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Atsuhiro Nakagawa, Miki Fujimura, Tatsuhiko Arafune, Ichiro Sakuma and Teiji Tominaga


Surgical revascularization for moyamoya disease prevents cerebral ischemic attacks by improving cerebral blood flow (CBF). Symptomatic cerebral hyperperfusion is a potential complication of this procedure, but its treatment is contradictory to that for ischemia. Because intraoperative techniques to detect hyperperfusion are still lacking, the authors performed intraoperative infrared monitoring in moyamoya disease using a novel infrared imaging system.


During superficial temporal artery–middle cerebral artery anastomosis in 25 patients (26 hemispheres) with moyamoya disease, the authors monitored the brain surface temperature intraoperatively with the IRIS-V infrared imaging system. The average gradation value change (indicating temperature change) was calculated using commercial software. Magnetic resonance imaging, MR angiography, and N-isopropyl-p-[123I]iodoamphetamine SPECT studies were performed routinely before and within 10 days after surgery.


Patency of bypass, detailed local hemodynamics, and changes in cortical surface temperature around the anastomosis site were well recognized by the IRIS-V infrared imaging system in all cases. In the present study, 10 patients suffered transient neurological symptoms accompanied by an increase in CBF around the anastomosis site, recognized as symptomatic hyperperfusion. The increase in temperature was significantly higher in these patients. Intensive blood pressure control was undertaken, and free-radical scavengers were administered. No patient in the present study suffered a permanent neurological deficit.


Although the present method does not directly monitor surface CBF, temperature rise around the anastomosis site during surgery might be an indicator of postoperative hyperperfusion. Prospective evaluation with a larger number of patients is necessary to validate this technique.

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Atsuhiro Nakagawa, Ching-Chan Su, Kiyotaka Sato and Reizo Shirane

Object. Circulating blood volume (cBV) is reported to decrease in patients who suffer a subarachnoid hemorrhage (SAH), but little is known about the correlation between changes in cBV, and patient clinical condition and time course after SAH, especially during the very acute stage. To determine appropriate management of patients with SAH, the authors measured cBV by using pulse spectrophotometry immediately after patient admission. They also evaluated whether the timing of surgery influenced changes in cBV.

Methods.Circulating blood volume was measured in a total of 73 patients who were divided into the following three groups: Group A (very acute SAH) consisted of 14 SAH cases, Group B (acute SAH) included 34 SAH cases, and Group C (controls) included 25 other neurosurgical cases. All patients in Group A underwent aneurysm clipping within 6 hours after onset of SAH, whereas all patients in Group B underwent aneurysm clipping within 72 hours after onset. Hypervolemic therapy was not performed in patients with SAH.

Before surgery, cBV was significantly lower in patients in Group B than in those in Group C, but there was no significant difference in this parameter when comparing Groups A and C. Although there was a transient drop in cBV in Group B patients for at least 3 days after surgery, there was no significant change in cBV in Group A patients during the study period. None of the Group A patients suffered from symptomatic vasospasm; however, four Group B patients did experience symptomatic vasospasm.

Conclusions. The authors assert that normovolemic fluid management is appropriate for patients who undergo surgery during the very acute stage of SAH, whereas a relatively hypervolemic therapy is necessary for 3 to 5 days after operation to prevent early hypovolemia in patients who undergo surgery during the acute stage of SAH.

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Atsuhiro Nakagawa, Yasuko Kusaka, Takayuki Hirano, Tsutomu Saito, Reizo Shirane, Kazuyoshi Takayama and Takashi Yoshimoto

Object. Shock waves have not previously been used as a treatment modality for lesions in the brain and skull because of the lack of a suitable shock wave source and concerns about safety. Therefore, the authors have performed experiments aimed at developing both a new, compact shock wave generator with a holmium:yttrium-aluminum-garnet (Ho:YAG) laser and a safe method for exposing the surface of the brain to these shock waves.

Methods. Twenty male Sprague—Dawley rats were used in this study. In 10 rats, a single shock wave was delivered directly to the brain, whereas the protective effect of inserting a 0.7-mm-thick expanded polytetrafluoroethylene (ePTFE) dural substitute between the dura mater and skull before applying the shock wave was investigated in the other 10 rats. Visualizations on shadowgraphy along with pressure measurements were obtained to confirm that the shock wave generator was capable of conveying waves in a limited volume without harmful effects to the target. The attenuation rates of shock waves administered through a 0.7-mm-thick ePTFE dural substitute and a surgical cottonoid were measured to determine which of these materials was suitable for avoiding propagation of the shock wave beyond the target.

