Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease

OBJECTIVE The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). METHODS The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson’s Disease Rating Scale–part III) and medication usage were also assessed pre- and postoperatively. RESULTS Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. CONCLUSIONS The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

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Acoustic Voice Modifications in Individuals with Parkinson Disease Submitted to Deep Brain Stimulation

International Archives of Otorhinolaryngology ◽

10.1055/s-0038-1675392 ◽

2019 ◽

Vol 23 (02) ◽

pp. 203-208 ◽

Cited By ~ 2

Author(s):

Aline Juliane Romann ◽

Bárbara Costa Beber ◽

Carla Aparecida Cielo ◽

Carlos Roberto de Mello Rieder

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Statistical Difference ◽

Rating Scale ◽

Acoustic Measures ◽

Disease Rating ◽

The Voice ◽

Stn Dbs ◽

Deep Brain

Introduction Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function in individuals with Parkinson disease (PD). The evidence about the effects of STN-DBS on the voice is still inconclusive. Objective To verify the effect of STN-DBS on the voice of Brazilian individuals with PD. Methods Sixteen participants were evaluated on the Unified Parkinson Disease Rating Scale—Part III, and by the measurement of the acoustic modifications in on and off conditions of stimulation. Results The motor symptoms showed significant improvement with STN-DBS on. Regarding the acoustic measures of the voice, only the maximum fundamental frequency (fhi) showed a statistical difference between on- and off-conditions, with reduction in off-condition. Conclusion Changes in computerized acoustic measures are more valuable when interpreted in conjunction with changes in other measures. The single finding in fhi suggests that DBS-STN increases vocal instability. The interpretation of this result should be done carefully, since it may not be of great value if other measures that also indicate instability are not significantly different.

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Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study

Operative Neurosurgery ◽

10.1093/ons/opaa049 ◽

2020 ◽

Vol 19 (3) ◽

pp. 234-240

Author(s):

Kyle T Mitchell ◽

John R Younce ◽

Scott A Norris ◽

Samer D Tabbal ◽

Joshua L Dowling ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Rating Scale ◽

Intracerebral Hemorrhages ◽

Disease Rating ◽

Equivalent Reduction ◽

Stn Dbs ◽

Deep Brain

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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The Benefit of Subthalamic Deep Brain Stimulation for Pain in Parkinson Disease: A 2-Year Follow-up Study

Neurosurgery ◽

10.1227/neu.0b013e3182266664 ◽

2011 ◽

Vol 70 (1) ◽

pp. 18-24 ◽

Cited By ~ 37

Author(s):

Han-Joon Kim ◽

Beom S. Jeon ◽

Jee-Young Lee ◽

Sun Ha Paek ◽

Dong Gyu Kim

Keyword(s):

Deep Brain Stimulation ◽

Beneficial Effect ◽

Parkinson Disease ◽

Brain Stimulation ◽

Rating Scale ◽

Motor Disorder ◽

Motor Symptoms ◽

Stn Dbs ◽

Deep Brain

Abstract BACKGROUND Pain is a well-recognized feature of Parkinson disease (PD), which is primarily a motor disorder. In a previous study, we showed that subthalamic deep brain stimulation (STN DBS) improves pain as well as motor symptoms 3 months after surgery in PD patients. OBJECTIVE To determine whether there is a long-term beneficial effect of STN DBS on pain in PD. METHODS We studied 21 patients with PD who underwent STN DBS. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging. Pain was evaluated by asking patients about the quality and severity of pain in each body part. Evaluations were performed at baseline and at 3 and 24 months after surgery. RESULTS At baseline, 18 of the 21 patients (86%) experienced pain. After surgery, most of the pain reported at baseline had improved or disappeared at 3 months and improved further at 24 months. The benefit of STN DBS for pain evaluated at 24 months was comparable to that with medication at baseline. At 24 months, 9 patients (43%) reported new pain that was not present at baseline. Most of the new pain was musculoskeletal in quality. Despite the development of new pain, the mean pain score at follow-up was lower than at baseline. CONCLUSION STN DBS improves pain in PD, and this beneficial effect persists, being observed after a prolonged follow-up of 24 months. In addition, in many of the PD patients new, mainly musculoskeletal pain developed on longer follow-up.

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Deep Brain Stimulation–Responsive Camptocormia in Parkinson Disease

Deep Brain Stimulation ◽

10.1093/med/9780190647209.003.0017 ◽

2020 ◽

pp. 89-92

Author(s):

Elena Call ◽

Helen Bronte-Stewart

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Rating Scale ◽

Freezing Of Gait ◽

Trunk Flexion ◽

Skeletal Deformity ◽

Dopaminergic Medication ◽

Stn Dbs ◽

Deep Brain

Camptocormia, involuntary flexion of the spine, is aggravated by action and improves when supine, if there is no skeletal deformity. Camptocormia in Parkinson disease (PD) is frequently refractory to dopaminergic medication. Deep brain stimulation (DBS) has been used to treat camptocormia with variable results. We present a PD patient with no camptocormia in the supine position but with progressive thoracic trunk flexion to about 90 degrees as he stood up. He had profound gait impairment and freezing of gait (FOG) off medication, but gait and FOG improved on medication. Camptocormia improved to about 30 degrees, but he had severe dyskinesias. Because he had no skeletal deformity, improved on medication, and had dyskinesias, he had bilateral 130 Hz subthalamic (STN) DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) Part III improved from 37 to 13 (off medication/on DBS), and after 14 months his camptocormia had resolved. Camptocormia that is responsive to dopaminergic medication, without a skeletal deformity, may respond to bilateral high-frequency STN DBS.

