mean 62 ± 5 seconds for IS-HI, p = 0.57) nor EEG background activity. Mice exposed to IS-HI had significantly more severe neural tissue damage at p30 as measured by neuropathologic scores (mean = 8 ± 1 vs 23 ± 3, p < 0.0001). In a neonatal mouse model of IS-HI, there was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI. Mice exposed to IS-HI did show more severe neuropathologic damage at a later age, which may indicate the presence of chronic inflammatory mechanisms of brain injury distinct from acute seizure activity.

Lateralized Rhythmic Delta Activity and Lateralized Periodic Discharges in Critically Ill Pediatric Patients.

To evaluate the clinical and electrographic characteristics of critically ill pediatric patients with lateralized rhythmic delta activity (LRDA) and compare them with patients with lateralized periodic discharges (LPDs). This was a retrospective study examining consecutive critically ill pediatric patients (1 month-18 years) with LRDA or LPDs monitored on continuous electroencephalography. Clinical, radiologic, and electrographic characteristics; disease severity; and acute sequelae were compared between the two groups. Of 668 pediatric patients monitored on continuous electroencephalography during the study period, 12 (1.79%) patients had LRDA and 15 (2.24%) had LPDs. The underlying etiologies were heterogeneous with no difference in the acuity of brain MRI changes between both groups. Lateralized rhythmic delta activity and LPDs were concordant with the side of MRI abnormality in most patients [85.7% (LRDA) and 83.3% (LPD)]. There was no difference in the measures of disease severity between both groups. Seizures were frequent in both groups (42% in the LRDA group and 73% in the LPD group). Patients in the LPD group had a trend toward requiring a greater number of antiseizure medications for seizure control (median of 4 vs. 2 in the LRDA group, p = 0.09), particularly those patients with LPDs qualifying as ictal-interictal continuum compared with those without ictal-interictal continuum (p = 0.02). Lateralized rhythmic delta activity and LPDs are uncommon EEG findings in the pediatric population. Seizures occur commonly in patients with these patterns. Seizures in patients with LPDs, especially those qualifying as ictal-interictal continuum, showed a trend toward being more refractory. Larger studies are needed in the future to further evaluate these findings.

Epilepsy monitoring unit practices and safety among NAEC epilepsy centers: A census survey

ObjectiveAn epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. MethodWe analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher’s exact tests to compare staff responsibilities. ResultsThe supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SignificanceEMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

Real-World Continuous EEG Utilization and Outcomes in Hospitalized Patients With Acute Cerebrovascular Diseases.

Continuous electroencephalography (cEEG) is recommended for hospitalized patients with cerebrovascular diseases and suspected seizures or unexplained neurologic decline. We sought to (1) identify areas of practice variation in cEEG utilization, (2) determine predictors of cEEG utilization, (3) evaluate whether cEEG utilization is associated with outcomes in patients with cerebrovascular diseases. This cohort study of the Premier Healthcare Database (2014-2020), included hospitalized patients age >18 years with cerebrovascular diseases (identified by ICD codes). Continuous electroencephalography was identified by International Classification of Diseases (ICD)/Current Procedural Terminology (CPT) codes. Multivariable lasso logistic regression was used to identify predictors of cEEG utilization and in-hospital mortality. Propensity score-matched analysis was performed to determine the relation between cEEG use and mortality. 1,179,471 admissions were included; 16,777 (1.4%) underwent cEEG. Total number of cEEGs increased by 364% over 5 years (average 32%/year). On multivariable analysis, top five predictors of cEEG use included seizure diagnosis, hospitals with >500 beds, regions Northeast and South, and anesthetic use. Top predictors of mortality included use of mechanical ventilation, vasopressors, anesthetics, antiseizure medications, and age. Propensity analysis showed that cEEG was associated with lower in-hospital mortality (Average Treatment Effect -0.015 [95% confidence interval -0.028 to -0.003], Odds ratio 0.746 [95% confidence interval, 0.618-0.900]). There has been a national increase in cEEG utilization for hospitalized patients with cerebrovascular diseases, with practice variation. cEEG utilization was associated with lower in-hospital mortality. Larger comparative studies of cEEG-guided treatments are indicated to inform best practices, guide policy changes for increased access, and create guidelines on triaging and transferring patients to centers with cEEG capability.

