The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group

Neonatal seizures: Is there a relationship between ictal electroclinical features and etiology? A critical appraisal based on a systematic literature review

The aim of this study was to evaluate whether specific etiologies of neonatal seizures have distinct ictal electroclinical features. A systematic review of English articles using the PubMed database since 2004 (last update 9/26/16). Search terms included text words and Medical Subject Headings (MeSH) terms related to neonatal seizures. Eligible articles included reports of neonates with seizures with a full description of seizure semiology and electroclinical findings. Independent extraction of data was performed by 2 authors using predefined data fields, including study quality indicators. Data were collected for every individual patient described in the articles. The dataset was analyzed with the Fisher exact test. The initial search led to 8507 titles; using filters, 2910 titles and abstracts were identified, with 177 full texts selected to be read. Fifty‐seven studies were included in the analysis with 151 neonates (37.7 male and 62.9% term). Genetic etiologies (51%) and sequential seizures (41.1%) predominated in this sample and hypoxic‐ischemic encephalopathy (HIE) accounted for only 4%. The low prevalence of HIE observed was probably due to a publication bias. A significant association was found between etiology and seizure type: hemorrhage with autonomic seizures (P = 0.003), central nervous system (CNS) infection and stroke with clonic seizures (P = 0.042, P < 0.001, respectively), metabolic/vitamin‐related disorders, and inborn errors of metabolism with myoclonic seizures (P < 0.001). There were also specific electroencephalography (EEG) patterns seen with certain etiologies: vascular disorders and electrolyte imbalance with focal ictal discharges (P < 0.001, P = 0.049 respectively), vitamin‐related disorders with multifocal (P = 0.003), and all categories of genetic disorders with burst‐suppression (P < 0.001). Clonic and autonomic seizures were more frequently present with focal EEG abnormalities (P = 0.001 and P < 0.001), whereas tonic and myoclonic seizures present with burst‐suppression (P = 0.001, P = 0.005). In conclusion, our data suggest that specific associations of etiologies of neonatal seizures with distinct clinical features and EEG patterns might help in the decision to establish appropriate treatment

Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

BACKGROUND: Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. METHODS: We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. RESULTS: We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. CONCLUSIONS: Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described

Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset

Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial. Participants: Subjects with the m.11778G&gt;A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included. Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 1010 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye. Main Outcome Measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4–treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96. Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4–treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4–treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from −0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4–treated and sham-treated eyes was −0.01 logMAR (P = 0.89); the primary end point of a −0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4–treated and sham-treated eyes, respectively. Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G&gt;A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes

Influence of depression and gender on symptom burden among patients with advanced heart failure: Insight from the pain assessment, incidence and nature in heart failure study

© 2019 Elsevier Inc. Introduction: Patients with advanced heart failure (HF) experience many burdensome symptoms that increase patient suffering. Methods: Comparative secondary analysis of 347 patients with advanced HF. Symptom burden was measured with the Memorial Symptom Assessment Scale-HF. Depression was measured using the Patient Health Questionnaire-9. Results: Mean number of symptoms was 13.6. The three most frequent symptoms were non-cardiac pain, shortness of breath, and lack of energy. Patients with depression reported higher symptom burden. Symptom burden differed when compared by gender. Women reported higher symptom burden for other pain, dry mouth, swelling of the arms and legs, sweats, feeling nervous, nausea, and vomiting. Men reported higher symptom burden with sexual problems. Conclusions: Given the high rates of symptoms and distress, interventions are needed to alleviate the symptom burden of patients with advanced HF. Reported symptom burden in patients with advanced heart failure was higher when depressive symptoms were present. Women reported varied number and severity of symptoms than men