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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.

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Yong Sup Hwang, Insop Shim and Jin Woo Chang

Object

Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus.

Methods

A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxlyase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining.

Results

The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y–immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxlyase–immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats.

Conclusions

These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the central dopamine system.

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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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Jong Hee Chang, Jin Woo Chang, Yong Gou Park and Sang Sup Chung

Object. The authors sought to evaluate the effects of gamma knife radiosurgery (GKS) on cerebral arteriovenous malformations (AVMs) and the factors associated with complete occlusion.

Methods. A total of 301 radiosurgical procedures for 277 cerebral AVMs were performed between December 1988 and December 1999. Two hundred seventy-eight lesions in 254 patients who were treated with GKS from May 1992 to December 1999 were analyzed. Several clinical and radiological parameters were evaluated.

Conclusions. The total obliteration rate for the cases with an adequate radiological follow up of more than 2 years was 78.9%. In multivariate analysis, maximum diameter, angiographically delineated shape of the AVM nidus, and the number of draining veins significantly influenced the result of radiosurgery. In addition, margin radiation dose, Spetzler—Martin grade, and the flow pattern of the AVM nidus also had some influence on the outcome. In addition to the size, topography, and radiosurgical parameters of AVMs, it would seem to be necessary to consider the angioarchitectural and hemodynamic aspects to select proper candidates for radiosurgery.

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Jin Woo Chang, Jong Hee Chang, Yong Gou Park and Sang Sup Chung

Object. The aim of this study was to identify pain relief and treatment morbidity following gamma knife radiosurgery (GKS) for idiopathic and secondary trigeminal neuralgia.

Methods. Between May 1992 and December 1999, 15 patients with idiopathic trigeminal neuralgia and 38 patients with secondary trigeminal neuralgia were treated with GKS. Pain improvement was achieved in 13 of the patients with idiopathic pain (pain response rate 86.7%). Seven patients were pain free and another six experienced pain reduction. There were no serious complications; however, two patients suffered a mild facial sensory change 8 months and 9 months, respectively, after GKS.

The patients with secondary trigeminal neuralgia were divided into two groups (Group I, 32 patients in whom the trigeminal root entry zone [REZ] near the tumor could not be visualized; and Group II, six patients in whom the trigeminal REZ near the tumor or brainstem lesion could be visualized).

In Group I, the pain subsided completely in eight patients and was reduced in seven (pain response rate 46.9%). In Group II, the pain subsided completely in one patient at 2.8 months and was reduced in three patients at a mean follow up of 0.8 months (range 0.6–1 month) after GKS. The pain response rate was 66.7%.

Conclusions. The authors believe that GKS is an effective treatment modalities for idiopathic and secondary trigeminal neuralgia, particularly in patients with inoperable lesions.

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Yong Sup Hwang, Insop Shim, Bom Bee Lee and Jin Woo Chang

Object

The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)–induced hemiparkinsonian model.

Methods

The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA–lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE).

Conclusions

The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.

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Do Heum Yoon, Yoon Ha, Yong Gou Park and Jin Woo Chang

Object

Compensatory hyperhidrosis is a major and troublesome complication of thoracoscopic sympathectomy for primary hyperhidrosis. The incidence of compensatory hyperhidrosis has been reported to be as high as 50 to 97% in the patients who underwent sympathetic ganglia resection. In this study the authors evaluate the role of thoracoscopic T-3 sympathicotomy for primary hyperhidrosis and the prevention of compensatory hyperhidrosis.

Methods

Thoracoscopic T-3 sympathicotomy was performed in 27 patients with either isolated palmar hyperhidrosis (24 cases) or that in combination with axillary hyperhidrosis (three cases) during a 3-year period. In the cases of combined palmar/axillary hyperhidrosis, the T-4 sympathetic ganglion also was coagulated. The mean follow-up period was 19.7 months. Surgery-related results were determined on the basis of complications, compensatory hyperhidrosis, and patient-related satisfaction.

In the immediate postoperative period all 24 patients with palmar hyperhidrosis reported complete alleviation of their symptoms. One patient with palmar/axillary hyperhidrosis in whom axillary hyperhidrosis did not completely resolve underwent a repeated T-4 sympathicotomy 1 month after the initial surgery. Another patient suffered mild compensatory hyperhidrosis of the trunk 1 month postoperatively. The long-term satisfaction rate in all 27 patients was high. One patient required placement of a chest tube to treat pneumothorax. Other complications such as Horner syndrome, intercostal neuralgia, gustatory hyperhidrosis, and pulmonary edema were not observed.

Conclusions

Thoracoscopic limited T-3 sympathicotomy is an effective method to treat primary hyperhidrosis, its rate of compensatory hyperhidrosis is low, and its rate of long-term patient satisfaction is high.

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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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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.

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Na Young Jung, Chang Kyu Park, Minsoo Kim, Phil Hyu Lee, Young Ho Sohn and Jin Woo Chang

OBJECTIVE

Recently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson’s disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia.

METHODS

A prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.

RESULTS

Unilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the “medication-off” UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects.

CONCLUSIONS

In the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.

Clinical trial registration no.: NCT02003248 (clinicaltrials.gov)