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In every hospital in Japan, until 2022, the primary treatment for preventing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) involved a combination of ozagrel sodium (Oz), fasudil hydrochloride (Fs), cilostazol, and statins. However, with the approval of clazosentan in January 2022, it has been used as a first-choice drug more frequently. Despite this shift, limited evidence exists regarding the use of clazosentan as the first choice for DCI prevention. In this study, we analyzed the efficacy and outcomes of these two treatments in aSAH patients. Patients treated with Oz+Fs were enrolled between January 2014 and March 2022. In April 2022, clazosentan was prescribed to prevent DCI. Clinical data were collected, and propensity-score matching was conducted based on the clazosentan group. The primary endpoint was the functional outcome at discharge and 6-12 months after admission; the secondary endpoints were the incidence of cerebral vasospasm (CV) and DCI. In this study, 221 patients were included, and 27 were selected from both groups after matching. The incidence of CV was significantly lower in the clazosentan group (11.1% vs. 55.6%, p<0.01), and the incidence of DCI tended to be lower in the clazosentan group (3.7% vs. 25.9%, p=0.05). No significant difference was observed in the primary endpoint of functional outcome at discharge; however, a significant improvement in functional outcome was observed in the clazosentan group at 6 months (96.3% vs. 70.4%, p<0.05). Clazosentan significantly reduced the incidence of CV and improved functional outcomes in patients with aSAH compared to Oz+Fs.

Background: Acute kidney injury (AKI) is a complication often observed in critically ill patients, indicating a worsening prognosis. However, factors predicting AKI in subarachnoid hemorrhage (SAH) patients are unclear. This study aims to elucidate the predictors of AKI occurrence., Methods: All patients with SAH admitted to the intensive care unit between 2013 and 2019 were included. Patients with very severe SAH who are unsuitable to receive aggressive treatment, those who previously received a contrast medium at another medical institution within 24 hours before admission, and those on maintenance dialysis were excluded. We retrospectively examined blood tests conducted upon admission, oral medications administered, and the total amount of contrast medium used after initiating treatment to investigate their association with AKI occurrence., Results: Of the 254 SAH patients treated during the relevant period, 195 (median age 64 years, 72 males) met the inclusion/exclusion criteria, and 32 patients (16.3%) developed AKI. When multivariate analysis was performed using sex, uric acid level, and hemoglobin, which obtained P < 0.01 in the univariate analysis, as variables, only uric acid level was found as an independent predictor of AKI (odds ratio, 1.501; 95% confidence interval, 1.109-2.033, P value of 0.009). There was no difference in the occurrence of AKI between survivors and nonsurvivors (12/163 vs. 2/32, P = 0.824)., Conclusions: AKI occurred in 16.3% of the patients with SAH. Patients who developed AKI had significantly higher uric acid levels. SAH with high uric acid levels warrants attention for AKI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This observational study examined morphological changes in superficial cerebral arteries and veins, which were correlated with increased intracranial pressure (ICP)-dependent and -independent hypoperfusion in hyperacute phase after subarachnoid hemorrhage (SAH). The prechiasmatic injection model was used, and 32 male Sprague-Dawley rats were divided into the sham-operated, saline-injected (V group, ICP increase), and arterial blood-injected (SAH group, subarachnoid blood and plus increase) groups. Morphological changes in cortical arteries and veins were observed through the cranial window with a microscope before and up to 10 min after the injection. At 24 h, the stenotic and obstructive cortical arteries and veins were counted. After 6 min, 60% of rats in the V group showed vasodilatation, whereas all rats in the SAH group demonstrated vasodilation and vasoconstriction (arterial instability) within 10 min. Similar acute venous congestive changes were observed within 10 min in the V and SAH groups. At 24 h, stenotic and obstructive arteries and veins were observed in the SAH group. Neurological deteriorations were observed at 1 h in the V and SAH groups, and at 23 h in the SAH group. The sham-operated group showed no evident vascular changes and neurological deterioration. The same phenomena, including arterial changes after 6 min and immediate venous changes in the V and SAH groups, may have resulted from ICP increase, whereas subarachnoid blood-related factors produced arterial instability within 5 min after blood injection. Subarachnoid blood plays a significant role in hyperacute SAH pathophysiology in addition to ICP increase., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Subarachnoid hemorrhage (SAH) is a life-threatening condition, and although its two main complications-cerebral vasospasm (CVS)/delayed cerebral ischemia (DCI) and early brain injury (EBI)-have been widely studied, prognosis has not improved over time. The sympathetic nerve (SN) system is important for the regulation of cardiovascular function and is closely associated with cerebral vessels and the regulation of cerebral blood flow and cerebrovascular function; thus, excessive SN activation leads to a rapid breakdown of homeostasis in the brain. In the hyperacute phase, patients with SAH can experience possibly lethal conditions that are thought to be associated with SN activation (catecholamine surge)-related arrhythmia, neurogenic pulmonary edema, and irreversible injury to the hypothalamus and brainstem. Although the role of the SN system in SAH has long been investigated and considerable evidence has been collected, the exact pathophysiology remains undetermined, mainly because the relationships between the SN system and SAH are complicated, and many SN-modulating factors are involved. Thus, research concerning these relationships needs to explore novel findings that correlate with the relevant concepts based on past reliable evidence. Here, we explore the role of the central SN (CSN) system in SAH pathophysiology and provide a comprehensive review of the functional CSN network; brain injury in hyperacute phase involving the CSN system; pathophysiological overlap between the CSN system and the two major SAH complications, CVS/DCI and EBI; CSN-modulating factors; and SAH-related extracerebral organ injury. Further studies are warranted to determine the specific roles of the CSN system in the brain injuries associated with SAH., (© 2021 International Society for Neurochemistry.)

