Combined depth and scalp electroencephalographic monitoring in acute brain injury: Yield and prognostic value.

BACKGROUND AND PURPOSE: Depth electroencephalography (dEEG) is an emerging neuromonitoring technology in acute brain injury (ABI). We aimed to explore the concordances between electrophysiological activities on dEEG and on scalp EEG (scEEG) in ABI patients. METHODS: Consecutive ABI patients who received dEEG monitoring between 2018 and 2022 were included. Background, sporadic epileptiform discharges, rhythmic and periodic patterns (RPPs), electrographic seizures, brief potentially ictal rhythmic discharges, ictal-interictal continuum (IIC) patterns, and hourly RPP burden on dEEG and scEEG were compared. RESULTS: Sixty-one ABI patients with a median dEEG monitoring duration of 114 h were included. dEEG significantly showed less continuous background (75% vs. 90%, p = 0.03), higher background amplitude (p < 0.001), more frequent rhythmic spike-and-waves (16% vs. 3%, p = 0.03), more IIC patterns (39% vs. 21%, p = 0.03), and greater hourly RPP burden (2430 vs. 1090 s/h, p = 0.01), when compared to scEEG. Among five patients with seizures on scEEG, one patient had concomitant seizures on dEEG, one had periodic discharges (not concomitant) on dEEG, and three had no RPPs on dEEG. Features and temporal occurrence of electrophysiological activities observed on dEEG and scEEG are not strongly associated. Patients with seizures and IIC patterns on dEEG seemed to have a higher rate of poor outcomes at discharge than patients without these patterns on dEEG (42% vs. 25%, p = 0.37). CONCLUSIONS: dEEG can detect abnormal electrophysiological activities that may not be seen on scEEG and can be used as a complement in the neuromonitoring of ABI patients.

Utility and rationale for continuous EEG monitoring: a primer for the general intensivist.

This review offers a comprehensive guide for general intensivists on the utility of continuous EEG (cEEG) monitoring for critically ill patients. Beyond the primary role of EEG in detecting seizures, this review explores its utility in neuroprognostication, monitoring neurological deterioration, assessing treatment responses, and aiding rehabilitation in patients with encephalopathy, coma, or other consciousness disorders. Most seizures and status epilepticus (SE) events in the intensive care unit (ICU) setting are nonconvulsive or subtle, making cEEG essential for identifying these otherwise silent events. Imaging and invasive approaches can add to the diagnosis of seizures for specific populations, given that scalp electrodes may fail to identify seizures that may be detected by depth electrodes or electroradiologic findings. When cEEG identifies SE, the risk of secondary neuronal injury related to the time-intensity "burden" often prompts treatment with anti-seizure medications. Similarly, treatment may be administered for seizure-spectrum activity, such as periodic discharges or lateralized rhythmic delta slowing on the ictal-interictal continuum (IIC), even when frank seizures are not evident on the scalp. In this setting, cEEG is utilized empirically to monitor treatment response. Separately, cEEG has other versatile uses for neurotelemetry, including identifying the level of sedation or consciousness. Specific conditions such as sepsis, traumatic brain injury, subarachnoid hemorrhage, and cardiac arrest may each be associated with a unique application of cEEG; for example, predicting impending events of delayed cerebral ischemia, a feared complication in the first two weeks after subarachnoid hemorrhage. After brief training, non-neurophysiologists can learn to interpret quantitative EEG trends that summarize elements of EEG activity, enhancing clinical responsiveness in collaboration with clinical neurophysiologists. Intensivists and other healthcare professionals also play crucial roles in facilitating timely cEEG setup, preventing electrode-related skin injuries, and maintaining patient mobility during monitoring.

Ictal-Interictal Continuum in the Pediatric Intensive Care Unit.

