Serum Neuron-Specific Enolase Levels from the Same Patients Differ Between Laboratories: Assessment of a Prospective Post-cardiac Arrest Cohort

Background

In comatose post-cardiac arrest patients, a serum neuron-specific enolase (NSE) level of >33 μg/L within 72 h was identified as a reliable marker for poor outcome in a large Dutch study (PROPAC), and this level was subsequently adopted in an American Academy of Neurology practice parameter. Later studies reported that NSE >33 μg/L is not a reliable predictor of poor prognosis. To test whether different clinical laboratories contribute to this variability, we compared NSE levels from the laboratory used in the PROPAC study (DLM-Nijmegen) with those of our hospital’s laboratory (ARUP) using paired blood samples.

Methods

We prospectively enrolled cardiac arrest patients who remained comatose after resuscitation. During the first 3 days, paired blood samples for serum NSE were drawn at a median of 10 min apart. After standard preparation for each lab, one sample was sent to ARUP laboratories and the other to DLM-Nijmegen.

Results

Fifty-four paired serum samples from 33 patients were included. Although the serum NSE measurements correlated well between laboratories (R = 0.91), the results from ARUP were approximately 30 % lower than those from DLM-Nijmegen. Therapeutic hypothermia did not affect this relationship. Two patients had favorable outcomes after hypothermia despite NSE levels measured by DLM-Nijmegen as >33 μg/L.

Conclusions

Absolute serum NSE levels of comatose cardiac arrest patients differ between laboratories. Any specific absolute cut-off levels proposed to prognosticate poor outcome should not be used without detailed data on how neurologic outcomes correspond to a particular laboratory’s method, and even then only in conjunction with other prognostic variables.     

Clinical Outcome After a Reactive Hypothermic EEG Following Cardiac Arrest

Background

Reactive electroencephalography (EEG) background during therapeutic hypothermia (TH) is related to favorable prognosis after cardiac arrest (CA), but its predictive value is not 100 %. The aim of this study was to investigate outcome predictors after a first reactive EEG recorded during TH after CA.

Methods

We studied a cohort of consecutive comatose adults admitted between February 2008 and November 2012, after successful resuscitation from CA, selecting patients with reactive EEG during TH. Outcome was assessed at three months, and categorized as survivors and non-survivors (no patient was in vegetative state). Demographics, clinical variables, EEG features, serum neuron-specific enolase (NSE) and procalcitonin, were compared using uni- and multivariable analyses.

Results

A total of 290 patients were treated with TH after cardiac arrest; 146 had an EEG during TH, which proved reactive in 90 of them; 77 (86 %) survived and 13 (14 %) died (without recovery from coma). The group of non-survivors had a higher occurrence of discontinuous EEG (p = 0.006; multivariate analysis p = 0.026), and a higher serum NSE peak (p = 0.021; multivariate analysis p = 0.014); conversely, demographics, and other clinical variables including serum procalcitonin did not differ.

Conclusions

A discontinuous EEG and high serum NSE are associated with mortality after CA in patients with poor outcome despite a reactive hypothermic EEG. This suggests more severe cerebral damage, but not to higher extent of systemic disease.     

Alpha EEG Activity Depends on the Individual Dominant Rhythm Frequency

Exploring the role of the electroencephalographic (EEG) alpha oscillations in the processes of central and autonomic regulation of the cognitive and psychomotor performance generates considerable interest. However, until now there was no accurate definition of what alpha activity is, and which indices characterize it. This is a theoretical article that attempts to define EEG alpha-activity phenomena; define their physical, molecular, and morphological nature; and highlight the difference in its indices connected with different individual alpha frequencies and their role in optimal functioning. Specifically, this article examines individual alpha activity indices: (a) the individual alpha peak frequency; (b) activation magnitude measured by estimating the amount of alpha amplitude suppression in response to eyes-open and individual alpha band width; and (c) three alpha “autorhythmicity” indices: intraspindle amplitude variability, spindle length, and steepness. Throughout, the article provides a number of suggestions on how alpha activity indices are connected with the individual spectral distribution of the alpha frequency and why these individual alpha activity peculiarities are important for neurofeedback training effectiveness.     

The Mental Deterioration in the Aged and the Computerized EEG Analysis

The relationship between the computerized EEG data and the mental function was studied in 73 subjects aged 60 and over in a home for the aged. The mental function was examined by Hasegawa Test (HT) (simplified dementia rating scale) and Bender Gestalt Test (BGT), and the degree of the mental deterioration was classified as normal, sub-normal, pre-dementia, dementia of HT, and as (-), (+), (++), (+++) of BGT. The EEG records were analyzed quantitatively at resting state with eye-closed and also at eye-opened state. EEG variables were compared in each group of the two tests and the both states. The following results were obtained.

