Makio Kaminogo

Incidence and Outcome of Multiple Intracranial Aneurysms in a Defined Population

Background and Purpose— Proportions of patients with single and multiple aneurysms among patients suffering from subarachnoid hemorrhage (SAH) are not well established. We evaluated these proportions and the differences in outcome between SAH patients with a single aneurysm and those with multiple aneurysms in a defined population. Methods— Between 1989 and 1998, 2037 patients (age, 20 to 89 years) with ruptured intracranial aneurysm were treated in 11 hospitals in Nagasaki Prefecture. Multiple aneurysms were found in 361 of these patients. Age- and sex-specific incidences of ruptured aneurysm per 100 000 people were calculated. Results— For both single and multiple aneurysms, the incidences were significantly higher in women than in men 60 to 69 and 70 to 79 years of age. In every age category except 80 to 89 years, the frequency of multiple aneurysms was higher in women than in men. The overall frequency of multiple aneurysms was 20.2% in women, which was significantly higher than the 12.4% in men (P <0.0001). In patients 70 to 89 years of age, outcome was significantly worse (in terms of surgical complications) in patients with multiple aneurysms (12.1%) than in patients with a single aneurysm (6.0%). Conclusions— Among all patients with SAH, women ≥50 years of age outnumber other age and sex categories. Female sex itself is also associated with an increased rate of multiple aneurysms among SAH patients. Among the elderly ≥70 years of age, prognosis is less favorable for SAH patients with multiple aneurysms than for those with a single aneurysm.

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain

Abstract Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

An Additional Monitoring of Regional Cerebral Oxygen Saturation to HMPAO SPECT Study During Balloon Test Occlusion

BACKGROUND AND PURPOSE To increase the reliability of 99mTc-hexamethyl propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) study in the evaluation of hemodynamic change with balloon test occlusion (BTO) of the internal carotid artery, we attempted to clarify the usefulness of additional monitoring of regional oxygen saturation of the brain (rSO2). METHODS During BTO, rSO2 monitoring with transcranial near infrared spectroscopy was performed 17 times on 16 patients. Asymmetrical distribution of the tracer was classified visually as follows: group 1, little or no asymmetry, and group 2, moderate or severe asymmetry. Seven regions of interest (ROI) were defined in the middle cerebral artery area of each hemisphere, and the asymmetry index (AI)=200x(Cnon-Coccl)/(Cnon+Coccl)), where Cnon=mean counts on the nonoccluded side, and Coccl=mean counts on the occluded side were also calculated. Then, mean AI (MAI) was obtained from AI of 7 ROIs for each study. RESULTS Of the 17 procedures, 10 BTOs were in group 1 and 5 BTOs were in group 2. Two patients did not undergo SPECT study because of the immediate appearance of a neurological deficit with BTO; they were defined as group 3. The MAI in group 1 was 2. 6+/-3.3%, which was significantly smaller than the MAI in group 2 (25.6+/-5.0%, P<0.02). The DeltarSO2 (baseline rSO2-rSO2 during ICA occlusion) with BTO in group 1 was 1.5+/-1.4% (n=10), which was statistically smaller than that in group 2 (5.5+/-1.3%, n=4, P<0.05). The DeltarSO2 in group 3 was 9.0+/-0.0% (n=2). In group 1, however, rSO2 began to decline when the stump pressure fell to 45 mm Hg and always declined when the stump pressure fell below 40 mm Hg. Furthermore, in group 1, a significant correlation was observed between the DeltarSO2 and stump pressure (r=0.85, P<0.0001). CONCLUSIONS This preliminary study reveals that an obvious asymmetrical SPECT pattern always accompanies a profound decrease in rSO2 and that rSO2 parallels a severe reduction in stump pressure in cases exhibiting a symmetrical SPECT pattern. Thus, the cerebral oximetry sensitively reflects the cerebral oxygenation, and simultaneous measurements of rSO2 and stump pressure with 99mTc-HMPAO SPECT study apparently are useful in evaluating hemodynamic integrity with BTO.

