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The accumulation of amyloid-beta and increased expression of its receptor RAGE (the receptor for advanced glycation end products) have been implicated in the pathogenesis of Alzheimer's disease (AD). Here we have used immunohistochemistry and double labelling to localize RAGE expression in Huntington's disease (HD) caudate nucleus (CN). Results showed that RAGE is expressed in at least two cell types in the CN, medium spiny projection neurons and astrocytes, with stronger staining in astrocytes than in neurons. The percentage of the total number of neurons positive for RAGE was significantly higher in G2 and G3 HD CN when compared with controls. What is more interesting however was the heterogeneous distribution of RAGE staining in CN. In controls, astrocytic RAGE staining was seen only in the superficial layer of the subependymal layer (SEL). In G1 HD cases, staining was seen throughout the entire width of SEL but extended into the CN in G2, 3 and 4. Neuronal RAGE staining was stronger in the medial CN than in the lateral CN in control and G1 cases. In G2, 3 and 4 cases, this staining gradient was not observed; more neuronal RAGE staining was however seen in the dorsal part of the CN when compared with the ventral part. The distribution of RAGE staining in neurons appeared to correlate with the ordered cell death seen in HD CN. Identification of the ligand for RAGE in HD brain and further functional studies are needed to clarify the role of RAGE in the pathogenesis of HD.

The germinal matrix (GM) located in the thick subependymal cell layer of the thalamostriate groove is a major site of cerebral hemorrhage in premature infants. Comparing the morphology of vasculature among GM, gray and white matter of the brain may help in understanding the pathogenesis of GM hemorrhage and also of periventricular leukomalacia. The objective of the present study was to determine the morphology of blood vessels in the GM, gray matter, and white matter and to examine maturational changes in the morphology of these vessels as a function of gestational age. We measured vessel density, percentage of blood vessel area, mean surface area, length, breadth, perimeter, radius, and shape of blood vessels in coronal sections of the GM, gray matter, and white matter in postmortem human brain samples for 17 fetuses and premature infants of gestational age 16-40 wk and 2 adults. We performed immunohistochemical staining using anti-laminin primary antibody, confocal microscopy to acquire images, and analysis using Metamorph version 6.1. Vessel density and the percentage of blood vessel area increased as a function of gestational age in the GM, gray matter, and white matter (p < 0.001 each). The blood vessel density and the percentage of blood vessel area were largest in the GM followed by gray matter and then white matter in all of the gestational age categories (p < 0.001 for all comparisons). Increased vascularity of the GM compared with gray and white matter may play a role in GM hemorrhage, whereas a relatively low vascularity of white matter may increase the propensity for the occurrence of periventricular leukomalacia in premature infants

Large brain specimens were prepared from 50 head-injured and 50 non-head-injured cases that underwent medicolegal autopsy to critically examine the morphological changes in the periventricular tissue caused by injury to the head. Hemorrhagic damage to the ventricular wall was observed in 30 (60%) of the head-injury cases but was not observed in any of the non-head injured cases. Of 14 cases with only wounds to the scalp, five cases (35.7%) had ventricular wall damage. Of 40 cases in which death occurred within 24 h after injury, 25 (62.5%) showed ventricular wall damage. Of five cases of dying more than 24 h post-injury, only one revealed ventricular wall damage. This ventricular wall damage was frequently detected in the posterior (46%) and anterior horns (19%) of the lateral ventricle, near the attachment of the choroid plexus (19%). These morphological changes are considered primary damage, formed at the moment of impact in that concomitant hemorrhagic damage to the ventricular wall was also observed in all immediate death cases. Accordingly, detection of ventricular wall damage is considered a reliable means for deducing the occurrence of traumatic injury even in the cases where death occurs soon after injury.

Reports of glioependymal cysts in the posterior fossa are uncommon. There are only a few documented cases of posterior fossa glioependymal cysts and, to our knowledge, this is the first documented case of a recurrent posterior fossa glioependymal cyst. We discuss the clinical presentation, pathological features, and treatment options for this lesion. A 55-year-old woman with a 10-year history of a recurrent cytic lesion in the left cerebellar hemisphere, which required two operations, presented with diplopia, dizziness, and ataxia. Magnetic resonance imaging revealed a multiloculted cytic lesion in the left cerebellar hemisphere. Resection, through a suboccipital craniectomy, resulted in improvement of the patient's neurologic status. Microscopic examination of a surgical specimen revealed complex cysts lined by a single layer of ependyma-like cells and underlying gliotic parenchyma with florid reactive changes. Glioependymal cysts of the posterior fossa may present with symptoms of increased intracranial pressure and compression of local structures. Recurrence in this case may be partly explained by subtotal resection in the previous two operations and may also be associated with a florid, proliferative ependymal element. Definitive diagnosis is by microscopic examination of surgically resected specimens. Total extirpation of these cystic lesions is recommended.

