Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM.

Mechanisms underlying increased vascular smooth muscle contractility in the rabbit basilar artery following subarachnoid hemorrhage.

Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Here, we summarize our current knowledge regarding molecular mechanisms that contribute to increased smooth muscle contractility of rabbit basilar artery following SAH. Our studies demonstrated that upregulation of receptor expression, impairment of feedback regulation of receptor activity, and enhancement of myofilament Ca²âº sensitization might lead to increased smooth muscle contractility following SAH.

Executive function and diffusion in frontal white matter of adults with moyamoya disease.

BACKGROUND: Cognitive impairment is a frequent complication of moyamoya disease (MMD) in adults. Chronic hypoperfusion in frontal lobes can lead to subtle brain injury, resulting in cognitive dysfunctions. Apparent diffusion coefficient (ADC) in normal-appearing white matter on conventional magnetic resonance imaging correlates with cerebral hemodynamics in the frontal lobe. OBJECTIVE: The purpose of this study was to examine the relationship of ADC with executive function in patients with MMD. METHODS: Thirty-one patients (25 women and 6 men; mean age, 32.6 ± 10.4 years) were included in this study. Executive function was evaluated by the Frontal Assessment Battery (FAB) at 21.5 ± 7.5 years after disease onset. ADC was measured in the normal-appearing frontal white matter. RESULTS: ADC was statistically related to the occurrence of executive dysfunction in multivariate analysis (P = .0179). Total FAB score and ADC were negatively correlated (r(2) = .22; P = .0072; Spearman correlation coefficient, -.41; P = .024). Elevated ADC predicted executive dysfunction (area under the receiver operating characteristic curve, .73; 95% confidence interval, .55-.91; P = .029). CONCLUSIONS: The association of ADC with executive function might suggest that ADC is useful in screening for executive dysfunction during follow-up in the outpatient setting.

Pediatric glioblastoma with oligodendroglioma component: aggressive clinical phenotype with distinct molecular characteristics.

The 2007 World Health Organization classification defined a new variant of glioblastoma (GBM) containing oligodendroglioma foci as GBM with an oligodendroglioma component (GBMO), which shows a favorable clinical outcome compared with "classic" GBM. However, all of the reported cases of GBMO have been adult cases, with no previous reports of pediatric cases. In this report, we demonstrated molecular characteristics of a pediatric GBMO case, showing aggressive clinical behavior with 8-month overall survival. The case showed neither isocitrate dehydrogenase 1/2 genes (IDH1/2) mutation nor 1p/19q co-deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite instability, leading to the putative mechanism of temozolomide (TMZ) resistance, was frequently detected. Molecular genetic analysis may provide critical prognostic and therapeutic insights, especially for the pediatric glioma containing oligodendroglioma components.

Usefulness of three-dimensional T1-weighted spoiled gradient-recalled echo and three-dimensional heavily T2-weighted images in preoperative evaluation of spinal dysraphism.

PURPOSE: The aim of this study was to evaluate the usefulness of three-dimensional T1-weighted spoiled gradient-recalled echo (3D T1-GRE) images for the preoperative anatomical evaluation of lumbosacral lipoma, thick filum terminale, and myelomeningocele as a means of compensating for the drawbacks of 3D heavily T2-weighted (3D hT2-W) images. METHODS: Nine patients with lumbosacral lipomas, one patient with tight filum terminale, and five patients with myelomeningoceles were included in this study. 3D T1-GRE images were compared with 3D hT2-W images or conventional magnetic resonance images in terms of delineation of lipomas and other structures in the patients with lipomas and tight filum terminale. For patients with myelomeningoceles, 3D T1-GRE images were compared with 3D hT2-W images in terms of artifacts in the cerebrospinal fluid (CSF) space. RESULTS: The 3D T1-GRE images demonstrated lipomas with good contrast to the spinal cord and CSF space and more clearly delineated the anatomical relationship between lipomas and these structures than did the 3D hT2-W images. The 3D T1-GRE images delineated dural defects through which extradural lipomas penetrated into the intradural space. The 3D T1-GRE images also demonstrated the presence or absence of lipomas in the filum terminale and the absence of artifact in the myelomeningoceles. Furthermore, they were useful for differentiating artifacts observed on the 3D hT2-W images from nerve elements. CONCLUSIONS: The complementary use of 3D T1-GRE and 3D hT2-W images may compensate for the drawbacks of 3D hT2-W images and may eventually improve lesion visualization and surgical decision making.

