[show abstract][hide abstract] ABSTRACT: Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background.
A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program. A genome-wide association analysis of 26 cases and 30 controls was performed using a GeneChip 10K mapping array. Significance levels for linkage and single single-nucleotide polymorphism association analyses were set at P<0.05 and P<0.0001, respectively. Genotyping was also performed using 58 960 single-nucleotide polymorphisms for 2 sets of discordant twins.
The linkage analysis revealed 7 candidate regions, with the highest logarithm of odds score of 1.88 (P=0.002) at chromosome 6q25. A significant association was observed for 4 single-nucleotide polymorphisms and 2 haplotypes, but none of them overlapped with candidate linkage regions. Genotyping of the twins showed no genetic heterogeneity.
The present study failed to identify genetic factors for arteriovenous malformation although the low statistical power may have resulted in such evidence being missed.
[show abstract][hide abstract] ABSTRACT: Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette-like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber-EP4, antisynaptophysin and anti-S100 protein in all cases. In two cases, LH-RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so-called "olfactory neuroblastoma" on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber-EP4 and LH-RH immunoreactivity.
[show abstract][hide abstract] ABSTRACT: Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette-like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber-EP4, antisynaptophysin and anti-S100 protein in all cases. In two cases, LH-RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so-called “olfactory neuroblastoma” on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber-EP4 and LH-RH immunoreactivity.
[show abstract][hide abstract] ABSTRACT: Medulloblastomas are highly lethal tumors when they recur. Very few patients survive with conventional treatment. This report documents the preliminary study results of a treatment for recurrent medulloblastomas consisting of stereotactic radiation therapy (SRT) with chemotherapy. Four patients had local recurrence without apparent metastases and 8 patients had metastases with or without local recurrence. Twelve patients with 18 lesions underwent SRT as a single session (n=8) or in a hypofractionated manner (n=10) using a gamma knife or modified linear accelerator. All patients then received systemic chemotherapy. Five patients were treated with one to two sequential courses of high-dose chemotherapy with peripheral blood stem cell transplantation. The reduction in tumor size after SRT was often remarkable. Fourteen of 18 lesions treated disappeared 1-6 months after SRT. Two of 4 patients who had local recurrences without apparent metastasis at the time of SRT are alive without evidence of disease 70 and 72 months after SRT, respectively. In contrast, all 8 patients with metastasis had new lesions either in the spinal canal or on the surface of the brain outside the target area of SRT. Median progression-free survival and overall survival from the time of SRT were 9 and 19 months, respectively. The Kaplan-Meier estimates of PFS and overall survival at 3 years were 17 and 25%, respectively. One patient had brainstem edema after SRT causing bulbar palsy and quadriparesis. One patient died of toxicity of chemotherapy. Our experience suggests that local recurrence can be controlled by SRT with chemotherapy but survival of patients with metastases can not be improved effectively by SRT in conjunction with aggressive chemotherapy.
[show abstract][hide abstract] ABSTRACT: Thrombi, encapsulated hematomas, and granulation tissue are frequently seen in cerebral cavernous malformations (CCMs). We investigated the role that these histological changes play in repeated hemorrhages in CCMs as well as lesion growth, examining specimens of CCMs surgically harvested from 20 patients. The immunohistochemical study included thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), which are important regulators of blood coagulation. Thick capsules, which contained blood degradation product, were seen in cases with encapsulated hematomas. Clusters of sinusoidal vessels were found outside of these thick capsules. Granulation tissue with inflammatory infiltrates and capillaries was seen in 4 cases with non-capsulated hematomas. Organizing thrombi were seen in sinusoidal vessels in 15 out of 20 cases. Factor VIII-related antigen staining demonstrated numerous capillaries in and around organizing thrombi and within the thickened vessel walls as well as in both the inner and outer sides of the hematoma capsule. TM and EPCR were positive in the endothelial cells of these capillaries, whereas they were negative in those of capillaries in the brain surrounding the lesions. Our study suggests that thrombosed sinusoidal blood vessels could gradually expand by repeated bleeding from numerous capillaries inside the wall and become encapsulated hematomas, and capillaries outside the thickened vessel wall could become sinusoidal blood vessels. Thrombosis within cerebral venules could be one of the causal factors of CCMs.
[show abstract][hide abstract] ABSTRACT: Capillary hemangiomas have rarely been reported to develop in the brain or spinal cord. Here we report the histological and immunohistochemical features of ten cases of central nervous system capillary hemangiomas (CNSCH) and compare these to those of lobular capillary hemangioma (LCH) of the skin. CNSCH showed a lobular architecture with lobules that were separated by fibrous tissue septa in six cases. The lobules were composed of numerous, tightly packed, capillary-sized vessels. A highly cellular area was seen in six cases. A blood-filled cavernous space and fibroendothelial papillae that mimicked papillary endothelial hyperplasia were seen in four cases. Stromal edema was observed in nine cases. These features were not statistically different from those of LCH of the skin, although the highly cellular area was more prominent and more frequent in cases of CNSCH. Immunohistochemical studies demonstrated no positive staining of endothelial cells within either lesion for erythrocyte-type glucose transporter protein, which is a selective marker for capillary hemangioma of infancy. Vascular endothelial growth factor immunostaining demonstrated positive cells in the solid or immature-appearing areas without vessel lumen formation in both lesions. Some of the endothelial cells and stromal cells were positive for glucocorticoid receptor immunostaining. The MIB-1 index of CNSCH was variable (mean 5.6%) and the apoptotic index of CNSCH was significantly lower than that of LCH of the skin. CNSCH are benign lesions with histological and immunohistochemical features similar to those of LCH of the skin.
