RESUMEN
Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. Infants with DS are especially vulnerable to the detrimental effects of prolonged and frequent seizures on development. Fenfluramine (FFA) is approved for the treatment of DS in patients aged 2 years and older. This study aims to evaluate the safety and efficacy of FFA in patients with DS younger than 2 years. We analyzed safety, tolerability, seizure, and neuropsychological outcome in a real-world setting. Developmental profile was investigated using Griffiths Mental Development Scales (GMDS). Five patients received FFA at a mean age of 14.9 months (9.6-18.6). Median follow-up was 13 months (interquartile range [IQR] = 12.9-24.4). All patients showed good tolerance to FFA. No significant variation of body mass index or echocardiographic issue was observed. Monthly median convulsive seizure frequency (MCSF) was 1.71 (IQR = 1.56-3.27) at the 6-month baseline period and .92 (IQR = .43-1.28) at last follow-up, with a median 54.43 (IQR = 40.91-60.83) percentage reduction in MCSF. Two of five patients had a performance improvement on GMDS subscales. Overall, the use of FFA below the age of 2 years in our small sample of patients was safe and represents a promising opportunity for seizure control and for protection of the neurodevelopmental outcome.
Asunto(s)
Epilepsias Mioclónicas , Fenfluramina , Lactante , Humanos , Fenfluramina/efectos adversos , Anticonvulsivantes/uso terapéutico , Resultado del Tratamiento , Epilepsias Mioclónicas/tratamiento farmacológico , Convulsiones/tratamiento farmacológicoRESUMEN
BACKGROUND: Epilepsy, a globally prevalent neurological condition, presents distinct challenges in management, particularly for focal-onset types. This study aimed at addressing the current challenges and perspectives in focal epilepsy management, with focus on the Italian reality. METHODS: Using the Delphi methodology, this research collected and analyzed the level of consensus of a panel of Italian epilepsy experts on key aspects of focal epilepsy care. Areas of focus included patient flow, treatment pathways, controlled versus uncontrolled epilepsy, follow-up protocols, and the relevance of patient-reported outcomes (PROs). This method allowed for a comprehensive assessment of consensus and divergences in clinical opinions and practices. RESULTS: The study achieved consensus on 23 out of 26 statements, with three items failing to reach a consensus. There was strong agreement on the importance of timely intervention, individualized treatment plans, regular follow-ups at Epilepsy Centers, and the role of PROs in clinical practice. In cases of uncontrolled focal epilepsy, there was a clear inclination to pursue alternative treatment options following the failure of two previous therapies. Divergent views were evident on the inclusion of epilepsy surgery in treatment for uncontrolled epilepsy and the routine necessity of EEG evaluations in follow-ups. Other key findings included concerns about the lack of pediatric-specific research limiting current therapeutic options in this patient population, insufficient attention to the transition from pediatric to adult care, and need for improved communication. The results highlighted the complexities in managing epilepsy, with broad consensus on patient care aspects, yet notable divergences in specific treatment and management approaches. CONCLUSION: The study offered valuable insights into the current state and complexities of managing focal-onset epilepsy. It highlighted many deficiencies in the therapeutic pathway of focal-onset epilepsy in the Italian reality, while it also underscored the importance of patient-centric care, the necessity of early and appropriate intervention, and individualized treatment approaches. The findings also called for continued research, policy development, and healthcare system improvements to enhance epilepsy management, highlighting the ongoing need for tailored healthcare solutions in this evolving field.
Asunto(s)
Consenso , Técnica Delphi , Epilepsias Parciales , Humanos , Italia , Epilepsias Parciales/terapia , Medición de Resultados Informados por el PacienteRESUMEN
The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5-23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (ρ = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed.
Asunto(s)
Espasmos Infantiles , Humanos , Espasmos Infantiles/genética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Convulsiones/patología , Atrofia/patología , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
OBJECTIVE: This study was undertaken to refine the spectrum of SCN1A epileptic disorders other than Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+) and optimize antiseizure management by correlating phenotype-genotype relationship and functional consequences of SCN1A variants in a cohort of patients. METHODS: Sixteen probands carrying SCN1A pathogenic variants were ascertained via a national collaborative network. We also performed a literature review including individuals with SCN1A variants causing non-DS and non-GEFS+ phenotypes and compared the features of the two cohorts. Whole cell patch clamp experiments were performed for three representative SCN1A pathogenic variants. RESULTS: Nine of the 16 probands (56%) had de novo pathogenic variants causing developmental and epileptic encephalopathy (DEE) with seizure onset at a median age of 2 months and severe intellectual disability. Seven of the 16 probands (54%), five with inherited and two with de novo variants, manifested focal epilepsies with mild or no intellectual disability. Sodium channel blockers never worsened seizures, and 50% of patients experienced long periods of seizure freedom. We found 13 SCN1A missense variants; eight of them were novel and never reported. Functional studies of three representative variants showed a gain of channel function. The literature review led to the identification of 44 individuals with SCN1A variants and non-DS, non-GEFS+ phenotypes. The comparison with our cohort highlighted that DEE phenotypes are a common feature. SIGNIFICANCE: The boundaries of SCN1A disorders are wide and still expanding. In our cohort, >50% of patients manifested focal epilepsies, which are thus a frequent feature of SCN1A pathogenic variants beyond DS and GEFS+. SCN1A testing should therefore be included in the diagnostic workup of pediatric, familial and nonfamilial, focal epilepsies. Alternatively, non-DS/non-GEFS+ phenotypes might be associated with gain of channel function, and sodium channel blockers could control seizures by counteracting excessive channel function. Functional analysis evaluating the consequences of pathogenic SCN1A variants is thus relevant to tailor the appropriate antiseizure medication.
Asunto(s)
Epilepsias Mioclónicas , Epilepsias Parciales , Canal de Sodio Activado por Voltaje NAV1.1 , Humanos , Causalidad , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/genética , Mutación con Ganancia de Función , Discapacidad Intelectual/genética , Canal de Sodio Activado por Voltaje NAV1.1/genética , Fenotipo , Bloqueadores de los Canales de Sodio/uso terapéuticoRESUMEN
CSNK2B encodes a regulatory subunit of casein kinase II, which is highly expressed in the brain. Heterozygous pathogenic variants in CSNK2B are associated with Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) (OMIM #618732), characterized by facial dysmorphisms, seizures, intellectual disability, and behavioral disturbances. We report ten new patients with CSNK2B-related Neurodevelopmental Syndrome associated with heterozygous variants of CSNK2B. In three patients, a pathogenic variant was inherited from an affected parent. We describe both molecular and clinical features, focusing on epileptic and neurodevelopmental phenotypes. The median age at follow-up was 8.5 years (range 21 months-42 years). All patients had epilepsy, with onset at a median age of 10.5 months range 6 days-10 years). Seizures were both focal and generalized and were resistant to anti-seizure medications in two out of ten patients. Six patients had mild to moderate cognitive delays, whereas four patients had no cognitive disability. Although all previously reported patients had a de novo CSNK2B pathogenic variant, here we report, for the first time, two familial cases of CSNK2B-related Neurodevelopmental Syndrome. We confirmed the highly variable expressivity of the disease among both interfamilial and intrafamilial cases. Furthermore, this study provides information about the long-term outcome in adult patients and underlines the importance of detailed family history collection before performing genetic testing in patients with epilepsy and neurodevelopmental disorders.
Asunto(s)
Epilepsia , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Adulto , Humanos , Lactante , Recién Nacido , Epilepsia/genética , Epilepsia/patología , Trastornos del Neurodesarrollo/complicaciones , Trastornos del Neurodesarrollo/genética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Discapacidad Intelectual/genética , Síndrome , FenotipoRESUMEN
AIM: To illustrate the epileptological and electroencephalographic (EEG) characteristics of a cohort of patients with KBG syndrome and epilepsy. METHOD: Clinical history, age at epilepsy onset, seizure types, EEG findings, duration of epilepsy, and response to therapies were retrospectively reviewed in 11 patients (three females, eight males) with KBG syndrome. RESULTS: All detected genetic mutations were pathogenic and affected the C-terminal region at exon 9 of ANKRD11. One patient had 16q24.3 microdeletion including the ANKRD11 gene. Mean age at onset was 67 months. Epilepsy type was focal in five patients and generalized in four. Two patients had developmental and epileptic encephalopathies. Seizure freedom was obtained after a period varying between 15 days and 6 years. INTERPRETATION: In our patients, epilepsy appeared to respond well to treatment and, in some cases, to be self-limiting. The molecular characteristics of our patients' genetic abnormalities did not point towards any specific epilepsy hot spot. Epilepsy should be considered in the diagnostic work-up of patients with KBG syndrome. WHAT THIS PAPER ADDS: Some of the epilepsy types of KBG syndrome appear to be self-remitting. The epilepsy phenotypes associated with KBG syndrome are quite variable.
Asunto(s)
Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Epilepsia Generalizada , Discapacidad Intelectual , Anomalías Dentarias , Masculino , Femenino , Humanos , Anomalías Múltiples/diagnóstico , Discapacidad Intelectual/diagnóstico , Enfermedades del Desarrollo Óseo/diagnóstico , Enfermedades del Desarrollo Óseo/genética , Anomalías Dentarias/diagnóstico , Anomalías Dentarias/genética , Facies , Estudios Retrospectivos , Proteínas Represoras/genética , Deleción Cromosómica , FenotipoRESUMEN
Health systems worldwide are challenged in the provision of basic medical services and access to treatments for chronic conditions. Epilepsy, the most common severe chronic neurological disorder, does not receive sufficient attention despite being officially declared a public health priority by the World Health Organization. More than 80% of people with epilepsy live in middle- and low-income countries (MICs and LICs, respectively), where most of the population lacks reliable access to antiseizure medications (ASMs), contributing significantly to the large epilepsy treatment gap in these regions. The International League Against Epilepsy (ILAE) Task Force on Access to Treatment administered a global survey to report on the current access to ASMs worldwide. The survey was developed and distributed online through the ILAE and International Bureau of Epilepsy (IBE) secretariats to the chapter representatives. The survey was completed by one representative per country. Response rate was 73.2% (101 countries of the 138 represented in ILAE and/or IBE organizations). Availability and access of ASMs, including distribution problems and costs, reimbursement procedures, general barriers to access to care, and presence of projects targeted toward improving care access, were studied, and descriptive statistics on available responses were performed. Among the 15 first-generation ASMs surveyed, carbamazepine was reported as the most widely available globally. At least one first-generation ASM is widely available in most countries, but their number differs dramatically across income levels. Second- and third-generation ASMs are even more limited in MICs and LICs. Additionally, average retail prices for ASMs were not significantly different across countries despite the differences in per capita income from high-income countries to LICs. This survey provides a worrisome picture of availability and accessibility of ASMs across the world, with wide disparities according to socioeconomic status. Recommendations for direct action on improving access to care will be discussed.
Asunto(s)
Epilepsia , Comités Consultivos , Costos y Análisis de Costo , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Accesibilidad a los Servicios de Salud , Humanos , Encuestas y CuestionariosRESUMEN
This study aimed to evaluate the consensus level between a representative group of Italian neurologists and people with Drug-Resistant Epilepsy (DRE) regarding a series of statements about different aspects involved in the management of epilepsy to identify the unmet needs of the People with Epilepsy (PwE) and the future perspectives for the management of this disease. This observational study was conducted using a classic Delphi technique. A 19-statement questionnaire was administered anonymously through an online platform to a panel of expert clinicians and a panel of PwE, analyzing three main topics of interest: drug resistance, access to care, and PwE's experience. The consensus was achieved on 8 of the 19 statements administered to the panel of medical experts and on 4 of the 14 submitted to the panel of PwE, particularly on the definition of DRE and its consequences on treatment, Quality of Life (QoL), and autonomy of PwE. Most of the items, however, did not reach a consensus and highlighted the lack of a shared univocal view on some topics, such as accessibility to care throughout the country and the role of emerging tools such as telemedicine, narrative medicine, and digital devices. In many cases, the two panels expressed different views on the statements. The results outlined many fields of possible intervention, such as the need for educational initiatives targeted at physicians and PwE - for example, regarding telemedicine, digital devices, and narrative medicine - as well as the spread of better knowledge about epilepsy among the general population, in order to reduce epilepsy stigma. Institutions, moreover, could take a cue from this survey to develop facilities aimed at enhancing PwE's autonomy and promoting more equal access to care throughout the country.
Asunto(s)
Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Humanos , Calidad de Vida , Epilepsia/epidemiología , Encuestas y Cuestionarios , Estigma Social , Epilepsia Refractaria/terapiaRESUMEN
PURPOSE OF REVIEW: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH). RECENT FINDINGS: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little specific data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conflicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to fill this information gap.
