Use of Stiripentol in Patients with Dravet Syndrome: Common Practice Among Experts in Spain.

Background: Despite considerable evidence for the efficacy and safety of stiripentol in Dravet syndrome (DS), some aspects of stiripentol use remain challenging in clinical practice, such as dose titration and the adjustment of concomitant antiseizure medications (ASMs) to prevent potential adverse effects.

Aim: To (1) provide practical recommendations on the initiation of stiripentol treatment in patients with DS, (2) evaluate its effectiveness in the patient, and (3) guide the management of drug interactions and other aspects of treatment monitoring.

Methods: Six Spanish neurologists (the authors) with expertise in the management of pediatric and adult patients with DS held a meeting in early 2024 to develop expert recommendations regarding the use of stiripentol in DS, based on a review of the literature and their common clinical experience.

Prevalence of orthopaedic conditions in Rett syndrome: a systematic review and meta-analysis.

Background: Rett syndrome (RTT), a developmental disorder primarily affecting girls and linked to methyl-CpG binding protein-2 (MECP2) gene mutations, presents musculoskeletal abnormalities with varying prevalence across studies and age groups. Our aim was to delineate the prevalence of orthopaedic conditions in individuals with RTT.

Method: Three databases were searched and independently screened by two reviewers to retrieve observational studies published after 2000 that recruited 10 or more patients diagnosed with RTT and reported the prevalence of any orthopaedic conditions (scoliosis, hip displacement, knee problems or foot deformities).

Orthopedic Conditions and Interplay with Functional Abilities and MECP2 Variant Subtype in Rett Syndrome Patients.

Purpose: Rett syndrome (RTT) is a rare multi-systemic disorder primarily linked to mutations in MECP2 gene. This study aims to describe the prevalence of orthopedic conditions in RTT patients, and examine their intricate interplay with functional capabilities, and MECP2 variant subtypes.

Methods: Conducted as a cross-sectional retrospective observational study, the research encompassed 55 patients meeting clinical RTT criteria and holding MECP2 mutations.

Sleep disorders in children with epilepsy.

Introduction: Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship.

Objective: Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy.

Cerebral and cerebellar pseudoatrophy associated with valproic acid. Report of three pediatric cases.

Introduction: Cerebral and cerebellar pseudoatrophy is a rare adverse effect of valproic acid (VPA) that we need to be aware of, due to its diagnostic and therapeutic implications.

Case Report: We report three cases of children between 5 and 9 years old, with epilepsy and previous normal brain magnetic resonance imaging, who were taking the drug at correct doses. Pseudoatrophy manifests subacutely with symptoms and images of cerebral and/or cerebellar atrophy, reversible after drug withdrawal.

Neuropsychiatric comorbidities and cognition in epilepsy with eyelid myoclonia: A retrospective pediatric case series.

Objective: Epilepsy with eyelid myoclonia (EEM) is a rare epileptic syndrome classified within the Genetic Generalized Epilepsies of childhood. It is characterized by a high drug resistance, and little is known about prognostic factors and neurodevelopmental comorbidities. The aim of this study was to describe the clinical features, cognitive profile, and prognostic factors in a series of children with EEM.

Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.

Background: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving cause KBG syndrome, but no genotype-phenotype correlation has been reported.

Methods: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

Aim: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP).

Methods: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included.

[Paediatric status epilepticus].

Introduction: Status epilepticus is defined as the situation resulting from the failure of the mechanisms responsible for terminating an epileptic seizure. In 2015, an operational concept was adopted internationally in which two times are identified: a first time, at which treatment must begin (five minutes for convulsive status, 10-15 minutes for focal and non-convulsive status); and a second time, after which there is considered to be a high risk of subsequent sequelae (30 minutes in the case of the convulsive). It occurs in 3-42/100,000 children per year, who are refractory or super-refractory in 10-40% of cases.

The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study.

Objective: The appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs).

Methods: This study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates.

Ketogenic dietary therapies for epilepsy: Experience in 160 patients over 18 years.

Aim: Ketogenic dietary therapies (KDT) produce anticonvulsant and neuroprotective effects, reduce seizures and improve the cognitive state in patients with epilepsy. Our purpose was to evaluate the effects of KDT in children with refractory epilepsy (effectiveness, side effects, impact on nutritional status and growth).

Methods: A retrospective and prospective observational descriptive study was conducted in a Spanish tertiary hospital (January 2000 to December 2018).

