Takeshi Hiu

Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells

Statins have a neuroprotective effect in neurological diseases, a pleiotropic effect possibly related to blood–brain barrier (BBB) function. We investigated the effect of pitavastatin on barrier functions of an in vitro BBB model with primary cultures of rat brain capillary endothelial cells (RBEC). Pitavastatin increased the transendothelial electrical resistance (TEER), an index of barrier tightness of interendothelial tight junctions (TJs), at a concentration of 10−8 M, and decreased the endothelial permeability for sodium fluorescein through the RBEC monolayer. The increase in TEER was significantly reduced in the presence of isoprenoid geranylgeranyl pyrophosphate, whereas farnesyl pyrophosphate had no effect on TEER. Our immunocytochemical and Western blot analyses revealed that treatment with pitavastatin enhanced the expression of claudin-5, a main functional protein of TJs. Our data indicate that pitavastatin strengthens the barrier integrity in primary cultures of RBEC. The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression.

Long-term follow-up of endovascular coil embolization for cerebral aneurysms using three-dimensional time-of-flight magnetic resonance angiography.

Abstract Objectives: As endovascular treatment becomes more prevalent, aneurysm recurrence from neck remnants, recanalization, incomplete obliteration and bleeding remain major concerns. In the current analysis, we attempted to identify factors related to disease progression and clinical outcome in patients treated with coil embolization. Methods: This study included 58 patients who underwent endovascular coil embolization for treatment of intracranial aneurysm. The result of embolization was evaluated with three-dimensional time-of-flight magnetic resonance angiography (TOF MRA) and classified as a complete occlusion, a residual neck (minor, central and marginal types), a residual dome (central and marginal types). Patients were followed up clinically and radiologically. Statistical analyses were performed to establish factors that influenced the occurrence of adverse events such as recurrence of aneurysm. Results: Overall, the complete occlusion rate was 18.8%, the occurrence of a residual neck was 67.2%, and the residual dome rate was 14.1%. The mean clinical follow-up was 31.2 months. Recurrences were found in 18 aneurysms, and major recurrences were retreated with coiling or surgery. The post-treatment study revealed that the marginal-type aneurysm filling has a significant impact on outcome. Thus, perianeurysmal edema was correlated with recurrence of the aneurysm. Conclusions: Three-dimensional TOF MRA was a sensitive tool for visualizing residual filling of embolized aneurysm and is useful for long-term follow-up of patients.

Microsurgical Clipping for Recurrent Aneurysms After Initial Endovascular Coil Embolization

OBJECTIVE Surgical treatment for recurrent lesions of embolized aneurysms is difficult and challenging for many neurosurgeons because intra-aneurysmal coil masses are sometimes scarred to the wall of the aneurysm or adherent to adjacent vital structures. To assess the efficacy and safety of surgical treatment without coil removal for recurrent aneurysms after previous coil embolization, we retrospectively studied clinical results, angiographic results, and complications in patients treated with additional microsurgical clipping. METHODS From April 2003 to April 2013, 7 patients with recurrent previous embolized aneurysms underwent microsurgical treatment. RESULTS This series included 1 man and 6 women receiving endovascular coiling as the first-line treatment. One patients aneurysm was unruptured, whereas the other 6 were ruptured. The aneurysm locations were posterior communicating (n = 3), anterior communicating (n = 2), ophthalmic (n = 1), and posterior inferior cerebellar (n = 1). The initial sizes ranged from 3-11.5 mm in diameter (mean, 6.6 mm), and the aspect ratios were 1.2 to 3.4 (mean, 1.9). In these aneurysms, the initial coiling result was complete occlusion in 5 patients, and neck remnants in 2 patients. The mechanism underlying aneurysm recurrence was coil compaction in 3 aneurysms, aneurysm regrowth in 3 aneurysms, and fundal migration in 1 aneurysm. The median recurrence latency was 28.8 months (range, 0.7-115 months). Microsurgical clippings without coil removal were used in 6 patients; a parent artery occlusion under bypass protection was done in 1 case with a posterior inferior cerebellar aneurysm. Fenestrated clips in combination with another type of clip were successfully used for 4 of 6 patients who were treated with direct neck clipping. No postoperative morbidity was observed, and postoperative imaging studies revealed complete occlusion of the aneurysms in all cases. There were no recurrences of aneurysms during the follow-up period (mean, 44.7 months; range, 0.5-118 months). CONCLUSIONS The microsurgical clipping without coil removal for recurrent lesions of embolized aneurysms is effective and safe when it is technically feasible. The tandem clipping in combination with a fenestrated clip is a crucial method for direct neck clipping without coil removal for previously coiled recurrent aneurysms. For unclippable lesions, a parent artery occlusion under bypass protection should be taken into consideration.

