Measurement of cerebral vascular reserves with I-123 IMP SPECT without an arterial input function using the microsphere model and radiopharmaceutical dose calibration.

OBJECTIVES: Cerebral vascular reserve (CVR) is an important indicator for the management of and therapy for cerebral arterial occlusive disease (CAOD). Vasodilatory function is measured using the standard IMP-ARG method. The IMP autoradiography (IMP-ARG) method employed here uses a standardized input function, which was derived from 12 patients between 31 and 71 years of age. Because the population of elderly patients continues to increase in Japan, additional therapies are required to assess CVR in elderly patients with chronic cardiopulmonary disease or a history of smoking, in particular. Despite its popularity, alternatives to the IMP-ARG method are necessary. Here, we proposed the microsphere (MS) method without an input function. METHOD: Using this method and the IMP-ARG method, we measured the CVRs of 18 CAOD patients. RESULTS: The CVRs derived with these two methods were significantly and linearly correlated (r = 0.89, p < 0.01). CVRs categorized by severity were also found to correspond between the two methods (κ = 0.87). CONCLUSIONS: Thus, the method proposed here may serve as a supplemental to and be compatible with the IMP-ARG method for the assessment of CVR. Furthermore, the two methods, when used in conjunction, may result in less error than either would alone.

Effect of Notch expression in glioma stem cells on therapeutic response to chemo-radiotherapy in recurrent glioblastoma.

Glioma stem cells (GSCs) have the capacity to repopulate tumors and mediate resistance to radiotherapy and chemotherapy. The Notch signaling pathway is important in proliferation, stem cell maintenance, cell differentiation, and tumorigenesis in GSCs. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. In vitro study, the γ-secretase inhibitor inhibited NICD, Hes1 and pVEGFR2 expressions in GSCs. GSCs cultured under endothelial conditions undergo endothelial differentiation. Tumor samples were collected from 27 patients at the time of tumor recurrence. We used immunohistochemical techniques to compare expression of CD133, Notch-1 and VEGF. Expressions of CD133-, Notch-1-, and VEGF-positive glioma cells were higher in recurrent glioblastoma after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence. OS was significantly longer in cases with Notch-1 negativity (8.8 months) than in those with I Notch-1 positivity (6.8 months). We noted that GSCs have the potential for endothelial differentiation with Notch activity. We believe that Notch-1 is a potential target and/or biomarker for antiangiogenic treatments.

An Intra-Abdominal Pseudocyst around a Ventriculoperitoneal Shunt due to Streptococcus Infection 7 Years after Shunt Surgery.

In 1999, a 50-year-old woman underwent ventriculoperitoneal (VP) shunt surgery for hydrocephalus after subarachnoid hemorrhage. She was hospitalized for fever and recurrent systemic seizures in November 2006. Head computed tomography (CT) showed only old changes. The seizures and fever were controlled by medicinal therapy. However, in December, her consciousness level suddenly decreased, and she showed progressive lower abdominal distension. Head CT showed marked ventriculomegaly, and abdominal CT showed a giant cystic mass at the shunt-tube tip in the lower abdominal cavity. Because thick pus was aspirated from the intra-abdominal mass, we diagnosed the patient with acute obstructive hydrocephalus due to an infected abdominal pseudocyst. Laparotomy and direct cyst drainage were performed, and antibiotic therapy against Streptococcus, the causative pathogen, was administered. The VP shunt tube was replaced. The postoperative course was uneventful, and postoperative CT showed hydrocephalus improvement and no pseudocyst recurrence. Abdominal pseudocysts, which are rare after VP shunt surgeries, usually occur after the subacute postoperative course in younger cerebral hemorrhagic cases. Our case was quite rare because the cyst developed in the chronic phase in an older patient and was caused by streptococcal infection. The cyst components should be examined before cyst drainage when choosing surgical strategies.

Treatment of moyamoya syndrome associated with systemic lupus erythematosus and hypothyroidism in an adult by encephaloduroarteriosynangiosis: a case report.

A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral (99) (m)Technetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.

Posttraumatic cranial cystic fibrous dysplasia.

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

Linezolid treatment for intracranial abscesses caused by methicillin-resistant Staphylococcus aureus--two case reports.

Two patients were treated for intracranial infections involving methicillin-resistant Staphylococcus aureus (MRSA). A 30-year-old woman was admitted to our hospital for intracerebral hemorrhage related to arteriovenous malformation. After decompressive craniectomy, the patient developed an epidural abscess. MRSA was isolated from the pus culture. The infection did not improve after intravenous vancomycin (VCM) administration for 15 days. However, after administration of linezolid (LZD) for 14 days, the infection had improved, and the white blood cell count and C-reactive protein values had normalized. A 53-year-old woman had previously undergone 3 operations for craniopharyngioma before the age of 35 years. She was admitted to our hospital with fever and disturbance of consciousness. Magnetic resonance imaging with contrast medium revealed a brain abscess caused by MRSA. After 14 days of intravenous administration of VCM, the infection had not improved and intravenous administration of LZD was initiated. After administration of LZD for 14 days intravenously and 14 days orally, the infection had improved, and the white blood cell count and C-reactive protein values had normalized. VCM is highly effective against MRSA infection, but penetration into the central nervous system (CNS) is poor. LZD has good CNS penetration, so should be considered for secondline antibiotic therapy for VCM-resistant intracranial MRSA infection.

Dynamics of global gene expression changes during brain metastasis formation.

As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1-9 after injection. We performed histological observation and genome-wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed "perivascular proliferations". Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k-means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase-specific expression.

[A case of encapsulated intracerebral hematoma mimicking metastatic brain tumor].

We report a case of encapsulated intracranial hematoma (EIH) mimicking metastatic brain tumor. A 77-year-old male with a medical history of prostate cancer was admitted to our hospital presenting with progressive left hemiparesis. Previous head CT scan and MRI findings during 3 weeks before admission revealed a subcortical acute to subacute hematoma under the right precentral gyrus with growing perifocal brainedema. The Head DSA showed tumor-stain with vascular compression corresponding to the hemorrhagic mass, and Tl-201 SPECT study revealed high L/N ratio (3.0) and high L/E ratio (0.8). The preoperative diagnosis was metastatic brain tumor originating from prostate cancer, and total removal of the mass was undergone with the postoperative diagnosis of EIH. Neither tumoral component nor vascular malformation was found even by detailed pathological study. EIH is a rare variant of intracranial hemorrhage and most of cases in past reports are preoperatively misdiagnosed as malignant brain tumor. In our case, even Tl-201 SPECT and DSA, which are reported as key studies for distinguishing EIH from other brain tumors, demonstrated brain tumor-like findings. It is necessary to consider the possibility of EIH when we encounter hemorrhagic mass in the brain parenchyma even with brain tumor-like radiographical images.