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SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.
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PURPOSE: To identify characteristics of patients undergoing cataract surgery associated with pathogenic and antibiotic-resistant conjunctival bacteria. SETTING: Spanish tertiary hospital. DESIGN: Retrospective cross-sectional study. METHODS: Records of consecutive patients undergoing cataract surgery between July 2005 and September 2014, contained data on patient characteristics and conjunctival bacteria systematically identified with preoperative tests and anesthetic evaluation. A multivariate logistic regression associated 12 bacterial groups with every category of 17 characteristics. Odds ratio (OR), 95% CIs expressed colonization risk. RESULTS: In 14883 patients, categories associated with pathogenic bacteria were age older than 79 years with nonfermentative gram-negative bacilli (NFGNB) (OR 1.74, 1.12-2.71), enterococci (OR 1.90, 1.36-2.65), Enterobacteriaceae (OR 2.17, 1.65-2.87), and Staphylococcus aureus (OR 1.37, 1.16-1.62); obesity with S aureus (OR 1.52, 1.30-1.78), enterococci (OR 1.99, 1.47-2.68), and Enterobacteriaceae (OR 2.17, 1.70-2.77); dacryocystorhinostomy history with S aureus (OR 1.90, 1.48-2.44), Haemophilus spp. (OR 2.06, 1.37-3.11), Streptococcus pneumoniae (OR 3.14, 2.14-4.62), NFGNB (OR 2.23, 1.28-3.88), and enterococci (OR 1.80, 1.16-1.81); diabetes with S aureus (OR 1.27, 1.13-1.44), enterococci (OR 1.49, 1.19-1.87), and Enterobacteriaceae (OR 1.27, 1.04-1.54); smoking habit with Enterobacteriaceae (OR 2.11, 1.56-2.86); autumn with NFGNB (OR 2.0, 1.35-3.0); hot weather with S aureus (OR 1.23, 1.03-1.47); and lung, renal, and some heart insufficiencies with S aureus. Other staphylococci, highly antibiotic-resistant, were associated with old age, obesity, and hot weather. CONCLUSIONS: Old age, obesity, diabetes, dacryocystorhinostomy history, smoking habit, and autumn and summer seasons increased the prevalence of enterococci, staphylococci, Enterobacteriaceae, and/or NFGNB. Obesity and humid-warm weather are key for choosing a cataract surgery prophylaxis.
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Bactérias , Catarata , Idoso , Antibacterianos/uso terapêutico , Estudos Transversais , Humanos , Testes de Sensibilidade Microbiana , Prevalência , Estudos RetrospectivosRESUMO
INTRODUCTION: Patients with moderate-severe cerebral palsy require the support of their caregivers to carry out the activities of daily living (ADLs). OBJECTIVES: To describe the comorbidities, need for care in children with cerebral palsy and to analyse the influence of the degree of motor involvement, nutritional status and other neurological disorders. METHODS: Cross-sectional and observational study. Patients with cerebral palsy degrees III-IV-V according to the Gross Motor Function Classification System (GMFCS) have been studied. A record of comorbidities has been made and body composition has been studied using anthropometry and bioimpedance. In addition, a caregiver burden survey on ADLs has been carried out (10 items on the different actions: hygiene, clothing, transfers, sleeping and feeding). Which variables have the greatest influence on the perception of difficulty in performing ADLs have been studied. RESULTS: A total of 69 patients (50.7% women, mean age 10.46 ± 0.4 years) were analysed, with GMFCS grades: grade III 36.2% (N=25), grade IV 29.0% (N=20), grade V 34.8% (N=24). A relationship was found between the caregiver burden score and GMFCS grade (P=0.003) and intellectual disability (P<0.001). However, regardless of the degree of GMFCS and intellectual disability, there is greater difficulty in performing ADLs in relation to lower values in weight (Z-score) (P=0.028), fat mass (kg) (P=0.035), fat mass (%) (P=0.094), body mass index (Z-score) (P=0.086). CONCLUSIONS: In addition to the degree of clinical impairment, nutritional status is a factor that influences the caregiver's difficulty in performing the ADLs in cerebral palsy patients on which we can act to improve this problem.
