Search Results (42)

Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30–50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities —synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE. Full article

Background/Objectives: One of the most abundant and growing neurodevelopmental disorders in recent decades is attention deficit hyperactivity disorder (ADHD). Many trials have been performed on using drugs for the improvement of ADHD signs. This study aimed to detect the possible interaction of naringin with Wnt/β-catenin signaling and its putative anti-inflammatory and protective effects in the mouse ADHD model based on bioinformatic, behavioral, and molecular investigations. Furthermore, molecular docking was applied to investigate possible interactions with the GSK-3β and HSP90 proteins. Methods: Male Swiss albino mice were divided into four groups, a normal control group, monosodium glutamate (SGL) control, SGL + naringin 50 mg/kg, and SGL + naringin 100 mg/kg. The psychomotor activity of the mice was assessed using the self-grooming test, rope crawling test, and attentional set-shifting task (ASST). In addition, biochemical analyses were performed using brain samples. Results: The results of the SGL group showed prolonged grooming time (2.47-folds), a lower percentage of mice with successful crawling on the rope (only 16.6%), and a higher number of trials for compound discrimination testing in the ASST (12.83 ± 2.04 trials versus 5.5 ± 1.88 trials in the normal group). Treatment with naringin (50 or 100 mg per kg) produced significant shortening in the grooming time (31% and 27% reductions), as well as a higher percentage of mice succeeding in crawling with the rope (50% and 83%, respectively). Moreover, the ELISA assays indicated decreased dopamine levels (0.36-fold) and increased TNF-α (2.85-fold) in the SGL control group compared to the normal mice, but an improvement in dopamine level was observed in the naringin (50 or 100 mg per kg)-treated groups (1.58-fold and 1.97-fold). Similarly, the PCR test showed significant declines in the expression of the Wnt (0.36), and β-catenin (0.33) genes, but increased caspase-3 (3.54-fold) and BAX (5.36-fold) genes in the SGL group; all these parameters were improved in the naringin 50 or 100 mg/kg groups. Furthermore, molecular docking indicated possible inhibition for HSP90 and GSK-3β. Conclusions: Overall, we can conclude that naringin is a promising agent for alleviating ADHD symptoms, and further investigations are required to elucidate its mechanism of action. Full article

Extremely preterm birth entails an increased risk for multimorbidity and the prevalence of developmental deficits because this risk is negatively correlated to the number of gestation weeks. This work evaluated subcortical volume changes in children born extremely preterm who received Katona neurohabilitation, as well as the effects of subcortical volume and treatment adherence on their three-year-old neurodevelopment outcomes. Fifteen extremely preterm-born participants were treated from two months to two years old and followed up until past three years of age. The participants received Katona neurohabilitation, which provides vestibular and proprioceptive stimulation and promotes movement integration through the early, intensive practice of human-specific elementary movements. Subcortical brain volumes from magnetic resonance images were obtained at the beginning and after treatment. Also, treatment adherence to Katona neurohabilitation and neurodevelopment outcomes were measured. The results showed that absolute subcortical volumes increased after treatment; however, when adjusted by intracranial volume, these volumes decreased. Subcortical function inhibition allows cortical control and increased connectivity, which may explain decreased adjusted volume. Regression analyses showed that after-treatment hippocampal volumes had a discrete predictive value. However, treatment adherence showed a clear effect on mental and psychomotor neurodevelopment. Thus, the effectiveness of Katona neurohabilitation is constrained by treatment adherence. Full article

According to the DSM-5, neurodevelopmental disorders represent a group of heterogeneous conditions, with onset during the developmental period, characterized by an alteration of communication and social skills, learning, adaptive behavior, executive functions, and psychomotor skills. These deficits determine an impairment of personal, social, scholastic, or occupational functioning. Neurodevelopmental disorders are characterized by an increased incidence and a multifactorial etiology, including genetic and environmental components. Data largely explain the role of genetic and environmental factors, also through epigenetic modifications such as DNA methylation and miRNA. Despite genetic factors, nutritional factors also play a significant role in the pathophysiology of these disorders, both in the prenatal and postnatal period, underscoring that the control of modifiable factors could decrease the incidence of neurodevelopmental disorders. The preventive role of nutrition is widely studied as regards many chronic diseases, such as diabetes, hypertension, and cancer, but actually we also know the effects of nutrition on embryonic brain development and the influence of prenatal and preconceptional nutrition in predisposition to various pathologies. These factors are not limited only to a correct caloric intake and a good BMI, but rather to an adequate and balanced intake of macro and micronutrients, the type of diet, and other elements such as exposure to heavy metals. This review represents an analysis of the literature as regards the physiopathological mechanisms by which food influences our state of health, especially in the age of development (from birth to adolescence), through prenatal and preconceptional changes, underlying how controlling these nutritional factors should improve mothers’ nutritional state to significantly reduce the risk of neurodevelopmental disorders in offspring. We searched key words such as “maternal nutrition and neurodevelopmental disorders” on Pubmed and Google Scholar, selecting the main reviews and excluding individual cases. Therefore, nutrigenetics and nutrigenomics teach us the importance of personalized nutrition for good health. So future perspectives may include well-established reference values in order to determine the correct nutritional intake of mothers through food and integration. Full article

