Katsuharu Kameda

Effect of tumor removal on tinnitus in patients with vestibular schwannoma.

OBJECT Tinnitus is one of the most common symptoms in patients with vestibular schwannomas (VSs), but the effect of surgery on this symptom has not been fully evaluated. The aim of this study was to define the effect on tinnitus of tumor removal, cochlear nerve resection, and useful hearing preservation in patients with VSs. METHODS The authors retrospectively analyzed the status of tinnitus before and after surgery in 242 patients with unilateral VSs who underwent surgery via the retrosigmoid lateral suboccipital approach. RESULTS Of 242 patients, 171 (70.7%) complained of tinnitus before surgery; the symptom disappeared in 25.2%, improved in 33.3%, remained unchanged in 31.6%, and worsened in 9.9% of these cases after tumor removal. In the 171 patients with preoperative tinnitus, the cochlear nerve was resected in 85 (49.7%) and preserved in 86 (50.3%), but there was no significant difference in the incidence of postoperative tinnitus between these 2 groups (p = 0.293). In the 71 patients without preoperative tinnitus, the symptom developed postoperatively in 6 cases (8.5%). Among those without preoperative tinnitus, the cochlear nerve was resected in 45 cases (63.4%) and tinnitus appeared postoperatively in 3 (6.7%). The authors also analyzed the association between postoperative tinnitus and useful hearing preservation, but could not find any statistically significant association between the 2 factors (p = 0.153). CONCLUSIONS Tumor removal via the retrosigmoid lateral suboccipital approach may provide some chance for improvement of tinnitus in patients with VSs; however, neither cochlear nerve resection nor useful hearing preservation affects the postoperative development of tinnitus.

Impaired feedback regulation of the receptor activity and the myofilament Ca2+ sensitivity contributes to increased vascular reactiveness after subarachnoid hemorrhage.

Cerebral vasospasm determines the prognosis of subarachnoid hemorrhage (SAH). The increased vascular reactiveness has an important role in the development of cerebral vasospasm. This study analyzed the roles of the receptor-mediated signaling and the myofilament Ca2+ sensitivity in the increased vascular reactiveness in SAH, using the basilar artery of a rabbit SAH model. Endothelin-1, thrombin, and phenylephrine induced transient increases in [Ca2+]i, myosin light chain phosphorylation, and contraction in the controls. All these responses were not only enhanced but also became sustained in SAH. In the sequential stimulation of thrombin receptor or α1-adrenoceptor, the second response was substantially attenuated in the controls, whereas it was maintained in SAH. The thrombin-induced contraction in SAH irreversibly persisted even after terminating the thrombin stimulation. This contraction was completely reversed by trypsin and a Gαq inhibitor YM254890, thus suggesting the sustained receptor activity during the sustained contraction. YM254890 also inhibited the endothelin-1- and phenylephrine-induced sustained contraction. Furthermore, the GTPγS-induced transient contraction in the control α-toxin-permeabilized strips was converted to a sustained contraction in SAH. The results provide the first evidence that the feedback inactivation of the receptor activity and the myofilament Ca2+ sensitivity was impaired in SAH, thus contributing to the increased vascular reactiveness.

Enhanced Contractile Response of the Basilar Artery to Platelet-Derived Growth Factor in Subarachnoid Hemorrhage

Background and Purpose— The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH. Methods and Results— A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in [Ca2+]i at 1 nmol/L and higher concentrations. The levels of [Ca2+]i and tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K+ depolarization. The PDGF-induced elevation of [Ca2+]i and contraction seen in SAH were abolished in the absence of extracellular Ca2+. In α-toxin–permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca2+, suggesting no direct effect on myofilament Ca2+ sensitivity. Genistein at 10 &mgr;mol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF. Conclusions— These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca2+-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH.

Mechanisms underlying potentiation of endothelin-1-induced myofilament Ca(2+) sensitization after subarachnoid hemorrhage.

