Evaluating the Impact of Point-of-Care Electroencephalography on Length of Stay in the Intensive Care Unit: Subanalysis of the SAFER-EEG Trial.

BACKGROUND: Electroencephalography (EEG) is needed to diagnose nonconvulsive seizures. Prolonged nonconvulsive seizures are associated with neuronal injuries and deleterious clinical outcomes. However, it is uncertain whether the rapid identification of these seizures using point-of-care EEG (POC-EEG) can have a positive impact on clinical outcomes. METHODS: In a retrospective subanalysis of the recently completed multicenter Seizure Assessment and Forecasting with Efficient Rapid-EEG (SAFER-EEG) trial, we compared intensive care unit (ICU) length of stay (LOS), unfavorable functional outcome (modified Rankin Scale score ≥ 4), and time to EEG between adult patients receiving a US Food and Drug Administration-cleared POC-EEG (Ceribell, Inc.) and those receiving conventional EEG (conv-EEG). Patient records from January 2018 to June 2022 at three different academic centers were reviewed, focusing on EEG timing and clinical outcomes. Propensity score matching was applied using key clinical covariates to control for confounders. Medians and interquartile ranges (IQRs) were calculated for descriptive statistics. Nonparametric tests (Mann-Whitney U-test) were used for the continuous variables, and the χ2 test was used for the proportions. RESULTS: A total of 283 ICU patients (62 conv-EEG, 221 POC-EEG) were included. The two populations were matched using demographic and clinical characteristics. We found that the ICU LOS was significantly shorter in the POC-EEG cohort compared to the conv-EEG cohort (3.9 [IQR 1.9-8.8] vs. 8.0 [IQR 3.0-16.0] days, p = 0.003). Moreover, modified Rankin Scale functional outcomes were also different between the two EEG cohorts (p = 0.047). CONCLUSIONS: This study reveals a significant association between early POC-EEG detection of nonconvulsive seizures and decreased ICU LOS. The POC-EEG differed from conv-EEG, demonstrating better functional outcomes compared with the latter in a matched analysis. These findings corroborate previous research advocating the benefit of early diagnosis of nonconvulsive seizure. The causal relationship between the type of EEG and metrics of interest, such as ICU LOS and functional/clinical outcomes, needs to be confirmed in future prospective randomized studies.

Comparison of Continuous Intracortical and Scalp Electroencephalography in Comatose Patients with Acute Brain Injury.

BACKGROUND: Depth electroencephalography (dEEG) is a recent invasive monitoring technique used in patients with acute brain injury. This study aimed to describe in detail the clinical manifestations of nonconvulsive seizures (NCSzs) with and without a surface EEG correlate, analyze their long-standing effects, and provide data that contribute to understanding the significance of certain scalp EEG patterns observed in critically ill patients. METHODS: We prospectively enrolled a cohort of 33 adults with severe acute brain injury admitted to the neurological intensive care unit. All of them underwent multimodal invasive monitoring, including dEEG. All patients were scanned on a 3T magnetic resonance imaging scanner at 6 months after hospital discharge, and mesial temporal atrophy (MTA) was calculated using a visual scale. RESULTS: In 21 (65.6%) of 32 study participants, highly epileptiform intracortical patterns were observed. A total of 11 (34.3%) patients had electrographic or electroclinical seizures in the dEEG, of whom 8 had both spontaneous and stimulus-induced (SI) seizures, and 3 patients had only spontaneous intracortical seizures. An unequivocal ictal scalp correlate was observed in only 3 (27.2%) of the 11 study participants. SI-NCSzs occurred during nursing care, medical procedures, and family visits. Subtle clinical manifestations, such as restlessness, purposeless stereotyped movements of the upper limbs, ventilation disturbances, jerks, head movements, hyperextension posturing, chewing, and oroalimentary automatisms, occurred during intracortical electroclinical seizures. MTA was detected in 18 (81.8%) of the 22 patients. There were no statistically significant differences between patients with MTA with and without seizures or status epilepticus. CONCLUSIONS: Most NCSzs in critically ill comatose patients remain undetectable on scalp EEG. SI-NCSzs frequently occur during nursing care, medical procedures, and family visits. Semiology of NCSzs included ictal minor signs and subtle symptoms, such as breathing pattern changes manifested as patient-ventilator dyssynchrony.

Electroencephalogram in the intensive care unit: a focused look at acute brain injury.