Asunto(s)
Trastornos de Cefalalgia , Adolescente , Adulto , Niño , Cefalea/diagnóstico , Cefalea/terapia , Trastornos de Cefalalgia/diagnóstico , Trastornos de Cefalalgia/terapia , HumanosRESUMEN
Close to one-third of patients with epilepsies are refractory to current anti-seizure medications; however, trials with cenobamate suggest effectiveness in such patients with focal onset seizures. We searched for data published or otherwise reported on cenobamate and outlined these here. Despite being marketed in the USA, few studies are yet published in full, and trials are ongoing. Nevertheless, cenobamate showed potential for a high degree of efficacy in reducing seizures with an unprecedented seizure-free rate of up to 28%. Rare cases of hypersensitivity reactions seen in early trials seem to be avoided by the current recommended titration schedule. Other adverse events were rated mild-to-moderate and most commonly included dizziness, drowsiness, and headache. If data are confirmed in further published trials, cenobamate will be a welcome new treatment and further analyses may identify those that will benefit the most.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Carbamatos/uso terapéutico , Clorofenoles/uso terapéutico , Epilepsia/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Tetrazoles/uso terapéutico , Epilepsia/patología , Humanos , Convulsiones/patologíaRESUMEN
OBJECTIVE: Autosomal recessive pathogenic variants of the SLC13A5 gene are associated with severe neonatal epilepsy, developmental delay, and tooth hypoplasia/hypodontia. We report on 14 additional patients and compare their phenotypic features to previously published patients to identify the clinical hallmarks of this disorder. METHODS: We collected clinical features of 14 patients carrying biallelic variants in SLC13A5 and performed a PubMed search to identify previously published patients. RESULTS: All patients presented clonic or tonic seizures in the first days of life, evolving into status epilepticus in 57%. Analysis of seizure frequency and developmental milestones divided into five epochs showed an evolutionary trajectory of both items. In the first 3 years of life, 72% of patients had weekly/monthly seizures, often triggered by fever; 14% were seizure-free. Between the ages of 3 and 12 years, 60% become seizure-free; in the following years, up to age 18 years, 57% were seizure-free. After the age of 18 years, all three patients reaching this age were seizure-free. Similarly, 86% of patients at onset presented mild to moderate developmental impairment and diffuse hypotonia. In late childhood, all had developmental delay that was severe in most. Benzodiazepines, phenobarbital, phenytoin, and carbamazepine were the most effective drugs. Eight probands carried heterozygous compound variants, and homozygous pathogenic variants occurred in six. Literature review identified 45 patients carrying SLC13A5 gene pathogenic variants whose clinical features overlapped with our cohort. A peculiar and distinguishing sign is the presence of tooth hypoplasia and/or hypodontia in most patients. SIGNIFICANCE: Autosomal recessive pathogenic variants in SLC13A5 are associated with a distinct neonatal epileptic encephalopathy evolving into severe cognitive and motor impairment, yet with seizures that settle down in late childhood. Tooth hypoplasia or hypodontia remains the peculiar feature. The SLC13A5 gene should be screened in neonatal epileptic encephalopathies; its recessive inheritance has relevance for genetic counseling.
Asunto(s)
Encefalopatías/genética , Discapacidades del Desarrollo/genética , Epilepsia/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Simportadores/genética , Adolescente , Encefalopatías/diagnóstico , Encefalopatías/fisiopatología , Niño , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/fisiopatología , Electroencefalografía/tendencias , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: Dravet syndrome (DS) is a drug-resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS. METHODS: DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add-on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months. RESULTS: Fifty-two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1-13.9). Forty-five (86.5%) patients completed the efficacy analysis. The median follow-up was 9.0 months (IQR = 3.2-9.5). At last follow-up visit, there was a 77.4% median reduction in convulsive seizures. Thirty-two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure-free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA. SIGNIFICANCE: In this real-world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.