A 51-year-old hypertensive man presented with subarachnoid haemorrhage. He had a past history of cerebellar infarction due to occlusion of the right posterior inferior cerebellar artery (PICA) 4 years earlier. Digital subtraction angiography showed a saccular aneurysm above an arterial loop extending from the vertebral artery to the distal part of the PICA, reminiscent of peripheral PICA branches. We performed aneurysmal neck clipping with excellent outcome. Aneurysms at anastomotic arteries are extremely rare and can result from increased haemodynamic stress. We report the first case of a ruptured aneurysm at an anastomotic artery in the posterior circulation territory.

Objective: To report the effectiveness of intrathecal selective administration of urokinase infusion (ITSUKI) therapy delivered via a special kit (ITSUKit), developed to prevent vasospasm in patients with ruptured aneurysms who had undergone Guglielmi detachable coil (GDC) placement, in patients with World Federation of Neurological Surgery (WFNS) grade V subarachnoid hemorrhage (SAH)., Methods: A study of ITSUKI therapy with or without ventricular drainage enrolled 6 patients with WFNS grade V SAH owing to ruptured intracranial aneurysms who were eligible for coil embolization. The procedures were performed within 48 hours of the occurrence of aneurysmal SAH. The incidence of symptomatic vasospasm and the clinical outcomes based on the Glasgow Outcome Scale (GOS) were assessed at 6 months after SAH onset., Results: All patients underwent complete coil embolization. There were no side effects or adverse reactions attributable to ITSUKI therapy. Symptomatic vasospasm occurred in one patient (16.7%). There were no patients with hydrocephalus. Based on the GOS, one patient had a good outcome, two manifested moderate disability, and three manifested severe disability., Conclusions: The results showed that the ITSUKit was useful for ITSUKI therapy. Although the combination of coil embolization and ITSUKI therapy did not completely eliminate WFNS grade V SAH, it significantly improved the treatment outcome in some patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A 71-year-old woman presented with an aneurysm at the trunk of the persistent primitive trigeminal artery (PPTA) manifesting as subarachnoid hemorrhage. Angiography and three-dimensional computed tomography revealed a wide-necked saccular aneurysm at the trunk of the left PPTA. Coil embolization with the balloon-assist technique was successful and PPTA patency was preserved. Preoperative conventional angiography should be performed to check for cross-filling of the PPTA. This case demonstrates that an aneurysm of the trunk of the PPTA can be successfully treated by coil embolization using the balloon-assist technique.

Purpose: In patients with perimedullary arteriovenous fistula (AVF) with subarachnoid hemorrhage (SAH), knowledge of lesion location is necessary to select the appropriate approach for catheter spinal angiography. We evaluated the utility of 3-dimensional (3D) fast imaging with steady-state precession (FISP) sequence for detecting type 1 perimedullary AVF with SAH., Materials and Methods: We evaluated 4 patients (2 men, 2 women, aged 53 to 68 years, mean age, 59.25 years) with type 1 perimedullary AVF who presented with SAH and underwent conventional spin-echo MR and contrast-enhanced 3D FISP imaging. Two neuroradiologists assessed detection of vascular lesions and delineation of their relationships to the adjacent vessels. Catheter angiography was used as the reference standard and compared with the MR findings., Results: Perimedullary AVF was located at the medullocervical junction in 2 patients, cervical spine in one, and thoracic spine in one. For all patients, use of contrast-enhanced 3D FISP in addition to conventional MR imaging improved lesion detection and delineation of the relationship between the lesion and surrounding vessels., Conclusion: Contrast-enhanced 3D FISP imaging was useful for detecting and delineating type 1 perimedullary AVF with SAH.

