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Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment.
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Estudios de Asociación Genética , Síndrome de Prader-Willi , Síndrome de Prader-Willi/genética , Humanos , Enfermedades del Sistema Endocrino/genética , FenotipoRESUMEN
PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).
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Epilepsia Refractaria , Electroencefalografía , Humanos , Masculino , Femenino , Estudios Retrospectivos , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Adolescente , Niño , Preescolar , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Dexametasona/uso terapéutico , Adulto , Adulto Joven , Resultado del Tratamiento , Anticonvulsivantes/uso terapéutico , Corticoesteroides/uso terapéutico , Hidrocortisona/uso terapéuticoRESUMEN
Background: Hereditary spastic paraplegia (HSP) encompass a variety of neurodegenerative disorders that are characterized by progressive deterioration of walking ability and a high risk for long-term disability. The management of problems associated with HSP, such as stiffness, deformity, muscle contractures, and cramping, requires strict adherence to recommended physiotherapy activity regimes. The aim of this paper is to conduct a critical narrative review of the available evidence focusing exclusively to the therapeutic advantages associated with various forms of physical therapy (PT) in the context of HSP, emphasizing the specific benefit of every distinct approach in relation to muscle relaxation, muscle strength, spasticity reduction, improvement of weakness, enhancement of balance, posture, walking ability, and overall quality of life. Methods: To conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched. Results: The PubMed search returned a total of 230 articles, Scopus returned 218, and DOAJ returned no results. After screening, the final list included 7 papers on PT treatment for HSP patients. Conclusion: Electrostimulation, magnetotherapy, hydrotherapy, PT, robot-assisted gait training, and balance rehabilitation have the potential to increase lower extremity strength and decrease spasticity in HSP patients.
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Pathogenic gene variants encoding nuclear pore complex (NPC) proteins were previously implicated in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). The NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS with limited genotype-phenotype information. We identified an Italian boy affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly, axial hypotonia, lack of achievement of motor milestones, and refractory seizures with an associated hypsarrhythmic pattern on electroencephalography. Brain magnetic resonance imaging (MRI) showed hypoplasia of the corpus callosum and a simplified gyration of the cerebral cortex. Since the age of 3 years, the boy was followed up at our Pediatric Nephrology Department for an SRNS, with a focal segmental glomerulosclerosis at renal biopsy. The boy died 32 months after SRNS onset, and a Whole-Exome Sequencing analysis revealed a novel compound heterozygous variant in NUP85 (NM_024844.5): 611T>A (p.Val204Glu), c.1904T>G (p.Leu635Arg), inherited from the father and mother, respectively. We delineated the clinical phenotypes of NUP85-related disorders, reviewed the affected individuals so far reported in the literature, and overall expanded both the phenotypic and the molecular spectrum associated with this ultra-rare genetic condition. Our study suggests a potential occurrence of severe neurological phenotypes as part of the NUP85-related clinical spectrum and highlights an important involvement of nucleoporin in brain developmental processes and neurological function.
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Neuronas , Podocitos , Niño , Preescolar , Humanos , Masculino , Mutación , Síndrome Nefrótico/genética , Síndrome Nefrótico/patología , Neuronas/metabolismo , Neuronas/patología , Proteínas de Complejo Poro Nuclear/genética , Podocitos/metabolismo , Podocitos/patologíaRESUMEN
BACKGROUND: P-21-activated kinases (PAKs) are protein serine/threonine kinases, part of the RAS/mitogen-activated protein kinase pathway. PAK1 is highly expressed in the central nervous system and crucially involved in neuronal migration and brain developmental processes. Recently, de novo heterozygous missense variants in PAK1 have been identified as an ultrarare cause of pediatric neurodevelopmental disorders. METHODS: We report a series of children affected with postnatal macrocephaly, neurodevelopmental impairment, and drug-resistant epilepsy. Repeated electroencephalographic (EEG) and video-EEG evaluations were performed over a two- to 10-year period during follow-up to delineate electroclinical histories. Genetic sequencing studies and computational evaluation of the identified variants were performed in our patient cohort. RESULTS: We identified by whole-exome sequencing three novel de novo variants in PAK1 (NM_001128620: c.427A>G, p.Met143Val; c.428T>C, p.Met143Thr; c.428T>A, p.Met143Lys) as the underlying cause of the disease in our families. The three variants affected the same highly conserved Met143 residue within the cysteine-rich inhibitor of PAK1 (CRIPaK) domain, which was identified before as a PAK1 inhibitor target. Computational studies suggested a defective autoinhibition presumably due to impaired PAK1 autoregulation as a result of the recurrent substitution. CONCLUSIONS: We delineated the electroclinical phenotypes of PAK1-related neurological disorders and highlight a novel mutational hotspot that may involve defective autoinhibition of the PAK1 protein. The three novel variants affecting the same hotspot residue within the CRIPaK domain highlight potentially impaired PAK1-CRIPaK interaction as a novel disease mechanism. These findings shed light on possible future treatments targeted at the CRIPaK domain, to modulate PAK1 activity and function.
