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Introduction: We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages. Material and methods: We analysed our 19-year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin. Results: The 19-year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them. Discussion: Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs. Resumen: Introducción: Consideramos encefalopatías prenatales las que tienen datos clínicos o prenatales de encefalopatía antes del nacimiento. Afectan a un número importante de niños controlados en las consultas de neuropediatría. Pueden ser disruptivas (por problemas vasculares durante el embarazo, drogas, tóxicos o infecciones congénitas), y genéticamente determinadas. Incluimos casos de trastorno del espectro autista y retardo mental sin historia de sufrimiento perinatal o postnatal. Material y métodos: Se revisa nuestra experiencia en el diagnóstico etiológico de las encefalopatías prenatales durante los últimos 19 años. Se analizan los estudios realizados en los casos sin diagnóstico etiológico. Resultados: En el periodo de estudio de 19 años y 5 meses, en la base de datos de neuropediatría figuran 11.910 niños. Tienen establecido el diagnóstico de encefalopatía prenatal 1596 (13,5%). De ellos no tienen diagnóstico etiológico preciso 1.307 niños (81,4%) pese a habérseles realizado múltiples estudios complementarios, fundamentalmente bioquímicos, genéticos y de neuroimagen. Discusión: Muchos de los niños incluidos en este estudio presentan enfermedades raras, estén o no identificadas, que demandan crecientemente un diagnóstico precoz. Enfermedades peroxisomales, lisosomales, mitocondriales, defectos congénitos de la glucosilación, entre otras enfermedades metabólicas hereditarias, infecciones congénitas, cromosomopatías y genopatías, pueden ser indistinguibles clínicamente y necesitan estudios específicos para su identificación. Un diagnóstico precoz precisa estrategias de estudios sistemáticos de forma escalonada, priorizando las enfermedades que tienen posibilidades terapéuticas y en muchos casos es necesaria también una aproximación individualizada. Creemos que las ventajas potenciales del diagnóstico precoz, incluido el ahorro de más pruebas, y la prevención, probablemente sobrepasan el gasto financiero. Keywords: Biochemical studies, Early diagnosis: aetiological diagnosis, Genetic studies, Neuroimaging, Prenatal encephalopathies, Rare diseases, Palabras clave: Diagnóstico etiológico, Diagnóstico precoz, Encefalopatías prenatales, Enfermedades raras, Estudios bioquímicos, Estudios genéticos, Neuroimagen

Resumen: Introducción: Consideramos encefalopatías prenatales las que tienen datos clínicos o prenatales de encefalopatía antes del nacimiento. Afectan a un número importante de niños controlados en las consultas de neuropediatría. Pueden ser disruptivas (por problemas vasculares durante el embarazo, drogas, tóxicos o infecciones congénitas), y genéticamente determinadas. Incluimos casos de trastorno del espectro autista y retardo mental sin historia de sufrimiento perinatal o postnatal. Material y métodos: Se revisa nuestra experiencia en el diagnóstico etiológico de las encefalopatías prenatales durante los últimos 19 años. Se analizan los estudios realizados en los casos sin diagnóstico etiológico. Resultados: En el periodo de estudio de 19 años y 5 meses, en la base de datos de neuropediatría figuran 11.910 niños. Tienen establecido el diagnóstico de encefalopatía prenatal 1596 (13,5%). De ellos no tienen diagnóstico etiológico preciso 1.307 niños (81,4%) pese a habérseles realizado múltiples estudios complementarios, fundamentalmente bioquímicos, genéticos y de neuroimagen. Discusión: Muchos de los niños incluidos en este estudio presentan enfermedades raras, estén o no identificadas, que demandan crecientemente un diagnóstico precoz. Enfermedades peroxisomales, lisosomales, mitocondriales, defectos congénitos de la glucosilación, entre otras enfermedades metabólicas hereditarias, infecciones congénitas, cromosomopatías y genopatías, pueden ser indistinguibles clínicamente y necesitan estudios específicos para su identificación. Un diagnóstico precoz precisa estrategias de estudios sistemáticos de forma escalonada, priorizando las enfermedades que tienen posibilidades terapéuticas y en muchos casos es necesaria también una aproximación individualizada. Creemos que las ventajas potenciales del diagnóstico precoz, incluido el ahorro de más pruebas, y la prevención, probablemente sobrepasan el gasto financiero. Abstract: Introduction: We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages. Material and methods: We analysed our 19 year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin. Results: The 19 year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them. Discussion: Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs. Palabras clave: Diagnóstico etiológico, Diagnóstico precoz, Encefalopatías prenatales, Enfermedades raras, Estudios bioquímicos, Estudios genéticos, Neuroimagen, Keywords: Biochemical studies, Early diagnosis: aetiological diagnosis, Genetic studies, Neuroimaging, Prenatal encephalopathies, Rare diseases

Objetivo: Analizar la trombocitopenia como marcador precoz de las sepsis tardías por Candida. Determinar la existencia en los recién nacidos sépticos de diferencias en el recuento plaquetario según el agente etiológico responsable de la infección. Material y métodos: Revisión retrospectiva de 42 recién nacidos con sepsis tardías confirmadas por hemocultivo en nuestro servicio desde el 1 de enero de 2003 hasta el 31 de diciembre de 2004, incluyéndose únicamente los primeros episodios infecciosos. El principal parámetro analizado fue la incidencia de trombocitopenia en función de los gérmenes causantes de sepsis (bacterias grampositivas, gramnegativas y hongos). El análisis estadístico se realizó con el paquete estadístico SPSS versión 11.5. Los datos se expresan como media ± desviación estándar. Para comparar los grupos se utilizaron en el caso de variables cualitativas la prueba de chi al cuadrado y en el caso de las variables cuantitativas tras realizar la prueba de Kolmogorov-Smirnov se usaron para las variables paramétricas la prueba de ANOVA y para las variables no paramétricas la prueba de Kruskal-Wallis. Se consideró significativo un valor de p ≤ 0,05. Resultados: De un total de 1.757 recién nacidos se diagnosticaron 42 sepsis tardías (2,3 %). La edad de gestación y peso de los recién nacidos sépticos fueron de 31 ± 4,9 semanas (24-41,5) y 1.618 ± 911 g (750-4.070 g). Había 34 varones (81 %) y 8 mujeres (19 %). El estudio comparativo no mostró diferencias estadísticamente significativas entre los tres grupos de gérmenes, excepto en el peso al nacer, días de estancia en la unidad de cuidados intensivos (UCI), días de tubo torácico, días de ventilación mecánica, antibioterapia previa a la sepsis y trombocitopenia.Fueron sepsis grampositivas el 47,6 %; gramnegativas, el 33%, y fúngicas, el 19 %. La única responsable de las sepsis fúngicas fue Candida, principalmente C. glabrata (50 %), seguida de C. albicans (37,5 %) y C. parapsilosis (12,5 %). El marcador de infección de sepsis por Candida más importante fue la trombocitopenia, que se constató en el 17,7 % de todas las sepsis tardías. Fue significativamente mayor en las fúngicas que en las no fúngicas (100 % frente a 5,9 %) (p < 0,001), aunque sólo se pudo comprobar en dos casos de sepsis bacterianas por gramnegativos. Conclusión: La trombocitopenia es un marcador muy específico de las sepsis neonatal por Candida. El recuento plaquetario es una prueba sencilla que facilita la orientación diagnóstica y la instauración de un tratamiento empírico precoz. : Objective: To analyze thrombocytopenia as an early marker of late-onset neonatal Candida sepsis and to determine whether there are significant differences in platelet count between neonates infected by different infectious agents. Material and methods: We retrospectively reviewed the medical charts of 42 neonates with late-onset sepsis with positive blood culture in our neonatology service between January 1, 2003 and December 31, 2004. Only the first episode of sepsis in any single patient was included. The principal parameter examined was the incidence of thrombocytopenia according to the microorganisms causing the sepsis (Gram-positive bacteria, Gram negative bacteria and fungi). The statistical analysis was performed using SPSS version 11.5. The data are expressed as mean ± standard deviation. The chi-squared test was used to compare qualitative variables. For quantitative variables, the Kolmogorov-Smirnov was used; ANOVA was used for parametric variables and the Kruskal-Wallis test for non-parametric variables. A value of p