[show abstract][hide abstract] ABSTRACT: Capillary hemangiomas are benign tumors or tumorlike lesions that originate from blood vessels and have rarely been reported to develop in the brain or spinal cord. The authors summarize the clinical and histological features of capillary hemangiomas of the central nervous system (CNS).
The clinical features, imaging characteristics, and outcomes in 10 patients with CNS capillary hemangiomas were reviewed. Histological studies included immunostaining with CD31, alpha-smooth muscle actin, vascular endothelial growth factor, and Ki-67 antigen. Three patients with lesions in the brain presented with symptoms of increased intracranial pressure or seizures. Seven patients with lesions in the spinal cord presented with progressive sensorimotor disturbances of the lower limbs. Computerized tomography and magnetic resonance imaging demonstrated well-defined, enhancing lesions associated with marked perifocal edema. Angiography demonstrated hypervascular lesions, which have not recurred after resection. In two cases, multiple satellite lesions resolved after the systemic administration of steroid drugs or interferon-alpha. Histologically, all lesions were consistent with findings of capillary hemangioma of the skin or soft tissues. The CNS lesions differed significantly from other vascular neoplasms, such as hemangioendotheliomas, hemangiopericytomas, and hemangioblastomas.
Capillary hemangiomas of the CNS are benign lesions that can be surgically removed and cured without adjuvant therapy.
Journal of Neurosurgery 08/2004; 101(1):73-81. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ischemic damage of the brain is one of the most important factors for the sequelae of acute subdural hematomas (ASDHs). However, ischemic damage is infrequently addressed in a systematic manner in the clinical setting.
The analysis of ischemic brain damage was performed based on serial computed tomography (CT) scans in 80 patients with traumatic ASDHs. Single photon emission computed tomography (SPECT) for regional blood flow and/or magnetic resonance imaging (MRI) were also performed.
Follow-up CT scans showed ischemic brain damage in 19 patients and no significant damage in 35 patients. The remaining 26 patients progressively deteriorated to the point of brain death. The ischemic brain damage was seen most frequently in the territory of the anterior cerebral artery (13 cases), followed by the territory of the posterior cerebral artery (12 cases). The ischemic damages in the pallidum, the hypothalamus and the thalamus were demonstrated in 4, 8, and 4 cases, respectively. The ischemic damage in the underlying brain that was probably because of the direct compression of the hematoma was seen in only two cases.
Most of the ischemic brain damage noted in this study was because of arterial compression secondary to the brain shift and brain herniation, rather than the direct effect of the hematoma upon the underlying brain. Ischemic brain damage adversely affects outcome morbidity, and the difficulty in preventing ischemic damage in cases with marked brain shift leads to poor outcome in patients with ASDHs.
[show abstract][hide abstract] ABSTRACT: The association of ventricular diverticula with intra- and paraventricular tumors causing obstructive hydrocephalus has rarely been reported.
Records and imaging findings for 57 patients with obstructive hydrocephalus caused by tumors who were treated at our institution were reviewed for the presence of ventricular diverticula. For the anatomic study of ventricular diverticula, data were collected from five cadaveric heads.
Ventricular diverticula were identified on magnetic resonance imaging scans in five cases. Diverticula were similarly located in the quadrigeminal cistern but originated from the medial wall of the atrium of the lateral ventricle in three cases and from the superior portion of the fourth ventricle in two cases. Regression of diverticula occurred in all cases after either insertion of a shunt or removal of the obstructing tumor. The cadaveric study suggested that the choroidal fissure and the rostral portion of the superior medullary velum might be the origins of diverticula from the atrium and from the superior portion of the fourth ventricle, respectively.
Ventricular diverticula should be distinguished from other cystic lesions in the quadrigeminal region. Detection of an ostium of a diverticulum or communication between the cyst and the ventricular system is important for diagnosis.
[show abstract][hide abstract] ABSTRACT: The term "venous angioma" (VA) usually refers to a developmental venous anomaly (DVA). However, a group of vascular malformations called VAs shows no venous abnormalities on angiography. The clinical and histological features of histologically classified VAs were studied in eight patients who presented with hemorrhage or seizures to reevaluate these venous anomalies. Angiography showed no venous abnormalities in six patients. Histological study included immunostaining for smooth muscle actin and glial fibrillary acidic protein. Surgical specimens of 10 cases of cavernous angiomas, 10 cases of arteriovenous malformations, and two cases of capillary telangiectasias were studied to compare these types of VAs. Angiographically occult VAs were surgically removed safely, whereas removal of DVAs was complicated by brain swelling and hemorrhagic infarction of the brain. Histological examination found angiographically occult VAs contained malformed and compactly arranged vessels with partly degenerated walls, whereas DVAs had dilated thin-walled vessels that were diffusely distributed in the normal white matter. This study of our cases and a review of the reported cases of VAs suggests that two different clinical and pathological entities are commonly categorized as "VA," angiographically occult VAs and DVAs. These two entities should be carefully distinguished.