Pitch perception deficits in nonverbal learning disability.

The nonverbal learning disability (NLD) is a neurological dysfunction that affects cognitive functions predominantly related to the right hemisphere such as spatial and abstract reasoning. Previous evidence in healthy adults suggests that acoustic pitch (i.e., the relative difference in frequency between sounds) is, under certain conditions, encoded in specific areas of the right hemisphere that also encode the spatial elevation of external objects (e.g., high vs. low position). Taking this evidence into account, we explored the perception of pitch in preadolescents and adolescents with NLD and in a group of healthy participants matched by age, gender, musical knowledge and handedness. Participants performed four speeded tests: a stimulus detection test and three perceptual categorization tests based on colour, spatial position and pitch. Results revealed that both groups were equally fast at detecting visual targets and categorizing visual stimuli according to their colour. In contrast, the NLD group showed slower responses than the control group when categorizing space (direction of a visual object) and pitch (direction of a change in sound frequency). This pattern of results suggests the presence of a subtle deficit at judging pitch in NLD along with the traditionally-described difficulties in spatial processing.

[Quality evaluation of a neuro-development follow-up program of very low birthweight infants]. / Valoración de la calidad de un programa de seguimiento del neurodesarrollo de prematuros de muy bajo peso al nacimiento.

INTRODUCTION: Advances in perinatology have been associated with improved survival of very low birth weight (VLBW;<1500 g) infants. These children have an increased risk of future neurological and development handicaps. A set of quality indicators have been recommended for the neurodevelopment follow-up programs in this group of patients. AIM: To analyze our neurodevelopment follow-up program according to these quality of care indicators in 5 post-discharge follow-up areas: general care; physical health; vision, hearing, speech and language; developmental and behaviour assessment; and psychosocial issues. PATIENTS AND METHODS: Fifty-one VLWB patients born in 2000 who have completed our 6-year follow-up program have been retrospectively studied. The agreement between our program and the standard of quality is evaluated. RESULTS: A copy of a discharge summary of the patient's neonatal course is present in the medical record in 92% of the cases. The inclusion of clinical data and general medical aspects in the medical summary is heterogeneous. Somatometric evaluation for the first two years of age is always present in a filled-in graphic. The international classification of the retinopathy of the preterm (RDP) is used in 100% of the patients. An ophthalmologic examination for RDP is performed in 72% (37/51) of the infants before hospital discharge; of the other 28%, only in 6 patients the date of the outpatient examination is present. Specific evaluations and interventions are performed within the recommended period of time in most of the children with suspected or neurosensory handicaps. More than ninety per cent of the patients are referred to the neurodevelopment specialist and most of them go to the visit (90.2% between 9 and 15 months and 78.4% between 21 and 30 months). Recommendations for a psycho-educational assessment are followed in the extremely premature (BW<1000 g and/or 28 weeks of gestational age) children. The number of patients who follow the program decreases with time. Psychosocial evaluation does not usually appear in the medical records of the patients. CONCLUSION: We have a good adherence to most of the recommended indicators in our follow-up program. The evaluation of these indicators is a useful tool to analyze the quality of a developmental follow-up program and to improve it.

Valoración de la calidad de un programa de seguimiento del neurodesarrollo de prematuros de muy bajo peso al nacimiento / Quality evaluation of a neuro-development follow-up program of very low birthweight infants

