Long-Term Outcomes of Patients with Stent Tips Embedded into Internal Carotid Artery Branches during Aneurysm Coiling.

BACKGROUND AND PURPOSE: During stent-assisted coiling of ICA aneurysms, stent tips are sometimes unintentionally embedded into ICA branches. Stent tips can be visualized because they have radiopaque markers. Concerns regarding stent tip misplacement include risks of artery perforation and occlusion. The aim of this study was to evaluate the long-term outcomes of ICA branches with embedded stent tips. MATERIALS AND METHODS: ICA branches with embedded stent tips were identified among 35 patients with unruptured ICA aneurysms treated with stent-assisted coiling between November 2003 and November 2014. Patient clinical and angiographic outcomes associated with the embedded stent tip were analyzed. RESULTS: Most of the 35 studied aneurysms were paraclinoid ICA aneurysms (n = 30). The most commonly involved ICA branch was the posterior communicating artery (26 patients, 74.3%), followed by the anterior choroidal artery (8 patients, 22.9%) and ophthalmic artery (1 patient, 2.9%). During the follow-up period (38.6 ± 17.9 months), no new neurologic deficits developed. Neither hemorrhagic nor thromboembolic events occurred. Angiography was performed during the final follow-up evaluation at a mean of 32.7 ± 18.0 months, and all ICA branches with embedded stent tips showed patent blood flow without severe luminal narrowing. CONCLUSIONS: In our experience, placement of a stent tip into ICA branches during stent-assisted coiling was not associated with any major adverse events.

Prophylactic Antiplatelet Medication in Endovascular Treatment of Intracranial Aneurysms: Low-Dose Prasugrel versus Clopidogrel.

BACKGROUND AND PURPOSE: Prophylactic antiplatelet medication is beneficial in decreasing thromboembolic complications during endovascular treatment of unruptured intracranial aneurysms. The efficacy may be limited by variability of individual response to antiplatelet medication, especially clopidogrel. We compared the efficacy of 2 antiplatelet medications, low-dose prasugrel and clopidogrel, in patients undergoing endovascular treatment of unruptured aneurysms. MATERIALS AND METHODS: From November 2014 to July 2015, 194 patients with a total of 222 unruptured aneurysms underwent endovascular treatment at a single institution. Laboratory and clinical data from the prospectively maintained registry were used in this study. Antiplatelet medication was given the day before endovascular treatment (prasugrel 20 mg or 30 mg or clopidogrel 300 mg). Response to the antiplatelet medication was measured by the VerifyNow system. Periprocedural adverse event rates between the 2 groups were compared. RESULTS: There were no significant differences in the baseline characteristics of patients and aneurysms between the 2 groups. The P2Y12 reaction unit values were lower (clopidogrel group versus prasugrel group, 242.7 ± 69.8 vs 125.7 ± 79.4; P < .0001) and percentage inhibition values were higher (22.1% ± 19.7% vs 60.2 ± 24.7%; P < .0001) in the prasugrel group. There were no thromboembolic events, but there was 1 procedural bleed in each group, without any clinical consequences. CONCLUSIONS: The prasugrel group showed more effective and consistent platelet inhibition. We may omit the antiplatelet response assay with the low-dose prasugrel premedication before the endovascular treatment of patients with unruptured aneurysms. Further study is required to determine whether there is benefit of this strategy regarding clinical outcome.

Determination of influence of food intake after a single oral dose of mosapride in beagle dogs using nonlinear mixed effect modeling.

The objective of this study was to describe the population pharmacokinetics (PK) of mosapride under fasting and fed conditions. A single 5-mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs. Plasma concentrations of mosapride were subsequently measured by liquid chromatography-tandem mass spectrometry. Data were analyzed using modeling approaches with the NONMEM 7.2 software. A one-compartment open PK model utilizing model event time (MTIME) with first-order absorption and first-order elimination was found to be more appropriate than all other PK models tested. The absorption rate constants of mosapride were significantly decreased under fed conditions, compared to fasting conditions. The observed bootstrap medians of PK parameters were generally consistent with the corresponding population mean estimates. Furthermore, with the exception of some mosapride concentrations, most of observed data fell into the range of the 5th and 95th percentiles of the simulated values. Overall, the final model was able to describe the observed mosapride concentrations reasonably well. These findings suggest that food intake affects both the rate and extent of absorption of mosapride and that the pharmacological effect of mosapride can differ significantly depending on food intake.

The characteristics and risk factors of headache development after the coil embolization of an unruptured aneurysm.

