Subthalamic somatosensory evoked potentials in Parkinson's disease.

Deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. It also provides an opportunity to record neural activity from the human basal ganglia. In this study, to investigate the involvement of the human STN in sensory functions, we recorded somatosensory evoked potentials (SEPs) elicited by contralateral median-nerve stimulation, from STN electrodes implanted for DBS in patients with Parkinson's disease. We suggest that the STN N18 component of SEPs in Parkinson's disease is a mainly local field potential elicited by muscle afferent input to the nucleus.     

Subthalamic Nucleus Deep Brain Stimulation in Primary Meige Syndrome: A 1-Year Follow-Up Study

ObjectiveTo investigate the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome.Materials and MethodsFifteen consecutive patients who underwent STN-DBS at the Peking University People’s Hospital between September 2017 and June 2018 were included in this study. The Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) movement score and the BFMDRS disability score were obtained prior to surgery, and at specific time points after surgery. Patients’ sleep status was also assessed before and after surgery.ResultsThe BFMDRS movement scores decreased from 15.3 ± 4.6 to 5.2 ± 6.2 after STN-DBS, with a mean improvement of 68.6% (p < 0.05). The BFMDRS disability scores were also significantly decreased, from 6.9 ± 3.3 to 3.5 ± 2.9, with a mean improvement of 51.7% (p < 0.05). The eye, mouth, speech, and swallowing movement scores also decreased significantly after STN-DBS compared to baseline (p < 0.05). The sleep quality of the patients was also improved after surgery.ConclusionsThese findings demonstrate that the STN is an effective brain target for the treatment of patients with Meige syndrome. STN-DBS was not only able to improve patients’ motor symptoms, but also their sleep status.     

Eight-years Failure of Subthalamic Stimulation Rescued by Globus Pallidus Implant

BackgroundDeep brain stimulation is the surgical procedure of choice in patients with Parkinson's disease. The subthalamic nucleus and the globus pallidus interna are the two most common targets used to treat Parkinson's disease.MethodsWe describe three patients with previous effective subthalamic deep brain stimulation in whom globus pallidus interna deep brain stimulation was performed as “rescue” surgery, 8 years after the original operation.ResultsTwo years after globus pallidus surgery the reduction of dystonia and dyskinesias led to an improvement of motor symptoms. In two patients, painful dystonias disappeared and motor fluctuations markedly improved. One patient achieved an improvement in freezing.ConclusionAfter 24 months of follow up, our observations suggest that globus pallidus deep brain stimulation, can improve motor fluctuations, dyskinesia and axial symptoms.     

Subthalamic Nucleus Activity during Cognitive Load and Gait Dysfunction in Parkinson's Disease

Background

Gait freezing is a common, disabling symptom of Parkinson's disease characterized by sudden motor arrest during walking. Adaptive deep brain stimulation devices that detect freezing and deliver real-time, symptom-specific stimulation are a potential treatment strategy. Real-time alterations in subthalamic nucleus firing patterns have been demonstrated with lower limb freezing, however, whether similar abnormal signatures occur with freezing provoked by cognitive load, is unknown.

Methods

We obtained subthalamic nucleus microelectrode recordings from eight Parkinson's disease patients performing a validated virtual reality gait task, requiring responses to on-screen cognitive cues while maintaining motor output.

Results

Signal analysis during 15 trials containing freezing or significant motor output slowing precipitated by dual-tasking demonstrated reduced θ frequency (3–8 Hz) firing compared to 18 unaffected trials.

Conclusions

These preliminary results reveal a potential neurobiological basis for the interplay between cognitive factors and gait disturbances including freezing in Parkinson's disease, informing development of adaptive deep brain stimulation protocols. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

丘脑底核高频刺激治疗帕金森病

目的：研究脑深部刺激（DBS）对帕金森病（PD）的治疗作用。观察术中丘脑底核（STN）刺激对PD震颤,肌僵直、运动缓慢的缓解效果及对语言的影响,探讨植入刺激电极的最佳位置。方法：17例帕金森病患者,利用MRI及微电极导向立体定向方法将刺激电极植入丘脑底核,其靶点：X=11mm,Y=-1mm,Z=-7mm。术中予以高频刺激（频率为150Hz,脉宽为150μz,脉宽为150μs,电压自0.5V开始,逐渐增至6-8V）;其中有2例进行了STN电极永久性植入慢性电刺激,术后随访6-8月,结果：17例术中刺激发现,STN中上部是其刺激、改善病人症状的最佳位置,而电极过深及过外则易引起言语障碍,2例永久性植入慢性电刺激经随访观察对肌僵直的控制非常满意,对运动缓慢有明显改善,并减少美多巴的服药量,UPDRS运动评分下降50%。结论：STN的高频刺激能改善PD的震颤,僵直,运动缓慢等主要症状,是PD慢性刺激的最理想靶点,其中上部是刺激效果的最佳位置。     

Psychiatric Symptoms and Subthalamic Nucleus Stimulation in Parkinson's Disease. A Retrospective Study in Our Japanese Patients

Objectives. With respect to postoperative activities of daily living (ADL), we retrospectively investigated associated psychiatric symptoms that influenced beneficial effects of subthalamic nucleus (STN) stimulation in our Japanese patients with Parkinson disease (PD). Materials and Methods. Twenty‐five patients underwent bilateral STN stimulation. Pre‐ and 3 months after the surgery, their parkinsonian symptoms were evaluated with Unified Parkinson Disease Rating Scale (UPDRS) and Schwab‐England (S‐E) ADL scale. Stepwise multiple analysis was performed to determine the factors affecting postoperative ADL. Results. Eleven out of 25 patients manifested drug‐induced psychosis preoperatively, although their mean dosage of levodopa was small (366.4 ± 152.7 mg). Disease duration positively affected the severity of the patients’ psychiatric symptoms. Postoperative S‐E score showed a significant improvement compared to the pretreatment baseline in both of “on” and “off” medication states, as all their cardinal motor symptoms were significantly ameliorated. Preoperative scores for thought disorder and axial disability negatively impact on the postoperative S‐E score in “on” state (p < 0.01). Preoperative score for intellectual impairment was only a significant predictor of worse postoperative ADL in “off” state. Conclusions. The markedly lower dose of levodopa may suggest ethnic characteristics of our Japanese patients with respect to tolerance for antiparkinsonian medications. Preoperative manifestation of drug‐induced psychosis and cognitive dysfunction were the major factor that strikingly suppressed daily activities after STN stimulation.     

Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis

Apathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta-analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre- and post-DBS or the cross-sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty-three articles were included in the meta-analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre-operatively (g = 0.34, 95% confidence interval [CI] = 0.19–0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03–0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta-analysis indicate that apathy is increased after STN DBS compared to the pre-operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

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 ± 0.7 mm), and the shifts in the inferior direction (z‐axis: 0.11 ± 0.43 mm) and lateral direction (x‐axis: 0.02 ± 0.39 mm) 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.     

Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease

Background: Subthalamic deep brain stimulation (STN‐DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. Objectives: To assess the relevance of pyramidal tract activation with STN‐DBS in PD. Methods: In a multimodal, blinded study in 20 STN‐DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Results: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a “lateral‐type” speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Conclusions: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society     

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016. © 2015 Wiley Periodicals, Inc .     

Effect of Subthalamic Nucleus Stimulation on Severe Striatal Hand Deformity in Parkinson's Disease: A Case Report

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa‐induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN‐DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN‐DBS on the hand deformity was a secondary effect on muscular rigidity. STN‐DBS is assumed to represent a useful treatment option for striatal hand deformity.     

Long Disease Duration Interferes With Therapeutic Effect of Globus Pallidus Internus Pallidal Stimulation in Primary Cervical Dystonia

Objectives: We retrospectively investigated the correlation between disease duration and the therapeutic effect of globus pallidus internus (GPi) stimulation in patients with primary cervical dystonia (CD). Materials and Methods: Eight patients with CD unresponsive to medical treatments underwent bilateral GPi deep brain stimulation (DBS). They were followed for 63.5 ± 38.2 months (mean ± standard deviation) and were assessed before and at 1, 12, 24, and 36 months after surgery and at their final visit to our outpatient clinic using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Univariate analysis was performed to identify factors that affected their postoperative TWSTRS score. Results: At last follow‐up, disease severity and the degree of disability and pain on the TWSTRS were significantly improved by 70.2%, 76.1%, and 87.1%, respectively (p < 0.05, Wilcoxon signed‐rank test). Neither age nor preoperative CD severity was predictive of postoperative improvement; however, the disease duration affected their reduction rate of TWSTRS severity score at each time point investigated (p < 0.05). Conclusions: Bilateral GPi‐DBS is an effective long‐term therapy in patients with CD. The delivery of GPi stimulation in the earlier course of CD may yield greater postoperative improvement.     

Impact of Subthalamic Nucleus Stimulation on Young‐Onset Parkinson's Disease

Objective. To clarify the efficacy of subthalamic nucleus (STN) stimulation in young‐onset Parkinson's disease (PD), we compared the effects of STN stimulation on the motor symptoms between young‐onset PD (YOPD) and late‐onset PD (LOPD). Methods. We analyzed the effects of STN stimulation on motor function and motor fluctuations in 15 patients with YOPD, and 113 patients with LOPD who underwent STN stimulation during the same period. The Unified Parkinson's Disease Rating Scale (UPDRS) was evaluated during the on‐period and off‐period, which are defined as the times at which the motor symptoms are the best and worst during the daily active time with sustaining anti‐parkinsonian drugs. The dyskinesia severity rating scale (DSRS) also was employed to assess the severity of peak‐dose dyskinesia. We analyzed the changes in levodopa equivalent daily dose (LED), motor fluctuations, DSRS, and UPDRS part 3 score after STN stimulation, and compared the changes in each score between the two groups (YOPD vs. LOPD). Results. The LED was reduced, and the on‐off motor fluctuation index, dyskinesia rating scale score (on‐period), and UPDRS part 3 score (on‐ and off‐periods) were improved in both the YOPD and LOPD groups. The improvement rates of the UPDRS part 3 scores in both the on‐ and off‐periods in the YOPD group were superior to those in the LOPD group. The results of multivariate logistic regression analysis demonstrated that YOPD itself is the best responder to STN stimulation. Conclusions. STN stimulation can reduce the LED and improve motor fluctuations in patients with YOPD. The effects of STN stimulation on the motor symptoms of YOPD patients are superior to those in LOPD. The present findings suggest that YOPD patients suffering from several problems related to pharmacological therapy are probably good candidates for STN stimulation.     

Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinson's disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% ± 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms. © 2009 Movement Disorder Society