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GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18â years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12â months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3â months and 1â day before starting treatment and 1, 3, 6 and 12â months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8â years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.
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Receptores de N-Metil-D-Aspartato , Serina , Humanos , Femenino , Masculino , Niño , Preescolar , Adolescente , Serina/uso terapéutico , Serina/genética , Receptores de N-Metil-D-Aspartato/genética , Encefalopatías/genética , Encefalopatías/tratamiento farmacológico , Resultado del Tratamiento , Calidad de VidaRESUMEN
The short pre-M1 helix within the S1-M1 linker (also referred to as the pre-M1 linker) between the agonist-binding domain (ABD, S1) and the M1 transmembrane helix of the NMDA receptor (NMDAR) is devoid of missense variants within the healthy population but is a locus for de novo pathogenic variants associated with neurological disorders. Several de novo variants within this helix have been identified in patients presenting early in life with intellectual disability, developmental delay, and/or epilepsy. In this study, we evaluated functional properties for twenty variants within the pre-M1 linker in GRIN1, GRIN2A, and GRIN2B genes, including six novel missense variants. The effects of pre-M1 variants on agonist potency, sensitivity to endogenous allosteric modulators, response time course, channel open probability, and surface expression were assessed. Our data indicated that virtually all of the variants evaluated altered channel function, and multiple variants had profound functional consequences, which may contribute to the neurological conditions in the patients harboring the variants in this region. These data strongly suggest that the residues within the pre-M1 helix play a key role in channel gating and are highly intolerant to genetic variation.
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Epilepsia , Discapacidad Intelectual , Receptores de N-Metil-D-Aspartato , Humanos , Epilepsia/genética , Mutación Missense/genética , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.
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Colestasis Intrahepática/etiología , Miopatías Estructurales Congénitas/complicaciones , Biopsia , Resultado Fatal , Humanos , Lactante , MasculinoRESUMEN
BACKGROUND: αB-crystallin is a promiscuous protein involved in numerous cell functions. Mutations in CRYAB have been found in patients with different pathological phenotypes that are not properly understood. Patients can present different diseases like cataracts, muscle weakness, myopathy, cardiomyopathy, respiratory insufficiency or dysphagia, but also a variable combination of these pathologies has been found. These mutations can show either autosomal dominant or recessive mode of inheritance and variable penetrance and expressivity. This is the first report of congenital cataracts and myopathy described in childhood due to a CRYAB mutation with autosomal dominant mode of inheritance. METHODS: The whole exome sequence was subjected to phenotype-driven analysis and a novel variant in CRYAB was detected: c.514delG, p.(Ala172ProfsTer14). The mutation was located in the C-terminal domain of the protein, which is essential for chaperone activity. The deduced protein was analyzed searching for alterations of the relevant physico-chemical properties described for this domain. A muscle biopsy was also tested for CRYAB with immunohistochemical and histoenzymatic techniques. RESULTS: CRYAB displayed a mild immunoreactivity in the subsarcolemmal compartment with no pathological sarcoplasmic accumulation. It agrees with an alteration of the physico-chemical properties predicted for the C-terminal domain: hydrophobicity, stiffness, and isomerization. CONCLUSIONS: The described mutation leads to elongation of the protein at the carboxi-terminal domain (CTD) with altered properties, which are essential for solubility and activity. It suggests that can be the cause of the severe conditions observed in this patient.
