Tatsuya Ishikawa

Incidence and Clinical Features of Disease Progression in Adult Moyamoya Disease

Background and Purpose— The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. Methods— For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography. Results— Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97). Conclusions— The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

Neovascularization (Angiogenesis) After Revascularization in Moyamoya Disease. Which Technique is Most Useful for Moyamoya Disease

Summary¶ The effects of direct and indirect revascularization for moyamoya disease were analyzed for each donor artery to determine which surgical procedure is most useful for the induction of neovascularization.In the past 12 years, 85 patients with moyamoya disease were surgically treated by combined surgery consisting of indirect revascularization via encephalo-duro-arterio-myo-synangiosis (EDAMS) and direct revascularization via the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass. Among those patients, the post-operative changes in digital subtraction angiography were examined in 56 sides, including 34 sides in paediatric cases and 22 sides in adult cases. The neovascularization after indirect revascularization using the 1) superficial temporal artery (skin), 2) middle meningeal artery (dura mater), 3) deep temporal artery (temporal muscle) was analyzed.As results, in paediatric cases, the deep temporal artery and middle meningeal artery induced good neovascularization. However, the induction of neovascularization from the superficial temporal artery was not always good in most pediatric and adult cases. On the other hand, the direct bypass was useful in 90% of adult cases.In indirect revascularization surgery for moyamoya disease, the temporal muscle (the deep temporal artery) and the dura mater (the middle meningeal artery) are useful donors to the ischemic brain. The simple encephalo-arterio-synangiosis is not always effective. The direct bypass is a useful technique for adult moyamoya disease.

Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia

The present study was aimed to evaluate the effect of the free radical scavenger Edaravone on infarct volume due to permanent MCA occlusion in mice and, if so, to elucidate the mechanism of its neuroprotective effects. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion and were treated with 3.0 mg/kg of Edaravone or vehicle 30 min before ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Furthermore, in situ detection of superoxide in the ipsilateral neocortex was carried out using the superoxide-sensitive dye dihydroethidium (DHE) staining technique. Pretreatment with 3.0 mg/kg of Edaravone ameliorated the tissue damage in the infarct rim and significantly reduced infarct volume to about 77% of the control (p<0.05). Semi-quantitative measurement of red fluorescence emitted from DHE revealed that the superoxide increased in the ischemic core at 1 h after the onset of ischemia and extended towards the infarct rim at 3 and 6 h, and that pretreatment with 3.0 mg/kg of Edaravone significantly inhibited the increase of superoxide in the infarct rim at 3 and 6 h (p<0.01). Double staining with DHE and monoclonal antibody against NeuN showed that the majority of the nuclei positive for DHE were also positive for NeuN. These findings suggest that Edaravone salvages the boundary zone of infarct by scavenging reactive oxygen species especially in the neurons during permanent focal cerebral ischemia.

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.

Performance of Bedside Transpulmonary Thermodilution Monitoring for Goal-Directed Hemodynamic Management After Subarachnoid Hemorrhage

Background and Purpose— Early goal-directed hemodynamic therapy is of particular importance for adequate cerebral circulation of patients with vasospasm after subarachnoid hemorrhage but is often precluded by the invasiveness of established cardiac output determination using a pulmonary artery catheter. This study was undertaken to validate the usefulness of less invasive goal-directed hemodynamic monitoring by transpulmonary thermodilution technique in patients after subarachnoid hemorrhage. Methods— One hundred sixteen patients with subarachnoid hemorrhage who underwent surgical clipping within 24 hours of ictus were investigated. Validation of transpulmonary thermodilution-derived intermittent/continuous cardiac output and cardiac preload (global end diastolic volume) were compared with pulmonary artery catheter-derived reference cardiac output and pulmonary capillary wedge pressure or central venous pressure in 16 patients diagnosed with vasospasm. In a subsequent trial of 100 consecutive cases, clinical results between the new and standard management paradigms were compared. Results— Transpulmonary thermodilution-derived intermittent cardiac output and transpulmonary thermodilution-derived continuous cardiac output showed close agreement to catheter-derived reference cardiac output with high correlation (r=0.85 and 0.77) and low percentage error (13.5% and 18.0%). Fluid responsiveness to defined volume loading was predicted better with global end diastolic volume than with pulmonary capillary wedge pressure and central venous pressure for larger receiver operating characteristic curve area. Patients receiving early goal-directed management by transpulmonary thermodilution experienced reduced frequencies of vasospasm and cardiopulmonary complications compared with those managed with standard therapy (P<0.05), whereas their functional outcomes at 3 months were not different (P=0.06). Conclusions— Goal-directed hemodynamic management guided by transpulmonary thermodilution appears to have a therapeutic advantage for optimizing the prognosis of patients with subarachnoid hemorrhage with vasospasm over conventional methods.