Introducción: Los avances en la perinatología condicionan un aumento del número de recién nacidos de muy bajo peso (RNMBP) (<1.500g) que sobreviven, con el consiguiente riesgo futuro de presentar problemas en el desarrollo. Se han propuesto unos indicadores de calidad para evaluar los programas de seguimiento en este grupo de pacientes. Objetivo: Analizar el cumplimiento de estos indicadores en el programa de seguimiento del neurodesarrollo para los RNMBP de este centro. Material y métodos: Estudio retrospectivo descriptivo de los 51 RNMBP nacidos en el 2000 e incluidos en el programa de seguimiento hasta los 6 años de edad. Se evaluó el cumplimiento de los indicadores en las siguientes áreas: inclusión de datos en la epicrítica; aspectos médicos generales; evaluación visual, auditiva, de la comunicación y del lenguaje; evaluación del desarrollo y del comportamiento; valoración psicosocial. Resultados: Se adjuntó la epicrítica a la historia clínica en el 92% de los casos; el cumplimiento de los datos médicos generales fue heterogéneo. La valoración somatométrica durante los primeros 2 años quedó reflejada en una gráfica. Se utilizó siempre la clasificación internacional de retinopatía. A 37 (72%) de los 51 pacientes se les realizó el fondo de ojo durante el ingreso; sólo en 6 de los 14 restantes se explicitó la fecha de la visita ambulatoria. Se cumplió con los plazos máximos recomendados para la valoración por los especialistas cuando se detectó algún déficit. Se envió a más del 90% de los pacientes al neuropediatra y la gran mayoría acudió a la consulta (el 90,2% entre los 9 y los 15 meses, y el 78,4% entre los 21 y los 30 meses). Se cumplió con las recomendaciones de una valoración psicológica sistemática en los prematuros extremos. La evaluación psicosocial quedó poco reflejada en la historia clínica. Conclusiones: Este programa de seguimiento para RNMBP cumple con la mayoría de los indicadores de calidad propuestos. El análisis de éstos es una herramienta muy útil para evaluar y mejorar los programas de seguimiento para este grupo de pacientes (AU)

Introduction: Advances in perinatology have been associated with improved survival of very low birth weight (VLBW;<1500g) infants. These children have an increased risk of future neurological and development handicaps. A set of quality indicators have been recommended for the neurodevelopment follow-up programs in this group of patients. Aim: To analyze our neurodevelopment follow-up program according to these quality of care indicators in 5 post-discharge follow-up areas: general care; physical health; vision, hearing, speech and language; developmental and behaviour assesment; and psychosocial issues. Patients and methods: Fifty-one VLWB patients born in 2000 who have completed our 6-year follow-up program have been retrospectively studied. The agreement between our program and the standard of quality is evaluated. Results: A copy of a discharge summary of the patient's neonatal course is present in the medical record in 92% of the cases. The inclusion of clinical data and general medical aspects in the medical summary is heterogeneous. Somatometric evaluation for the first two years of age is always present in a filled-in graphic. The international classification of the retinopathy of the preterm (RDP) is used in 100% of the patients. An ophthalmologic examination for RDP is performed in 72% (37/51) of the infants before hospital discharge; of the other 28%, only in 6 patients the date of the outpatient examination is present. Specific evaluations and interventions are performed within the recommended period of time in most of the children with suspected or neurosensory handicaps. More than ninety per cent of the patients are referred to the neurodevelopment specialist and most of them go to the visit (90.2% between 9 and 15 months and 78.4% between 21 and 30 months). Recommendations for a psycho-educational assessment are followed in the extremely premature (BW<1000g and/or 28 weeks of gestational age) children. The number of patients who follow the program decreases with time. Psychosocial evaluation does not usually appear in the medical records of the patients. Conclusion: We have a good adherence to most of the recommended indicators in our follow-up program. The evaluation of these indicators is a useful tool to analyze the quality of a developmental follow-up program and to improve it (AU)

X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism.

We describe the first two unrelated Spanish patients with creatine transporter deficiency initially identified by brain proton magnetic resonance spectroscopy (MRS). The clinical phenotype was characterized by severe mental retardation, epilepsy, autism, severe speech delay and absence of brain creatine by MRS. Urine creatine/creatinine ratio was increased and creatine uptake in fibroblasts was impaired in both patients. On DNA sequence analysis of the SLC6A8/creatine transporter gene, one hemizygous mutation was found in each patient: one mutation was novel and consisted of a deletion of two nucleotides c.878-879delTC in exon 5, resulting in a frameshift (p.Lys293fsX3), and in the other patient a known deletion of three nucleotides 1222-1224delTTC in exon 8 resulting in p.Phe408del. Creatine treatment for one year failed to improve the neurological symptoms and was associated with a striking increase in body weight in both patients (13 and 16 kg, respectively).