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Sobrecarga do Cuidador , Paralisia Cerebral , Estado Nutricional , Atividades Cotidianas , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/terapia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
PURPOSE: Rasmussen's encephalitis (RE) is a chronic neurological disorder characterized by inflammation of the cerebral cortex, mainly unilateral, that leads to drug-resistant epilepsy and progressive neurological impairment. Central Precocious Puberty (CPP) is uncommon, albeit increased in frequency in patients with neurological conditions and the physiopathological bases of these associations remains unclear in most cases. Epilepsy has been proposed to play a role, as well as the accumulation of substances produced as a result of metabolism or tissue degeneration in some neurodegenerative diseases. However, CPP has not been previously described in patients with RE. METHODS: From a series of patients affected by RE followed-up at a referral center, an in-depth review of the characteristics of those who developed CCP was carried out. RESULTS: Three cases were identified, representing a relative frequency of 21.4 % for CPP. They were girls, of Caucasian ethnicity, without family history of CPP or any image-identified abnormalities in the hypothalamic area. In two cases CPP manifested immediately before the onset of the epilepsy (prior to the diagnosis of RE) and in the other, after epilepsy onset but coinciding with a worsening of the seizures. A GnRH test with pubertal response confirmed CPP in the three cases. CONCLUSION: The high proportion of CPP in patients affected by RE suggested a plausible relationship between these two entities. Various factors involved, including neuroinflammation, are hypothesized in the present study. However, further studies are needed to elucidate the pathophysiological bases, which could provide insight in the understanding of both entities.
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Encefalite/fisiopatologia , Epilepsia/fisiopatologia , Puberdade Precoce/fisiopatologia , Convulsões/fisiopatologia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia , Encefalite/diagnóstico , Epilepsia/diagnóstico , Feminino , Humanos , Puberdade Precoce/diagnóstico , Convulsões/diagnósticoRESUMO
Bone health problems may be related to the nutritional deficit in pediatric patients with cerebral palsy. It is common to find asymptomatic vertebral fractures when they have low bone mineral density. Fat mass deficit could be related to a lower bone mineral density and a higher risk of vertebral fractures. OBJECTIVES: To study the bone health of patients with CP and its relationship with neurological and nutritional status. PURPOSE: Cerebral palsy (CP) is the most common cause of motor disability in pediatric age. METHODS: Cross-sectional, observational, descriptive, and analytical study in which patients with CP between 4 and 5 years with Gross Motor Function Classification System (GMFCS) grades III-IV-V were included. It was carried out: survey, anthropometric study, bioimpedanciometry (BIA), and bone densitometry. Patients with low bone mineral density (BMD Z score less than - 2.0) underwent lumbar radiography looking for vertebral fractures to be diagnosed with osteoporosis. RESULTS: Total sample: 51 patients (51.0% women). Mean age: 11.0 ± 0.5 years. BMD Z score average: - 2.1 (95% CI - 2.5, - 1.7). BMD Z score according to GMFCS: grade III - 1.6 (- 2.2; - 1.), grade IV - 1.6 (- 2.4; - 0.9), grade V - 3.1 (- 3.9, - 2.2) (p = 0.013). Bone health classification according to the International Society for Clinical Densitometry was: 47.1% normal, 52.9% low BMD. Relationship between low BMD and low fat mass (p = 0.030) and low cell mass (p = 0.040) was found. Prevalence of vertebral fractures in lumbar radiography: 25.9%, increasing as the degree of neurological involvement. Vertebral fractures were found in 5/13 GMFCS grade V, 2/6 GMFCS grade IV, and 0/10 GMFCS grade III. CONCLUSIONS: Bone health in the pediatric population with CP is compromised in relation to the degree of neurological involvement and nutritional status. Those patients with moderate-severe cerebral palsy and low BMD seem to present an increased risk of fracture.