• 1) EEG variables correlated more closely with the score of BGT than that of HT in general.
• 2) The percent time alpha and alpha continuity at the eye-closed state decreased significantly in dementia group of HT and (+++) group of BGT.
• 3) With the progress of the deterioration of BGT, the percent time alpha at the eye-opened state gradually increased, and the ratio of the percent time alpha at the eye-opened state to the eye-closed state increased lineally.
• 4) With the progress of the deterioration of BGT, the percent time theta increased gradually, and the number of theta waves over the amplitude of 30 μV increased lineally especially in the central area at eye-closed state.
• 5) By eye opening the number of theta waves over 30 μV decreased significantly in (-) and (+) groups of BGT, but did not change in (++) and (+++) groups.
• 6) The peak frequency and the percent time beta did not correlate with the mental function in the aged.

Parts of this paper were presented at the 5th Annual Meeting of Japan EEG and EMG Society, Tokyo, December, 1975 and at the 6th Annual Meeting, Fukuoka, November, 1976.     

Background EEG reactivity in auditory event-related potentials

Mental activity has influences on auditory event-related potentials (AERP) as well as onme EEG rhythms, notably the alpha rhythm. In this study background reactivity (BR) of the EEG was investigated in the context of AERPs.Single responses of 14 healthy subjects were analysed in 3 reaction time AERP experiments of increasing difficulty: the first involved one type of tone delivered at random intervals, the second offered two types of tone (an “oddball” design), and the third offered 3 types of tone. Averages were formed and subtracted from the separate responses to reduce their contribution to the EEG. The 1526 msec EEG epoch was divided in 9 overlapping periods, and averaged power spectra were calculated for these periods. Changes in area of the delta, theta, alpha and beta bands in the course of the epoch were calculated.Background alpha and beta activity decreased following infrequent but not following frequent tones. The decrease was larger for more difficult tasks and reached a maximum in the period in which the AERP P3 and N3 peaks fell. Delta and theta powers showed increases rather than decreases; these could be attributed to the contribution of AERP activity to total EEG power. No clear relationships were found between the amount of background reactivity and peak latencies or reaction times.The occurrence of background reactivity, not apparent in an average, shows that the averaged AERP reveals only part of the EEG changes related to mental activity. Background reactivity proved to be more sensitive to task difficultythan P300 latency. The results are discussed in the context of the additive model of evoked potentials.     

Background EEG reactivity in auditory event-related potentials.

Mental activity has influences on auditory event-related potentials (AERP) as well as on some EEG rhythms, notably the alpha rhythm. In this study, background reactivity (BR) of the EEG was investigated in the context of AERPs. Single responses of 14 healthy subjects were analysed in 3 reaction time AERP experiments of increasing difficulty: the first involved one type of tone delivered at random intervals, the second offered two types of tone (an "oddball" design), and the third offered 3 types of tone. Averages were formed and subtracted from the separate responses to reduce their contribution to the EEG. The 1526 msec EEG epoch was divided in 9 overlapping periods, and averaged power spectra were calculated for these periods. Changes in area of the delta, theta, alpha and beta bands in the course of the epoch were calculated. Background alpha and beta activity decreased following infrequent but not following frequent tones. The decrease was larger for more difficult tasks and reached a maximum in the period in which the AERP P3 and N3 peaks fell. Delta and theta powers showed increases rather than decreases; these could be attributed to the contribution of AERP activity to total EEG power. No clear relationships were found between the amount of background reactivity and peak latencies or reaction times. The occurrence of background reactivity, not apparent in an average, shows that the averaged AERP reveals only part of the EEG changes related to mental activity. Background reactivity proved to be more sensitive to task difficulty than P300 latency. The results are discussed in the context of the additive model of evoked potentials.     

The Development of EEG Background Activities in El Mouse

Abstract: The development of background activities of cortical EEG in El mouse, the seizure susceptible mutant strain of ddN mouse, were investigated. Furthermore, it was compared to that of the ddN control mouse.
The average peak frequency of EEG background activity was much slower than that of the ddN mouse. After seizures in the El mouse were completed, the average energy distribution rates of the main frequency band, theta band, have decreased because of an increase in the delta band compared to those in seizure-free periods (the 5th to 8th week).     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Delayed Fever and Neurological Outcome after Cardiac Arrest: A Retrospective Clinical Study

Background

The aim of this study was to evaluate the association between fever after the first days of ICU stay and neurological outcome after cardiac arrest (CA).

