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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Acute brain failure in severe sepsis: a prospective study in the medical intensive care unit utilizing continuous EEG monitoring

Purpose: Investigate the prevalence, risk factors and impact of continuous EEG (cEEG) abnormalities on mortality through the 1-year follow-up period in patients with severe sepsis. Methods: Prospective, single-center, observational study of consecutive patients admitted with severe sepsis to the Medical ICU at an academic medical center. Results: A total of 98 patients with 100 episodes of severe sepsis were included; 49 patients (50%) were female, median age was 60 (IQR 52–74), the median non-neuro APACHE II score was 23.5 (IQR 18–28) and median non-neuro SOFA score was 8 (IQR 6–11). Twenty-five episodes had periodic discharges (PD), of which 11 had nonconvulsive seizures (NCS). No patient had NCS without PD. Prior neurological history was associated with a higher risk of PD or NCS (45 vs. 17%; CI 1.53–10.43), while the non-neuro APACHE II, non-neuro SOFA, severity of cardiovascular shock and presence of sedation during cEEG were associated with a lower risk of PD or NCS. Clinical seizures before cEEG were associated with a higher risk of nonconvulsive status epilepticus (24 vs. 6%; CI 1.42–19.94) while the non-neuro APACHE II and non-neuro SOFA scores were associated with a lower risk. Lack of EEG reactivity was present in 28% of episodes. In the survival analysis, a lack of EEG reactivity was associated with higher 1-year mortality [mean survival time 3.3 (95% CI 1.8–4.9) vs. 7.5 (6.4–8.7) months; p = 0.002] but the presence of PD or NCS was not [mean survival time 3.3 (95% CI 1.8–4.9) vs. 7.5 (6.4–8.7) months; p = 0.592]. Lack of reactivity was more frequent in patients on continuous sedation during cEEG. In patients with available 1-year data (34% of the episodes), 82% had good functional outcome (mRS ≤ 3, n = 27). There were no significant predictors of functional outcome, late cognition, and no patient with complete follow-up data developed late seizure or new epilepsy. Conclusions: NCS and PD are common in patients with severe sepsis and altered mental status. They were less frequent among the most severely sick patients and were not associated with outcome in this study. Lack of EEG reactivity was more frequent in patients on continuous sedation and was associated with mortality up to 1 year after discharge. Larger studies are needed to confirm these findings in a broader population and to further evaluate long-term cognitive outcome, risk of late seizure and epilepsy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Interrater agreement for consensus definitions of delayed ischemic events after aneurysmal subarachnoid hemorrhage

Background: Thirty percent of patients with subarachnoid hemorrhage experience delayed cerebral ischemia or delayed ischemic neurologic decline (DIND). Variability in the definitions of delayed ischemia makes outcome studies difficult to compare. A recent consensus statement advocates standardized definitions for delayed ischemia in clinical trials of subarachnoid hemorrhage. We sought to evaluate the interrater agreement of these definitions. Methods: Based on consensus definitions, we assessed for: (1) delayed cerebral infarction, defined as radiographic cerebral infarction; (2) DIND type 1 (DIND1), defined as focal neurologic decline; and (3) DIND2, defined as a global decline in arousal. Five neurologists retrospectively reviewed electronic records of 58 patients with subarachnoid hemorrhage. Three reviewers had access to and reviewed neuroradiology imaging. We assessed interrater agreement using the Gwet kappa statistic. Results: Interrater agreement statistics were excellent (95.83%) for overall agreement on the presence or absence of any delayed ischemic event (DIND1, DIND2, or delayed cerebral infarction). Agreement was "moderate" for specifically identifying DIND1 (56.58%) and DIND2 (48.66%) events. We observed greater agreement for DIND1 when there was a significant focal motor decline of at least 1 point in the motor score. There was fair agreement (39.20%) for identifying delayed cerebral infarction; CT imaging was the predominant modality. Conclusions: Consensus definitions for delayed cerebral ischemia yielded near-perfect overall agreement and can thus be applied in future large-scale studies. However, a strict process of adjudication, explicit thresholds for determining focal neurologic decline, and MRI techniques that better discriminate edema from infarction seem critical for reproducibility of determination of specific outcome phenotypes, and will be important for successful clinical trials.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Cyclic seizures in critically ill patients: Clinical correlates, DC recordings and outcomes

