Tetsuyuki Yoshimoto

Angiogenic Factors in Moyamoya Disease

BACKGROUND AND PURPOSE We previously reported that the level of basic fibroblast growth factor (bFGF) is high in cerebrospinal fluid (CSF) taken from patients with moyamoya disease. The present study investigated the levels of other angiogenic growth factors in the CSF of moyamoya patients and the clinical significance of bFGF in moyamoya disease. METHODS The levels of bFGF, interleukin-8, platelet-derived growth factor, transforming growth factor-beta, endothelial growth factor, and vascular endothelial cell growth factor in CSF, taken from 38 patients with moyamoya disease and 16 patients with atherosclerotic occlusive disease (control group), were measured by an enzyme-linked immunosorbent assay. We analyzed the correlation between the level of bFGF and the clinical factors of age, onset pattern, development of neovascularization, and cerebral circulation. RESULTS The CSF of moyamoya patients contained a high concentration of bFGF to a significant (P < .05) extent. The bFGF level was apparently elevated in the patients in whom neovascularization from indirect revascularization, such as encephaloduroarteriosynangiosis, was well developed (P < .01). A linear correlation between the values of bFGF and cerebral vascular response to acetazolamide (r = .7; P < .05) was revealed. The other angiogenic factors were not significantly high compared with the control group. CONCLUSIONS The elevation of bFGF in moyamoya disease seems to be specific and is not related simply to cerebral ischemia. Clinically, the bFGF level is a useful indicator to predict the efficacy of indirect revascularization after surgery.

Direct and indirect revascularization for Moyamoya disease surgical techniques and peri-operative complications

We have performed surgical treatment for Moyamoya disease using the superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-arterio-myo-synangiosis (EDAMS). In this paper, the surgical technique of combined revascularization for Moyamoya disease as well as peri-operative complications are discussed. Craniotomy and dural opening were extensively carried out to expose the brain surface as widely as possible. Dissection of the STA, which is the most powerful resource of direct revascularization, should be carefully carried out using a surgical microscope. The temporal muscle and middle meningeal artery, which have the most potential as sources of indirect revascularization, must be preserved. STA-MCA anastomosis to the frontal branch of the middle cerebral artery is indispensable for improving cerebral circulation of the frontal lobe. A small arachnoid membrane opening and water-tight closure are also important to avoid post-operative subdural and subcutaneous fluid collection. Ischemic events disappeared immediately after surgery in most cases. However, in several cases, transient ischemic attacks recurred for several months after the surgery. Chronic subdural hematoma was seen in two cases.

Low cerebral blood flow and perfusion reserve induce hyperperfusion after surgical revascularization: Case reports and analysis of cerebral hemodynamics

BACKGROUND Hyperperfusion syndrome after surgical revascularization is a rare complication and there has not been any systematic study on factors that induce hyperperfusion after surgery. In this paper, we retrospectively analyzed the factors related to this syndrome. PATIENTS AND METHODS We performed 46 cases of surgical revascularization including 33 cases of carotid endarterectomy (CEA) and 13 cases of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis during the past 5 years. Among these, we encountered three cases of hyperperfusion syndrome despite well-controlled blood pressure postoperatively. To evaluate factors related to the occurrence of hyperperfusion syndrome, we examined four parameters: (1) regional cerebral blood flow (rCBF), (2) the increase in the ratio of the postoperative rCBF compared to the preoperative rCBF (increase ratio), (3) cerebral perfusion reserve presented by the increase of rCBF after acetazolamide administration (delta rCBF), and (4) the difference in mean blood pressure between the preoperative and postoperative state (delta BP). RESULTS Preoperative rCBF was significantly lower in cases of hyperperfusion syndrome than the control cases (p < 0.01 Mann-Whitney U-test). Moreover delta rCBF was evidently lower in the hyperperfusion cases than the control (p < 0.05 Fishers exact method). However, there was no significant difference in the delta BP between the hyperperfusion cases and the control cases. CONCLUSION In cases of marked low perfusion (low rCBF) with poor perfusion reserve (low delta rCBF), hyperperfusion after surgical revascularization can occur even if blood pressure is adequately controlled.

