The "plus" side of epilepsy phenotyping

No abstract available

Pathophysiological mechanisms in neurodevelopmental disorders caused by rac GTPases dysregulation: What’s behind neuro-RACopathies

Rho family guanosine triphosphatases (GTPases) regulate cellular signaling and cytoskele-tal dynamics, playing a pivotal role in cell adhesion, migration, and cell cycle progression. The Rac subfamily of Rho GTPases consists of three highly homologous proteins, Rac 1–3. The proper function of Rac1 and Rac3, and their correct interaction with guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs) are crucial for neural development. Pathogenic variants affecting these delicate biological processes are implicated in different medical conditions in humans, primarily neurodevelopmental disorders (NDDs). In addition to a direct deleterious effect produced by genetic variants in the RAC genes, a dysregulated GTPase activity resulting from an abnormal function of GEFs and GAPs has been involved in the pathogenesis of distinctive emerging conditions. In this study, we reviewed the current pertinent literature on Rac-related disorders with a primary neurological involvement, providing an overview of the current knowledge on the pathophysiological mechanisms involved in the neuro-RACopathies

La narrazione come dispositivo conoscitivo ed ermeneutico

La lettura che la narrazione offre dell’agire umano è di tipo idiografico, giacché intende conferire un senso ed un significato a specifiche azioni compiute da particolari attori in determinati contesti; in questo senso, essa sostanzia un dispositivo di descrizione / interpretazione / comprensione dell’agire individuale e sociale piuttosto che di osservazione/analisi/esplicazione dello stesso; si rivela, quindi, particolarmente utile ed efficace in una prospettiva euristica che sia: a) fortemente orientata alla individuazione di elementi di contesto e di implicazioni personali, storiche, culturali e sociali; b) focalizzata sulla fenomenologia dell’agire piuttosto che sull’azione intesa come singola unità di analisi, decontestualizzata e sezionata nelle sue diverse componenti o possibili declinazioni

Management of epilepsy in elderly

The prevalence of seizures and epilepsy in the elderly is generally underestimated. Epileptic seizures are not a rare occurrence in the elderly and their prevalence increases with age. The clinical manifestations of seizures, the aetiology, the treatment and the psychosocial impact of the epilepsy diagnosis may differ in the elderly. Differential diagnosis with episodes of unconsciousness and/or fall or other non-epileptic manifestations is often difficult. The presence of comorbidities, the polypharmatherapy and the age-related pharmacokinetic changes can represent a problem for the treatment of epilepsy in the elderly, with a higher risk of adverse effects and potentially inappropriate drug interactions. Epileptic seizures in the elderly can have semiological characteristics similar to those of other age groups. On the other hand, the richness of the electroclinical syndromes of childhood and adolescence is not found in the elderly, and, in particular, idiopathic generalized epilepsies are rarely expressed at this age. Symptomatic seizures related to acute structural injury or metabolic causes are particularly frequent. Therapy management of the elderly with an epileptic seizure should concern not only neurologists, but also general practitioners, geriatricians, and cardiologists, therefore involving a wide range of clinical specialties. This review aims to summarize the management of epilepsy in the elderly, reporting also differences in epidemiology, electroclinical features, aetiology and diagnostic procedures

Photopolymer-based volume holographic optical elements: design and possible applications

In this paper, Volume Holographic Optical Elements (V-HOEs), such as holographic gratings and spherical lenses, are designed and fabricated by using a prototype of photopolymer. The recording process of V-HOEs and their appropriate characterization are described. Moreover, V-HOEs possible applications as solar concentrator are investigated and results are discussed. Finally, a system that allows passive solar tracking is proposed and preliminary results are reported

Ictal epileptic headache: When terminology is not a moot question

open7noThe relationship between headache and epilepsy is complex and despite the nature of this association is not yet clear. In the last few years, it has been progressively introduced the concept of the “ictal epileptic headache” that was included in the recently revised International Classification of Headaches Disorders 3rd edition (ICHD-3-revised). The diagnostic criteria for ictal epileptic headache (IEH) suggested in 2012 were quite restrictive thus leading to the underestimation of this phenomenon. However, these criteria have not yet been included into the ICHD-3 revision published in 2018, thus creating confusion among both, physicians and experts in this field. Here, we highlight the importance to strictly apply the original IEH criteria explaining the reasons through the analysis of the clinical, historical, epidemiological and pathophysiological characteristics of the IEH itself. In addition, we discuss the issues related to the neurophysiopathological link between headache and epilepsy as well as to the classification of these epileptic events as “autonomic seizure”.openParisi P.; Paolino M.C.; Raucci U.; Vecchia N.D.; Belcastro V.; Villa M.P.; Striano P.Parisi, P.; Paolino, M. C.; Raucci, U.; Vecchia, N. D.; Belcastro, V.; Villa, M. P.; Striano, P

