Tetsuya Hashimoto

Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation

Intracellular amyloid β‐protein (Aβ) contributes to neurodegeneration in Alzheimer disease (AD). Apomorphine (APO) is a dopamine receptor agonist for Parkinson disease and also protects against oxidative stress. Efficacy of APO for an AD mouse model and effects of APO on cell cultures are studied.

Histopathologic Analysis of Retrieved Thrombi Associated With Successful Reperfusion After Acute Stroke Thrombectomy

Background and Purpose— Histopathologic evaluation of occlusive thrombi retrieved from cerebral arteries using endovascular therapy is possible. We investigated the relationship between successful reperfusion after thrombectomy and histopathologic characteristics of retrieved thrombi. Methods— Among consecutive patients with acute ischemic stroke treated with endovascular therapy at our institute from December 2010 to July 2015, we retrospectively reviewed those with acute major arterial occlusion from which retrieved thrombi were evaluated histopathologically. Obtained thrombi were assessed for the existence of atheromatous gruel, organization, and the ratios of erythrocyte and fibrin/platelet components. Successful reperfusion was defined as the modified Treatment in Cerebral Ischemia grade of 2b to 3. Results— Of 83 patients studied, 58 (70%) underwent successful reperfusion. Atheromatous gruel was less frequently identified (3% versus 20%; P=0.024), and the proportion of erythrocyte components was higher (57±23% versus 47±24%; P=0.042) in thrombi retrieved from the reperfused than the unreperfused group. On multivariate logistic regression analysis, atheromatous gruel was inversely related (odds ratio, 0.062; 95% confidence interval, 0.002–0.864), and >64% erythrocyte components (cutoff obtained from receiver operating characteristic curve) were positively related (odds ratio, 4.352; 95% confidence interval, 1.185–19.363) to successful reperfusion. Conclusions— Successful reperfusion could be associated with the histopathology of occlusive thrombi, including the existence of atheromatous gruel and proportion of erythrocyte components. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665.

Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy

Background and purpose Hemorrhagic complications during neurointerventional procedures have various etiologies and can result in severe morbidity and mortality. This study investigated the possible association between low platelet reactivity measured by the VerifyNow assay and increased hemorrhagic complications during elective neurointervention under dual antiplatelet therapy. Methods From May 2010 to April 2013 we recorded baseline characteristics, P2Y12 reaction units (PRU), and aspirin reaction units using VerifyNow. The primary endpoint was post-procedural hemorrhagic complications. Results A total of 279 patients were enrolled and 31 major hemorrhagic complications (11.1%) were identified. From receiver-operating characteristic curve analysis, PRU values could discriminate between patients with and without major hemorrhagic complications (area under the curve 0.63). Aspirin reaction unit values had no association with the primary outcome. The optimal cut-off for the primary outcome (PRU ≤175) was used to identify the low platelet reactivity group. The incidence of hemorrhagic complications was 20.0% in this group and 8.9% in the non-low platelet reactivity group. Multivariate analysis identified low platelet reactivity as an independent predictor for hemorrhagic complications. Conclusions The risk of hemorrhagic complications during elective neurointervention including cerebral aneurysm coil embolization and carotid artery stenting under dual antiplatelet therapy is associated with the response to clopidogrel but not to aspirin. A PRU value of ≤175 discriminates between patients with and without hemorrhagic complications. Future prospective studies are required to validate whether a specific PRU value around 170–180 is predictive of hemorrhagic complications.

Rapid Formation of Cerebral Microbleeds after Carotid Artery Stenting

Background: Recent studies reported that cerebral microbleeds (CMBs), i.e. small areas of signal loss on T2*-weighted gradient-echo (GE) imaging, could develop rapidly after acute ischemic stroke. We hypothesized that CMBs rapidly emerge after carotid artery stenting (CAS). Objective: We investigated the frequency of and predisposing factors for CMBs after CAS. Methods: We retrospectively examined MRI before and after CAS in 88 consecutive patients (average age: 71.7 ± 7.2 years, average rates of carotid stenosis: 72.6 ± 12.8%) who underwent CAS for carotid artery stenosis between March 1, 2009, and September 30, 2010. We defined new CMBs as signal losses that newly appeared on the follow-up GE. We examined the association of new CMBs with demographics, risk factors, and baseline MBs. Results: Among 88 patients, 18 (20.5%) had CMBs initially, and 7 (8.0%) developed new CMBs right after CAS. New CMBs appeared on the same side of CAS in all of the 7 patients. New CMBs appeared significantly more frequently in the CMB-positive group than in the CMB-negative one (22% vs. 4%, p = 0.03) on the pre-CAS MRI. Multivariate analysis also revealed that the presence of CMBs before CAS was an independent predictor of new development of CMBs after CAS (odds ratio: 8.09, 95% confidence interval: 1.39–47.1). Conclusion: CMBs can develop rapidly after CAS, especially in patients with pre-existing CMBs. Since the existence of CMBs prior to CAS suggests a latent vascular damage which is vulnerable to hemodynamic stress following CAS, particular attention should be paid to the prevention of intracerebral hemorrhage due to hyperperfusion after CAS.