Antecedentes: A pesar de su creciente importancia en nutrición infantil, los estudios en España sobre los niveles de selenio en recién nacidos son escasos y, a menudo, contradictorios. Objetivos: Establecer unos niveles de normalidad de selenio sérico en neonatos a término sanos de nuestro medio y contribuir al mejor conocimiento de aquellos factores perinatales que influyen sobre éstos. Métodos: Determinamos la seleniemia sérica por espectrofotometría de absorción atómica de 247 recién nacidos, distribuidos en 70 a término sanos, 60 a término patológicos, 18 con retraso de crecimiento intrauterino (> 37 semanas y peso al nacimiento < 2.500 g), 44 pretérmino sanos y 55 pretérmino patológicos. Resultados: Los a término sanos presentaron concentraciones de selenio séricas superiores a los pretérmino sanos (35,11 6 6,94 μg/l, rango 18,4-48 μg/l frente a 28,65 6 5,95 μg/l, rango 15-44,4 μg/l; p < 0,001). Los retrasos de crecimiento presentaron valores superiores a los pretérmino sanos (30,80 6 6,97 μg/l, rango 20-45,6 μg/l frente a 28,65 6 5,95 μg/l; límites 15-44,4 μg/l), pero inferiores a los a término con normopeso al nacimiento (ídem frente a 35,11 6 6,94 μg/l, rango 18,4-48 μg/l). Asimismo, los de bajo peso al nacimiento (inferior a 2.500 g) presentaron valores medios inferiores a los neonatos con normopeso (27,98 6 6,75 μg/l, límites, 15-48 μg/l frente a 33,09 6 7,52 μg/l, límites, 14,4-48 μg/l; p < 0,001). Conclusiones: Prematuridad y bajo peso al nacimiento son los mejores predictores de riesgo de hiposeleniemia neonatal. : Background: Despite their increasing importance in children's nutrition, studies on selenium levels in neonates in Spain are scarce and often contradictory. Objectives: To establish the standard serum levels of selenium in healthy full term neonates in our area and to contribute knowledge of the perinatal factors that influence these levels. Methods: We determined selenium levels in serum by atomic absorption spectrophotometry in 247 neonates: 70 healthy full term neonates, 60 sick full term neonates, 18 neonates with intrauterine growth retardation (> 37 weeks; birthweight < 2500 g), 44 healthy preterm neonates and 55 sick preterm neonates. Results: Healthy full term newborns showed higher serum selenium levels than healthy preterm neonates (35.11 6 6.94 μg/l, range: 18.4-48 μg/l versus 28.65 6 5.95 μg/l, range: 15-44.4 μg/l, p < 0.001). In the group with intrauterine growth retardation, serum selenium levels were higher than in the healthy preterm group (30.80 6 6.97 μg/l, range: 20-45.6 μg/l versus 28.65 6 5.95 mg /L, range: 15-44.4 μg/l) but lower than in the full term and normal birthweight group (idem versus 35.11 6 6.94 μg/l, range 18.4-48 μg/l). Likewise, the low birthweight group (< 2500 g) showed lower mean serum selenium levels than the normal birthweight group (27.98 6 6.75 μg/l, range 15-48 μg/l versus 33.09 6 7.52 μg/l, range 14.4-48 μg/l; p < 0.001). Conclusions: Prematurity and low birthweight are the best predictors for risk of neonatal hyposeleniemia.

Introducción: La infección neonatal es una importante causa de morbilidad en el período neonatal. Se han utilizado diferentes parámetros como marcadores de sepsis neonatal. La proteína C reactiva (PCR) ofrece una alta especificidad en las infecciones bacterianas pero su incremento no se observa hasta 12–24 h después de iniciarse la infección neonatal Objetivo: Evaluar la utilidad de interleucina 6 (IL-6) y factor de necrosis tumoral alfa (TNF-α) en el diagnóstico precoz de la infección neonatal bacteriana de transmisión vertical Material y métodos: Se incluyeron 34 recién nacidos ingresados en la unidad de cuidados intensivos neonatales con el diagnóstico inicial de dificultad respiratoria. En 12 recién nacidos se constató la existencia de criterios clínicos de sepsis o neumonía (grupo I); en 6 con hemocultivo positivo. Los restantes pacientes no cumplían criterios clínicos de infección (grupo II). Se determinaron a las 8,8 ± 7,3 h de vida niveles de IL-6, TNF-α, PCR e índice de (c/s). En 17 pacientes se determinaron los mismos parámetros a las 67,4 ± 24,8 h. Se utilizó test de Mann-Whitney en el análisis estadístico. Se determinó la sensibilidad y especificidad de los marcadores analizados Resultados: No se encontraron diferencias significativas en las variables perinatales analizadas en ambos grupos. Al analizar los marcadores de infección encontramos diferencias significativas en: índice de c/s: (0,25 ± 0,21 frente a 0,12 ± 0,09; p = 0,048), PCR primer control: 1,4 ± 0,8 mg/dl frente a 1 ± 0,5 mg/dl; p = 0,036; segundo control: 3,8 ± 1,8 mg/dl frente a 1,4 ± 1,1 mg/dl; p = 0,008; IL-6 primer control: 582,2 ± 810,5 pg/ml frente a 31,3 ± 24,2 pg/ml; p = 0,000. Sensibilidad/especificidad (%): índice c/s: 41,6/83,6; PCR primer control: 16,6/90,9; PCR segundo control: 83,3/87,5; IL-6 (punto de corte óptimo: 55 pg/ml): 100/72,7 y TNF-α: 16,6/85 Conclusiones: La determinación en las primeras horas de vida de IL-6 contribuye de una forma más rápida al diagnóstico de infección neonatal que otros marcadores clásicos, debido a su elevación precoz. La determinación precoz de TNF-α ha mostrado, al igual que la PCR, una alta especificidad pero con escasa sensibilidad : Introduction: Neonatal infection is a major cause of morbidity in the neonatal period. Several parameters have been used to assess neonatal sepsis. C-reactive protein (CRP) shows high specificity for bacterial infections, but an increase in CRP is often not detected until 12 to 24 hours after onset of the infection Objective: To evaluate the usefulness of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the early diagnosis of vertically-transmitted neonatal bacterial infection Methods: Thirty-four newborns admitted to the neonatal intensive care unit with an initial diagnosis of respiratory distress were included. Twelve newborns presented the criteria for clinical sepsis or pneumonia (group I) and six had positive blood culture. The remaining patients did not present the clinical criteria for infection (group II). IL-6, TNF-α, CRP levels and the ratio between immature and mature neutrophil count were assessed at 8.8 ± 7.3 hours of life. In 17 patients the same parameters were assessed at 67.4 ± 24.8 hours of life. The statistical analysis was performed using the Mann-Whitney test. The sensitivity and specificity of these markers were assessed Results: No differences were found in the perinatal features of either group. Analysis of markers of infection revealed the following significant differences: ratio between immature and mature neutrophil count: (0.25 ± 0.21 vs 0.12 ± 0.09; p = 0.048), CRP first determination (1.4 ± 0.8 mg/dL vs 1 ± 0.5 mg/dL; p = 0.036), CRP second determination: (3.8 ± 1.8 mg/dL vs 1.4 ± 1.1 mg/dL; p = 0.008), IL-6 first determination: (582.2 ± 810.5 pg/mL vs 31.3 ± 24.2 pg/mL; p = 0.000). Sensitivity/specificity (%): ratio between immature and mature neutrophil count: 41.6/83.6; CRP first determination: 16.6/90.9; CRP second determination: 83.3/87.5; IL-6 (optimum cut-off value: 55 pg/mL): 100/72.7, and TNF-α: 16.6/85 Conclusions: IL-6 determination in the first hours of life is a more sensitive early marker of neonatal infection than other classical markers because of its early elevation. Like CRP, early TNF-α determination has high specificity but low sensitivity

