[Neurological dysfunction induced by bilirrubin]. / Disfunción neurológica inducida por bilirrubina.

INTRODUCTION: "Kernicterus" is a term currently used to describe bilirrubin induced brain injury in the neuro-pathological studies. This is a confusing term and nowadays we prefer bilirrubin encephalopathy or bilirrubin induced neurological dysfunction. The clinical signs vary and it is clearly decreasing in prevalence in developed countries. MATERIAL AND METHODS: We review a series of 7 patients with bilirrubin encephalopathy and variable neurological manifestations, who were seen in the Neuropaediatric Department in the last 10 years. Only one patient died in the neonatal period with hyperbilirubinaemia, sepsis and multi-organ failure. RESULTS: Diverse aetiological factors were related to hyperbilirubinaemia. All patients had clinical symptoms due to hyperbilirubinaemia. Neuroimaging during the neonatal period showed involvement of the nucleus pallidus, with hyperintensity in T1 in the brain MR scan as the most consistent finding. All the patients who survived developed neurological signs and we try to correlate them with biochemical, clinical, neuroimaging and neurophysiological parameters. CONCLUSIONS: An increase in the number of patients with bilirrubin encephalopathy has been observed over the last few years, and we attempt to find out the causes. The increased survival of the low birth weight newborns, the increase in the immigration population and the use of diagnostic neuroimaging contribute to this increase. It is a great challenge for the neonatologist and for neuropaediatricians to prevent its occurrence and to minimise the effects of bilirrubin encephalopathy.

Schinzel-Giedion syndrome: report of two sibs.

We report on two further cases, a sister and a brother, with Schinzel-Giedion syndrome. Both presented the following manifestations: "coarse face" with midface retraction, agenesis of corpus callosum, bilateral hydronephrosis, and typical skeletal anomalies. Patient 1 had a malignant sacrococcygeal teratoma. This is the third case of malignancy in this syndrome. Patient 2 died shortly after birth.

Immunohistological signposts in central nervous system tumours with neuronal differentiation.

25 neuronal tumours with a panel of antibodies were studied and it was found that vimentin was present in 15 tumours. It was also found in a few cells within rosettes. PGP 9.5 showed a somatic pattern of staining with nuclear and perinuclear positivity in 23. Neurofilament reactivity was found in 14. Retinal S-antigen was detected only in one medulloblastoma, 3/4 pineal tumours and 2/2 retinoblastomas. Reactivity, for synaptophysin was present in 2/5 medulloblastomas, 3/10 neuroblastomas and 2/2 retinoblastomas. GFAP was demonstrated in scattered tumour cells in 4/5 medulloblastomas. Two of these were the only tumours featuring bipolar differentiation whilst it was unipolar in the remainder. The significance of these findings in relation to the ontogeny of these tumours is discussed.

Dégénérescence systématisée optico-cochléo-dentelée.

During the first year of life a girl, the first child of non-consanguineous parents, developed a progressive neurological disease characterized by blindness, severe hypotonia, impaired motor development, microcephaly and mental retardation. Later she became unresponsive to auditory stimuli. She died at the age of 13 months. Post-mortem examination revealed atrophy of the optic nerves and chiasm, lateral geniculate nuclei and superior colliculi, degeneration of the cochlear nerve roots, dorsal and ventral cochlear nuclei, superior olives, lateral lemnisci, medial geniculate nuclei and inferior colliculi and atrophy of the dentate nuclei, hilus and superior cerebellar peduncles. These were consistent with dégénérescence systématisée optico-cochleéo-dentelée. Additional abnormalities included degeneration of the posterior columns in the spinal cord, gracilis and cuneate nuclei and medial lemnisci, atrophy of the spinocerebellar tracts and Clarke's columns, cerebral cortex, cerebellum, chiefly involving the rostral vermis, inferior olivary nuclei and demyelination of the sural nerves.

An atypical French form of pyruvate carboxylase deficiency.

A further case of pyruvate carboxylase deficiency, French type, with a particular clinical presentation and evolution is described. The initial neonatal symptoms started with respiratory distress, severe metabolic acidosis and a tendency to hypoglycemia. However, the clinical course was not rapidly deteriorating. At the age of 6 months he presented acute neurological symptoms, respiratory difficulty, lactic acidosis and hyperammonemia. Amino and organic acid abnormalities strongly suggested pyruvate carboxylase deficiency, which was confirmed by enzymatic studies in cultured fibroblasts and liver necropsy. Progressive deterioration and bronchopneumonia with cardiac failure and renal insufficiency led to death. Anatomic-pathologic studies revealed periventricular cysts and diffuse hypomyelination. Prenatal diagnosis of a further sibling was performed. The neonatal clinical presentation, biochemical abnormalities, and the presence of periventricular cysts suggested a French phenotype. However, the clinical course was less severe, suggesting a residual enzymatic activity and a possible milder mutation.

A Golgi study of cerebellar malformation in 13 trisomy.

The structure of cerebellar malformations in the brains of two infants with 13 trisomy has been studied by means of the Golgi method. Poorly organized cerebellar dysplasias (heterotaxias) are composed of Purkinje, Golgi and granule cells arranged and oriented in a disorderly fashion. The variable orientation and organization of the dendritic arbor of Purkinje cells within these cellular aggregates is supposed to be related to abnormal distribution of parallel fibers. Large ganglion cell heterotopias are not a homogeneous group, but two distinct types may be defined. First, Purkinje cell heterotopias which are located in the white matter of the cerebellum below the normally formed folia; these are composed of large neurons with arrested migration to the cortex. Secondly, multipolar cell heterotopias which are located in the deep white matter near the dentate and the roof nuclei, formed of neurons belonging to the deep cerebellar nuclei.

Neural tube defect and amniotic band sequence.

A 28-years-old pregnant woman was examined by fetal ultrasonography at 18 weeks' gestation. Anencephaly was diagnosed, followed by prostaglandin induced abortion and fetotomy. Fetal fragments showed a very small head, bilateral anophthalmy, absence of nasal structures and calvarium, intact cranial skin and a very small cranial cavity. The right lower limb was reduced to a few toes covered by a large amniotic adhesion. The left lower limb showed an amniotic band from sole to thigh. The abdominal wall was absent. The diagnoses were amniotic adhesion syndrome and cephalic pole induction failure. The pathogenesis of these defects has been the subject of controversy. Vascular disruption and secondary reduction of the paraaxial mesodermal cells can explain the anomalies observed in this case.

Radiohumeral synostosis, femoral bowing, other skeletal anomalies and anal atresia, a variant example of Antley-Bixler syndrome?

We report a newborn with radiohumeral synostosis, femoral bowing, anal atresia, a prominent nose (pear shaped nose), slender ribs, long tapering fingers with distal camptodactyly, genital hypoplasia and a neonatal humeral fracture. Among the possible differential diagnoses a variant example of Antley-Bixler syndrome is considered to be the most likely final diagnosis.

[Primary leptomeningeal melanomatosis in a 6-year-old child]. / Melanomatosis leptomeníngea primaria en un niño de 6 años.

A case of primary leptomeningeal melanomatosis without cutaneous lesions is reported. The clinical findings for a six months period were: intracranial hypertension syndrome, progressive cranial polineuropathy and a spinal involvement in a six years old child. CT brain scan showed enlarged subarachnoid spaces without contrast enhancement. MRI brain scan evidenced furthermore a focal lesion in right talamus. MRI spinal scan was normal. Examination of CSF showed elevated protein and reduced glucose concentrations as well as mild pleocytosis. Serologies and cultures investigating viral, bacterial, mycobacterial, fungal or parasitic infections resulted negative. CSF cytologic examination failed to show malignant cells. Postmortem diagnosis after neuropathological examination was made. This is an uncommon case of primary leptomeningeal melanomatosis, presenting the difficulty of diagnosis when cutaneous lesions are not present.

[Mesenteric flow in an experimental model of ischaemia-reperfusion in rats]. / Flujo mesentérico en un modelo experimental por isquemia-reperfusión en ratas.

