Bilateral STN-DBS Research Articles

Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson\u2019s disease

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and sleep symptoms in Parkinson’s disease (PD). However, the long-term effects of STN-DBS on sleep and its relationship with QoL outcome are unclear.MethodsIn this prospective, observational, multicenter study including 73 PD patients undergoing bilateral STN-DBS, we examined PDSleep Scale (PDSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, -activities of daily living, and -complications (SCOPA-A, -B, -C), and levodopa-equivalent daily dose (LEDD) preoperatively, at 5 and 24 months follow-up. Longitudinal changes were analyzed with Friedman-tests or repeated-measures ANOVA, when parametric tests were applicable, and Bonferroni-correction for multiple comparisons. Post-hoc, visits were compared with Wilcoxon signed-rank/t-tests. The magnitude of clinical responses was investigated using effect size.ResultsSignificant beneficial effects of STN-DBS were observed for PDSS, PDQ-8, SCOPA-A, -B, and -C. All outcomes improved significantly at 5 months with subsequent decrements in gains at 24 months follow-up which were significant for PDSS, PDQ-8, and SCOPA-B. Comparing baseline and 24 months follow-up, we observed significant improvements of PDSS (small effect), SCOPA-A (moderate effect), -C, and LEDD (large effects). PDSS and PDQ-8 improvements correlated significantly at 5 and 24 months follow-up.ConclusionsIn this multicenter study with a 24 months follow-up, we report significant sustained improvements after bilateral STN-DBS using a PD-specific sleep scale and a significant relationship between sleep and QoL improvements. This highlights the importance of sleep in holistic assessments of DBS outcomes.

Three-Year Gait and Axial Outcomes of Bilateral STN and GPi Parkinson's Disease Deep Brain Stimulation.

Objective: To examine the short- and long-term clinical outcomes of the bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) on gait and axial symptoms in Parkinson’s disease (PD) patients. Available data have been inconsistent and mostly short-term regarding the effect of both brain targets on gait and axial symptoms. We aimed to identify potential target specific differences at 3-year follow-up from a large single-center experience.Methods: We retrospectively reviewed short-term (6-month follow-up) and long-term (36-month follow-up) changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III total scores of 72 PD patients (53 with bilateral STN-DBS and 19 with bilateral GPi-DBS). An interdisciplinary team made target-specific decisions for each DBS patient. We analyzed changes in gait and axial subscores derived from UPDRS II and III.Results: In both the STN- and GPi-DBS cohorts, we observed no significant differences in gait and axial UPDRS derived subscores in the off-med/on stimulation state at long-term follow-up when compared to baseline. On-med axial scores remained similar in the short-term but worsened in both groups (STN, 2.23 ± 3.43, p < 0.001; GPi, 2.53 ± 2.37, p < 0.01) in the long-term possibly due to disease progression. At long-term follow-up, the UPDRS III off-med/on stimulation scores worsened but were persistently improved from baseline in both groups (−9.07 ± 13.9, p < 0.001).Conclusions: The study showed that long-term both STN- and GPi-DBS had a similar effect on gait and axial symptoms in UPDRS derived subscores at 36-month follow-up despite potential baseline differences in criteria for selection of each target. More sophisticated measures of gait and balance beyond the categorical UPDRS score will be needed for future studies.

A 3-year observation of excessive daytime sleepiness after subthalamic deep brain stimulation in patients with Parkinson’s disease

ObjectiveSubthalamic nucleus deep brain stimulation (STN DBS) has a positive effect on sleep quality, but its effect on wake functions is controversial. This study evaluated the longitudinal changes of the quality of sleep and excessive daytime sleepiness (EDS) in Parkinson’s disease (PD) patients undergoing STN DBS and identify which factors are associated with the presence of EDS before and after STN DBS. Patient and methodsA total of 33 PD patients who underwent bilateral STN DBS between July 2011 and October 2015 were recruited. We evaluated subjective sleep quality assessed by Parkinson’s Disease Sleep Scale (PDSS) and EDS using Epworth Sleepiness Scale (ESS) preoperatively and 6 months, 1 year, and 3 years postoperatively. ResultsThere is a significant improvement in PDSS, and a noticeable change occurs immediately after the surgery. After DBS, the number of patients with persistent EDS gradually decreased, but patients with newly developed EDS were added. Baseline ESS score was highly correlated with EDS at 6 months and 1 year postoperatively, and older age of PD onset was highly associated with EDS at 1 year after DBS. At 3 years after DBS, the total PDSS score is a main contributing factor for EDS. There was no significant difference in dopamine agonist dose (agonist LED) and levodopa equivalent daily dose (LEDD) between groups with and without EDS at any time points. ConclusionBilateral STN DBS improves the subjective sleep quality, but EDS may improve or worsen. The risk factors for EDS change over time after STN DBS. Interestingly, dopaminergic medication did not affect EDS in DBS-treated PD patients.

