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A 31-year-old woman presented with sudden onset of weakness in her left upper limb. Magnetic resonance imaging revealed acute cerebral infarctions in the right frontal and parietal lobes. Magnetic resonance angiography showed stenosis in the proximal portions of the bilateral middle cerebral arteries and terminal portions of the bilateral internal carotid arteries. The patient also complained of thyrotoxic symptoms, such as tachycardia, goiter, and fine finger tremor. She was diagnosed with acute ischemic stroke due to moyamoya vasculopathy (MMV) associated with Basedow disease. The patient’s thyroid hormone status normalized and intracranial artery stenosis gradually improved. However, after 6 months, she developed transient left hemiparesis during the 7th week of gestation. Her thyroid function deteriorated, and MMV progressed. Then, MMV improved again with the normalization of her thyroid function. This case shows that MMV associated with Basedow disease could worsen or improve depending on the thyroid hormone status.

Meningitis retention syndrome (MRS), comprising aseptic meningitis and urinary retention, is a self-limiting disease that resolves within a few weeks. Refractory urinary retention and encephalitic syndromes are rare. A 32-year-old man presented with acute fever and headache followed by acute urinary retention (UT). Neurological examination revealed meningeal irritation, UT, constipation and ataxic gait. The cerebrospinal fluid showed mononuclear leukocytosis, and the etiological examination was negative. We suspected MRS. However, magnetic resonance imaging demonstrated an abnormally intense lesion in the splenium of the corpus callosum (SCC). He also developed delirium on day 4 of hospitalization. We diagnosed the patient with MRS associated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). While his delirium and constipation improved, and the SCC lesion disappeared, UT was refractory and required 6 months to complete recovery. Our case suggests that severe MRS can exhibit refractory UT and may associate with MERS.

Objective Aneurysm recurrence after coiling is a major complication in some cases, including cases of repeated recurrences. In this study, we identified a relationship between the recurrence of a coiled aneurysm and angle change of the parent artery. Methods From April 2008 to December 2019, we performed 283 coil embolizations to treat 256 aneurysms in 251 patients. Among these, 21 cases of recurrent saccular aneurysms were selected. The parent artery angle changes between the initial treatment and the first re-treatment were compared between those who underwent single re-treatment and showed no recurrence after the first re-treatment (Group SR, n = 14) and those who required multiple re-treatments (Group MR, n = 7). Results The parent artery angles at the first treatment [medians (interquartile ranges)] were 121.6° (109.3–135.6°) in Group SR and 104.9° (89.9–131.0°) in Group MR; at the second treatment, these angles were 121.2° (105.5–132.7°) and 81.9° (67.0–111.4°), respectively, revealing angle changes of -2.2° (−4.0 to −0.4°) and −16.4° (−30.1 to −8.6°) in Groups SR and MR between the first and second treatments. The between-group differences in the parent artery angles at the second treatment and the changes in the parent artery angle between the first and second treatments were statistically significant. Conclusion In patients with recurrent aneurysms, simple aneurysm coiling is not effective when the angle of the parent artery becomes narrower after treatment, relative to that before treatment. Stent placement should be considered for straightening the parent artery or diverting blood flow.

OBJECTIVEAlthough heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities.METHODSThey analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis.RESULTSPatients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3–6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate.CONCLUSIONSDespite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.

Background In the diagnosis of nonconvulsive status epilepticus (NCSE), capture of ongoing ictal electroencephalographic (EEG) findings is the gold standard; however, this is practically difficult without continuous EEG monitoring facilities. Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and perfusion MRI with arterial spin labeling (ASL), have been applied mainly in emergency situations. Recent reports have described that ictal MRI findings, including ictal hyperperfusion on ASL and cortical hyperintensity of cytotoxic edema on DWI, can be obtained from epileptically activated cortex. We demonstrate the characteristics and clinical value of ictal MRI findings. Methods Fifteen patients diagnosed as having NCSE (eight had complex partial status epilepticus (SE) and seven subtle SE) who underwent an initial MRI and subsequent EEG confrmation, participated in this study. Follow-up MRI and repeated routine EEG were performed. Results In 11 patients (73%), ictal MRI findings were obtained on both DWI and ASL, while in four (27%) patients, ictal hyperperfusion was found on ASL without any DWI findings being obtained. In all 10 patients with an epileptogenic lesion, there was a tight topographical relationship between the lesion and the localization of ictal MRI findings. In the other five patients, ictal MRI findings were useful to demonstrate the pathophysiological mechanism of NCSE of non-lesional elderly epilepsy, or ‘de novo’ NCSE of frontal origin as situation-related NCSE. Ictal MRI findings are generally transient; however, in three cases they still persisted, even though ictal EEG findings had completely improved. Conclusion The present study clearly demonstrates that the initial use of ASL and DWI could help to diagnose partial NCSE and also combined use of the MRI and EEG allows documentation of the pathophysiological mechanism in each patient.