BACKGROUND AND PURPOSE: Development of a headache after aneurysm coil embolization is not uncommon but has received little attention. The authors prospectively analyze the characteristics and risk factors of a headache after coiling in patients treated for an unruptured cerebral aneurysm. MATERIALS AND METHODS: Ninety patients treated for an unruptured cerebral aneurysm over a period of 1 year, and without a headache history within a month before coiling, were enrolled in this study. All coilings were successfully performed without neurologic complications. After coiling, headache development and intensities were recorded. RESULTS: Fifty (55.6%) patients experienced a headache (VAS score, 4.5 ± 2.02) at 7.9 (range, 0-72) hours, on average, after coiling, and all headaches resolved within an average of 73.0 (range, 3-312) hours. Univariate analysis showed that the following were significantly associated with the development of a headache: age ≤ 50 years (OR 4.636, 95% CI, 1.414-15.198), hypertension (OR 0.232, 95% CI, 0.095-0.571), a packing attenuation of >25% (OR 3.619, 95% CI, 1.428-9.174), and a previous headache history (OR 2.769, 95% CI, 1.120-6.849). However, binary logistic regression showed that only a packing attenuation of >25% (P = .013, adjusted OR 3.774, 95% CI, 1.320-10.790) and no history of hypertension (P = .019, adjusted OR 3.515, 95% CI, 1.233-10.021) were independently associated with the development of a headache. CONCLUSIONS: A headache frequently developed after the coiling of unruptured aneurysms. However, headaches were relatively benign and resolved within several days. The present study shows that no hypertension history and a packing attenuation of >25% are risk factors of headache development.

Comparison of 2-year angiographic outcomes of stent- and nonstent-assisted coil embolization in unruptured aneurysms with an unfavorable configuration for coiling.

BACKGROUND AND PURPOSE: Stents are known to have hemodynamic and biologic effects in addition to their mechanical scaffold effect. To determine whether stents affect long-term outcomes after coiling of unruptured aneurysms, we compared angiographic outcomes at 2 years postembolization for stent- and nonstent-assisted coiled unruptured aneurysms. MATERIALS AND METHODS: Stent-assisted coiling was used in unruptured aneurysms unfavorable for simple coiling (neck size >4 mm and dome-to-neck ratio <1.5) in our practice. Therefore, 126 coiled unruptured aneurysms in total (40 [31.7%] stent group and 86 [68.3%] nonstent group) with these conditions were selected for this study. The nonstent group aneurysms were treated with multiple microcatheter technique (53 cases) or balloon-assisted technique (33 cases). Self-expandable stents were used for coiling in stent group aneurysms. No significant difference in aneurysmal characteristics (aneurysm type [sidewall/bifurcation], diameter, neck size, and dome-to-neck ratio) or angiographic outcome at embolization (packing attenuation, obliteration grade, and contrast filling) were observed between the 2 study groups. RESULTS: At 2-year follow-up visits, rates of progressive occlusion (stent group, 17/40 [42.5%] versus nonstent group, 34/86 [39.5%]) and recanalization (7/40 [17.5%] versus 18/86 [21.0%]) did not show a statistically significant difference between the 2 groups (P = .895). CONCLUSIONS: The present study did not show that additional hemodynamic and biologic effects of stents designed for neck remodeling were enough to enhance progressive occlusion and prevent the recanalization of unruptured aneurysms. Our finding suggests that stent placement provides no better long-term angiographic outcomes for unruptured aneurysms with an unfavorable configuration for coiling.

Endovascular treatment for unruptured intracranial aneurysms in elderly patients: single-center report.

BACKGROUND AND PURPOSE: The optimal management of patients with unruptured intracranial aneurysms remains controversial in elderly populations. The aim of this study was to evaluate technical results and clinical outcomes in a single center of consecutive elderly patients with unruptured intracranial aneurysms treated with endovascular embolization. MATERIALS AND METHODS: Between May 2003 and February 2010, 96 patients older than 70 years (men, 16 patients; women, 80 patients; mean age, 73 years) with 122 saccular unruptured intracranial aneurysms were treated in our hospital with an endovascular approach. The endovascular procedures and technique, angiographic follow-up, and complications were evaluated. RESULTS: Successful embolizations without complications were completed in 95.9%. Five patients had procedure-related events, including thromboembolism in 1 patient, aneurysm perforation during the procedure in 1, and 3 postoperative transient minor symptoms (headache, otalgia, and trigeminal pain) in 3. The degree of occlusion of the treated aneurysm was complete in 46.7%; there was a small neck remnant in 40.9% and residual filling in 12.2%. Imaging (MR angiography) follow-up was performed in 68.7% of the patients. The mean follow-up duration was 19.4 months (range, 5-57 months). Fifty-five patients (93.9%) showed no interval change of the residual neck. Four (6%) demonstrated recanalizations, all of which were successfully recoiled. CONCLUSIONS: Endovascular treatment of unruptured intracranial aneurysms in patients older than 70 years of age appears to be safe. Favorable outcomes with low morbidities may replace surgery or conservative treatment as an active management alternative.

Is fasting necessary for elective cerebral angiography?

