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Although hemorrhagic complications may arise with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA), deterioration following administration of rt-PA for hemorrhagic disease is an iatrogenic complication. Caution has recently been raised regarding aortic dissection. A case of cervical epidural hematoma treated with rt-PA is reported herein. The patient was an 87-year-old woman with a history of hemodialysis, brainstem infarction, and stenosis of bilateral internal carotid arteries treated with ticlopidine. She was transferred to our hospital with severe occipital and neck pain. Diffusion-weighted imaging revealed patchy signal hyperintensity in the left cerebellar hemisphere. Right hemiparesis appeared 2 h later, but repeat magnetic resonance imaging (MRI) revealed no new lesions. Administration of rt-PA was performed under a diagnosis of hyper-acute cerebral infarction. Irregular hemodialysis was initiated for pulmonary edema. Complete tetraplegia appeared after hemodialysis, 10 h after rt-PA administration. Repeat MRI revealed cervical epidural hematoma, and hematoma removal was performed. After 10 days, hemiparesis recovered to manual muscle testing (MMT) 2 in the left extremities but remained at MMT0 in the right extremities. Cervical epidural hematoma is a rare complication in stroke practice. Although rt-PA should be administered as soon as possible, since “time is brain,” spending a few minutes on spinal MRI is preferable to prevent iatrogenic deterioration. For atypical cases of cerebral infarction, the possibility of cervical epidural hematoma should be considered.

Ynamides are versatile building blocks in organic synthesis. However, the synthesis of amino acid-derived ynamides is difficult but in high demand. Herein, we disclose the copper-catalyzed Csp-N coupling of sulfonamide, including amino acid and peptide derivatives, to give ynamides by using alkynyl benziodoxolones with broad functional group tolerance under mild reaction conditions. The electron-rich bipyridine as a ligand and ethanol as solvent were used for the success of this reaction. The usefulness of the obtained amino acid-derived ynamide as building block was showcased by further derivatization to unique amino acid derivatives. A control experiment to elucidate the mechanistic insight was also described.

The stereoselective synthesis of cis-β-N-alkoxyamidevinyl benziodoxolones (cis-β-N-RO-amide-VBXs) from O-alkyl hydroxamic acids in the presence of an ethynyl benziodoxolone-acetonitrile complex (EBX-MeCN) is reported herein. The reaction was performed under mild conditions including an aqueous solvent, a mild base, and room temperature. The reaction tolerated various O-alkyl hydroxamic acids derived from carboxylic acids, such as amino acids, pharmaceuticals, and natural products. Vinyl dideuterated cis-β-N-MeO-amide-VBXs were also synthesized using deuterium oxide as the deuterium source. Valine-derived cis-β-N-MeO-amide-VBX was stereospecifically derivatized to hydroxamic acid-derived cis-enamides without the loss of stereoselectivity or reduction in the deuterium/hydrogen ratio.

The synthesis of cis-β-amidevinyl benziodoxolones from the ethynyl benziodoxolone–chloroform complex and sulfonamides is reported. Evidence indicates that highly reactive unsubstituted ethynyl benz...

The synthesis of a crystalline ethynyl-1,2-benziodoxol-3(1 H)-one (EBX)-acetonitrile complex is described. EBX has been widely used as an active species for a variety of reactions; however, its high instability has so far prevented its isolation. The EBX-acetonitrile is self-assembled into a double-layered honeycomb structure through weak hypervalent iodine secondary interactions and hydrogen bonding. The N-ethynylation of a variety of sulfonamides using the EBX-acetonitrile complex as a substrate under mild conditions is also described.

Background The pathological mechanisms of early brain injury (EBI) have remained obscure. Several studies have reported on the neuroradiological findings of EBI. However, to our knowledge, no study has attempted to explore the mechanism of EBI after subarachnoid hemorrhage (SAH). Therefore, this study evaluates whether the initial plasma D-dimer levels were associated with EBI, classifies magnetic resonance imaging (MRI) findings, and speculates about the mechanism of EBI. Methods This study included 97 patients hospitalized within 24 h from the onset of nontraumatic SAH. The patients underwent MRI within 0–5 days from onset (before vasospasm) to detect EBI. EBI was radiologically defined as diffusion-weighted imaging (DWI)-positive lesions that appear dark on apparent diffusion coefficient maps, excluding procedure-related lesions. EBI, plasma D-dimer levels, and clinical features were retrospectively investigated. Results Elevated D-dimer levels were associated with poor outcomes. Patients with EBI had significantly higher D-dimer levels than those without EBI. EBI was detected in 24 patients (27.3%) of all, and in 22 (45%) of 49 patients with World Federation of Neurosurgical Societies (WFNS) grade 4–5 SAH. EBI was frequently observed in the paramedian frontal lobe. There were several types of the pathology in EBI, including widespread symmetrical cerebral cortex lesions, focal cortex lesions, periventricular injury, and other lesions impossible to classify due to unknown mechanisms such as thrombotic complication and microcirculatory disturbance, ultra-early spasm, and spreading depolarization. Conclusions This study suggests that D-dimer levels predict poor outcomes in patients with SAH and that EBI was associated high D-dimer levels.

