Long-term postoperative prognosis and associated risk factors of chronic subdural hematoma in the elderly.

Surgical treatment for chronic subdural hematoma（CSDH）has contributed to good outcome. However, several recent studies have revealed that surgical outcomes for elderly patients were not decisively good. In this study, prognosis of CSDH patients in elderly were analyzed. This study included 232 CSDH patients who were treated in our department and 2 affiliated hospitals, and poor prognosis was defined as aggravation of modified Rankin scale (mRS) at examination comparing with that at discharge, or mRS 3 and higher at examination. We collected data from medical records and questionnaires on the following clinical characteristics of patients: age, sex, findings at admission, medication of antiplatelets and anticoagulants, radiological findings on computed tomography, recurrence, place of discharge, perioperative systemic complications, and mRS at discharge and at examination. The cut-off value of age for poor prognosis of all CSDH patients was 74 years old in this study. In multivariate analysis of all cases, age was prognostic factor for poor outcome:75 years old or higher（p=0.0002）. In this group, mRS at discharge(p=0.0184) and postoperative medical diseases(p<0.0001) were the risk factors of poor prognosis. In this present study, high age and activities of daily life（ADL） at discharge were significant prognostic factors for poor outcome of CSDH. Improvement of ADL at discharge with care for postoperative systemic complications and careful rehabilitation can contribute to good prognosis for CSDH in elderly patients.

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.

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.

A Practical Grading Scale for Predicting Outcomes of Radiosurgery for Dural Arteriovenous Fistulas: JLGK 1802 Study.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. METHODS: This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. RESULTS: The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01). CONCLUSIONS: SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

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.

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 ).

Gamma Knife Surgery for Residual or Recurrent Craniopharyngioma After Surgical Resection: A Multi-institutional Retrospective Study in Japan.

Objective The optimal treatment for a craniopharyngioma has been controversial. Complete resection is ideal, but it has been difficult to obtain total resection in many cases because of intimate proximity to critical structures such as the optic pathway, hypothalamus, and pituitary gland. A growing number of studies have demonstrated the utility of radiosurgery in controlling residual or recurrent craniopharyngioma. However, most of them are small series. The aim of this multi-institutional study was to clarify the efficacy and safety of Gamma Knife (Elekta, Stockholm, Sweden) surgery for patients with a craniopharyngioma. Methods This was a multi-institutional retrospective study by 16 medical centers of the Japan Leksell Gamma Knife Society. Data on patients with craniopharyngiomas treated with Gamma Knife Surgery (GKS) between 1991 and 2013 were obtained from individual institutional review board-approved databases at each center. A total of 242 patients with craniopharyngioma were included in this study. The mean age of the patients was 41 (range, 3 to 86) years. The median follow-up time was 61.4 months (range, 3 to 180 months). The mean radiosurgery target volume was 3.1 ml (range, 0.03-22.3 ml), and the mean marginal dose was 11.4 Gy (range, 8-20.4 Gy). Results Two-hundred twenty patients were alive at the time of the last follow-up visit. The three-, five-, and 10-year overall survival rates after GKS were 95.4%, 92.5%, and 82.0%, respectively. The three-, five-, and 10-year progression-free survival rates after GKS were 73.1%, 62.2%, and 42.6% respectively. The rate of radiation-induced complications was 6.2%. Conclusion GKS is effective for controlling the tumor growth of craniopharyngiomas with an acceptable complication rate.

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 Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence: Multi-Center Randomized Controlled Study.

The relatively high rate of post-operative recurrence in the treatment of chronic subdural hematoma (CSDH) is a significant problem. Goreisan is an herbal medicine that exhibits a hydragogue effect by inhibiting the expression of aquaporins, and its efficacy in preventing post-operative CSDH recurrence has been suggested by several case trials. This multi-center prospective randomized controlled trial was performed to investigate the preventative effect of goreisan on post-operative CSDH recurrence. Patients with symptomatic CSDH over 60 years old undergoing burr hole surgery were enrolled in this study. The patients were randomly allocated to the control group or the goreisan group, in which oral administration of goreisan (7.5 g daily) was continued for 12 weeks. The primary end-point was the post-operative recurrence rate at 12 weeks and the secondary end-point was hematoma volume reduction rates on computed tomography scan at 12 weeks. The analyses were performed not only on patients of all ages older than 60 years, but also on patients divided into those over or under 75 years old. One hundred and eighty patients were followed and analyzed (the control group, n = 88; the goreisan group, n = 92). The recurrence rates considering patients of all ages and patients under 75 years old were relatively low in the goreisan group but without a significant difference. The hematoma volume reduction rates showed no significant difference. Based on the results of the present study, a larger-scale study including more cases is necessary in future to confirm the efficacy of goreisan.

Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial.

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. METHODS: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. RESULTS: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. CONCLUSIONS: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

The peroxisomal Acyl-CoA thioesterase Pte1p from Saccharomyces cerevisiae is required for efficient degradation of short straight chain and branched chain fatty acids.

