Kerguelen plateau : a volcanic passive margin fragment ?

The 21-25-km-thick crust of the southern Kerguelen Plateau consists of three units: (1) a ≤ 2.3-km-thick sedimentary cover; (2) a 3-6-km-thick basaltic layer with velocities ranging from 4.5 to 6.2 km/s; and (3) a 15-17-km-thick lower crust with velocities from 6.6 to 6.9 km/s, including a 3-6-km-thick transition zone located at the base of the crust. The low-velocity transition zone has an average velocity of 6.7 km/s and exhibits several internal wide-angle reflections. The velocity-depth structure of the crust differs significantly from that of other hotspot-related oceanic plateaus and suggests that the southern Kerguelen Plateau may be a fragment of a volcanic passive margin composed of a thinned continental crust overlain by basalt flows

High-resolution imaging of basin-bounding normal faults in the Southern Apennines seismic belt (Italy) by traveltime and frequency-domain full-waveform tomography

We apply a two-step seismic imaging flow by combined first-arrival traveltime and frequency-domain waveform tomographies to dense wide aperture data collected in the Val d’Agri basin (southern Italy). A large wavelength Vp model determined by first-arrival traveltime tomography is used as a starting model for waveform tomography. The multiscale waveform tomography consisting of successive inversion of increasing frequencies allows to progressively reconstruct the short wavelengths of the velocity model, providing valuable information on the Quaternary basin and on range-bounding normal-faulting systems

Topiramate in children and adolescents with epilepsy and mental retardation: a prospective study on behavior and cognitive effects.

The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents. 2007 Elsevier Inc. All rights reserved

Role of folic acid depletion on homocysteine serum level inchildren and adolescents with epilepsy and different MTHFR C677T genotypes.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. An elevated total plasma Hcy concentration (tHcy) is a risk factor for vascular disease. The present study aimed to assess the role of antiepileptic drugs (AEDs) and C677T methylenetetrahydrofolate (MTHFR) polymorphisms on tHcy in pediatric patients with epilepsy treated for at least 6 months with various treatment regimens protocols including the newer AEDs. The study group was recruited from children and adolescents with epilepsy followed up in the Child Neuropsychiatry Clinic of the Second University of Naples, between January 2007 and March 2008. Inclusion criteria were: (1) patients with epilepsy, treated with one or more anticonvulsant drugs for at least 6 months; (2) age between 2 and 16 years. Plasma tHcy concentrations were considered elevated when they exceeded 10.4 mmol/L, and folate concentrations <3 ng/mL were considered deficient. Serum vitamin B12 levels were considered normal between 230 and 1200 pg/mL. The study group was composed of 78 patients (35 males, 43 females), aged between 3 and 15 years (mean 8.9 years). Thirtyfive patients were taking AED monotherapy, 43 polytherapy. Sixty-three healthy sex- and age-matched children and adolescents served as controls. The mean tHcy value in the patient group was higher than the mean value in the control group (12.11 7.68 mmol/L vs 7.4 4.01 mmol/L; p < 0.01). DNA analysis for the MTHFR C677T polymorphism showed the CT genotype in 46%, CC in 35% and TT in 17.8% of cases. Decreased folic acid serum levels significantly correlated with increased tHcy levels (p < 0.003). Female sex was a less significant risk factor for increased tHcy levels (p = 0.039). Our study confirms the association between hyperhomocysteinemia and epilepsy. The elevation of tHcy is essentially related to low folate levels. Correction of poor folate status, through supplementation, remains the most effective approach to normalize tHcy levels in patients on AED mono- or polytherapy

Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet.

Objective – The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. Methods – The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. Results – While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg ⁄ l 1.0), valproic acid showed a slight but not significant decrease (mean decresase of 6.7 mg ⁄ l 3.2), 2 weeks after the start of the diet. Conclusions – Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified

The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy

Glutamate is the brain’s main excitatory neurotransmitter. Glutamatergic neurons primarily compose basic neuronal networks, especially in the cortex. An imbalance of excitatory and inhibitory activities may result in epilepsy or other neurological and psychiatric conditions. Among glutamate receptors, AMPA receptors are the predominant mediator of glutamate-induced excitatory neurotransmission and dictate synaptic efficiency and plasticity by their numbers and/or properties. Therefore, they appear to be a major drug target for modulating several brain functions. Perampanel (PER) is a highly selective, noncompetitive AMPA antagonist approved in several countries worldwide for treating different types of seizures in various epileptic conditions. However, recent data show that PER can potentially address many other conditions within epilepsy and beyond. From this perspective, this review aims to examine the new preclinical and clinical studies—especially those produced from 2017 onwards—on AMPA antagonism and PER in conditions such as mesial temporal lobe epilepsy, idiopathic and genetic generalized epilepsy, brain tumor-related epilepsy, status epilepticus, rare epileptic syndromes, stroke, sleep, epilepsy-related migraine, cognitive impairment, autism, dementia, and other neurodegenerative diseases, as well as provide suggestions on future research agenda aimed at probing the possibility of treating these conditions with PER and/or other AMPA receptor antagonists

NeAT: a Nonlinear Analysis Toolbox for Neuroimaging

NeAT is a modular, flexible and user-friendly neuroimaging analysis toolbox for modeling linear and nonlinear effects overcoming the limitations of the standard neuroimaging methods which are solely based on linear models. NeAT provides a wide range of statistical and machine learning non-linear methods for model estimation, several metrics based on curve fitting and complexity for model inference and a graphical user interface (GUI) for visualization of results. We illustrate its usefulness on two study cases where non-linear effects have been previously established. Firstly, we study the nonlinear effects of Alzheimer’s disease on brain morphology (volume and cortical thickness). Secondly, we analyze the effect of the apolipoprotein APOE-ε4 genotype on brain aging and its interaction with age. NeAT is fully documented and publicly distributed at https://imatge-upc.github.io/neat-tool/

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability