Naoki Toma

Determinants of Poor Outcome After Aneurysmal Subarachnoid Hemorrhage when both Clipping and Coiling Are Available: Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) in Japan

OBJECTIVE To examine current determinants of poor outcome after aneurysmal subarachnoid hemorrhage (SAH) when ruptured aneurysms are treated with either microsurgery (clipping) or endovascular treatment (coiling) depending on each patients characteristics. METHODS Between March 2006 and February 2007, 534 patients with SAH were enrolled in the Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) project. Patients were treated according to the preference of investigators who were experienced in performing both clipping and coiling. Factors influencing poor outcome (12-month modified Rankin Scale [mRS], 3-6) were determined using multivariate logistic regression analyses. RESULTS In this cohort, 32.4% of patients were World Federation of Neurosurgical Societies (WFNS) grade IV-V, and 28.1% had a poor outcome. Clipping was preferably performed for small aneurysms with a wide neck and for middle cerebral artery (MCA) aneurysms, whereas coiling was preferred for larger, internal carotid artery (ICA) and posterior circulation aneurysms. In addition to increasing age, admission WFNS grade IV-V, preadmission aneurysmal rerupture, vasospasm-induced cerebral infarct, pneumonia, sepsis, shunt-dependent hydrocephalus and seizure, postclipping hemorrhagic complications (odds ratio 4.8, 95% confidence interval 1.5-15.3, P < 0.01), and postcoiling ischemic complications (odds ratio 4.4, 95% confidence interval 1.3-15.2, P < 0.05) significantly caused poor outcomes, although the complications did not affect mortality. Type of treatment modality and size and location of aneurysms did not influence outcome. CONCLUSIONS Introducing an endovascular treatment option has made aneurysm characteristics less important to outcome, but procedural complications are problematic and should be reduced to improve outcome.

Development of Nanofiber-Covered Stents Using Electrospinning: In Vitro and Acute Phase In Vivo Experiments

There are some technical difficulties in treating for a broad necked aneurysm and a higher incidence of recurrence. Because of these drawbacks, more innovative techniques for superior endovascular reconstructive treatment are required. We developed a novel covered stent employing electrospinning to deposit fine polyurethane (PU) fibers onto stents. An in vitro water leak test was designed and applied prior to animal testing to estimate the performance of covered stents and to determine the appropriate amount of PU fibers on a stent. Two tenths of a milligram of PU fibers proved to be sufficient to prevent water leakage. Then, the efficacy of the covered stents to that of bare stents was compared using 10 rabbits in which model aneurysms had been formed at the right common carotid artery by the elastase method. Angiographic evaluation on day 1 posttreatment (acute phase) revealed complete occlusion of the aneurysms and the patency of the parent arteries in animals treated with covered stents. At 10 days poststenting (subacute phase), the aneurysm neck was completely covered with neointimal layer as shown by scanning electron microscopic examination. The PU-covered stent holds promise as a device for treating cerebral aneurysms.

Inflammatory Biomarkers in Atherosclerosis: Pentraxin 3 Can Become a Novel Marker of Plaque Vulnerability

Inflammation is crucially involved in the development of carotid plaques. We examined the relationship between plaque vulnerability and inflammatory biomarkers using intraoperative blood and tissue specimens. We examined 58 patients with carotid stenosis. Following carotid plaque magnetic resonance imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery (systemic) and common carotid artery immediately before and after CAS (local). Seventeen resected CEA tissue samples were embedded in paraffin, and histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin, adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL-1β, IL-10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were measured by multiplex bead array system and ELISA. CAS-treated patients were classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and TNFα), endothelial activation markers (E-selectin and VCAM-1), and inflammation markers (hs-CRP and PTX3) and downregulation of the anti-inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and intracarotid samples before and after CAS were higher in the vulnerable group than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed in the endothelial and perivascular cells. Our findings reveal that carotid plaque vulnerability is modulated by the upregulation and downregulation of proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a potential predictive marker of plaque vulnerability.

Periprocedural hemodynamic instability with carotid angioplasty and stenting

BACKGROUND Carotid angioplasty and stenting is used for treatment of carotid stenosis. Stent deployment may induce HDI and thereby cause systemic or neurologic deficits. This study defines characteristics and predictors of HDI with CAS. METHODS A total of 132 patients who had undergone CAS were evaluated for periprocedural and postprocedural HDI (hypertension, systolic blood pressure >160 mm Hg; hypotension, systolic blood pressure <90 mm Hg; or bradycardia, heart rate <60 beats per minute). RESULTS Frequencies of HDI were 6.8% for hypertension, 32.6% for hypotension, and 15.9% for bradycardia. In addition, CAS of the right side (P < .01), carotid bulb lesions (P < .05), eccentric posterior carotid plaque (P < .0001), and general anesthesia (P < .05) were associated significantly with postprocedural HDI. Male sex (OR, 3.4; 95% CI, 1.8-67.2; P < .001), age of 80 years or older (OR, 0.4; 95%CI, 0.1-1.4; P = .011), and plaque ulceration (OR, 0.5; 95% CI, 0.1-9.5; P = .008) independently predicted postprocedural hypertension. Male sex (OR, 2.5; 95% CI, 1.3-24.9; P < .001), preprocedural major stroke (OR, 0.1; 95% CI, 0.01-0.8; P = .002), carotid bulb lesions (OR, 1.6; 95% CI, 1.1-25.9; P = .024), and contralateral carotid occlusion (OR, 0.6; 95% CI, 0.2-4.9; P = .040) all predicted postprocedural hypotension. Bradycardia was associated with diabetes mellitus (OR, 0.7; 95% CI, 0.3-2.4; P = .033), preprocedural TIA (OR, 1.7; 95% CI, 1.4-17.9; P = .020), and minor stroke (OR, 1.5; 95% CI, 1-10.9; P = .037). In 5 patients, HDI predisposed neurologic or systemic deterioration. CONCLUSIONS Hemodynamic instability is common with CAS; hypotension and bradycardia are more frequent than hypertension. Some clinical, angiographic, and procedural variables can predict these HD changes.

