Hye Ran Park

A Short Review on the Current Understanding of Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.

Multiple Densities of the Chronic Subdural Hematoma in CT Scans

Objective Density of the chronic subdural hematoma (cSDH) is variable. It often appears to be mixed density. Multiple densities of cSDH may result from multiple episodes of trauma. We investigated the frequency of mixed density and the causes of head injuries representing each density. Methods We could collect 242 cases of chronic SDH. The cSDHs were classified into four groups; hypodensity, homogeneous isodensity, layered type, and mixed type on the basis of CT scans. Results The density of cSDH was isodense in 115 patients, hypodense in 31 patients, mixed in 79 cases, and layered in 17 cases. The cSDH was on the left side in 115 patients, on the right side in 70 patients, and bilateral in 40 patients. The history of trauma was identifiable in 122 patients. The etiology could be identified in 67.7% of the hypodense hematomas, while it was obscure in 59.5% of the mixed hematomas. Conclusion Mixed density of cSDH results from multiple episodes of trauma, usually in the aged. It is hard to remember all the trivial traumas for the patients with the mixed density cSDHs. Although there were membranes within the mixed density hematomas, burr-holes were usually enough to drain the hematomas.

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study.

Purpose Stereotactic radiosurgery (SRS) is widely used for brain metastases but has been relatively contraindicated for large lesions (>3 cm). In the present study, we analyzed the efficacy and toxicity of hypofractionated Gamma Knife radiosurgery to treat metastatic brain tumors for which surgical resection were not considered as the primary treatment option. Methods and Materials Thirty-six patients, forty cases were treated with Gamma Knife-based fractionated SRS for three to four consecutive days with the same Leksell frame on their heads. The mean gross tumor volume was 18.3 cm³, and the median dose was 8 Gy at 50% isodose line with 3 fractions for three consecutive days (range, 5 to 11 Gy and 2 to 4 fractions for 2 to 4 consecutive days). Survival rates and prognostic factors were analyzed. Results The overall survival rate at one and two years was 66.7 and 33.1%, respectively. The median survival time was 16.2 months, and the local control rate was 90%. RTOG toxicity grade 1 was observed in 3 (8.3%) patients, grade 2 in 1 (2.7%) patient and grade 3 in 1 (2.7%) patient respectively. Radiation necrosis was developed in 1 (2.7%) patient. KPS scores and control of primary disease resulted in significant differences in survival. Conclusions Our findings suggest that consecutive hypofractionated Gamma Knife SRS could be applied to large metastatic brain tumors with effective tumor control and low toxicity rates.

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

Background GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. Objectives This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. Methods Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84) Results The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement. Conclusions GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl

Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson’s disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.

Time-Staged Gamma Knife Stereotactic Radiosurgery for Large Cerebral Arteriovenous Malformations: A Preliminary Report.

Objective We retrospectively analyzed our experience with time-staged gamma knife stereotactic radiosurgery (GKS) in treating large arteriovenous malformation(AVM)s;≥ 10 cm3). Methods Forty-five patients who underwent time-staged GKS (2-stage, n = 37;3-stage,n = 8) between March 1998 and December 2011 were included. The mean volume treated was 20.42±6.29 cm3 (range, 10.20–38.50 cm3). Obliteration rates of AVMs and the associated complications after GKS were evaluated. Results Mean AVM volume (and median marginal dose) at each GKS session in the 37 patients who underwent 2-stage GKS was 19.67±6.08 cm3 (13 Gy) at session 1 and 6.97±6.92 cm3 (17 Gy) at session 2. The median interval period was 39 months. After follow-up period of 37 months, the complete obliteration rate was 64.9%. The mean AVM volume (and median marginal dose) at each GKS session in the 8 patients who underwent 3-stage GKS was 23.90±6.50 cm3 (12.25 Gy), 19.43±7.46 cm3 (13.5 Gy), 7.48±6.86 cm3 (15.5 Gy) at session 1, 2, and 3, respectively. The median interval duration between each GKS session was 37.5 and 38 months, respectively. After a median follow-up period of 47.5 months, 5 patients (62.5%) achieved complete obliteration. Postradiosurgical hemorrhage developed in 5 patients (11.1%) including one case of major bleeding and 4 cases of minor bleeding. No patient suffered from clinically symptomatic radiation necrosis following radiation. Conclusion Time-staged GKS could be an effective and safe treatment option in the management of large AVMs.

Geographic Analysis of Neurosurgery Workforce in Korea

Objective In respect of the health and safety of the public, universal access to health care is an issue of the greatest importance. The geographic distribution of doctors is one of the important factors contributing to access to health care. The aim of this study is to assess the imbalances in the geographic distribution of neurosurgeons across Korea. Methods Population data was obtained from the National Statistical Office. We classified geographic groups into 7 metropolitan cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and neurosurgeons per 100000 populations in each county unit was calculated using the total number of doctors and neurosurgeons at the country level from 2009 to 2015. The density levels of neurosurgeon and doctor were calculated and depicted in maps. Results Between 2009 and 2015, the number of neurosurgeons increased from 2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison of the geographic distribution of neurosurgeons in 2009 and 2015 showed an increase in the regional gap. The neurosurgeon density was affected by country unit characteristics (p=0.000). Conclusion Distribution of neurosurgeons throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in a limited number of metropolitan cities. This phenomenon will need to be accounted when planning for a supply of neurosurgeons, allocation of resources and manpower, and the provision of regional neurosurgical services.

Optimal Surgical Timing of Aspiration for Spontaneous Supratentorial Intracerebral Hemorrhage

Objective Minimally invasive techniques such as stereotactic aspiration have been regarded as promising alternative methods to replace craniotomy in the treatment of intracerebral hemorrhage (ICH). The aim of this study was to identify the optimal timing of stereotactic aspiration and analyze the factors affecting the clinical outcome. Materials and Methods This retrospective study included 81 patients who underwent stereotactic aspiration for spontaneous supratentorial ICH at single institution. Volume of hematoma was calculated based on computed tomography scan at admission, just before aspiration, immediately after aspiration, and after continuous drainage. The neurologic outcome was compared with Glasgow outcome scale (GOS) score. Results The mean volume ratio of residual hematoma was 59.5% and 17.6% immediately after aspiration and after continuous drainage for an average of 2.3 days, respectively. Delayed aspiration group showed significantly lower residual volume ratio immediately after aspiration. However, there was no significant difference in the residual volume ratio after continuous drainage. The favorable outcome of 1-month GOS 4 or 5 was significantly better in the group with delayed aspiration after more than 7 days (p = 0.029), despite no significant difference in postoperative 6-months GOS score. A factor which has significant correlation with postoperative 6-months favorable outcome was the final hematoma volume ratio after drainage (p = 0.028). Conclusion There is no difference in final residual volume of hematoma or 6-months neurologic outcome according to the surgical timing of hematoma aspiration. The only factor affecting the postoperative 6-months neurologic outcome is the final volume of remaining hematoma after drainage.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm3 who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm3 (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.