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Parálisis Cerebral , Humanos , Parálisis Cerebral/epidemiología , Sistema de Registros , AprendizajeAsunto(s)
Parálisis Cerebral , Parálisis Cerebral/diagnóstico , Niño , Electromiografía , Humanos , Lactante , Articulación de la Rodilla , PronósticoRESUMEN
The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin.
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Encéfalo/metabolismo , Proteína de Unión a CREB/genética , Proteínas del Citoesqueleto/metabolismo , Proteína p300 Asociada a E1A/genética , Células Madre Embrionarias/metabolismo , Factor Nuclear 1 de Respiración/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular , Cromatina/química , Femenino , Genómica , Células HEK293 , Heterocigoto , Humanos , Masculino , Ratones , Neuronas/metabolismo , Unión Proteica , Dominios Proteicos , Proteómica , Activación TranscripcionalRESUMEN
INTRODUCTION: Demographic and clinical data were collected from three cross-sectional samples, from the headache and epilepsy clinics according to respective protocols. During structured interviews, we examined the co-occurrence of headaches and epilepsy in children and their families: (1) 172 children from the headache clinic, were questioned for the number and type of epileptic seizures and epilepsy diagnosis. (2) Around 70 children from the epilepsy clinic for the frequency and type of headaches and headache syndrome diagnosis. (3) A total of 149 parents of children with benign childhood epilepsy with centro-temporal spikes (BCECTS) and childhood absence epilepsy (CAE), for the relative frequency of headaches in first- and second-degree relatives. RESULTS: Out of 172, 84 (48.8%) children with headache had a migraine and 60 (34.9%) had tension headaches; 3 children (1.7%) had epilepsy or unprovoked seizures. Migraine and epilepsy, co-occurred in 2/84 (2.3%). Eight out of 70 patients with epilepsy had headaches (11.4%); none had migraine. Around 43% of patients with BCECTS or CAE had a family history of headache, more prevalent in first-degree relatives of children with BCECTS than CAE. CONCLUSION: Contrary to existing literature, migraine and epilepsy, co-occurred infrequently in these highly selected samples. Family history of headache was frequent in patients with BCECTS and CAE, without any significant difference between the two.
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Epilepsia/epidemiología , Trastornos de Cefalalgia/epidemiología , Cefalea/epidemiología , Adolescente , Niño , Preescolar , Comorbilidad , Estudios Transversales , Epilepsia Tipo Ausencia/epidemiología , Femenino , Humanos , Masculino , PediatríaRESUMEN
This retrospective study aimed to examine the safety of botulinum toxin A (BoNT-A) treatment in a paediatric multidisciplinary cerebral palsy clinic. In a sample of 454 patients who had 1515 BoNT-A sessions, data on adverse events were available in 356 patients and 1382 sessions; 51 non-fatal adverse events were reported (3.3% of the total injections number, 8.7% of the patients). On five occasions, the adverse reactions observed in GMFCS V children were attributed to the sedation used (rectal midazolam plus pethidine; buccal midazolam) and resulted in prolongation of hospitalization. Of the reactions attributed to the toxin, 23 involved an excessive reduction of the muscle tone either of the injected limb(s) or generalized; others included local pain, restlessness, lethargy with pallor, disturbance in swallowing and speech production, seizures, strabismus, excessive sweating, constipation, vomiting, a flu-like syndrome and emerging hypertonus in adjacent muscles. Their incidence was associated with GMFCS level and with the presence of epilepsy (Odds ratio (OR) = 2.74 - p = 0.016 and OR = 2.35 - p = 0.046, respectively) but not with BoNT-A dose (either total or per kilogram). In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not necessitate major changes in our practice.
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Toxinas Botulínicas Tipo A/efectos adversos , Parálisis Cerebral/tratamiento farmacológico , Fármacos Neuromusculares/efectos adversos , Adolescente , Sistemas de Registro de Reacción Adversa a Medicamentos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Niño , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Grecia , Humanos , Incidencia , Masculino , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Índice de Severidad de la EnfermedadAsunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/fisiopatología , Fármacos Neuromusculares/uso terapéutico , Adulto , Niño , Utilización de Medicamentos , Familia , Encuestas de Atención de la Salud , Humanos , Destreza Motora , Desempeño Psicomotor/fisiologíaRESUMEN
This study assessed treatment consistency of botulinum toxin administration in spastic upper limbs under pragmatic conditions, as derived through stability of dosages and between injections intervals. Over a period of 8 years, 153 children (81 with bilateral spastic cerebral palsy, 72 with unilateral) were treated according to accepted, experience-based guidelines with Botox and Dysport. Treatment response was based on assessment of spasticity and attainment of pre-determined goals at 3, 6 and 12 months post each treatment. Mean age at treatment onset was 6y 4mo (SD: 4y 10mo), median F/U, 2.5 years (4 months-6 8/12 years). Number of injection sessions was 1-10; few had more than 6 sessions. In 106 (69.28%) children, more than one anatomic regions of the limb were injected. Most (56.2%), had at least two injection sessions; median time interval between the sessions was 9 months (IQR: 4-35 months, similar for unilateral and bilateral cerebral palsy, p = 0.874). Children >4 years old at the first treatment had longer intervals between sessions (25.8%) compared to younger ones (p = 0.010). The mixed effects models demonstrated that botulinum toxin dosage was stable over subsequent visits (p = 0.144) and that intermediate intervals for subsequent visits were similar to the first one (p = 0.279).