We report a 19-year-old woman with Behcet's disease who suffered a subarachnoid hemorrhage and had bilateral peripheral middle cerebral artery aneurysms. After steroid therapy for 3 days, the smaller aneurysm disappeared. The larger aneurysm was excised and the artery reconstructed using a superficial temporary artery graft. Histological examination showed vasculitis restricted to the wall of the aneurysm. This is the first report of arterial reconstruction for an aneurysm associated with Behcet's disease. Steroid therapy before the operation may facilitate repair of the arterial wall.

Although three-dimensional computed tomographic angiography (3D-CTA) is less complicated and time-consuming than conventional cerebral angiography (CCA) and represents a reliable alternative for evaluating cerebral aneurysms, some patients experience aneurysmal rerupture during 3D-CTA. Two women, 79 and 71 years old, who presented with severe subarachnoid hemorrhage (SAH) underwent 3D-CTA within 3 h after SAH onset. Their images clearly indicated extravasation from their aneurysms. Neither patient recovered from deep coma, and both died within 2 days. We reviewed the literature with special reference to the condition of SAH patients at admission and the interval between SAH onset and 3D-CTA, and discuss serious complications of 3D-CTA study. Although aneurysmal rerupture may reflect the natural course, rerupture during 3D-CTA, especially in SAH patients who are in poor clinical condition during the acute stage, should be recognized as a potentially fatal complication. Their blood pressure must be strictly controlled and factors such as their clinical condition and the interval from the ictus must be considered.

A 67-year-old man presented with devastating intracranial hemorrhage (ICH) from an anterior cranial fossa dural arteriovenous fistula (DAVF). Four years earlier, digital subtraction angiography had disclosed a DAVF at the right anterior cranial fossa fed mainly by the ethmoidal branches of the bilateral sphenopalatine arteries and slightly by the ethmoidal arteries of the bilateral ophthalmic arteries, and drained primarily by the sphenoparietal and cavernous sinuses via two dilated cortical veins and slightly by the superior sagittal sinus via a frontal ascending vein. Three-dimensional computed tomography angiography revealed the development of a venous aneurysm on the main draining vein over a 4-year period, but no other changes. Venous aneurysm development may be part of the natural history of DAVF with cortical venous drainage and may contribute to the occurrence of ICH.

Background and Purpose: Cases with spinal perimedullary arteriovenous fistulas (SPAVFs) or spinal dural arteriovenous fistulas (SDAVFs) at the cervicomedullary junction are rare. We performed a retrospective, angiographic study of 6 such patients to assess whether available angiographic data were predictive of the risk for hemorrhage., Methods: We report 6 patients with arteriovenous fistulas at the cervicomedullary junction. All presented with subarachnoid hemorrhage (SAH). Angiography demonstrated that 4 of the 6 fistulas were SDAVFs fed by the meningeal branch of the vertebral artery; the other 2 were SPAVFs fed by the anterior spinal artery. Drainage was via the perimedullary vein of the cervicomedullary junction., Results: An ascending venous route into the intracranial sinus was recognized in all 6 cases; in 3 the draining system contained varices. In 2 cases, the venous route was on the ventral side of the brain stem with drainage into the cavernous sinus. In 4 cases, the venous route was lateral at the brain stem with drainage into the inferior petrosal sinus., Conclusion: SPAVFs and SDAVFs at the cervicomedullary junction that manifest an ascending venous route into the intracranial sinus present an increased risk for SAH.

Objective: We analyzed the community incidence and early prognosis of first-ever aneurysmal subarachnoid hemorrhages (SAHs) to obtain the same prognostic information used by physicians and families in a defined geographic area in Japan., Methods: During the 5-year period from January 1, 1996, to December 31, 2000, 2115 patients were registered in the Data Bank for Cerebral Aneurysms of Kumamoto Prefecture, a defined area in Japan with a population of 1.86 million. Registration was based on a comprehensive referral system for SAH patients; computed tomographic scans were available for all patients, including those who were moribund or dead on arrival. We compared the treatment outcomes at 3 months after the first-ever SAH in surgically and conservatively treated patients., Results: The age-adjusted annual incidence of SAH for men, women, and both sexes was 15.9, 26.6, and 21.6 per 100,000 person-years, respectively. In men, the incidence reached a plateau after age 40 years. In women, conversely, it rose after age 40 and peaked in the 9th decade of life. Of the 1634 surgically treated patients, 1153 (70.6%) had a favorable outcome; this was true for only 27 of 477 (5.7%) conservatively treated patients. Four patients were lost to follow-up. The clinical outcome did not differ between patients treated by open surgery and those treated endovascularly. Approximately 30% of our patients were older than 70 years at the time they experienced their first SAH., Conclusion: The incidence of SAH obtained in this study was similar to earlier Japanese reports and Finnish studies. The importance of managing elderly patients with cerebral aneurysms will continue to increase.

