橋本 哲也

We investigated the changes in antibody titers after intravenous immunoglobulin (IVIg) administration in patients with neuromuscular diseases. Among patients who received IVIg from April 1, 2020, to August 31, 2022, we retrospectively evaluated 15 patients with antibody measurements before and after IVIg administration for any rise in the following antibody levels and examined the data for subsequent changes of false positive results to negative ones. The levels of anti SS-A, anti-thyroglobulin, anti-thyroid peroxidase, anti-glutamic acid decarboxylase, HBs, and HBc antibodies transiently increased after IVIg administration and showed false-positive results. However, levels of rheumatoid factor and anti-nuclear and antineutrophil cytoplasmic antibodies were not elevated. The false-positive results became negative after 3 months. Here, we report on the changes in antibody levels before and after IVIg administration and note that levels of hepatitis B virus-related antibodies and various autoantibodies transiently rise after IVIg administration.

Behçet's disease commonly affects 20-40-year-old men and shows ophthalmo-dermatological manifestations. Here, we report a man in his 70s with acute onset of dysarthria, dysphagia and hemiplegia showing brainstem and subcortical lesions, which responded to steroid and colchicine therapy. He had a history of uveitis and was homozygous for the human leucocyte antigen-B51 allele, and we clinically diagnosed him with acute neuro-Behçet's disease. Old-age onset neuro-Behçet's disease is uncommon, and as far as we know, this is the oldest case of the first attack of neuro-Behçet's disease. Clinicians should consider Behçet's disease even for elderly patients.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disorder of the central nervous system caused by opportunistic infection of the JC virus (JCV). CASE PRESENTATION: A 58-year-old Japanese woman was admitted to our hospital for aphasia. She had a 5-year history of untreated sarcoidosis and was a human T cell lymphotropic virus-1 (HTLV-1) carrier. Serum angiotensin-converting enzyme, soluble interleukin-2 receptor, lysozyme, and calcium levels were elevated. JCV-DNA was not detected in cerebrospinal fluid by PCR testing. Skin biopsy revealed noncaseating granuloma formation. Bilateral multiple nodular lesions were present on chest X-ray. Brain magnetic resonance imaging showed left frontal and temporal lesions without gadolinium enhancement. As we suspected that systemic sarcoidosis had developed into neurosarcoidosis, we started steroid and infliximab administration. After treatment, the chest X-ray and serum abnormalities ameliorated, but the neurological deficits remained. At 1 month after immunotherapy, she developed right hemiparesis. Cerebrospinal fluid was positive for prototype (PML-type) JCV on repeated PCR testing. Brain biopsy revealed demyelinating lesions with macrophage infiltration, atypical astrocytes, and JCV antigen-positive cells. We diagnosed her with PML and started mefloquine, leading to partial remission. CONCLUSIONS: Sarcoidosis and HTLV-1 infection both affect T cell function, especially CD4+ T cells, and may developped the patient's PML. The comorbidity of sarcoidosis, PML, and HTLV-1 infection has not been reported, and this is the world's first report of PML associated with HTLV-1 infection and sarcoidosis.

症例は57歳男性，30代発症の多発性硬化症に対し，9年前からフィンゴリモドを開始し，再発なく経過していた．某日より，顔面を含む左半身の運動障害と自発性の低下が出現し進行した．頭部MRIでは右前頭葉にガドリニウム造影効果を伴う腫瘤性病変を認めた．髄液検査では細胞数増多はなかった．その後も病変は拡大し，入院9日目に開頭減圧術と脳生検術を施行した．脳病理で脱髄性病変を認め，tumefactive demyelinating lesion（TDL）と診断，ステロイド治療により病変は縮小，ナタリズマブを導入した．