Aims: Paediatric tumours affecting the central nervous system (CNS) constitute the second most frequent group of tumours at this age. Taking the WHO 2000 classification as our starting point, our intention was to describe the more important clinical and pathological features in the differential diagnosis of the different tumourous entities with the highest incidence in childhood. We highlight, above all, the characteristics that justify the need for a smooth flow of information between neurologists, neurosurgeons, neuroradiologists, neuropathologists and oncologists. We do not deal with familial tumourous syndromes, genetic aspects or clinical information derived from analyses of molecular alterations., Development: Among CNS tumours, enough age related differences exist to be able to consider those appearing during childhood in their own right. Their topographic specificity is very characteristic and while 50% of them are infratentorial, 90% of those that occur in adults are supratentorial. Embryonic tumours are very frequent in childhood, but rare in adults, and the opposite happens with meningiomas. They are also different as regards their histological features, clinical characteristics, the early tendency to spread throughout the nervous system in the course of the disease and their biological behaviour. These data make us think that, in the pathogenesis of brain tumours in children, the molecular and epigenetic factors involved are different from those at play in the case of adults., Conclusions: A correct diagnosis requires a multidisciplinary approach and an understanding of the histological criteria and nomenclature by the health professionals involved in treating these patients.

We encountered a brain tumor arising in the right lateral ventricle of a 14-week-old, female Donryu rat and investigated its histological and immunohistochemical characteristics. Macroscopically, the tumor appeared as a grayish mass with a size of 10 mm in diameter, present in front of the right hemicerebrum and well circumscribed on the cut surface. Histological examination revealed the tumor to be a hypercellular mass occupying the front part of the right lateral ventricle and expanding into the area in front of the hemicerebrum, continuing to the ependymal area at its edge. The tumor was constituted by columnar- or pleomorphic-shaped, highly atypical cells of epithelial origin surrounding fibrovascular cores as single or multiple cell layers. Growth was papillary with high proliferating activity. Immunohistochemically, the tumor cells proved positive for cytokeratin but negative for vimentin, S100 protein or glial fibrillary acidic protein, a profile characteristic for the epithelial cells of the choroid plexus, whereas the ependymal cells were found to be positive for all 4 items. In conclusion, the present tumor was diagnosed as a rat choroid plexus carcinoma, only the third such case to be reported in the world literature, with particular features.

The germinal matrix contains a concentrated network of blood vessels. The unusual structural qualities of these vessels are implicated as a factor underlying the high incidence of hemorrhage that occurs in the germinal matrix of prematurely born neonates. The present study is a histologic analysis of an postmortem examination series of brains collected from neonates born between 23 weeks gestation and term and is designed to determine if subependymal veins can be recognized in neonates born at the limits of viability, approximately 23 weeks gestation. Alkaline phosphatase histochemistry is used to differentiate cerebral afferent from efferent vessels. The results demonstrate that precursors of the subependymal veins can be recognized as early as the twenty-third gestational week. These veins increase progressively in diameter from 23 weeks to term, but the wall of the veins, which at early stages consists of endothelial cells only, does not thicken until after postconception week 36. Thus in all premature neonates, including the youngest capable of independent existence, the subependymal veins are present and appear vulnerable to rupture. These data support our suggestion that the structural immaturity of these veins in premature neonates is causally related to the high incidence of germinal matrix hemorrhage in these patients.

Objectives: To investigate the hypothesis that idiopathic intracranial hypertension is associated with diffuse brain oedema, using quantitative magnetic resonance imaging., Methods: Values for the mean diffusivity of water () and the proton longitudinal relaxation time (T1) were measured for various brain regions in 10 patients with idiopathic intracranial hypertension and 10 age, sex, and weight matched controls., Results: No significant differences in and T1 values were found between patient and control groups in any of the brain regions investigated., Conclusions: The results suggest that idiopathic intracranial hypertension is not associated with abnormalities of convective transependymal water flow leading to diffuse brain oedema.

We report five cases of tumors occurring in three children and in two adults. The tumors had unusual histomorphology and a mixture of ependymal and piloid-like astrocytic features and a myxoid stroma similar to myxopapillary ependymomas. MR imaging in three of the cases showed aggressive, intensely enhancing partially cystic hypothalamic-suprasellar masses near midline and near the floor of the third ventricle. In the three pediatric cases, the tumor encased the circle of Willis. This newly characterized tumor, the tanycytoma, has neoplastic cells with histomorphologic and ultrastructural characteristics similar to those of the tanycyte.

Two phases may be recognized in the development of congenital hydrocephalus in the hyh mutant mouse. During embryonic life the detachment of the ventral ependyma is followed by a moderate hydrocephalus. During the first postnatal week the cerebral aqueduct becomes obliterated and a severe hydrocephalus develops. The aim of the present investigation was to elucidate the cellular phenomena occurring at the site of aqueduct obliteration and the probable participation of the subcommissural organ in this process. Electron microscopy, immunocytochemistry, and lectin histochemistry were used to investigate the aqueduct of normal and hydrocephalic hyh mice from embryonic day 14 (E-14) to postnatal day 7 (PN-7). In the normal hyh mouse, the aqueduct is an irregularly shaped cavity with 3 distinct regions (rostral, middle, and caudal) lined by various types of ependyma. In the hydrocephalic mouse, these 3 regions behave differently; the rostral end becomes stenosed, the middle third dilates, and the caudal end obliterates. The findings indicate that the following sequence of events lead to hydrocephalus: 1) denudation of the ventral ependyma (embryonic life); 2) denudation of dorsal ependyma and failure of the subcommissural organ to form Reissner fiber (first postnatal week); 3) obliteration of distal end of aqueduct; and 4) severe hydrocephalus. No evidence was obtained that NCAM is involved in the detachment of ependymal cells. The process of ependymal denudation would involve alterations of the surface sialoglycoproteins of the ependymal cells and the interaction of the latter with macrophages.

