Intraparenchymal meningioma mimicking cavernous malformation: a case report and review of the literature.

INTRODUCTION: A primary intraparenchymal meningioma located in the subcortical region of the brain without a dural attachment is extremely rare. To the best of our knowledge, this is the first report showing that meningioma can mimic cavernous malformations. CASE PRESENTATION: We present the case of a 42-year-old German man who presented to our institution with seizure. Both computed tomography and magnetic resonance imaging scans showed characters of an intra-axial subcortical lesion with a 'popcorn' appearance and hemosiderin deposits in the right parietal lobe. The initial diagnosis was cavernous malformation. Intraoperatively, the lesion presented as a subcortical mass that had no connection to the dura or the ventricle. The histological diagnosis showed a WHO Grade 1 'raddled' psammomatous meningioma with extensive metaplastic ossification. A literature review of 29 cases of intraparenchymal meningiomas regarding their clinical presentations, location and management was performed. CONCLUSIONS: Meningiomas can be found in any region of the brain with and without dural attachment. Intraparenchymal meningiomas can have multiple entities mimicking their presentation. Caution must be used regarding the preoperative differential diagnosis.

Recurrent paraganglioma of Meckel's cave: Case report and a review of anatomic origin of paragangliomas.

BACKGROUND: Paragangliomas are rare, usually benign tumors of neural crest origin. They account for only 0.6% of all head and neck tumors. In the craniocervical area, they are more common in the carotid body and tympanico-jugular regions. To the authors' knowledge, a case of paraganglioma in Meckel's cave has not yet been reported in the medical literature. The pathogenesis and natural history of paragangliomas are still not well understood. We present a case of recurrent paraganglioma in Meckel's cave. CASE DESCRIPTION: A 53-year-old woman was diagnosed with trigeminal neuralgia, dysesthesia and hypoesthesia on the left side of the face, hearing disturbance and a history of chronic, persistent temporal headaches. Magnetic resonance imaging (MRI) showed a lesion located in Meckel's cave on the left side, extending to the posterior cranial fossa and compressing the left cerebral peduncle. The lesion was first thought to be a recurrence of an atypical meningioma, as the pathologist described it in the tissue specimen resected 3 years earlier, and a decision for re-operation was made. A lateral suboccipital approach to the lesion was used under neuronavigational guidance. The tumor was removed, and histological examination proved the lesion to be a paraganglioma. Five months later, the follow-up MRI showed local regrowth, which required subsequent surgical intervention. CONCLUSIONS: A paraganglioma in Meckel's cave is an uncommon tumor in this location. Although ectopic paragangliomas have been described in the literature, a paraganglioma atypically located in Meckel's cave makes a topographic correlation difficult, mainly because paraganglionic cells are usually not found in Meckel's cave. Another peculiarity of the case is the local recurrence of the tumor in a relatively short time despite an attempted, almost gross total resection.

Primary meningeal hemangiosarcoma in a grower pig.

A juvenile female pig found dead was submitted for necropsy. A focal meningeal red mass measuring 3.5 cm in diameter was located over the left olfactory bulb. Histologically, the mass was composed of polygonal-to-spindle-shaped cells forming vascular clefts with focal invasion of the neuropil of the olfactory bulb. Immunohistochemistry revealed strong expression of vimentin, and a variable labeling of factor VIII-related antigen, smooth muscle actin, and neurotrophin receptor p75. The final diagnosis was a primary meningeal hemangiosarcoma.

Desmoplastic ganglioglioma of the spinal cord in a western European hedgehog (Erinaceus europaeus).

Gangliogliomas are composed of neoplastic glial and neuronal cells and are extremely rare tumors of the central nervous system of domestic animals. The present report describes the clinical presentation and the pathomorphological and immunophenotypical characteristics of a desmoplastic ganglioglioma in the spinal cord of a 3-year-old male western European hedgehog (Erinaceus europaeus). Clinically, the hedgehog exhibited a skin wound and therapy-resistant paresis of the left hind limb. Necropsy showed dilatation of the urinary bladder. Histologic examination of the thoracic spinal cord revealed a focally extensive infiltrative mass, which consisted of multiple nodules of smaller bipolar or oligopolar glial cells and variably sized polygonal, ganglionic, neuron-like cells embedded in variable amounts of microcystic neuropilic matrix. An area of spindle-shaped cells arranged in interwoven fascicles and surrounded by a prominent network of reticulin fibers was interpreted as desmoplastic leptomeningeal stroma. Immunohistochemistry revealed a moderate number of glial fibrillary acidic protein and S-100-positive cells and processes. In addition, the ganglionic neuron-like cells expressed neurofilament, microtubule-associated protein-2, and neuron-specific enolase. In summary, this spinal cord tumor was composed of astroglial and neuronal cellular elements, justifying the diagnosis of a desmoplastic ganglioglioma.