Hypothermic Protection in Neocortex Is Topographic and Laminar, Seizure Unmitigating, and Partially Rescues Neurons Depleted of RNA Splicing Protein Rbfox3/NeuN in Neonatal Hypoxic-Ischemic Male Piglets.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

Hyperacute autonomic and cortical function recovery following cardiac arrest resuscitation in a rodent model.

There is a complex interaction between nervous and cardiovascular systems, but sparse data exist on brain-heart electrophysiological responses to cardiac arrest resuscitation. Our aim was to investigate dynamic changes in autonomic and cortical function during hyperacute stage post-resuscitation. Ten rats were resuscitated from 7-min cardiac arrest, as indicators of autonomic response, heart rate (HR), and its variability (HRV) were measured. HR was monitored through continuous electrocardiography, while HRV was assessed via spectral analysis, whereby the ratio of low-/high-frequency (LF/HF) power indicates the balance between sympathetic/parasympathetic activities. Cortical response was evaluated by continuous electroencephalography and quantitative analysis. Parameters were quantified at 5-min intervals over the first-hour post-resuscitation. Neurological outcome was assessed by Neurological Deficit Score (NDS, range 0-80, higher = better outcomes) at 4-h post-resuscitation. A significant increase in HR was noted over 15-30 min post-resuscitation (p < 0.01 vs.15-min, respectively) and correlated with higher NDS (rs = 0.56, p < 0.01). LF/HF ratio over 15-20 min was positively correlated with NDS (rs = 0.75, p < 0.05). Gamma band power surged over 15-30 min post-resuscitation (p < 0.05 vs. 0-15 min, respectively), and gamma band fraction during this period was associated with NDS (rs ≥0.70, p < 0.05, respectively). Significant correlations were identified between increased HR and gamma band power during 15-30 min (rs ≥0.83, p < 0.01, respectively) and between gamma band fraction and LF/HF ratio over 15-20 min post-resuscitation (rs = 0.85, p < 0.01). Hyperacute recovery of autonomic and cortical function is associated with favorable functional outcomes. While this observation needs further validation, it presents a translational opportunity for better autonomic and neurologic monitoring during early periods post-resuscitation to develop novel interventions.

The differing effects of sleep on ictal and interictal network dynamics in drug-resistant epilepsy.

Sleep has important influences on focal interictal epileptiform discharges (IEDs), and the rates and spatial extent of IEDs are increased in non-rapid eye movement (NREM) sleep. In contrast, the influence of sleep on seizures is less clear and its effects on seizure topography are poorly documented. We evaluated the influences of NREM sleep on ictal spatiotemporal dynamics and contrasted these with interictal network dynamics. We included patients with drug-resistant focal epilepsy who underwent continuous intracranial EEG with depth electrodes. Patients were selected if they had 1-3 seizures from each vigilance state, wakefulness and NREM sleep, within a 48-hour window and under the same anti-seizure medication. A 10-min epoch of the interictal iEEG was selected per state, and IEDs were detected automatically. Twenty-five patients (13 females; 32.5±7.1 years) were included. The seizure onset pattern, duration, spatiotemporal propagation and latency of ictal high-frequency activity did not differ significantly between wakefulness and NREM sleep (all p>0.05). In contrast, IED rates and spatial distribution were increased in NREM compared to wakefulness (p<0.001, Cliff's d=0.48 and 0.49). The spatial overlap between vigilance states was higher for seizures (57.1±40.1%) than IEDs (41.7±46.2%) (p=0.001, Cliff's d=0.51). In contrast to its effects on IEDs, NREM sleep does not affect ictal spatiotemporal dynamics. This suggests that once the brain surpasses the seizure threshold, it will follow the underlying epileptic network irrespective of the vigilance state. These findings offer valuable insights into neural network dynamics in epilepsy and have important clinical implications for localizing seizure foci. This article is protected by copyright. All rights reserved.