Dorsal location of the cochlear nerve on vestibular schwannoma: preoperative evaluation, frequency, and functional outcome.

The cochlear nerve is most commonly located on the caudoventral portion of the capsule of vestibular schwannomas and rarely on the dorsal portion. In such a condition, total removal of the tumor without cochlear nerve dysfunction is extremely difficult. The purpose of our study was to identify the frequency of this anatomical condition and the status of postoperative cochlear nerve function; we also discuss the preoperative radiological findings. The study involved 114 patients with unilateral vestibular schwannomas operated on via a retrosigmoid (lateral suboccipital) approach. Locations of the cochlear nerve on the tumor capsule were ventral, dorsal, caudal, and rostral. Ventral and dorsal locations were further subdivided into rostral, middle, and caudal third of the tumor capsule. The postoperative cochlear nerve function and preoperative magnetic resonance (MR) findings were reviewed retrospectively. In 56 patients that had useful preoperative hearing, useful hearing was retained in 50.0% (28 of 56) of patients after surgery. The cochlear nerve was located on the dorsal portion of the tumor capsule in four patients (3.5%), and useful hearing was preserved in only one of these patients (25%) in whom the tumor had been partially resected. This tumor-nerve anatomical relationship was identified in all tumors of <2 cm at preoperative MR cisternography. MR cisternography has the potential to identify the tumor-nerve anatomical relationship, especially in small-sized tumors that usually require therapeutic intervention that ensures hearing preservation. Hence, careful evaluation of the preoperative MR cisternography is important in deciding the therapeutic indications.

Proposed mechanism of cerebral vasospasm: our hypothesis and current topics.

Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Increased vascular contractility can be attributed to either endothelial dysfunction or increased contractility of vascular smooth muscle. Endothelial damage and dysfunction cause impairment of endothelium-dependent vasodilation of the cerebral artery after SAH. In addition to endothelial damage and dysfunction, receptor upregulation in vascular smooth muscle contributes to the induction and enhancement of contractile responses to agonists. Our recent data revealed that feedback regulation of the activity of the G protein-coupled receptor and myofilament Ca(2+) sensitivity is impaired after SAH. This impaired feedback regulation is suggested to cause a sustained contractile response to various agonists, thereby contributing to increased vascular contractility. In addition, three current topics are reviewed: endothelin type A receptor antagonists, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for treatment, and cortical spreading depolarization for the mechanism of cerebral vasospasm.

Surgical techniques for the dissection of encased perforators in giant clinoidal meningiomas.

BACKGROUND: Surgical treatment of giant clinoidal meningiomas remains a challenging task for neurosurgeons. Here, we present details of the surgical techniques for the dissection of encased perforators. METHODS: The dissection of encased perforators is summarized as follows: (1) split the tumor above the encased arteries and perforators; (2) find the entrance and exit points of the perforators, and estimate the running course of the perforators within the tumor; (3) dissect and expose the perforators along the estimated line. CONCLUSIONS: The surgical techniques described in this article will aid in achieving maximum tumor resection while preserving encased perforators.

The transventricular preforniceal approach for exophytic chiasmatic/hypothalamic astrocytomas extending into the anterior third ventricle.

BACKGROUND: Surgical treatment of large exophytic chiasmatic/hypothalamic astrocytomas extending into the anterior third ventricle remains a challenging task for neurosurgeons. In particular, when the tumor extends from the chiasmatic region upward to the foramen of Monro, damage to the fornix and other neurovascular structures is a major concern. OBJECTIVE: To describe the technique used in the transventricular preforniceal surgical approach to remove the superior and superoposterior part of the tumor in the third ventricle for treatment of exophytic chiasmatic/hypothalamic astrocytoma. METHODS: The transventricular preforniceal approach was used in two cases of exophytic chiasmatic/hypothalamic astrocytoma. The approach is summarized in 4 procedures: 1) exposure of the anterior horn of the lateral ventricle by the transcallosal approach, 2) identification of the foramen of Monro and the fornix, 3) incision of the septum pellucidum or the wall of the lateral ventricle, in front of the columns of the fornix, and 4) removal of the tumor through the space between the anterior commissure and the columns of the fornix. RESULTS: Because the tumor compressed the foramen of Monro posteriorly and stretched the space between the anterior commissure and the columns of the fornix, the posterosuperior part of the tumor in the third ventricle was successfully removed through the surgical corridor in front of the columns of the fornix. In both cases, tumors were successfully removed using this approach without damaging the fornix and the anterior commissure. Residual tumor was removed using an anterior interhemispheric translamina terminalis approach in a two-stage surgery. CONCLUSIONS: The transventricular preforniceal approach can be applied for removing the superior part of exophytic chiasmatic/hypothalamic astrocytomas, because the space between the anterior commissure and the fornix is stretched by the tumor, providing an appropriate surgical corridor.