BACKGROUND: The ictal-interictal continuum (IIC) consists of several electroencephalogram (EEG) patterns that are common in critically ill adults. Studies focused on the IIC are limited in critically ill children and have focused primarily on associations with electrographic seizures (ESs). We report the incidence of the IIC in the pediatric intensive care unit (PICU). We then compare IIC patterns to rhythmic and periodic patterns (RPP) not meeting IIC criteria looking for associations with acute cerebral abnormalities, ES, and in-hospital mortality. METHODS: This was a retrospective review of prospectively collected data for patients admitted to the PICU at Children's National Hospital from July 2021 to January 2023 with continuous EEG. We excluded patients with known epilepsy and cerebral injury prior to presentation. All patients were screened for RPP. The American Clinical Neurophysiology Society standardized Critical Care EEG terminology for the IIC was applied to each RPP. Associations between IIC and RPP not meeting IIC criteria, with clinical and EEG variables, were calculated using odds ratios (ORs). RESULTS: Of 201 patients, 21% (42/201) had RPP and 12% (24/201) met IIC criteria. Among patients with an IIC pattern, the median age was 3.4 years (interquartile range (IQR) 0.6-12 years). Sixty-seven percent (16/24) of patients met a single IIC criterion, whereas the remainder met two criteria. ESs were identified in 83% (20/24) of patients and cerebral injury was identified in 96% (23/24) of patients with IIC patterns. When comparing patients with IIC patterns with those with RPP not qualifying as an IIC pattern, both patterns were associated with acute cerebral abnormalities (IIC OR 26 [95% confidence interval {CI} 3.4-197], p = 0.0016 vs. RPP OR 3.5 [95% CI 1.1-11], p = 0.03), however, only the IIC was associated with ES (OR 121 [95% CI 33-451], p < 0.0001) versus RPP (OR 1.3 [0.4-5], p = 0.7). CONCLUSIONS: Rhythmic and periodic patterns and subsequently the IIC are commonly seen in the PICU and carry a high association with cerebral injury. Additionally, the IIC, seen in more than 10% of critically ill children, is associated with ES. The independent impact of RPP and IIC patterns on secondary brain injury and need for treatment of these patterns independent of ES requires further study.

Diagnosing nonconvulsive status epilepticus: Defining electroencephalographic and clinical response to diagnostic intravenous antiseizure medication trials.

OBJECTIVE: The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology 2021 include a diagnostic trial with intravenous (IV) antiseizure medications (ASMs) to assess electroencephalographic (EEG) and clinical response as a diagnostic criterion for definite NCSE and possible NCSE. However, how to perform this diagnostic test and assessing the EEG and clinical responses have not been operationally defined. METHODS: We performed a Delphi process involving six experts to standardize the diagnostic administration of IV ASM and propose operational criteria for EEG and clinical response. RESULTS: Either benzodiazepines (BZDs) or non-BZD ASMs can be used as first choice for a diagnostic IV ASM trial. However, non-BZDs should be considered in patients who already have impaired alertness or are at risk of respiratory depression. Levetiracetam, valproate, lacosamide, brivaracetam, or (if the only feasible drug) fosphenytoin or phenobarbital were deemed appropriate for a diagnostic IV trial. The starting dose should be approximately two thirds to three quarters of the full loading dose recommended for treatment of status epilepticus, with an additional smaller dose if needed. ASMs should be administered during EEG recording under supervision. A monitoring time of at least 15 min is recommended. If there is no response, a second trial with another non-BDZ or BDZs may be considered. A positive EEG response is defined as the resolution of the ictal-interictal continuum pattern for at least three times the longest previously observed spontaneous interval of resolution (if any), but minimum of one continuous minute. For a clinical response, physicians should use a standardized examination before and after IV ASM administration. We suggest a definite time-locked improvement in a focal deficit or at least one-step improvement on a new dedicated one-domain 10-level NCSE response scale. SIGNIFICANCE: The proposed standardized approach of a diagnostic IV ASM trial further refines the ACNS and Salzburg diagnostic criteria for NCSE.

Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury.

BACKGROUND: Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal-interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs. METHODS: In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal-interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration. RESULTS: Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs. CONCLUSIONS: Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal-interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.

Periodic and rhythmic patterns in critically ill children: Incidence, interrater agreement, and seizures.