BACKGROUND AND PURPOSE: In order to prevent unexpected events such as aspiration pneumonia, cerebral angiography has been performed under fasting in most cases. We investigated prospectively the necessity of fasting before elective cerebral angiography. MATERIALS AND METHODS: The study is an open-labeled clinical trial without random allocation. In total, 2554 patients who underwent elective cerebral angiography were evaluated on development of nausea, vomiting, and pulmonary aspiration during and after angiography. Potential risks and benefits associated with fasting were provided in written documents and through personal counseling to patients before the procedure. The patients chose their fasting or nonfasting option. No restriction in diet was given after angiography. The patients were observed for 24 hours. Nausea and vomiting during and within 1 hour after angiography was considered as a positive event associated with cerebral angiography. RESULTS: The overall incidence of nausea and vomiting during and within 1 hour after angiography was 1.05% (27/2554 patients). There was no patient with pulmonary aspiration. No statistical difference in nausea and vomiting development between the fasting and the diet groups was found. CONCLUSIONS: The incidence of nausea and vomiting associated with cerebral angiography is low and not affected by diet or fasting. Pulmonary aspiration had no difference between the diet and the fasting group. Our study suggests that fasting may not be necessary for patients who undergo elective cerebral angiography.

Intracranial stent placement for recanalization of acute cerebrovascular occlusion in 32 patients.

BACKGROUND AND PURPOSE: Stents have been reported as an option for improvement of the recanalization rate in AIS. The authors have also used intracranial stents in failed cases of IAT with pharmacologic and mechanical methods since 2004. We retrospectively reviewed our cases of intracranial stent use for IAT of AIS for recanalization and as a rescue procedure for iatrogenic intracranial vascular dissection during IAT. MATERIALS AND METHODS: Thirty-two patients, who were diagnosed with AIS, were treated with intracranial stents (28 balloon-mounted and 7 self-expandable stents) at our neurovascular center between April 2004 and December 2008. The stent use for all 32 patients was the final attempt to recanalize occluded vessels after various trials of pharmacologic or mechanical thrombolysis or to treat iatrogenic vascular dissection. RESULTS: Among the 32 patients, immediate poststenting angiographic recanalization was achieved in 100% with TIMI/TICI 2 (15 of 32 lesions, 46.9%) or TIMI/TICI 3 (17 of 32 lesions, 53.1%). However, complication rates were also high. Major symptomatic intracerebral hemorrhage (1 case of procedural symptomatic hemorrhage and 3 cases of delayed symptomatic hemorrhage) occurred in 4 (12.5%); intracranial vascular dissection, in 4 (12.5%); extracranial vascular dissection, in 3 (9.4%); immediate IST, in 4 (12.5%); subacute (within 1 week) IST, in 2; late (>1 week) IST, in 1, and 1 case of in-stent restenosis occurred twice (at 5 and 17 months). CONCLUSIONS: Intracranial stent placement for AIS management has an excellent recanalization rate. However, it is associated with high complication risks as our series showed. We believe that the decision to treat AIS with intracranial stent placement should be made after careful consideration of potential benefits and risks.

In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy.

Although the current clinical formulation of paclitaxel (Taxol) has a promising clinical activity against a wide variety of tumors, it has significant toxic side effects, some of which are associated with its formulation in a 1:1 (v/v) mixture of Cremophor EL and dehydrated alcohol. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and efficacy of a paclitaxel (Genexol)-containing biodegradable polymeric micellar system (Genexol-PM) in comparison to Taxol. Genexol-PM was newly developed by using a low molecular weight, nontoxic and biodegradable amphiphilic diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) and paclitaxel (Genexol, Samyang Genex Co., Seoul, Korea). In a human cancer cell line model, Genexol-PM and Taxol showed comparable in vitro cytotoxicity against human ovarian cancer cell line OVCAR-3 and human breast cancer cell line MCF7. The maximum tolerated dose (MTD) of Genexol-PM and Taxol in nude mice was determined to be 60 and 20 mg/kg, respectively. The median lethal dose (LD(50)) in Sprague--Dawley rats was 205.4 mg/kg (male) and 221.6 mg/kg (female) for Genexol-PM, while 8.3 mg/kg (male) and 8.8 mg/kg (female) for Taxol. After intravenous administration of Genexol-PM in murine B16 melanoma-induced female SPF C57BL/6 mice at a dose of 50 mg/kg, the area under the plasma concentration-time curve (AUC) was similar to Taxol((R)) at a dose of 20 mg/kg, but biodistribution of paclitaxel after administration of Genexol-PM showed 2 to 3-fold higher levels in tissues including liver, spleen, kidneys, lungs, heart and tumor as compared to Taxol. The in vivo antitumor efficacy of Genexol-PM as measured by reduction in tumor volume of SKOV-3 human ovarian cancer implanted in nude (nu/nu) athymic mice and MX-1 human breast cancer implanted in Tac:Cr:(NCr)-nu athymic mice was significantly greater than that of Taxol. The results of cytotoxicity, MTD, LD(50) and antitumor efficacy suggest that Genexol-PM may have a great advantage over present-day chemotherapy with Taxol.