Subthalamic Nucleus Deep Brain Stimulation For Parkinson's Disease Research Articles

Effects of Unilateral High Frequency Stimulation of the Subthalamic Nucleus on Risk-avoidant Behavior in a Partial 6-hydroxydopamine Model of Parkinson's Disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for the motor symptoms of Parkinson's disease (PD). While PD is primarily characterized by motor symptoms such as tremor, rigidity, and bradykinesia, it also involves a range of non-motor symptoms, and anxiety is one of the most common. The relationship between PD and anxiety is complex and can be a result of both pathological neural changes and the psychological and emotional impacts of living with a chronic progressive condition. Managing anxiety in PD is critical for improving the patients' quality of life. However, patients undergoing STN DBS can occasionally experience increased anxiety. This study investigates changes in risk-avoidant behavior following STN DBS in a pre-motor animal model of PD under chronic and acute unilateral high frequency stimulation. No significant changes in risk-avoidant behaviors were observed in rats who underwent STN DBS compared with sham stimulation controls. Chronic stimulation prevented sensitization in the elevated zero maze. These results suggest that unilateral stimulation of the STN may have minimal effects on risk-avoidant behaviors in PD. However, additional research is required to fully understand the mechanisms responsible for changes in anxiety during STN DBS for PD.

Intraoperative microelectrode recording under general anesthesia guided subthalamic nucleus deep brain stimulation for Parkinson's disease: One institution's experience.

Microelectrode recording (MER) guided subthalamic nucleus deep brain stimulation (STN-DBS) under local anesthesia (LA) is widely applied in the management of advanced Parkinson's disease (PD). Whereas, awake DBS under LA is painful and burdensome for PD patients. We analyzed the influence of general anesthesia (GA) on intraoperative MER, to assess the feasibility and effectiveness of GA in MER guided STN-DBS. Retrospective analysis was performed on the PD patients, who underwent bilateral MER guided STN-DBS in Wuhan Union Hospital from July 2019 to December 2021. The patients were assigned to LA or GA group according to the anesthetic methods implemented. Multidimensional parameters, including MER signals, electrode implantation accuracy, clinical outcome and adverse events, were analyzed. A total of 40 PD patients were enrolled in this study, including 18 in LA group and 22 in GA group. There were no statistically significant differences in patient demographics and baseline characteristics between two groups. Although, the parameters of MER signal, including frequency, inter-spike interval (ISI) and amplitude, were obviously interfered under GA, the waveforms of MER signals were recognizable and shared similar characteristics with LA group. Both LA and GA could achieve effective electrode implantation accuracy and clinical outcome. They also shared similar adverse events postoperatively. GA is viable and comparable to LA in MER guided STN-DBS for PD, regarding electrode implantation accuracy, clinical outcome and adverse events. Notably, GA is more friendly and acceptable to the patients who are incapable of enduring intraoperative MER under LA.

Carbohydrate metabolism and lipid profile in patients with Parkinson's disease with subthalamic deep brain stimulation.

Assessment of potential effect of subthalamic nucleus deep brain stimulation (STN-DBS) on glucose metabolism in patients with Parkinson's disease (PD). Although a valuable alternative to pharmacotherapy in advanced PD, STN-DBS is thought to negatively affect the cardiometabolic profile of patients (including body mass, lipid profile). Exacerbation of glucose metabolism dysregulation after DBS could therefore be assumed. Two groups of patients with Parkinson's disease were included: 20 treated pharmacologically (PHT) and 20 newly qualified for STN-DBS (DBS) - with the first assessment prior to surgery, and the second 11 months after surgery on average. Body mass index (BMI), plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and glucose levels during a three-point oral glucose tolerance test were measured three times (median intervals between visits 12 and 14 months respectively). Significant differences between the two groups were noted with respect to changes in BMI, and serum concentration of TG and HDL-C over the course of the study. In the DBS group, a significant increase in BMI (26.42 vs. 27.24 kg/m2, p = 0.03) and TG level (103.8 vs. 142.8 mg/dL, p < 0.001) with a simultaneous decrease in HDL-C level (54.4 vs. 46 mg/dL, p < 0.01) was observed. Mean glucose level after oral glucose administration was lower in the DBS than in the PHT group (147.4 vs. 120.2 mg/dL, p = 0.03 after one hour and 109.9 vs. 82.3 mg/dL, p < 0.01 after two hours) during the second visit. Also inter-visit changes in fasting glucose levels (8.4 mg/dL in the PHT group and -5.8 mg/dL in the DBS group, p = 0.02) differed over the study duration. Our observations are similar to previous ones indicating less favourable changes in BMI and some lipid fractions in patients treated surgically. Interestingly, such a trend was not observed for glucose metabolism parameters, suggesting that mechanisms other than simple body mass changes are involved in early biochemical changes after STN-DBS in PD patients. The metabolic consequences of DBS require further investigation as an additional factor potentially affecting the outcome of therapy, and routine patient follow-up should not be limited to neurological and psychological assessments.

Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson's Disease: 10 Years and Beyond

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. To investigate the survival rate and long-term outcome of DBS. We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

P.124 Subnuclear contact localization within the subthalamic nucleus in deep brain stimulation for Parkinson Disease

Background: Therapeutic response from subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD) has been associated with proximity to an ideal target, commonly in the dorsal sensorimotor STN. Automated registration and atlas-based segmentation has allowed for contact localization within STN subnuclei. We sought to apply these methods to characterize the spatial distribution of our active contact placements. Methods: We conducted a retrospective analysis of 55 patients who underwent bilateral STN DBS for PD. Post-operative CT/MRI scans were non-linearly registered into a standard space, and DBS-electrodes were localized using Lead-DBS. 3-dimensional meshes from a segmented atlas (Ewert 2017) were utilized. Analysis was performed in MATLAB R2019b. Results: Mean active contacts were within sensorimotor STN bilaterally, located posteroinferiorly compared to reported ideal targets. Centroids fell within (left/right): sensorimotor (46%/40%), associative (22%/22%), limbic (0%/2%) and outside STN (32%/36%). Principal components analysis demonstrated most spatial variance is explained by the first component (left 65.8%, right 61.9%). Conclusions: We obtained contact locations in relation to STN subnuclei, allowing for an anatomically guided approach to our analysis. 66% of the active contacts were located within the STN, and most of the spatial variation occurred along a single dimension. Future directions include utilizing subnuclei localizations to investigate clinical outcomes.

The Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease on Associative Learning of Verbal and Non-Verbal Information by Trial and Error or with Corrective Feedback.

Parkinson's disease (PD) and subthalamic nucleus deep brain stimulation (STN-DBS) are both known to induce cognitive changes. The aim of our study was to investigate the impact of STN-DBS on two forms of conditional associative learning (CAL), trial and error or corrective feedback learning, which differed in difficulty to test the load-dependency hypothesis of the cognitive effects of STN-DBS in PD. We recruited two groups of PD patients, those who had STN-DBS surgery bilaterally (n = 24) and a second unoperated group (n = 9) who were assessed on two versions of a task of visual CAL involving either a more difficult trial and error learning or a relatively easier corrective feedback learning. Each task was completed twice by both groups, On and Off STN-DBS for the operated group and a first and second time by the unoperated group. With STN-DBS Off, corrective feedback learning was superior to trial and error CAL, but not with STN-DBS On. The unoperated PD group had improved performance during the second assessment. To control for the improvement observed with repeated assessment in the PD control group, we split the STN-DBS group into two subgroups based on the condition of the first assessment (Off first vs. On first). While we found no STN-DBS effects for the Off first subgroup (N = 14), we observed improved performance during the second STN-DBS Off session for the On first subgroup (N = 10). The findings suggest that in PD, STN-DBS interferes with use of corrective feedback and its integration in the conditional associative learning process. Also STN stimulation affected the ability of operated patients to resolve proactive interference during learning of the arbitrary visual associations by trial and error or with corrective feedback.

Modeling of Electric Fields in Individual Imaging Atlas for Capsular Threshold Prediction of Deep Brain Stimulation in Parkinson's Disease: A Pilot Study.