Endovascular management of vertebral artery dissecting aneurysms: review of 25 patients.

AIM Management of Vertebral Artery (VA) dissections remains controversial. The clinical and angiographic variables of VA dissections were evaluated to demonstrate the safety and efficacy of endovascular intervention in treatment of VA dissecting aneurysms. MATERIAL AND METHODS 25 patients with 27 VAdissecting aneurysms were treated with endovascular intervention during the last 10 years.17 patients were admitted with subarachnoid hemorrhage. 23 aneurysms treated using destructive endovascular trapping, while reconstructive techniques were used in 3 aneurysms treated with stent-assisted coiling and one aneurysm treated with false lumen embolization. RESULTS The right VA was involved in 14 patients, the left VA in 9 patients, while 2 patients had bilateral VA dissection. The pearl and string sign was the commonest angiographic sign in 12 aneurysms. Perioperative complications included; rebleeding in one patient, symptomatic brain stem infarction in two patients and silent cerebellar ischemic lesion in one patient. Afavorable outcome was evident more in patients with unruptured VA dissection (100%) versus (76.5%) in patients presented with SAH. CONCLUSION The endovascular technique should be individualized according to the clinical status of the patient, angiographic variables, condition of the posterior circulation and the available supplies.

High-Risk Plaque for Carotid Artery Stenting Evaluated With 3-Dimensional T1-Weighted Gradient Echo Sequence

Background and Purpose— Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS. Methods— We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli. Results— SIR (2.17 [interquartile range 1.50–3.07] versus 1.35 [interquartile range 1.08–1.97]; P=0.010) and plaque volume (456 mm3 [interquartile range 256–696] versus 301 mm3 [interquartile range 126–433]; P=0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR (P=0.007) and plaque volume (P=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR (rs=0.42, P=0.005) and plaque volume (rs=0.36, P=0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm3, respectively. Conclusions— Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.

Novel Dynamic Four-Dimensional CT Angiography Revealing 2-Type Motions of Cerebral Arteries

Background and Purpose— We developed a novel dynamic 4-dimensional CT angiography to accurately evaluate dynamics in cerebral aneurysm. Methods— Dynamic 4-dimensional CT angiography achieved high-resolution 3-dimensional imaging with temporal resolution in a beating heart using dynamic scanning data sets reconstructed with a retrospective simulated R-R interval reconstruction algorithm. Results— Movie artifacts disappeared on dynamic 4-dimensional CT angiography movies of 2 kinds of stationary phantoms (titanium clips and dry bone). In the virtual pulsating aneurysm model, pulsation on the dynamic 4-dimensional CT angiography movie resembled actual movement in terms of pulsation size. In a clinical study, dynamic 4-dimensional CT angiography showed 2-type motions: pulsation and anatomic positional changes of the cerebral artery. Conclusions— This newly developed 4-dimensional visualizing technique may deliver some clues to clarify the pathophysiology of cerebral aneurysms.

Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage

OBJECTIVE Chronic hydrocephalus develops in association with the induction of tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective inhibitor of phosphodiesterase Type III, suppresses the development of chronic hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The authors retrospectively reviewed the factors influencing the development of chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH using multivariate logistic regression analyses. Cilostazol (50 or 100 mg administered 2 or 3 times per day) was administered from the day following aneurysmal obliteration according to the preference of the attending neurosurgeon. As a separate study, the effects of different dosages of cilostazol on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of 36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to 200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23, 95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the development of chronic hydrocephalus and reduce shunt surgery, possibly by the inhibition of TNC induction after SAH.

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism

BACKGROUND This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. METHODS Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-β), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. RESULTS Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 ± 7.1%; GSCC, 54.2 ± 18.3%; GSCC-TNC, 82.5 ± 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-β, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-β, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. CONCLUSIONS This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-β and MMP-9 upregulation.

Angiotensin II type 1 receptor blockers suppress neointimal hyperplasia after stent implantation in carotid arteries of hypercholesterolemic rabbits.

Abstract Objectives: The purpose of this study was to examine whether oral administration of an angiotensin II type 1 receptor blocker (ARB) inhibited in-stent neointimal hyperplasia in carotid arteries of hypercholesterolemic rabbits. Methods: Eleven male New Zealand white rabbits were subjected to endothelial injuries of the right common carotid arteries using a balloon catheter and then received chow containing 1% cholesterol for 6 weeks. A balloon-expandable stainless steel stent was subsequently inserted at the injured sites of the arteries. After stenting, five rabbits were randomly treated with an oral ARB, candesartan cilexetil (5 mg/kg per day orally), while the remaining six rabbits acted as untreated controls. Four weeks after the implantation, the rabbits were killed, followed by collection of the arteries including the stents. After careful removal of the stents, tissue sections were prepared and analyzed by morphometric and immunohistochemical methods. Results: The mean thickness of the neointima was 53·6±17·0 μm in the ARB-treated group, which was significantly reduced compared to 95·9±16·7 μm in the control group (P = 0·0012). Immunohistochemistry showed a decrease in accumulation of macrophages and tenascin-C expression in the arterial wall in the ARB-treated animals. Discussion: This study suggested that systemic administration of an ARB suppressed neointimal hyperplasia in the carotid artery following stent implantation by the anti-inflammatory effects, although the animal cohort tested was rather small. This finding implies that ARBs may be useful and practical agents for protection against in-stent restenosis in humans, and warrants further basic and clinical studies.