Endovascular thrombectomy (EVT) is the preferred treatment strategy for patients with acute ischemic stroke (AIS). However, clinical outcome and prognosis in patients who undergo EVT in response to AIS with concomitant malignancy have not been fully elucidated. Data of patients with malignancy who underwent EVT at participating institutions between January 2015 and April 2019 were retrospectively analyzed. Patient characteristics, treatment methods, posttreatment strategy, and long-term prognosis were evaluated in 12 patients with prediagnoses of malignancy. Good revascularization (TICI 2b or higher) was achieved in 10 of 12 patients. Among the eight patients who survived more than 2 weeks from onset, four patients showed good clinical outcome [modified Rankin Scale (mRS)

The stereoselective synthesis of cis-β-phenoxyvinyl benziodoxolones (cis-β-phenol-VBXs) from an ethynyl benziodoxolone-acetonitrile complex (EBX-MeCN) and various phenols is reported herein. The reaction tolerates different phenol derivatives, including complex natural products, and can be conducted under mild conditions. The synthesis was performed in an aqueous solvent in the absence and presence of a catalytic amount of a base. Selectively mono- and di-deuterated cis-β-phenol-VBXs were also prepared. cis-β-Phenol-VBXs were stereospecifically derivatized to cis-alkynylvinyl ethers and cis-iodovinyl ethers without loss of stereoselectivity or reduction in the deuterium/hydrogen ratio.

Arachnoid cysts comprise approximately 1% of all intracranial space-occupying lesions and etiologies of its formation are believed to be both congenital and acquired. However, very few cases of symptomatic acquired arachnoid cyst have been reported so far in the elderly. Here we report a case of acquired symptomatic arachnoid cyst in an elderly patient. We present here a case of 75 years-old male presenting with seizure-like episode. He was diagnosed bilateral subdural hygroma and left-sided arachnoid cyst by CT. However, he was performed CT 12 years ago, which showed no arachnoid cyst then. We performed microsurgical cyst excision and fenestration to the subarachnoid space. Postoperatively his condition has been excellent so far, with no cyst recurrence.

Background: The development of cerebral infarction after transient ischemia is attributed to postischemic delayed hypoperfusion in the microvascular region. In the present study, we assessed the microvascular perfusion capacity of infused liposome-encapsulated hemoglobin (LEH) in a therapeutic approach for transient middle cerebral artery occlusion (tMCAO). Methods: Two-hour middle cerebral artery occlusion rats were immediately subjected to intra-arterial infusion of LEH (LEH group) or saline (vehicle group) or no treatment (control group), and then to recanalization. Neurological findings, infarct and edema progression, microvascular endothelial dysfunction, and inflammatory reactions were compared between the 3 groups after 24 hours of reperfusion. Microvascular perfusion in the early phase of reperfusion was evaluated by hemoglobin immunohistochemistry and transmission electron microscopy. Results: The LEH group achieved significantly better results in all items evaluated than the other groups. Hemoglobin immunohistochemistry revealed that the number of hemoglobin-positive microvessels was significantly greater in the LEH group than in the other groups (P < .01), with microvascular perfusion being more likely in narrow microvessels (≤ 5 µm in diameter). An electron microscopic examination revealed that microvessels in the control group were compressed and narrowed by swollen astrocyte end-feet, whereas those in the LEH group had a less deformed appearance and contained LEH particles and erythrocytes. Conclusion: The results of the present study demonstrated that the infusion of LEH reduced infarctions after tMCAO with more hemoglobin-positive and less deformed microvessels at the early phase of reperfusion, suggesting that the superiority of the microvascular perfusion of LEH mediates its neuroprotective effects.

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR]90, respiratory rate [RR]20, temperature38 °C or36 °C, and WBC count4000 or12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.