De Novo Ivy Sign Indicates Postoperative Hyperperfusion in Moyamoya Disease

Background and Purpose— The ivy sign on fluid-attenuated inversion recovery MRI is a specific finding in moyamoya disease (MMD). This sign indicates decreased cerebral perfusion, dilated pial vasculature, and slow leptomeningeal collateral flow. This study aimed to clarify the characteristics of perioperative changes in the ivy sign in relation to cerebral hyperperfusion, which frequently occurs in MMD of unknown pathogenesis. Methods— This prospective study included patients with MMD who underwent superior temporal artery–middle cerebral artery single bypass. Fluid-attenuated inversion recovery MRI was performed to evaluate the appearance of the ivy sign in the ipsilateral hemisphere preoperatively and on postoperative days 2 and 30. The ivy sign was assessed in combination with perioperative symptoms and cerebral hemodynamics using single-photon emission computed tomography. Results— Of 42 consecutive patients (55 sides) who underwent bypass surgery, 32 (58.2%) showed an increase in the ivy sign (de novo ivy sign) on postoperative day 2; this had disappeared by day 30. Interestingly, these 32 patients had a significantly higher incidence of hyperperfusion on single-photon emission computed tomography and hyperperfusion syndrome, and there was no correlation between the de novo ivy sign and a preoperative ivy sign or the preoperative cerebral hemodynamics. In multivariate analysis, a de novo ivy sign was significantly correlated with postoperative hyperperfusion. Conclusions— In MMD, a de novo ivy sign could indicate postoperative hyperperfusion after bypass, which is not always correlated with preoperative hemodynamic impairment. Additional factors other than preoperative cerebral hemodynamics might be involved in postoperative hyperperfusion in MMD.

Progressive perianeurysmal edema preceding the rupture of a small basilar artery aneurysm.

We herein report the first case of progressive perianeurysmal edema preceding the rupture of a small saccular aneurysm, without any intervention or intraluminal thrombosis. A 71-year-old woman was incidentally noted to have a cerebral aneurysm (5mm in diameter) at the lower basilar artery. Twelve months later, magnetic resonance (MR) imaging showed a T2-elongated area around a dome of the aneurysm buried in the brain stem, suggesting perianeurysmal edema formation. Interestingly, the edema progressed with the formation of a bleb, in addition to an increase in size of the aneurysm over the following 3-year period. The aneurysm eventually ruptured as a brain stem hemorrhage without any subarachnoid clots 3 days after the final check-up with MR imaging, by which a significant increase of edema formation with an increase in size of the aneurysm and a marked expansion of the bleb was observed. These findings raise the possibility that bleb formation and an enlargement of a small cerebral aneurysm might also be associated with perianeurysmal edema and a subsequent aneurysmal rupture. In addition to the pulsatile flow and/or compression from the expanded aneurysm, local inflammation in the aneurysm wall may play an important role in such edema formation.

Stem cell transplantation enhances endogenous brain repair after experimental stroke.

Stem cell transplantation for stroke treatment has been a promising therapy in small and large animal models, and many clinical trials are ongoing to establish this strategy in a clinical setting. However, the mechanism underlying functional recovery after stem cell transplantation has not been fully established and there is still a need to determine the ideal subset of stem cells for such therapy. We herein reviewed the recent evidences showing the underlying mechanism of functional recovery after cell transplantation, focusing on endogenous brain repair. First, angiogenesis/neovascularization is promoted by trophic factors including vascular endothelial growth factor secreted from stem cells, and stem cells migrated to the lesion along with the vessels. Second, axonal sprouting, dendritic branching, and synaptogenesis were enhanced altogether in the both ipsilateral and contralateral hemisphere remapping the pyramidal tract across the board. Finally, endogenous neurogenesis was also enhanced although little is known how much these neurogenesis contribute to the functional recovery. Taken together, it is clear that stem cell transplantation provides functional recovery via endogenous repair enhancement from multiple ways. This is important to maximize the effect of stem cell therapy after stroke, although it is still undetermined which repair mechanism is mostly contributed.