Asunto(s)
Epilepsias Mioclónicas/tratamiento farmacológico , Fenfluramina/administración & dosificación , Convulsiones/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adolescente , Adulto , Anorexia/inducido químicamente , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Epilepsias Mioclónicas/diagnóstico por imagen , Epilepsias Mioclónicas/fisiopatología , Femenino , Fenfluramina/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Convulsiones/diagnóstico por imagen , Convulsiones/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1-DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely pathogenic variant p.Gly112Ser. The p.Arg114His variant is associated with an earlier onset and more severe phenotype. One patient carried a chromosomal microduplication involving FHF1. Twelve patients carried a de novo variant, five (29.5%) inherited from parents with gonadic or somatic mosaicism. Seizure onset was between 1 day and 41 months; in 76.5% it was within 30 days. Tonic seizures were the most frequent seizure type. Twelve patients (70.6%) had drug-resistant epilepsy, 14 (82.3%) intellectual disability, and 11 (64.7%) behavioral disturbances. Brain magnetic resonance imaging (MRI) showed mild cerebral and/or cerebellar atrophy in nine patients (52.9%). Overall, our findings expand and refine the clinical, EEG, and imaging phenotype of patients with FHF1-DEE, which is characterized by early onset epilepsy with tonic seizures, associated with moderate to severe ID and psychiatric features.
Asunto(s)
Encefalopatías/genética , Epilepsia/genética , Factores de Crecimiento de Fibroblastos/genética , Discapacidad Intelectual/genética , Fenotipo , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encefalopatías/diagnóstico por imagen , Encefalopatías/fisiopatología , Niño , Preescolar , Electroencefalografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/fisiopatología , Femenino , Humanos , Lactante , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/fisiopatología , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The present Italian multicenter study aimed at investigating whether the course of primary headache disorders in children and adolescents was changed during the lockdown necessary to contain the COVID-19 emergency in Italy. METHODS: During the lockdown, we submitted an online questionnaire to patients already diagnosed with primary headache disorders. Questions explored the course of headache, daily habits, psychological factors related to COVID-19, general mood and school stress. Answers were transformed into data for statistical analysis. Through a bivariate analysis, the main variables affecting the subjective trend of headache, and intensity and frequency of the attacks were selected. The significant variables were then used for the multivariate analysis. RESULTS: We collected the answers of 707 patients. In the multivariate analysis, we found that reduction of school effort and anxiety was the main factor explaining the improvement in the subjective trend of headache and the intensity and frequency of the attacks (p < 0.001). The greater the severity of headache, the larger was the clinical improvement (p < 0.001). Disease duration was negatively associated with the improvement (p < 0.001). It is noteworthy that clinical improvement was independent of prophylaxis (p > 0.05), presence of chronic headache disorders (p > 0.05) and geographical area (p > 0.05). CONCLUSIONS: Our study showed that lifestyle modification represents the main factor impacting the course of primary headache disorders in children and adolescents. In particular, reduction in school-related stress during the lockdown was the main factor explaining the general headache improvement in our population.
Asunto(s)
Infecciones por Coronavirus , Cefalea/epidemiología , Cefalea/psicología , Estilo de Vida , Pandemias , Neumonía Viral , Aislamiento Social/psicología , Adolescente , Ansiedad/etiología , Ansiedad/psicología , Betacoronavirus , COVID-19 , Niño , Femenino , Humanos , Italia/epidemiología , Masculino , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The objective of this study was to educate the school staff for a correct management of epileptic seizures in order to increase the safety of young people at school and promoting the administration of rescue drugs and in order to improve care and reduce improper calls to the health emergency number. METHODS: This project started in January 2016, and it is still ongoing at the Department of Neuroscience of Bambino Gesù Children's Hospital in Rome, Italy. There has been a data cut-off evaluation in November 2018. Two-hour training meetings with the school staff have been organized. The major topics of the training activities were as follows: report what epilepsy is, how to manage students with epileptic seizures, and how to administer rescue medications. During the meetings, the following two questionnaires were administered: one pretest in order to collect personal information and information on awareness of epilepsy, willingness to administer rescue medications, and anxiety in facing a seizure; and one posttest in order to check the knowledge acquired after the training sessions. Statistical analysis was performed using R version 3.2.3 (R Foundation for Statistical Computing, http://www.R-project.org/). Demographics (sex and age) and teaching experience were summarized with descriptive statistics for each variable. Demographics, teaching experience, awareness of disability, and knowledge of epilepsy were correlated to the management of seizures occurring in the classroom before the course; results are reported as odds ratios [OR] and 95% confidence interval (95 CI). RESULTS: Nine hundred school staff members (95% school staff and 5% social workers) entered in the project between January 2016 and November 2018. Seven hundred and forty (82%) returned the questionnaires fulfilled, and not all of them were completely filled. Ninety-eight percent of school staff (676/691) were aware about epilepsy; however, only in 16% (110) the awareness of epilepsy came from medical staff, scientific brochures, or participation in conventions. Thirty-five percent of school staff (248/707) believed that epilepsy reduces learning abilities, and 58% (409/703) believed that children with epilepsy need school support. After the training, 68% of school staff (496/734) correctly filled in the questionnaire related to the management of acute seizures versus 8% of them (57/718) in the prequestionnaire. After the training, 89% of school staff (601/675) were ready to administer rescue medications versus 54% (384/712) before the training. The majority of participants reported that the level of anxiety related to the management of seizures after the training significantly reduced. CONCLUSIONS: Results of this project documented an increase in knowledge of epilepsy, a better knowledge on management of acute seizures in the school settings, a reduction in anxiety, and an increase in willingness to administer rescue medications. Further studies should be planned in order to document the changes in the real-world management of seizures, to evaluate if a reduction in hospital admittances might be reached, and to extend the project by assessing, through a questionnaire, the stigma and prejudices against the children affected by epilepsy by their classmates.