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Densidade Óssea/fisiologia , Paralisia Cerebral/complicações , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Paralisia Cerebral/epidemiologia , Criança , Estudos Transversais , Pessoas com Deficiência , Feminino , Fraturas Ósseas/diagnóstico , Humanos , Masculino , Transtornos Motores/epidemiologia , Transtornos Motores/etiologia , Osteoporose/epidemiologiaRESUMO
INTRODUCTION: Cerebral palsy (CP) is the most frequent cause of motor disability in the paediatric age. The aim of this article is the study of the nutritional status of patients with CP followed-up in a reference hospital, as well as the relationship between neurological and nutritional state. MATERIAL AND METHODS: A cross-sectional, observational, descriptive and analytical study was conducted on a sample consisting of 4-15years old patients with CP with Gross Motor Function Classification System (GMFCS) gradesIII-IV-V, from a specialised paediatric hospital reference area. An interview (collection of general data, medications and nutritional habits), anthropometric study and bioimpedance (BIA) measurements were carried out. RESULTS: The study included 69 patients (recruitment 84.15%), with a mean age of 10.46±0.43years, and 50.7% females. The distribution according to GMFCS scale was: gradeIII (36.2%), gradeIV (29%), and gradeV (34.8%). According to weight for height: moderate malnutrition 21.8% (gradeV: 33.3%), severe malnutrition 5.8% (gradeV: 12.6%), overweight/obesity 23.2% (gradeIII: 24%, gradeIV: 35%). Adequate level of lean mass for height: gradeIII (36%), gradeIV (55%), and gradeV (16.7%). Fat excess: gradeIII (36%), gradeIV (40%), and gradeV (29.2%). Fat mass comparison: BIA 6.89±0.64kg versus anthropometry 5.56±4.43kg. CONCLUSIONS: In CP grade GMFCSV, the weight deficit associated with a decrease in lean body mass is common. Patients with CP grades GMFCSIII-IV have a significant prevalence of overweight/obesity. Anthropometry is a useful tool for nutritional assessment in children with CP, although fat levels could be underestimated.
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Paralisia Cerebral/fisiopatologia , Desnutrição/etiologia , Obesidade Infantil/etiologia , Magreza/etiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Estado Nutricional , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Magreza/diagnóstico , Magreza/epidemiologiaRESUMO
INTRODUCTION: Radiotherapy techniques associated with breast-conserving surgery have evolved in early breast cancer thanks to a better knowledge of tumor radiobiology, highlighting intraoperative radiotherapy (IORT). However, complications have been documented with this procedure, mainly fibrosis. Transforming growth factor beta (TGF-ß) is a cytokine with an active role in radiation-induced fibrosis, which could be used as an early biomarker for the development of fibrosis. METHODS: Multicentric prospective analysis of 60 patients with breast cancer who underwent breast-conserving surgery, 30 of whom had received additional IORT. TGF-ß values were evaluated in serum pre-surgery and in serum collected 24h after surgery. In addition, we evaluated surgical wound fluids collected 6h and 24h following surgery. RESULTS: Serum and surgical wound fluids TGF-ß values collected over 24h following surgery were significantly higher in patients who received additional IORT (P<.0001). Notably, 8 of these patients showed values above 1,000pg/ml. There were no differences between the samples (serum or surgical wound fluids) (P=.5881). CONCLUSIONS: Although further investigation is needed, higher TGF-ß values in IORT during breast-conserving surgery can be used as an early biomarker for the development of fibrosis.
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Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Radioterapia/efeitos adversos , Fator de Crescimento Transformador beta/sangue , Anormalidades Induzidas por Radiação/patologia , Idoso , Mama/patologia , Feminino , Fibrose/epidemiologia , Humanos , Cuidados Intraoperatórios/métodos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
There are many medicinal products that, although having shown efficacy and safety in different ophthalmological indications, they are not authorized or commercially available for ophthalmic administration. This implies, on one hand, that they must be used according to legislation that regulates the availability of medicines in special situations and, on the other hand, that they must be prepared in the pharmacy services for ophthalmic administration, according to quality criteria to ensure its effectiveness, stability and sterility. This document gathers the consensus between the Spanish Society of Ophthalmology and the Spanish Society of Hospital Pharmacy about these selected preparations which have shown enough evidence in their efficacy and safety for their ophthalmic use (off label) and ophthalmic administration. This document includes recommendations about its use according to the current legislation. In addition, with the aim of harmonizing the preparation of intraocular injections in the hospital pharmacy services, general recommendations are set in this document to ensure the compliance with standards established in the Spanish Guideline for Good Preparation Practices of Medicinal Products in Hospital Pharmacies. These recommendations include sections such as the area of preparation, material, technique, packaging, stability, quality control, prescription and traceability of intraocular preparations.