Background: Modeling of deep brain stimulation electric fields and anatomy-based software might improve post-operative management of patients with Parkinson's disease (PD) who have benefitted from subthalamic nucleus deep brain stimulation (STN-DBS).Objective: We compared clinical and software-guided determination of the thresholds for current diffusion to the pyramidal tract, the most frequent limiting side effect in post-operative management of STN-DBS PD patients.Methods: We assessed monopolar reviews in 16 consecutive STN-DBS PD patients and retrospectively compared clinical capsular thresholds, which had been assessed according to standard clinical practice, to those predicted by volume of tissue activated (VTA) model software. All the modeling steps were performed blinded from patients' clinical evaluations.Results: At the group level, we found a significant correlation (p = 0.0001) when performing statistical analysis on the z-scored capsular thresholds, but with a low regression coefficient (r = 0.2445). When considering intra-patient analysis, we found significant correlations (p < 0.05) between capsular threshold as modeled with the software and capsular threshold as determined clinically in five patients (31.2%).Conclusions: In this pilot study, the VTA model software was of limited assistance in identifying capsular thresholds for the whole cohort due to a large inter-patient variability. Clinical testing remains the gold standard in selecting stimulation parameters for STN-DBS in PD.

The probable REM sleep behavior disorder negatively affects health-related quality of life in Parkinson's disease with bilateral subthalamic nucleus stimulation

ObjectiveThe aim of this study was to compare the short- and long-term outcomes of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients with and without probable REM sleep behavior disorder (RBD). MethodsWe retrospectively reviewed 127 patients who underwent bilateral STN-DBS for PD with probable RBD from September 2011 to November 2018. Motor performance, physical and mental health-related quality of life (HRQoL), cognitive function, and depressive severity were compared between with or without probable RBD at the baseline and at the 1-, 3- or 5-year follow-up. ResultsOne hundred three PD patients (55 with RBD; 48 without RBD) were evaluated at the baseline and at the 1-year follow-up and 33 (17 with RBD, 16 without RBD) of them were examined at the 5-year follow-up. Motor performances were significantly improved in the non-RBD group compared to the RBD group at the 1-year follow-up, and there was a trend toward a greater difference in the physical HRQoL compared with the 1-year follow-up. There were also marked improvements of axial symptom and physical HRQoL in the non-RBD group compared with the RBD group from baseline to 5 years after STN-DBS. ConclusionOur study showed that RBD negatively affected the short- and long-term outcomes on motor performances, especially axial symptom and HRQoL after STN-DBS in PD patients.

The Effect of Unilateral Subthalamic Nucleus Deep Brain Stimulation on Contralateral Subthalamic Nucleus Local Field Potentials

Unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) improves ipsilateral symptoms, but how this occurs is not well understood. We investigated whether unilateral STN DBS suppresses contralateral STN beta activity in the local field potential (LFP), since previous research has shown that activity in the beta band can correlate with the severity of contralateral clinical symptoms and is modulated by DBS. We recorded STN LFPs from 14 patients who underwent bilateral STN DBS for PD. Following a baseline recording, unilateral STN stimulation was delivered at therapeutic parameters while LFPs were recorded from the contralateral (unstimulated) STN. Unilateral STN DBS suppressed contralateral beta power (p = 0.039, relative suppression = -5.7% ± [SD] 16% when averaging across the highest beta peak channels; p = 0.033, relative suppression = -5.2% ± 13% when averaging across all channels). Unilateral STN DBS produced a 17% ipsilateral (p = 0.016) and 29% contralateral (p = 0.002) improvement in upper limb hemi-body bradykinesia-rigidity (UPDRS-III, items 3.3-3.6). The ipsilateral clinical improvement and the change in contralateral beta power were not significantly correlated. Unilateral STN DBS suppresses contralateral STN beta LFP. This indicates that unilateral STN DBS modulates bilateral basal ganglia networks. It remains unclear whether this mechanism accounts for the ipsilateral motor improvements.

Tailoring Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease Using Evoked Resonant Neural Activity.