Bilateral osteomas arising from the internal auditory canal: case report.

OBJECTIVE: Osteomas arising from the internal auditory canal and developing in the cerebellopontine angle have rarely been reported. We present the first case of bilateral osteomas in this region and describe our management strategy. CLINICAL PRESENTATION: A 30-year-old woman presented with strong vertigo, tinnitus, and hypacusis on the left side. Brain magnetic resonance imaging and computed tomographic scans displayed bilateral cerebellopontine angle osteomas arising from the internal auditory canal. The larger tumor on the left side was found to be compressing the vestibulocochlear nerve. INTERVENTION: Surgery was performed on the symptomatic side via the retrosigmoid approach, and the tumor was removed completely. The vertigo resolved completely after surgery, and the patient had no further tinnitus attacks. An audiogram showed slightly improved hearing with a mean of 20 dB in the main speech area. CONCLUSION: Osteomas should be considered in patients with bilateral cerebellopontine angle tumors. Surgical removal might provide resolution of symptoms.

Bilateral malignant melanoma metastases to the internal auditory canal/cerebellopontine angle: surgical management and preservation of function.

Although intracranial metastases of malignant melanomas are common, localization at the cerebellopontine angle (CPA) or in the internal auditory canal (IAC) is rare, and bilateral presentation especially so. We present the case of a 46-year-old Caucasian woman with bilateral IAC/CPA lesions and a prior history of malignant melanoma on the right leg. During preoperative investigations, the presence of the bilateral IAC/CPA lesions along with several radiologically identified lesions along the neural axis led to the suspicion that she had neurofibromatosis Type 2 despite her history of malignant melanoma and the lack of characteristic skin lesions and family history. Histopathological analysis of the resected lesion confirmed the intraoperative diagnosis of bilateral CPA malignant melanoma metastases. Surgical removal of the tumors via the retrosigmoid approach with preservation of normal bilateral facial nerve function and unilateral serviceable hearing, combined with control of the systemic disease, provided this patient with a near-normal quality of life for at least 42 months after the initial diagnosis of melanoma.

Expression of bcl-2 is associated with microvessel density in olfactory neuroblastoma.

Erythropoietin (Epo) expression is regulated via hypoxia-inducible factor (HIF)-1alpha-directed gene transcription. Activation of the erythropoietin receptor (EpoR) by Epo leads to elevated expression of the anti-apoptotic protein, bcl-2, which has recently been shown to promote angiogenesis in malignant tumors. Expression of HIF-1alpha, Epo, EpoR, and bcl-2 was studied by immunohistochemistry in a series of 20 olfactory neuroblastoma (ONB) samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens and survival analysis was performed to investigate the prognostic value of the examined factors. Immunohistochemical analysis revealed robust expression of HIF-1alpha, Epo, EpoR, and bcl-2 in ONB. Ninety percent of the samples showed HIF-1alpha immunoreactivity and in 60% of the cases, bcl-2 immunoreactivity was observed. A significant positive correlation between the expression levels of HIF-1alpha and bcl-2 and the microvessel density was found. Survival analysis did not reveal any prognostic significance for the tested factors. Expression of HIF-1alpha, Epo, Epo-R, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 may act as a stimulator of angiogenesis in ONB, and thus represents a novel target for anti-angiogenic treatment strategies in the therapy of ONB.

Solitary fibrous tumor of the foramen of Monro.

Solitary fibrous tumors have been described rarely in the central nervous system and only exceptionally within the ventricular system. This benign entity shows histoimmunochemically strong positivity for vimentin and calretinin. Little is known about the pathophysiological aspects. The authors report on a 75-year-old woman who presented with clinical signs of occlusive hydrocephalus including cognitive deficits, urine incontinence and gait disturbance. Imaging studies demonstrated a tumor at the foramen of Monro which was thought to be a colloid cyst and she underwent CSF shunting. After recurrent episodes of shunt dysfunction the tumor was removed via a transventricular approach guided by endoscopic ventriculoscopy. The histopathological examination revealed a solitary fibrous tumor. This is the first report on a solitary fibrous tumor located at the foramen of Monro in an elderly patient. Surgical removal has been considered to be the best therapeutic strategy in treating this rare entity with no need of postoperative adjuvant therapy. Further imaging and histological studies are needed to improve understanding of the pathophysiological aspects behind it.