Methods

We retrospectively analyzed CA patients admitted to intensive care unit (ICU). Inclusion criteria: age ≥18 years, Glasgow Coma Scale score ≤8 at ICU admission and assessment of body core temperature (BCT) using bladder or intravascular probes. Exclusion criteria: ICU length of stay (LOS) <3 days and pregnancy. The primary endpoint was neurological outcome assessed with Cerebral Performance Category (CPC) scale 6 months after CA.

Results

One hundred thirty-two patients were analyzed. Fever was present in 105 (79.6 %) patients. Variables associated with unfavorable outcome were (1) older age (p < 0.0025); (2) non-shockable cardiac rhythms (p < 0.0001); (3) higher Simplified Acute Physiology Score (SAPS) II (p < 0.0001); (4) pupillary abnormalities at ICU admission (p < 0.018); and (5) elevated degree of maximal BCT (Tmax) during ICU stay (p < 0.046). After multivariate analysis, Tmax maintained a significant relationship with neurological outcome. An increase of 1 °C in Tmax during ICU stay decreased the odds ratio for a favorable outcome by a factor of 31 % (p < 0.001). Moreover, we discovered a significant interaction between the day of Tmax (t-Tmax) and Tmax (p = 0.004); the later Tmax occurs, the more deleterious effects are observed on outcome.

Conclusions

Fever is frequent after CA, and Tmax in ICU is associated with worsened neurological outcome. This association becomes stronger as the timing of Tmax extends further from the CA.

     

脑电图预测急性CO中毒后迟发性脑病研究

目的探讨急性CO中毒后迟发性脑病(DEACMP)的脑电图(EEG)演变规律与临床症状的关系。方法对136例急性CO中毒患者进行EEG跟踪检查,首次EEG检查均在中毒后48 h内完成。结果136例急性CO中毒患者共行EEG检查360次,其中异常EEG140例次(38.89%),EEG的异常程度与临床症状严重程度呈正相关。首次EEG有异常改变者43例,其中31例(72.09%)最终发生了DEACMP。第二次EEG仍有异常改变者30例,其中24例(80%)最终发生了DEACMP。结论EEG可预测DEACMP,急性CO中毒患者经抢救即使中毒症状已缓解或消失,只要EEG仍有异常改变就不应终止治疗。     

Evaluation of Two Circadian Rhythm Questionnaires for Screening for the Delayed Sleep Phase Disorder

Objective

Delayed sleep phase disorder (DSPD) is a condition in which patients often fall asleep some hours after midnight and have difficulty waking up in the morning. Circadian chronotype questionnaires such as Horne-Östberg Morningness-Eveningness Questionnaire (MEQ) and Basic Language Morningness (BALM) scale have been used for screening for DSPD. This study was to evaluate these two chronotype questionnaires for screening of DSPD.

Methods

The study samples were 444 DSPD and 438 controls. Cronbach''s alpha coefficient was calculated to evaluate for internal consistency. An exploratory factor analysis was conducted using principal-axis factoring. The diagnostic performance of a test was evaluated using Receiver Operating Characteristic (ROC) curve analysis. A discriminant function analysis was also performed.

Results

For internal consistency, Cronbach''s alpha of 0.898 for BALM was higher than the 0.837 for MEQ, though both have acceptable internal consistency. BALM has better construct validity than the MEQ because some MEQ items measure different dimensions. However, when we evaluated the efficiency of two questionnaires for DSPD diagnosis by using the ROC curve, the BALM was similar to the MEQ. In a discriminant analysis with the BALM to classify the two groups (DSPD vs. normal), 6 items were identified that resulted in good classification accuracy. Upon examination of the classification procedure, 94.2% of the originally grouped cases were classified correctly.

Conclusion

These findings suggest that the BALM has better psychometric properties than the MEQ in screening and discriminating DSPS.     

