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

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Power spectrum analysis and outcomes of non-convulsive status epilepticus: a single-center study.

OBJECTIVES: Diagnosis of non-convulsive status epilepticus (NCSE) is challenging and outcomes during follow-up are not clear. This study aimed to conduct power spectrum analysis in NCSE and measure outcomes of patients. METHODS: We searched continuous EEG monitoring (cEEG) recordings to identify patients of NCSE. An artifact-free cEEG epoch of continuous 60 s was chosen for spectral power analysis. We also collected electronic medical records of the patients for extracting clinical information. Patients recruited were followed up at least every half a year. RESULTS: There were 48 patients with 64 independent NCSE episodes during different course of disease recruited in the study, with a mean age of 40.3 ± 19.1 years (range, 12-72 years), including 24 males (50%) and 24 females (50%). When the spectral power of 60 s equaled to 11.30 µV2 for predicting impairment of consciousness, (sensitivity, specificity) = (0.979, 0.625). When the spectral power of 60 s equaled to 52.70 µV2 for predicting myoclonic jerks, (sensitivity, specificity) = (0.783, 0.756). There were 27 patients (56.3%) followed up with a duration over 12 months. Nineteen patients (70.4%) continued to have seizures. Eleven (40.7%) resisted to at least two kinds of appropriate anti-seizure medication at maximum tolerated levels. Five patients with prolonged NCSE suffered from loss of brain parenchymal volume on follow-up MRI scans. CONCLUSION: Spectral power analysis can be used to detect mental status and limb jerks. Early diagnosis and treatment of NCSE are important, which can influence outcomes of the patients during follow-up.

Optimizing Electrode Configurations for Wearable EEG Seizure Detection Using Machine Learning.

Epilepsy, a prevalent neurological disorder, profoundly affects patients' quality of life due to the unpredictable nature of seizures. The development of a reliable and user-friendly wearable EEG system capable of detecting and predicting seizures has the potential to revolutionize epilepsy care. However, optimizing electrode configurations for such systems, which is crucial for balancing accuracy and practicality, remains to be explored. This study addresses this gap by developing a systematic approach to optimize electrode configurations for a seizure detection machine-learning algorithm. Our approach was applied to an extensive database of prolonged annotated EEG recordings from 158 epilepsy patients. Multiple electrode configurations ranging from one to eighteen were assessed to determine the optimal number of electrodes. Results indicated that the performance was initially maintained as the number of electrodes decreased, but a drop in performance was found to have occurred at around eight electrodes. Subsequently, a comprehensive analysis of all eight-electrode configurations was conducted using a computationally intensive workflow to identify the optimal configurations. This approach can inform the mechanical design process of an EEG system that balances seizure detection accuracy with the ease of use and portability. Additionally, this framework holds potential for optimizing hardware in other machine learning applications. The study presents a significant step towards the development of an efficient wearable EEG system for seizure detection.

Serum neuron-specific enolase: a new tool for seizure risk monitoring after status epilepticus.

BACKGROUND AND PURPOSE: There is a need for accurate biomarkers to monitor electroencephalography (EEG) activity and assess seizure risk in patients with acute brain injury. Seizure recurrence may lead to cellular alterations and subsequent neurological sequelae. Whether neuron-specific enolase (NSE) and S100-beta (S100B), brain injury biomarkers, can reflect EEG activity and help to evaluate the seizure risk was investigated. METHODS: Eleven patients, admitted to an intensive care unit for refractory status epilepticus, who underwent a minimum of 3 days of continuous EEG concomitantly with daily serum NSE and S100B assays were included. At 103 days the relationships between serum NSE and S100B levels and two EEG scores able to monitor the seizure risk were investigated. Biochemical biomarker thresholds able to predict seizure recurrence were sought. RESULTS: Only NSE levels positively correlated with EEG scores. Similar temporal dynamics were observed for the time courses of EEG scores and NSE levels. NSE levels above 17 ng/ml were associated with seizure in 71% of patients. An increase of more than 15% of NSE levels was associated with seizure recurrence in 80% of patients. CONCLUSIONS: Our study highlights the potential of NSE as a biomarker of EEG activity and to assess the risk of seizure recurrence.

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.

Diagnostic Value of Electroencephalography with Ten Electrodes in Critically Ill Patients.