Paradigmatic De Novo Variants Recapitulate Pathophysiological Mechanisms Underlying GRIN1-Related Disorder Clinical Spectrum.

Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting genes (mostly , and genes), which encode for the GluN subunit of the -methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present.

Methods: In this study, we aimed to delineate the structural and functional alterations of disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants.

[Variability of the clinical expression of KCNB1 encephalopathy].

Introduction: The KCNB1 gene encodes a voltage-dependent potassium channel that regulates transmembrane currents in pyramidal neurons. Heterozygous variants have recently been associated with early-onset epileptic encephalopathies and intellectual disability, but their clinical characterisation has not yet been fully defined.

Aim: To describe the clinical spectrum associated with variants of KCNB1 in paediatric patients.

Efficacy of Brivaracetam in children with epilepsy.

Background And Objectives: To determine the efficacy, tolerance, and safety of BRV in children with epilepsy.

Methods: A retrospective study of patients with epilepsy who received treatment with BRV before age 16 years and underwent a minimum follow-up of 3 months.

Method And Results: Sixty-six patients were included in the study.

Sleep disorders in children with epilepsy.

Introduction: Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship.

Objective: Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy.

Cannabidiol for the treatment of Lennox-Gastaut syndrome and Dravet syndrome: experts' recommendations for its use in clinical practice in Spain.

Introduction: Cannabidiol (CBD) is one of the main components of the cannabis plant that has demonstrated anti-epileptic seizure effect. Following its clinical development, in September 2019 the European Medicines Agency approved its indication for the adjunctive therapy of epileptic seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), combined with clobazam (CLB), in patients of 2 years of age and older.

Aim: To establish recommendations on the use of plant-derived highly purified CBD on which Spanish experts have reached consensus for the treatment of epilepsy in patients with DS and LGS based on their clinical experience and the scientific evidence.

[Ketogenic dietary therapies for epilepsy: Experience in 160 patients over 18 years].

Aim: Ketogenic dietary therapies (KDT) produce anticonvulsant and neuroprotective effects, reduce seizures and improve the cognitive state in patients with epilepsy. Our purpose was to evaluate the effects of KDT in children with refractory epilepsy (effectiveness, side effects, impact on nutritional status and growth).

Methods: A retrospective and prospective observational descriptive study was conducted in a Spanish tertiary hospital (January 2000 to December 2018).

Sodium channel blockers for the treatment of epilepsy in CDKL5 deficiency disorder: Findings from a multicenter cohort.

Objective: This study was aimed to analyze the effectiveness of sodium channel blockers (SCBs) in CDKL5 deficiency disorder (CDD)-related epilepsy.

Methods: A retrospective, observational study was performed, including patients with CDD diagnosis evaluated between 2016 and 2019 at three tertiary Epilepsy Centers. Demographic, electroclinical and genetic features, as well as ASM treatments and their outcomes were analyzed, with special focus on SCBs.

Dystonia and Contractures are Potential Early Signs of -Related Epileptic Encephalopathy.

Epileptic encephalopathy related to has been described as a severe neurodevelopmental disorder presenting with early-onset refractory seizures, hypotonia, macrocephaly, hyperkinetic movements, and contractures and is associated with an autosomal dominant inheritance pattern. Most pathogenic variants described to date are missense variants with a gain of function effect, and the role of haploinsufficiency has yet to be clarified. We describe 2 cases of encephalopathy.

[The role of eslicarbazepine acetate in the treatment of focal-onset epilepsy in pediatric age: practical issues].

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) of the carboxamide family and structurally related to carbamazepine and oxcarbazepine, although it has pharmacological differences that may have relevant implications of clinical utility. Since 2009 in Europe, ESL has been indicated for use in adults as adjuvant therapy in patients with partial-onset seizures (currently called focal-onset), with or without secondary generalization (with or without evolution to bilateral tonic-clonic, in current terminology). In 2017, the indication for adjunctive therapy of patients with partial-onset seizures with or without secondary generalization was extended to its use as monotherapy in adults and as adjuvant therapy in adolescents and children older than 6 years.

Emergency implementation of telemedicine for epilepsy in Spain: Results of a survey during SARS-CoV-2 pandemic.

Unlabelled: Teleneurology in Spain had not been implemented so far in clinical practice, except in urgent patients with stroke. Telemedicine was hardly used in epilepsy, and patients and neurologists usually preferred onsite visits. Our goal was to study impressions of adult and pediatric epileptologists about the use of telemedicine after emergent implementation during the new coronavirus 2019 (COVID-19) pandemic.