Prognostic value of early electrographic biomarkers of epileptogenesis in high-risk ischaemic stroke patients.

Post-stroke epilepsy (PSE) is frequent. Better prediction of PSE would enable individualized management and improve trial design for epilepsy prevention. The aim was to assess the complementary value of continuous electroencephalography (EEG) data during the acute phase compared with clinical risk factors currently used to predict PSE. A prospective cohort of 81 patients with ischaemic stroke who received early continuous EEG monitoring was studied to assess the association of early EEG seizures, other highly epileptogenic rhythmic and periodic patterns, and regional attenuation without delta (RAWOD, an EEG pattern of stroke severity) with PSE. Clinical risk factors were investigated using the SeLECT (stroke severity; large-artery atherosclerosis; early clinical seizures; cortical involvement; territory of middle cerebral artery) scores. Twelve (15%) patients developed PSE. The presence of any of the investigated patterns was associated with a risk of epilepsy of 46%, with a sensitivity and specificity of 83% and 78%. The association remained significant after adjusting for the SeLECT score (odds ratio 18.8, interquartile range 3.8-72.7). It was found that highly epileptogenic rhythmic and periodic patterns and RAWOD were associated with the development of PSE and complemented clinical risk factors. These findings indicate that continuous EEG provides useful information to determine patients at higher risk of developing PSE and could help individualize care.

Neurophysiologic Features Reflecting Brain Injury During Pediatric ECMO Support

BackgroundExtracorporeal membrane oxygenation (ECMO) provides lifesaving support to critically ill patients who experience refractory cardiopulmonary failure but carries a high risk for acute brain injury. We aimed to identify characteristics reflecting acute brain injury in children requiring ECMO support.MethodsThis is a prospective observational study from 2019 to 2022 of pediatric ECMO patients undergoing neuromonitoring, including continuous electroencephalography, cerebral oximetry, and transcranial Doppler ultrasound (TCD). The primary outcome was acute brain injury. Clinical and neuromonitoring characteristics were collected. Multivariate logistic regression was implemented to model odds ratios (ORs) and identify the combined characteristics that best discriminate risk of acute brain injury using the area under the receiver operating characteristic curve.ResultsSeventy-five pediatric patients requiring ECMO support were enrolled in this study, and 62 underwent neuroimaging or autopsy evaluations. Of these 62 patients, 19 experienced acute brain injury (30.6%), including seven (36.8%) with arterial ischemic stroke, four (21.1%) with hemorrhagic stroke, seven with hypoxic-ischemic brain injury (36.8%), and one (5.3%) with both arterial ischemic stroke and hypoxic-ischemic brain injury. A univariate analysis demonstrated acute brain injury to be associated with maximum hourly seizure burden (p = 0.021), electroencephalographic suppression percentage (p = 0.022), increased interhemispheric differences in electroencephalographic total power (p = 0.023) and amplitude (p = 0.017), and increased differences in TCD Thrombolysis in Brain Ischemia (TIBI) scores between bilateral middle cerebral arteries (p = 0.023). Best subset model selection identified increased seizure burden (OR = 2.07, partial R2 = 0.48, p = 0.013), increased quantitative electroencephalographic interhemispheric amplitude differences (OR = 2.41, partial R2 = 0.48, p = 0.013), and increased interhemispheric TCD TIBI score differences (OR = 4.66, partial R2 = 0.49, p = 0.006) to be independently associated with acute brain injury (area under the receiver operating characteristic curve = 0.92).ConclusionsIncreased seizure burden and increased interhemispheric differences in both quantitative electroencephalographic amplitude and TCD MCA TIBI scores are independently associated with acute brain injury in children undergoing ECMO support.