Asunto(s)
Manejo de la Enfermedad , Conocimientos, Actitudes y Práctica en Salud , Instituciones Académicas , Convulsiones/terapia , Estudiantes , Formación del Profesorado/métodos , Adolescente , Adulto , Anciano , Niño , Escolaridad , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Maestros/psicología , Convulsiones/epidemiología , Convulsiones/psicología , Estigma Social , Estudiantes/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth. Invitations were sent to 6631 contacts of all patients diagnosed with epilepsy within the last 5â¯years at the BambinoGesù Children's Hospital in Rome. Of the 3321 responses received, 55.6% of patients were seizure-free for at least 1â¯year before the COVID-19-related lockdown, 74.4% used anti-seizure medications (ASMs), and 59.7% had intellectual disability. Only 10 patients (0.4%) became infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Seizure frequency remained stable for most patients during the lockdown period (increased in 13.2%; decreased in 20.3%), and seizure duration, use of rescue medications, and adherence to treatment were unchanged. Comorbidities were more affected (behavioral problems worsened in 35.8%; sleep disorder worsened in 17.0%). Visits were canceled/postponed for 41.0%, but 25.1% had remote consultation during the lockdown period (93.9% were satisfied). Most responders (67.2%) considered continued remote consultations advantageous. Our responses support that patients/caregivers are willing to embrace telemedicine for some scenarios.
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COVID-19/psicología , Cuidadores/psicología , Cuidadores/tendencias , Epilepsia/psicología , Telemedicina/tendencias , Adolescente , COVID-19/epidemiología , COVID-19/terapia , Niño , Preescolar , Epilepsia/epidemiología , Epilepsia/terapia , Femenino , Humanos , Lactante , Recién Nacido , Italia/epidemiología , Masculino , Pandemias , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study aimed to provide information on the burden of illness and health-related quality of life (HRQoL) in children with epilepsy who experience prolonged acute convulsive seizures (PACS) in the community setting, and to investigate factors that may predict poor HRQoL in this population. METHODS: Noninstitutionalized children (aged 3-16â¯years) who had experienced at least one PACS within the past year and had currently prescribed PACS rescue medication were enrolled in a cross-sectional study in Germany, Italy, Spain, and the United Kingdom (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3 [PERFECT-3]). Clinicians, parents/guardians, and patients completed web-based questionnaires regarding clinical characteristics, PACS frequency, and day-to-day impairment. Patients' HRQoL was rated by clinicians, parents/guardians, and patients themselves using the 5-dimension EuroQol questionnaire (EQ-5D) and summarized as a utility score. Potential predictors of poor HRQoL were tested in individual univariate generalized linear models and a global multivariable model. RESULTS: Enrolled children (Nâ¯=â¯286) had experienced 1-400 PACS (median: 4) in the past year. Clinicians reported that 216/281 patients (76.9%) had learning disabilities of varying severity. Mean EQ-5D utility scores rated by clinicians (nâ¯=â¯279), parents (nâ¯=â¯277), and patients (nâ¯=â¯85) were 0.52 (standard deviation: 0.41), 0.51 (0.39), and 0.74 (0.29), respectively. Increasing PACS frequency, increasing severity of learning disability, and specialist school attendance were significantly associated with decreasing EQ-5D utility score. In the multivariable model, having learning disabilities was the best predictor of poor HRQoL. SIGNIFICANCE: Health-related quality of life was very poor in many children with epilepsy whose PACS were managed with rescue medication in the community, with learning disability being the most powerful predictor of patients' HRQoL. Mean EQ-5D utility scores were lower (worse) than published values for many other chronic disorders, indicating that optimal treatment should involve helping children and their families to manage learning disabilities and day-to-day impairments, in addition to preventing seizures.