Son muchos los medicamentos que, aun habiendo demostrado eficacia y seguridad en diferentes indicaciones oftalmológicas, no están autorizados ni disponibles comercialmente en una forma adecuada para esta vía de administración.Esto implica, por un lado, que se deban utilizar según la legislación que regula la disponibilidad de medicamentos en situaciones especiales y, por otro, que se deban preparar en los Servicios de Farmacia para su administración por vía oftálmica, conforme a unos criterios de calidad que aseguren su efectividad, estabilidad y esterilidad. Este documento recoge un consenso entre la Sociedad Española de Oftalmología y la Sociedad Española de Farmacia Hospitalaria sobre aquellas preparaciones con suficiente evidencia respecto a su eficacia y seguridad para su uso no autorizado en indicaciones y vía de administración oftálmicas. Se incluyen recomendaciones para su utilización de acuerdo con la legislación vigente. Además, con el ánimo de armonizar la preparación de inyecciones intraoculares en los Servicios de Farmacia Hospitalaria, se establecen unas recomendaciones generales para su elaboración siguiendo los estándares establecidos en la Guía de Buenas Prácticas de Preparación de Medicamentos en los Servicios de Farmacia Hospitalaria. En estas recomendaciones se incluyen apartados como el lugar de preparación, el material, la técnica, el envasado, el periodo de validez, el control de calidad, la prescripción y la trazabilidad de las preparaciones intraoculares.
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Soluções Oftálmicas/síntese química , Soluções Oftálmicas/uso terapêutico , Consenso , Composição de Medicamentos/normas , Indústria Farmacêutica/normas , Humanos , Injeções Intraoculares , Serviço de Farmácia HospitalarRESUMO
INTRODUCTION: We present our experience on idiopathic intracranial hypertension (IIH), before and after the introduction of a specific diagnosis and management protocol. METHOD: A descriptive retrospective study was conducted on patients with IIH over a 25year period (1990-2015), comparing the last 7years (after introduction of the protocol) with the previous 18years. RESULTS: Among the 18,865 patients evaluated, there were 54 cases of IIH (29 infants and 25 children). A comparison was made between the two time periods: 32 cases in 1990-2008 -published in An Pediatr (Barc). 2009;71:400-6-, and 23 cases in 2008-2015. In post-protocol period, there were 13 patients aged between 3-10months (62% males) with transient bulging fontanelle, and 10 aged between 2-14years (50% males), with papilloedema. A total of 54% of infants had recently finished corticosteroid treatment for bronchitis. In the older children, there was one case associated with venous thrombosis caused by otomastoiditis, one case on corticosteroid treatment for angioma, and another case treated with growth hormone. Transfontanelle ultrasound was performed on all infants, and CT, MRI and angio-MRI was performed on every child. Lumbar puncture was performed on 2 infants in whom meningitis was suspected, and in all children. All patients progressed favourably, with treatment being started in 3 of them. One patient relapsed. DISCUSSION: Characteristics and outcomes of patients overlap every year. IIH usually has a favourable outcome, although it may be longer in children than in infants. It can cause serious visual disturbances, so close ophthalmological control is necessary. The protocol is useful to ease diagnostic decisions, monitoring, and treatment.
