Takashi Inoue

Accuracy and limitation of functional magnetic resonance imaging for identification of the central sulcus: comparison with magnetoencephalography in patients with brain tumors.

The aim of the present study was to clarify the accuracy and limitation of functional magnetic resonance imaging (fMRI) for the identification of the central sulcus affected by brain tumors. Twelve normal volunteers and 11 patients with intracranial tumors adjacent to the central sulcus underwent fMRI and magnetoencephalography (MEG). Three patients were evaluated again after surgery. fMRI was performed with a 1.5 Tesla scanner during repetitive opening and closing of each hand. Cross-correlation function was used to identify activation areas, and the central sulcus was defined as the nearest sulcus to the highest activation spots that were determined by elevating correlation coefficient threshold. Somatosensory-evoked fields were measured using a whole head MEG system. The central sulcus was defined as the nearest sulcus to the N20m for the median nerve stimulus. fMRI and MEG coincided in defining the central sulcus in all 24 hemispheres of volunteers and all 10 examined nonaffected hemispheres of patients. The fMRI-defined central sulcus coincided with the MEG-defined central sulcus in nine (82%) but did not in two (18%) affected hemispheres of patients. The preoperative mismatch disappeared after surgery in one of the two patients. The present study indicates that fMRI successfully defined the central sulcus in most of the patients with brain tumors. However, in a few cases, fMRI was not reliable probably due to venous flow changes by tumor compression and/or compensational activity by brain tissues surrounding the primary sensorimotor cortex. For precise functional assessment of the brain affected by intracranial tumors, combination of fMRI and MEG will be recommended.

Significance of Focal Cerebral Hyperperfusion as a Cause of Transient Neurologic Deterioration After Extracranial-Intracranial Bypass for Moyamoya Disease: Comparative Study With Non-Moyamoya Patients Using N-Isopropyl-p-[123I]Iodoamphetamine Single-Photon Emission Computed Tomography

BACKGROUND:Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis prevents cerebral ischemic attack by improving cerebral blood flow in patients with occlusive cerebrovascular disease and hemodynamic compromise. Recent evidence suggests that focal cerebral hyperperfusion is a potential complication of this procedure for moyamoya disease. OBJECTIVE:To clarify the exact differences in the incidence and clinical manifestations of this phenomenon between patients with and without moyamoya disease. METHODS:N-isopropyl-p-[123I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 121 hemispheres from 86 consecutive patients with moyamoya disease (2-67 years of age; mean, 34.3 years) and on 28 hemispheres from 28 non-moyamoya patients (12-67 years of age; mean, 56.5 years). The incidence of symptomatic hyperperfusion, defined as a significant focal increase in cerebral blood flow at the site of the anastomosis that is responsible for the apparent neurological signs, was compared between groups. RESULTS:Symptomatic cerebral hyperperfusion including mild focal neurological signs was seen in 25 patients with moyamoya disease (26 hemispheres, 21.5%) but in none of the patients without moyamoya disease (P = .0069). Multivariate analysis revealed that moyamoya disease was significantly associated with the development of symptomatic cerebral hyperperfusion (P = .0008). All patients with symptomatic hyperperfusion were relieved by intensive blood pressure control, and no patients suffered from permanent neurological deficit caused by hyperperfusion. CONCLUSION:Symptomatic cerebral hyperperfusion is a potential complication of STA-MCA anastomosis, especially in patients with moyamoya disease. Accurate diagnosis and adequate management of hyperperfusion are recommended, especially in patients with moyamoya disease.