Objective The use of antithrombotic agents such as anticoagulants and antiplatelet agents is widespread, and the opportunities to treat patients with chronic subdural hematoma (CSDH) under antithrombotic therapy are growing. However, whether antithrombotic therapy contributes to postoperative complications and recurrences of CSDH and how these agents should be managed in the surgical treatment of CSDH remains unclear. Methods We retrospectively analyzed 150 consecutive patients with CSDH who underwent neurosurgical interventions at Kyushu Rosai Hospital from 2011 to 2015 and followed them for more than 3 months. Results Of the 150 study patients, 44 received antithrombotic therapy. All anticoagulants and 76% of the antiplatelet agents were discontinued before surgical treatment of CSDH and resumed within 1 week except in 4 patients whose treatment was terminated and 7 patients who developed postoperative complications or underwent reoperations before resumption of these agents. Postoperative hemorrhagic complications associated with surgical treatment of CSDH occurred in 8 patients (5.3%), and there was no significant difference in the incidence of these complications between patients with and without antithrombotic therapy (6.8% vs. 4.7%, respectively; p = 0.90). Postoperative thromboembolic complications occurred in 5 patients (5.4%), including 4 patients with antithrombotic therapy; these complications developed before resumption of antithrombotic agents in 2 patients. There was a significant difference in the incidence of postoperative thromboembolic complications between patients with and without antithrombotic therapy (9.1% vs. 0.9%, respectively; p = 0.04). There were no significant differences in the incidence of radiographic deterioration or reoperation of ipsilateral or contralateral hematomas between patients with and without antithrombotic therapy after surgical treatment of unilateral CSDH. Conclusion A history of antithrombotic therapy was significantly correlated with the incidence of postoperative thromboembolic complications in patients with CSDH. Antithrombotic agents should be resumed as soon as possible when no hemorrhagic complication is confirmed after neurosurgical intervention for CSDH.

Background Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on the arterial transit time (ATT). With the commonly used single postlabeling delay (PLD) of 1.5 seconds, slow flow through collateral vessels may be underestimated. We used both 1.5 and 2.5 seconds to overcome this problem. We validated these PLD settings by measuring the ATT and identifying the angiographic circulation using digital subtraction angiography (DSA). Methods We retrospectively selected 5 patients with unilateral occlusion or stenosis of the internal carotid artery (ICA) in whom ASL-MRI showed low CBF with 1.5-second PLD in the target area and improved CBF with 2.5-second PLD. We then compared the ASL-MRI findings visually with DSA findings at 1.5 and 2.5 seconds after injection of the contrast. When arterial transit artifacts (ATAs), attributed to stagnant intravascular spin-labeled blood, were observed, DSA findings were analyzed visually at 4.5 seconds. Results DSA revealed that the hypovascular area seen at 1.5 seconds was improved via the primary and secondary collaterals and delayed anterograde flow at 2.5 seconds. Serpiginous or round-shaped ATAs, which appeared in nearly the same configuration on dual PLD ASL-MRI, were attributed to stagnant collaterals and flow in the M2 portion of the middle cerebral artery and ICA during the late venous phase. Conclusions Use of dual PLD times was validated by the DSA findings. ATA detection using the dual PLDs also differentiated well-developed and stagnant collateral vessels from focal hyperperfusion.

BACKGROUND AND PURPOSE: The champagne bottle neck sign represents a rapid reduction in the extracranial ICA diameters and is a characteristic feature of Moyamoya disease. However, the clinical significance of the champagne bottle neck sign is unclear. We investigated the relationship between the champagne bottle neck sign and the clinical and hemodynamic stages of Moyamoya disease. MATERIALS AND METHODS: We analyzed 14 patients with Moyamoya disease before revascularization (5 men, 9 women; age, 43.2 ± 19.3 years). The ratio of the extracranial ICA and common carotid artery diameters was determined using carotid ultrasonography or cerebral angiography; a ratio of < 0.5 was considered champagne bottle neck sign–positive. The clinical disease stage was determined using the Suzuki angiographic grading system. CBF and cerebral vasoreactivity also were measured. RESULTS: The ICA/common carotid artery ratio (expressed as median [interquartile range]) decreased as the clinical stage advanced (stages I–II, 0.71 [0.60–0.77]; stages III–IV, 0.49 [0.45–0.57]; stages V–VI, 0.38 [0.34–0.47]; P < .001). Lower ICA/common carotid artery ratio tended to occur in symptomatic versus asymptomatic arteries (0.47 [0.40–0.53] versus 0.57 [0.40–0.66], respectively; P = .06). Although the ICA/common carotid artery ratio was not related to cerebral perfusion, it decreased as cerebral vasoreactivity decreased (P < .01). All champagne bottle neck sign–positive arteries were classified as Suzuki stage ≥III, 73% were symptomatic, and 89% exhibited reduced cerebral vasoreactivity. In contrast, all champagne bottle neck sign–negative arteries were Suzuki stage ≤III, 67% were asymptomatic, and all showed preserved cerebral vasoreactivity. CONCLUSIONS: The champagne bottle neck sign was related to advanced clinical stage, clinical symptoms, and impaired cerebral vasoreactivity. Thus, detection of the champagne bottle neck sign might be useful in determining the clinical and hemodynamic stages of Moyamoya disease.

We conducted this study to clarify the current trends and healthcare resource usage in the treatment of inpatients with primary malignant brain tumors. The Diagnostic Procedure Combination (DPC) data of all inpatients treated between 2013 and 2014 in the 370 core and branch hospitals enrolled in the Japanese Neurosurgical Society training program were collected. DPC is a discharge abstract and administrative claims database of inpatients. We assessed 6,142 primary, malignant brain tumor patients. Patient information, diagnostic information, treatment procedure, and healthcare resource usage were analyzed. Chemotherapy was the most frequent treatment (27% of cases), followed by surgery (13%) and surgery + chemo-radiotherapy (11%). Temozolomide (TMZ), the most frequently used chemotherapeutic drug, was administered to 1,236 patients. Concomitant TMZ and radiotherapy was administered to 816 patients, and was performed according to the Stupp regimen in many cases. The mean length of hospital stay (LOS) was 16 days, and the mean medical cost was 1,077,690 yen. The average medical cost of TMZ-only treatment was 1,138,620 yen whilst it was 4,424,300 yen in concomitant TMZ patients. The LOS was significantly shorter in high-volume than in low-volume hospitals, and the medical cost was higher in hospitals treating 21–50 patients compared to those treating 1–10 patients. However, the direct medical cost of TMZ treatment was the same across different volume hospitals. This is the first report of current trends and healthcare resource usage in the treatment of primary malignant brain tumor inpatients in the TMZ era in Japan.