Anoxic depolarization determines ischemic brain injury

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shifts, electrocorticogram, and cortical blood flow (CoBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of 28 animals. Circulation was reinitiated 15 min after AD onset in 11 rats (group A) and 10 min after onset in 10 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 12 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 14 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of 5 rats from group A. Ischemic neuronal changes were absent or minimal in only 1/5 of group A animals, a much lower fraction than in group B (4/4, p < 0.05) or in group C (5/5, p < 0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 15 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37 degrees C.

N-acetylcysteine inhibited nuclear factor-κB expression and the intimal hyperplasia in rat carotid arterial injury

Abstract Neointima formation associated with vascular restenosis is a complex local inflammatory process actively involving the vascular smooth muscle cell (SMC) proliferation. Nuclear factor-κB (NF-κB) is a transactivator of a diverse group of genes whose activation has been strongly associated with the cellular response to inflammation. Since anti-oxidant N-acetylcysteine (NAC) inhibit NF-κB activity in vascular SMC in vitro , we examined the in vivo effect of the NAC on balloon-induced neointimal formation in the carotid artery of rats. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. One group of these rats (n = 9) were treated with daily intraperitoneal injection of NAC (200 mg kg-1) for 14 consecutive days, whereas the control group (n = 9) was treated with saline. Fourteen days after the injury, the left carotid arteries were removed and analyzed under microscope. Several rats underwent the same treatment as above and were sacrificed three days after injury for immunohistochemistry and Western blot studies. A morphometric analysis revealed that there were significant differences in intima/media ratio between the two groups. Immunohistochemical and Western blotting studies demonstrated that NAC suppressed the injury-induced NF-κB activity in the medial SMC layer. Treatment with NAC suppresses vascular NF-κB activation and this inhibition reduced the pathological thickening of the arterial wall. The NF-κB pathway, therefore, represents an attractive therapeutic target for strategies to prevent vascular restenosis. [Neurol Res 2001; 23: 731-738]

Endovascular treatment for cervical carotid artery stenosis presenting with progressing stroke: three case reports

BACKGROUND Progressing stroke is said to occur when symptoms and signs worsen in cases of ischemic stroke. Although conservative methods using volume expansion with antithrombotic or anticoagulative agents are widely used for progressing stroke, in some hospitals, emergency carotid endarterectomy (CEA) has been performed for carotid stenosis, with mixed results. Here we report three cases with progressing ischemic stroke that were managed by endovascular surgical intervention. CASE DESCRIPTION We performed endovascular surgery in three patients with cervical carotid artery stenosis presenting with progressing stroke or crescendo transient ischemic attacks. Endovascular treatment was less invasive and feasible for acute phase treatment. While local thrombolysis alone was found to be less effective, stent placement induced complete resolution of stenosis, but may result in hyperperfusion syndrome or hemorrhagic infarction. CONCLUSIONS In an emergency, percutaneous transluminal angioplasty with proper dilatation is preferred, and then CEA or stenting should be considered after the patients condition stabilizes.

Effect of Acetazolamide on Regional Cerebral Oxygen Saturation and Regional Cerebral Blood Flow

BACKGROUND AND PURPOSE To verify whether the monitoring of regional cerebral oxygen saturation (rSO2) with transcranial near-infrared spectroscopy would successfully reflect changes in intracranial hemodynamics but not changes in extracranial compartment, we measured rSO2 and regional cerebral blood flow (rCBF) simultaneously in seven patients with cerebral ischemia and five normal volunteers before and after acetazolamide administration. SUMMARY OF REPORT The baseline values of rSO2 and rCBF were 64.2 +/- 5.6% and 53.9 +/- 11.1 mL/100 g per minute, respectively. rCBF increased by 44.4 +/- 23.3% and rSO2 significantly increased to 69.6 +/- 5.6% after acetazolamide administration. Bilateral simultaneous measurement of rSO2 indicated a tendency that the larger the delta rSO2, the greater the delta%rCBF. The relationship between rSO2 level and rCBF value fit significantly on the theoretical curve calculated from Ficks equation. CONCLUSIONS It is suggested that monitoring of rSO2 with INVOS-3100 could be a useful indicator in the evaluation of intracranial hemodynamic changes.

Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion

Although malignant gliomas are highly invasive tumors, a characteristic that contributes to the commonly observed therapeutic failures and local disease recurrences, the molecular events that regulate invasion in these tumors remain poorly understood. Because the transcription factor RelA/NF-κB has been shown to regulate invasion during several cellular processes, we have examined immunohistochemically expression of the constitutively activated RelA/NF-κB in tissues obtained from 49 astrocytic tumors [8 diffuse astrocytomas, 9 anaplastic astrocytomas (AAs) and 32 glioblastomas (GBMs)]. In addition, we examined the in vitro effects of antisense oligonucleotides and curcumin on the expression and activation of RelA/NF-κB, urokinase-type plasminogen activator (u-PA) expression, migration, and invasion in the T98G glioma cell line. Expression of the constitutively activated RelA/NF-κB was observed in 2 (25%) of 8 cases of diffuse astrocytomas, 5 (55.6%) of 9 cases of AAs, and 30 (93.8%) of 32 cases of GBMs. This expression was significantly correlated with the malignant potential in astrocytic tumors (P < 0.001). Moreover, antisense oligonucleotides and curcumin inhibited phorbol-12-myristate-13-acetate (PMA)-induced RelA/NF-κB expression or activation (or both), down-regulated u-PA expression, and reduced the migration and invasive potentials of T98G glioma cells. Thus, the expression of constitutively activated RelA/NF-κB is associated with malignancy potential in astrocytic tumors and may play a critical role in the regulation of u-PA expression and invasiveness in gliomas. RelA/NF-κB may therefore be an intriguing candidate for studies aimed at understanding and prevention of the invasiveness of gliomas.

Proton MR spectroscopy and diffusion-weighted MR imaging for the diagnosis of intracranial tuberculomas. Report of two cases

Abstract With the current prevalence of tuberculosis, the incidence of intracranial tuberculoma may be on the rise in industrialized nations. However, clinical findings suggestive of systemic tuberculosis are frequently subtle or absent in patients with intracranial tuberculoma, and no specific neuroradiologic characteristics of tuberculoma have been defined as yet. We report two cases of ring-enhanced intracranial tuberculoma in which magnetic resonance (MR) proton spectroscopy and diffusion-weighted (DW) imaging were useful in the differential diagnosis between tuberculoma and other ring-enhanced mass lesions. Pulmonary tuberculosis had been diagnosed in one patient, but radiologic lung study and tuberculin skin test were negative in the other. DW imaging showed bright signal intensity in the core of all lesions in both patients. Malignant gliomas and metastatic brain tumors do not have this characteristic. Proton MR spectroscopy of lesion cores showed lipid peaks and a choline peak in one, and a lipid/lactate mixture pattern in the other, which differed distinctively from those of the pyogenic brain abscess. In each case, one lesion was surgically removed. Antituberculosis drugs were started before surgery for one patient and after surgery for the other. In both, the remaining lesions were reduced significantly in size. We discuss the diagnostic potential of these MR techniques and management options of intracranial tuberculoma. [Neurol Res 2002; 24: 537-543]

Immunohistochemical expression of E-cadherin in metastatic brain tumors

The adhesion molecule E-cadherin has been shown to influence malignant transformation of tumors, including local and distant metastases. We examined the expression of E-cadherin to determine its relationship to the development of metastasis in metastatic brain tumors. Immunohistochemistry for E-cadherin and Ki-67 was carried out in 76 formalin-fixed, paraffin-embedded archival specimens of metastatic brain tumors and in 14 corresponding available primary tumors from patients who received treatment for metastatic brain tumors. The primary tumors were mainly lung cancers (51.3%), followed by gastrointestinal tumors (28.9%). E-cadherin was expressed in 62 (81.5%) of 76 cases examined. In metastatic adenocarcinomas, a consistent tendency for E-cadherin expression was noted, regardless of the degree of differentiation or the extent of spread of the disease (P=0.4). There was a direct correlation between E-cadherin expression and high MIB-1 index in all metastatic brain tumors (P=0.0007). Pairwise analysis in 14 primary tumors and the corresponding metastatic specimens revealed high E-cadherin and MIB-1 staining in metastatic brain tumors. These results provide a unique association between E-cadherin, systemic metastasis, and proliferation potential in metastatic brain tumors.