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Dong Gyu Kim, Chul-Kee Park and Sun Ha Paek

✓ Bo Sung Sim (1924–2001) stands as a prominent figure in the history of Korean neurosurgery. His devoted contributions have led to the fruitful development of modern neurosurgery in Korea. Sim practiced advanced neurosurgical techniques, undertook basic research, was passionate about education in the early years of neurosurgery in Korea, and played an essential role in founding the Korean Neurosurgical Society. Sim was a true neurosurgeon—a teacher, a scientist, and a superb pioneer in Korean neurosurgery.

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Xiao-Fei Hou, Dong-Wei Fan, Chui-Guo Sun and Zhong-Qiang Chen

Object

The primary object of this investigation was to study recombinant human bone morphogenetic protein–2 (rhBMP-2)–induced ossification of the ligamentum flavum and associated histone H3 modification in a rat model. In an additional set of studies the authors investigated spinal cord and behavioral changes in the same model.

Methods

The authors report on 2 separate sets of studies. A total of 90 rats were used for the 2 sets of studies (45 each); in each study, a lyophilized rhBMP-2 and collagen mixture (20 μg rhBMP-2 and 200 μl collagen) was implanted in the lumbar extradural space in 18 rats; another 18 animals were used for a sham-operation control group and underwent implantation of lyophilized collagen without rhBMP-2 at the same level; an additional 9 animals were used as untreated controls. Lumbar spinal samples were harvested from the rhBMP-2 groups and the shamoperation control groups at 1 week, 3 weeks, and 9 weeks after the operation. Samples were also obtained from untreated controls at the same time points. All samples were scanned using micro-CT and then made into paraffinembedded sections. The sections from the first set of 45 rats were stained using elastica van Gieson and toluidine blue, and the expression of histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) was detected by immunohistochemistry. In the second set of studies, hindlimb motor function was assessed at 1 week, 3 weeks, and 9 weeks after surgery. After behavioral evaluation, samples were harvested, scanned using micro-CT, and then made into paraffin-embedded sections. The sections were stained using Luxol fast blue. The expression of NeuN was also detected using immunohistochemistry.

Results

Ossification was seen in the rhBMP-2 group from 1 week after insertion, and the volume of ossified mass increased at 3 and 9 weeks. There was no ossification seen in the sham-surgery and normal controls. The pathological changes of ossification involved ligament degeneration, cartilage formation, and, finally, bone replacement. Spinal cord evaluation showed a significant decrease in white matter content and number of neurons at 9 weeks after operation in the rhBMP-2–treated group (compared with findings in the sham-surgery and control groups as well as findings at the earlier time points in the rhBMP-2 group).

Using immunohistochemical staining, histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) all were found to be expressed in the fibrocartilage area of the rat ossified ligamentum flavum samples (rhBMP2 group).

Conclusions

This rhBMP-2–induced OLF is a typical endochondral ossification, which is similar to clinical OLF. The compressed spinal cord around the ossification site showed signs of a chronic degenerative process. Histone H3 modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) may play an important role in OLF.

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Youngseok Kwak, Wonsoo Son, Yong-Sun Kim, Jaechan Park and Dong-Hun Kang

OBJECTIVE

The authors evaluated the sensitivity and accuracy of MRA in identifying the shape of small-sized unruptured intracranial aneurysms.

METHODS

Small (< 7 mm) unruptured intracranial aneurysms initially detected by MRA and confirmed by DSA between January 2017 and December 2018 were morphologically reviewed by neuroradiologists. Regularity or irregularity of aneurysm shape was analyzed by two independent reviewers using MRA without DSA results. DSA findings served as the reference standard for aneurysm shape. Irregular shape, which in small aneurysms is associated with a higher likelihood of rupture, was defined as positive, and MRA sensitivity, specificity, and accuracy were determined by using evaluations based on location, size, and MRA magnetic strength (1.5T vs 3T MRA). Multivariate analysis was performed to determine risk factors for false-negative MRA results for irregularly shaped aneurysms.

RESULTS

In total, 652 unruptured intracranial aneurysms in 530 patients were reviewed for this study. For detecting aneurysm shape irregularity, the overall MRA sensitivity was 60.4% for reviewer 1 and 60.9% for reviewer 2. Anterior cerebral artery aneurysms had the lowest sensitivity for location (36.7% for reviewer 1, 46.9% for reviewer 2); aneurysms sized < 3 mm had the lowest sensitivity for size (26.7% for both reviewers); and 1.5T MRA had lower sensitivity and accuracy than 3T MRA. In multivariate analysis, location, size, and magnetic strength of MRA were independent risk factors for false-negative MRA results for irregularly shaped aneurysms.

CONCLUSIONS

MRA had a low sensitivity for detecting the irregular shape of small intracranial aneurysms. In particular, anterior cerebral artery location, aneurysm size < 3 mm, and detection with 1.5T MRA were associated with a higher risk of irregularly shaped aneurysms being misjudged as regular.

