Surgical treatment of epileptic encephalopathy with spike-and-wave activation in sleep: A systematic review and meta-analysis.

OBJECTIVE: Epileptic Encephalopathy / Developmental Epileptic Encephalopathy with spike-and-wave activation during sleep (EE/DEE-SWAS) is a self-limiting childhood epilepsy syndrome but may cause permanent neurocognitive impairment. Surgical interventions have been controversial in the treatment of EE/DEE-SWAS. This systematic review aims to evaluate the efficacy of various surgical procedures on the outcomes of EE/DEE-SWAS. METHODS: A systematic review was performed per the PRISMA guidelines. A total of 14 retrospective studies were identified, comprising 131 cases of EE/DEE-SWAS treated with epilepsy surgery. The review analyzed presurgical data, surgical interventions, as well as outcomes related to seizures, EEG, and neuropsychological assessments. RESULTS: Epilepsy surgery was successfully performed in 131 cases with minor complications. The average age was 2.6 years at seizure onset and 5.0 years at diagnosis of SWAS. Excellent seizure control (Engel I and II) was achieved in 80.6 %, 78.6 %, 77.4 % and 27.2 % of patients receiving hemispherectomies, focal resections, multiple subpial transections (MSTs), and corpus callosotomies (CCTs), respectively. EEG SWAS resolution was seen in 79.7 % of hemispherectomy cases, 78.6 % in focal resections, 63.9 % in MSTs, and 8.3 % in CCTs. Neurocognitive and behavioral improvement was noted in 58.0 %, 71.4 %, 58.3 % and 16.7 % for patients receiving hemispherectomies, focal resections, MSTs, and CCTs, respectively. A correlation between improved seizure control and SWAS resolution was observed with improved neuropsychological outcomes. CONCLUSION: Epilepsy surgery is a safe and effective treatment for carefully selected children with drug-resistant EE/DEE-SWAS. Patients who underwent epilepsy surgery had reduction of seizure burden, SWAS resolution and improvements in neurocognitive and behavioral function.

Strong cardiovascular prognostic implication of quantitative left atrial contractile function assessed by cardiac magnetic resonance imaging in patients with chronic hypertension.

BACKGROUND: Progressive left ventricular (LV) diastolic dysfunction due to hypertension (HTN) alters left atrial (LA) contractile function in a predictable manner. While increased LA size is a marker of LV diastolic dysfunction and has been shown to be predictive of adverse cardiovascular outcomes, the prognostic significance of altered LA contractile function is unknown. METHODS: A consecutive group of patients with chronic hypertension but without significant valvular disease or prior MI underwent clinically-indicated CMR for assessment of left ventricular (LV) function, myocardial ischemia, or viability. Calculation of LA volumes used in determining LA emptying functions was performed using the biplane area-length method. RESULTS: Two-hundred and ten patients were included in this study. During a median follow-up of 19 months, 48 patients experienced major adverse cardiac events (MACE), including 24 deaths. Decreased LA contractile function (LAEF(Contractile)) demonstrated strong unadjusted associations with patient mortality, non-fatal events, and all MACE. For every 10% reduction of LAEF(Contractile), unadjusted hazards to MACE, all-cause mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds, respectively. In addition, preservation of the proportional contribution from LA contraction to total diastolic filling (Contractile/Total ratio) was strongly associated with lower MACE and patient mortality. By multivariable analyses, LAEF(Contractile) was the strongest predictor in each of the best overall models of MACE, all-cause mortality, and non-fatal events. Even after adjustment for age, gender, left atrial volume, and LVEF, LAEF(Contractile) maintained strong independent associations with MACE (p < 0.0004), all-cause mortality (p < 0.0004), and non-fatal events (p < 0.0004). CONCLUSIONS: In hypertensive patients at risk for left ventricular diastolic dysfunction, a decreased contribution of LA contractile function to ventricular filling during diastole is strongly predictive of adverse cardiac events and death.

The association between early ventricular arrhythmias, renin-angiotensin-aldosterone system antagonism, and mortality in patients with ST-segment-elevation myocardial infarction: Insights from Global Use of Strategies to Open coronary arteries (GUSTO) V.