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections. Full article

Background: Autism spectrum disorder (ASD) is a complex neurological development with social and communication deficits and sensory abnormalities. Sensory problems have a significant impact on daily life. Multisensory environments (MSEs), such as Snoezelen^® rooms, offer controlled sensory stimulation. This study aims to evaluate the effect of MSE intervention with self-controlled sensory interactions on adaptive developmental skills and sensory responses in preschool ASD children. Methods: This pilot study was single-blind, randomized, controlled, and adhered to the CONSORT guidelines. Twenty participants were recruited and randomized into two groups: the control group (CG) underwent treatment as usual (TAU) with individual rehabilitation sessions of psychomotor therapy. The experimental group (EG) underwent TAU integrated with the use of an MSE. Developmental abilities and severity levels were assessed, pre-post, with the Psychoeducational Profile, Third Edition (PEP-3) and the Second Edition Childhood Autism Rating Scale (CARS-2). Results: A significant difference in taste, smell, and tactile behaviors according to the CARS-2, as well as in gross motor skills according to the PEP-3, was observed in the EG. Conclusions: This pilot study suggests that MSE-integrated intervention may be a valid strategy to improve self-management of the sensory profile in autistic individuals. Further studies are needed to better identify the intervention methodology and effectiveness. Full article

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry. Full article

Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cognitive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states. Full article

Vigilance refers to the capability of humans to respond accordingly to relevant and unpredictable tasks and surrounding environment changes over prolonged periods of time. Identifying vigilance decrements can, therefore, have huge and vital impacts on several operational environments in which a simple slip of mind or a deficit in attention can bear life-threatening and disastrous consequences. Several methodologies have been proposed to assess and characterize vigilance, and the results have indicated that the sole measure of performance and self-reports are not enough to obtain reliable and real-time vigilance measure. Nowadays, monitoring head and body movements to obtain information about performance in daily activities, health conditions, and mental states has become very simple and cheap due to the miniaturization of inertial measurement units and their widespread integration into common electronic devices (e.g., smart glasses, smartwatches). The present study aimed to understand the relationship between head micromovements and body posture changes to vigilance decrease while performing the psychomotor vigilance task. The results highlighted that head micromovements can be employed to track vigilance decrement during prolonged periods of time and discriminate between conditions of high or low vigilance. Full article

Chromosomal submicroscopic imbalances represent well-known causes of neurodevelopmental disorders. In some cases, these can cause specific autosomal dominant syndromes, with high-to-complete penetrance and de novo occurrence of the variant. In other cases, they result in non-syndromic neurodevelopmental disorders, often acting as moderate-penetrance risk factors, possibly inherited from unaffected parents. We describe a three-generation family with non-syndromic neuropsychiatric features segregating with a novel 19q13.32q13.33 microduplication. The propositus was a 28-month-old male ascertained for psychomotor delay, with no dysmorphic features or malformations. His mother had Attention-Deficit/Hyperactivity Disorder and a learning disability. The maternal uncle had an intellectual disability. Chromosomal microarray analysis identified a 969 kb 19q13.32q13.33 microduplication in the proband. The variant segregated in the mother, the uncle, and the maternal grandmother of the proband, who also presented neuropsychiatric disorders. Fragile-X Syndrome testing was negative. Exome Sequencing did not identify Pathogenic/Likely Pathogenic variants. Imbalances involving 19q13.32 and 19q13.33 are associated with neurodevelopmental delay. A review of the reported microduplications allowed to propose BICRA (MIM *605690) and KPTN (MIM *615620) as candidates for the neurodevelopmental delay susceptibility in 19q13.32q13.33 copy number gains. The peculiarities of this case are the small extension of the duplication, the three-generation segregation, and the full penetrance of the phenotype. Full article

