The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease.

BACKGROUND: Norrie disease (ND) is a rare X-linked disorder characterized by bilateral congenital blindness. ND is caused by a mutation in the Norrie disease pseudoglioma (NDP) gene, which encodes a 133-amino acid protein called norrin. Intragenic deletions including NDP and adjacent genes have been identified in ND patients with a more severe neurologic phenotype. We report the biochemical, molecular, clinical and radiological features of two unrelated affected males with a deletion including NDP and MAO genes. METHODS: Biochemical and genetic analyses were performed to understand the atypical phenotype and radiological findings. Biogenic amines in cerebrospinal fluid (CSF) were measured by high-performance liquid chromatography. The coding exons of NDP gene were amplified by polymerase chain reaction. Multiplex ligation-dependent probe amplification and chromosomal microarray were carried out on both affected males. Computed tomography and magnetic resonance imaging were performed on the two patients. RESULTS: In one patient, the serotonin and catecholamine metabolite levels in CSF were virtually undetectable. In both patients, genetic studies revealed microdeletions in the Xp11.3 region, involving the NDP, MAOA and MAOB genes. Radiological examination demonstrated brain and cerebellar atrophy. CONCLUSIONS: We suggest that alterations caused by MAO deficit may remain during the first years of life. Clinical phenotype, biochemical findings and neuroimaging can guide the genetic study in patients with atypical ND and help us to a better understanding of this disease.

Posterior fossa clear cell meningioma without dural attachment in a child.

INTRODUCTION: Meningiomas are relatively uncommon in childhood. They represent 1% to 2% of all intracranial tumours of infancy and childhood and 1.5% to 1.8% of all intracranial meningiomas. Occasionally, meningiomas may develop without dural attachment. Clear cell meningioma is a histological distinctive uncommon variant of meningioma that may behave aggressively with local recurrence and progression as well as cerebrospinal fluid-borne metastasis. Meningiomas near the craniocervical junction represent challenging tumours, requiring special considerations because of the vicinity of the medulla oblongata, the lower cranial nerves and the vertebral artery. CASE REPORT: In this study, the authors present a rare case of posterior fossa clear cell meningioma without dural attachment in a child with severe brainstem and cervical spinal cord displacement and discuss the clinical and radiological features as well as treatment considerations.

[Clinico-radiological profile of acute disseminated encephalomyelitis in the childhood population. A retrospective analysis of a series of 20 patients in a tertiary hospital]. / Perfil clinicorradiológico de la encefalomielitis aguda diseminada en la población infantil. Análisis retrospectivo de una serie de 20 pacientes de un hospital terciario.

INTRODUCTION: Acute disseminated encephalomyelitis (ADE) is an inflammatory disorder of the central nervous system that is mediated immunologically and of unknown pathogenesis. It can present at any age, but is much more frequent in children. ADE has no specific biological marker and diagnosis is based on findings from clinical and neuroimaging studies. AIM: To enhance our knowledge of the clinico-radiological profile of this disease. PATIENTS AND METHODS: This retrospective study involved patients under 14 years of age who were admitted to a tertiary hospital over the last 15 years with a diagnosis of ADE. History, clinical presenting symptoms, lab findings from blood/cerebrospinal fluid analyses and radiological semiology were reviewed. In 16 cases an average follow-up of 25 months was performed. RESULTS: The study examined 20 patients, 70% children, with a mean age of 4.4 years. Forty per cent had a previous febrile episode. Eighty-five per cent presented fever or vomiting, and 70% had altered states of mind. Motor deficits (45%), convulsions (35%) and involvement of the cranial nerves (30%) were predominant. Three children progressed with relapses and three others were left with motor sequelae. Magnetic resonance imaging showed hyperintense lesions in T2, with a pattern of scarce/no enhancement, which were predominantly located in the thalamus (70%), the spinal cord (67%) and the white matter of the sub-cortex (50%). Haemorrhagic ADE was diagnosed in two patients. CONCLUSIONS: ADE is a condition with an important degree of general involvement and neurological repercussions, as well as considerable potential to leave the patient with sequelae. Clinico-analytical data and magnetic resonance scans of the head and spinal cord are relevant for the initial diagnosis and follow-up of patients with ADE.

TITLE: Perfil clinicorradiologico de la encefalomielitis aguda diseminada en la poblacion infantil. Analisis retrospectivo de una serie de 20 pacientes de un hospital terciario.Introduccion. La encefalomielitis aguda diseminada (EAD) es un trastorno inflamatorio del sistema nervioso central mediado inmunologicamente y de patogenia desconocida. Puede presentarse en cualquier edad, pero es mucho mas frecuente en niños. La EAD no tiene marcador biologico especifico y el diagnostico se basa en hallazgos clinicos y neurorradiologicos. Objetivo. Mejorar el conocimiento del perfil clinicorradiologico de esta enfermedad. Pacientes y metodos. Estudio retrospectivo con inclusion de pacientes menores de 14 años ingresados en un hospital terciario en los ultimos 15 años con el diagnostico de EAD. Se revisaron antecedentes, signos clinicos de presentacion, datos analiticos en sangre/liquido cefalorraquideo y la semiologia radiologica. En 16 casos se realizo un seguimiento medio de 25 meses. Resultados. Se revisaron 20 pacientes, un 70% niños, con una edad media de 4,4 años. El 40% tuvo un episodio febril previo. El 85% presento fiebre o vomitos, y el 70%, afectacion del estado de consciencia. Predominaron los deficits motores (45%), las convulsiones (35%) y la afectacion de pares craneales (30%). Tres niños presentaron una evolucion recidivante, y otros tres, secuelas motoras. Los estudios de resonancia magnetica mostraron lesiones hiperintensas en secuencias T2, con patron de realce escaso o nulo, que predominaron en los talamos (70%), la medula (67%) y la sustancia blanca subcortical (50%). En dos pacientes se diagnostico EAD hemorragica. Conclusiones. La EAD representa una entidad con importante afectacion general y repercusion neurologica, que muestra un potencial secuelar considerable. Los datos clinicoanaliticos y la resonancia magnetica cerebral y medular son relevantes para el diagnostico inicial y seguimiento de pacientes con EAD.

