Bilateral STN Research Articles

Intraoperative clinical testing overestimates the therapeutic window of the permanent DBS electrode in the subthalamic nucleus

Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P<0.001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds (P<0.001). Intraoperative testing may lead to an overestimation of the therapeutic window. The two different electrodes lead to distinct spreading of the electric field in the STN and surrounding tissues that causes different volume of tissue activated (VTA). Clinicians involved in DBS surgery and programming should be aware of the differences in both stimulation settings, concerning electrodes geometry, stimulation modes as well as the impact of time. Therapeutic and side effects of permanent stimulation are not predictable by intraoperative test stimulation. Test stimulation may be an orientating test for very low thresholds of side effects instead.

Measurement of effect of variable deep brain stimulation frequencies on static postural control in Parkinson Disease (PD) patients with Bilateral STN or GPi stimulators by employing force plate (P5.015)

Measurement of effect of variable deep brain stimulation frequencies on static postural control in Parkinson Disease (PD) patients with Bilateral STN or GPi stimulators by employing force plate (P5.015)

SP 6. Preliminary experience with chronic directional DBS in the STN

Introduction STN DBS has been shown to drastically improve motor symptoms of PD. However, the occurrence of disabling side effects may limit the benefit of the therapy. Computed models have suggested that directional stimulation could increase its efficacy. Intraoperative studies performed in human have shown that directional stimulation provides differents thresholds for clinical effects. In the present study, we investigate the effect of directional stimulation on beneficial and side effects, in chronically implanted patients compared to omnidirectional stimulation. Methods 7 bilateral STN implanted PD patients have been prospectively included in this study. In the trajectory determined after microrecording and intraoperative clinical testing, the definitive directional lead (1-3-3-1 electrode configuration, Vercise, Boston Scientific) was implantated with one electrode oriented medially, one anterolaterally and the third posterolaterally, under intraoperative fluoroscopic control. Monopolar omnidirectional stimulation was initially performed. At least 1 month after surgery, directional stimulation was assessed. The current threshold for beneficial and side effects was assessed for each of the 3 directions and compared to omnidirectional stimulation. Results So far 4 patients (8 sides) have been fully assessed. A best direction of stimulation was observed on all sides for positive effect on rigidity as well as thresholds of side effects. The current required to obtain a beneficial effect in the best direction varied from 50% to 100% of the one required in the omni-directional state The current required to achieve a sustained side effect in the worst direction was comparable to the in the omni-directional situation. The medially oriented directional electrode war found in 5/8 sides to have the highest threshold for side effects. Conclusion Our preliminary experience using Directional DBS in the STN performed postoperatively suggests the persistence of different thresholds for the appearance of clinical effects in directional stimulation conditions, compared to omnidirectional stimulation. Further data are needed to confirm these observations

ID 97 – Correlations between intraoperative microelectrode recording, microstimulation and macrostimulation with optimal post-operative programming of deep brain stimulation

Introduction Microelectrode recording (MER) is a means of analyzing the electrical activity of the brain, and assessing whether we have found the target for the deep brain stimulator (DBS) electrode. However, no evidence exists that microelectrode recording improves patient outcomes. DBS electrical pulses should activate the intended target structure alone without spreading electrical current to adjacent neural structures which would result in adverse effects being recorded. Intraoperative microstimulation (mSTIM) can test this aspect quite precisely but it is not always performed. Objective Asses the influence of MER and mSTIM over optimal post-operative programming of DBS. Material and methods Prospective transversal study of 15 patients with Parkinson disease who underwent a MRI navigated DBS surgery of bilateral STN, with MER, mSTIM and macrostimulation (MSTIM). Results The overall outcome in these patients was satisfactory after an optimal DBS programming was established. The chosen optimal position of electrodes was correlated with MER results and type of stimulation (monopolar/bipolar) or intensity was guided by mSTIM. MSTIM was only able to predict adverse effects that would be encountered with high intensities. Discussion Through the use of intraoperative MER, with mSTIM, neurologist can assure for optimal post-operative programming of the DBS.