Background and purpose: Hyperperfusion syndrome (HPS) occurs in only 1-3% of patients after carotid endarterectomy (CEA). However, it can cause severe cerebral hemorrhage and may be lethal. Therefore, nurses need to be able to recognize the early signs of HPS and report them to the physician. In this study, we aimed to investigate the applicability of using the Intensive Care Delirium Screening Checklist (ICDSC) to discover early signs of postoperative HPS after CEA, allowing nurses to report the signs and possibly prevent disease progression. Method: The study included 96 Japanese patients average age 71.9 ± 8.3 years old undergoing CEA from May 2008 to May 2017. There were 9 patients in the HPS group and 87 in the non-HPS group. Research design was a methodological study. To analyze differences between normally distributed continuous variables, the average value ± standard deviation was calculated and a t test used to compare between groups. For non-normally distributed continuous variables, the median and the range were calculated, and the Wilcoxon rank sum test was used to compare between groups. Ethical approval was granted by the Ethics Review Committee of the research execution facility. Result: There was no significant difference in the patient characteristics in both groups. There was also no significant difference in the number of patients exhibiting signs of delirium (>4 points in total on the ICDSC) between the HPS group (n=8) and the non-HPS group (n=10). However, patients in the HPS group were unable to engage in conversation, while those in the non-HPS group responded to the nurses’ questions and several patients were able to engage in lucid conversation. The HPS group thus scored significantly higher than the non-HPS group on the "inappropriate speech or mood" ICDSC item (100% in the HPS group vs. 20% in the non-HPS group, P Conclusion: A total ICDSC score >4 and the presence of "inappropriate speech or mood" or "symptom fluctuation" strongly suggest the presence of HPS. In conclusion suggest that ICDSC is effective in identifying the early clinical signs of HPS after CEA.

Introduction: Certification system of the primary and comprehensive stroke center (PSC and CSC) is still under discussion in Japan. This study attempts to examine associations between the variation of stroke center capabilities and the improvement of outcomes for acute ischemic stroke on a national scale. Hypothesis: Improvements in hospital stroke center capabilities leads to better outcome of acute ischemic stroke patients. Methods: Using a validated score for evaluating CSC capabilities, which consists of 5 categories (personnel, diagnostic techniques, specific expertise, infrastructure, and education) on a 25 point scale, we assessed CSC capabilities for 137 certified training hospitals in 2011 and 2015 (Kada et al. BMC Neurol 2017). A consecutive health insurance claims data known as the Japanese Diagnosis Procedure Combination/Per Diem Payment Systems of 2011 and 2015 was obtained from the hospitals. The proportion of favorable outcome—score 0 to 1 on the modified Rankin Scale (mRS)—at discharge was quantified as the primary outcome. The change in CSC score with more than two points over time was quantified as an independent variable. We regressed the change of CSC score on morbidity with adjustment of average age and sex in the hospitals. Results: In total, 18,658 in 2011 and 29,999 in 2015 ischemic stroke patients were admitted to 137 hospitals. Median annual number of ischemic stroke patients per hospital increased from 115 to 183 over time. Mean age (74.5 year vs 74.2 years) and proportions of men (56.8% vs 58.2%) were almost the same. The mean CSC scores increased from 15.9±4.0/25 to 17.2±4.2/25 point. The mean hospital mortality decreased from 6.1% to 4.3%. The mean proportion of patients with the favorable outcome at discharge increased from 39.2% to 45.5%. We selected random-effect model based on Housman test. In regression analyses, the increase of CSC score over time was significantly associated with the increasing proportion of the favorable outcome at discharge (coefficient, 2.76; 95% CI, 0.04-5.47; p-value, 0.047). Conclusions: Improvements in CSC capabilities overtime was significantly related to the improvement of functional outcome at discharge in ischemic stroke patients.

Background Although extracranial-intracranial (EC-IC) bypass is an effective treatment strategy for symptomatic moyamoya disease, surgeons need to be cautious regarding the possibility of postoperative hemorrhagic complications in patients with a concurrent coagulation disorder. Here, we describe a case of EC-IC bypass for moyamoya disease concurrent with von Willebrand disease type 1. Case Description Following perioperative replacement of the von Willebrand factor, the patient showed an uneventful and uncomplicated clinical course. Conclusion This is the first reported case of EC-IC bypass being performed for moyamoya disease in a patient with concurrent von Willebrand disease. We emphasize the importance of appropriate management with replacement of the von Willebrand factor during the perioperative period to avoid hemorrhagic complications.

