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OBJECTIVE: We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit. METHODS: Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score. RESULTS: Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset. CONCLUSIONS: A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology.
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Sleep disorders are frequent in tuberous sclerosis complex (TSC) during the developmental age but are not well characterized. Forty-six TSC patients and 46 healthy age- and sex-matched controls were enrolled. Their parents completed the Sleep Disturbances Scale for Children (SDSC) and the Child Behavior Checklist (CBCL). A total of 17.4% of the TSC patients obtained a total pathologic score at the SDSC versus 4.4% in the control group (p = 0.024). 45.7% of individuals with TSC reported a pathologic score in at least one of the factors. We found a statistically significant difference between the TSC cohort and healthy controls for most of the CBCL scales scores. A significant relationship was found between the Total SDSC score and the Total CBCL score (R-square = 0.387, p < 0.0001), between the Total SDSC score and the Internalizing and Externalizing areas scores (R-square = 0.291, p < 0.0001 and R-square = 0.350, p < 0.0001, respectively) of the CBCL. Sleep disorders are more frequent in TSC than in the general population and correlate with behavior. The use of SDSC and CBCL is proposed as part of the surveillance of TSC patients in the developmental age.
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Trastornos de la Conducta Infantil/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño/fisiología , Esclerosis Tuberosa/fisiopatología , Adolescente , Niño , Trastornos de la Conducta Infantil/complicaciones , Trastornos de la Conducta Infantil/epidemiología , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Padres , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Encuestas y Cuestionarios , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/epidemiologíaRESUMEN
OBJECTIVES: Little is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic. MATERIALS AND METHODS: We collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities. RESULTS: Out of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug-resistant; 59 (32.8%) seizure-free, at a median age of 18 years. 22% of the seizure-free patients (13/59) discontinued medication. Median age at seizure onset was 9 months. Seventy-six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p < 0.001) and subependymal nodules (SENs) (p < 0.001) were more frequent in those who developed epilepsy. Cognitive functioning was lower (p < 0.001) and psychiatric disorders more frequent (p = 0.001). We did not find significant differences regarding age, gender, mutation and tubers/SENs in seizure-free vs drug-resistant individuals. Intellectual disability (p < 0.001) and psychiatric disorders (p = 0.004) were more common among drug-resistant patients. CONCLUSIONS: Epilepsy in TSC can be a lifelong disorder, but one-third of individuals reach seizure freedom by early adulthood. In the long term, age at epilepsy onset has a crucial role in drug resistance and in developing intellectual disability, both in drug-resistant and drug-sensible patients. Patients with drug-refractory seizures tend to develop psychiatric issues, which should be recognized and adequately treated.
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Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/epidemiología , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/epidemiología , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/epidemiología , Adolescente , Adulto , Niño , Preescolar , Epilepsia Refractaria/psicología , Epilepsia/diagnóstico , Epilepsia/epidemiología , Epilepsia/psicología , Estudios de Seguimiento , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/psicología , Masculino , Estudios Retrospectivos , Espasmos Infantiles/psicología , Esclerosis Tuberosa/psicologíaRESUMEN
Missense variants in HNRNPH2 cause Bain type syndromic X-linked intellectual disability (XLID). To date, only six affected females and three affected males have been reported in the literature, and the phenotype has yet to be delineated in detail. Here, we report on a 35-year-old female with a novel de novo variant in HNRNPH2, providing further evidence that missense changes in the nuclear localization sequence cause Bain type XLID and that aminoacid 206 likely represents a mutational hotspot. We expand the phenotype of Bain type XLID to include breathing, sleep and movement disorders, cerebellar vermis hypoplasia, stereotypies, and hypersensitivity to noise. Our data indicate that the phenotype may be broader and more variable than initially reported, and suggest Rett syndrome as a possible differential diagnosis.