Deep brain stimulation (DBS) applied to the subthalamic nucleus (STN) can be a highly effective therapy for Parkinson's disease (PD); however, there are significant issues which limit its effectiveness, reliability, and tolerability. Inaccurate electrode implantation is common, which can reduce efficacy and cause side-effects due to the undesired activation of neighboring brain regions (Okun et al., 2005; Paek et al., 2013; Rolston et al., 2016). Consequently, in most centers patients are typically kept awake during implantation surgery so that clinical assessments can help determine whether the positioning of electrodes is acceptable (Chakrabarti et al., 2014). The programming of stimulation is also often suboptimally performed, and there are many examples of patients being suddenly liberated from poor movement when chronically applied settings are changed (Okun et al., 2005; Sommer et al., 2015). Programming also confers a high burden to patients and neurologists, especially in the era of directional electrodes, often requiring multiple sessions over several months to identify the most effective DBS settings (Cagnan et al., 2019). Moreover, once programmed, DBS is then applied invariantly without “adapting” to the real-time fluctuating needs of the patient (Little et al., 2013; Priori et al., 2013). A realistic solution to these issues is to use neuronal signals recorded from DBS electrodes to guide accurate electrode implantation (ideally with patients under general anesthesia), to automate programming, and to act as a feedback signal for continuous “adaptive” control. To achieve these aims, such a neuronal biomarker would likely need to localize to the STN (preferably the dorsal motor region where DBS is usually most effective; Herzog et al., 2004), reflect patient state and therapeutic effects with a reasonable time resolution, and, crucially, be reliably detectable in all patients and conditions, including under general anesthesia. Potential biomarkers that may fulfill these criteria for STN DBS in PD include measures from spontaneous neural activity, such as beta oscillations (Little and Brown, 2012; Priori et al., 2013). However, beta band (13–30 Hz) activity is typically of small magnitude (microvolts) and can be variable across patients (Giannicola et al., 2010), making it challenging to reliably record with high fidelity, particularly using implantable, miniaturized systems (Neumann et al., 2016). Evoked responses elicited by DBS pulses offer alternative biomarkers (Ashby et al., 2001; Baker et al., 2002; Walker et al., 2012; Gmel et al., 2015; Kent et al., 2015; Romeo et al., 2019), including the recently identified phenomenon of evoked resonant neural activity (ERNA) (Sinclair et al., 2018).

Postoperative Confusion in Patients with Parkinson Disease Undergoing Deep Brain Stimulation of the Subthalamic Nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for patients with Parkinson disease. One adverse event is the development of postoperative confusion. The aim of this study was to report the incidence and associated factors of postoperative confusion after STN DBS surgery. This was a retrospective cohort study by chart review of patients with Parkinson disease who underwent STN DBS in a Brazilian public academic hospital from January 2013 to October 2017. The primary outcome was the incidence of postoperative confusion. The association of the outcome and imaging and clinical variables was evaluated. Among 49 patients who underwent STN DBS for Parkinson disease, the incidence of postoperative confusion was 26.5% (95% confidence interval 15%-41.1%). Univariate analysis identified the following variables associated with development of confusion: age (63.2 ± 7.8 years vs. 55.4 ± 9.1 years, P= 0.009), disease duration (16.5 ± 5.1 years vs. 13.2 ± 4.2 years, P= 0.027), Charlson comorbidity index (2 [interquartile range 1-3] vs. 1 [0-1 interquartile range], P= 0.002), width of the third ventricle (5.4 ± 2.1 mm vs. 4 ± 1.6 mm, P= 0.018), and cella media index (5 ± 1 vs. 5.6 ± 0.8, P= 0.018). After adjustment, Charlson comorbidity index remained significant (adjusted relative risk 1.64, 95% confidence interval 1.17-2.3, P= 0.004). The incidence of postoperative confusion in this cohort was 26.5%. After analysis of confounding factors, the Charlson comorbidity index was significantly associated with postoperative confusion.

Alternate Subthalamic Nucleus Deep Brain Stimulation Parameters to Manage Motor Symptoms of Parkinson's Disease: Systematic Review and Meta-analysis.

