[Prevalence estimation of Autism Spectrum disorders in chilean urban population]. / Estimación de la prevalencia de trastorno del Espectro Autista en población urbana chilena.

INTRODUCTION: The prevalence of Autism Spectrum Disorder has increased, varying between 0.5 and 1% around the world. The prevalence of ASD in Chile is unknown. OBJECTIVE: To estimate the prevalence of ASD in two urban communes of Santiago, Chile. SUBJECTS AND METHOD: Cross-sectional epidemiological study. 272 children aged between 18-30 months who attended well-child visits at two Family Health Centers in two urban communes of Santiago participated. Consecutive sampling was used and chil dren who were already being monitored by neurology were excluded. Screening was performed using the Modified Checklist for Autism in Toddlers (M-CHAT). Those children with altered M-CHAT were evaluated by a pediatric neurologist at the San Borja Arriarán Clinical Hospital and diagnosed with ASD according to clinical criteria. The Autism Diagnostic Observation Schedule - Second Ver sion (ADOS-2) was used as a diagnostic complement. The prevalence of ASD was estimated with a 95% confidence interval. RESULTS: 44 children had altered M-CHAT; 5 of them were clinically diagno sed with ASD. A 1.95% prevalence of ASD (95% CI 0.81-4.63) was obtained, with a sex distribution of 4 boys per 1 girl. CONCLUSIONS: This study is the first estimate of ASD prevalence in two communes of Santiago, Chile. A high prevalence of this condition was observed, which highlights the need for obtaining resources for an early multidisciplinary approach for these patients.

[Children and adolescents with intellectual disabilities studied with genetic tests according to their clinical phenotype]. / Estudio genético de acuerdo a características fenotípicas de niños y adolescentes con discapacidad intelectual de etiología indeterminada.

INTRODUCTION: Intellectual disability (ID) is a neurodevelopmental disorder characterized by limitations in intellec tual and adaptive functioning, of various etiologies, including genetic causes. OBJECTIVE: to describe genetic studies carried out in a series of children and adolescents with ID of previously undetermined etiology, considering their phenotypic characteristics. PATIENTS AND METHOD: Descriptive study of a series of patients with ID aged 6 to 18 years. Clinical records, cognitive assessment results (Wechsler -TADI), and genetic study performed were reviewed. They were classified according to phenotypic characteristics into Group 1 patients without a specific phenotype, Group 2: patients with Angel- man- and Rett-like neurodevelopmental disorders phenotype, and Group 3: patients with difficult- to-control seizures. Group 1 was studied with CMA and Groups 2 and 3 with specific genetic panels. RESULTS: 18 patients were described, average age 11 years, male predominance, non-consanguineous parents, and with history of psychomotor retardation. Common comorbidities were epilepsy, autism spectrum disorder (ASD), and behavioral difficulties. Most had a neurological examination without focus and had TADI with very poor developmental ages. In Group 1, there was one patient with a 16p11.2 microdeletion and in Group 3 a duplication of the IQSEC2 gene was found in a patient with difficult-to-control seizures. CONCLUSIONS: The phenotypic characteristics allow to guide the choice of specific genetic studies in children and adolescents with ID of previously undetermined etiology to approach the etiological diagnosis.

The phenotypic spectrum of SCN8A encephalopathy.

OBJECTIVE: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. METHODS: We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. RESULTS: Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. CONCLUSION: SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent.

Zinc en la terapia del síndrome de déficit de atención e hiperactividad en niños: Un estudio controlado aleatorio preliminar / Zinc in the therapy of the attention-deficit/ hyperactivity disorder in children: A preliminar randomized controlled trial

El síndrome de déficit de atención e hiperactividad (ADHD) es un trastorno neurológico /conductual que se inicia en la infancia. Se ha propuesto que el zinc tendría un potencial rol como terapia adjunta para el ADHD. Nuestro objetivo fue evaluar el efecto de la suplementación con zinc sobre la conducta, como terapia complementaria al metilfenidato, en niños con ADHD. En un estudio controlado, doble ciego, se seleccionaron 40 pacientes con criterios clínicos y psicométricos de ADHD, (31 niños, 9 niñas, 7-14 años de edad). Ellos fueron seleccionados aleatoriamente para recibir ya sea metilfenidato 0,3 mg/kg/d + placebo (sacarosa) (grupo placebo, GPL), o metilfenidato 0,3 mg/kg/d + zinc (sulfato) 10 mg/d (grupo Zn, GZN) por 6 semanas; se excluyeron 4 niños. Se tomó una muestra de 3 mL de sangre en el tiempo 0 y a las 6 semanas para el análisis de Zn plasmático; se aplicó en ambos tiempos a padres y profesores la escala abreviada de Conners para ADHD. Entre los resultados, El Zn plasmático fue normal en el tiempo 0 en ambos grupos, disminuyendo después de 6 sem., especialmente en el grupo GPL (GPL: 95,9 ± 21,5 a 77,9 ± 15,5; GZN: 90.3 ± 9.1 a 85,0 ± 12,0 μg/dl, NS). El test de Conners aplicado por los profesores mostró una aparente mejoría en GZN: GPL: 18 (9-28) a 16 puntos (2-26); GZN: 19 (6-24) a 11 puntos (3-23) (p= 0,07), sin mejoría en el Conners aplicado por los padres: GPL: 19 (7-25) a 13 (3-22); GZN: 19 (7-25) a 11 (2-19). Se concluye que se observa una disminución en las concentraciones plasmáticas de Zn en ambos grupos, pero mayor en el grupo placebo. Con el suplemento de zinc se observa una aparente mejoría en los síntomas de ADHD, de acuerdo con la evaluación de Conners aplicada por profesores. Se requiere avanzar en el estudio de esta probable interacción entre zinc y metilfenidato.