Posterior transjugular and transcervical approach for glomus tumours within the head and neck.

Glomus tumours within the head and neck are highly vascular in nature and are surrounded by vital neurovascular structures. The aim of this study is to review the step-by-step surgical techniques for a posterior transjugular approach and transcervical approach and to clarify the advantages of these approaches in the treatment of glomus tumours within the head and neck. The advantage of these approaches is that a wide operative field from the jugular bulb to the cervical portion can be obtained. In addition, the bloodless operative field that is achieved by the preoperative embolisation appeared to contribute to reducing the risk of cranial nerve injury.

Preoperative evaluation and surgical strategies for craniocervical junction dural arteriovenous fistula with multiple feeders: case report and review of the literature.

Craniocervical junction dural arteriovenous fistula (CCJDAVF) fed by bilateral vertebral arteries (VAs) is extremely rare. We report a case of a 63-year-old man presenting with progressive myelopathy caused by a CCJDAVF, which was fed by bilateral VAs and occipital and ascending pharyngeal arteries with multiple shunting points and that drained into intracranial sinus and spinal veins. The dural arteriovenous fistula (DAVF) was successfully treated surgically using stepwise indocyanine green (ICG) videoangiography. After surgery, the DAVF disappeared and myelopathy was markedly improved. We show detailed preoperative images and intraoperative findings of this rare DAVF and emphasize the importance of selective angiography for preoperative evaluation of feeding arteries and the usefulness of intraoperative ICG videoangiography for both identification of the fistula and confirmation of its obliteration.

Focal cortical dysplasia type IIa underlying epileptogenesis in patients with epilepsy associated with Sturge-Weber syndrome.

In patients with epilepsy associated with Sturge-Weber syndrome (SWS), epileptogenesis has been suggested to be caused by chronic ischemia in cortical areas affected by leptomeningeal angiomatosis or by ischemia-related cortical malformations. However, this has not been fully verified electrophysiologically. We herein present two cases of SWS with medically intractable epilepsy in which the epileptogenic area involved focal cortical dysplasia (FCD) type IIa near the region of leptomeningeal angiomatosis. In both cases, the ictal-onset zones were identified by chronic subdural electrodes, and the presence of FCD type IIa was shown histopathologically. In SWS, especially in association with focal leptomeningeal angiomatosis, FCD may thus play a major role in epileptogenesis. FCD should therefore be demonstrated by the collective findings of perioperative neurophysiologic examination, anatomic and functional neuroimaging, and histopathologic examination.

Concurrent spinal nerve root schwannoma and meningioma mimicking single-component schwannoma.

We present a first case of concurrent tumors consisting of schwannoma and meningioma arising at the same spinal level in a patient without neurofibromatosis. A 49-year-old man without clinical evidence of neurofibromatosis presented with a 5-month history of right neck pain. MRI demonstrated an extradural tumor involving the right-sided C2 nerve root with a small intradural component. T1- and T2-weighted and contrast-enhanced MRI could not differentiate the intradural tumor as different from the extradural tumor. Total removal of the tumors was performed. No contiguity of the extradural tumor with the intradural tumor was seen. The intradural tumor attached strongly to the dura mater around the C2 nerve root exits. Intraoperative pathological diagnosis confirmed the extradural tumor as schwannoma and the intradural tumor as meningioma. We therefore thoroughly coagulated the dura mater adjacent to the intradural tumor and resected the dura mater around the nerve root exits together with the tumor. Pathological examination revealed that the resection edge of the extradural component consisted of a spinal nerve with thickened epineurium and was free of neoplastic cells. No schwannoma component was evident in the intradural tumor. No obvious transition thus existed between the extra- and intradural tumors. Distinguishing these tumors prior to surgery is critical for determining an optimal surgical plan, as schwannoma and meningioma require different surgical procedures. We therefore recommend a careful review of preoperative imaging with the possibility of concurrent tumors in mind.