Exon/Intron Organization, Chromosome Localization, Alternative Splicing, and Transcription Units of the Human Apolipoprotein E Receptor 2 Gene

Apolipoprotein E receptor 2 is a recently identified receptor that resembles low and very low density lipoprotein receptors. Isolation and characterization of genomic clones encoding human apolipoprotein E receptor 2 revealed that the gene spans ~60 kilobases and contains 19 exons. The positions of the exon/intron boundaries of the gene are almost identical to those of low and very low density lipoprotein receptors. Fluorescent in situ hybridization of human chromosomes revealed that the gene is located on chromosome 1p34. Isolation of a cDNA encoding a variant receptor and reverse transcription-polymerase chain reaction indicate the presence of multiple variants with different numbers of cysteine-rich repeats in the binding domain of the receptor. We also found a variant receptor lacking a 59-amino acid insertion in the cytoplasmic domain. The transcription start site was mapped to the position 236 base pairs upstream of the AUG translation initiator codon by primer extension analysis. Sequence inspection of the 5′-flanking region revealed potential DNA elements: AP-2, GC factor, PEA3, and Sp1. The minimal promoter region and a region required for nerve growth factor inducibility in PC12 cells were also determined.

Local Hemodynamics at the Rupture Point of Cerebral Aneurysms Determined by Computational Fluid Dynamics Analysis

Background: Cerebral aneurysms carry a high risk of rupture and so present a major threat to the patient’s life. Accurate criteria for predicting aneurysm rupture are important for therapeutic decision-making, and some clinical and morphological factors may help to predict the risk for rupture of unruptured aneurysms, such as sex, size and location. Hemodynamic forces are considered to be key in the natural history of cerebral aneurysms, but the effect on aneurysm rupture is uncertain, and whether low or high wall shear stress (WSS) is the most critical in promoting rupture remains extremely controversial. This study investigated the local hemodynamic features at the aneurysm rupture point. Methods: Computational models of 6 ruptured middle cerebral artery aneurysms with intraoperative confirmation of rupture point were constructed from 3-dimensional rotational angiography images. Computational fluid dynamics (CFD) simulations were performed under pulsatile flows using patient-specific inlet flow conditions. Time-averaged WSS (TAWSS) and oscillatory shear index (OSI) were calculated, and compared at the rupture point and at the aneurysm wall without the rupture point. We performed an additional CFD simulation of a bleb-removed model for a peculiar case in which bleb formation could be confirmed by magnetic resonance angiography. Results: All rupture points were located at the body or dome of the aneurysm. The TAWSS at the rupture point was significantly lower than that at the aneurysm wall without the rupture point (1.10 vs. 4.96 Pa, p = 0.031). The OSI at the rupture point tended to be higher than at the aneurysm wall without the rupture point, although the difference was not significant (0.0148 vs. 0.0059, p = 0.156). In a bleb-removed simulation, the TAWSS at the bleb-removed area was 6.31 Pa, which was relatively higher than at the aneurysm wall (1.94 Pa). Conclusion: The hemodynamics of 6 ruptured cerebral aneurysms of the middle cerebral artery were examined using retrospective CFD analysis. We could confirm the rupture points in all cases. With those findings, local hemodynamics of ruptured aneurysms were quanti-tatively investigated. The rupture point is located in a low WSS region of the aneurysm wall. Bleb-removed simulation showed increased WSS of the bleb-removed area, associated with the flow impaction area. Although the number of subjects in this study was relatively small, our findings suggest that the location of the rupture point is related to a low WSS at the aneurysm wall. Further investigations will elucidate the detailed hemodynamic effects on aneurysm rupture.

Efficacy of prophylactic blood pressure lowering according to a standardized postoperative management protocol to prevent symptomatic cerebral hyperperfusion after direct revascularization surgery for moyamoya disease.

