Bilateral STN-DBS Research Articles

Association of heart rate variability with clinical outcome in Parkinsonian patients after subthalamic deep brain stimulation: A retrospective cohort study

Lower sympathetic and parasympathetic function increases the morbidity in Parkinsonian patients. We conducted this retrospective study to elucidate theeffect of subthalamic deep brain stimulation (STN-DBS) on autonomic cardiovascular regulation of patients with Parkinson's disease. Twelve men and four women with advanced Parkinson's disease (mean age: 63 years) who underwent bilateral STN-DBS were followed up for 9-32 months. Daytime electrocardiography for 5 minutes and rating scores were recorded before and after surgery. Good response was defined as improvement >50% in the Unified Parkinson's Disease Rating Scale (UPDRS), and a fair response as improvement between 10% and 50% after surgery. Digitalized electrocardiography signals such as high-frequency power [HF; 0.15-0.45Hz, to reflect vagal (parasympathetic) regulation], low-frequency power (LF; 0.04-0.15Hz, contributed from mixed sympathetic and parasympathetic divisions), and the fraction of LF/(HF+LF) in normalized units (LF%, to reflect sympathetic regulation) were transformed with fast Fourier transformation to power spectrum and heart rate variables. Six male and two female patients were good responders and the others were fair responders. There were no significant differences in height, weight, duration of disease, levadopa equivalent daily dose, preoperative and postoperative UPDRS, and DBS-off and levodopa-off UPDRS between the good and fair response groups. There were no significant differences between the good and fair response groups for preoperative heart rate interval, LF values, LF% values, and HF values. Compared with preoperative values, the good response group showed a significant increase in LF but not in heart rate, LF%, and HF after surgery. Incontrast, the fair response group showed no significant change in all heart rate variables postoperatively. Our study showed an improvement in autonomic cardiovascular regulation in Parkinsonian patients with >50% improvement in rating scale after STN-DBS, which implied morbidity reduction in nonmotor symptoms among such patients.

Ten-Year Outcome of Subthalamic Stimulation in Parkinson Disease

To assess the 10-year motor outcome of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson disease (PD). Patients with PD with bilateral STN-DBS were assessed according to the Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease protocol and videotaped at baseline and 1, 5, and 10 years after surgery. An independent rater blinded to stimulation and medication condition scored the 10-year video assessments. Movement Disorders Centre, Toronto Western Hospital, University Health Network, University of Toronto. Eighteen patients with advanced PD and 10-year follow-up of STN-DBS. Bilateral STN-DBS surgery. The primary outcome was the change in blinded Unified Parkinson's Disease Rating Scale (UPDRS) motor scores/subscores between the no medication/stimulation condition vs the no medication/no stimulation condition at 10 years. Secondary outcomes were the changes in blinded UPDRS motor scores between the medication/no stimulation and medication/stimulation conditions, UPDRS II scores, UPDRS IV dyskinesia and motor fluctuations scores, and anti-PD medication dose (levodopa equivalent daily dose) at different points. In the 18 patients available for follow-up at 10 years, STN-DBS still significantly improved the UPDRS total motor score (P = .007) and resting and action tremor (P < .01 and P = .02, respectively) and bradykinesia (P = .01) subscores. The UPDRS II scores in the medication and no medication conditions, UPDRS IV dyskinesia and motor fluctuations scores, and the levodopa equivalent daily dose were also significantly reduced compared with baseline. Axial signs showed the most progressive decline in stimulation and levodopa response over the years. This class III study provides evidence that stimulation-induced motor improvement was sustained overall at 10 years, although part of the initial benefit wore off mainly because of progressive loss of benefit on axial signs over time.

P.07 The role of amantadine in motor complications after deep brain stimulation for Parkinson's disease

Subthalamic deep brain stimulation (STN DBS) for Parkinson's disease typically enables a 50% reduction in dopaminergic medication postoperatively. This reduction in medication is accompanied by a 60% reduction in dyskinesia...

Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD

Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case–control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode.

