Verification of a Three-day Hospitalization Protocol for Chronic Subdural Hematoma Surgery.

Chronic subdural hematoma (CSH) is predominantly a disease of the elderly. Aging societies in advanced countries are seeing the number of CSH cases increasing. We applied a three-day hospitalization protocol for CSH surgery to reduce healthcare costs and more efficiently manage hospital beds. We investigated the clinical factors that influenced prolonged hospitalization. From January 2015 to December 2020, we performed irrigation, evacuation, and drainage of CSH cases in 221 consecutive patients. The χ2 test and logistic regression analysis were conducted to detect clinical factors influencing prolonged hospitalization. A p-value below 0.05 was considered statistically significant. Applying a three-day hospitalization protocol showed no adverse outcomes. Fifty-two (24%) of 221 patients experienced prolonged hospitalization. The χ2 test showed that female gender, atrial fibrillation, alcohol abuse, preoperative consciousness level, verbal function disturbance, and perioperative activities of daily living were significantly related to prolonged hospitalization. Female gender, atrial fibrillation, and alcohol abuse were significant factors in the logistic regression analysis. A three-day hospitalization protocol for CSH is suitable for patient care; however, particular attention needs to be focused on the female gender, atrial fibrillation, and alcohol abuse, all three of which prolong hospitalization.

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.

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.

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.

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.

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.

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.

Use of Preprocedural, Multiple Antiplatelet Medications for Coil Embolization of Ruptured Cerebral Aneurysm in the Acute Stage Improved Clinical Outcome and Reduced Thromboembolic Complications without Hemorrhagic Complications.

BACKGROUND: The most uncontrollable complication during coil embolization of a ruptured cerebral aneurysm is thromboembolic ischemia. We analyzed whether thromboembolic complications could be reduced by using preoperative antiplatelet medications for acute subarachnoid hemorrhage in multicenter fashion. METHODS: We selected antiplatelet medicines according to an official protocol: a combination of 200 mg aspirin, 150 or 300 mg clopidogrel, and 200 mg cilostazol. Systemic heparinization was done after sheath insertion in all cases. One hundred and ten consecutive, ruptured cerebral saccular aneurysms that underwent coiling at our institute were analyzed. Procedure-related thrombus formation on digital subtraction angiography and clinical evidence of ischemia and procedure-related stroke on computed tomography scan were reviewed. RESULTS: Eighty cases (73%) were medicated with multiple antiplatelet medications, 22 cases (20%) were treated with a single medication, and 8 cases (7%) were treated without antiplatelet medication. Thromboembolic complications were reduced in an inverse relationship with the number of antiplatelet medications. Hemorrhagic complications because of antiplatelet medications did not occur. Postoperative symptomatic vasospasm tended to decrease, and outcome also tended to improve in the multiple medications groups. Reduction of thromboembolic complications significantly improved clinical outcome in logistic regression analysis. CONCLUSIONS: Preoperative multiple antiplatelet medication reduced thromboembolic events in coiling during acute stage subarachnoid hemorrhage and improved clinical outcomes.

The Role of Intracranial Pressure and Subarachnoid Blood Clots in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.

OBJECTIVE: Early brain injury after subarachnoid hemorrhage (SAH), which is considered a main factor leading to poor outcome, is believed to be caused by the increase of intracranial pressure (ICP) and/or the presence of subarachnoid blood clots (SBC) itself. The purpose of this study was to examine whether ICP or SBC is more important to neurologic deficit in the presence of apoptosis or edema. METHODS: A total of 50 rats were allocated to 3 groups: an endovascular perforation SAH model (the SAH group), a cisterna magna saline injection model (the saline injection group), and a cisterna magna sham injection model (the sham injection group). Statistical analysis of correlations among the ICP, the grade of clot volume, neuronal apoptosis, brain water content (brain edema), and neurologic deficit was performed. RESULTS: In the SAH group, each of increased ICP and clot volume was correlated with neuronal apoptosis and brain edema. In the saline injection group, increased ICP was associated with apoptosis, but it did not correlate with brain edema. Neuronal apoptosis (r = 0.75; P < 0.01) and brain edema (r = 0.89; P < 0.01) correlated independently with neurologic deficit in the SAH group. CONCLUSIONS: The present study suggests that neuronal apoptosis is caused mainly by increased ICP, whereas brain edema is induced by SBC, and increased ICP could aggravate it in the presence of SBC. Brain edema could affect neurologic deficit, but apoptosis alone may be less influential. Not only ICP but also SBC seem important for brain damage in the acute stage of SAH.

The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage.

Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was administered prophylactically by intraperitoneal injection. SAH grade, neurological score, brain water content, and BBB permeability were measured at 24 h after SAH induction. In addition, cortical samples taken at 24 h after SAH were analyzed to explore oxidative stress, microvascular mural cell apoptosis, microspasm, and microthrombosis. Edaravone treatment significantly ameliorated neurological deficits, brain edema, and BBB disruption. In addition, oxidative stress-induced modifications and subsequent apoptosis of microvascular endothelial cells and pericytes increased after SAH induction, while the administration of edaravone suppressed this. Consistent with apoptotic cell inhibition, microthromboses were also inhibited by edaravone administration. Oxidative stress plays a pivotal role in the induction of multiple pathological changes in microvessels in EBI. Antioxidants are potential candidates for the treatment of microvascular disturbances after SAH.

Intra-arterial oxidative stress correlates negatively with cognitive function and positively with postoperative ischemic lesions in carotid artery stenosis stenting.

BACKGROUND AND PURPOSE: Carotid plaque contains biologically active substances released into the blood during carotid artery stenting (CAS). The main purpose of this prospective study was to analyse sequential changes in oxidative stress during CAS and their relationship to clinical factors. METHODS: Twenty-two consecutive CAS procedures were performed between May 2014 and April 2016. Arterial blood was collected four times: (1) after the sheath insertion without edaravone; (2) pre-angioplasty with edaravone from the carotid artery; (3) after post-stenting angioplasty from an occluded carotid artery; and (4) before sheath removal. Derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured photometrically. The relationship between d-ROMs or BAP and preoperatively investigated biochemical parameters, cognitive function, and number of diffusion-weighted image (DWI) high spot lesions was analysed using one-way ANOVA and the Tukey-Kramer HSD test. RESULTS: The d-ROM values for CAS were 355±58.8 Carratelli Units at sheath insertion, 315±57.2 after edaravone infusion, 328±56.8 after post-stenting angioplasty, and 315±53.0 just before sheath removal. The d-ROM values were reduced significantly after edaravone infusion (P<0.05). The BAP at sheath insertion was reduced significantly according to age (P<0.05). The d-ROMs at sheath insertion correlated negatively with the dementia scale and positively with the post-CAS DWI high spots (1.00±1.07; P<0.05). Other biochemical parameters did not correlate with the d-ROM values or BAP. CONCLUSION: Oxidative stress is correlated negatively with cognitive function and positively with postoperative ischemic lesions. Antioxidant potential decreases with ageing.

Aneurysmal Subarachnoid Hemorrhage in the Elderly over Age 75: A Systematic Review.

The number of elderly patients with an aneurysmal subarachnoid hemorrhage (aSAH) has been increasing in aging- or aged societies in many countries. A treatment strategy for the elderly with aSAH has not been established, although many studies have been published emphasizing poor outcome for aSAH. The aim of this study was to analyze the factors and treatments affecting outcome in aSAH in the elderly in a systematic review of the literature by investigating patients over age 75. A literature search was done for "elderly aSAH" in PubMed and Embase. Literature with a clear description of treatment measures for aneurysmal occlusion and outcome was selected. Twelve studies, consisted of 816 cases, met the eligibility criteria. Patient characteristics included 83.2% female, 33.8% poor clinical grade on admission, 57.1% Fischer group 3, and 41% internal carotid artery aneurysm. As complications, symptomatic vasospasm was seen in 25.5% of patients, hydrocephalus in 31.1%, and medical complication in 38.4%. Favorable outcome was 35.0% in total, 45.3% for clipping, 36.3% for coiling, and 9.0% for conservative treatment. Several studies by multivariate analysis indicated that poor clinical grade on admission could be a risk factor for neurological outcome and mortality. Advanced age and selection of conservative treatment without aneurysmal occlusion could be a risk factor for mortality. Patients under age 85 with good clinical grade on admission can be candidates for treatment of aneurysm repair. However, treatment for patients over age 85 or with poor clinical grade should be carefully determined.

Rehabilitation and the Neural Network After Stroke.

Stroke remains a major cause of disability throughout the world: paralysis, cognitive impairment, aphasia, and so on. Surgical or medical intervention is curative in only a small number of cases. Nearly all stroke cases require rehabilitation. Neurorehabilitation generally improves patient outcome, but it sometimes has no effect or even a mal-influence. The aim of this review is the clarification of the mechanisms of neurorehabilitation. We systematically reviewed recently published articles on neural network remodeling, especially from 2014 to 2016. Finally, we summarize progress in neurorehabilitation and discuss future prospects.

Stem Cell Therapies for Intracerebral Hemorrhages.