Increased vascular smooth muscle contractility has an important role in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Myofilament Ca2+ sensitivity is a major determinant of smooth muscle contractility. We investigated changes in the Ca2+-sensitizing effect of endothelin-1 (ET-1) and the mechanisms underlying ET-1-induced Ca2+ sensitization after SAH using a rabbit SAH model. After SAH, the contractile response to ET-1 was enhanced, and the ETA receptor expression was upregulated in the basilar artery. In α-toxin-permeabilized preparations, ET-1 induced enhanced and prolonged contraction after SAH, suggesting that ET-1-induced Ca2+ sensitization is potentiated after SAH. Endothelin-1-induced Ca2+ sensitization became less sensitive to inhibitors of Rho-associated coiled-coil protein kinase (ROCK) and protein kinase C (PKC) after SAH. The expression of PKCα, ROCK2, PKC-potentiated phosphatase inhibitor of 17 kDa (CPI-17) and myosin phosphatase target subunit 1 (MYPT1) was upregulated, and the level of phosphorylation of CPI-17 and MYPT1 was elevated after SAH. This study demonstrated for the first time that the Ca2+-sensitizing effect of ET-1 on myofilaments is potentiated after SAH. The increased expression and activity of PKCα, ROCK2, CPI-17, and MYPT1, as well as the upregulation of ETA receptor expression are suggested to underlie the enhanced and prolonged Ca2+ sensitization induced by ET-1.

Combined argatroban and anti-oxidative agents prevents increased vascular contractility to thrombin and other ligands after subarachnoid haemorrhage

BACKGROUND AND PURPOSE Increased vascular contractility plays a fundamental role in cerebral vasospasm in subarachnoid haemorrhage (SAH). We investigated the role of thrombin and its receptor, proteinase‐activated receptor 1 (PAR1), and other G protein‐coupled receptors in the increased contractility, and examined the preventive effects of the thrombin inhibitor, argatroban, and anti‐oxidative agents, vitamin C and tempol.

Epstein‐Barr virus‐positive diffuse large B‐cell primary central nervous system lymphoma associated with organized chronic subdural hematoma: A case report and review of the literature

We here report on a rare case of Epstein‐Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) detected in both brain parenchyma and in an organized chronic subdural hematoma (OCSH). A 96‐year‐old man diagnosed with asymptomatic OCSH in the left frontal convexity was referred to our hospital because of a de novo mass lesion just beneath the OCSH on contrast‐enhanced magnetic resonance imaging. The size of the OCSH remained stable. We diagnosed the lesion as a malignant tumor. At surgery, the organized hematoma and the soft fragile tumor were removed. Histological examinations revealed pleomorphic lymphoid cells not only in the brain tissue but also in the OCSH component with tumor necrosis, and these were immunopositive for B‐cell markers. In situ hybridization revealed positive signals for EBV‐encoded small RNAs, consistent with EBV‐positive DLBCL. Since the membranes of the subdural hematoma were fibrous and the tumor progression resulted in necrosis of the tumor, the DLBCL may have originally developed in the OCSH and infiltrated into the brain parenchyma. We believe that this rare case provides crucial information for the understanding of DLBCLs associated with OCSH.

Hemodynamic state of periictal hyperperfusion revealed by arterial spin-labeling perfusion MR images with dual postlabeling delay

