Hideaki Takahata

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.

PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrP(C).

A hydrophobic, fibrillogenic peptide fragment of human prion protein (PrP 106–126) had in vitro toxicity to neurons expressing cellular prion protein (PrPC). In this study, we proved that primary cultures of mouse cerebral endothelial cells (MCEC) express PrPC. Incubation of MCEC with PrP 106–126 (25–200 μM) caused a dose-dependent toxicity assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase release, bis-benzimide staining for nuclear morphology, and trypan blue exclusion test. Pentosan polysulphate (50–100 μg/ml), a drug effective in scrapie prophylaxis, dose-dependently attenuated the injury. MCEC cultures from mice homogenous for the disrupted PrP gene were resistant to the toxicity of PrP 106–126. In conclusion, cerebral endothelium expressing PrPC may be directly damaged during spongiform encephalopathies.

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.

Early intervention to promote oral feeding in patients with intracerebral hemorrhage: a retrospective cohort study

BackgroundStroke is a major cause of dysphagia, but little is known about when and how dysphagic patients should be fed and treated after an acute stroke. The purpose of this study is to establish the feasibility, risks and clinical outcomes of early intensive oral care and a new speech and language therapist/nurse led structured policy for oral feeding in patients with an acute intracerebral hemorrhage (ICH).MethodsA total of 219 patients with spontaneous ICH who were admitted to our institution from 2004 to 2007 were retrospectively analyzed. An early intervention program for oral feeding, which consisted of intensive oral care and early behavioral interventions, was introduced from April 2005 and fully operational by January 2006. Outcomes were compared between an early intervention group of 129 patients recruited after January 2006 and a historical control group of 90 patients recruited between January 2004 and March 2005. A logistic regression technique was used to adjust for baseline differences between the groups. To analyze time to attain oral feeding, the Kaplan-Meier method and Cox proportional hazard model were used.ResultsThe proportion of patients who could tolerate oral feeding was significantly higher in the early intervention group compared with the control group (112/129 (86.8%) vs. 61/90 (67.8%); odds ratio 3.13, 95% CI, 1.59-6.15; P < 0.001). After adjusting for baseline imbalances, the odds ratio was 4.42 (95% CI, 1.81-10.8; P = 0.001). The incidence of chest infection was lower in the early intervention group compared with the control group (27/129 (20.9%) vs. 32/90 (35.6%); odds ratio 0.48, 95% CI, 0.26-0.88; P = 0.016). A log-rank test found a significant difference in nutritional supplementation-free survival between the two groups (hazard ratio 1.94, 95% CI, 1.46-2.71; P < 0.001).ConclusionsOur data suggest that the techniques can be used safely and possibly with enough benefit to justify a randomized controlled trial. Further investigation is needed to solve the eating problems that are associated with patients recovering from a severe stroke.

Tissue plasminogen activator inhibits P-glycoprotein activity in brain endothelial cells

Tissue plasminogen activator (0.01-30 microgram/ml) dose-dependently inhibited the functional activity of P-glycoprotein, assessed by rhodamine 123 accumulation in GP8 immortalized rat brain endothelial cells, but this effect was unrelated to its proteolytic activity. Elevation of intra-endothelial cyclic AMP concentration and stimulation of protein kinase C increased P-glycoprotein activity in GP8 cells and also attenuated the tissue plasminogen activator-induced inhibition.

Pediatric moyamoya disease presenting with intracerebral hemorrhage—Report of three cases and review of the literature

Intracerebral hemorrhage in patients with moyamoya disease is rare in children. We report three unique cases of pediatric moyamoya disease with hemorrhagic onset. Two 7-year-old girls and a 9-year-old girl were admitted to our hospital because of intracerebral hemorrhage associated with angiographically verified moyamoya disease. Two of them did not demonstrate either an ischemic episode or cerebral infarct on the magnetic resonance images. A decreased regional cerebral blood flow was revealed on single photon emission computed tomography in two patients, who developed cerebral infarction in the acute stage following hemorrhage. They underwent superficial temporal artery-middle cerebral artery anastomoses combined with encephalo-myo-synangiosis, and have not experienced any further ischemic episodes thereafter. Hemodynamic insufficiency associated with moyamoya disease could cause intracerebral hemorrhage even in children. Adequate management in the acute stage of hemorrhage and revascularization surgery are recommended to prevent cerebral infarction, which may easily occur in pediatric patients with moyamoya disease.

