Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model

Purpose@#Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect.This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. @*Materials and Methods@#Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm2 using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm2 . Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. @*Results@#A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC. @*Conclusion@#Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.

Characteristics of Focused Ultrasound Mediated Blood-Brain Barrier Opening in Magnetic Resonance Images

Objective@#: The blood-brain barrier (BBB) is an obstacle for molecules to pass through from blood to the brain. Focused ultrasound is a new method which temporarily opens the BBB, which makes pharmaceutical delivery or removal of neurodegenerative proteins possible. This study was demonstrated to review our BBB opening procedure with magnetic resonance guided images and find specific patterns in the BBB opening. @*Methods@#: In this study, we reviewed the procedures and results of two clinical studies on BBB opening using focused ultrasound regarding its safety and clinical efficacy. Magnetic resonance images were also reviewed to discover any specific findings. @*Results@#: Two clinical trials showed clinical benefits. All clinical trials demonstrated safe BBB opening, with no specific side effects. Magnetic resonance imaging showed temporary T1 contrast enhancement in the sonication area, verifying the BBB opening. Several low-signal intensity spots were observed in the T2 susceptibility-weighted angiography images, which were also reversible and temporary. Although these spots can be considered as microbleeding, evidence suggests these are not ordinary microbleeding but an indicator for adequate BBB opening. @*Conclusion@#: Magnetic resonance images proved safe and efficient BBB opening in humans, using focused ultrasound.

Dual Pallidal and Thalamic Deep Brain Stimulation for Complex Ipsilateral Dystonia

Purpose@#Globus pallidus pars interna (GPi) has become an established target for deep brain stimulation (DBS) in dystonia. Previous studies suggest that targeting the ventralis oralis (Vo) complex nucleus improves dystonic tremor or even focal dystonia. Research has also demonstrated that multi-target DBS shows some benefits over single target DBS. In this study, we reviewed patients who had undergone unilateral DBS targeting the GPi and Vo. @*Materials and Methods@#Five patients diagnosed with medically refractory upper extremity dystonia (focal or segmental) underwent DBS. Two DBS electrodes each were inserted unilaterally targeting the ipsilateral GPi and Vo. Clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Disability Rating Scale. @*Results@#BFMDRS scores decreased by 55% at 1-month, 56% at 3-month, 59% at 6-month, and 64% at 12-month follow up. Disability Rating Scale scores decreased 41% at 1-month, 47% at 3-month, 50% at 6-month, and 60% at 12-month follow up. At 1 month after surgery, stimulating both targets improved clinical scores better than targeting GPi or Vo alone. @*Conclusion@#Unilateral thalamic and pallidal dual electrode DBS may be as effective or even superior to DBS of a single target for dystonia. Although the number of patients was small, our results reflected favorable clinical outcomes.

Temporal Volume Change of Cavernous Sinus Cavernous Hemangiomas after Gamma Knife Surgery

Cavernous hemangiomas occur very rarely in the cavernous sinus. This study aimed to evaluate the efficacy of Gamma Knife surgery (GKS) on cavernous sinus cavernous hemangioma (CSCH) and to analyze the temporal volume change. We retrospectively reviewed the clinical data of 26 CSCH patients who were treated with GKS between 2001 and 2017. Before GKS, 11 patients (42.3%) had cranial neuropathies and 5 patients (19.2%) complained of headache, whereas 10 patients (38.5%) were initially asymptomatic. The mean pre-GKS mass volume was 9.3 mL (range, 0.5–31.6 mL), and the margin dose ranged from 13 to 15 Gy according to the mass volume and the proximity to the optic pathway. All cranial neuropathy patients and half of headache patients showed clinical improvement. All 26 patients achieved mass control; remarkable responses (less than 1/3 of the initial mass volume) were shown in 19 patients (73.1%) and moderate responses (more than 1/3 and less than 2/3) in 7 patients (26.9%). The mean final mass volume after GKS was 1.8 mL (range, 0–12.6 mL). The mean mass volume at 6 months after GKS was 45% (range, 5–80%) compared to the mass volume before GKS and 21% (range, 0–70%) at 12 months. The higher radiation dose tended to induce more rapid and greater volume reduction. No treatment-related complication was observed during the follow-up period.GKS could be an effective and safe therapeutic strategy for CSCH. GKS induced very rapid volume reduction compared to other benign brain tumors.