Background: Cancer-related cognitive impairment (CRCI) is one of the most serious side effects of cancer that negatively impacts the quality of life of cancer patients and survivors. There is evidence of CRCI in Hodgkin lymphoma patients (HL); however, there is a lack of studies examining the presence of cognitive deficits before starting any treatment in HL patients. Methods: Forty adult patients (N = 40) newly diagnosed with HL (with no previous cancer diagnoses) and 40 healthy controls (N = 40) matched for age, sex, education, and premorbid intellect completed the neuropsychological battery and subjective and objective measures of affective distress and quality of life. Results: The results showed impairment in three out of six cognitive domains: verbal memory and learning, speed of processing/psychomotor speed, and abstraction/executive functions in the HL patients before the initiation of any treatment. The speed of processing/psychomotor speed domain is negatively correlated with depression. Conclusion: Cognitive deterioration in verbal memory and learning and abstraction/executive functions domains in HL patients seems to occur before the initiation of treatment independently of anxiety, depression, or physical symptoms. This suggests that HL itself may cause cognitive deficits in these cognitive domains. However, the underlying causes of CRCI still remain unclear. Full article

Biallelic pathogenic variants in subunits of succinyl-CoA synthetase (SCS), a tricarboxylic acid (TCA) cycle enzyme, are associated with mitochondrial encephalomyopathy in humans. SCS catalyzes the interconversion of succinyl-CoA to succinate, coupled to substrate-level phosphorylation of either ADP or GDP, within the TCA cycle. SCS-deficient encephalomyopathy typically presents in infancy and early childhood, with many patients succumbing to the disease during childhood. Common symptoms include abnormal brain MRI, basal ganglia lesions and cerebral atrophy, severe hypotonia, dystonia, progressive psychomotor regression, and growth deficits. Although subunits of SCS were first identified as causal genes for progressive metabolic encephalomyopathy in the early 2000s, recent investigations are now beginning to unravel the pathomechanisms underlying this metabolic disorder. This article reviews the current understanding of SCS function within and outside the TCA cycle as it relates to the complex and multifactorial mechanisms underlying SCS-related mitochondrial encephalomyopathy. Full article

Background: Preterm birth is one of the world’s critical health problems, with an incidence of 5% to 18% of living newborns according to various countries. White matter injuries due to preoligodendrocytes deficits cause hypomyelination in children born preterm. Preterm infants also have multiple neurodevelopmental sequelae due to prenatal and perinatal risk factors for brain damage. The purpose of this work was to explore the effects of the brain risk factors and MRI volumes and abnormalities on the posterior motor and cognitive development at 3 years of age. Methods: A total of 166 preterm infants were examined before 4 months and clinical and MRI evaluations were performed. MRI showed abnormal findings in 89% of the infants. Parents of all infants were invited to receive the Katona neurohabilitation treatment. The parents of 128 infants accepted and received Katona’s neurohabilitation treatment. The remaining 38 infants did not receive treatment for a variety of reasons. At the three-year follow-up, Bayley’s II Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) were compared between treated and untreated subjects. Results: The treated children had higher values of both indices than the untreated. Linear regression showed that the antecedents of placenta disorders and sepsis as well as volumes of the corpus callosum and of the left lateral ventricle significantly predicted both MDI and PDI, while Apgar < 7 and volume of the right lateral ventricle predicted the PDI. Conclusions: (1) The results indicate that preterm infants who received Katona’s neurohabilitation procedure exhibited significantly better outcomes at 3 years of age compared to those who did not receive the treatment. (2) The presence of sepsis and the volumes of the corpus callosum and lateral ventricles at 3–4 months were significant predictors of the outcome at 3 years of age. Full article

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies. Full article

Hepatic encephalopathy (HE) is a chronic metabolic disease accompanied by neuropathological and neuropsychiatric features, including memory deficits, psychomotor dysfunction, depression, and anxiety. Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by tau hyperphosphorylation, excessive amyloid beta (Aβ) accumulation, the formation of fibrillary tangles, hippocampus atrophy, and neuroinflammation. Recent studies have suggested a positive correlation between HE and AD. Some studies reported that an impaired cholesterol pathway, abnormal bile acid secretion, excessive ammonia level, impaired Aβ clearance, astrocytic dysfunction, and abnormal γ-aminobutyric acid GABAergic neuronal signaling in HE may also be involved in AD pathology. However, the mechanisms and related genes involved in AD-like pathology in the HE brain are unclear. Thus, we compared the cortical transcriptome profile between an HE mouse model, bile duct ligation (BDL), and an AD mouse model, the 5×FAD. Our study showed that the expression of many genes implicated in HE is associated with neuronal dysfunction in AD mice. We found changes in various protein-coding RNAs, implicated in synapses, neurogenesis, neuron projection, neuron differentiation, and neurite outgrowth, and non-coding RNAs possibly associated with neuropathology. Our data provide an important resource for further studies to elucidate AD-like pathophysiology in HE patients. Full article