BACKGROUND: An insult due to intracerebral hemorrhage (ICH) is critical to patients. So, breakthroughs in ICH treatment are very important. OBJECTIVE: Advances in the stem cell treatment of stroke have been remarkable. And stem cell experimentation on ischemic stroke, however, preceded such work on ICH and did not emphasized ICH therapy. METHOD: We review recent stem cell treatments for ICH, an experimental model of ICH, the medical care of ICH, and several stem cell therapies for ICH along with future prospects. RESULTS: Stem cell therapy for ICH is effective in rodent or animal models. For humans, only a small number of clinical trials have been done, and significant functional recovery was recorded. CONCLUSION: We need to reveal the mechanism of stem cell therapy and develop a reliable, definitive treatment strategy for treatment of ICH. In the future, several types of stem cells will be available for the treatment of ICH.

Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit.

Endothelial dysfunctions that include decreased nitric oxide (NO) bioactivity and increased endothelin-1 (ET-1) bioactivity have been considered to be involved in the pathogenesis of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH). Recent cardiovascular studies have revealed that cyclooxygenase-2 (COX-2) is involved in a disturbance in cross-talk between NO and ET-1. COX-2 expression was detected in the endothelial cells of a spastic artery after experimental SAH; however, the pathophysiological significance of COX-2 in relation to CVS remains unclear. The aim of this study was to investigate the role of COX-2 in relation to NO and ET-1 in the pathogenesis of CVS by using the COX-2 selective inhibitor, celecoxib. In the SAH group, SAH was simulated using the double-hemorrhage rabbit model. In the celecoxib group, SAH was simulated and celecoxib was administered. The basilar artery was extracted on day 5 and examined. The cross-section area of the basilar artery in the celecoxib group was significantly larger than in the SAH group. An increased expression of COX-2, ET-1, and ETA receptor (ETAR), and a decreased expression of endothelial NO synthase (eNOS) were seen in the SAH group. In the celecoxib group compared to the SAH group, expression of COX-2, ET-1, and ETAR were statistically significantly decreased, and eNOS expression was significantly increased. COX-2 might be involved in the pathogenesis of CVS due to up-regulation of ET-1 and ETAR and down-regulation of eNOS, and celecoxib may potentially serve as an agent in the prevention of CVS after SAH.

Analysis of Factors That Influence Long-Term Independent Living for Elderly Subarachnoid Hemorrhage Patients.

BACKGROUND: The number of elderly subarachnoid hemorrhage (SAH) patients has been increasing. The aim of this study was to analyze long-term outcome for elderly (≥75 years) SAH patients and to establish a treatment strategy. METHODS: From January 2005 to December 2013, 86 consecutive cases were treated. We used a modified Rankin Scale (mRS) at the outpatient clinic or a telephone interview of patients and/or families. Kaplan-Meier plots were done for mortality and independent (mRS 0 ∼ 2) state. Multivariate analysis was done to distinguish factors that influence on outcome. RESULTS: Median age was 79, Hunt-Kosnik grade 1 ∼ 3 was 79%, and the radical intervention (clipping or coiling) rate was 78%. Mean follow-up period was 28.7 ± 3.4 standard error months. Half of deaths occurred during the first two months. The number of cases of independent living gradually decreased to 50% at 28 months after SAH. Half of patients lived independently for 36 months at HK grades 1 to 3, and 3 months at HK grades 4 to 5 (p < 0.05). Half of patients lived independently for 40 months in the radical intervention group, and 14 months in the conservative treatment group (p < 0.05). Multivariate analysis for independent living revealed that gender, pre-morbid condition, HK grade, and postoperative complication were significant (p < 0.05). CONCLUSIONS: Good-grade elderly SAH cases that were independent pre-stroke should have radical intervention performed for aneurysm. Avoiding perioperative complications have a positive influence on long-term independent living.

Comparing the influences of age and disease on the Brief Assessment of Cognition in Schizophrenia in Japanese patients with schizophrenia.

BACKGROUND: The Brief Assessment of Cognition in Schizophrenia (BACS) is an evaluation of cognitive function that can be completed with more cases. However, there are few studies that compare which factor, disease or aging, is a better determinant of performance on the BACS. The present study aimed to investigate the influences of disease and aging on BACS performance in schizophrenic patients using subjects with a wide range of ages. METHODS: Schizophrenic patients (n = 165) and a comparison group (n = 171) were recruited as subjects. All participants completed the Japanese language version of the BACS (BACS-J), and the influences of disease and aging on performance in the BACS were examined with the use of multiple regression analysis. RESULTS: There was a significant influence of diagnosis and level of education on all six tasks of the BACS and the performance and composite scores. In addition, age was found to influence five tasks and the composite score, the duration of illness influenced four tasks and the composite score, and gender influenced one task and the composite score. CONCLUSION: The present study suggests that performance on the BACS was impaired not only by disease but also by level of education and aging.