Intra-Operative Premature Rupture of the Cerebral Aneurysms. Analysis of the Causes and Management

Summary¶ The causes and management of intra-operative premature rupture are analysed and discussed. During the past 6 years, the authors, performed 398 consecutive direct surgical interventions for ruptured cerebral aneurysms. Intra-operative premature rupture is defined as a rupture which occurs before the securing of the parent arteries or the neck of the aneurysm and is out of control, at least temporarily. The causes and management were retrospectively analysed by reviewing video tape recordings. Intra-operative premature ruptures which met the above definition occurred in 24 cases (6.0%). The causes were as follows: 1.) dural opening and arachnoid opening (8.3%), 2.) haematoma removal (12.5%), 3.) brain retraction (16.7%), 4.) aneurysm dissection (62.5%). A double suction technique was used to control bleeding and haemostasis with a small piece of cotton or a temporary clip, performed in 20 cases (83.3%). However, in cases with premature rupture immediately after the dural or arachnoid opening, the extension of the haematoma into the subarachnoid space resulted in severe brain swelling and partial resection of the brain had to be done to secure temporary clipping. The double suction technique and primary haemostasis using a small piece of cotton or temporary clip resulted in good outcome even in cases with premature rupture. However, very early premature rupture also occurred although its incidence was extremely rare. The removal of part of the brain can secure the working space but the outcome was poor.

FK506 reduces infarct volume due to permanent focal cerebral ischemia by maintaining BAD turnover and inhibiting cytochrome c release

It has been reported that immunosuppressant FK506 inhibited ischemic neuronal injury in forebrain ischemia or transient focal cerebral ischemia, but the mechanisms of the neuroprotective effect have not been clarified. In permanent focal cerebral ischemia, we investigated whether FK506 caused remission of brain infarction, and how mechanism was concerned. Male Balb/c mice were subjected to permanent middle cerebral artery (MCA) occlusion. They were treated with 1.0 or 3.0 mg/kg FK506 or vehicle 30 min before ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Cytochrome c release from mitochondria was evaluated by Western blotting and immunocytochemistry after ischemia. Simultaneously, the immunoreactivity of total and phosphorylated BAD was also studied using immunocytochemistry. We demonstrated that pretreatment with 3.0 mg/kg FK506 salvaged the tissue damage in the infarct rim and significantly reduced infarct volume to 75.5% (P<0.05), and FK506 inhibited cytochrome c release on 6 h after ischemia for Western blot analysis (P<0.05). Immunocytochemical study showed that permanent MCA occlusion increased the amount of cytochrome c and total BAD in the cytosol, but not phosphorylated BAD, in the ischemic core and the infarct rim as early as 1 h after ischemia, and FK506 inhibited the increases in the infarct rim. The results suggest that FK506 may, at least in part, ameliorate tissue damage due to permanent focal cerebral ischemia in the infarct rim through maintaining BAD turnover and inhibiting cytochrome c release from mitochondria.

Induction of macrophage migration inhibitory factor messenger ribonucleic acid in rat forebrain by reperfusion.

OBJECTIVE Macrophage migration inhibitory factor (MIF) is a cytokine that has the potential to immobilize and activate monocytes/macrophages. To examine whether MIF may potentially be involved in the pathogenesis of reperfusion injury of the brain, we investigated the expression of MIF in a rat model of reperfusion. METHODS A four-vessel occlusion procedure was performed for 30 minutes using male Wistar rats to obtain a moderate reperfusion in the forebrains. Semiquantitatively calibrated reverse-transcription polymerase chain reaction analysis was conducted to examine temporal profiles of messenger ribonucleic acid (mRNA) expression for MIF and macrophage chemoattractant protein 1. MIF protein assays expression was assessed with specific Western blot analysis. For anatomic mapping of MIF, an immunohistochemical study was performed. RESULTS Reverse-transcription polymerase chain reaction demonstrated that the mRNA level of MIF increased depending on the duration of reperfusion (< or = 24 h) subsequent to global ischemia. The macrophage chemoattractant protein 1 mRNA was also observed to increase after reperfusional stress, but its maximum expression was reached earlier (1 h after the stress) than was MIF mRNA. Increase of MIF protein was also shown by Western blot. MIF-positive staining was observed in the neuronal processes (neuropil) in the cortex and basal growth ganglia of a rat forebrain. CONCLUSION This protein is up-regulated and may modulate immunological reaction in secondary brain damage after ischemia and reperfusion stress.

Proximal clipping and bypass between bilateral vertebral arteries using a radial arterial graft for the treatment of a dissecting aneurysm of the vertebral artery.

