Toshihiro Ishibashi

Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies

BACKGROUND The decision of whether to treat incidental intracranial saccular aneurysms is complicated by limitations in current knowledge of their natural history. We combined individual patient data from prospective cohort studies to determine predictors of aneurysm rupture and to construct a risk prediction chart to estimate 5-year aneurysm rupture risk by risk factor status. METHODS We did a systematic review and pooled analysis of individual patient data from 8382 participants in six prospective cohort studies with subarachnoid haemorrhage as outcome. We analysed cumulative rupture rates with Kaplan-Meier curves and assessed predictors with Cox proportional-hazard regression analysis. FINDINGS Rupture occurred in 230 patients during 29,166 person-years of follow-up. The mean observed 1-year risk of aneurysm rupture was 1·4% (95% CI 1·1-1·6) and the 5-year risk was 3·4% (2·9-4·0). Predictors were age, hypertension, history of subarachnoid haemorrhage, aneurysm size, aneurysm location, and geographical region. In study populations from North America and European countries other than Finland, the estimated 5-year absolute risk of aneurysm rupture ranged from 0·25% in individuals younger than 70 years without vascular risk factors with a small-sized (<7 mm) internal carotid artery aneurysm, to more than 15% in patients aged 70 years or older with hypertension, a history of subarachnoid haemorrhage, and a giant-sized (>20 mm) posterior circulation aneurysm. By comparison with populations from North America and European countries other than Finland, Finnish people had a 3·6-times increased risk of aneurysm rupture and Japanese people a 2·8-times increased risk. INTERPRETATION The PHASES score is an easily applicable aid for prediction of the risk of rupture of incidental intracranial aneurysms. FUNDING Netherlands Organisation for Health Research and Development.

Unruptured Intracranial Aneurysms Incidence of Rupture and Risk Factors

Backgrounds and Purpose— The authors evaluated the incidence of rupture of unruptured intracranial saccular aneurysm during observation. Methods— Between January 2003 and December 2006, a total of 419 patients with 529 unruptured intracranial saccular aneurysms were observed without treatment. The mean follow-up duration was 905.3 days. Aneurysm size was measured by 3-dimensional CT angiography. Clinical and 3-dimensional CT angiography follow-up were obtained every 6 months. Results— Nineteen aneurysms ruptured during observation resulting in a 1.4% rupture rate per year. A history of subarachnoid hemorrhage (hazard ratio, 7.3; 95% CI, 2.5 to 21.2), posterior circulation aneurysm (hazard ratio, 2.9; 95% CI, 1.1 to 8), and large size were significant independent predictors for aneurysm rupture. Conclusions— Size, history of subarachnoid hemorrhage, and posterior circulation aneurysms were significant risk factors for prediction of rupture of unruptured intracranial saccular aneurysms.

Low-frequency ultrasound penetrates the cranium and enhances thrombolysis in vitro

OBJECTIVE Refinements of treatment methods are sought to rapidly reduce the volume of intracranial clots and to decrease patient exposure to possible complications of thrombolytic therapy for intracranial hematomas. We assessed the possibility of adding ultrasonication using model systems including human blood clots and temporal bone in vitro. METHODS The transmittance of ultrasound through temporal bone obtained at autopsy was compared between the frequencies 211.5 KHz and 1.03 MHz, using a meter to determine the power delivered. The frequency 211.5 KHz was chosen to assess the ultrasound effect on the weight of 24-hour-old clots prepared from human blood after exposures at 37 degrees C to 2 mg/ml urokinase with no additional treatment, ultrasound, or agitation during an interval of up to 12 hours. At these times, fibrin degradation products also were measured. RESULTS The transmittance of low-frequency ultrasound (211.5 KHz) through temporal bone was approximately 40%, which is four times higher than that of high-frequency ultrasound (1.03 MHz). Ultrasound but not agitation significantly increased clot lysis (140% of lysis with urokinase alone), with correspondingly increased fibrin degradation products. CONCLUSION We conclude that low-frequency ultrasound transmits well through human temporal bone and enhances thrombolysis in vitro. Clinically, this method may be promising for reducing dosages of thrombolytic agents and shortening the period of clot removal.