Over the past decades, electroencephalography (EEG) has become a widely applied and highly sophisticated brain monitoring tool in a variety of intensive care unit (ICU) settings. The most common indication for EEG monitoring currently is the management of refractory status epilepticus. In addition, a number of studies have associated frequent seizures, including nonconvulsive status epilepticus (NCSE), with worsening secondary brain injury and with worse outcomes. With the widespread utilization of EEG (spot and continuous EEG), rhythmic and periodic patterns that do not fulfill strict seizure criteria have been identified, epidemiologically quantified, and linked to pathophysiological events across a wide spectrum of critical and acute illnesses, including acute brain injury. Increasingly, EEG is not just qualitatively described, but also quantitatively analyzed together with other modalities to generate innovative measurements with possible clinical relevance. In this review, we discuss the current knowledge and emerging applications of EEG in the ICU, including seizure detection, ischemia monitoring, detection of cortical spreading depolarizations, assessment of consciousness and prognostication. We also review some technical aspects and challenges of using EEG in the ICU including the logistics of setting up ICU EEG monitoring in resource-limited settings.

Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

Duration of nonconvulsive seizures in critically ill patients.

INTRODUCTION: Non-convulsive seizures (NCSz) and non-convulsive status epilepticus (NCSE) are frequent in critically ill patients. Specific temporal thresholds to define both are lacking and may be needed to guide appropriate treatment. METHOD: Retrospective review of 995 NCSz captured during continuous EEG monitoring of 111 consecutive critically ill patients. Seizures were classified according to their type and underlying etiology (acute or progressive brain injury, seizure-related disorders and acute medical illness). Median and interquartile ranges [IQR] were calculated. Suggested temporal threshold for NCSE was defined as the 95 percentile of seizure duration. RESULTS: Most (69%) patients had an underlying acute or progressive brain injury. The 95 percentile of seizure duration was 518 s, overall, with variation according to underlying etiology (median 86 [47-137] s for brain injury, 73 [45-115] s for seizure-related disorders, and 92 [58-223] s for acute medical illness, respectively; p = 0.0025; 95 percentile 424, 304, and 1725 s, respectively). Forty-one (37%) patients were comatose and had significantly longer seizures than non-comatose patients (median 99 [49-167] vs. 73 [46-123] s; p < 0.001; 95 percentile: 600 vs 444 s). CONCLUSION: To define NCSE, a temporal threshold of 10 min in critically ill patients with a primary neurological diagnosis can be applied, while a temporal threshold of 30 min might be suitable for patients with an underlying acute medical illness.

Prolonged encephalopathy and associated nonconvulsive seizures from suspected pregabalin and tapentadol: Two case reports and review of literature.

A combination of pregabalin and tapentadol may be associated with prolonged encephalopathy.

Brief potentially ictal rhythmic discharges and paroxysmal fast activity as scalp electroencephalographic biomarkers of seizure activity and seizure onset zone.

OBJECTIVE: The electroencephalographic (EEG) terms "brief potentially ictal rhythmic discharges" (BIRDs) and "paroxysmal fast activity" (PFA) are considered distinct entities; however, their definitions overlap, and they may have similar clinical significance. We investigated their clinical significance and their association with seizures and the seizure onset zone (SOZ). METHODS: We retrospectively identified an adult cohort (July 2015 to March 2018) whose long-term (>12 h) EEGs in any setting reported BIRDs (>4 Hz, lasting .5-10 s) and/or PFA. Different frequency cutoffs for PFA (>13 Hz or ≥8 Hz) were tested to compare their clinical significance. Patient demographics, clinical history, and EEG features were recorded. RESULTS: We identified 94 patients with BIRDs/PFA out of 3520 patients (3%); 36 were critically ill (12 with epilepsy), and 58 were noncritically ill (all with epilepsy). The frequency of BIRDs/PFA was largely dependent on EEG background: it tended to be slower (theta) in the absence of a posterior dominant rhythm or in the presence of continuous focal slowing in the same region (p = .01). Sixty-two of 94 patients (66%; 32/36 [89%] critically ill, 30/58 [52%] noncritically ill) had electrographic seizures during the recording. The scalp EEG SOZ colocalized with BIRDs/PFA in all cases. BIRDs with faster frequency (also qualifying as PFA by definition) had similar seizure risk to that of slower BIRDs (62%-71%), regardless of frequency cutoff used to define PFA. In addition, 30 of 30 (100%) patients with evolving BIRDs/PFA (which lasted a median of 6 s, range = 2-9.5 s) had electrographic seizures (>10 s), compared to 32 of 64 (50%) with nonevolving BIRDs (median = 1 s, range = .5-3.5 s; p < .01). SIGNIFICANCE: A high proportion of patients with BIRDs/PFA had seizures on EEG, regardless of their frequency (i.e., whether they also qualified as PFA), and their location colocalized with scalp SOZ in all cases. BIRDs appear to be a scalp EEG biomarker of uncontrolled seizure activity and a reliable localizing sign of the SOZ.