Conclusions. Using the shock wave generator with the Ho:YAG laser, a localized shock wave (with a maximum overpressure of 50 bar) can be generated from a small device (external diameter 15 mm, weight 20 g). The placement of a 0.7-mm-thick ePTFE dural substitute over the dura mater reduces the overpressure of the shock wave by 96% and eliminates damage to surrounding tissue in the rat brain. These findings indicate possibilities for applying shock waves in various neurosurgical treatments such as cranioplasty, local drug delivery, embolysis, and pain management.

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Kaoruko Kato, Miki Fujimura, Atsuhiro Nakagawa, Atsushi Saito, Tomohiro Ohki, Kazuyoshi Takayama and Teiji Tominaga


Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave–induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis.


Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at over-pressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave–induced brain injury.

High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons.


The threshold for shock wave–induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.

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Tomohiro Kawaguchi, Atsuhiro Nakagawa, Toshiki Endo, Miki Fujimura, Yukihiko Sonoda and Teiji Tominaga


Neuroendoscopic surgery allows minimally invasive surgery, but lacks effective methods to control bleeding. Water jet dissection with continuous flow has been used in liver and kidney surgery since the 1980s, and is effective for tissue manipulation with vascular preservation, but involves some potential risks, such as elevation of intracranial pressure during application in the ventricles. The authors previously reported the efficacy of the actuator-driven pulsed water jet device (ADPJ) to dissect soft tissue with vascular preservation in microscopic neurosurgery. This feasibility study investigated the use of the ADPJ to reduce the amount of water usage, leading to more safety with sustained efficacy.


A small-diameter pulsed water jet device was developed for use with the flexible neuroendoscope. To identify the optimal conditions for the water jet, the flow rate, water pressure, and distance between the nozzle and target were analyzed in an in vitro study by using a gelatin brain phantom. A ventricle model was used to monitor the internal pressure and temperature. For ex vivo experiments the porcine brain was harvested and ventricle walls were exposed, and subsequently immersed into physiological saline. For in vivo experiments the cortex was microsurgically resected to make the small cortico-ventricle window, and then the endoscope was introduced to dissect ventricle walls.


In the in vitro experiments, water pressure was approximately 6.5 bar at 0.5 mm from the ADPJ nozzle and was maintained at 1 mm, but dropped rapidly toward 50% at 2 mm, and became 10% at 3.5 mm. The ADPJ required less water to achieve the same dissection depth compared with the continuous-flow water jet. With the ventricle model, the internal pressure and temperature were well controlled at the baseline, with open water drainage. These results indicated that the ADPJ can be safely applied within the ventricles. The ADPJ was introduced into a flexible endoscope and the ventricle walls were dissected in both the ex vivo and in vivo conditions. The ventricle wall was dissected without obscuring the view, and the vascular structures were anatomically preserved under direct application. Histological examination revealed that both the vessels on the ventricle wall and the fine vessels in the parenchyma were preserved.


The ADPJ can safely and effectively dissect the ventricle wall, with vascular preservation in immersed conditions. To achieve the optimal result of tissue dissection with minimal surgical risk, the ADPJ is a potential device for neuroendoscopic surgery of the ventricles.

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Taro Nimura, Keiichiro Yamaguchi, Tadashi Ando, Satoshi Shibuya, Takanori Oikawa, Atsuhiro Nakagawa, Reizo Shirane, Masatoshi Itoh and Teiji Tominaga

Object. The “wearing-off” phenomenon often hampers the treatment of Parkinson disease (PD). Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to ameliorate the wearing-off phenomenon, the mechanism by which it does this remains unclear. As part of an inquiry into the mechanism of STN DBS, the authors measured synaptic dopamine levels in the striatum by performing positron emission tomography (PET) with [11C]raclopride.

Methods. Three patients with PD who were experiencing the wearing-off phenomenon underwent PET scanning before and after DBS of the STN. The clinical features in these patients were evaluated by applying the Hoehn and Yahr, United Parkinson's Disease Rating, and Schwab and England Activities of Daily Living Scales. Before and after surgery, PET scans were obtained using [11C]raclopride prior to and 1 hour following an oral administration of levodopa. Regions of interest for the [11C]raclopride binding potential (RacloBP) were set in the bilateral putamen and the caudate nucleus.

All clinical scores were dramatically improved postoperatively. Deep brain stimulation of the STN reduced the baseline RacloBP in both the putamen and caudate nucleus, but the differences between the pre- and postoperative levels were insignificant. Before DBS of the STN, the levodopa administration significantly reduced RacloBP in the putamen (p < 0.0001). Postoperatively the drug-induced reduction in RacloBP became statistically insignificant. The drug-induced increase in synaptic dopamine concentrations in the putamen preoperatively was estimated to be approximately four times higher than that after surgery (p < 0.01). The drug-induced RacloBP change in the caudate nucleus was similar to that in the putamen, although the magnitude of the change was lower (p < 0.005). The drug-induced increase in the caudate nucleus was also reduced postoperatively (p < 0.05).