Newly developed back pain after subthalamic nucleus stimulation in Parkinson’s disease

Dear editor, Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely performed for medically refractory Parkinson’s disease (PD). We have encountered patients with newly developed back pain after successful STNDBS surgery. In this report, we review these cases and discuss the pathogenesis of newly developed back pain after STN-DBS. Between November 2003 and December 2008, 148 patients with medically refractory PD underwent implantation of bilateral STN-DBS electrodes in Nagoya City University Hospital, Nagoya, Japan. STN-DBS was indicated in most patients for significant motor complications from levodopa such as fluctuation and dyskinesia. Among these patients, seven complained of newly developed back pain in the early period after STN-DBS despite having had no experience of back pain before STN-DBS. None of the patients showed camptocormia. The demographic details for all patients are shown in Table 1. STN-DBS yielded marked improvement in the UPDRS III motor score and UPDRS IV dyskinesia/fluctuation score, and reduced the need for dopaminergic medication in all patients. The time until they complained of back pain varied from 2 weeks to 5 months after surgery. Imaging study of lumbar X-ray, CT or MRI revealed various lumbar spine pathologies such as lumbar disc herniation, lumbar spinal stenosis, scoliosis, spondylolisthesis, and old compression fracture. Two patients subsequently underwent lumbar surgery for their lumbar pathology. We performed lumbar laminectomy and discectomy for disc herniation, and laminectomy and pedicle screw-rod fixation for spondylolisthesis. One patient was treated with epidural injections, and the other four patients were treated conservatively with analgesic medication. Consequently, the back pain was controlled well in all of the patients. Several types of pain occur frequently in PD. Ford classified pain in PD into several categories: musculoskeletal pain, radicular or neuropathic pain, dystonia-related pain, central or primary pain, and akathitic discomfort [2]. The most prevalent painful sensations in PD seem to be musculoskeletal pain and dystonia-related pain. Depression in PD may also confound and aggravate pain. Back problems in particular seem to be common in PD. Broetz et al. reported that the prevalence of back pain in PD (74%) was significantly higher than in control patients (27%) [1]. Postural abnormalities or truncal dystonia in PD seem to put stress on the lumbar disc structures and cause lumbar disc herniation. Increased muscle tone and reduced flexibility of the spine may also cause nonradicular back pain originating from the muscle, soft tissues, and skeletal structures. Some previous studies demonstrated that STN-DBS improved fluctuating pain, namely, pain in the "off" period [3, 6]. STN-DBS also improves painful "off" period dystonia [4]. Nevertheless, we showed that a significant incidence (approximately 5%) of newly developed back pain occurs after STN-DBS in spite of the marked improvement of cardinal PD symptoms. Kim et al. also reported that new pain developed in some patients A. Umemura (*) :Y. Oka :A. Okura :K. Yamada Department of Neurosurgery, Nagoya City University Graduate School of Medicine, 1 Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan e-mail: aume@med.nagoya-cu.ac.jp

Subthalamic nucleus stimulation for Parkinson disease with severe medication-induced hallucinations or delusions

Subthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson disease (PD) and reduces antiparkinsonian medication. Therefore, STN DBS seems to be well indicated for patients suffering from medication-induced psychotic symptoms. However, there are few available data dealing with the effect of STN DBS in this kind of patient. The authors studied the effect of STN DBS in patients with PD and severe medication-induced hallucinations or delusions. The authors retrospectively reviewed the clinical course of 10 patients who suffered from severe medication-induced hallucinations or delusions and underwent bilateral STN DBS. Patients whose preoperative thought disorder score (Unified Parkinson's Disease Rating Scale Part I, item 2) was 3 or more were enrolled in this study. All patients underwent cognitive function examination and brain perfusion SPECT preoperatively to exclude dementia with Lewy bodies. Subthalamic nucleus DBS yielded significant improvement of motor function in all patients. In 8 patients, psychotic symptoms completely disappeared with significant reduction of dopaminergic medication. In 2 patients, hallucinations and delusions deteriorated immediately after surgery despite complete withdrawal of antiparkinsonian medication. However, these psychotic symptoms completely disappeared after a few months with administration of antipsychotics, and no recurrence was observed afterward in either patient. Subthalamic nucleus DBS is a good treatment option for patients with PD who are suffering severe medication-induced hallucinations or delusion. However, vigilance is needed, because temporary deterioration of psychotic symptoms may occur after surgery.

