Vincent Alvarez

New-onset refractory status epilepticus Etiology, clinical features, and outcome

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in comatose survivors of cardiac arrest: Characteristics and prognostic value

OBJECTIVES To analyze the prevalence of stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) in patients with coma after cardiac arrest (CA) and therapeutic hypothermia (TH) and to examine their potential association with outcome. METHODS We studied our prospective cohort of adult survivors of CA treated with TH, assessing SIRPIDs occurrence and their association with 3-month outcome. Only univariated analyses were performed. RESULTS 105 patients with coma after CA who underwent electroencephalogram (EEG) during TH and normothermia (NT) were studied. Fifty-nine patients (56%) survived, and 48 (46%) had good neurological recovery. The prevalence of SIRPIDs was 13.3% (14/105 patients), of whom 6 occurred during TH (all died), and 8 in NT (3 survived, 1 with good neurological outcome); none had SIRPIDs at both time-points. SIRPIDs were associated with discontinuous or non-reactive EEG background and were a robustly related to poor neurological outcome (p < 0.001). CONCLUSION This small series provides preliminary univariate evidence that in patients with coma after CA, SIRPIDs are associated with poor outcome, particularly when occurring during in therapeutic hypothermia. However, survival with good neurological recovery may be observed when SIRPIDs arise in the post-rewarming normothermic phase. SIGNIFICANCE This study provides clinicians with new information regarding the SIRPIDs prognostic role in patients with coma after cardiac arrest.

Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison.

Benzodiazepines (BZD) are recommended as first‐line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date.

Therapeutic coma for status epilepticus: Differing practices in a prospective multicenter study

Objective: Our aim was to analyze and compare the use of therapeutic coma (TC) for refractory status epilepticus (SE) across different centers and its effect on outcome. Methods: Clinical data for all consecutive adults (>16 years) with SE of all etiologies (except postanoxic) admitted to 4 tertiary care centers belonging to Harvard Affiliated Hospitals (HAH) and the Centre Hospitalier Universitaire Vaudois (CHUV) were prospectively collected and analyzed for TC details, mortality, and duration of hospitalization. Results: Two hundred thirty-six SE episodes in the CHUV and 126 in the HAH were identified. Both groups were homogeneous in demographics, comorbidities, SE characteristics, and Status Epilepticus Severity Score (STESS); TC was used in 25.4% of cases in HAH vs 9.75% in CHUV. After adjustment, TC use was associated with younger age, lower Charlson Comorbidity Index, increasing SE severity, refractory SE, and center (odds ratio 11.3 for HAH vs CHUV, 95% confidence interval 2.47–51.7). Mortality was associated with increasing Charlson Comorbidity Index and STESS, etiology, and refractory SE. Length of stay correlated with STESS, etiology, refractory SE, and use of TC (incidence rate ratio 1.6, 95% confidence interval 1.22–2.11). Conclusions: Use of TC for SE treatment seems markedly different between centers from the United States and Europe, and did not affect mortality considering the whole cohort. However, TC may increase length of hospital stay and related costs. Classification of evidence: This study provides Class III evidence that for patients with SE, TC does not significantly affect mortality. The study lacked the precision to exclude an important effect of TC on mortality.

Characteristics and role in outcome prediction of continuous EEG after status epilepticus: A prospective observational cohort

Continuous electroencephalography (cEEG) is important for treatment guidance in status epilepticus (SE) management, but its role in clinical outcome prediction is unclear. Our aim is to determine which cEEG features give independent outcome information after correction for clinical predictor.

Evaluation of a clinical tool for early etiology identification in status epilepticus

Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment.

Clinical Use of EEG in the ICU: Technical Setting.

Summary: Neurophysiology is an essential tool for clinicians dealing with patients in the intensive care unit. Because of consciousness disorders, clinical examination is frequently limited. In this setting, neurophysiological examination provides valuable information about seizure detection, treatment guidance, and neurological outcome. However, to acquire reliable signals, some technical precautions need to be known. EEG is prone to artifacts, and the intensive care unit environment is rich in artifact sources (electrical devices including mechanical ventilation, dialysis, and sedative medications, and frequent noise, etc.). This review will discuss and summarize the current technical guidelines for EEG acquisition and also some practical pitfalls specific for the intensive care unit.