Se comunica un nuevo caso de monosomía r(13) en un recién nacido varón con diagnóstico prenatal. Cuarto hijo de padres sanos y con descendencia normal. Presenta una dismorfia y múltiples malformaciones características de la afección. El estudio citogenético mostró un cariotipo 46,XY, r(13) (p11.2-q32)/45, XY,?13. Nuestra observación es bastante similar a otras comunicaciones de la bibliografía y confirma la relación entre los síntomas clínicos y el seg-mento ausente del cromosoma 13. Se revisan los aspectos clínicos y citogenéticos de la afección : We report a new case of monosomy r-13 in a male new-born infant with prenatal diagnosis. He was the fourth child of a healthy couple of normal lineage. On physical examination typical dysmorphism and multiple congenital anomalies were found. Chromosome analysis revealed a 46, XY, r(13) (p11.2-q32) /45, XY,-13 karyotype. Our ob-servations are almost identical to those of previously published reports and confirm that the clinical severity of the symptoms depends on the location of the chromosome breakpoint. The clinical and cytogenetics features of this disorder are reviewed

Objetivos: Definir el síndrome de déficit de la fosforilación oxidativa neonatal, en función de su incidencia, características perinatales, clínicas, bioquímicas y genéticas. Material y métodos: Se revisan los casos de 9 recién nacidos catalogados como déficit de la fosforilación oxidativa en los últimos 8 años en nuestro centro, mediante valoración clínica, metabólica, histopatológica, enzimática y molecular, además de otras evaluaciones. El diagnóstico se estableció en función del déficit enzimático de la cadena respiratoria, asociadoa alteraciones del ADNmt en un caso, y en cinco a anomalías ultraestructurales mitocondriales. Resultados: La incidencia fue de 1/3.555 y de 1/832 recién nacidosingresados en nuestra unidad neonatal. Cuatro tenían antecedentes familiares positivos, y dos polihidramnios. La mayoría (8/9) fueron recién nacidos a término, de embarazo y parto normales, con Apgar y somatometría también normales. La clínica se inició en el período neonatal inmediato, como sufrimiento neurológico agudo en la mayoría. La evolución fue grave (5 fallecieron y 4 sobreviven gravemente afectados). Todos presentaban un fenotipo clínico de encefalopatía grave precoz, asociada a dismorfia, hipotonía, alteraciones neurosensoriales, atrofia y disgenesia cerebral, electroencefalograma patológico, y en 5 de ellos, además, a anomalías viscerales (principalmente cardiopatía). La alteración bioquímica más frecuente fue un aumento significativo del cociente lactato/piruvato. Cinco pacientes presentaron alteraciones ultraestructurales mitocondriales en la biopsia muscular pero la tinción de Cox no resultó claramente patológica en ningún caso. Tres tenían un déficit del complejo IV, tres de I-IV, dos del I y uno del I-IIIIV. Sólo en un paciente se detectaron deleciones múltiples del ADNmt. Conclusiones: Se trata de enfermedades frecuentes y graves, de comienzo prenatal con escasa repercusión fetal, fenotipo clínico homogéneo con afectación predominante del SNC y extraneurológica variable, y perfil bioquímico inconstante. El diagnóstico exige el estudio enzimático de la cadenarespiratoria en todos los casos sospechosos. : Objetives: To define the oxidative phosporilation deficit syndrome in the neonatal in terms of incidence and clinical, biochemical and genetic features. Material and methods: We report 9 newborns diagnosed as oxidatic phosporilation deficit during the last 8 years in our hospital by means of clinical, metabolic, pathological and molecular studies, among other evaluations. The diagnosis was established based on ensymatic deficit of the respiratory chain, associated with alterations in the mtDNA in one case, and with mitochondrial ultrastructural anomalies in 5 cases. Results: There was an incidence of 1/3.555 newborns and 1/832 newborns admitted in our Neonatal Unit. In four of them there were familial antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at term after anormal pregnancy and delivery, with normal Apgar score and auxological examination. Symptomatology started immediately at the neonatal period as acute neurological damage in most of them. There was a severe evolution as 5 children died and 4 survived with severe damage. All of them had the classical phenotype of early severe encefalopathy, associated with dismorphicfeatures, hypotomía, neurosensorial defects, brain dysgenesis and atrophy, anomalies in the EEG and in 5 of therm there were also systemic anomalies, mainly cardiopathy. The most freqyent biochemicalalteration was a significative increment of the quotient lactate/piruvate. Five patients presented ultrastructural alterations of the mitochondria in thr musclebiopsy but Cox stain was not positive in any case.three cases has a deficit of the complex IV, e of the complex I-IV, 2 of the complex I and one the complex I-III-IV.Only one patient had multiple deletions in the mtDNA. Conclusions: Oxidatic phosporilation deficit are frequent and severe diseases of prenatal onset with limited fetal effects, homobeneous clinical phenotipe with frequent damage of the central nervous system and variable extraneurological alteration and inconsistent biochemical pattern. Enzymatic studies ar need for making the diagnosis in all suspected cases.

