Factors Affecting Outcomes of Poor-Grade Subarachnoid Hemorrhage.

OBJECTIVE: Poor-grade subarachnoid hemorrhage (SAH) accounts for 20% of all SAH and is associated with poor outcomes. The first step in improving outcomes is to analyze the factors that contribute to poor outcomes. METHODS: This was a multicenter, retrospective, observational, cohort study. Data fields included demographic, clinical, radiological, and outcome data for all spontaneous patients with SAH treated at 4 hospitals in Aomori Prefecture in Japan. Patients with modified Rankin Scale score 0-2 at discharge were defined as the good outcome group, and those with modified Rankin Scale score 3-6 were defined as the poor outcome group, and comparisons were made between the 2 groups. RESULTS: There were 329 eligible patients with poor-grade SAH, 41 with good outcome group, and 288 with poor outcome group. On multivariate analysis of the outcome, conservative treatment (P < 0.001), Fisher group 4 (P < 0.007), age ≥65 years (P = 0.011), and Hunt and Kosnik grade V on admission (P = 0.021) were significant factors contributing to a poor outcome. CONCLUSIONS: Nonelderly patients who are not in grade V and Fisher group 4 should undergo aneurysm treatment as soon as possible because they are more likely to have a good outcome, whereas elderly patients in grade V and Fisher group 4 are unlikely to benefit from aneurysm treatment at present. The development of a treatment for early brain injury may be important to improve the outcomes of patients with poor-grade SAH.

Superiority of Endovascular Coiling Over Surgical Clipping for Clinical Outcomes at Discharge in Patients With Poor-Grade Subarachnoid Hemorrhage: A Registry Study in Japan.

BACKGROUND AND OBJECTIVES: The differences in clinical outcomes between endovascular coiling (EC) and surgical clipping (SC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) are controversial. Therefore, this study aimed to evaluate whether EC is superior to SC and identify risk factors in patients with poor-grade aSAH. METHODS: We used data from the "Predict for Outcome Study of aneurysmal SubArachnoid Hemorrhage." World Federation of Neurological Societies (WFNS) grade III-V aSAH was defined as poor-grade aSAH, and unfavorable clinical outcomes (modified Rankin Scale scores 3-6) were compared between SC and EC after propensity score matching (PSM). In-hospital mortality was similarly evaluated. Predictors of unfavorable clinical outcomes were identified using multivariable analysis. RESULTS: Ultimately, 1326 (SC: 847, EC: 479) and 632 (SC: 316, EC: 316) patients with poor-grade aSAH were included before and after PSM, respectively. Unfavorable clinical outcomes at discharge were significantly different between SC and EC before (72.0% vs 66.2%, P = .026) and after PSM (70.6% vs 63.3%, P = .025). In-hospital mortality was significantly different between groups before PSM (10.5% vs 16.1%, P = .003) but not after PSM (10.4% vs 12.7%, P = .384). Predictors of unfavorable clinical outcomes in both SC and EC were WFNS grade V, older than 70 years, and Fisher computed tomography (CT) grade 4. Predictors of unfavorable clinical outcomes only in SC were WFNS grade IV (odds ratio: 2.46, 95% CI: 1.22-4.97, P = .012) and Fisher CT grade 3 (4.90, 1.42-16.9, P = .012). Predictors of unfavorable clinical outcome only in EC were ages of 50s (3.35, 1.37-8.20, P = .008) and 60s (3.28, 1.43-7.52, P = .005). CONCLUSION: EC resulted in significantly more favorable clinical outcomes than SC in patients with poor-grade aSAH, without clear differences in in-hospital mortality. The benefit of EC over SC might be particularly remarkable in patients with WFNS grade IV and Fisher CT grade 3.

Analysis of Factors Influencing Delayed Presentation in Japanese Patients with Subarachnoid Hemorrhage.

OBJECTIVE: Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer rerupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation. METHODS: Aneurysmal SAH patients treated at 9 stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale, World Federation of Neurological Surgeons grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and modified Rankin scaleat discharge were assessed retrospectively. We formed 2 groups based on the day of presentation after the onset of SAH: day 0-3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A P- value <0.05 was considered significant. RESULTS: Delayed presentation comprised 282 cases (6.3%) of 4507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge. CONCLUSIONS: Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender, and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study.

Recent Declining Trend of Incidence Rate of Subarachnoid Hemorrhage in Shimane, Japan: The Japan Incidence of Subarachnoid Hemorrhage (JIS) Study.