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Catarata/genética , Miotonía Congénita/genética , Fenotipo , Cadena B de alfa-Cristalina/genética , Catarata/patología , Preescolar , Genes Dominantes , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación , Miotonía Congénita/patología , Síndrome , Gemelos , Cadena B de alfa-Cristalina/químicaRESUMEN
BACKGROUND: Patients with eating disorders (ED) are very sensitive and responsive to psychosocial stress. Stress response includes changes in immune cell distribution and may be modulated by the capability to cope with stressors. Thus, the present study sought to analyze the association between coping strategies and immune response (natural killer [NK] cell redistribution following psychosocial stress) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) and healthy controls (HC). METHOD: Twenty-four AN patients, 29 BN patients, and 58 HC were studied. A multidimensional assessment tool, the COPE Inventory, was used to assess coping strategies. The number of NK cells was quantified in peripheral blood before and after the application of the Trier Social Stress Test (TSST). Potentially mediating variables, such as weight status, severity of eating pathology, depression, anxiety, and impulsivity were controlled. RESULTS: The three groups differed in intensity and direction of cell redistribution: The TSST was followed in BN patients by a significant decrease in the number of NK cells, whereas HC displayed a moderate decrease and AN a clear increase. Specific correlations between coping strategies and NK cell mobilization were found, especially in BN patients (positive for "planning" and negative for "substance abuse"). CONCLUSION: Recognition and subsequent modification of the dysfunctional coping strategies used by patients with ED could contribute to improving their immune status, strengthening their resilience and increasing their ability to overcome the disease.
ANTECEDENTES: Los pacientes con trastornos de la conducta alimentaria (TCA) son muy sensibles y respondedores ante el estrés psicosocial. La respuesta al estrés incluye cambios en la distribución de las células inmunes y parece estar modulada por la capacidad de afrontamiento del individuo. En este contexto, el objetivo del presente estudio fue analizar la asociación entre estrategias de afrontamiento y redistribución tras el estrés de las células agresoras naturales (natural killer, NK) en pacientes de sexo femenino con anorexia nervosa (AN) y bulimia nervosa (BN), y controles sanos (CS). MÉTODO: Treinta y cuatro pacientes con AN, 29 pacientes con BN y 58 CS fueron estudiados. Para evaluar las estrategias de afrontamiento se utilizó un instrumento multidimensional, el Inventario COPE. El número de células NK en sangre periférica fue cuantificado antes y después de la aplicación del Trier Social Stress Test (TSST). Las posibles variables mediadoras, como el estado ponderal, la gravedad de la patología alimentaria, depresión, ansiedad e impulsividad fueron control. RESULTADOS: Los tres grupos difirieron en la intensidad y la dirección de la redistribución de células NK: el TSST fue seguido de una notable reducción en el número de células NK en las pacientes con BN, de una disminución moderada en las CS y de un claro incremento en las pacientes con AN. Se encontraron correlaciones específicas entre estrategias de afrontamiento y movilización de células NK, especialmente en las pacientes con BN (positiva para "planificación" y negativa para "abuso de sustancias"). CONCLUSIÓN: El reconocimiento y la modificación consiguiente de las estrategias de afrontamiento disfuncionales utilizadas por las pacientes con TCA pueden contribuir a mejorar su estado inmunológico, incrementando su resistencia y su capacidad para superar la enfermedad.
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Adaptación Psicológica/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Células Asesinas Naturales/metabolismo , Estrés Psicológico/psicología , Adulto , Bulimia Nerviosa/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Adulto JovenRESUMEN
OBJECTIVE: Integrated primary care (IPC) is intended to address the gap in access to behavioral health care. This may be particularly true in urban settings; however, there is a paucity of research on treatment engagement in urban IPC. This study explored factors associated with treatment engagement. METHOD: Data were collected via retrospective chart review for 410 patients of diverse backgrounds who received an IPC referral in an urban primary care site. Patient-related factors included having multiple types of referral concerns, patient primary care show rate, and number of visits with referring clinician. Service-related factors included referral type (warm handoff/ electronic), number of days between referral and intake, and average number of days between IPC treatment sessions. Engagement outcomes included attendance at IPC intake, total IPC sessions attended, overall IPC show rate, and IPC treatment attrition. RESULTS: Of referred patients, 348 (84.9%) were encouraged to or scheduled an intake. Of those, 289 (83.1%) scheduled and 57.2% attended; the average number of sessions attended was 1.73. Patients who had more primary care office visits and higher primary care show rates were more likely to attend an IPC intake. Shorter average duration between follow-up sessions was associated with higher overall IPC show rates for those who initiated IPC follow-up care. CONCLUSIONS: Supporting engagement in primary care broadly and building scheduling capacity for IPC treatment may increase IPC service engagement in an urban primary care context.