The potential neuromodulatory impact of subthalamic nucleus deep brain stimulation on Parkinson’s disease progression

IntroductionSTN-DBS has been claimed to change progressionsymptomsin animal models of PD, but information is lacking about the possible neuromodulatory role of STN-DBS in humans. The aim of this prospective controlled study was to evaluate the long-term impact of STN-DBS on motor disabilities and cognitive impairment in PD patients in comparison to Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) groups. Material and methodsPatients were divided into 3 groups: the BMT-group consisted of 20 patients treated only with pharmacotherapy, the DBS-group consisted of 20 PD patients who underwent bilateral STN-DBS (examined pre- and postoperatively) and the POP-group consisted of 14 long-term postoperative patients in median 30 month-time after DBS. UPDRS III scale was measured during 3 visits in 9 ± 2 months periods (V1, V2, V3) in total-OFF phase. Cognitive assessment was performed during each visit in total-ON phase. ResultsThe comparable UPDRS III OFF gain was observed in both BMT-group and POP-group evaluations (p < 0.05). UPDRS III OFF results in DBS-group revealed significant UPDRS III OFF increase in ΔV2-V1 assessment (p < 0.05) with no significant UPDRS III OFF alteration in ΔV3-V2 DBS-group evaluation (p > 0.05). Cognitive assessment revealed significant alterations between DBS-group and BMT-group in working memory, executive functions and learning abilities (p < 0.05). ConclusionsThe impact of STN-DBS on UPDRS III OFF score and cognitive alterations suggest its neuromodulatory role, mainly during the first 9–18 months after surgery.

Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease

IntroductionDeep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. MethodsUsing freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. ResultsBased on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. ConclusionsOur data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

Speech Intelligibility During Clinical and Low Frequency.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson’s disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation—LFS), and the typical clinical setting of 185 Hz (High frequency—HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. On the average, speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated existing voice problems and may have introduced new articulatory abnormalities. The results from individual DBS subjects showed both improved and reduced intelligibility varied as a function of DBS, with perceived changes in voice appearing to be more reflective of intelligibility than perceived changes in articulation.

Motor effects of deep brain stimulation correlate with increased functional connectivity in Parkinson's disease: An MEG study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established symptomatic treatment in Parkinson's disease, yet its mechanism of action is not fully understood. Locally in the STN, stimulation lowers beta band power, in parallel with symptom relief. Therefore, beta band oscillations are sometimes referred to as "anti-kinetic". However, in recent studies functional interactions have been observed beyond the STN, which we hypothesized to reflect clinical effects of DBS. Resting-state, whole-brain magnetoencephalography (MEG) recordings and assessments on motor function were obtained in 18 Parkinson's disease patients with bilateral STN-DBS, on and off stimulation. For each brain region, we estimated source-space spectral power and functional connectivity with the rest of the brain. Stimulation led to an increase in average peak frequency and a suppression of absolute band power (delta to low-beta band) in the sensorimotor cortices. Significant changes (decreases and increases) in low-beta band functional connectivity were observed upon stimulation. Improvement in bradykinesia/rigidity was significantly related to increases in alpha2 and low-beta band functional connectivity (of sensorimotor regions, the cortex as a whole, and subcortical regions). By contrast, tremor improvement did not correlate with changes in functional connectivity. Our results highlight the distributed effects of DBS on the resting-state brain and suggest that DBS-related improvements in rigidity and bradykinesia, but not tremor, may be mediated by an increase in alpha2 and low-beta functional connectivity. Beyond the local effects of DBS in and around the STN, functional connectivity changes in these frequency bands might therefore be considered as "pro-kinetic".

Subthalamic Stimulation for Camptocormia in Parkinson's Disease: Association of Volume of Tissue Activated and Structural Connectivity with Clinical Effectiveness.

Background:Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been reported to be effective for camptocormia in Parkinson’s disease (PD). However, the association between clinical effectiveness and the stimulated volumes or structural connectivity remains unexplored.Objective:To investigate the effectiveness of STN-DBS for treating camptocormia in PD and its association with volumes of tissue activated (VTA) and structural connectivity.Methods:We reviewed video recordings of patients who had undergone STN-DBS. The total and upper camptocormia (TCC and UCC) angles were measured to quantify changes in camptocormia. The Movement Disorders Society Unified Parkinson’s Disease Rating Scale III (MDS-UPDRS III) was used to assess motor symptoms. Pre- and postoperative brain images were collected for modeling volume of VTA and structural connectivity using Lead-DBS software.Results:Participants included 36 patients with PD (8 with TCC-camptocormia and 2 with UCC-camptocormia) treated with bilateral STN-DBS. After surgery, patients showed a significant improvement in postural alignment at follow-up (mean follow-up duration: 6.0±2.2 months). In the entire sample, higher structural connectivity to the right supplementary motor area (SMA) and right lateral premotor cortex along the dorsal plane (PMd) was associated with larger postsurgical improvements in axial signs and TCC angles after stimulation was turned on. In patients diagnosed with camptocormia, larger improvement in camptocormia angles after STN-DBS was associated with a larger VTA overlap with STN (R = 0.75, p = 0.032).Conclusion:This study suggests that both VTA overlap with STN and structural connectivity to cortical motor regions are associated with the effectiveness of STN-DBS for managing camptocormia in PD.

Deep Brain Stimulation for Parkinson's Disease: Currents Status and Emerging Concepts.

The clinical application of DBS has become manifold and there has been a tremendous growth in DBS technology in the last few decades making it safer and user friendly. The earlier concept of its delayed application in motor fluctuations of Parkinson's disease has been replaced by Class-I evidence of EARLY-STIM trial in 2013, leading to its FDA approval to be used in early-stage despite criticism. Various studies have provided evidence of beneficial effects of bilateral STN-DBS on both motor as well as nonmotor symptoms and different new targets such as the pedunculopontine nucleus, posterior subthalamic area or caudal zona incerta, centromedian-parafascicular complex, and substantia nigra pars reticulata have now become a new area of interest in addition to the subthalamic nucleus and globus pallidus internus for the alleviation of both motor and nonmotor symptoms of Parkinson's disease. New data has confirmed that the DBS is clinically as effective and safe in elderly patients as it is in younger ones. Technological advances like current steering, directional leads, and closed-loop DBS are directed towards reducing the stimulation-induced adverse effects and preservation of the battery life for a longer period. Results of the long-term efficacy of DBS on Parkinson's disease are now available. These have shown that as the motor benefit continues, the clinical progression of Parkinson's disease also continues. We plan to discuss all these in this paper.

White matter tracts involved by deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: a connectivity study based on preoperative diffusion tensor imaging tractography

Purpose: To depict the specific brain networks that are modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD), using diffusion tensor imaging-based fibre tractography (DTI-FT).Materials and methods: Nine patients who received bilateral STN-DBS for PD were included. Electrodes were localized by co-registering preoperative magnetic resonance imaging and postoperative computed tomography. The volume of tissue activated (VTA) was estimated as an isotropic, spherical electric field distribution centred at each effective electrode contact’s centroid coordinates, taking into account individual stimulation parameters (i.e. voltage, impedance). Brain connectivity analysis was undertaken using a deterministic DTI-FT method, seeded from a single region of interest corresponding to the VTA. The labelling of the reconstructed white matter fibre tracts relied on their path and (sub)cortical termination territories.Results: Six months after surgery, we observed a statistically significant reduction in both the Unified Parkinson Disease Rating Scale part III and L-dopa equivalent daily dose. Areas consistently connected to the VTA included the brainstem (100%), cerebellum (94%), dorsal (i.e. supplementary motor area) and lateral premotor cortex (94%), and primary motor cortex (72%). An involvement of the hyperdirect pathway (HDP) connecting the STN and the (pre)motor cortex was demonstrated.Conclusions: The connectivity patterns observed in this study suggest that the therapeutic effects of STN-DBS are mediated through the modulation of distributed, large-scale motor networks. Specifically, the depiction of projection neurons connecting the stimulated area/STN to the (pre)motor cortex, reinforce the growing evidence that the HDP might be a potential therapeutic target in PD. If further replicated, these findings could raise the possibility that DTI-FT reconstruction of the HDP may critically improve DBS targeting and stimulation parameters selection, through the development of programming tools that incorporate VTA modelling and patient-specific DTI-FT data.

Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery

BackgroundSubthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. MethodsWestern aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected. ResultsAlthough motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. ConclusionPresent results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

Long-term effect of subthalamic nucleus deep brain stimulation on freezing of gait in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN DBS) is effective against freezing of gait (FOG) in Parkinson's disease (PD); however, whether this effect persists over the long term is debated. The aim of the current study was to investigate the long-term effect of STN DBS on FOG in patients with PD. Data on 52 cases in which PD patients received bilateral STN DBS were obtained from a prospective registry. The authors blindly analyzed FOG incidence and its severity from the videotapes of a 5-m walking task at the baseline and at the 1-, 2-, and 5- or 7-year follow-up visits. They also compared the axial score from the Unified Parkinson's Disease Rating Scale (UPDRS) part III, UPDRS part II (UPDRS-II) item 14, and the FOG questionnaire (FOG-Q). Postoperatively, video-based FOG analysis and the axial score were evaluated under 4 conditions (off-medication/off-stimulation, off-medication/on-stimulation, on-medication/off-stimulation, and on-medication/on-stimulation), and UPDRS-II item 14 and the FOG-Q score were evaluated under 2 conditions (off-medication/on-stimulation and on-medication/on-stimulation). During the off-medication state, the on-stimulation condition improved FOG outcomes, except for video-based FOG severity, up to the last follow-up compared with the baseline. Video-based FOG outcomes and the axial score during the off-medication state were improved with the on-stimulation condition up to the last follow-up compared with the off-stimulation condition. During the on-medication state, the on-stimulation condition did not improve any FOG outcome compared with the baseline; however, it improved video-based FOG outcomes up to the 2-year follow-up and the axial score up to the last follow-up compared with the off-stimulation condition. Our findings suggest that STN DBS has a long-term effect on FOG in the off-medication state. However, STN DBS did not show a long-term effect on FOG in the on-medication state, although it had a short-term effect until the 2-year follow-up.

Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R– group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R– group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R– group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.

Analysis of intra-operative target location of subthalamic nucleus in deep brain stimulation surgery for Parkinson′s disease with bispectral index monitoring under general anesthesia

Objective To explore the feasibility of using electrophysiology to locate STN targets in the treatment of Parkinson′s disease (PD) by deep brain stimulation (DBS) with bispectral index (BIS) monitoring under general anesthesia. Methods The data of 22 PD patients treated by bilateral STN-DBS at Department of Neurosurgery, the First Hospital of China Medical University from September 2017 to May 2019 were retrospectively analyzed. All patients completed surgery with BIS monitoring under general anesthesia. All STN nuclei were located based on microelectrode recording (MER). Postoperative MRI was fused with preoperative MRI to evaluate the accuracy of electrode implantation. Results The discharge in the sensory-motor area of STN were recorded by MER in all 44 sides during asleep DBS. Microelectrodes were implanted and STN electrophysiological signals were recorded for 40 sides when BIS value was maintained above 70. For the other 4 sides when BIS value was maintained between 30 and 60, and the discharge frequency and amplitude were only about 50% of those when BIS value was maintained above 70. The electrophysiological length of STN was 3.5-7.5(5.2±0.9) mm on the right side and 3.5-7.5(5.5±1.0)mm on the left side, respectively. After intracranial electrode was implanted and when BIS value ≥80, 18 patients could complete the stimulation test for clinical symptoms and side effects, and 4 patients could only complete the test for motor side effects. Postoperative MRI showed that all electrode targets were located in STN nucleus, and the radial error was (1.10±0.45)mm on the right side and (1.24±0.56)mm on the left side. No intracranial hemorrhage, infection or other complications occurred. Conclusions During the surgery of asleep STN-DBS, clear and typical STN discharge could be recorded in MER with BIS (≥70) monitoring. The target localization seems accurate. Key words: Parkinson disease; Anesthesia, general; Deep brain stimulation; Bispectral index; Microelectrode recording

Subthalamic nucleus deep brain stimulation improves dyskinesias in Parkinson's disease beyond levodopa reduction.

Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor fluctuations and dyskinesias in patients with Parkinson's disease (PD). Dyskinesia improvement with STN DBS is believed to result entirely from levodopa reduction. However, some studies suggest that STN DBS may also directly suppress dyskinesias. To determine whether bilateral STN DBS improves dyskinesias beyond what would be expected from levodopa reduction alone,weanalyzed pre-operative and post-operative dyskinesia scores (sum of MDS-UPDRS items 4.1 and 4.2) from 61 PD patients with bilateral STN DBS. A multiple regression model (adjusted for disease severity, disease duration, active contacts above the STN, use of amantadine, high pre-operative levodopa-equivalent dose (LED), sex, and interaction between active contacts above the STN and amantadine use) was created to describe the relationship between dyskinesia scores and LED prior to DBS. Using this model, a post-operative dyskinesia score was estimated from post-operative LED and compared to the actual post-operative dyskinesia score. The regression model was statistically significant overall (p = 0.003, R2 = 0.34, adjusted R2 = 0.24). The actual post-operative dyskinesia score (1.0 ± 1.4) was significantly lower than the score predicted by the model (3.0 ± 1.1, p < 0.0001). Dyskinesias after STN DBS improved more than predicted by levodopa reduction alone. Our data support the idea that STN stimulation may directly improve dyskinesias.

Subthalamic Nucleus (STN) Deep-Brain Stimulation (DBS) in the Management of Idiopathic Parkinson's Disease: Results of our First 20 Cases

AbstractBackground: Idiopathic Parkinson's Disease (iPD) is one of the most disabling chronic neurologic diseases and leads to a significant loss of quality of life. Interest in surgical therapy for PD was renewed in the early 1990s. The most common functional stereotactic procedures that are performed worldwide for PD are lesioning and Deep-Brain Stimulation (DBS).Aim of Study: Is to review and evaluate the results of STN-DBS in management of iPD in our first 20 patients.Patients and Methods: This study was conducted in Department of Neurosurgery, Tanta University from January 2007 to March 2014. It included 20 patients with iPD, they must had positive L-dopa challenge test with at least a 33% decrease in the UPDRS III score. All patients were assessed by UPDRS in off and on phases. Stereotactic STN-DBS was done. The total off UPDRS III score was considered the primary outcome measurement.Results: We had 14 males and 6 females with a mean age at PD onset of 46.5 years, a mean age at implant of 54.5 years with mean duration of symptoms of 10 years. 14 patients had moderate PD while 6 patients had severe PD. The post-operative OFF and ON UPDRS III score improved by 45.5%, and 63.9% respectively. The post-operative OFF and ON bradykinesia score improved by 55.5%, and 62.9% respec-tively. The post-operative OFF and ON tremor score was improved by 68.01% and 76.5% respectively. The post-operative OFF and ON rigidity score was improved by 71.81% and 78.8%. The post-operative OFF and ON postural instability and gait score was improved by 45.42% and 61.9% respec-tively. 60% of patients had good outcome and 40% had fair outcome. We reported one transient post-operative confusion, one infection, one lead displacement, and one lead fracture. Dyskinesia occurred in two patients, speech problems in two patients and emotional lability in one patient.Conclusion: Bilateral STN-DBS provides significant symptom relief for the majority of well-screened patients with iPD.

Bilateral subthalamic nucleus deep brain stimulation increases fixational saccades during movement preparation: evidence for impaired preparatory set.

People with Parkinson's disease (PD) exhibit an increase in fixational saccades during the preparatory period prior to target onset in the antisaccade task and this increase is related to an increase in prosaccade errors in the antisaccade task. It was previously shown that bilateral, but not unilateral, subthalamic nucleus deep brain stimulation (STN DBS) in people with PD further increases the prosaccade error rate on the antisaccade task. We investigated whether bilateral STN DBS also increases the number of fixational saccades in the preparatory period of the antisaccade task and if this increase in the number of fixational saccades is related to prosaccade errors. We found that: (1) there were a greater number of fixational saccades during the preparatory period of the antisaccade task during bilateral STN DBS compared to no STN DBS (p < 0.001), unilateral STN DBS (p < 0.001), and healthy controls (p = 0.02), and (2) the increase in the number of fixational saccades increased the probability of a prosaccade error for the antisaccade task during bilateral STN DBS (p = 0.005). This association between number of fixational saccades and probability of a prosaccade error was similar across no STN DBS, unilateral stimulation, and healthy controls. In addition, we found that the proportion of express prosaccade errors and prosaccade error latencywere similar across stimulation conditions. We propose that bilateral STN DBS disrupts the integrated activity of cortico-basal ganglia-collicular processes underlying antisaccade preparation and that this disruption manifests as an increase in both fixational saccades and prosaccade error rate.

