Nobuyuki Yasui

Long-term Follow-up Study of Unruptured Intracranial Aneurysms

OBJECTIVE The purpose of this study was to clarify the risk of rupture of unruptured intracranial aneurysms among large groups of patients with various underlying diseases or conditions. METHODS A long-term follow-up study of unruptured intracranial aneurysms was performed with 360 patients who were treated conservatively during the period from April 1969 to December 1992. RESULTS Follow-up evaluation (between February and June 1994) could be performed for 234 (65%) of the patients. The underlying diseases included multiple aneurysms with subarachnoid hemorrhage for 60 patients, cerebral infarction for 108, intracerebral hemorrhage for 27, and other diseases for 39. Single aneurysms were present in 171 patients and multiple aneurysms in 63. The mean follow-up period was 75 months (range, 3-270 mo). Of the 234 patients, 132 (56.4%) survived, 59 (25.2%) died because of other diseases, 9 (3.8%) underwent surgery, and 34 (14.5%) showed bleeding from unruptured aneurysms, which was fatal for 18 of the patients. The average annual rupture rate for all patients was 2.3% (subarachnoid hemorrhage, 3.2%; cerebral infarction, 2.2%; intracerebral hemorrhage, 3.2%; other diseases, 3.6%). There were no significant differences among the patients according to underlying disease or aneurysm site. The cumulative rate of bleeding for all patients was 20% at 10 years after diagnosis and 35% at 15 years. The cumulative probability of rupture was significantly higher for the multiple aneurysms than the single aneurysms (P < 0.001). CONCLUSION The risk of rupture of unruptured aneurysms is high, especially for multiple aneurysms, but there are no significant differences in the risk of rupture according to the underlying disease or the aneurysm location. Radical treatment should be considered for patients with unruptured intracranial aneurysms.

Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury

We studied 15 patients clinically suspected to have recurrent brain tumor or radiation injury, using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) and L-methyl-11C-methionine (11C-Met). PET with 11C-Met (Met-PET) clearly delineated the extent of recurrent brain tumor as focal areas of increased accumulation of 11C-Met, and was useful for early detection of recurrent brain tumor. PET with 18FDG (FDG-PET) showed focal 18FDG-hypermetabolism in one patient with malignant transformation of low grade glioma, and demonstrated its usefulness for evaluation of malignant transformation. 18FDG-hypometabolism was observed in all patients with radiation injury, but was also found in one patient with recurrent malignant brain tumor. 11C-Met uptake in 3 patients with radiation injury was similar to that of the normal cortical tissue. FDG-PET can be used to initially exclude recurrent brain tumor which is seen as 18FDG-hypermetabolism. The combined use of Met-PET in addition to FDG-PET can improve the accuracy of differentiation of recurrent brain tumor with 18FDG-hypometabolism from radiation injury.

Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL.

Mild hypothermia is considered to have a protective effect during ischemic neuronal cell death. The present study provides experimental evidence for this beneficial role of mild hypothermia using reversible middle cerebral artery occlusion (MCAo) in a Sprague–Dawley (SD) rat model. MCAo was induced in rats for 1 h followed by reperfusion at different periods. Hematoxylin–eosin (HE) staining in normothermic (NT) 37°C and hypothermic (HT) 33°C groups of rats confirmed cerebral infarcts. The mean per cent infarct area was significantly reduced in the HT group of rats. Immunohistochemical analysis was done using anti‐Fas and caspase‐3 antibodies. The immunohistochemical expression of Fas and caspase‐3 was demonstrable as early as 5 h after reperfusion, but the expression pattern maximized at 24 h after reperfusion. The expression of Fas and caspase‐3 proteins showed a clear decrease in the HT group over the NT group. In situ detection of DNA fragmentation was done using the terminal deoxy‐nucleotidyl transferase‐mediated dUTP‐biotin nick end‐ labeling method (TUNEL). TUNEL‐positive cells were first observed at 5 h after reperfusion and progressively increased by 24 h. A higher number of TUNEL‐positive cells was found in the NT group, but they were significantly decreased in the HT group. Further, DNA fragmentation was confirmed by size fractionation in agarose gel. These findings demonstrate a positive relation between the expression of Fas, caspase‐3 and TUNEL‐positive cells. Mild expression of Fas and caspase‐3 proteins and a reduced number of TUNEL‐positive cells in the HT group is clear evidence for the protective role of hypothermia in ischemia‐induced cell death.

Diffusion-weighted magnetic resonance imaging in patients with subarachnoid hemorrhage.