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School-based mental health programs are increasingly recognized as methods by which to improve children's access to evidence-based practices (EBPs), particularly in urban under resourced communities. School-wide positive behavior interventions and supports (PBIS) is one approach to integrating mental health services into school-based programming; however, school providers require training and support to implement programs as intended. We have conducted a randomized controlled trial to compare two models for training school-based personnel to deliver group EBPs to children at high risk of developing internalizing or externalizing problems. School personnel (N = 24) from 6 schools in a large urban school district were trained with either a basic training and consultation strategy, or an enhanced training and consultation strategy. Preliminary findings show that the enhanced strategy resulted in 9% higher content fidelity than the basic strategy. School personnel who were switched to the basic strategy had slightly lower content fidelity for the last two years of the trial and school personnel who continued to receive basic consultation during the step-down phase saw their fidelity decline. The two conditions did not differ with regard to process fidelity.
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INTRODUCCIÓN: El síndrome de West (SW) es una encefalopatía epiléptica dependiente de la edad con pronóstico variable según la etiología subyacente, no siempre identificada. OBJETIVOS: Definir el perfil del SW criptogénico en nuestro medio, subgrupo menos estudiado de forma aislada. Estudiar su evolución, respuesta a los distintos tratamientos y establecer factores pronósticos. PACIENTES Y MÉTODOS: Revisión de historias clínicas de 16 pacientes diagnosticados de SW criptogénico durante el período 2000-2015. El tiempo de seguimiento medio fue 6,6 años y mínimo de 2 años. RESULTADOS: 11 de 16 fueron varones, la edad media de inicio fue de 6 meses y 6/16 presentaban antecedente familiar de epilepsia idiopática. El tratamiento de primera línea con vigabatrina tuvo respuesta electroclínica en 5/16 pacientes, respondiendo los casos restantes a hormona adrenocorticotropa (ACTH). El 44% de los pacientes evolucionaron a otras epilepsias, sin diferencia entre los tratados con vigabatrina o ACTH. Se obtuvo un mayor número de efectos adversos con la ACTH, no se evidenció afectación retiniana con la vigabatrina. Durante el seguimiento se llegó a la causa etiológica en 2/16. El sexo femenino, el comienzo tardío y el control precoz de la hipsarritmia resultaron factores de buen pronóstico. CONCLUSIONES: El pronóstico global del SW criptogénico resultó más grave de los esperado. Aunque la incidencia de síndrome de Lennox-Gastaut fue baja, la epilepsia focal resultó la evolución más frecuente apareciendo en los 2 primeros años del diagnóstico. La respuesta inicial a vigabatrina fue menor a la esperada, pero el resultado a largo plazo resultó superponible a la ACTH
INTRODUCTION: West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. OBJECTIVES: To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. PATIENTS AND METHODS: The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. RESULTS: The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. CONCLUSIONS: The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH
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Humanos , Masculino , Femenino , Lactante , Pronóstico , Espasmos Infantiles/etiología , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/administración & dosificación , Hormona Liberadora de Corticotropina , Estudio Observacional , Neuroimagen , NeuropsicologíaRESUMEN
Public schools are an ideal setting for the delivery of mental health services to children. Unfortunately, services provided in schools, and more so in urban schools, have been found to lead to little or no significant clinical improvements. Studies with urban school children seldom report on the effects of clinician training on treatment fidelity and child outcomes. This study examines the differential effects of two levels of school-based counselor training: training workshop with basic consultation (C) vs. training workshop plus enhanced consultation (C+) on treatment fidelity and child outcomes. Fourteen school staff members (counselors) were randomly assigned to C or C+. Counselors implemented a group cognitive behavioral therapy protocol (Coping Power Program, CPP) for children with or at risk for externalizing behavior disorders. Independent coders coded each CPP session for content and process fidelity. Changes in outcomes from pre to post were assessed via a parent psychiatric interview and interviewer-rated severity of illness and global impairment. Counselors in C+ delivered CPP with significantly higher levels of content and process fidelity compared to counselors in C. Both C and C+ resulted in significant improvement in interviewer-rated impairment; the conditions did not differ from each other with regard to impairment. Groups did not differ with regard to pre- to- posttreatment changes in diagnostic severity level. School-based behavioral health staff in urban schools are able to implement interventions with fidelity and clinical effectiveness when provided with ongoing consultation. Enhanced consultation resulted in higher fidelity. Enhanced consultation did not result in better student outcomes compared to basic consultation. Implications for resource allocation decisions with staff training in EBP are discussed.
