Lennox-Gastaut Syndrome: A State of the Art Review.

Lennox-Gastaut syndrome (LGS) is a severe age-dependent epileptic encephalopathy usually with onset between 1 and 8 years of age. Functional neuroimaging studies recently introduced the concept of Lennox-Gastaut as "secondary network epilepsy" resulting from dysfunctions of a complex system involving both cortical and subcortical structures (default-mode network, corticoreticular connections, and thalamus). These dysfunctions are produced by different disorders including hypoxic-ischemic encephalopathies, meningoencephalitis, cortical malformations, neurocutaneous disorders, or tumors. The list of etiologies was expanded to pathogenic copy number variants at whole-genome array comparative genomic hybridization associated with late-onset cases or pathogenic mutations involving genes, such as GABRB3, ALG13, SCN8A, STXBP1, DNM1, FOXG1, or CHD2. Various clinical trials demonstrated the usefulness of different drugs (including rufinamide, clobazam, lamotrigine, topiramate, or felbamate), ketogenic diet, resective surgery, corpus callosotomy, and vagus nerve stimulation in the treatment of epileptic manifestations. The outcome of LGS often remains disappointing regarding seizure control or cognitive functioning. The realization of animal models, which are still lacking, and the full comprehension of molecular mechanisms involved in epileptogenesis and cognitive impairment would give a relevant support to further improvements in therapeutic strategies for LGS patients

Can User Experience affect buying intention? A case study on the evaluation of exercise equipment.

Treadmills are increasingly loaded with digital technology for assisting the individual during the workout sessions by providing information for tracking relevant training parameters. Also, this technology makes exercise more pleasurable by keeping the user connected to her/his digital ecosystem (e.g. social networking, access to multimedia content). Although there is an increasing interest in digital technologies to be used in fitness, a cursory literature search shows that the interest towards gym equipment is currently limited to the hardware component, thus making biomechanics the focus of the investigation. Other types of contributions are very rare and mostly focused on the design of tools for special populations (e.g. elderly, disabilities) as well as for promoting physical activity monitoring (eHealth). In the present study information on the perceived usability of the interface was collected and analysed along with opinions about buying intention and estimated pricing. Twenty-three individuals were tested after using a treadmill (Technogym S.p.A.) equipped with an interface allowing equipment and training management, activity monitoring and user entertainment. Results indicated a significant influence of perceived usability of the interface on the intention of buying the whole system, thus suggesting the existence of a ROI of Human-Centred Design strategies

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). Patients and methods: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. Results: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. Conclusions: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

BACKGROUND: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). PATIENTS AND METHODS: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. RESULTS: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. CONCLUSIONS: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG

Biochemical data from the characterization of a new pathogenic mutation of human pyridoxine-5'-phosphate oxidase (PNPO)

PNPO deficiency is responsible of severe neonatal encephalopathy, responsive to pyridoxal-5’-phosphate (PLP) or pyridoxine. Recent studies widened the phenotype of this condition and detected new genetic variants on PNPO gene, whose pathogenetic role and clinical expression remain to be established. One of these mutations, Arg116Gln, is of particular interest because of its later onset of symptoms (beyond the first months of life) and its peculiar epileptic manifestations in patients. This protein variant was expressed as recombinant protein in E coli, purified to homogeneity, and characterized with respect to structural and kinetic properties, stability, binding constants of cofactor flavin mononucleotide (FMN) and product (PLP) in order to define the molecular and structural bases of its pathogenicity. For interpretation and discussion of reported data, together with the description of clinical studies, refer to the article [7][1] (doi: 10.1016/j.ymgme.2017.08.003)

The burden of epilepsy on long-term outcome of genetic developmental and epileptic encephalopathies: A single tertiary center longitudinal retrospective cohort study

Background: This retrospective cohort analysis highlighted neurodevelopmental outcome predictors of genetic developmental and epileptic encephalopathies (DEE). Patients and methods: Patients' demographic, clinical and molecular genetics data were collected. All patients underwent clinical, developmental, and neuropsychological assessments. Results: We recruited 100 participants (53 males, 47 females) with a mean follow-up lasting 10.46 ± 8.37 years. Age at epilepsy-onset was predictive of poor adaptive and cognitive functions (VABS-II score, r = 0.350, p = 0.001; BRIEF control subscale, r = -0.253; p = 0.031). Duration of epilepsy correlated negatively with IQ (r = -0.234, p = 0.019) and VABS-II score (r = -0.367, p = 0.001). Correlations were found between delayed/lacking EEG maturation/organization and IQ (r = 0.587, p = 0.001), VABS-II score (r = 0.658, p = 0.001), BRIEF-MI and BRIEF-GEC scores (r = -0.375, p = 0.001; r = -0.236, p = 0.033), ASEBA anxiety (r = -0.220, p = 0.047) and ADHD (r = -0.233, p = 0.035) scores. The number of antiseizure medications (ASMs) correlated with IQ (r = -0.414, p = 0.001), VABS-II (r = -0.496, p = 0.001), and BRIEF-MI (r = 0.294, p = 0.012) scores; while age at the beginning of therapy with ASEBA anxiety score (r = 0.272, p = 0.013). The occurrence of status epilepticus was associated with worse adaptive performances. The linear regression analysis model showed that delayed/lacking EEG maturation/organization had a significant influence on the IQ (R2 = 0.252, p < 0.001) and the BRIEF-GEC variability (R2 = 0.042, p = 0.036). The delayed/lacking EEG maturation/organization and the duration of epilepsy also had a significant influence on the VABS-II score (R2 = 0.455, p = 0.005). Conclusions: Age at seizure-onset, EEG maturation/organization, duration of epilepsy, occurrence of status epilepticus, age at the introduction and number of ASMs used are reliable predictors of long-term outcomes in patients with genetic DEE

The impact of a newly established specialized pediatric epilepsy center in Tanzania: An observational study

Purpose: This study evaluated the impact of a newly established clinic for the diagnosis of pediatric epilepsy in a resource-limited center (Ifakara, Tanzania). Methods: Patients aged 0-18 years referred to the Pediatric Epilepsy Unit of Saint Francis Referral Hospital were recruited. Demographic and clinical data were collected through Kobo Toolbox and analyzed through a descriptive analysis.. Results: 143 patients were evaluated, and for 48 of them an EEG was recorded (abnormalities were detected in 80.85% of the cases). The diagnosis of epilepsy was confirmed in 87 patients. Focal epilepsy was diagnosed in 57 patients, generalized epilepsy in 24 patients, and forms of unknown onset in 6 patients. Epilepsy was excluded for 9 children. Etiologies included hypoxic-ischemic encephalopathy (39%), central nervous system infections (3.4%), and genetic diseases (3.4%). A specific epilepsy syndrome was diagnosed in 16 patients. 74 patients were under treatment; the most used antiseizure medication (ASM) was phenobarbital (43.36%), followed by carbamazepine (16.08%), sodium valproate (11.19%), phenytoin (2.8%), and lamotrigine (0.7%). Therapeutic changes were proposed to 95 patients, more frequently consisting of withdrawing phenobarbital (39.16%), switching to sodium valproate (27.97%), switching to or adjusting carbamazepine dosage (27.27%), and starting prednisone (2.8%). 76% of the patients with confirmed epilepsy achieved complete seizure freedom at the fourth follow-up consultation. Conclusions: Our data depicted the epilepsy spectrum and highlighted the prognostic implications of improving the availability of ASMs such as sodium valproate and second- and third-generation ones in resource-limited countries