Se comunican tres nuevas obervaciones de síndrome de Klippel-Trenaunay (SKT) de distinta evolución y extensión, que reúnen criterios diagnósticos, evaluados por examen físico, técnicas de imagen, estudios radiológicos y de laboratorio. La malformación vascular e hipertrofia de tejidos blandos era evidente en los tres casos, en dos de ellos existían lesiones internas y agrandamiento óseo, y en uno anomalías digitales. Se revisan, además, los principales aspectos de esta importante angiodisplasia. : We report three new cases of Klippel-Trenaunay Syndrome (KTS), with differing evolution and involvement, in which the diagnostic criteria were confirmed by physical evaluation, imaging techniques, radiologic and laboratory studies. Vascular malformation and soft tissue hypertrophy were evident in all three patients: two showed internal lesions and bony hypertrophy and one patient showed digital deformities. We review the main features of this important angiodysplasia.

El síndrome de megavejiga-microcolon-hipoperistaltismo intestinal es una rara alteración genética caracterizada por distensión vesical e hipoperistaltismo intestinal que afecta a todo el tracto gastrointestinal. Presentamos un nuevo caso que presenta los hallazgos clínicos y radiológicos típicos de este síndrome. El diagnóstico debe ser sospechado en un recién nacido que presenta clínica de obstrucción intestinal y retención urinaria; siendo confirmado mediante estudios de imagen, fundamentalmente radiografía simple de abdomen y ecografía urinaria. Los hallazgos histológicos no son específicos; encontramos un adelgazamiento de la capa muscular intestinal y proliferación de tejido conectivo. El pronóstico es generalmente grave. Nuestro paciente falleció por sepsis a los 25 días de vida. : Megacystis-microcolon-intestinal hypoperistalsis is a rare congenital disorder characterized by urinary bladder distention and hypoperistalsis throughout the entire gastrointestinal tract. We present a new case with the typical clinical and radiological findings of the syndrome. This diagnosis should be suspected in patients who present with intestinal obstruction and urine retention and should be confirmed with imaging techniques, including abdominal plain films and urinary ultrasonography. Histological findings are non-specific; we found thinning of the intestinal muscle layer and connective tissue proliferation. The prognosis is generally very poor. Our patient died from sepsis at the age of 25 days.

We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages.We analysed our 19 year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin.The 19 year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them.Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs.

Recién nacido con déficit aislado de citocromo C oxidasa (COX), con afectación multisistémica grave, en la que predominaba desde el nacimiento una encefalopatía severa, que falleció precozmente por miocardiopatía hipóxico- isquémica. Segundo hijo de un matrimonio sano no consanguíneo, con otra hija afectada de encefalopatía crónica. Presentaba además, fenotipo dismórfico, afectación hepática y muscular y una posible tubulopatía. En la valoración metabólica resaltaba una relación láctico/pirúvico aumentada. El diagnóstico se estableció por estudio enzimático muscular y por las alteraciones ultraestructurales mitocondriales, siendo normales el ADNmt y la tinción para COX. En el examen anatomopatológico se evidenció un infarto subendocárdico masivo. Se comentan aspectos de interés sobre esta entidad, dada la importancia de su conocimiento para el correspondiente consejo genético. : We report a neonate with isolated cytochrome c oxidase (COX) defect and severe multisystemic involvement. The patient had severe encephalopathy, predominant since birth, and died due to hypoxic-ischemic myocardiopathy. He was the second son of non-consanguineous, healthy parents who also had a daughter with chronic encephalopathy. The neonate presented dysmorphic phenotype, hepatic and muscular involvement, and possibly tubular involvement. Metabolic studies revealed markedly increased lactic/pyruvic concentrations. Diagnosis was based on muscular enzymatic studies and ultrastructural mitochondrial anomalies, while the mitochondrial DNA and results of the COX technique were normal. Histological examination revealed a massive subendocardial infarction. Aspects of this entity with relevance for genetic counseling are discussed.

Myotonic dystrophy is a highly variable autosomic dominant inherited multisystemic disease. We review our 18 years experience with patients suffering from this disease.Eleven patients were identified following a molecular genetic study: 2 patients died, 5 are still under control, 2 are being controlled in another Centre, and 3 dropped out. Three of them were relatives. Seven newborns started with hypotonic symptoms in the neonatal period, with hypotonic symptoms, of which 4 had foetal suffering. One child was diagnosed at age of 3 due to her father being affected. One girl was seen at age of 10 due to stiffness and tightening of her hands for years. One boy, aged 5, was examined due to abnormal hands posture, and a 4 year old child due to psychomotor delay. Associated disorders: 7 children with psychomotor delay, 2 cases of cataracts, 1 case of diabetes type I, 3 cases of hypercholesterolemia, 1 abdominal sarcoma, 1 case of femur and hip fracture, 2 cases of interatrial communication. The diagnostic was made in 5 cases by a clinic due to mother-son relation phenotype, in 3 cases after the family diagnosis and in another 3 cases non-congenital symptoms exclusively in the child's clinic.In our experience, myotonic dystrophy is uncommon; it is often congenital, and is associated with perinatal suffering. Genetics can identify or exclude the process. This must be done on newborns who are hypotonic for an unknown reason. It should be suspected in a child who presents with motor abnormalities in the fingers and hands.

In neuropaediatrics, the aetiological diagnosis rarely allows a causal treatment to be established. In many cases, all we can offer is referral to early intervention (EI) and botulinum toxin type A (BTA). The only requirement before starting both interventions is a functional or syndromic diagnosis.Here we analyse the experience gained from an EI programme carried out in the region of Aragon since February 2003 and with the BTA service in the Neuropaediatric Unit of the Hospital Universitario Miguel Servet since November 2003.By the end of 2007, 2629 requests had been made for admission to the EI programme and in the year 2007 a total of 702 children were treated. In four years and four months 122 children with infantile cerebral palsy (ICP) were infiltrated with BTA, with positive results in 70% of cases and mild, transient side effects in 13.1%.The children, parents and professionals involved all view EI and BTA with satisfaction. Neuropaediatrics is one of the medical specialties that are best suited to child development and early intervention centres (CDIAT). The neuropaediatrician participates in all the stages of the EI: detection, diagnosis, information and intervention. He or she may act as the coordinating and homogenising element in EI, that is to say, as a link between CDIAT and health care services. Neuropaediatricians are also essential in EI training and education, in family training, information and awareness campaigns, primary care, social services and nurseries. Treatment with BTA cannot be viewed as an isolated technique, but instead as part of a programme in which physiotherapy, orthosis and sometimes surgery play a fundamental role. Coordination among the different professionals involved in treating the child with ICP is absolutely crucial.

