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Hidetoshi Kasuya and Takashi Shimizu

✓ The cerebrospinal fluid (CSF) and plasma levels of the complement components C3a and C4a in 40 patients suffering from subarachnoid hemorrhage (SAH) were quantitated by radioimmunoassay. Serial measurements of the lumbar CSF levels revealed that the C3a and C4a levels were significantly elevated in the initial stage of SAH, but decreased rapidly. Within 48 hours after SAH, the mean C3a and C4a levels in the cisternal, lumbar, and ventricular CSF were significantly higher in patients with delayed ischemic neurological deficits (DIND) than in those without DIND. The serially measured plasma levels of C3a and C4a in patients with DIND were elevated more than in those without DIND, but they did not show a significant change over time. Simultaneous levels of fibrinopeptide A (FPA), an indicator of thrombin activity in CSF, were also measured by radioimmunoassay. There was a significant correlation between CSF-activated complement components and CSF FPA. These results suggest that complement activation occurred in the subarachnoid space soon after SAH, chiefly due to activation of the coagulation system. The higher CSF levels of C3a and C4a in patients with DIND may indicate a relationship between these components and the pathogenesis of cerebral vasospasms.

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Kenichi Hirasawa, Hidetoshi Kasuya, and Tomokatsu Hori

Object. The importance of monitoring circulating blood volume (CBV) during perioperative management is widely recognized in critically ill patients. The purpose of this study was to investigate the change in CBV following craniotomy by using indocyanine-green pulse spectrophotometry.

Methods. Circulating blood volume and plasma hormones related to stress and fluid regulation were measured five times: preoperatively, immediately postoperatively, and 1, 2, and 7 days after craniotomy was performed in 17 patients with a brain tumor or an unruptured aneurysm.

The mean value of CBV preoperatively was 82 ml/kg, which decreased to 64 ml/kg (78%) immediately postoperatively and gradually recovered to 82 ml/kg on Day 7 postsurgery (p = 0.0069). The mean values of adrenaline, noradrenaline, arginine vasopressin, renin, and aldosterone were highest immediately postoperatively. The mean intraoperative balances of water and sodium were 1090 ml and 113 mEq, respectively. Partial correlation coefficients of CBV to noradrenaline and serum sodium during the entire study were −0.430 (p = 0.0036) and 0.418 (p = 0.0048), respectively.

Conclusions. Attention should be paid to decreased CBV following craniotomy, which is caused by the shift of fluid to interstitial spaces due to surgical stress. Hypovolemia can be suspected from a postoperative decrease in serum sodium.

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Takashi Shimizu, Hiroto Kawasaki, Hidetoshi Kasuya, and Koki Kurita

✓ The authors describe the use of stereoscopic short-range magnetic resonance (MR) angiography to diagnose whether and by what means the brainstem is compressed in a case of facial spasm. The MR images were obtained on a 1.5-tesla imaging system with three-dimensional time-of-flight pulse sequence (repetition time 39 msec, echo time 9 msec). Six-source MR images, in which the internal acoustic meatuses were described, were processed using a maximum-intensity projection technique to reconstruct the MR angiograms. The internal acoustic meatuses, the posterior fossa, and the nearby arteries are shown on a single MR angiogram. When two MR angiograms with projection angles 10° apart are placed side by side and observed through polarized glasses, a stereoscopic view of the compressing artery can easily be seen.

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Hidetoshi Kasuya, Bryce K. A. Weir, David M. White, and Kari Stefansson

✓ Release of endothelin-1 from cultured endothelial cells can be induced with oxyhemoglobin (oxyHb). The present study was conducted to explore whether oxyHb affects the release of endothelin-1 and the induction of endothelin-1 messenger ribonucleic acid (mRNA) and to examine the mechanism whereby oxyHb induces endothelin-1 production in cultured vascular smooth-muscle cells as well as in cultured endothelial cells.

Oxyhemoglobin produces concentration-dependent (0.1 to 10 µM) and time-dependent (0 to 24 hours) increases in immunoreactive endothelin-1 in conditioned medium from bovine arterial endothelial cells. Oxyhemoglobin induces immunoreactive endothelin-1 in rat aortic smooth-muscle cells in the same fashion, although the rate is 30-fold less than that of endothelial cells. This promoting effect is much higher than that of other stimulators such as thrombin and phorbol 12-myristate 13-acetate. Northern blot analysis of total RNA from endothelial cells also showed endothelin-1 mRNA induction. Staurosporine, a protein kinase C (PKC) inhibitor inhibited oxyHb-induced endothelin-1 production in both vascular endothelial and smooth-muscle cells, whereas an increase of intracellular cyclic adenosine monophosphate (cAMP) by forskolin or an addition of 8-bromo-cAMP only inhibited this effect in smooth-muscle cells.

