Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel / Acute monoarthritis in a third level hospital

Resumen Introducción: La monoartritis aguda (MA) represen ta una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sino vial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bur sitis agudas que ocurrieron en pacientes de ≥18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secun daria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sino vial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

Abstract Introduction: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes re levant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. Methods: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. Results: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). Discussion: The main cause of AM was septic arthri tis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key ele ment when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

[Acute monoarthritis in a third level hospital]. / Estudio de los pacientes con monoartritis aguda en un hospital de tercer nivel.

INTRODUCTION: Acute monoarthritis (AM) represents a relevant cause of morbidity that requires prompt medical care. The study of synovial fluid becomes relevant to allow a rapid diagnostic approach. The main objective of the study was to determine the frequency and clinical-analytical characteristics of episodes of AM and acute bursitis evaluated in a hospital during a period of 6 years. METHODS: Cross-sectional retrospective analytical study in a hospital at Córdoba, Argentina. All episodes of acute monoarthritis and bursitis that occurred in patients aged 18 years or older between 2012 and 2017 were included. AM in pregnant women and chronic monoarthritis were excluded. RESULTS: One hundred and eighty episodes of AM and 12 of acute bursitis were included. Among the AM, 120 (66.7%) occurred in male patients and the average age was 62.1±16.9 years. The main cause of AM was septic, identifying 70 (36%) cases, followed by microcrystalline AM identify 54 (28%) cases, which corresponded to gout and calcium pyrophosphate dihydrate (CPPD) with 27 (14%) cases each one. Monosodium urate crystals were identified in 26 (14.3%) patients, CPPD in 28 (15.6%) and cholesterol in 1 (0.6%). DISCUSSION: The main cause of AM was septic arthritis, followed by microcrystalline AM (gout and secondary to CPPD). The main affected joint was the knee, followed by the shoulder. Synovial fluid analysis was a key element when making the differential diagnosis between the different causes of acute monoarthritis and bursitis.

Introducción: La monoartritis aguda (MA) representa una causa relevante de morbilidad que requiere de atención médica oportuna: El estudio del líquido sinovial constituye un elemento clave para su diagnóstico. El objetivo del estudio fue determinar la frecuencia y características clínicas-analíticas de los episodios de MA y bursitis agudas valoradas en un hospital durante un período de 6 años. Métodos: Estudio analítico retrospectivo de corte transversal en un hospital de Córdoba, Argentina. Se identificaron todos los episodios de monoartritis y bursitis agudas que ocurrieron en pacientes de =18 años entre 2012 y 2017. Se excluyeron los cuadros de MA en embarazadas y las monoartritis crónicas. Resultados: Se incluyeron 180 episodios de MA y 12 de bursitis aguda. Entre las MA, 120 (66.7%) ocurrieron en hombres, la edad promedio fue 62.1±16.9 años. La principal causa de MA fue séptica, identificándose 70 (36%) casos, seguida la secundaria a microcristales con 54 episodios (28%) que correspondieron 27 (14%) a MA por gota y 27 (14%) a MA por depósitos de pirofosfato de calcio dihidratado (CPPD). Se identificaron cristales de urato monosódico en 26 (14.3%) pacientes, CPPD en 28 (15.6%) y de colesterol en 1 (0.6%). Discusión: La principal causa de MA fue séptica, seguida de la secundaria a microcristales (gota y secundaria a CPPD). La principal articulación afectada fue la rodilla, seguida del hombro. El análisis del líquido sinovial fue un elemento clave a la hora de poder realizar el diagnóstico diferencial entre las distintas causas de monoartritis aguda y bursitis.

The effect of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes in drug-resistant epilepsy.