Background Cerebrospinal fluid hypovolemia (CSFH) is sometimes associated with chronic subdural hematomas (CSHs). Affected patients often develop enlargement and recurrence of the CSH, even if appropriate treatments such as epidural blood patch (EBP) and/or burr-hole surgery for the CSH are performed. This situation may lead to subclinical coagulopathy, including low coagulation factor XIII (CFXIII) activity. We retrospectively analyzed whether CFXIII activity was involved in the development of CSHs and post-treatment exacerbation of CSHs in patients with CSFH. Methods We diagnosed CSFH by radioisotope (RI), magnetic resonance imaging (MRI) and computed tomography (CT) findings, and CSH by CT and/or MRI findings. The plasma CFXIII activity was assessed on admission. All patients with CSFH initially received conservative treatments. When these treatments were ineffective, the patients underwent EBP and/or CSH surgery according to previously reported therapeutic strategies. Results Among 206 patients with CSFH, 19 developed CSHs. Fourteen patients with a thin hematoma underwent EBP and three with a thick hematoma underwent CSH surgery immediately after EBP on the same day. We were unable to diagnose two patients with CSFH at the time of admission, and one of these two patients underwent repeated CSH surgery before obtaining the correct diagnosis. Seven patients (36.8%) developed CSH exacerbation after the treatment. The CFXIII activity was significantly lower in patients with than without a CSH (42.1% vs. 12.8%, respectively; P = 0.003). The CFXIII activity was significantly lower in patients with than without post-treatment CSH exacerbation (P = 0.046). All five patients with low CFXIII activity who developed CSH exacerbation received intravenous injection of CFXIII and had no recurrence of CSH after the additional treatment. Conclusion In patients with CSFH, low CFXIII activity is one of the risk factors for both the development of a CSH and the post-treatment exacerbation CSH.

Objective: This study aimed to investigate recent nationwide trends in the epidemiology of acute ischemic stroke (AIS) in Japan. Methods: We analyzed 328,147 acute ischemic stroke patients in 350 certified training hospitals in Japan using data obtained from the Japanese Diagnosis Procedure Combination Database. Data between the period April 1, 2010 and May 31, 2014 were used. We divided patients into three treatment groups: medical treatment only (group M), intravenous t-PA infusion only (group IVT), and endovascular treatment (group ET). Outcome was assessed by in-hospital mortality and modified Rankin Scale (mRS) score at discharge, and poor outcome was defined as a mRS score of 3-6. Results: The patient proportion in groups M, IVT, and ET changed from 94.3%, 3.2%, and 1.6% in 2010 to 90.9%, 4.3%, and 3.7% in 2014, respectively (P Conclusion: In Japan, during the 5-year period before the guidelines concerning proper use of ET for AIS were revised in 2015, a significant improvement in in-hospital mortality and functional outcomes of AIS patients undergoing medical treatment and intravenous rt-PA infusion was observed. This was probably due to a gradual increase in the proportion of patients undergoing IVT; the outcomes of ET, however, remained the same.

Background Aberrant internal carotid artery (aICA) is an anatomic anomaly whereby the internal carotid artery courses through the tympanic cavity without separation by bone. Because aICA is rare, there are no definite treatment strategies for aICA and its complications. Case Description We report a case of aICA accompanied by pseudoaneurysm formation and massive bleeding. The patient was a 31-year-old woman with a 2-year history of hearing loss, ear fullness, and pulsatile tinnitus in her left ear. After a diagnosis of otitis media with effusion, she underwent a myringotomy and massive arterial bleeding occurred. After the bleeding was temporarily stopped, aICA and pseudoaneurysm formation on the aICA were shown. To prevent rebleeding, we performed endovascular internal trapping around the pseudoaneurysm after performing common carotid artery to radial artery to middle cerebral artery bypass grafting. After surgery, the aneurysm disappeared. In addition, no new neurologic complications were observed, and the patient's hearing improved and the tinnitus diminished. Conclusions This is the first case report of an aICA complicated by pseudoaneurysm formation successfully treated with simultaneous endovascular trapping and high-flow bypass in a hybrid operating room.

Background: The effectiveness of comprehensive stroke center (CSC) capabilities on outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital outcome of CEA and CAS. Methods: We analyzed 12,943 carotid artery stenosis patients treated with CEA or CAS in 350 certified training hospitals in Japan. Data between April 1, 2013 and May 31, 2015 was obtained from Japanese Diagnosis Procedure Combination Database. Among the institutions that responded, outcome was assessed by in-hospital mortality, ischemic stroke and myocardial infarction. CSC capabilities were evaluated from the 749 certified training institutions in Japan, which responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Total CSC scores of the participating hospitals were classified into quartiles (Q1: 0-15, Q2: 16-17, Q3: 18-19, Q4: 20-24). Results: The proportion of CEA and CAS were 5068 and 7875 (2013: 1685 and 2590, 2014: 1668 and 2564, 2015: 1715 and 2721). Between CEA and CAS, mortality rates were 0.24% and 0.75%, ischemic stroke were 8.41% and 7.56% and myocardial infarction were 0.76% and 0.17%. These outcomes had no differences among the years. There was tendency that mortality rates were lower with high total CSC scores in patients with CEA (Q1: 0.42%, Q2: 0.26%, Q3: 0.12%, Q4: 0%, P=0.16), but there were no differences with CAS (Q1: 1.0%, Q2: 0.74%, Q3: 0.63%, Q4: 0.83%, P=0.73). Ischemic stroke were significantly lower with high CSC scores in CEA (Q1: 9.76%, Q2: 10.77%, Q3: 9.14%, Q4: 6.59%, P Conclusion: It is reported using the data of Nationwide Inpatient Sample that operator volume was an important predictor of postprocedural outcomes in CAS. We demonstrated that CSC capabilities were associated with reduced in-hospital ischemic stroke in patients with CEA and CAS.