We encountered seven children with symptomatic congenital cytomegalovirus (CMV) infection from 1988 to 1995, of whom two (28.6%) developed typical autistic disorder. Case 1: A boy born at 38 weeks' gestation with a birth weight of 3164 g showed generalized petechiae, hepatosplenomegaly, and positive serum CMV-specific IgM antibodies. He was profoundly deaf, mentally retarded, and exhibited a lack of eye contact, stereotyped repetitive play, and hyperactivity. Case 2: A boy delivered at 39 weeks gestation with a birthweight of 2912 g showed non-progressive dilatation of the lateral ventricles observed postnatally. CMV-specific IgM antibodies were positive and CMV-DNA in the urine was confirmed by PCR. The boy was mentally retarded but not deaf. He showed no interest in people and delayed speech development. Subependymal cysts were detected by cranial ultrasound after birth in both patients. This is the first report describing subependymal cysts and the later development of AD. Cranial magnetic resonance imaging revealed an abnormal intensity area in the periventricular white matter suggestive of disturbed myelination; however, no migration disorders were found in our patients. These findings suggest that the timing of injury to the developing brain by CMV may be in the third trimester in some patients with autistic disorder.

Introduction: Acquired fetal brain disorders represent the third indication of fetal brain MRI, after ventricular dilatation and malformations of the central nervous system., Discussion: MRI is an adequate imaging technique for evaluating fetal brain damage. Fetal brain response to brain injury may be acute, chronic or a combination of acute and chronic. An acute response is not as common in the fetal brain as in the postnatal period. A chronic response or the combination of chronic and acute response are the most common responses of the fetal brain to injury, whatever its origin. MRI also provides the natural history of acquired fetal brain lesions with regard to the stage of development.

Ubiquitin-positive inclusions (UbIs) have not been well studied in ependymal cells. Since we detected such UbIs in the central canals of the medulla and spinal cord while investigating UbIs in neurodegenerative diseases, we studied UbIs in the entire ependymal system of 42 patients with various neurological diseases and of 10 non-neurological controls. UbIs were located in the cytoplasm of the ependymal cells, and were round to oval in shape, measuring 4-11 microm in diameter. The UbIs were non-argyrophilic and undetectable by hematoxylin and eosin staining, but mildly reactive to periodic acid-Schiff staining with and without digestion. The UbIs were variably immunoreactive for anti-epithelial membrane antigen (EMA) antibody, but did not react with several other antibodies. The co-existence of ubiquitin and EMA was confirmed by confocal laser microscopy. Throughout the ependymal system, UbIs were variably found in ependymal cells as well as in subependymal cells. There was no significant difference in the overall incidence of either ependymal or subependymal UbIs between the patients with neurological diseases and controls. However, ependymal UbIs in the central canal were more frequent in the neurological disease patients than in controls, although there was no disease specificity. This is the first comprehensive report to show common occurrence of UbIs in the ependymal cells of adult human brains.

A chordoid glioma in the third ventricle was studied immunohistochemically and ultrastructurally. In this report, special attention is paid to the histogenesis in relation to the pathological appearance and unique anatomic location of this tumor. Light microscopic and immunohistochemical findings were similar to those reported previously. Ultrastructurally, microvilli were frequently seen, but three types of abnormal cilia were rarely observed. Basement membrane around the tumor cells and microvessels was extensive. Poorly to moderately developed intermediate (adherent) junctions were frequently seen. Resemblance of these ultrastructural features of the tumor to embryonic tanycytes suggests the tanycytic differentiation of chordoid glioma. Neuroradiologically, all of the previously reported cases of chordoid gliomas seem to arise in the anterior part of the third ventricular floor. This region includes the lamina terminalis, infundibular recess and median eminence, which corresponds to a tanycyte-rich area. These findings suggest a tanycytic origin of chordoid glioma.

Choroid plexus papillomas are rare tumors that are confined to areas in which the choroid plexus is normally located. In children, choroid plexus papillomas are predominantly located in the lateral ventricles. Clinically they present with signs of raised intracranial pressure, such as vomiting and increasing head size. Here we report on the clinical, radiologic, and histologic findings of a 4-year-old female who was found to have a tumor in the posterior fossa that had all the histologic hallmarks of a choroid plexus papilloma. This tumor did not originate from the roof of the fourth ventricle as expected but from the ependymal lining covering the median rostral medulla near the pontomedullary junction, a location that so far has not been reported.

Periventricular enhancement in adults at MRI is a significant finding since it often indicates the presence of an underlying disease requiring prompt medical attention. From a review of patients with periventricular enhancement, the main imaging features based on the underlying infectious or tumoral etiology will be described. The presented differential diagnosis is based on the immune status of the patient, type of enhancement, and response to a trial therapy. In immunocompromised patients, the main considerations are lymphoma and viral ependymitis. The pattern of enhancement is important. The presence of thin linear enhancement suggests a viral etiology (cytomegalovirus or varicella-zoster virus) that can be confirmed at CSF evaluation whereas the presence of nodular enhancement suggests a diagnosis of primary CNS lymphoma that can be confirmed by the presence of lymphomatous cells in the CSF or, more frequently, at stereotactic surgical biopsy performed after failure of response to anti-toxoplasmosis treatment. The presence of band enhancement is less specific and can be seen with viral, lymphomatous and even tuberculous involvement. In immunocompetent patients, a clinical context of infection will suggest bacterial or tuberculous ventriculitis and the presence of cystic lesions will suggest cysticercosis; in the absence of constitutional symptoms, the presence of nodular enhancement will suggest a tumoral process (lymphoma, ependymoma, germ cell tumor, or metastases). Rarely, linear enhancement will be due to sarcoidosis or Whipple's disease.