Auditory midbrain implant: histomorphologic effects of long-term implantation and electric stimulation of a new deep brain stimulation array.

HYPOTHESIS: Chronic implantation and electric stimulation with a human prototype auditory midbrain implant (AMI) array within the inferior colliculus achieves minimal neuronal damage and does not cause any severe complications. BACKGROUND: An AMI array has been developed for patients with neural deafness and, based on animal studies, has shown to possess potential as an auditory prosthesis in humans. To investigate the safety of the AMI for clinical use, we characterized the histomorphologic effects of chronic implantation and stimulation within its target structure, the inferior colliculus. METHODS: Eight cats were chronically implanted for 3 months, and histologic sections were analyzed to assess long-term tissue effects. Four of the 8 cats were additionally stimulated for 60 days (4 h/d) starting 4 weeks after implantation to assess if clinically relevant stimuli further affected the tissue response. RESULTS: In general, both neurons and neuropil surrounding the implant track were apparently unaffected, whereas a fibrillary sheath (approximately 50 microm thick) developed around the array. There was a significant decrease in neuron density 50 to 100 microm away from the track with a significantly elevated number of glial cells out to approximately 250 to 350 microm. Chronic stimulation seemed to improve the tissue response and neuronal survival around the implant, although further studies are needed to confirm this finding. CONCLUSION: The histomorphologic effects and extent of neuronal damage observed for our AMI array are similar to those of other neural implants currently and safely used in humans. The minimal tissue damage surrounding the implanted array is encouraging with regard to the safety of the array for human use.

Cavernous hemangioma of the cavernous sinus, skin, and retina: hemodynamic changes after treatment: case report.

OBJECTIVE: There are several reports concerning cavernous hemangiomas of the skin and central nervous system. Additional retinal involvement has also been reported. CLINICAL PRESENTATION: The authors report a 69-year-old woman with a giant extra-axial cavernous hemangioma of the right cavernous sinus involving the supra- and parasellar region, retina, and skin. INTERVENTION: Shrinkage of its cutaneous part lead to subsequent increase of the volume of the intracranial part. Owing to compression of the optic and the oculomotor nerves, oculomotor disturbances, ptosis, and visual impairment to 0.2 occurred. Via a pterional approach microsurgical removal of the tumor except for a remnant of the intracavernous part was performed. CONCLUSION: Hemodynamic connection between cutaneous, retinal, and intracranial hemangiomas should be considered.

Efficacy of clonal deletion vs. anergy of self-reactive CD4 T-cells for the prevention and reversal of autoimmune diabetes.

The self-reactive CD4 T-cells play an essential role in triggering and sustaining organ-specific autoimmune diseases. Silencing or elimination of these cells can prevent and reverse an autoimmune process. We have previously showed that a single dose-administration of a soluble dimeric MHC II-peptide chimera (DEF) in double-transgenic mice delayed the onset autoimmune diabetes, and restored the euglycemia in already diabetic mice for a period of 1 week. DEF dimer protection relied on induction of anergy of diabetogenic CD4 T-cells in spleen, and stimulation of IL-10-secreting T regulatory type 1 cells in pancreas. Herein, we show that an octameric form of DEF has doubled the period of protection and reversal of disease by clonal deletion of diabetogenic CD4 T-cells in both the thymic and peripheral compartments. Deletion occurred by activation-induced cell death subsequent to repartitioning and signaling of FAS-FADD apoptotic module in the plasma membrane lipid rafts. Our previous and present data indicated first, that DEF valence translates into various effects on the antigen-specific CD4 T-cells, i.e., Th2 immune deviation, anergy, and apoptosis. Second, the present findings argue for a better efficacy of clonal deletion than anergy of diabetogenic CD4 T-cells for the protection and reversal of autoimmune diabetes.

Supracallosal longitudinal fiber bundle: heterotopic cingulum, dorsal fornix or Probst bundle?

A thick longitudinal fiber bundle found within the dorsal corpus callosum in two unrelated adults (in a micrencephalic female patient and incidentally in another male patient) is considered to be a congenital aberrant cingulum. Agenesis or apparent hypoplasia of the indusium griseum of the limbic-cingular system as an accompanying finding in the present cases may support this hypothesis. The dorsal fornix and Probst bundle are discussed in terms of differential diagnosis, although there was no further support for this possibility. The hyperplastic dorsocallosal gray substance is excluded.

Halofuginone inhibition of COL1A2 promoter activity via a c-Jun-dependent mechanism.