INTRODUCTION: Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. METHOD AND MATERIAL: Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intra-abdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. RESULTS: The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<.01) when associated with the MVH (rs = -0,495; rs = -0,452; rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518). CONCLUSIONS: The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level.

Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate carboxylase deficiency.

Pyruvate carboxylase deficiency is a rare metabolic disorder, with three different phenotypes. We aim to report the case of a newborn presenting the severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia and rigidity being the main features) and the results of the study of classic neurotransmitters involved in movement control. Hyperdopaminergic transmission (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic transmission (in the substantia nigra) were found. Both gamma-aminobutyric acid and dopamine markers were found coexisting in individual neurons of the substantia nigra. This is the first time this phenomenon has been reported in the literature. We discuss the possible role of GABAergic deficiency, its interaction with other neurotransmitters and its implication in neurotransmitter homeostasis. A better comprehension of that field would increase understanding of the pathophysiology of neurological symptoms and neurotransmitter plasticity.

The prevalence of coeliac disease is significantly higher in children compared with adults.

BACKGROUND: Some limited studies of coeliac disease have shown higher frequency of coeliac disease in infancy and adolescence than in adulthood. This finding has remained unnoticed and not adequately demonstrated. AIM: To assess whether there are age and gender differences in coeliac disease prevalence. METHODS: A total of 4230 subjects were included consecutively (1 to ≥80 years old) reproducing the reference population by age and gender. Sample size was calculated assuming a population-based coeliac disease prevalence of 1:250. After an interim analysis, the paediatric sample was expanded (2010 children) due to high prevalence in this group. Anti-transglutaminase and antiendomysial antibodies were determined and duodenal biopsy was performed if positive. Log-linear models were fitted to coeliac disease prevalence by age allowing calculation of percentage change of prevalence. Differences between groups were compared using Chi-squared test. RESULTS: Twenty-one subjects had coeliac disease (male/female 1:2.5). Coeliac disease prevalence in the total population was 1:204. Coeliac disease prevalence was higher in children (1:71) than in adults (1:357) (P = 0.00005). A significant decrease of prevalence in older generations was observed [change of prevalence by age of -5% (95% CI: -7.58 to -2.42%)]. In the paediatric expanded group (1-14 years), a decrease of coeliac disease prevalence was also observed [prevalence change: -17% (95% CI: -25.02 to -6.10)]. CONCLUSIONS: The prevalence of coeliac disease in childhood was five times higher than in adults. Whether this difference is due to environmental factors influencing infancy, or latency of coeliac disease in adulthood, remains to be demonstrated in prospective longitudinal studies.

Una forma excepcional de combinación de retorno venoso pulmonar y sistémico en un caso de síndrome de heterotaxia / An exceptional combination of pulmonary and systemic venous return in a case of heterotaxia syndrome

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Flujo mesentérico en un modelo experimental por isquemia-reperfusión en ratas / Mesenteric flow in an experimental model of ischaemia-reperfusion in rats

INTRODUCCIÓN: La oclusión aguda mantenida seuida de la reperfusión de la arteria mesentérica superior (AMS) puede desencadenar en pocas horas el daño irreversible del intestino. Nuestro objetivo fue determinar los cambios de flujo mesentérico medidos por ecografía Doppler color y la correlación con las lesiones histológicas en un modelo experimental de isquemia-reperfusión. MATERIAL Y MÉTODO: Se estudiaron 3 grupos (control, isquemia y reperfusión) de ratas Sprague-Dawley de 17 días de vida. El modelo utilizado fue de isquemia-reperfusión sobre la AMS. Posteriormente, realizamos una ecografía intraabdominal. Las variables ecográficas fueron: velocidad sistólica máxima (VSM), velocidad media (Vm), flujo diastólico (FD) y los índices de pulsatilidad (IP), resistencia (IR) y sístole/diástole (S/D). Las variables histológicas fueron: lesión intestinal (escala Wallace/Keenan y Chiu), morfométricas (altura [AMV] y espesor medio de vellosidades) y células caliciformes. Utilizamos la correlación de Sperman (rs). RESULTADOS: En el grupo reperfusión la VSM (74,3 cm/s), el IP (7,33) y S/D (25,75) en la AMS se encuentran aumentados respecto a los controles (41,35 cm/s [3,12]; [12.45]). La VSM, IP y S/D establecieron regresiones significativas (p < 0,01) con: Wallace/Keenan (rs = 0,655; rs = 0,593; rs = 0,63), Chiu delgado (rs = 0,569; rs = 0,522; rs = 0,47), la AMV (rs = -0,495; rs = -0,452; rs = -0,459), y células caliciformes del colon (rs = -0,525; rs = -0,45; rs = -0,518). CONCLUSIONES: En la fase de reperfusión el incremento del flujo mesentérico expresado por la VSM y el IP podría pronosticar de forma significativa el potencial daño intestinal que ocurre a nivel macroscópico y microscópico