OBJECTIVES: We aimed to determine the incidence of periodic and rhythmic patterns (PRP), assess the interrater agreement between electroencephalographers scoring PRP using standardized terminology, and analyze associations between PRP and electrographic seizures (ES) in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children undergoing continuous electroencephalographic monitoring (CEEG). PRP were identified by one electroencephalographer, and then two pediatric electroencephalographers independently scored the first 1-h epoch that contained PRP using standardized terminology. We determined the incidence of PRPs, evaluated interrater agreement between electroencephalographers scoring PRP, and evaluated associations between PRP and ES. RESULTS: One thousand three hundred ninety-nine patients underwent CEEG. ES occurred in 345 (25%) subjects. PRP, ES + PRP, and ictal-interictal continuum (IIC) patterns occurred in 142 (10%), 81 (6%), and 93 (7%) subjects, respectively. The most common PRP were generalized periodic discharges (GPD; 43, 30%), lateralized periodic discharges (LPD; 34, 24%), generalized rhythmic delta activity (GRDA; 34, 24%), bilateral independent periodic discharges (BIPD; 14, 10%), and lateralized rhythmic delta activity (LRDA; 11, 8%). ES risk varied by PRP type (p < .01). ES occurrence was associated with GPD (odds ratio [OR] = 6.35, p < .01), LPD (OR = 10.45, p < .01), BIPD (OR = 6.77, p < .01), and LRDA (OR = 6.58, p < .01). Some modifying features increased the risk of ES for each of those PRP. GRDA was not significantly associated with ES (OR = 1.34, p = .44). Each of the IIC patterns was associated with ES (OR = 6.83-8.81, p < .01). ES and PRP occurred within 6 h (before or after) in 45 (56%) subjects. SIGNIFICANCE: PRP occurred in 10% of critically ill children who underwent CEEG. The most common patterns were GPD, LPD, GRDA, BIPD, and LRDA. The GPD, LPD, BIPD, LRDA, and IIC patterns were associated with ES. GRDA was not associated with ES.

Functional neuroimaging in nonepileptiform electroencephalographic patterns in status epilepticus.

BACKGROUND: The diagnosis of nonconvulsive status epilepticus (NCSE) in patients with nonepileptiform EEG patterns remains a challenge. OBJECTIVE: To evaluate the usefulness of single photon emission computerized tomography (SPECT) and its quantification (QtSPECT) in the diagnosis of NCSE. METHODS: We retrospectively reviewed patients admitted with clinical suspicion of NCSE who underwent an HMPAO-SPECT simultaneously with scalp EEG showing nonepileptiform patterns, in a 5-year period. After a complete diagnostic workup, treatment, and clinical evolution, disregarding the SPECT results, patients were classified into confirmed NCSE (n = 11) and non-NCSE (n = 8). Then, we compared the EEG and SPECT results in both groups. RESULTS: Lateralized rhythmic delta activity (LRDA) was predominant in the NCSE group (45.4%, p = .045), while lateralized irregular slowing was observed equally in both groups. Patients with NCSE showed significant hyperperfusion compared with non-NCSE patients (p = .026). QtSPECT correctly classified 91% of patients in NCSE and 75% patients with non-NCSE (p = .006). CONCLUSIONS: Regional cerebral blood flow measured with SPECT could be useful in the diagnosis of NCSE in cases of an EEG pattern with lateralized slow activity and high clinical suspicion.

Electrographic seizures and ictal-interictal continuum (IIC) patterns in critically ill patients.

Critical care long-term continuous electroencephalogram (cEEG) monitoring has expanded dramatically in the last several decades spurned by technological advances in EEG digitalization and several key clinical findings: 1-Seizures are relatively common in the critically ill-large recent observational studies suggest that around 20% of critically ill patients placed on cEEG have seizures. 2-The majority (~75%) of patients who have seizures have exclusively "electrographic seizures", that is, they have no overt ictal clinical signs. Along with the discovery of the unexpectedly high incidence of seizures was the high prevalence of EEG patterns that share some common features with archetypical electrographic seizures but are not uniformly considered to be "ictal". These EEG patterns include lateralized periodic discharges (LPDs) and generalized periodic discharges (GPDs)-patterns that at times exhibit ictal-like behavior and at other times behave more like an interictal finding. Dr. Hirsch and colleagues proposed a conceptual framework to describe this spectrum of patterns called the ictal-interictal continuum (IIC). In the following years, investigators began to answer some of the key pragmatic clinical concerns such as which patients are at risk of seizures and what is the optimal duration of cEEG use. At the same time, investigators have begun probing the core questions for critical care EEG-what is the underlying pathophysiology of these patterns, at what point do these patterns cause secondary brain injury, what are the optimal treatment strategies, and how do these patterns affect clinical outcomes such as neurological disability and the development of epilepsy. In this review, we cover recent advancements in both practical concerns regarding cEEG use, current treatment strategies, and review the evidence associating IIC/seizures with poor clinical outcomes.

The PET Sandwich: Using Serial FDG-PET Scans with Interval Burst Suppression to Assess Ictal Components of Disease.