OBJECTIVE: The impact of responsive neurostimulation (RNS) on neuropsychiatric and psychosocial outcomes has not been extensively evaluated outside of the original clinical trials and post-approval studies. The goal of this study was to ascertain the potential real-world effects of RNS on cognitive, psychiatric, and quality of life (QOL) outcomes in relation to seizure outcomes by examining 50 patients undergoing RNS implantation for drug-resistant epilepsy (DRE). METHODS: We performed a retrospective review of all patients treated at our institution with RNS for DRE with at least 12 months of follow-up. In addition to baseline demographic and disease-related characteristics, we collected cognitive (Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning Index), psychiatric (Beck Depression and Anxiety Inventory Scores), and QOL (QOLIE-31) outcomes at 6 and 12 months after RNS implantation and correlated them with seizure outcomes. RESULTS: Fifty patients (median age 39.5 years, 64% female) were treated with RNS for DRE in our institution from 2005 to 2020. Of the 37 of them who had well-documented pre and post-implantation seizure diaries, the 6-month median seizure frequency reduction was 88%, the response rate (50% or greater seizure frequency reduction) was 78%, and 32% of patients were free of disabling seizures in this timeframe. There was no statistically significant difference at a group level in any of the evaluated cognitive, psychiatric, and QOL outcomes at 6 and 12 months post-implantation compared to the pre-implantation baseline, irrespective of seizure outcomes, although a subset of patients experienced a decline in mood or cognitive variables. SIGNIFICANCE: Responsive neurostimulation does not appear to have a statistically significant negative or positive impact on neuropsychiatric and psychosocial status at the group level. We observed significant variability in outcome, with a minority of patients experiencing worse behavioral outcomes, which seemed related to RNS implantation. Careful outcome monitoring is required to identify the subset of patients experiencing a poor response and to make appropriate adjustments in care.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

BACKGROUND AND OBJECTIVES: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC. METHODS: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability. RESULTS: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds. DISCUSSION: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.

[Creatine phosphokinase enzyme elevation in two third-level hospitals of Córdoba]. / Estudio de los pacientes con elevación de enzima Creatinfosfokinasa en dos hospitales de tercer nivel de la ciudad de córdoba.

Introduction: HyperCKemia is defined as the elevation of creatine phosphokinase (CK) levels greater than 1.5 times the upper limit (CK>285 U/L), being produced by multiple causes, which vary according different populations. The main objective of the study was to know the frequency of hyperCKemia in two hospitals in Córdoba and its main causes. Methods: Retrospective analytical study in two hospitals in Córdoba, Argentina, where all patients over 18 years of age who presented CK values ​​greater than 285 U/L on at least 2 occasions in a period between 1 and 4 weeks were identified, between the years 2015 and 2017. Results: 254 patients with hyperCKemia were identified, the majority were male (n=181, 71.3%) and their median age was 65 years (interquartile range 25-75%=50-73 years). The main causes of hyperCKemia were ischemic myopathy in 99 (39%) patients and drug-induced myopathies in 45 (17.7%), with statins being the most frequently involved drugs in 31 cases. In only 3.1% of the cases the final diagnosis was not reached. Drug-induced hyperCKemias, when compared to other causes, occurred more frequently in patients with a history of chronic kidney disease (9/45 [20%] vs 18/209 [8.6%], p = 0.025) and in non-smokers (41/45 [91.1%] vs. 157/209 [75.1%], p=0.019). Main conclusion: 254 cases of hyperCKemia were observed, the main causes being of ischemic origin and secondary to drug use, especially statins.

Introducción: Se denomina hiperCKemia a la elevación de niveles de creatinfosfoquinasa (CK) mayor a 1,5 veces el límite superior(CK>285 U/L), siendo producida por múltiples causas, que varían según las poblaciones de estudio. El objetivo principal del estudio fue conocer la frecuencia de hiperCKemia en dos hospitales de la Ciudad de Córdoba y sus principales causas. Metodología: Estudio analítico retrospectivo en dos hospitales de la ciudad de Córdoba en Argentina, donde se identificaron todos los pacientes mayores de 18 años que presentaron valores de CK mayores a 285 U/L en al menos 2 oportunidades en un período entre 1 y 4 semanas, entre los años 2015 y 2017. Resultados: Se identificaron 254 pacientes con hiperCKemia, la mayoría eran de sexo masculino (n=181, 71.3%) y su mediana de edad fue 65 años (rango intercuartil 25-75%=50-73 años). Las principales causas de hiperCKemia fueron la miopatía isquémica en 99 (39%) pacientes y las miopatías inducidas por drogas en 45 (17.7%), siendo las estatinas las drogas más frecuentemente involucradas en 31 casos. En sólo el 3.1% de los casos no se arribó al diagnóstico final. Las hiperCKemias inducidas por drogas al compararse con las otras causas, se presentaron más frecuentemente en pacientes con antecedente de enfermedad renal crónica (9/45[20%] vs 18/209[8.6%], p=0.025) y en no tabaquistas(41/45[91.1%] vs 157/209[75.1%], p=0.019) . Conclusión: Se observaron 254 casos de hiperCKemia, siendo sus principales causas de origen isquémico y secundario a consumo de fármacos, especialmente por estatinas.