The synthesis of

Although microsurgery is an established treatment modality for intracranial dural arteriovenous fistula (dAVF), data regarding the perioperative complication rate, cure rate, and long-term outcomes remain scarce. The aims of this study were to describe our original experience with microsurgery, including the surgical complications and pitfalls, and conduct a systematic review of the relevant literature. A multicenter cohort of patients with dAVF treated by microsurgery was retrospectively assessed. In addition, the PubMed database was searched for published studies involving microsurgery for dAVF, and the complication rate, cure rate, and long-term outcomes were estimated. The total number of patients in our multicenter series and published articles was 553 (593 surgeries). The overall rates of transient complications, permanent complications, death, and incomplete treatment were 11.4, 4.0, 1.2, and 6.5%, respectively. A favorable outcome was achieved for 90.1% patients, even though almost half of the patients presented with intracranial hemorrhage. Of note, the incidence of recurrence was only one per 8241 patient-months of postoperative follow-up. Surgeries for anterior cranial fossa dAVF were associated with a lower complication rate, whereas those for tentorial dAVF were associated with higher complication and incomplete treatment rates. The complication and incomplete treatment rates were lower with simple disconnection of cortical venous drainage than with radical occlusion/resection of dural shunts. Our findings suggest that the cure rate, complication rates, and outcomes of microsurgery for dAVF are acceptable; thus, it could be a feasible second-line treatment option for dAVF. However, surgeons should be aware of the specific adverse events of microsurgery.

Introduction: As mechanical thrombectomy (MT) for acute ischemic stroke has become standard therapy, interest has grown in treatment of milder strokes. Minor complications might therefore be important in mild strokes. The primary objective of the systematic review was to report the rate of emboli in new territory (ENT) following MT. Secondary objectives included describing rates other non-CNS hemorrhage procedural complications of arterial perforation, dissection, vasospasm and access site complications. Methods: We searched randomized controlled trials (RCTs) published in MEDLINE/PubMed from 2010 to 2018 supplemented by a hand-search of reference lists and review articles. Random-effects models using the inverse variance method were used to estimate the pooled complication rates. We also performed subgroup analyses by technique (stent retriever first group or other devices) and year of publication (2010-2015 or 2016-2018). Results: A total 19 RCTs with 2454 procedures for MT were included in our analysis. ENT, perforation, dissection, vasospasm, and access site complications were reported in 9 (47%), 11 (58%), 7 (37%), 7 (37%), 8 (42%) studies, respectively. The pooled ENT rate was 3.5% (95% CI 2.0-5.4), and there was no significant difference in the rate of ENT between stent retriever first group (2.8%, 95% CI 0.4-6.7) and other devices group (4.4%, 95% CI 2.6-6.7, p=0.43). There was no differences in ENT rates by year of publication. Other complication rates were perforation 2.2% (95% CI 0.9-4.0), dissection 2.0% (95% CI 1.1-3.3), vasospasm 10.7% (95% CI 3.8-20.2), and access site complication 2.9% (95% CI 0.9-5.9). There were no differences in the subgroups of perforation, dissection, and vasospasm by procedural methods or year of publication, but the rates of access site complications from 2016-2018 was significant lower compared to 2010-2015 (0.6% vs 5.2%, p Conclusions: The risks of 3.5% rate of ENT and low rates of other complications might become relevant in treatment of mild stroke.

Background: Mobile stroke units (MSUs) permit advanced cerebrovascular diagnosis, triage, and treatment to be delivered in the field. While the range of acute cerebral ischemia and intraparenchymal hemorrhage patients encountered by MSUs has been described, the frequency, determinants, and outcomes of patients presenting with extraparenchymal intracranial hemorrhages (subdurals/subarachnoid/epidural) has not been well delineated. Methods: We analyzed consecutive transports among MSU programs in 3 cites, Los Angeles, Houston and Cleveland from program inception through August 2018 in the two former and through 2015 in the latter. Frequency and demographic, presenting, and treatment features of patients with subdural hematoma (SDH) and subarachnoid hemorrhage (SAH) were quantified. Results: Among 850 overall transports, extraparenchymal intracranial hemorrhages accounted for 18 (2.1%), and included 11 (1.3%) SDH and 7 (0.8%) SAH. Among the SDH patients, age was mean 70/median 77 (range 28 to 85). Special features of SDH cases included: acute on chronic blood on CT in 36%, seizures in 9%, and isolated head trauma in 9%. Among SAH patients, mean age was 57 (range 41-75). Special features of SDH/SAH cases included accompanying intraparenchymal hemorrhage in 17%. Of the 18 combined SDH/SAH patients (67% women), 4 (22%) required field intubation, 1 (5%) was actively treated in the field with KCentra to reverse anticoagulation, and 5 (28%) were treated in the field with antihypertensives. (See Figure for exemplar cases.) Conclusions: Extraparenchymal intracranial hemorrhages account for about 1 in 50 cases managed in Mobile Stroke Units. MSU response permits immediate definitive diagnosis by CT imaging, earlier start of indicated medical therapies, and direct routing to neurosurgically-capable stroke centers.