BACKGROUND: Determining the cause of refractory seizures and/or interictal continuum (IIC) findings in the critically ill patient remains a challenge. These electrographic abnormalities may represent primary ictal pathology or may instead be driven by an underlying infectious, inflammatory, or neoplastic pathology that requires targeted therapy. In these cases, it is unclear whether escalating antiepileptic therapy will be helpful or harmful. Herein, we report the use of serial [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) coupled with induced electrographic burst suppression to distinguish between primary and secondary ictal pathologies. We propose that anesthetic suppression of hypermetabolic foci suggests clinical responsiveness to escalating antiepileptic therapy, whereas non-suppressible hypermetabolic foci are suggestive of non-ictal pathologies that likely require multimodal therapy. METHODS: We describe 6 patients who presented with electrographic findings of seizure or IIC abnormalities, severe neurologic injury, and clinical concern for confounding pathologies. All patients were continuously monitored on video electroencephalography (cvEEG). Five patients underwent at least two sequential FDG-PET scans of the brain: one in a baseline state and the second while under electrographic burst suppression. FDG-avid loci and EEG tracings were compared pre- and post-burst suppression. One patient underwent a single FDG-PET scan while burst-suppressed. RESULTS: Four patients had initially FDG-avid foci that subsequently resolved with burst suppression. Escalation of antiepileptic therapy in these patients resulted in clinical improvement, suggesting that the foci were related to primary ictal pathology. These included clinical diagnoses of electroclinical status epilepticus, new-onset refractory status epilepticus, stroke-like migraine attacks after radiotherapy, and epilepsy secondary to inflammatory cerebral amyloid angiopathy. Conversely, two patients with high-grade EEG abnormalities had FDG-avid foci that persisted despite burst suppression. The first presented with a poor examination, fever, and concern for encephalitis. Postmortem pathology confirmed suspicion of herpes simplex virus encephalitis. The second patient presented with concern for checkpoint inhibitor-induced autoimmune encephalitis. The persistence of the FDG-avid focus, despite electrographic burst suppression, guided successful treatment through escalation of immunosuppressive therapy. CONCLUSIONS: In appropriately selected patients, FDG-PET scans while in burst suppression may help dissect the underlying pathophysiologic cause of IIC findings observed on EEG and guide tailored therapy.

The Ictal-Interictal Continuum: To Treat or Not to Treat (and How)?

Continuous electroencephalography (cEEG) monitoring is becoming increasingly used in neurologic and non-neurologic intensive care units (ICUs). Non-convulsive seizures (NCSz) and periodic discharges (PDs) are commonly seen in critically ill patients. Some of these PD patterns, also known as the ictal-interictal continuum (IIC), are associated with an increased risk of seizures and poor outcome. However, we do not fully understand the significance of these periodic patterns and the decision of how aggressively to treat remains controversial. IIC patterns are associated with pathophysiologic changes that closely resemble those of seizures. Here we make the argument that, rather than feature description on EEG, associated changes in brain physiology should dictate management choices.

Early Epileptiform Discharges and Clinical Signs Predict Nonconvulsive Status Epilepticus on Continuous EEG.

BACKGROUND: Critical care continuous electroencephalography (CCEEG) represents the gold standard for detection of nonconvulsive status epilepticus (NCSE) in neurological critical care patients. It is unclear which findings on short-term routine EEG and which clinical parameters predict NCSE during subsequent CCEEG reliably. The aim of the present study was to assess the prognostic significance of changes within the first 30 min of EEG as well as of clinical parameters for the occurrence of NCSE during subsequent CCEEG. METHODS: Systematic analysis of the first 30 min and the remaining segments of prospective CCEEG recordings according to the ACNS Standardized Critical Care EEG Terminology and according to recently proposed NCSE criteria as well as review of clinical parameters of 85 consecutive neurological critical care patients. Logistic regression and binary classification tests were used to determine the most useful parameters within the first 30 min of EEG predicting subsequent NCSE. RESULTS: The presence of early sporadic epileptiform discharges (SED) and early rhythmic or periodic EEG patterns of "ictal-interictal uncertainty" (RPPIIIU) (OR 15.51, 95% CI 2.83-84.84, p = 0.002) and clinical signs of NCS (OR 18.43, 95% CI 2.06-164.62, p = 0.009) predicted NCSE on subsequent CCEEG. Various combinations of early SED, early RPPIIIU, and clinical signs of NCS showed sensitivities of 79-100%, specificities of 49-89%, and negative predictive values of 95-100% regarding the incidence of subsequent NCSE (p < 0.001). CONCLUSIONS: Early SED and early RPPIIIU within the first 30 min of EEG as well as clinical signs of NCS predict the occurrence of NCSE during subsequent CCEEG with high sensitivity and high negative predictive value and may be useful to select patients who should undergo CCEEG.