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Toxinas Botulínicas Tipo A/administración & dosificación , Parálisis Cerebral/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Espasticidad Muscular/tratamiento farmacológico , Extremidad SuperiorRESUMEN
UNLABELLED: There is great demand for effective management of children with Autistic Spectrum Disorders (ASD). This study aimed to investigate the effect of an individually tailored psycho-educational program for autistic children on the scores of the Childhood Autism Rating Scale (CARS) and the Short Sensory Profile (SSP). METHODS: Forty children (36 males) were enrolled into an intervention program which consisted of occupational therapy including sensory integration techniques, speech therapy, social skills therapy and parent-directed approaches. Autism severity was assessed using CARS; sensory response capability with the SSP pre- and post-treatment. RESULTS: Eight children were intellectually normal; 12 borderline and 20 of low intelligence. Pre-treatment CARS showed that 8 were mildly autistic, 32 moderately-severely autistic. Post-treatment, 24 children changed category; 11 were no longer autistic. The percentage of children performing in the definitive difference region, according to total SSP score, changed slightly (45% vs 32.5%). Comparison of the pre- and post-treatment values revealed that CARS decreased significantly (p < 0.001), whereas total SSP did not (p = 0.294). Tactile sensitivity and low energy/weakness sections, though, were significantly different pre- and post-treatment. Longitudinal analysis, taking into account other confounding factors besides time, further revealed a significant decrement for CARS score with time but not for SSP score (p < 0.001 and p = 0.288, respectively). Similarly, intelligence levels affected CARS but not SSP values (p < 0.001 and p = 0.813, respectively). CONCLUSION: Individually tailored psycho-educational therapy had a significant effect on autism severity according to CARS. Changes in the SSP scores were not significant.
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Trastornos Generalizados del Desarrollo Infantil/psicología , Trastornos Generalizados del Desarrollo Infantil/terapia , Intervención Educativa Precoz/métodos , Educación Especial/métodos , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Preescolar , Femenino , Humanos , Masculino , Terapia Ocupacional/métodos , Terapia Ocupacional/psicología , Logopedia/métodos , Logopedia/psicologíaRESUMEN
Although the efficacy of midazolam in refractory status epilepticus and as a first-line agent in children with established status epilepticus has been reported, differences in starting doses, continuation method, timing of efficacy assessment, and discontinuation pose limitations in deriving a specific protocol for midazolam use. An audit of clinical experience with a protocol of midazolam as first-line agent for impending status epilepticus (defined as a continuous, generalized, convulsive seizure lasting >5 minutes) in 76 episodes of unprovoked convulsive status epilepticus in children 1-15 years old with treatment-refractory epilepsy demonstrated that: (1) repeated bolus midazolam 0.1mg/kg (every 5 minutes, maximum 5) controlled 91% of events; (2) three bolus doses controlled 89% of the episodes, with minimal chance of response beyond that; (3) treating impending status resulted in lower doses (mean 0.17 mg/kg) than reported and infrequent utilization of additional anticonvulsants (9%); and (4) adverse events were infrequent (respiratory depression 13%, assisted ventilation 3%).
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Ansiolíticos/administración & dosificación , Midazolam/administración & dosificación , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/fisiopatología , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Medicamentos , Electroencefalografía , Femenino , Humanos , Lactante , Inyecciones Intraventriculares/métodos , Masculino , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Currently there is no specific treatment for the brain insults leading to motor dysfunction in cerebral palsy. The available symptomatic therapeutic options place cerebral palsy among the costliest chronic childhood conditions. Therefore, it is necessary to make well-informed decisions in an effort to match cost-effectiveness with patient and family needs. This presentation aims to analyze the efficacy of rehabilitation therapy, orthoses, oral medications, botulinum toxin, intrathecal baclofen, complementary or alternative treatments and discuss guidelines for a goal oriented approach. Despite insufficient reporting of trials, physiotherapy has shifted from traditional to goal oriented approaches, based on principles of motor learning, strength and fitness training. Correct choice and use of orthoses is stressed, yet evidence from primary studies is limited. Pharmacological treatments of spasticity (oral agents, botulinum toxin, intrathecal baclofen) may be alternatives or supplements to orthopaedic surgery. There is evidence that botulinum toxin combined with conservative treatments reduces the number of complex orthopaedic interventions. Intrathecal baclofen effectively reduces spasticity; criteria describing the ideal candidate are needed. Complementary or alternative treatment use is widespread; research needs to determine what factors make these modalities desirable and effective in cerebral palsy. It is concluded that the introduction of new therapies facilitates an individualized management plan. Multimodal treatment is optimized with a multidisciplinary team. Outcome measurement according to the World Health Organization's new International Classification of Functioning, Disability and Health is emphasized.
