Tomografía computada y resonancia magnética de variantes normales/congénitas de apariencia quística y presentación frecuente en el encéfalo / CT and MRI of Normal/Congenital Variables with Cystic Appearance and Frequent Presence in the Brain

La presentación de una imagen de apariencia quística durante el estudio del encéfalo constituye un hallazgo incidental cada vez más frecuente, pudiendo encontrarse en el espacio extra o intraaxial. Las mismas pueden ser de naturaleza congénita o adquirida, benigna o maligna, ocupantes de espacio con desplazamiento de la línea media o simplemente presentarse sin efecto compresivo alguno. De localización supra o infratentorial, esas imágenes constituyen un desafío diagnóstico, siendo imprescindible su reconocimiento para no solicitar estudios o tratamientos innecesarios. Valoraremos las imágenes de apariencia quística más frecuentes empleando tomografía computada o imágenes de resonancia magnética.

Presence of a cystic formation in brain examination is frequently an incidental finding. They can be intra or extra-axial in location, congenital or acquired, benign or malignant with or without mass effect. Intracranial cysts can be a diagnostic challenge and we should know them to avoid unnecessary exams or treatment. We will analyze the most common cystic formations seen in computed tomography and magnetic resonance.

Hydrocephalus due to multiple ependymal malformations is caused by mutations in the MPDZ gene.

Congenital hydrocephalus is considered as either acquired due to haemorrhage, infection or neoplasia or as of developmental nature and is divided into two subgroups, communicating and obstructive. Congenital hydrocephalus is either syndromic or non-syndromic, and in the latter no cause is found in more than half of the patients. In patients with isolated hydrocephalus, L1CAM mutations represent the most common aetiology. More recently, a founder mutation has also been reported in the MPDZ gene in foetuses presenting massive hydrocephalus, but the neuropathology remains unknown. We describe here three novel homozygous null mutations in the MPDZ gene in foetuses whose post-mortem examination has revealed a homogeneous phenotype characterized by multiple ependymal malformations along the aqueduct of Sylvius, the third and fourth ventricles as well as the central canal of the medulla, consisting in multifocal rosettes with immature cell accumulation in the vicinity of ependymal lining early detached from the ventricular zone. MPDZ also named MUPP1 is an essential component of tight junctions which are expressed from early brain development in the choroid plexuses and ependyma. Alterations in the formation of tight junctions within the ependyma very likely account for the lesions observed and highlight for the first time that primary multifocal ependymal malformations of the ventricular system is genetically determined in humans. Therefore, MPDZ sequencing should be performed when neuropathological examination reveals multifocal ependymal rosette formation within the aqueduct of Sylvius, of the third and fourth ventricles and of the central canal of the medulla.

Cortical hypoplasia and ventriculomegaly of p73-deficient mice: Developmental and adult analysis.

Trp73, a member of the p53 gene family, plays a crucial role in neural development. We describe two main phenotypic variants of p73 deficiency in the brain, a severe one characterized by massive apoptosis in the cortex leading to early postnatal death and a milder, non-/low-apoptosis one in which 50% of pups may reach adulthood using an intensive-care breeding protocol. Both variants display the core triad of p73 deficiency: cortical hypoplasia, hippocampal malformations, and ventriculomegaly. We studied the development of the neocortex in p73 KO mice from early embryonic life into advanced age (25 months). Already at E14.5, the incipient cortical plate of the p73 KO brains showed a reduced width. Examination of adult neocortex revealed a generalized, nonprogressive reduction by 10-20%. Area-specific architectonic landmarks and lamination were preserved in all cortical areas. The surviving adult animals had moderate ventricular distension, whereas pups of the early lethal phenotypic variant showed severe ventriculomegaly. Ependymal cells of wild-type ventricles strongly express p73 and are particularly vulnerable to p73 deficiency. Ependymal denudation by apoptosis and reduction of ependymal cilia were already evident in young mice, with complete absence of cilia in older animals. Loss of p73 function in the ependyma may thus be one determining factor for chronic hydrocephalus, which leads to atrophy of subcortical structures (striatum, septum, amygdala). p73 Is thus involved in a variety of CNS activities ranging from embryonic regulation of brain size to the control of cerebrospinal fluid homeostasis in the adult brain via maintenance of the ependyma.

Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking.

BACKGROUND: The ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking. RESULTS: Our results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy. CONCLUSIONS: We conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly.

Hydrocephalus is a common and variegated pathology often emerging in newborn children after genotoxic insults during pregnancy (Hicks and D'Amato, 1980). Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle and survival. Here we show, by using three independent nestin Cre transgenic lines, that high levels of Cre recombinase expression into the nucleus of neuronal progenitors can compromise normal brain development. The transgenics analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase with a nuclear localization signal, and two nestin CreER(T2) (Cre recombinase fused with a truncated estrogen receptor) mice lines with different levels of expression of a hybrid CreER(T2) recombinase that translocates into the nucleus after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed reduced neuronal proliferation, increased aneuploidy and cell death, as well as defects in ependymal lining and lamination of the cortex, leading to microencephaly and to a form of communicating hydrocephalus. An essentially overlapping phenotype was observed in the two nestin CreER(T2) transgenic lines after tamoxifen mediated-CreER(T2) translocation into the nucleus. Neither tamoxifen-treated wild-type nor nestin CreER(T2) oil-treated control mice displayed these defects. These results indicate that some forms of hydrocephalus may derive from a defect in neuronal precursors proliferation. Furthermore, they underscore the potential risks for developmental studies of high levels of nuclear Cre in neurogenic cells.

