Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia.

Background And Purpose: Juvenile- or adult-onset forms of severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described.

Methods: Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies.

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial.

Background: Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF).

Methods: A multicentre, randomised double-blind, clinical trial was conducted in children with CF.

Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy.

De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data.

Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like clinical syndrome.

Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency of one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy and stroke-like episodes. Multiple OXPHOS defects and decreased mtDNA copy number (40%) were detected in muscle homogenate.

Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly.

Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations.

Hemicerebellitis can drive handedness shift.

Background: Hemicerebellitisis a rare acquired condition, typical of the pediatric age. A residual switched handedness may develop after remission of acute cerebellar symptoms.

Case Presentation: Herein we describe a motor functional MRI studyperformed in a 35-year old girl who had switched to left-handedness after acute right hemicerebellitis in childhood.

Alexithymic trait is associated with right IFG and pre-SMA activation in non-emotional response inhibition in healthy subjects.

Event-related fMRI studies have explored emotion inhibitory processes in alexithymic individuals and have demonstrated abnormal BOLD activations in the processing of emotional stimuli. So far, no study has explored the relationship between the alexithymic trait and the general inhibition process, namely utilizing stimuli devoid of emotional valence. In this study 26 healthy subjects were administered the Toronto Alexithymic Scale (TAS-20) questionnaire to measure the alexithymic trait and performed an event related Go/Nogo task build up with letters during fMRI acquisition.

SSADH deficiency in an Italian family: a novel ALDH5A1 gene mutation affecting the succinic semialdehyde substrate binding site.

SSADH deficiency (SSADHD) is a rare autosomal recessively inherited metabolic disorder. It is associated with mutations of ALDH5A1 gene, coding for the homotetrameric enzyme SSADH. This enzyme is involved in γ-aminobutyric acid (GABA) catabolism, since it oxidizes succinic semialdehyde (SSA) to succinate.

The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression.

Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients.

Lissencephaly: Expanded imaging and clinical classification.

Lissencephaly ("smooth brain," LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS-LIS1 (PAFAH1B1) and DCX.

The utility of the basophil activation test in the diagnosis of immediate amoxicillin or amoxicillin-clavulanate hypersensitivity in children and adults.

Background: The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults.

Material And Methods: Eighteen children and 21 adults, with clinical history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer Children's Hospital and San Giovanni di Dio Hospital, respectively.

Comparative Study of 27-Gauge versus 25-Gauge Vitrectomy for the Treatment of Primary Rhegmatogenous Retinal Detachment.

. To compare the vitrectomy time, clinical outcomes, and complications between 27-gauge (27-G) and 25-gauge (25-G) vitrectomy in patients with primary rhegmatogenous retinal detachment (PRRD). .

encephalopathy: Broadening the phenotype and evaluating treatment and outcome.

Objective: To describe better the motor phenotype, molecular genetic features, and clinical course of -related disease.

Methods: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site mutations, detected by next-generation sequencing techniques.

Results: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study.

Purpose: To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE).

Materials And Methods: Multicenter randomized controlled trial. Term newborns with precocious metabolic, clinical and electroencephalographic (EEG) signs of HIE were selected according to their amplified integrated EEG pattern and randomized to receive either TPM (10 mg/kg once a day for the first three days of life) plus moderate hypothermia or hypothermia alone.

Clinical and genetic factors predicting Dravet syndrome in infants with mutations.

Objective: To explore the prognostic value of initial clinical and mutational findings in infants with mutations.

Methods: Combining sex, age/fever at first seizure, family history of epilepsy, EEG, and mutation type, we analyzed the accuracy of significant associations in predicting Dravet syndrome vs milder outcomes in 182 mutation carriers ascertained after seizure onset. To assess the diagnostic accuracy of all parameters, we calculated sensitivity, specificity, receiver operating characteristic (ROC) curves, diagnostic odds ratios, and positive and negative predictive values and the accuracy of combined information.

The Impact of Next-Generation Sequencing on the Diagnosis and Treatment of Epilepsy in Paediatric Patients.

Next-generation sequencing (NGS) has contributed to the identification of many monogenic epilepsy syndromes and is favouring earlier and more accurate diagnosis in a subset of paediatric patients with epilepsy. The cumulative information emerging from NGS studies is rapidly changing our comprehension of the relations between early-onset severe epilepsy and the associated neurological impairment, progressively delineating specific entities previously gathered under the umbrella definition of epileptic encephalopathies, thereby influencing treatment choices and limiting the most aggressive drug regimens only to those conditions that are likely to actually benefit from them. Although ion channel genes represent the gene family most frequently causally related to epilepsy, other genes have gradually been associated with complex developmental epilepsy conditions, revealing the pathogenic role of mutations affecting diverse molecular pathways that regulate membrane excitability, synaptic plasticity, presynaptic neurotransmitter release, postsynaptic receptors, transporters, cell metabolism, and many formative steps in early brain development.

Age-related differences in audiovisual interactions of semantically different stimuli.

Converging results have shown that adults benefit from congruent multisensory stimulation in the identification of complex stimuli, whereas the developmental trajectory of the ability to integrate multisensory inputs in children is less well understood. In this study we explored the effects of audiovisual semantic congruency on identification of visually presented stimuli belonging to different categories, using a cross-modal approach. Four groups of children ranging in age from 6 to 13 years and adults were administered an object identification task of visually presented pictures belonging to living and nonliving entities.

Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.

Germline and somatic mutations in the gene in focal cortical dysplasia and epilepsy.

Objective: To assess the prevalence of somatic mutations in focal cortical dysplasia (FCD) and of germline mutations in a broad range of epilepsies.

Methods: We collected 20 blood-brain paired samples from patients with FCD and searched for somatic variants using deep-targeted gene panel sequencing. Germline mutations in were assessed in a French research cohort of 93 probands with focal epilepsies and in a diagnostic Danish cohort of 245 patients with a broad range of epilepsies.

Quality of life in persons after traumatic brain injury as self-perceived and as perceived by the caregivers.

The primary aim of the study was to adopt QOLIBRI (quality of life after brain injury) questionnaire in a proxy version (Q-Pro), i.e., to use caregivers for comparison and to evaluate whether TBI patients' judgment corresponds to that of their caregivers since the possible self-awareness deficit of the persons with TBI.

Epilepsy in ring chromosome 20 syndrome.

Objective: Ring chromosome 20 syndrome is characterized by severe, drug resistant childhood onset epilepsy, often accompanied by cognitive impairment. We characterized the electro-clinical phenotype and the long-term course of epilepsy in a large series.

Methods: We reviewed the electro-clinical phenotype of 25 patients (aged 8-59 years), and assessed the relationship between epilepsy severity and clinical and/or genetic variables.

Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

Objective: Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis.

Methods: In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent.

Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia.

Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in NEDD4L mapping to the HECT domain of the encoded E3 ubiquitin ligase lead to PNH associated with toe syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed sensitivity of PNH-associated mutants to proteasome degradation.