Can Transcranial Ultrasonication Increase Recanalization Flow With Tissue Plasminogen Activator

Background and Purpose— In thrombolytic therapy for acute ischemic stroke, it is essential to obtain rapid thrombolysis before ischemic neuronal injury occurs. To develop a new technique of thrombolysis for acute ischemic stroke, the effect of transcranially applied ultrasound (TUS) on thrombolysis was examined. Methods— An occlusion model of rabbit femoral artery was produced with thrombin after establishment of stenotic flow and endothelial damage. After stable occlusion was confirmed, monteplase (mtPA) was administered intravenously, and ultrasound (490 kHz, 0.13 W/cm2) was applied through a piece of temporal bone (TUS group; n=9). The control group received mtPA alone (tissue plasminogen activator [tPA] group; n=12). To verify the efficacy of TUS, femoral artery flow was measured during the procedure. Results— The recanalization ratio was 16.7% (2 of 12) in the tPA group and 66.7% (6 of 9) in the TUS group. The recanalization ratio in the TUS group was higher than that in the tPA group (P =0.03). Patency flow ratio, which was defined as recanalization flow divided by baseline flow, of the TUS group (44.6±13.9%) was significantly greater than that of the tPA group (9.9±6.8%) at 60 minutes (P =0.025). Patency flow ratio became higher in the TUS group than in the tPA group between 20 and 30 minutes from the start of thrombolysis. Conclusions— Low-frequency and low-intensity TUS enhanced thrombolysis by mtPA in a rabbit femoral artery occlusion model. This technique should be clinically useful for thrombolysis in acute ischemic stroke.

Risk Analysis of Unruptured Intracranial Aneurysms: Prospective 10-Year Cohort Study.

Background and Purpose— The natural history of unruptured intracranial aneurysms remains unclear, and management strategy is not well defined. Methods— From January 2003 to December 2012, we enrolled patients with aneurysm in our institution. In total, 2252 patients with 2897 aneurysms were eligible for analysis, and 1960 eligible aneurysms were conservatively managed. Precise 3-dimensional evaluation was conducted using computed tomography angiography, digital subtraction angiography, or magnetic resonance angiography. We then assessed the risk of aneurysm rupture, mortality, and morbidity associated with aneurysm characteristics, demographics, and known health/lifestyle risk factors. Results— The mean follow-up duration was 7388 aneurysm-years. During observation, 56 aneurysms ruptured, resulting in an overall rupture rate per year of 0.76% (95% confidence interval, 0.58–0.98). The mean initial visit to rupture interval was 547 days. Aneurysm size, location, daughter sac, and history of subarachnoid hemorrhage were significant independent predictors for aneurysm rupture. Aneurysms that were ≥5 mm were associated with a significantly increased risk of rupture when compared with 2- to 4-mm aneurysms (unadjusted hazard ratio, 12.24; 95% confidence interval, 7.15–20.93). Of 56 patients who experienced hemorrhage, 29 (52 %) died or were rendered severely disabled. Of the patients who had large or giant aneurysms, none recovered without deficits, and the mortality rate after rupture was 69%. For aneurysms sized <5 mm, the mortality rate was 18%. Conclusions— Larger aneurysms are at greater risk for rupture and poor outcome. Ethnic factors may play a role in the risk of rupture.

Robotic digital subtraction angiography systems within the hybrid operating room.

BACKGROUND:Fully equipped high-end digital subtraction angiography (DSA) within the operating room (OR) environment has emerged as a new trend in the fields of neurosurgery and vascular surgery. OBJECTIVE:To describe initial clinical experience with a robotic DSA system in the hybrid OR. METHODS:A newly designed robotic DSA system (Artis zeego; Siemens AG, Forchheim, Germany) was installed in the hybrid OR. The system consists of a multiaxis robotic C arm and surgical OR table. In addition to conventional neuroendovascular procedures, the system was used as an intraoperative imaging tool for various neurosurgical procedures such as aneurysm clipping and spine instrumentation. RESULTS:Five hundred one neurosurgical procedures were successfully conducted in the hybrid OR with the robotic DSA. During surgical procedures such as aneurysm clipping and arteriovenous fistula treatment, intraoperative 2-/3-dimensional angiography and C-arm-based computed tomographic images (DynaCT) were easily performed without moving the OR table. Newly developed virtual navigation software (syngo iGuide; Siemens AG) can be used in frameless navigation and in access to deep-seated intracranial lesions or needle placement. CONCLUSION:This newly developed robotic DSA system provides safe and precise treatment in the fields of endovascular treatment and neurosurgery.

Dynact soft-tissue visualization using an angiographic C-arm system: initial clinical experience in the operating room.