Carotid artery stenting with proximal embolic protection via the transbrachial approach: sheathless navigation of a 9-F balloon-guiding catheter

PurposeTransbrachial carotid artery stenting (TB-CAS) is performed as an alternative procedure for patients with hostile vascular anatomy of the aortic arch and aortic or peripheral artery disease. Proximal protection during TB-CAS is not generally feasible because a small size of the brachial artery may preclude using a large-diameter sheath introducer. We, herein present a novel method that enables proximal protection during TB-CAS by sheathless navigation of a 9-F balloon-guiding catheter equivalent to a 7-F sheath.MethodsWe analyzed eight consecutive patients who underwent TB-CAS with proximal protection using the sheathless method from April 2016 to June 2017. Relevant demographic, radiographic, and procedural features were retrospectively reviewed.ResultsWe performed TB-CAS using our method for five patients with a bovine or type 3 aortic arch, for one patient with combined peripheral artery disease, and for two patients with a type 1 or 2 aortic arch. We successfully navigated the balloon-guiding catheter via the brachial artery and performed CAS under proximal flow control in all patients. However, we experienced kinking and exchange of the balloon-guiding catheter in one patient and a periprocedural thromboembolic event occurred. A pseudoaneurysm at the access site developed in one patient.ConclusionTB-CAS with proximal embolic protection using the sheathless method is feasible and may provide an alternative approach in carefully selected patients who have difficult anatomy in the transfemoral approach and plaques with a high risk of distal embolization.

Overshunting-associated myelopathy: Flattened spinal cord compressed by epidural venous plexus

A 50-year-old woman presented with a 1-month history of progressive spastic quadriparesis. She had undergone nonprogrammable ventriculoperitoneal (VP) shunt placement after intraventricular hemorrhage due to a ruptured arteriovenous malformation 16 years previously. Neurologically, she had neck extensor weakness (Medical Research Council [MRC] grade 4), symmetrical weakness of her upper extremities (right/left MRC grades 4/4), and weakness of her right proximal lower extremity (MRC grade 4). She also had spasticity and hyperreflexia in all 4 extremities with extensor plantar reflexes. Light touch and vibratory sensation was impaired in the right distal lower extremity. Neck MRI demonstrated that the cervical spinal cord was compressed from both sides by an engorged epidural venous plexus (figure 1). Brain MRI revealed diffuse pachymeningeal enhancement and slit ventricles. Overshunting-associated myelopathy (OSAM) was diagnosed. Her symptoms resolved completely 3 months after VP shunt revision (figure 2).

Vascular wall components in thrombi obtained by acute stroke thrombectomy: clinical significance and related factors

Background and purpose Vascular wall components (VWCs) are sometimes identified as collagen fibers in specimens retrieved by thrombectomy from acute stroke patients. However, their clinical significance and associated factors remain unclear. The purpose of this study was to clarify the factors associated with VWCs in retrieved thrombi. Methods Consecutive acute stroke patients treated endovascularly using the Penumbra aspiration catheter or stent retrievers (SRs) at our institute from November 2013 to April 2016 were retrospectively reviewed, and the retrieved thrombi were evaluated histopathologically. VWCs were defined as banded collagen fibers with a distinct boundary observed at the rim or outside of the retrieved thrombi. Factors associated with the presence of VWCs were studied. Results A total of 150 specimens (76 specimens retrieved by the Penumbra, 74 by SRs) from 101 patients (47 women, age 74.9±11.1 years) were investigated. Applied thrombectomy devices were aspiration catheters in 42 patients, SRs in 21 patients, and both in 38 patients. VWCs were observed in 24 specimens (16%) from 22 patients. A low proportion of erythrocyte components (41.7±24.8% vs 55.0±26.3%, P=0.01), a high frequency of the devices reaching the M2/P2 (75% vs 50%, P=0.02), and a high number of device passages (P for trend=0.02) were associated with VWC positive thrombi. Successful recanalization (Treatment in Cerebral Ischemia ≥2b) tended to be less frequent in patients with VWC positive thrombi than in those without (73% vs 89%, P=0.06). Conclusions The histopathology of occlusive thrombi, arterial sites where devices reached, and number of device passages, might affect the presence of VWCs in retrieved thrombi.

The Early Spectroscopy of Supernovae

The spectroscopy of a supernova (SN) just after its discovery is quite important not only for the spectral type classification but also for the planning further follow-up observations or the target-of-opportunity observations (ToOs). The early spectroscopy is needed also because the information from the outermost envelope of such exploding objects as SNe cannot be obtained in the later phase. In order to obtain the early spectrum, the quick circulation of the discovery information is important. We introduce our contributions with the public astronomical observatories in Japan, including the case of “hypernova” SN 2002ap discovered by a Japanese amateur astronomer. We summarize the time interval between the discoveries, the announcements, and the first spectral classifications of recent SNe, and discuss what would be required for the early spectroscopy. Present address: National Astronomical Observatory, Japan