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Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/terapia , Adolescente , Algoritmos , Criança , Pré-Escolar , Protocolos Clínicos , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: We aimed to develop a grading system based on preoperative parameters that would predict surgical difficulty and morbidity in elective laparoscopic splenectomy. STUDY DESIGN: We retrospectively assessed morbidity in 439 patients who underwent laparoscopic splenectomy for benign and malignant disorders between 1993 and 2013. Medical and surgical records were reviewed and analyzed. We compared preoperative data concerning demographic, clinical, pathological, anatomical, laboratory, and radiological factors with three surgical outcomes: operative time, intraoperative bleeding, and surgical conversion. Univariate and multivariate analyses were performed to identify statistically significant variables. A logistic regression model was used to identify determinant variables and to compose a predictive score. External validation of the score was performed using an independent cohort of 353 patients. RESULTS: Four preoperative parameters (age, male sex, type of pathology, and spleen size based on final spleen weight) were significantly related with operative time, operative bleeding, and conversion to open surgery. Using these results, we developed a classification system with three levels of difficulty: low (≤4 points), medium (4.5-5.5 points), and high (≥6 points), based on the four preoperative parameters. The correlation was highly significant (p = <0.001) according to Spearman's correlation. The area under the ROC curve was 0.671 (95 % CI 0.596-0.745). The external validation showed significant correlations with the present model. CONCLUSIONS: The grading score described here is simple to calculate from the physical examination, laboratory tests, and US or CT images, and we believe it could be useful to preoperatively assess the technical complexity of laparoscopic splenectomy.
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Laparoscopia/efeitos adversos , Medição de Risco , Esplenectomia/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Conversão para Cirurgia Aberta , Feminino , Hemorragia/etiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Tamanho do Órgão , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Baço/patologia , Adulto JovemRESUMO
OBJECTIVE: A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. PATIENTS AND METHODS: Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. RESULTS: A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. CONCLUSIONS: The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies.
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Epilepsia/classificação , Adolescente , Idade de Início , Criança , Pré-Escolar , Epilepsia/etiologia , Síndromes Epilépticas/classificação , Síndromes Epilépticas/etiologia , Feminino , Unidades Hospitalares , Humanos , Lactente , Masculino , Neurologia , Pediatria , Fatores de TempoRESUMO
AIM: To analyze the factors involved in the prognosis of symptomatic epilepsies in relation to their age at onset, monitored at a neuropediatric section of regional reference over a period of three years. PATIENTS AND METHODS: Children diagnosed with symptomatic epilepsy, supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established at 605 (13.17%): 277 (45.79%) symptomatic epilepsies. Symptomatic etiology predomininates in epileptic patients that started below one year of age, 67.72%, and between 1-3 years, 61.39%. 37.54% of symptomatic epilepsy is refractory, 72.92% have cognitive impairment, 55.23% have motor impairment and 17.32% have autism spectrum disorder. The younger the patient, the higher the percentage of refractoriness and display of any neurological or associated development impact. Some etiologies have higher rates of refractoriness. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is overshadowed by refractoriness and associated neurodevelopmental disorders, which are generally worse at an earlier onset and in certain etiologies.
TITLE: Pronostico de las epilepsias sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias sintomaticas en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante tres años. Pacientes y metodos. Revision de los pacientes con diagnostico de epilepsia sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos y evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 277 (45,79%) son epilepsias sintomaticas. En los pacientes que iniciaron la epilepsia por debajo del año de vida predominan las de etiologia sintomatica (67,72%), y tambien entre 1-3 años (61,39%). El 37,54% de las epilepsias sintomaticas son refractarias, el 72,92% asocian un deficit cognitivo, el 55,23%, alguna afectacion motora, y el 17,32%, algun trastorno del espectro autista. A menor edad, mayor porcentaje de refractariedad y de presentar alguna repercusion neurologica o del desarrollo asociada. Algunas etiologias tienen mayores tasas de refractariedad. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz es el inicio y en etiologias concretas.
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Epilepsia/terapia , Adolescente , Idade de Início , Criança , Pré-Escolar , Epilepsia/diagnóstico , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
AIM: To analyze the factors involved in the prognosis of non-symptomatic epilepsy (idiopathic and cryptogenic) in relation to their age of onset, monitored at a regional section of Neuropediatry reference over a period of three years. PATIENTS AND METHODS: Patients with diagnosis of non-symptomatic epilepsy supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical, complementary examinations and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established in 605 (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. 15.7% of cryptogenic epilepsies and 14.1% of idiopathic epilepsies are refractory to treatment. Some epileptic syndromes, such as reflex epilepsies, Dravet syndrome, Ohtahara syndrome or Lennox-Gastaut syndrome, have higher rates of drug resistance. 84.62% of idiopathic epilepsies and 79.77% of cryptogenic epilepsies present no other associated neurological disorder. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain etiologies.
