Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients.

BACKGROUND: Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. METHODS: The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries ≥34% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. RESULTS: Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg/h clazosentan, p < 0.0001; placebo vs. 10 mg/h clazosentan, p < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg/h clazosentan, p = 0.0151; placebo vs. 10 mg/h clazosentan, p = 0.0165). The overall incidence of all-cause death and/or vasospasm-related morbidity/mortality was significantly reduced in the 10 mg/h clazosentan group compared with the placebo group (p = 0.0003). CONCLUSION: These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients.

Perimesencephalic Nonaneurysmal Subarachnoid Hemorrhage After Clipping of an Unruptured Aneurysm.

BACKGROUND: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is a benign form of subarachnoid hemorrhage with an excellent clinical outcome. The cause of PNSAH remains unknown. We report a case of PNSAH in a patient with a history of clipping of an unruptured aneurysm. PNSAH after clipping of an unruptured aneurysm is extremely rare. CASE DESCRIPTION: A 56-year-old man with a history of clipping surgery for an unruptured aneurysm 10 months previously presented with severe headache. No precipitating causes were shown; however, the patient had been engaged in an exertional activity before the event. After conservative treatment, he was discharged home without any complication from the hemorrhage. CONCLUSIONS: On the basis of this case report, clinicians should consider the possibility of PNSAH in a patient who had an unruptured aneurysm previously treated with clipping. Nevertheless, diagnostic workup can be more important than keeping in mind that a subarachnoid hemorrhage might be a PNSAH.

Multidisciplinary management for the treatment of proximal posterior inferior cerebellar artery aneurysms.

OBJECTIVES: Aneurysms of the proximal posterior inferior cerebellar artery (PICA) are rare. The management of proximal PICA aneurysms is challenging with either surgical or endovascular treatment. We report our successful experience of treating PICA aneurysms with a multimodal approach. METHODS: Of 2382 treated aneurysms, 22 aneurysms in 21 patients (male:female 8:13, mean age 48.9 years) were enrolled from March 1998 to December 2015. We treated the aneurysms with a multimodal approach and performed angiography to examine aneurysm regrowth at the 12 months follow-up. Clinical outcomes were evaluated based on the modified Rankin Score (mRS) at the time of discharge and 12 months postoperatively. The treatment modality was mainly dependent on the character of the aneurysms and the clinical presentation of the patients. RESULTS: Microsurgery was performed in seven patients, which entailed proximal occlusion with distal revascularization in two and microsurgical clipping in five. Endovascular treatment was performed in 10 patients because of a serious medical condition, or vertebral artery (VA)/ or PICA tortuosity. Four were treated with coil embolization and six with stent or balloon-assisted coil embolization. Combined surgical and endovascular treatment was applied in four patients. They were treated with distal revascularization followed by occlusion with coils of the aneurysm-incorporated PICA. All patients achieved complete cure of the PICA aneurysms without complications except for one case of cerebrospinal fluid (CSF) leakage. DISCUSSION: Endovascular and microvascular neurosurgeons should work closely in managing these challenging problems. Neurosurgeons should consider multimodal treatment in these cases including trapping after occipital artery (OA)-PICA bypass.

Borderline basal ganglia hemorrhage volume: patient selection for good clinical outcome after stereotactic catheter drainage.

OBJECTIVE The purpose of this study was to determine predisposing factors for good clinical outcome in patients with spontaneous basal ganglia hemorrhage with borderline volumes (defined as a hematoma volume between 20 and 50 cm3) who had undergone treatment by stereotactic catheter drainage. METHODS From the 298 patients whose information had been prospectively collected in the institutional database between January 2010 and December 2013, 93 patients were included in this retrospective study and divided into 2 groups: best medical treatment alone (Group A, n = 44) and best medical treatment plus catheterization (Group B, n = 49). All patients met the following criteria: 1) a diagnosis of spontaneous basal ganglia hemorrhage, and 2) a borderline hematoma volume (20 to 50 cm3). Postoperative modified Rankin Scale (mRS) scores and recovery of motor weakness were compared between the 2 groups, and predisposing factors for good clinical outcome were evaluated. RESULTS Patients in Group B showed earlier recovery of motor weakness and improved mRS scores than patients in Group A. The final mRS score at 12 months was better in Group B than in Group A (p = 0.006). Predisposing factors for a good clinical outcome were a hematoma volume < 30 cm3 (OR 6.158, 95% CI 1.221-31.053, p = 0.028), an initial Glasgow Coma Scale (GCS) score ≥ 13 (OR 6.331, 95% CI 1.129-35.507, p = 0.036), the absence of internal capsule involvement (OR 4.680, 95% CI 1.152-19.010, p = 0.031), and catheterization (OR 13.376, 95% CI 2.423-73.842, p = 0.003) based on logistic regression analysis. CONCLUSIONS Good clinical outcome can be expected after stereotactic catheter drainage in patients with a hematoma volume between 20 and 30 cm3, an initial GCS score ≥ 13, and the absence of internal capsule involvement. Among these patients, stereotactic catheter drainage may have a beneficial effect on early recovery of motor weakness and functional outcome, indicating that lateral-type basal ganglia hematoma compression not involving the internal capsule may be better treated using stereotactic catheter drainage than treated medically.

