Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. METHODS: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. RESULTS: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. CONCLUSION: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. PLAIN LANGUAGE SUMMARY: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Neural correlates of mindfulness meditation and hypnosis on magnetic resonance imaging: similarities and differences. A scoping review.

BACKGROUND: Mindfulness meditation (MM) and hypnosis practices are gaining interest in mental health, but their physiological mechanisms remain poorly understood. This study aimed to synthesize the functional, morphometric and metabolic changes associated with each practice using magnetic resonance imaging (MRI), and to identify their similarities and differences. METHODS: MRI studies investigating MM and hypnosis in mental health, specifically stress, anxiety, and depression, were systematically screened following PRISMA guidelines from four research databases (PubMed, Web of Science, Embase, PsycINFO) between 2010 and 2022. RESULTS: In total, 97 references met the inclusion criteria (84 for MM and 13 for hypnosis). This review showed common and divergent points regarding the regions involved and associated brain connectivity during MM practice and hypnosis. The primary commonality between mindfulness and hypnosis was decreased default mode network intrinsic activity and increased central executive network - salience network connectivity. Increased connectivity between the default mode network and the salience network was observed in meditative practice and mindfulness predisposition, but not in hypnosis. CONCLUSIONS: While MRI studies provide a better understanding of the neural basis of hypnosis and meditation, this review underscores the need for more rigorous studies.

Hypnosis therapy for self-esteem in pediatric neurology practice: A pilot exploratory study.

BACKGROUND: A number of pediatric conditions are chronic, such as attention-deficit/hyperactivity disorder (ADHD), idiopathic epilepsies, or anxiety disorder. They all have an impact on self-esteem with consequences on the quality of life. Hypnosis is a therapeutic strategy that consists in putting into trance an individual who becomes receptive to appropriate suggestions. Such an approach is now considered a simple and safe therapy with limited cost. The aim of the present study was to show the feasibility of hypnosis for improving self-esteem in children with the aforementioned conditions. METHODS: We conducted a single-center study with prospectively collected data during routine care. Patients with ADHD, idiopathic epilepsies, or anxiety disorder and a low self-esteem were included between April 2018 and February 2020. They all underwent the same hypnosis protocol conducted by the same therapist. Self-esteem was assessed using two self-evaluation scales, the Jodoin 40 scale and Piers-Harris Self-Concept Scale, and a self-assigned self-esteem score at the beginning and at the end of the hypnosis session. RESULTS: Among the 14 children included, 11 were studied (6 ADHD, 1 anxiety disorder, 4 idiopathic epilepsies). The median age at inclusion was 12.2 years and the sex ratio was 4:3 (boys:girls). Final comparisons showed that self-esteem had improved, which was statistically significant regarding the Jodoin 40 scale and the self-assigned self-esteem score (p ≤ 0.05). Neither side effect nor disease worsening was observed. CONCLUSION: This study illustrates the feasibility of therapeutic hypnosis in clinical practice for improving self-esteem in chronic pediatric conditions.

Proton MR spectroscopic imaging of basal ganglia and thalamus in neurofibromatosis type 1: correlation with T2 hyperintensities.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is frequently associated with hyperintense lesions on T2-weighted images called "unidentified bright objects" (UBO). To better characterize the functional significance of UBO, we investigate the basal ganglia and thalamus using spectroscopic imaging in children with NF1 and compare the results to anomalies observed on T2-weighted images. METHODS: Magnetic resonance (MR) data of 25 children with NF1 were analyzed. On the basis of T2-weighted images analysis, two groups were identified: one with normal MR imaging (UBO- group; n = 10) and one with UBO (UBO+ group; n = 15). Within the UBO+ group, a subpopulation of patients (n = 5) only had lesions of the basal ganglia. We analyzed herein seven regions of interest (ROIs) for each side: caudate nucleus, capsulo-lenticular region, lateral and posterior thalamus, thalamus (lateral and posterior voxels combined), putamen, and striatum. For each ROI, a spectrum of the metabolites and their ratio was obtained. RESULTS: Patients with abnormalities on T2-weighted images had significantly lower NAA/Cr, NAA/Cho, and NAA/mI ratios in the lateral right thalamus compared with patients with normal T2. These abnormal spectroscopic findings were not observed in capsulo-lenticular regions that had UBO but in the thalamus region that was devoid of UBO. CONCLUSION: Multivoxel spectroscopic imaging using short-time echo showed spectroscopic abnormalities in the right thalamus of NF1 patients harboring UBO, which were mainly located in the basal ganglia. This finding could reflect the anatomical and functional interactions of these regions.

Thalamo-striatal T2-weighted hyperintensities (unidentified bright objects) correlate with cognitive impairments in neurofibromatosis type 1 during childhood.

Learning disabilities represent the main childhood complication in neurofibromatosis type 1 (NF1). Patients frequently exhibit T2-weighted hyperintensities called unidentified bright objects (UBOs) on brain magnetic resonance imaging (MRI), with unclear relationship to such cognitive disabilities. This study aimed to determine whether thalamo-striatal UBOs correlate with cognitive disturbances. Thirty-seven NF1 children were studied: 24 with UBOs (18 of which were thalamo-striatal UBOs), and 13 without UBOs. NF1 subjects carrying thalamo-striatal UBOs had significantly lower IQs and visuospatial performances than those without UBOs in this location. These results suggest that UBOs may contribute to NF1 cognitive impairments through thalamo-cortical dysfunction.

Lamotrigine is neuroprotective in the energy deficiency model of MPTP intoxicated mice.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits the mitochondrial complex I of the respiratory chain. This results in ATP and ion homeostasis disturbances, which lead to selective death of the substantia nigra dopaminergic neurons. Well known as a Parkinson's disease model, the MPTP animal model also provides a potential paradigm of the energy deficiencies found in childhood. In these conditions, anticonvulsants may provide neuroprotection by limiting cellular energy consumption. We tested valproate, topiramate and lamotrigine in the MPTP mouse model. Dopamine transporter (DAT) density was assessed by quantitative autoradiography, tyrosine hydroxylase (TH) was evaluated by immunohistochemistry and dopamine (DA) levels by HPLC-ED whereas neuronal apoptosis was monitored through active caspase-3. Expectedly, the DAT density, TH immunoreactive neurons and DA content in the MPTP group were respectively reduced to 51%, 40% and 26% versus control animals. Unlike valproate and topiramate, lamotrigine provided a significant neuroprotection against MPTP in maintaining these levels at 99%, 74% and 58% respectively and reducing the induced apoptosis. Altogether, the data indicate that lamotrigine limits dopaminergic neuronal death in the substantia nigra and promotes striatal dendrites sprouting. Lamotrigine, a widely used and well-tolerated molecule in young patients, could represent a valuable adjuvant therapy in various energy deficiency conditions during childhood.