Significant improvement of motor symptoms by deep brain stimulation of bilateral subthalamic nucleus in patients with moderate or advanced Parkinson's disease

To study the effects of deep brain stimulation (DBS) of bilateral subthalamic nucleus (STN) on the motor and non-motor symptoms in moderate or advanced Parkinson's disease (PD) patients. From August 2006 to January 2010, 21 consecutive PD patients with refractory motor fluctuations or dyskinesia underwent operations at our hospital. All patients were evaluated by unified Parkinson's disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Parkinson's disease questionnaire (PDQ-39), mini mental state examination (MMSE), Parkinson's disease sleep scale-Chinese vision (PDSS-CV), Pittsburgh sleep quality index (PSQI), Hamilton depression rating scale (HAMD) and Hamilton anxiety rating scale (HAMA). And the daily dosage of dopaminergic agents was recorded at 1 week pre-operation and 3, 6 and 12 months post-operation. Ten patients finished a 12-month follow-up. Their motor functions showed significant improvement. And the scores of UPDRS-motor, tremor, rigidity, bradykinesia and axial symptoms reduced significantly in the on-stimulation-off-medication condition and the on-stimulation-on-medication condition vs the on-medication condition pre-operation. And the improvement of tremor was the most pronounced (52.1% and 77.7% respectively). The H&Y stage decreased significantly from 3.2 ± 0.7 to 2.5 ± 0.4 post-operation. The activities of daily living improved while PDQ-39 declined significantly from 56 ± 9 pre-operation to 32 ± 13 at 12 months follow-up. The score changes of MMSE, PDSS-CV, PSQI, HAMA and HAMD were statistically insignificant. The levo-dopa equivalent dose of 1-year post-operation decreased significantly by 49.2% versus that of pre-operation (P < 0.05). Bilateral STN-DBS can significant ameliorate the motor symptoms of moderate or advanced PD patients, reduce the dosage of anti-PD medications and improve the quality of life. This procedure has the advantages of a greater safety, minor side effects and an easy controllability.

Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson’s disease

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS - NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS - Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

The Dominant-STN phenomenon in bilateral STN DBS for Parkinson's disease

In some patients with Parkinson's disease (PD) and bilateral STN-DBS the motor benefit from one STN alone appears similar to the improvement obtained with bilateral STN-DBS. Thus, we hypothesized that some patients have a “dominant-STN,” whose stimulation achieves similar results than bilateral stimulation. Twenty-two consecutive PD patients with bilateral STN-DBS were assessed in 4 randomized conditions: bilateral off-stimulation, bilateral on-stimulation, unilateral right- and unilateral left-stimulation. A hierarchical agglomerative cluster analysis of the motor UPDRS scores in these 4 conditions showed that 11 patients (50%) presented with a “dominant-STN.” Interestingly, in 3 of these patients the dominant-STN was ipsilateral to the most affected side of the body. Our results support the presence of different phenotypes of response to bilateral STN stimulation. In our sample 50% of the patients presented with a dominant-STN, suggesting that a non-negligible part of PD patients might not need bilateral STN-DBS surgery.

Subthalamic nucleus deep brain stimulation changes velopharyngeal control in Parkinson's disease

Purpose Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal control, and whether these changes were correlated with limb function and stimulation settings. Methods Seventeen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when STN DBS was on, and again 1 h after STN DBS was turned off, and included aerodynamic measures during syllable production, and standard neurological ratings of limb function. Results We found that PD participants exhibited changes with STN DBS, primarily consistent with increased intraoral pressure ( n = 7) and increased velopharyngeal closure ( n = 5). These changes were modestly correlated with measures of limb function, and were correlated with stimulation frequency. Conclusion Our findings suggest that STN DBS may change velopharyngeal control during syllable production in PD, with greater benefit associated with low frequency stimulation. However, DBS demonstrates a more subtle influence on speech-related velopharyngeal control than limb motor control. This distinction and its underlying mechanisms are important to consider when assessing the impact of STN DBS on PD. Learning outcomes: As a result of this activity, the participant will be able to (1) describe the effects of deep brain stimulation on limb and speech function; (2) describe the effects of deep brain stimulation on velopharyngeal control; and (3) discuss the possible reasons for differences in limb outcomes compared with speech function with deep brain stimulation of the subthalamic nucleus.

