Lawrence J. Hirsch

Detection of electrographic seizures with continuous EEG monitoring in critically ill patients

Objective: To identify patients most likely to have seizures documented on continuous EEG (cEEG) monitoring and patients who require more prolonged cEEG to record the first seizure. Methods: Five hundred seventy consecutive patients who underwent cEEG monitoring over a 6.5-year period were reviewed for the detection of subclinical seizures or evaluation of unexplained decrease in level of consciousness. Baseline demographic, clinical, and EEG findings were recorded and a multivariate logistic regression analysis performed to identify factors associated with 1) any EEG seizure activity and 2) first seizure detected after >24 hours of monitoring. Results: Seizures were detected in 19% (n = 110) of patients who underwent cEEG monitoring; the seizures were exclusively nonconvulsive in 92% (n = 101) of these patients. Among patients with seizures, 89% (n = 98) were in intensive care units at the time of monitoring. Electrographic seizures were associated with coma (odds ratio [OR] 7.7, 95% CI 4.2 to 14.2), age <18 years (OR 6.7, 95% CI 2.8 to 16.2), a history of epilepsy (OR 2.7, 95% CI 1.3 to 5.5), and convulsive seizures during the current illness prior to monitoring (OR 2.4, 95% CI 1.4 to 4.3). Seizures were detected within the first 24 hours of cEEG monitoring in 88% of all patients who would eventually have seizures detected by cEEG. In another 5% (n = 6), the first seizure was recorded on monitoring day 2, and in 7% (n = 8), the first seizure was detected after 48 hours of monitoring. Comatose patients were more likely to have their first seizure recorded after >24 hours of monitoring (20% vs 5% of noncomatose patients; OR 4.5, p = 0.018). Conclusions: CEEG monitoring detected seizure activity in 19% of patients, and the seizures were almost always nonconvulsive. Coma, age <18 years, a history of epilepsy, and convulsive seizures prior to monitoring were risk factors for electrographic seizures. Comatose patients frequently required >24 hours of monitoring to detect the first electrographic seizure.

Treatment of Refractory Status Epilepticus with Pentobarbital, Propofol, or Midazolam: A Systematic Review

Summary:  Background: New continuous infusion antiepileptic drugs (cIV‐AEDs) offer alternatives to pentobarbital for the treatment of refractory status epilepticus (RSE). However, no prospective randomized studies have evaluated the treatment of RSE. This systematic review compares the efficacy of midazolam (MDL), propofol (PRO), and pentobarbital (PTB) for terminating seizures and improving outcome in RSE patients.

American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2012 version.

Continuous EEG Monitoring is becoming a commonly used tool in assessing brain function in critically ill patients. However, there is no uniformly accepted nomenclature for EEG patterns frequently encountered in these patients such as periodic discharges, fluctuating rhythmic patterns, and combinatio

Which EEG patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns

Continuous electroencephalographic monitoring in critically ill patients has improved detection of nonconvulsive seizures and periodic discharges, but when and how aggressively to treat these electrographic patterns is unclear. A review of the literature was conducted to understand the nature of periodic discharges and the strength of the data on which management recommendations have been based. Periodic discharges are seen from a wide variety of etiologies, and the discharges themselves are electrographically heterogeneous. This spectrum suggests a need to consider these phenomena along a continuum between interictal and ictal, but more important clinically is the need to consider the likelihood of neuronal injury from each type of discharge in a given clinical setting. Recommendations for treatment are given, and a modification to current criteria for the diagnosis of nonconvulsive seizures is suggested.

ELECTROGRAPHIC SEIZURES AND PERIODIC DISCHARGES AFTER INTRACEREBRAL HEMORRHAGE

Objective: To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH). Methods: We reviewed 102 consecutive patients with ICH who underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge. Results: Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%. Conclusions: Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH. GLOSSARY: BIPLEDs = bilateral independent PLEDs; cEEG = continuous EEG monitoring; CLUES = clinically unrecognized electrographic seizures; EVD = external ventricular drain; IRDA = frontal intermittent rhythmic delta activity; GCS = Glasgow Coma Score; GOS = Glasgow Outcome Scale; GPDs = generalized periodic discharges; ICH = intracerebral hemorrhage; ICP = intracranial pressure; ICU = intensive care unit; IVH = intraventricular hemorrhage; NICU = neuroICU; PEDs = periodic epileptiform discharges; PLEDs = periodic lateralized epileptiform discharges; SAH = subarachnoid hemorrhage; SDH = subdural hematomas; SE = status epilepticus; SIRPIDS = stimulus-induced rhythmic, periodic, or ictal discharges.

Extreme delta brush A unique EEG pattern in adults with anti-NMDA receptor encephalitis

Objectives: To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder. Methods: We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers. Results: Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1−123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2−200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named “extreme delta brush” because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089). Conclusions: Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.

Continuous electroencephalography in the medical intensive care unit.