症例は13歳女性．5歳時に右半身の運動感覚障害を突然発症し，脳梗塞と診断された．若年性脳梗塞の原因を検索されたが，心疾患や血栓素因などは認めず，アスピリン内服で再発予防された．アスピリンは3年後に中止，その後は再燃なく経過していた．12歳時，再び突然発症の右上下肢麻痺を生じ，頭部MRIで左基底核に脳梗塞病変を認めた．各種原因を再検索されたが，心疾患，血栓素因，血管異常などは認めず，当科紹介となった．患者は左額から頭頂部にかけて皮膚陥凹と菲薄化，同部位の脂肪組織萎縮を認め，剣創状強皮症の所見だった．剣創状強皮症は一側の頭部に生じる限局性強皮症で，時に頭蓋内病変を伴う．本症例は剣創状強皮症の頭蓋内病変として脳梗塞様症状を呈したと考えられた．本症例は神経症状が皮膚症状に先行したため，診断に難渋した点が特徴的だった．

BACKGROUND AND PURPOSE: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment. MATERIALS AND METHODS: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment. RESULTS: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10-6 mm2/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10-6 mm2/s. The mean ADC threshold was 520 × 10-6 mm2/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (P < .0001). CONCLUSIONS: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10-6 mm2/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.

BACKGROUND: The potential heterogeneity in occlusive thrombi caused by in situ propagation by secondary thrombosis after embolic occlusion could obscure the characteristics of original thrombi, preventing the clarification of a specific thrombus signature for the etiology of ischemic stroke. We aimed to investigate the heterogeneity of occlusive thrombi by pretreatment imaging. METHODS: Among consecutive stroke patients with acute embolic anterior circulation large vessel occlusion treated with thrombectomy, we retrospectively reviewed 104 patients with visible occlusive thrombi on pretreatment non-contrast computed tomography admitted from January 2015 to December 2018. A region of interest was set on the whole thrombus on non-contrast computed tomography under the guidance of computed tomography angiography. The region of interest was divided equally into the proximal and distal segments and the difference in Hounsfield unit densities between the two segments was calculated. RESULTS: Hounsfield unit density in the proximal segment was higher than that in the distal segment (mean difference 4.45; p < 0.001), regardless of stroke subtypes. On multivariate analysis, thrombus length was positively correlated (β = 0.25; p < 0.001) and time from last-known-well to imaging was inversely correlated (β = -0.0041; p = 0.002) with the difference in Hounsfield unit densities between the proximal and distal segments. CONCLUSIONS: The difference in density between the proximal and distal segments increased as thrombi became longer and decreased as thrombi became older after embolic occlusion. This time/length-dependent thrombus heterogeneity between the two segments is suggestive of secondary thrombosis initially occurring on the proximal side of the occlusion.

Paraneoplastic tumefactive demyelination (TD) is a rare disorder of the central nervous system that can be challenging to diagnose. Here, we describe a 32-year-old Japanese man with a TD associated with testicular seminoma. He presented with symptoms of right-sided motor and sensory impairment 2 days after vaccination for coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) showed a high-intensity lesion in the left internal capsule. He had a 3-year history of enlargement of the left testicle. Blood examination showed tumor marker elevation and the presence of anti-amphiphysin antibodies. Whole-body computed tomography (CT) revealed mass lesions in the left testicle and enlargement of the retroperitoneal lymph nodes. Radical orchiectomy was performed. As the pathology showed testicular seminoma, chemotherapy was administered. After surgery, his neurological symptoms deteriorated. MRI revealed that the brain lesion had enlarged and progressed to a tumefactive lesion without gadolinium enhancement. The cerebrospinal fluid (CSF) examination was normal without pleocytosis or protein elevation. Steroid pulse therapy was added; however, his symptoms did not improve. A brain stereotactic biopsy was performed and the sample showed demyelinating lesions without malignant cells. As the initial corticosteroid therapy was ineffective, gamma globulin therapy was administered in parallel with chemotherapy, and the clinical symptoms and imaging findings were partially ameliorated. TD seldom appears as a paraneoplastic neurological syndrome. In addition, there are few reports of COVID-19 vaccination-associated demyelinating disease. Clinicians should recognize paraneoplastic TD, and the further accumulation of similar cases is needed.