Background and Purpose: We developed an experimental canine subarachnoid hemorrhage (SAH) model in which one-time blood injection by means of a microcatheter into the ventral cisterna magna (CM) is performed without direct CM puncture. We assessed the severity and duration of the vasospasm produced in this model., Methods: Fresh autologous blood (0.25 or 0.5 ml/kg) or saline (0.5 ml/kg) was injected into the ventral CM of dogs through a microcatheter inserted at the lumbar region. Serial angiograms were obtained on days 3, 7, 10, and 14, and chronologic changes in the mean diameter of the basilar artery (BA) were recorded. The BA was examined histologically on day 7 after injection., Results: A remarkable amount of clot was present in front of the brain stem at 24 hours after SAH induction. The clot was smaller in the 0.25 ml/kg SAH than in the 0.5 ml/kg SAH group. On day 3, narrowing of the BA was apparent in both SAH groups compared with the control (P <.05). The BA gradually returned to nearly normal on day 14 in the 0.25 ml/kg SAH group. Arterial narrowing was more severe and persistent in the 0.5 ml/kg SAH than in the 0.25 ml/kg SAH group (P <.05). Histologic examination of the BA on the 7th postinjection day confirmed narrowing of the lumen, indicative of arterial spasm, in both SAH groups., Conclusion: Our method of SAH induction by means of a single injection of blood directly into the ventral CM through a microcatheter induced severe, prolonged spasms in the canine BA. Because our model facilitates the induction of different-sized clots, we could control of the severity and duration of the induced vasospasms.

Background and Purpose: Our preliminary report on intrathecal urokinase (UK) infusion into the cisterna magna (CM) with a microcatheter showed good results in terms of vasospasm prevention in humans. In this study, we evaluated the relationship between different urokinase (UK) infusion sites and their effect on vasospasm prevention by using our canine subarachnoid hemorrhage (SAH) model., Methods: At 24 hours after SAH induction, we injected 1000 IU/kg UK into the cisterna magna (CM) or lumbar sac (LS) of dogs by using a microcatheter inserted at the lumbar region. We then obtained serial angiograms and chronologically examined the changes in the mean diameter of the basilar artery (BA) during a 14-day period to determine the effect of the different injection sites on vasospasm prevention. At 24 hours after UK injection, one dog from each group was killed for gross inspection of the subarachnoid clot. To measure its concentration in the CM and sylvian fissure, UK (1000 IU/kg) was injected into the CM or LS of dogs without SAH; measurements were taken at 15-minute intervals until 4 hours after injection., Results: At 24 hours after UK injection, subarachnoid clot in front of the brain stem persisted strongly in the LS group; it had almost disappeared in the CM group. In the LS group, there was severe and persistent BA constriction during the 14-day observation period. In the CM group, the BA was constricted on day 3; however, gradual dilatation occurred over time. The mean diameter of the BA on days 7, 10, and 14 was 48.2%, 53.9%, and 58.9% in the LS group and 62.6%, 70.5%, and 82.3% in the CM group. The difference between the two groups was significant on days 7, 10, and 14 (P <.05). In dogs without SAH, the average maximum UK concentration in the CM and the sylvian fissure was 2.5 and 6.7 times higher, respectively, in the CM group than in the LS group., Conclusions: In our canine SAH model, the administration of UK into the CM was significantly more effective in preventing cerebral vasospasms than was administration into the LS.

Background: This study was conducted to define general guidelines for rational clinical decision-making with respect to patients older than 80 years who present with ruptured anterior circulation aneurysms and a Hunt and Hess clinical grade of III., Methods: The 29 consecutive patients enrolled in this study were treated at 4 participating centers between 1995 and 1998. All were 80 years or older on admission and met 7 eligibility criteria. The decision to treat surgically or non-surgically was made individually at each center. The outcome at discharge was assessed using the Glasgow Outcome Scale (GOS); the Barthel Score (BS) was used to determine the patients' quality of life after discharge., Results: Of 15 surgically treated patients, 4 died before discharge and 8 were discharged in poor condition. Of these, 7 died of unrelated causes within 2 years of the SAH and one is living in a nursing home. Three patients with middle cerebral artery (MCA) aneurysms made a good recovery; they are currently living at home. Of the 14 conservatively treated patients, 10 died during their hospital stay mainly because of rebleeding that occurred within 3 weeks of the subarachnoid hemorrhage (SAH). Three others who were discharged in poor condition died of systemic illness within 2 years. The remaining patient is living in a nursing home with a BS value of 0., Conclusions: The outcomes for patients treated conservatively were catastrophic. Even in surgically treated patients, favorable outcomes were rare; the best results were achieved in surgically treated patients with MCA aneurysms.