Outcomes of Intrathecal Baclofen Therapy Compared With Deep Brain Stimulation in a Patient With Dystonic Cerebral Palsy: A Case Report

Deep brain stimulation (DBS) in internal globus pallidus is considered to be a good option for controlling generalized dystonia in patients with this condition. In this relation, it is known that DBS has already been shown to have significant effects on primary dystonia, but is seen as controversial in secondary dystonia including cerebral palsy (CP). On the other hand, intrathecal baclofen (ITB) has been known to reduce spasticity and dystonia in patients who did not respond to oral medications or botulinum toxin treatment. Here, we report a patient with dystonic CP, who received the ITB pump implantation long after the DBS and who noted remarkable improvement in the 36-Item Short Form Health Survey, Dystonia Rating Scale, Modified Barthel Index, and visual analog scale scores for pain after an ITB pump implantation was used as compared with DBS. To our knowledge, the present case report is the first to demonstrate the effects of an ITB pump on reducing pain and dystonia and improving quality of life and satisfaction, compared with DBS in a patient with CP.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

Effect of Placenta-Derived Mesenchymal Stem Cells in a Dementia Rat Model via Microglial Mediation: a Comparison between Stem Cell Transplant Methods

PURPOSE: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.

Focused ultrasound treatment for central nervous system disease: neurosurgeon's perspectives

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21(st) century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson's disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a preclinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.

Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The Role and Timing of Radiosurgery

BACKGROUND: Up to 15% of all patients with brain metastases have no clearly detected primary site despite intensive evaluation, and this incidence has decreased with the use of improved imaging technology. Radiosurgery has been evaluated as one of the treatment modality for patients with limited brain metastases. In this study, we evaluated the effectiveness of radiosurgery for brain metastases from unknown primary tumors. METHODS: We retrospectively evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain metastases radiologically diagnosed between August 1992 and September 2007 in our institution. First, the brain metastases were grouped into metachronous, synchronous, and precocious presentations according to the timing of diagnosis of the brain metastases. Then, synchronous and precocious brain metastases were further grouped into 1) unknown primary; 2) delayed known primary; and 3) synchronous metastases according to the timing of diagnosis of the primary origin. We analyzed the survival time and time to new brain metastasis in each group. RESULTS: Of the 540 patients, 29 (5.4%) presented precocious or synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor was not found even after intensive and repeated systemic evaluation in 10 patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed known primary, 1.2%); and diagnosed at the same time as the brain metastases in 16 patients (synchronous metastasis, 55.2%). No statistically significant differences in survival time and time to new brain metastasis were found among the three groups. CONCLUSION: Identification of a primary tumor before GKRS did not affect the patient outcomes. If other possible differential diagnoses were completely excluded, early GKRS can be an effective treatment option for brain metastases from unknown primary tumor.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Hearing Restoration in Neurofibromatosis Type II Patients

Patients with neurofibromatosis type II will eventually succumb to bilateral deafness. For patients with hearing loss, modern medical science technology can provide efficient hearing restoration through a number of various methods. In this article, several hearing restoration methods for patients with neurofibromatosis type II are introduced.

Dose-dependent Changes in Gait Pattern after Intrathecal Baclofen Bolus Injection in Adult Ambulatory Cerebral Palsy: A Case Report

Intrathecal baclofen (ITB) therapy has been proven to reduce severe spasticity in cerebral palsy (CP). However, few results reported the objective gait pattern change after ITB bolus injection in adult ambulatory CP. We therefore evaluated observational and kinematic gait patterns at different ITB bolus injection doses. We performed a test trial of 3-day ITB bolus injections at doses of 12.5 microg, 25 microg, and 50 microg in ambulatory CP. We evaluated modified Ashworth scale, visual analogue scale, observational gait scale, and kinematic gait analysis after ITB bolus injection. Intrathecal administration of low-dose baclofen 25 microg was successfully used not only for the treatment of spasticity but also for the treatment of gait disturbance, whereas the higher dose baclofen 50 microg induced foot drop and deteriorated gait pattern. We experienced dose-dependent changes in gait pattern confirmed by the observational and kinematic gait assessments after ITB bolus injection in adult ambulatory CP.