Subthalamic nucleus deep brain stimulation changes speech respiratory and laryngeal control in Parkinson’s disease

Adequate respiratory and laryngeal motor control are essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on respiratory and laryngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of respiratory and laryngeal control, and whether these changes were correlated with limb function and stimulation parameters. Eighteen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when DBS was on, and again 1 h after DBS was turned off, and included aerodynamic measures during syllable production, and standard clinical ratings of limb function. We found that PD participants exhibited changes with DBS, consistent with increased respiratory driving pressure (n = 9) and increased vocal fold closure (n = 9). However, most participants exceeded a typical operating range for these respiratory and laryngeal control variables with DBS. Changes were uncorrelated with limb function, but showed some correlation with stimulation frequency and pulse width, suggesting that speech may benefit more from low-frequency stimulation and shorter pulse width. Therefore, high-frequency STN DBS may be less beneficial for speech-related respiratory and laryngeal control than for limb motor control. It is important to consider these distinctions and their underlying mechanisms when assessing the impact of STN DBS on PD.

Effect of subthalamic deep brain stimulation on postural abnormality in Parkinson disease

Parkinson disease (PD) is often accompanied by various postural abnormalities such as camptocormia (bent spine) or Pisa syndrome (lateral flexion). The authors studied the effect of subthalamic nucleus deep brain stimulation (STN DBS) on postural abnormality in patients with PD. The authors retrospectively reviewed the clinical course of 18 patients who suffered from significant postural abnormality and underwent bilateral STN DBS. Patients whose preoperative posture score (Unified Parkinson's Disease Rating Scale III, item 28) was 2 or more in the "medication-on" state were enrolled in this study. Eight patients were considered to have camptocormia, and 10 patients were considered to have so-called Pisa syndrome. Nine patients showed apparent thoracolumbar spinal deformity on radiography. Most patients had significant motor fluctuations from levodopa. In 13 patients with moderate postural abnormality (score of 2 on item 28), 9 patients improved soon after surgery, but 1 patient relapsed. Two patients improved gradually over a long period after surgery, whereas 2 patients did not improve at all. In 5 patients with severe postural abnormality (score of 3 or 4 on item 28), 2 patients improved slightly in the long-term follow-up period after surgery, but 3 patients did not improve at all. Postural abnormality in patients with PD could be ameliorated by STN DBS, and therefore surgery should be considered before irreversible spinal deformity develops.

P2.148 Bilateral STN DBS improves manual performance time in Parkinson's disease

P2.148 Bilateral STN DBS improves manual performance time in Parkinson's disease

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 Parkinson's 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.

Delimiting subterritories of the human subthalamic nucleus by means of microelectrode recordings and a Hidden Markov Model

Positive therapeutic response without adverse side effects to subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson's disease (PD) depends to a large extent on electrode location within the STN. The sensorimotor region of the STN (seemingly the preferred location for STN DBS) lies dorsolaterally, in a region also marked by distinct beta (13-30 Hz) oscillations in the parkinsonian state. In this study, we present a real-time method to accurately demarcate subterritories of the STN during surgery, based on microelectrode recordings (MERs) and a Hidden Markov Model (HMM). Fifty-six MER trajectories were used, obtained from 21 PD patients who underwent bilateral STN DBS implantation surgery. Root mean square (RMS) and power spectral density (PSD) of the MERs were used to train and test an HMM in identifying the dorsolateral oscillatory region (DLOR) and nonoscillatory subterritories within the STN. The HMM demarcations were compared to the decisions of a human expert. The HMM identified STN-entry, the ventral boundary of the DLOR, and STN-exit with an error of -0.09 +/- 0.35, -0.27 +/- 0.58, and -0.20 +/- 0.33 mm, respectively (mean +/- standard deviation), and with detection reliability (error < 1 mm) of 95, 86, and 91%, respectively. The HMM was successful despite a very coarse clustering method and was robust to parameter variation. Thus, using an HMM in conjunction with RMS and PSD measures of intraoperative MER can provide improved refinement of STN entry and exit in comparison with previously reported automatic methods, and introduces a novel (intra-STN) detection of a distinct DLOR-ventral boundary.