Adjunctive Cenobamate for Focal-Onset Seizures in Adults: A Systematic Review and Meta-Analysis

Background: Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. This drug can enhance the inactivated state of voltage-gated sodium channels, preferentially inhibiting the persistent component of the sodium channel current, and acts as a positive allosteric modulator of GABAA receptors, binding at a non-benzodiazepine site. Objective: We assessed the efficacy and safety of adjunctive cenobamate for the treatment of focal-onset seizures in adult patients with epilepsy using meta-analytical techniques. Methods: We systematically searched (May, week 4, 2020) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov). There were no date limitations or language restrictions. Randomized, placebo-controlled, single or double-blinded, add-on trials of cenobamate in adult patients with uncontrolled focal-onset seizures were identified. Main outcomes included the proportion of patients with ≥ 50 and 100% reduction in seizure frequency during the maintenance treatment period compared with baseline and the incidence of treatment withdrawal and adverse events (AEs). Risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome. Results: Two trials were included, overall enrolling 659 patients (442 for the add-on cenobamate group and 217 for the add-on placebo group). Seizure frequency reduction by at least 50% occurred during the maintenance phase in 50.1% of the patients randomized to cenobamate and 23.5% of the placebo-treated participants (RR 2.18, 95% CI 1.67–2.85; p < 0.001). The pooled estimated RR to achieve seizure freedom for the cenobamate group in comparison with placebo was 3.71 (95% CI 1.93–7.14; p < 0.001). Withdrawal from randomized treatment occurred in 16.7 and 11.1% of participants receiving cenobamate and placebo, respectively (RR 1.34, 95% CI 0.85–2.09; p = 0.205). Treatment was discontinued due to AEs in 12.2 and 4.1% of the patients in the active and control arms (RR 2.27, 95% CI 1.08–4.79; p = 0.031). AEs were reported in 76.9 and 66.8% of the patients during treatment with cenobamate and placebo (RR 1.14, 95% CI 1.02–1.26; p = 0.021). The cenobamate-associated AEs included somnolence, dizziness, fatigue, balance disorder, and diplopia. Conclusions: Adjunctive cenobamate in adult patients with uncontrolled focal-onset seizures is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

Mutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early-onset epilepsies with wide phenotypic expression, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic EEG and neuroradiological features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early-onset epilepsy and neurocognitive deficits segregated with a novel mutations in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity

The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations

Objective To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series. Methods Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000\u20132014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed. Results Out of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20 years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or d\ue9j\ue0-vu). Tonic\u2013clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory. By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group. Significance Heterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations

Emotional engagements predict and enhance social cognition in young chimpanzees

Social cognition in infancy is evident in coordinated triadic engagements, that is, infants attending jointly with social partners and objects. Current evolutionary theories of primate social cognition tend to highlight species differences in cognition based on human-unique cooperative motives. We consider a developmental model in which engagement experiences produce differential outcomes. We conducted a 10-year-long study in which two groups of laboratory-raised chimpanzee infants were given quantifiably different engagement experiences. Joint attention, cooperativeness, affect, and different levels of cognition were measured in 5- to 12-month-old chimpanzees, and compared to outcomes derived from a normative human database. We found that joint attention skills significantly improved across development for all infants, but by 12 months, the humans significantly surpassed the chimpanzees. We found that cooperativeness was stable in the humans, but by 12 months, the chimpanzee group given enriched engagement experiences significantly surpassed the humans. Past engagement experiences and concurrent affect were significant unique predictors of both joint attention and cooperativeness in 5- to 12-month-old chimpanzees. When engagement experiences and concurrent affect were statistically controlled, joint attention and cooperation were not associated. We explain differential social cognition outcomes in terms of the significant influences of previous engagement experiences and affect, in addition to cognition. Our study highlights developmental processes that underpin the emergence of social cognition in support of evolutionary continuity