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Anomalías Múltiples/etiología , Ribonucleoproteína Heterogénea-Nuclear Grupo F-H/genética , Discapacidad Intelectual/etiología , Discapacidad Intelectual Ligada al Cromosoma X/etiología , Mutación Missense , Anomalías Múltiples/patología , Adulto , Exoma , Femenino , Humanos , Discapacidad Intelectual/patología , Discapacidad Intelectual Ligada al Cromosoma X/patología , FenotipoRESUMEN
Individuals with comorbidities are at higher risk of coronavirus disease 2019 (COVID-19) and worse outcome, but little information has been available about patients with genetic diseases and COVID-19. This study aims at evaluating the presence and outcome of COVID-19 in a cohort of Italian patients with tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM), and at reviewing the possible effects of mTOR inhibitors on SARS-CoV-2 infection. We included 102 unselected individuals with a diagnosis of TSC and/or LAM assessed between January 1, 2020 and April 24, 2020 (29% children, 71% adults). Twenty-six patients were on mTOR inhibitors. Demographic data, TSC manifestations, presence, and outcomes in individuals with confirmed or suspected SARS-CoV-2 infection were evaluated. Health status and outcomes of all patients on mTOR inhibitors were assessed. One patient with severe TSC had polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection, was admitted to ICU, and died. Nine additional patients either met the definition of suspect case or presented with at least two of the most common symptoms of SARS-CoV-2 infection. All recovered fully. None of the patients treated with mTOR inhibitors for their underlying comorbidities was diagnosed with COVID-19, and those who showed suspicious respiratory symptoms recovered fully. This cohort study provides preliminary information on COVID-19 in people with TSC in Italy and suggests feasibility to systematically evaluate the role of mTOR inhibitors in SARS-CoV-2 infection.
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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Linfangioleiomiomatosis/epidemiología , Pandemias , Neumonía Viral/epidemiología , Esclerosis Tuberosa/epidemiología , Adolescente , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/virología , Femenino , Hospitalización , Humanos , Lactante , Italia/epidemiología , Masculino , Persona de Mediana Edad , Neumonía Viral/virología , Estudios Retrospectivos , SARS-CoV-2 , Adulto JovenRESUMEN
Sleep and epilepsy interact with each other in a complex bidirectional way. The main objective of this study was to characterize and determine the prevalence of sleep and behavioral disorders among Italian children and adolescents with epilepsy. We asked 84 consecutive parents/caregivers of patients with epilepsy aged between 6 and 17â¯years old to fill out the Sleep Disturbances Scale for Children (SDSC) and Child Behavior Checklist (CBCL). An abnormal total sleep score was found in 20 subjects with epilepsy (23.8%), compared with 4 (4.4%) of control group (Pâ¯<â¯.001). Forty-eight patients (57.1%) had an abnormal score in at least one SDSC factor: disorders in initiating and maintaining sleep (DIMS; 13.1%), sleep breathing disorders (SBD; 13.1%), disorders of arousal (DA; 5.9%), sleep-wake transition disorders (SWTD; 15.5%), disorders of excessive somnolence (DOES; 20.2%), and sleep hyperhidrosis (SHY; 5.9%). Patients with epilepsy showed higher prevalence of behavioral/emotional disturbances in all CBCL domains but one compared with patients without epilepsy. The SDSC and CBCL total scores showed a significant correlation (R-squareâ¯=â¯0.256; Pâ¯<â¯.001). Sleep and behavioral/emotional disorders are common in epilepsy during childhood and adolescence. The SDSC could be a valid tool to screen sleep disturbances in this group of patients.