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Terapia Cognitivo-Conductual/métodos , Trastornos del Neurodesarrollo/psicología , Trastornos del Neurodesarrollo/terapia , Servicios de Salud Escolar , Instituciones Académicas , Población Urbana , Adaptación Psicológica , Adolescente , Niño , Preescolar , Análisis por Conglomerados , Terapia Cognitivo-Conductual/tendencias , Femenino , Humanos , Masculino , Servicios de Salud Mental/tendencias , Trastornos del Neurodesarrollo/epidemiología , Derivación y Consulta/tendencias , Servicios de Salud Escolar/tendencias , Instituciones Académicas/tendencias , Estudiantes/psicología , Resultado del Tratamiento , Población Urbana/tendenciasRESUMEN
INTRODUCTION: West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. OBJECTIVES: To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. PATIENTS AND METHODS: The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. RESULTS: The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. CONCLUSIONS: The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH.
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Espasmos Infantiles/diagnóstico , Espasmos Infantiles/tratamiento farmacológico , Femenino , Humanos , Lactante , Masculino , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Despite co-segregation of two different genetic neurological disorders within a family is rare, clinicians should take into consideration this possibility in patients presenting with unusual complex phenotypes or with unexpected electrophysiological findings. Here, we report a Spanish 11-month-old patient with spinal muscular atrophy type 2 and Charcot-Marie-Tooth 1A.
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OBJECTIVE: To report 14 patients with immune-mediated relapsing symptoms post-herpes simplex encephalitis (HSE) and to compare the clinical and immunologic features of the teenage and adult group with those of young children. METHODS: Prospective observational study of patients diagnosed between June 2013 and February 2015. Immunologic techniques have been reported previously. RESULTS: Among the teenage and adult group (8 patients, median age 40 years, range 13-69; 5 male), 3 had an acute symptom presentation suggesting a viral relapse, and 5 a presentation contiguous with HSE suggesting a recrudescence of previous deficits. Seven patients developed severe psychiatric/behavioral symptoms disrupting all social interactions, and one refractory status epilepticus. Blepharospasm occurred in one patient. Five patients had CSF antibodies against NMDA receptor (NMDAR) and 3 against unknown neuronal cell surface proteins. In 5/6 patients, the brain MRI showed new areas of contrast enhancement that decreased after immunotherapy and clinical improvement. Immunotherapy was useful in 7/7 patients, sometimes with impressive recoveries, returning to their baseline HSE residual deficits. Compared with the 6 younger children (median age 13 months, range 6-20, all with NMDAR antibodies), the teenagers and adults were less likely to develop choreoathetosis (0/8 vs 6/6, p < 0.01) and decreased level of consciousness (2/8 vs 6/6, p < 0.01) and had longer delays in diagnosis and treatment (interval relapse/antibody testing 85 days, range 17-296, vs 4 days, range 0-33, p = 0.037). CONCLUSION: In teenagers and adults, the immune-mediated relapsing syndrome post-HSE is different from that known in young children as choreoathetosis post-HSE and is underrecognized. Prompt diagnosis is important because immunotherapy can be highly effective.