The "Izumo Study" revealed the incidence rate of subarachnoid hemorrhage (SAH) in Izumo City, Shimane Prefecture, Japan, from 1980 to 1998. However, no study has been published regarding the incidence of SAH in Shimane Prefecture after 1998. Most studies reporting the incidence of SAH in Japan have been conducted before 2000, although a few have been reported after 2000. This study aimed to assess the estimated age-adjusted incidence rate (AAIR) of SAH in Shimane Prefecture after 1998, following the Izumo Study. A retrospective study was conducted to identify the estimated AAIR of SAH in Shimane Prefecture, using the age-adjusted SAH mortality rate for this population from 1999 to 2017 and assuming that the case-fatality rate of SAH decreased by 0.7% annually from 45% in 1999 to 32.4% in 2017. We used linear regression analysis for trend to the estimated AAIR of SAH. Sensitivity analyses were also conducted by various case-fatality rates of SAH using assuming case-fatality rate based on previous reports. The estimated AAIR of SAH in Shimane Prefecture declined from 33.6 (95% confidence interval [CI]: 29.7-37.9) per 100,000 person-years in 1999, by 26.5%, to 24.7 (95% CI: 21.4-28.5) in 2017 (p < 0.01, r = 0.58). Declining trend of incidence rate of SAH in Shimane Prefecture from 1999 to 2017 was confirmed in this study.

Dysembryoplastic Neuroepithelial Tumor of the Infratentorial Multiple Lesions: A Case Report and Review of the Literature.

A dysembryoplastic neuroepithelial tumor (DNT) is a benign neoplasm that usually occurs in the supratentorial cerebral cortex. Here, we report a rare case of an infratentorial DNT in a 42-year-old woman who presented with dizziness and a gait disturbance. Magnetic resonance imaging of the lesion demonstrated hyperintensity on T2-weighted images and hypointensity on T1-weighted images of the left cerebellar hemisphere with a multifocal lesion. Macroscopically, the lesion appeared soft, avascular, and slightly torose at the cortical surface. Histologically, dysplastic disorganization of the cortex and floating neurons were observed. The pathological and immunochemical features of this case agree with the diagnosis of a DNT. The lesion partially included cortical heterotopia, which is a novel observation in an infratentorial DNT. On the basis of the previous reports, we discussed the surgical resection of the infratentorial DNT.

Clinicopathological risk factors for a poor prognosis of primary central nervous system lymphoma in elderly patients in the Tohoku and Niigata area: a multicenter, retrospective, cohort study of the Tohoku Brain Tumor Study Group.

Clinicopathological risk factors for a poor prognosis were investigated in elderly patients with malignant lymphoma of the central nervous system. A total of 82 pathologically confirmed, CD20-positive, diffuse large B-cell lymphoma patients aged 71 years or older who underwent therapeutic intervention in the Tohoku and Niigata area in Japan were retrospectively reviewed. A univariate analysis was performed by the log-rank test using the Kaplan-Meier method. A Cox proportional hazards model was used for multivariate analysis of risk factors. Of the 82 patients, 39 were male and 43 were female, and their median age at onset was 75 years. At the end of the study, there were 34 relapse-free patients (41.5%), 48 relapse cases (58.5%), median progression-free survival was 18 months, and median overall survival (OS) was 26 months; there were 41 deaths and 41 survivors. Multivariate analysis of median OS showed that Karnofsky Performance Status less than 60% 3 months after treatment (p = 0.022, hazard ratio (HR) = 2.591) was the clinical risk factor, and double expressor lymphoma (p = 0.004, HR = 3.163), expression of programmed death-ligand 1 in tumor infiltrating lymphocytes or tumor-associated macrophages (p < 0.001, HR = 5.455), and Epstein-Barr virus infection (p = 0.031, HR = 5.304) were the pathological risk factors.

Multiple Spontaneous Arteriovenous Fistulas of the Superficial Temporal Artery.