Postinfectious inflammation in cerebrospinal fluid is associated with nonconvulsive seizures in subarachnoid hemorrhage patients.

PURPOSE: It was unclear how nonconvulsive seizures (NCS) occurred after subarachnoid hemorrhage (SAH). The aim of this prospective observational study was to determine the association between cerebrospinal fluid postinfectious inflammation and NCS in patients with SAH. METHODS: Demographics and parameters were retrieved from pooled data of all SAH patients monitored by continuous electroencephalography (cEEG) in our Stroke-Intensive Care Unit (Stroke-ICU) over six years period. Patients were divided into two groups (NCS group and non-NCS group). According to clinical and cerebrospinal fluid (CSF) parameters, a logistic regression model was used to analyze the association between CSF inflammation and NCS. RESULTS: The data of 143 SAH patients were analyzed (25 patients with NCS and 118 patients with non-NCS). Median age was 53 years (min - max: 19 years - 90 years). 4.8 % SAH patients were accompanied with NCS. Among these 25 NCS patients, only 2 (8%) had complete control of EEG discharges. After confounders correction, logistic regression analysis showed: SAH patients with older age [P = 0.003, OR = 1.193, 95 %CI (1.062-1.341)], intracranial infections [P = 0.000, OR = 171.939, 95 %CI (18.136-1630.064)] and higher increased modified Fisher Scale (mFS) [P = 0.003, OR = 8.884, 95 %CI (2.125-37.148)] were more likely to develop NCS; furthermore, a high level of CSF interleukin-6 (IL-6) was an independent risk factor for NCS [P = 0.000, OR = 1.015, 95 %CI (1.010-1.020)], with a threshold of 164.9 pg/mL (sensitivity = 0.84, specificity = 0.96). Compared with non-NCS patients, NCS patients were more likely to have poor Glasgow outcome scale (GOS) (1-3) at 3 months after discharge (88 %). CONCLUSIONS: SAH patients with NCS were associated with poor neurological prognosis. With the increase of age and mFS, these patients were more likely to develop NCS. As an intracranial infective mark, a high level of CSF IL-6 was an independent risk factor for NCS. For brain protection of severe brain injury after SAH, we should focus on the increasingly important role of inflammatory response.

ICU-cEEG Monitoring.

The neurological application of long-term electroencephalography (EEG) monitoring in the intensive care unit (ICU) has been implemented in many healthcare institutions. The use of EEG as a monitoring tool in the ICU affords many potential benefits. Uses include the identification of seizures, vasospasm following subarachnoid hemorrhage (SAH), the assessment of coma and the determination of brain death. Neurologic critical care is focused on recognition and treatment of secondary insults. Often treatment is withheld because these insults are not recognized early enough until an irreversible deficit manifest. Continuous EEG (cEEG) monitoring provides a unique potential to recognize these insults and offers an opportunity for early intervention. Why should we continuously monitor the brain with EEG in the ICU? Nonconvulsive seizures (NCS) are common in comatose patients. Nonconvulsive Status Epilepticus (NCSE) and NCS 1 are damaging to brain tissue; thus, rapid control of seizures is essential to preserving brain function. With the increased use of cEEG in critical care areas, the purpose of this paper is to examine the use and benefits of EEG monitoring of ICU patients, review the indications for the use of cEEG and discuss technical issues and concerns when performing cEEG monitoring. This article has been divided into six distinct sections: (1) Seizures, NCS, and NCSE (2) Periodic Discharges 2 and Patterns on the Ictal-interictal Continuum, (3) Cerebral Ischemia, SAH, and Delayed Cerebral Ischemia (DCI), (4) Encephalopathy and Coma (5) ECI and Brain Death, and (6) ICU-cEEG Monitoring Techniques.

Validation of an algorithm of time-dependent electro-clinical risk stratification for electrographic seizures (TERSE) in critically ill patients.

