Akira Handa

Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery

Six aneurysms in five patients with acute aneurysmal subarachnoid hemorrhages were treated with direct thrombosis using cellulose acetate polymer within 4 hours of rupture. The aneurysms involved the internal carotid and posterior communicating arteries (two patients), the anterior choroidal artery (one patient), the bifurcation of the basilar artery (one patient), and the middle cerebral artery (two patients). Four patients underwent aggressive volume expansion after direct thrombosis with cellulose acetate polymer. The aneurysms remained thrombosed until operations on the necks were performed 2 to 7 weeks after the subarachnoid hemorrhages. Three patients were given intrathecal tissue plasminogen activator. One patient, who remained at neurological Grade V, was not treated surgically and died from cardiac failure. Five aneurysms in the remaining four patients were successfully clipped. These preliminary data suggest that immediate aneurysmal thrombosis, then aggressive preoperative prophylactic volume expansion and/or administration of intrathecal tissue plasminogen activator, can help prevent new bleeding and reduce delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhages.

Partial thrombosis of canine carotid bifurcation aneurysms with cellulose acetate polymer.

OBJECTIVE To investigate the usefulness of a cellulose acetate polymer (CAP) solution for partial thrombosis of aneurysms. METHODS We created 14 canine cervical carotid bifurcation aneurysms, 11 of which were subsequently thrombosed partially with CAP solution. We then conducted angiographic and histological investigations. RESULTS Nine aneurysms were thrombosed 50 to 70% by volume, although a significant crescent crevice between the aneurysmal sac and the CAP mass was left in four of the aneurysms. In the remaining two aneurysms in which a crescent crevice had been seen in the initial stage of CAP injection, 80% and more than 95% thrombosis were needed to occlude the crevice, respectively. Follow-up angiograms of the seven aneurysms with no crescent crevice revealed no shifts of position of the CAP mass toward the bottom of the aneurysm sac, but slight ballooning of the remnants was observed in two of them. The angiograms of the other four aneurysms with significant crescent crevices demonstrated rupture with a massive hematoma in one and shifts of the CAP mass with marked enlargement of remnants in three. Histologically, the seven aneurysms with no enlarged remnants had newly developed membranes consisting of endothelium, infiltrated spindle-shaped cells, collagen, and elastic fibers. In contrast, in the three markedly enlarged aneurysms, there were only recent clots between the CAP mass and the aneurysm lumen and no development of endothelium. CONCLUSION Partial thrombosis with CAP solution is useful to keep aneurysms in a stable configuration, unless a crescent crevice has been left.

Carotid artery plaque assessment using quantitative expansive remodeling evaluation and MRI plaque signal intensity

OBJECTIVE Plaque characteristics and morphology are important indicators of plaque vulnerability. MRI-detected intraplaque hemorrhage has a great effect on plaque vulnerability. Expansive remodeling, which has been considered compensatory enlargement of the arterial wall in the progression of atherosclerosis, is one of the criteria of vulnerable plaque in the coronary circulation. The purpose of this study was risk stratification of carotid artery plaque through the evaluation of quantitative expansive remodeling and MRI plaque signal intensity. METHODS Both preoperative carotid artery T1-weighted axial and long-axis MR images of 70 patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) were studied. The expansive remodeling ratio (ERR) was calculated from the ratio of the linear diameter of the artery at the thickest segment of the plaque to the diameter of the artery on the long-axis image. Relative plaque signal intensity (rSI) was also calculated from the axial image, and the patients were grouped as follows: Group A = rSI ≥ 1.40 and ERR ≥ 1.66; Group B = rSI< 1.40 and ERR ≥ 1.66; Group C = rSI ≥ 1.40 and ERR < 1.66; and Group D = rSI < 1.40 and ERR < 1.66. Ischemic events within 6 months were retrospectively evaluated in each group. RESULTS Of the 70 patients, 17 (74%) in Group A, 6 (43%) in Group B, 7 (44%) in Group C, and 6 (35%) in Group D had ischemic events. Ischemic events were significantly more common in Group A than in Group D (p = 0.01). CONCLUSIONS In the present series of patients with carotid artery stenosis scheduled for CEA or CAS, patients with plaque with a high degree of expansion of the vessel and T1 high signal intensity were at higher risk of ischemic events. The combined assessment of plaque characterization with MRI and morphological evaluation using ERR might be useful in risk stratification for carotid lesions, which should be validated by a prospective, randomized study of asymptomatic patients.

