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John W. Peterson, Byung-Duk Kwun, John D. Hackett and Nicholas T. Zervas

✓ The short-term (≤ 72-hour) cerebral vascular reaction to subarachnoid injectates of various specific blood components was determined by angiography in a canine model of cerebral vasospasm. Cell-free subarachnoid clots of autologous plasma in the basal cistern were found to produce no significant reaction of the basilar artery, while whole-blood clots induced a small (15%) chronic constriction after 24 hours. Because the plasma clots were not well retained in the basal cistern, however, small beads (dextran or latex) were added to stabilize them. Injection of beads and plasma led to moderate-to-severe chronic vasoconstriction (35% to 40%) with rapid onset. Control experiments demonstrated that these foreign bodies (beads) alone induced this vascular reaction. Histological examination showed that severe inflammation followed the introduction of subarachnoid beads. The experiments demonstrate that inflammation alone, in the absence of other processes associated with subarachnoid hemorrhage, may induce persistent and severe cerebroarterial constriction and raises the possibility that inflammation in response to subarachnoid blood may play a role in clinical vasospasm.

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Jung-Ho Yun, Do Hoon Kwon, Eun Jung Lee, Do Heui Lee, Jae Sung Ahn and Byung Duk Kwun

New nidi are rarely found adjacent to the resection margin following treatment for an arteriovenous malformation (AVM), especially in adults. In addition, there are no reports in adults of new nidus formation adjacent to the targeted site of an AVM that angiography has verified to be completely obliterated by radiosurgery. The authors present their experience with recurrent AVMs following AVM radiosurgery in 3 patients whose ages were 9 years, 10 years, and 33 years. None of the patients had been treated with embolization before radiosurgery. Two patients had a history of intracerebral hemorrhage before radiosurgery. New lesions developed around the obliterated nidi in all 3 cases. Angiography performed after the first radiosurgery confirmed complete removal of the nidus in all 3 patients, and new nidus formation was detected 31, 132, and 36 months after the initial GKS. The new lesions were also treated by GKS. Occasionally, in patients with recurrent AVMs, such as those described in this paper, long-term clinical and angiographic follow-up may be required, even if complete occlusion is originally shown on angiograms.

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John W. Peterson, Lawrence Roussos, Byung-Duk Kwun, John D. Hackett, Christopher J. Owen and Nicholas T. Zervas

✓ The short-term (≤ 72-hour) reaction to subarachnoid injections of various blood components was determined in a canine model of cerebral vasospasm. Platelet-rich plasma (PRP) formed durable clots in the basal cistern surrounding the basilar artery and provoked no vascular reaction in 72 hours or more. Freshly isolated autologous erythrocytes resuspended in PRP likewise provoked no vasoconstriction in 72 hours, although a second injection of fresh erythrocytes in PRP induced significant reaction, as in the conventional “double subarachnoid hemorrhage (SAH)” canine model. Hemolysate of fresh erythrocytes led to a severe immediate vascular reaction after introduction into the basal cistern using PRP as the carrier/clotting medium, as did the injection of intact erythrocytes incubated ex vivo for 72 hours. Resolution of the initial reaction was rapid for hemolysate, but slow and (depending on hematocrit) incomplete for intact “aged” erythrocytes. In vitro measurements of erythrocyte lysis in these media and histological examination indicate that the production of erythrocyte lysate was responsible for the vascular reaction observed, suggesting that the rate of lysis of erythrocytes in the subarachnoid clot is a major factor in the genesis of vasospasm after SAH.

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Yang Kwon, Sang Ryong Jeon, Jeong Hoon Kim, Jung Kyo Lee, Dong Sook Ra, Dong Joon Lee and Byung Duk Kwun

Object. The authors sought to analyze causes for treatment failure following gamma knife radiosurgery (GKS) for intracranial arteriovenous malformations (AVMs), in cases in which the nidus could still be observed on angiography 3 years postsurgery.

Methods. Four hundred fifteen patients with AVMs were treated with GKS between April 1990 and March 2000. The mean margin dose was 23.6 Gy (range 10–25 Gy), and the mean nidus volume was 5.3 cm3 (range 0.4–41.7 cm3). The KULA treatment planning system and conventional subtraction angiography were used in treatment planning.

One hundred twenty-three of these 415 patients underwent follow-up angiography after GKS. After 3 years the nidus was totally obliterated in 98 patients (80%) and partial obliteration was noted in the remaining 25.

There were several reasons why complete obliteration was not achieved in all cases: inadequate nidus definition in four patients, changes in the size and location of the nidus in five patients due to recanalization after embolization or reexpansion after hematoma reabsorption, a large AVM volume in five patients, a suboptimal radiation dose to the thalamic and basal ganglia in eight patients, and radioresistance in three patients with an intranidal fistula.

Conclusions. The causes of failed GKS for treatment of AVMs seen on 3-year follow-up angiograms include inadequate nidus definition, large nidus volume, suboptimal radiation dose, recanalization/reexpansion, and radioresistance associated with an intranidal fistula.

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Immunological reaction against the aging human subarachnoid erythrocyte

A model for the onset of cerebral vasospasm after subarachnoid hemorrhage

John W. Peterson, Byung-Duk Kwun, Atsushi Teramura, John D. Hackett, Jeffrey A. Morgan, Shigeru Nishizawa, Takao Bun and Nicholas T. Zervas

✓ The role of the aging human erythrocyte in the mechanisms leading to cerebral vasospasm after subarachnoid hemorrhage was investigated using an in vitro model for the environment of the erythrocyte in a subarachnoid blood clot. It has long been suspected that, due to its potent vasoactivity, erythrocyte lysate provides the major vasoconstrictive input to cerebral arteries during vasospasm. Under the model conditions (incubation at 37°C in an artificial cerebrospinal fluid), however, the rate of spontaneous hemolysis was quite slow (about 1%/day), becoming only somewhat more rapid after 4 days' incubation. The rate of hemolysis of aging erythrocytes was dramatically increased (500- to 1000-fold) by the addition of plasma proteins, but only after the erythrocytes had aged 2 to 3 days, or more. The mechanism of age-dependent, plasma-induced hemolysis of originally autologous erythrocytes is shown to involve activation of the plasma complement protein pathway, analogous to the mechanisms of innate immunity which lead to lysis of nonautologous cell types and activate the inflammatory response.

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Jung Cheol Park, Deok Hee Lee, Jae Kyun Kim, Jae Sung Ahn, Byung Duk Kwun, Dae Yoon Kim and Choong Gon Choi


The incidence and risk factors of microembolic lesions on MR diffusion-weighted imaging (DWI) were analyzed after the endovascular coiling of unruptured intracranial aneurysms (UIAs).


Data obtained from 271 consecutive patients (70 men and 201 women; median age 57 years; range 23–79 years) who presented with UIA for coil embolization between July 2011 and June 2013 were analyzed. Two independent reviewers examined the DWI and apparent diffusion coefficient maps obtained the following day for the presence of restrictive diffusion spots and counted the number of spots. Multivariate analysis was then performed to identify independent risk factors for developing microembolism following the coiling of an aneurysm.


Microembolic lesions were noted in 101 of 271 patients (37.3%). The results of the multivariate analysis showed that the following factors significantly influenced the risk for microembolism: age, diabetes, previous history of ischemic stroke, high-signal FLAIR lesions in the white matter, multiple aneurysms, and the insertion of an Enterprise stent (all ORs > 1.0 and all p values < 0.05). Previously known risk factors such as prolonged procedure duration, aneurysm size, and decreased antiplatelet function did not show any significant influence.


The incidence of microembolism after endovascular coiling of UIA was not low. Lesions occurred more frequently in patients with vascular status associated with old age, diabetes, and previous stroke. Aneurysm multiplicity and the type of stent used for treatment also influenced lesion occurrence.

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Yang Kwon, Jae Sung Ahn, Sang Ryong Jeon, Jeong Hoon Kim, Chang Jin Kim, Jung Kyo Lee, Byung Duk Kwun, Do Hee Lee and Sun Young Kim

Object. The authors evaluated whether gamma knife radiosurgery (GKS) could be a causative factor in intratumoral bleeding in meningiomas.

Methods. Gamma knife radiosurgery was used in the treatment of 173 meningiomas during a 10-year period. Four patients suffered post-GKS intratumoral hemorrhage. The course in these patients was reviewed.

Four of 173 patients suffered an intratumoral hemorrhage during a follow-up period of 1 to 8 years. The risk of intratumoral bleeding after GKS for meningioma was 2.3%. Intracystic hemorrhage occurred in two patients 1 and 5 years, respectively, after radiosurgery. In the other two cases intratumoral bleeding occurred 2 and 8 years, respectively, after radiosurgery. Histological examination in three cases found no specific findings related to the postradiosurgical changes.

Conclusions. Because the reported risk of spontaneous intratumoral bleeding in meningiomas is 1.3 to 2.7%, the incidence in this series was not unduly high. Radiosurgery itself could not be shown to be a significant factor in the development of the intratumoral bleeding.

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Jaewoo Chung, Wonhyoung Park, Seok Ho Hong, Jung Cheol Park, Jae Sung Ahn, Byung Duk Kwun, Sang-Ahm Lee, Sung-Hoon Kim and Ji-Ye Jeon


Somatosensory and motor evoked potentials (SEPs and MEPs) are often used to prevent ischemic complications during aneurysm surgeries. However, surgeons often encounter cases with suspicious false-positive and false-negative results from intraoperative evoked potential (EP) monitoring, but the incidence and possible causes for these results are not well established. The aim of this study was to investigate the efficacy and reliability of EP monitoring in the microsurgical treatment of intracranial aneurysms by evaluating false-positive and false-negative cases.


From January 2012 to April 2016, 1514 patients underwent surgery for unruptured intracranial aneurysms (UIAs) with EP monitoring at the authors’ institution. An EP amplitude decrease of 50% or greater compared with the baseline amplitude was defined as a significant EP change. Correlations between immediate postoperative motor weakness and EP monitoring results were retrospectively reviewed. The authors calculated the sensitivity, specificity, and positive and negative predictive values of intraoperative MEP monitoring, as well as the incidence of false-positive and false-negative results.


Eighteen (1.19%) of the 1514 patients had a symptomatic infarction, and 4 (0.26%) had a symptomatic hemorrhage. A total of 15 patients showed motor weakness, with the weakness detected on the immediate postoperative motor function test in 10 of these cases. Fifteen false-positive cases (0.99%) and 8 false-negative cases (0.53%) were reported. Therefore, MEP during UIA surgery resulted in a sensitivity of 0.10, specificity of 0.94, positive predictive value of 0.01, and negative predictive value of 0.99.


Intraoperative EP monitoring has high specificity and negative predictive value. Both false-positive and false-negative findings were present. However, it is likely that a more meticulously designed protocol will make EP monitoring a better surrogate indicator of possible ischemic neurological deficits.

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Yang Kwon, Jun Seok Bae, Jae Myung Kim, Do Hee Lee, Soon Young Kim, Jae Sung Ahn, Jeong Hoon Kim, Chang Jin Kim, Byung Duk Kwun and Jung Kyo Lee

✓ Tumors involving the optic nerve (optic glioma, optic nerve sheath meningioma) are benign but difficult to treat. Gamma knife surgery (GKS) may be a useful treatment. The authors present data obtained in three such cases and record the effects of GKS.