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Standard treatment options for primary central nervous system lymphoma (PCNSL) include high-dose methotrexate (HD-MTX)-based drug therapy and whole-brain radiation therapy. However, there are many cases in which these standard treatment options are not tolerated for various reasons. In the present study, five cases of refractory/relapsed PCNSL that are difficult to treat with standard treatment were successfully treated by tirabrutinib.A total of 5 patients (4 women, 1 man) with refractory (n=3) and relapsed (n=2) PCNSL were included. The patients had a median age of 76 years and a median Karnofsky performance status (KPS) of 40. The reasons why standard treatment cannot be given to these patients are the low KPS, renal dysfunction, and resistance to HD-MTX. Administration of a drug via the oral route was challenging in three patients; thus, these patients were administered tirabrutinib in suspension through a nasogastric tube.Imaging findings showed that the patients achieved a 100% response rate to tirabrutinib, with a median survival of 8 months. As symptoms improved, 2 of the 3 patients who were initially administered tirabrutinib via a nasogastric tube were able to receive the drug via the oral route. Three patients developed adverse reactions; however, treatment was not interrupted because they were manageable.Tirabrutinib was effective in the treatment of patients who were unable to receive standard treatment options. Tirabrutinib may be considered one of the novel treatment strategies that could improve the prognosis of PCNSL patients in the future.

Hairdresser dystonia is one of the occupational dystonias and task-specific movement disorders occurring as a result of long-term repetitive cutting with scissors. The task-specific dystonia manifests itself as a loss of voluntary motor control during extensive practice of cutting requiring a high level of technical proficiency. The prevalence rate of hairdresser dystonia is not well-known worldwide. A questionnaire regarding dystonia was prepared for hairdressers. After sending the questionnaires to 800 hairdressers by direct mail, 134 answers were received by mail. Five of the 134 were suspected to have hairdresser-associated focal dystonia. Thus, 3.7% of hairdressers might have task-specific dystonia. This report was limited because of the small number of participants. However, this research is valuable because it was difficult to find a patient with suspected dystonia due to concerns related to job security.

Purpose Although intracranial dural arteriovenous fistula (DAVF) without retrograde leptomeningeal venous drainage (Borden type I) is reported to have a benign nature, no study has prospectively determined its clinical course. Here, we report a 3-year prospective observational study of Borden type I DAVF. Methods From April 2013 to March 2016, consecutive patients with DAVF were screened at 13 study institutions. We collected data on baseline characteristics, clinical symptoms, angiography, and neuroimaging. Patients with Borden type I DAVF received conservative care while palliative intervention was considered when the neurological symptoms were intolerable, and were followed at 6, 12, 24, and 36 months after inclusion. Results During the study period, 110 patients with intracranial DAVF were screened and 28 patients with Borden type I DAVF were prospectively followed. None of the patients had conversion to higher type of Borden classification or intracranial hemorrhage during follow-up. Five patients showed spontaneous improvement or disappearance of neurological symptoms (5/28, 17.9%), and 5 patients showed a spontaneous decrease or disappearance of shunt flow on imaging during follow-up (5/28, 17.9%). Stenosis or occlusion of the draining sinuses on initial angiography was significantly associated with shunt flow reduction during follow-up (80.0% vs 21.7%, p = 0.02). Conclusion In this 3-year prospective study, patients with Borden type I DAVF showed benign clinical course; none of these patients experienced conversion to higher type of Borden classification or intracranial hemorrhage. The restrictive changes of the draining sinuses at initial diagnosis might be an imaging biomarker for future shunt flow reduction.

Cerebral hyperperfusion syndrome (CHS) after surgical clipping for cerebral aneurysm is a rare entity. The authors present a 76-year-old woman with a large left internal carotid-posterior communicating artery aneurysm. After successful clipping with temporary occlusion of the internal carotid artery, the patient exhibited motor aphasia. 15O-gas positron emission tomography (PET) showed extreme elevation of the regional cerebral blood flow (rCBF) along with a mildly decreased regional cerebral metabolic rate for oxygen (rCMRO2) and a remarkable decrease in the oxygen extraction fraction (OEF) in the territory of the ipsilateral superior trunk of the middle cerebral artery. These data indicated local hyperperfusion. She had fully recovered from the aphasia by postoperative day (POD) 18. PET showed normalization of CBF on POD 27. To our knowledge, this is the first case report to show hyperperfusion syndrome, clearly detected by 15O-gas PET, after aneurysmal neck clipping.