Plasma D-dimer may predict poor functional outcomes through systemic complications after aneurysmal subarachnoid hemorrhage

OBJECTIVE Plasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes. METHODS A total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. RESULTS D-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer. CONCLUSIONS Elevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

Reduced cerebrovascular reserve is associated with an increased risk of postoperative ischemic lesions during carotid artery stenting

Background Reduced cerebrovascular reserve (CVR) is associated with increased risk of ischemic events in carotid steno-occlusive diseases. Objective To determine whether pretreatment CVR can predict postoperative ischemic lesions after carotid artery stenting (CAS) by retrospective analysis. Methods We retrospectively reviewed the medical records of 46 patients (42 men; mean age 74.2±8.3 years) who underwent CAS and preprocedural cerebral blood flow measurement by quantitative single-photon emission CT. Ischemic lesions were evaluated by diffusion-weighted image (DWI) within 72 h after the intervention. We also evaluated plaque characteristics using black-blood MR plaque imaging. Results New ipsilateral DWI-positive lesions were found in 11 cases (23.9%). Patients were classified into two groups based on the presence or absence of new DWI-positive lesions, and no significant differences in characteristics were found between the DWI-positive and DWI-negative groups, except for age and CVR of the ipsilateral middle cerebral artery (MCA) territory. The DWI-positive group was significantly older than the DWI-negative group (79.7±4.1 vs 72.5±8.6 years; p=0.0085) and had lower average regional CVR (1.4±18.2% vs 22.4±25.8%; p=0.016). MR plaque imaging showed no significant difference in relative overall plaque MR signal intensity between the two groups (1.53±0.37 vs 1.34±0.26; p=0.113). In multivariate logistic regression analysis, lower CVR of the ipsilateral MCA territory (<11%) was the only independent risk factor for new ischemic lesions following CAS (OR=6.99; 95% CI 1.17 to 41.80; p=0.033). Conclusions Impaired pretreatment CVR was associated with increased incidence of new infarction after CAS.

Percutaneous balloon angioplasty for acute occlusion of intracranial arteries.

BACKGROUND The benefits of intravenous thrombolysis for acute ischemic stroke are still limited. OBJECTIVE To evaluate the safety and efficacy of double-lumen balloon catheter-based reperfusion therapy with or without intra-arterial thrombolysis for acute occlusion of intracranial arteries. METHODS Fifty-nine patients with acute occlusion of intracranial arteries were enrolled. A Gateway balloon catheter was used to disrupt clots or dilate atheromatous plaques in every patient. The technical details, technique-related complications, recanalization rates, and clinical outcomes were analyzed. RESULTS The occlusion sites were internal carotid arteries in 17 patients, M1 segments in 32 patients, the M2 segment in 1 patient, a vertebral artery in 1 patient, and basilar arteries in 8 patients. Twenty-four patients (41%) were treated with thrombolysis first, and 20 patients (34%) were treated with percutaneous transluminal angioplasty (PTA) followed by thrombolysis. PTA alone was performed in 15 patients (25%). The mean dose of urokinase was 205 × 103 U. The extent of recanalization was complete (Thrombolysis in Myocardial Infarction [TIMI] score of 3) in 17 patients (29%), and partial (TIMI 1/2) in 28 patients (47%). Functional independence at discharge was preserved in 76%, 25%, and 7% of patients with TIMI 3, TIMI 1/2, and TIMI 0, respectively. A combination of PTA and thrombolysis resulted in a significantly higher recanalization rate than PTA only. Seven patients (12%) experienced hemorrhagic events after treatment. Severe parenchymal hemorrhage with neurologic deterioration was observed in 2 patients (4%), and vessel rupture was encountered in 1 atherosclerotic case. CONCLUSIONS Mechanical angioplasty using a Gateway catheter combined with a low-dose thrombolytic agent is a safe and effective treatment for acute intracranial embolic and atherosclerotic occlusion with a low risk of hemorrhagic complications.

Effect of intrathecal milrinone injection via lumbar catheter on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI. METHODS The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables. RESULTS After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups. CONCLUSIONS In propensity score-matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.