TITLE: Pronostico de las epilepsias no sintomaticas segun la edad de inicio, controladas durante tres años en una unidad de neuropediatria de referencia regional.Objetivo. Analizar los factores implicados en el pronostico de las epilepsias no sintomaticas (idiopaticas y criptogenicas) en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante un periodo de tres años. Pacientes y metodos. Analisis de los pacientes con diagnostico de epilepsia no sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos, examenes complementarios y datos evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 156 (25,79%) fueron epilepsias idiopaticas, y 172 (28,43%), criptogenicas. El 15,7% de las epilepsias criptogenicas y el 14,1% de las idiopaticas son refractarias al tratamiento. Algunos sindromes epilepticos, como las epilepsias reflejas, el sindrome de Dravet, el sindrome de Ohtahara o el sindrome de Lennox-Gastaut, tienen mayores tasas de farmacorresistencia. No presentan otra alteracion neurologica asociada el 84,62% de las epilepsias idiopaticas y el 79,77% de las epilepsias criptogenicas. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz sea el inicio y en etiologias concretas.
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Epilepsia/epidemiologia , Adolescente , Idade de Início , Transtorno do Espectro Autista/epidemiologia , Criança , Pré-Escolar , Comorbidade , Deficiências do Desenvolvimento/epidemiologia , Epilepsia Resistente a Medicamentos/epidemiologia , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/etiologia , Epilepsia/genética , Epilepsia/terapia , Feminino , Humanos , Lactente , Deficiência Intelectual/epidemiologia , Masculino , Transtornos dos Movimentos/epidemiologia , Prognóstico , Estudos Retrospectivos , Espanha/epidemiologia , Síndrome , Resultado do TratamentoRESUMO
INTRODUCTION: Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. Two cases are described in detail below caused by RNASEH2B gene mutation, one of which displays a mutation no described to date. CASE REPORTS: Case 1: male consulting because from 5-month-old shows loss of maturity items acquired until then, coming with several fever episodes. Case 2: a 4-month-old boy showing since 2-month-old great irritability and oral-feeding trouble with severe psychomotor impairment. In both cases it was found an increase of pterines in the cerebrospinal fluid, mainly neopterine, with calcifications in the basal ganglia. The diagnosis was proved by sequencing RNASEH2B gene, founding in case 2 a new mutation not described previously. CONCLUSIONS: The reported cases belong to the description already done by Aicardi-Goutieres, it should be noticed this syndrome in a patient with a subacute encephalopathy of debut in the first year of life, dystonia/spasticity in variable degree and important affectation/regression of psychomotor development, particularly in those with increase of pterines (neopterine) in the cerebrospinal fluid and calcifications in the basal ganglia.
TITLE: Variaciones fenotipicas en el sindrome de Aicardi-Goutieres causado por mutaciones en el gen RNASEH2B: presentacion de dos nuevos casos.Introduccion. El sindrome de Aicardi-Goutieres es un trastorno inmunitario raro debido a mutaciones en siete genes que codifican proteinas llamadas TREX1, el complejo ribonucleasa H2, SAMHD1, ADAR e IFIH1 (MAD5), las cuales estan implicadas en el metabolismo de los acidos nucleicos. A continuacion se presentan dos nuevos casos por mutacion en el gen RNASEH2B, uno de los cuales presenta una mutacion no descrita hasta la fecha. Casos clinicos. Caso 1: varon que consulto porque desde los 5 meses, coincidiendo con cuadros febriles de repeticion, presentaba perdida de los items madurativos adquiridos hasta la fecha. Caso 2: niño de 4 meses que desde los 2 meses mostraba gran irritabilidad con dificultades en la alimentacion, asociado a un grave retraso psicomotor. En ambos casos se constato un aumento de las pterinas en el liquido cefalorraquideo, principalmente de la neopterina, con calcificaciones en los ganglios basales. El diagnostico se confirmo mediante secuenciacion del gen RNASEH2B; el caso 2 presentaba una mutacion no descrita en la literatura medica. Conclusiones. Los casos corresponden a la descripcion clasica realizada por Aicardi-Goutieres. Debe tenerse en cuenta este sindrome ante un paciente con un cuadro de encefalopatia subaguda de comienzo en el primer año de vida, distonia/espasticidad en grado variable e importante afectacion/regresion del desarrollo psicomotor, especialmente si asocia aumento de las pterinas (neopterina) en el liquido cefalorraquideo y calcificaciones en los ganglios basales.