BACKGROUND: In critical care settings, electroencephalography (EEG) with reduced number of electrodes (reduced montage EEG, rm-EEG) might be a timely alternative to the conventional full montage EEG (fm-EEG). However, past studies have reported variable accuracies for detecting seizures using rm-EEG. We hypothesized that the past studies did not distinguish between differences in sensitivity from differences in classification of EEG patterns by different readers. The goal of the present study was to revisit the diagnostic value of rm-EEG when confounding issues are accounted for. METHODS: We retrospectively collected 212 adult EEGs recorded at Massachusetts General Hospital and reviewed by two epileptologists with access to clinical, trending, and video information. In Phase I of the study, we re-configured the first 4 h of the EEGs in lateral circumferential montage with ten electrodes and asked new readers to interpret the EEGs without access to any other ancillary information. We compared their rating to the reading of hospital clinicians with access to ancillary information. In Phase II, we measured the accuracy of the same raters reading representative samples of the discordant EEGs in full and reduced configurations presented randomly by comparing their performance to majority consensus as the gold standard. RESULTS: Of the 95 EEGs without seizures in the selected fm-EEG, readers of rm-EEG identified 92 cases (97%) as having no seizure activity. Of 117 EEGs with "seizures" identified in the selected fm-EEG, none of the cases was labeled as normal on rm-EEG. Readers of rm-EEG reported pathological activity in 100% of cases, but labeled them as seizures (N = 77), rhythmic or periodic patterns (N = 24), epileptiform spikes (N = 7), or burst suppression (N = 6). When the same raters read representative epochs of the discordant EEG cases (N = 43) in both fm-EEG and rm-EEG configurations, we found high concordance (95%) and intra-rater agreement (93%) between fm-EEG and rm-EEG diagnoses. CONCLUSIONS: Reduced EEG with ten electrodes in circumferential configuration preserves key features of the traditional EEG system. Discrepancies between rm-EEG and fm-EEG as reported in some of the past studies can be in part due to methodological factors such as choice of gold standard diagnosis, asymmetric access to ancillary clinical information, and inter-rater variability rather than detection failure of rm-EEG as a result of electrode reduction per se.

Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage.

OBJECTIVES: Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI. METHODS: We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T-tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome. RESULTS: Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2 months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055-1.680. P = .016]. CONCLUSION: Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI.

The Use of Continuous EEG Monitoring in Intensive Care Units in The Netherlands: A National Survey.

BACKGROUND: Currently, continuous electroencephalographic monitoring (cEEG) is the only available diagnostic tool for continuous monitoring of brain function in intensive care unit (ICU) patients. Yet, the exact relevance of routinely applied ICU cEEG remains unclear, and information on the implementation of cEEG, especially in Europe, is scarce. This study explores current practices of cEEG in adult Dutch ICU departments focusing on organizational and operational factors, development over time and factors perceived relevant for abstaining its use. METHODS: A national survey on cEEG in adults among the neurology and adult intensive care departments of all Dutch hospitals (n = 82) was performed. RESULTS: The overall institutional response rate was 78%. ICU cEEG is increasingly used in the Netherlands (in 37% of all hospitals in 2016 versus in 21% in 2008). Currently in 88% of university, 55% of teaching and 14% of general hospitals use ICU cEEG. Reasons for not performing cEEG are diverse, including perceived non-feasibility and lack of data on the effect of cEEG use on patient outcome. Mostly, ICU cEEG is used for non-convulsive seizures or status epilepticus and prognostication. However, cEEG is never or rarely used for monitoring cerebral ischemia and raised intracranial pressure in traumatic brain injury. Review and reporting practices differ considerably between hospitals. Nearly all hospitals perform non-continuous review of cEEG traces. Methods for moving toward continuous review of cEEG traces are available but infrequently used in practice. CONCLUSIONS: cEEG is increasingly used in Dutch ICUs. However, cEEG practices vastly differ between hospitals. Future research should focus on uniform cEEG practices including unambiguous EEG interpretation to facilitate collaborative research on cEEG, aiming to provide improved standard patient care and robust data on the impact of cEEG use on patient outcome.

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.

Extended EEG and non-convulsive status epilepticus: Benefit over routine EEG?