Anterior nucleus of the thalamus deep brain stimulation vs temporal lobe responsive neurostimulation for temporal lobe epilepsy.

OBJECTIVE: Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used increasingly in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare the seizure benefits and adverse effects associated with these therapies in this patient population. We, therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE at our center. METHODS: We performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient's epilepsy, seizure frequency was recorded throughout each patient's postoperative clinical course. RESULTS: Twenty-six patients underwent ANT-DBS implantation and 32 patients underwent TL-RNS for drug-resistant TLE. The epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > .05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > .05). The incidence of complications and stimulation-related side effects did not significantly differ between therapies. SIGNIFICANCE: We demonstrate in our single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may, therefore, depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another.

Epileptiform Abnormalities in Acute Ischemic Stroke: Impact on Clinical Management and Outcomes.

PURPOSE: Studies examining seizures (Szs) and epileptiform abnormalities (EAs) using continuous EEG in acute ischemic stroke (AIS) are limited. Therefore, we aimed to describe the prevalence of Sz and EA in AIS, its impact on anti-Sz drug management, and association with discharge outcomes. METHODS: The study included 132 patients with AIS who underwent continuous EEG monitoring >6 hours. Continuous EEG was reviewed for background, Sz and EA (lateralized periodic discharges [LPD], generalized periodic discharges, lateralized rhythmic delta activity, and sporadic epileptiform discharges). Relevant clinical, demographic, and imaging factors were abstracted to identify risk factors for Sz and EA. Outcomes included all-cause mortality, functional outcome at discharge (good outcome as modified Rankin scale of 0-2 and poor outcome as modified Rankin scale of 3-6) and changes to anti-Sz drugs (escalation or de-escalation). RESULTS: The frequency of Sz was 7.6%, and EA was 37.9%. Patients with Sz or EA were more likely to have cortical involvement (84.6% vs. 67.5% P = 0.028). Among the EAs, the presence of LPD was associated with an increased risk of Sz (25.9% in LPD vs. 2.9% without LPD, P = 0.001). Overall, 21.2% patients had anti-Sz drug changes because of continuous EEG findings, 16.7% escalation and 4.5% de-escalation. The presence of EA or Sz was not associated with in-hospital mortality or discharge functional outcomes. CONCLUSIONS: Despite the high incidence of EA, the rate of Sz in AIS is relatively lower and is associated with the presence of LPDs. These continuous EEG findings resulted in anti-Sz drug changes in one-fifth of the cohort. Epileptiform abnormality and Sz did not affect mortality or discharge functional outcomes.

Translating Phenomenology of Psychogenic Nonepileptic Seizures Into Nosology: Insights From Patients' and Caregivers' Profiles.

