Antagonism of metabotropic glutamate receptor type 5 prevents levodopa-induced dyskinesia development in a male rat model of Parkinson's disease: Electrophysiological evidence.

Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model). Saline was intraperitoneally administered to dopamine lesioned (DL) rats (n = 6), levodopa/benserazide (L/B) was administered to LID rats (n = 8), and L/B combined with MTEP was administered to MTEP rats (n = 6) twice daily for 14 days. We administered L/B to LID and MTEP rats 48 h after the final administration of MTEP to examine the chronic effect of MTEP. The control and DL groups did not have LID. The MTEP group had less LID than the LID group (p < .01) on day 1 and day 18. The control group had a typical triphasic pattern consisting of early excitation (early-Ex), inhibition, and late excitation (late-Ex). However, the inhibition phase disappeared, was partially observed, and was fully suppressed in the DL, LID, and MTEP groups, respectively. The cortico-striato-entopeduncular pathway is important in the pathophysiology of LID. mGluR5 antagonism suppresses LID progression by preventing physiological changes in the cortico-striato-entopeduncular pathway. Future studies are required to validate these results.

Implications of DNA Methylation Classification in Diagnosing Ependymoma.

BACKGROUND: Ependymoma is a central nervous system (CNS) tumor that arises from the ependymal cells of the brain's ventricles and spinal cord. The histopathology of ependymomas is indistinguishable regardless of the site of origin, and the prognosis varies. Recent studies have revealed that the development site and prognosis reflect the genetic background. In this study, we used genome-wide DNA methylation array analysis to investigate the epigenetic background of ependymomas from different locations treated at our hospital. METHODS: Four cases of posterior fossa ependymomas and 11 cases of spinal ependymomas were analyzed. RESULTS: DNA methylation profiling using the DKFZ methylation classifier showed that the methylation diagnoses of the 2 cases differed from the histopathological diagnoses, and 2 cases could not be classified. Tumor that spread from the brain to the spinal cord was molecularly distinguishable from other primary spinal tumors. CONCLUSIONS: Although adding DNA methylation classification to conventional diagnostic methods may be helpful, the diagnosis in some cases remains undetermined. This may affect decision-making regarding treatment strategies and follow-up. Further investigations are required to improve the diagnostic accuracy of these tumors.

Effectiveness and safety of MR-guided focused ultrasound thalamotomy in patients with essential tremor and low skull density ratio: a study of 101 cases.

OBJECTIVE: The objective was to investigate the effectiveness and safety of MR-guided focused ultrasound (MRgFUS) treatment in patients with essential tremor, particularly those with low skull density ratio (SDR) and including those with very low SDR, and to identify the factors influencing treatment effectiveness and to provide insights into therapeutic approaches for patients with lower SDR. METHODS: Real-world data from 101 patients who underwent MRgFUS between July 2019 and March 2022 at a single institution were analyzed. Tremor severity was assessed using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST). The patients were categorized into quartile groups based on their mean SDR, and the characteristics, treatment effectiveness, treatment parameters, and adverse events were evaluated among these subgroups. RESULTS: Patients were classified into 4 quartiles based on the mean SDR: quartile 1 (Q1) (SDR 0.26-0.37), Q2 (SDR 0.38-0.42), Q3 (SDR 0.43-0.49), and Q4 (SDR 0.50-0.75). MRgFUS significantly improved total CRST and tremor score across all SDR subgroups. Additionally, there were no significant differences in the improvement rates among the 4 subgroups. Analysis of the treatment parameters revealed that lower mean SDR was associated with lower target maximum temperature and smaller coagulation volume after focused ultrasound (FUS). Regarding adverse events, headache and nausea during FUS and facial and head edema on the day after surgery were more frequent in the Q1 subgroup (very low-SDR group). In contrast, numbness was more common in the Q4 subgroup. However, all these adverse events had resolved by the 3-month follow-up except numbness. CONCLUSIONS: This study suggested that MRgFUS is effective and safe for patients with medication-resistant essential tremor, including those with very low mean SDR. However, the very low-SDR group had insufficient temperature elevation at the target site compared with the high-SDR group, suggesting the need for a different strategy. Notably, with careful adjustments and considerations, positive outcomes can still be achieved in patients with very low SDR. Therefore, very low SDR should not be considered an absolute exclusion criterion because it is expected to increase the number of patients who benefit from MRgFUS.

Video Motion Analysis as a Quantitative Evaluation Tool for Essential Tremor during Magnetic Resonance-Guided Focused Ultrasound Thalamotomy.

The Clinical Rating Scale for Tremor (CRST) is commonly used to evaluate essential tremor (ET) during focused ultrasound (FUS) thalamotomy. However, it faces challenges such as the ceiling effect and test-retest variability. This study explored the utility of videographic motion analysis as an evaluation index for ET. Forty-three patients with ET performed postural tremor and line-drawing tasks recorded on video, and the data were analyzed using motion analysis software. The test-retest and inter-rater reliability, correlations with the CRST and tremor scores, and pre/post-FUS treatment comparisons were analyzed. The video motion analysis showed excellent test-retest and inter-rater reliability. In the postural tremor tasks, video parameter amplitude significantly correlated with the CRST and tremor scores. Similarly, for the line-drawing task, video parameter amplitude showed significant correlations with CRST and tremor scores, effectively addressing the ceiling effect. Regarding post-FUS treatment improvements, changes in the CRST and tremor scores were significantly associated with changes in video parameter amplitude. In conclusion, quantitative analysis of the video motion of ET enables precise evaluation of kinematic characteristics and effectively resolves the ceiling effect and test-retest variability. The video motion analysis score accurately reflected the tremor severity and treatment effects, demonstrating its high clinical utility.

Three-dimensional gait analysis of the effect of directional steering on gait in patients with Parkinson's disease.

INTRODUCTION: Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system. METHODS: Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control. RESULTS: Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°. CONCLUSION: Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.

Improvement in Intraoperative Image Quality in Transcranial Magnetic Resonance-Guided Focused Ultrasound Surgery Using Transmitter Gain Adjustment.

INTRODUCTION: Transcranial magnetic resonance-guided focused ultrasound surgery (TcMRgFUS) has the advantage of allowing immediate evaluation of therapeutic effects after each sonication and intraoperative magnetic resonance imaging (MRI) to visualize the lesion. When the image shows that the lesion has missed the planned target and the therapeutic effects are insufficient, the target of the subsequent ablation can be finely adjusted based on the image. The precision of this adjustment is determined by the image quality. However, the current intraoperative image quality with a 3.0T MRI system is insufficient for precisely detecting the lesion. Thus, we developed and validated a method for improving intraoperative image quality. METHODS: Because intraoperative image quality is affected by transmitter gain (TG), we acquired T2-weighted images (T2WIs) with two types of TG: the automatically adjusted TG (auto TG) and the manually adjusted TG (manual TG). To evaluate the character of images with 2 TGs, the actual flip angle (FA), the image uniformity, and the signal-to-noise ratio (SNR) were measured using a phantom. Then, to assess the quality of intraoperative images, T2WIs with both TGs were acquired during TcMRgFUS for 5 patients. The contrast-to-noise ratio (CNR) of the lesion was retrospectively estimated. RESULTS: The images of the phantom with the auto TG showed substantial variations between the preset and actual FAs (p < 0.01), whereas on the images with the manual TG, there were no variations between the two FAs (p > 0.05). The total image uniformity was considerably lower with the manual TG than with the auto TG (p < 0.01), indicating that the image's signal values with the manual TG were more uniform. The manual TG produced significantly higher SNRs than the auto TG (p < 0.01). In the clinical study, the lesions were clearly detected in intraoperative images with the manual TG, but they were difficult to identify in images with the auto TG. The CNR of lesions in images with manual TG was considerably higher than in images with auto TG (p < 0.01). CONCLUSION: Regarding intraoperative T2WIs using a 3.0T MRI system during TcMRgFUS, the manual TG method improved image quality and delineated the ablative lesion more clearly than the current method with auto TG.

Deep brain stimulation in posterior subthalamic area for Holmes tremor: Case reports with review of the literature.