Background and purpose: The incidence of non-traumatic intracranial hemorrhage (ICH) during treatment with direct oral anticoagulants (DOACs) is lower than that during warfarin treatment. The characteristics of intracranial hemorrhage during DOAC therapy, however, remain unclear. Therefore, we performed a nationwide survey in Japan to examine the clinical characteristics and outcomes of DOAC-associated ICH using data obtained from the Japanese Diagnosis Procedure Combination (DPC)-based Payment System. Methods: We analyzed the data of 1,567 patients with ICH (DOAC-associated ICH, 88; warfarin-associated ICH, 1,479) who were urgently hospitalized at 575 institutions across Japan from April 2010 to March 2013 for whom prescription data before admission were available. Results: The annual number of patients with all anticoagulant (DOAC or warfarin)- associated ICH in each year from 2010 to 2013 was 226, 252, 426, and 663, representing 15.7%, 15.4%, 16.1%, and 16.1% of all ICH cases in the same period, respectively. There was an increase in the proportion of patients who presented with DOAC-associated ICH in all anticoagulant-associated ICH in each year from 2010 to 2013 (0%→0.4%→3.8%→10.7%). The proportion of patients with impaired consciousness (three-digit score on Japan Coma Scale) at admission (DOAC, 19.3%; Warfarin, 25.4%; P=0.20), in-hospital mortality within 7 days (DOAC, 11.4%; Warfarin, 19.5%; P=0.06), and mRS score of 5-6 at discharge (DOAC, 27.3%; Warfarin, 37.4%; P=0.06) were lower in the patients with DOAC-associated ICH. The rates of surgery for hematoma removal were significantly lower in the patients with DOAC-associated ICH (NOAC, 2.3%; Warfarin, 9.7%; P=0.019). Conclusions: This is the largest nationwide study of DOAC-associated ICH in a real-world situation in Japan, revealing that the patients with DOAC-associated ICH had better clinical outcomes compared with warfarin-associated ICH, probably due to milder hemorrhage at admission.

Background and purpose: The outcomes of subarachnoid hemorrhage (SAH) in aged patients are more severe than those in non-aged patients. There are few reports about the relationship between the age and the effect of perioperative care for SAH patients. We performed a nationwide survey in Japan to determine the relationship between perioperative care and SAH outcomes in aged and non-aged patients. Methods: We analyzed 17,343 subarachnoid hemorrhage (SAH) patients treated with clipping or coiling in 579 hospitals who participated in the J-ASPECT study. Data between 2010 and 2013 were obtained from the Japanese Diagnosis Procedure Combination Database. We stratified patients into two groups according to their age (aged group >75 y.o., n=3885; non-aged group < 75 y.o., n=13,458) and analyzed the association between perioperative care and poor outcome (modified Rankin Scale score 3-6 at the time of discharge). With respect to perioperative care, we evaluated time from onset to surgery (days), treatment (clipping or coiling), and drugs delivered after surgery (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, EPA, edaravone). Results: In the non-aged group, coiling (OR=0.84; P Conclusion: Coiling and treatment with fasudil hydrochloride, statins, and EPA improved outcomes of non-aged patients. Although perioperative care did not improve the outcome of aged SAH patients, in cases of relatively mild SAH, perioperative care had the potential to improve the outcome.

Patients with severe intracranial hemorrhage (ICH) often develop infectious complications during the acute stage. Animal experiments have demonstrated that enteral immunonutrition with a dietary fluid containing whey peptide (WP) enhances immunoactivity and prevents infection. The aim of the current study was to investigate the infection control effect of WP in the clinical management of patients with severe ICH.Fourteen patients with ICH were given enteral nutrition from January 2012 to December 2012. Nine patients were given WP (WP group) and the other five were given control dietary fluid (Non-WP group) for two weeks. We retrospectively analyzed the incidence of infectious complications and chronological changes in white blood cell (WBC) count, C-reactive protein (CRP), and total lymphocyte count.All patients in the Non-WP Group experienced infectious complications, whereas 5 out of 9 patients in the WP Group did not experience them. There was a tendency for a decrease in WBC count and CRP value in the WP group. In contrast, WBC and CRP increased in 3 patients in the Non-WP Group. Total lymphocyte count tended to increase earlier in the WP Group; however this tendency was not noted in the Non-WP Group.Although the number of cases was small, our study suggests that WP might have an infection control effect, capable of preventing infectious complications associated with severe ICH in the acute stage.

Dematiaceous fungi have melanin-like pigment in the cell wall and usually cause a variety of dermal infections in humans. Infections of the central nervous system(cerebral phaeohyphomycosis)are rare but serious, since they commonly occur in immunocompromized patients. A 76-year-old man was admitted with mild motor aphasia and underwent total excision of a mass in the left frontal lobe. With the postoperative diagnosis of brain abscess due to infection with dematiaceous fungi (C. bantiana) associated with hypogammaglobulinemia following gastrectomy, intravenous antifungal drugs including amphotericin B and fluconazole were administered. Regrowth of the abscess with intraventricular rupture was noted at about the 88th day after the initial surgery, and the patient underwent neuroendoscopic aspiration of the pus and placement of a ventricular drain. Following intraventricular administration of miconazole through ventricular drainage or an Ommaya reservoir, neuroradiological findings improved, but general and neurological conditions worsened. Further treatment was discontinued and the patient died 9 months after onset. The poor outcome in this patient is attributed to 1)intractability of dematiaceous fungi, 2)development of ventriculitis and the need for intraventricular administration of antifungal drugs, and 3)untreatable hypogammaglobulinemia following gastrectomy.