Introduction: Mobile stroke Units (MSU) can shorten the time to intravenous thrombolytic therapy (IVT) in patients with acute ischemic stroke. We aimed to demonstrate the effects of pre-hospital IVT on clinical outcomes. Methods: We reviewed patients received IVT from July 2014 to December 2017, and compared patients with pre-hospital IVT on MSU with patients brought to the ED via a conventional ambulance. The primary outcome was the modified Rankin scale score (mRS) of 1 or better at 90 days. Binary logistic regression model of 90-day mRS for 0-1 vs 2-6 was adjusted for age, initial National Institutes of Health Stroke Scale (NIHSS) score, and pre-morbid mRS. Results: Seventy eight patients were treated in the MSU and 153 patients were received IVT in the ED. There were no significant differences in gender, age, pre-morbid mRS, initial NIHSS score, and risk factors between the MSU group and the ED group. The MSU patients received thrombolysis 38 minutes earlier from onset than the ED patients (median 79 minutes compared to117 minutes, p Conclusion: Pre-hospital IVT on MSU compared to conventional care shortened the time to thrombolytic treatment and was associated with improved functional outcomes in patients with acute ischemic stroke.

Introduction: Mobile Stroke Units (MSU) allow for the administration of intravenous tissue plasminogen activator (IV tPA) to eligible patients more quickly than those treated in the emergency department (ED). We aimed to describe whether patients who received IV tPA in the MSU had better short term outcomes than those treated in the ED. Methods: We reviewed the medical records of patients who received IV tPA for ischemic stroke or transient ischemic attack on the MSU from 2014-2017 and in the ED from 2015-2017 at a single tertiary referral center. Outcome measures including symptom onset to treatment time, post-thrombolysis National Institute of Health Stroke Scale (NIHSS) over the first 24 hours, length of hospital stay, and disposition after discharge were compared. Results: Of 270 patients diagnosed with ischemic stroke or transient ischemic attack and received IV tPA, 98 were treated on the MSU and 172 were treated in the ED. Both groups had similar pre-morbid modified Rankin scores and pre-treatment NIHSS. Patients treated on the MSU received IV tPA at a median of 76 minutes from their last known well (interquartile range (IQR) 56-117), while those in the ED were treated at a median of 116.5 minutes (IQR 84.75-162) (p Conclusion: Patients treated with IV tPA on the MSU had a shorter symptom onset to treatment time, a shorter length of stay, were discharged with a more favorable disposition, and had a lower NIHSS 24 hours after treatment than those who received treatment in the ED indicating favorable short term outcomes.

Background Although transarterial regional hypothermia is an attractive alternative to general hypothermia, its efficacy and underlying mechanisms remain unclear. Objective To confirm transarterial regional hypothermia therapeutic effects on ischemia/reperfusion (I/R) injury and to elucidate the mechanisms responsible. Methods The therapeutic effects of transarterial regional hypothermia were initially investigated in 2-hour middle cerebral artery occlusion rats regionally infused with 10°C saline (cold saline group) or 37°C saline (warm saline group) and untreated rats (control group) just before the onset of 24 hours of reperfusion. The time course of infarct and edema progression, inflammatory reactions, microvascular morphological changes, and aquaporin-4 (AQP4) expression was analyzed after 0, 2, 6, and 24 hours of reperfusion. Results Cold saline infusion only lowered brain temperatures for 30 minutes but mediated strong neuroprotective effects with infarct volume reductions of less than one-third. The time-course analysis revealed the following sequence of ischemia/reperfusion injury-related events in the control group: upregulated expression of AQP4 (2 hours); microvascular narrowing resulting from swollen astrocytic end-feet (2-6 hours); infarct and edema progression, blood-brain barrier disruption, and upregulated expression of intracellular adhesion molecule-1 (6-24 hours); and the activation of other inflammatory reactions (24 hours). These sequential events were inhibited in the cold saline group. Conclusion Transarterial regional hypothermia initially inhibited the acute AQP4 surge and then attenuated microvascular narrowing, blood-brain barrier disruption, and activation of other inflammatory reactions, leading to strong neuroprotective effects. More direct and intensive cooling of the endothelium and its surroundings may contribute to these effects. Abbreviations AQP4, aquaporin-4BBB, blood-brain barrierIba1, ionized calcium-binding adapter molecule 1ICA, internal carotid arteryICAM-1, intracellular adhesion molecule-1I/R, ischemia/reperfusionMCAO, middle cerebral artery occlusionMMP-9, matrix metalloproteinase-9.

