The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease

Abstract BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective adjunctive therapy for Parkinson disease. Studies have shown improvement of motor function but often exclude patients older than 75 yr. OBJECTIVE To determine the safety and effectiveness of STN DBS in patients 75 yr and older. METHODS A total of 104 patients (52 patients >75 yr old, 52 patients <75 yr old) with STN DBS were paired and retrospectively analyzed. The primary outcome was change in Unified Parkinson Disease Rating Scale (UPDRS) subscale III at 1 yr postoperatively, OFF medication. Secondary outcomes were changes in UPDRS I, II, and IV subscales and levodopa equivalents. Complications and all-cause mortality were assessed at 30 d and 1 yr. RESULTS Both cohorts had significant improvements in UPDRS III at 6 mo and 1 yr with no difference between cohorts. Change in UPDRS III was noninferior to the younger cohort. The cohorts had similar worsening in UPDRS I at 1 yr, no change in UPDRS II, similar improvement in UPDRS IV, and similar levodopa equivalent reduction. There were similar numbers of postoperative intracerebral hemorrhages (2/52 in each cohort, more severe in the older cohort) and surgical complications (4/52 in each cohort), and mortality in the older cohort was similar to an additional matched cohort not receiving DBS. CONCLUSION STN DBS provides substantial motor benefit and reduction in levodopa equivalents with a low rate of complications in older patients, which is also noninferior to the benefit in younger patients. STN DBS remains an effective therapy for those over 75 yr.

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Postmortem analysis following 71 months of deep brain stimulation of the subthalamic nucleus for Parkinson disease

Journal of Neurosurgery ◽

10.3171/jns/2008/109/8/0325 ◽

2008 ◽

Vol 109 (2) ◽

pp. 325-329 ◽

Cited By ~ 38

Author(s):

David A. Sun ◽

Hong Yu ◽

John Spooner ◽

Armanda D. Tatsas ◽

Thomas Davis ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Tissue Reaction ◽

Tissue Response ◽

Zona Incerta ◽

Foreign Body Giant Cell ◽

Stn Dbs ◽

Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective neurosurgical treatment for Parkinson disease. Tissue reaction to chronic DBS therapy and the definitive location of active stimulation contacts are best studied on a postmortem basis in patients who have undergone DBS. The authors report the postmortem analysis of STN DBS following 5 years and 11 months of effective chronic stimulation including the histologically verified location of the active contacts associated with bilateral implants. They also describe tissue response to intraoperative test passes with recording microelectrodes and stimulating semimacroelectrodes. The results indicated that 1) the neural tissue surrounding active and nonactive contacts responds similarly, with a thin glial capsule and foreign-body giant cell reaction surrounding the leads as well as piloid gliosis, hemosiderin-laden macrophages, scattered lymphocytes, and Rosenthal fibers; 2) there was evidence of separate tracts in the adjacent tissue for intraoperative microelectrode and semimacroelectrode passes together with reactive gliosis, microcystic degeneration, and scattered hemosiderin deposition; and 3) the active contacts used for ~ 6 years of effective bilateral DBS therapy lie in the zona incerta, just dorsal to the rostral STN. To the authors' knowledge, the period of STN DBS therapy herein described for Parkinson disease and subjected to postmortem analysis is the longest to date.

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Experience with Microelectrode Guided Subthalamic Nucleus Deep Brain Stimulation

Operative Neurosurgery ◽

10.1227/01.neu.0000192690.45680.c2 ◽

2006 ◽

Vol 58 (suppl_1) ◽

pp. ONS-96-ONS-102 ◽

Cited By ~ 20

Author(s):