Nonconvulsive status epilepticus (NCSE) is generally defined as a change in behavior and/or mental process from the baseline, which is associated with ongoing seizure activity or continuous epileptiform discharges on electroencephalography (EEG) in the absence of convulsive seizures. The present study investigated NCSE incidence using serial EEG during the perioperative periods of cerebrovascular surgery at a medium-sized, local hospital. A total of 54 patients were admitted to our department and underwent various neurosurgical procedures over a course of one year. If clinical symptoms worsened without clear explanation, EEG was performed, resulting in a diagnosis of NCSE in four patients (7.4%). The EEG abnormalities included periodic lateralized epileptiform discharges in 1 patient, triphasic waves in 2 patients, and repeated ictal discharges in 1 patient. Improved mental status and consciousness level, together with disappearance of EEG abnormalities, after appropriate anticonvulsant treatment supported the diagnosis of NCSE. The present study stressed the importance of EEG if no adequate explanation for neurological deterioration can be determined from the clinical course, laboratory data, or neuroimaging examination.

We report a case of lesional medial temporal lobe epilepsy (TLE) associated with cortical dysplasia extending from the right medial temporal lobe to the fornix via the basal and medial aspects of the frontal lobe and septum pellucidum. A 23-year-old man had had medically intractable psychomotor seizures since 11 years of age. Interictal EEG demonstrated paroxysmal activities in the right temporal region, and functional imaging by positron emission tomography with [18F] fluorodeoxyglucose revealed a functional deficit zone in the apex and medial part of the right temporal lobe. An intraoperative electrocorticogram demonstrated frequent paroxysmal activities in the medial temporal lobe. An anterior temporal lobectomy was performed, with an additional hippocampectomy including the focus of the paroxysmal activities on the intraoperative hippocampal EEG. Postoperatively, he became seizure-free. The surgical strategies for intractable TLE with widely distributed cortical dysplasia lesion are discussed.

A 77-year-old man developed cerebral hyperperfusion syndrome with temporal deterioration of consciousness and worsening of left hemiparesis on the 6(th) postoperative day following superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for right M(1) occlusion. Electroencephalography (EEG) revealed frequent ictal discharges in the right hemisphere, although convulsive seizures were not apparent. Administration of anticonvulsants was performed based on the diagnosis of non-convulsive status epilepticus (NCSE). Complete recovery from hyperperfusion syndrome was achieved with rapid improvement of EEG findings. The present case demonstrates the pathophysiological mechanism of hyperperfusion syndrome associated with NCSE after STA-MCA anastomosis.

We report the case of a 62-year-old woman with delayed hydrocephalus following endovascular embolization with hydrogel coils for an unruptured aneurysm at the tip of the basilar artery. She underwent the first and second embolizations with bare platinum coils and matrix coils, respectively. However, recanalization and regrowth of the aneurysm was observed, and a successful third embolization with hydrogel coils(2 mm/4 cm×2)was performed. However, progressive ventricular enlargement was observed during 8 months after the third treatment. MRI with fluid-attenuated inversion recovery sequence showed edema in the perianeurysmal white matter, as well as marked communicating hydrocephalus. The aneurysmal wall was enhanced with the administration of gadolinium-DTPA. The cerebrospinal fluid(CSF)protein level was 113 mg/dL. A ventriculo-peritoneal shunt was placed, and the patient was discharged without symptoms. It was postulated that endovascular embolization with hydrogel coils causes inflammation of the aneurysmal wall and perianeurysmal white matter, followed by elevation of CSF protein and subsequent communicating hydrocephalus.

Background Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. Subjects and methods A dual PLD method of 1.5 and 2.5 seconds was compared with 123 I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. Results In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. Conclusions Although dual PLD methods may not be a completely alternative test for 123 I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting.

We report a rare case of cerebellar abscess produced by anaerobic bacteria. A 76-year-old man was admitted to our hospital with a history of fever, vomiting, and dizziness lasting 14 days. Computed tomography(CT)scan and magnetic resonance images showed the presence of a multiloculated cerebellar abscess with a right subdural abscess. The patient underwent aspiration of the abscess through a suboccipital craniotomy. Fusobacterium nucleatum, which is an anaerobic bacteria naturally present in the human oral cavity, was detected in cultures of the aspirated abscess. The patient was administered antibiotic treatment combined with hyperbaric oxygen therapy(HBO). The symptoms were briefly relieved but the cerebellar abscess recurred, which required a second aspiration. The combined treatment with antibiotics and HBO was maintained after the second operation. After 6 weeks of treatment, the cerebellar abscess was completely controlled. We conclude that antibiotic treatment combined with HBO is useful for treatment of cerebellar abscesses caused by infection with anaerobic bacteria.

