Management of Cervical Internal Carotid Artery Stenosis or Occlusion in Tandem Lesion with Acute Ischemic Stroke: Which Is More Appropriate Percutaneous Transluminal Angioplasty or Stent?

OBJECTIVE: Carotid artery stenting (CAS) is the established treatment strategy of the cervical internal carotid artery (cICA) stenosis, but its use for acute tandem lesions remains controversial. We investigated the clinical and procedural outcomes of management of cICA lesions and evaluated the risk factors for complications. METHODS: Fifty patients who underwent acute mechanical thrombectomy for tandem lesion between January 2014 and June 2022 were included. Treatment of the cICA lesion was classified into the CAS group or the non-CAS group. The risk factors for postoperative ischemic events or symptomatic intracranial hemorrhage (sICH) were analyzed. RESULTS: The CAS group included 36 patients (72%) and the non-CAS group 14 (28%). Postoperative complications were observed in 9 patients (18%). Thromboembolic complications occurred in 4 patients (29%) of the non-CAS group but in 1 patient (3%) of the CAS group. Severe calcification of the cICA (P = 0.04), non-CAS (P = 0.018), and more than 60% residual stenosis (P = 0.016) were significant risk factors associated with thromboembolic complications. sICH occurred in 4 patients (11%) of the CAS group but in none of the non-CAS group. More than 80% stenosis improvement was significantly associated with sICH (P = 0.049). Twenty-nine patients (58%) had a good clinical outcome at 90 days after onset. CONCLUSIONS: Acute CAS is effective for the management for cICA tandem lesions during mechanical thrombectomy, but care not to overextend may be important to reduce the risk of sICH. Severe calcification of the cICA may increase the risk of postoperative thromboembolic complications using non-CAS treatment.

A case of craniocervical junction pial arteriovenous fistula causing postoperative medullary and spinal cord edema.

OBJECTIVES: Pial arteriovenous fistulas (pAVFs) are direct connections between the pial artery and vein without an intervening nidus. We report a rare case of craniocervical junction (CCJ) pAVF causing medullary and spinal cord edema resulting from surgical removal of the varix with remnant shunt after coil embolization. CASE DESCRIPTION: A 16-year-old man presented with subarachnoid hemorrhage. Digital subtraction angiography revealed a CCJ pAVF with multiple fistulas at the 2 varices (varix A and varix B), which was fed by the bilateral lateral spinal arteries and anterior spinal artery (ASA), and drained into the median posterior vermian vein with varix (varix C) and anterior spinal vein (ASV). Varices A and B were embolized using coils, but the shunts remained in varix C. Then, varix C was surgically removed. After this operation, medullary and spinal cord edema occurred. Digital subtraction angiography showed the ASV drainage responsible for edema. Finally, surgical removal of varices A and B was performed. However, arteriovenous shunts, supplied by the ASA and drained into the ASV via the intrinsic vein, were found in the medulla oblongata and coagulated, resulting in disappearance of edema. CONCLUSIONS: Edema was probably caused by concentration of drainage from the arteriovenous shunt in the medulla oblongata into the ASV by surgical removal of varix C acting as another draining route. High flow AVF can induce angiogenesis and secondary arteriovenous shunt. Precise analysis of the angioarchitecture is important to treat such cases without complications.

Analysis of the Pial Arterial Supply as a Cause of Intraprocedural Hemorrhage During Transarterial Liquid Embolization of Tentorial Dural Arteriovenous Fistulas.

OBJECTIVE: Tentorial dural arteriovenous fistulas (AVFs) are bridging vein shunts, and are therefore sometimes supplied by the pial artery as well as the dural artery. Recently, intraprocedural hemorrhage from the pial artery was reported, and we experienced 2 tentorial dural AVFs with the same complication. Pure pial artery has a glomus-like structure and forms direct shunts along the draining vein, and is likely to bleed after restriction of the draining vein caused by the transarterial embolization. This study investigated the characteristics of the pial arterial supply as a cause of hemorrhage. METHODS: Twenty-six tentorial dural AVFs in 25 patients treated in our institute were retrospectively investigated and the characteristics of the pial feeders responsible for bleeding were analyzed. RESULTS: Thirteen pial arterial feeders (pure pial feeder in 7, dilated dural branch of the pial artery in 4, and undefined in 2) were identified in 10 of the 26 tentorial dural AVFs. Pure pial feeders were responsible for bleeding in 2 tentorial dural AVFs. CONCLUSIONS: To prevent intraprocedural hemorrhage, differentiation of the pure pial supply from the dural branch of the pial artery is important. The infratentorial artery will supply supratentorial fistula as the dural branch after passing through the tentorium. In contrast, the supratentorial artery can supply supratentorial fistula not only as a dural branch but also as a pure pial feeder. Therefore, attribution of the fistula and the pial supply, supratentorial or infratentorial, is useful in identifying pure pial supply.