Novel bypass surgery for moyamoya disease using pericranial flap: its impacts on cerebral hemodynamics and long-term outcome.

OBJECTIVEWe reviewed our 11-year experience with a novel bypass procedure, superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-arterio-pericranio-synangiosis (EDMAPS), for moyamoya disease regarding cerebral hemodynamics and long-term outcome. METHODSThis prospective study included 75 patients with moyamoya disease, including 28 children and 47 adults. We performed STA-MCA anastomosis and EDMAPS on 123 hemispheres of 75 patients. In addition to conventional STA-MCA anastomosis and indirect bypass for the MCA territory, the medial frontal lobe was revascularized using the frontal pericranial flap through medial frontal craniotomy. Surgical results were analyzed with magnetic resonance imaging, cerebral angiography, and single-photon emission computed tomography/positron emission tomography. RESULTSOverall incidences of mortality and morbidity were 0% and 5.7%, respectively. The annual risk of cerebrovascular events during the follow-up periods was very low: 0% in pediatric patients and 0.4% in adults over approximately 67 months. Postoperative cerebral angiography showed that the pericranial flap functioned well as donor tissue for indirect bypass, especially in pediatric patients. Follow-up single-photon emission computed tomography/positron emission tomography studies revealed that cerebral blood flow and its reactivity to acetazolamide markedly improved in both the MCA and anterior cerebral artery territories. CONCLUSIONThese findings strongly suggest that STA-MCA anastomosis and EDMAPS using a frontal pericranial flap is a safe and effective surgical procedure to further improve the long-term prognosis in moyamoya disease by improving cerebral hemodynamics in both the MCA and anterior cerebral artery territories.

Increased Expression of Hepatocyte Growth Factor in Cerebrospinal Fluid and Intracranial Artery in Moyamoya Disease

Background and Purpose— The etiology of moyamoya disease still remains unknown. This study was aimed to explore the role of hepatocyte growth factor (HGF), a strong inducer of angiogenesis, in development of moyamoya disease. Methods— We studied cerebrospinal fluid (CSF) from 39 patients with moyamoya disease (24 children and 15 adults), 6 control patients with cervical spondylosis, and 7 control patients with internal carotid artery occlusion. CSF level of HGF was determined by enzyme-linked immunosorbent assay technique. We also evaluated the distribution of HGF and its cellular receptor c-Met in the carotid fork obtained from 2 patients with moyamoya disease and 2 control patients. Results— CSF level of HGF was 408.2±201.6 pg/mL and 443.2±193.5 pg/mL in patients with cervical spondylosis and internal carotid artery occlusion, respectively (mean±SD). On the other hand, CSF level of HGF was 820.3±319.0 pg/mL in patients with moyamoya disease, being significantly higher than those in 2 control groups (P<0.01). Both HGF and c-Met were widely distributed in the media and thickened intima of the carotid fork in patients with moyamoya disease but not in control patients. Conclusions— This study revealed that HGF is densely found in the carotid fork, and its CSF level is markedly elevated in moyamoya disease, suggesting that HGF may be a key protein for pathogenesis of moyamoya disease.

Dissociation of Vasoreactivity to Acetazolamide and Hypercapnia Comparative Study in Patients With Chronic Occlusive Major Cerebral Artery Disease