BACKGROUND: Patients with psychogenic nonepileptic seizures (PNES) can be semiologically dichotomized into those with hyperkinetic and those with paucikinetic events. The objective of this study was to compare characteristics of patients with diverse phenomenology and their caregivers to evaluate for differences that could inform about disease nosology. METHODS: Patients and caregivers monitored at the Epilepsy Monitoring Unit completed surveys about sociodemographic and disease characteristics, treatment and health care utilization, physical and psychosocial impact, and epilepsy knowledge. Patients were classified into hyperkinetic versus paucikinetic based on their recorded events. Comparison of the 2 populations was performed using Student t test for continuous variables and Fischer exact test for categorical variables. RESULTS: Forty-three patients with Epilepsy Monitoring Unit confirmed PNES and 28 caregivers were enrolled. Patients with hyperkinetic events were more commonly non-White patients and necessitated greater caregiving time. Otherwise, no statistically significant differences were seen between the 2 semiologically diverse groups of patients and caregivers in their sociodemographic (age, sex, employment, income, marital, and education) and disease (age of onset, duration, seizures frequency) characteristics, treatment (number of antiseizure medications before diagnosis, side effects) and health care utilization (emergency room visits, hospitalizations, clinic visits), physical (injuries) and psychosocial (depression, anxiety, quality of life, stigma, burden) characteristics, nor in their knowledge about seizures. CONCLUSIONS: Hyperkinetic events were more frequently encountered in non-White patients and required more caregiving time. Further research is required to elucidate if phenomenological dichotomy of PNES can inform about their nosological basis, and if it can guide treatment and define prognosis.

Bioreactor Platform for Biomimetic Culture and in situ Monitoring of the Mechanical Response of in vitro Engineered Models of Cardiac Tissue.

In the past two decades, relevant advances have been made in the generation of engineered cardiac constructs to be used as functional in vitro models for cardiac research or drug testing, and with the ultimate but still challenging goal of repairing the damaged myocardium. To support cardiac tissue generation and maturation in vitro, the application of biomimetic physical stimuli within dedicated bioreactors is crucial. In particular, cardiac-like mechanical stimulation has been demonstrated to promote development and maturation of cardiac tissue models. Here, we developed an automated bioreactor platform for tunable cyclic stretch and in situ monitoring of the mechanical response of in vitro engineered cardiac tissues. To demonstrate the bioreactor platform performance and to investigate the effects of cyclic stretch on construct maturation and contractility, we developed 3D annular cardiac tissue models based on neonatal rat cardiac cells embedded in fibrin hydrogel. The constructs were statically pre-cultured for 5 days and then exposed to 4 days of uniaxial cyclic stretch (sinusoidal waveform, 10% strain, 1 Hz) within the bioreactor. Explanatory biological tests showed that cyclic stretch promoted cardiomyocyte alignment, maintenance, and maturation, with enhanced expression of typical mature cardiac markers compared to static controls. Moreover, in situ monitoring showed increasing passive force of the constructs along the dynamic culture. Finally, only the stretched constructs were responsive to external electrical pacing with synchronous and regular contractile activity, further confirming that cyclic stretching was instrumental for their functional maturation. This study shows that the proposed bioreactor platform is a reliable device for cyclic stretch culture and in situ monitoring of the passive mechanical response of the cultured constructs. The innovative feature of acquiring passive force measurements in situ and along the culture allows monitoring the construct maturation trend without interrupting the culture, making the proposed device a powerful tool for in vitro investigation and ultimately production of functional engineered cardiac constructs.

Validation of the 2HELPS2B Seizure Risk Score in Acute Brain Injury Patients.