Successful Wean Despite Emergence of Ictal-Interictal EEG Patterns During the Weaning of Prolonged Burst-Suppression Therapy for Super-Refractory Status Epilepticus.

BACKGROUND: Management of refractory status epilepticus (SE) commonly involves the induction of burst suppression using intravenous anesthetic agents. However, the endpoints of these therapies are not well defined. Weaning anesthetic agents are complicated by the emergence of electroencephalogram (EEG) patterns along the ictal-interictal continuum (IIC), which have uncertain significance given that IIC patterns may worsen cerebral metabolism and oxygenation, have a dissociation between scalp and depth EEG recordings, or may indicate a late stage of SE itself. Determining the significance of IIC patterns in the unique context of anesthetic weaning is important to prevent the potential for unnecessarily prolonging anesthetic coma. METHODS: Among 118 individuals with SE, we retrospectively identified a series of patients who underwent at least 24 h of burst-suppression therapy, experienced two or more weaning trials, and developed IIC patterns during anesthetic weaning. Anesthetic titration strategies during the emergence of these patterns were examined. RESULTS: Each of the six individuals who met inclusion criteria experienced aggressive weaning despite the emergence of IIC patterns. The IIC patterns that were encountered during anesthetic weaning (including generalized and lateralized periodic discharges) are described in detail. Favorable outcomes were reported in each subject. CONCLUSION: IIC patterns encountered during anesthetic weaning may be transitional and warrant observation, allowing for the emergence of more definitive clinical or electrographic results. The metabolic impact of these IIC patterns on brain activity is uncertain, but weaning strategies that treat IIC as a surrogate of recurrent SE risk further prolonging anesthetic management and its known toxicity. We speculate that these patterns may have a context-specific association with SE relapse, with less-risk conferred when these patterns are observed during the weaning of anesthetic agents after prolonged burst-suppression therapy. Other electrographic features aside from this clinical context may discriminate the risk of SE relapse, such as EEG background activity.

Clinical Correlates of Periodic Discharges and Nonconvulsive Seizures in Posterior Reversible Encephalopathy Syndrome (PRES).

IMPORTANCE: The pathophysiological mechanisms of Posterior Reversible Encephalopathy Syndrome (PRES) and related seizures remain poorly understood. The prevalence and clinical significance of nonconvulsive seizures (NCSz) and related epileptiform patterns during continuous electroencephalography monitoring (CEEG) in PRES have not been well described. OBJECTIVE: To report the prevalence, characteristics and risk factors for NCSz and related highly epileptiform patterns in patients with PRES, and to determine their relation to imaging abnormalities and outcome. DESIGN, SETTING AND PARTICIPANTS: From a prospective CEEG database, we retrospectively identified patients with PRES and reviewed their medical charts. Based on CEEG findings, we designed a retrospective cohort study comparing two groups defined based on the presence or the absence of NCSz and/or periodic discharges (PDs). MAIN OUTCOMES AND MEASURES: The prevalence and risk factors for PDs and NCSz, description of EEG and magnetic resonance imaging (MRI) abnormalities and functional outcome as measured by the Glasgow Outcome Scale (GOS) at hospital discharge. RESULTS: Among 37 eligible patients, 23 (62%) had PDs or NCSz. The presence of NCSz was associated with the presence of PDs (15/22 vs. 1/15; p = 0.0002). NCSz and PDs were usually either lateralized or bilateral independent and predominated in the posterior regions. No clinical features were associated with the occurrence of PDs or NCSz. Cortical restricted diffusion on MRI was more frequent in the PDs/NCSz group (17/23 vs. 1/14; p < 0.001). PDs/NCSz were associated with worse outcome, with 3 deaths vs. 0 in the no PDs/NCSz group and fewer cases with low disability (4 vs. 9 cases with GOS = 5, p < 0.04). CONCLUSIONS AND RELEVANCE: Our results reveal a high prevalence of NCSz and PDs in critically ill patients with PRES and an association with restricted diffusion and worse outcome, whether treating or preventing these EEG findings can improve outcome requires further research.

Metabolic Correlates of the Ictal-Interictal Continuum: FDG-PET During Continuous EEG.