OBJECTIVE: EEG monitoring is increasingly used in critically ill patients, but impact on clinical outcome remains unclear. We aimed to investigate the benefit of repeated extended EEG in the prognosis of patients with non-convulsive status epilepticus (SE). MATERIALS & METHODS: We retrospectively collected 29 consecutive patients with non-convulsive SE without coma, who underwent repeated extended EEG between 2013 and 2015. We compared these patients with an historical age-matched group of 58 patients managed between 2011 and 2013 with routine EEG only. We excluded patients treated with therapeutic coma for SE treatment. Outcome at hospital discharge was categorized as return to baseline conditions, new disability, and death. RESULTS: Severity of SE was similar in the two groups, with similar proportion of potential fatal etiologies (58% in the extended EEG group vs 60%, P=.529), similar STESS scores (median was three in both groups, P=.714), and comparable acute hospitalization duration (median of 15 vs 11 days, P=.131). The extended EEG group received slightly more anti-epileptic drugs (median was three in both groups, P=.026). Distribution of the outcome categories at hospital discharge was similar (P=.129). CONCLUSIONS: Extended EEG used for the management of non-convulsive status epilepticus does not seem to improve clinical outcome, but is associated with a higher number of prescribed anti-epileptic drugs. The benefit of continuous EEG monitoring in non-convulsive SE without coma SE should be addressed through a randomized trial.

Delayed Deterioration of EEG Background Rhythm Post-cardiac Arrest.

BACKGROUND: Electroencephalogram (EEG) background continuity is associated with a favorable prognosis in cardiac arrest patients post-therapeutic hypothermia. However, the continuous EEG in a subset of patients will undergo 'delayed EEG deterioration'; they will invariably have poor outcome. The aim of this study was to characterize this phenomenon. METHODS: We studied a prospectively collected cohort of consecutive cardiac arrest patients who underwent therapeutic hypothermia between July 2012 and May 2015. We identified patients with an initially favorable EEG rhythm post-cooling and characterized a subset of patients with delayed EEG deterioration. RESULTS: A total of 133 patients were included in the analysis. Of these, 69/133 (51.9%) had an initially favorable EEG. Of those patients with initially favorable EEG, 7/69 (10.1%) had a subsequent deterioration. Delayed EEG deterioration was associated with poor outcome. The median time to deterioration was 55 h. CONCLUSIONS: Delayed EEG deterioration is associated with poor clinical outcomes. We hypothesize that this is the result of delayed neuronal degeneration, the exact mechanism requiring further exploration. Identifying patients with delayed EEG deterioration post-therapeutic hypothermia is paramount as further interventions may yet salvage their outcomes, though further study is needed.

EEG Characteristics of Successful Burst Suppression for Refractory Status Epilepticus.

BACKGROUND: Refractory status epilepticus (RSE) is often treated with continuous intravenous medications with the goal of EEG burst suppression. Standard advice is to titrate medications to at least 10-s interburst intervals; however, this has not been shown to improve outcome. We examined EEG characteristics in patients treated with IV anesthetic therapy (IVAT) for RSE to determine which EEG characteristics were associated with successful lifting of IVAT (i.e., without recurrence of status epilepticus). METHODS: We screened the clinical continuous EEG database for adult patients treated with IVAT for RSE (excluding patients with anoxic injury). We measured the length of bursts and interburst intervals for each patient, calculated EEG burst suppression ratios, and graded bursts for the amount of epileptiform activity. We compared these characteristics in successful versus unsuccessful IVAT lifting attempts. RESULTS: We included 17 successful and 20 unsuccessful lifting attempts in 19 patients (5 used as a holdout validation set). The interburst intervals, burst suppression ratios, and length of bursts did not differentiate successful and unsuccessful lifting attempts; the amount of epileptiform activity in bursts correlated with success or failure to wean IVAT (p = 0.008). Maximum burst amplitude <125 µV had 84.6 % sensitivity and 61.1 % specificity for predicting successful lifting. CONCLUSION: The length of interburst intervals and burst suppression did not predict successful termination of RSE in this small cohort. This may suggest that EEG characteristics, rather a strict interburst interval goal, could guide IVAT for RSE.

Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage: A Pilot Study.