Objective: Multiple spontaneous arteriovenous fistulas (AVFs) of the external carotid artery (ECA) are rare. We present a case of multiple spontaneous AVFs treated by coil embolization using a combination of the transarterial and transvenous approach. Case Presentation: A 59-year-old woman complained of right pulsatile tinnitus and a mass lesion at the ventral region of the right ear. 3D CTA and cerebral angiography revealed two AVFs on the superficial temporal artery (STA) with an aneurysm 9.8 mm in diameter. A balloon guiding catheter was navigated to the right STA via the right femoral artery. Another balloon guiding catheter was navigated to the right external jugular vein. The STA distal to the aneurysm was embolized with platinum coils by a transvenous approach. The STA proximal to the aneurysm was embolized transarterially and draining veins were embolized transvenously. Her symptoms were cured after endovascular embolization. MRA at 1 day and 6 months postoperatively showed no recurrence of AVFs or aneurysm. Conclusion: Coil embolization of multiple spontaneous AVFs of the ECA using a combined transarterial and transvenous approach is a curable treatment option. Transvenous embolization of an STA distal to an aneurysm is useful.

Brain tumor-related epilepsy and risk factors for metastatic brain tumors: analysis of 601 consecutive cases providing real-world data.

OBJECTIVE: It is necessary to accurately characterize the epidemiology and trends of brain tumor-related epilepsy (BTE) in patients with metastatic brain tumors. This study aimed to determine the incidence of BTE associated with metastatic brain tumors and retrospectively investigate the risk factors for BTE. METHODS: This retrospective analysis included 601 of 631 consecutive patients with metastatic brain tumors who received treatment, including surgery, radiotherapy, and/or other treatments. BTE and the clinical course were examined retrospectively. Logistic regression multivariate analyses were performed to identify risk factors for BTE. RESULTS: BTE was reported in 148 (24.6%) of 601 patients during the entire course. Of these 148 patients, 81 (54.7%) had first-onset epilepsy (13.5% of all patients). Of the 520 cases of nonepileptic onset, 53 were in the prophylactic antiepileptic drug (AED) group. However, 12 of these patients and 55 of the no-prophylactic AED group developed epilepsy during the course of the study. Including these 67 patients, 148 patients were examined as the group of all epilepsy cases during the entire course. In 3 patients, the seizure progressed to status epilepticus. In most patients, the BTE (n = 83, 56.1%) manifested as focal aware seizures. Logistic regression analysis identified young age (p = 0.037), male sex (p = 0.026), breast cancer (p = 0.001), eloquent area (p < 0.001), peritumoral edema (p < 0.001), dissemination (p = 0.013), and maximum tumor volume (p = 0.021) as significant risk factors for BTE. BTE was more common with tumor volumes greater than the cutoff value of 1.92 ml. CONCLUSIONS: BTE appears to be more likely to occur in cases with young age, male sex, breast cancer, tumors involving eloquent areas, brain edema, dissemination, and giant tumors.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

BACKGROUND: Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. METHODS: Patients aged ≥ 71 years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76 years and < 76 years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. CONCLUSIONS: Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

Role of microcirculatory impairment in delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage.

Early brain injury (EBI) is considered an important cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). As a factor in EBI, microcirculatory dysfunction has become a focus of interest, but whether microcirculatory dysfunction is more important than angiographic vasospasm (aVS) remains unclear. Using data from 128 cases, we measured the time to peak (TTP) in several regions of interest on digital subtraction angiography. The intracerebral circulation time (iCCT) was obtained between the TTP in the ultra-early phase (the baseline iCCT) and in the subacute phase and/or at delayed cerebral ischemia (DCI) onset (the follow-up iCCT). In addition, the difference in the iCCT was calculated by subtracting the baseline iCCT from the follow-up iCCT. Univariate analysis showed that DCI was significantly increased in those patients with a prolonged baseline iCCT, prolonged follow-up iCCT, increased differences in the iCCT, and with severe aVS. Poor outcome was significantly increased in patients with prolonged follow-up iCCT and increased differences in the iCCT. Multivariate analysis revealed that increased differences in the iCCT were a significant risk factor that increased DCI and poor outcome. The results suggest that the increasing microcirculatory dysfunction over time, not aVS, causes DCI and poor outcome after aneurysmal aSAH.

Isolated Bone Recurrence of Medulloblastoma With MYCN Amplification and TP53 Loss: A Case Report.

Extraneural recurrence of a medulloblastoma is rare with dismal prognosis. A 9-year-old girl with medulloblastoma was treated with gross total resection followed by a combination of chemotherapy and radiotherapy. Fourteen months after treatment completion, she developed multifocal bone metastases. Despite chemotherapy combined with irradiation, she died 18 months after recurrence due to progressive disease. Fluorescence in situ hybridization on formalin-fixed paraffin-embedded tissue sections revealed MYCN amplification and TP53 loss, consistent with the genetic alterations of a rapidly progressive subgroup of recurrent medulloblastomas. In clinical practice, dismal biologic features can be determined using fluorescence in situ hybridization in defective materials.