The term chordoid glioma of the third ventricle was first used to describe a rare and slowly growing neoplasm of uncertain histogenesis, with chordoid appearance, occurring preferentially in middle-aged women. Herein we report two additional examples of this novel entity together with a literature review based on the 25 cases previously published. Our review fully confirms the strikingly stereotyped clinical, neuroradiologic, and pathologic features of this unique tumor. The female/male ratio was 1.7:1, and the age range was 24-70 years (mean 44.9 years). In all 27 cases imaging findings were similar showing a well-defined mass (mean 2.8 cm in largest dimension), ovoid in shape, hyperdense on CT scans, with uniform and intense contrast enhancement, arising in the hypothalamic/suprasellar/third ventricular region. Histologically, the main consistent characteristics were cords and clusters of epithelioid cells within an abundant mucinous and often vacuolated background. Mitoses were sparse or absent and anaplastic features, endothelial proliferation, and necrosis were not identified. Lymphoplasmacytic infiltrates with Russell bodies were frequent throughout the tumor and its interface with adjacent brain parenchyma. Most of the tumor cells revealed a strong and diffuse expression of vimentin and glial fibrillary acidic protein. Additionally, the vast majority of tumors showed focal coexpression of cytokeratins, CD34, S-100 protein, and epithelial membrane antigen; the MIB-1 labeling indices were uniformly low. Surprisingly for a glioma assigned WHO grade II, the 19 patients with an available but short follow-up (mean 22.5 months; range 6-68 months) experienced a rather poor outcome (three recurrences and seven deaths), probably reflecting the anatomic site of the neoplasm that precludes a complete surgical excision rather than its histologic composition. Ultrastructural examination of 10 cases demonstrated findings in line with a glial derivation and a putative ependymal origin such as cytoplasmic intermediate filaments, microvilli, intermediate junctions or desmosomes, and focal basal lamina formation. In our case no. 1, and for the first time in this tumor, we observed sparse and abnormal cilia in an aberrant juxtanuclear location, a further argument for considering chordoid glioma as a subtype of ependymoma. However, a better understanding of the biologic behavior and histogenesis of this distinctive clinicopathologic entity needs to be investigated with a larger series. Nevertheless, taking into account its strikingly consistent anatomic localization, its unique histopathologic and immunohistochemical profile, in conjunction with the most recent and convincing ultrastructural arguments, we suggest that chordoid glioma of the third ventricle could be better classified as chordoid ependymoma of the lamina terminalis area.

Abnormalities of the ependyma can serve as a marker of early brain insults. The presence of ependymal abnormalities was determined in sections containing ependyma of the temporal horn obtained from the Stanley Neuropathology Consortium: 15 subjects with schizophrenia, 15 with bipolar illness, 15 with major depression and 15 normal controls. There were no significant differences in numbers of subjects with ependymal discontinuities or subventricular rosettes. Subjects with schizophrenia had significantly less nodular gliosis than normal subjects (p=0.02); there was a trend for subjects with depression to have less nodular gliosis than normal subjects (p=0.06). Control subjects had unexpectedly high rates of ependymal abnormalities, indicating that ependymal abnormalities may not be a useful marker of pre- or perinatal events associated with schizophrenia and other psychiatric disorders in adult postmortem tissue.

UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from conjugated proteins. Here we present the first report of dysregulation of protein ISG15 modification by the generation of UBP43 knockout mice. In the absence of UBP43, brain tissue showed an elevated level of ISG15 conjugates, and cellular necrosis was evident in the ependyma. Such disruption of the blood-brain barrier resulted in severe neurologic disorders. These results demonstrate that UBP43 plays a critical role in maintaining the homeostatic balance of ISG15-conjugated protein, and that regulation of cellular levels of ISG15 protein modification is essential for brain cell function.

Gene targeting was used to create mice lacking sperm-associated antigen 6 (Spag6), the murine orthologue of Chlamydomonas PF16, an axonemal protein containing eight armadillo repeats predicted to be important for flagellar motility and stability of the axoneme central apparatus. Within 8 weeks of birth, approximately 50% of Spag6-deficient animals died with hydrocephalus. Spag6-deficient males surviving to maturity were infertile. Their sperm had marked motility defects and was morphologically abnormal with frequent loss of the sperm head and disorganization of flagellar structures, including loss of the central pair of microtubules and disorganization of the outer dense fibers and fibrous sheath. We conclude that Spag6 is essential for sperm flagellar motility and that it is important for the maintenance of the structural integrity of mature sperm. The occurrence of hydrocephalus in the mutant mice also implicates Spag6 in the motility of ependymal cilia.

No previous case of hemifacial spasm associated with an ependymal cyst has been reported in the literature. In this article the authors report the first case in which hemifacial spasm accompanied an ipsilateral cerebellopontine angle ependymal cyst in a 27-year-old woman. Cyst fenestration and arterial decompression of the facial nerve at the root exit zone resulted in complete resolution of the patient's symptoms. A histopathological study including immunohistochemical methods identified an ependymal cyst.