OBJECTIVE: The clinical implementation of continuous electroencephalography (CEEG) monitoring in critically ill patients is hampered by the substantial burden of work that it entails for clinical neurophysiologists. Solutions that might reduce this burden, including by shortening the duration of EEG to be recorded, would help its widespread adoption. Our aim was to validate a recently described algorithm of time-dependent electro-clinical risk stratification for electrographic seizure (ESz) (TERSE) based on simple clinical and EEG features. METHODS: We retrospectively reviewed the medical records and EEG recordings of consecutive patients undergoing CEEG between October 1, 2015 and September, 30 2016 and assessed the sensitivity of TERSE for seizure detection, as well as the reduction in EEG time needed to be reviewed. RESULTS: In a cohort of 407 patients and compared to full CEEG review, the model allowed the detection of 95% of patients with ESz and 97% of those with electrographic status epilepticus. The amount of CEEG to be recorded to detect ESz was reduced by two-thirds, compared to the duration of CEEG taht was actually recorded. CONCLUSIONS: TERSE allowed accurate time-dependent ESz risk stratification with a high sensitivity for ESz detection, which could substantially reduce the amount of CEEG to be recorded and reviewed, if applied prospectively in clinical practice. SIGNIFICANCE: Time-dependent electro-clinical risk stratification, such as TERSE, could allow more efficient practice of CEEG and its more widespread adoption. Future studies should aim to improve risk stratification in the subgroup of patients with acute brain injury and absence of clinical seizures.

Seizure detection using heart rate variability: A prospective validation study.

Although several validated seizure detection algorithms are available for convulsive seizures, detection of nonconvulsive seizures remains challenging. In this phase 2 study, we have validated a predefined seizure detection algorithm based on heart rate variability (HRV) using patient-specific cutoff values. The validation data set was independent from the previously published data set. Electrocardiography (ECG) was recorded using a wearable device (ePatch) in prospectively recruited patients. The diagnostic gold standard was inferred from video-EEG monitoring. Because HRV-based seizure detection is suitable only for patients with marked ictal autonomic changes, we defined responders as the patients who had a>50 beats/min ictal change in heart rate. Eleven of the 19 included patients with seizures (57.9%) fulfilled this criterion. In this group, the algorithm detected 20 of the 23 seizures (sensitivity: 87.0%). The algorithm detected all but one of the 10 recorded convulsive seizures and all of the 8 focal impaired awareness seizures, and it missed 2 of the 4 focal aware seizures. The median sensitivity per patient was 100% (in nine patients all seizures were detected). The false alarm rate was 0.9/24 h (0.22/night). Our results suggest that HRV-based seizure detection has high performance in patients with marked autonomic changes.

Poststroke seizures as stroke mimics: Clinical assessment and management.

Epileptic seizures with postictal negative symptoms represent 20% of all suspected strokes and should be considered in the differential diagnosis of stroke in any patient presenting with an acute neurological deficit, mostly in absence of convulsions. Seizures may also occur at stroke onset, and the latter need to be promptly recognized in order to timely administer reperfusion therapies and reduce the risk of irreversible brain injury. Neuroimaging is essential in differentiating between postictal negative symptoms and deficits due to stroke. After the acute phase, poststroke seizures may worsen or cause the reappearance of neurological deficits and consciousness impairment; they can be also misinterpreted as stroke recurrence and lead to delayed treatment with antiepileptic drugs. It is mandatory to maintain a low threshold for suspecting epileptic seizures, and require appropriate electroencephalographic and neuroimaging investigations to promptly ascertain the etiology of any unexplained change in the neurological status and provide the most adequate treatment. This article is part of the Special Issue "Seizures & Stroke".

Clinical Characteristics and Nonconvulsive Seizures in Young Children With Abusive Head Trauma.

AIM: We aimed to evaluate putative predictors of symptoms and signs at admission for nonconvulsive seizure and to examine the impact of nonconvulsive seizures on short-term outcomes. METHOD: We retrospectively collected consecutive abusive head trauma patients (<36 months of age) from the trauma registry at Children's Healthcare of Atlanta between 2009 and 2014. Multiple logistic regression was performed to assess the putative predictors for the occurrence of nonconvulsive seizures including clinical seizures, altered mental status, respiratory difficulty, and cardiac arrest at admission, while controlling for age, sex, and injury severity. The Mann-Whitney U test and the Fisher exact test were used to compare the short-term outcomes between patients with and without nonconvulsive seizures. RESULTS: Two hundred seventy patients with abusive head trauma were identified (male = 55.6%). The median age was 4 months (interquartile range = 2-8 months). Among 70 patients who underwent continuous electroencephalography (EEG), 40 had nonconvulsive seizures (57%) and 21 developed nonconvulsive status epilepticus (30%). Altered mental status at admission was associated with the occurrence of nonconvulsive seizures (odds ratio = 6.8, 95% confidence interval = 1.2-38.2, P = .03). Comparing patients with no seizures, those with nonconvulsive seizures were more likely to stay longer at hospital (9 days vs 14 days, P = .04) and to need rehabilitation (50.0% vs 63.2%, P = .03). CONCLUSIONS: Nonconvulsive seizures and nonconvulsive status epilepticus was highly prevalent in young pediatric patients with abusive head trauma. Presenting with altered mental status at admission was found to predict the occurrence of nonconvulsive seizures. Nonconvulsive seizures had an unfavorable impact on short-term outcomes.