Long-Term Durability and Recurrence Patterns After Endovascular Treatment for Basilar Tip Aneurysms.

BACKGROUND: Treating recurrence after coil embolization of basilar tip aneurysm remains challenging even with the development of endovascular procedures. The present study evaluated long-term durability and recurrence patterns after endovascular treatment of basilar tip aneurysms. METHODS: Data of 116 consecutive patients treated with endovascular therapy at 3 regional hospitals from 2002-2019 were retrospectively analyzed. Aneurysms were ruptured in 51 cases and unruptured in 65 cases, with a mean maximal diameter of 7.8 mm (>15 mm in 14 patients) and a mean follow-up period of 5.8 ± 4.3 years. RESULTS: Recurrence was observed in 24 of the 116 patients (21%), and 14 patients were retreated. The 5-year recurrence-free survival rate was 75.3%. Cox proportional hazards analysis found that recurrence correlated significantly with maximal aneurysm diameter >10 mm (P = 0.001; hazard ratio: 3.95, 95% confidence interval: 1.76-8.90) and incomplete occlusion (P = 0.003; hazard ratio: 4.43, 95% confidence interval: 1.63-12.00). Recurrence pattern was classified into 3 types: neck type (9 patients), regrowth type (10 patients), and regrowth type of initially thrombosed aneurysms (3 patients). Rerupture occurred in neck type with de novo aneurysm formation adjacent to the neck (n = 3) and regrowth type with dome filling (n = 4). CONCLUSIONS: Recurrence after coil embolization for basilar tip aneurysms is associated with large aneurysms and incomplete occlusion at initial embolization. Understanding the patterns of recurrence is useful for predicting recurrence and selecting treatment strategies.

Endovascular Treatment Strategy and Clinical Outcomes for Ruptured Blood Blister-Like Aneurysms of the Internal Carotid Artery Using Low-Profile Visualized Intraluminal Support Stent.

OBJECTIVE: It is challenging to safely treat blood blister-like aneurysms (BBAs) of the internal carotid artery. Endovascular surgery has been reported, but the optimal strategy is yet to be established. We report our endovascular treatment strategy using the Low-profile Visualized Intraluminal Support (LVIS) stent. METHODS: Twelve patients with ruptured BBAs including 1 patient with 2 separate aneurysmal bulges were treated from December 2017 to January 2020. Single LVIS stent-assisted coil embolization was performed as the initial treatment. If the coil could not be placed in the aneurysm, or follow-up angiography showed persistent filling or regrowth of the aneurysm, a second LVIS stent was deployed as an overlapping stent. Clinical characteristics, treatment details, and clinical outcomes were retrospectively examined. RESULTS: Single stent-assisted coiling was performed in 8 patients (69%), 2 overlapping stents with coiling in 1 (8%), a single stent in 2 (15%), and 2 overlapping stents in 2 (15%). Three patients with persistent filling or regrowth of the aneurysm were re-treated with overlapping stents. Follow-up angiography confirmed complete occlusion in 12 aneurysms (92%). No re-rupture occurred. Postoperative symptomatic ischemia was confirmed in 4 patients (33%), and all 4 patients suffered severe subarachnoid hemorrhage. Modified Rankin scale was 0-2 in 8 patients (67%). CONCLUSIONS: LVIS stent-assisted coil embolization is effective in preventing re-rupture of BBAs. However, the morphology of the aneurysm may change within a short period, so careful angiographic follow-up is needed. Appropriate preoperative antiplatelet administration and optimal timing of the treatment may reduce the risk of postoperative ischemic complication.

Successful basilar artery dilatation in pure bilateral cerebral peduncular infarctions using balloon angioplasty.

•An extremely rare case of bilateral cerebral peduncular infarctions (BCPI) is reported.•The detection of the pure Mickey Mouse ears sign on MRI is an indicator of a need for reperfusion therapy.•Severe stenosis of the basilar artery (BA) and a poor collateral supply from both posterior cerebral arteries were seen.•Balloon angioplasty for the BA stenosis ameliorated the stenosis and produced a favorable outcome.