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Doenças Autoimunes do Sistema Nervoso/genética , Mutação de Sentido Incorreto , Malformações do Sistema Nervoso/genética , Ribonuclease H/genética , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Doenças Autoimunes do Sistema Nervoso/enzimologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Biopterinas/líquido cefalorraquidiano , Calcinose/etiologia , Calcinose/patologia , Transtornos de Alimentação na Infância/genética , Estudos de Associação Genética , Heterozigoto , Humanos , Lactente , Deficiência Intelectual/genética , Imageamento por Ressonância Magnética , Masculino , Espasticidade Muscular/genética , Neopterina/líquido cefalorraquidiano , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/enzimologia , Neuroimagem , Fenótipo , Ribonuclease H/deficiência , Análise de Sequência de DNARESUMO
INTRODUCTION: The dynamic increase in the number of triplet repeats of cytosine-guanine-guanine (CGG) in the FMR1 gene mutation is responsible for three OMIM syndromes with a distinct clinical phenotype: Fragile X syndrome (FXS) and two pathologies in adult carriers of the premutation (55-200 CGG repeats): Primary ovarian insufficiency (FXPOI) and tremor-ataxia syndrome (FXTAS) associated with FXS. CLINICAL OBSERVATION AND METHODS: CGG mutation dynamics of the FMR1 gene were studied in DNA samples from peripheral blood from the index case and other relatives of first, second and third degree by TP-PCR, and the percentage methylation. RESULTS: Diagnosis of FXS was confirmed in three patients (21.4%), eight patients (57.1%) were confirmed in the premutation range transmitters, one male patient with full mutation/permutation mosaicism (7.1%) and two patients (14.3%) with normal study. Of the eight permutated patients, three had FXPOI and one male patient had FXTAS. DISCUSSION: Our study suggests the importance of making an early diagnosis of SXF in order to carry out a family study and genetic counselling, which allow the identification of new cases or premutated patients with FMR1 gene- associated syndromes (FXTAS, FXPOI).
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Ataxia/genética , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Insuficiência Ovariana Primária/genética , Tremor/genética , Repetições de Trinucleotídeos , Adolescente , Adulto , Idoso , Ataxia/diagnóstico , Criança , Pré-Escolar , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Marcadores Genéticos , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Insuficiência Ovariana Primária/diagnóstico , Tremor/diagnósticoRESUMO
We report herein an efficient, fast, and simple synthesis of an imine-based covalent organic framework (COF) at room temperature (hereafter, RT-COF-1). RT-COF-1 shows a layered hexagonal structure exhibiting channels, is robust, and is porous to N2 and CO2 . The room-temperature synthesis has enabled us to fabricate and position low-cost micro- and submicropatterns of RT-COF-1 on several surfaces, including solid SiO2 substrates and flexible acetate paper, by using lithographically controlled wetting and conventional ink-jet printing.
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Novel π-conjugated topologies based on oligothiophenes and phenanthroline have been assembled by combining their outstanding electronic and structural benefits with the specific properties of the topological structure. Macrocycles and catenanes are prepared by using an optimized protocol of transition metal-templated macrocyclization followed by efficient Pd-catalyzed cross-coupling reaction steps. By using this method, [2]catenanes comprising two interlocked π-conjugated macrocycles with different ring sizes have been synthesized. The structures of the [2]catenanes and corresponding macrocycles are confirmed by detailed (1) Hâ NMR spectroscopy and high resolution mass spectrometry. Single crystal X-ray structural analysis of the quaterthiophene-diyne macrocycle affords important insight into the packing features and intermolecular interaction of the new systems. The fully conjugated interlocked [2]catenanes are fully characterized by spectroscopic and electrochemical measurements.