Long-Term Results of Gamma Knife Radiosurgery for Intracranial Meningioma

BACKGROUND: The predominant treatment modality for meningioma is surgical resection. However, gamma knife radiosurgery is also an important treatment modality for meningioma that is small or cannot be completely removed because of its location. In this study, we evaluated the effectiveness and long-term results of radiosurgical treatment for meningioma in our institution. METHODS: We studied 628 patients (130 men and 498 women) who underwent gamma knife radiosurgery for intracranial meningioma, which is radiologically diagnosed, from Jan 2008 to Nov 2012. We included patients with single lesion meningioma, and followed up after 6 months with imaging, and then at 24 months with a clinical examination. Patients with high-grade meningioma or multiple meningiomas were excluded. We analyzed each of the factors associated with progression free survival. The median patient's age was 56.8 years. Maximal dosage was 27.8 Gy and marginal dosage was 13.9 Gy. RESULTS: The overall tumor control rate was 95%. Twenty-eight patients (4.4%) showed evidence of tumor recurrence. Ninety-eight patients (15%) developed peritumoral edema (PTE) after gamma-knife surgery; two of them (2%) underwent surgical resections due to PTE. Nine patients had craniotomy and tumor removal after gamma knife surgery. CONCLUSION: Gamma knife surgery for intracranial meningioma has proven to be a safe and effective treatment tool with successful long-term outcomes. Gamma knife radiosurgery can be especially effective in cases of remnant meningioma after surgical resection or where PTE is not present.

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

PURPOSE: To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peakdose dyskinesia in patients with Parkinson's disease (PD). MATERIALS AND METHODS: A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads. RESULTS: Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048). CONCLUSION: Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.

Delayed Dural Arteriovenous Fistula after Microvascular Decompression for Hemifacial Spasm

Dural arteriovenous fistula (AVF) is very rare, acquired lesion that may present with intracranial hemorrhage or neurological deficits. The etiology is not completely understood but dural AVF often has been associated with thrombosis of the involved dural sinuses. To our knowledge, this is the first well documented intracranial hemorrhage case caused by dural AVF following microvascular decompression for hemifacial spasm. A 49-year-old male patient had left microvascular decompression of anterior inferior cerebellar artery via retrosigmoid suboccipital craniotomy. The patient was in good condition without any residual spasm or surgery-related complications. However, after 10 months, he suffered sudden onset of amnesia and dysarthria. Computed tomography and magnetic resonance imaging revealed the presence of dural AVF around the left transverse-sigmoid sinus. The dural AVF was treated with Onyx(R) (ev3) embolization. At the one-year follow up visit, there were no evidence of recurrence and morbidity related to dural AVF and its treatment. This case confirms that the acquired etiology of dural AVF may be associated with retrosigmoid suboccipital craniotomy for hemifacial spasm, even though it is an extremely consequence of this procedure.

Two-Year Outcomes of Deep Brain Stimulation in Adults With Cerebral Palsy

OBJECTIVE: To investigate the effect of deep brain stimulation (DBS) on reducing dystonia and disability in adults with cerebral palsy (CP) and to compare the therapeutic outcomes between primary dystonia patients and CP patients over two years after bilateral pallidal DBS. METHODS: Five patients with primary dystonia and seven CP patients with dystonia were recruited. All subjects received DBS surgery in both globus pallidus. Burke-Fahn-Marsden dystonia rating scale consisting of dystonia movement score and disability score and subjective satisfaction scale were assessed after 1 month and every 6 months over two years following DBS treatment. RESULTS: On the dystonia movement scale, both groups of primary dystonia patients and CP patients showed a significant decrease over time following DBS. On the disability scale, patients with primary dystonia showed a significant decrease over time, whereas the disability score of CP patients did not change over the two years. Comparing the dystonia movement and disability scores of CP patients at each assessment, patients with primary dystonia showed a significant reduction after 6 months. Comparing the satisfaction scores of CP patients after DBS, patients with primary dystonia showed significantly higher subjective satisfaction. CONCLUSION: Whereas dystonia can be significantly reduced in patients with primary dystonia, CP patients showed a modest improvement on the dystonia movement scale, but not on the disability scale. Therefore, DBS may be considered with caution as a treatment modality of CP patients with dystonia.

Two-Year Outcomes of Deep Brain Stimulation in Adults With Cerebral Palsy

OBJECTIVE: To investigate the effect of deep brain stimulation (DBS) on reducing dystonia and disability in adults with cerebral palsy (CP) and to compare the therapeutic outcomes between primary dystonia patients and CP patients over two years after bilateral pallidal DBS. METHODS: Five patients with primary dystonia and seven CP patients with dystonia were recruited. All subjects received DBS surgery in both globus pallidus. Burke-Fahn-Marsden dystonia rating scale consisting of dystonia movement score and disability score and subjective satisfaction scale were assessed after 1 month and every 6 months over two years following DBS treatment. RESULTS: On the dystonia movement scale, both groups of primary dystonia patients and CP patients showed a significant decrease over time following DBS. On the disability scale, patients with primary dystonia showed a significant decrease over time, whereas the disability score of CP patients did not change over the two years. Comparing the dystonia movement and disability scores of CP patients at each assessment, patients with primary dystonia showed a significant reduction after 6 months. Comparing the satisfaction scores of CP patients after DBS, patients with primary dystonia showed significantly higher subjective satisfaction. CONCLUSION: Whereas dystonia can be significantly reduced in patients with primary dystonia, CP patients showed a modest improvement on the dystonia movement scale, but not on the disability scale. Therefore, DBS may be considered with caution as a treatment modality of CP patients with dystonia.

Factors Related to Outcomes of Subthalamic Deep Brain Stimulation in Parkinson's Disease

OBJECTIVE: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment of choice for patients with advanced idiopathic Parkinson's disease (PD) who have motor complication with medication. The objectives of this study are to analyze long-term follow-up data of STN DBS cases and to identify the factors related to outcomes. METHODS: Fifty-two PD patients who underwent STN DBS were followed-up for more than 3 years. The Unified Parkinsons Disease Rating Scale (UPDRS) and other clinical profiles were assessed preoperatively and during follow-up. A linear regression model was used to analyze whether factors predict the results of STN DBS. We divided the study individuals into subgroups according to several factors and compared subgroups. RESULTS: Preoperative activity of daily living (ADL) and the magnitude of preoperative levodopa response were shown to predict the improvement in UPDRS part II without medication, and preoperative ADL and levodopa equivalent dose (LED) were shown to predict the improvement in UPDRS part II with medication. In UPDRS part III with medication, the magnitude of preoperative levodopa response was a predicting factor. CONCLUSION: The intensity of preoperative levodopa response was a strong factor for motor outcome. And preoperative ADL and LED were strong factors for ADL improvement. More vigorous studies should be conducted to elucidate how levodopa-induced motor complications are ameliorated after STN DBS.

Treatment Options of Metastatic Brain Tumors from Hepatocellular Carcinoma: Surgical Resection vs. Gamma Knife Radiosurgery vs. Whole Brain Radiation Therapy

OBJECTIVE: Although metastasis of hepatocellular carcinoma to the brain is uncommon, it is associated with a very high mortality rate and most patients usually expire within 1 year after brain metastasis. The aim of this study is to identify the effectiveness of the active interventions such as gamma knife radiosurgery or surgical intervention for these patients. METHODS: We retrospectively reviewed the medical records and imaging data of 59 patients with metastatic brain tumors from hepatocellular carcinoma from May 2004 to September 2012. The study included patients with available clinical and radiological data who had been diagnosed with metastatic hepatocellular carcinoma of the brain, confirmed by magnetic resonance imaging. The overall survival time was analyzed and compared according to each risk factor. RESULTS: The mean age at diagnosis of metastatic brain tumor was 52.2 years (14-77). The mean follow-up duration was 13.3 weeks (0.1-117.6). Overall median survival was 4.3 weeks (95% confidence interval, 2.2-6.4). The results from an analysis of clinical factors related to survival revealed that treatment modalities were significantly related to the patient's survival (log rank, p=0.006). Twenty patients (32.8%) experienced tumor bleeding, and the survival time of the patients with tumor bleeding tended to be shorter, although the result was not statistically significant (log rank, p=0.058). Hepatic reserve, by Child-Pugh classification, was grade A in 38 patients (64.4%), grade B in 16 patients (27.1%), and grade C in 5 patients (8.5%), and was significantly related to the patient's survival (log rank, p=0.000). CONCLUSION: Although patients with metastatic brain tumors from hepatocellular carcinoma showed poor survival, active intervention including surgical resection or gamma knife radiosurgery may result in better survival, especially if patients have preserved liver function.