Treatment of a Scalp Arteriovenous Malformation by a Combination of Embolization and Surgical Removal.

BACKGROUND: Scalp arteriovenous malformation is a rare disease. In terms of treatment, surgical removal is often effective and performed. With the development of endovascular treatments, a combination of surgical removal and embolization is now often performed. CASE DESCRIPTION: A 44-year-old man presented with a mass in his left occipital region. Cerebral angiography led to a diagnosis of scalp arteriovenous malformation. Although he had no neurologic deficits, perfusion computed tomography (CT) scan showed a slight decrease in blood flow in the left cerebral hemisphere, which was presumed to have been caused by the scalp arteriovenous malformation. He suffered from a sleep disorder caused by tinnitus, and a discomfort with the lesion itself; therefore, we decided to surgically remove the lesion. To suppress intraoperative bleeding and safely perform the surgery, preoperative embolization was also planned. After treatment, he had no neurologic deficits and the sleep disorder improved. Perfusion CT scan performed after the surgery showed an improvement in cerebral blood flow in the left cerebral hemisphere. CONCLUSIONS: Because cerebral blood flow may decrease depending on the progression of the lesion, the cerebral blood flow should be evaluated. Considering the treatment modalities depending on the lesion can provide treatment with less recurrence and higher patient satisfaction.

Surgical Strategies and Clinical Results of Site-Specific Treatment Using High-Flow Bypass for Ruptured Blood Blister-Like Anterior Wall Aneurysms of the Internal Carotid Artery.

OBJECTIVE: Surgical treatment of ruptured blood blister-like aneurysms (BBAs) arising from the internal carotid artery (ICA) is challenging. We retrospectively reviewed the results of our surgical strategies tailored for each aneurysm site. METHODS: All ruptured ICA BBAs treated between 2003 and 2015 were reviewed. Aneurysms on the lateral side of the ICA were classified as type A, on the medial side of C2 as type B, and on the medial side of C1 as type C. The principal strategy was high-flow bypass (HFB) by use of a radial artery graft, with clipping, trapping, or proximal occlusion selected on the basis of aneurysm type. The results of each treatment were examined. RESULTS: This study included 20 patients. There were 11 type A aneurysms (55%), 2 type B (10%), and 7 type C (35%). HFB was used in 13 patients (65%) and low-flow bypass in 4 (20%). Except for 1 case, no other cases of rerupture or recurrence occurred. Severe ischemia due to cerebral vasospasm was confirmed in 4 of 20 patients (20%), 3 of whom had not received HFB. Modified Rankin Scale score was 0-2 in 16 of 20 patients (80%). CONCLUSION: Inadequate cerebral blood flow is a distinct possibility even with HFB, so parent artery flow should be preserved to protect against ischemia whenever possible. However, if preservation of the anterior choroidal artery or posterior communicating artery during clipping or trapping is difficult, HFB combined with occlusion of the proximal portion of the ICA in the neck is a feasible option.

Predictive factors of medullary infarction after endovascular internal trapping using coils for vertebral artery dissecting aneurysms.

OBJECTIVE The first choice of treatment in cases of vertebral artery dissecting aneurysms (VADAs) is endovascular internal trapping (EIT) of the dissecting segment using coils. However, this procedure carries the risk of medullary infarction, and the risk factors for this complication are not well understood. This study investigated the risk factors causing medullary infarction. METHODS One hundred patients who underwent EIT for VADAs were included in this study. Ninety-three patients presented with subarachnoid hemorrhage. In cases involving the posterior inferior cerebellar artery (PICA), partial internal trapping targeting the ruptured site was performed to preserve the PICA. The VADAs were classified into the distal VA stump group, proximal VA stump group, and entire VA stump group, according to the location of VA segments without adequate flow-out vessels (such as the PICA [VA stump]) at risk of delayed thrombosis. The occurrence of medullary infarction was examined in each group using diffusion-weighted MRI and/or clinical symptoms. Various measurements were performed on digital subtraction angiography, and the risk factors for medullary infarction were analyzed. RESULTS Medullary infarction occurred in 30 patients, affecting the posterolateral medulla in 27 patients and the anteromedial medulla in 3 patients. Medullary infarction occurred in 3 of 47 patients (6%) in the distal VA stump group, 10 of 19 patients (53%) in the proximal VA stump group, and 17 of 34 patients (50%) in the entire VA stump group. The length of trapping was significantly longer in the infarction group than in the noninfarction group but did not differ among the 3 groups. Total length (length of trapping plus VA stump) was a risk factor for medullary infarction in the proximal VA stumps. CONCLUSIONS The primary risk factor for medullary infarction after EIT is not the length of trapping; rather, it is the anatomical location of the VADAs. The risk of medullary infarction is low in cases with distal VA stumps, but the symptoms are severe. Preservation of the origin of the anterior spinal artery can reduce the risk of medullary infarction. The risk of medullary infarction is high in cases with proximal VA stumps, but the symptoms are mild. A shorter length of trapping, although less likely to lead to complications, cannot prevent medullary infarction because the total length depends on the anatomical location of the PICA and not on the surgical technique. Reconstructive therapy should be indicated for patients with ruptured VADAs at high risk of severe ischemic complications (e.g., patients with hypoplasia of the contralateral VA or cases involving the PICA or anterior spinal artery, which are inappropriate for partial internal trapping) or for patients with unruptured VADAs.