[Hypomyelination with atrophy of the basal ganglia and cerebellum. Contribution of two new cases to a recently reported entity]. / Hipomielinización con atrofia de ganglios basales y de cerebelo. Aportación de dos nuevos casos a una entidad de descripción reciente.

INTRODUCTION: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare condition that has only recently been reported. Here we present two new cases belonging to the same family. CASE REPORTS: Case 1: 17-month-old boy with severe underdevelopment in all areas, absence of language and eye contact. The examination revealed microcephaly with spastic tetraparesis. A magnetic resonance imaging scan showed predominantly vermian atrophy of the cerebellum with loss of volume of both nuclei of the putamen and the head of the caudate, and a pattern of hypomyelination of the white matter. Electromyography recording highlighted the presence of a predominantly motor pattern of chronic polyneuropathy. Homovallinic acid and 5-hydroxyindoleacetic acid values were lower than usual. Treatment with levodopa/carbidopa was not effective. Case 2: 11-month-old girl, the sister of the boy in the previous case. The patient presented severe underdevelopment in all areas and microcephaly with spastic tetraparesis was detected in the clinical examination. Magnetic resonance imaging of the head showed findings that could be superimposed upon those of the brother, with hypomyelination, cerebellar atrophy and involvement of the putamen and both caudates; electromyography findings were consistent with motor polyneuropathy of a demyelinating nature. Homovallinic acid and 5-hydroxyindoleacetic acid values in cerebrospinal fluid were lower than usual. Treatment with levodopa/carbidopa was ineffective. CONCLUSIONS: These two new cases help characterise this condition better and reinforce the hypothesis of the genetic origin of the syndrome, given that the two cases occurred in the same family.

TITLE: Hipomielinizacion con atrofia de ganglios basales y de cerebelo. Aportacion de dos nuevos casos a una entidad de descripcion reciente.Introduccion. La hipomielinizacion con atrofia de ganglios basales y de cerebelo (H-ABC) es una rara entidad descrita recientemente. Se presentan dos nuevos casos pertenecientes a una misma familia. Casos clinicos. Caso 1: niño de 17 meses con retraso grave en todas las areas, ausencia de lenguaje y de contacto visual. En la exploracion destacaba una microcefalia con tetraparesia espastica. En la resonancia magnetica cerebral se apreciaba atrofia cerebelosa de predominio vermiano con perdida de volumen de ambos nucleos del putamen y la cabeza del caudado, y patron de hipomielinizacion de la sustancia blanca. En la electromiografia se objetivo un patron de polineuropatia cronica de predominio motor. Presento un descenso de los valores de acido homovalinico y de acido 5-hidroxindolacetico. El tratamiento con levodopa/carbidopa no fue efectivo. Caso 2: niña de 11 meses, hermana del caso anterior. Presentaba un retraso grave en todas las areas y en la exploracion clinica se detecto una microcefalia con tetraparesia espastica. La resonancia magnetica cerebral mostro hallazgos superponibles a los del hermano, con hipomielinizacion, atrofia cerebelosa y afectacion putaminal y de ambos caudados; en la electromiografia, hallazgos compatibles con polineuropatia motora de caracter desmielinizante. Presento un descenso de los valores de acido homovalinico y acido 5-hidroxindolacetico en el liquido cefalorraquideo. El tratamiento con levodopa/carbidopa resulto ineficaz. Conclusiones. Estos dos nuevos casos ayudan a caracterizar mejor esta entidad y refuerzan la hipotesis del origen genetico del sindrome, dado que se trata de dos casos pertenecientes a una misma familia.

Craniopharyngiomas: identification of different semiological patterns with MRI.

Our objectives were to analyze different semiological patterns in craniopharyngiomas studied with CT and MR sequences. Retrospective study of 26 patients with confirmed craniopharyngiomas. All cases were examined with CT and MR imaging using a variety of pulse sequences (spin echo, inversion recovery, gradient echo in-phase and opposed-phase). The analyzed component patterns were classified as solid, calcium, proteic-like, cerebrospinal fluid (CSF)-like, hematic-like, and fatty patterns. The different patterns were related by means of contingency tables and the Fisher exact test and also to epidemiological findings and tumor size. A solid pole was detected in all patients, whereas a cystic component was present in 92.3% of the cases. Calcification was visualized in 65.3%, proteic-like in 53.8%, CSF-like in 23%, hematic-like in 19.2%, and fatty component in 15.3%. There were no statistical associations between patterns, with the exception that in no case did CSF-like and proteic-like patterns coexist ( P=0.004). Tumor size was related to components. Hematic-like (17.0+/-18.9 vs 3.9+/-2.6 mm, non-present vs present) and CSF-like (16.9+/-19.6 vs 6.5+/-4.0 mm) patterns were observed most frequently in smaller tumors, whereas larger tumors usually had proteic-like (5.9+/-5.4 vs 21.1+/-21.0 mm) and calcified (4.6+/-1.9 vs 19.1+/-19.9 mm) patterns. Computed tomography and a combination of different MR images frequently allow the detection of different semiological patterns in these tumors. Semiological patterns were correlated only to tumor size.