Impulse control disorders in Parkinson's disease and effect of bilateral STN DBS on them

Impulse control disorders in Parkinson's disease and effect of bilateral STN DBS on them

Micro-Neuro-Sensor Recording of STN Neurons of the Human Brain

What cause to the neurons of the human brain cells when they are damaged. They become inactive. So damage to subthalamiuc ucleus STN neurons of the human brain causing larger involuntary movements and thereby attacking the Parkinson’s disease PD. Deep brain stimulation DBS of bilateral sub thalamic nuclei STN is an efficient method of rehabilitation technique in subjects with advanced idiopathic Parkinson’s or Parkinson disease. Accurate targeting of STN neurons and placement of microelectrodes/ neurosensors are paramount importance for optimal results after STN-DBS method.In this paper, microminiaturized electrode recordings

Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson’s disease (PD). However, some aspects of executive control are impaired with STN DBS.Objective: We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent.Methods: Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos.Results: The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared.Conclusions: We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.

The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior.

Pharmacotherapy accompanied by deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease

To analyze pharmacotherapy accompanied by deep brain stimulation of the subthalamic nucleus. The study included 54 patients, who underwent bilateral STN DBS from 2003 to 2012. The severity of motor disturbances, activities of daily living and complications of dopaminergic therapy were estimated in accordance with II, III and IV parts of the Unified Parkinson's Disease Rating Scale (UPDRS) before operation and one, three and four years after it. L-dopa equivalent daily dose (LEDD) was assessed along with an analysis of the pharmacotherapy in whole. By the end of the 1st year, the severity of motor disturbances in OFF-period decreased by 52.3% and remained stable for 3 years (51.8%), a slight increase of severity of motor disturbances was observed later, however it didn't reach the pre-operative level. The severity of motor fluctuations and drug-induced dyskinesia fell by 64.9%, 70.7% and 42.7% by the end of the first, third and fourth year of observation. The maximal decrease in LEDD was reached by the end of the 1st year and accounted for 57.7%; by the end of the third and fourth years it was 52.4% and 38.2%, respectively. During the 1st year, 16.7% of patients didn't take levodopa. The dose of pure levodopa decreased by the end of the 1st year by 64.6%, and by 56.7% and 43.7% by the end of the 3rd and 4th years, respectively. Monotherapy by an agonist of dopamine receptors (ADR) was received by 12.9% of patients, thus the share of ADR as part of the combined therapy increased in the postoperative period from 24.1% to 35.2%.

Physical Activity in Advanced Parkinson's Disease: Impact of Subthalamic Deep Brain Stimulation

Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery.

Effect of subthalamic nucleus deep brain stimulation on dual-task cognitive and motor performance in isolated dystonia

ObjectiveSubthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor complications of Parkinson's disease (PD) but may worsen specific cognitive functions. The effect of STN DBS on cognitive function in...

Quality of life in advanced Parkinson’s disease after bilateral subthalamic stimulation: 2 years follow-up study

ObjectiveThe aims of this study were to assess the quality of life (QoL) using Parkinson’s Disease Questionnaire PDQ-39 after bilateral subthalamic deep brain stimulation (STN DBS), and to identify correlations between changes in UPDRS score and separate PDQ-39 QoL dimensions and PDQ summary index (SI) score at long-term follow-up. MethodsWe evaluated 16 patients with advanced PD after bilateral STN DBS. All 16 patients were assessed 1 year after surgery and 14 were studied 2 years after surgery. The patients were assessed using Unified Parkinson’s Disease Rating Scale (UPDRS) in medication-on and medication-off conditions, both preoperatively and postoperatively. All UPDRS evaluations were performed postoperatively during stimulation-on condition. QoL levels were determined by applying PDQ-39 questionnaire. ResultsThe UPDRS scores after 1 and 2 years in medication-off and -on conditions when bilateral STN DBS was switched on showed a significant difference between baseline scores and follow-up scores (both in -off and -on conditions) in every UPDRS measurement except for mentation after 2 years. Most of P-values indicated that the differences were highly significant (P<0.01) based on Wilcoxon signed-rank test. All dimensions of PDQ-39 as well PDQ-39 SI score were highly significantly improved after 1 year. The same improvements were visible in 2 years follow-up with the exception of social support and communication. We found a positive correlation between ADL UPDRS, motor off UPDRS scores and PDQ-39 ADL and PDQ-39 SI scores. A further analysis of separate motor PD features revealed that tremor, bradykinesia and axial features were correlated with improvements mostly seen in PDQ-39 ADL and PDQ-39 SI scores. Moreover, in medication-on condition, we found a strong correlation between dyskinesia UPDRS score and PDQ-39 mobility, ADL, and PDQ-39 SI score. We observed a negative correlation between improved fluctuation UPDRS score and PDQ-39 mobility. We identified no correlation between the duration of the off period and levodopa dose and changes in PDQ-39. ConclusionSTN DBS significantly improved important aspects of QoL as measured by PDQ-39. The improvements were maintained at 2 years follow-up except for social support and communication. We demonstrated a positive correlation between changes in the off condition of motor UPDRS scores and dyskinesia UPDRS scores in several PDQ-39 dimensions, whereas fluctuation UPDRS scores were negatively correlated with PDQ-39 mobility scores.