Tentorial dural arteriovenous fistula(dAVF)is a relatively rare disease which accounts for about 4.8% of all types of dAVF reported in Japan. Approximately 12.5% of intracranial dAVFs manifest with dementia-like symptoms. However, a tentorial dAVF typically presents more aggressively and rarely manifests as dementia. Here, we report the case of a patient with a tentorial dAVF manifesting as dementia, who was successfully treated with surgical interruption of the draining vein using indocyanine green video angiography(ICG-VA).A case of a 69-year-old man with a history of colon cancer, hypertension, and previous stroke presenting with cognitive impairment. CT showed multiple intracranial hemorrhages in the left parietal and occipital lobes, and MRI demonstrated flow void in the left cerebellopontine angle. DSA revealed left tentorial dAVF with venous reflux. We performed surgical interruption of the draining vein. The patient's mental status immediately returned to baseline. Serial MRIs showed decreasing edema in the left occipital lobe and thalamus.Cognitive impairment is an uncommon but curable symptom of tentorial dAVF. Surgical interruption of the draining vein using ICG-VA is a relatively simple and safe procedure to perform in such a case.

Background and Purpose— A hemoglobin-albumin cluster, 1 core of hemoglobin covalently bound with 3 shell albumins, designated as HemoAct was developed as a hemoglobin-based oxygen carrier. We aim to investigate neuroprotection by HemoAct in transient cerebral ischemia and elucidate its underlying mechanisms. Methods— Male rats were subjected to 2-hour transient middle cerebral artery occlusion and were then administered HemoAct transarterially at the onset of reperfusion. Neurological and pathological findings were examined after 24 hours of reperfusion to identify neuroprotection by HemoAct. Intermittent measurements of cortical blood flow and oxygen content were performed, and a histopathologic analysis was conducted on rats during the early phase of reperfusion to assess the therapeutic mechanism of HemoAct. In addition, the antioxidant effects of HemoAct were examined in hypoxia/reoxygenation-treated rat brain microvascular endothelial cells. Results— Neurological deterioration, infarct and edema development, and the activation of MMP-9 (matrix metalloprotease-9) and lipid peroxidation after 24 hours of reperfusion were significantly ameliorated by the HemoAct treatment. Reductions in blood flow and tissue partial oxygen pressure in the cortical penumbra after 6 hours of reperfusion were significantly ameliorated by the HemoAct treatment. The histopathologic analysis of the cortical penumbra revealed that HemoAct in HemoAct-treated rats showed superior microvascular perfusion with the mitigation of microvascular narrowing changes than autologous erythrocytes in nontreated rats. Although HemoAct extravasated into the ischemic core with serum protein, it did not induce an increase in serum extravasation or reactive oxygen species production in the ischemic core. In vitro experiments with rat brain microvascular endothelial cells revealed that HemoAct significantly suppressed cellular reactive oxygen species production in hypoxia/reoxygenation-treated cells, similar to albumin. Conclusions— HemoAct exerted robust neuroprotection in transient cerebral ischemia. Superior microvascular perfusion with an oxygen delivery capability and possible antioxidant effects appear to be the underlying neuroprotective mechanisms.

Intravenous thrombolysis using tissue plasminogen activator and endovascular treatment for acute ischemic stroke is becoming an established standard therapy. However, there is no consensus in the treatment of patients who are suffering from progressive neurologic symptoms in the later stages. The purpose of this study was to evaluate the safety and efficacy of microsurgical revascularization in such patients with progressive stroke.We retrospectively reviewed the clinical and radiological records of 14 consecutive patients with progressive stroke who underwent emergency open surgery for anterior circulation occlusion within 7 days after onset. Surgical candidates were carefully selected on the basis of symptom severity, diffusion-weighted imaging, and perfusion study. Superficial temporal artery to middle cerebral artery bypass was applied for atherosclerotic occlusion, and microsurgical embolectomy was applied for embolic occlusion.Superficial temporal artery to middle cerebral artery bypass was performed in 12 patients, microsurgical embolectomy in 1, and the combination of these modalities in 1. As a result, complete revascularization was achieved in all patients. The National Institutes of Health Stroke Scale scores significantly improved after surgery (at third postoperative day, P0.05; at 14th postoperative day, P0.01). A favorable outcome (modified Rankin Scale 0-2) was achieved in 12 of the 14 (85.7%) patients. Minor intracerebral hemorrhage occurred in 1 patient and hyperperfusion syndrome occurred in 1 patients; however, the patients subsequently recovered without additional treatment.Microsurgical revascularization is a feasible treatment option for patients with progressive stroke due to anterior circulation major vessel occlusion.