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Epilepsia/epidemiología , Epilepsia/psicología , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/psicología , Encuestas y Cuestionarios , Adolescente , Cuidadores/psicología , Niño , Trastornos de la Conducta Infantil/diagnóstico , Trastornos de la Conducta Infantil/epidemiología , Trastornos de la Conducta Infantil/psicología , Estudios de Cohortes , Epilepsia/diagnóstico , Femenino , Humanos , Italia/epidemiología , Masculino , Padres/psicología , Prevalencia , Sueño/fisiología , Trastornos del Sueño-Vigilia/diagnósticoRESUMEN
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease affecting approximately 1 in 6,000 people, and represents one of the most common genetic causes of epilepsy. Epilepsy affects 90% of the patients and appears in the first 2 years of life in the majority of them. Early onset of epilepsy in the first 12 months of life is associated with high risk of cognitive decline and neuropsychiatric problems including autism. Prenatal or early infantile diagnosis of TSC, before the onset of epilepsy, provides a unique opportunity to monitor EEG before the onset of clinical seizures, thus enabling early intervention in the process of epileptogenesis. In this review, we discuss the current status of knowledge on epileptogenesis in TSC, and present recommendations of American and European experts in the field of epilepsy.
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Anticonvulsivantes/uso terapéutico , Epilepsia/etiología , Epilepsia/terapia , Esclerosis Tuberosa/complicaciones , Cannabidiol/uso terapéutico , Disfunción Cognitiva/etiología , Dieta Cetogénica , Electroencefalografía , Epilepsia/diagnóstico , Humanos , Lactante , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Estimulación del Nervio Vago/métodosRESUMEN
Epilepsy is the most common neurological symptom in tuberous sclerosis complex (TSC), occurring in 72-85% of affected individuals. Despite the large number of patients reported, their electroclinical phenotype has been rarely described. We analyzed seizure semiology through ictal video-electroencephalography (V-EEG) recordings in a large series of patients. In this multicenter study, we reviewed V-EEGs of 51 patients: ictal recordings were analyzed in correlation with their clinical variables. The median age of epilepsy onset was six months (one day-16â¯years), with onset in the first year of life in 71% patients (36/51), in 10 of them during the neonatal period. Sixty-five percent of patients (33/51) experienced epileptic spasms in their life, with late-onset (>two years) in five; 42% of the epileptic spasms persisted after age two years, despite the onset in the first year of life. We identified four different electroclinical subsets: focal epilepsy (35%, 18/51), Lennox-Gastaut Syndrome evolution (27%, 14/51), focal seizures with persisting spasms (33%, 17/51), and spasms only (4%, 2/51). We reviewed 45 focal seizures, 13 clusters of epileptic spasms, and seven generalized seizures. In 12 patients, we recorded different seizure types. In 71% of the focal seizures (32/45), the ictal pattern was focal without diffusion. In 38% of the patients (5/13) epileptic spasms were related to typical diffuse slow wave pattern associated with superimposed fast activity, with focal predominance. Focal seizures and focal spasms resulted as the most frequent seizure types in TSC. Seizure onset was variable but showing a predominant involvement of the frontocentral regions (40%). Discrete clinical signs characterized the seizures, and behavioral arrest was the predominant first clinical objective sign. Epileptic spasms were a typical presentation at all ages, frequently asymmetrical and associated with lateralizing features, especially in older patients.
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Epilepsia/complicaciones , Convulsiones/complicaciones , Esclerosis Tuberosa/complicaciones , Adolescente , Adulto , Niño , Preescolar , Electroencefalografía/métodos , Epilepsia/fisiopatología , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Convulsiones/fisiopatología , Esclerosis Tuberosa/fisiopatología , Grabación en Video , Adulto JovenRESUMEN
Approximately 60-80% of girls with Rett Syndrome (RTT) have epilepsy, which represents one of the most severe problems clinicians have to deal with, especially when patients are 7-12years old. The aim of this study was to analyze the antiepileptic drugs (AEDs) prescribed in RTT, and to assess their effectiveness and tolerability in different age groups from early infancy to adulthood. We included in this study 104 girls, aged 2-42years (mean age 13.9years): 89 had a mutation in MECP2, 5 in CDKL5, 2 in FOXG1, and the mutational status was unknown in the remaining 8. Epilepsy was present in 82 patients (79%). Mean age at epilepsy onset was 4.1years. We divided the girls into 5 groups according to age: <5, 5-9, 10-14, 15-19, 20years and older. Valproic acid (VPA) was the most prescribed single therapy in young patients (<15years), whereas carbamazepine (CBZ) was preferred by clinicians in older patients. The most frequently adopted AED combination in the patients younger than 10years and older than 15 was VPA and lamotrigine (LTG). Seizures in the group aged 10-14years were the most difficult to treat, requiring a mean of three different AEDs, often used in combination and mostly including VPA. Seizures in fifteen patients (18%) were considered drug resistant. VPA was reported as the most effective AED in younger girls (in 40% of the patients aged <5years, in 19% of the girls aged 5-9years), and CBZ the most effective in the patients 15years or older. Adverse reactions did not differ from expected: agitation, drowsiness, and weight loss were the most frequently reported. In our sample, LTG was the least tolerated AED. We did not find correlations with MECP2 mutations in terms of effectiveness or adverse reactions. CONCLUSION: in this study we observed different effectiveness of AEDs based on age, and suggest that clinicians consider age-dependency when prescribing appropriate AEDs in the RTT population.