Acute changes in mood induced by subthalamic deep brain stimulation in Parkinson disease are modulated by psychiatric diagnosis.

Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood. The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS. Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal. STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS. PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.

Neuronavigation using susceptibility-weighted venography: application to deep brain stimulation and comparison with gadolinium contrast.

Careful trajectory planning on preoperative vascular imaging is an essential step in deep brain stimulation (DBS) to minimize risks of hemorrhagic complications and postoperative neurological deficits. This paper compares 2 MRI methods for visualizing cerebral vasculature and planning DBS probe trajectories: a single data set T1-weighted scan with double-dose gadolinium contrast (T1w-Gd) and a multi-data set protocol consisting of a T1-weighted structural, susceptibility-weighted venography, and time-of-flight angiography (T1w-SWI-TOF). Two neurosurgeons who specialize in neuromodulation surgery planned bilateral STN DBS in 18 patients with Parkinson's disease (36 hemispheres) using each protocol separately. Planned trajectories were then evaluated across all vascular data sets (T1w-Gd, SWI, and TOF) to detect possible intersection with blood vessels along the entire path via an objective vesselness measure. The authors' results show that trajectories planned on T1w-SWI-TOF successfully avoided the cerebral vasculature imaged by conventional T1w-Gd and did not suffer from missing vascular information or imprecise data set registration. Furthermore, with appropriate planning and visualization software, trajectory corridors planned on T1w-SWI-TOF intersected significantly less fine vasculature that was not detected on the T1w-Gd (p < 0.01 within 2 mm and p < 0.001 within 4 mm of the track centerline). The proposed T1w-SWI-TOF protocol comes with minimal effects on the imaging and surgical workflow, improves vessel avoidance, and provides a safe cost-effective alternative to injection of gadolinium contrast.

Effects of deep brain stimulation in relatively young-onset multiple system atrophy Parkinsonism

ObjectiveThe aim of this study was to analyze outcomes after 1year of bilateral STN deep brain stimulation (DBS) in relatively young-onset patients with multiple system atrophy-Parkinsonism (MSA-P). BackgroundThe efficacy of DBS has been demonstrated in idiopathic Parkinson's disease. However, the experience with DBS in relatively young-onset MSA-P is limited and controversial. MethodsInformation about the demographic and clinical data from five MSA patients treated with STN DBS was entered into a database and analyzed. ResultsFive patients with relatively young-onset MSA (mean age at onset 42.2±2.2years, 3 women, 2 men) have been treated with bilateral STN stimulators, the mean duration between DBS surgery and disease onset was 7.0±3.5years. All of the patients had dyskinesia and postural instability, and subjective benefit from levodopa. During the 6months after surgery, the clinical status of three patients improved with a decrease of dyskinesia. However, by 1year, the symptoms reappeared and progressed in all patients. Overall, the mean “off” medication UPDRS-III score worsened 23.5±15.3 1year after surgery and the levodopa dosage was not reduced. ConclusionsThis data does not support the use of STN DBS for relatively young-onset MSA-P.