OBJECTIVE To evaluate the occurrence and distribution of direct brain injury caused by acute subarachnoid hemorrhage (SAH) by the use of magnetic resonance imaging. METHODS Computed tomography and magnetic resonance imaging, including diffusion-weighted imaging (DWI), were performed in 32 patients with SAH by use of a 1.5-T whole-body superconductive scanner equipped with an echo planar imaging system. In all cases, computed tomographic and magnetic resonance imaging scans were obtained at the time of admission, before angiography and surgical intervention. RESULTS No abnormalities were revealed by DWI in any of the low-grade SAH patients. However, five (71%) of seven patients diagnosed as having poor-grade SAH (World Federation of Neurosurgical Societies Grades 4 and 5) displayed multiple, patchy focal abnormalities on DWI. Computed tomographic scans obtained at admission failed to clearly demonstrate all of the damaged areas of the brain that were visualized by DWI. These lesions were located in supratentorial cerebral parenchyma, but not in the thalamus, basal ganglia, or cerebellar hemisphere. These multiple widespread lesions exhibiting laminar involvement of the cerebral cortex were not associated with the site of the ruptured aneurysm. CONCLUSION DWI revealed widespread multifocal lesions in the cerebral cortex of acute poor-grade SAH patients. DWI provides accurate images of all areas of brain damage directly attributable to SAH.

Morbidity and mortality from surgical treatment of unruptured cerebral aneurysms at Research Institute for Brain and Blood Vessels-Akita.

OBJECTIVE:Although the necessity of craniotomy for an unruptured cerebral aneurysm (UCA) is controversial, surgery is warranted if surgical risks are less than the risks of natural history. In this study, we investigated the need for craniotomy for UCAs on the basis of surgical risk. METHODS:History of cerebrovascular disorders, aneurysm site and size, surgical complications, and clinical outcome were investigated in 368 patients (134 men, 234 women; ages 31–79 yr) who underwent craniotomy for treatment of UCA at our institute between 1993 and 2000. RESULTS:We investigated 549 aneurysms. The mean size was 6.0 mm. Sites affected were the anterior cerebral artery (101 aneurysms), internal carotid artery (224 aneurysms), middle cerebral artery (201 aneurysms), and vertebrobasilar artery (23 aneurysms). The most common previous cerebrovascular disorders were subarachnoid hemorrhage (58 patients, 15.8%) and cerebral infarction (41 patients, 11.1%). Eight patients experienced permanent neurological deficits, for a total morbidity of 2.2%. One patient died, for a total mortality of 0.3%. For UCAs less than 10 mm in size, the morbidity was 0.6% and the mortality was 0%. For UCAs greater than 10 mm in size, the morbidity was 6.1% and the mortality was 1.2%. For UCAs in the anterior cerebral artery or middle cerebral artery, the morbidity was 0.3%. Temporary deficits were more frequently observed in patients older than 70 years of age than in patients 70 years of age or less. CONCLUSION:Surgical treatment is a viable alternative for patients 70 years of age or less with UCAs less than 10 mm in size or UCAs located in the anterior cerebral artery or middle cerebral artery, because the surgical risk of treating such UCAs is sufficiently lower than the annual rupture rate of UCAs (2.3%) and the mental stress suffered by patients with untreated UCAs.

Human brain tumor O6-methylguanine-DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy

O6‐methylguanine‐DNA methyltransferase (MGMT) removes and repairs chloroethylnitrosourea (CENU)‐induced O6‐methylguanine‐DNA by accepting the alkyl group at a cysteine moiety. MGMT activity is, therefore, predictive of resistance or sensitivity to CENU chemotherapy. We measured the levels of MGMT mRNA expression in human brain tumors using a reverse transcription‐polymerase chain reaction (RT‐PCR) method, and studied the significance of MGMT mRNA levels in CENU chemotherapy. The level of MGMT mRNA was represented as a percentage relative to the MGMT mRNA in UI38MG brain tumor cells. Forty‐three patients with brain tumors were entered into the study. High‐grade gliomas had significantly lower levels of MGMT mRNA than did low‐grade gliomas and non‐glial tumors (p < 0.05 determined by analysis of co‐variance). Out of 14 high‐grade gliomas, 4 had a level of MGMT mRNA below 10%, indicating chemosensitivity to CENU. Out of 11 patients who received CENU chemotherapy, 3 had a partial response. All 3 responders had a low level of MGMT mRNA. The time to tumor progression (TTP) for 6 patients with a level lower than the median was short, but significantly longer than the TTP for 5 patients with a higher level (p < 0.05 determined by Gehans Wilcoxon test). These results indicate that a fraction of brain tumors have a low expression of MGMT mRNA, and that the level of MGMT mRNA is a useful indicator of effectiveness in selective CENU chemotherapy.