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Anticonvulsivantes/farmacología , Carbamazepina/farmacología , Epilepsia/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Síndrome de Rett/tratamiento farmacológico , Triazinas/farmacología , Ácido Valproico/farmacología , Adolescente , Adulto , Factores de Edad , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Carbamazepina/administración & dosificación , Carbamazepina/efectos adversos , Niño , Preescolar , Quimioterapia Combinada , Epilepsia/etiología , Femenino , Humanos , Lamotrigina , Síndrome de Rett/complicaciones , Triazinas/administración & dosificación , Triazinas/efectos adversos , Ácido Valproico/administración & dosificación , Ácido Valproico/efectos adversos , Adulto JovenRESUMEN
Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with childhood onset that usually continues through adolescence and into adulthood. In the long term, patients with this condition still have intractable seizures, intellectual disability, behavioral problems, and physical comorbidities. The aim of this study was to describe the clinical and EEG characteristics of a group of adults with Lennox-Gastaut syndrome. We identified 38 (22 females, 16 males) patients with LGS older than age 18years at their last evaluation, with mean age of 43.3±10.6years. Median follow-up was 14.4years (range: 2-40). All of our patients had 3 or more seizure types during their clinical history. The most prevalent seizure types at follow-up were atypical absences (28/38), tonic (28/38), generalized tonic-clonic (17/38), focal (11/38), and myoclonic seizures (9/38). All patients had drug-resistant seizures. Besides epilepsy, intellectual disability and behavioral problems were prominent features. Surprisingly, paroxysmal nonepileptic seizures were reported in 3 patients. Our observations confirm the poor outcome of Lennox-Gastaut syndrome through adulthood, regardless of age at seizure onset, etiology, and history of previous West syndrome.
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Encéfalo/fisiopatología , Síndrome de Lennox-Gastaut/diagnóstico , Problema de Conducta , Convulsiones/diagnóstico , Adulto , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Discapacidad Intelectual/fisiopatología , Síndrome de Lennox-Gastaut/fisiopatología , Masculino , Persona de Mediana Edad , Convulsiones/fisiopatología , Evaluación de SíntomasRESUMEN
Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months-74 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.25%); median age at diagnosis was 37.5 years (range of 1.6-58). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non-renal malignancy (3.3%), but we did not find a more prevalent type of cancer. No patient developed more than one malignancy. The prevalence of all malignant tumors was compatible with the prevalence in the general population (5.6%, 95%CI 2.99-9.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6-44.7, vs. 66.0 years). Two patients (13.3%) died of their cancer, while outcome was favorable in the remaining individuals. Malignant tumors were more frequently diagnosed in patients with mutations in TSC1 when compared to TSC2 and patients with no mutation identified (P = 0.032). Our study demonstrated that TSC patients do not seem to have an increased risk for malignancies besides renal cell carcinoma. However, when cancer develops, age at diagnosis is lower than in the general population, and malignant tumors are more frequently diagnosed in patients with mutations in TSC1. Further studies are needed to confirm these data. ©2016 Wiley Periodicals, Inc.