These findings suggest that oxyHb-induced endothelin-1 production in endothelial cells is regulated by PKC, and in smooth-muscle cells by both PKC and the cAMP-dependent pathway. The production of endothelin, the most potent vasoconstrictor, in both vascular endothelial and smooth-muscle cells by oxyHb may have significance in the pathogenesis of cerebral vasospasm.

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Yasuhiro Kuroi, Kazufumi Suzuki, and Hidetoshi Kasuya

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Masaaki Yamamoto, Atsuya Akabane, Yuji Matsumaru, Yoshinori Higuchi, Hidetoshi Kasuya, and Yoichi Urakawa

Object

Little information is available on staged Gamma Knife surgery (GKS) with an interval of 3 years or more when used to treat arteriovenous malformations (AVMs) with volumes larger than 10 cm3. The goal of this study was to increase knowledge in this area by reporting the authors' experience.

Methods

The authors describe an institutional review board–approved retrospective study in which they examined databases including information on 250 patients who consecutively underwent GKS for cerebral AVMs during a 16-year period (1988–2004). Among the 250 patients the authors identified 31 patients (12.4%, 15 female and 16 male patients with a mean age of 29 years [range 10–63 years]) in whom 2-stage GKS was intentionally planned at the time of initial treatment because the volume of the AVM nidus was larger than 10 cm3. The most common presentation was bleeding (14 patients), followed by seizures (9 patients), incidental findings (7 patients), and headache with scintillation (1 patient). One patient underwent GKS for the treatment of 2 AVMs simultaneously, and thus 32 AVMs are included in this study. The mean nidus volume was 16.2 cm3 (maximum 55.8 cm3). In all 31 patients, relatively low radiation doses (12–16 Gy directed at the periphery of the lesion) were intentionally used for the first GKS. The second GKS was scheduled for at least 36 months after the first.

Results

Complete nidus obliteration was obtained after the first GKS in 1 patient. To date, 26 patients have undergone a second procedure with a post-GKS mean interval of 41 months (range 24–83 months); 2 other patients refused to undergo the second GKS, and no further treatment was given because of severe morbidity in 1 case and death due to bleeding in the other case. Among the 26 patients who did undergo a second procedure, 3 patients refused follow-up digital subtraction (DS) angiography, another is scheduled for follow-up DS angiography, and 2 patients died, one of bleeding and the other of an unknown cause. The remaining 20 patients underwent follow-up DS angiography. Complete nidus obliteration was confirmed in 13 patients (65.0%) and remarkable nidus shrinkage in the other 7 patients (35.0%). In 2 of these 7 patients, a third GKS achieved complete nidus obliteration. Therefore, the cumulative complete obliteration rate in this series was 76.2% (16 of 21 eligible patients). Seven patients (22.6%) experienced bleeding. The bleeding rates were 9.7%, 16.1%, 16.1%, and 26.1%, respectively, at 1, 2, 5, and 10 years post-GKS. There were 2 deaths and 3 cases of morbidity (persistent coma, mild hemimotor weakness, and hemianopsia in 1 patient each). Hemorrhage did not produce neurological deficits in the other 2 patients. During the mean post-GKS follow-up period of 105 months (range 42–229 months) to date, mild symptomatic GKS-related complications occurred in 2 patients (6.5%); these were classified as Radiation Oncology Group Neurotoxicity Grade 1 in 1 patient and Grade 2 in the other. Among various pre-GKS clinical factors, univariate analysis showed only patient age to impact complications (hazard ratio 0.675, 95% CI 0.306–0.942, p = 0.0085). The rate of complications in the pediatric cases was 33.3%, whereas that in the adolescent and adult cases was 0% (p = 0.0323).

Conclusions

Although a final conclusion awaits further studies and patient follow-up, these results suggest 2-stage GKS to be beneficial even for relatively large AVMs.

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Martin Barth, Claudius Thomé, Peter Schmiedek, Christel Weiss, Hidetoshi Kasuya, and Peter Vajkoczy

Object

The use of nicardipine prolonged-release implants (NPRIs) is associated with a significant improvement in the therapy of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) regarding the occurrence and severity of cerebral vasospasm, new infarcts, and functional outcome (FO). Because quality of life (QOL) measurements more reliably seem to describe the patient's true condition, the present study was conducted to assess FO and QOL 1 year after aneurysm rupture in patients with and without NPRIs.

Methods

From the initial series of 32 patients, 18 were assessed 1 year after aSAH (7 of the control and 11 of the NPRI group). The patients underwent neurological investigation, a structured interview followed by a measurement of QOL (Mini-Mental State Examination [MMSE]; 36-Item Short Form Health Survey [SF-36]; and the Hamilton Depression Rating Scale). There were no intergroup differences in the patient characteristics (that is, localization of aneurysm, initial Hunt and Hess grade, or age).