Proximal clipping has been performed recently as the main surgical treatment for a dissecting aneurysm of the vertebral artery. When there is a contralateral vertebral artery of a smaller size with arteriosclerotic changes, some form of bypass to prevent cerebellar and brain stem infarction is needed in addition to proximal clipping. We treated a 50-year-old man with a ruptured dissecting aneurysm of the left vertebral artery and stenosis at the V3 segment of the right vertebral artery. The caliber of the right vertebral artery was smaller than the left. After an anastomosis between bilateral vertebral arteries using a radial arterial graft, dissecting aneurysm was clipped at the proximal portion of the aneurysm.

New Criteria for the Sonographic Diagnosis of a Plaque Ulcer in the Extracranial Carotid Artery

OBJECTIVE The diagnostic power of carotid sonography in detecting plaque ulcers may be inadequate when using the conventional criteria. We aimed to evaluate the usefulness of new criteria that we devised through a preliminary analysis of 50 endarterectomy cases before the present series. SUBJECTS AND METHODS Thirty carotid arteries of 30 consecutive patients who underwent endarterectomy (28 men; age range, 46-83 years) were studied. In the long- and short-axis B-mode images of carotid arteries, the concavity of the plaque surface and the surface echo intensity were carefully investigated. The conventional criteria stipulate a concavity larger than 2 × 2 mm with a well-defined back wall and flow reversal within the recess. Our new criteria specify a concavity in the plaque with the basal border echo weaker than that of the adjacent plaque surface, regardless of size. The final diagnosis was based on surgical and histologic findings. RESULTS Among the 30 carotid arteries, 14 arteries had 14 ulcers at surgery. Seventeen concavities were detected by sonography, and 12 of them, including six smaller than 2 × 2 mm, were truly ulcers. Two concavities with an echo intensity of the basal border equal to or greater than that of the adjacent surface were not true ulcers. Only two of 14 ulcers were not detected by sonography. The sensitivity and specificity of the conventional criteria were 35.7% and 75.0%, respectively, and those of our new criteria were 85.7% and 81.3%, respectively. CONCLUSION Our new criteria for the sonographic diagnosis of plaque ulcer are more useful than the conventional ones.

Evaluation of cytokines in cerebrospinal fluid from patients with Moyamoya disease

We investigated the levels of angiogenic growth factors in cerebrospinal fluid (CSF) from patients with Moyamoya disease and from those with atherosclerotic occlusive disease to evaluate the relationship of these factors to the pathogenesis of Moyamoya disease. CSF from Moyamoya patients contained significantly higher concentrations of basic fibroblast growth factor (b-FGF) (P < 0.05). The b-FGF level was apparently elevated in patients with well developed neovascularization after indirect revascularization surgery (P < 0.01). The other angiogenic factors were not significantly elevated compared with those of the control group.

Identification of high-risk carotid artery stenosis: motion of intraplaque contents detected using B-mode ultrasonography

OBJECT Identification of the risk of rupture and vulnerability of arterial plaque is not yet clearly understood. The aim of this study was to assess the clinical features of the motion of intraplaque contents (MIC) detected by B-mode ultrasonography. The MIC is characterized by the peculiar movement of the intraplaque contents that is not synchronized with the heartbeat; however, the movement of the carotid artery (CA) wall depends on the heartbeat. METHODS From January 2008 to November 2010, 1798 consecutive patients with transient ischemic attacks (TIAs) or acute ischemic stroke underwent CA ultrasonography for the examination of the MIC. Patients with CA stenosis greater than 50% were followed up until they underwent carotid endarterectomy or CA angioplasty and stent placement. If neither of these procedures were used, the patients were followed up at 90 days. Chi-square and Mann-Whitney tests were performed to compare the categorical and continuous demographic data and risk factors. The effect of the MIC on the rate of recurrent cerebral ischemia was examined using Kaplan-Meier and univariate Cox regression analyses. RESULTS One hundred and fifteen patients had CA stenosis greater than 50%. Among these 115 patients, 58 with a total of 59 CA stenoses had MIC. Twenty-four recurrent ischemic events were associated with MIC, whereas only 6 such events occurred in the absence of MIC. The MIC decreased event-free survival (log-rank test = 15.8, p < 0.001); univariate Cox analysis confirmed that MIC increased the risk of a recurrent ischemic event (HR 5.12, 95% CI 2.08-12.58; p < 0.001). CONCLUSIONS The MIC is one of the findings of vulnerable plaques. The MIC is more useful in predicting the recurrence of TIAs or ischemic events in patients with symptomatic CA stenosis.