Preoperative embolization of intracranial meningiomas using n-butyl cyanoacrylate.

INTRODUCTION: Preoperative embolization for intracranial meningioma has been controversial for several decades. This study retrospectively reviewed our experience using n-butyl cyanoacrylate (n-BCA) to identify the factors for effective devascularization and procedure-related complications. METHODS: Fifty-seven patients who underwent preoperative embolization with n-BCA were analyzed to collect the following data: age, sex, tumor size, location, pathology, and presence or absence of pial arterial supply. The predictive factors for total devascularization and complications were examined using univariate and multivariate analyses. RESULTS: Injected n-BCA penetrated into the tumor vessels in 51 cases (89%) but resulted in feeder occlusion in 6 (11%). Angiographic total devascularization was achieved in 29 cases (51%) and partial devascularization in 28 (49%). Small size, superficial location, and absence of pial supply were independent factors for total devascularization. No major complication was encountered, but asymptomatic or transient adverse events occurred in nine patients and were significantly associated with elderly patients and large tumors. CONCLUSION: Preoperative embolization for intracranial meningiomas using n-BCA can attain effective devascularization without major complications. The effect of preoperative embolization on surgical resection or patient outcome is still unknown.

Novel ß-amyloid aggregation inhibitors possessing a turn mimic.

Amyloid ß peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of ß-secretase, γ-secretase, and Aß aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aß antibodies. Recently, we reported potent small-sized ß-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel ß-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid ß peptides contain a turn structure within the molecule. Here, we designed and synthesized novel ß-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid ß peptides.

Efficacy and limitations of transarterial acrylic glue embolization for intracranial dural arteriovenous fistulas.

The efficacy and limitations of transarterial acrylic glue embolization for the treatment of intracranial dural arteriovenous fistulas (DAVFs) were investigated. Thirty-four DAVFs treated by transarterial embolization using n-butyl cyanoacrylate were retrospectively reviewed. The locations of DAVFs were the transverse-sigmoid sinus in 11, tentorium in 10, cranial vault in 9, and superior sagittal sinus, jugular bulb, foramen magnum, and middle cranial fossa in 1 each. Borden classification was type I in 7, type II in 3, and type III in 24. Eight patients had undergone prior transvenous coil embolization. Complete obliteration rate was 56% immediately after embolization, 71% at follow-up angiography, and 85% after additional treatments (1 transvenous embolization and 4 direct surgery). Complications occurred in three patients, consisting of asymptomatic vessel perforations during cannulation in two patients and leakage of contrast medium resulting in medullary infarction in one patient. Transarterial glue embolization is highly effective for Borden type III DAVF with direct cortical venous drainage, but has limitations for Borden type I and II DAVFs in which the affected sinus is part of the normal venous circulation. Onyx is a new liquid embolic material and is becoming the treatment of choice for DAVF. The benefits of glue embolization compared to Onyx embolization are high thrombogenicity, and relatively low risks of cranial nerve palsies and of excessive migration into the draining veins of high flow fistula. Transarterial glue embolization continues to be useful for selected patients, and complete cure can be expected in most patients with fewer complications if combined with transvenous embolization or direct surgery.

Visual outcomes of endovascular and microsurgical treatment for large or giant paraclinoid aneurysms.