[Neurological follow-up of very low birth weight newborns at the age of two years (1998-1999)]. / Seguimiento neurológico de recién nacidos menores de 1.500 gramos a los dos años de edad.

BACKGROUND: Because of improved obstetric and neonatal care, there is growing interest in the later outcome of very low birth weight newborns. OBJECTIVES: The aim of this study was to evaluate the survival rate of very low birth weight newborns and to identify disabilities at the age of 2 years. MATERIAL AND METHODS: An observational, follow-up study was performed of neonates with a birth weight of under 1,500 grams born between 1998 and 1999. The follow-up program included pediatric, maturative, neurological, psychological, ophthalmological, and audiological evaluation. Neurosensorial disabilities were classified as mild, moderate, or severe. RESULTS: One hundred thirty-six very low birth weight newborns were admitted. The survival rate was 77.9 % and 83.9 % completed the follow-up to the age of 2 years. The neurosensorial disability rate was 20.2 %; disability was severe in 9 %, moderate in 1.1 %, and mild in 10.1 %. In patients lost to follow-up, birth weight was higher, gestational age was older, and sonographic findings were more frequently normal. CONCLUSION: Survival in very low birth weight newborns has increased with improved neonatal care. The presence of sequelae was similar to that found in other follow-up studies. A substantial number of patients were lost to follow up, which influenced the disability rates.

Seguimiento neurológico de recién nacidos menores de 1.500 gramos a los dos años de edad / Neurological follw-up of very low birth weight newborns at the age of two years (1998-1999)

Antecedentes: Existe un interés creciente en el seguimiento de los recién nacidos de muy bajo peso al nacimiento con la mejoría de la asistencia obstétrica y neonatal. Objetivos: Evaluar las cifras de supervivencia de los recién nacidos de muy bajo peso, junto con la proporción y los tipos de secuelas que se observan a los 2 años de edad. Material y métodos Estudio observacional de seguimiento de los recién nacidos de menos de 1.500 g nacidos entre los años 1998-1999. Se evalúan los datos obtenidos en el programa de seguimiento compuesto por visitas a pediatría, maduración, neurología, psicología y oftalmología; y la realización de potenciales evocados visuales y auditivos. Las secuelas obtenidas se clasifican en leves, moderadas o graves. Resultados: Ingresan un total de 136 recién nacidos de muy bajo peso. La supervivencia es del 77,9 por ciento. Completaron el seguimiento hasta los 2 años un 83,9 por ciento de los supervivientes. La aparición de secuelas se observa en el 20,2 por ciento de los niños, de las cuales el 9 por ciento son graves, el 1,1 por ciento moderadas y el 10,1 por ciento leves. Los pacientes perdidos en el seguimiento presentan mayor peso al nacimiento, mayor edad gestacional y mayor normalidad ecográfica que los pacientes seguidos. Conclusión: Se obtiene un incremento en la supervivencia de los recién nacidos de muy bajo peso con la mejoría de los cuidados neonatales. La presencia de secuelas es similar a la obtenida en otros estudios de seguimiento. Se considera relevante la muestra de pacientes perdidos y su influencia en los porcentajes de secuelas obtenidas (AU)

[Varicella induced rhabdomyolysis]. / Rabdomiólisis por varicela.

Primary varicella-zoster infection is very common during childhood and few patients develop complications. The most frequent complications are bacterial infection of the lesions, laryngitis and varicella pneumonia. In the nervous system it can produce encephalitis and especially cerebellitis. We describe a case of primary varicella-zoster induced rhabdomyolysis in a 5-year-old girl with mental retardation, microcephalia and mild diplegia who, in the context of varicella infection, presented extreme muscular weakness and prostration. Blood and urine tests showed high creatine phosphokinase concentrations and myoglobinuria. The patient received aggressive intravenous hydration. Evolution was favorable with no renal failure. Rhabdomyolysis can produce life-threatening complications such as renal failure, intravascular disseminated coagulation and hyperkaliemia. The disease can be precipitated by alcohol ingestion, compression injury and generalized seizures. Infectious etiology is less common. Few reports have been published on primary varicella-zoster induced rhabdomyolysis but, because creatine phosphokinase concentrations are not routinely performed in varicella infection, very mild cases might have been under-diagnosed. Despite its rarity, this disease should be considered in cases of infection, since early treatment with hyperhydration can prevent complications.