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Trastornos del Neurodesarrollo , Quinasas p21 Activadas , Niño , Humanos , Quinasas p21 Activadas/genética , Quinasas p21 Activadas/química , Quinasas p21 Activadas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Mutación/genética , Trastornos del Neurodesarrollo/genética , Mutación MissenseRESUMEN
McCune-Albright Syndrome (MAS) is a rare mosaic (post-zygotic) genetic disorder presenting with a broad continuum clinical spectrum. MAS arises from somatic, activating mutations in the GNAS gene, which induces a dysregulated Gsα-protein signaling in several tissues and an increased production of intracellular cyclic adenosine monophosphate (cAMP). Overall, MAS is a rare disorder affecting less than 1/100,000 children and, for this reason, data establishing genotype-phenotype correlations remain limited. Affected individuals clinically present with a variable combination of fibrous dysplasia of bone (FD), extra-skeletal manifestations (including cafeí-au-lait spots) and precocious puberty which might also be associated to broad hyperfunctioning endocrinopathies, and also gastrointestinal and cardiological involvement. Central nervous system (CNS) and eye involvement in MAS are among the less frequently described complications and remain largely uncharacterized. These rare complications mainly include neurodevelopmental abnormalities (e.g., delayed motor development, cognitive and language impairment), CNS anomalies (e.g., Chiari malformation type I) and a wide array of ophthalmological abnormalities often associated with vision loss. The pathophysiological mechanisms underlying abnormal neurological development have not been yet fully elucidated. The proposed mechanisms include a deleterious impact of chronically dysregulated Gsα-protein signaling on neurological function, or a secondary (damaging) effect of (antenatal and/or early postnatal) hypercortisolism on early pre- and post-natal CNS development. In this Review, we summarize the main neurological and ophthalmological features eventually associated with the MAS spectrum, also providing a detailed overview of the potential pathophysiological mechanisms underlying these clinical complications.
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Síndrome de Cushing , Enfermedades del Sistema Endocrino , Displasia Fibrosa Ósea , Displasia Fibrosa Poliostótica , Embarazo , Femenino , Humanos , Displasia Fibrosa Poliostótica/complicaciones , Displasia Fibrosa Poliostótica/genética , Enfermedades del Sistema Endocrino/complicaciones , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Síndrome de Cushing/complicaciones , EncéfaloRESUMEN
BACKGROUND: The COVID-19 pandemic has dramatically affected all aspects of the patient's pathway to cancer diagnosis and subsequent treatment. Our main objective was to evaluate the status of cancer trials in Ukraine as of September 2022. METHODS: Initially, we examined with a narrative review the state of breast, colorectal, and cervical cancer population-based screening. Subsequently, we assessed each trial status for the years 2021 and 2022. RESULTS: Estimates of participation in breast and cervical cancer screening are different from region to region. Moreover, regarding cervical cancer screening, extremely different participation estimates were reported: 73% in 2003 vs. <10% 2020. Our data show that from 2014 to 2020, despite the pandemic, cancer trials in Ukraine significantly increased from 27 to 44. In 2021 no trials were completed; in fact, we observed that out of 41 trials, 8 were active not recruiting, 33 were recruiting, and 0 were completed or terminated. In 2022 in Ukraine, for oncological pathologies, only 3 trials were registered, while in 2021, 41 trials were registered. The suspension of trials regarded above all concern hematological tissue (66.7%) and the genitourinary tract (60%). CONCLUSIONS: Our work has highlighted how the areas most affected by the conflict present criticalities in oncological care.