The Role of Tissue Expansion in Deep Brain Stimulation Surgery for Parkinson's Disease

Abstract INTRODUCTION Scalp defects (SD) after neurosurgical-procedures in patients with Parkinson's disease (PD) are challenging especially when implants like DBS-leads lie underneath. Tissue expanders (TE) have been widely used in reconstructive surgery. The scanty neurosurgical literature on this topic deals with reconstruction after trauma/multiple craniotomies for neuro-oncological cases. The use of TE for complicated DBS cases has not yet been reported. We illustrate this use with the case of a 60-yr-old male patient. METHODS A patient with bilateral STN-DBS for idiopathic PD had undergone a total of 6 revision-procedures due to infections both at the impulse generator (IPG)-site and on the scalp above the DBS-electrodes. Both had to be eventually explanted due to bacterial contamination with an open frontal SD. Worsening of the QoL deemed re-implantation necessary. Occipital implantation of a 200 mL Polytech-TE was followed by gradual tissue expansion in 10 mL-steps over 7 mo with concomitant antibiotics. This was followed by TE-removal, DBS-re-implantation, and rotational-flap-mobilization providing strain-free scalp-closure. RESULTS Strain-free scalp closure was possible. Planning and carrying out of the DBS was not impeded by the MRI-compatible TE. Combining the DBS-re-implantation and TE-removal during a single general anesthesia (GA) proved feasible. The wound-healing at 180 d was optimal. CONCLUSION TEs are feasible for challenging DBS cases with large SDs. There are many important considerations including MRI-compatibility and TE-placement being conducive to frame-based or frameless stereotaxy. Interdisciplinary boards for such cases are indispensable.

Determinants of Functional Independence or Its Loss following Subthalamic Nucleus Stimulation in Parkinson’s Disease

Objective: This study aimed to describe the change in functional status following bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson’s disease (PD) and to identify predictors of postoperative functional dependence. Methods: We included PD patients with bilateral STN-DBS who had complete Schwab & England Activities of Daily Living (S&E ADL) Scale data at baseline and 6 months after surgery from our prospective registry. Functional dependence was defined as an S&E ADL score of less than 80%. All data were collected from the on-medication state and on-stimulation state (after surgery). Logistic regression analyses were performed to determine the factors predictive of functional dependence after surgery. Results: A total of 196 patients were included. At baseline, 41 patients were functionally dependent and the other 155 were functionally independent. Among the patients with preoperative dependence, 32 (78%) became functionally independent after surgery, and this conversion was associated with a lower baseline axial score (p = 0.012). Among the patients with preoperative independence, 21 (14%) developed postoperative dependence, and this conversion was associated with a higher baseline axial score (p = 0.013) and its smaller improvement (p < 0.001). Female sex (odds ratio [OR] 3.214; 95% confidence interval [CI] 1.210–8.542; p = 0.019) and a higher baseline axial score (OR 1.184; 95% CI 1.056–1.327; p = 0.004) significantly predicted the risk of postoperative functional dependence. Conclusions: We found that functional status following bilateral STN-DBS is closely related to preoperative axial symptoms. When loss of independence is a potential target for STN-DBS, clinicians should take into consideration the severity of axial impairment before surgery.

Acute Effects of Subthalamic Deep Brain Stimulation on Motor Outcomes in Parkinson's Disease; 13 Year Follow Up.

Objective: Deep brain stimulation of the Subthalamic nucleus (STN-DBS) is a safe and well-established therapy for the management of refractory motor symptoms in Parkinson's disease (PD). Marked improvement in axial symptoms has been reported in the short term with STN-DBS but questions remain regarding the long-term efficacy of this intervention. We assessed the acute ON and OFF effects of STN-DBS in PD patients who have been treated with STN-DBS for over a decade.Methods: We assessed 11 patients with early-onset PD (9 men, 2 women; mean age, 57.1 ± 7.2 y; mean age at illness onset, 38.9 ± 7.5 y) managed with long-term bilateral STN-DBS (mean treatment duration, 13.4 ± 1.3 y). Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS)-III, Timed Up and Go test (TUG), and Hoehn-Yahr scale. Motor assessments in the medication ON and OFF states with stimulation ON and OFF conditions were documented and video recorded.Results: Patients showed a significant improvement in motor symptoms both in the off-medication and on-medication state by a 54% reduction (off-medication/on-stimulation vs. off-medication/off-stimulation) and a 48% reduction (on-medication/on-stimulation vs. on-medication/off-stimulation) in the total UPDRS-III score. Specifically, improvement in axial symptoms (off-medication: 51% reduction; on-medication: 44% reduction), including gait but not posture. Similarly, STN-DBS reduced TUG scores (off-medication: 70% reduction; on-medication: 47% reduction).Conclusions: On stimulation long-term, bilateral STN-DBS can improve appendicular and axial symptoms of patients with early-onset PD in the acute setting.