Rabdomiólisis por varicela / Primary varicella-zoster induced rhabdomyolysis

La primoinfección por virus de la varicela-zoster (VVZ) es muy frecuente durante la infancia y en pocos casos cursa con complicaciones. Las más frecuentes son la sobreinfección de las lesiones, la laringitis y la neumonía varicelosas y como complicaciones neurológicas la encefalitis con especial predominio de cerebelitis. Se describe un caso de rabdomiólisis como complicación de la varicela. Se trataba de una niña de 5 años de edad con retraso mental, microcefalia y diplejía leve que, en el contexto de una primoinfección con varicela, presentó debilidad muscular extrema y postración. Se practicaron determinaciones analíticas sanguíneas y de orina que mostraron hipercreatinfosfatemia y mioglobinuria. Se realizó sueroterapia inmediata y el cuadro mejoró progresivamente, sin signos de insuficiencia renal aguda. La rabdomiólisis puede presentar complicaciones importantes, que no se dieron en nuestra paciente, como insuficiencia renal aguda, coagulación intravascular diseminada (CID) e hiperpotasemia. Suele deberse a intoxicación etílica, traumatismo o crisis generalizadas, siendo otra causa menos frecuente las infecciones. La rabdomiólisis por virus de la varicela-zoster es rara, poco descrita en la bibliografía, aunque en grado leve puede pasar desapercibida ya que no se determinan las concentraciones de creatinfosfocinasa de manera sistemática. A pesar de su rareza, es importante tenerla en cuenta en el contexto de una infección ya que el abordaje terapéutico precoz con sueroterapia abundante evita complicaciones (AU)

[The newborn infant at neurologic risk in the year 2000. Recommendations for the follow-up, incorporation of new instruments]. / Recién nacido de riesgo neurológico en el año 2000. Recomendaciones para el seguimiento, incorporación de nuevos instrumentos.

INTRODUCTION: Perinatal mortality has dropped markedly in recent years. However, there is still a considerable prevalence of neurological sequelas. Symptoms may present during the first months of life or later. Thus it is necessary to follow-up children with a clinical history of risk of neurological disorders. DEVELOPMENT: The various programmes for follow-up show slight variations in criteria of inclusion, calendar and methods of evaluation. We report the results of our follow-up of children at risk: long and short term sequelae in children of very low birth-weight and their correlation with neuroimaging findings. We review the use of some investigations (clinical examination, cranial ultrasound, CAT, magnetic resonance, EEG, visual and auditory evoked potentials and different biological, hemodynamic and nerve damage markers. CONCLUSIONS: It is necessary to: 1. Restrict the criteria for inclusion in hospital follow-up programmes; 2. Match a suitable investigative calendar to the pathology of the newborn baby; 3. Coordinate with the pediatricians of primary care areas and centres of early health care; 4. Use specific instruments for detection of mild sequelae at an earlier age; 5. Prolong follow-up at least until the age of 6-7 years old, and 6. To seek new biological markers to allow early detection of brain damage.

Recién nacido de riesgo neurológico en el año 2000. Recomendaciones para el seguimiento, incorporaciónde nuevos instrumentos / Newborn babies with the risk of having neurological disorders in the year 2000. Recommendations for follow-up and the use of new instruments