Background: Cerebral hyperperfusion is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease, but the optimal postoperative management has not been determined. Aggressive blood pressure lowering is controversial because of the risk of ischemic complications. Objective: To establish the optimal postoperative management protocol to prevent symptomatic cerebral hyperperfusion in moyamoya disease. Methods: N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 152 hemispheres from 108 consecutive patients with moyamoya disease (2–69, mean 33.3 years). Between 2004 and 2007 (period 1), 65 patients were maintained under normotensive conditions after 93 operations, and only patients with cerebral hyperperfusion underwent blood pressure lowering. Between 2008 and 2010 (period 2), all 43 patients were prospectively subjected to intensive blood pressure lowering (<130 mm Hg of systolic blood pressure) immediately after 59 operations. Then the incidence of symptomatic cerebral hyperperfusion was compared between the two groups. Results: Systolic blood pressure the day after surgery was significantly lower in period 2 (mean, 120.9 mm Hg) than in period 1 (133.9 mm Hg) (p < 0.0001). Symptomatic cerebral hyperperfusion was seen in 22 patients during period 1 (23 hemispheres, 24.7%), but only in 4 patients during period 2 (6.7%, p = 0.0047). Multivariate analysis revealed that prophylactic blood pressure lowering was significantly associated with the prevention of symptomatic cerebral hyperperfusion (p = 0.015). Symptomatic cerebral hyperperfusion was relieved in all patients without developing a permanent neurological deficit due to cerebral hyperperfusion. Conclusion: Prophylactic blood pressure lowering prevents symptomatic cerebral hyperperfusion after STA-MCA anastomosis in patients with moyamoya disease. Accurate diagnosis of cerebral hyperperfusion and blood pressure lowering, and considering the severity of hemodynamic compromise in the contralateral and/or remote areas are essential for postoperative management of moyamoya disease.

Imaging the pyramidal tract in patients with brain tumors.

The clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) of the pyramidal tract was evaluated in patients with brain tumors. Five normal volunteers and seven patients with glioma (n = 4) or meningioma (n = 3) near the pyramidal tract underwent coronal echo planar DWI. Greyscale DWIs in each of the three orthogonal diffusion gradients were transformed into graduations, color-coded as red, green or blue, respectively, and then composited to form a combined color image. The entire pyramidal tract was visualized on a single fiber mapping image by combining the upper half of the image slice including the primary motor cortex, the corona radiata and the internal capsule with the lower half of the image slice including the internal capsule, the cerebral peduncle and the ventral brain stem. Fiber mapping images demonstrated the pyramidal tract as a distinct band indicating nerve fiber integrity in all volunteers. The entire pyramidal tract from the primary motor subcortex to the ventral brain stem could be traced. Fiber mapping images showed the ipsilateral pyramidal tract as either discontinuous due to impaired anisotropy or compressed due to mass effect in patients with brain tumors. These findings corresponded well with the pre- and postoperative motor functions. Fiber mapping images are useful for evaluating the white matter neuronal tracts and can provide indications for determining surgical strategy.

Minocycline Prevents Focal Neurological Deterioration Due to Cerebral Hyperperfusion After Extracranial-Intracranial Bypass for Moyamoya Disease

BACKGROUNDnCerebral hyperperfusion (CHP) is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), and optimal postoperative management has not yet been established. Minocycline, a neuroprotective antibiotic agent, plays a role in blocking matrix metalloproteinase 9 (MMP-9), which contributes to edema formation and hemorrhagic conversion after cerebral ischemia-reperfusion. Patients with MMD have been shown to have increased serum MMP-9 levels.nnnOBJECTIVEnTo examine the effect of minocycline on the prevention of postoperative CHP after STA-MCA anastomosis for MMD.nnnMETHODSnN-isopropyl-p-[I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 109 hemispheres in 86 consecutive patients with MMD (ages, 9-69 years; mean, 37.2 years). Postoperative systolic blood pressure was strictly maintained at lower than 130 mm Hg in all 109 surgeries. The most 60 recent hemispheres were managed by the intraoperative and postoperative intravenous administration of minocycline hydrochloride (200 mg/d). The incidence of focal neurological deterioration (FND) due to CHP was then compared with that in 36 patients undergoing 49 surgeries managed without minocycline.nnnRESULTSnFND due to CHP was observed in 4 operated hemispheres in patients treated without minocycline (4/49, 8.16%), and in none in the minocycline-treated group (0/60) (P = .0241). Multivariate analysis revealed that minocycline administration (P < .001), surgery on the left hemisphere (P = .031), and a smaller recipient artery diameter (P < .001) significantly correlated with FND due to CHP.nnnCONCLUSIONnThe administration of minocycline with strict blood pressure control may represent secure and effective postoperative management to prevent symptomatic CHP after STA-MCA anastomosis for MMD.