BACKGROUND: The optimal treatment for large or giant paraclinoid aneurysms is still controversial. The present study evaluated the results of endovascular coiling and microsurgical clipping with special reference to visual outcomes. METHODS: The clinical data and treatment outcomes of 39 cases of large (>15 mm) paraclinoid aneurysms were retrospectively reviewed. Presenting symptoms were subarachnoid hemorrhage in 16 aneurysms and visual impairment in 18. Twenty-one aneurysms were treated by endovascular therapy and 18 were treated by direct surgery. RESULTS: Maximal aneurysm diameter ≥25 mm and preoperative visual acuity <20/100 were significantly related to poor visual outcome in univariate analysis. However, preoperative visual acuity was the only significant prognostic factor in multivariate analysis (odds ratio [OR] 0.12, 95 % confidence interval [CI] 0.01-0.95, p = 0.04). Although patients treated with endovascular coiling tended to have more favorable outcome than those with surgical clipping, adjustment for other confounding factors reduced the OR of favorable outcome following each treatment modality to nearly one (OR 1.14, 95 % CI 0.17-7.46, p = 0.89). Deteriorations in the visual field showed different patterns: upper visual field deficit after endovascular coiling, and inferior nasal quadrantanopia after microsurgical clipping. CONCLUSIONS: Preoperative visual acuity was the only independent predictor of visual outcome in patients with large paraclinoid aneurysms. Although adjusted visual outcomes with microsurgical clipping and endovascular coiling were almost the same, selection of the optimal treatment for each aneurysm is essential with recognition of the potential risks and mechanisms of visual impairment.

Spinal epidural arteriovenous fistulas with unusual manifestation of sudden onset of severe neurological deficits: case report.

Spinal epidural arteriovenous fistulas with perimedullary venous drainage cause venous hypertension, and usually manifest as slowly progressive myelopathy. We treated two patients presenting with sudden onset of severe neurological deficits. Moreover, in Case 1, the venous drainage was exclusively epidural and no perimedullary venous drainage was present. Angiographic findings of this patient were characterized by a slow-flow fistula with marked retention of the epidural venous drainage. Rapidly progressing thrombosis of the epidural venous plexus may have caused the sudden onset of the symptoms. In Case 2, hematomyelia may also be possibly associated with the sudden onset of the symptoms. Early diagnosis and treatment are essential to achieve favorable outcome in such cases because venous congestion results in irreversible venous infarction within a short period.

Novel combined GPIHBP1 mutations in a patient with hypertriglyceridemia associated with CAD.

AIM: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia. Similar clinical phenotypes have been reported with respect to defects in several LPL-associated proteins. However, it remains controversial whether severe hypertriglyceridemia itself is atherogenic. We herein present a case of LPL deficiency due to novel combined mutations of glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1) in a patient with coronary artery disease (CAD). PATIENT: We evaluated a 54-year-old woman with severe hypertriglyceridemia and double vessel CAD. Although the LPL mass and activity in the postheparin plasma were extremely low, no mutations were detected in the LPL gene itself. RESULTS: Genetic analyses revealed that the patient had double homozygous mutations at 41 bp (c.41 G > T) and 202 bp (c.202 T > C) in the GPIHBP1 gene, resulting in C14F and C68R, respectively. Although the C14F/C68R GPIHBP1 exhibited a normal LPL-binding activity, the levels of mutant proteins were extremely reduced compared to those of the wild-type proteins in vitro. CONCLUSION: We found novel combined mutations of GPIHBP1 in a patient with hypertriglyceridemia and severe CAD. The present case provides important insight into the pathogenesis of severe hypertriglyceridemia associated with atherosclerosis.

Significance of interactions of BACE1-Arg235 with its ligands and design of BACE1 inhibitors with P2 pyridine scaffold.

Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P(2) position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P(2) position, that were optimized for the interactions with Arg235 of BACE1.

Clinical and angiographic characteristics of cavernous sinus dural arteriovenous fistulas manifesting as venous infarction and/or intracranial hemorrhage.

INTRODUCTION: Cavernous sinus (CS) dural arteriovenous fistulas (DAVFs) rarely cause venous infarction (VI) and/or intracranial hemorrhage (ICH) despite the presence of cortical venous drainage (CVD). The present study investigated the characteristics of CS DAVFs manifesting as VI/ICH. MATERIALS AND METHODS: Fifty-four patients treated for CS DAVFs were retrospectively studied. RESULTS: Six patients presented with VI/ICH. Two of the three patients presenting with ICH had CVD only to the superficial sylvian vein (SSV) or the deep sylvian vein (DSV). Three patients presenting with VI had multiple drainages, and angiography of these patients showed a varix on the SSV, drainage into the DSV with agenesis of the second and third segment of basal vein of Rosenthal, and thrombosis of the distal petrosal vein. CS DAVF with CVD only carries higher risk of VI/ICH than multiple drainages. Many CS DAVFs presenting with VI, especially those with drainage into the petrosal vein, have multiple drainages in the early stage. Thrombosis of the inferior and superior petrosal sinuses and superior orbital vein gradually increases pressure of the CVD, and then, VI may occur. In contrast, CS DAVFs with CVD only from the beginning, common in the patients with drainage into the SSVs and DSVs, are likely to cause ICH. CONCLUSION: Angiographic risk factors causing VI/ICH are CVD only, varix formation, agenesis of the second and third segment of basal vein of Rosenthal, and thrombosis of the superior orbital vein, lateral half of the superior petrosal sinus, and distal CVD.