Detailed neuropathological examination for vacuolar lesions was performed on the brains of 42 sheep with clinical signs compatible with scrapie. The sheep were grouped according to their breed (Poll-Dorset, Cheviot, Welsh Mountain, Shetland and Suffolk), their PrP genotype at codons 136, 154 and 171 (VRQ/VRQ, VRQ/ARQ, VRQ/ARR and ARQ/ARQ) and the type of infection (experimental infection with SSBP/1, or natural disease). Twenty-two neuroanatomical sites from seven brain regions were examined for vacuolation in the neuropil and five sites at the level of the obex were examined for intraneuronal vacuolation. In 36 sheep, immunohistochemical examination for disease-specific PrP (PrP(d)) accumulation had also been performed in the same brain regions in an earlier study. The magnitude of total neuropil vacuolation was highest in the naturally affected ARQ/ARQ Suffolk sheep and lowest in the experimentally infected VRQ/VRQ Cheviot sheep and VRQ/ARR Poll-Dorset sheep. The severity of neuropil vacuolation at nine of the 22 neuroanatomical sites examined was used to generate a vacuolar lesion profile, which showed variations between the different sheep groups. These variations could be attributed to both PrP genotype and sheep breed and also possibly to scrapie agent; there was, however, considerable individual variation in lesion profile within sheep groups. All groups showed a similar ratio of neuropil vacuolation to neuronal vacuolation at the level of the obex. Although a positive correlation between neuropil vacuolation and PrP(d) deposition was generally observed, it was low except for the astrocyte-associated pattern of PrP(d) accumulation. The study suggests that vacuolar lesion profiles in sheep are affected by several factors and, by comparison with lesion profiles in mice, are of no more than limited value for discriminating between scrapie strains.

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.

The proliferative activity in the subependymal layer of lateral brain ventricles in adulthood is known. We were interested in the reaction of this layer to ibotenic acid lesions, which simulate neurodegenerative processes in Huntington's disease. Animals with a unilateral ibotenic acid lesion were compared with sham-lesioned animals and control animals with intact brains at 5 and 13 weeks after surgery. Five weeks after surgery, increased proliferation was found in most GFAP-positive astrocytes and to a lesser extent in CNPase-positive oligodendrocytes in comparison with controls. Interestingly, a slight increase in proliferation was found as well in the contralateral non-lesioned hemispheres. Moderate elevation of cell proliferation was found after induction of sham-lesions as well. The intensity of the reaction in the subependymal layer decreased in the following 8 weeks. Only a few scattered cells that originated from the subependymal layer had migrated over a short distance to adjacent brain tissue. We conclude that the reaction of the subependymal layer is (a) non-specific, as it is a response to any type of lesion, and (b) slowly decreases in time.

Cerebral hypoxia/ischemia (H/I) of the premature infant is a major cause of cerebral palsy and mental retardation. An important determinant of the ultimate outcome from this insult is the extent to which the stem cells and progenitors in the brain are affected. Irreversible injury to these cells will impair normal development of the infant's brain and, hence, its function. In the present study, we examine early intervals after H/I to identify which cells in the periventricular region are most vulnerable. At 0 h of recovery from a perinatal H/I insult, the choroid plexus shows extensive necrotic damage. The adjacent ependymal and subependymal cells are also affected. Swelling of the ependymal and medial subependymal cells is observed; however, these cells rarely sustain permanent damage. By contrast, cells in the most lateral aspect of the subventricular zone (SVZ) show more delayed, but extensive apoptotic and hybrid cell deaths. Interestingly, activated macrophages/microglia are observed adjacent to the swollen ependymal cells as well as within the affected subependyma. We conclude that the choroid plexus is an especially vulnerable structure in the immature brain, whereas the ependymal and adjacent subependymal cells are relatively resistant to damage. As the medial aspect of the SVZ contains neural stem cells, we predict that neural stem cells will be especially resistant to perinatal H/I brain damage., (Copyright 2002 S. Karger AG, Basel)

Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day the aqueduct becomes obliterated and severe hydrocephalus develops. The aim of the present investigation was to investigate the mechanism of this hydrocephalus, probably starting during fetal life when the cerebral aqueduct is still patent. By use of immunocytochemistry and scanning electron microscopy, mutant (n = 54) and normal (n = 61) hyh mouse embryos were studied at various developmental stages to trace the earliest microscopic changes occurring in the brains of embryos becoming hydrocephalic. The primary defect begins at an early developmental stage (E-12) and involves cells lining the brain cavities, which detach following a well-defined temporo-spatial pattern. This ependymal denudation mostly involves the ependyma of the basal plate derivatives. There is a relationship between ependymal denudation and ependymal differentiation evaluated by the expression of vimentin and glial fibrillary acidic protein. The ependymal cells had a normal appearance before and after detachment, suggesting that their separation from the ventricular wall might be due to abnormalities in cell adhesion molecules. The process of detachment of the ventral ependyma, clearly visualized under scanning electron microscope, is almost completed before the onset of hydrocephalus. Furthermore, this ependymal denudation does not lead to aqueductal stenosis during prenatal life. Thus, the rather massive ependymal denudation appears to be the trigger of hydrocephalus in this mutant mouse, raising the question about the mechanism responsible for this hydrocephalus. It seems likely that an uncontrolled bulk flow of brain fluid through the extended areas devoid of ependyma may be responsible for the hydrocephalus developed by the hyh mutant embryos. The defect in these embryos also includes loss of the hindbrain floor plate and a delayed in the expression of Reissner fiber glycoproteins by the subcommissural organ.

