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Jung-Hee Lee, Ki-Tack Kim, Kyung-Soo Suk, Sang-Hun Lee, Bi-O Jeong, Hyun-Seok Oh, Chul-Hee Lee and Myung-Seo Kim

Intraspinal cystic lesions with different pathogeneses have been reported to cause neurological deficits; however, no one has focused on the intraspinal extradural cysts that develop after osteoporotic compression fracture. The reported case features a 66-year-old woman presenting with progressive neurological deficit, back pain, and no history of additional trauma after undergoing conservative treatment for an osteoporotic fracture of L-1. The authors present serial radiographs and MR images demonstrating an epidural cyst successfully treated via a single posterior approach. This appears to be the first such case reported in the literature.

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Yun-Sik Dho, Young Jae Kim, Kwang Gi Kim, Sung Hwan Hwang, Kyung Hyun Kim, Jin Wook Kim, Yong Hwy Kim, Seung Hong Choi and Chul-Kee Park

OBJECTIVE

The aim of this study was to analyze the positional effect of MRI on the accuracy of neuronavigational localization for posterior fossa (PF) lesions when the operation is performed with the patient in the prone position.

METHODS

Ten patients with PF tumors requiring surgery in the prone position were prospectively enrolled in the study. All patients underwent preoperative navigational MRI in both the supine and prone positions in a single session. Using simultaneous intraoperative registration of the supine and prone navigational MR images, the authors investigated the images’ accuracy, spatial deformity, and source of errors for PF lesions. Accuracy was determined in terms of differences in the ability of the supine and prone MR images to localize 64 test points in the PF by using a neuronavigation system. Spatial deformities were analyzed and visualized by in-house–developed software with a 3D reconstruction function and spatial calculation of the MRI data. To identify the source of differences, the authors investigated the accuracy of fiducial point localization in the supine and prone MR images after taking the surface anatomy and age factors into consideration.

RESULTS

Neuronavigational localization performed using prone MRI was more accurate for PF lesions than routine supine MRI prior to prone position surgery. Prone MRI more accurately localized 93.8% of the tested PF areas than supine MRI. The spatial deformities in the neuronavigation system calculated using the supine MRI tended to move in the posterior-superior direction from the actual anatomical landmarks. The average distance of the spatial differences between the prone and supine MR images was 6.3 mm. The spatial difference had a tendency to increase close to the midline. An older age (> 60 years) and fiducial markers adjacent to the cervical muscles were considered to contribute significantly to the source of differences in the positional effect of neuronavigation (p < 0.001 and p = 0.01, respectively).

CONCLUSIONS

This study demonstrated the superior accuracy of neuronavigational localization with prone-position MRI during prone-position surgery for PF lesions. The authors recommend that the scan position of the neuronavigational MRI be matched with the surgical position for more precise localization.

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Kyung Hwan Kim, Doo-Sik Kong, Kyung Rae Cho, Min Ho Lee, Jung-Won Choi, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.

METHODS

The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.

RESULTS

Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.

CONCLUSIONS

In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

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Kyung Hwan Kim, So Jeong Kang, Jung-Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

This study aimed to verify the effect of proactive Gamma Knife surgery (GKS) in the treatment of asymptomatic meningioma compared with the natural course without any therapeutic intervention.

METHODS

From January 2006 to May 2017, 354 patients newly diagnosed with asymptomatic meningioma were reviewed and categorized into GKS (n = 153) and observation (n = 201) groups. Clinical and radiological progression rates were examined, and changes in volume were analyzed.