Ramin Amirnovin ◽

Ziv M. Williams ◽

G. Rees Cosgrove ◽

Emad N. Eskandar

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Pulse Generator ◽

Computed Tomographic ◽

Pass Through ◽

The Right ◽

Stn Dbs ◽

Deep Brain

Abstract OBJECTIVE: Subthalamic deep brain stimulation (DBS) has rapidly become the standard surgical therapy for medically refractory Parkinson disease. However, in spite of its wide acceptance, there is considerable variability in the technical approach. This study details our technique and experience in performing microelectrode recording (MER) guided subthalamic nucleus (STN) DBS in the treatment of Parkinson disease. METHODS: Forty patients underwent surgery for the implantation of 70 STN DBS electrodes. Stereotactic localization was performed using a combination of magnetic resonance and computed tomographic imaging. We used an array of three microelectrodes, separated by 2 mm, for physiological localization of the STN. The final location was selected based on MER and macrostimulation through the DBS electrode. RESULTS: The trajectory selected for the DBS electrode had an average pass through the STN of 5.6 ± 0.4 mm on the left and 5.7 ± 0.4 mm on the right. The predicted location was used in 42% of the cases but was modified by MER in the remaining 58%. Patients were typically discharged on the second postoperative day. Eighty-five percent of patients were sent home, 13% required short-term rehabilitation, and one patient required long-term nursing services. Seven complications occurred over 4 years. Four patients suffered small hemorrhages, one patient experienced a lead migration, one developed an infection of the pulse generator, and one patient suffered from a superficial cranial infection. CONCLUSION: Simultaneous bilateral MER-guided subthalamic DBS is a relatively safe and well-tolerated procedure. MER plays an important role in optimal localization of the DBS electrodes.

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Unilateral deep brain stimulation of the subthalamic nucleus for Parkinson disease

Journal of Neurosurgery ◽

10.3171/jns.2007.106.4.626 ◽

2007 ◽

Vol 106 (4) ◽

pp. 626-632 ◽

Cited By ~ 49

Author(s):

Jerzy L. Slowinski ◽

John D. Putzke ◽

Ryan J. Uitti ◽

John A. Lucas ◽

Margaret F. Turk ◽

...

Keyword(s):

Quality Of Life ◽

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Mental Flexibility ◽

Stn Dbs ◽

Updrs Part ◽

Deep Brain

Object The object of this study was to assess the results of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for management of advanced Parkinson disease (PD). Methods A clinical series of 24 patients (mean age 71 years, range 56–80 years) with medically intractable PD, who were undergoing unilateral magnetic resonance imaging–targeted, electrophysiologically guided STN DBS, completed a battery of qualitative and quantitative outcome measures preoperatively (baseline) and postoperatively, using a modified Core Assessment Program for Intracerebral Transplantations protocol. The mean follow-up period was 9 months. Statistically significant improvement was observed in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and scores for axial motor features (19%), contralateral tremor (88%), rigidity (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's Disease Quality of Life questionnaire score (15%) in the on-stimulation state compared with baseline. Ipsilateral symptoms improved by approximately 15% or less. Performance on the Purdue pegboard test improved in the contralateral hand in the on-stimulation state compared with the off-stimulation state (38%, p < 0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018). Neuropsychological tests revealed an improvement in mental flexibility and a trend toward reduced letter fluency. There were no permanent surgical complications. Of the 16 participants with symmetrical disease, five required implantation of the DBS unit on the second side. Conclusions Unilateral STN DBS is an effective and safe treatment for selected patients with advanced PD. Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as well as quality of life, reduces requirements for medication, and possibly enhances mental flexibility. This method of surgical treatment may be associated with a reduced risk and may provide an alternative to bilateral STN DBS for PD, especially in older patients or patients with asymmetry of parkinsonism.

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FC24.2 Effects of subthalamic nucleus deep brain stimulation (STN-DBS) on saccade performance in patients with Parkinson disease

Clinical Neurophysiology ◽

10.1016/j.clinph.2006.06.081 ◽

2006 ◽

Vol 117 ◽

pp. 1-2

Author(s):

A. Yugeta ◽

Y. Terao ◽

H. Fukuda ◽

R. Okiyama ◽

R. Hanajima ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Stn Dbs ◽

Deep Brain

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Rescue Ventral Intermediate Thalamus Deep Brain Stimulation to Address Refractory Tremor Following Subthalamic Nucleus Deep Brain Stimulation With Brittle Dyskinesia

Deep Brain Stimulation ◽

10.1093/med/9780190647209.003.0023 ◽

2020 ◽

pp. 115-118

Author(s):

Mitra Afshari ◽

Jill L. Ostrem ◽

Marta San Luciano ◽

Paul S. Larson

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Essential Tremor ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Target Selection ◽

Hand Tremor ◽

Learning Points ◽

Stn Dbs ◽

Deep Brain

This chapter discusses a case in which a “rescue” deep brain stimulation (DBS) lead was implanted to address suboptimal tremor control. The patient was a 52-year-old woman with disabling bilateral postural and action hand tremor who also had mild parkinsonian signs. An essential tremor (ET)–Parkinson disease (PD) syndrome was suspected, and subthalamic nucleus (STN) DBS was pursued. Attempts at optimizing tremor control by reprogramming were limited by the induction of brittle dyskinesia even with small amounts of stimulation. Bilateral ventral intermediate thalamus DBS leads were then implanted, and the tremors improved significantly. Troubleshooting strategies for optimizing tremor control and reducing STN DBS–induced brittle dyskinesia are discussed. The chapter reviews important learning points on DBS target selection for ET, PD, and ET-PD spectrum syndromes.