The attention-deficit/hyperactivity disorder (ADHD) is a neurological/behavioral disorder which begins in childhood. Zinc has a potential role as an adjuvant therapy for ADHD. The objective was to evaluate the effect of Zn supplementation on behavior, as a complementary therapy to metylphenidate, in pediatrics patients with ADHD. In a controlled, double blind design, 40 patients with clinical criteria of ADHD (DSMIV) and psychometric evaluation (WISC-R), were selected (31 boys and 9 girls, 7-14 years of age). They were randomized to receive methylphenidate 0.3 mg/kg/d + placebo (sucrose) (group placebo, GPL) or methylphenidate 0.3 mg/kg/d + zinc (sulfate) 10 mg/d (group Zn, GZN) for 6 weeks. A blood sample was drawn at time 0 and 6 weeks, for plasma Zn analysis. The teacher and parent ADHD rating scale (Conners` global index, CGI) was applied at both times. Among the results, plasma Zn was normal at time 0, decreasing especially in the GPL after 6 weeks (GPL: 95.9 ± 21.5 to 77.9 ± 15.5; GZN: 90.3 ± 9.1 to 85.0± 12.0 μg/dL; NS). The CGI by teachers showed a non-significant improvement with Zn: GPL: 18 (9- 28) to 16 points (2-26); GZN: 19 (6-24) to 11 points (3-23) (p=0.07); no significant difference in the CGI by parents by groups was found: GPL: 19 (7-25) to 13 (3- 22); GZN: 19(7-25) to 11(2-19). We conclude that a decrease in plasma Zn levels in both groups was found, greater in the placebo group. An apparent improvement in ADHD signs in children was observed with the Zn supplementation, according to the Conners global index by teachers.

Normalización de trastornos de sueño y su efecto en pacientes con epilepsia refractaria / Effects of sleep disorders normalization in patients during the use of antiepileptic drugs

Los trastornos del sueño son un problema frecuente y subdiagnosticado en niños con cuadros neurológicos y en particular con epilepsias refractarias. Evaluamos los efectos de normalización rápida de los patrones de sueño sobre la refractariedad de la epilepsia. Pacientes y Método: Se ingresaron al estudio todos los pacientes pediátricos con alteración severa del ciclo sueño-vigilia y epilepsia refractaria en control en el Servicio de Neuropsiquiatría Infantil del Hospital Clínico San Borja-Arriarán y Liga contra la Epilepsia, Santiago, Chile, entre Marzo 2004 y Marzo 2008. Cada paciente fue su propio control. Durante el primer mes se solicitó a los padres completar un registro diario de frecuencia y tipo de crisis epiléptica y del ciclo sueño-vigilia de su hijo (a). A contar del segundo mes se implementó un tratamiento para normalizar el ciclo sueño-vigilia utilizando luminoterapia, hábitos estrictos de sueño y melatonina, 30 min antes de la hora de dormir. La terapia antiepiléptica no se modificó durante los primeros seis meses de tratamiento. Resultados: Los once pacientes ingresados normalizaron el ciclo sueño-vigilia durante el primer mes de tratamiento. Diez de 11 casos mostraron una reducción dramática de la frecuencia de crisis por día, mayor a un 85 por ciento, durante los primeros tres meses de intervención, independientemente del tipo de crisis, que se mantuvo por más de un año de seguimiento (13-43 meses). En cinco pacientes se discontinuó la melatonina después de un año de tratamiento, sin que hubiese deterioro del patrón de sueño o aumento en la frecuencia de crisis. Conclusión: Es frecuente el subdiagnóstico de trastorno de sueño en niños con epilepsias refractarias. La normalización del patrón de ciclo sueño-vigilia puede disminuir dramáticamente la frecuencia de crisis y por lo tanto mejorar la calidad de vida de los pacientes y sus familias...