INTRODUCTION: Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. Method and material: Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intraabdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. RESULTS: The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<0.01) when associated with the MVH (rs = -0,495; rs = -0,452;rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518).CONCLUSIONS: The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level

Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations.

Congenital disorder of glycosylation Ia (CDG-Ia) is a metabolic disease with a broad spectrum of clinical signs, including recently described mild phenotypes. Our aim was to describe the clinical presentation and follow-up of eight CDG-Ia patients highlighting atypical features and aspects of evolution of the disease. CDG diagnosis was confirmed by enzymatic analysis of phosphomannomutase (PMM2) and molecular studies of the PMM2 gene. Four neonates presented with cerebral haemorrhage (1), failure to thrive (2) and non-immune hydrops (1) and a fatal course to death (2); pathological examination of the brain in one case revealed olivopontocerebellar atrophy of prenatal origin. During infancy failure to thrive, coagulopathy and hepatopathy were the most significant causes of morbidity, but these disappeared after the first years of life in most patients. Three patients are currently in their 20s; they present mental retardation and severe motor impairment but no acute decompensations were noticed after the first decade of life. They do not present spinal or thoracic deformities otherwise observed in patients from northern countries. A 10-year-old patient who manifested gastrointestinal dysfunction in early childhood showed normal neurodevelopment. Mutation analysis of the PMM2 gene showed great variability, with all patients being compound heterozygous for two different mutations. Long-term evolution in our patients indicates that CDG-Ia is a stable systemic and neurological condition after the first decade of life. The diverse phenotypes and atypical manifestations in our series may be due to their genetic heterogeneity.

Macrodactyly of the hands and feet.

Sixteen patients with macrodactyly have been reviewed; the hand was involved in 9 (one was bilateral) and the feet in 7. The condition was familial in 3. No qualitative difference was found between the static and progressive types. In the hand, the digital nerve was enlarged and lengthened whereas in the foot it looked normal. Microscopy showed infiltration of the nerve by fat and fibrous tissue in the hand and only slight perineural fibrosis in the foot.

Dystonia as a presenting sign of subacute necrotising encephalomyelopathy in infancy.

A case of subacute necrotising encephalomyelopathy is reported with such note worthy features as early onset, dystonic manifestations and the presence of low attenuation areas in the basal ganglia on computerised tomography of the brain. Laboratory findings were normal and the diagnosis was confirmed at postmortem examination.

CT scan appearance in subacute necrotising encephalomyelopathy.

Three patients with subacute necrotising encephalolmyelopathy are reported, all of whose CT brain-scans showed areas of low attenuation in the basal ganglia, especially in the lenticular nucleus. The authors suggest that this brain-scan appearance may help in the diagnosis of this disorder during life.

Management of tracheal agenesis.

Complete tracheal agenesis is a very rare congenital anomaly that is only compatible with life in some cases with associated tracheo-oesophageal or broncho-oesophageal fistula. In most cases, concomitant congenital anomalies of the heart, digestive tract or genitourinary tract are present. It should be suspected in any neonate with a history of hydramnios, absent crying, respiratory distress and difficulty in intubation. The possibility for surgical correction or palliation rests on the extent of atresia present. We present a case of complete tracheal agenesis without tracheo nor broncho-oesophageal fistula (type II by Floyd's classification) - the diagnosis of which was prenatally suspected - and discuss the important features of the airway management of this condition.