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BACKGROUND: We evaluated the changes in lifestyle during the COVID-19 pandemic lockdown in a sample of children and adolescents in order to assess any increase in risk factors for the onset of cardiovascular diseases in later ages. METHODS: We conducted a cross-sectional study involving 965 parents who completed an online survey about dietary habits and lifestyle during the first lockdown in Italy (from 9 March 2020 to 18 May 2020) and compared their findings with the period before the pandemic. The inclusion criteria were parents (or caregivers) with Italian residency and with children aged between 5 and 18 years. RESULTS: We identified 563 adolescents and 402 children. The mean age was 12.28 years (SD 3.754). The pandemic was associated with an increase in the consumption of high-calorie snack foods. The total amount of food in homes during lockdown compared with before the pandemic increased 50%. Relating to the parent-perceived child weight status, more parents reported obesity in their children after lockdown (+0.6% in the 5-11 age group and +0.2% in the 12-18 age group). We reported a reduction of physical activity, an increase of sedentary lifestyle and sleep habits changes. CONCLUSION: The COVID-19 pandemic was associated with changes in the lifestyles of children and adolescents; this could cause an increase in the incidence of obesity and of cardiovascular and metabolic diseases in adulthood.
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COVID-19 , Dieta , Estilo de Vida , Adolescente , COVID-19/epidemiología , Niño , Preescolar , Control de Enfermedades Transmisibles , Estudios Transversales , Conducta Alimentaria , Humanos , Obesidad/epidemiología , PandemiasRESUMEN
Obstructive sleep apnea syndrome (OSAS) in childhood is a complex disease primarily due both to adenotonsillar hypertrophy and pediatric obesity. Notably, inflammation has been recognized as one of the most important shared pathogenic factor between obesity and OSAS resulting in an increased cardiometabolic risk for these patients. To date, evidence is still limited in non-obese population with OSAS. We aimed to evaluate the cardiometabolic risk profile of a pediatric population of non-obese subjects affected by OSAS. A total of 128 school-aged children (mean age 9.70 ± 3.43) diagnosed with OSAS and 213 non-OSAS children (mean age 9.52 ± 3.35) as control group were enrolled. All subjects underwent a complete clinical and biochemical assessment (including white blood cell count (WBC), platelet count (PLT), mean platelet volume (MPV), % of neutrophils (NEU%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), uric acid, fasting insulin, iron, ferritin, and transferrin levels). A significant association between inflammation markers (including WBC, PLT, MPV, NEU%, ferritin, CPR, and ESR) and OSAS was found (all p < 0.001). Children with OSAS also showed increased transaminase, glucose, uric acid, and insulin levels (all p < 0.001) compared to healthy controls. CONCLUSION: Taken together, these findings suggested a worse cardiometabolic profile in non-obese children with OSAS. Given the pivotal pathogenic role of inflammation both for hypoxiemia and metabolic derangements, therapeutic strategies for OSAS might also counteract the increased cardiometabolic risk of these patients, by improving their long-term quality of life. WHAT IS KNOWN: ⢠Pediatric OSAS has shown a close relationship with obesity and its cardiometabolic comorbidities. ⢠Inflammation represents the hallmark of both obesity and OSAS. WHAT IS NEW: ⢠Non obese children with OSAS presented with a worse cardiometabolic risk profile. ⢠OSAS treatment might serve as an effective approach also for the increased cardiometabolic risk of these children.
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Enfermedades Cardiovasculares , Obesidad Infantil , Apnea Obstructiva del Sueño , Adolescente , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Niño , Humanos , Obesidad Infantil/complicaciones , Calidad de Vida , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiologíaRESUMEN
BACKGROUND: Social robots (SRs) have been used for improving anxiety in children in stressful clinical situations, such as during painful procedures. However, no studies have yet been performed to assess their effect in children while waiting for emergency room consultations. OBJECTIVE: This study aims to assess the impact of SRs on managing stress in children waiting for an emergency room procedure through the assessment of salivary cortisol levels. METHODS: This was an open randomized clinical trial in children attending a pediatric emergency department. Children accessing the emergency room were randomized to 1 of 3 groups: (1) playing with a NAO SR, (2) playing with a study nurse, or (3) waiting with parents. The salivary cortisol levels of all children were measured through a swab. Salivary cortisol levels before and after the intervention were compared in the 3 groups. We calculated the effect size of our interventions through the Cohen d-based effect size correlation (r). RESULTS: A total of 109 children aged 3-10 years were enrolled in the study, and 94 (86.2%) had complete data for the analyses. Salivary cortisol levels significantly decreased more in the group exposed to robot interaction than in the other two groups (r=0.75). Cortisol levels decreased more in girls (r=0.92) than in boys (r=0.57). CONCLUSIONS: SRs are efficacious in decreasing stress in children accessing the emergency room and may be considered a tool for improving emotional perceptions of children and their families in such a critical setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT04627909; https://clinicaltrials.gov/ct2/show/study/NCT04627909.