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Long-term Outcomes (15 Years) After Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease

Neurology ◽

10.1212/wnl.0000000000012246 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012246

Author(s):

Francesco Bove ◽

Delia Mulas ◽

Francesco Cavallieri ◽

Anna Castrioto ◽

Stephan Chabardès ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Motor Complications ◽

Dopaminergic Drugs ◽

Stn Dbs ◽

Deep Brain

Objective:To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson disease (PD) patients on motor complications beyond 15 years after surgery.Methods:Data about motor complications, quality of life (QoL), activities of daily living, the UPDRS motor scores, dopaminergic treatment, stimulation parameters, and side effects of STN-DBS were retrospectively retrieved and compared between before surgery, at 1 year and beyond 15 years after bilateral STN-DBS.Results:Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the off state were reduced by 75% (p<0.001) and by 58.7% (p<0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p<0.001). The PDQL total score, and the emotional function and social function domains improved of 13.8% (p=0.005), 13.6% (p=0.01) and 29.9% (p<0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up.Conclusions:STN-DBS is still effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and non-motor symptoms over the years, STN-DBS patients could maintain an improvement in QoL.Classification of Evidence:This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.

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A novel composite targeting method using high-field magnetic resonance imaging for subthalamic nucleus deep brain stimulation

Journal of Neurosurgery ◽

10.3171/2008.12.jns0861 ◽

2009 ◽

Vol 111 (4) ◽

pp. 737-745 ◽

Cited By ~ 23

Author(s):

Hiroki Toda ◽

Nobukatsu Sawamoto ◽

Takashi Hanakawa ◽

Hidemoto Saiki ◽

Sadayuki Matsumoto ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Mr Imaging ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

High Field ◽

Rating Scale ◽

The Mean ◽

Stn Dbs ◽

Deep Brain

Object Accurate localization of the subthalamic nucleus (STN) is important for proper placement of the electrodes in deep brain stimulation (DBS) surgery for patients with advanced Parkinson disease. The authors evaluated the accuracy of our modified composite targeting method and the value of using high-field MR imaging for targeting the STN. Methods Thirteen patients with advanced Parkinson disease underwent bilateral STN DBS based on 3-T MR imaging, and 13 patients underwent surgery based on 1.5-T MR imaging. By sequentially referring to the postmammillary commissure, the red nucleus, the mammillothalamic tract, and the STN, the modified composite targeting method determined the stereotactic coordinates for targeting the STN. The accuracy and efficacy of the composite targeting method and 3-T MR imaging were evaluated by using the intraoperative microelectrode recording, the postoperative imaging study, and the postoperative clinical improvement. Results The landmark structures for targeting the STN were visualized clearly with 3-T MR imaging. The mean (± SD) path length through the STN of the central track was 4.9 ± 1.1 mm in the 3-T group and 3.1 ± 2.0 mm in the 1.5-T group (p < 0.001). Twenty-one (81%) of 26 electrodes were placed in the central track in the 3-T group, whereas 8 (31%) of 26 electrodes were placed in the central track in the 1.5-T group (p = 0.006). The rest of the electrodes were placed in the noncentral optimum track for alleviating parkinsonian motor symptoms. The mean Unified Parkinson's Disease Rating Scale motor part score during off period was reduced by 53% in the 3-T group and by 41% in the 1.5-T group (p = 0.14). The mean reductions of levodopa equivalent daily doses were 48.6% in the 3-T group and 43.7% in the 1.5-T group (p = 0.61). Conclusions The use of the modified composite targeting method referring to the multiple landmarks with 3-T MR imaging offers reliable and clinically effective target for STN DBS surgery.

