Randomized Double-Blind Crossover Study for Evaluating a Probiotic Mixture on Gastrointestinal and Behavioral Symptoms of Autistic Children.

Autism spectrum disorders (ASDs) represent a diagnostic challenge with a still partially uncertain etiology, in which genetic and environmental factors have now been assessed. Among the hypotheses underlying the involvement of biological and environmental factors, the gut-brain axis is of particular interest in autism spectrum disorders. Several studies have highlighted the related incidence of particular gastrointestinal symptoms (GISs) in children suffering from ASDs.

The Usefulness of a Targeted Next Generation Sequencing Gene Panel in Providing Molecular Diagnosis to Patients With a Broad Spectrum of Neurodevelopmental Disorders.

Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%-5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs.

EEG at onset and MRI predict long-term clinical outcome in Aicardi syndrome.

Objective: Descriptions of electroencephalographic (EEG) patterns in Aicardi syndrome (AIC) have to date referred to small cohorts of up to six cases and indicated severe derangement of electrical activity in all cases. The present study was conducted to describe the long-term EEG evolution in a larger AIC cohort, followed for up to 23 years, and identify possible early predictors of the clinical and EEG outcomes.

Methods: In a retrospective study, two experienced clinical neurophysiologists systematically reviewed all EEG traces recorded in 12 AIC cases throughout their follow-up, from epilepsy onset to the present.

Impact and management of drooling in children with neurological disorders: an Italian Delphi consensus.

Background: The rate of chronic drooling in children older than 4 years is 0.5%, but it rises to 60% in those with neurological disorders. Physical and psychosocial consequences lead to a reduction in the quality of Life (QoL) of affected patients; however, the problem remains under-recognized and under-treated.

Video game-induced reflex seizures via a smartphone.

Reflex seizures are consistently evoked by a specific afferent stimulus or by patient activity. Patients experiencing reflex seizures when playing a game on a mobile phone are rarely reported. We describe a boy with reflex seizures after prolonged exposure to the game, Cut the rope, on his mobile phone.

The epileptology of Aicardi-Goutières syndrome: electro-clinical-radiological findings.

Objective: Although epileptic seizures occur in approximately a quarter of patients with Aicardi-Goutières syndrome (AGS), their phenotypic and electrophysiological characterization remains elusive. The aim of our study was to characterize epilepsy phenotypes and electroencephalographic (EEG) patterns in AGS and look for possible correlations with clinical, genetic and neuroradiological features.

Methods: We selected patients with an established AGS diagnosis followed at three Italian reference centers.

Anakinra usage in febrile infection related epilepsy syndrome: an international cohort.

Febrile-infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin-1 receptor antagonist, as an immunomodulator for FIRES.

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

Background: Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.

Patient Description: We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization.

Mild Lafora disease: clinical, neurophysiologic, and genetic findings.

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty-three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.

Does the co-occurrence of FGFR3 gene mutation in hypochondroplasia, medial temporal lobe dysgenesis, and focal epilepsy suggest a syndrome?

Background: Hypochondroplasia is a rare skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, and limited extension of the elbow caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that plays a role in controlling nervous system development. Hypochondroplasia with FGFR3 mutation associated with bilateral medial temporal lobe anomalies and focal epilepsy was previously reported in several patients.

Patient: We report clinical, electroclinical, and neuroradiological findings of one patient affected by hypochondroplasia.

Vaccination and occurrence of seizures in SCN1A mutation-positive patients: a multicenter Italian study.

Background: The relation between epileptic seizures and vaccinations is sometimes debated. In the present work, the impact of vaccination on seizure onset and clinical outcome of SCN1A mutation-positive patients is addressed.

Methods: Seventy-two patients diagnosed with Dravet syndrome or generalized epilepsy with febrile seizure plus, carrying SCN1A mutations or not, were included.

Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.

Purpose: To dissect the genetics of benign familial epilepsies of the first year of life and to assess the extent of the genetic overlap between benign familial neonatal seizures (BFNS), benign familial neonatal-infantile seizures (BFNIS), and benign familial infantile seizures (BFIS).

Methods: Families with at least two first-degree relatives affected by focal seizures starting within the first year of life and normal development before seizure onset were included. Families were classified as BFNS when all family members experienced neonatal seizures, BFNIS when the onset of seizures in family members was between 1 and 4 months of age or showed both neonatal and infantile seizures, and BFIS when the onset of seizures was after 4 months of age in all family members.

Lacosamide in pediatric and adult patients: comparison of efficacy and safety.

Purpose: This multicenter, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in pediatric and adult patients with uncontrolled epilepsy.

Method: This study was carried out between September 2010 and December 2011 at 16 Italian and 1 German neurologic centers. Lacosamide was added to the baseline therapy at a starting dose of 1 mg/kg/day in patients aged <16 years (group A) and 100 mg daily in subjects aged 16 and older (group B), and titrated to the target dose, ranging from 3 to 12 mg/kg/day or from 100 to 600 mg daily, respectively.

Electroclinical presentation and genotype-phenotype relationships in patients with Unverricht-Lundborg disease carrying compound heterozygous CSTB point and indel mutations.

Purpose: Unverricht-Lundborg disease (EPM1A) is frequently due to an unstable expansion of a dodecamer repeat in the CSTB gene, whereas other types of mutations are rare. EPM1A due to homozygous expansion has a rather stereotyped presentation with prominent action myoclonus. We describe eight patients with five different compound heterozygous CSTB point or indel mutations in order to highlight their particular phenotypical presentations and evaluate their genotype-phenotype relationships.

Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences.

Heterozygous mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We report a consanguineous Italian family with BFIS/PKD phenotype that contained 14 living members with 6 affected individuals (four men, ranging in age from 6-44 years). We identified the reported c.

PRRT2 mutations are the major cause of benign familial infantile seizures.

Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis (PKD with infantile seizures), and recently also in some families with benign familial infantile seizures (BFIS) alone. We analyzed PRRT2 in 49 families and three sporadic cases with BFIS only of Italian, German, Turkish, and Japanese origin and identified the previously described mutation c.649dupC in an unstable series of nine cytosines to occur in 39 of our families and one sporadic case (77% of index cases).

Seizures and EEG patterns in Pallister-Killian syndrome: 13 new Italian patients.

Background And Objectives: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by a tissue-limited mosaic supernumerary isochromosome 12p. Typical facial dysmorphisms, pigmentary abnormalities, and some major malformations are frequently present. Neurological manifestations include mental retardation, hypotonia, and seizures.

Neuropsychological and behavioural aspects in children and adolescents with idiopathic epilepsy at diagnosis and after 12 months of treatment.

Purpose: To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment and after 1 year of therapy and to identify factors associated with cognitive impairment.

Methods: 43 Subjects aged 5.2-16.

Short and long interval cortical inhibition in patients with Unverricht-Lundborg and Lafora body disease.

Myoclonus has different clinical and neurophysiological features in patients with Unverricht-Lundborg (ULD) and Lafora body disease (LBD), probably because of a different cortical hyperexcitability profile. To investigate the role of intracortical inhibition in such different presentations, we used paired-pulse transcranial magnetic stimulation (TMS) in ten ULD and five LBD patients, all with a positive molecular diagnosis. All of the patients were treated with antiepileptic drugs (AEDs).

Seizures and EEG pattern in Kabuki syndrome.

Purpose: Kabuki syndrome (KS) is a rare dysmorphogenic disorder that is characterized by multiple congenital abnormalities with central nervous system involvement. The diagnosis is clinical and a variable degree of mental retardation is always present. Epilepsy is frequently reported, but a typical electroclinical pattern has not been described.