Objective To describe EEG and clinical correlates, DC recordings and prognostic significance of cyclic seizures (CS). Methods We reviewed our prospective continuous EEG database to identify patients with CS, controls with non-cyclic status epilepticus (SE) and controls without seizure matched for age and etiology. EEG was reviewed with DC settings. Results 39/260 (15%) patients with electrographic seizures presented with CS. These patients were older (62 vs. 54 years; p = 0.04) and more often had acute or progressive brain injury (77% vs. 52%; p = 0.03) than patients with non-cyclic SE and had a lower level of consciousness, were more severely ill, than matched controls. CS almost always had focal onset, often from posterior regions. Patients with CS trended towards worse prognosis. When available (12 patients), DC recordings showed an infraslow cyclic oscillation of EEG baseline synchronized to the seizures in all cases. Conclusions CS occur mostly in older patients with acute or progressive brain injury, are more likely to be associated with poor outcome than patients with other forms of nonconvulsive SE, and are accompanied by synchronous oscillations of the EEG baseline on DC recordings. Significance CS are a common form of non-convulsive status epilepticus in critically ill patients and provide further insights into the relationship between infraslow activity and seizures; further study on this relationship may shed light on the mechanisms of seizure initiation and termination.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Electro-clinical characteristics and prognostic significance of post anoxic myoclonus

Objective: To systematically examine the electro-clinical characteristics of post anoxic myoclonus (PAM) and their prognostic implications in comatose cardiac arrest (CA) survivors. Methods: Fifty-nine CA survivors who developed myoclonus within 72 h of arrest and underwent continuous EEG monitoring were included in the study. Retrospective chart review was performed for all relevant clinical variables including time of PAM onset (“early onset” when within 24 h) and semiology (multi-focal, facial/ocular, whole body and limbs only). EEG findings including background, reactivity, epileptiform patterns and EEG correlate to myoclonus were reviewed at 6, 12, 24, 48 and 72 h after the return of spontaneous circulation (ROSC). Outcome was categorized as either with recovery of consciousness (Cerebral Performance Category (CPC) 1–3) or without recovery of consciousness (CPC 4–5) at the time of discharge. Results: Seven of the 59 patients (11.9%) regained consciousness, including 6/51 (11.8%) with early onset PAM. Patients with recovery of consciousness had shorter time to ROSC, and were more likely to have preserved brainstem reflexes and normal voltage background at all times. No patient with suppression burst or low voltage background (N = 52) at any point regained consciousness. In the subset where precise electro-clinical correlation was possible, all (5/5) those with recovery of consciousness had multi-focal myoclonus and most (4/5) had midline-maximal spikes over a continuous background. No patient with any other semiology (N = 21) regained consciousness. Conclusions: Early onset PAM is not always associated with lack of recovery of consciousness. EEG can help discriminate between patients who may or may not regain consciousness by the time of hospital discharge.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study

Purpose: Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury. Methods: This is a case-control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy. Results: Lateralized periodic discharges were found in 145/1785 (8.1%) of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive brain injury. Those with LPDs were more likely to have abnormal consciousness (86% vs. 57%; P 0.005), seizures (70% vs. 24%; P 0.0002), and functional decline (62% vs. 27%; P 0.005), and were less likely to be discharged home (24% vs. 62%; P 0.002). On multivariate analysis, LPDs and status epilepticus were associated with abnormal consciousness (P 0.009; odds ratio 5.2, 95% CI 1.60-20.00 and P 0.017; odds ratio 5.0, 95% CI 1.4-21.4); and LPDs were independently associated with functional decline (P 0.001; odds ratio 4.8, 95% CI 1.6-15.4) and lower likelihood of being discharged home (P 0.009; odds ratio 0.2, 95% CI 0.04-0.6). Conclusions: Despite absence of acute or progressive brain injury, LPDs were independently associated with abnormal consciousness and worse outcome at hospital discharge.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prognostication of post-cardiac arrest coma: early clinical and electroencephalographic predictors of outcome

