Hiroshi Yoneda

Preoperative Prediction of Outcome in 283 Poor-Grade Patients with Subarachnoid Hemorrhage: A Project of the Chugoku-Shikoku Division of the Japan Neurosurgical Society

Background: The management of patients with poor-grade subarachnoid hemorrhage (SAH) continues to be controversial. The objective of this study was to examine predictors of outcome of poor-grade SAH after surgical obliteration of the aneurysm. Methods: The study was performed as a retrospective review of 283 patients with poor-grade SAH who underwent surgical obliteration of the aneurysm at multiple centers in Chugoku and Shikoku, Japan. Results: A favorable outcome at discharge was achieved in 97 of the 283 patients (34.3%). Age (p < 0.001), World Federation of Neurosurgical Societies (WFNS) grade V at admission (p = 0.002), improvement in WFNS grade after admission (p = 0.002), Fisher grade (p = 0.039) and a low-density area (LDA) associated with vasospasm on computed tomography (CT; p < 0.001) showed a significant association with outcome. Further analysis of WFNS grades indicated that most patients who only improved to preoperative grade IV from grade V at admission did not have a favorable outcome. Multivariate analysis identified age (especially of ≧65 years; p < 0.001), WFNS grade V (p < 0.001) and LDA associated with vasospasm on CT (p < 0.001) as predictors of a poor outcome, and improvement in WFNS grade (p = 0.001) as a predictor of a favorable outcome after surgical obliteration of the aneurysm. Conclusions: Advanced age, WFNS grade V, improvement in WFNS grade, and LDA associated with vasospasm on CT were found to be independent predictors of clinical outcome, whereas rebleeding, early aneurysm surgery and treatment modality (surgical clipping or Guglielmi detachable coil embolization) were not independently associated with outcome in patients with poor-grade aneurysm.

Comparison of outer membrane protein genes omp and pmp in the whole genome sequences of Chlamydia pneumoniae isolates from Japan and the United States.

Chlamydia pneumoniae is a widespread pathogen of the respiratory tract that is also associated with atherosclerosis. The whole genome sequence was determined for a Japanese isolate, C. pneumoniae strain J138. The sequence predicted a variety of genes encoding outer membrane proteins (OMPs) including ompA and porB, another 10 predicted omp genes, and 27 pmp genes. All were detected in the whole genome sequence of strain CWL029, a strain isolated and sequenced in the United States. A comparative study of the OMPs of the two strains revealed a nucleotide sequence identity of 89.6%-100% (deduced amino acid sequence identity, 71.1%-100%). The overall genomic organization and location of genes are identical in both strains. Thus, a few unique sequences of the OMPs may be essential for specific attributes that define the differential biology of two C. pneumoniae strains.

Inhibitory Effects of Eicosapentaenoic Acid on Chronic Cerebral Vasospasm after Subarachnoid Hemorrhage: Possible Involvement of a Sphingosylphosphorylcholine-Rho-Kinase Pathway

Background and Purpose: Rho-kinase (ROK)-mediated Ca2+ sensitization of vascular smooth muscle (VSM) contraction plays a pivotal role in cerebral vasospasm (CV). We previously demonstrated that sphingosylphosphorylcholine (SPC) induces Ca2+ sensitization through sequential activation of the Src family protein tyrosine kinases (Src-PTKs) and ROK in vitro, and that Ca2+ sensitization is inhibited by eicosapentaenoic acid (EPA) through the selective inactivation of Src-PTK. In this study, we examined whether SPC induced CV in vivo, and, if it did, whether EPA would inhibit CV, as induced by SPC or in an in vivo model of subarachnoid hemorrhage (SAH). Methods: Changes in the diameter of the canine basilar artery were investigated by angiography after administering SPC into the cisterna magna. Then, Y27632, a specific Rho-kinase inhibitor, or EPA was injected intracisternally and the effects of both agents were investigated. In another experiment using a single-hemorrhage model, Y27632 or EPA was injected on day 7 after SAH and the changes in the diameter of the canine basilar artery were investigated. Results: At cerebrospinal fluid concentrations of 100 and 300 µmol/l, SPC induced severe vasoconstriction (maximum vasoconstriction by SPC (100 µmol/l): 61.8 ± 8.2%), which was markedly reversed by Y27632 (96.3 ± 4.4%) or EPA (92.6 ± 12.8%). SAH caused severe vasospasm on day 7 (67.6 ± 7.8%), which was significantly blocked by Y27632 (95.5 ± 10.6%) or EPA (90.0 ± 4.4%). Conclusions: SPC is a novel mediator of ROK-induced CV in vivo. The inhibition of CV induced by SPC or after SAH by EPA suggests beneficial roles of EPA in the treatment of CV. Our findings are compatible with the notion that the SPC-ROK pathway may be involved in CV.

