Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol.

COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants.

Morphometric network-based abnormalities correlate with psychiatric comorbidities and gene expression in PCDH19-related developmental and epileptic encephalopathy.

Protocadherin-19 (PCDH19) developmental and epileptic encephalopathy causes an early-onset epilepsy syndrome with limbic seizures, typically occurring in clusters and variably associated with intellectual disability and a range of psychiatric disorders including hyperactive, obsessive-compulsive and autistic features. Previous quantitative neuroimaging studies revealed abnormal cortical areas in the limbic formation (parahippocampal and fusiform gyri) and underlying white-matter fibers. In this study, we adopted morphometric, network-based and multivariate statistical methods to examine the cortex and substructure of the hippocampus and amygdala in a cohort of 20 PCDH19-mutated patients and evaluated the relation between structural patterns and clinical variables at individual level.

A registry for Dravet syndrome: The Italian experience.

Objectives: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality.

Methods: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis.

Seizure Outcome of Temporal Lobe Epilepsy Surgery in Adults and Children: A Systematic Review and Meta-Analysis.

Background: Temporal lobe epilepsy (TLE) surgery is associated with the best seizure outcome in adults, although its long-term results remain suboptimal. Retrospective pediatric studies suggest better figures whose determinants are poorly understood.

Objective: To conduct a systematic review and meta-analysis of studies on the efficacy of TLE surgery in children (age younger than 18 years) and adults.

Surgical outcome of temporal plus epilepsy is improved by multilobar resection.

Objective: Temporal plus epilepsy (TPE) represents a rare type of epilepsy characterized by a complex epileptogenic zone including the temporal lobe and the close neighboring structures. We investigated whether the complete resection of temporal plus epileptogenic zone as defined through stereoelectroencephalography (SEEG) might improve seizure outcome in 38 patients with TPE.

Methods: Inclusion criteria were as follows: epilepsy surgery performed between January 1990 and December 2001, SEEG defining a temporal plus epileptogenic zone, unilobar temporal operations ("temporal lobe epilepsy [TLE] surgery") or multilobar interventions including the temporal lobe ("TPE surgery"), magnetic resonance imaging either normal or showing signs of hippocampal sclerosis, and postoperative follow-up of at least 12 months.

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

Objective: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers.

Methods: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons.

Patterns and predictors of language representation and the influence of epilepsy surgery on language reorganization in children and young adults with focal lesional epilepsy.

Mapping brain functions is crucial for neurosurgical planning in patients with drug-resistant seizures. However, presurgical language mapping using either functional or structural networks can be challenging, especially in children. In fact, most of the evidence on this topic derives from cross-sectional or retrospective studies in adults submitted to anterior temporal lobectomy.

Customized multigene panels in epilepsy: the best things come in small packages.

Over the past 10 years, the increasingly important role played by next-generation sequencing panels in the genetic diagnosis of epilepsy has led to a growing list of gene variants and a plethora of new scientific data. To date, however, there is still no consensus on what constitutes the "ideal panel design," or on the most rational criteria for selecting the best candidates for gene-panel analysis, even though both might optimize the cost-benefit ratio and the diagnostic efficiency of customized gene panels. Even though more and more laboratories are adopting whole-exome sequencing as a first-tier diagnostic approach, interpreting, "in silico," a set of epilepsy-related genes remains difficult.

Clinical and electroencephalographic correlates of psychiatric features in children with frontal lobe epilepsy.

Background And Objective: Frontal lobe epilepsy (FLE) is often associated with psychiatric features, although the factors predisposing to the concurrence of these conditions have yet to be determined, especially in younger children. We aimed at defining possible clinical and electroencephalography (EEG) features that may enhance the psychiatric risk in pediatric FLE.

Method: We performed a structured psychiatric assessment of 59 children with FLE, using both categorical and dimensional approaches, correlated psychopathology with epilepsy data, and cognitive development.

Internalizing and externalizing symptoms in preschool and school-aged children with epilepsy: Focus on clinical and EEG features.

Introduction: Psychiatric and behavioral problems are frequent comorbidities of epilepsy, although their clinical and electroencephalographic (EEG) correlates remain uncertain. In this study, we have assessed the frequency of psychopathological problems in a cohort of children with epilepsy, and established their main clinical and EEG-associated features.

Methods: One hundred fifty-nine young patients with epilepsy were recruited and assessed through the Child Behavior Checklist for preschool-aged children (CBCL 1 1/2-5) or for school-aged children (CBCL 6-18).

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

Objective: The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014.

Methods: A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014.

Results: Retrospective data on 527 surgical procedures were collected.

Unilobar surgery for symptomatic epileptic spasms.