Intracranial chondrosarcoma located in the region of the posterior clinoid process: a case report.

Intracranial chondrosarcomas located in the region of the posterior clinoid process have not been focused on. Here, we report the case of a 29-year-old woman with a skull base tumor in that region. Seven years after the diagnosis, the tumor had grown and showed calcification and tumor stain; chondrosarcoma, posterior clinoid meningioma, and chordoma were suspected. The patient underwent subtotal tumor resection, and the histopathological study revealed that the tumor was a low-grade chondrosarcoma. Chondrosarcomas can be located in the region of the posterior clinoid process, and not only chordomas but also posterior clinoid meningiomas should be considered as a differential diagnosis of tumors located in that region, especially when the tumor has calcification or receives a vascular supply.

Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells.

Glioblastoma multiforme is the most undifferentiated type of brain tumor, and its prognosis is extremely poor. Glioblastoma cells exhibit highly migratory and invasive behavior, which makes surgical intervention unsuccessful. Here, we showed that glioblastoma cells express Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors assembled from the GluR1 and/or GluR4 subunits, and that their conversion to Ca(2+)-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA inhibited cell locomotion and induced apoptosis. In contrast, overexpression of Ca(2+)-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. These findings indicate that Ca(2+)-permeable AMPA receptors have crucial roles in growth of glioblastoma. Blockage of these Ca(2+)-permeable receptors may be a useful therapeutic strategy for the prevention of glioblastoma invasion.

Focal cortical dysplasia coexisting with diffuse astrocytoma in childhood: a case report and reappraisal of the glial component in archival FCD cases.

We report a rare case of focal cortical dysplasia (FCD) concurring with diffuse astrocytoma and arachnoid cyst, and also re-evaluate the glial component in archival FCD cases for the differential diagnosis of diffuse gliomas. A 7-year-old boy with a 9-month history of psychomotor seizures disclosed a hyperintense area accompanied by a cystic lesion in the left temporal lobe on MRI. The surgical specimen displayed dyslamination of the cortices and ectopic neurons in the white matter, associated with dysmorphic neurons, indicating FCD type IIA. Additionally, the lesion showed diffuse proliferation and infiltration of glial cells, immunopositive for infiltrating glioma markers (nestin, doublecortin, MAP-2e) and p53, and MIB-1 index was 2.0%. These findings indicated coexisting diffuse astrocytoma. Coexistence of diffuse glioma with FCD is unusual, but we often notice increased population of small glial cells in FCD lesions. Re-evaluation of archival FCD cases with diverse markers revealed that reactive microglia significantly proliferate in the white matter lesions. Therefore, a careful pathological assessment has to be made to define a rare case of diffuse glioma occurring in FCD.

Clinicopathological study on chronic encapsulated expanding hematoma associated with incompletely obliterated AVM after stereotactic radiosurgery.

BACKGROUND: Chronic encapsulated expanding hematoma is a rare, but highly morbid, severe complication after stereotactic radiosurgery for intracerebral arteriovenous malformations (AVMs). The aim of this study was to clarify the clinical features and possible mechanisms of formation and expansion of this type of hematoma based on histopathological findings. METHODS: The patients were comprised of three males and one female. Three of these patients had AVMs in the basal ganglia, while the remaining one in the frontal lobe. RESULTS: Cerebral angiograms performed 6 months to 11 years after radiosurgery demonstrated major, but incomplete, obliteration of the nidi. Each patient developed localized enhancing mass lesions at 2, 3, 5, and 11 years after radiosurgery. The lesions expanded slowly, but progressively over time in association with marked perifocal edema. The perifocal edema disappeared immediately after removal of the hematoma; their neurological symptoms improved partially or completely. Histopathologically, the hematomas were well-encapsulated and the capsule walls uniformly consisted of an outer fibrocollagenous layer and an inner granulation layer. Immunohistochemistry revealed vascular endothelial growth factor (VEGF) expression in the endothelium of newly formed blood vessels and myofibroblasts in the hematoma capsule inner layer. Myofibroblasts also expressed VEGFR-1. CONCLUSIONS: The activation of VEGF pathway may lead to neovascularization in the granulation layer of the hematoma capsule that serves as a continual source of bleeding and perifocal edema. Thus, radical resection of the capsule and residual nidus is strongly recommended for the management of both bleeding and edema.

