Redefining drug-resistant epilepsy: Insights from an Italian Delphi consensus study.

Objective: Drug-resistant epilepsy (DRE) affects approximately one-third of people with epilepsy (PwE) despite advancements in anti-seizure medications and presents significant challenges in epilepsy care. This Delphi consensus study aimed to examine key aspects of DRE, including its definition, predictors, and therapeutic strategies.

Methods: A steering committee consisting of clinicians and researchers with expertise in epilepsy was responsible for formulating the statements.

Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?

Objective: This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug-resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD).

Methods: We recruited subjects with genetically confirmed typical RTT and CDD with drug-resistant seizures who received add-on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20 mg/kg/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated.

Italian report on RARE epilepsies (i-RARE): A consensus on multidisciplinarity.

Objective: Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives.

Methods: Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics.

Electroclinical Features of Epilepsy in Kleefstra Syndrome.

Background: Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described.

BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations.

Targeted re-sequencing for early diagnosis of genetic causes of childhood epilepsy: the Italian experience from the 'beyond epilepsy' project.

Background: Childhood epilepsies are a heterogeneous group of conditions differing in diagnostic criteria, management, and outcome. Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative condition caused by biallelic TPP1 variants. This disorder presents with subtle and relatively non-specific symptoms, mimicking those observed in more common paediatric epilepsies and followed by rapid psychomotor deterioration and drug-resistant epilepsy.

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.

Objective: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE).

Methods: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies.

Long term neurocognitive improvement after "late" right hemispherectomy: case report and review of the literature.

Objective: To study the long-term neurocognitive changes of a right-handed girl with intractable epilepsy after late right hemispherectomy and compare them with data in the literature.

Method: The girl was affected by an epileptic encephalopathy associated with right fronto-temporo-parietal polymicrogyria; she was submitted to right hemispherectomy at the age of 5 and examined with cognitive and neuropsychological tests at the age of 17 years. The girl took advantage of neurocognitive rehabilitation for several years; she is currently seizure-free and off therapy.

A relatively mild phenotype associated with mutation of SCN8A.

Mutations in SCN8A gene have been described in relation to infantile onset epilepsy with movement disorders and developmental delay. Recently various authors have reported patients carrying autosomal dominant heterozygous SCN8A mutations and a milder phenotype expression. We discuss the case of a 6-year-old girl with a positive family history for epilepsy, early benign focal epilepsy, well controlled by Carbamazepine, upper limb tremor since birth, ataxia, slight motor delay and normal cognitive development.

Sleep in children with attention-deficit/hyperactivity disorder (ADHD) before and after 6-month treatment with methylphenidate: a pilot study.

Unlabelled: Children with ADHD may present with sleep disturbances that add to the impairment of the disorder. The long-term sleep effects of the first-line pharmacological treatment for ADHD, i.e.

Different electroclinical picture of generalized epilepsy in two families with 15q13.3 microdeletion.

15q.13.3 microdeletion has been described in a variety of neurodevelopmental disorders.

Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome.

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17-74 kb in 9% of the patients.

Cognitive evolution of a girl submitted to right hemispherotomy when five years old.

Since the age of three years the patient suffered from early drug-resistant partial epilepsy with electric status during slow sleep, owing to a micropolygyric malformation of the right fronto-temporo-parietal lobes. The hemispherotomy (when five years of age) was followed by immediate and persistent disappearance of the seizures and withdrawal of the treatment. The transfer of right hemispheric functions to the left hemisphere occurred very early; the child's development was examined in relation to the restoration of these functions and the age at surgery.

Verbal dichotic listening and manual performance in children with congenital unilateral brain lesions.

The authors assessed manual performance and verbal dichotic listening performance in 16 epilepsy-free children with congenital unilateral brain lesions and normal IQ to investigate cerebral reorganization. In all children, the paretic hand had fair grip function, but reaction times were impaired, and cerebral reorganization of hand function in those with right hemiplegia was shown by the high incidence of pathological left-handedness. The dichotic listening results showed that most children with left lesions had a left ear advantage significantly related to the extent of brain damage.

Oligoyric microcephaly in a child with Williams syndrome.

We report a 19-month-old boy with microcephaly, growth and developmental delay, facial dysmorphisms, and simplified gyral pattern. Magnetic resonance imaging (MRI) examination demonstrated microcephaly with simplified gyral pattern or oligogyric microcephaly. The facial phenotype was interpreted as suggestive of Williams syndrome (WS).