Malformations of cortical development: high-resolution MR and diffusion tensor imaging of fiber tracts at 3T.

Patients with malformations of cortical development and epilepsy may have a variety of abnormal brain findings, including abnormal gyral patterns, cortical thickening, decreased volume of white matter, and increased diffusion of white matter. The status of individual white matter fiber tracts, however, is unknown. We present a case of bilateral frontal schizencephaly and subcortical heterotopia and illustrate alterations of white matter fascicles by combined structural and functional diffusion tensor imaging at 3 T.

Gelastic seizure with tectal tumor, lobar holoprosencephaly, and subependymal nodules: clinical report.

Gelastic seizures are characterized by inappropriate, stereotyped laughter and are often first recognized when other epileptic manifestations occur. They are frequently associated with hypothalamic hamartomas. Central nervous system developmental abnormalities are rarely reported with gelastic seizures. There is only one case report of gelastic seizure caused by holoprosencephaly. We report a 2-year-old girl with multiple brain structural abnormalities including tectal tumor (possibly hamartoma), multiple subependymal nodules, and holoprosencephaly. She developed seizures during the newborn period and presented with gelastic seizure and simple partial seizure at 3 months of age.

Novel cerebral lesions in the Eker rat model of tuberous sclerosis: cortical tuber and anaplastic ganglioglioma.

The Eker rat is a model for human tuberous sclerosis (TSC) caused by a mutation in the Tsc2 gene. We describe here histological and immunohistochemical findings of the brain lesions in Eker rats, with emphasis on 2 novel lesions found in this study: a cortical tuber and an anaplastic ganglioglioma. The rat cortical tuber resembled those of humans, and further confirmed the value of this animal model as a tool for investigating the molecular pathology of tuberous sclerosis. On the other hand, the rat anaplastic ganglioglioma had features of a malignant neoplasm that are absent from human subependymal giant cell astrocytomas.

Antenatal diagnosis of subependymal heterotopia.

Subependymal heterotopia consist of gray matter nodules along the lateral ventricular walls and are associated with epilepsy and other cerebral malformations. Some cases have an X-linked inheritance, and early antenatal diagnosis of affected fetuses is important for appropriate management. We present a case of heterotopia diagnosed by sonography and MR imaging at 23 weeks' gestation and discuss the differential diagnosis, reviewing the evolution and imaging appearances of the germinal matrix and its implications for detection of heterotopia.

Clinical analyses and short-term prognoses of neonates with subependymal cysts.

Twenty-one neonates with subependymal cysts detected by neurosonography soon after birth were prospectively examined. The clinical and cranial sonographic findings were evaluated with respect to short-term prognosis. The prognosis was poor in 6 patients with congenital viral infection (4 with cytomegalovirus infection and 2 with rubella infection). Five patients also had neurodevelopmental abnormalities (2 with neonatal epileptic seizures, 2 with chromosomal abnormalities, and 1 with lissencephaly). The remaining 10 patients had normal psychomotor development. The incidence of congenital viral infection was statistically correlated with a poor neurodevelopmental outcome. A correlation did not exist between the short-term prognosis and each of the other clinical factors or cranial sonographic findings. Our evidence suggests that further investigation of possible subependymal cyst etiologies is required during a careful, long-term follow-up period.

Frontal horn coarctation: CT demonstration. A report of two cases.

The CT aspects of frontal horn coarctation by ependymal fusion in two cases are described with post-mortem verification. These ependymal fusions in the lateral ventricles are seen frequently on air ventriculograms, especially in the occipital horns. Ependymal fusions in the frontal horns are rare and not very well known. These fusions are clearly seen on CT and post-mortem examinations. The frontal horns appear asymmetrical on CT and this asymmetry evokes frontal horn compression (by an isodense tumour for instance), or contralateral frontal horn dilatation. Some CT details of ventricular coaractation makes it easy to differentiate tumoural compression from controlateral subcortical atrophy.

The evaluation of ependymal and subependymal lesions by cranial computed tomography.

Lesions of the ventricular ependyma and its derivatives can be visualized by CT scans, and their nature and extent can be determined. Generalized enhancement of the ependyma following the administration of intravenous contrast media can be seen with spendymoma, medulloblastoma, metastatic dysgerminoma, glioblastoma multiforme, and ependymitis. Localized ependymal enhancement can often be identified in the presence of acute ventriculitis, vascular anomalies or malformations, cerebral infarctions with luxury perfusion, and vascular neoplasms.