Background: The present pilot study was undertaken to analyze the long-term results of surgery for ruptured anterior circulation aneurysms in patients in their 9th decade of life., Methods: Between 1992 and 1997, we treated 10 consecutive patients with ruptured anterior circulation aneurysms who were 80 years or older on admission and judged eligible for surgery based on stringent criteria. The outcomes at discharge and the latest outcomes (obtained at a median of 41.6 months) were assessed using the Glasgow Outcome Scale and the Barthel Score, respectively., Results: Upon discharge, six of the 10 patients showed good recovery, two patients were moderately disabled, and two patients who suffered symptomatic vasospasm were severely disabled. As for the latest outcomes, assessed using Barthel Score, four patients had the maximum score of 100, two a score of 90, one a score of 35, two a score of 10, and one patient died. Of four patients who were in poor condition, two experienced deterioration attributable to unrelated causes 18 and 32 months after the ictus., Conclusion: Advanced age alone does not preclude successful surgery for ruptured anterior circulation aneurysms. Carefully selected patients over 80 years should also be considered for surgical treatment.

Objective and Importance: Accessory anterior cerebral artery (ACA), which is a type of median artery of anomalous triplicate ACA, is not rare, but aneurysmal formation is extremely rare. We report a rare case with ruptured aneurysm arising from a distal accessory ACA. We discuss the characteristics and causes of this type of aneurysm and classification of this anomaly., Clinical Presentation: A 63-year-old man suddenly developed severe headache and then loss of consciousness and paraplegia. Computed tomography disclosed thick and diffuse subarachnoid hemorrhage and interhemispheric hematoma. Subsequent bleeding occurred 2 hours after the first hemorrhage. Cerebral angiography disclosed a saccular aneurysm arising from the distal accessory ACA., Intervention: Neck clipping of the aneurysm was performed 22 hours after the second episode, using an interhemispheric approach., Conclusion: Although transient paraplegia occurred 8 days after onset, the patient recovered well after surgery without neurological deficit. The characteristics of the aneurysm arising from distal accessory ACA are considered similar to those of distal ACA aneurysm. There is, however, some confusion regarding the terminology of the anterior communicating artery complex anomalies, which we discuss.

Thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) were examined in the acute stage in 51 patients with nontraumatic subarachnoid hemorrhage. TAT and PIC values were correlated with severity at the time of onset and with outcome. In the patients whose TAT levels were 25 ng/ml or more and PIC levels were 3.0 micrograms/ml or more (n = 16), only 25% had a good or fair outcome. In the patients with TAT levels less than 25 ng/ml or PIC levels less than 3.0 micrograms/ml (n = 35), on the other hand, 82.9% had a good or fair outcome. There were no significant differences in TAT and PIC levels between patients who experienced arterial spasm and those who did not. These results indicate that TAT and PIC values may reflect the severity of the brain damage induced by subarachnoid hemorrhage. It is speculated that marked coagulation and fibrinolytic disorders occur in the acute stage of subarachnoid hemorrhage.

A gauze sponge wrapping method to prevent recurrent subarachnoid hemorrhage (SAH) after incomplete obliteration of intracranial aneurysm or a residual neck after clipping was developed and tested. The authors performed the gauze wrapping for aneurysms with incomplete obliteration by clipping alone, abnormal changes of the parent artery wall which had the possibility of regrowth or rerupture, and surgical difficulties. The residual neck of the aneurysm or the abnormal arterial wall was tightly and completely wrapped, including the parent artery, and cemented with plastic adhesive. Seventy-eight (22.3%) of 349 surgically treated aneurysms were treated by gauze wrapping (26 wrapping only, 52 clipping and wrapping). The incidence of complications such as infection, angiospasm, and normal pressure hydrocephalus, and the clinical outcome were not significantly different for the wrapping and non-wrapping groups. No recurrent SAH was observed in the wrapping group during 3 months to 8.5 years follow-up. These results suggest that wrapping with gauze sponge is useful in the treatment for ruptured aneurysms which cannot be totally obliterated.