BACKGROUND: Ictal-interictal continuum (IIC) continuous EEG (cEEG) patterns including periodic discharges and rhythmic delta activity are associated with poor outcome and in the appropriate clinical context, IIC patterns may represent "electroclinical" status epilepticus (SE). To clarify the significance of IIC patterns and their relationship to "electrographic" SE, we investigated FDG-PET imaging as a complementary metabolic biomarker of SE among patients with IIC patterns. METHODS: A single-center prospective clinical database was ascertained for patients undergoing FDG-PET during cEEG. Following MRI-PET co-registration, the maximum standardized uptake value in cortical and subcortical regions was compared to contralateral homologous and cerebellar regions. Consensus cEEG review and clinical rating of etiology and treatment response were performed retrospectively with blinding. Electrographic SE was classified as discrete seizures without interictal recovery or >3-Hz rhythmic IIC patterns. Electroclinical SE was classified as IIC patterns with electrographic and clinical response to anticonvulsants; clonic activity; or persistent post-ictal encephalopathy. RESULTS: Eighteen hospitalized subjects underwent FDG-PET during contemporaneous IIC patterns attributed to structural lesions (44 %), neuroinflammatory/neuroinfectious disease (39 %), or epilepsy (11 %). FDG-PET hypermetabolism was common (61 %) and predicted electrographic or electroclinical SE (sensitivity 79 % [95 % CI 53-93 %] and specificity 100 % [95 % CI 51-100 %]; p = 0.01). Excluding electrographic SE, hypermetabolism also predicted electroclinical SE (sensitivity 80 % [95 % CI 44-94 %] and specificity 100 % [95 % CI 51-100 %]; p = 0.01). CONCLUSIONS: In hospitalized patients with IIC EEG patterns, FDG-PET hypermetabolism is common and is a candidate metabolic biomarker of electrographic SE or electroclinical SE.

"Ictal" lateralized periodic discharges.

OBJECTIVE: Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or the other, remains highly controversial. Lateralized periodic discharges are, however, widely accepted as being ictal when they are time-locked to clinically apparent symptoms. We sought to investigate the characteristics of "ictal" lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms in order to explore the utility of using this definition to dichotomize LPDs into "ictal" and "nonictal" categories. METHODS: Our archive of all continuous EEG (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 was searched to identify all reports describing LPDs. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms; LPDs lacking a clear time-locked correlate were considered to be "nonictal" lateralized periodic discharges (NILPDs). Patient charts and available neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs, imaging findings, presence of seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. p-Values were adjusted for false discovery rate (FDR). RESULTS: One thousand four hundred fifty-two patients underwent cEEG monitoring at our institution between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor symptoms, and the remaining patient experienced stereotyped sensory symptoms. Ictal lateralized periodic discharges had significantly increased odds for involving central head regions (odds ratio [OR]=11; 95% confidence interval [CI]=2.16-62.6; p=0.018, FDR adjusted), with a trend towards higher proportion of lesions involving the primary sensorimotor cortex (p=0.09, FDR adjusted). CONCLUSIONS: When defined by the presence of a time-locked clinical correlate, ILPDs appear to be strongly associated with a central EEG localization. This is likely due to cortical irritability in central head regions having greater propensity to manifest with positive, clinically apparent, and time-locked symptoms. Thus, dichotomization of ILPDs and NILPDs on this basis principally reflects differences in underlying anatomical locations of the periodic discharges rather than providing a clinically salient categorization.

Automated Quantification of Periodic Discharges in Human Electroencephalogram.

Periodic discharges (PDs) are pathologic patterns of epileptiform discharges repeating at regular intervals, commonly detected in the human electroencephalogram (EEG) signals in patients who are critically ill. The frequency and spatial extent of PDs are associated with the tendency of PDs to cause brain injury, existing automated algorithms do not quantify the frequency and spatial extent of PDs. The present study presents an algorithm for quantifying frequency and spatial extent of PDs. The algorithm quantifies the evolution of these parameters within a short (10-14 second) window, with a focus on lateralized and generalized periodic discharges. We test our algorithm on 300 ``easy'', 300 ``medium'', and 240 ``hard'' examples (840 total epochs) of periodic discharges as quantified by interrater consensus from human experts when analyzing the given EEG epochs. We observe $95.0\%$ agreement with a 95\% confidence interval (CI) of $[94.9\%, 95.1\%]$ between algorithm outputs with reviewer clincal judgement for easy examples, $92.0\%$ agreement (95\% CI $[91.9\%, 92.2\%]$) for medium examples, and $90.4\%$ agreement (95\% CI $[90.3\%, 90.6\%]$) for hard examples. The algorithm is also computationally efficient and is able to run in $0.385 \pm 0.038$ seconds for a single epoch using our provided implementation of the algorithm. The results demonstrate the algorithm's effectiveness in quantifying these discharges and provide a standardized and efficient approach for PD quantification as compared to existing manual approaches.