Pentosan Polysulfate Regulates Scavenger Receptor- Mediated, But Not Fluid-Phase, Endocytosis in Immortalized Cerebral Endothelial Cells

AbstractSUMMARY 1. Effects of pentosan polysulfate (PPS) and the structurally related sulfated polyanions dextran sulfate, fucoidan, and heparin on the scavenger receptor-mediated and fluid-phase endocytosis in GP8 immortalized rat brain endothelial cells were investigated.2. Using 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarboxyamine perchlorate-labeled acetylated low-density lipoprotein (DiI-AcLDL), we found a binding site with high affinity and low binding capacity, and another one with low affinity and high binding capacity. Increasing ligand concentrations could not saturate DiI-AcLDL uptake. DiI-AcLDL uptake, but not binding, was sensitive to pretreatment with filipin, an inhibitor of caveola formation.3. PPS (20–200 μg/ml) significantly reduced the binding of DiI-AcLDL after coincubation for 3 hr, though this effect was less expressed after 18 hr. Among other polyanions, only fucoidan decreased the DiI-AcLDL binding after 3 hr, whereas dextran sulfate significantly increased it after 18 hr. PPS treatment induced an increase in DiI-AcLDL uptake, whereas other polysulfated compounds caused a significant reduction.4. Fluid-phase endocytosis determined by the accumulation of Lucifer yellow was concentration and time dependent in GP8 cells. Coincubation with PPS or other sulfated polyanions could not significantly alter the rate of Lucifer yellow uptake.5. In conclusion, PPS decreased the binding and increased the uptake of DiI-AcLDL in cerebral endothelial cells, an effect not mimicked by the other polyanions investigated.

Restenosis after endovascular PTA/stenting for supra-aortic branches in Takayasu aortitis: report of three cases and review of the literature

Recently, endovascular management has been reported as a feasible option for Takayasu aortitis. However, few papers have focused on restenosis in the follow-up, and therefore, it is important to predict high-risk cases for restenosis after endovascular treatment. We herein report three cases with Takayasu aortitis showing repeated restenosis after endovascular percutaneous transluminal angioplasty (PTA)/stenting and discuss its clinical implications with a review of the literature. We should keep in mind that endovascular PTA/stenting for Takayasu aortitis does not always keep the patency of the affected vessels, and severity of the stenosis and/or uncontrollable systemic inflammation could be a risk factor for restenosis. Therefore, careful follow-up under strict control of inflammation is mandatory. Overall, this method is effective as an initial treatment since repeated PTA is available until collateral supply develops.

Strategy for the treatment of inaccessible unruptured giant and large aneurysms of the internal carotid artery

Abstract Our goal was to clarify the optimum management of the inaccessible unruptured giant and large aneurysms of the internal carotid artery (ICA). Since 1981, we have treated 18 patients with unclippable unruptured giant or large aneurysms of the ICA. Aneurysms were classified as either intracavernous or intradural. We performed proximal carotid occlusion in 12 patients and conservatively treated six patients. We retrospectively analyzed long-term outcomes in these patients. Four of seven patients with intradural aneurysm underwent proximal carotid occlusion, with good long-term outcomes. The three patients with intradural aneurysm, who were treated conservatively, died of subarachnoid hemorrhage. Eight of 11 patients with intracavernous aneurysm underwent proximal carotid occlusion, one dying of massive nasal bleeding 25 months after the procedure. In this case, the aneurysm was partially thrombosed, and residual lumen growth was revealed 22 months after proximal carotid occlusion. Cranial nerve paresis improved in five of the eight patients (63%), and two patients had a minor ischemic attack. Neurological problems failed to occur in the three patients with intracavernous aneurysm who were treated conservatively. The risk of rupture is relatively high in intradural giant and large aneurysms. Proximal carotid occlusion can effectively prevent bleeding from intradural aneurysms. Aggressive management is justified for intradural aneurysms with poor collateral circulation. Operative procedures in the management of an intracavernous aneurysm require careful consideration.