Feasibility of intraoperative motor-evoked potential monitoring for skull base tumors with a high risk of postoperative motor deterioration.

OBJECTIVE: To establish the validity and utility of motor-evoked potential (MEPs) monitoring for skull base tumor resection, we explored the relationship between MEP monitoring results and postoperative motor function. METHODS: MEPs were successfully monitored during 76 operations in 68 patients with a high risk of motor morbidity. MEP monitoring data were correlated with perioperative clinical motor function. RESULTS: MEPs remained stable in 56 operations (73.7%), and no postoperative motor deterioration was observed. Transient or permanent deterioration of MEPs (<50% of the initial amplitude before surgery) occurred in 20 operations (26.3%). This deterioration was reversible after intervention in seven cases (9.2%). Irreversible deterioration in MEPs was seen in 13 cases (17.1%). In five cases, the final amplitude was greater than 10%. Two of these patients experienced transient loss of MEPs and moderate to severe hemiparesis. Both patients showed full recovery within 6 months after the operation. The other three patients experienced no postoperative worsening of motor function. The final MEP amplitude was less than 10% in the other eight patients, including five with permanent MEP loss. All of these patients experienced severe postoperative motor dysfunction. Recovery of motor function was worse in most participants in this group compared with those in the other groups. CONCLUSION: Intraoperative MEP monitoring is a valid indicator of pyramidal tract pathway function for skull base tumor surgery.

Pineal region pilocytic astrocytoma showing uncommon growth: a case report.

Pineal region pilocytic astrocytomas are extremely rare, and there is limited information about their radiological features. We report the case of a 22-year-old woman with a cystic lesion in the pineal region. In the 2 years after diagnosis, the lesion irregularly extended along the bilateral internal cerebral veins and the inferolateral surface of the corpus callosum. Gross total resection was achieved, and the histopathological study revealed that the lesion was a pilocytic astrocytoma. The lesion exhibited uncommon growth, leading to difficulty in establishing an accurate preoperative diagnosis. It should be noted that pineal region pilocytic astrocytomas can demonstrate atypical appearances.

Utility of 3-T FLAIR and 3D short tau inversion recovery MR imaging in the preoperative diagnosis of hippocampal sclerosis: direct comparison with 1.5-T FLAIR MR imaging.

PURPOSE: To examine the utility of fluid-attenuated inversion recovery (FLAIR) imaging and three-dimensional short tau inversion recovery (3DSTIR) imaging using a 3-Tesla (3-T) magnetic resonance (MR) imager in the preoperative evaluation of hippocampal sclerosis (HS). METHODS: Thirteen patients with intractable medial temporal lobe epilepsy who underwent anterior temporal lobectomy with amygdalohippocampectomy were studied. MR images were obtained twice, once with a 1.5-T imager and once with a 3-T imager. The extent of hippocampal resection was determined according to the findings on intraoperative hippocampal electroencephalography. We compared the diagnostic utility of FLAIR for HS between 1.5-T and 3-T MR imaging. In addition, the relationship between the existence of hypointense areas in the hippocampus (HIAs) on 3DSTIR and the severity of HS pathology (as evaluated using Watson's grading) was examined. The relationship between postoperative seizure outcome and postoperatively remaining HIAs was also evaluated. RESULTS: There was no difference between FLAIR images from 1.5-T and 3-T imaging in the detection of HS. With 3DSTIR, an HIA in unilateral hippocampus was observed in all of the nine cases exhibiting severe pathologic HS (Watson's grade III-V). In seven cases with HIA, the extent of hippocampal resection was smaller than the HIAs. Every case showed good seizure outcome (Engel's class I and II). DISCUSSION: In the diagnosis of HS, no substantial difference was noted between 1.5-T and 3-T MR imaging. However, 3DSTIR using 3-T MR imaging is useful for evaluating the extent of HS, although postoperative HS remnants are not correlated with surgical outcomes.