Correlations Between Quantitative EEG Parameters and Cortical Blood Flow in Patients Undergoing Extracorporeal Membrane Oxygenation With and Without Encephalopathy.

PURPOSE: The neurologic examination of patients undergoing extracorporeal membrane oxygenation (ECMO) is crucial for evaluating irreversible encephalopathy but is often obscured by sedation or neuromuscular blockade. Noninvasive neuromonitoring modalities including diffuse correlation spectroscopy and EEG measure cerebral perfusion and neuronal function, respectively. We hypothesized that encephalopathic ECMO patients with greater degree of irreversible cerebral injury demonstrate less correlation between electrographic activity and cerebral perfusion than those whose encephalopathy is attributable to medications. METHODS: We performed a prospective observational study of adults undergoing ECMO who underwent simultaneous continuous EEG and diffuse correlation spectroscopy monitoring. (Alpha + beta)/delta ratio and alpha/delta Rartio derived from quantitative EEG analysis were correlated with frontal cortical blood flow index. Patients who awakened and followed commands during sedation pauses were included in group 1, whereas patients who could not follow commands for most neuromonitoring were placed in group 2. (Alpha + beta)/delta ratio-blood flow index and ADR-BFI correlations were compared between the groups. RESULTS: Ten patients (five in each group) underwent 39 concomitant continuous EEG and diffuse correlation spectroscopy monitoring sessions. Four patients (80%) in each group received some form of analgosedation during neuromonitoring. (Alpha + beta)/delta ratio-blood flow index correlation was significantly lower in group 2 than group 1 (left: 0.05 vs. 0.52, P = 0.03; right: -0.12 vs. 0.39, P = 0.04). Group 2 ADR-BFI correlation was lower only over the right hemisphere (-0.06 vs. 0.47, P = 0.04). CONCLUSIONS: Correlation between (alpha + beta)/delta ratio and blood flow index were decreased in encephalopathic ECMO patients compared with awake ones, regardless of the analgosedation use. The combined use of EEG and diffuse correlation spectroscopy may have utility in monitoring cerebral function in ECMO patients.

Systematic Evaluation of Research Priorities in Critical Care Electroencephalography.

PURPOSE: The Critical Care EEG Monitoring Research Consortium (CCEMRC) is an international research group focusing on critical care EEG and epilepsy. As CCEMRC grew to include 50+ institutions over the past decade, members met to establish research priorities. METHODS: The authors used an analytical hierarchy process-based research prioritization method, adapted from an approach previously applied to a Department of Defense health-related research program. Forty-six CCEMRC members identified and scored a set of eight clinical problems (CPs) and 15 research topic areas (RTAs) at an annual CCEMRC meeting. Members scored CPs on three criteria using a five-point ordinal scale: Incidence, Impact, and Gap Size; and RTAs on four additional criteria: Niche, Feasibility, Scientific Importance, and Medical Importance, each of which was assigned a weight. The first three RTA criteria were scored using a five-point scale, and CPs were mapped to RTAs using a four-point scale. The Medical Importance score was a weighted average of its mapping scores and the CP score. Finally, a Priority score was calculated for each RTA as a product of the four RTA criteria scores. RESULTS: The CPs with the highest scores were "Altered mental status" and "Long-term neurologic disability after hospital discharge." The RTAs with the highest priority scores were "Development of risk prediction tools," "Multicenter observational studies," and "Outcome prediction." CONCLUSIONS: Research prioritization helped CCEMRC evaluate its current research trajectory, identify high-priority near-term research pursuits, and create a roadmap for future research plans aligned with its mission. This approach may be helpful to other academic consortia and research programs.

Minimum Technical Requirements for Performing Ambulatory EEG.

SUMMARY: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.

Cerebral Blood Flow Hemispheric Asymmetry in Comatose Adults Receiving Extracorporeal Membrane Oxygenation.

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

Association of the Verbal Component of the GCS With Mortality in Patients With Encephalopathy Who Are Not Undergoing Mechanical Ventilation.