The use of alternate frequencies, amplitudes, and pulse widths to manage motor symptoms in Parkinson's disease (PD) patients with subthalamic nucleus deep brain stimulation (STN-DBS) is of clinical interest, but currently lacks systematic evidence. Systematically review whether alternate STN-DBS settings influence the therapy's efficacy for managing PD motor symptoms. Systematic searches identified studies that; involved bilateral STN-DBS PD patients; manipulated ≥ 1 STN-DBS parameter (e.g., amplitude); assessed ≥ 1 motor symptom (e.g., tremor); and contrasted the experimental and chronic stimulation settings. A Mantel-Haenszel random-effects meta-analysis compared the UPDRS-III sub-scores at low (60-Hz) and high frequencies ( ≥ 130 Hz). Inter-study heterogeneity was assessed with the Cohen's χ2 and I2 index, while the standard GRADE evidence assessment examined strength of evidence. Of the 21 included studies, 17 investigated the effect of alternate stimulation frequencies, five examined alternate stimulation amplitudes, and two studied changes in pulse width. Given the available data, meta-analyses were only possible for alternate stimulation frequencies. Analysis of the heterogeneity amongst the included studies indicated significant variability between studies and, on the basis of the GRADE framework, the pooled evidence from the meta-analysis studies was of very low quality due to the significant risks of bias. The meta-analysis reported a very low quality of evidence for the efficacy of low-frequency STN-DBS for managing PD motor symptoms. Furthermore, it highlighted that lower amplitudes lead to the re-emergence of motor symptoms and further research is needed to understand the potential benefits of alternate STN-DBS parameters for PD patients.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson’s disease

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5–25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD.

Subthalamic deep brain stimulation and levodopa in Parkinson's disease: a meta-analysis of combined effects.

While subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa improve motor symptoms in Parkinson disease (PD) to a similar magnitude, their combined effect remains unclear. We sought to evaluate whether STN-DBS and levodopa yield differential effects on motor outcomes, dyskinesia, and activities of daily living (ADL) when combined compared to when administered alone. We conducted a meta-analysis of all studies reporting motor, dyskinesia, and ADL outcomes after bilateral STN-DBS in PD with presurgical Unified Parkinson's Disease Rating Scale (UPDRS-III) in Medication-OFF and Medication-ON states and postsurgical assessments in four conditions: Stimulation-ON/Medication-ON, Stimulation-ON/Medication-OFF, Stimulation-OFF/Medication-ON, and Stimulation-OFF/Medication-OFF. Dyskinesia duration (UPDRS item 32) and ADL (UPDRS-II) were compared between high and low postsurgical levodopa equivalent daily dose (LEDD) reduction. Random-effects meta-analyses using generic-inverse variance were conducted. Confidence in outcomes effect sizes was assessed. Twelve studies were included (n = 401 patients). Stimulation-ON/Medication-ON was associated with an UPDRS-III improvement of - 35.7 points [95% confidence interval, - 40.4, - 31.0] compared with Stimulation-OFF/Medication-OFF, - 11.2 points [- 14.0, - 8.4] compared with Stimulation-OFF/Medication-ON, and - 9.5 points [- 11.0, - 8.0] compared to Stimulation-ON/Medication-OFF within 5years. The difference was maintained beyond 5years by - 28.6 [- 32.8, - 24.4], - 8.1 [- 10.2, - 5.9], and - 8.0 [- 10.3, - 5.6], respectively. No difference was observed between Stimulation-ON/Medication-OFF and Stimulation-OFF/Medication-ON within and beyond 5years. Dyskinesia duration and ADL outcomes were similar in high vs. low postsurgical LEDD reduction. Subthalamic nucleus deep brain stimulation and levodopa independently lessened motor severity in PD to a similar magnitude, but their combined effect was greater than either treatment alone, suggesting therapeutic synergism.

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60μs, but there is limited data available on the effect of shorter PWs. To define the TW of STN-DBS in PD at PW of 30μs (PW30) relative to standard PW settings at 60μs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. STN-DBS in PD patients using a PW of 30μs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30μs settings.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease

Background/Aims: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. Methods: In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. Results: We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Conclusion: Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS.

Connectivity Predicts deep brain stimulation outcome in Parkinson disease.