Introducción. La mortalidad perinatal ha disminuido de forma notable en los últimos años, si bien la prevalencia de secuelas neurológicas continúa siendo elevada. Los síntomas pueden presentarse en los primeros meses o en edades más tardías, de ahí la necesidad de un seguimiento de los niños con antecedentes de riesgo de patología neurológica. Desarrollo. Los distintos programas de seguimiento presentan ligeras variaciones en los criterios de inclusión, calendario y métodos de valoración. Presentamos algunos resultados de nuestra experiencia en el seguimiento de niños de riesgo: secuelas a corto y largo plazo en recién nacidos de muy bajo peso y correlación con los hallazgos en la neuroimagen. Se revisa la utilidad de algunas exploraciones (examen clínico, ecografía transfontanelar, TAC, resonancia magnética, EEG, potenciales evocados visuales y auditivos, y de distintos marcadores biológicos, hemodinámicos, del daño neuronal). Conclusiones. Es necesario: 1. Restringir los criterios de inclusión en el seguimiento hospitalario; 2. Adecuar las exploraciones y el calendario en función de la patología que haya presentado el neonato; 3. Coordinarse con los pediatras de áreas básicas y centros de atención precoz; 4. Utilizar instrumentos más específicos para detectar las secuelas leves a una edad más temprana; 5. Prolongar el seguimiento como mínimo hasta los 6-7 años de edad, y 6. Buscar nuevos marcadores que permitan identificar precozmente el daño cerebral (AU)

[Embryonic pathology caused by maternal phenylketonuria. A cause of underdiagnosed mental retardation. A report of 8 cases]. / Embriopatía por fenilcetonuria materna. Una causa de retardo mental poco diagnosticada. Revisión de ocho observaciones.

OBJECTIVE: Maternal phenylketonuria (MPKU) is characterized by intrauterine growth retardation, microcephaly, congenital malformations (mainly cardiac defects), dysmorphic facial features and mental retardation. There are women of child-bearing age that do not know that they are affected by phenylketonuria (PKU) and their pregnancies could result in damage to the fetus expressed as different neurological and congenital abnormalities. PATIENTS AND METHODS: We report 8 patients from 4 families. The first family had two offspring with intrauterine growth retardation, microcephaly and psychomotor retardation. The second family consisted of a daughter with mental retardation (without further data), a second baby which died during the first day of life, and a third child which died at 7 months of age with cardiac defects, microcephaly and dysmorphic features. Another child had intrauterine growth retardation, microcephaly psychomotor retardation, dysmorphic features and cardiac defects (coarctation of the aorta and subaortic stenosis). The third family had a son with microcephaly and mental retardation. The fourth family had a boy that died at 3 weeks of age with microcephaly, dysmorphic facial features, congenital heart disease (mitral atresia and septal defects) and Meckel diverticulum and a girl 5 years of age with intrauterine growth retardation, microcephaly and mental retardation. In all cases the mothers were unaware that they were affected by PKU and had mild intellectual defects. Two of them had PKU phenotypes. CONCLUSIONS: The offspring of PKU mothers untreated during pregnancy are affected by characteristic embriopathies related to the level of phenylalanine during pregnancy. In Spain, massive routine newborn screening was introduced around 1980-1985 and at present there are women of child-bearing age and are unaware that they are affected by the disease and that their pregnancies may result in fetal damage, as we demonstrate in these 8 patients. When faced with women with mental handicap or with antecedents of offspring with mental retardation, cardiac defects, microcephaly or intrauterine growth retardation, the determination of maternal phenylalanine concentrations is recommended. These teratogenic pathologies tend to disappear, but for the moment it is necessary to prevent this teratogenicity. The diagnosis is easy, avoids complementary exams, may help family studies and allows the implementation of dietary restriction during the subsequent pregnancy that would prevent fetal damage.

[Periventricular leukomalacia: its retrospective diagnosis in children with spastic diplegia]. / Leucomalacia periventricular: diagnóstico retrospectivo en niños con diplejía espástica.