Oxidative Stress Mediates Vascular Tortuosity.

Vascular tortuosity is associated with various disorders and is being increasingly detected through advances in imaging techniques. The underlying mechanisms for vascular tortuosity, however, remain unclear. Here, we tested the hypothesis that oxidative stress mediates the generation of tortuous vessels. We used the bilateral common carotid artery (CCA) ligation model to induce vascular tortuosity. Both young and adult rats showed basilar artery tortuous morphological changes one month after bilateral CCA ligation. These tortuous changes were permanent but more pronounced in the adult rats. Microarray and real-time PCR analysis revealed that these tortuous changes were accompanied by the induction of oxidative stress-related genes. Moreover, the indicated model in rabbits showed that tortuous morphological changes to the basilar artery were suppressed by antioxidant treatment. These results are highly suggestive of the significance of oxidative stress in the development of vascular tortuosity. Although further studies will be needed to elucidate the possible mechanisms by which oxidative stress enhances vascular tortuosity, our study also points toward possible prophylaxis and treatment for vascular tortuosity.

Combination chemoradiotherapy with temozolomide, vincristine, and interferon-ß might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma.

BACKGROUND: This investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-ß for glioblastoma. METHODS: The initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-ß. Maintenance chemotherapy comprised monthly TMZ, continued for 24-50 cycles, plus weekly IFN-ß continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status. RESULTS: Forty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5-55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9-34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%. CONCLUSIONS: The 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-ß tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor. TRIAL REGISTRATION: University Hospital Medical Information Network (number UMIN000040599 ).

Assessment of cerebrovascular reserve with N-isopropyl-p-[123I]-iodoamphetamine time series analysis in patients with cerebrovascular disease.

ABSTRACT: Using N-isopropyl-p-[123I]-iodoamphetamine(123I-IMP) and single-photon emission computed tomography (SPECT), the relationship between cerebrovascular reserve and the 123I-IMP redistribution phenomenon was investigated.The 50 patients who matched the inclusion criteria were divided into control and ischemia groups, and the redistribution phenomenon was examined on resting images. The delayed images showed higher 123I-IMP accumulation in lesions in the middle cerebral artery(MCA) area and anterior cerebral artery(ACA) area, these watershed areas in the ischemia group than in the control group, confirming that the redistribution phenomenon exists with statistical significance (Wilcoxon test; control group vs ischemic group in the ACA area[P = .002], ACA-MCA watershed area(P = .014), MCA area(P = .025), and MCA-posterior cerebral artery(PCA) watershed area(P = .002). The patients were then divided into 4 types according to the Kuroda grading system, and the difference in the redistribution phenomenon was investigated between type III and the other 3 types.Compared with type I and type II, type III had a significantly lower rate of decrease in the radioisotope (RI) count, verifying the redistribution phenomenon (Student t test: type I vs type III in the ACA area(P = .008), ACA-MCA watershed area(P = .009), MCA area(P < .001), and MCA-PCA watershed area(P = .002); type II vs type III in the ACA area(P = .004), ACA-MCA watershed area(P = .2575), MCA area(P < .001), and MCA-PCA watershed area(P < .001). No significant difference between type III and type IV was observed in any area [(Student t test: type III vs type IV in the ACA area(P = .07), ACA-MCA watershed area(P = .38), MCA area(P = .05), and MCA-PCA watershed area(P = .24)].The redistribution phenomenon is associated with resting cerebral blood flow (CBF), but not necessarily with cerebral vascular reactivity (CVR).

[How Can We Manage Skin Incision and Craniotomy for Avoidance of Postoperative Esthetic Concern?]