Object: Stereotactically guided implantation of biodegradable microspheres is a promising strategy for delivery of neurotrophic factors in a precise and spatially defined brain area. The goal in this study was to show the biocompatibility of poly(D,L,lactide-co-glycolide) microspheres with brain tissue at the ultrastructural level and to analyze the three-dimensional (3D) ultrastructure after intrastriatal implantation of these microparticles., Methods: Scanning and transmission electron microscopy were used to study the microspheres and their environment after implantation in an inert material (gelatin) and in the rat striatum. Observations were made at different time periods, ranging from 24 hours to 2 months postimplantation., Conclusions: The progressive degradation of the microspheres, with vacuolization, deformation, and shrinkage, was well visualized. This degradation was identical in microspheres implanted in the inert material and in the rat brain tissue, independent of the presence of macrophages. The studies preformed in the striatum permitted the authors to demonstrate the structural integrity of axons in contact with microspheres, confirming the biocompatibility of the polymer. Furthermore, scanning electron microscopy showed the preservation of the 3D ultrastructure of the striatum around the microparticles. These microparticles, which can be stereotactically implanted in functional areas of the brain and can release neurotrophic factors, could represent, for some indications, an alternative to gene therapy.

Objective: We describe a 29-year-old man with gliosarcoma in the lateral ventricle., Case: The patient presented with headache and impairment of consciousness. Computed tomography and magnetic resonance imaging localized the tumor to the right lateral ventricle and showed heterogeneous enhancement with administration of contrast agents. The tumor was partially removed via a transcallosal approach. Histologic examination disclosed gliosarcoma arising by malignant transformation of an ependymoma. POST-OPERATIVE COURSE: The patient died of tumor progression 78 days after admission, despite intensive radiotherapy and chemotherapy.

Primary benign cystic lesions in the brain are uncommon. However, extracerebral cysts like arachnoid cyst, epidermoid cyst and craniopharyngiomas are fairly common lesions. Also, colloid cyst in the third ventricle, dermoid cyst and endodermal cyst in the extracerebral location are not uncommon. On the contrary, intraventricular ependymal and choroidal cysts in the intraventricular location are infrequent. Surgical intervention is warranted in cysts, which produce a mass effect and raised intracranial pressure. We present an interesting case of a giant intraventricular ependymal cyst in the temporal horn in a 14-year-old boy, who presented with recent onset of headaches and epilepsy. He also had long-standing progressive proptosis of the left eye and left temporal bossing. Excision of this cystic lesion was curative. Interesting clinical and neuroimaging features are presented., (Copyright 2001 S. Karger AG, Basel)

The neural adhesion molecule L1, a member of the immunoglobulin superfamily of cell recognition molecules, performs important functions in the developing and adult nervous system. This view is confirmed by the fact that mutations in the human L1 gene cause a severe neurological disease, termed CRASH (acronym for: corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus). X-linked hydrocephalus is certainly the most prominent symptom of CRASH syndrome. Mouse mutants deficient in L1 also develop enlarged ventricles. Here, we report that ventricular dilation in L1-deficient mice is not correlated with stenosis of the aqueduct of Sylvius nor with ultrastructural abnormalities of ependymal cells lining the lateral ventricles or the aqueduct. However, a few L1 mutant mice displayed severe hydrocephalus, characterized by a significant enlargement of the skull and an almost complete atrophy of the cerebral cortex. The aqueduct of these severely affected animals was completely closed. Since mutant animals from two independently generated L1-deficient mouse lines displayed a similar phenotype, we consider severe hydrocephalus as a specific consequence of L1-deficiency. However, results of the present study also indicate that severe hydrocephalus represents a secondary rather than a primary defect of the L1 mutation; our combined data suggest that deformations of the brain as a result of massively enlarged ventricles secondarily cause stenosis of the aqueduct and subsequently high pressure hydrocephalus.

Object: In many cases communicating hydrocephalus is the result of impairments in cerebrospinal fluid absorption in the arachnoid villi at the cranial convexity. Reported methods of creating experimental hydrocephalus have not sought to produce an arachnoidal adhesion in the cranial convexity. In this study the authors investigate alterations in cerebral blood flow (CBF) in experimental communicating hydrocephalus induced by the injection of kaolin into the subarachnoid space at the convexity in neonatal rats., Methods: In neonatal rats, kaolin was injected into the subarachnoid space at the cranial convexity. Assessment of CBF alterations was performed using transcranial Doppler ultrasonography preinjection and at 10 days, 4 weeks, and 8 weeks postinjection. Light microscopy examination was also performed at 4 weeks and 8 weeks postinjection. Conspicuous lateral ventricle enlargements of different dimensions were observed in kaolin-injected rats at 4 to 8 weeks postinjection. The third and fourth ventricles were dilated to a lesser extent. Resistance to CBF and increased mean CBF velocity were apparent 8 weeks after kaolin injection. Further, destruction and even loss of ependymal layers were more prominent at the chronic stage., Conclusions: The present model may be considered a progressive communicating hydrocephalus because of marked changes in blood flow dynamics and destruction of the ependymal layer at the chronic stage.

Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the tumors consisted of monotonous proliferation of long spindle cells with markedly eosinophilic cell processes; focally forming perivascular pseudorosettes. The tumor cells were strongly immunopositive for glial fibrillary acidic protein, S-100 protein and vimentin. Ultrastructurally, in addition to massive intermediate filaments, many tumor cells showed abundant microtubules. Well-developed desmosomes and microvilli/cilia-lined microlumina were occasionally observed. The tumors were grossly totally removed and the patients remain recurrence free at 9, 9, and 2 years postoperatively. Reviewing reported cases including our three cases, tanycytic ependymoma may occur frequently in spinal cord, especially in the cervical region of the spinal cord. Since histologically it resembles pilocytic astrocytoma and schwannoma, tanycytic ependymoma should be included in the differential diagnosis of benign spindle cell tumors of the central nervous system.

Considerable structural plasticity is possible in the damaged neocortex and connected brain areas, and the potential for significant functional recovery remains even during the chronic phases of the recovery process. In this article, the authors review the literature on use-dependent morphologic events, focusing on the direct interaction of behavioral experience and structural changes associated with plasticity and degeneration. Experience-associated neural changes have the potential to either hinder or enhance functional recovery; therefore, issues concerning the nature, timing, and intensity of behavior-based intervention strategies are addressed.

Primary intracranial ependymal cysts are extremely rare. These are congenital, benign ependyma lined, commonly intraparenchymal and uncommonly extraparenchymal cysts in leptomeningeal location of variable size seen in the adult life. The authors report two cases of symptomatic ependymal cysts: one in the perimesencephalic cistern in a 10-month-old infant presenting with delayed mile stones and another in the cerebello-pontine cistern in a morbidly obese 35-year-old woman with known benign intracranial hypertension now presenting with hemifacial spasm. Neurosurgical intervention was curative in both cases. Interesting clinical, radiological and histological features are presented and discussed., (Copyright 2000 Harcourt Publishers Ltd.)

This 17-year-old man was admitted to the hospital due to progressive headache and diplopia. Neuroradiological studies revealed a cystic mass in the pineal region without a parenchymal lesion. In addition, serum alpha-fetoprotein (AFP) levels were elevated. A cyst-to-third-ventricle and cistern fenestration was performed, but the cyst enlarged 3 months after the first operation. In the second operation, subtotal resection of the cyst was performed. The AFP level in the cyst fluid was very high preoperatively but was decreased postoperatively. The patient was discharged with no neurological deficit. Pathological examination of resected tissue showed a single layer of cuboidal cells that resembled an ependymal structure. The cells were immunoreactive for AFP immunostain, which indicated AFP production from these cells.

A spontaneous cerebellar malformation was found in a 32-day-old male Fischer 344 rat. The cerebellar malformation was composed of a vermis defect and markedly dilated fourth ventricle. The cerebellar hemispheres were separated, with the left hemisphere being smaller than the right one. Degenerative/inflammatory lesions consisting of macrophage/lymphocyte infiltration, spheroidal calcium depositions, and astrocytic gliosis were seen adjacent to the cerebral aqueduct. Abnormally arranged hyperplastic ependymal cells were observed beneath the fourth ventricle in the medulla oblongata. The gross findings of the present case resemble those of the human Dandy-Walker malformation. While a precise mechanism remains to be elucidated, degenerative/inflammatory lesions in the present rat may be involved in the pathogenesis of this malformation.

We report a case of a 22-year-old female who presented with a solid tumor in the frontal lobe having no continuity with the wall of the lateral ventricle. The tumor was excised. The patient has been free from clinical symptoms and tumor recurrence for over nine years. Microscopically, the tumor was composed of extremely large ependymal true rosettes, resembling medulloepithelioma, and thick fibrous septa, which were surrounded by thick reactive gliosis. There were no histological signs of malignancy. In our case, the tumor is assumed to be a variant of gliofibroma for which we propose the term "desmoplastic ependymoma".

This report describes a neonatal case in whom a large interhemispheric cyst associated with agenesis of the corpus callosum was revealed by fetal ultrasonography and demonstrated by MRI to be multilobulated. Endoscopic fenestration of cysts was initially designed in view of the development of the patient's brain and surgical invasiveness. One year later, when motor paresis of the left arm and progressive enlargement of the cyst on MRI were revealed, open surgery was performed. The histological diagnosis was a neuroepithelial cyst with the feature of choroid plexus epithelia. The clinicopathological features of interhemispheric epithelial cysts associated with agenesis of the corpus callosum are reviewed in the light of differential diagnosis and therapeutic considerations., (Copyright 2000 S. Karger AG, Basel.)

Ependyma-lined cystic lesions of the subarachnoid space are uncommon. They form a histologically heterogeneous group and have been referred to as epithelial, ependymal, glioependymal and neuroepithelial cysts depending on their respective histological characteristics. In this report, we describe two cases of ependyma-lined cysts in the posterior fossa that support a common pathogenesis for this diverse group of lesions.