Is Favorable Outcome Possible After Prolonged Refractory Status Epilepticus

Summary: When status epilepticus (SE) remains refractory to appropriate therapy, it is associated with high mortality and with substantial morbidity in survivors. Many outcome predictors such as age, seizure type, level of consciousness before treatment, and mostly, etiology, are well-established. A longer duration of SE is often associated with worse outcome, but duration may lose its prognostic value after several hours. Several terms and definitions have been used to describe prolonged, refractory SE, including “malignant SE,” “prolonged” SE, and more recently, “super refractory” SE, defined as “SE that has continued or recurred despite 24 hours of general anesthesia (or coma-inducing anticonvulsants).” There are few data available regarding the outcome of prolonged refractory SE, and even fewer for SE remaining refractory to anesthetic drugs. This article reviews reports of outcome after prolonged, refractory, and “super refractory” SE. Most information detailing the clinical outcome of patients surviving these severe illnesses, in which seizures can persist for days or weeks (and especially those concerning “super-refractory” SE) come from case reports and retrospective cohort studies. In many series, prolonged, refractory SE has a mortality of 30% to 50%, and several studies indicate that most survivors have a substantial decline in functional status. Nevertheless, several reports demonstrate that good functional outcome is possible even after several days of SE and coma induction. Treatment of refractory SE should not be withdrawn from younger patients without structural brain damage at presentation solely because of the duration of SE.

Effect of stimulus type and temperature on EEG reactivity in cardiac arrest

OBJECTIVE Electroencephalogram (EEG) background reactivity is a reliable outcome predictor in cardiac arrest patients post therapeutic hypothermia. However, there is no consensus on modality testing and prior studies reveal only fair to moderate agreement rates. The aim of this study was to explore different stimulus modalities and report interrater agreements. METHODS We studied a multicenter, prospectively collected cohort of cardiac arrest patients who underwent therapeutic hypothermia between September 2014 and December 2015. We identified patients with reactivity data and evaluated interrater agreements of different stimulus modalities tested in hypothermia and normothermia. RESULTS Of the 60 patients studied, agreement rates were moderate to substantial during hypothermia and fair to moderate during normothermia. Bilateral nipple pressure is more sensitive (80%) when compared to other modalities in eliciting a reactive background in hypothermia. Auditory, nasal tickle, nailbed pressure and nipple pressure reactivity were associated with good outcomes in both hypothermia and normothermia. CONCLUSIONS EEG reactivity varies depending on the stimulus testing modality as well as the temperature during which stimulation is performed, with nipple pressure emerging as the most sensitive during hypothermia for reactivity and outcome determination. SIGNIFICANCE This highlights the importance of multiple stimulus testing modalities in EEG reactivity determination to reduce false negatives and optimize prognostication.

The use and yield of continuous EEG in critically ill patients: A comparative study of three centers

OBJECTIVE Continuous EEG (cEEG) monitoring of critically ill patients has gained widespread use, but there is substantial reported variability in its use. We analyzed cEEG and antiseizure drug (ASD) usage at three high volume centers. METHODS We utilized a multicenter cEEG database used daily as a clinical reporting tool in three tertiary care sites (Emory Hospital, Brigham and Womens Hospital and Yale - New Haven Hospital). We compared the cEEG usage patterns, seizure frequency, detection of rhythmic/periodic patterns (RPP), and ASD use between the sites. RESULTS 5792 cEEG sessions were analyzed. Indication for cEEG monitoring and recording duration were similar between the sites. Seizures detection rate was nearly identical between the three sites, ranging between 12.3% and 13.6%. Median time to first seizure and detection rate of RPPs were similar. There were significant differences in doses of levetiracetam, valproic acid, and lacosamide used between the three sites. CONCLUSIONS There was remarkable uniformity in seizure detection rates within three high volume centers. In contrast, dose of ASD used frequently differed between the three sites. SIGNIFICANCE These large volume data are in line with recent guidelines regarding cEEG use. Difference in ASD use suggests discrepancies in how cEEG results influence patient management.