The quality of the health care in a major part of neuropaediatrics benefits from appropriate communication and strategies that have been agreed with primary care (PC) paediatricians.We analyse the children who were assessed in the Neuropaediatric service at the Hospital Universitario Miguel Servet in Saragossa over a period of eight years and we also discuss the most important courses of action followed in the most prevalent problems.Eight reasons for visiting accounted for 86% of the total number: paroxysmal disorders (33%), headache (27%), psychomotor retardation (11.5%), alterations affecting the shape or size of the head (5.6%), problems at school and/or attention deficit (4.5%), behavioural disorders (4.25%), gait disorders (3.5%) and perinatal distress (3.4%). The most frequent diagnoses are headaches/migraines (26%), non-epileptic paroxysmal disorders (16.5%), prenatal encephalopathy (10.5%), epilepsy (8%), mental retardation (7.5%), infantile cerebral palsy (4.6%), cryptogenic attention deficit hyperactivity disorder (ADHD) (3.8%) and cryptogenic autism (3.6%).The PC paediatrician working in close relation with the children and their families in all cases is the person mainly responsible for conducting a follow-up on some of the most prevalent problems, such as headaches, many non-epileptic paroxysmal disorders and ADHD. The processes must be established, clearly specified, based on the best evidence, with the participation and within reach of all the professionals involved, in order to favour homogeneity and keep variability in the interventions to a minimum. Channels of communication, including the information and communications technologies, need to be set up to allow health professionals to be permanently up-to-date and capable of controlling their patients in the best possible way.

The aetiology and clinical features of peroxisomal diseases vary widely. An altered very-long-chain fatty acid (VLCFA) profile is commonly found in many of these diseases, and this makes it easier to point the diagnosis in the right direction.We review our experience in the diagnosis of cases of peroxisomal diseases with an altered VLCFA pattern; these were determined in serum only when there was a strong clinical suspicion up to the end of 1998, when their quantification by chromatography was introduced into our laboratory.The neuropaediatric database included 10,239 cases between May 1990 and 1st October 2007. Ten cases of peroxisomal disease with an altered VLCFA pattern were identified, all of them males. There were two cases of Zellweger syndrome spectrum, one unclassified peroxisomal oxidation defect and seven X-linked adrenoleukodystrophies (four with neurological compromise and three with no neurological damage; two were identified in siblings of patients and the other due to the presence of Addison's syndrome).In our 10 cases, the diagnosis was guided by the clinical or familial features that led to the determination of VLCFA. Being able to determine VLCFA makes early systematic diagnosis of patients possible. At present, VLCFA determination is performed when there is a clinical suspicion of Zellweger spectrum, suspected X-linked adrenoleukodystrophy/adrenomyeloneuropathy of unclear causation, Addison's disease, both in males and females, and above all in cases of chronic encephalopathy of unknown causation, with or without prenatal onset.

To analyze thrombocytopenia as an early marker of late-onset neonatal Candida sepsis and to determine whether there are significant differences in platelet count between neonates infected by different infectious agents.We retrospectively reviewed the medical charts of 42 neonates with late-onset sepsis with positive blood culture in our neonatology service between January 1, 2003 and December 31, 2004. Only the first episode of sepsis in any single patient was included. The principal parameter examined was the incidence of thrombocytopenia according to the microorganisms causing the sepsis (Gram-positive bacteria, Gram negative bacteria and fungi). The statistical analysis was performed using SPSS version 11.5. The data are expressed as mean+/-standard deviation. The chi-squared test was used to compare qualitative variables. For quantitative variables, the Kolmogorov-Smirnov was used; ANOVA was used for parametric variables and the Kruskal-Wallis test for non-parametric variables. A value of p0.5 was considered significant.Late-onset sepsis was diagnosed in 42 (2.3%) of 1,757 newborn admissions. Gestational age at birth was 31+/-4.9 weeks (24-41.5 weeks) with a mean birth weight of 1,618+/-911 g (750-4,070 g). There were 34 boys (81%) and eight girls (19%). When patients infected with the three groups of microorganisms were compared, no significant differences were found except for birth weight, days of stay in the neonatal intensive care unit, thoracotomy, days of mechanical ventilation, antibiotic therapy before sepsis, and thrombocytopenia. Gram-positive sepsis was found in 47.6%, Gram-negative sepsis in 33 % and fungal sepsis in 19%. The only cause of fungal sepsis was Candida, mainly C. glabrata (50%), followed by C. albicans (37.5%) and C. parapsilosis (12.5%). The most reliable marker of Candida sepsis was thrombocytopenia, which was found in 17.7% of the episodes of late-onset sepsis. The incidence of thrombocytopenia was significantly higher in Candida sepsis than in bacterial sepsis (100% vs 5.9%) (p0.001). Only two patients with bacterial sepsis had thrombocytopenia and both cases were caused by Gram-negative bacteria.Thrombocytopenia is a highly specific marker of neonatal Candida sepsis. Analysis of platelet counts is a simple laboratory test that helps to guide diagnosis and the use of early empirical therapy.

Neonatal alloimmune thrombocytopenia (NAT) is due to the transplacental transfer of circulating maternal alloantibodies developed against fetal platelet antigens inherited from the father. Intracranial hemorrhage occurs in 15-30% of the cases, and very important neurological sequelaes can be due to it.We present the clinical and immunohematologic findings of a case of severe NAT that had two siblings who died by this illness. In the 31st week of gestation an intracranial hemorrhage is detected by echography, the birth was by caesarean section. Apgar score of 8 and 9, it wasn't necessary reanimation procedures. Cutaneous purpura and pallor were presented since birth. Neonatal complete blood count showed a platelet count of 6,000/mm3 (whereas maternal blood count was normal), haemoglobin of 8.8 g/dL and hematocrit of 26.1%, without other biological alterations. In maternal blood alloantibodies antiHPA-1a were detected, being the father homozigous for 1a/1a and the mother homozigous for 1b/1b. The patient was treated with transfusions, endovenous gammaglobulin and corticosteroids and his condition improved.Intraparenchymatous hemorrhage is an uncommon pathology in neonates, but when this occurs it's obligated to rule out a coagulation inherited illness, NTA especially, because of its prevalence and potentially serious neurological sequelaes, sometimes having a good neurological development. Prevention, early treatment and neuroimaging studies should be done in all newborn babies with alloimmune thrombocytopenia even when no neurological clinic is seen.

Hereditary neuromuscular diseases are disorders which can vary largely in their age of onset, symptoms and severity. Many are severe, disabling and have an important personal, familial and social impact and can restrict the prognosis for survival. The constant progress being made in diagnostics makes it necessary to continually update knowledge and information.We carried out a review of the hereditary neuromuscular diseases contained in the Neuropaediatrics database at the Hospital Miguel Servet in Zaragoza from May 1990 to October 2004.Of the 7,805 patients in the database, 123 (1.5% of the total) were patients with hereditary neuromuscular diseases, of whom 71 were males and 52 females. These included: 35 sensory-motor hereditary neuropathies, 17 dystrophinopathies, 10 myotonic dystrophies, 10 spinal muscular atrophies, four merosin-deficient congenital dystrophies, four other muscular dystrophies, three mitochondrial myopathies, three myasthenias, two familial neuropathies with insensitivity to pain, two Friedreich's ataxias, one familial neuropathy with liability to pressure palsies, one case of Walker-Warburg syndrome, five polyneuropathies associated to leukodystrophy and another 25 cases that could not be classified. Genetic studies provided a diagnosis in 36 cases (29.2%): nine myotonic dystrophies, eight dystrophinopathies, eight cases of spinal muscular atrophy, four demyelinating sensory-motor hereditary neuropathies, two instances of Friedreich's ataxia, two limb-girdle muscular dystrophies, one congenital myasthenia, one McArdle's disease and one case of Kearns-Sayre syndrome.Genetic studies enable us to establish diagnoses that were previously limited to the realm of assumption, and allow us to avoid the need for muscle tissue biopsies, which is a welcome development, especially when dealing with children. Immunohistochemical studies need to be updated and biological samples should be systematically saved in cases where no diagnosis is reached.