BACKGROUND AND PURPOSE: Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. MATERIALS AND METHODS: Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. RESULTS: Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status. CONCLUSIONS: Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p>Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection.</jats:p> </jats:sec> <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>A total of 22 studies encompassing 1623 patients met inclusion criteria. Clots associated with good angiographic outcome had higher red blood cell (RBC) content (mean difference [MD] 9.60%, 95% CI 3.85-15.34, P = .008). Thrombi retrieved by aspiration had less fibrin (MD −11.39, 95% CI −22.50 to −0.27, P = .046) than stent-retrieved thrombi. Fibrin/platelet-rich clots were associated with longer procedure times (MD 13.20, 95% CI 1.30-25.10, P = .037). Hyperdense artery sign was associated with higher RBC content (MD 14.17%, 95% CI 3.07-25.27, P = .027). No relationship was found between composition and etiology.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSION</jats:title> <jats:p>RBC-rich thrombi were associated with better recanalization outcomes and shorter procedure times, suggesting that preinterventional compositional characterization may yield important prognostic and therapeutic guidance.</jats:p> </jats:sec>

<jats:sec id="sec001"> <jats:title>Objective</jats:title> <jats:p>Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients’ clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247–0.987, p &lt; .001) and IDI (0.068, 95% CI: 0.021–0.116, p = .005).</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.</jats:p> </jats:sec>

<jats:sec id="sec001"> <jats:title>Background and purpose</jats:title> <jats:p>The impact of the paraoxonase-1 (<jats:italic>PON1</jats:italic>) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of <jats:italic>PON1</jats:italic> Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>Post-clopidogrel platelet reactivity was measured using a VerifyNow<jats:sup>®</jats:sup> P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for <jats:italic>PON1</jats:italic> Q192R and <jats:italic>CYP2C19*2</jats:italic> and <jats:italic>*3</jats:italic> (no function alleles), and <jats:italic>*17</jats:italic>. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 <jats:italic>PON1</jats:italic> 192R allele and HPR defined as original and corrected PRU ≥208.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 <jats:italic>PON1</jats:italic> 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 <jats:italic>PON1</jats:italic> 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 <jats:italic>CYP2C19</jats:italic> no function allele.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>Carrying ≥1 <jats:italic>PON1</jats:italic> 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.</jats:p> </jats:sec>

Background and Purpose: To determine whether acute major-vessel occlusion (MVO) predicts atrial fibrillation (AF) in cryptogenic stroke (CS) patients, we analyzed the association between acute MVO and AF detected by insertable cardiac monitoring (ICM). Methods: We conducted a retrospective, multicenter, observational study of patients with CS who underwent ICM implantation between October 2016 and March 2018. In this analysis, we included follow-up data until June 2018. We analyzed the association of MVO with AF detected by ICM. Results: We included 84 consecutive patients with CS who underwent ICM implantation. The proportion of patients with newly detected AF by ICM was higher in patients with MVO than in those without (41% [12/29] vs. 13% [7/55], p < 0.01) within 90 days of ICM implantation. The MVO was associated with AF after adjustment for each clinically relevant factor. Conclusions: MVO was independently associated with AF detection in patients with CS, which suggests that MVO may be a useful predictor of latent AF. It is therefore essential to actively assess latent AF in patients with CS presenting with MVO.

<jats:p>Objective: To determine whether frequent premature atrial contractions (PAC) predict atrial fibrillation (AF) in cryptogenic stroke patients, we analyzed the association between frequent PACs in 24-h Holter electrocardiogram recording and AF detected by insertable cardiac monitoring (ICM). Methods: We retrospectively analyzed a database of 66 consecutive patients with cryptogenic stroke who received ICM implantation between October 2016 and March 2018 at 5 stroke centers. We included the follow-up data until June 2018 in this analysis. We defined frequent PACs as the upper quartile of the 66 patients. We analyzed the association of frequent PACs with AF detected by ICM. Results: Frequent PACs were defined as &gt;222 PACs per a 24-h period. The proportion of patients with newly detected AF by ICM was higher in patients with frequent PACs than those without (50% [8/16] vs. 22% [11/50], p &lt; 0.05). Frequent PACs were associated with AF detection and time to the first AF after adjustment for CHADS2 score after index stroke, high plasma ­B-type natriuretic peptide (BNP; &gt;100 pg/mL) or serum ­N-terminal pro-BNP levels (&gt;300 pg/mL), and large left atrial diameter (≥45 mm). Conclusion: High frequency of PACs in cryptogenic stroke may be a strong predictor of AF detected by ICM.</jats:p>