Annual rupture risk of growing unruptured cerebral aneurysms detected by magnetic resonance angiography

OBJECTnIn this paper, the authors goals were to clarify the characteristics of growing unruptured cerebral aneurysms detected by serial MR angiography and to establish the recommended follow-up interval.nnnMETHODSnA total of 1002 patients with 1325 unruptured cerebral aneurysms were retrospectively identified. These patients had undergone follow-up evaluation at least twice. Aneurysm growth was defined as an increase in maximum aneurysm diameter by 1.5 times or the appearance of a bleb.nnnRESULTSnAneurysm growth was observed in 18 patients during the period of this study (1.8%/person-year). The annual rupture risk after growth was 18.5%/person-year. The proportion of females among patients with growing aneurysms was significantly larger than those without growing aneurysms (p=0.0281). The aneurysm wall was reddish, thin, and fragile on intraoperative findings. Frequent follow-up examination is recommended to detect aneurysm growth before rupture.nnnCONCLUSIONSnDespite the relatively short period, the annual rupture risk of growing unruptured cerebral aneurysms detected by MR angiography was not as low as previously reported. Surgical or endovascular treatment can be considered if aneurysm growth is detected during the follow-up period.

Molecular cloning and nucleotide sequence of the 1,2-α-d-mannosidase gene, msdS, from Aspergillus saitoi and expression of the gene in yeast cells

A full-length cDNA encoding 1,2-alpha-D-mannosidase (EC 3.2.1.113) from Aspergillus saitoi was cloned. Analysis of the 1718 bp nucleotide sequence of the cDNA revealed a single open reading frame with 1539 nucleotides of 1,2-alpha-D-mannosidase gene, msdS. The predicted amino-acid sequence of 1,2-alpha-D-mannosidase consists of 513 residues with a molecular mass of 55,767 and is 70%, 26% and 35% identity with those of Penicillium citrinum 1,2-alpha-D-mannosidase, yeast alpha-mannosidase, and mouse alpha-mannosidase. The cDNA of the msdS gene has been cloned and expressed in yeast cells. To identify the activity of expression product methyl-2-O-alpha-mannopyranosyl-alpha-mannopyranoside (Man alpha 1-->2Man-OMe) was used as a substrate at pH 5.0.

Acute-stage diffusion-weighted magnetic resonance imaging for predicting outcome of poor-grade aneurysmal subarachnoid hemorrhage

We investigated the role of acute-stage diffusion-weighted images (DWIs) for predicting outcome of poor-grade subarachnoid hemorrhage (SAH). This study included 38 patients with poor-grade SAH who underwent DWI within 24 h after onset. DWI findings were divided into three groups on the basis of lesion area: none (N), spotty (S, ≦10 mm2), or areal (A, >10 mm2). We evaluated the correlation between preoperative DWI findings and clinical outcome, and the characteristics of DWI abnormalities. DWI abnormalities were revealed in 81.6% of cases (group S 34.2%; group A 47.3%). All patients in groups N and S and 73.3% of patients in group A were treated radically. For those patients without rerupture, favorable outcomes were achieved in 100% of group N, 53.8% of group S, and 0% of group A. Abnormal lesions on initial DWI, which resulted in permanent lesions, showed a mean apparent diffusion coefficient ratio to the control value of 0.71, which was significantly lower than 0.95 observed in reversible lesions (P<0.01). We recommend radical treatment for even poor-grade SAH as long as the preoperative DWI shows no or only spotty lesions. DWI may provide an objective means to estimate the outcome of poor-grade SAH.