BACKGROUND AND OBJECTIVES: The utility of the Glasgow Coma Scale (GCS) in intubated patients is limited due to reliance on language function evaluation. The Full Outline of Unresponsiveness (FOUR) Score was designed to circumvent this shortcoming, instead adding evaluations of brainstem reflexes (FOUR B) and specific respiratory patterns (FOUR R). We aimed to determine whether the verbal component of the GCS (GCS V) among nonintubated patients with encephalopathy significantly contributes to mortality prediction and to assess GCS vs FOUR Score performance. METHODS: All prospectively consented patients ≥18 years of age admitted to the Internal Medicine service at Zambia's University Teaching Hospital from October 3, 2017, to May 21, 2018, with a GCS score ≤10 have undergone simultaneous GCS and FOUR Score assessments. The patients were not eligible for mechanical ventilatory support per local standards. Patients' demographics and clinical characteristics were presented as either percentage frequencies or numerical summaries of spread. The predictive power of the GCS without the Verbal component vs total GCS vs FOUR Score on mortality was estimated with the area under the receiver operating characteristic curve (AU ROC). RESULTS: Two hundred thirty-five patients (50% women, mean age 47.5 years) were enrolled. All patients were Black. Presumed etiology was CNS infection (64, 27%), stroke (63, 27%), systemic infection (39, 16.6%), and metabolic encephalopathy (3, 14.5%); 14.9% had unknown etiology. In-hospital mortality was 83%. AU ROC for GCS Eye + Motor score (0.662) vs total GCS score (0.641) vs total FOUR Score (0.657) did not differ. Odds ratio mortality for GCS score >6 vs ≤6 was 0.32 (95% confidence interval [CI] 0.14-0.72, p = 0.01); for FOUR Score >10 vs ≤10, it was 0.41 (95% CI 0.19-0.86, p = 0.02). DISCUSSION: Absence of a verbal component of GCS had no significant impact on the performance of the total GCS, and either GCS or FOUR Score is an acceptable scoring tool for mortality prediction in the resource-limited setting. These findings need further validation in the countries with readily available mechanical ventilatory support. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the verbal component of the GCS does not significantly contribute to a total GCS score in mortality prediction among patients with encephalopathy who are not intubated.

Towards detection of brain injury using multimodal non-invasive neuromonitoring in adults undergoing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass that provides life-saving support to critically ill patients whose illness is progressing despite maximal conventional support. Use in adults is expanding, however neurological injuries are common. Currently, the existing brain imaging tools are a snapshot in time and require high-risk patient transport. Here we assess the feasibility of measuring diffuse correlation spectroscopy, transcranial Doppler ultrasound, electroencephalography, and auditory brainstem responses at the bedside, and developing a cerebral autoregulation metric. We report preliminary results from two patients, demonstrating feasibility and laying the foundation for future studies monitoring neurological health during ECMO.

Estimating the period prevalence of non-convulsive status epilepticus among comatose adults at the University Teaching Hospital in Lusaka, Zambia.

OBJECTIVE: In Western settings, non-convulsive status epilepticus (NCSE) and non-convulsive seizures (NCSz) are associated with high mortality. In comatose patients, interictal epileptiform discharges (IEDs) identified on routine electroencephalogram (EEG) are predictive of NCSE/NCS. Little is known regarding the prevalence, causes, or outcomes of NCSE/NCSz in sub-Saharan Africa (SSA). We sought to investigate the prevalence of IEDs and NCSE/NCSz at a single teaching institution in SSA. METHODS: From October 3, 2017, to May 21, 2018, adult inpatients on the internal medicine service at Zambia's University Teaching Hospital (UTH) with a Glasgow Coma Score (GCS) of ≤10 were identified, excluding patients with mechanical ventilation or open head wounds. Signed consent by a proxy was required for enrollment and 30-minute EEG. Chart abstractions provided coma duration, presence/absence of clinical seizures during/prior to admission, history of epilepsy, and presumed coma etiology. A structured neurological examination was completed. Patients were followed to discharge or death. Risk factors for IEDs were evaluated. RESULTS: Of 392 eligible patients, 250 had EEGs. EEGs were not completed on eligible patients due to death (74), improved GCS (37), transfer within UTH (25), or lack of proxy (6). NCSE occurred in 22 of 250 (8.8%), NCSz in 3 of 250 (1.2%), and IEDs in 46 of 250 (18.4%) patients. Of the 250, 197 (78.8%) died. No specific risk factors for IEDs were identified. SIGNIFICANCE: If the association between IEDs and NCSE among monitored populations in developed settings holds true for SSA, a projected 17%-21% of comatose African adults have NCSE. No clinical characteristics identified those at risk.