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Parálisis Cerebral/complicaciones , Parálisis Cerebral/terapia , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/rehabilitación , Niño , Terapias Complementarias , Humanos , Modalidades de FisioterapiaRESUMEN
UNLABELLED: Attention deficit hyperactivity disorder (ADHD) is treated with stimulants and psycho-educational remedial programs despite limited literature support for the latter. This study aimed to examine changes in a "Test of Visual Perceptual Skills" (TVPS) that has not been previously reported in children with ADHD enrolled in such a program. METHODS: Sixteen children, 7-11 years old, with ADHD were involved in occupational therapy and special education geared towards attention training. Six months later methylphenidate 1 mg/kg/day was prescribed. It was not taken by eight children because of family choice. The TVPS was given twice, upon diagnosis, and 8 months post-intervention. The groups were compared by a repeated measures analysis of variance (ANOVA) with medication as a between groups factor and test-retest scores as within factor. RESULTS: All children demonstrated increases in total scores in the second measurement. Medicated children scored higher but ANOVA showed a nonsignificant F for the two groups, medicated and unmedicated (F = 0.0031, p = 0.9563), indicating a nondifferential effect of the two levels of treatment. It revealed a significant F for the pre- and post-treatment total TVPS scores (F = 30.91, p < 0.0001) indicating a significant difference between pre- and post-treatment tests. The interaction between pre-post treatment and level of treatment (medicated-unmedicated) was nonsignificant (F = 2.20, p = 0.1604). CONCLUSION: TVPS scores improved in all children following intervention. Medicated children did better, but differences were nonsignificant.
RESUMEN
To examine the efficacy of a rehabilitation protocol, focusing on spasticity management through botulinum toxin A injections in the lower limbs, an etiologically homogeneous group of 57 prematurely born children with cerebral palsy was prospectively evaluated (minimum follow-up 18 months) under pragmatic conditions. Gross Motor Function Classification System categories were: I = 12, II = 9, III = 16, IV = 15, V = 4. Outcome was evaluated with goniometry, Gross Motor Function Measure, functional goal attainment at baseline and in subsequent months, the Gross Motor Function Classification System, functional mobility status, and parents' satisfaction at more than 18 months after first botulinum toxin. Goniometry demonstrated significantly improved range of movement in lower limbs at 10 days and 1 month after botulinum toxin. Differences persisted >18 months at the popliteal angles (P < 0.001). Gross Motor Function Measure changed significantly in 20 children (8 points in total score) at 3 months after first botulinum toxin (P < 0.0001) with less significant results thereafter. Predetermined functional goals were achieved in 61% at >18 months. Parents were satisfied in approximately 90% of the cases. Eighteen of 57 children (31.57%) changed Gross Motor Function Classification System status over a mean of 33.8 months (18-48) follow-up. Most significant gains were recorded in the severely involved group IV, where 10 of 15 (66.66%) improved. The high percentage of change in group IV implies the importance of gained sitting balance due to spasticity management.
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Toxinas Botulínicas Tipo A/administración & dosificación , Recien Nacido Prematuro , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/rehabilitación , Fármacos Neuromusculares/administración & dosificación , Adolescente , Toxinas Botulínicas Tipo A/efectos adversos , Parálisis Cerebral/complicaciones , Parálisis Cerebral/tratamiento farmacológico , Parálisis Cerebral/rehabilitación , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Destreza Motora , Espasticidad Muscular/etiología , Fármacos Neuromusculares/efectos adversos , Modalidades de Fisioterapia , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Transient mutism after posterior fossa surgery in children or associated with cerebellar hemorrhage or trauma is a recognized phenomenon. However, its association with parainflammatory cerebellitis has been rarely described. We report on a previously healthy 3-year-old child with severe cerebellitis after acute gastroenteritis of unidentified cause. Severe ataxia and transient mutism were the prevailing clinical features. Magnetic resonance imaging revealed swelling of the cerebellum with protruding cerebellar tonsils at the level of the occipital foramen. Recovery from the acute illness was slow and incomplete. Residual cerebellar dysfunction manifested with dysphonic and dysarthric speech, as well as motor coordination problems and was associated with atrophy of the vermis and cerebellar hemispheres in follow-up studies.