Neurophysiological assessment of cortical activity in DEPDC5- and NPRL3-related epileptic mTORopathies.

Background: Mutations in the GATOR1 complex genes, DEPDC5 and NPRL3, play a major role in the development of lesional and non-lesional focal epilepsy through increased mTORC1 signalling. We aimed to assess the effects of mTORC1 hyperactivation on GABAergic inhibitory circuits, in 3 and 5 individuals carrying DEPDC5 and NPRL3 mutations respectively using a multimodal approach including transcranial magnetic stimulation (TMS), magnetic resonance spectroscopy (MRS), and electroencephalography (EEG).

Results: Inhibitory functions probed by TMS and MRS showed no effect of mutations on cortical GABAergic receptor-mediated inhibition and GABA concentration, in both cortical and subcortical regions.

Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial.

Purpose: To determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS).

Methods: The Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6-18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months.

Exploration of a putative susceptibility locus for idiopathic generalized epilepsy on chromosome 8p12.

Purpose: A recent genome-wide scan revealed a major susceptibility locus for idiopathic generalized epilepsies (IGEs) in the chromosomal region 8p12 in 32 IGE families without members with juvenile myoclonic epilepsy (JME). This study explored the presence of an IGE locus in the chromosomal region 8p12.

Methods: Our study included 176 multiplex families of probands with common IGE syndromes.

Ictal SPECT in children with epilepsy: comparison with intracranial EEG and relation to postsurgical outcome.

In order to validate the ability of ictal single photon emission computed tomography (SPECT) to localize the epileptogenic zone (EZ) in children, we compared in 20 patients aged from 10 months to 17 years (mean 6.5 years) the topography of the area of increased ictal perfusion (IPA), determined on the basis of ictal minus interictal scan values, with that of the EZ determined by intracranial EEG recordings and assessed its relationship with the postsurgical outcome. Eighteen patients had symptomatic epilepsy and 10 had extratemporal epilepsy.