Concurrent Bilateral Vim and STN DBS in a Patient with ET/PD (P7.055)

Concurrent Bilateral Vim and STN DBS in a Patient with ET/PD (P7.055)

Acute Lower Urinary Tract Dysfunction After Bilateral STN Deep Brain Stimulation Surgery For PD: Case Reports And Literature Review (P7.051)

Acute Lower Urinary Tract Dysfunction After Bilateral STN Deep Brain Stimulation Surgery For PD: Case Reports And Literature Review (P7.051)

Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in Parkinson’s disease

The effect of subthalamic deep brain stimulation (STN DBS) on cognition in Parkinson's disease (PD) remains controversial, and it is unclear which factors are related to cognitive decline and dementia after STN DBS, especially over the long term. To this end, we analyzed the cognitive outcome of 103 non-demented patients with PD who were followed-up for at least 12 months after bilateral STN DBS surgery. Preoperatively, the patients were evaluated with the Unified Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global cognitive decline and the incidence of dementia during follow-up for up to 7 years (mean 42.4 ± 24.5 months) were calculated, and preoperative clinical and neuropsychological factors associated with postoperative global cognitive decline or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and its relation to later cognitive decline or dementia were also evaluated. The annual decline in the mini-mental state examination score was 0.4 ± 1.7 with impaired attention and executive function and a higher levodopa equivalent dose at baseline being the predictors of a faster global cognitive decline after STN DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000 person-years. Impaired executive function at baseline predicted dementia. At baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely to develop dementia than those without PD-MCI. This study showed that dysfunctions in the frontostriatal circuitry at baseline were associated with a risk of subsequent global cognitive decline and dementia in patients with PD who underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for dementia after STN DBS.

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement

BackgroundEvidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect. ObjectiveWe investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6–24 months after surgery. MethodsWe retrospectively analyzed 50 PD patients who underwent bilateral STN DBS. Off medication UPDRS III motor scores were obtained before surgery and before stimulation was initiated. Neuropsychological testing was completed pre- and post-operatively in 28 patients at a mean of 377 days. Coordinates of lead tip and active stimulation site were calculated. ResultsThere was no improvement in off-medication UPDRS III motor scores at a mean 33.9 days following surgery, with mean change of 0.04 ± 10.48 (p = 0.98). There was no correlation between the number of MER passes and change in individual UPDRS motor score (r = −0.0001, p = 1.0). We observed significant decline in phonemic verbal fluency by 16% (p = 0.003) but it was not correlated with number of left hemisphere (r = −0.15, p = 0.46), or total number of passes (r = −0.02, p = 0.94) or coordinates of the lead tip or active stimulation site. There was a trend toward correlation with age (r = 0.38, p = 0.07). ConclusionsSignificant decline in phonemic verbal fluency did not correlate with surgical passes nor with location of the lead tip or active stimulation site. These data suggest that age may influence verbal fluency decline more than surgical technique.

Gender influence on selection and outcome of deep brain stimulation for Parkinson′s disease

Background:Gender differences exist in Parkinson's disease (PD), both in clinical manifestations and response to medical treatment. We investigated whether gender differences occur in the clinical characteristics of patients selected for bilateral subthalamic nucleus deep brain stimulation (STN DBS) or in the outcome when resource limits influence treatment choices made by patients.Materials and Methods:Fifty-one consecutive patients were evaluated 1 month before, and 12 months after bilateral STN DBS. All patients were rated using Unified Parkinson's Disease Rating Scale, Parkinson's Disease Quality of Life (PDQL) Scale, Addenbrooke's Cognitive Examination and Beck Depression Inventory.Results:Pre-operative characteristics did not differ between the genders except for lower doses of drugs (P = 0.03), worse emotional scores in PDQL (P = 0.01) and worse depression (P = 0.03) in women. There was no gender difference in the surgical outcome, except a lesser reduction of dopaminergic drugs in women. Depression and quality of life (QOL) improved equally well in women and men.Conclusion:Bilateral STN DBS is equally efficacious in both genders as a treatment for motor complications of PD and for improving QOL. Women are likely to be undertreated because of more severe dyskinesia and may experience less emotional well-being, and could therefore potentially benefit from earlier surgical treatment.