BACKGROUND AND PURPOSE The aim of this study was to compare the effect of vasodilative stimuli for the measurement of cerebrovascular reactivity obtained by acetazolamide and hypercapnia in patients with chronic occlusive major cerebral artery disease. METHODS We examined 24 patients with unilateral occlusive lesions of a major cerebral artery using the 133Xe inhalation technique and single-photon emission CT. Regional cerebral blood flow (CBF) was measured during a resting state, during inhalation of 5% CO2, and 15 minutes after the administration of acetazolamide consecutively in the same patients. Normative values of resting CBF and acetazolamide reactivity were obtained in 21 normal subjects. RESULTS All patients with the exception of 1 showed an increase in CBF during hypercapnia ipsilateral to the occlusive lesion. Ipsilateral acetazolamide reactivity was preserved in 13 patients. Conversely, 11 patients showed an absent response or paradoxical CBF reduction. Ipsilateral CO2 reactivity did not correlate with acetazolamide reactivity when all 24 patients were considered. However, there was a significant correlation between acetazolamide and CO2 in the 13 patients who showed preserved acetazolamide reactivity (r = .60, P < .05). No significant correlation was present in the remaining 11 patients with reduced acetazolamide reactivity. Although significant blood pressure augmentation was observed in hypercapnia, we could not find a correlation between change of blood pressure and CO2 reactivity. CONCLUSIONS Acetazolamide identified patients with reduced vasomotor reactivity who appeared to have preserved CO2 reactivity. Acetazolamide testing may be useful in the assessment of cerebral hemodynamics. However, further investigations are necessary to assess the clinical utility of these tests.

The frequency of postoperative stroke in moyamoya disease following combined revascularization: a single-university series and systematic review

OBJECT Although combined direct and indirect anastomosis in patients with moyamoya disease immediately increases cerebral blood flow, the surgical procedure is more complex. Data pertinent to the postoperative complications associated with combined bypass are relatively scarce compared with those associated with indirect bypass. This study investigated the incidence and characteristics of postoperative stroke in combined bypass and compared them with those determined from a literature review to obtain data from a large population. METHODS A total of 358 revascularization procedures in 236 patients were retrospectively assessed by reviewing clinical charts and radiological data. PubMed was searched for published studies on surgical treatment to determine the incidence of postoperative complications in a larger population. RESULTS Seventeen instances of postoperative stroke were observed in 16 patients (4.7% per surgery, 95% CI 2.8%-7.5%). Postoperative stroke was more frequent (7.9% per surgery) in adults than in pediatric patients (1.7% per surgery, OR 4.07, 95% CI 1.12-14.7; p < 0.05). Acute progression of stenoocclusive changes were identified in the major cerebral arteries (anterior cerebral artery, n = 3; middle cerebral artery, n = 1; posterior cerebral artery, n = 2). The postoperative stroke rate was comparable with that (5.4%) determined from a literature search that included studies reporting more than 2000 direct/combined procedures. No differences in the stroke rates between the direct/combined and indirect procedures were found. In the literature review, direct/combined bypass was more often associated with excellent revascularization (angiographic opacification greater than two-thirds) than indirect bypass (p < 0.05). CONCLUSIONS This experience of 358 consecutive procedures is one of the largest series for which the postoperative stoke rate for direct/combined bypass performed with a unified strategy has been reported. A systematic review confirmed that the postoperative stroke rate for the direct/combined procedure was comparable to that for the indirect procedure.

Neuroprotective effect of a heat shock protein inducer, geranylgeranylacetone in permanent focal cerebral ischemia

Previous studies have strongly suggested that heat shock protein 70 (HSP70) has protective effects in ischemia/reperfusion in tissues such as brain, heart, and liver. This study was performed to assess the efficacy of the HSP70 inducer geranylgeranylacetone (GGA) in experiments involving permanent middle cerebral artery (MCA) occlusion. Male Balb/c mice were subjected to permanent MCA occlusion by direct occlusion through small craniectomy. Vehicle or GGA (200 or 1000 mg/kg) was injected intraperitoneally 1 h prior to the onset of ischemia. Infarct volumes were evaluated at 24 h of ischemia by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. The effect of GGA on the induction of HSP70 was studied at 3 h after ischemia with fluorescence immunocytochemistry. The percentage of infarct volume in the control mice (n=10) was 23.0+/-4.0% (mean+/-SD) of the contralateral hemisphere, while those in the treated groups were 22.6+/-7.3% (200 mg/kg group; n=5, P>0.05) and 15.7+/-3.8% (1000 mg/kg group; n=5, P<0.05). Pretreatments with 1000 mg/kg of GGA enhanced the ischemia-related induction of HSP in the neurons and astrocytes in the boundary zone of infarct. The results demonstrate that GGA significantly reduces infarct volume due to permanent MCA occlusion when given 1 h prior to the induction of ischemia.