PURA-Related Neurodevelopmental Disorders with Epilepsy Treated with Ketogenic Diet: A Case-Based Review.

PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the PURA gene, identified through whole exome sequencing (WES). In addition to the classical PURA deficiency phenotype, our patient exhibited pronounced sialorrhea and seizures, which were effectively treated with the ketogenic diet (KD). Our integrative approach, combining a literature review and bioinformatics data, has led to the first documented clinical case showing improvement in both sialorrhea and seizures with KD treatment, a phenomenon not previously reported. Although a direct relationship between the de novo PURA mutation and the KD was not established, we identified a novel frameshift deletion associated with a new clinical phenotype.

How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

Nutritional interventions improve quality of life of caregivers of children with neurodevelopmental disorders.

Introduction: Children with neurodevelopmental disorders are at high risk for malnutrition. We aimed to investigate the impact of nutritional interventions to children with neurodevelopmental disorders and the quality of life of caregivers.Materials/Method: This is a prospective interventional study of 91 children with neurodevelopmental disorders. The children were separated into two groups: the intervention group and control group. The intervention group was selected from among children who had not been evaluated for nutrition and feeding problems by a pediatric gastroenterologist or dietician for the past one year. Children in the intervention group were called for follow-up visits and their nutritional intervention and anthropometric measurements were initiated by a pediatric gastroenterologist and dietician, at one month, three months, six months, and one year. The WHOQoL-BREF quality of life scale was completed by the caregivers of the children at baseline and at one year.Results: The intervention group had increased malnutrition (p < 0.001) and gastrointestinal system pathologies such as dysphagia (p < 0.001), constipation (p = 0.02), gastroesophageal reflux (p = 0.03) at baseline. After the nutritional intervention, 77.7% of the intervention group gained weight and 55.5% reached the target weight. The quality of life scale scores at baseline were lower among caregivers of the intervention group; however, they reached those of the control group after the nutritional intervention.Conclusion: Close multidisciplinary nutrition monitoring enables children with neurodevelopmental disorders to thrive appropriately and improves the quality of life of caregivers.

Role of fruit and vegetables for the mental health of children: a systematic review

Background: About 10-20% of children and adolescents worldwide experience a mental health problems, while among the factors which may be preventive, there is a diet, especially fruit and vegetables intake. Objective: The aim of the study was to conduct a systematic review of the observational studies analyzing the association between the fruit and vegetables intake and the mental health in pre-schoolers and school-aged children. Material and methods: The systematic review was conducted based on PubMed and Web of Science databases, while the human studies, published in English until June 2019, conducted in populations of pre-schoolers and/ or school-aged children, verifying the influence of fruit and/ or vegetables and products (e.g. juices) intake on a various aspects of mental health were included. Results: The number of 12 studies were included, while a wide area of aspects of mental health was taken into account, including general well-being, emotions, stress, behavioral difficulties and problems, as well as depressive symptoms, or depressive symptoms combined with anxiety. Conclusions: In majority of studies included to the systematic review of the observational studies analyzing the association between the fruit and vegetables intake and mental health in pre-schoolers and school-aged children, the supposed positive influence was confirmed. However, it must be indicated that it was studied only in a few research and the issue must be analyzed in other populations. At the same time, in a number of studies, not fruit and vegetables intake alone was stated to be beneficial, but rather a more general dietary pattern, including also other elements of healthy diet and healthy lifestyle.

Fruit and vegetables intake in adolescents and mental health: a systematic review

Background: The proper nutrition is indicated as a factor of a potential importance for the mental health early in life span, and among the potential products, which may influence, there are fruit and vegetables. Objective: The aim of the study was to conduct a systematic review of the observational studies analyzing the association between the fruit and vegetables intake and the mental health in adolescents. Material and methods: On the basis of PubMed and Web of Science databases, the papers presenting human studies and published in English until June 2019, analyzing the association between intake of fruit and/ or vegetables, as well as related products (e.g. juices) and the mental health were included to the systematic review, while they analyzed a group of adolescents. Results: Based on the conducted systematic review, 17 studies were indicated as those which assess the influence of fruit and vegetables intake on the mental health in adolescents. For the assessment of mental health, diverse variables were taken into account, including positive (happiness, self-esteem), neutral (health-related quality of life, mental health status), and negative ones (loneliness, general difficulties, feeling worried, anxiety, stress and distress, depressive symptoms, depression, suicidal behaviors). Conclusions: Based on the conducted systematic review of observational studies, it may be indicated that in a groups of adolescents there was a positive association between intake of fruit and vegetable products and mental health. Especially beneficial for general mental health in adolescents, were such products as green vegetables, yellow vegetables and fresh fruit.

The Therapeutic Potential of Ketogenic Diet Throughout Life: Focus on Metabolic, Neurodevelopmental and Neurodegenerative Disorders.