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Deep Brain Stimulation of the Subthalamic Nucleus Does Not Affect the Decrease of Decision Threshold during the Choice Process When There Is No Conflict, Time Pressure, or Reward

Journal of Cognitive Neuroscience ◽

10.1162/jocn_a_01252 ◽

2018 ◽

Vol 30 (6) ◽

pp. 876-884 ◽

Cited By ~ 5

Author(s):

Friederike Leimbach ◽

Dejan Georgiev ◽

Vladimir Litvak ◽

Chrystalina Antoniades ◽

Patricia Limousin ◽

...

Keyword(s):

Decision Making ◽

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Time Pressure ◽

Decision Threshold ◽

Healthy Controls ◽

Stn Dbs ◽

Deep Brain

During a decision process, the evidence supporting alternative options is integrated over time, and the choice is made when the accumulated evidence for one of the options reaches a decision threshold. Humans and animals have an ability to control the decision threshold, that is, the amount of evidence that needs to be gathered to commit to a choice, and it has been proposed that the subthalamic nucleus (STN) is important for this control. Recent behavioral and neurophysiological data suggest that, in some circumstances, the decision threshold decreases with time during choice trials, allowing overcoming of indecision during difficult choices. Here we asked whether this within-trial decrease of the decision threshold is mediated by the STN and if it is affected by disrupting information processing in the STN through deep brain stimulation (DBS). We assessed 13 patients with Parkinson disease receiving bilateral STN DBS six or more months after the surgery, 11 age-matched controls, and 12 young healthy controls. All participants completed a series of decision trials, in which the evidence was presented in discrete time points, which allowed more direct estimation of the decision threshold. The participants differed widely in the slope of their decision threshold, ranging from constant threshold within a trial to steeply decreasing. However, the slope of the decision threshold did not depend on whether STN DBS was switched on or off and did not differ between the patients and controls. Furthermore, there was no difference in accuracy and RT between the patients in the on and off stimulation conditions and healthy controls. Previous studies that have reported modulation of the decision threshold by STN DBS or unilateral subthalamotomy in Parkinson disease have involved either fast decision-making under conflict or time pressure or in anticipation of high reward. Our findings suggest that, in the absence of reward, decision conflict, or time pressure for decision-making, the STN does not play a critical role in modulating the within-trial decrease of decision thresholds during the choice process.

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Fully Automated Targeting Using Nonrigid Image Registration Matches Accuracy and Exceeds Precision of Best Manual Approaches to Subthalamic Deep Brain Stimulation Targeting in Parkinson Disease

Neurosurgery ◽

10.1227/neu.0000000000000714 ◽

2015 ◽

Vol 76 (6) ◽

pp. 756-765 ◽

Cited By ~ 21

Author(s):

Srivatsan Pallavaram ◽

Pierre-François D'Haese ◽

Wendell Lake ◽

Peter E. Konrad ◽

Benoit M. Dawant ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Image Registration ◽

Parkinson Disease ◽

Brain Stimulation ◽

Red Nucleus ◽

Nonrigid Image Registration ◽

Direct Targeting ◽

Fully Automatic ◽

Stn Dbs ◽

Deep Brain

Abstract BACKGROUND: Finding the optimal location for the implantation of the electrode in deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic benefit to the patient. Such targeting is challenging for several reasons, including anatomic variability between patients as well as the lack of consensus about the location of the optimal target. OBJECTIVE: To compare the performance of popular manual targeting methods against a fully automatic nonrigid image registration-based approach. METHODS: In 71 Parkinson disease subthalamic nucleus (STN)-DBS implantations, an experienced functional neurosurgeon selected the target manually using 3 different approaches: indirect targeting using standard stereotactic coordinates, direct targeting based on the patient magnetic resonance imaging, and indirect targeting relative to the red nucleus. Targets were also automatically predicted by using a leave-one-out approach to populate the CranialVault atlas with the use of nonrigid image registration. The different targeting methods were compared against the location of the final active contact, determined through iterative clinical programming in each individual patient. RESULTS: Targeting by using standard stereotactic coordinates corresponding to the center of the motor territory of the STN had the largest targeting error (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic coordinates of active contacts from this study (3.02 mm), red nucleus-based targeting (2.75 mm), and nonrigid image registration-based automatic predictions using the CranialVault atlas (2.70 mm). The CranialVault atlas method had statistically smaller variance than all manual approaches. CONCLUSION: Fully automatic targeting based on nonrigid image registration with the use of the CranialVault atlas is as accurate and more precise than popular manual methods for STN-DBS.

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