Cornelia de Lange syndrome is a rare polimalformative association that shows an expresivity of unknown etiology being most cases sporadic. The diagnosis is clinical.Two female newborns without remarkable antecedents affected of intrauterine growth retardation were born by cesarean section due to risk of perinatal asphyxia. Both cases had a harmonic hypotrophy and a very similar clinical phenotype, especially the craniofacial anomalies, with typical facial features and limb alterations. Besides, the evolution confirms the diagnosis because in both cases the delay of somatic development and microcephaly, as well as moderate-severe psychomotor delay and behavior alterations were present. Likewise, both cases have developed typical medical complications of the condition. The complementary study showed in both patients an important dysfunction of the auditory ways and a atrial septal defect. They were soon included in sensory and motor program of rehabilitation.We present two cases of Cornelia de Lange syndrome of neonatal diagnosis that we consider of interest due to the importance of an early recognition of the clinical condition for the family advice and the medical aid and for an appropriate development.

The first contact between the patient and clinician takes place when the former visits because of some health problem.We carried out a review of the clinical records of children who had visited the Neuropaediatric Service because of, among other reasons, an isolated or associated microcephalus over a period of 12 years and 9 months. Factors that were considered included whether or not there was a cephalic perimeter below p3 and evidence of encephalopathy, as well as its prenatal, perinatal or postnatal origin, functional diagnoses and the aetiological diagnosis.In 58 cases (0.92%) out of a total number of 6257 children the visit was due to microcephalus. The mean age at the last visit was 3.9 years. In five children (8.6%) the cephalic perimeter was not below p3. No encephalopathy was found in 20 patients (34.4%) and 38 (65.5%) were seen to have encephalopathy, 37 with a prenatal origin: nine genetic, three disruptive and 22 unspecified. Functional diagnoses were as follows: mental retardation in 29 patients, infantile cerebral palsy in 18, autistic spectrum in four and epilepsy in four. Neuroimaging studies aided diagnosis in 13 cases, i.e. 43.3% of those carried out.Visits to the doctor because of microcephalus, as well as in normal children, include the whole range of prenatal encephalopathies and are associated, ordered according to the frequency of occurrence, with mental retardation and with infantile cerebral palsy. Individual evaluation and clinical progression allow the orientation of each case. Neuroimaging is the most useful complementary examination for diagnostic purposes.

Neonatal infection is a major cause of morbidity in the neonatal period. Several parameters have been used to assess neonatal sepsis. C-reactive protein (CRP) shows high specificity for bacterial infections, but an increase in CRP is often not detected until 12 to 24 hours after onset of the infection.To evaluate the usefulness of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in the early diagnosis of vertically-transmitted neonatal bacterial infection.Thirty-four newborns admitted to the neonatal intensive care unit with an initial diagnosis of respiratory distress were included. Twelve newborns presented the criteria for clinical sepsis or pneumonia (group I) and six had positive blood culture. The remaining patients did not present the clinical criteria for infection (group II). IL-6, TNF-alpha, CRP levels and the ratio between immature and mature neutrophil count were assessed at 8.8 +/- 7.3 hours of life. In 17 patients the same parameters were assessed at 67.4 +/- 24.8 hours of life. The statistical analysis was performed using the Mann-Whitney test. The sensitivity and specificity of these markers were assessed.No differences were found in the perinatal features of either group. Analysis of markers of infection revealed the following significant differences: ratio between immature and mature neutrophil count: (0.25 +/- 0.21 vs 0.12 +/- 0.09; p=0.048), CRP first determination (1.4 +/- 0.8 mg/dL vs 1 +/- 0.5 mg/dL; p=0.036), CRP second determination: (3.8 +/- 1.8 mg/dL vs 1.4 +/- 1.1 mg/dL; p=0.008), IL-6 first determination: (582.2 +/- 810.5 pg/mL vs 31.3 +/- 24.2 pg/mL; p=0.000). Sensitivity/specificity (%): ratio between immature and mature neutrophil count: 41.6/83.6; CRP first determination: 16.6/90.9; CRP second determination: 83.3/87.5; IL-6 (optimum cut-off value: 55 pg/mL): 100/72.7, and TNF-alpha: 16.6/85.IL-6 determination in the first hours of life is a more sensitive early marker of neonatal infection than other classical markers because of its early elevation. Like CRP, early TNF-alpha determination has high specificity but low sensitivity.

Citrullinemia is an autosomal recessive disease, which is caused by a deficiency of the argininosuccinate synthetase. The neonatal forms are serious and many times are associated with a high level of mortality.A newborn that came in again on her third day of life due to a apneic episodes which required mechanical ventilation. Previously, she rejected feeding, had poor suction, lethargy and remarkable hypoactivity. During the following hours, she showed serious neurologycal deterioration with multifocal convulsions and coma, passing away 20 hours after admission due to endocraneal hypertension. The metabolic evaluation confirmed very significant hyperammonemia, with important increase of citrullin and glutamin, and arginine in the low limits of normality. She was treated with sodium benzoate and arginine and she also needed exanguinotransfusion. It was not possible to put her on hemodyalisis. The findings of the autopsy confirmed massive cerebral edema and characteristic hystological changes in the liver. The determination of the enzymatical activity in liver tissue showed a partial deficiency, with a residual activity of 25% of the average control.This is a case of fulminant neonatal citrullinemia that we considered of interest in order to draw the attention of the clinical on this type of diseases. The prognosis depends on early diagnosis, witch is based on clinical suspicion and analytical determination of ammonia in every newborn with unexplained vomiting, lethargy or other symptoms of encephalopathy.

Smith Lemli Opitz syndrome is an autosomal recessive metabolic disease, two forms can be differentiated: type I and type II.We present the clinical case of a female newborn with antecedents of oligoamnios and intrauterine growth retardation who presented a characteristic malformative syndrome, severe neurological impairment, anomalies of the limbs, pyloric stenosis, and renal and cardiac defects. Determination of cholesterol and its precursors by gas chromatography confirmed the clinical diagnosis of a severe form with exitus at six months of age. At the same time a review of the syndrome is presented.