Background intracranial EEG spectral changes with anti-epileptic drug taper

ObjectivePrevious studies have revealed a surprising decrease in spike counts and Teager energy between on- and off-AEDs states during intracranial EEG (icEEG) monitoring. Here, we expand the measures evaluated to icEEG power and frequency band power.MethodsTwo icEEG epochs, on- and off-AEDs, each 1 h in duration, were studied for each of 21 unselected adult patients. Spike counts, Teager energy and total power were evaluated for each electrode contact. Power was also evaluated for delta (0–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–25 Hz), gamma (25–55 Hz) and high (65–128 Hz) frequency bands.ResultsA decrease in power accompanies AED taper and the previously reported decrease in spike counts and Teager energy. The decrease in power was underpinned by a spatially widespread and broadband decrease in power in delta through gamma frequency bands with maximum decrease in the lowest frequency bands. An increase in high-frequency power was observed in some patients.ConclusionsThere is a decrease in spike counts, Teager energy and power from on- to off-AEDs state during intracranial monitoring. The decrease in power is spatially widespread and broadband including power in the delta through gamma frequency bands.SignificanceThe decrease in cortical activity with AED taper suggests that seizure generation during intracranial monitoring may not be mediated solely by poorly regulated cortical excitation.     

The Prognostic Value of 48-h Continuous EEG During Therapeutic Hypothermia After Cardiac Arrest

Background

The aim of this study was to evaluate the prognostic value of continuous electroencephalogram (cEEG) during the first 48 h following cardiac arrest (CA) in patients treated with targeted temperature management (TTM).

Methods

We reviewed data from 92 comatose post-CA patients over a 6 year-period; cEEG recordings were performed during TTM and restoration of normothermia. EEG findings were divided into four time-periods: 0–8, 8–16, 16–24, and 24–48 h after CA. Background EEG findings were defined as moderate encephalopathy (diffuse slowing with reactivity/variability), severe encephalopathy (diffuse slowing without reactivity/variability), burst suppression or suppression, and dichotomized as malignant (suppression/burst suppression/severe encephalopathy) or benign (moderate encephalopathy). Epileptiform activity was defined as the presence of seizures, sporadic epileptiform discharges, or periodic discharges. Neurological outcome was assessed at 3 months using the cerebral performance categories (CPC) score (good outcome: CPC 1–2).

Results

26/92 (28 %) patients had a good outcome. Malignant patterns were associated with a poor outcome at all time-points, with a high positive predictive value (94–97 %) but a poor negative predictive value (44–56 %). Epileptiform activity did not influence the prognostic value of EEG patterns. All patients with moderate encephalopathy and seizures or generalized periodic discharges had a poor outcome.

Conclusions

cEEG can identify patients with poor outcome from the first hours following CA, with limited predictive value for good outcome. Epileptiform activity did not improve the prognostic accuracy of EEG, but seizures and generalized periodic discharges were associated with poor outcome even when developing on a benign EEG pattern.

     

EEG Background as Predictor of Electrographic Seizures in High-Risk Neonates

Summary: Purpose: Experience with continuous EEG monitoring in 29 consecutive infants at risk of neonatal seizures demonstrated that background abnormalities on the initial EEG were strongly associated with electrographic seizures in the subsequent 18–24 h. To test this association prospectively, we examined the relationship between EEG background and the presence of electrographic seizures in the next 22 at-risk infants monitored for seizures.
Methods: A standard EEG was recorded for each infant at risk for seizures. Based on specific criteria, the background was graded as normal; immature for age; or mildly, moderately, or severely abnormal. The EEG was then monitored continuously until no electrographic seizures were recorded for 18–24 h.
Results: Findings in the retrospective group of 29 infants and the prospective group of 22 infants did not differ. For the combined 51 infants, a normal or immature initial EEG background predicted the absence of seizures in the subsequent 18–24 h with a sensitivity of 96% [confidence interval (CI) 0.88, 1.01 and specificity of 81% (CI 0.67, 0.96). Administration of antiepileptic drugs (AEDs) before the start of the EEG recording did not affect this association.
Conclusions: In 51 consecutively monitored infants at risk for neonatal seizures, a normal or immature EEG background strongly predicted the absence of electrographic seizures in the subsequent 18–24 h; background abnormalities strongly predicted the occurrence of electrographic seizures concomitantly or in the subsequent 18–24 h of recording. Screening infants at risk for neonatal seizures with a routine EEG allows identification of infants at highest risk for seizures, thus conserving resources required for continuous EEG monitoring and facilitating early intervention for seizures.     

失神发作的背景脑电图定量分析

１０例（男７，女３）失神发作儿童的背景脑电图，以功率、相对功率及ＳＰＭ进行定量分析和１０例年龄性别相匹配的健康儿童为对照。结果提示背景ＥＥＧ的慢频（尤以δ活动）功率增高，主要在矢旁区和脑后部（尤以枕部）。β功率有普遍减弱的趋向。其原因尚未完全明了，长期服用ＶＰＡ可能是因素之一。