Sleep disorders are a frequent and underdiagnosed problem in children with neurological problems, specially in children with refractory epilepsies. We evaluated the effects of fast normalization of sleep pattern on epilepsy refractoriness. Patients and methods: We enrolled all pediatric patients from March 2004 to March 2008, with severe alterations of the sleep-wake pattern and refractory epilepsy, attending to the Neuropsychiatry Service, Hospital Clínico San Borja-Arriarán and League against Epilepsy from Santiago, Chile. Each patient was his own control. Parents were asked to complete a diary during the first month after enrollment with frequency, type of seizures and sleep-wake cycle of each patient. After the month, sleep-wake cycle was normalized using morning luminotherapy, strict sleep habits and melatonin, 30 minutes before bedtime. Antiepileptic therapy was not modified during the first six months. Results: All patients normalized the sleep-wake cycle during the first month treatment. Ten of 11 patients showed a dramatic reduction of seizure frequency (over 85 percent of total day seizures) during the first three months of intervention, independently from the seizure type that has maintained for more than a year (13–43 months) follow-up. Melatonin was discontinued in five patients after a year of treatment, with no deterioration of sleep pattern or seizures frequency. Conclusions: Sleep disorders in children with refractory epilepsies are frequently underestimated. The normalization of the sleep-wake pattern can diminish seizures dramatically, improving patients and family quality of life. This point must be always taken into account before considering a patient refractory to antiepileptic drugs and adding new drugs to polytherapy.

[Zinc in the therapy of the attention-deficit/hyperactivity disorder in children. A preliminar randomized controlled trial]. / Zinc en la terapia del sindrome de déficit de atención e hiperactividad en niños. Un estudio controlado aleatorio preliminar.

The attention-deficit/hyperactivity disorder (ADHD) is a neurological/behavioral disorder which begins in childhood. Zinc has a potential role as an adjuvant therapy for ADHD. The objective was to evaluate the effect ofZn supplementation on behavior, as a complementary therapy to metylphenidate, in pediatrics patients with ADHD. In a controlled, double blind design, 40 patients with clinical criteria ofADHD (DSM-IV) and psychometric evaluation (WISC-R), were selected (31 boys and 9 girls, 7-14 years of age). They were randomized to receive methylphenidate 0.3 mg/kg/d + placebo (sucrose) (group placebo, GPL) or methylphenidate 0.3 mg/kg/d + zinc (sulfate) 10 mg/d (group Zn, GZN) for 6 weeks. A blood sample was drawn at time 0 and 6 weeks, for plasma Zn analysis. The teacher and parent ADHD rating scale (Conners' global index, CGI) was applied at both times. Among the results, plasma Zn was normal at time 0, decreasing especially in the GPL after 6 weeks (GPL: 95.9 +/- 21.5 to 77.9 +/- 15.5; GZN: 90.3 +/- 9.1 to 85.0 +/- 12.0 microg/dL; NS). The CGI by teachers showed a non-significant improvement with Zn: GPL: 18 (9-28) to 16 points (2-26); GZN: 19 (6-24) to 11 points (3-23) (p = 0.07); no significant difference in the CGI by parents by groups was found: GPL: 19 (7-25) to 13 (3-22); GZN: 19(7-25) to 11(2-19). We conclude that a decrease in plasma Zn levels in both groups was found, greater in the placebo group. An apparent improvement in ADHD signs in children was observed with the Zn supplementation, according to the Conners global index by teachers.

Barber-Say syndrome: further delineation of the clinical spectrum

Apresentamos uma paciente de 14 anos, de sexo feminino, portadora de um quadro de múltiplas anomalias congênitas: hipertelorismo, telecanto, macrostomia, agenesia da hélice em ambos os pavilhöes auriculares, pele grossa e redundante e hirsutismo severo, que corresponde ao 5º caso reportado de síndrome de Barber-Say. Esta paciente tem praticamente o mesmo fenótipo que a paciente descrita por Martínez Santana et al. (Am. J. Med. Genet. 47:20-23, 1992), incluindo o mesmo padräo dermatoglífico que näo havia sido descrito até entäo.

Simposio de epilepsia 1996: convulsiones neonatales / Epilepsy simposium 1996: neonatal convulsions

Durante el mes de octubre de 1996, se llevó a cabo el VIII Simposio de Epilepsia dentro del Congreso de Neurología y Psiquiatría Infantil.El tema tratado fue: Convulsiones Neonatales, diagnóstico, manejo y pronóstico. Durante el desarrollo del simposio se aplicó una prueba diagnóstica sobre el tema, a los asistentes, a partir de la cual se llevó a cabo la mesa redonda. A continuación presentaremos la discusión y análisis de cada pregunta,de acuerdo a lo tratado en esa oportunidad

Infarto cerebral embólico de probable origen cardíaco / Embolic cerebral infarct probable of cardiac origin

En relación a tres casos de accidente vascular encefálico oclusivo secundario a fuente cardiogénica, se efectúa una revisión del tema discutiendo los aspectos clínicos más relevantes, con énfasis en los métodos de estudio y en especial la ecocardiografía, las opciones terapéuticas y el pronóstico de la entidad. Se insiste en la necesidad de hacer un estudio cardiovascular minucioso en los niños afectados de esta patología