Objective: To assess factors associated with favorable seizure outcome after surgery for symptomatic epileptic spasms and improve knowledge on pathophysiology of this seizure type.

Methods: Inclusion criteria were: (1) age between 6 months and 15 years at surgery; (2) active epileptic spasms; (3) follow-up after surgery >1 year.

Results: We retrospectively studied 80 children (aged 1.

The Revolution in Migraine Genetics: From Aching Channels Disorders to a Next-Generation Medicine.

Channelopathies are a heterogeneous group of neurological disorders resulting from dysfunction of ion channels located in cell membranes and organelles. The clinical scenario is broad and symptoms such as generalized epilepsy (with or without fever), migraine (with or without aura), episodic ataxia and periodic muscle paralysis are some of the best known consequences of gain- or loss-of-function mutations in ion channels. We review the main clinical effects of ion channel mutations associated with a significant impact on migraine headache.

Effectiveness of antiepileptic therapy in patients with PCDH19 mutations.

Purpose: PCDH19 mutations cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life, epilepsy is known to be highly pharmacoresistant. The aim of our study was to evaluate the effectiveness of antiepileptic therapy in patients with PCDH19 mutations.

Dysgraphia as a Mild Expression of Dystonia in Children with Absence Epilepsy.

Background: Absence epilepsy (AE) is etiologically heterogeneous and has at times been associated with idiopathic dystonia.

Objectives: Based on the clinical observation that children with AE often exhibit, interictally, a disorder resembling writer's cramp but fully definable as dysgraphia, we tested the hypothesis that in this particular population dysgraphia would represent a subtle expression of dystonia.

Methods: We ascertained the prevalence of dysgraphia in 82 children with AE (mean age 9.

Making memories: the development of long-term visual knowledge in children with visual agnosia.

There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood.

A pharmacokinetic study and correlation with clinical response of rufinamide in infants with epileptic encephalopathies.

Aim: To evaluate the relationship between the pharmacokinetic (PK) parameters and therapeutic and adverse effects of rufinamide (RUF) in children with epileptic encephalopathies (EE) aged <4 years.

Methods: PK analysis was conducted at the steady state using a previously validated liquid chromatography tandem-mass spectrometric method in 15 children aged 6-42 months treated with RUF in add-on. Responders were defined as patients who achieved >50% decrease of seizures.

Benign childhood focal epilepsies.

The idiopathic focal epilepsies comprise a group of syndromes characterized by focal-onset seizures for which there is no detectable structural brain abnormality and for which there is a proposed functional mechanism for the epilepsy and electroencephalography (EEG) abnormalities. This group includes benign rolandic epilepsy (BRE), benign epilepsy with occipital paroxysms (both early onset and late-onset types), idiopathic photosensitive occipital lobe epilepsy, and some less well-defined syndromes. The limits of the early onset idiopathic occipital epilepsy syndrome are not clear, and perhaps this entity represents part of a larger syndrome group of "autonomic" age-related epilepsies.

Impaired object identification in idiopathic childhood occipital epilepsy.

Purpose: To investigate whether children with epilepsy primarily affecting the occipital cortex exhibit impairment of visual object identification and to what extent such a hypothesized dysfunction is related to an interfering functional, rather than structural, process.

Method: We studied nine children with idiopathic childhood occipital epilepsy (ICOE) and compared them to eight children with lesional posterior cortex epilepsy (PCEs) and to 60 age-matched controls. We applied an "ascendent" paradigm of object identification, using a coarse-to-fine order procedure, which gradually integrated spatial frequency information from the most blurred image to the complete figure.

Patterns of prescription of antiepileptic drugs in patients with refractory epilepsy at tertiary referral centres in Italy.

Purpose: To evaluate the pattern of prescription of antiepileptic drugs (AEDs) and other medications in a representative population of patients with refractory epilepsy attending tertiary referral centres in Italy.

Methods: Descriptive analysis of data obtained at baseline from 933 adults and 191 children with refractory epilepsy enrolled consecutively in an observational study at 11 tertiary referral centres in Italy. Multivariate logistic regression analysis was used to assess predictors of utilization of the most commonly prescribed AEDs.

Rapid assay of rufinamide in dried blood spots by a new liquid chromatography-tandem mass spectrometric method.

Rufinamide (RUF) is a new antiepileptic drug with efficacy in several types of seizures. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate RUF levels during treatment. Therapeutic drug monitoring of RUF could be useful in routine clinical practice.

A 7 Mb duplication at 22q13 in a girl with bipolar disorder and hippocampal malformation.

We identified a duplication of 22q13.1-q13.2 in a 10-year-old girl and demonstrated that this duplication was the recombinant product of a maternal intrachromosomal insertion.