Continuous EEG Monitoring Predicts a Clinically Meaningful Recovery Among Adult Inpatients.

PURPOSE: Continuous EEG (cEEG) monitoring is primarily used for diagnosing seizures and status epilepticus, and for prognostication after cardiorespiratory arrest. The purpose of this study was to investigate whether cEEG could predict survival and meaningful recovery. METHODS: The authors reviewed inpatient cEEG reports obtained between January 2013 and November 2015 and recorded demographics, preadmission modified Rankin Scale, history of preexisting epilepsy, Glasgow Coma Scale for those admitted to the intensive care unit, and EEG data (posterior dominant rhythm, reactivity, epileptiform discharges, seizures, and status epilepticus). Associations between clinical outcomes (death vs. survival or clinically meaningful recovery [inpatient rehabilitation, home-based rehabilitation, or home] vs. other [death, skilled nursing facility]) and cEEG findings were assessed with logistic regression models. P < 0.05 was considered significant. RESULTS: For 218 cEEG reports (197 intensive care unit admits), the presence of at least a unilateral posterior dominant rhythm was associated with survival (odds ratio for death, 0.38; 95% confidence interval, 0.19-0.77; P = 0.01) and with a clinically meaningful outcome (odds ratio, 3.26; 95% confidence interval, 1.79-5.93; P < 0.001); posterior dominant rhythm remained significant after adjusting for preadmission disability. Those with preexisting epilepsy had better odds of a meaningful recovery (odds ratio, 3.31; 95% CI, 1.34-8.17; P = 0.001). Treated seizures and status epilepticus were not associated with a worse mortality (P = 0.6) or disposition (P = 0.6). High Glasgow Coma Scale (≥12) at intensive care unit admission was associated with a clinically meaningful recovery (odds ratio, 16.40; 95% confidence interval, 1.58-170.19; P = 0.02). CONCLUSIONS: Continuous EEG findings can be used to prognosticate survival and functional recovery, and provide guidance in establishing goals of care.

Evaluation of phenytoin serum levels following a loading dose in the acute hospital setting.

PURPOSE: Due to the complex pharmacokinetic profiles of phenytoin (PHT) and fosphenytoin (FOS), achieving sustained, targeted serum PHT levels in the first day of use is challenging. METHODS: A population based approach was used to analyze total serum PHT (tPHT) level within 2-24h of PHT/FOS loading with or without supplementary maintenance or additional loading doses among PHT-naïve patients in the acute hospital setting. Adequate tPHT serum level was defined as ≥20µg/mL. RESULTS: Among 494 patients with 545 tPHT serum levels obtained in the first 2-24h after the loading dose (LD), tPHT serum levels of either

American Clinical Neurophysiology Society Guideline 6: Minimum Technical Standards for EEG Recording in Suspected Cerebral Death.

This revision to the EEG Guidelines is an update incorporating current EEG technology and practice. The role of the EEG in making the determination of brain death is discussed as are suggested technical criteria for making the diagnosis of electrocerebral inactivity.

American Clinical Neurophysiology Society Guideline 5: Minimum Technical Standards for Pediatric Electroencephalography.