Background and Purpose: Several studies reported the association between nonbacterial thrombotic endocarditis (NBTE) and Trousseau syndrome (TS). NBTE is regarded as the formation of platelet and fibrin vegetation on cardiac valves with no evidence of inflammation. We report our therapeutic experience including the mechanical thrombectomy for patients with TS and evaluate the histological findings of the retrieved clots. Methods: Between 2011 and 2016, we treated 13 patients with TS in the department neurosurgery. Patient characteristics and clinical history were retrospectively reviewed. Results: There were 7 females and 6 males aged 56-83 years. Cancer types were as follows: 5 were lung, 3 were bile duct, 3 were pancreas, 1 was ovary and 1 was colon. There were 12 patients with stage IV cancer. Almost patients experienced multiple infarctions in all vascular territories and there were 9 patients with occlusion of main trunk. Eleven patients had received anticoagulation treatment with unfractionated heparin by continuous intravenous drip. Seven patients were treated with oral anticoagulants. Recurrent ischemia were detected in 7 patients and 5 patients experienced the recurrence in hospital. Only 4 patients were discharged from our hospital with favorable outcome (modified Rankin Scale 2). Nine patients were confirmed dead and the average time from the onset of ischemia to death was 44 days. We performed mechanical thrombectomy for 3 patients and evaluated the histological findings of the retrieved clots from one patient. Histological evaluation showed that the clots consisted fibrin and platelets without blood cells (Figure). Transthoracic echocardiography revealed NBTE on the aortic valve of this patient. These findings suggested that NBTE was embolic source of ischemic stroke in this patient. Conclusions: Patients with TS have an extremely poor prognosis. We demonstrated that NBTE is a main cause of cerebral artery occlusion in patients with TS.

Background Intracerebral hemorrhage (ICH) associated with antithrombotic therapy (AT) is becoming more common as the use of those medications increases in the aging population. Methods This study included 490 consecutive patients hospitalized for nontraumatic ICH in a single center during an 8-year period, which was subdivided into former (2008-2011) and latter (2012-2015). Patients were classified into those with no antithrombotic drugs (NATs) and those with AT. The AT group was divided into 4 subgroups according to medications: antiplatelet (AP1), multiple antiplatelets (AP2), anticoagulant (AC), and antiplatelet and anticoagulant (APC). We evaluated the clinical characteristics and prognosis and compared the number of patients on AT between the former and latter groups. Results There were 125 patients treated with AT (25.5%), including 50 (10.2%) on AP1, 14 (2.9%) on AP2, 32 (6.5%) on ACs, and 29 (5.9%) on APCs. Compared with the former group, the latter group had a higher number of patients on AT (19.3% versus 31.7%), AP1 (9.8% versus 10.6%), AP2 (1.6% versus 4.1%), ACs (4.9% versus 8.1%), and APCs (2.90% versus 8.9%). Compared with the NAT group, the patients in the AT group had a larger ICH volume, more frequent hematoma expansion, and higher rate of poor outcome, particularly for those on APCs. Conclusion The number of ICH patients on AT has increased; these patients were more likely to have a poor prognosis than those who were not on AT. Care should be taken when giving a combination of antiplatelets and anticoagulants in ICH.