Complications of the superficial temporal artery-middle cerebral artery(STA-MCA)bypass procedure include skin necrosis, MCA vessel wall injury, and thrombotic occlusion of the anastomotic site. First, deprivation of the STA per se induces ischemia of the skin flap. Skin incisions must be designed carefully to avoid isolating some areas from the blood supply. Secondly, the MCA walls can be extremely thin in moyamoya disease; therefore, the fragile vascular walls must be manipulated gently. The MCA walls should not be grasped directly by forceps. Thirdly, intraluminal thrombi can develop after the completion of the anastomosis. Heparin should be administered intravenously as soon as possible when intraluminal thrombi are detected, followed by aspirin loading via a nasogastric tube. Platelet(white)thrombi are fragile and easily disrupted with mechanical vibration. It is essential to treat them before they develop into a large, firm fibrin thrombus that completely occludes the anastomotic site, which would require suture cutting and surgical thrombus removal.

Purpose Measuring regional cerebral blood flow (rCBF) after revascularization for moyamoya disease, as a type of ischemic cerebrovascular disease, is crucial. This study aims to validate our novel technology that combines near-infrared spectroscopy (NIRS) with a frequency filter to extract the arterial component. Methods We measured rCBF before and after revascularization for moyamoya disease and at the end of the surgery using NIRO-200NX (Hamamatsu Photonics, Japan) and indocyanine green (ICG). rCBF was calculated using Fick’s principle, change in arterial ICG concentrations, and maximum arterial ICG concentration. rCBF measured with NIRS (rCBF_N) was compared with pre- and postoperative rCBF measured with SPECT (rCBF_S). Results Thirty-four procedures were analyzed. rCBF_N increased from baseline to end of the surgery (mean difference (MD), 2.99 ml/min/100 g; 95% confidence interval (CI), 0.40–5.57 ml/min/100 g on the diseased side; MD, 4.94 ml/min/100 g; 95% CI, 2.35–7.52 ml/min/100 g on the non-diseased side). Similar trends were observed for rCBF_S (MD, 3.98 ml/min/100 g; 95% CI, 2.30–5.67 ml/min/100 g on the diseased side; MD, 2.77 ml/min/100 g; 95% CI, 1.09–4.45 ml/min/100 g on the non-diseased side). Intraclass correlations 3 (ICC3s) between rCBF_N and rCBF_S were weak on the diseased side (ICC3, 0.25; 95% CI, -0.03–0.5; p = 0.07) and the non-diseased side (ICC3, 0.24; 95% CI, -0.05–0.5; p = 0.08). Conclusions rCBF measurements based on this novel method were weakly correlated with rCBF measurements with SPECT.

In case of symptomatic varix associated with cerebral arteriovenous malformations (AVM), nidus is usually treated with transarterial embolization (TAE). However, TAE is not always possible due to inaccessible nidus. A man in his 40s presented with numbness and clumsiness in the right hand. Magnetic resonance imaging (MRI) and cerebral angiography revealed a giant varix associated with an AVM nidus in the left parietal lobe. The varix severely compressed the postcentral gyrus with edema. The main feeder was occluded, and tiny collateral vessels fed the nidus. After admission, his symptoms deteriorated rapidly due to the enlarging varix. To extirpate the varix, selective transvenous embolization (TVE) of a small compartment, the varix neck, between the varix and the main cortical drainer with coils was performed. After treatment, the thrombosed varix gradually shrank, and his symptoms improved. The transvenous coil-plugging technique is a potential strategy for symptomatic varix with a varix neck.

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

While endovascular coil embolization has become one of the major therapeutic modalities for intracranial aneurysms, long-term imaging follow-up is required because of the higher rate of retreatment compared with surgical clipping. The purpose of this study was to show the usefulness of craniograms to discriminate coiled intracranial aneurysms that required retreatment. Under the study protocol approved by institutional review board, a retrospective review of the medical record was done regarding coil embolization for intracranial aneurysms performed between January 2014 and December 2018. Coil embolization performed as the initial treatment and followed up for more than 1 year without additional treatment, and those performed as retreatment after the initial coil embolization performed at our institution were recruited. Craniograms obtained just after the initial treatment were compared with those obtained just before the additional treatment in the retreated cases and compared with the latest ones in the non-recurrence cases. Correlation between the morphological changes in the coil mass on the craniograms and retreatments was evaluated. During the study period, 288 coil embolization procedures for intracranial aneurysms were performed. From these, 191 treatments that were followed up for more than 1 year without any additional treatments and 30 retreatments were included. Morphological change of the coil mass was observed in 4 of the 191 non-recurrence treatments and 26 of the 30 retreatments, which was significantly correlated with retreatments (p0.001). Craniogram was a useful modality in following up the coiled intracranial aneurysms to detect those required retreatments.

We report that tirabrutinib was administered via nasogastric tubes to treat an elderly patient with primary central nervous system lymphoma (PCNSL). The patient was a 76-year-old woman who underwent endoscopic biopsy of multiple intracerebral masses, which resulted in the diagnosis of diffuse large B-cell lymphoma. The patient was diagnosed with PCNSL and was started on an induction regimen of systemic chemotherapy with rituximab in combination with high-dose methotrexate. However, after the second cycle of chemotherapy, the tumor grew rapidly, and the patient went into a coma. As a result, the treatment was changed to nasogastric tube administration of tirabrutinib suspension. After 1 week of tirabrutinib administration, the patient’s level of consciousness improved, and furthermore, after 2 weeks of tirabrutinib administration, the patient was able to take tirabrutinib orally. Although oral administration is the standard route of administration for tirabrutinib, this case study showed that the nasogastric tube administration of tirabrutinib suspension is a therapeutic option for patients with impaired consciousness or dysphagia.

Background/aim Leptomeningeal carcinomatosis (LMC) with hydrocephalus is particularly difficult to treat, and its prognosis is extremely poor. The therapeutic outcomes of 14 patients with LMC-associated hydrocephalus who were treated with cerebrospinal fluid shunting are reported. Patients and methods The study subjects were 14 LMC patients with solid primary cancer who had developed hydrocephalus. Results Postoperatively, both symptoms and Karnofsky performance status improved in 100% of patients. Postoperative therapy consisted of whole-brain radiotherapy in 4 cases and molecular targeted therapy in 4, with 6 patients not receiving any postoperative treatment. Median overall survival was 3.7 months, with no significant difference between those who underwent postoperative therapy and those who did not. However, two of those who received molecular targeted therapy survived for more than one year. Conclusion Cerebrospinal fluid shunting for LMC-associated hydrocephalus is an effective therapeutic procedure from the palliative viewpoint. Patients for whom molecular targeted therapy is indicated may have better long-term survival.

Aim The number of maternal deaths due to pregnancy-associated hemorrhagic stroke has not decreased despite a gradual decrease of maternal death in Japan. This study aimed to clarify the risk factors of hypertensive disorders of pregnancy-associated hemorrhagic stroke. Methods This retrospective study analyzed pregnancy-associated hemorrhagic stroke patients with hypertensive disorders of pregnancy between 2013 and 2017 among 407 Japanese maternal and perinatal centers. Patients were divided into good or poor outcome groups and their maternal backgrounds and neonatal prognoses were compared. Results We analyzed 61 cases, including 41 survival and 20 death cases, obtained from a secondary survey. Among the 61 hemorrhagic stroke cases, 62% were related to hypertensive disorders. Hypertensive disorders of pregnancy were observed in 75% of death cases. Use of MgSO4 or antihypertensive medication did not differ between the poor and good outcomes groups. In cases with antepartum onset of hypertensive disorders of pregnancy, outcomes were poor in 12 and good in 6 cases. Nine patients with poor outcomes and one with a good outcome had hypertension at the outpatient department without systemic evaluation (p = 0.043). Six poor outcomes patients and one good outcome spent more than 1 day from diagnosis at an outpatient clinic. Neurosurgery was performed in 11 poor outcome patients. Conclusion Pregnant women who present with a hypertensive disorder at an outpatient clinic probably need to undergo blood tests and careful observation. Delayed systemic evaluation and intensive care for only a few days may result in the development of hemorrhage.

The Japan Adult Moyamoya (JAM) Trial was a unique randomized controlled trial demonstrating the effectiveness of direct bypass surgery for hemorrhagic moyamoya disease. Prespecified subgroup analysis undertaken as part of the trial demonstrated that posterior-dominant initial hemorrhage is a significant predictor of rebleeding and an effect modifier for surgery. Periventricular anastomosis—fragile collaterals formed by the lenticulostriate arteries, thalamic perforators, and choroidal arteries—might present a clue to the mechanism of high rebleeding risk linked to posterior hemorrhage. Angiographic analyses of the JAM Trial revealed that choroidal collaterals and the involvement of the posterior cerebral artery are associated with posterior hemorrhage, and subsequent cohort analysis of the nonsurgical group has revealed that choroidal anastomosis is a strong predictor of rebleeding. A better understanding of periventricular anastomosis might contribute to further progress in the surgical treatment of hemorrhagic moyamoya disease.

Although numerous surgical techniques have been developed for moyamoya disease treatment, direct/combined bypass has recently been more popular than pure-indirect bypass due to its advantage of rapid increase of cerebral blood flow with less-frequent postoperative ischemic complications. This is especially true in adult cases, in which pure-indirect bypass is sometimes ineffective. In the Japan Adult Moyamoya Trial, a randomized controlled trial, which has proven the effectiveness of bypass surgery in preventing rebleeding attacks, surgical procedures are strictly confined to that including direct anastomosis. With all these benefits, however, surgeons should be alert to the adverse events after direct/combined bypass, such as postoperative hyperperfusion syndrome, and wound-related complications, especially when double procedures, which use both branches of the STA, are adopted.

Background: Clinicians may choose to administer antiplatelet medications to patients with cerebral aneurysms following endovascular coiling to prevent thrombus formation and vascular occlusion, if they fear a thrombus will form on the platinum wire where it diverges into the vessel from the aneurysm sac. However, the mechanism by which vascular endothelial cells repair a vessel in the living body in the event of a coil deviation and the effects of antiplatelet drugs on these cells have not been fully elucidated. We aimed to investigate the association between endothelial progenitor cells (EPCs) and endothelium formation at the surface of the platinum coils deployed in the carotid artery of rats, and to determine the effects of different antiplatelet drugs on this process. Subjects and Methods: We established an experimental model using normal and diabetic rats at 12 months of age. The diabetic rats were assigned to 4 different diet groups, distinguished by whether they were fed plain rat feed, or the same feed supplemented by 1 of 3 antiplatelet drugs (cilostazol, aspirin, or clopidogrel: all 0.1%) for 2 weeks, and the carotid artery was perforated by an embolization coil (“carotid coil model”). We monitored the process by which vascular endothelial cells formed the new endothelium on the surface of the coil by sampling and evaluating the region at 1, 2, and 4 weeks after placement. This repair process was also compared among 3 groups treated with different antiplatelet drugs (i.e. aspirin, clopidogrel, and cilostazol). One-way analysis of variance tests were performed to evaluate the differences in vascular thickness between groups, and P Results: The diabetic rats showed delayed neoendothelialization and marked intimal hyperplasia. Cilostazol and clopidogrel effectively counteracted this delayed endothelial repair process. Flk1 immunostaining revealed greater expression in the diabetic rats administered cilostazol, second only to normal rats, suggesting that this agent acted to recruit EPCs. Conclusion: Neoendothelialization is delayed when vascular endothelial cells fail to function normally, which consequently leads to the formation of hyperplastic tissue. Cilostazol may remedy this dysfunction by recruiting EPCs to the site of injury.

Patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) should be triaged to an endovascular-capable hospital by the emergency medical service (EMS). We designed a prehospital LVO prediction scale based on EMS assessments. In the derivation cohort, 1157 patients transferred to our hospital by the EMS because of suspected stroke within 24 h of onset were retrospectively examined. Factors associated with AIS due to LVO were identified based on the EMS assessment, and a prehospital scale identifying LVO was developed. The accuracy of this scale was validated in 502 consecutive patients who were transferred to 4 stroke centers, and its accuracy was compared with those of 4 previously reported scales. AIS due to LVO was diagnosed in 149 of 1157 patients (13%) in the derivation cohort. One point each was assigned for facial palsy, arm weakness, consciousness impairment (cannot say his/her name), atrial fibrillation, and diastolic blood pressure ≤ 85 mmHg, with two points for conjugate eye deviation (FACE

BACKGROUND Moyamoya disease is a cerebrovascular disease characterized by bilateral stenosis of the intracranial internal carotid arteries and an abnormal collateral vascular network at the base of the brain. Transient neurological events (TNEs), which are episodes of neurological dysfunction lasting

This study aimed to evaluate the selection and outcomes of multimodal interventional treatment for unruptured brain arteriovenous malformations (uAVMs) in ARUBA-eligible patients in a single institution.We retrospectively reviewed the data of 94 patients with uAVMs treated between 2002 and 2014. They were divided into an intervention group and a conservative group. The primary outcome was defined as the composite of death or symptomatic stroke. Functional outcome was assessed using the modified Rankin Scale (mRS).The intervention and conservative groups included 75 and 19 patients, respectively, with mean follow-up periods of 59.2 ± 41.6 and 72.8 ± 39.2 months (P = 0.20), among whom the primary outcome occurred in 9 (12.3%) and 3 (17.6%) patients, respectively (P = 0.91). The proportion of patients with an mRS score ≥ 2 at last follow-up was not significantly different between the two groups (6.9% vs. 11.7%). In the intervention group, the incidence of death or stroke was lower and functional outcomes were better among patients with grade I/II AVMs than among patients with grade III AVMs.For patients with uAVMs, interventional treatment is not inferior to medical treatment alone, and careful selection should be made for patients with grade III AVMs.

Biotubes, i.e., in vivo tissue-engineered connective tubular tissues, are known to be effective as vascular replacement grafts with a diameter greater than several millimeters. However, the performance of biotubes with smaller diameters is less clear. In this study, MicroBiotubes with diameters 1 mm were prepared, and their patency was evaluated noninvasively by optical coherence tomography (OCT) and magnetic resonance angiography (MRA). MicroBiotube molds, containing seven stainless wires (diameter 0.5 mm) covered with silicone tubes (outer diameter 0.6 mm) per mold, were embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with the surrounding capsular tissues to obtain seven MicroBiotubes (internal diameter 0.59 ± 0.015 mm, burst pressure 4190 ± 1117 mmHg). Ten-mm-long MicroBiotubes were allogenically implanted into the femoral arteries of rats by end-to-end anastomosis. Cross-sectional OCT imaging demonstrated the patency of the MicroBiotubes immediately after implantation. In a 1-month follow-up MRA, high patency (83.3 %, n = 6) was observed without stenosis, aneurysmal dilation, or elongation. Native-like vascular structure was reconstructed with completely endothelialized luminal surfaces, mesh-like elastin fiber networks, regular circumferential orientation of collagen fibers, and α-SMA-positive cells. Although the long-term patency of MicroBiotubes still needs to be confirmed, they may be useful as an alternative ultra-small-caliber vascular substitute.

To clarify the perinatal outcomes in pregnancy complicated with intracranial arteriovenous malformation (i-AVM).A retrospective study was performed in 36 pregnancies complicated by i-AVM from 1981 to 2013 at one institution.In total, 6 women miscarried, and 30 had live births. The median (range) gestational age at delivery was 38 (24-40) weeks; 11 cases experienced initial i-AVM rupture during pregnancy (first, second and third trimester: 18%, 64% and 18%, respectively). At onset, 4 cases had a Glasgow Coma Scale ≤10, 10 cases needed emergency maternal transport, 4 underwent neurosurgery with the fetus in utero and 4 had termination of pregnancy in the second trimester for emergent treatment for i-AVM. Two cases delivered vaginally. Another 25 cases had already been diagnosed as i-AVM at conception. Of these, as an indication for epidural birth, 18 cases had either residual lesion of i-AVM or neurological symptoms, although 18 cases had received treatments of i-AVM before conception. Without rupture of i-AVM and worsening of symptoms, 15 cases succeeded in epidural birth. One case was delivered by cesarean section for residual i-AVM with indication of treatment. Another case who had refused treatment of i-AVM experienced rupture of i-AVM 1 year after delivery.Most of the cases with residual i-AVM lesion and neurological symptoms could deliver vaginally without worsening of symptoms. However, pregnancy with i-AVM can be complicated by rupture of i-AVM. In cases with a residual lesion with indication of treatment and rupture of i-AVM during pregnancy, meticulous care is required during pregnancy and after delivery.

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.

Background: The ulcerated atheroma of the carotid artery is a risk factor of ipsilateral ischemic stroke. Contrast-enhanced ultrasound (CEUS) is a novel noninvasive technique useful for evaluating the morphology of carotid plaques, and can detect small disruptions on plaque surface. However, it remains unclear whether the disrupted carotid plaque detected by CEUS is related to the symptomatic internal carotid artery stenosis (ICS). Methods: A total of 79 ICS patients who underwent carotid endarterectomy (CEA) were enrolled from July 2010 to July 2015. Before operation, ICA lesions were examined by color Doppler ultrasound (CDUS) and CEUS using perflubutane. The ulceration was diagnosed when both of the color Doppler signal on CDUS and the pooling of microbubbles on CEUS were observed within the plaque. The disruption was diagnosed only by CEUS when microbubbles pooled through the fissured surface, unlike the linear delineation of neovessels. We validated findings on ultrasound compared with the histopathological findings of ulceration and present/recent plaque rupture. The associations between ulceration/disruption on ultrasound and symptomatic ICS (with a history of ipsilateral transient ischemic attack and/or ischemic stroke) were investigated. Results: Of 79 subjects (mean age 71.2±6.8 years old, 78 men), 55 had symptomatic ICS. The ulceration by CEUS and CDUS was recognized in 20 patients (25%), and the disruption on plaque surface was seen by CEUS solitary in 26 patients (33%). The sensitivity and specificity of detecting plaque ulceration or disruption using CEUS compared with histopathological findings were 0.57 (45/66) and 1.00 (13/13), respectively. The detection rate of ulceration or disruption using CEUS was higher in symptomatic ICS than in asymptomatic ICS (66% vs 42%, P=0.049). Compared to plaques without ulceration/disruption on ultrasound, prevalence of symptomatic ICS was higher in plaques with the disruption (88% vs 58%, P=0.01), whereas it was similar in plaques with the ulceration (65% vs 58%, P=0.77) Conclusion: Small disruptions on carotid plaque surface detected by CEUS were significantly related to symptomatic ICS and this results may help the detailed assessment of plaque vulnerability.

Background: Cerebrovascular accidents (CVAs), including ischemic stroke, transient ischemic attack, and intracranial hemorrhage, are major and devastating complications of left ventricular assist devices (LVADs). However, little is known about their incidence and risk factors. Materials and methods: We retrospectively reviewed the medical records of 75 consecutive cases supported with a LVAD (mean age of 39 years, 60 men, paracorporeal pulsatile-flow LVAD in 31, implantable centrifugal-flow in 18, and implantable axial-flow in 26) in our institution between December 2009 and June 2014. The incidence rate of CVAs was estimated as events per patient-year, and baseline characteristics (age, sex, etiologies of heart failure, comorbid diseases, and types of LVAD) were assessed to determine their contribution to the incidences of total, ischemic and hemorrhagic CVAs. Results: During 113.7 patient-years of observation, a total of 59 CVA events (26 hemorrhagic and 33 ischemic) were identified in 31 cases, yielding an incidence rate of 0.52 events per patient-year. Univariate negative binomial regression (NBR) analysis demonstrated that patients with an axial-flow LVAD had significantly lower incidence of total CVAs [incidence rate ratio (IRR) 0.29, 95% confidence interval (CI) 0.10 - 0.88, p=0.03] and subsignificantly of both of ischemic (0.30, 0.05 - 1.69, p=0.17) and hemorrhagic CVAs (0.29, 0.08 - 1.02, p=0.05) than those with a paracorporeal LVAD (reference), whereas those with a centrifugal-flow LVAD did not. Patients with diabetes had a significantly higher incidence of total CVAs (IRR 2.39, 95% CI 1.03 - 5.57, p=0.04) and ischemic CVAs (4.01, 1.31 - 12.2, p=0.02) than those without diabetes but not of hemorrhagic CVAs (1.41, 0.54 - 3.66, p=0.48). Results of multivariate NBR analysis were similar with those of univariate analysis. Conclusion: Among patients on LVAD support, CVA occurred at a rate of 0.52 events per patient-year. Axial-flow LVADs reduced the incidence of CVAs, regardless of ischemic or hemorrhagic subtype, compared with paracorporeal LVADs. Diabetes was associated with an increased risk of CVAs, but the influence was different between ischemic and hemorrhagic CVAs.

Here, we report three cases of moyamoya disease with a history of Kawasaki disease. A 33-year-old man was found to have stenotic lesions of the internal carotid arteries(ICAs)on both sides at a nearby hospital where he visited complaining of headache and lisping. He had received immunoglobulin therapy for Kawasaki disease at the ages of 1, 2, and 6 years. MRI showed only a chronic ischemic lesion in the white matter. Angiography showed occlusion at the terminal portion of the ICAs on both sides. He was diagnosed with moyamoya disease, but as he had no symptoms and preserved cerebral blood flow (CBF), he was kept under observation. An 8-year-old boy was diagnosed with moyamoya disease and underwent right encephaloduroarteriosynangiosis at a nearby hospital. He had received immunoglobulin therapy for Kawasaki disease at the age of 1 year. His ischemic symptoms worsened. Although MRI detected no apparent ischemic lesion, angiography revealed severe stenosis at the terminal portions of the ICAs on both sides, and 123I-IMP SPECT showed CBF impairment. Bilateral direct bypass was performed. His father was subsequently also diagnosed with moyamoya disease. A 4-year-old girl with epilepsy was diagnosed with moyamoya disease at a nearby hospital. She had been treated with aspirin for Kawasaki disease at the age of 1 year. MRI detected no remarkable ischemic lesions, but angiography revealed mild stenosis at the terminal portions of the ICAs on both sides. Five months later, her ischemic symptoms were worsening with progressing stenotic lesions, and she underwent bilateral direct bypass.

Background and Purpose— The primary results of the Japan Adult Moyamoya Trial revealed the statistically marginal superiority of bypass surgery over medical treatment alone in preventing rebleeding in moyamoya disease. The purpose of this analysis is to test the prespecified subgroup hypothesis that the natural course and surgical effects vary depending on the hemorrhagic site at onset. Methods— The hemorrhagic site, classified as either anterior or posterior, was the only stratifying variable for randomization. Statistical analyses were focused on the assessment of effect modification according to the hemorrhagic site and were based on tests of interaction. Results— Of 42 surgically treated patients, 24 were classified as anterior hemorrhage and 18 as posterior hemorrhage; of 38 medically treated patients, 21 were classified as anterior and 17 as posterior. The hazard ratio of the primary end points (all adverse events) for the surgical group relative to the nonsurgical group was 0.07 (95% confidence interval, 0.01–0.55) for the posterior group, as compared with 1.62 (95% confidence interval, 0.39–6.79) for the anterior group ( P =0.013 for interaction). Analysis within the nonsurgical group revealed that the incidence of the primary end point was significantly higher in the posterior group than in the anterior group (17.1% per year versus 3.0% per year; hazard ratio, 5.83; 95% confidence interval, 1.60–21.27). Conclusions— Careful interpretation of the results suggests that patients with posterior hemorrhage are at higher risk of rebleeding and accrue greater benefit from surgery, subject to verification in further studies. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: C000000166.

Background and Purpose: Vulnerable plaques of carotid arteries are characterized as the presence of large necrotic core, intraplaque hemorrhage (IPH), intraplaque neovascularization (IPN), and active inflammation with thin fibrous cap. MRI is widely used for the qualitative evaluation of the plaques in vivo and the high-intensity plaques (HIP) on magnetization-prepared rapid acquisition with gradient echo (MPRAGE) images indicate containing necrotic cores with IPH, which indicates vulnerable plaques. However, we encounter the symptomatic cases without the presence of HIP on MPRAGE in clinical practice. Recent studies showed the efficacy for the evaluation of IPN using contrast-enhanced ultrasound (CEUS). We aimed to assess the vulnerability of the plaques without high intensity on MPRAGE images using CEUS. Methods: Between July 2010 and June 2014, we enrolled 69 patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and preoperatively examined CEUS and MRI (MPRAGE). All plaques were evaluated with CEUS and the contrast effects were classified semi-quantitatively (grade 0: absent, 1: small, 2: large, 3: extensive). We also divided the plaques into two groups (HIP group or non-HIP group) based on the signal intensity of the plaques on MPRAGE images. The results of MRI and CEUS were compared with histopathological findings of CEA specimens. Results: Fifty-eight plaques of all 69 patients showed HIP (41 were symptomatic), and eleven plaques were non-HIP (five were symptomatic: amaurosis fugax in three, cerebral infarction in two). In non-HIP group, symptomatic plaques were more enhanced (three in grade 2, two in grade 3) than asymptomatic plaques (one in grade 0, five in grade 1) using CEUS. Histopathological findings of all five CEA specimens from symptomatic patients showed that extensive IPN, large necrotic core, and active inflammation with thin fibrous cap which indicated vulnerable plaques, but small amount of IPH. These histological findings were compatible with the results of CEUS and MRI findings. Conclusion: CEUS may be useful for diagnosis of vulnerable plaques without high intensity on MPRAGE images.

Mixed pial-dural arteriovenous malformation(AVM) is currently defined as a malformation fed by both the pial and meningeal arteries. Although many cases of mixed pial-dural AVM have been reported, few papers have addressed its pathological locations. The authors report a case of a 43-year-old male patient with mixed pial-dural AVM in the occipital lobe, consisting of two distinct nidi located on the tentorium and in the cerebral parenchyma respectively. The lesions were surgically resected, and the pathological examination confirmed that both were indeed AVM. The authors discuss this rare type of AVM, focusing on the possible pathogenic mechanism thereof.

Cesarean section is commonly selected in pregnancy with Moyamoya disease. We consider vaginal delivery with epidural anesthesia a viable alternative in such cases.Mode of delivery and outcomes were examined in 27 pregnancies in 19 women with Moyamoya disease treated at the Department of Perinatology, National Cardiovascular Center, Japan, from 1983 to 2013. Of these 27 pregnancies, 20 were delivered vaginally with epidural anesthesia. The cerebral circulation, mode of delivery, maternal outcome (presence of symptoms due to Moyamoya disease intrapartum) and neonatal outcome (gestational week, birthweight, Apgar score at 5 min and pH of umbilical artery) were investigated.The cerebral circulation was judged to be good in all pregnancies. No symptoms due to Moyamoya disease intrapartum were seen in the vaginal delivery cases.Our findings indicate that vaginal delivery is viable in pregnancy with Moyamoya disease and that unnecessary cesarean section may be avoided. These findings are limited by the retrospective nature of the study.

Background and Purpose— About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial–intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. Methods— This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial–intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Results— Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan–Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P =0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148–1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan–Meier survival analysis (2.7%/y versus 7.6%/y; P =0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125–1.009). Conclusions— Although statistically marginal, Kaplan–Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: C000000166.

In the study of pediatric moyamoya disease, information on long-term social outcomes and risk factors for unfavorable social outcomes remains insufficient. The authors analyzed the long-term results of surgical revascularization for pediatric patients with moyamoya disease to determine whether the involvement of a stenoocclusive lesion in the posterior cerebral artery (PCA), relatively common in pediatric moyamoya disease, represents an underlying predictor for unfavorable social outcomes.Prospectively collected data on 61 consecutive patients with moyamoya disease who had undergone combined bypass surgery were analyzed. Neuroradiological features and other baseline clinical factors were incorporated into univariate and multivariate analyses to determine any association with an unfavorable social outcome, defined as difficulty attending regular school or obtaining regular employment.Posterior cerebral artery involvement detected by angiography on admission was noted in 22 (36.1%) of the 61 patients. Follow-up data were acquired in 56 patients (91.8%), and the mean follow-up period was 15.8 years. While transient ischemic attacks were eliminated in 52 (92.9%) of these 56 patients after surgery, and late-onset ischemic stroke was observed in only 1 patient during the follow-up period, 10 (17.9%) experienced an unfavorable social outcome. Although younger age at onset, longer duration between onset and surgery, infarction present on preoperative neuroradiological images, and PCA involvement had been identified as risk factors for an unfavorable social outcome in univariate analysis, only infarction present on preoperative images and PCA involvement remained statistically significant after multivariate adjustment.Posterior cerebral artery involvement can be considered one of the underlying risk factors for unfavorable social outcome and should be studied further to improve social outcome in pediatric moyamoya disease.