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Servicios de Salud Comunitaria/tendencias , Costo de Enfermedad , Servicios Médicos de Urgencia/tendencias , Epilepsia/psicología , Calidad de Vida/psicología , Convulsiones/psicología , Adolescente , Anticonvulsivantes/administración & dosificación , Niño , Preescolar , Servicios de Salud Comunitaria/métodos , Estudios Transversales , Servicios Médicos de Urgencia/métodos , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Alemania/epidemiología , Humanos , Italia/epidemiología , Masculino , Padres/psicología , Convulsiones/tratamiento farmacológico , Convulsiones/epidemiología , España/epidemiología , Encuestas y Cuestionarios , Factores de Tiempo , Reino Unido/epidemiologíaRESUMEN
Seizure threshold 2 (SZT2) gene mutations have been associated with developmental and epileptic encephalopathies (DEEs). Following a literature review, we collected 22 patients and identified the main clinical features related to SZT2 variants that are epilepsy with onset within the first years of life, intellectual disability (ID), macrocephaly with dysmorphic facial features, corpus callosum (CC) shape abnormalities, and cortical migration disorders. Moreover, we identified the c.7825T>G homozygous missense variant in SZT2 in two female siblings presenting with focal seizures, mild-moderate ID, behavioral disturbances, and facial dysmorphisms. Interictal Electroencephalogram (EEG) and ictal EEG were both informative and revealed, respectively, temporal bilateral asynchronous slow and epileptiform abnormalities and a focal onset in both of them. Neuroimaging study revealed a thick and abnormally shaped CC. Seizure threshold 2 has been identified as a component of the KICSTOR complex, a newly recognized protein complex involved in the mammalian target of rapamycin (mTOR) pathway. mTOR signaling dysregulation represents common pathogenetic mechanisms that can explain the presence of both epileptogenesis and ID. Even if few cases had been reported, a new clinical phenotype is emerging, and recent hypothesis of hyperactivation of mTORC1 signaling might also open to targeted treatments, challenging an early diagnosis as of paramount importance.
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Síndromes Epilépticos/genética , Variación Genética/genética , Genómica/métodos , Discapacidad Intelectual/genética , Mutación Missense/genética , Proteínas del Tejido Nervioso/genética , Niño , Preescolar , Electroencefalografía/métodos , Síndromes Epilépticos/complicaciones , Síndromes Epilépticos/diagnóstico , Femenino , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/diagnóstico , LinajeRESUMEN
Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.
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Ataxia/genética , Corea/genética , Fenotipo , Ataxia/clasificación , Ataxia/diagnóstico , Corea/clasificación , Corea/diagnóstico , Pruebas Genéticas/métodos , Humanos , MutaciónRESUMEN
POGZ (# 614787) encodes a multidomain nuclear protein involved in transcriptional regulation and its defective function has been recently associated with a syndromic neurodevelopmental disorder, known as White-Sutton syndrome (# 616364). While originally epileptic seizures were unreported, it seems that epilepsy represents a recurrent feature in affected subjects. Few data, however, are available on electroclinical features of POGZ-related epilepsy. We report a 5-year-old girl with a de novo inactivating POGZ mutation with a complex neurological phenotype characterized by hypotonia, severe developmental delay, and paroxysmal epileptic and nonepileptic events. Comparing this patient with the previously reported nine cases exhibiting epilepsy as associated feature, we detected that epilepsy onset is mostly during infancy (1-4 years of age), with both focal and generalized seizures. EEGs reveal that epileptic abnormalities mainly are localized in the frontal regions, and seizure control might be reached with one or multiple antiepileptic drugs. Besides dysmorphic features and other comorbidities (microcephaly, intellectual disability, absent speech, sensorineural hearing loss, and autistic spectrum disorder) major brain MR features include cortical and cerebellar atrophy, delayed myelination, and brainstem hypoplasia. Although the small number of patients reported, we were able to delineate primary electroclinical epileptic phenotype related to POGZ mutations. This would be crucial for an early identification and management of the condition.