This revision to the EEG Guidelines is an update incorporating the current electroencephalography technology and practice. It was previously published as Guideline 2. Similar to the prior guideline, it delineates the aspects of Guideline 1 that should be modified for neonates and young children. Recording conditions for photic stimulation and hyperventilation are revised to enhance the provocation of epileptiform discharges. Revisions recognize the difficulties involved in performing an EEG under sedation in young children. Recommended neonatal EEG montages are displayed for the reduced set of electrodes only since the montages in Guideline 3 should be used for a 21-electrode 10-20 system array. Neonatal documentation is updated to use current American Academy of Pediatrics term "postmenstrual age" rather than "conceptional age." Finally, because therapeutic hypothermia alters the prognostic value of neonatal EEG, the necessity of documenting the patient's temperature at the time of recording is emphasized.

American Clinical Neurophysiology Society Guideline 6: Minimum Technical Standards for EEG Recording in Suspected Cerebral Death.

This revision to the EEG Guidelines is an update incorporating current EEG technology and practice. The role of the EEG in making the determination of brain death is discussed as are suggested technical criteria for making the diagnosis of electrocerebral inactivity.

American Clinical Neurophysiology Society Guideline 7: Guidelines for EEG Reporting.

This EEG Guideline incorporates the practice of structuring a report of results obtained during routine adult electroencephalography. It is intended to reflect one of the current practices in reporting an EEG and serves as a revision of the previous guideline entitled "Writing an EEG Report." The goal of this guideline is not only to convey clinically relevant information, but also to improve interrater reliability for clinical and research use by standardizing the format of EEG reports. With this in mind, there is expanded documentation of the patient history to include more relevant clinical information that can affect the EEG recording and interpretation. Recommendations for the technical conditions of the recording are also enhanced to include post hoc review parameters and type of EEG recording. Sleep feature documentation is also expanded upon. More descriptive terms are included for background features and interictal discharges that are concordant with efforts to standardize terminology. In the clinical correlation section, examples of common clinical scenarios are now provided that encourages uniformity in reporting. Including digital samples of abnormal waveforms is now readily available with current EEG recording systems and may be beneficial in augmenting reports when controversial waveforms or important features are encountered.

American Clinical Neurophysiology Society Guideline 5: Minimum Technical Standards for Pediatric Electroencephalography.

This revision to the EEG Guidelines is an update incorporating the current electroencephalography technology and practice. It was previously published as Guideline 2. Similar to the prior guideline, it delineates the aspects of Guideline 1 that should be modified for neonates and young children. Recording conditions for photic stimulation and hyperventilation are revised to enhance the provocation of epileptiform discharges. Revisions recognize the difficulties involved in performing an EEG under sedation in young children. Recommended neonatal EEG montages are displayed for the reduced set of electrodes only since the montages in Guideline 3 should be used for a 21-electrode 10-20 system array. Neonatal documentation is updated to use current American Academy of Pediatrics term "postmenstrual age" rather than "conceptional age." Finally, because therapeutic hypothermia alters the prognostic value of neonatal EEG, the necessity of documenting the patient's temperature at the time of recording is emphasized.

Characteristic Features of the Interictal EEG Background in 2 Patients With Malignant Migrating Partial Epilepsy in Infancy.

PURPOSE: To describe chronological electrographic features of the interictal EEG background observed in two patients with malignant migrating partial epilepsy in infancy from neonatal to early infantile period. METHODS: EEGs of two patients who fulfilled diagnostic criteria for malignant migrating partial epilepsy in infancy were acquired over the period of 6 months to monitor treatment efficacy and characterize seizures and other paroxysmal events. RESULTS: Both patients followed a similar sequential pattern. A distinctive evolution from a dysmature term neonatal EEG pattern to an asynchronous suppression burst pattern was observed before the interictal background becoming continuous. CONCLUSIONS: Physicians providing care to infants with intractable epilepsy and burst suppression EEG pattern should be alert to the possibility of malignant migrating partial epilepsy in infancy. An earlier diagnosis of malignant migrating partial epilepsy in infancy would help to guide diagnostic workup including genetic testing.