RESULTS

Clinical progression (i.e., clinician-judged progression), combining symptomatic progression (n = 43) and clinician-judged increase in size using images routinely acquired (n = 34), occurred in 4 patients (2.6%) and 73 patients (36.3%) in the GKS and observation groups, respectively (p < 0.001). The clinical progression-free survival (PFS) rates in the GKS and observation groups were 98.7% and 64.6%, respectively, at 5 years (p < 0.001), and 92.9% and 42.7%, respectively, at 10 years (p < 0.001). The radiological tumor control rate was 94.1% in the GKS group, and radiological progression was noted in 141 patients (70.1%) in the observation group. The radiological PFS rates in the GKS and observation groups were 94.4% and 38.5%, respectively, at 5 years (p < 0.001), and 88.5% and 7.9%, respectively, at 10 years (p < 0.001). Young age, absence of calcification, peritumoral edema, and high T2 signal intensity were correlated with clinical progression in the observation group. Volumetric analysis showed that untreated tumors gradually increased in size. However, GKS-treated tumors shrank gradually, although transient volume expansion was observed in the first 6 months. Adverse events developed in 26 of the 195 GKS-treated patients (13.3%), including 1 (0.5%) major event requiring microsurgery due to severe edema after GKS. Peritumoral edema was related to the development of adverse events (p = 0.004).

CONCLUSIONS

Asymptomatic meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting. GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy.

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Hong Joo Moon, Bong-Kyung Shin, Joo Han Kim, Jong-Hyun Kim, Taek-Hyun Kwon, Hung-Seob Chung and Youn-Kwan Park

Intramedullary teratomas, particularly adult cervicothoracic lesions, are extremely rare. Up to now only 6 cases of intramedullary cervical teratomas have been reported in adults, and all of these were histologically mature. The authors present the case of a 35-year-old man with progressive myelopathic symptoms who was admitted through an outpatient clinic and was surgically treated. The characteristics, diagnosis, epidemiology, and treatment of cervical intramedullary teratomas in adults are also reviewed. Postoperative MR imaging showed that the tumor had been near totally removed, and severely adherent tissue remained ventrocranially with tiny focal enhancement on follow-up MR imaging. Pathological examinations revealed immature teratoma without any malignant component. Adjuvant therapy was not performed. Although no change in neurological findings and symptoms was apparent postoperatively, lesion regrowth was demonstrated on MR imaging 4 months after surgery. At 8 months postoperatively, myelopathic symptoms had developed and a huge intramedullary tumor recurred according to MR imaging. This case is the seventh reported instance of intramedullary cervical teratoma in an adult, and the first case report of the immature type with malignant features.

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Min Ho Lee, Kyung Hwan Kim, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS.

METHODS

The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non–small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3–5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6–10 Gy) with a 50% isodose line.

RESULTS

On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9–94 weeks). During the follow-up period, local recurrence occurred in 5 lesions.

CONCLUSIONS

The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

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Hyun-Seung Kang, Youn-Joo Moon, Young-Yim Kim, Woong-Yang Park, Ae Kyung Park, Kyu-Chang Wang, Jeong Eun Kim, Ji Hoon Phi, Ji Yeoun Lee and Seung-Ki Kim

Object

Moyamoya disease (MMD) is a cerebrovascular occlusive disease affecting bilateral internal carotid termini. Smooth-muscle cells are one of the major cell types involved in this disease process. The characteristics of circulating smooth-muscle progenitor cells (SPCs) in MMD are poorly understood. The authors purified SPCs from the peripheral blood of patients with MMD and sought to identify differentially expressed genes (DEGs) in SPCs from these patients.

Methods

The authors cultured and isolated SPCs from the peripheral blood of patients with MMD (n = 25) and healthy control volunteers (n = 22). After confirmation of the cellular phenotype, RNA was extracted from the cells and DEGs were identified using a commercially available gene chip. Real-time quantitative reverse transcription polymerase chain reaction was performed to confirm the putative pathogenetic DEGs.

Results

The SPC-type outgrowth cells in patients with MMD invariably showed a hill-and-valley appearance under microscopic examination, and demonstrated high α–smooth muscle actin, myosin heavy chain, and calponin expression (96.5% ± 2.1%, 42.8% ± 18.6%, and 87.1% ± 8.2%, respectively), and minimal CD31 expression (less than 1%) on fluorescence-activated cell sorter analysis. The SPCs in the MMD group tended to make more irregularly arranged and thickened tubules on the tube formation assay. In the SPCs from patients with MMD, 286 genes (124 upregulated and 162 downregulated) were differentially expressed; they were related to cell adhesion, cell migration, immune response, and vascular development.