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Wilson P. Daugherty, Joseph E. Levasseur, Dong Sun, Gaylan L. Rockswold and M. Ross Bullock

Object. In the current study, the authors examined the effects of hyperbaric O2 (HBO) following fluid-percussion brain injury and its implications on brain tissue oxygenation (PO2) and O2 consumption (VO2) and mitochondrial function (redox potential).

Methods. Cerebral tissue PO2 was measured following induction of a lateral fluid-percussion brain injury in rats. Hyperbaric O2 treatment (100% O2 at 1.5 ata) significantly increased brain tissue PO2 in both injured and sham-injured animals. For VO2 and redox potential experiments, animals were treated using 30% O2 or HBO therapy for 1 or 4 hours (that is, 4 hours 30% O2 or 1 hour HBO and 3 hours 100% O2). Microrespirometer measurements of VO2 demonstrated significant increases following HBO treatment in both injured and sham-injured animals when compared with animals that underwent 30% O2 treatment. Mitochondrial redox potential, as measured by Alamar blue fluorescence, demonstrated injury-induced reductions at 1 hour postinjury. These reductions were partially reversed at 4 hours postinjury in animals treated with 30% O2 and completely reversed at 4 hours postinjury in animals on HBO therapy when compared with animals treated for only 1 hour.

Conclusions. Analysis of data in the current study demonstrates that HBO significantly increases brain tissue PO2 after injury. Nonetheless, treatment with HBO was insufficient to overcome injury-induced reductions in mitochondrial redox potential at 1 hour postinjury but was able to restore redox potential by 4 hours postinjury. Furthermore, HBO induced an increase in VO2 in both injured and sham-injured animals. Taken together, these data demonstrate that mitochondrial function is depressed by injury and that the recovery of aerobic metabolic function may be enhanced by treatment with HBO.

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Jaechan Park, Hyunjin Woo, Dong-Hun Kang, Yong-Sun Kim, Min Young Kim, Im Hee Shin and Sang Gyu Kwak

OBJECT

While the incidence of a recurrent hemorrhage is highest within 24 hours of subarachnoid hemorrhage (SAH) and increases with the severity of the clinical grade, a recurrent hemorrhage can occur anytime after the initial SAH in patients with both good and poor clinical grades. Therefore, the authors adopted a 24-hour-a-day, formal protocol, emergency treatment strategy for patients with ruptured aneurysms to secure the aneurysms as early as possible. The incidences of in-hospital rebleeding and clinical outcomes were investigated and compared with those from previous years when broadly defined early treatment was used (< 3 days of SAH).

METHODS

During an 11-year period, a total of 1224 patients with a ruptured aneurysm were managed using a strategy of broadly defined early treatment between 2001 and 2004 (Period B, n = 423), a mixture of early or emergency treatment between 2005 and 2007, and a formal emergency treatment protocol between 2008 and 2011 (Period A, n = 442). Propensity score matching was used to adjust the differences in age, sex, modified Fisher grade, World Federation of Neurosurgical Societies (WFNS) clinical grade at admission, size and location of a ruptured aneurysm, treatment modality (clip placement vs coil embolization), and time interval from SAH to admission between the two time periods. The matched cases were allotted to Group A (n = 280) in Period A and Group B (n = 296) in Period B and then compared.

RESULTS

During Period A under the formal emergency treatment protocol strategy, the catheter angiogram, endovascular coiling, and surgical clip placement were started at a median time from admission of 2.0 hours, 2.9 hours, and 3.1 hours, respectively. After propensity score matching, Group A showed a significantly reduced incidence of in-hospital rebleeding (2.1% vs 7.4%, p = 0.003) and a higher proportion of patients with a favorable clinical outcome (modified Rankin Scale score 0–3) at 1 month (87.9% vs 79.7%, respectively; p = 0.008). In particular, the patients with good WFNS grades in Group A experienced significantly less in-hospital rebleeding (1.7% vs 5.7%, respectively; p = 0.018) and better clinical outcomes (1-month mRS score of 0–3: 93.8% vs 87.7%, respectively; p = 0.021) than the patients with good WFNS grades in Group B.

CONCLUSIONS

Patients with ruptured aneurysms may benefit from a strategy of emergency application of surgical clip placement or endovascular coiling due to the reduced incidence of recurrent bleeding and improved clinical outcomes.

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Kyu-Won Shim, Sun-Young Joo, Se-Hoon Kim, Joong-Uhn Choi and Dong-Seok Kim

Object

Medulloblastoma is the most common malignant neuroepithelial tumor found in children. Several reports have described efforts to identify the prognostic significance of various patterns of pathological and immunohistochemical features in medulloblastoma, but the published data appear to be controversial. The authors therefore attempted to demonstrate these prognostic factors convincingly in a retrospective study performed in patients with medulloblastoma.