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Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/inmunología , Herpes Simple/diagnóstico , Herpes Simple/inmunología , Adolescente , Adulto , Anciano , Encefalitis por Herpes Simple/tratamiento farmacológico , Femenino , Herpes Simple/tratamiento farmacológico , Humanos , Inmunoterapia/tendencias , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Adulto JovenRESUMEN
No disponible
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Humanos , Niño , Psicosis Inducidas por Sustancias/diagnóstico , Metilfenidato/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológicoAsunto(s)
Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Psicosis Inducidas por Sustancias/etiología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Humanos , Masculino , Metilfenidato/uso terapéutico , Psicosis Inducidas por Sustancias/fisiopatologíaRESUMEN
Introducción. El síndrome de West es una epilepsia dependiente de la edad que asocia espasmos infantiles, hipsarritmia y un retraso o detención en el desarrollo psicomotor, aunque este último no es imprescindible. Objetivos. Definir el perfil del síndrome de West en nuestro medio atendiendo a la etiología, semiología, respuesta a distintas opciones terapéuticas y aparición de efectos adversos, y establecer factores pronósticos que determinen la evolución. Pacientes y métodos. Se ha elaborado un documento de recogida de datos en el que se constatan los criterios de inclusión. La recogida de datos se ha realizado mediante la revisión de historias clínicas de los pacientes diagnosticados de síndrome de West en el período comprendido entre enero de 2003 y enero de 2009. Posteriormente, se ha realizado un estudio estadístico con análisis descriptivo y se ha establecido el nivel de significación estadística de los posibles factores pronósticos. Resultados. El estudio abarcó 70 pacientes. La etiología sintomática fue predominante, destacando la hipoxia-isquemia como causa principal. Respondió a vigabatrina el 58% de los pacientes, independientemente de la etiología. Más del 80% de los pacientes en tratamiento con hormona adrenocorticotropa quedaron libres de crisis y sin hipsarritmia. Casi la mitad de los pacientes evolucionó a otras epilepsias. Conclusiones. Los factores de mal pronóstico estadísticamente significativos fueron: existencia de antecedentes prenatales, antecedentes neonatales, etiología sintomática, edad de inicio inferior a 4 meses, crisis epilépticas antes del inicio de los espasmos y fuera del período neonatal, y retraso en el desarrollo psicomotor previo al inicio de los espasmos (AU)
Introduction. West syndrome is an age-specific form of epilepsy that associates infantile spasms, hypsarrhythmia and a delay in or the complete stoppage of psychomotor development, although this last case is not essential. Aims. To define the profile of West syndrome in our environment by taking into account its aetiology, semiology, response to different therapeutic options and the appearance of side effects, as well as to establish prognostic factors that determine its course. Patients and methods. A data collection document stating the eligibility criteria was drafted. Data were collected by reviewing the medical records of patients diagnosed with West syndrome during the period between January 2003 and January 2009. Later, a statistical study was conducted with descriptive analysis and the level of statistical significance of the possible prognostic factors was established. Results. The study included 70 patients. There was a predominance of symptomatic aetiology, with hypoxia-ischaemia as the main cause. Regardless of the aetiology, 58% of patients responded to treatment with vigabatrine. Over 80% of patients being treated with adrenocorticotropic hormone were finally seizure-free and without hypsarrhythmia. Almost half the patients progressed to other epilepsies. Conclusions. The statistically significant poor prognostic factors were: existence of a prenatal history, neonatal history, symptomatic aetiology, age of onset below 4 months, epileptic seizures before the onset of the spasms and outside the neonatal period, and delayed psychomotor development prior to the onset of the spasms (AU)
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Humanos , Masculino , Femenino , Lactante , Espasmos Infantiles/etiología , Epilepsia/tratamiento farmacológico , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/uso terapéutico , Estudios Retrospectivos , Hormona Adrenocorticotrópica/uso terapéutico , Quimioterapia CombinadaRESUMEN
Rett Syndrome (RS; MIM_312750) is a severe and progressive neurodevelopmental disorder affecting principally females. Mutations in X-Linked MECP2 gene (methyl CpG-binding protein 2; MIM_300005) have been reported as being the major cause of RS. Mutations in this gene have been described as cause of wide spectrum of neurological disorders and mental retardation in males. In some cases, mutations in MECP2 in males produce clinical picture similar to RS. Here we report the identification of the novel truncating mutation Y120X in a 4-year-old child with atypical RS phenotype. Chromosome analysis showed a normal karyotype, and blood DNA and tissue DNA analysis reveal a mosaic for the mutation. Patient's mother DNA analysis showed that this is a de novo mutation, that has never been described before in any female or male case of RS.