A successful microsurgical neck clipping of cerebral aneurysm is one of the milestones for neurosurgeons. However, a 'complete clip closure of aneurysm without neurological deficit' is not enough for the patient, as esthetic problems can occur several months after the surgery. In this paper, we describe a series of surgical tips concerning the surgical steps starting from skin incision to craniotomy to minimize the esthetic impact. First, the skin incision should be oriented perpendicular to the fall pattern of hair follicles in the temporal area so that the hair covers the scar line and the scalpel is tilted about 50° to face in the frontal area for preservation of hair roots. After minimum coagulation and skin clip application, interfascial fat pad is dissected at 2 cm dorsal to McCarty keyhole to root of zygomatic process, in order to protect facial nerve. Subgaleal connective tissue with periosteum is harvested as a flap for reconstruction of the calvarial defect. The temporal muscle should be dissected from the caudal to rostral position to avoid delayed muscular atrophy. Central dural tenting sutures are placed at the dural incision. The craniotomy line should be filled with bone crust and covered by subgaleal connective tissue with the periosteum. Single, short-distance galeal sutures, and loose skin sutures can reduce post-operative granulation. From the day after surgery, the patient can shampoo his/her head.

Follow-Up DSA at Day 9 ± 2 after Subarachnoid Hemorrhage Predicts Long-Term Recurrence of Ruptured Cerebral Aneurysm after Coiling.

Objective: The recurrence rate of coiled ruptured cerebral aneurysms is greater than that of clipped aneurysms. The aim of this study is to determine the factors that relate to the recurrence of embolized, ruptured cerebral aneurysms, and the evidence thereto. Methods: From April 2007 through July 2017, we treated 134 ruptured cerebral aneurysm cases by coiling. DSA and/or MRI were done in 98 saccular aneurysm cases one year after the coiling. Recurrence was defined as enlargement of the aneurysm neck or contrast opacification along the aneurysm wall. A chi-square test and a logistic regression analysis were done to analyze the relationship between aneurysm recurrence and clinical factors. Results: The median follow-up period was 58 months (interquartile range [IQR]: 33-107). Ten cases (10.2%) were subjected to aneurysm recurrence. Internal carotid artery (ICA) aneurysms proximal to the posterior communicating artery, incomplete obliteration of an aneurysm at initial embolization and postoperative DSA during day 9 ± 2, and increased contrast medium in the aneurysm at postoperative DSA during day 9 ± 2 were all statistically related to the recurrence of the aneurysm. Logistic regression analysis showed that the increased contrast medium in the aneurysm at day 9 ± 2 was statistically related to aneurysm recurrence (p <0.0001). Recurrence or retreatment of the aneurysm did not influence the outcome. Conclusion: Complete obliteration of the aneurysm at the first session is important. Recurrence of an embolized ruptured aneurysm can be estimated by postoperative DSA at day 9 ± 2 days.

Irreversible Neuronal Damage Begins Just After Aneurysm Rupture in Poor-Grade Subarachnoid Hemorrhage Patients.

Pathophysiological findings of early brain injury in humans have not permitted conclusive determinations. We explored the essence of this phenomenon by taking intraoperative cortical specimens of Hunt-Kosnik grades IV~V (poor-grade) subarachnoid hemorrhages (SAH). From 2013 to 2017, we treated 39 consecutive poor-grade patients in 226 cases of aneurysmal SAH. Fourteen of the 39 patients agreed to this study following written informed consent. We took specimens from untouched areas prior to surgical intervention: cortex near the ruptured aneurysm for clipping, convexity cortex for cerebral ventricular drainage. Cortical specimens were stained with hematoxylin-eosin, anti-cleaved caspase-3, and anti-DNA/RNA damage staining. Positive signals were calculated in six random, high-power fields for quantitative assessment. Double immunofluorescence was done to evaluate neural damage. Chi-square analyses were carried out to assess the correlation between the Glasgow Outcome Scale at 90 days after the ictus and the number of positive cells. Cortical specimens were taken at 12.7 ± 7.00 h after the first ictus. All 14 cases showed dense nuclei, with the appearance of acidic and shrunken cytoplasms. Diffuse positivity of anti-cleaved caspase-3 and anti-DNA/RNA damage was detected. Cleaved caspase-3 was detected in 68% of neurons, and DNA/RNA damage was detected in 64% of neurons. Positive reactions of both antibodies indicated poor outcome. With poor-grade cases, irreversible ischemic, apoptotic, and oxidative changes were detected in the cerebral cortex within several hours after the ictus. Those changes occurred far from the aneurysm. Our findings suggest that a revolution is needed in the treatment strategy for poor-grade SAH.

Intra-arterial anti-oxidant power negatively correlates with white matter injury, and oxidative stress positively correlates with disability in daily activities.

