Psychiatric phenotype in neurodevelopmental myoclonus-dystonia is underpinned by abnormality of cerebellar modulation on the cerebral cortex.

Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms.

Hemidystonia with polymicrogyria is part of ATP1A3-related disorders.

Introduction: Pathogenic variants in ATP1A3 cause various phenotypes of neurological disorders, including alternating hemiplegia of childhood 2, CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) and rapid-onset dystonia-parkinsonism (RDP). Early developmental and epileptic encephalopathy has also been reported. Polymicrogyria has recently been added to the phenotypic spectrum of ATP1A3-related disorders.

A novel pathogenic variant in DYNC1H1 causes various upper and lower motor neuron anomalies.

Objective: To perform genotype-phenotype, clinical and molecular analysis in a large 3-generation family with autosomal dominant congenital spinal muscular atrophy.

Methods: Using a combined genetic approach including whole genome scanning, next generation sequencing-based multigene panel, whole genome sequencing, and targeted variant Sanger sequencing, we studied the proband and multiple affected individuals of this family who presented bilateral proximal lower limb muscle weakness and atrophy.

Results: We identified a novel heterozygous variant, c.

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study.

To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day.

Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases.

The molecular diagnosis of early-onset epileptic encephalopathy (EOEE), an expanding field in child neurology, is becoming increasingly possible thanks to the widespread availability of next-generation sequencing and whole-exome sequencing. In the past 15 years, mutations in STXBP1, KCNQ2, SCN2A, SCN8A and numerous other genes have been reported, giving a more accurate insight for these rare diseases. Among these genes, germline mutations in Phosphatidyl Inositol Glycan A (PIGA) gene were first reported in 2012.

Magnetic resonance imaging diagnosis of subependymal giant cell astrocytomas in follow-up of children with tuberous sclerosis complex: should we always use contrast enhancement?

Background: Subependymal giant cell astrocytomas (SEGAs) arise in 10-26% of tuberous sclerosis complex (TSC) patients. SEGAs cause obstructive hydrocephalus and increase morbi-mortality. It is recommended that TSC patients be followed with contrast enhanced magnetic resonance imaging (CE-MRI), but repetitive use of gadolinium-based contrast-agents (GBCAs) may cause organ deposits.

Expanding the Spectrum of Neurological Manifestations in Cutis Laxa, Autosomal Recessive, Type IIIA.

Cutis laxa is a heterogeneous group of diseases, characterized by abundant and wrinkled skin and a variable degree of intellectual disability. Cutis laxa, autosomal recessive, type IIIA and autosomal dominant 3 syndromes are caused by autosomal recessive or de novo pathogenic variants in . Autosomal recessive variants are known to lead to the most severe neurological phenotype, and very few patients have been described.

Xq28 copy number gain causing moyamoya disease and a novel moyamoya syndrome.

Background: The molecular anomalies causing moyamoya disease (MMD) and moyamoya syndromes (MMS) are unknown in most patients.

Objective: This study aimed to identify de novo candidate copy number variants (CNVs) in patients with moyamoya.

Methods: Rare de novo CNVs screening was performed in 13 moyamoya angiopathy trios using whole exome sequencing (WES) reads depth data and whole genome high density SNP array data.

Visual sensory processing is altered in myoclonus dystonia.

Background: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes.

Objective: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates.

Methods: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination.

Early magnetic resonance imaging to detect presymptomatic leptomeningeal angioma in children with suspected Sturge-Weber syndrome.

Aim: We aimed to evaluate the contribution of early magnetic resonance imaging (MRI) for the presymptomatic diagnosis of Sturge-Weber syndrome (SWS) in infants with a facial port-wine birthmark (PWB).

Method: Asymptomatic infants with a facial PWB who performed a first MRI scan before 3 months and a second MRI scan after 9 months were included in this study. Leptomeningeal enhancement on T1-weighted imaging and four indirect signs of leptomeningeal angioma (choroid plexus enlargement, cerebral atrophy, signal inversion of the white matter with T2 hyposignal, and T1 hypersignal) were screened on the first MRI scan and correlated with clinical and/or radiological diagnosis of SWS.

Three new cases of ataxia-telangiectasia-like disorder: No impairment of the ATM pathway, but S-phase checkpoint defect.

Ataxia-telangiectasia-like disorder (ATLD) is a rare genomic instability syndrome caused by biallelic variants of MRE11 (meiotic recombination 11) characterized by progressive cerebellar ataxia and typical karyotype abnormalities. These symptoms are common to those of ataxia-telangiectasia, which is consistent with the key role of MRE11 in ataxia-telangiectasia mutated (ATM) activation after DNA double-strand breaks. Three unrelated French patients were referred with ataxia.

Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures.

Objective: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers.

Methods: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types.

Delineating syndrome: From congenital microcephaly to hyperkinetic encephalopathy.

Objective: To provide new insights into the related clinical and imaging phenotypes and refine the phenotype-genotype correlation in syndrome.

Methods: We analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenic variant and performed phenotype-genotype correlations.

Results: A total of 37 different heterozygous mutations were identified, of which 18 are novel.

Childhood idiopathic spinal cord infarction: Description of 7 cases and review of the literature.

Objectives: To describe the clinical course, neuroimaging findings and functional outcome of idiopathic spinal cord infarction (SCI) in adolescents.

Methods: Retrospective and descriptive analyses of seven patients with idiopathic SCI and 50 additional cases from the literature were included. Data collected concerned clinical presentation, MRI findings, initial diagnosis, treatments and functional outcome at the last medical visit.

Recurrent KIF2A mutations are responsible for classic lissencephaly.

Kinesins play a critical role in the organization and dynamics of the microtubule cytoskeleton, making them central players in neuronal proliferation, neuronal migration, and postmigrational development. Recently, KIF2A mutations were identified in cortical malformation syndromes associated with microcephaly. Here, we detected two de novo p.

EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

Background: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be effective and safe in the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide everolimus access to patients with SEGA associated with TSC and to mainly assess the safety and also efficacy of everolimus in a real-world setting.

Methods: EFFECTS was a phase 3b, open-label, noncomparative, multicenter, expanded access study.