Background Magnetic resonance imaging (MRI), including perfusion MRI with arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in the periictal detection of circulatory and metabolic consequences associated with epilepsy. Although previous report revealed that prolonged ictal hyperperfusion on ASL can be firstly detected and cortical hyperintensity of cytotoxic edema on DWI secondarily obtained from an epileptically activated cortex, the hemodynamic state of the periictal hyperperfusion has not been fully demonstrated. Methods: study-1 We retrospectively analyzed the relationship between seizure manifestations and the development of periictal MRI findings, in Case 1 with symptomatic partial epilepsy, who underwent repeated periictal ASL/DWI examination for three epileptic ictuses (one examination for each ictus). Study-2: We evaluated the hemodynamic state of periictal hyperperfusion with the ASL technique using a dual postlabeling delay (PLD) of 1.5 and 2.5 s in nine patients, according to the presence or absence of the localized epileptogenic lesion (EL) on conventional 3 T-MRI, who were divided into Group EL+ (six patients) and Group EL− (three patients). Results Study-1 confirmed that the stratified representation of the periictal MRI findings depends on the time interval between the ictal cessation and MRI examination in addition to the magnitude and duration of the epileptic activity. In Study-2, two types of periictal hyperperfusion were noted. In all six Group EL+ patients, periictal ASL findings showed “fast flow type”. Markedly increased ASL signals were noted at the epileptically activated cortex, having a tight topographical relationship with EL, on ASL with a PLD of 1.5 s, which is decreased on ASL with a PLD of 2.5 s. In all three Group EL− patients, periictal ASL findings showed “gradual flow type”, which is characterized by gradual signal increase of the epileptically activated cortex on ASL with a PLD of 1.5 and 2.5 s. Conclusion We confirmed that ASL hyperperfusion is superior to DWI in the periictal detection of epileptic events. ASL with dual PLD offers the ability to document two types of hemodynamics of periictal hyperperfusion.

Abstract WP355: Evaluation of a Checklist to Identify Early Signs of Hyperperfusion Syndrome After Carotid Endarterectomy

Background and purpose: Hyperperfusion syndrome (HPS) occurs in only 1-3% of patients after carotid endarterectomy (CEA). However, it can cause severe cerebral hemorrhage and may be lethal. Therefo...

Abstract WP12: Mechanical Thrombectomy for Basilar Artery Occlusion

Background and Purpose: Basilar artery occlusion (BAO) is an infrequent cause of stroke, accounting for 1.1% of acute ischemic stroke cases. The natural history of patients with BAO is devastating, with morbidity rates of up to 80%. No previous randomized controlled studies on the efficacy of recanalization therapy have been reported. Methods: In the present single-center study, consecutive BAO patients were treated with mechanical thrombectomy (MT) using the stent retriever and the Penumbra system. Computed tomography perfusion was used for patient evaluation. Clinical outcomes were correlated with demographic, clinical, and radiographic findings. Results: Between October 2011 and March 2017, MT was performed in 37 patients with BAO (mean age 70.1±10.9). Mean baseline National Institutes of Health Stroke Scale was 23±11. Recanalization rate (≧thrombolysis in cerebral infarction 2b) was 100%. Mean onset to recanalization time (OTR) was 226.3±117.8minutes. Favorable outcome at 90 days (modified Rankin scale≦2) was 60.6%. Mortality rate at 90 days was 10.8%. In an univariate analysis, IV rt-PA use, and OTR were significantly associated with favorable outcomes. In a multivariate logistic regression model, IV rt-PA use and lower NIHSS score were significantly related to favorable outcomes. Conclusions: Multimodal endovascular therapy using the Penumbra system and/or stent retriever demonstrated high recanalization rates and improved outcomes in BAO. Both devices were feasible and effective in the treatment of BAO. An approach combining MT with IV thrombolysis provided better recanalization rates and improved clinical outcomes.

Mechanisms Underlying Increased Vascular Smooth Muscle Contractility in the Rabbit Basilar Artery Following Subarachnoid Hemorrhage

Increased vascular contractility plays an important role in the development of cerebral vasospasm following subarachnoid hemorrhage (SAH). Here, we summarize our current knowledge regarding molecular mechanisms that contribute to increased smooth muscle contractility of rabbit basilar artery following SAH. Our studies demonstrated that upregulation of receptor expression, impairment of feedback regulation of receptor activity, and enhancement of myofilament Ca²⁺ sensitization might lead to increased smooth muscle contractility following SAH.