Conclusions

With adequate culture conditions, SPCs could be established from the peripheral blood of patients with MMD. These cells showed specific DEGs compared with healthy control volunteers. This study provides a novel experimental cell model for further research of MMD.

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Jinhyung Kim, Sang Baek Ryu, Sung Eun Lee, Jaewoo Shin, Hyun Ho Jung, Sung June Kim, Kyung Hwan Kim and Jin Woo Chang

OBJECT

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways.

METHODS

Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity.

RESULTS

MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS.

CONCLUSIONS

This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

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Young Mi Yoo, Yong Jung Kim, Uhn Lee, Doo Jin Paik, Hyun Tae Yoo, Cheol Wan Park, Young Bo Kim, Sang Goo Lee, Woo Kyung Kim and Chan Jong Yoo

Object

Parkinson disease (PD) is a well-known degenerative disease resulting in the depletion of dopamine-producing neurons in the pars compacta of the substantia nigra. Adenoviral vector delivery of neurotrophic factors may provide a potential therapy for PD. The authors examined whether glial cell line–derived neurotrophic factor (GDNF) delivered via adenoviral vector (Ad-GDNF) could promote functional recovery in a rat model of PD. Additionally, they examined whether neural precursor cells (NPCs) provide the therapeutic potential of cultured neural cells for cell regeneration and replacement in PD.

Methods

All animals underwent stereotactic injection of 6-hydroxydopamine into the right substantia nigra. Eight weeks later, the rats were tested for apomorphine-induced rotational asymmetry and evaluation of explanted grafts infected with the complementary DNA for GDNF containing NPCs and NPCs alone. In the NPC cultures of embryonic rat striata, the authors found that basic fibroblast growth factor induced the proliferation of stem cells, which give rise to spheres of undifferentiated cells that generate neurons and glia.

Conclusions

In this study the authors found that the reduction of apomorphine-induced rotation was more prominent in parkinsonian rats that received Ad-GDNF-treated grafts containing NPCs (61%) than in those that received grafts of NPCs alone (16%).

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Eun Ju Lee, Hyun Joo Lee, Min Kyung Hyun, Ji Eun Choi, Jong Hee Kim, Na Rae Lee, Jin Seub Hwang and Jin-Won Kwon

Object

The authors investigated the rupture rate among patients with untreated unruptured intracranial aneurysms (UIAs) in South Korea during 2006–2009.

Methods

A longitudinal study using national representative health-claim data, including all hospital records for every Korean citizen, was used. Patients with a UIA who were 18–80 years old in 2006 were identified using the I67.1 ICD-10 code. To select eligible patients, a historical period of 1 year prior to the first diagnosis of a UIA in 2006 was utilized. Patients with a previous UIA diagnosis, subarachnoid hemorrhage (SAH), or treatments, such as clipping or coiling, during the historical period were excluded from analysis. Patients with head trauma or a brain tumor during the historical period were also excluded. Eligible patients were followed up for at least 3 years from the index date. Rupture was defined as SAH events with at least 14 days of hospitalization, using the I60 ICD-10 code and excluding the I60.8 code, or death within 14 days of hospitalization.

Results

Seven thousand four hundred four patients with UIAs were identified, including 1441 treated patients (20%) and 5963 untreated patients (80%), with a median follow-up of 3.3 years. Rupture events occurred in 163 (0.9 cases/100 person-years) of the 5963 untreated patients. The rupture rate was highest in the 1st year after UIA diagnosis. An older age was a risk factor for rupture among patients with UIAs.

Conclusions

The overview of the incidence of rupture indicates the need for a preventive strategy and future studies to prevent rupture in Asian patients with UIAs.