BACKGROUND: Detection and treatment of atrial fibrillation (AF) is a major goal in preventing secondary stroke. Insertable cardiac monitors (ICMs) are available for diagnosis of arrhythmia monitoring in patients with cryptogenic stroke. Magnetic resonance imaging (MRI)-based diagnostic evaluation for acute ischemic stroke subtype classification is common in Japan and can be useful for specific diagnosis of cryptogenic stroke. PURPOSE: We aimed to investigate the detection rate of AF with an ICM in patients with cryptogenic stroke who were diagnosed by MRI. METHODS: We performed a retrospective, multicenter, observational study. AF monitoring data of an ICM (Reveal LINQ) in patients with cryptogenic stroke were registered from 5 stroke centers in Japan between October 2016 and March 2018. ICM candidates in cryptogenic stroke were diagnosed by MRI-based evaluation and selected according to the criteria proposed by the Japan Stroke Society. Detection of AF was defined as AF for longer than 120 seconds. RESULTS: Eighty-four consecutive patients (64 men; aged 38-90 years) underwent ICM implantation after diagnosis of cryptogenic stroke. AF was detected in 22 of 84 (26.2%) patients with an ICM during a median follow-up of 221.5 days (range: 93-365 days). The detection rate of AF within 3 months after ICM implantation was 21.4%. CONCLUSIONS: The AF detection rate with an ICM is approximately one fifth within 3 months in patients with cryptogenic stroke as diagnosed by MRI. Our data suggest that the Japanese criteria based on MRI may be useful for selecting adequate candidates for ICM implantation.

BACKGROUND: Experimental evidence that stent retriever thrombectomy (SRT) may cause arterial wall damage is increasing, although histopathologic findings focused on vessel wall injury after SRT have not fully been reported in humans. CASE DESCRIPTION: We describe an autopsy case of an 82-year-old woman who presented with acute left intracranial internal carotid artery occlusion and received SRT. When we attempted to catheterize the M1 segment of the normal middle cerebral artery (MCA), we were not aware of a duplicated MCA and advanced the microcatheter into the main MCA trunk with a smaller caliber than that of the normal M1 segment. A 6-mm Trevo thrombectomy device was deployed from the main MCA trunk but was insufficiently expanded in the MCA segment. Two passes with a Trevo resulted in failed recanalization. The patient died on postoperative day 4 because of extensive infarction. Autopsy revealed a duplicated MCA and subintimal arterial dissection in the proximal segment of the main MCA trunk. The supraclinoid internal carotid artery also revealed endothelial denudation and mural thrombus. CONCLUSIONS: We provide a histopathologic report of vessel wall injury after SRT that caused failed recanalization. Anatomic variations of the MCA should be considered when selecting suitable thrombectomy devices in order to avoid vessel wall injury.

<jats:sec><jats:title>Background and purpose</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The histopathology of occlusive thrombi, arterial sites where devices reached, and number of device passages, might affect the presence of VWCs in retrieved thrombi.</jats:p></jats:sec>

Background: To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. Objective: To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named "Task Calc. Stroke" (TCS), and aimed to investigate the impact of TCS on AIS care. Methods: TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS ("TCS-based CS"), one not using TCS ("phone-based CS"), and one not based on CS ("non-CS"). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. Results: During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min (p = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, p = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. Conclusions: TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.

PURPOSE: Transbrachial 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: TB-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.