BACKGROUND: The long-term prognostic significance of early (<48 hours) ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) in patients with an acute myocardial infarction remains controversial. Emerging data suggest that some of the benefit of renin-angiotensin-aldosterone system (RAAS) antagonism may be derived from a reduction in the incidence of these arrhythmias in the setting of acute myocardial infarction. METHODS: We assessed the relationship between early VF/VT (defined as within 48 hours after admission) and mortality in 16,588 patients from global use of strategies to open coronary arteries (GUSTO) V trial. Furthermore, we examined the relationship between baseline use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), early VF/VT, and mortality. RESULTS: Early VF or VT occurred in 732 (4.4%) patients. Compared to patients without VF/VT, those experiencing early VF or VT had a significant increase in 30-day mortality (22% vs 5%, P < .001). Baseline use of an ACEI/ARB was associated with a decreased incidence of early VF/VT (odds ratio 0.65, 0.47-0.89, P = .008). A lower 30-day mortality was seen in patients with early VF/VT on baseline ACEI/ARB compared with patients with early VF/VT not receiving an ACEI/ARB at baseline (17.7% vs 24.2%, respectively, P = .04). The association between baseline RAAS antagonism and mortality persisted after adjustment for multiple confounders. CONCLUSIONS: In patients presenting with acute myocardial infarction, early VF/VT identifies those at increased risk for 30-day mortality. Baseline use of RAAS antagonists is associated with a reduced incidence of malignant arrhythmias. Identifying how this association impacts short-term mortality in this patient population requires further prospective evaluation.

Left atrial passive emptying function during dobutamine stress MR imaging is a predictor of cardiac events in patients with suspected myocardial ischemia.

OBJECTIVES: The aim of this study was to determine the prognostic value of assessing left atrial function during dobutamine stress testing. BACKGROUND: Left ventricular diastolic dysfunction precedes systolic wall motion abnormalities in the ischemic cascade. Severity of left ventricular diastolic function during cardiac stress is not characterized well by current clinical imaging protocols but may be an important prognostic factor. We hypothesized that abnormal early left atrial emptying measured during dobutamine stress cardiac magnetic resonance will reflect these diastolic changes and may be associated with cardiovascular outcomes. METHODS: We enrolled 122 consecutive patients referred for dobutamine stress cardiac magnetic resonance for suspected myocardial ischemia. Left atrial volumes were retrospectively measured by the biplane area-length method at left ventricular end-systole (VOL(max)) and before atrial contraction (VOL(bac)). Left atrial passive emptying fraction defined by (VOL(max) - VOL(bac)) × 100%/VOL(max) and the absolute percent increase in left atrial passive emptying fraction during dobutamine stress (ΔLAPEF) were quantified. RESULTS: Twenty-nine major adverse cardiac events (MACE) occurred during follow-up (median 23 months). By Kaplan-Meier analysis, patients with ΔLAPEF <10.8 (median) experienced higher incidence of MACE than did patients with a ΔLAPEF >10.8 (p = 0.004). By univariable analysis, ΔLAPEF was strongly associated with MACE (unadjusted hazard ratio for every 10% decrease = 1.56, p < 0.005). By multivariable analysis, every 10% decrease in ΔLAPEF carried a 57% increase in MACE, after adjustment to presence of myocardial ischemia and infarction. CONCLUSIONS: Reduced augmentation of left atrial passive emptying fraction during dobutamine stress demonstrated strong association with MACE. We speculate that reduced left atrial passive emptying reserve during inotropic stress may represent underlying diastolic dysfunction and warrants further investigation.

High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal.

Protein adducts of the lipid peroxidation product trans-4-hydroxy-2-nonenal (HNE) are features of oxidative damage in neuronal cell bodies in Alzheimer's disease but are also seen in axons of normal as well as diseased individuals. In this study, focusing on the axons of the mouse sciatic nerve, we found that HNE adducts characterize axons of mice from birth to senility. Immunoblots of axonal proteins showed that HNE adducts are only detected in neurofilament heavy subunit (NFH) and, to a lesser extent, neurofilament medium subunit (NFM), both lysine-rich proteins, consistent with the adducts being limited to lysine residues. In vitro, HNE treatment of permeabilized sciatic nerve showed the same specificity, i.e. NFH and NFM are the only proteins that reacted with HNE, providing they are phosphorylated. Quantitative immunoblot analysis of two strains of mice ages 1-33 months showed that the levels of HNE adducts on NFH are consistent throughout life. Additionally, mice transgenic for human superoxide dismutase-1 with G85R mutation show no difference in HNE adduction to NFH compared with controls. Taken together, these studies indicate that HNE adduction to NFH is physiological, and its constancy from birth to senility as well as its dependence on phosphorylation argues that NFH and NFM modification may play a role in protecting the membrane-rich axon from toxic aldehydes resulting from oxidative damage.