Objective There are no established treatment strategies for aneurysms that recur after clipping. In this study, we present cases of patients who experienced recurrent aneurysms after clipping and subsequently underwent surgical intervention. Methods Between 2004 and 2015, we surgically treated 23 aneurysms that recurred at a previously clipped site. Patient characteristics and clinical history were retrospectively reviewed. Results Patients included 19 women and 4 men 45–81 years old. Aneurysms recurred 3–31 years (mean, 15.4 years) after the initial operation. For 18 cases, the first clinical presentation was a subarachnoid hemorrhage; aneurysms were incidentally diagnosed in 5 patients. Aneurysm locations were as follows: 9 on the internal carotid artery; 4 on the middle cerebral artery; 7 on the anterior communicating artery; 2 on the distal anterior cerebral artery; and 1 on the basilar artery. The reasons for retreatment included subarachnoid hemorrhage (n = 9) and aneurysm regrowth detected on follow-up examinations (n = 14). Endovascular treatment was performed in 10 cases, and direct surgery was performed in 13 cases (clipping in 8, clipping or trapping with bypass in 5). Various complex vascular reconstructions, including high-flow bypass and intracranial-intracranial in situ bypass, were performed for recurrent aneurysms. Conclusions In our experience, coil embolization is a safe and effective procedure for treating recurrent aneurysms. When cases are unsuitable for coil embolization, surgical treatment often requires neurosurgeons not only to overcome the general technical difficulty of reoperative clipping but also to perform challenging vascular reconstruction.

A 10-year-old boy presented with an intraparenchymal meningioma, which had no attachment to the dura, manifesting as grand-mal seizure. Neurological examination showed no abnormalities. Magnetic resonance (MR) imaging revealed a round, well demarcated mass in the left frontal lobe, which was homogeneously enhanced. The tumor appeared to be intraaxial and caused marked peritumoral white matter edema. At operation, the mass was totally embedded in the frontal lobe and gross total resection was accomplished. The histological diagnosis was meningothelial meningioma with chordoid components in World Health Organization grade I. His postoperative course was uneventful and postoperative MR imaging revealed no residual tumor. Intraparenchymal meningioma should be considered in the differential diagnosis of an intraaxial lesion in a child.

Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

Background and Purpose: We previously presented the robust neuroprotective effects of post-ischemic trans-arterial regional hypothermia therapy in I/R injury model rats (ISC 2014, San Diego). This treatment showed a significant suppression of infarct volume and inflammatory reaction at 24hrs after reperfusion. To characterize the neuroprotective effects in terms of microvascular integrity, we investigated microvascular morphological changes and inflammatory reactions by a time course analysis within 24hrs. Methods: At reperfusion onset, 2hr-MCAO rats were divided into cold saline group (10°C, 20ml/kg of trans-arterial infusion from the recanalized artery for 15mins), warm saline group (37°C, in the same manner as cold saline group), and control group (recanalization only). Microvascular morphological changes were examined by vWF Immunohistochemistry (IHC) and transmission electron microscopy (TEM), and inflammatory reactions were examined by Western blotting and IHC at the time point of 0hr, 2hrs, 6hrs, and 24hrs of reperfusion. Results: IHC analysis and TEM observation revealed that astrocyte end-feet swelling occurred at 2hrs and progressed to 6hrs, and microvascular narrowing due to the swelling occurred at 6hrs in control group. This microvascular morphological change was attenuated in cold saline group. While endothelial ICAM1 overexpression started at 6hrs in control group, MPO, MMP9, and Iba-1 overexpression occurred only at 24hrs in the same group. These inflammatory reactions were also inhibited in cold saline group. Conclusions: Post-ischemic trans-arterial regional hypothermia therapy attenuated astrocyte end-feet swelling from 2hrs and the swelling induced microvascular narrowing at 6hrs. The treatment also inhibited endothelial ICAM-1 overexpression at 6hrs, and subsequently inhibited inflammatory reactions at 24hrs. The maintenance of microvascular morphological and functional integrity may be the primary cause of the neuroprotective effects by the regional hypothermia.

Background: Liposome-encapsulated hemoglobin (LEH) containing human hemoglobin (Hb) is an artificial oxygen carrier with 1/40th the size of erythrocytes. We previously demonstrated that post-ischemic intra-arterial (IA) infusion of LEH for 2 hours can reduce ischemia reperfusion (I/R) injury in the rat transient MCAO model (2013, ISC Honolulu). In the present study we examine whether short-time (15-minute) infusion of LEH can also have the same effect on I/R injury and explore the mechanism of the effect. Methods: Male SD rats were subjected to 2-hour MCAO and then were divided into three groups: 1) LEH group (n=9) infused with LEH (20 ml/kg) through the recanalized internal carotid artery for 15 minutes, 2) vehicle group (n=8) infused with saline (20 ml/kg) in the same manner as the LEH group, and 3) control group subjected to recanalization only (n=8). Results: Compared with the control and vehicle groups, the LEH group showed significantly better neurological score, smaller infarction and brain edema, and less Evans blue leakage (p Conclusions: Short-time IA infusion of LEH can reduce I/R injury like long-time infusion. This therapeutic approach is likely to suppress endothelial and neutrophil inflammatory activation accompanied by maintaining microvascular perfusion because of LEH’s small size compared with erythrocyte.