Ruptured anterior spinal artery aneurysm: a case report

BACKGROUND Spinal artery aneurysms are rare, and are usually found in association with arteriovenous malformations or coarctation of the aorta. CASE REPORT A 42-year-old man with a ruptured anterior spinal artery aneurysm is presented here. He experienced subarachnoid hemorrhage, which was confirmed by computed tomography. Magnetic resonance imaging revealed an aneurysm in front of the upper part of the medulla. Angiography demonstrated bilateral vertebral artery occlusion. Distal vertebral arteries and the basilar artery were perfused via the dilated anterior spinal artery, which originates in the right subclavian artery. The aneurysm was located at the distal part of the anterior spinal artery, and was successfully clipped through a lateral suboccipital craniotomy 2 months after bleeding from the aneurysm. After rehabilitation, the patient was able to walk with no apparent neurologic deficit. CONCLUSIONS This case suggests that the anterior spinal artery as a collateral route after bilateral vertebral artery occlusion is under hemodynamic stress, resulting in aneurysm formation and rupture.

Evaluation of the FloTrac uncalibrated continuous cardiac output system for perioperative hemodynamic monitoring after subarachnoid hemorrhage.

Early hemodynamic assessment is of particular importance for adequate cerebral circulation in patients with aneurysmal subarachnoid hemorrhage (SAH), but is often precluded by the invasiveness and complexity of the established cardiac output determination techniques. We examined the utility of an uncalibrated arterial pressure-based cardiac output monitor (FloTrac) for intraoperative and postoperative hemodynamic management after SAH. In 16 SAH patients undergoing surgical clipping, arterial pulse contour cardiac index, and stroke volume variation (SVV) were analyzed via the radial FloTrac system. The hemodynamic values after induction of anesthesia until 12 hours after surgery were compared with reference transpulmonary thermodilution cardiac index (TPCI), calibrated pulse contour CI, and global end-diastolic volume index determined by the PiCCO system and central venous pressure. Arterial pulse contour cardiac index underestimated CI as overall bias±SD of 0.57±0.44 L/min/m2 and 0.54±0.46 L/min/m2 compared with TPCI and calibrated pulse contour CI, resulting in a percentage error of 24.8% and 26.6%, respectively. Subgroup analysis revealed a percentage error of 29.3% for values obtained intraoperatively and 20.4% for values measured under spontaneously breathing after tracheal extubation. Better prediction of cardiac responsiveness to defined volume loading for increasing stroke volume index >10% was observed for SVV under mechanical ventilation with greater area under the receiver operating characteristics curve than that for global end-diastolic volume index or central venous pressure. These data suggest that the FloTrac underestimates the reference CI, and is not as reliable as transpulmonary thermodilution for perioperative hemodynamic monitoring after SAH. SVV is considered to be an acceptable preload indicator under mechanical ventilation.

Quantitative evaluation of neutral amino acid transport in cerebral gliomas using positron emission tomography and fluorine-18 fluorophenylalanine

To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and18F-Phe. By employing two-compartment model analysis, the influx rateK1, the efflux ratek2 and the distribution volume (Vd) of18F-Phe were estimated in tumour tissue and contralateral normal grey matter.18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P <0.05). However, it was difficult to evaluate the tumour grade only from the18F-Phe accumulation in individual cases. Values ofK1 andVd were significantly increased in the tumour tissue. TheK1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

Carotid artery resection: preoperative temporary occlusion is not always an accurate predictor of collateral blood flow.

Conclusion The morbidity predicted by means of preoperative PET studies does not always correlate with the morbidity experienced after permanent carotid artery occlusion. A pre-resection extracranial–intracranial bypass may be necessary to reduce the risk of neurologic morbidity, in particular when carotid artery resection is planned for tumors involving the skull base. Objectives Carotid artery resection is generally considered the only curative treatment for patients with advanced head and neck carcinoma involving the carotid artery. PET can be used during temporary occlusion of the internal carotid artery to assess the safety of the procedure. The aims of this paper were to clarify the risk of carotid artery resection and the benefit of extracranial–intracranial bypass. Material and methods Twelve patients diagnosed with head and neck cancer adherent to the carotid artery and in proximity to the skull base who had shown good hemispheric collateral blood flow by means of PET underwent carotid artery resection without preoperative bypass. Results Of the 12 patients who underwent carotid artery resection without reconstruction, 10 suffered no serious neurologic complications; however, 2 suffered cerebral infarctions intraoperatively.