INTRODUCTION: Early identification of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) is a major challenge. The aim of this study was to investigate whether quantitative EEG (qEEG) features can detect DCI prior to clinical or radiographic findings. METHODS: A prospective cohort study was performed in aSAH patients in whom continuous EEG (cEEG) was recorded. We studied 12 qEEG features. We compared the time point at which qEEG changed with the time point that clinical deterioration occurred or new ischemia was noted on CT scan. RESULTS: Twenty aSAH patients were included of whom 11 developed DCI. The alpha/delta ratio (ADR) was the most promising feature that showed a significant difference in change over time in the DCI group (median -62% with IQR -87 to -39%) compared to the control group (median +27% with IQR -32 to +104%, p = 0.013). Based on the ROC curve, a threshold was chosen for a combined measure of ADR and alpha variability (AUC: 91.7, 95% CI 74.2-100). The median time that elapsed between change of qEEG and clinical DCI diagnosis was seven hours (IQR -11-25). Delay between qEEG and CT scan changes was 44 h (median, IQR 14-117). CONCLUSION: In this study, ADR and alpha variability could detect DCI development before ischemic changes on CT scan was apparent and before clinical deterioration was noted. Implementation of cEEG in aSAH patients can probably improve early detection of DCI.

Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome.

OBJECTIVE: Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation-mediated changes in blood-brain barrier permeability have been experimentally linked to seizures. METHODS: In this prospective observational study of aneurysmal subarachnoid hemorrhage (SAH) patients, we explored the link between the inflammatory response following SAH and in-hospital NCSz studying clinical (systemic inflammatory response syndrome [SIRS]) and laboratory (tumor necrosis factor receptor 1 [TNF-R1], high-sensitivity C-reactive protein [hsCRP]) markers of inflammation. Logistic regression, Cox proportional hazards regression, and mediation analyses were performed to investigate temporal and causal relationships. RESULTS: Among 479 SAH patients, 53 (11%) had in-hospital NCSz. Patients with in-hospital NCSz had a more pronounced SIRS response (odds ratio [OR]=1.9 per point increase in SIRS, 95% confidence interval [CI]=1.3-2.9), inflammatory surges were more likely immediately preceding NCSz onset, and the negative impact of SIRS on functional outcome at 3 months was mediated in part through in-hospital NCSz. In a subset with inflammatory serum biomarkers, we confirmed these findings linking higher serum TNF-R1 and hsCRP to in-hospital NCSz (OR=1.2 per 20-point hsCRP increase, 95% CI=1.1-1.4; OR=2.5 per 100-point TNF-R1 increase, 95% CI=2.1-2.9). The association of inflammatory biomarkers with poor outcome was mediated in part through NCSz. INTERPRETATION: In-hospital NCSz were independently associated with a proinflammatory state following SAH as reflected in clinical symptoms and serum biomarkers of inflammation. Our findings suggest that inflammation following SAH is associated with poor outcome and that this effect is at least in part mediated through in-hospital NCSz.

Generalized epileptiform discharges in postanoxic encephalopathy: Quantitative characterization in relation to outcome.

OBJECTIVE: Electrographic status epilepticus is observed in 10-35% of patients with postanoxic encephalopathy. It remains unclear which electrographic seizure patterns indicate possible recovery, and which are a mere reflection of severe ischemic encephalopathy, where treatment would be futile. We aimed to identify quantitative electroencephalography (EEG) features with prognostic significance. METHODS: From continuous EEG recordings of 47 patients with generalized electrographic status epilepticus after cardiac arrest, 5-min epochs were selected every hour. Epochs were visually assessed and categorized into seven categories, including epileptiform discharges. Five quantitative measures were extracted, reflecting background continuity, discharge frequency, discharge periodicity, relative discharge power, and interdischarge waveform correlation. The best achieved outcome within 6 months after cardiac arrest was categorized as "good" (Cerebral Performance Category 1-2, i.e., no or moderate neurologic disability) or "poor" (CPC 3-5, i.e., severe disability, coma, or death). RESULTS: Ten patients (22%) had a good outcome. Status epilepticus in patients with good outcome started later (45 vs. 29 h after cardiac arrest, p < 0.001), more often ceased for at least 12 h (90% vs. 16%, p = 0.02), and was less often treated with antiepileptic drugs (30% vs. 73%, p = 0.02). Status epilepticus in patients with a good outcome always evolved from a continuous background pattern, as opposed to evolution from a discontinuous background pattern in 14 patients (38%) with a poor outcome. Epileptiform patterns of patients with good outcome had higher background continuity (1.00 vs. 0.83, p < 0.001), higher discharge frequency (1.63 vs. 0.90 Hz, p = 0.002), lower relative discharge power (0.29 vs. 0.40, p = 0.01), and lower discharge periodicity (0.32 vs. 0.45, p = 0.04). SIGNIFICANCE: Our results can be used to identify patients with possible recovery. We speculate that quantitative features associated with poor outcome reflect low neural network complexity, resulting from extensive ischemic damage.