Results

In addition to the previously reported improvement of the National Institutes of Health Stroke Scale and modified Rankin Scale scores, the NPRI group's Karnofsky Performance Scale and the MMSE scores were markedly to significantly improved (p < 0.05 [Karnofsky Performance Scale] and p = 0.053 [MMSE]). In contrast, anxiety, oblivion, and mild symptoms of depression were equally present in both study groups (p = 0.607 [anxiety]; p = 0.732 [oblivion]; and p = 0.509 [Hamilton Depression Rating Scale]). Furthermore, no intergroup differences were observed in any of the SF-36 domains. The scores in the SF-36 domains of Role-Physical, Vitality, and Role-Emotional were significantly reduced in the NRPI group compared with those observed in an age-matched control population (p < 0.001 [Role-Physical]; p = 0.001 [vitality]; and p = 0.01 [Role-Emotional]). Considering consequent costs, no difference was detectable regarding the duration of in- and outpatient rehabilitation (p = 0.135 and 0.171, respectively) or the Prolo score (p = 0.094).

Conclusions

Despite FO improvement in terms of a lower incidence of cerebral vasospasm, new infarcts, morbidity in the treatment of aSAH in patients with NPRIs, a patient's QOL seems to be related to the severity of the aSAH itself.

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Shinya Watanabe, Masaaki Yamamoto, Takuya Kawabe, Takao Koiso, Tetsuya Yamamoto, Akira Matsumura, and Hidetoshi Kasuya

OBJECTIVE

The aim of this study was to reappraise long-term treatment outcomes of stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs). The authors used a database that included patients who underwent SRS with a unique dose-planning technique, i.e., partial tumor coverage designed to avoid excess irradiation of the facial and cochlear nerves, focusing on tumor control and hearing preservation. Clinical factors associated with post-SRS tumor control and long-term hearing preservation were also analyzed.

METHODS

This institutional review board–approved, retrospective cohort study used the authors' prospectively accumulated database. Among 207 patients who underwent Gamma Knife SRS for VSs between 1990 and 2005, 183 (who were followed up for at least 36 post-SRS months) were studied. The median tumor volume was 2.0 cm3 (range 0.05–26.2 cm3). The median prescribed dose at the tumor periphery was 12.0 Gy (range 8.8–15.0 Gy; 12.0 Gy was used in 171 patients [93%]), whereas tumor portions facing the facial and cochlear nerves were irradiated with 10.0 Gy. As a result, 72%–99% of each tumor was irradiated with the prescribed dose. The mean cochlear doses ranged from 2.3 to 5.7 Gy (median 4.1 Gy).

RESULTS

The median durations of imaging and audiometric follow-up were 114 months (interquartile range 73–144 months) and 59 months (interquartile range 33–109 months), respectively. Tumor shrinkage was documented in 110 (61%), no change in 48 (27%), and enlargement in the other 22 (12%) patients. A further procedure (FP) was required in 15 (8%) patients. Thus, the tumor growth control rate was 88% and the clinical control rate (i.e., no need for an FP) was 92%. The cumulative FP-free rates were 96%, 93%, and 87% at the 60th, 120th, and 180th post-SRS month, respectively. Six (3%) patients experienced facial pain, and 2 developed transient facial palsy. Serviceable hearing was defined as a pure tone audiogram result better than 50 dB. Among the 66 patients with serviceable hearing before SRS who were followed up, hearing acuity was preserved in 23 (35%). Actuarial serviceable hearing preservation rates were 49%, 24%, and 12% at the 60th, 120th, and 180th post-SRS month, respectively. On univariable analysis, only cystic-type tumor (HR 3.36, 95% CI 1.18–9.36; p = 0.02) was shown to have a significantly unfavorable association with FP. Multivariable analysis followed by univariable analysis revealed that higher age (≥ 65 years: HR 2.66, 95% CI 1.16–5.92; p = 0.02), larger tumor volume (≥ 8 cm3: HR 5.36, 95% CI 1.20–17.4; p = 0.03), and higher cochlear dose (mean cochlear dose > 4.2 Gy: HR 2.22, 95% CI 1.07–4.77; p = 0.03) were unfavorable factors for hearing preservation.

CONCLUSIONS

Stereotactic radiosurgery achieved good long-term results in this series. Tumor control was acceptable, and there were few serious complications in patients with small- to medium-sized VSs. Unfortunately, hearing preservation was not satisfactory. However, the longer the observation period, the more important it becomes to compare post-SRS hearing decreases with the natural decline in untreated cases.