Although focal cerebral ischemic or hemorrhagic lesions are infrequent in the term newborn, they must be considered when neurologic symptoms appear, especially when seizures are present.Possible risk factors to suffer from these pathologies have been studied, as well as their evolution, to try to give a prognosis.The term newborns with focal ischemic or hemorrhagic cerebral lesions who presented symptoms in the neonatal period have been studied for 10 years (January 1990-March 2000) in our Children s Hospital Miguel Servet of Zaragoza (Spain). The newborns have been studied in our hospital, and their evolution followed in the Neuropediatric Consulting Room. From each case data about familiar history, pregnancy, labor, clinical manifestations, physical examination, complementary studies, diagnosis and neurodevelopment evolution have been collected. RESULTS. From the nine cases found, four were infarctions of the left medial cerebral artery, and five were hemorrhages. Except in two cases in which an important birth trauma was present, any other antecedent that could be the cause was found. All except one manifested as seizures. Neuroimaging studies visualized the stroke in all of them. A slight motor deficit remains in seven children, and it is severe in one.Cerebrovascular strokes are infrequent in term newborns. Most of the times their etiology is not found. These accidents usually manifestate as focal seizures in the immediate neonatal period, and neuroimaging studies (ECO-TC) are essential for the diagnosis. The long term evolution is favorable in most of the cases, although focal motor deficit remains present frequently.

The objective of this study was to analyze, from an aetiological angle, the cases seen with symptomatic epilepsy by the Seccion de Neuropaediatria del Hospital Miguel Servet de Zaragoza.We studied the cases diagnosed as having symptomatic epilepsy between May 1990 and November 1999.Of a total of 4,466 children assessed during the study period, the diagnosis of epilepsy was established in 461 children (10.3% of the total). This included idiopathic epilepsy in 110 cases (23.9%), cryptogenic epilepsy in 119 cases (25.8%) and symptomatic epilepsy in 232 cases (50.3%). The aetiologies of the symptomatic epilepsies were: prenatal encephalopathies in 137 cases (59%), perinatal encephalopathies in 33 (14.3%), postnatal encephalopathies (due to accidents, acquired infections and postnatal cerebrovascular accidents) in 20 (9%), tumours ( including the post-operative period) in 14 (6%), neurocutaneous syndromes in 13 (5.6%), metabolic and degenerative disorders in 13 (5.6%) and one case of vascular malformation.The symptomatic epilepsies make up half the epilepsies evaluated by the department of neuropaediatrics. In 59% the cause was prenatal. Other causes of symptomatic epilepsy were also represented in the series. A detailed study of these should help us to understand and manage them better. We consider aetiological aspects to be very important in the study of epilepsy, since the aetiology is one of the most important factors in prognosis.

Megacystis-microcolon-intestinal hypoperistalsis is a rare congenital disorder characterized by urinary bladder distention and hypoperistalsis throughout the entire gastrointestinal tract. We present a new case with the typical clinical and radiological findings of the syndrome. This diagnosis should be suspected in patients who present with intestinal obstruction and urine retention and should be confirmed with imaging techniques, including abdominal plain films and urinary ultrasonography. Histological findings are non-specific; we found thinning of the intestinal muscle layer and connective tissue proliferation. The prognosis is generally very poor. Our patient died from sepsis at the age of 25 days.

We report a neonate with isolated cytochrome c oxidase (COX) defect and severe multisystemic involvement. The patient had severe encephalopathy, predominant since birth, and died due to hypoxic-ischemic myocardiopathy. He was the second son of non-consanguineous, healthy parents who also had a daughter with chronic encephalopathy. The neonate presented dysmorphic phenotype, hepatic and muscular involvement, and possibly tubular involvement. Metabolic studies revealed markedly increased lactic/pyruvic concentrations. Diagnosis was based on muscular enzymatic studies and ultrastructural mitochondrial anomalies, while the mitochondrial DNA and results of the COX technique were normal. Histological examination revealed a massive subendocardial infarction. Aspects of this entity with relevance for genetic counseling are discussed.

To define the oxidative phosporilation deficit syndrome in the neonatal in terms of incidence and clinical, biochemical and genetic features.We report 9 newborns diagnosed as oxidatic phosporilation deficit during the last 8 years in our hospital by means of clinical, metabolic, pathological and molecular studies, among other evaluations. The diagnosis was established based on ensymatic deficit of the respiratory chain, associated with alterations in the mtDNA in one case, and with mitochondrial ultrastructural anomalies in 5 cases.There was an incidence of 1/3.555 newborns and 1/832 newborns admitted in our Neonatal Unit. In four of them there were familial antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at term after a normal pregnancy and delivery, with normal Apgar score and auxological examination. Symptomatology started immediately at the neonatal period as acute neurological damage in most of them. There was a severe evolution as 5 children died and 4 survived with severe damage. All of them had the classical phenotype of early severe encefalopathy, associated with dismorphic features, hypotomía, neurosensorial defects, brain dysgenesis and atrophy, anomalies in the EEG and in 5 of them there were also systemic anomalies, mainly cardiopathy. The most frequent biochemical alteration was a significative increment of the quotient lactate/piruvate. Five patients presented ultrastructural alterations of the mitochondria in thr muscle biopsy but Cox stain was not positive in any case. Three cases has a deficit of the complex IV, e of the complex I-IV, 2 of the complex I and one the complex I-III-IV. Only one patient had multiple deletions in the mtDNA.Oxidatic phosporilation deficit are frequent and severe diseases of prenatal onset with limited fetal effects, homogeneous clinical phenotype with frequent damage of the central nervous system and variable extraneurological alteration and inconsistent biochemical pattern. Enzymatic studies ar need for making the diagnosis in all suspected cases

Torticollis is a very non-specific symptom occurring in different conditions and may therefore be the reason for consultation in many specialties including neuropaediatrics. Analysis of torticollis as a cause for consultation in neuropaediatrics may contribute to the establishment of a suitable strategy for diagnosis.We review, from the diagnostic point of view, the clinical histories of cases in which the reasons for consultation included torticollis. These cases were included in the database of all the patients assessed by the neuropaediatric department of the Hospital Miguel Servet in Zaragoza between May 1990 and February 1999.Of the 4,138 new patients evaluated during the period studied, in 60 patients torticollis was either the sole symptom or was one of the symptoms leading to consultation. The diagnoses established were: 30 congenital torticollis (50%), 6 secondary to space-occupying intracranial lesions (10%), 5 benign paroxystic torticollis (8.3%), 4 post-traumatic, 3 secondary to ocular disorders, 3 Sandifer syndrome, 1 focal dystonia of the neck, 1 secondary to a submandibular adeno-phlegmon, 1 secondary to an epidural hematoma of the cervical spine, 1 to encephalomyelitis and 1 to spondylodiscitis, with 4 cases unclassified.The clinical history, physical examination and follow-up of the course of the disorder orientate or permit the diagnosis to be established in many cases of torticollis. The indications for complementary investigations, particularly neuroimaging, should be considered individually in each case.