Typical images of residual periventricular leukomalacia (PVL) have been searched for in a review of the CT scans of 135 children with spastic diplegia. Among the 135 children studied, 90 (66.6%) of them had had a CT scan with 51 (56.6%) showing typical images of residual PVL. Only 6 (11.7%) of these 51 children were identified in the early stages by cranial ultrasound and 11 (21.5%) of the 51 were diagnosed by CT scan. The remaining 34 (66.6%) were diagnosed retrospectively during our study and none of them were identified as PVL in the first examination by CT scan. In addition to CT scan examination, 3 children were explored by MRI that confirmed the diagnosis of PVL. The results of our study indicate that images in CT scans reported as slight ventricular dilation, normotensive hydrocephalus, hydrocephalus with irregular limits, subcortical atrophy or periventricular heterotopia could corresponds to images of residual PVL in the appropriate context. We emphasize the importance of CT scan examination for the retrospective diagnosis of PVL in elder children in which cranial ultrasound examination had not been performed during the neonatal period.

[Severe and mild forms of nemaline myopathy: a report of three cases]. / Miopatía nemalínica: forma congénita neonatal y moderada a propósito de tres observaciones.

Three new cases of two different forms of congenital nemaline myopathy are reported. Two of them represent a severe neonatal form. These cases were presented as a floppy infant syndrome. Although neither of them needed intensive care, they had feeding difficulties and one needed a feeding-tube for a period of time. Both of the patients showed a very severe motor delay and neither could manage to walk independently. During their lives, they suffered from repeated pneumonias, which was the cause of death in both cases before the age of two years. The mild congenital type represents a more benign form. Although hypotonic and weak, the patient managed to walk independently before two years of age. The weakness was spread all over, but was focused in the face, extensors of the neck and axial muscles. At 9 years of age, the patient has not experienced any respiratory trouble. The CK (creatine kinase) test were normal in all patients, but the EMG (electromyogram) showed different electromyographic patterns. The rods were in subsarcolemic positions, cytoplasmic positions or in both positions.

[Peripheral neuropathy as a presenting form of Cockayne syndrome]. / Neuropatía periférica como forma de presentación del síndrome de Cockayne.

We report a clinical observation of an infant aged 5 months with Cockayne syndrome whose symptomatology included failure to thrive, microcephaly, peripheral neuropathy and elevated level of protein in CSF. More typical signs of this syndrome appeared lately with progeroid facies, photosensitivity and intracranial calcifications that computed tomography revealed at 13 months of age. The early onset of clinical manifestations, the association with peripheral neuropathy, and the high level of protein in CSF are unusual facts that led us to do the differential diagnosis with other demyelinating disorders.

[Multicystic encephalomalacia in twin pregnancies]. / Encefalomalacia multiquística en gestaciones gemelares.

Multicystic encephalomalacia (ME) is a rare entity in the pediatric age. In ME brain tissue in substituted by cavities of variable size. ME has different etiologies being asphyxia and circulatory alterations the most important factors. In monozygotic twins there is an increased incidence of structural anomalies than dizygotic twins. We present four twin patients with ME. Three of them had a prenatal dead sibling. The fourth pair of twins had a twin-twin transfusion. We want to stress the utility of brain echography in early diagnosis of ME.

[Metachromatic leukodystrophy. Late juvenile form. Review of 6 cases]. / Leucodistrofia metacromática. Forma infantil tardía. Revisíon de seis observaciones.

Six cases of late infantile metachromatic leucodystrophy are presented. Behavioral changes and walking disturbances are the initial symptoms which tend to occur around 18 months of age. Slowing of nerve velocity conductions is a constant finding. Two out of six observations had normal CSF protein levels throughout their disease. Diagnosis was confirmed by sural nerve biopsy in two cases and by leucocyte arylsulfatase A measurement in the four remaining patients. Studies for carrier detection were performed in 4 of the 5 affected families.

[Clinical-therapeutical correlations in meningococcal infection: prophylactic heparin therapy (author's transl)]. / Correlaciones clinicoterapéuticas en la infección meningocócica (heparinoterapia profiláctica).

A number of 241 patients with meningococcal infection, treated between 1972 and 1978, is analysed. Some new therapeutic patterns are established based on the application of the prognosis score of Stiehm. With these patterns consisting in the use of volume expansors with anti-aggregating properties and low dosage prophylactic heparin administration, authors have considerably improved their results reported in 1972, succeeding in diminishing the global mortality to 3.73%, a figure inferior to that of all known series to date.