Objectives:To examine predictors and the prognostic value of electrographic seizures (ESZs) and periodic epileptiform discharges (PEDs) in medical intensive care unit (MICU) patients without a primary acute neurologic condition. Design:Retrospective study. Setting:MICU in a university hospital. Patients:A total of 201 consecutive patients admitted to the MICU between July 2004 and January 2007 without known acute neurologic injury and who underwent continuous electroencephalography monitoring (cEEG) for investigation of possible seizures or changes in mental status. Intervention:None. Measurements and Main Results:Median time from intensive care unit (ICU) admission to cEEG was 1 day (interquartile range 1–4). The majority of patients (60%) had sepsis as the primary admission diagnosis and 48% were comatose at the time of cEEG. Ten percent (n = 21) of patients had ESZs, 17% (n = 34) had PEDs, 5% (n = 10) had both, and 22% (n = 45) had either ESZs or PEDs. Seizures during cEEG were purely electrographic (no detectable clinical correlate) in the majority (67%) of patients. Patients with sepsis had a higher rate of ESZs or PEDs than those without sepsis (32% vs. 9%, p < 0.001). On multivariable analysis, sepsis at ICU admission was the only significant predictor of ESZs or PEDs (odds ratio 4.6, 95% confidence interval 1.9–12.7, p = 0.002). After controlling for age, coma, and organ dysfunction, the presence of ESZs or PEDs was associated with death or severe disability at hospital discharge (89% with ESZs or PEDs, vs. 39% if not; odds ratio 19.1, 95% confidence interval 6.3–74.6, p < 0.001). Conclusion:In this retrospective study of MICU patients monitored with cEEG, ESZs and PEDs were frequent, predominantly in patients with sepsis. Seizures were mainly nonconvulsive. Both seizures and periodic discharges were associated with poor outcome. Prospective studies are warranted to determine more precisely the frequency and clinical impact of nonconvulsive seizures and periodic discharges, particularly in septic patients.

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.

Comparison and predictors of rash associated with 15 antiepileptic drugs

Objective: To determine predictors and relative incidence of antiepileptic drug (AED)–related rash in patients taking all common AEDs. Methods: We reviewed 1,890 outpatients. Eighty-one variables were tested as potential predictors of rash. We compared the rate of rash attributed to each AED (AED rash) with the average rate of rash attributed to the other AEDs in all adults (aged ≥16 years; n = 1,649) when taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproate (VPA), or zonisamide (ZNS). We repeated this analysis for patients with and without the identified nondrug predictors of AED rash. Results: The average rate of AED rash was 2.8%. The only nondrug predictor significant in multivariate analysis was occurrence of another AED rash (odds ratio 3.1, 95% CI 1.8 to 5.1; p < 0.0001); the rate of rash in this subgroup was 8.8%, vs 1.7% in those without another AED rash. Higher AED rash rates were seen with PHT (5.9% overall, p = 0.0008; 25.0% in those with another AED rash, p = 0.001), LTG (4.8%, p = 0.00095; 14.4%, p = 0.025), and CBZ (3.7%, not significant; 16.5%, p = 0.01). Lower rates were seen with LEV (0.6% overall; p = 0.00042), GBP (0.3%, p = 0.00035), and VPA (0.7%, p = 0.01). Rash rates were also low (<1% overall) with FBM, PRM, TPM, and VGB (not significant). These AED differences remained similar in patients with and without other AED rashes. There were four cases of Stevens–Johnson syndrome involving four AEDs. Conclusions: The rate of an antiepileptic drug (AED) rash is approximately five times greater in patients with another AED rash (8.8%) vs those without (1.7%). Rash rates were highest with phenytoin, lamotrigine, and carbamazepine and low (<1%) with several AEDs.

Continuous Electroencephalogram Monitoring in the Intensive Care Unit

Because of recent technical advances, it is now possible to record and monitor the continuous digital electroencephalogram (EEG) of many critically ill patients simultaneously. Continuous EEG monitoring (cEEG) provides dynamic information about brain function that permits early detection of changes in neurologic status, which is especially useful when the clinical examination is limited. Nonconvulsive seizures are common in comatose critically ill patients and can have multiple negative effects on the injured brain. The majority of seizures in these patients cannot be detected without cEEG. cEEG monitoring is most commonly used to detect and guide treatment of nonconvulsive seizures, including after convulsive status epilepticus. In addition, cEEG is used to guide management of pharmacological coma for treatment of increased intracranial pressure. An emerging application for cEEG is to detect new or worsening brain ischemia in patients at high risk, especially those with subarachnoid hemorrhage. Improving quantitative EEG software is helping to make it feasible for cEEG (using full scalp coverage) to provide continuous information about changes in brain function in real time at the bedside and to alert clinicians to any acute brain event, including seizures, ischemia, increasing intracranial pressure, hemorrhage, and even systemic abnormalities affecting the brain, such as hypoxia, hypotension, acidosis, and others. Monitoring using only a few electrodes or using full scalp coverage, but without expert review of the raw EEG, must be done with extreme caution as false positives and false negatives are common. Intracranial EEG recording is being performed in a few centers to better detect seizures, ischemia, and peri-injury depolarizations, all of which may contribute to secondary injury. When cEEG is combined with individualized, physiologically driven decision making via multimodality brain monitoring, intensivists can identify when the brain is at risk for injury or when neuronal injury is already occurring and intervene before there is permanent damage. The exact role and cost-effectiveness of cEEG at the current time remains unclear, but we believe it has significant potential to improve neurologic outcomes in a variety of settings.