In order to determine the requirements for neuropaediatric attention in the Hospital Miguel Servet of Zaragoza, we studied the diagnoses of the 2,046 children evaluated during the 5 year period-May 1990 to May 1995-, when a neuropediatrician was appointed to the hospital (which previously did not have such a specialist).The most frequent problems were non-epileptic paroxystic disorders, epilepsies and febrile crises. The following is a list in descending order, of diseases affecting these children: Prenatal encephalopathies, disorders of development and behaviour, head injury (TCE), peripheral nervous system and cranial nerve disorders (which were neither traumatic nor secondary to space-occupying lesions), headaches, perinatal encephalopathies, infections and para-infectious diseases of the nervous system, cardiovascular problems, hydrocephalus, metabolic disorders, hypovision and eye disorders, neuromuscular disorders, tumours, dyskinesias, medulla problems and neurocutaneous syndromes.The frequency and diversity of the neurological pathology seen in childhood and the continual advances in knowledge and the related sciences are more than a single professional person can be expected to cope with. Experts are required in areas such as electroencephalography and epilepsy, neonatal neurology, the neurological aspects of intensive care, neuropsychology, neuro-oncology, neurometabolic disorders, neurogenetics and neuromuscular disorders. Neuropediatricians are required to control illnesses with great personal, family and social impact, such as the neurocutaneous syndromes and myelomeningocoele. Neuropaediatric services working in close inter-disciplinary collaboration with other specialists are necessary.

Diagnosis in neuropediatrics requires a detailed personal and family history and thorough physical examination. In this paper we study the psychomotor development and physical examination of children evaluated during a 5 year period, from May 1990 to May 1995 by a neuropediatrician newly appointed to the Hospital Miguel Servet in Zaragoza, which previously did not have such a specialist.Psychomotor retardation was seen in 19% of the children. In 50% of the children evaluated, significant data was obtained from the physical examination. The commonest finding, observed in 14% of the children, was of anomalous behaviour or an impression of mental deficiency. In decreasing order of frequency other data were: Diffuse pyramidal involvement, cranial nerve involvement, anomalous phenotype, microcephaly, microsomy, signs of neuromuscular involvement, hemiparesia, macrocephaly, skin markings, scoliosis, signs of extrapyramidal involvement, signs of cerebellar involvement, macrosomy and sensory disorders.Diagnosis in neuropediatrics is directed or established, sometimes exclusively, by an extensive personal and family history and adequate interpretation of this, which in the end depends on the skill of the clinician.

Complementary tests orientated by the clinical findings and correctly interpreted, are useful in some cases in order to exclude certain pathologies and on other occasions to help to orientate towards or to confirm diagnoses. Material and methods. In this paper we analyze the complementary tests most often used in children evaluated during a five year period, from May 1990 to May 1995, by a neuropaediatrician who recently joined the staff of the Hospital Miquel Servet in Zaragoza (which had no neuropaediatrician before then).Neuroimaging is the technique which was most often useful in establishing the diagnosis. CT or MR orientated or established the diagnosis in 21% of the total number of children evaluated and in 39% of the children in whom this investigation was carried out. The EEG contributed to the diagnosis of epilepsy in 11% of the children. In 16% of the cases of epilepsy the EEG was normal or with nonspecific changes and diagnosis was made on clinical grounds alone. Biochemical tests enabled some pathologies to be ruled out, but contributed to diagnosis on few occasions, most frequently the CSF (basically in meningitis and encephalitis) and muscle enzyme tests were also useful. Routinely used investigations such as those involving amino acids, ammonia, lactate and pyruvate established the diagnosis in a smaller proportion of cases than those used more selectively. Genetics were not found to be very useful in diagnosis. Reallocation of resources is necessary to permit the population as a whole to benefit from the continuous advances being made in techniques of direct study of molecular genetics.

The ambit of the work of each medical specialty is determined initially by the consultations it receives. Study of this will contribute to discovering the needs of the population, to establishing diagnostic strategies in the commonest clinical conditions and to the design of the healthcare organization necessary to fulfil these needs. Material and methods. We reviewed the reasons for consultations for neurological problems in 2,046 children evaluated during a 5 year period, between May 1990 and May 1995 in the Hospital Miguel Servet in Zaragoza, which did not previously have such a specialist.The commonest reason for consultation was paroxystic disorders, which led to 33% of the consultations and affected 40% of the children seen. Other common causes of consultation, in decreasing order of frequency were: psychomotor retardation, head injury, perinatal distress, headache, disorders of movement, morphological changes, disorders of oculomotricity, visual disorders and acute encephalopathy.

The need for healthcare in neuropediatric pathology has always existed. It increases with changes in the needs of the population determined by medical scientific and social advances. These needs, together with the frequency and diversity of the neurological pathology of infancy justify the existence of neuropediatricians and neuropediatric services in regional reference hospitals. To organize a regional neuropediatric service, it is first necessary to know the real needs of the population. The objective of this study was to determine the need for neuropediatric care in the Pediatric Department of the Hospital Miguel Servet in Zaragoza, the regional reference centre for Aragón, La Rioja and Soria.We studied the work carried out over 5 years by a neuropediatrician, newly arrived in a department which did not formerly have such a specialist, principally evaluating diagnostic work. In this first part we describe the material and methods used and the general results obtained.We analyzed the children studied during a 5 year period (May 1990 to May 1995). We evaluated 1,294 children seen in the Outpatient department and 752 during hospital admission (not followed up in Outpatients). This gave an annual average of 409 new patients in neuropediatrics.There is a great demand for neuropediatric attention. Its importance is due to the great frequency, diversity and the complexity of many of these conditions.

Introduccion. Las enfermedades peroxisomales tienen una gran heterogeneidad etiologica y clinica. Un perfil alterado de acidos grasos de cadena muy larga (AGCML) es comun a muchas de ellas, lo que facilita su orientacion diagnostica. Pacientes y metodos. Se revisa nuestra experiencia diagnostica en los casos de enfermedad peroxisomal con patron alterado de AGCML, que se determinaban en suero solo ante fuerte sospecha clinica hasta finales de 1998, fecha en que se introdujo en nuestro laboratorio su cuantificacion por cromatografia. Resultados. En la base de datos de neuropediatria de mayo de 1990 a 1 de octubre de 2007 figuran 10.239 casos. Se han identificado 10 casos de enfermedad peroxisomal con patron alterado de AGCML, todos varones: dos casos de espectro de sindrome de Zellweger, un defecto de la beta-oxidacion peroxisomal sin tipificar y siete adrenoleucodistrofias ligadas a X (cuatro con afectacion neurologica y tres sin dano neurologico; dos identificados por ser hermanos de enfermos y el otro por presentar un sindrome de Addison). Conclusiones. En nuestros 10 casos, el diagnostico se oriento por el cuadro clinico o familiar que llevo a la determinacion de AGCML. La disponibilidad de la determinacion de AGCML permite el diagnostico sistematico de pacientes de forma precoz. Actualmente, la realizamos ante sospecha clinica del espectro Zellweger, sospecha de adrenoleucodistrofia/adrenomieloneuropatia ligada a X, leucoencefalopatias de causa no aclarada, enfermedad de Addison, tanto en varones como mujeres, y ante toda encefalopatia cronica de causa no aclarada de inicio prenatal o no.