Conclusions. Deep brain stimulation of the STN induces the stabilization of synaptic dopamine concentrations in the striatum and may attribute to the alleviation of levodopa-related motor fluctuations.

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Atsuhiro Nakagawa, Takayuki Hirano, Hidefumi Jokura, Hiroshi Uenohara, Tomohiro Ohki, Tokitada Hashimoto, Viren Menezes, Yasuhiko Sato, Yasuko Kusaka, Hideki Ohyama, Tsutomu Saito, Kazuyoshi Takayama, Reizo Shirane and Teiji Tominaga

Object. A pressure-driven continuous jet of water has been reported to be a feasible tool for neuroendoscopic dissection owing to its superiority at selective tissue dissection in the absence of thermal effects. With respect to a safe, accurate dissection, however, continuous water flow may not be suitable for intraventricular use. The authors performed experiments aimed at solving problems associated with continuous flow by using a pulsed holmium:yttrium-aluminum-garnet (Ho:YAG) laser-induced liquid jet (LILJ). They present this candidate neuroendoscopic LILJ dissection system, having examined its mechanical characteristics and evaluated its controllability both in a tissue phantom and in a rabbit cadaveric ventricle wall.

Methods. The LILJ generator was incorporated into the tip of a No. 4 French catheter so that the LILJ could be delivered via a neuroendoscope. Briefly, the LILJ was generated by irradiating an internally supplied column of physiological saline with a pulsed Ho:YAG laser (pulse duration time 350 µsec; laser energy 250–700 mJ/pulse) within a No. 4 French catheter (internal diameter 1 mm) and ejecting it from a metal nozzle (internal diameter 100 µm). The Ho:YAG laser energy pulses were conveyed by an optical fiber (core diameter 400 µm) at 3 Hz, whereas physiological saline (4°C) was supplied at a rate of 40 ml/hour. The mechanical characteristics of the pulsed LILJ were investigated using high-speed photography and pressure measurements; thermal effects and controllability were analyzed using an artificial tissue model (10% gelatin of 1 mm thickness). Finally, the ventricle wall of a rabbit cadaver was dissected using the LILJ.

Jet pressure increased in accordance with laser energy from 0.1 to 2 bar; this translated into a penetration depth of 0.08 to 0.9 mm per shot in the ventricle wall of the rabbit cadaver. The gelatin phantom could be cut into the desired shape without significant thermal effects and in the intended manner, with a good surgical view.

Conclusions. The present results show that the pulsed LILJ has the potential to become a safe and reliable dissecting method for endoscopic procedures.

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Daddy Mata-Mbemba, Shunji Mugikura, Atsuhiro Nakagawa, Takaki Murata, Kiyoshi Ishii, Shigeki Kushimoto, Teiji Tominaga, Shoki Takahashi and Kei Takase


The objective of this study was to test the hypothesis that midline (interhemispheric or perimesencephalic) traumatic subarachnoid hemorrhage (tSAH) on initial CT may implicate the same shearing mechanism that underlies severe diffuse axonal injury (DAI).


The authors enrolled 270 consecutive patients (mean age [± SD] 43 ± 23.3 years) with a history of head trauma who had undergone initial CT within 24 hours and brain MRI within 30 days. Six initial CT findings, including intraventricular hemorrhage (IVH) and tSAH, were used as candidate predictors of DAI. The presence of tSAH was determined at the cerebral convexities, sylvian fissures, sylvian vallecula, cerebellar folia, interhemispheric fissure, and perimesencephalic cisterns. Following MRI, patients were divided into negative and positive DAI groups, and were assigned to a DAI stage: 1) stage 0, negative DAI; 2) stage 1, DAI in lobar white matter or cerebellum; 3) stage 2, DAI involving the corpus callosum; and 4) stage 3, DAI involving the brainstem. Glasgow Outcome Scale–Extended (GOSE) scores were obtained in 232 patients.


Of 270 patients, 77 (28.5%) had DAI; tSAH and IVH were independently associated with DAI (p < 0.05). Of tSAH locations, midline tSAH was independently associated with both overall DAI and DAI stage 2 or 3 (severe DAI; p < 0.05). The midline tSAH on initial CT had sensitivity of 60.8%, specificity of 81.7%, and positive and negative predictive values of 43.7% and 89.9%, respectively, for severe DAI. When adjusted for admission Glasgow Coma Score, the midline tSAH independently predicted poor GOSE score at both hospital discharge and after 6 months.


Midline tSAH could implicate the same shearing mechanism that underlies severe DAI, for which midline tSAH on initial CT is a probable surrogate.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010