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.

Increased Expression of Epileptiform Spike/Wave Discharges One Year after Mild, Moderate, or Severe Fluid Percussion Brain Injury in Rats.

In this study, we describe increased expression of cortical epileptiform spike/wave discharges (SWD) in rats one year after mild, moderate, or severe fluid percussion traumatic brain injury (fpTBI). Groups of rats consisted of animals that had received mild, moderate, or severe fpTBI, or sham operation one year earlier than electrocorticography (ECoG) recordings. In addition, we included a group of age-matched naïve animals. ECoG was recorded from awake animals using epidural electrodes implanted on the injured hemisphere (right), sham-operated hemisphere (right), or right hemisphere in naïve animals. The SWDs were detected automatically using Fast Fourier Transformation and a novel algorithm for comparing changes in spectral power to control (nonepileptical) ECoG. The fpTBI resulted in increased expression of SWDs one year after injury compared with sham-operated or naïve animals. The number of SWD-containing ECoG epochs recorded in a 1 h recording session were: naïve 12.9 ± 10.3, n = 8, sham 23.6 ± 8.2, n = 10, mild TBI 78.9 ± 23.9, n = 10, moderate TBI 61.3 ± 32.5, n = 12, severe TBI 72.5 ± 28.3, n = 11 (mean ± standard error of the mean). Increased expression of SWDs was not related to injury severity. SWDs were observed to a lesser extent even in sham-operated and naïve animals. The data indicate that fpTBI exacerbates expression of SWDs in the rat and that this increase may be observed at least one year after injury. As others have discussed, the spontaneous occurrence of these epileptiform events in rodents limits the use of this model for investigations of acquired epilepsy, at least of the nonconvulsive type, after TBI.

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".

Difficulty of Early Diagnosis and Requirement of Long-Term Follow-Up in Benign Infantile Seizures.

PURPOSE: We investigated whether benign infantile seizures can be diagnosed in the acute phase. METHODS: We retrospectively analyzed the medical records of 44 patients initially diagnosed with acute phase benign infantile seizures. All patients were followed for more than 12 months, and we reviewed patients' psychomotor development and presence or absence of seizure recurrence at the last visit. Patients were divided into the following three groups according to the final diagnosis: benign infantile seizures, benign infantile seizures associated with mild gastroenteritis, and non-benign infantile seizures. We defined benign infantile seizures associated with mild gastroenteritis and benign infantile seizures as those associated with normal psychomotor development and no seizure recurrence 3 months after onset of the first seizure, whereas non-benign infantile seizures were associated with delayed psychomotor development and/or seizure recurrence after 3 months of onset of the first seizure. We analyzed the clinical features in the acute phase and compared them between the groups. RESULTS: The median age of seizure onset was 7.6 months. A final diagnosis of benign infantile seizures associated with mild gastroenteritis was made in three patients. In the remaining 41 patients, the final diagnosis was benign infantile seizures in 30 (73.2%) and non-benign infantile seizures in 11 (26.8%). In the non-benign infantile seizure group, intellectual disability was diagnosed in eight patients and seizure recurrence in six. There were no significant differences in clinical features between the groups in the acute phase, such as seizure type or seizure duration. CONCLUSION: About 30% of patients initially diagnosed as having benign infantile seizures did not experience a benign clinical course. Our findings suggest that clinical features in the acute phase are not helpful for predicting benign outcomes in benign infantile seizures and that only long-term follow-up can discriminate benign infantile seizures from non-benign infantile seizures.

Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG with early epileptiform discharges.