Effects of preventive surgery for unruptured intracranial aneurysms on attention, executive function, learning and memory: a prospective cohort study.

BACKGROUND: We prospectively evaluated the effects of preventive surgery for unruptured intracranial aneurysms on attention, executive function, learning and memory. METHODS: Between March 2012 and June 2013, 56 patients were recruited for this study. Fifty-one patients met the inclusion criteria and were enrolled. Inclusion criteria were as follows: (1) age ≤65 years and (2) planned microsurgery or endovascular surgery for unruptured intracranial aneurysm. Exclusion criteria were as follows: (1) preoperative intelligence quotient <80 (n = 3); (2) initial modified Rankin scale ≥1 (n = 1); (3) loss to follow-up (n = 1). An auditory controlled continuous performance test (ACCPT), word-color test (WCT) and verbal learning test (VLT) were performed before and after (6 months) preventive surgery. RESULTS: ACCPT (attention), WCT (executive function) and VLT (learning and memory) scores did not change significantly between the pre- and postoperative evaluations. The ACCPT, WCT, total VLT scores (verbal learning) and delayed VLT scores (memory) did not differ significantly between patients undergoing microsurgery and those undergoing endovascular surgery. However, ACCPT, WCT and delayed VLT scores decreased postoperatively in patients with leukoaraiosis on preoperative FLAIR images (OR 9.899, p = 0.041; OR 11.421, p = 0.006; OR 2.952, p = 0.024, respectively). CONCLUSIONS: Preventive surgery for unruptured intracranial aneurysms did not affect attention, executive function, learning or memory. However, patients with leukoaraiosis on FLAIR images might be prone to deficits in attention, executive function and memory postoperatively, whereas learning might not be affected.

Headache After Cerebral Angiography: Frequency, Predisposing Factors, and Predictors of Recovery.

BACKGROUND AND PURPOSE: Headache after cerebral angiography is frequent but has received little attention. The purpose of this study was to evaluate the incidence and risk factors of headache after cerebral angiography. This study also addressed the predisposing factors that facilitate headache recovery. METHODS: A total of 327 patients were included. The patients were ≥20 years old, had alert consciousness, and had received digital subtraction cerebral angiography (DSA) for cerebrovascular diseases or intracranial tumors. All the patients stayed in the hospital for ≥24 hours after DSA. Among them, 277 patients who did not complain of headache on admission were analyzed for headache risk factors and incidence after DSA. RESULTS: Headache developed after DSA in 154 (55.6%) patients. Headache occurrence was independently associated with history of headache (odds ratio [OR] 4.625; P = .014), the indication for DSA (OR 4.141; P < .001), and the education level (OR 1.366; P = .036). Of the 154 patients who experienced headache after DSA, 120 (77.9%) patients recovered within 24 hours. Both diabetes (OR 2.469; P = .043) and the indication for DSA (OR 2.276; P = .028) were independent predisposing factors for headache recovery. CONCLUSIONS: The incidence of headache after DSA was 55.6%. Patients with a previous history of headaches, cerebrovascular disease, or a college education may have a higher risk of developing post-DSA headaches than do those without such history. Headache recovery may be associated with a patient history of diabetes or cerebrovascular disease.

Deep Intracerebral Hemorrhage Caused by Rupture of Distal Lenticulostriate Artery Aneurysm : A Report of Two Cases and a Literature Review.

Intracerebral hemorrhage (ICH) is common among various types of storkes; however, it is rare in young patients and patients who do not have any risk factors. In such cases, ICH is generally caused by vascular malformations, tumors, vasculitis, or drug abuse. Basal ganglia ICH is rarely related with distal lenticulostriate artery (LSA) aneurysm. Since the 1960s, a total of 29 distal LSA aneurysm cases causing ICH have been reported in the English literature. Despite of the small number of cases, various treatment methods have been attempted : surgical clipping, endovascular treatment, conservative treatment, superficial temporal artery-middle cerebral artery anastomosis, and gamma-knife radiosurgery. Here, we report two additional cases and review the literature. Thereupon, we discerned that young patients with deep ICH are in need of conventional cerebral angiography. Moreover, initial conservative treatment with follow-up cerebral angiography might be a good treatment option except for cases with a large amount of hematoma that necessitates emergency evacuation. If the LSA aneurysm still persists or enlarges on follow-up angiography, it should be treated surgically or endovascularly.