IMPROVEMENT OF TICS AFTER SUBTHALAMIC NUCLEUS DEEP BRAIN STIMULATION

Deep brain stimulation (DBS) of the medial thalamic nuclei and globus pallidus internus (GPi)1,2 has been tried in the treatment of medically refractory Tourette syndrome (TS). Subthalamic nucleus (STN) is the target most commonly used for DBS in Parkinson disease (PD). A double-blind randomized study has shown the efficacy of STN-DBS in obsessive compulsive disorder (OCD),3 which is considered within the spectrum of TS. We report a patient with PD who also had a history of TS in whom bilateral STN-DBS improved both PD and tics. ### Case report. A 38-year-old man with an 8-year history of PD was referred for DBS consideration. He had a history of tics that began at the age of 7 and improved by the age of 12. Tics increased in adulthood prior to the diagnosis of PD. No changes of tics were noticed following the onset of PD or dopaminergic medication. No treatment for tics was ever prescribed. Prior to surgery he had motor and phonic tics and compulsion of checking that doors were locked. A single exon 5 deletion in the parkin gene was detected. Quadripolar 3389 DBS electrodes (Medtronic, Minneapolis, MN) were implanted bilaterally in the STN …

Weight changes associated with unilateral STN DBS and advanced PD

Weight gain following bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson disease (PD) has been characterized previously, but little is known about changes in weight following unilateral STN DBS. Weight gain of approximately 10kg at one year after bilateral STN DBS for PD has been noted in previous studies, and PD in the absence of DBS has been associated with weight loss. A case-control comparison evaluated the change in weight following unilateral STN DBS in PD. In 39 patients who underwent unilateral STN DBS for PD, we measured the weight change over 1 year versus both preoperative weight change and the weight change in 40 age- and disease severity-matched PD controls without DBS. Regression analyses incorporating age, gender, baseline weight in case or control were conducted to assess weight changes. At 12 months following surgery, the mean weight of unilateral STN DBS patients increased by 4.3±7.2kg versus the preoperative baseline weight (p<0.001) and this increase was 4.8kg compared with the controls (p=0.015). Over a 1 year time interval, weight gain occurred in 41% of the preoperative unilateral STN DBS patients and 45% of the PD controls, while 85% of the unilateral STN DBS patients had gained weight at 12 months after surgery (p<0.0001, respectively, chi square test). We conclude that unilateral STN DBS in PD is associated with weight gain, which offsets weight loss associated with advanced PD.

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 Parkinson's 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 Parkinson's 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.

Direction and Predictive Factors for the Shift of Brain Structure During Deep Brain Stimulation Electrode Implantation for Advanced Parkinson’s Disease

Objectives. The aims of this study were to clarify the direction and degree of brain shift, and to determine the predictive factors for a brain shift during deep brain stimulation (DBS) of the subthalamic nucleus (STN). Materials and Methods. To evaluate the brain shift during bilateral STN-DBS, the position of the anterior commissure (AC), posterior commissure (PC), midcommissure point (MC), and tip of the frontal lobe and anterior horn of the lateral ventricle were calculated pre- and poststereotactic operations in the three-dimensional direction employing special software (Leksell SurgiPlan). To determine the predictive factors for a brain shift, patient's age, operation hours, width of the third ventricle, bicaudate index (BCI), and cella media index (CMI) were compared with the shift of MC. Results. In 50 patients, the MC shifted mainly in the posterior direction (y-axis: 1.27±0.7mm), and the shifts in the inferior direction (z-axis: 0.11±0.43mm) and lateral direction (x-axis: 0.02±0.39mm) were small. The shift of the MC in the posterior direction correlated well with the shift of the tip of the anterior lobe and anterior horn. Among the predictive factors examined, namely, the patient's age, operation hours, width of the third ventricle, BCI, and CMI, only the CMI showed a correlation with the shift of the MC (r=0.42, p<0.01, Pearson's correlation coefficient; and p<0.05, logistic regression analysis). Conclusions. In bilateral STN-DBS, brain shift occurred mainly in the posterior direction, and the CMI is useful for the prediction of a brain shift. Enlargement of the body part of the lateral ventricle is the most reliable factor for predicting a brain shift.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.