Yong Hoon Lim

Chronic subthalamic deep brain stimulation improves pain in Parkinson disease

BackgroundPain is a well recognized feature of Parkinson disease (PD). Like motor fluctuations, pain in PD may fluctuate as ‘non-motor fluctuations’. Subthalamic deep brain stimulation (STN DBS) is an established treatment for motor fluctuations in PD. However, the effect of STN DBS on the pain in PD is only partially investigated.MethodsPD patients who were considered for STN DBS were asked if they had pain. The severity of pain was scored in each body part. In patients with motor fluctuation, the pain in the ‘on’ and ‘off ’ state were recorded separately. Patients were evaluated preoperatively and 3 months after surgery. Some patients were followed for 6 months.ResultsTwenty-three of 29 patients had pain preoperatively. Of 24 with motor fluctuation, 21 had pain, and 18 had fluctuating pain. Pain improved in 20 out of 23 with preoperative pain at 3 months postoperatively. Of 18 with fluctuating pain, 12 reported a decrease in, and 5 complete disappearance of the ‘off ’ pain. Of 4 with nonfluctuating preoperative pain, 2 reported improvement. Pain was severe and functionally disabling in some. The STN DBS improved pain to a tolerable degree. In 7 of 29, new pain developed during the 3 month follow-up. Sixteen patients were followed for 6 months. All 11 patients who had improvement at 3 months continued to get benefit from STN DBS. Two additional patients who had no improvement at 3 months reported improvement at 6 months.ConclusionsPain is frequent in PD and STN DBS improves pain, especially the ‘off ’ pain in PD.

The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease

The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinsons disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinsons disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function.

Two-year follow-up on the effect of unilateral subthalamic deep brain stimulation in highly asymmetric Parkinson's disease.

Although bilateral subthalamic deep brain stimulation (STN DBS) provides greater relief from the symptoms of Parkinsons disease (PD) than unilateral STN DBS, it has been suggested that unilateral STN DBS may be a reasonable treatment option in selected patients, especially those with highly asymmetric PD. In previous studies on the effect of unilateral STN DBS, the asymmetry of PD symptoms was not prominent and the mean follow‐up durations were only 3 to 12 months. In this study, we report our findings in a series of 8 patients with highly asymmetric PD who were treated with unilateral STN DBS and were followed for 24 months. Serial changes in Unified Parkinsons Disease Rating Scale (UPDRS) motor score and subscores in the ipsilateral, contralateral, and axial body parts were analyzed. Unilateral STN DBS improved the UPDRS motor score and the contralateral subscore in the on‐medication state for 5 nonfluctuating patients and in the off‐medication state for 3 fluctuating patients. However, the ipsilateral subscore progressively worsened and reversed asymmetry became difficult to manage, which led to compromised medication and stimulator adjustment. At 24 months, all the patients were considering the second‐side surgery. Our results suggest that bilateral STN DBS should be considered even in highly asymmetric PD.

Reprogramming guided by the fused images of MRI and CT in subthalamic nucleus stimulation in Parkinson disease

OBJECTIVE To evaluate the usefulness of the visual information about the location of the contacts in deep brain stimulation (DBS) programming, we compared the outcomes of subthalamic nucleus (STN) stimulation before and after reprogramming guided by the fused images of MRI and CT. METHODS Of the 65 patients with Parkinsons disease, who underwent bilateral STN-DBS surgery between March 2005 and September 2006 and had been managed for at least 6 months with conventional programming which was only based on the physiological responses from the patients, 54 patients were reprogrammed based on the 3D anatomical location of the contacts revealed by the fused images of pre-operative MRI and post-operative CT scans taken at 6 months after surgery. A total 51 patients completed the evaluation after reprogramming. RESULTS Reprogramming significantly improved the UPDRS part III scores during the on- and off-medication condition. The daily levodopa-equivalent dose was significantly reduced. Improvement in the UPDRS part III scores after reprogramming was greater in the patients with electrodes in the STN than the patients with electrodes off the STN. CONCLUSIONS CT-MR fusion images helped to reprogram stimulation parameters with ease and confidence in a time-saving manner and resulted in further clinical improvement. This method could complement the conventional method of adjusting stimulation parameters after bilateral STN-DBS.

Electrode Position and the Clinical Outcome after Bilateral Subthalamic Nucleus Stimulation

We compared the surgical outcome with electrode positions after bilateral subthalamic nucleus (STN) stimulation surgery for Parkinsons disease. Fifty-seven patients treated with bilateral STN stimulations were included in this study. Electrode positions were determined in the fused images of preoperative MRI and postoperative CT taken at six months after surgery. The patients were divided into three groups: group I, both electrodes in the STN; group II, only one electrode in the STN; group III, neither electrode in the STN. Unified Parkinsons Disease Rating Scale (UPDRS), Hoehn and Yahr stage, and activities of daily living scores significantly improved at 6 and 12 months after STN stimulation in both group I and II. The off-time UPDRS III speech subscore significantly improved (1.6 ± 0.7 at baseline vs 1.3 ± 0.8 at 6 and 12 months, P < 0.01) with least L-dopa equivalent daily dose (LEDD) (844.6 ± 364.1 mg/day at baseline; 279.4 ± 274.6 mg/day at 6 months; and 276.0 ± 301.6 mg/day at 12 months, P < 0.001) at 6 and 12 months after STN deep brain stimulation (DBS) in the group I. Our findings suggest that the better symptom relief including speech with a reduced LEDD is expected in the patients whose electrodes are accurately positioned in both STN.