Proneural and mesenchymal are two subtypes of glioblastoma identified by gene expression profiling. In this study, the primary aim was to detect markers to develop a clinically applicable method for distinguishing proneural and mesenchymal glioblastoma. The secondary aims were to investigate the temporospatial dynamics of these markers and to explore the association between these markers and the expression of chromatin-modifying genes. One hundred thirty-three glioma samples (grade II: 14 samples, grade III: 18, grade IV: 101) were analyzed. We quantified the expression of 6 signature genes associated with proneural and mesenchymal glioblastoma by quantitative reverse transcription-polymerase chain reaction. We assigned proneural (PN) and mesenchymal (MES) scores based on the average of the 6 markers and calculated a predominant metagene (P-M) score by subtracting the MES from the PN score. We used these scores to analyze correlations with malignant transformation, tumor recurrence, tumor heterogeneity, chromatin-modifying gene expression, and HDAC7 expression. The MES score positively correlated with tumor grade, whereas the PN score did not. The P-M score was able to distinguish the proneural and mesenchymal subtypes. It was decreased in cases of tumor recurrence and malignant transformation and showed variability within a tumor, suggesting intratumoral heterogeneity. The PN score correlated with the expression of multiple histone-modifying genes, whereas the MES score was associated only with HDAC7 expression. Thus, we demonstrated a simple and straightforward method of quantifying proneural/mesenchymal markers in glioblastoma. Of note, HDAC7 expression might be a novel therapeutic target in glioblastoma treatment.

Objective: Recommendations for comprehensive stroke centers (CSC) have been launched, but evaluations of these with respect to accessibility and mortality have not been clear. We thus examined the relationship between stroke centers and transfer time on mortality of subarachnoid hemorrhage (SAH) from a nationwide survey: J-ASPECT Study in Japan. Methods: We approached 1,369 certified training institutions in Japan with a survey regarding acute stroke care capabilities, and 749 hospitals responded. The CSC score was generated to evaluate the capabilities of CSC (Iihara K et al. PLOS One 2014). Data for patients hospitalized with stroke were gathered from the Japanese Diagnosis Procedure Combination database from April 1, 2010 to May 31, 2012. Transfer time was measured using an electronic mapping system based on patients’ postal addresses and hospitals. We examined the effects of CSC scores on mortality using instrumental variable analysis with log-transferred transfer time as an instrumental variable, adjusted by age, gender, and scores of the Japan coma scale (JCS) which was grading with the 1-, 2-, and 3-digit codes (Iihara K et al. PLOS One 2014). Results: Data from 265 institutions and 9,648 emergency-hospitalized patients with SAH were analyzed. Mortality rate was 28.8% and median transfer time was 22 min. Longer transfer times were associated with high CSC scores (p < 0.001). Adjusting for log-transformed transfer time, high CSC scores corresponded to lower mortality in patients with SAH, and the adjusted difference between high and low scores was 25.6% (95%CI= 8.5 - 42.6%). The severe SAH patients with JCS of 2- or 3-digit code showed more influence of CSC score on mortality, and the difference was 33.5% (95%CI= 21.5 - 45.5%). Conclusion: Longer transfer times were associated with the choice of highly qualified stroke centers measured by CSC scores, and highly qualified stroke centers were associated with lower mortality of SAH.

Objective: The nation-wide mortality and morbidity of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on asymptomatic internal carotid artery stenosis in Japanese have not been clear. We thus examined the comparison of CEA and CAS from a nationwide survey in Japan. Methods: Certified neurosurgical training institutions in Japan provided data from the DPC database on patients hospitalized with neurosurgical diseases between April 1, 2012 and March 31, 2013. Patients hospitalized owing to asymptomatic internal carotid artery stenosis (ICS) for male patients were identified from the DPC database based on the International Classification of Diseases (ICD)-10 diagnosis code (I65). We excluded patients with emergency admissions. We compared the mortality rates, modified Rankin Scale (mRS) scores, and postoperative complications who underwent CEA and CAS based on propensity score matching. A propensity-matched cohort was constructed with CEA group and CAS group matched on a 1:1 basis by a nearest neighbor matching method within a caliper 0.05 SD of the propensity score for age, Charlson score, BMI and admission conscious level. Result: We identified 2216 patients with asymptomatic ICS (1381 CAS and 835 CAS cases). After propensity matching, Patient characteristics (age, hypertension, DM , hyperlipidemia, smoking and Charlson score) were well balanced between two groups. Patients who underwent CAS had a significantly lower number of complications than patients who underwent CEA (delta= -9.74; P < 0.001).Length of hospital stay was significantly shorter for CAS group. (delta= -9.90; P < 0.001). 30 day mortality and mRS at discharge were not significantly different between two groups. Conclusions: Our results estimate the baseline national rates of outcomes in patients with asymptomatic ICS that were treated with CAS or CEA in Japan. CAS treated group showed lower complication rates compared to CEA treated group.

We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.

Surgery of vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysms is not easy because there is a close anatomical relationship between aneurysms and the surrounding neurovascular structures, and bony structures in the lateral foramen magnum. The preoperative evaluation for a circumstantial comprehension of anatomical relationships is very important for the surgical treatment of the VA-PICA aneurysms. Our experience in using three-dimensional CT angiography (3D-CTA) for the surgical management of VA-PICA aneurysms is herein reported.We successfully performed neck clipping in 5 cases of VA-PICA aneurysm using 3D-CTA. On 3D reconstructed images, we could see the characteristics of the aneurysms such as their relationships to the jugular tubercle and hypoglossal canal, the projecting direction of the dome, and the configuration of the neck in each case. 3D-CTA also provided a clear surgical view as well as the relationships of the aneurysms to the VA and origin of the PICA. Based on such information, we selected the most appropriate surgical approach among the transcondylar fossa approach, the transcondylar approach, or the far lateral approach with a C1 laminectomy.Since 3D-CTA demonstrates the surgical anatomy of VA-PICA aneurysms in detail, it is very useful for helping surgeons to select the optimal approach.