Lacosamide in status epilepticus: Update on the TRENdS study.

Many patients with critical illness have been noted to have nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE). How aggressively these seizures should be treated is unclear. Many investigators feel that the morbidity of NCSs and NCSE is different from that of generalized convulsive status epilepticus (GCSE), so treatment should be less urgent. Consequently, many nonsedating AEDs have been used to treat NCSs and NCSE in patients with critical illness. Randomized, controlled trials demonstrating the efficacy of AEDs in NCSs and NCSE are lacking. The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) study compared lacosamide to fosphenytoin in the treatment of NCSs. An update of the study is presented. This article is part of a Special Issue entitled "Status Epilepticus".

Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. CLINICAL CASE: An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition, occasional focal areas of ischemic injury showing filiform neurons with reactive astrocytic gliosis background consistent with acute lesions were observed in CA3. CONCLUSIONS: Fat embolism should be considered a potential cause of sr-NCSE. This article is part of a Special Issue entitled "Status Epilepticus".

Interrater agreement for Critical Care EEG Terminology.

OBJECTIVE: The interpretation of critical care electroencephalography (EEG) studies is challenging because of the presence of many periodic and rhythmic patterns of uncertain clinical significance. Defining the clinical significance of these patterns requires standardized terminology with high interrater agreement (IRA). We sought to evaluate IRA for the final, published American Clinical Neurophysiology Society (ACNS)-approved version of the critical care EEG terminology (2012 version). Our evaluation included terms not assessed previously and incorporated raters with a broad range of EEG reading experience. METHODS: After reviewing a set of training slides, 49 readers independently completed a Web-based test consisting of 11 identical questions for each of 37 EEG samples (407 questions). Questions assessed whether a pattern was an electrographic seizure; pattern location (main term 1), pattern type (main term 2); and presence and classification of eight other key features ("plus" modifiers, sharpness, absolute and relative amplitude, frequency, number of phases, fluctuation/evolution, and the presence of "triphasic" morphology). RESULTS: IRA statistics (κ values) were almost perfect (90-100%) for seizures, main terms 1 and 2, the +S modifier (superimposed spikes/sharp waves or sharply contoured rhythmic delta activity), sharpness, absolute amplitude, frequency, and number of phases. Agreement was substantial for the +F (superimposed fast activity) and +R (superimposed rhythmic delta activity) modifiers (66% and 67%, respectively), moderate for triphasic morphology (58%), and fair for evolution (21%). SIGNIFICANCE: IRA for most terms in the ACNS critical care EEG terminology is high. These terms are suitable for multicenter research on the clinical significance of critical care EEG patterns. A PowerPoint slide summarizing this article is available for download in the Supporting Information section http://dx.doi.org/10.1111/epi.12653/supinfo.

EEG patterns compatible with nonconvulsive status epilepticus are common in elderly patients with delirium: a prospective study with continuous EEG monitoring.

INTRODUCTION: Delirium is a leading cause of hospitalization and morbidity in elderly persons. Nonconvulsive status epilepticus (NCSE) and delirium share many risk factors. We tested the hypothesis that NCSE plays an important role in delirium by performing continuous EEG (cEEG) monitoring in elderly patients with delirium of any cause. MATERIAL AND METHODS: Patients over 65 years old presenting with delirium in the emergency room were prospectively included and underwent either routine 20-minute EEG or cEEG within 24h after admission. Clinical, biological, and imaging characteristics, length of hospitalization, and outcome were compared between patients with possible NCSE and patients without epileptic discharges. RESULTS: There were 32 patients in each group. Continuous EEG detected patterns compatible with NCSE in 28% and focal interictal epileptiform discharges (IEDs) in 16% of the patients. Routine EEG detected patterns compatible with NCSE in 6% and focal IEDs in 16% of the patients. History of cognitive impairment and use of antibiotics and hypernatremia were significantly associated with the presence of possible NCSE. Delirium in patients with possible NCSE was initially attributed to another cause in over 80% of the cases. Patterns compatible with NCSE were associated with a longer hospitalization stay and a higher mortality rate. CONCLUSION: Electroencephalographic patterns compatible with NCSE are found in 28% of elderly with delirium when cEEG monitoring is performed. No clinical or paraclinical parameter can reliably distinguish elderly patients with delirium with or without patterns compatible with NCSE in the absence of cEEG monitoring. Elderly patients with delirium and patterns compatible with NCSE have significantly higher mortality rates and longer hospital stays.

"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.