INTRODUCTION DynaCT is a clinical application protocol to create computed tomographic (CT)-like images allowing soft-tissue visualization acquired from an angiography system. A cone beam three-dimensional CT reconstruction is produced from the acquisition of two-dimensional projection images by rotating the c-arm with x-ray source and image receptor around the patient. The purpose of this study is to evaluate the clinical efficacy of DynaCT in the operating room. METHODS DynaCT was performed in 100 patients undergoing cerebral or spinal interventional procedures in the new-concept operating room. Specially designed AXIOM Artis BA (conventional image intensifier system; 55 patients; Siemens Medical Solutions, Erlangen, Germany) and AXIOM Artis dBA (flat-panel detector; 45 patients; Siemens Medical Solutions) biplane neuroangiographic systems (Siemens Medical Solutions, Germany) were installed in the operating room. The volumetric data set from the AXIOM Artis systems were reconstructed immediately on the three-dimensional workstation in the operating room. We compared DynaCT images with the use of multidetector computed tomography. RESULTS DynaCT was performed successfully in all patients. High-contrast structures, such as bone, calcified lesions, and metallic materials, were visualized on DynaCT as well as in multidetector computed tomography for each group. Although contrast differentiation of soft tissue such as cerebral cortex, muscle, and hematoma on DynaCT were inferior to multidetector CT scans, the images were sufficiently used as intraoperative CT-like images. However, DynaCT images acquired from flat panel detector-based systems were found to be superior to those images acquired from image intensifier-based systems. Striking ring artifacts were exhibited and resulted in major limitations in the image intensifier group. CONCLUSION DynaCT has the potential to be used as a powerful tool for endovascular and neurosurgical procedures and will open new possibilities for neurosurgical management.

Effective and safe conditions of low-frequency transcranial ultrasonic thrombolysis for acute ischemic stroke: neurologic and histologic evaluation in a rat middle cerebral artery stroke model.

Background and Purpose— Transcranial ultrasound (TUS) enhances thrombolysis and is expected to be useful for the treatment of ischemic stroke. However, neither its effectiveness in improving neurologic outcome nor its safety in living tissue has been fully established. We examined the efficacy and safety of low-frequency TUS under appropriate conditions of ultrasound for thrombolytic treatment in a rat middle cerebral artery stroke model. Methods— Sixty-five male Wistar rats were used. Rats with right middle cerebral artery stroke exhibiting left hemiparesis were blindly selected and randomly assigned to 1 of 3 groups: (1) control, no therapy; (2) tPA, intravenous administration of tissue plasminogen activator 3 hours after middle cerebral artery stroke, or (3) TUS, tPA administration and application of TUS (490 kHz, continuous wave, at an intensity of 0.8 W/cm2). Twenty-four hours after the onset of stroke, neurologic improvement was evaluated and brains were then removed. Thrombolysis at the origin of the right middle cerebral artery was examined. Thrombolysis ratio, cerebral infarct ratio, and rate of histologic evidence of hemorrhage were compared in the 3 groups. Results— Significantly better neurologic improvement (P=0.008), a higher thrombolysis ratio (P=0.041), and a reduction of cerebral infarct volume (P=0.047) were obtained in the TUS group compared with the tPA group, without an increase in hemorrhagic transformation. Conclusions— Our findings suggest that thrombolytic treatment with low-frequency TUS under appropriate conditions could be an effective and safe method of treatment for ischemic stroke.

Prediction model for 3‐year rupture risk of unruptured cerebral aneurysms in Japanese patients

To build a prediction model that estimates the 3‐year rupture risk of unruptured saccular cerebral aneurysms.

Combined surgical and endovascular treatment of complex cerebrovascular diseases in the hybrid operating room

Background Although most neurovascular diseases can be treated either by microsurgical or endovascular means, a subset of patients may require a combined approach. Patient transfer from the operating room (OR) to the angiosuite has been a fundamental drawback of this type of approach. Objective The purpose of this study is to report our clinical experience performing combined surgical and endovascular procedures for neurovascular diseases in the hybrid OR. Methods 29 patients with neurovascular diseases underwent combined endovascular and surgical procedures in a single session: 16 were scheduled combined treatment and 13 were emergency combined procedures. Of the emergency cases, three were rescue surgeries after endovascular complications. Three patients had ruptured intracranial aneurysms, eight had unruptured intracranial aneurysms, eight had arteriovenous malformations and eight had arteriovenous fistulae; two patients had either a spinal tumor or dural arteriovenous fistulae. Results All combined procedures were performed in a single session without changing the patients surgical position. In cases of ruptured arteriovenous malformations or aneurysms with hematoma, an emergency embolization was performed to assist the surgical procedure. Combined superficial temporal artery–middle cerebral artery (STA–MCA) bypass followed by endovascular parent artery trapping were successfully performed for complex large or giant aneurysms. There were two periprocedural ischemic complications. Of the three patients who underwent surgical rescue after endovascular complications, two remained intact and one died despite immediate surgical procedures. Conclusion A combined endovascular and surgical approach conducted in a hybrid OR provides a new strategy for the treatment of complex neurovascular diseases.