BACKGROUND AND OBJECTIVE: Seizures are common after traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (aSAH), subdural hematoma (SDH), and non-traumatic intraparenchymal hemorrhage (IPH)-collectively defined herein as acute brain injury (ABI). Most seizures in ABI are subclinical, meaning that they are only detectable with EEG. A method is required to identify patients at greatest risk of seizures and thereby in need of prolonged continuous EEG monitoring. 2HELPS2B is a simple point system developed to address this need. 2HELPS2B estimates seizure risk for hospitalized patients using five EEG findings and one clinical finding (pre-EEG seizure). The initial 2HELPS2B study did not specifically assess the ABI subpopulation. In this study, we aim to validate the 2HELPS2B score in ABI and determine its relative predictive accuracy compared to a broader set of clinical and electrographic factors. METHODS: We queried the Critical Care EEG Monitoring Research Consortium database for ABI patients age ≥ 18 with > 6 h of continuous EEG monitoring; data were collected between February 2013 and November 2018. The primary outcome was electrographic seizure. Clinical factors considered were age, coma, encephalopathy, ABI subtype, and acute suspected or confirmed pre-EEG clinical seizure. Electrographic factors included 18 EEG findings. Predictive accuracy was assessed using a machine-learning paradigm with area under the receiver operator characteristic (ROC) curve as the primary outcome metric. Three models (clinical factors alone, EEG factors alone, EEG and clinical factors combined) were generated using elastic-net logistic regression. Models were compared to each other and to the 2HELPS2B model. All models were evaluated by calculating the area under the curve (AUC) of a ROC analysis and then compared using permutation testing of AUC with bootstrapping to generate confidence intervals. RESULTS: A total of 1528 ABI patients were included. Total seizure incidence was 13.9%. Seizure incidence among ABI subtype varied: IPH 17.2%, SDH 19.1%, aSAH 7.6%, TBI 9.2%. Age ≥ 65 (p = 0.015) and pre-cEEG acute clinical seizure (p < 0.001) positively affected seizure incidence. Clinical factors AUC = 0.65 [95% CI 0.60-0.71], EEG factors AUC = 0.82 [95% CI 0.77-0.87], and EEG and clinical factors combined AUC = 0.84 [95% CI 0.80-0.88]. 2HELPS2B AUC = 0.81 [95% CI 0.76-0.85]. The 2HELPS2B AUC did not differ from EEG factors (p = 0.51), or EEG and clinical factors combined (p = 0.23), but was superior to clinical factors alone (p < 0.001). CONCLUSIONS: Accurate seizure risk forecasting in ABI requires the assessment of EEG markers of pathologic electro-cerebral activity (e.g., sporadic epileptiform discharges and lateralized periodic discharges). The 2HELPS2B score is a reliable and simple method to quantify these EEG findings and their associated risk of seizure.

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.

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 Women's 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.

Diagnostic accuracy between readers for identifying electrographic seizures in critically ill adults.

OBJECTIVE: Electrographic seizures in critically ill patients are often equivocal. In this study, we sought to determine the diagnostic accuracy of electrographic seizure annotation in adult intensive care units (ICUs) and to identify affecting factors. METHODS: To investigate diagnostic accuracy, interreader agreement (IRA) measures were derived from 5,769 unequivocal and 6,263 equivocal seizure annotations by five experienced electroencephalogram (EEG) readers after reviewing 74 days of EEGs from 50 adult ICU patients. Factors including seizure equivocality (unequivocal vs. equivocal) and laterality (generalized, partial, or bilaterally independent), cyclicity (cyclic vs. noncyclic), persistency (occurrence of status epilepticus), and patient consciousness level (coma vs. noncoma) were further investigated for their influence on IRA measures. RESULTS: On average, 70% of seizures marked by a reference reader overlapped, at least in part, with those marked by a test reader (any-overlap sensitivity, AO-Sn). Agreed seizure duration between reader pairs (overlap-integral sensitivity, OI-Sn) was 62%, while agreed nonseizure duration (overlap-integral specificity, OI-Sp) was 99%. A test reader would annotate one additional seizure not overlapping with a reference reader's annotation in every 11.7 h of EEG, that is, the false-positive rate (FPR) was 0.0854/h. Classifying seizure patterns into unequivocal and equivocal improved specificity and FPR (unequivocal patterns) but compromised sensitivity only for equivocal patterns. Sensitivity of all and unequivocal annotations was higher for patients with status epilepticus. Specificity was higher for partial than for bilaterally independent unequivocal seizure patterns, and lower for cyclic all seizure patterns. SIGNIFICANCE: Diagnosing electrographic seizures in critically ill adults is highly specific and moderately sensitive. Improved criteria for diagnosing electrographic seizures in the ICU are needed.

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 < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (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.

Development and Feasibility Testing of a Critical Care EEG Monitoring Database for Standardized Clinical Reporting and Multicenter Collaborative Research.

PURPOSE: The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use. METHODS: Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports. RESULTS: A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days. CONCLUSIONS: The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.