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Neoplasias/epidemiología , Neoplasias/etiología , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Femenino , Mutación de Línea Germinal , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/mortalidad , Fenotipo , Vigilancia de la Población , Estudios Retrospectivos , Riesgo , Programa de VERF , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/terapia , Adulto JovenRESUMEN
PURPOSE: To estimate the association between myocardial fatty foci (MFF) on chest computed tomographic (CT) images and type of gene mutation or multiorgan involvement in patients with tuberous sclerosis complex (TSC). MATERIALS AND METHODS: This retrospective case-control study was approved by the ethics committee, which waived the need for patient consent. Forty-eight patients with definite TSC (41 women; mean age, 35 years ± 11 [standard deviation]) and 96 age- and sex-matched patients without TSC who had undergone chest CT were evaluated. Two blinded readers independently scored MFF as low-attenuation areas within the myocardium. Patient history, gene mutation, and multiorgan involvement were obtained from clinical records. Cohen κ, Mann-Whitney U, χ(2) or Fisher exact, Kruskal-Wallis, and Spearman statistics were calculated. RESULTS: One or more MFF was detected in 50% (24 of 48) of patients with TSC; however, no MFF was detected in control patients (P < .001). MFFs were oval (62%, 15 of 24) or linear (38%, nine of 24) and involved the left ventricle in 13 patients and both ventricles in 24 patients (mostly the apical or midleft ventricle); median size was 127 mm(2). After four patients with TSC and unknown mutational status (two with MFF) were excluded, MFF was detected in 53% (10 of 19) of patients with TSC1 mutation, 65% (11 of 17) of patients with TSC2 mutation, and 12% (one of eight) of patients with TSC but without an identified mutation (P = .044). MFF presence was associated with brain (P = .011) and multiorgan (P = .008) involvement. The number of MFF per patient correlated with the degree of multiorgan involvement (P = .014). With MFF considered predictive of TSC, 50% (24of 48) sensitivity, 100% (96 of 96) specificity, 100% (24 of 24) positive predictive value, and 80% (96 of 120) negative predictive value were obtained. CONCLUSION: MFF was highly specific for TSC. MFF presence was associated with TSC gene mutations and with brain or multiorgan involvement; their number per patient was correlated with the degree of multiorgan involvement.
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Tejido Adiposo/diagnóstico por imagen , Corazón/diagnóstico por imagen , Miocardio/patología , Tomografía Computarizada por Rayos X , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/genética , Tejido Adiposo/patología , Adolescente , Adulto , Anciano , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Esclerosis Tuberosa/patologíaRESUMEN
BACKGROUND: The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. OBJECTIVE: The EDU-COM study is a randomised, pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity. METHODS: 174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6-month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes. RESULTS: The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups. CONCLUSIONS: A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. Registered at ClinicalTrials.gov, identifier NCT01804322, (http://www.clinicaltrials.gov).
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Epilepsia/complicaciones , Epilepsia/terapia , Educación del Paciente como Asunto/métodos , Adolescente , Adulto , Anciano , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Sesgo , Costo de Enfermedad , Interpretación Estadística de Datos , Interacciones Farmacológicas , Determinación de Punto Final , Epilepsia/economía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Atención Dirigida al Paciente , Calidad de Vida , Tamaño de la Muestra , Método Simple Ciego , Factores Socioeconómicos , Resultado del Tratamiento , Adulto JovenRESUMEN
A 9-year-old Caucasian boy affected by hot water epilepsy, with positive family history, experienced complex partial seizures during contact with hot water. A video-EEG recording was taken while hot water was poured onto his chest. Hot water epilepsy is rarely described in European countries, where bathing epilepsy in younger children is more common and often confused with this type of epilepsy.