Multicenter Prospective Cohort Study on Volume Management After Subarachnoid Hemorrhage Hemodynamic Changes According to Severity of Subarachnoid Hemorrhage and Cerebral Vasospasm

Background and Purpose— Systemic circulation management has not been established for patients with poor grade aneurysmal subarachnoid hemorrhage (SAH) or delayed cerebral ischemia (DCI) after SAH. The aims of the study were to examine hemodynamic variables in these patients and to establish treatment strategies. Methods— A multicenter prospective cohort study of hemodynamic variables from days 1 to 14 was performed using a transpulmonary thermodilution system (PiCCO Plus). Parameters were analyzed by Mann–Whitney test. Multivariate analysis was performed to identify parameters involved in onset of DCI. Results— The subjects were 204 patients, including 138 with poor grade SAH (World Federation of Neurological Surgeons grades IV and V) and 52 who developed DCI. The extravascular lung water index, pulmonary vascular permeability index, and systemic vascular resistance index were significantly greater in patients with poor grade SAH compared with those with good grade SAH (World Federation of Neurological Surgeons I–III) on day 2 (P=0.049, P=0.039, and P=0.038). Cardiac index was significantly lower in patients with poor grade SAH on days 1 and 2 (P=0.027 and P=0.011). In patients with DCI, the global end-diastolic volume index was significantly lower than in those without DCI on days 3 to 5 (P=0.0053; P=0.048; and P=0.048). In multivariate analysis, median global end-diastolic volume index, cardiac index, and systemic vascular resistance index at an early stage of SAH (days 3–6) were independently related to onset of DCI (P=0.023, P=0.013, and P=0.003). Conclusions— Patients with poor grade SAH developed heart failure–like afterload mismatch at an early stage, and those with DCI had decreased global end-diastolic volume index (hypovolemia) in the early stage of SAH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: UMIN000003794.

Association of intra- and extradural developmental venous anomalies, so-called venous angioma and sinus pericranii.

IntroductionWe report a case of cerebellar venous angioma and parietal sinus pericranii.DiscussionVenous angioma is classified as a developmental venous anomaly (DVA) because it is not a neoplasm but a variant that develops during embryogenesis. Sinus pericranii should be classified as extradural-type DVA. Although there have been few reports of association between these conditions, both are suspected to have the same pathogenesis, i.e., transient venous hypertension in the late embryonic period influencing venous development.

Does eicosapentaenoic acid (EPA) inhibit cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage

Background –  Cerebral vasospasm following subarachnoid hemorrhage (SAH) is a significant cause of morbidity and mortality and recent studies indicate that Rho‐kinase plays an important role in the occurrence of such cerebral vasospasm. Eicosapentaenoic acid (EPA), an n‐3 polyunsaturated fatty acid, inhibits sphingosylphosphorylcholine (SPC)‐induced Rho‐kinase activation in vitro, so this study examined whether EPA prevented cerebral vasospasm occurrence after SAH in patients.

A proposed definition of symptomatic vasospasm based on treatment of cerebral vasospasm after subarachnoid hemorrhage in Japan: Consensus 2009, a project of the 25 Spasm Symposium.