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Robótica , Aminoacridinas , Niño , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Padres , Interacción SocialRESUMEN
Juvenile idiopathic arthritis (JIA) is the most common inflammatory chronic disease affecting children and adolescents. Today, there are no specific biomarkers of inflammation. Therefore, it is important to identify new markers as predictors of disease activity. Recently, some researchers have directed their interest toward a protein, calprotectin (CLP), as a potential biomarker. The primary objective of our systematic review and meta-analysis was to analyze the possible role of CLP in JIA. METHOD: A literature search was conducted using PubMed, EMBASE, Scopus, Science Direct on 10 August 2021. The selection of studies was made using the PRISMA 2020 guidelines. Cohen's d with 95% CI and p-value were used as a measure of effect size. The random effects model was used to account for different sources of variation among studies. Heterogeneity was assessed using Q statistics and I2. The publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger's test. RESULTS: Our results at follow-up showed a statistically significant difference between patients with active disease compared to patients with inactive disease: 0.39 (0.16; 0.62), p = 0.001; without statistical heterogeneity. Another important aspect that emerged were the differences between the systemic disease form and any form of inactive disease showing a different concentration of calprotectin: 0.74 (0.40; 1.08), p < 0.001; without statistical heterogeneity. On the other hand, meta-regression analyses performed on gender, age, duration of disease, percentage of patients with ANA+ or RF+, medium value of ESR or CRP were not statistically significant. A statistically significant difference in serum calprotectin concentration between patients with JIA and healthy controls were observed. In fact, it presented lower values in the control group. CONCLUSIONS: The use of serum CLP could represent, in the future, a useful tool in JIA in order to stratify disease activity more accurately and may aid a more tailored approach to drug of choice in children with JIA. Further studies are needed to evaluate CLP as a predictor of flare in combination with other potential biomarkers of subclinical disease activity.
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BACKGROUND: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. AIMS: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). PATIENTS AND METHODS: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years' standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5-15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4-15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. RESULTS: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). CONCLUSIONS: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Obesidad Infantil/tratamiento farmacológico , Polisacáridos/administración & dosificación , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Niño , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Complejos Multiproteicos , Obesidad Infantil/sangre , Obesidad Infantil/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
AIM: The aim of this study was to describe the characteristics of Posterior Reversible Encephalopathy Syndrome (PRES) in infants and young children (<6 years) and to compare them with the older pediatric population affected by PRES. METHODS: we retrospectively reviewed records of 111 children (0-17 years) diagnosed with PRES from 2000 to 2018 in 6 referral pediatric hospitals in Italy. The clinical, radiological and EEG features, as well as intensive care unit (ICU) admission rate and outcome of children aged <6 years were compared to those of older children (6-17 years). Factors associated with ICU admission in the whole pediatric cohort with PRES were also evaluated. RESULTS: Twenty-nine patients younger than 6 years (26%) were enrolled with a median age at onset of PRES of 4 years (range: 6 months-5 years). Epileptic seizures were the most frequent presentation at the disease onset (27/29 patients). Status epilepticus (SE) was observed in 21/29 patients: in detail, 11 developed convulsive SE and 10 presented nonconvulsive SE (NCSE). SE was more frequent in children <6 years compared with older children (72% vs 45%) as well as NCSE (35% vs 10%). Seventeen children aged <6 years required ICU admission. Prevalence of ICU admissions was higher within younger population compared to older (59% vs 37%). In the whole study population SE was significantly associated with ICU admission (p = 0.001). CONCLUSIONS: PRES in children < 6 years differs from older children in clinical presentation suggesting a more severe presentation at younger age.
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Síndrome de Leucoencefalopatía Posterior/complicaciones , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Italia , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5-1% and a lifetime incidence of 1-3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols.
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Dieta Sin Gluten/métodos , Dieta Cetogénica/métodos , Dieta Reductora/métodos , Epilepsia/dietoterapia , HumanosRESUMEN
INTRODUCTION: Most of the patients usually achieve seizure freedom under treatment with antiseizure medications (ASMs). Drug withdrawal in seizure-free patients is still one of the most challenging issues in the management of epilepsy. The decision-making process of whether the treatment should be discontinued must be based on the evaluation of possible long-term side effects of chronic treatment and, on the other hand, the risk of seizure relapse. AREAS COVERED: This review aims to describe and discuss possible predictors and risk factors for seizure relapse during and after discontinuation, according to the available literature evidence. The most important risk factors for withdrawal failure are the etiology of the epilepsy syndrome and epilepsy-related factors, worsening or persistence of epileptiform abnormalities on EEG recordings at the time of discontinuation or during drug tapering, and brain MRI abnormalities. Each single risk factor should be considered together with possible other concurrent predictors. EXPERT OPINION: The decision to withdrawal antiseizure medication in seizure-free patients should be carefully planned and based on the evaluation of predictors. A discontinuation program should include tailored discussion with patients and family members and individualized decision, the taper schedule, and plans for monitoring during and after drug tapering.