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Baños/efectos adversos , Epilepsia/fisiopatología , Convulsiones/fisiopatología , Niño , Electroencefalografía/métodos , Epilepsia/diagnóstico , Europa (Continente) , Calor , Humanos , Masculino , Linaje , Convulsiones/diagnóstico , Grabación en Video/métodos , AguaRESUMEN
Since the first cases of abnormal paroxystic movements in normal infants were described, the importance of accurate characterization of this medical condition has been increasingly confirmed in the literature. Non-epileptic attacks mimic epileptic paroxysms in clinical presentation, but they have a typically benign course and are unresponsive to pharmacological treatment. An evident feature of the syndrome is its extreme variability in clinical manifestation. Here, we describe three normal infants with two similar forms of non-epileptic paroxysms. Electroclinical manifestations and profile of evolution were investigated. Ictal video-EEG polygraphic recordings were obtained for each patient. The increasing number of such reported clinical cases in the literature may contribute to high quality systematic reviews and the development of useful guidelines in the future. The clinical heterogeneity of non-epileptic attacks, together with the relative rarity of the condition, may make differential diagnosis with epileptic attacks very challenging. [Published with video sequences].
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Electroencefalografía , Mioclonía/diagnóstico , Mioclonía/fisiopatología , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Masculino , Grabación de Cinta de VideoRESUMEN
Interstitial deletions of the long arm of chromosome 6 represent a rare genomic disorder. Variable phenotypes has been reported in patients carrying this deletion, including facial dysmorphisms, intellectual disability/developmental delay, growth retardation and hypotonia, upper limb and cardiac malformations, and Prader-Willi (PWS)-like features. We describe a new patient with an interstitial 6q deletion of 11.58 Mb detected by CGH-Array, who showed facial dysmorphic features, small hands and feet, and severe dorsal scoliosis. Ataxic gait and frequent hand stereotypies were also noted. She started having seizures at 14 years, characterized by loss of consciousness, clonic jerks of the limbs, roaring breathing, fixed gaze, and generalized hypotonia. In the course of the disease she experienced cluster of seizures requiring intensive treatment. The electroencephalographic recording showed slowing of the background activity and bilateral paroxysmal activity over the posterior regions. Review of the literature done to pinpoint the epileptological features of the syndrome identified heterogeneous descriptions of the electro-clinical picture in patients with interstitial 6q deletions. Genotype-phenotype correlations of this syndrome have been lacking until recently, when patients can be characterized with microarray-based comparative genomic hybridization. Description of additional patients with interstitial 6q deletions will help to delineate candidate genes associated with particular phenotypes.
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Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 6/genética , Epilepsia/genética , Adolescente , Hibridación Genómica Comparativa , Electroencefalografía , Epilepsia/complicaciones , Femenino , Estudios de Asociación Genética , Humanos , Hibridación Fluorescente in Situ , Literatura de Revisión como AsuntoRESUMEN
PURPOSE: Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial. METHODS: We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background. KEY FINDINGS: Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure-free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug-resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition. SIGNIFICANCE: Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype-phenotype correlations.
Asunto(s)
Epilepsia/etiología , Esclerosis Tuberosa/complicaciones , Adolescente , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Niño , Preescolar , Trastornos del Conocimiento/etiología , Resistencia a Medicamentos , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/etiología , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: People with epilepsy have a higher prevalence of behavioral and neuropsychiatric comorbidities compared to the general population and those with other chronic medical conditions, although the underlying clinical features remain unclear. The goal of the current study was to characterize behavioral profiles of adolescents with epilepsy, assess the presence of psychopathological disorders, and investigate the reciprocal interactions among epilepsy, psychological functioning, and their main clinical variables. METHODS: Sixty-three adolescents with epilepsy were consecutively recruited at the Epilepsy Center, Childhood and Adolescence Neuropsychiatry Unit of Santi Paolo e Carlo hospital in Milan (five of them were excluded) and assessed with a specific questionnaire for psychopathology in adolescence, such as the Questionnaire for the Assessment of Psychopathology in Adolescence (Q-PAD). Q-PAD results were then correlated with the main clinical data. RESULTS: 55.2% (32/58) of patients presented at least one emotional disturbance. Body dissatisfaction, anxiety, interpersonal conflicts, family problems, uncertainty about the future, and self-esteem/well-being disorders were frequently reported. Gender and poor control of seizures are associated with specific emotional features (p < 0.05). CONCLUSIONS: These findings highlight the importance of screening for emotional distress, recognition of the impairments, and provision of adequate treatment and follow-up. A pathological score on the Q-PAD should always require the clinician to investigate the presence of behavioral disorders and comorbidities in adolescents with epilepsy.