Background: Holmes tremor (HT) is a refractory tremor associated with cortico-basal ganglia loops and cerebellothalamic tract abnormalities. Various drug treatments have been attempted; however, no treatment method has yet been established. Historically, thalamic deep brain stimulation (DBS) has been performed in medically refractory cases. Recently, the posterior subthalamic area (PSA) has been used for HT. Here, we report cases of HT and review the effectiveness and safety of PSA-DBS for HT. Cases: We conducted a retrospective chart review of two patients with HT who underwent PSA-DBS. Improvement in tremors was observed 1 year after surgery without apparent complications. Literature review: We identified 12 patients who underwent PSA-DBS for HT, including our cases. In six patients, PSA was targeted alone; for the rest, the ventralis intermediate nucleus (Vim) of the thalamus and PSA were simultaneously targeted. The Fahn-Tolosa-Marin Tremor Rating Scale improvement rates were 56.8% (range, 33.9-82.1%; n = 6) and 77.8% (range, 42.6-100%; n = 5) for the PSA-DBS and PSA+Vim-DBS, respectively. Conclusion: Reasonable improvements in HT were observed after PSA-DBS. PSA might be an appropriate target for improving the symptoms of HT. Long-term observations, accumulation of cases, and randomized studies are required in future.

Role of the subthalamic nucleus in perceiving and estimating the passage of time.

Sense of time (temporal sense) is believed to be processed by various brain regions in a complex manner, among which the basal ganglia, including the striatum and subthalamic nucleus (STN), play central roles. However, the precise mechanism for processing sense of time has not been clarified. To examine the role of the STN in temporal processing of the sense of time by directly manipulating STN function by switching a deep brain stimulation (DBS) device On/Off in 28 patients with Parkinson's disease undergoing STN-DBS therapy. The test session was performed approximately 20 min after switching the DBS device from On to Off or from Off to On. Temporal sense processing was assessed in three different tasks (time reproduction, time production, and bisection). In the three temporal cognitive tasks, switching STN-DBS to Off caused shorter durations to be produced compared with the switching to the On condition in the time production task. In contrast, no effect of STN-DBS was observed in the time bisection or time reproduction tasks. These findings suggest that the STN is involved in the representation process of time duration and that the role of the STN in the sense of time may be limited to the exteriorization of memories formed by experience.

Cavitation with low-energy sonication during focused ultrasound thalamotomy for a patient with tremor-dominant Parkinson's disease: a potential risk.

We report a patient with tremor-dominant Parkinson's disease who had a mild cavitation bioeffect during magnetic resonance-guided focused ultrasound thalamotomy. During the aligning phase with low-energy sonication, cavitation caused mild dysarthria and paresthesia, prompting treatment cessation. At the same time, tremor and rigidity improved. MRI revealed extensive high-intensity lesions in the thalamus 1 day after the procedure followed by steroid infusion, which resulted in resolution of adverse events. Tremor and rigidity improved 1.5 years after the procedure. Although cavitation can relieve tremors and rigidity, it should be carefully monitored due to potential permanent adverse events by unpredictable and unknown behaviors.

Short-Term Motor Outcomes in Parkinson's Disease after Subthalamic Nucleus Deep Brain Stimulation Combined with Post-Operative Rehabilitation: A Pre-Post Comparison Study.

Background: The effects of subthalamic nuclear deep brain stimulation therapy (STN-DBS) and combined postoperative rehabilitation for patients with Parkinson's disease with postural instability have yet to be well reported. This study investigated the effects of short-term postoperative rehabilitation with STN-DBS on physical function in patients with Parkinson's disease. Methods: Patients diagnosed with Parkinson's disease who were admitted to our hospital for STN-DBS surgery were included in this study. Data were prospectively collected and retrospectively analyzed. Postoperative rehabilitation consisted of muscle-strengthening exercises, stretching, and balance exercises for 40-60 minutes per day for approximately 14 days. The Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go test (TUG) seconds and steps, Trunk Impairment Scale (TIS), seconds for 10 times toe-tapping, lower limb extension torque using StrengthErgo240, and center of pressure sway in the quiet standing posture were evaluated preoperatively, postoperatively, and at discharge. Mini-BESTest changes were also evaluated in the two groups classified by the presence or absence of postural instability. One-way and two-way repeated measures analyses of variance were performed for each of the three periods of change, and paired t-tests with the Bonferroni method were performed as multiple comparison tests. A stepwise multiple regression model was used to identify factors associated with balance improvement. Results: A total of 60 patients with Parkinson's disease were included, and there were significant increases in Mini-BESTest, TIS, StrengthErgo240, and postural sway during closed-eye standing compared to pre- and postoperative conditions at discharge (p < 0.05), and they decreased significantly compared to the postoperative period (p < 0.05). On stepwise multiple regression analysis, decreased steps of TUG and improvement of TIS scores were related to improvement of the Mini-BESTest (p < 0.05). In addition, Mini-BESTest scores in both groups with and without postural instability were significantly increased at discharge compared to preoperative and postoperative conditions (p < 0.01). Conclusion: Postoperative rehabilitation combined with STN-DBS may provide short-term improvements in physical function compared with the preoperative medicated status. The improvements in gait step length and trunk function may be important factors for obtaining improvement of postoperative postural stability.