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Anticonvulsivantes/administración & dosificación , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Humanos , Recurrencia , Factores de RiesgoRESUMEN
BACKGROUND: A high prevalence (9.5-30%) of eosinophilic esophagitis (EoE) in patients with esophageal atresia (EA) has been reported. The application of the EoE criteria to EA patients might be problematic. To date, only studies using a "routine" biopsy approach, even in asymptomatic patients, have been performed. The aim of the study was to establish the prevalence of EoE among symptomatic EA patients (EA/EoE group) without anastomotic stricture (AS) and to compare their characteristics with those of EoE patients from general population (EoE group). METHODS: From 2005 to 2018, we reviewed charts of children with EA and EoE. "Selective" biopsy approach only in EA children without AS and/or endoscopic feature of EoE was performed. Characteristics of EA/EoE and EoE groups were compared. RESULTS: Among 370 EA and 118 EoE, 15 EA/EoE patients were detected (4.0% of EA patients). Male predominance and a high prevalence of allergy without differences between EA/EoE and EoE groups was observed. EA/EoE children were significantly younger (p < 0.0001). PPI-responder patients were significantly more prevalent in EA/EoE group (p = 0.045). CONCLUSION: Our data confirm that EA patients are at high risk for developing EoE. High incidence, early onset, and high prevalence of PPI-responders might suggest that esophageal motility disorders interact to increase propensity to EoE in EA patients. However, our study also suggests that overdiagnosis of EoE may occur in EA and that adapted criteria for EoE diagnosis should be developed for EA patients. TRIAL REGISTRATION: Not applicable for this retrospective study.
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Introduction: Antiepileptic polytherapy may be indicated in patients experiencing drug-resistant epilepsy. To date, there are no evidence-based criteria on how to combine different antiepileptic drugs (AEDs) together, in order to obtain the best therapeutic response.Areas covered: This paper reviews the available data about the various associations of AEDs in patients undergoing polytherapy, focusing on the most effective and well-tolerated polytherapies. Moreover, some controversial aspects of this topic are addressed.Expert opinion: Nowadays, there are no guidelines on polytherapy in patients with epilepsy; thus, the management of pharmacoresistant epilepsy is still uncertain, except for valproate/lamotrigine combination, which seems to be the only one recommended. Data regarding mechanism of action, pharmacokinetics, tolerability, and, more importantly, the analysis of the valuable clinical studies of drug combinations can help physicians to choose the best and most effective AED association for each patient.
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Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada/normas , HumanosRESUMEN
PURPOSE: Infantile spasms (IS) represent a severe seizure disorder of infancy and early childhood characterized by epileptic spasms along with hypsarrhythmia often accompanied by intellectual disability. According to the current classification and terminology (3) IS can be categorized as known etiology, formerly known as "symptomatic", when an underlying cause has been observed prior to the onset of spasms, or of "unknown cause" with "unfavorable" and "favorable" outcome (previously referred as "cryptogenic" or "idiopathic", respectively). Single reports described children with "unknown cause and favorable outcome" (UC/FO) IS who later developed childhood absence epilepsy (CAE). This study aims to determine the prevalence of CAE following IS. METHODS: a multicenter retrospective chart review was performed; children with UC/FO IS who subsequently developed CAE during follow-up were identified. Eight Italian pediatric epilepsy centers participated in this study. RESULTS: seven out of 24 (29 %) children (3 males) showing a favorable outcome (UC/FO) IS received a second diagnosis of CAE during follow-up. Mean age at IS presentation was 5.8 months (SD ± 0.9). All achieved seizure control of IS at a mean age of 8.5 months (SD ± 1.3) (3 monotherapy, 4 polytherapy). CAE was diagnosed at a mean age of 8.0 years (SD ± 3.0). Six children achieved sustained remission of CAE with valproic acid, whereas 1 child required dual therapy by adding ethosuximide. CONCLUSION: although it is not possible to determine whether the association between UC/FO IS and CAE implies a causality relationship, the later occurrence of CAE in patients with UC/FO IS might support a possible role of thalamo-cortical dysfunction.