Tonic phase of a generalized convulsive seizure is an independent predictor of postictal generalized EEG suppression.

PURPOSE: To determine the incidence, duration, risk factors for, and clinical correlates of postictal generalized electroencephalography (EEG) suppression (PGES), and to further delineate the significance of PGES in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). METHODS: We retrospectively reviewed the video-EEG studies of 109 consecutive patients with 151 generalized convulsive seizures (GCS) during video-EEG monitoring. We determined the incidence, duration, and clinical correlates of PGES. We also investigated whether factors such as age, sex, seizure type, total seizure duration, and duration of tonic and clonic phases influenced PGES. KEY FINDINGS: PGES was observed in 64 (58.7%) of 109 patients and in 98 (64.9%) of 151 GCS. Average duration of PGES was 42.4 ± 19.1 s. Statistical analysis showed that patients with PGES had no difference in age, gender, total seizure duration, total convulsive duration, clonic phase, seizure type, and seizure termination, as compared to those without PGES. However, tonic phase was significantly prolonged in patients with PGES than in those without PGES (p = 0.00086). A 1 s increase in tonic phase duration was associated with a 0.06 increase in log odds of PGES (odds ratio = 1.1, p = 0.00055). Clinically, 95.3% patients were unresponsive or immobile during PGES, whereas only 26.7% patients without PGES were unresponsive or immobile immediately after seizure termination. SIGNIFICANCE: PGES is a common EEG pattern of GCS. Tonic phase of GCS is an independent predictor of PGES, which is well correlated with postictal unresponsiveness or immobile, and may play a significant role in the mechanism of SUDEP.

Interictal regional delta slowing is an EEG marker of epileptic network in temporal lobe epilepsy.

PURPOSE: Several studies have suggested that interictal regional delta slowing (IRDS) carries a lateralizing and localizing value similar to interictal spikes and is associated with favorable surgical outcomes in patients with temporal lobe epilepsy (TLE). However, whether IRDS reflects structural dysfunction or underlying epileptic activity remains controversial. The objective of this study is to determine the cortical electroencephalography (EEG) correlates of scalp-recorded IRDS, in so doing, to further understand its clinical and biologic significances. METHODS: We examined the cortical EEG substrates of IRDS with electrocorticography (ECoG-IRDS) and delineated the spatiotemporal relationship between ECoG-IRDS and both interictal and ictal discharges by recording simultaneously scalp and intracranial EEG in 18 presurgical candidates with TLE. KEY FINDINGS: Our results demonstrated that ECoG-IRDS is typically a mixture of delta/theta slowing and spike-wave potentials. ECoG-IRDS was predominantly recorded from basal and anterolateral temporal cortex, occasionally in mesial, posterior temporal, and extratemporal regions. Abundant IRDS was most commonly observed in patients with neocortical temporal lobe epilepsy (NTLE), whereas infrequent to moderate IRDS was usually observed in patients with mesial temporal lobe epilepsy (MTLE). The anatomic distribution of ECoG-IRDS was highly correlated with the irritative and seizure-onset zones in 10 patients with NTLE. However, it was poorly correlated with the irritative and seizure-onset zones in the 8 patients with MTLE. SIGNIFICANCE: These findings demonstrate that IRDS is an EEG marker of epileptic network in patients with TLE. Although IRDS and interictal/ictal discharges likely arise from the same neocortical generator in patients with NTLE, IRDS in patients with MTLE may reflect a network disease that involves temporal neocortex.

Induction of early post-transplant graft-versus-leukemia effects using intentionally mismatched donor lymphocytes and elimination of alloantigen-primed donor lymphocytes for prevention of graft-versus-host disease.

Graft-versus-leukemia (GVL) effects can be induced in tolerant mixed chimeras prepared with nonmyeloablative conditioning. GVL effects can be amplified by post-grafting donor lymphocyte infusion (DLI). Unfortunately, DLI is frequently associated with graft-versus-host disease (GVHD). We investigated the feasibility of induction of potent GVL effects by DLI using intentionally mismatched lymphocytes followed by elimination of alloreactive donor T cells by cyclophosphamide for prevention of lethal GVHD following induction of very short yet most potent GVL effects. Mice inoculated with B-cell leukemia (BCL1) and mismatched donor lymphocytes were treated 2 weeks later with low-dose or high-dose cyclophosphamide. All mice receiving cyclophosphamide 2 weeks after DLI survived GVHD, and no residual disease was detected by PCR; all control mice receiving DLI alone died of GVHD. Analysis of host (female) and donor (male) DNA showed that cyclophosphamide treatment eradicated most alloreactive donor cells, yet mixed chimerism was converted to full donor chimerism following transient self-limited GVHD. Our working hypothesis suggests that short-term yet effective and safe adoptive immunotherapy of leukemia may be accomplished early post-transplantation using alloreactive donor lymphocytes, with prevention of GVHD by elimination of GVL effector cells.

Sensitivity to mental effort and test-retest reliability of heart rate variability measures in healthy seniors.

OBJECTIVES: To determine (1) whether heart rate variability (HRV) was a sensitive and reliable measure in mental effort tasks carried out by healthy seniors and (2) whether non-linear approaches to HRV analysis, in addition to traditional time and frequency domain approaches were useful to study such effects. METHODS: Forty healthy seniors performed two visual working memory tasks requiring different levels of mental effort, while ECG was recorded. They underwent the same tasks and recordings 2 weeks later. Traditional and 13 non-linear indices of HRV including Poincaré, entropy and detrended fluctuation analysis (DFA) were determined. RESULTS: Time domain, especially mean R-R interval (RRI), frequency domain and, among non-linear parameters - Poincaré and DFA were the most reliable indices. Mean RRI, time domain and Poincaré were also the most sensitive to different mental effort task loads and had the largest effect size. CONCLUSIONS: Overall, linear measures were the most sensitive and reliable indices to mental effort. In non-linear measures, Poincaré was the most reliable and sensitive, suggesting possible usefulness as an independent marker in cognitive function tasks in healthy seniors. SIGNIFICANCE: A large number of HRV parameters was both reliable as well as sensitive indices of mental effort, although the simple linear methods were the most sensitive.

Heart rate variability analysis of effect of nicotine using periodograms.

Heart rate variability (HRV) is frequently used to measure autonomic nervous system (ANS) activity. However, little is known about the mechanism underlying pharmacologically induced changes in HRV. Previous research has shown that nicotine exposure stimulates the ANS, mediating a wide spectrum of physiological and behavioral effects, including altered respiratory sinus arrhythmia and enhanced arousal and attention. Using Lomb-Welch periodograms, the effect of nicotine on the ANS in 14 nicotine-naive human subjects are studied. Results showed an increase in the low frequency (LF) to high frequency (HF) ratio with little change in mean heart rate. Results suggest that nicotine affects both sympathetic and parasympathetic reactivities and that the LF/HF best characterizes early ANS activated nicotine changes in HRV. The Lomb-Welch periodogram of the HRV is also compared to the conventional interpolated Welch periodogram. The attenuation of the high frequency components due to interpolation of the non-uniform R-R intervals is found to be a function of the power of the high frequency components, increasing with increasing power. Thus analyses using Welch periodograms that make use of the high frequency components may yield erroneous results.