Continuous Electroencephalography (EEG) Protocol Improves Seizure Detection in Children on Extracorporeal Membrane Oxygenation.

Seizures are a complication for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). There are no standardized guidelines regarding continuous electroencephalography (EEG) monitoring to detect seizures in these patients, and the impact of protocolized monitoring has not been evaluated. Here we examined the effects of continuous EEG protocol implementation in our pediatric ECMO population. Retrospective chart reviews were conducted on 57 patients who underwent extracorporeal membrane oxygenation and concurrent continuous EEG out of 165 patients supported on extracorporeal membrane oxygenation. Timing of continuous EEG initiation and seizures detected by continuous EEG was determined for 5 years prior to and 15 months after protocol implementation. Protocol implementation was associated with increased ECMO-supported patients who were concurrently monitored by continuous EEG. Time from ECMO cannulation to continuous EEG initiation was shorter (median 7 hours after versus 16.2 hours before; P < .001). Patients who had ongoing seizures at the start of continuous EEG recording decreased from 64% preprotocol to 0% postprotocol (P < .001), and there was an associated earlier time to break in status epilepticus postprotocol. Seizures were detected past 48 hours after cannulation in 50% of patients in the postprotocol group. Protocol implementation resulted in earlier continuous EEG initiation and more EEGs initiated before seizure onset with evidence of altered seizure dynamics. Although current recommendations suggest that continuous EEG duration of 24-48 hours results in seizure detection for >90% of critically ill adults, longer monitoring may be needed to reliably detect seizures in children supported with ECMO, particularly if monitoring is initiated earlier in the post-cannulation period.

Diagnosis of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage and Triggers for Intervention

IntroductionDelayed cerebral ischemia (DCI) is a major determinant for poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). Detection and treatment of DCI is a key component in the neurocritical care of patients with aSAH after initial aneurysm repair.MethodsNarrative review of the literature.ResultsOver the past 2 decades, there has been a paradigm shift away from macrovascular (angiographic) vasospasm as a main diagnostic and therapeutic target. Instead, the pathophysiology of DCI is hypothesized to derive from several proischemic pathomechanisms. Clinical examination remains the most reliable means for monitoring and treatment of DCI, but its value is limited in comatose patients. In such patients, monitoring of DCI is usually based on numerous neurophysiological and/or radiological diagnostic modalities. Catheter angiography remains the gold standard for the detection of macrovascular spasm. Computed tomography (CT) angiography is increasingly used instead of catheter angiography because it is less invasive and may be combined with CT perfusion imaging. CT perfusion permits semiquantitative cerebral blood flow measurements, including the evaluation of the microcirculation. It may be used for prediction, early detection, and diagnosis of DCI, with yet-to-prove benefit on clinical outcome when used as a screening modality. Transcranial Doppler may be considered as an additional noninvasive screening tool for flow velocities in the middle cerebral artery, with limited accuracy in other cerebral arteries. Continuous electroencephalography enables detection of early signs of ischemia at a reversible stage prior to clinical manifestation. However, its widespread use is still limited because of the required infrastructure and expertise in data interpretation. Near-infrared spectroscopy, a noninvasive and continuous modality for evaluation of cerebral blood flow dynamics, has shown conflicting results and needs further validation. Monitoring techniques beyond neurological examinations may help in the detection of DCI, especially in comatose patients. However, these techniques are limited because of their invasive nature and/or restriction of measurements to focal brain areas.ConclusionThe current literature review underscores the need for incorporating existing modalities and developing new methods to evaluate brain perfusion, brain metabolism, and overall brain function more accurately and more globally.

Incidence of Neonatal Seizures in China Based on Electroencephalogram Monitoring in Neonatal Neurocritical Care Units

Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. To determine the incidence of neonatal seizures in infants with high risk in China. A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. The incidence of neonatal seizures, categorized by etiology, and seizure burden. A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4h before and 24h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24h, hourly neurologic assessments for at least 12h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.