Effects of Prophylactic Antiepileptic Drugs on Clinical Outcomes in Patients with a Good Clinical Grade Suffering from Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Routine use of prophylactic antiepileptic drugs (AED) has been debated. We retrospectively evaluated the effects of prophylactic AED on clinical outcomes in patients with a good clinical grade suffering from aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between September 2012 and December 2014, 84 patients who met the following criteria were included: (1) presence of a ruptured aneurysm; (2) Hunt-Hess grade 1, 2, or 3; and (3) without seizure presentation. Patients were divided into two groups; the AED group (n = 44) and the no AED group (n = 40). Clinical data and outcomes were compared between the two groups. RESULTS: Prophylactic AEDs were used more frequently in patients who underwent microsurgery (84.1%) compared to those who underwent endovascular surgery (15.9%, p < 0.001). Regardless of prophylactic AED use, seizure episodes were not observed during the six-month follow-up period. No statistical difference in clinical outcomes at discharge (p = 0.607) and after six months of follow-up (p = 0.178) were between the two groups. After six months, however, favorable outcomes in the no AED group tended to increase and poor outcomes tended to decrease. CONCLUSION: No difference in the clinical outcomes and systemic complications at discharge and after six months of follow-up was observed between the two groups. However, favorable outcomes in the no AED group showed a slight increase after six months. These findings suggest that discontinuation of the current practice of using prophylactic AED might be recommended in patients with a good clinical grade.

Preliminary experience with self-expanding closed-cell stent placement in small arteries less than 2 mm in diameter for the treatment of intracranial aneurysms.

OBJECT: The purpose of this study was to report the authors' preliminary experience using self-expanding closed-cell stents deployed in small arteries (< 2 mm in diameter) to treat intracranial aneurysms. METHODS: A total of 31 patients were studied. All subjects met the following criteria: 1) they received an Enterprise stent for treatment of a wide-necked aneurysm or a dissecting aneurysm or as part of a stent-salvage procedure; and 2) they had an Enterprise stent deployed in a small parent artery (< 2 mm in diameter) that had no atherosclerotic stenosis. Procedure-related complications and follow-up sizes of the parent arteries were evaluated for safety and patency. RESULTS: There were 16 ruptured aneurysms and 15 unruptured aneurysms. Three (9.7%) of the 31 patients experienced procedure-related complications, and they all were asymptomatic. Follow-up angiography was performed in 27 patients (87.1%) (at a mean 15.5 months after surgery). Parent arteries with 2 acute angles (n = 4) were occluded in 3 cases (75.0%), and those with no acute angles (n = 13) or 1 acute angle (n = 6) showed 100% patency on follow-up angiography. There was a significant difference between the follow-up sizes (mean 1.72 ± 0.30 mm) of parent arteries and their sizes (mean 1.59 ± 0.26 mm) before treatment (95% CI - 0.254 to - 0.009 mm; p = 0.037, paired-samples t-test). CONCLUSIONS: In the current series the deployment of self-expanding closed-cell stents in small arteries was safe and resulted in good patency, especially when the stents were deployed in segments of the parent artery with no acute angles or only 1 acute angle.

The role of endovascular treatment for ruptured distal anterior cerebral artery aneurysms: comparison with microsurgical clipping.

BACKGROUND AND PURPOSE: The purpose of this study was to compare clinical outcomes and treatment-related complications between coiling and clipping for ruptured distal anterior cerebral artery (DACA) aneurysms. METHODS: Eighty-four consecutive patients (M:F = 36:48; mean 53.8 years) with ruptured DACA aneurysms were treated by either clipping (n = 46, 54.8%) or coiling (n = 38, 45.2%). The clinical outcomes and procedure-related complications were evaluated and compared between the two groups. RESULTS: Procedure-related complications tend to occur more frequently in the clipping (n = 6, 13.0%) than coiling group (n = 1, 2.6%) (P = .121). At discharge, 51 patients (60.7%) had favorable outcomes (Glasgow outcome scale [GOS], 4 or 5). There was no significant difference between the two groups in favorable outcome (63.2% vs. 58.7%; P = .677). Hunt and Hess (HH) grade (P < .001; 95% CI, 3.354-29.609) and treatment modality (P = .044; 95% CI, 1.039-16.325) were independent risk factors for poor outcome (GOS, 1-3). CONCLUSIONS: Coiling was more favorable to clipping in clinical outcomes and incidence of treatment-related complications for ruptured DACA aneurysms.

