Prognostic value of beta-blocker doses in patients with ventricular tachyarrhythmias.

The study investigates the prognostic significance of beta-blocker (BB) dose in patients with ventricular tachyarrhythmias. Limited data regarding the prognostic impact of BB dose in ventricular tachyarrhythmias is available. A large retrospective registry was used including consecutive patients on BB treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Discharge BB doses were grouped as > 0-12.5%, > 12.5-25%, > 25-50%, and > 50% according to doses used in randomized trials. The primary endpoint was all-cause mortality at three years. Secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias and appropriate ICD therapies) and cardiac rehospitalization. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied for statistics. A total of 1313 patients with BB were included; most patients were discharged with > 25-50% of BB target dose (59%). At three years, > 12.5-25% of BB target dose was associated with improved long-term mortality as compared to the > 0-12.5% group (HR = 0.489; 95% CI 0.297-0.806; p = 0.005), whereas higher BB doses did not improve survival (> 25-50%: HR = 0.849; p = 0.434; > 50%: HR = 0.735; p = 0.285). In contrast, the composite endpoint and risk of rehospitalization were not affected by BB target dose. In conclusion, > 12.5-25% of BB target dose is associated with best long-term survival among patients with ventricular tachyarrhythmias. In contrast, risk of the composite arrhythmic endpoint and risk of cardiac rehospitalization were not affected by BB dose.

Facilitation of drug-resistant epilepsy and catastrophic status epilepticus in children with combined pituitary hormone deficiency.

PURPOSE: Clinicians and researchers often focus on the primary cause of seizures and epilepsy, but outcomes in individual patients also depend on multiple other variables, which might be easy to adjust. Previous studies suggest mutual interactions between endocrine disorders and epilepsy. We therefore hypothesized that combined pituitary hormone deficiency (CPHD) facilitates seizures and epilepsy. METHODS: This is a retrospective study from a pediatric center. We determined the proportion of CPHD patients with epilepsy and examined basic clinical features in this group. Patients with super-refractory status epilepticus (SRSE) were reviewed to identify subjects with co-morbid CPHD. Those cases were analyzed in detail. RESULTS: 12 of 73 CPHD patients (16%) also had epilepsy. Various etiologies of CPHD were represented, though five subjects had a cranial tumor or cortical malformation. Epilepsy was drug resistant in all but one patient. Among 12 identified patients with SRSE, 4 were unexpected new-onset cases. Three of these subjects also had CPHD with ACTH deficiency and a febrile infection prior to SRSE. Another common feature was the devastating clinical course: In all three patients, initial MRI already suggested severe neuronal damage, SRSE persisted for at least one week with ongoing need for anesthetic coma, and outcome was poor (two patients survived with major sequelae, one child deceased during the episode). CONCLUSION: Our findings indicate that CPHD may predispose for drug-resistant epilepsy and refractory seizures with catastrophic outcome. We suggest that in children with new-onset SRSE, screening for CPHD should be considered.

Anxiety of families after first unprovoked or first febrile seizure - A prospective, randomized pilot study.

OBJECTIVES: Parents of children with a first unprovoked seizure report high levels of stress and anxiety. Little is known however about interventions that might help to reduce anxiety. We aimed to evaluate anxiety of parents and children after a first unprovoked seizure and assess the anxiety-reducing effect of a semi-structured follow-up in a first seizure clinic (FSC). In comparison, parents of children with febrile seizures are also evaluated, as an example of anxiety evolution without follow-up intervention after provoked seizures. STUDY DESIGN: In this prospective, interventional study, patients presenting with a first unprovoked seizure were randomized to early care (EC) with follow-up in FSC within 3 weeks and late care (LC), follow-up in FSC after 4 months. Anxiety levels of parents and patients were scored with the State Trait Anxiety Inventory (STAI) after the initial seizure (T0), 3 and 12 months (T1, T2). To assess the effect of the semi-structured follow-up, anxiety scores were compared between the two groups at baseline, at T1 (i.e., after intervention in EC but prior to intervention in LC) and at T2. Parents of children with febrile seizures (FS) were prospectively followed up without intervention. RESULTS: Fifty two patients were included (EC n = 18, LC n = 18, FS n = 15). Initial state anxiety in parents was high in all groups. At T1 (i. e. after intervention in EC but not LC) state anxiety was significantly higher in LC (52.2 (16.7) vs. 33.3 (5.3), p < 0.01). This effect persisted after 12 months, despite intervention in LC in the meantime (39.0 (11.7) vs. 28.8 (6.2); p < 0.01)). The effect in children was similar (T1: 40.6 (8.3) vs. 29.8 (5.1); p < 0.05 and T2: 33.5 (4.7) vs. 24.7 (3.6); p < 0.01). State anxiety in FS decreased within 3 months without intervention (50.0 (14.5) to 33.7 (9.2)). CONCLUSIONS: A timely and structured follow-up in a FSC offers effective and sustained reduction of anxiety-levels after first unprovoked seizure in children. In contrast, anxiety after a first febrile seizure decreases over time without additional intervention.

Scalp Ripples Can Predict Development of Epilepsy After First Unprovoked Seizure in Childhood.

OBJECTIVE: Identification of children at risk of developing epilepsy after a first unprovoked seizure can be challenging. Interictal epileptiform discharges are associated with higher risk but have limited sensitivity and specificity. High frequency oscillations (HFOs) are newer biomarkers for epileptogenesis. We prospectively evaluated the predictive value of HFOs for developing epilepsy in scalp electroencephalogram (EEG) of children after a first unprovoked seizure. METHODS: After their first seizure, 56 children were followed prospectively over 12 months and then grouped in "epilepsy" or "no epilepsy." Initial EEGs were visually analyzed for spikes, spike ripples, and ripples. Inter-group comparisons of spike-rates and HFO-rates were done by Mann-Whitney U test. Predictive values and optimal thresholds were calculated by receiver operating characteristic (ROC) curves. RESULTS: In the epilepsy group (n = 26, 46%), mean rates of ripples (0.3 vs 0.09 / minute, p < 0.0001) and spike ripples (0.6 vs 0.06 / minute, p < 0.05) were significantly higher, with no difference in spike rates (1.7 vs 3.0 / minute, p = 0.38). Of those 3 markers, ripples showed the best predictive value (area under the curve [AUC]ripples = 0.88). The optimal threshold for ripples was calculated to be ≥ 0.125 / minute with a sensitivity of 87% and specificity of 85%. Ripple rates were negatively correlated to days passing before epilepsy-diagnosis (R = -0.59, p < 0.0001) and time to a second seizure (R = -0.64, 95% confidence interval [CI] = -0.77 to 0.43, p < 0.0001). INTERPRETATION: We could show that in a cohort of children with a first unprovoked seizure, ripples predict the development of epilepsy better than spikes or spike ripples and might be useful biomarkers in the estimation of prognosis and question of treatment. ANN NEUROL 2021;89:134-142.