Urgent stenting for patients with acute stroke due to atherosclerotic occlusive lesions of the cervical internal carotid artery.

Acute symptomatic occlusion of the cervical internal carotid artery (ICA) can be treated by intravenous administration of tissue plasminogen activator, percutaneous transluminal angioplasty, and carotid endarterectomy. Carotid artery stenting (CAS) is now indicated for cervical ICA stenosis, but the safety and the efficacy of urgent CAS have not been established. We retrospectively reviewed 10 patients treated by urgent CAS for atherosclerotic occlusive lesions of cervical ICA with acute stroke. Five patients had complete occlusions and five had near total occlusions. Five of the 10 patients had intracranial tandem occlusions. Indication for urgent CAS was determined by mismatch of diffusion-weighted and perfusion-weighted magnetic resonance imaging findings. Stents were successfully deployed in all lesions. Three of five patients with concomitant intracranial tandem occlusions were treated by additional intraarterial fibrinolysis after the CAS. Intracranial artery occlusions were completely recanalized in one patient, and partially recanalized in two by fibrinolysis. Hyperperfusion syndrome did not occur in any of the patients. A favorable outcome (modified Rankin Scale < or =1) was obtained in all of the five patients with isolated cervical ICA occlusion and one of the five patients with intracranial tandem occlusions. Urgent CAS is a safe and effective treatment in patients with isolated cervical ICA occlusion. Treatment of intracranial tandem occlusions is an issue that must be resolved.

Novel non-peptidic and small-sized BACE1 inhibitors.

Recently, we reported substrate-based beta-secretase (BACE1) inhibitors with a hydroxymethylcarbonyl (HMC) isostere as a substrate transition-state mimic. These inhibitors showed potent BACE1 inhibitory activities (approximately 1.2 nM IC(50)). In order to improve in vivo enzymatic stability and permeability across the blood-brain barrier, these penta-peptidic inhibitors would need to be further optimized. On the other hand, non-peptidic inhibitors possessing isophthalic residue at the P(2) position were reported from other research groups. We selected isophthalic-type aromatic residues at the P(2) position and an HMC isostere at the P(1) position as lead compounds. On the basis of the design approach focused on the conformer of docked inhibitor in BACE1, we found novel non-peptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P(2) position.

A survey of Blastocystis infection in anuran and urodele amphibians.

Blastocystis infection in amphibians was surveyed in three species of anuran and one species of urodele amphibians captured at two distinct locations in Japan. All three species of frogs were highly infected with Blastocystis, while 69 individual urodele newts, Cynopus pyrrhogaster, were negative for infection. Eleven Blastocystis isolates (47.8%) were recovered from 23 Rana nigromaculata leopard frogs. Twenty-three (92%) of 25 Rana catesbeiana bullfrogs and all (100%) of 24 Bufo japonicus japonicus toads were positive for Blastocystis. Two distinct populations of the toad and bullfrog showed a high prevalence (100 or 84.6%) of Blastocystis infection, while in two populations of the leopard frog only one population was positive for Blastocystis (84.6%). Three Blastocystis isolates from different species of the frogs were established. Since none of the three isolates could survive at 37 degrees C, a temperature tolerance assay was performed to assess the optimal growth temperature and to determine the range of non-lethal temperatures. During the exponential growth phase of 3- or 4-day cultures at 25 degrees C, three isolates were exposed to 4, 28, 31, or 34 degrees C for 3 days and then returned to 25 degrees C to monitor the cell growth. Based on the optimal growth temperatures and different ranges of temperature tolerance among the three new isolates from frogs and two known species, Blastocystis hominis and Blastocystis lapemi, it was established that the three isolates recovered from different species of frogs had different physiological features from B. hominis and B. lapemi.