Predictors of thermal increase in magnetic resonance-guided focused ultrasound treatment for essential tremor: histogram analysis of skull density ratio values for 1024 elements.

OBJECTIVE: Sufficient thermal increase capable of generating thermocoagulation is indispensable for an effective clinical outcome in patients undergoing magnetic resonance-guided focused ultrasound (MRgFUS). The skull density ratio (SDR) is one of the most dominant predictors of thermal increase prior to treatment. However, users currently rely only on the average SDR value (SDRmean) as a screening criterion, although some patients with low SDRmean values can achieve sufficient thermal increase. The present study aimed to examine the numerical distribution of SDR values across 1024 elements to identify more precise predictors of thermal increase during MRgFUS. METHODS: The authors retrospectively analyzed the correlations between the skull parameters and the maximum temperature achieved during unilateral ventral intermediate nucleus thalamotomy with MRgFUS in a cohort of 55 patients. In addition, the numerical distribution of SDR values was quantified across 1024 elements by using the skewness, kurtosis, entropy, and uniformity of the SDR histogram. Next, the authors evaluated the correlation between the aforementioned indices and a peak temperature > 55°C by using univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis was performed to compare the predictive ability of the indices. The diagnostic performance of significant factors was also assessed. RESULTS: The SDR skewness (SDRskewness) was identified as a significant predictor of thermal increase in the univariate and multivariate logistic regression analyses (p < 0.001, p = 0.013). Moreover, the receiver operating characteristic curve analysis indicated that the SDRskewness exhibited a better predictive ability than the SDRmean, with area under the curve values of 0.847 and 0.784, respectively. CONCLUSIONS: The SDRskewness is a more accurate predictor of thermal increase than the conventional SDRmean. The authors suggest setting the SDRskewness cutoff value to 0.68. SDRskewness may allow for the inclusion of treatable patients with essential tremor who would have been screened out based on the SDRmean exclusion criterion.

White matter and nigral alterations in multiple system atrophy-parkinsonian type.

Multiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson's disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson's disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson's disease patients. Our results shed light on alterations to brain microstructure in MSA.

Case Report: Chronic Adaptive Deep Brain Stimulation Personalizing Therapy Based on Parkinsonian State.

We describe the case of a 51-year-old man with Parkinson's disease (PD) presenting with motor fluctuations, who received bilateral subthalamic deep brain stimulation (DBS) with an adaptive DBS (aDBS) device, Percept™ PC (Medtronic, Inc. , Minneapolis, MN). This device can deliver electrical stimulations based on fluctuations of neural oscillations of the local field potential (LFP) at the target structure. We observed that the LFP fluctuations were less evident inside the hospital than outside, while the stimulation successfully adapted to beta oscillation fluctuations during the aDBS phase without any stimulation-induced side effects. Thus, this new device facilitates condition-dependent stimulation; this new stimulation method is feasible and provides new insights into the pathophysiological mechanisms of PD.

[Micro-electrode Recordings in Stereotactic Functional Neurosurgery].

Accurate targeting to the sensorimotor territory of the globus pallidus internus (GPi), the subthalamic nucleus (STN), and the thalamic ventral intermediate nucleus (Vim) is crucial for the stereotactic neurosurgery of lesioning or implantation of a deep brain stimulation electrode. Intra-operative micro-electrode recording can aid in the localization of these structures. Neurons in the GPi are characterized by high-frequency tonic discharge. The STN has a high density of neurons that show irregular discharge. The majority of neurons in the sensorimotor territory of the GPi and STN exhibit neuronal responses to passive manipulation or active movement of the limbs and orofacial parts, and they are somatotopically arranged. Neurons responding to movements of the legs, arms, and face were found along the dorsal-ventral axis in the posterolateral GPi and along the medial-lateral axis in the posterolateral STN. Similarly, in the lateral part of the thalamic Vim nucleus, most neurons exhibit kinesthetic responses that show well-organized somatotopic arrangement, with the leg on the dorsolateral side, arm on the medioventral side, and face on the more medial side. Some Vim neurons have rhythmic bursting discharges synchronous with limb tremor. These electrophysiological findings allow us to achieve better surgical results.