Oxidative stress influences many kinds of diseases. Our hypothesis is that oxidative stress and antioxidant potentials correlate with cognitive function, activities of daily life and white matter injury. (UMIN-CTR R000016770) Thirty-two consecutive patients participated to this study after informed consent. A routine biochemical analysis, modified-Rankin Scale (m-RS), revised Hasegawa Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE) and fluid-attenuated-inversion-recovery imaging (FLAIR) were performed before admission. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured photometrically using arterial blood. Statistical analyses were done by analysis variance or logistic regression analysis. Median age was 72 (IQR: 64.3 -- 75.8). The d-ROMS were 367 ± 55.4, and BAP was 1967 ± 284. HDS-R and m-RS deteriorated with d-ROMs elevation (p < 0.05). Uric acid and creatinine decreased with d-ROMs elevation (p < 0.05). Both periventricular hyperintensity grade and deep and subcortical white matter hyperintensity grade worsened with BAP reduction (p < 0.05). Oxidative stress correlates negatively with cognitive function and activities of daily life. Low antioxidative potentials correlate with aggravation of white matter injury. We should control both oxidative stress and antioxidative potential to maintain healthy lives.

Effect of Surgical Arachnoid Plasty on Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Various techniques have been performed to reduce subarachnoid clotting during aneurysmal neck clipping surgery. We considered that maintaining the physiologic cerebrospinal fluid circulation by performing arachnoid plasty after clipping during surgery would lead to the accelerated clearance of the subarachnoid clot. METHODS: Patients in a prospectively maintained aneurysmal subarachnoid hemorrhage (aSAH) database at our institution and with aSAH that fulfilled the criteria were selected for this study. The incidence of delayed cerebral ischemia, angiographic vasospasm, 3-month functional outcome, and the amount of subarachnoid clot on computed tomography were compared between the 2 groups after matching. RESULTS: From 2006 through 2016, 228 clipping cases met the inclusion criteria. Using propensity score matching, 89 cases of clipping without arachnoid plasty were matched to 89 cases of clipping with arachnoid plasty. Univariate analyses showed that arachnoid plasty significantly reduced the occurrence of hydrocephalus and incidence of poor outcome. Arachnoid plasty statistically significantly reduces the occurrence of hydrocephalus (odds ratio 0.267, 95% confidence interval 0.074-0.963, P < 0.05). Multivariate analysis also showed that arachnoid plasty was the factor reducing poor outcome at 3 months after aSAH (odds ratio 0.222, 95% confidence interval 0.075-0.661, P < 0.01). CONCLUSIONS: The present study suggests that good hematoma clearance due to arachnoid formation reduced brain damage, cerebral vasospasm, and hydrocephalus, resulting in significantly fewer cases with poor functional prognosis. It therefore follows that procedures such as arachnoid plasty should be taken into consideration in order to improve outcome in surgical clipping.

Aging Changes of Aneurysmal Subarachnoid Hemorrhage: A 35-year, Hospital-Based Study.

BACKGROUND: The etiology and background factors which cause decreases in the size of ruptured intracranial aneurysms remain unclear. OBJECTIVE: To clarify the age- and sex-related differences in aneurysmal subarachnoid hemorrhage (SAH) based on a 35-year-old hospital database and demographic data. METHODS: A database of patients admitted to our hospital with aneurysmal SAH from 1983 to 2017 was split into 5-year intervals and analyzed. Demographic data of the general population were also analyzed for reference. RESULTS: Altogether, 1,523 aneurysmal SAH events were enrolled in the analysis. Age (p<0.001), proportion of elderly patients ≥ 65 years old (p<0.001), female sex (p=0.005), very small aneurysms less than 5 mm (p<0.001), and the yearly-averaged number of fatal events showed increasing trends. The proportion of aneurysm size of 10 mm or more (p = 0.011) and the yearly-averaged population of Shimane prefecture (p < 0.001) showed declining trends. In the subgroup analyses, the proportion of very small aneurysms was found to increase significantly in the non-elderly male and elderly female subgroups. The proportion of large aneurysms (10 mm or more) decreased in the non-elderly subgroup (p<0.05). As for the elderly subgroups, the yearly-averaged number of events did not show a significant tendency, although the yearly-averaged population of Shimane prefecture showed an increasing trend. CONCLUSION: We found an increasing trend in the prevalence of very small aneurysms in elderly females. Recent aging may contribute to this trend. The number of aneurysmal SAH events was confirmed to not increase, despite the increased aging population of Shimane prefecture.