Objective Vasospasm after subarachnoid hemorrhage (SAH) may result from hemoglobin-mediated removal of nitric oxide (NO) from the arterial wall. We tested the ability of the long-acting, water-soluble, NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-1,2-diolate (DETA/NO), delivered via continuous intracisternal infusion, to prevent vasospasm in a nonhuman primate model of SAH. Methods First, vasorelaxation in response to DETA/NO was characterized in vitro by using monkey basilar artery rings under isometric tension. Next, monkeys were randomized to undergo angiography, unilateral SAH, and no treatment (SAH only, n = 4) or treatment with DETA/NO (1 mmol/L, 12 ml/d, n = 4) or decomposed DETA/NO (at the same dose, n = 4). Vasospasm was assessed by angiography, which was performed on Day 0 and Day 7. Levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) were measured in cerebral arteries on Day 7. Results DETA/NO produced significant relaxation of monkey arteries in vitro, which reached a maximum at concentrations of 10(-5) mol/L. In monkeys, angiography demonstrated significant vasospasm of the right intradural cerebral arteries in all three groups, with no significant difference in vasospasm among the groups (P > 0.05, analysis of variance). The ratios of cGMP or cyclic adenosine monophosphate levels in the right and left middle cerebral arteries were not different among the groups (P > 0.05, analysis of variance). There was no significant correlation between arterial cGMP contents and the severity of vasospasm. Conclusion DETA/NO did not prevent vasospasm. There was no correlation between the severity of vasospasm and cyclic adenosine monophosphate and cGMP levels in the cerebral arteries. These results suggest that events downstream of cyclic nucleotides may be abnormal during vasospasm.

Background: Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on arterial transit time (ATT). To overcome this problem, we developed a simple ASL technique with dual postlabeling delay (PLD) settings. In addition to the routinely used PLD of 1.5 seconds, we selected another PLD of 2.5 seconds to assess slowly streaming blood flow and detect arterial transit artifacts (ATAs) resulting from stagnant intravascular magnetically labeled spins. Case Description: We validated the dual PLD method with digital subtraction angiography (DSA) findings in a patient with an unruptured right giant internal carotid artery (ICA) aneurysm who underwent proximal ligation of the right cervical ICA followed by right superficial temporal artery–middle cerebral artery anastomosis. The giant aneurysm was detected as a strongly hyperintense signal area of ATA using both values of PLD. Decreased signal in the right hemisphere at PLD 1.5 seconds was somewhat improved at PLD 2.5 seconds. DSA revealed that this laterality resulted from the different ATT values between hemispheres due to stagnation of the labeled spin within the aneurysm. Postoperatively, with gradual but complete thrombosis and regression of the aneurysm, the size of the ASL hyperintense signal area decreased markedly. At postoperative 2 years, the aneurysm was not demonstrated as an ATA; furthermore, the decreased signals in the right hemisphere at PLD 1.5 seconds had mostly improved. Conclusion: Serial ASL-MRI with dual PLDs could show dynamic changes of giant aneurysms and the associated hemodynamic state following the surgery.

Vagal nerve stimulation(VNS)is an effective adjunctive therapy for medically intractable epilepsy. However, VNS is a palliative therapy, and craniotomy should preferably be performed when complete seizure remission can be expected after craniotomy. We report here three patients who were referred for VNS therapy, but underwent craniotomy instead of VNS based on the results of a comprehensive preoperative evaluation, and achieved good seizure control. Case 1 was a 48-year-old woman with left temporal lobe epilepsy and amygdalar enlargement. Even though no left hippocampal sclerosis was observed on magnetic resonance imaging, she underwent left anterior temporal lobectomy and hippocampectomy. Case 2 was a 36-year-old woman with multiple bilateral subependymal nodular heterotopias, who underwent resection of the left medial temporal lobe including subependymal nodular heterotopias adjacent to the left inferior horn. Case 3 was a 25-year-old man with posttraumatic epilepsy. As the right hemisphere was most affected, multiple subpial transections were performed on the left frontal convexity. These three patients were referred to us for VNS therapy because there was a dissociation between the interictal electroencephalogram and magnetic resonance imaging findings, or because they had multiple or extensive epileptogenic lesions. Comprehensive preoperative evaluation including ictal electroencephalography can help to identify patients who are suitable candidates for craniotomy.

Angiography in a 35-year-old man, with a history of transient ischaemic attacks and a convulsive seizure, showed bilateral stenosis of the distal internal carotid arteries, and positron-emission tomography (PET) revealed inadequate blood flow in the right frontal lobe (decreased blood flow, increased oxygen extraction). A lupus anticoagulant and an elevated anticardiolipin antibody concentration were detected in serum. The patient's condition progressed from ischaemia to infarction resulting in the diagnosis of antiphospholipid syndrome and steroid and antiplatelet treatment resulted in an improved neurologic state and laboratory findings. PET showed better correlation with clinical features than carotid angiography in this case of antiphospholipid syndrome leading to stroke.

We studied the incidence and timing of hyponatremia (Na135 mEq l-1) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na130 mEq l-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p0.01) and severe hyponatremia (p0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p0.05), in cases with vasospasm (p0.001), and in cases with hydrocephalus (p0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 +/- 4.4 and day 10.6 +/- 5.8 following SAH, representing a 3-day delay for hyponatremia (p0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm.