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Won Seok Chang, Hae Yu Kim, Jin Woo Chang, Yong Gou Park and Jong Hee Chang

Object

Whole-brain radiation therapy (WBRT), open resection, and stereotactic radiosurgery (SRS) are widely used for treatment of metastatic brain lesions, and many physicians recommend WBRT for multiple brain metastases. However, WBRT can be performed only once per patient, with rare exceptions. Some patients may require SRS for multiple metastatic brain lesions, particularly those patients harboring more than 10 lesions. In this paper, treatment results of SRS for brain metastasis were analyzed, and an attempt was made to determine whether SRS is effective, even in cases involving multiple metastatic brain lesions.

Methods

The authors evaluated the cases of 323 patients who underwent SRS between October 2005 and October 2008 for the treatment of metastatic brain lesions. Treatment was performed using the Gamma Knife model C or Perfexion. The patients were divided into 4 groups according to the number of lesions visible on MR images: Group 1, 1–5 lesions; Group 2, 6–10 lesions: Group 3, 11–15 lesions; and Group 4, > 15 lesions. Patient survival and progression-free survival times, taking into account both local and distant tumor recurrences, were analyzed.

Results

The patients consisted of 172 men and 151 women with a mean age at SRS of 59 years (range 30–89 years). The overall median survival time after SRS was 10 months (range 8.7–11.4 months). The median survival time of each group was as follows: Group 1, 10 months; Group 2, 10 months; Group 3, 13 months; and Group 4, 8 months. There was no statistical difference between survival times after SRS (log-rank test, p = 0.554), although the probability of development of new lesions in the brain was greater in Group 4 (p = 0.014). Local tumor control rates were not statistically different among the groups (log-rank test, p = 0.989); however, remote disease progression was more frequent in Group 4 (log-rank test, p = 0.014).

Conclusions

In this study, patients harboring more than 15 metastatic brain lesions were found to have faster development of new lesions in the brain. This may be due to the biological properties of the patients' primary lesions, for example, having a greater tendency to disseminate hematogenously, especially to the brain, or a higher probability of missed or invisible lesions (microscopic metastases) to treat on stereotactic MR images at the time of radiosurgery. However, the mean survival times after SRS were not statistically different between groups. According to the aforementioned results, SRS may be a good treatment option for local control of metastatic lesions and for improved survival in patients with multiple metastatic brain lesions, even those patients who harbor more than 15 metastatic brain lesions, who, after SRS, may have early and easily detectable new metastatic lesions.

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Hae Yu Kim, Won Seok Chang, Dong Joon Kim, Jae Whan Lee, Jin Woo Chang, Dong Ik Kim, Seung Kon Huh, Yong Gou Park and Jong Hee Chang

Object

Treatment of arteriovenous malformations (AVMs) is problematic due to many factors, including lesion size, lesion location, unacceptable complications, and negative outcomes. To overcome the limitation imposed by a large nidus volume, neurosurgeons have used Gamma Knife surgery (GKS) in a variety of ways, including combined with other treatment modalities, as volume-staged radiosurgery, and as repeat radiosurgery. We performed repeat radiosurgeries in patients who harbored large AVMs (> 30 cm3) and analyzed the AVM obliteration rates and complications.

Methods

The authors reviewed the cases of 44 patients at a single institution who underwent GKS between 1992 and 2007 for treatment of an AVM whose nidus was 30 cm3 or larger. The mean age of the patients was 27 years (range 4.5–62.3 years), and the median duration of follow-up was 109.4 months (range 27–202 months). The mean AVM nidus volume was 48.8 cm3 (range 30.3–109.5 cm3), and the mean radiation dose delivered to the margin of the nidus was 13.9 Gy (range 8.4–17.5 Gy). The authors determined complete AVM nidus obliteration based on findings on both MR images and digital subtraction angiograms. When they did not detect complete obliteration after GKS, they performed 1 or more additional GKSs separated by a minimum interval of 3 years.

Results

The overall obliteration rate following repeat GKS was 34.1%, and the estimated obliteration rate at 120 months was 41.8%. Three patients (6.8%) experienced hemorrhages after GKS, and 2 patients (4.5%) developed cysts. One patient (2.3%) experienced a newly developed seizure following GKS, and another patient (2.3%) was found to have radiation necrosis.

Conclusions

Even though complete obliteration of the large AVMs after repeat GKS took a long time, the complication rate was quite acceptable. In addition, the estimated obliteration rate at long-term follow-up was respectable. Repeat GKS should be considered as a primary treatment option for symptomatic large AVMs to overcome the limitation imposed on successful obliteration by the large volume of the nidus.

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Hyung-Sun Won, Seung-Ho Han, Chang-Seok Oh, In-Hyuk Chung, Seung Min Kim and So Young Lim

Object

The authors have observed that the ulnar nerve (UN) passes through the medial intermuscular septum (MIMS) into the posterior compartment of the upper arm in more complicated patterns than those described in anatomy textbooks. Given that these unreported patterns might be related to the idiopathic UN entrapment at the midarm, this study focused on the relationship between the MIMS and the UN.

Methods

One hundred upper arms were dissected. The site at which the UN pierced the MIMS was analyzed and measured from the medial epicondyle.

Results

The relationship between the MIMS and the UN could be classified into 3 types according to whether the nerve pierced the MIMS and whether it ran through a fibrous tunnel within the septum. The UN pierced the MIMS in the middle third of the upper arm.

Conclusions

The results of this study are expected to further understanding of the relationship between the MIMS and the UN. They could also be helpful for surgeons aiming to relieve UN entrapment at the midarm, especially in nerve lesions of idiopathic origin.

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Ju Hyung Moon, Won Seok Chang, Hyun Ho Jung, Kyu Sung Lee, Yong Gou Park and Jong Hee Chang

Object

The aim of this study was to evaluate the tumor control rate and functional outcomes after Gamma Knife surgery (GKS) among patients with a facial nerve schwannoma.

Methods

The authors reviewed the radiological data and clinical records for 14 patients who had consecutively undergone GKS for a facial nerve schwannoma. Before GKS, 12 patients had facial palsy, 7 patients had hearing disturbance, and 5 patients had undergone partial or subtotal tumor resection. The mean and median tumor volumes were 3707 mm3 and 3000 mm3, respectively (range 117–10,100 mm3). The mean tumor margin dose was 13.2 Gy (range 12–15 Gy), and the mean maximum tumor dose was 26.4 Gy (range 24–30 Gy). The mean follow-up period was 80.7 months (range 2–170 months).

Results

Control of tumor growth was achieved in all 12 (100%) patients who were followed up for longer than 2 years. After GKS, facial nerve function improved in 2 patients, remained unchanged in 9 patients, and worsened in 3 patients. All patients who had had serviceable hearing at the preliminary examination maintained their hearing at a useful level after GKS. Other than mild tinnitus reported by 3 patients, no other major complications developed.

Conclusions

GKS for facial nerve schwannomas resulted in excellent tumor control rates and functional outcomes. GKS might be a good primary treatment option for patients with a small- to medium-sized facial nerve schwannoma when facial nerve function and hearing are relatively preserved.

Free access

Ji Hee Kim, Hyun Ho Jung, Jong Hee Chang, Jin Woo Chang, Yong Gou Park and Won Seok Chang

Object

Intracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma.

Methods

The authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified.

Results

A total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and chondrosarcoma, respectively (p = 0.05). No tumor progression was observed when margin doses greater than 16 Gy for chordoma and 14 Gy for chondrosarcoma were prescribed.

Conclusions

Outcomes after GKS were more favorable for patients with chondrosarcoma than for those with chordoma. The data also indicated that at 2 years after GKS, the rate of volume change is significantly higher for chordomas than for chondrosarcomas. The authors conclude that radiosurgery with a margin dose of more than 16 Gy for chordomas and more than 14 Gy for chondrosarcomas seems to enhance local tumor control with relatively few complications. Further studies are needed to determine the optimal dose of GKS for patients with intracranial chordoma or chondrosarcoma.

Full access

Hyun Ho Jung, Won Seok Chang, Itay Rachmilevitch, Tal Tlusty, Eyal Zadicario and Jin Woo Chang

OBJECT

The authors report different MRI patterns in patients with essential tremor (ET) or obsessive-compulsive disorder (OCD) after transcranial MR-guided focused ultrasound (MRgFUS) and discuss possible causes of occasional MRgFUS failure.

METHODS

Between March 2012 and August 2013, MRgFUS was used to perform unilateral thalamotomy in 11 ET patients and bilateral anterior limb capsulotomy in 6 OCD patients; in all patients symptoms were refractory to drug therapy. Sequential MR images were obtained in patients across a 6-month follow-up period.

RESULTS

For OCD patients, lesion size slowly increased and peaked 1 week after treatment, after which lesion size gradually decreased. For ET patients, lesions were visible immediately after treatment and markedly reduced in size as time passed. In 3 ET patients and 1 OCD patient, there was no or little temperature rise (i.e., < 52°C) during MRgFUS. Successful and failed patient groups showed differences in their ratio of cortical-to-bone marrow thickness (i.e., skull density).

CONCLUSIONS

The authors found different MRI pattern evolution after MRgFUS for white matter and gray matter. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise.

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Won Seok Chang, Hyun Ho Jung, Eyal Zadicario, Itay Rachmilevitch, Tal Tlusty, Shuki Vitek and Jin Woo Chang

OBJECT

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson’s disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS.

METHODS

The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined.

RESULTS

Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r2 = 0.206, y = 64.156 − 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r2 = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate.

CONCLUSIONS

Some skull-related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates.

Free access

Na Young Jung, Chang Kyu Park, Won Seok Chang, Hyun Ho Jung and Jin Woo Chang

OBJECTIVE

Although neurosurgical procedures are effective treatments for controlling involuntary tremor in patients with essential tremor (ET), they can cause cognitive decline, which can affect quality of life (QOL). The purpose of this study is to assess the changes in the neuropsychological profile and QOL of patients following MR-guided focused ultrasound (MRgFUS) thalamotomy for ET.

METHODS

The authors prospectively analyzed 20 patients with ET who underwent unilateral MRgFUS thalamotomy at their institute in the period from March 2012 to September 2014. Patients were regularly evaluated with the Clinical Rating Scale for Tremor (CRST), neuroimaging, and cognition and QOL measures. The Seoul Neuropsychological Screening Battery was used to assess cognitive function, and the Quality of Life in Essential Tremor Questionnaire (QUEST) was used to evaluate the postoperative change in QOL.

RESULTS

The total CRST score improved by 67.3% (from 44.75 ± 9.57 to 14.65 ± 9.19, p < 0.001) at 1 year following MRgFUS thalamotomy. Mean tremor scores improved by 68% in the hand contralateral to the thalamotomy, but there was no significant improvement in the ipsilateral hand. Although minimal cognitive decline was observed without statistical significance, memory function was much improved (p = 0.031). The total QUEST score also showed the same trend of improving (64.16 ± 17.75 vs 27.38 ± 13.96, p < 0.001).

CONCLUSIONS

The authors report that MRgFUS thalamotomy had beneficial effects in terms of not only tremor control but also safety for cognitive function and QOL. Acceptable postoperative changes in cognition and much-improved QOL positively support the clinical significance of MRgFUS thalamotomy as a new, favorable surgical treatment in patients with ET.

Free access

Jaewoo Shin, Chanho Kong, Jae Sung Cho, Jihyeon Lee, Chin Su Koh, Min-Sik Yoon, Young Cheol Na, Won Seok Chang and Jin Woo Chang

OBJECTIVE

The application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals.

METHODS

Changes in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage.

RESULTS

Acoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication.

CONCLUSIONS

The study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.