Cefepime-Induced Neurotoxicity or Nonconvulsive Status Epilepticus (NCSE): A Controversy Revisited.

Neurotoxicity is a well-known side effect of cefepime among patients commonly present with altered mental status and typical electroencephalogram (EEG) findings of generalized periodic discharges (GPDs). Some practitioners consider this pattern as encephalopathy and often treat it with the withdrawal of cefepime only, while others are at times concerned with non-convulsive status epilepticus (NCSE) and treat it with antiseizure medications (ASMs) in addition to the withdrawal of cefepime to accelerate the recovery. We present a case series of two patients who developed cefepime-induced altered mental status and EEG findings of GPDs at a rate of 2-2.5 Hz concerning for the ictal-interictal continuum (IIC). Both cases were treated as possible NCSE with ASMs in addition to the withdrawal of cefepime, resulting in different clinical outcomes. The first case showed clinical and EEG improvement shortly after the administration of parenteral benzodiazepines and ASMs. The other case showed electrographic improvement but did not show significant improvement in mentation, and the patient died eventually.

Independent risk factors for seizures in critically ill patients on continuous EEG.

OBJECTIVE: The objective of this study was to characterize the independent risk factors for seizures in critically ill patients monitored with continuous EEG (cEEG). METHODS: We retrospectively investigated variables associated with cEEG seizures, first in the entire cohort of 156 patients and, subsequently, in the subgroup without seizures in the first 30 minutes of monitoring. RESULTS: Seizures were observed in 19.2% of recordings, and in 50% of these, seizures occurred in the first 30 minutes. In the entire cohort, epilepsy, acute seizures prior to cEEG, interictal epileptiform discharges (IEDs), lateralized periodic discharges (LPDs), and brief potentially ictal rhythmic discharges (BIRDs) were associated with a higher incidence of cEEG seizures, whereas coma, intravenous anaesthetic drugs, and generalized periodic discharges (GPDs) were associated with a lower incidence of seizures. On multivariate analysis, this association was maintained for acute seizures before cEEG (OR: 5.92) and IEDs (OR: 6.81). Excluding patients with seizures at the beginning of monitoring, acute seizures before cEEG, IEDs, LPDs, and BIRDs were associated with an increased risk of seizures. The presence of IEDs or LPDs in the first 30 minutes was associated with a 4.14-fold greater chance of seizures on cEEG. On multivariate analysis, acute seizures prior to recording (OR 7.29) and LPDs (OR: 5.38) remained associated with seizures on cEEG. Due to the sample size, BIRDs were not included in multivariate models. SIGNIFICANCE: Acute seizures prior to monitoring, IEDs, LPDs and BIRDs are important risk factors for cEEG seizures in critically ill patients.

Neurocritical Care and Brain Monitoring.

The goal of neurocritical care (NCC) is to improve the outcome of patients with neurologic insults. NCC includes the management of the primary brain injury and prevention of secondary brain injury; this is achieved with standardized clinical care for specific disorders along with neuromonitoring. Neuromonitoring uses multiple modalities, with certain modalities better suited to certain disorders. The term "multimodality monitoring" refers to using multiple modalities at the same time. This article reviews pediatric NCC, the various physiologic parameters used, especially continuous electroencephalographic monitoring.

Critical care EEG standardized nomenclature in clinical practice: Strengths, limitations, and outlook on the example of prognostication after cardiac arrest.

We discuss the achievements of the ACNS critical care EEG nomenclature proposed in 2013 and, from a clinical angle, outline some limitations regarding translation into treatment implications. While the recently proposed updated 2021 version of the nomenclature will probable improve some uncertainty areas, a refined understanding of the mechanisms at the origin of the EEG patterns, and a multimodal integration of the nomenclature to the clinical context may help improving the rationale supporting therapeutic procedures. We illustrate these aspects on prognostication after cardiac arrest.