White matter alterations in Parkinson's disease with levodopa-induced dyskinesia.

INTRODUCTION: Levodopa-induced dyskinesia is a complication of levodopa therapy and negatively impacts the quality of life of patients. We aimed to elucidate white matter alterations in Parkinson's disease with levodopa-induced dyskinesia using advanced diffusion magnetic resonance imaging techniques. METHODS: The enrolled subjects included 26 clinically confirmed Parkinson's disease patients without levodopa-induced dyskinesia, 25 Parkinson's disease patients with levodopa-induced dyskinesia, and 23 healthy controls. Subjects were imaged using a 3-T magnetic resonance scanner. Diffusion tensor imaging, diffusion kurtosis imaging, and neurite orientation dispersion and density imaging findings were compared between groups with a group-wise whole brain approach and a region-of-interest analysis for each white matter tract. Additionally, logistic regression analysis was used to calculate odds ratios for levodopa-induced dyskinesia. RESULTS: Group-wise tract-based spatial statistical analysis revealed significant white matter differences in isotropic diffusion, complexity, or heterogeneity, and neurite density between healthy controls and Parkinson's disease patients without levodopa-induced dyskinesia and between patients with and without levodopa-induced dyskinesia. Region-of-interest analysis revealed similar alterations using a group-wise whole-brain approach in the external capsule, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. These tracts had an odds ratio of approximately 2.3 for the presence of levodopa-induced dyskinesia. CONCLUSIONS: Our findings suggest that Parkinson's disease with levodopa-induced dyskinesia produces less white matter microstructural disruption, especially in temporal lobe fibers, than Parkinson's disease without levodopa-induced dyskinesia. These fibers has a more than 2-fold odds ratio for the presence of levodopa-induced dyskinesia and might be associated with the pathogenesis of the sequela.

Correction of the skull density ratio for transcranial MRI-guided focused ultrasound thalamotomy: clinical significance of predicting therapeutic temperature.

OBJECTIVE: In transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS), a high skull density ratio (SDR) is advantageous to achieve a sufficiently high temperature at the target. However, it is not easy to estimate the temperature rise because the SDR shows different values depending on the reconstruction filter used. The resolution characteristic of a computed tomography (CT) image depends on a modulation transfer function (MTF) defined by the reconstruction filter. Differences in MTF induce unstable SDRs. The purpose of this study was both to standardize SDR by developing a method to correct the MTF and to enable effective patient screening prior to TcMRgFUS treatment and more accurate predictions of focal temperature. METHODS: CT images of a skull phantom and five subjects were obtained using eight different reconstruction filters. A frequency filter (FF) was calculated using the MTF of each reconstruction filter, and the validity of SDR standardization was evaluated by comparing the variation in SDR before and after FF correction. Subsequently, FF processing was similarly performed using the CT images of 18 patients who had undergone TcMRgFUS, and statistical analyses were performed comparing the relationship between the SDRs before and after correction and the maximum temperature in the target during TcMRgFUS treatment. RESULTS: The FF was calculated for each reconstruction filter based on one manufacturer's BONE filter. In the CT images of the skull phantom, the SDR before FF correction with five of the other seven reconstruction filters was significantly smaller than that with the BONE filter (p < 0.01). After FF correction, however, a significant difference was recognized under only one condition. In the CT images of the five subjects, variation of the SDR due to imaging conditions was significantly improved after the FF correction. In 18 cases treated with TcMRgFUS, there was no correlation between SDR before FF correction and maximum temperature (rs = 0.31, p > 0.05); however, a strong positive correlation was observed after FF correction (rs = 0.71, p < 0.01). CONCLUSIONS: After FF correction, the difference in SDR due to the reconstruction filter used is smaller, and the correlation with temperature is stronger. Therefore, the SDR can be standardized by applying the FF, and the maximum temperature during treatment may be predicted more accurately.