OBJECTIVE: The naturally occurring compound halofuginone has been shown to antagonize collagen synthesis by fibroblasts both in vitro and in vivo. We previously demonstrated that this inhibitory property was related to the ability of halofuginone to disrupt transforming growth factor beta signal transduction. The present study further analyzed the ability of halofuginone to affect transcription factors that can regulate type I collagen gene expression by examining its effect on c-Jun, the negative regulator of collagen gene transcription. METHODS: The phosphorylation state of c-Jun in the presence of halofuginone was examined via direct Western blotting, and the transcriptional activity of the activator protein 1 (AP-1) binding element via electrophoretic mobility shift assay and luciferase reporter assay. We determined whether the effect of halofuginone on collagen synthesis was dependent on the presence of c-Jun by ectopic expression of a wild-type or dominant-negative c-Jun construct in the presence of halofuginone and assaying alpha2(I) collagen promoter strength via luciferase reporter assay. The effect of halofuginone on alpha2(I) collagen message levels in fibroblasts when wild-type or dominant-negative c-Jun was overexpressed was determined. We also determined whether halofuginone had an effect on the phosphorylation state of c-Jun in the skin of TSK/+ mice via immunohistochemistry. RESULTS: Treatment of fibroblasts with 10(-8)M halofuginone enhanced basal and mitogen-mediated phosphorylation of c-Jun in culture. This elevated phosphorylation of c-Jun correlated with enhanced DNA binding and transcriptional activation of an AP-1 complex consisting of c-Jun and Fos but lacking the c-Jun antagonist JunB. Overexpression of c-Jun enhanced in a dose-dependent manner the ability of halofuginone to inhibit the activity of a luciferase reporter construct under control of the -3200-bp to +54-bp COL1A2 promoter, whereas the expression of a dominant-negative c-Jun construct abolished this effect. Northern blotting showed that overexpression of c-Jun enhanced the ability of halofuginone to reduce collagen alpha2(I) messenger RNA levels in fibroblasts, whereas expression of the dominant-negative c-Jun abolished this effect. Topical administration of a halofuginone-containing cream for 20 days to TSK mice, which spontaneously develop dermal fibrosis, greatly increased the phosphorylated form of c-Jun in the skin; this was followed by a decrease in skin thickness and type I collagen messenger RNA expression. CONCLUSION: Our findings illustrate the powerful down-regulatory property of c-Jun toward type I collagen and establish that halofuginone exerts its effect on collagen synthesis in a c-Jun-dependent manner.

Expression of JC virus agnoprotein in progressive multifocal leukoencephalopathy brain.

To examine the function of JC virus (JCV) agnoprotein, we examined the brains of cases of progressive multifocal leukoencephalopathy (PML), which is caused by JCV infection, using a newly generated antibody. The antibody reacted with 8 kDa protein specific for JCV agnoprotein by Western blotting. In vitro analyses showed that JCV capsid protein VP1 and large T antigen (T-Ag) were localized in the nuclei, but that agnoprotein was mainly detected in the cytoplasm of JCV-infected cells with an occasional nuclear staining. In the PML brain, an immunoreactive signal for agnoprotein was distributed in the perinuclear areas and cytoplasmic processes with occasional punctate staining in demyelinating lesions as well as adjacent myelinated areas. Agnoprotein presented mostly in the infected oligodendrocytes and partly in the astrocytes. Using double immunostaining, agnoprotein was seen to be expressed in the cytoplasmic processes of the cells, the nuclei of which were labeled with VP1 and T-Ag, where virus particles existed. Thus, JCV agnoprotein was mostly expressed in the infected oligodendrocytes and mainly localized in the cytoplasmic processes apart from virus particles in the demyelinated lesions.

De novo development of a cavernous malformation of the brain: significance of factors with paracrine and endocrine activity: case report.

OBJECTIVE AND IMPORTANCE: De novo development of cavernous malformations is poorly documented in the literature. CLINICAL PRESENTATION: We report the case of a 37-year old woman with de novo growth of a cavernous malformation of the brain. The patient presented with a 12-month history of nonspecific headaches and paresthesias after two pregnancies. After computed tomographic scanning of the cranium, a cavernous malformation located parieto-occipitally within the right brain hemisphere was diagnosed. Control magnetic resonance imaging scans obtained 12 years earlier did not reveal a similar lesion. INTERVENTION: Surgery was performed, and the specimen was analyzed histopathologically. CONCLUSION: Immunohistochemistry demonstrated lack of expression of pituitary hormones as well as of androgen, estrogen, and progesterone hormone receptors. However, strong expression of both basic fibroblast growth factor and CD44 was detected in surrounding tissue, and expression of CD44 was noted within the matrix of the cavernous malformation.