Purpose: To determine the temporal evolution, clinical correlates, and prognostic significance of electroencephalographic (EEG) patterns in post-cardiac arrest comatose patients treated with hypothermia. Methods: Prospective cohort study of consecutive post-anoxic patients receiving hypothermia and continuous EEG monitoring between May 2011 and June 2014 (n = 100). In addition to clinical variables, 5-min EEG clips at 6, 12, 24, 48, and 72 h after return of spontaneous circulation (ROSC) were reviewed. EEG background was classified according to the American Clinical Neurophysiological Society critical care EEG terminology. Clinical outcome at discharge was dichotomized as good [Glasgow outcome scale (GOS) 4–5, low to moderate disability] vs. poor (GOS 1–3, severe disability to death). Results: Non-ventricular fibrillation/tachycardia arrest, longer time to ROSC, absence of brainstem reflexes, extensor or no motor response, lower pH, higher lactate, hypotension requiring >2 vasopressors, and absence of reactivity on EEG were all associated with poor outcome (all p values ≤0.01). Suppression-burst at any time indicated a poor prognosis, with a 0 % false positive rate (FPR) [95 % confidence interval (CI) 0–10 %]. All patients (54/54) with suppression-burst or a low voltage (70 % for good outcome. Conclusions: Suppression-burst or a low voltage at 24 h after ROSC was not compatible with good outcome in this series. Normal background voltage without epileptiform discharges predicted a good outcome.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

EEG Reactivity Evaluation Practices for Adult and Pediatric Hypoxic-Ischemic Coma Prognostication in North America

PURPOSE: The aim of this study was to assess the variability in EEG reactivity evaluation practices during cardiac arrest prognostication. METHODS: A survey of institutional representatives from North American academic hospitals participating in the Critical Care EEG Monitoring Research Consortium was conducted to assess practice patterns involving EEG reactivity evaluation. This 10-question multiple-choice survey evaluated metrics related to technical, interpretation, personnel, and procedural aspects of bedside EEG reactivity testing and interpretation specific to cardiac arrest prognostication. One response per hospital was obtained. RESULTS: Responses were received from 25 hospitals, including 7 pediatric hospitals. A standardized EEG reactivity protocol was available in 44% of centers. Sixty percent of respondents believed that reactivity interpretation was subjective. Reactivity bedside testing always (100%) started during hypothermia and was performed daily during monitoring in the majority (71%) of hospitals. Stimulation was performed primarily by neurodiagnostic technologists (76%). The mean number of activation procedures modalities tested was 4.5 (SD 2.1). The most commonly used activation procedures were auditory (83.3%), nail bed pressure (63%), and light tactile stimuli (63%). Changes in EEG amplitude alone were not considered consistent with EEG reactivity in 21% of centers. CONCLUSIONS: There is substantial variability in EEG reactivity evaluation practices during cardiac arrest prognostication among North American academic hospitals. Efforts are needed to standardize protocols and nomenclature according with national guidelines and promote best practices in EEG reactivity evaluation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Comparison of machine learning models for seizure prediction in hospitalized patients

Objective: To compare machine learning methods for predicting inpatient seizures risk and determine the feasibility of 1-h screening EEG to identify low-risk patients (<5% seizures risk in 48 h). Methods: The Critical Care EEG Monitoring Research Consortium (CCEMRC) multicenter database contains 7716 continuous EEGs (cEEG). Neural networks (NN), elastic net logistic regression (EN), and sparse linear integer model (RiskSLIM) were trained to predict seizures. RiskSLIM was used previously to generate 2HELPS2B model of seizure predictions. Data were divided into training (60% for model fitting) and evaluation (40% for model evaluation) cohorts. Performance was measured using area under the receiver operating curve (AUC), mean risk calibration (CAL), and negative predictive value (NPV). A secondary analysis was performed using Monte Carlo simulation (MCS) to normalize all EEG recordings to 48 h and use only the first hour of EEG as a “screening EEG” to generate predictions. Results: RiskSLIM recreated the 2HELPS2B model. All models had comparable AUC: evaluation cohort (NN: 0.85, EN: 0.84, 2HELPS2B: 0.83) and MCS (NN: 0.82, EN; 0.82, 2HELPS2B: 0.81) and NPV (absence of seizures in the group that the models predicted to be low risk): evaluation cohort (NN: 97%, EN: 97%, 2HELPS2B: 97%) and MCS (NN: 97%, EN: 99%, 2HELPS2B: 97%). 2HELPS2B model was able to identify the largest proportion of low-risk patients. Interpretation: For seizure risk stratification of hospitalized patients, the RiskSLIM generated 2HELPS2B model compares favorably to the complex NN and EN generated models. 2HELPS2B is able to accurately and quickly identify low-risk patients with only a 1-h screening EEG.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients

IMPORTANCE Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear. OBJECTIVE To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures. DESIGN, SETTING, AND PARTICIPANTS We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures. INTERVENTIONS Continuous electroencephalography. MAIN OUTCOMES AND MEASURES Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures. RESULTS Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P .10). CONCLUSIONS AND RELEVANCE In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.SCOPUS: ar.jinfo:eu-repo/semantics/publishe