BACKGROUND: Continuous EEG (cEEG) is necessary to document nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIU) including periodic discharges, rhythmic delta activity, and spike-and-wave complexes in neurological intensive care patients. However, cEEG is associated with significant recording and analysis efforts. Therefore, predictors from short-term routine EEG with a reasonably high yield are urgently needed in order to select patients for evaluation with cEEG. OBJECTIVE: The aim of this study was to assess the prognostic significance of early epileptiform discharges (i.e., within the first 30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during the ICU stay, and (3) functional outcome after 6 months of follow-up. METHODS: We conducted a separate analysis of the first 30 min and the remaining segments of prospective cEEG recordings according to the ACNS Standardized Critical Care EEG Terminology as well as NCS criteria and review of clinical data of 32 neurological critical care patients. RESULTS: In 17 patients with epileptiform discharges within the first 30 min of EEG (group 1), electrographic seizures were observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of 'ictal-interictal uncertainty' in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in 11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG, RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly different between the two groups (p = 0.008). Patients with early epileptiform discharges developed acute seizures more frequently than patients without early epileptiform discharges (p = 0.009). Finally, functional outcome six months after discharge was significantly worse in patients with early epileptiform discharges (p=0.01). CONCLUSIONS: Epileptiform discharges within the first 30 min of EEG recording are predictive for the occurrence of ictal EEG patterns and for RPPIIU on subsequent cEEG, for acute convulsive seizures during the ICU stay, and for a worse functional outcome after 6 months of follow-up. This article is part of a Special Issue entitled Status Epilepticus.

Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury.

Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C-10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. Neuroinflammation was evaluated by immunohistochemical markers, for example, glial fibrillary acidic protein and major histocompatibility complex class I, for activation of astrocytes and microglia, respectively. Neurofunction was tested using rotarod and Morris water maze tasks. Three infusion doses of C-10068 (1.0, 2.5, and 5.0 mg/kg/h × 72 h) were tested in the antiseizure study. Neuroinflammation and neurofunction were evaluated in animals treated with 5.0 mg/kg/h × 72 h C-10068. Compared to vehicle treatment, C-10068 dose dependently reduced PBBI-induced NCS incidence (40-50%), frequency (20-70%), and duration (30-82%). The most effective antiseizure dose of C-10068 (5.0 mg/kg/h × 72 h) also significantly attenuated hippocampal astrocyte activation and perilesional microglial reactivity post-PBBI. Within C-10068-treated animals, a positive correlation was observed in reduction in NCS frequency and reduction in hippocampal astrocyte activation. Further, C-10068 treatment significantly attenuated astrocyte activation in seizure-free animals. However, C-10068 failed to improve PBBI-induced motor and cognitive functions with the dosing regimen used in this study. Overall, the results indicating that C-10068 exerts both potent antiseizure and antiinflammatory effects are promising and warrant further investigation.

Nonconvulsive seizures and status epilepticus in pediatric head trauma: A national survey.

OBJECTIVES: It remains uncertain whether nonconvulsive seizures and nonconvulsive status epilepticus in pediatric traumatic brain injury are deleterious to the brain and/or impact the recovery from injury. Consequently, optimal electroencephalographic surveillance and management is unknown. We aimed to determine specialists' opinion regarding the detection and treatment of nonconvulsive seizures or nonconvulsive status epilepticus in pediatric traumatic brain injury, regardless of their practice. METHODS: In 2012, 183 surveys were sent to all 93 neurologists, 27 neurosurgeons, and 63 intensivists in the14 tertiary pediatric hospitals across Canada. The survey included an initial scenario of pediatric TBI that evolved into three further scenarios. Each scenario had required responses and an embedded branching logic algorithm ascertaining clinical management. The survey instrument assimilated data about the importance of nonconvulsive status epilepticus and nonconvulsive seizures detection and treatment, and whether they are a cause of brain injury that adversely affects neurologic outcomes. RESULTS: Of the 79 specialists who replied (43% response rate), 68%-78% elected to order an electroencephalographic across all four scenarios, and one-third (31%-36%; scenario dependent) would request an urgent electroencephalographic (within the hour) in the comatose pediatric traumatic brain injury patient. In the absence of pharmacologic paralysis or intracranial pressure spikes, half-hour electroencephalographic (41%-55%) was preferred over ⩾24-h continuous electroencephalographic monitoring (29%-40%). Finally, nonconvulsive status epilepticus (81%-87%) and nonconvulsive seizures (61%-73%) were considered to be a cause of poor neurologic outcomes warranting aggressive pharmacologic management. CONCLUSION: The Canadian specialists' opinion is that nonconvulsive seizures and nonconvulsive status epilepticus are biomarkers of brain injury and contribute to worsened outcomes. This suggests the urgency of future outcome-oriented research in the identification and management of nonconvulsive seizures or nonconvulsive status epilepticus.