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INTRODUCTION: Legius syndrome is an autosomal dominant disorder caused by the mutation in the SPRED1 gene involving a negative regulator of the RAS-MAPK pathway, similar to neurofibromin and therefore shows some clinical similarities to neurofibromatosis type I (NF1) but less severe. These patients have multiple cafe-au-lait spots, sometimes associated with skin fold freckling, dysmorphic features, lipomas, and mild learning disabilities. However, this syndrome is not associated with neurofibromas, optic gliomas, Lisch nodules or tumor predisposition. CASE REPORT: We present a 10 months child, without a personal interest history, consulting by hypotonic extremities, cafe-au-lait spots and mild psychomotor difficult. Mother's sister and grandfather have some cafe-au-lait spots. In our patient, NF1 genetic study was negative, but we observe a mutation in the SPRED1 gene, compatible with Legius syndrome. Asymptomatic mother shows the same mutation in SPRED1 gene. CONCLUSION: We emphasize the relevance of the differential diagnosis of NF1 with respect to numerous complications to appear, with a better prognosis recently described entity as it is Legius syndrome.
TITLE: Un nuevo sindrome neurocutaneo: sindrome de Legius. A proposito de un caso.Introduccion. El sindrome de Legius es un trastorno autosomico dominante resultante de la mutacion del gen SPRED1, que implica perdida de funcion de una de las proteinas implicada en la via patogenica RAS-MAPK, similar a la neurofibromina y por ello muestra similitudes clinicas con la neurofibromatosis tipo 1 (NF1), pero con menor gravedad. Estos pacientes presentan multiples manchas cafe con leche y pueden asociar efelides, rasgos dismorficos, lipomas y trastornos del aprendizaje sin relacionarse con la aparicion de neurofibromas, gliomas opticos, nodulos de Lisch o predisposicion tumoral. Caso clinico. Niño de 10 meses, sin antecedentes personales de interes, que consulta por hipotonia de extremidades, manchas cafe con leche y leve retraso psicomotor. En los antecedentes familiares destaca una hermana de la madre y el abuelo materno con manchas cafe con leche. En nuestro paciente, el estudio genetico fue negativo para NF1, pero se hallo una mutacion en el gen SPRED1, compatible con el sindrome de Legius. La madre asintomatica presenta la misma mutacion en el gen SPRED1. Conclusion. Es de destacar la importancia del diagnostico diferencial de NF1, con las numerosas complicaciones que puede conllevar, con una entidad recientemente descrita de mejor pronostico como es el sindrome de Legius.
Assuntos
Manchas Café com Leite/diagnóstico , Humanos , Lactente , MasculinoRESUMO
INTRODUCTION: The aim of this study is to evaluate the sentinel lymph node mapping (SLNM) with methylene blue staining "ex vivo" in colon cancer, as well as calculate the upstaging obtained by the determination of micrometastases and its correlation with the evolution of the disease. METHODS: Between 2008 and 2011, 101 patients with colon cancer undergoing resection were studied prospectively with SLNM and detection of micrometastases. The correlation of SLN micrometastases with the disease evolution was evaluated in patients with a follow-up of more than one year. RESULTS: The SLNM rate was 92 cases (91%). Only SLN was positive for micrometastases in 9 cases, with a 14% upstaging. The incidence of false negatives was 9 patients (10%). Mean follow of N0 patients (n=74) was 38 months. The SLN- (negative) group (65 patients) had a recurrence rate of 4 patients (7%), whereas this rate was 2 patients (22%) in the group of SLN+(positive) (9 patients), but without significant differences. No differences in survival were observed. CONCLUSIONS: SLNM is a reproducible technique without significant increase in time and costs. Upstaging was obtained in 14% of patients staged as N0 by conventional technique. At follow-up of N0 patients with SLN+there seems to be a higher rate of recurrence, which could change the guidelines of adjuvant treatment, but we must interpret the results it with caution because the sample is small.