Asymptomatic Carotid T1-High-Intense Plaque as a Risk Factor for a Subsequent Cerebrovascular Ischemic Event

Background: Intraplaque hemorrhage, detected as a high-signal intensity on carotid MRI, is also strongly associated with ischemic events in symptomatic patients. However, in asymptomatic patients, the relationship of the T1-high intense plaque and the subsequent stroke is not clear. The aim of this study is to test the hypothesis that asymptomatic carotid T1-high intense plaque is a risk factor for a subsequent cerebrovascular ischemic event. Methods: Of the 1,353 consecutive patients, who underwent head and carotid MRI as part of their annual medical check-up, the imaging quality of 13 was poor and 150 did not present for follow-up examination, thus leaving 1,190 subjects for evaluation. Of the 1,190 patients, 96 patients had findings of high-signal intensity on carotid MRI and 1,094 patients did not. Cerebrovascular events were retrospectively evaluated. Results: During a mean follow-up period of 53 months, 4 patients with high-signal intensities on carotid MRI (4%) and 3 with no findings (0.3%) had a cerebrovascular ischemic event, with the occurrences significantly higher in the high-signal-intensity group. (p < 0.01) Cox regression analysis indicated that the presence of the high-intense plaque on carotid MRI (hazard ratio [HR] 4.2; 95% CI 1.0-17.1; p = 0.04), age (HR 1.1; 95% CI 1.0-1.2; p = 0.003), and diabetes mellitus (HR 7.2; 95% CI 1.8-27.4; p = 0.004) were associated with the occurrence of subsequent ischemic cerebrovascular events. Conclusions: Asymptomatic carotid T1-high-intense plaque might be a potential high-risk factor for a subsequent cerebrovascular ischemic event.

Endovascular Therapy for Ruptured Cerebral Aneurysms in the Elderly: Poor Accessibility of the Guiding Catheter and Use of Local Anesthesia as the Predictors of Procedure-Related Rupture.

BACKGROUND Endovascular therapy is favored for ruptured intracranial aneurysms in the elderly. However, poor accessibility to the aneurysm through the parent artery and use of local anesthesia in this age group may predispose to intraprocedural complications. OBJECTIVE To evaluate whether age-related poor access to the ruptured target aneurysm and use of local anesthesia are associated with increased incidence of procedure-related rupture during endovascular embolization. METHODS A total of 117 patients with 117 ruptured aneurysms underwent endovascular embolization at a single institution. Correlation of increasing age with poor accessibility of the guiding catheter was analyzed. In addition, the distance from the aneurysm to the guiding catheter was investigated to identify an association with incidence of procedure-related rupture. Correlation of local anesthesia with procedure-related rupture was also evaluated in the multivariable analysis. RESULTS Increasing age was significantly associated with poor accessibility of the guiding catheter (P = .001, Mann-Whitney U test). Procedure-related rupture occurred in 9 of 117 aneurysms (7.7%). Longer distance between distal aneurysms and low-positioned guiding catheters carried a higher risk of procedure-related rupture than a shorter distance between proximal aneurysms and high-positioned guiding catheters (odds ratio, 19.3; 95% confidence interval, 1.84-201; P = .01, multivariable analysis). Use of local anesthesia was also a significant risk factor of procedure-related rupture by multivariable analysis. CONCLUSION Increasing age was correlated with poor accessibility of the guiding catheter in endovascular embolization of ruptured intracranial aneurysms. Distally located aneurysms treated through a low-positioned guiding catheter and use of local anesthesia increased the risk of procedure-related rupture.

Reflux of Anterior Spinal Artery Predicts Recurrent Posterior Circulation Stroke in Bilateral Vertebral Artery Disease

Backgrounds and Purpose— Predictive value of reflux of anterior spinal artery for recurrent posterior circulation ischemia in bilateral vertebral arteries steno-occlusive disease was evaluated. Methods— We retrospectively reviewed 55 patients with symptomatic posterior circulation stroke caused by bilateral stenotic (>70%) lesions of the vertebral artery. We investigated any correlation of clinical and angiographic characteristics including collateral flow patterns, with recurrent stroke. Risk factors for poor 3-month functional outcome were also evaluated. Results— Recurrent posterior circulation stroke was observed in 15 (27.3%) patients. Multivariable analysis using Cox proportional hazards model showed anterior spinal artery reflux as a significant risk factor for stroke recurrence (adjusted hazard ratio, 19.3 [95% confidence interval, 5.35–69.9]; P<0.001). Anterior spinal artery reflux was also correlated with poor functional outcome (modified Rankin Scale score, 3–6; adjusted odds ratio, 7.41 [95% confidence interval, 1.24–44.4]; P=0.028). Conclusions— In patients with symptomatic bilateral vertebral artery occlusive disease, anterior spinal artery reflux predicted recurrent posterior circulation stroke and poor functional outcome.