The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.

High incidence of carpal tunnel syndrome after deep brain stimulation in Parkinson's disease.

We observed several cases of carpal tunnel syndrome (CTS) revealed after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). 115 consecutive PD patients who underwent STN-DBS between 2010 and 2014 at the Neurological Hospital in Lyon were retrospectively included. CTS was accepted as the diagnosis only if clinical examination and ENMG both confirmed it. Nine patients (7.8%) developed CTS in the 2years following surgery, which is far beyond the 2.7/1000 incidence in the general population. The present study shows an overrepresentation of CTS occurrence after STN-DBS in PD.

Greater improvement in LRRK2 G2019S patients undergoing Subthalamic Nucleus Deep Brain Stimulation compared to non-mutation carriers.

BackgroundBilateral subthalamic nucleus deep brain stimulation (STN-DBS) of parkinson’s disease (PD) patients has demonstrated to improve motor performance and to reduce dopa-induced dyskinesia. An association between the occurrence of dyskinesias and LRRK2 (leucine-rich repeat kinase 2) G2019S gene mutations has recently been suggested. The aim of this study is to discover the impact of the G2019S mutation (with high incidence in the authors’ native Algeria) on the symptom response of PD in patients who underwent STN-DBS.MethodsWe carried out a comparative statistical study for the clinical evaluation and neuropsychological assessment of 27 Algerian PD STN-DBS patients, both G2019S mutation carriers (MC) and non-carriers (NC). A multiple correspondence analysis (MCA) was then conducted to compare the results with those from groups of individuals with similar modalities.ResultsThe MCA revealed that MC and NC PD patients showed two different patterns of clinical evaluations. The group of idiopathic patients showed some differences compared to the clinical evaluations, depending on gender. No association was found between the G2019S mutation and the Mini Mental State Examination scores (MMSE), and MC patients appeared more susceptible to dyskinesia than NC patients. In NC patients, we found two cases with Parkin mutations who had a different “honeymoon” period and different initial symptoms. The results showed considerable improvement of motor unified parkinson’s disease rating scale III (UPDRS-III) in a situation of stimulation without medication in the MC patients with a percentage of improvement (51.1 %) over the required 30 % compared to the NC patients (25.5 %). The same result was observed for the Schwab and England’s activities of daily living scale (S and E scale), which thus demonstrated a greater effectiveness of DBS for MC patients than for NC patients. However, the Hoehn and Yahr scale (H and Y Scale) showed the same significance in a situation of stimulation for MC and NC patients. In this later group, the best scores of UPDRS-III were observed for patients with the Parkin mutation before they underwent surgery.ConclusionsThis study shows that surgical treatment probably has a more significant impact on LRRK2 G2019S MC than on idiopathic patients.

Awake Neurophysiologically Guided versus Asleep MRI-Guided STN DBS for Parkinson Disease: A Comparison of Outcomes Using Levodopa Equivalents

Background: Deep brain stimulation (DBS) for Parkinson's disease (PD) has traditionally been performed in awake patients. Some patients are unable to tolerate awake surgery or extensive time off their medication to allow for neurophysiological testing during traditional DBS implantation, which has previously limited surgical options for these patients. Recently, asleep image-guided lead placement using intraoperative MRI or CT for verification has been proposed as an alternative for patients unable or unwilling to undergo awake DBS surgery. Methods: We conducted a retrospective chart review comparing PD patients who underwent asleep MRI-guided subthalamic nucleus (STN) DBS lead placement (n = 14) and awake neurophysiologically guided STN DBS lead placement (n = 23) at our institution. Both groups' levodopa equivalent daily doses (LEDDs) and complications at approximately 6 months of follow-up were compared, along with operative times. Results: Both groups showed statistically similar reductions in LEDD at 6 months of therapy (38.27% for awake, 49.27% for asleep; p = 0.4447), and similar complications. Operative times were initially longer for MRI-guided DBS but improved with surgical experience. Conclusion: Asleep MRI-guided DBS is a viable option for PD patients unable or unwilling to undergo awake placement, with similar results in terms of LEDD reduction and complications.