The role of the Saccharomyces cerevisae peroxisomal acyl-coenzyme A (acyl-CoA) thioesterase (Pte1p) in fatty acid beta-oxidation was studied by analyzing the in vitro kinetic activity of the purified protein as well as by measuring the carbon flux through the beta-oxidation cycle in vivo using the synthesis of peroxisomal polyhydroxyalkanoate (PHA) from the polymerization of the 3-hydroxyacyl-CoAs as a marker. The amount of PHA synthesized from the degradation of 10-cis-heptadecenoic, tridecanoic, undecanoic, or nonanoic acids was equivalent or slightly reduced in the pte1Delta strain compared with wild type. In contrast, a strong reduction in PHA synthesized from heptanoic acid and 8-methyl-nonanoic acid was observed for the pte1Delta strain compared with wild type. The poor catabolism of 8-methyl-nonanoic acid via beta-oxidation in pte1Delta negatively impacted the degradation of 10-cis-heptadecenoic acid and reduced the ability of the cells to efficiently grow in medium containing such fatty acids. An increase in the proportion of the short chain 3-hydroxyacid monomers was observed in PHA synthesized in pte1Delta cells grown on a variety of fatty acids, indicating a reduction in the metabolism of short chain acyl-CoAs in these cells. A purified histidine-tagged Pte1p showed high activity toward short and medium chain length acyl-CoAs, including butyryl-CoA, decanoyl-CoA and 8-methyl-nonanoyl-CoA. The kinetic parameters measured for the purified Pte1p fit well with the implication of this enzyme in the efficient metabolism of short straight and branched chain fatty acyl-CoAs by the beta-oxidation cycle.

[Basal interhemispheric approach for distal anterior cerebral aneurysms].

PURPOSE: To investigate retrospectively the usefulness of basal interhemispheric approach for neck clipping of aneurysms located on genu or infracallosal portion of anterior cerebral artery. CLINICAL MATERIALS AND METHODS: Seventeen aneurysms in 17 patietns treated by clipping with basal inter-hemispheric approach in our department for past 8 years were reviewed. Of them, 12 were ruptured aneurysm and 5 were unruptured one. The distance between frontal base and most frontally located bridging vein and the shortest distance from cranium to aneurysm were measured from angiograms of lateral view, and the point on cranium of the shortest distance was identified in each cases. Bridging vein damage suffered during surgical approach and the duration of brain retractor use were examined from operative videotapes. The clinical outcome was rated at discharge by Modified Rankin Scale. RESULTS: The distance between frontal base and most frontally located bridging vein was ranged as 15-69 mm (mean, 32 mm). The shortest distance between cranium and aneurysm in each case was ranged as 25-48 mm (mean, 33 mm), and the point on cranium of the shortest distance was these within 20 mm from frontal base in 11 cases. Any damage or cut of bridging vein were not seen in all cases. The duration of brain retractor for unilateral frontal lobe and for bifrontal lobe in recent 14 cases was ranged 0-46 minutes 41 seconds (mean, 8 minutes 55 seconds) and 0-16minutes (mean, 2minutes 24 seconds), respectively. No brain damage caused by operative procedure was detected on postoperative CT scan. All five patients of unruptured one and 8 patients of ruptured one were rated as 0 by Modified Rankin scale, 2 patients of ruptured one as 3 and 5, and 2 patients of ruptured one died. CONCLUSION: The basal interhemispheric approach for neck clipping of aneurysm located on genu or infracallosal portion of anterior cerebral artery would provide wide view of aneurysm and its surrounding structures with minimum retraction of frontal lobe, short distance to the aneurysm, and low risk of bridging vein damage.

Extravasation from rupturing aneurysm demonstrated by 3D digital subtraction angiography.

We describe the 3D digital subtraction angiography (3D-DSA) image of extravasation from a rupturing aneurysm. This image clearly showed that the extravasation was coming from a pseudoaneurysm on an aneurysmal wall. To the best of our knowledge, this is the first demonstration of a 3D-DSA image of a rupturing aneurysm.

[Surgical treatment for dissecting aneurysm of the anterior cerebral artery presenting only with headache: a case report].

The authors reported the first case of a dissecting aneurysm of the anterior cerebral artery (ACA) presenting only with headache successfully treated by trapping. A 23-year-old man was admitted to our department due to headache. CT scan and MRI showed neither hemorrhage nor infarction. Angiography demonstrated an aneurysmal dilatation at the right A1 segment with venous pooling which suggested a dissecting aneurysm. We performed trapping and resection of the aneurysm without neurological deficits. The natural history of intracranial dissecting aneurysm without ischemia and/or hemorrhage is still unclear, and therefore it is controversial about the necessity of surgical intervention. Our case and review of the literature suggest that surgical treatment should be considered even in patients without ischemia and/or hemorrhage, if it is possible in consideration of hemodynamic condition.

[Basi-parallel anatomical scanning (BPAS) MRI: a simple MRI technique for demonstrating the surface appearance of the intracranial vertebrobasilar artery].

We modified surface anatomy scanning (SAS) MRI to reveal the surface appearance of the vertebrobasilar artery in the cistern. Two-cm-thick heavily T2-weighted coronal imaging using the fast spin-echo sequence with gray-scale reversal in post-processing was best for our purposes. Basi-parallel anatomical scanning (BPAS) MRI could clearly demonstrate fusiform aneurysm and its disappearance at the acutely occluded segment of the dissected vertebral artery. This simple MRI scanning technique can provide useful information on vertebrobasilar vascular lesions especially in patients with arterial dissection.

[Experiences in bereavement care for caregivers].

PURPOSE: To investigate the mental and physical changes of bereaved caregivers. METHODS: We had 5 patients under residential care (1 with prostate cancer, 3 with urinary bladder cancer and 1 bedridden patient without malignant disease) and one month and one year after their death, we visited their family to provide bereavement care. RESULTS: Before the patient's death, all caregivers were uneasy and confused. At the deathbed, all of them were filled with deep grief and prostration. One month later, unrest and fatigue were reduced, all had the satisfaction of having taken care of their patients. One year later, only grief persisted and prostration was deserved in one caregiver. CONCLUSION: We provided bereavement care to 5 caregivers. It is suggested that in some cases long-term bereavement care is necessary.