Influence of Propofol and Fentanyl on Deep Brain Stimulation of the Subthalamic Nucleus

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinsons disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7±16.8 spikes/sec, n=78) and the right side MERs (35.5±17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinsons Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinsons disease improving the overall experience of the patients. Graphical Abstract

The clinical impact of precise electrode positioning in STN DBS on three-year outcomes

Few studies have analyzed the clinical impact of subthalamic nucleus (STN) deep brain stimulation (DBS) as a function of the positioning of the inserted electrode. We investigated retrospectively the three-year outcomes in Parkinsons disease (PD) patients following bilateral STN DBS in terms of the electrode positions. Forty-one advanced PD patients were followed up for over three years following bilateral STN DBS. Patients were evaluated with the Unified Parkinsons Disease Rating Scale (UPDRS), Hoehn and Yahr staging, Schwab and England Activities of Daily Living (ADL), and the Short Form-36 Health Survey (SF-36) before surgery and one, two, and three years after surgery. The patients were divided into two groups according to the electrode position based on the fused preoperative MRI and postoperative CT images: group I included patients who had both electrodes in the STN (n=30) while group II included patients who had one of the electrodes in the STN (n=11). The UPDRS, the Hoehn & Yahr staging, the Schwab and England ADL, and the SF-36 scores showed significant improvements with decreased l-dopa equivalent daily doses (LEDDs) in both groups as well as in the group as a whole for up to three years following bilateral STN DBS. However, the off-medication UPDRS total and motor (part III) scores significantly deteriorated with increased LEDDs for patients in group II three years after STN DBS compared to that of the group I patients. We conclude that more accurate electrode positioning in the STN leads to better long-term outcomes in advanced PD patients following DBS.

Fusion Image―Based Programming After Subthalamic Nucleus Deep Brain Stimulation

OBJECTIVE To propose fusion image-based programming to adjust patients with advanced Parkinson disease (PD) effectively after subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS Between January 2007 and July 2008, 38 patients with advanced PD were consecutively treated with STN DBS. The electrode positions and information regarding their contacts with STN were determined via fusion of the images of preoperative magnetic resonance imaging (MRI) and of postoperative computed tomography (CT) obtained 1 month after STN DBS. Postoperative programming was performed using the information of electrode positions based on the fused images. All patients were evaluated with a prospective protocol of the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr Staging, Schwab and England Activities of Daily Living (SEADL), levodopa equivalent daily dose (LEDD), short-form-36 health survey (SF-36), and neuropsychological tests before and at 3 months and 6 months after surgery. RESULTS There was a rapid and significant improvement of motor symptoms, especially tremor and rigidity, after STN stimulation, with low morbidity. Stimulation led to an improvement in the off-medication UPDSR III scores of the patients of approximately 55% at 3 months and 6 months after STN DBS. Dyskinesia was significantly improved (74% at 3 months and 95% at 6 months) after STN DBS. In addition, LEDD values decreased to 50% of the level observed before surgery within 1 month after STN DBS. CONCLUSIONS Programming based on fused images of preoperative MRI and postoperative CT after STN DBS was performed quickly, easily, and efficiently.

Patients' reluctance to undergo deep brain stimulation for Parkinson's disease

BACKGROUND Many patients with advanced Parkinsons disease (PD) are reluctant to undergo the subthalamic nucleus deep brain stimulation (STN-DBS) when surgery is warranted. Reasons for this reluctance have not been examined. We undertook to establish the rate and causes of this reluctance for STN-DBS in patients with advanced PD. METHODS A reluctant group was defined as patients who were hesitant to undergo DBS. Clinical information included age, onset age, disease duration, the Unified Parkinson Disease Rating Scale, Hoehn and Yahr stage and levodopa equivalent dose when they were evaluated with a view to consider surgery. RESULTS We enrolled 186 patients who underwent STN-DBS. 84 patients (45%) belonged to the reluctant group. Between the reluctant and the non-reluctant, there were no differences in preoperative characteristics. Main reasons for hesitation were fear of complications (74%) and economic burden (50%). The main reasons that they finally underwent the DBS were confidence in the doctors decision (80%) and encouragement from their family (36%). CONCLUSIONS Building trust between patients and physicians is an important factor in guiding patients to undergo this treatment. To reduce the reluctance to undergo DBS at the appropriate time, we need to find effective ways of reducing their psychological and economic burden.

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.