Observation of the embolus protection filter for carotid artery stenting

BACKGROUND Carotid artery stenting in patients with high surgical risk is considered as an effective alternative to carotid endarterectomy. Because the occurrence of distal embolization with CAS is still a major concern, an embolus protection device is usually used during the procedure. We developed a technique for observation of embolus protection filter and evaluated the debris or thrombus microscopically, and the pathologic findings were compared with preoperative imaging studies. METHODS After completing CAS, the filter membrane was stained with HE solution and removed from filter strut. Mounting onto a glass slide, the filter was evaluated under a microscope. Plaque debris and appearance of filter membrane were evaluated, and the covered area was measured. The pathologic findings were compared with preoperative imaging studies. RESULTS Microscopic observation of the slide revealed atheromatous debris as well as thrombotic material to the filter membrane. Hematoxylin-eosin stain facilitates the characterization of the debris composition, namely, thrombotic debris, calcified debris, organized debris, fibrous debris, and lipid-rich debris. The subtypes of debris were consistent with preoperative imaging studies. Thus, in cases of intraprocedural flow impairment, more than 50% of the filter area was covered with debris or thrombotic material. CONCLUSION Carotid plaque debris captured during carotid stenting with protection filter can be visualized with HE stain on the glass side. This simple method allows us to better understand the plaque debris and appearance of embolus protection filter.

Recurrence of the cavernous sinus dural arteriovenous fistula at adjacent sinuses following repeated transvenous embolizations: case report and literature review.

We present a unique case of a cavernous sinus (CS) dural arteriovenous fistula (DAVF), which recurred at adjacent sinuses following repeated transvenous embolizations (TVEs). A 68-year-old woman presented with progressive left conjunctival chemosis and diplopia. Cerebral angiography revealed a left CS DAVF, which was completely obliterated by TVE via the left inferior petrosal sinus (IPS). Two years later, the DAVF recurred in the left IPS, and again in the left sigmoid sinus (SS) 3 years after the initial treatment in spite of a second TVE. Moreover, the left SS and the left internal jugular vein, which had been previously stenotic, had been occluded. The third TVE resulted in the complete obliteration of the SS DAVF. CS DAVFs may recur at adjacent sinuses even after complete obliteration by TVE. Careful follow-up is necessary to check for the recurrence of DAVFs, especially in cases with venous flow changes, such as sinus occlusion, following endovascular treatment.

MicroNester coil for neurointervention

A MicroNester coil (MNC) was developed from the Nester coil with a 0.018-in microcatheter. The most specific feature of the MNC is the extended length of 14 cm. Neurointervention involving the MNC was undertaken in 11 patients. Intervention procedures were transvenous embolization for a dural arteriovenous fistula in 4 patients, transarterial embolization for a dural arteriovenous fistula in 2, parent artery occlusion for a cerebral aneurysm in 4, and stent-assisted embolization for a carotid artery dissection in 1. A push technique through microcatheter was used to deploy the MNCs. The MNCs were successfully placed into the venous sinus lesion, feeding artery, parent artery of the aneurysm, and the pseudoaneurysm. There were no major technical complications resulting in morbidity. The postoperative course was uneventful except in 2 cases in which the occluded vessel recanalized. Use of MNCs was safe and feasible for embolization of cerebrovascular lesions. Fewer coils are required in embolization when using MNCs.

Progressing takayasu arteritis successfully treated by common carotid-internal carotid crossover bypass grafting: technical case report.

OBJECTIVE This report describes a unique case of Takayasu arteritis with occlusion of the left common carotid artery (CCA) and the right internal carotid artery (ICA), which was successfully treated by right CCA-left ICA crossover bypass grafting using the saphenous vein. The histological findings of the original occluded prosthetic graft are also described. CLINICAL PRESENTATION A 63-year-old woman with a history of Takayasu arteritis was admitted to our hospital with a history of progressive dizziness, frequent syncopal attacks, and repetitive blurred vision in the left eye. She had undergone repeat transthoracic bypass surgeries, including grafting with the use of a Gore-Tex (W.L. Gore & Associates, Inc., Flagstaff, AZ) prosthesis between the left external ilioaxillary bypass and the left CCA. However, cerebral angiography demonstrated total occlusion of the left CCA, the right ICA, and the bilateral subclavian arteries. On admission, I-iodoamphetamine single-photon emission computed tomography showed a decreased cerebrovascular reactivity to acetazolamide in the bilateral cerebral hemispheres. Moreover, cerebral angiography revealed an occlusion of the Gore-Tex graft, whereas the left ICA was opacified through the retrograde filling in the left external carotid artery. INTERVENTION Crossover bypass grafting was performed using the saphenous vein between the right CCA and the left ICA. The Gore-Tex graft was partially removed, and myointimal hypertrophy with an inflammatory response around the wall was found histologically. The postoperative course was uneventful. A normalized cerebrovascular reserve in both cerebral hemispheres was demonstrated on I-iodoamphetamine single-photon emission computed tomography. CONCLUSION Although it is not frequently indicated, crossover bypass grafting using the saphenous vein between bilateral carotid arteries is considered to be a feasible alternative procedure in patients with Takayasu arteritis.