Benefits of surgical treatment for unruptured intracranial aneurysms in elderly patients.

OBJECTIVE: Due to longer life spans, patients newly diagnosed with unruptured intracranial aneurysms (UIAs) are increasing in number. This study aimed to evaluate how management of UIAs in patients age 65 years and older affects the clinical outcomes and post-procedural morbidity rates in these patients. METHODS: We retrospectively reviewed 109 patients harboring 136 aneurysms across 12 years, between 1997 and 2009, at our institute. We obtained the following data from all patients : age, sex, location and size of the aneurysm(s), presence of symptoms, risk factors for stroke, treatment modality, and postoperative 1-year morbidity and mortality. We classified these patients into three groups : Group A (surgical clipping), Group B (coil embolization), and Group C (observation only). RESULTS: Among the 109 patients, 56 (51.4%) underwent clipping treatment, 25 (23%) patients were treated with coiling, and 28 observation only. The overall morbidity and mortality rates were 2.46% and 0%, respectively. The morbidity rate was 1.78% for clipping and 4% for coiling. Factors such as hypertension, diabetes mellitus, hypercholesterolemia, smoking, and family history of stroke were correlated with unfavorable outcomes. Two in the observation group refused follow-up and died of intracranial ruptured aneurysms. The observation group had a 7% mortality rate. CONCLUSION: Our results show acceptable favorable outcome of treatment-related morbidity comparing with the natural history of unruptured cerebral aneurysm. Surgical clipping did not lead to inferior outcomes in our study, although coil embolization is generally more popular for treating elderly patients. In the treatment of patients more than 65 years old, age is not the limiting factor.

Dural arteriovenous fistula associated with meningioma: spontaneous disappearance after tumor removal.

A 45-year-old woman presented with a non-dominant transverse-sigmoid sinus dural arteriovenous fistula (AVF) associated with convexity meningioma on the same side. The dural AVF disappeared spontaneously after surgical removal of the meningioma, even though there was no manipulation of the dural AVF. Dural AVFs are usually acquired lesions, and may develop after trauma, surgery, and dural sinus thrombosis. Dural AVFs of the acquired origins are rarely associated with brain tumor. Dural AVFs associated with a tumor may develop even in the absence of sinus occlusion.

Expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in astrocytic tumors.

BACKGROUND: DNA is continuously damaged due to exposure to alkylating compounds or oxygen free radicals generated during normal cellular metabolism as well as to environmental mutagens. Several studies have shown that N-methylpurine-DNA-glycosylase (MPG) mRNA levels were lower in adult brain than in other tissues. Terminally differentiated and nonproliferating cells have a lower DNA repair capacity than proliferating cells from various organs, embryo, ovary and testis. If the DNA repair are not efficient, the damaged DNA may lead to tumorigenesis or cell death. This study was designed to investigate the association of tumorigenesis with MPG in astrocytic tumors. MATERIALS AND METHODS: MPG mRNA expression and localization in astrocytic tumors and tumor-adjacent brain tissues was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization. The expression and intracellular localization of MPG protein was determined by immunohistochemistry. RESULTS: MPG mRNA expression in RT-PCR was slightly higher in astrocytic tumor tissues than in brain tissues adjacent to tumor and in astrocytic tumor tissues, regardless of the tumor grades. MPG protein localization in immunohistochemical study was detected only in the nucleus of all tumor tissues. Interestingly, in brain tissues adjacent to tumor, immunohistochemical staining for MPG was not observed either in the nucleus or the cytoplasm. However, we could not detect MPG protein in the brain tissues adjacent to the tumor although MPG mRNA was detected in the tissues. CONCLUSION: These results suggest an MPG's role in human astrocytic tumors and raise the possibility that the altered MPG expression and intracellular localization could be associated with astrocytic tumorigenesis.

Chronic granulomatous neuritis in idiopathic trigeminal sensory neuropathy. Report of two cases.

Idiopathic trigeminal sensory neuropathy is a clinically benign disorder in which the main feature is facial numbness limited to the territory of one or more divisions of the trigeminal nerve; the disorder persists for a few weeks to several years. and no underlying disease can be identified. Magnetic resonance (MR) imaging findings are occasionally consistent with a small trigeminal neuroma of the left gasserian ganglion associated with idiopathic trigeminal sensory neuropathy. The authors report on two patients who were treated using a skull base approach in which the gasserian ganglion was exposed and the lesion was removed. The pathological diagnosis was chronic granulomatous neuritis. The authors conclude that, in patients with MR findings suggestive of a small trigeminal neuroma, benign idiopathic trigeminal sensory neuropathy should also be considered in the differential diagnosis. A conservative approach featuring sequential MR imaging studies may avoid an unnecessary surgical exploration.