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is known to be a rare but devastating complication of carotid artery revascularization. Because patients with acute ischemic stroke due to acute major cerebral and/or cervical artery occlusion treated with endovascular reperfusion therapy may have impaired autoregulation in the cerebral vasculature, these patients may also develop CHS. Despite the growing number of endovascular reperfusion procedures for acute ischemic stroke, this complication has only rarely been reported. CASE DESCRIPTION: A 77-year-old man developed acute cerebral infarction as the result of occlusions of the right internal carotid artery and right middle cerebral artery. After systemic intravenous injection of recombinant tissue-type plasminogen activator, endovascular reperfusion therapy was initiated. The occluded arteries were successfully recanalized with thrombectomy by using a stent retriever for the middle cerebral artery and stent placement for the origin of the internal carotid artery. However, head computed tomography obtained 12 hours after treatment showed acute intracranial hemorrhage that did not involve the ischemic lesions. Under evaluation with transcranial near-infrared spectroscopy and single-photon emission computed tomography, the hemorrhage was considered to have been caused by CHS after reperfusion therapy. CONCLUSIONS: CHS may lead to unfavorable outcomes after reperfusion therapy for acute ischemic stroke. Recognizing clinical deterioration caused by CHS can be challenging in patients with neurologic disorders of acute ischemic stroke. Therefore, it is important to perform routine monitoring of regional cerebral oxygen saturation by using near-infrared spectroscopy, perform single-photon emission computed tomography promptly to evaluate cerebral blood flow, and maintain strict antihypertensive therapy to prevent CHS after reperfusion therapy.

BACKGROUND: Previous reports have shown significant delays in treatment of in-hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. METHODS: Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008-March 2014) and after implementation (April 2014-December 2016). RESULTS: Fifty-five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5min, p<0.01) and to first neuroimaging (50 vs. 26.5min, p<0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16min, p=0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53min, p=0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. CONCLUSION: Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety.

OBJECTIVE: 11C-Pittsburgh compound-B (11C-PIB) positron emission tomography (PET) is used to visualize and quantify amyloid deposition in the brain cortex in pathological conditions such as Alzheimer's disease (AD). Intense 11C-PIB retention is also observed in the white matter (WM) of both healthy individuals and AD patients. However, the clinical implications of this retention in brain WM have not been clarified. We investigated the relationship between the extent of white matter lesions (WMLs) and the binding potential of 11C-PIB (BPND) in the WM in patients with hypertensive small vessel disease. We further examined the relationship between the extent of WMLs and BPND in WML and in normal-appearing white matter (NAWM). METHODS: Twenty-one hypertensive vasculopathy patients, without AD and major cerebral arterial stenosis and/or occlusion, were enrolled (9 women, 68 ± 7 years). Regions of WML and NAWM were extracted using magnetization-prepared rapid gradient-echo and fluid-attenuated inversion recovery of magnetic resonance images. Volumes of interest (VOIs) were set in the cortex-subcortex, basal ganglia, and centrum semiovale (CS). BPND in the cortex-subcortex, basal ganglia, CS, WML, and NAWM were estimated on 11C-PIB PET using Logan graphical analysis with cerebellar regions as references. The relationships between WML volume and BPND in each region were examined by linear regression analysis. RESULTS: BPND was higher in the CS and basal ganglia than in the cortex-subcortex regions. WML volume had a significant inverse correlation with BPND in the CS (Slope = -0.0042, R 2  = 0.44, P < 0.01). For intra WM comparison, BPND in NAWM was significantly higher than that in WML. In addition, although there were no correlations between WML volume and BPND in WML, WML volume was significantly correlated inversely with BPND in NAWM (Slope = -0.0017, R 2  = 0.26, P = 0.02). CONCLUSIONS: 11C-PIB could be a marker of not only cortical amyloid-β deposition but also WM injury accompanying the development of WMLs in hypertensive small vessel disease.

<jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> Of 83 patients studied, 58 (70%) underwent successful reperfusion. Atheromatous gruel was less frequently identified (3% versus 20%; <jats:italic>P</jats:italic> =0.024), and the proportion of erythrocyte components was higher (57±23% versus 47±24%; <jats:italic>P</jats:italic> =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 &gt;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. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Successful reperfusion could be associated with the histopathology of occlusive thrombi, including the existence of atheromatous gruel and proportion of erythrocyte components.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration—</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: NCT02251665. </jats:p> </jats:sec>

<jats:sec><jats:title>Background and purpose</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>

OBJECTIVE: Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease. METHODS: We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and (15)O-labeled gases. The functional values in the cortex-subcortex, basal ganglia, and centrum semiovale were compared between the two groups. RESULTS: Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1-91.5 mL vs. median: 11.3; range: 4.2-73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups. CONCLUSIONS: Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.

staged頸動脈ステント留置術(CAS)を試みたが、二期的治療に失敗した2例を経験した。症例1は72歳男で、左眼の一過性黒内障を主訴に受診し、左前頭葉に散在性に塞栓性梗塞、左内頸動脈起始部に高度狭窄病変を認めた。術前SPECTにて過灌流症候群(CHS)ハイリスク症例であることからstagedCASにて治療することとした。待機期間中の遠位塞栓の危険が高いと判断されたため、一期的にステントを留置した。術後、意識障害や神経脱落徴候は認めず過灌流症候群はきたさなかった。症例2は71歳男で、5分程度の左上下肢の脱力発作を頻回に認めた。症候性内頸動脈高度狭窄病変に対する精査加療目的で入院した。術前SPECTにてCHSハイリスク症例であることからstagedCASにて治療することとした。術翌日に左上下肢運動障害が出現し、ステントを留置した。意識障害や神経脱落徴候は認めず過灌流症候群はきたさなかった。

【目的】未破裂脳動脈瘤に対するコイル塞栓術中にEnterprise VRDのデリバリーワイヤーが離断し，血管内に遺残した症例を報告する．【症例】63歳女性．ネッククリッピング術後遠隔期に再発した右内頚動脈―後交通動脈分岐部の広頚動脈瘤に対しステント併用コイル塞栓術を企図した．ステント留置の際にデリバリーワイヤーが離断し，グースネックスネアを用いて回収を試みたが回収不能であり，直達手術にて回収した．【結論】Enterprise VRDのデリバリーワイヤー離断は稀ではあるが起こり得る．屈曲部に留置する場合，デリバリーワイヤーに過度のトルクがかかる場合などは本合併症を念頭に対処することが必要である．

BACKGROUND: Recent studies reported that cerebral microbleeds (CMBs), i.e. small areas of signal loss on T(2)*-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.

OBJECTIVE: 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. METHODS: The triple transgenic AD mouse model (3xTg-AD) has 2 familial AD-related gene mutations (APP(KM670/671NL) /PS1(M146V)) and a tau gene mutation (Tau(P301L)). Six-month-old 3xTg-AD mice were treated with subcutaneous injections of APO once a week for 1 month. Memory function was evaluated by Morris water maze before and after the treatment. Brain tissues were examined by immunohistochemical staining and Western blotting. Effects of APO on intracellular Aβ degradation, activity of Aβ-degrading enzymes, and protection against oxidative stress were studied in cultured SH-SY5Y cells. RESULTS: After APO treatment, short-term memory function was dramatically improved. Significant decreases in the levels of intraneuronal Aβ, hyper-phosphorylated tau (p-tau), p53, and heme oxygenase-1 proteins were observed. Moreover, APO promoted degradation of intracellular Aβ, increased activity of proteasome and insulin-degrading enzyme, protected against H(2) O(2) toxicity, and decreased p53 protein levels in the cultured cells. INTERPRETATION: 3xTg-AD mice show intraneuronal Aβ accumulation and memory disturbances before extracellular Aβ deposition. Our data demonstrating improvement of memory function of 3xTg-AD mice with decreases in intraneuronal Aβ and p-tau levels by APO treatment strongly suggest that intraneuronal Aβ is an important therapeutic target and APO will be a novel drug for AD.