Methods

The data used were obtained in 58 patients with medulloblastoma who were > 3 years of age and in whom > 1 year of follow-up was available after the maximal resection, craniospinal irradiation, and chemotherapy treatments. These assessments were performed to compare the immunohistochemical features to cellular differentiation, the proliferation index (PI), the apoptotic index (AI), and oncogenesis revealed by TrkC and c-erbB-3. In addition, the authors tried to determine the prognostic utility of these results in this tumor category.

Results

There was no statistically significant correlation between the prognosis and the degree of cell differentiation, but a positive correlation was noted between the PI and the AI in a tumor mass. The number of cases with a PI > 10% was significantly greater in the group of tumors in patients with recurrent medulloblastoma. A close association between the PI as a continuous variable and the progression-free and overall survival was also found. Most importantly, the PI is the only significant prognostic factor for the overall survival of patients with medulloblastoma.

Conclusions

Therefore, the authors suggest that the PI is directly linked to the prognostic factor for medulloblastoma and that immunohistochemical staining is a potentially powerful tool for predicting the prognosis of patients with medulloblastoma.

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Ji Hoon Phi, Sun Ha Paek, Hyun-Tai Chung, Sang Soon Jeong, Chul-Kee Park, Hee-Won Jung and Dong Gyu Kim

Object

The current study was undertaken to evaluate the tumor control rate and functional outcome after Gamma Knife surgery (GKS) in patients with a trigeminal schwannoma. The conditions associated with the development of cranial neuropathies after radiosurgery were scrutinized.

Methods

The authors reviewed the clinical records and radiological data in 22 consecutive patients who received GKS for a trigeminal schwannoma. The median tumor volume was 4.1 ml (0.2–12.0 ml), and the mean tumor margin dose was 13.3 ± 1.3 Gy at an isodose line of 49.9 ± 0.6% (mean ± standard deviation). The median clinical follow-up period was 46 months (range 24–89 months), and the median length of imaging follow-up was 37 months (range 24–79 months).

Results

Tumor growth control was achieved in 21 (95%) of the 22 patients. Facial pain responded best to radio-surgery, with two thirds of patients showing improvement. However, only one third of patients with facial hypesthesia improved. Six patients (27%) experienced new or worsening cranial neuropathies after GKS. Ten patients (46%) showed tumor expansion after radiosurgery, and nine of these also showed central enhancement loss. Loss of central enhancement, tumor expansion, and a tumor in a cavernous sinus were found to be significantly related to the emergence of cranial neuropathies.

Conclusions

The use of GKS to treat trigeminal schwannoma resulted in a high rate of tumor control and functional improvement. Cranial neuropathies are bothersome complications of radiosurgery, and tumor expansion in a cavernous sinus after radiosurgery appears to be the proximate cause of the complication. Loss of central enhancement could be used as a warning sign of cranial neuropathies, and for this vigilant patient monitoring is required.

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Jin Wook Kim, Hee-Won Jung, Yong Hwy Kim, Chul-Kee Park, Hyun-Tai Chung, Sun Ha Paek, Dong Gyu Kim and Sang Hyung Lee

OBJECTIVE

A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.

METHODS

Ninety-two patients with petroclival meningiomas were treated surgically at the authors’ institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1–368 months) and 105 months (range 1–348 months), respectively.

RESULTS

A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.

CONCLUSIONS

The authors’ preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

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Sang-Hoon Yoon, Sun Ha Paek, Sung-Hye Park, Dong Gyu Kim and Hee-Won Jung

✓Primary skeletal non-Hodgkin lymphoma is rare. The authors report a case of a small lymphocytic B-cell lymphoma of the skull occurring in a 53-year-old man who presented with right-hand apraxia. Initial computed tomography and magnetic resonance imaging revealed a hematoma-mimicking lesion in the left frontoparietal subdural area. A frontotemporoparietal craniectomy and biopsy procedure yielded a diagnosis of small lymphocytic B-cell lymphoma, with a metastatic nodule in the retrobulbar area. Three years after undergoing radiation therapy and surgery, the patient has shown neurological improvement without systemic dissemination of the malignancy. The lesion in this case was misdiagnosed as a subdural hematoma, and shows the importance of including lymphoma in the differential diagnosis of subdural mass lesions.

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Dae Kyu Lee, Hee-Won Jung, Dong Gyu Kim, Sun Ha Paek, Ho-Shin Gwak and Gheeyoung Choe

✓ The authors present a case of postoperative spinal seeding of papillary craniopharyngioma. This 27-year-old man who had previously undergone subtotal removal of a suprasellar craniopharyngioma was admitted because of low-back and right leg pain. Results of neurological examination showed a limitation in straight-leg raising in the right side with no sensorimotor changes. Magnetic resonance imaging of the lumbar spine demonstrated multiple enhanced intradural extramedullary masses causing spinal cord compression. Pathological examination of the tumor tissue obtained via laminectomy revealed papillary craniopharyngioma, which had the same histological features as those of the previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have been reported; however, the authors believe that this is the first published report of the spinal seeding of craniopharyngioma.