Background and Purpose: Although the neuroprotective effect of hypothermia on cerebral ischemia is well known, the clinical application of systemic hypothermia is limited because of management problems and complications. We examined whether focal hypothermia induced by post-ischemic intra-arterial infusion of cold saline attenuates cerebral ischemia reperfusion (I/R) injury in the rat transient middle cerebral artery occlusion (MCAO) model. Methods: Male Sprague-Dawley rats were subjected to 2-hour MCAO and then were divided into three groups: 1) cold saline group (n=7) infused with 10°C saline (20ml/kg) through the recanalized internal carotid artery for 15 minutes, 2) warm saline group (n=7) infused with 37°C warm saline in the same manner as the cold saline group, and 3) control group subjected to recanalization only (n=7). After 24-hour reperfusion, all rats were tested for neurological score and then sacrificed to examine infarction, brain edema, and Evans blue leakage. Results: In the cold saline group, brain temperature at basal ganglia rapidly decreased from 37.7±0.8°C to 35.4±0.7°C and remained significantly lower than pretreatment temperatures (p Conclusions: The results of the present study suggest that focal hypothermia induced by post-ischemic intra-arterial infusion of cold saline has a neuroprotective effect on I/R injury. This therapeutic strategy is promising because of its feasibility in the clinical situation of endovascular approach.

Background: We sometimes encounter severe brain edema and hemorrhagic transformation due to ischemic reperfusion (I/R) injury after thrombolysis and/or thromboectomy. The mechanism of I/R injury is thought to depend on blood-brain barrier disruption mediated by matrix metalloproteinase-9 (MMP-9) mainly produced by circulating neutrophils. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an efficient oxygen carrier without blood cells including neutrophils, can reduce I/R injury through reducing the effect of neutrophil MMP-9 in the rat transient middle cerebral artery occlusion (MCAO) model. Methods: Male Sprague-Dawley rats were subjected to transient MCAO for 2 hours and then were divided into three groups: 1) LEH group infused with LEH (10ml/kg/h) through the recanalized internal carotid artery for 2 hours, 2) vehicle group infused with saline, and 3) control group subjected to recanalization only. After 24-hour reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, MMP-9 expression, MMP-9 activity and reactive oxygen species (ROS) production. Results: Compared with the control group, the LEH group showed significantly better neurological score (p Conclusion: The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of neutrophil MMP-9. LEH may be a promising candidate to prevent I/R injury.

Cerebrospinal fluid (CSF) shunts are commonly employed to treat patients with hydrocephalus. A large number of papers have been published focusing on complications and failures of CSF shunts. However, there appears to be a paucity of knowledge comprehensively covering both common complications and rare ones. In this systematic review, we surveyed articles about surgical complications of CSF shunts as comprehensively as possible. Quantitative analysis was performed to determine the frequency of well-known complications, mortality and revision rates of CSF shunts. Furthermore, rare complications of CSF shunts have also been reviewed.

A 10-year-old boy presented with an intraparenchymal meningioma, which had no attachment to the dura, manifesting as grand-mal seizure. Neurological examination showed no abnormalities. Magnetic resonance (MR) imaging revealed a round, well demarcated mass in the left frontal lobe, which was homogeneously enhanced. The tumor appeared to be intraaxial and caused marked peritumoral white matter edema. At operation, the mass was totally embedded in the frontal lobe and gross total resection was accomplished. The histological diagnosis was meningothelial meningioma with chordoid components in World Health Organization grade I. His postoperative course was uneventful and postoperative MR imaging revealed no residual tumor. Intraparenchymal meningioma should be considered in the differential diagnosis of an intraaxial lesion in a child.

Rhabdoid meningioma (RM) is a rare aggressive phenotype and is classified as a grade III neoplasm by the World Health Organization. A 29-year-old woman initiated treatment with clomiphene citrate for infertility. Two weeks later, she presented with acute headache and nausea. Brain computed tomography and magnetic resonance imaging demonstrated a tumor with hematoma in the left frontoparietal region. Surgical resection was performed, and the tumor was subtotally removed. The tumor was diagnosed as a rhabdoid meningioma (RM). Despite radiation and chemotherapy, she experienced regrowth and dissemination to the spinal cord. She died 11 months after onset of symptoms. Spontaneous hemorrhage is an unusual presentation of RM. In our case, infertility treatment may have triggered progression and bleeding because of an imbalance of sex hormones.