Background: There is a lack of unified information on diagnosis and treatment of cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) among the hospitals in Japan. Thus, the aim of the study was to define the current practice in this area based on a survey by Japanese neurosurgeons. Methods: A survey on diagnosis and treatment of CV was sent to 414 hospitals each of which performs >100 neurosurgeries annually. Results: Responses were received from 240 hospitals (58.0%). Because accurate criteria for diagnosis of symptomatic vasospasm (SVS) were used in only 33.8% of the hospitals, we proposed a clinical definition of SVS that was approved at the 25th Spasm Symposium (Consensus 2009). This definition is simplified as follows: (1) the presence of neurological worsening; (2) no other identifiable cause of neurological worsening; and (3) confirmation of vasospasm by medical examinations. The results also showed that the Fisher CT scale is used differently for patients with ICH or IVH, with 41.3% of cases with ICH/IVH based on SAH that met Fisher criteria classified into Fisher group 1, 2 or 3, and 46.3% classified into Fisher group 4. There were no major differences in prophylactic therapies of CV and therapy for cerebral ischemia among the hospitals. Endovascular treatment for vasospasm was performed in most hospitals (78.7%); however, the criteria differed among the hospitals: (1) angiographic vasospasm and SVS appeared (37.9%), (2) only when aggressive therapy was ineffective (41.4%). Conclusion: We established a clinical definition of SVS based on the results of this survey (Consensus 2009).

A Prospective, Multicenter, Randomized Study of the Efficacy of Eicosapentaenoic Acid for Cerebral Vasospasm: The EVAS Study

OBJECTIVE The sphingosylphosphorylcholine-Rho-kinase pathway plays an important role in Ca(2+) sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine -Rho-kinase-activated Ca(2+)-sensitization in vitro and in subarachnoid hemorrhage (SAH) models in vivo and has also been shown to inhibit the occurrence of cerebral vasospasm (CIV) after the onset of SAH in a prospective, nonrandomized study. The current prospective, multicenter, randomized study was performed to confirm the preventive effects of EPA on CIV in patients with SAH. METHODS The trial population comprised 162 patients who underwent surgical clipping within 72 hours of the onset of SAH. Of these patients, 81 received 2700 mg/day EPA from the day after surgery until day 30 (EPA group), and 81 did not receive EPA (control group). The primary end point was the occurrence of symptomatic vasospasm (SV) or cerebral infarction caused by CIV. RESULTS The occurrences of SV (15% vs. 30%; P = 0.022) and CIV (7% vs. 21%; P = 0.012) were lower in the EPA group. Multivariate analysis revealed an adjusted odds ratio of 0.39 (95% confidence interval, 0.17-0.89; P = 0.028) for SV inhibition by EPA and 0.27 (95% confidence interval, 0.09-0.72; P = 0.012) for CIV inhibition. CONCLUSIONS These results indicate that oral EPA reduces the frequency of SV and CIV after the onset of aneurysmal SAH.

Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage.

OBJECTIVE Subarachnoid clots play an important role in development of delayed vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to compare clearance of subarachnoid clots using external ventricular drainage (EVD) or lumbar drainage (LD) after Guglielmi detachable coil (GDC) embolization for aneurysmal SAH. METHODS The subjects were 51 treated with GDC coil embolization for aneurysmal Fisher group 3 SAH within 72 h of ictus. Software-based volumetric quantification of the subarachnoid clots was performed on CT scans and the hemoglobin (Hb) level was measured in CSF drained from each catheter. RESULTS Clearance of subarachnoid clots was more rapid in patients treated with LD (n=34) compared to those treated with EVD (n=17). The Hb level in CSF was significantly higher in the LD group on Days 4-5 after onset of SAH (P<0.05), but was higher in the EVD group on Days 8-9. The incidence of symptomatic vasospasm did not differ between the two groups. The rate of occurrence of a new low density area on CT scans was higher in patients treated with EVD, but not significantly higher than the rate in the LD group. CONCLUSION GDC embolization followed by lumbar drainage accelerates the reduction of subarachnoid clots, but EVD may contribute to stasis of hemorrhage within subarachnoid spaces.

Reproducibility of cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose 123I-iodoamphetamine in institutions with different γ-cameras and collimators.

Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. The quantitative SPECT (QSPECT) software package has been developed for standardization of CBF. Using the QSPECT/dual-table autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at rest and after acetazolamide challenge can be evaluated using 123I-iodoamphetamine in a single SPECT session. In this study, we examined the reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using different SPECT models at two facilities. The subjects were nine patients with chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities with use of different γ-cameras and collimators. There were significant correlations for CBF at rest and after acetazolamide challenge measured at the two facilities. The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.