RESUMEN
Rett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene mutations in the majority of cases, which results in severe disability and is associated with several comorbidities. The clinical condition of RTT patients tends to stabilize over time, and prolonged survival has recently been demonstrated. However, limited information is available on the long-term course of older patients with RTT, especially among those in Southern Europe. The aim of our study is to evaluate the main clinical features and state of health of adult Italian patients with RTT and to present their evolution over time, identifying major clinical issues present at different ages. A total of 130 families of patients with RTT aged ≥14 years were asked to complete a questionnaire, 84 of which were returned (65%). Among the clinical characteristics of RTT, stereotypies and poor hand function and feeding ability remained stable over time, while nonverbal communication tended to improve. With regard to the main pathologies, sleep, behavioral, and autonomic disorders persisted into adulthood, while epilepsy improved and musculoskeletal problems worsened. In our sample, older patients with R294X and R133C mutations and with C-terminal deletions showed lower levels of clinical severity. The development of guidelines for the clinical management of patients with RTT will assist health care providers in dealing with the complex RTT phenotype. More extensive data about the long-term course of the condition could help in the design of programs for secondary prevention of disabilities for younger females affected by the syndrome.
Asunto(s)
Síndrome de Rett/genética , Síndrome de Rett/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Eliminación de Gen , Guías como Asunto , Humanos , Lactante , Italia , Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/metabolismo , Mutación , Fenotipo , Síndrome de Rett/fisiopatología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
PURPOSE: To classify the grade of antiepileptic drug (AED) resistance in a cohort of patients with focal epilepsies, to recognize the risk factors for AED resistance, and to estimate the helpfulness of "new-generation" AEDs. METHODS: We included 1,155 adults with focal epilepsies who were observed consecutively after 1990 and followed regularly at two epilepsy centers. We systematically collected the clinical, diagnostic, and therapeutic data using a custom-written database. We classified the patients as seizure-free or AED resistant according to the International League Against Epilepsy (ILAE) criteria, and we evaluated the risk factors associated with AED resistance using logistic regression analysis. We further grouped AED-resistant patients in different grades (I, II, and III) according to the number of AEDs already tried as proposed by Perucca. KEY FINDINGS: AED resistance occurred in 57.8% of the 729 patients with symptomatic focal epilepsies and was positively associated with electroencephalography (EEG) abnormalities, seizure type, and the presence of mesial temporal sclerosis. Among 426 patients without detectable causes, the percentage of AED resistance was significantly lower (39.2%) and correlated with EEG abnormalities and psychiatric symptoms. Among AED-resistant patients, the majority (64.6%) had tried three or more AEDs, which fit the more severe grade III proposed by Perucca. Among seizure-free patients, more than one-half (57%) needed to try two or more AEDs before reaching seizure control (14.9% needed three or more AEDs). Furthermore, among seizure-free patients who could be previously classified as resistant to two or more AEDs, 52.2% reached seizure freedom while receiving treatment with "new generation" AEDs. SIGNIFICANCE: The ILAE classification of AED resistance, as well the graded classification proposed by Perucca, was easily exploitable in our patients, although these classifications systems appear to have a limited value in predicting seizure outcome. Actually, a small but not negligible percentage of patients reached seizure freedom after trying several AEDs (including "new" AEDs), suggesting repeated trials may be necessary for seizure control.