Closed-loop programming using external responses for deep brain stimulation in Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD). Clinicians face various challenges in adjusting stimulation parameters and configurations in clinical DBS settings owing to inexperience, time constraints, and recent advances in DBS technology that have expanded the number of possible contact configurations. We aimed to assess the efficacy of a closed-loop algorithm (CLA) for the DBS-programming method using external motion sensor-based motor assessments in patients with PD. METHODS: In this randomized, double-blind, crossover study, we enrolled 12 patients who underwent eight-ring-contact DBS lead implantations bilaterally in the subthalamic nucleus. The DBS settings of the participants were programmed using a standard of care (SOC) and CLA method. The clinical effects of both programming methods were assessed in a randomized crossover fashion. The outcomes were evaluated using the Unified Parkinson's Disease Scale part III (UPDRS-III) and sensor-based scores for baseline (medication-off/stimulation-off) and both programming methods. The number of programming steps required for each programming method was also recorded. RESULTS: The UPDRS-III scores and sensor-based scores were significantly improved by SOC and CLA settings compared to the baseline. No statistical difference was observed between SOC and CLA. The programming steps were significantly reduced in the CLA settings compared to those in the SOC. No serious adverse events were observed. CONCLUSION: CLA can optimize DBS settings prospectively with similar therapeutic benefits as that of the SOC and reduce the number of programming steps. Automated optimization of DBS settings would reduce the burden of programming for both clinicians and patients.

[Management of Spinal Disorders in Parkinson's Disease].

Parkinson's disease(PD)is a degenerative disorder of the central nervous system. Its cardinal features are resting tremor, rigidity, bradykinesia, and postural instability. Several years after disease onset, many patients with PD exhibit postural deformities, including camptocormia, Pisa syndrome, and dropped head syndrome, which can lead to spinal deformities. In addition, spinal degenerative disorders are frequently associated with PD and can further impact the patients' quality of life. Current evidence suggests a multifactorial etiology for postural deformities and spinal degenerative disorders in PD, which includes abnormal stress on the spine(biomechanical factors), postural instability and impairment of postural compensation(physiological factors), and imbalance of dopaminergic signals(pharmacological factors). The relative contribution of these factors varies between patients and across symptoms. Consequently, neurologists have difficulty treating these axial problems. Moreover, many studies have reported poor outcomes and high complication rates of spinal surgery in patients with PD, which embarrasses spinal surgeons. An improved understanding of the mechanisms underlying spinal problems in PD might ultimately lead to more effective management of these disabling complications.

Single arm prospective multicenter case series on the use of burst stimulation to improve pain and motor symptoms in Parkinson's disease.

BACKGROUND: In this study we analyze new clinical data in the use of spinal cord stimulation (SCS) for the treatment of pain and motor symptoms in patients with Parkinson's Disease (PD), as both a singular bioelectric therapy and as a salvage therapy after deep brain stimulation (DBS). METHODS: Fifteen patients were recruited and had percutaneous electrodes implanted at the level of the thoracic or cervical spine. Participants were set to one of three stimulation modes: continuous tonic stimulation, continuous Burst stimulation (40 Hz, 500 Hz, 1000 µs), or cycle mode (on time of 10-15 s, off time of 15-30 s) with Burst (40 Hz, 500 Hz, 1000 µs). Patients completed the Visual Analogue Scale (VAS), Unified Parkinson's Disease Rating Scale, Self-Rating Depression Scale, Hamilton Depression Rating Scale, Profile of Mood State, 10-meter walking test, and the Timed Up and Go (TUG). RESULTS: All patients experienced significant improvement in VAS scores with a mean reduction of 59% across all patients. Patients who chose the cycling burst stimulation parameter had an average 67% reduction in VAS scores, as compared to the continuous burst parameter group, which had an average 48% reduction in VAS scores. Seventy-three percent of patients experienced improvement in the 10-meter walk, with an average improvement of 12%. Sixty-four percent of patients experienced clinically relevant improvements in the TUG, with an average improvement of 21%. CONCLUSIONS: This study points to the potential utility of SCS to address both pain and certain aspects of motor symptoms in PD patients who have and have not received DBS therapy.