Objective and Importance: Symptomatic lateral ventricular ependymal cysts are rare. Two previous cases of this lesion have been reported in the literature. We report a third case and provide radiological and histopathological criteria for differentiating this entity from common intracranial cysts., Clinical Presentation: A 43-year-old man presented with a 6-year history of seizures and progressive right occipitoparietal headaches. Computed tomography and magnetic resonance imaging demonstrated a 4- x 3- x 3-cm nonenhancing cystic mass, expanding the trigone of the right lateral ventricle., Intervention: The patient underwent a right occipital craniotomy. The cyst was opened, fluid was aspirated, the cyst wall was biopsied, and a cyst-subarachnoid communication was established. The patient did well postoperatively, with no seizures and with resolution of headaches., Conclusion: Lateral ventricular ependymal cysts are a rare cause of neurological symptoms, including headache and seizure. Distinctive radiographic characteristics distinguish these cysts at preoperative evaluation. Careful analysis of the histopathology and immunohistochemistry studies correctly identifies these lesions, gives insight into the natural history of ependymal cysts, and guides clinical management decisions.

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.

Background and Purpose: Gray matter heterotopia have been divided into three groups based on clinical and imaging characteristics: subependymal, subcortical, and band heterotopia. Nonetheless, subcortical heterotopia can have variable morphologic findings. The purpose of this study was to perform a morphologic analysis of a series of cases of subcortical heterotopia based on MR images, to correlate the morphologic appearance with clinical characteristics, and to speculate about the embryologic implications of our results., Methods: The MR imaging studies and clinical records of 24 patients with subcortical heterotopia were retrospectively reviewed. The morphologic findings of the heterotopia were recorded along with presence and type of associated malformations. These results were correlated with available data on development and neurologic status., Results: Analysis revealed that, in six cases, the heterotopia were composed exclusively of multiple nodules, in 13, they appeared primarily as curvilinear ribbons of cortex extending into the white matter, and in five, they had deep nodular regions with curvilinear areas more peripherally. All of the curvilinear regions were contiguous with the cerebral cortex in at least two locations. In eight cases, curvilinear heterotopia contained curvilinear areas of flow void that were thought to be blood vessels; in 10, they contained fluid resembling CSF. No difference in developmental or neurologic manifestations was noted among patients with heterotopia of different morphologic appearances., Conclusion: Subcortical heterotopia can have nodular or curvilinear morphologic appearances. Although no difference was found in the clinical conditions of the patients with differing morphologic appearances, additional analysis of these patients or studies of animal models of these malformations may further our understanding of normal and abnormal brain development.

Background: Spinal intramedullary ependymal cysts are extremely rare. Only seven pathologically proven cases have been reported in the literature., Method: We present an 18-month-old female with thoracic spinal intramedullary ependymal cyst that was diagnosed pathologically., Results: Histological diagnosis was made by light microscopy after immunostaining. After partially removing the cyst wall and establishing communication between the cyst and the subarachnoid space, the patient improved neurologically., Conclusions: For spinal intramedullary ependymal cyst we recommend diagnosis by MR imaging without myelography, then enucleation of the cyst, if possible. Otherwise, we remove the cyst wall as much as possible and create adequate communication between the cyst and the subarachnoid space.

We investigated immunocytochemically the expression of tuberin, the TSC2 gene product, in brain resections from children with and without tuberous sclerosis, to characterize the phenotype of balloon and tumor cells, and to elucidate the relationship between tuberin and formation of subependymal giant-cell tumors. In cortical tubers, tuberin was expressed in processes and cell bodies of balloon cells, which also showed consistent vimentin and nestin immunoreactivity, but no glial fibrillary acidic protein, neurofilament, or galactocerebroside positivity by immunofluorescence confocal microscopy. The majority of balloon cells in white matter showed weaker tuberin immunoreactivity than similar cells in cortical tubers. In subependymal giant-cell tumors, there was minimal to no immunoreactivity. Why tuberin is expressed in tubers but not in subependymal giant-cell tumors is not known. If tuberin plays a role in tumor suppression, then lack of tuberin might be a marker for deletion of both alleles, leading to enhanced cellular growth in subependymal giant-cell hamartomas, eventually of sufficient size to cause clinical symptoms.

The development of kaolin-induced hydrocephalus in adult hamsters was monitored by measuring changes in intracranial pressure (ICP), ventriculomegaly (VG) and whole-brain specific gravity (SG). Controls were intact or sham operated animals. Relative to controls, ICP of experimental animals increased at 24 h post intracisternal kaolin injection (by approximately 7-fold), reached a maximum on day 6 (by approximately 12-fold) and remained markedly elevated through day 15 (by approximately 5-fold). Ventricles differed in time of onset of distension (third: day 1, lateral: day 2, fourth: day 4) and in time of maximum ventriculomegaly (fourth: day 6; third: day 7; and lateral: day 9). Ventricular distension resulted in alterations in the ependyma; cilia were lost and apical cell surfaces were distorted. The ependyma was ruptured and the subjacent neuropil was exposed to the cerebrospinal fluid in some regions. Whole-brain SG remained constant in controls but declined in hydrocephalic hamsters after day 3 post-kaolin injection and reached its nadir on day 9 when whole-brain water content was 18% greater than in controls. Consistent with the fact that causal relationships exist between increased ICP, ventricular distension and brain edema, the alterations in each parameter occurred sequentially rather than simultaneously, and the time-course of each manifestation of hydrocephalus differed. The data suggest that the pathophysiology of kaolin-induced hydrocephalus in the hamster is tri-phasic: an initial period of rapid change, a brief interval of maximum alteration, and a subsequent period of compensation.