This chapter reviews the efficacy of the ketogenic diet in a variety of neurodegenerative, neurodevelopmental and metabolic conditions throughout different stages of life. It describes conditions affecting children, metabolic disorders in adults and disorderrs affecting the elderly. We have focused on application of the ketogenic diet in clinical studies and in preclinical models and discuss the benefits and negative aspects of the diet. Finally, we highlight the need for further research in this area with a view of discovering novel mechanistic targets of the ketogenic diet, as a means of maximising the potential benefits/risks ratio.

Neurodevelopment of children born very preterm and/or with a very low birth weight: 8-Year follow-up of a nutritional RCT.

BACKGROUND: Children born very preterm are at risk for cognitive deficits and motor impairment. Enhanced protein intake immediately after very preterm birth has been associated with favorable growth and improved neurodevelopment. It is unknown whether increased protein intake after discharge from the hospital affects long-term neurodevelopment. OBJECTIVE: The primary objective was to assess neurodevelopment from infancy to 8 years in preterm-born children who received either protein-enriched formula (PDF), standard term formula (TF), or human milk (HM) after discharge. The secondary objective was to assess the correlation between outcomes obtained at 24 months corrected age (CA) and at 8 years. METHODS: This RCT included 152 children born very preterm (gestational age ≤32 weeks) and/or with a very low birth weight (≤1500 g) of whom 102 were randomly assigned to receive PDF (n = 54) or TF (n = 48) from term age to 6 months CA. A control group of infants fed HM (n = 50) was also included. Neurodevelopmental outcomes were assessed at 24 months CA (cognitive and motor functioning; n = 123) and at 8 years (estimated Full Scale Intelligence Quotient, visual-motor skills, verbal memory, attention, and motor functioning; n = 76). RESULTS: The PDF and TF groups were not significantly different in neurodevelopmental outcomes. The HM group had a better cognitive score compared with the PDF group: at 24 months CA 92.9 ± 12.5 vs. 105.2 ± 18.6, P < 0.001 and at 8 years 98.1 ± 11.3 vs. 105.8 ± 9.1, P = 0.017 (P = 0.002 and P = 0.080, respectively, after adjustment for parental educational level). Correlations between outcomes at 24 months CA and 8 years were weak: r = 0.35 and r = 0.37 for cognitive and motor outcomes, respectively. CONCLUSIONS: PDF did not improve long-term neurodevelopmental outcomes as compared with TF. However, these results should be interpreted with caution considering the substantial attrition at follow-up. Furthermore, the correlation between outcomes at different ages was weak, emphasizing the need for long-term follow-up of nutritional intervention studies in preterm-born children.

Recent developments in understanding the role of the gut microbiota in brain health and disease.

There is a growing appreciation of the role of the gut microbiota in all aspects of health and disease, including brain health. Indeed, roles for the bacterial commensals in various psychiatric and neurological conditions, such as depression, autism, stroke, Parkinson's disease, and Alzheimer's disease, are emerging. Microbiota dysregulation has been documented in all of these conditions or in animal models thereof. Moreover, depletion or modulation of the gut microbiota can affect the severity of the central pathology or behavioral deficits observed in a variety of brain disorders. However, the mechanisms underlying such effects are only slowly being unraveled. Additionally, recent preclinical and clinical evidence suggest that targeting the microbiota through prebiotic, probiotic, or dietary interventions may be an effective "psychobiotic" strategy for treating symptoms in mood, neurodevelopmental disorders, and neurodegenerative diseases.

Epigenetics, nutrition and mental health. Is there a relationship?

Many aspects of human development and disease are influenced by the interaction between genetic and environmental factors. Understanding how our genes respond to the environment is central to managing health and disease, and is one of the major contemporary challenges in human genetics. Various epigenetic processes affect chromosome structure and accessibility of deoxyribonucleic acid (DNA) to the enzymatic machinery that leads to expression of genes. One important epigenetic mechanism that appears to underlie the interaction between environmental factors, including diet, and our genome, is chemical modification of the DNA. The best understood of these modifications is methylation of cytosine residues in DNA. It is now recognized that the pattern of methylated cytosines throughout our genomes (the 'methylome') can change during development and in response to environmental cues, often with profound effects on gene expression. Many dietary constituents may indirectly influence genomic pathways that methylate DNA, and there is evidence for biochemical links between nutritional quality and mental health. Deficiency of both macro- and micronutrients has been associated with increased behavioural problems, and nutritional supplementation has proven efficacious in treatment of certain neuropsychiatric disorders. In this review we examine evidence from the fields of nutrition, developmental biology, and mental health that supports dietary impacts on epigenetic processes, particularly DNA methylation. We then consider whether such processes could underlie the demonstrated efficacy of dietary supplementation in treatment of mental disorders, and whether targeted manipulation of DNA methylation patterns using controlled dietary supplementation may be of wider clinical value.

Ketogenic diet and childhood neurological disorders other than epilepsy: an overview.

INTRODUCTION: In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.