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Effect of subthalamic deep brain stimulation on postural abnormality in Parkinson disease

Journal of Neurosurgery ◽

10.3171/2009.10.jns09917 ◽

2010 ◽

Vol 112 (6) ◽

pp. 1283-1288 ◽

Cited By ~ 46

Author(s):

Atsushi Umemura ◽

Yuichi Oka ◽

Kenji Ohkita ◽

Takemori Yamawaki ◽

Kazuo Yamada

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Spinal Deformity ◽

Rating Scale ◽

Pisa Syndrome ◽

Long Term Follow Up ◽

Disease Rating ◽

Stn Dbs ◽

Deep Brain

Object Parkinson disease (PD) is often accompanied by various postural abnormalities such as camptocormia (bent spine) or Pisa syndrome (lateral flexion). The authors studied the effect of subthalamic nucleus deep brain stimulation (STN DBS) on postural abnormality in patients with PD. Methods The authors retrospectively reviewed the clinical course of 18 patients who suffered from significant postural abnormality and underwent bilateral STN DBS. Patients whose preoperative posture score (Unified Parkinson's Disease Rating Scale III, item 28) was 2 or more in the “medication-on” state were enrolled in this study. Eight patients were considered to have camptocormia, and 10 patients were considered to have so-called Pisa syndrome. Nine patients showed apparent thoracolumbar spinal deformity on radiography. Most patients had significant motor fluctuations from levodopa. Results In 13 patients with moderate postural abnormality (score of 2 on item 28), 9 patients improved soon after surgery, but 1 patient relapsed. Two patients improved gradually over a long period after surgery, whereas 2 patients did not improve at all. In 5 patients with severe postural abnormality (score of 3 or 4 on item 28), 2 patients improved slightly in the long-term follow-up period after surgery, but 3 patients did not improve at all. Conclusions Postural abnormality in patients with PD could be ameliorated by STN DBS, and therefore surgery should be considered before irreversible spinal deformity develops.

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Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006162 ◽

2018 ◽

Vol 91 (11) ◽

pp. e1013-e1021 ◽

Cited By ~ 13

Author(s):

Olga Klepitskaya ◽

Ying Liu ◽

Saloni Sharma ◽

Stefan H. Sillau ◽

Jean Tsai ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Restless Legs Syndrome ◽

Mixed Model ◽

Rating Scale ◽

Restless Legs ◽

Sum Score ◽

Stn Dbs ◽

Deep Brain

ObjectiveTo study the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease (PD) and moderate to severe restless legs syndrome (RLS) on their RLS symptoms.MethodsPatients undergoing STN DBS surgery for PD completed the International RLS Study Group Rating Scale (IRLS) and RLS Quality of Life (QoL) questionnaires preoperatively and postoperatively at 6 months, 1 year, and 2 years. The primary outcome measure was IRLS sum score and subscales (severity and impact) and the secondary measure was RLS QoL scores. Differences among the mean scores over time were analyzed using mixed model regression.ResultsTwenty-two patients were enrolled. The preoperative IRLS sum scores were 19.59 ± 6.95, severity subscale 12.91 ± 4.33, impact subscale 4.45 ± 2.72, and transformed RLS QoL score 68.30 ± 20.26. The differences between preoperative and averaged postoperative scores were IRLS sum score −7.80, severity subscale −5.50, impact subscale −1.20, and RLS QoL 4.73. The overall F tests demonstrated differences among the times for the means of the IRLS sum and subscales: p < 0.05. There were no correlations between RLS symptoms improvement and PD motor symptoms improvement or reduction in PD medications. Half of the patients had at least 50% improvement and 27% had resolution of their RLS symptoms (IRLS = 0).ConclusionsSTN DBS significantly decreased RLS symptoms in patients with PD despite a decrease in dopaminergic treatment. This improvement was sustained over a 2-year period.Classification of evidenceThis study provides Class IV evidence that for patients with PD and moderate to severe RLS, STN DBS improves RLS symptoms.

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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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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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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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Speech changes induced by deep brain stimulation of the subthalamic nucleus in Parkinson disease: involvement of the dentatorubrothalamic tract

Journal of Neurosurgery ◽

10.3171/2016.5.jns16243 ◽

2016 ◽

Vol 126 (6) ◽

pp. 2017-2027 ◽

Cited By ~ 19

Author(s):

Albert J. Fenoy ◽

Monica A. McHenry ◽

Mya C. Schiess

Keyword(s):

Deep Brain Stimulation ◽

Parkinson Disease ◽

Brain Stimulation ◽

Spontaneous Speech ◽

Active Electrode ◽

Fiber Tract ◽

Speech Performance ◽

Stn Dbs ◽

Left Electrode ◽

Deep Brain

OBJECTIVEPatients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) often develop a deterioration in speech performance, but there is no clear consensus on the specific effects seen or the mechanism involved and little description of the impact of DBS on conversational speech. Furthermore, there has been no fiber tract connectivity analysis to identify the structures potentially modulated by DBS to cause such deficits. The main objective of this study was to quantify spontaneous speech performance and identify potential involvement of the dentatorubrothalamic tract (DRTt) in patients who underwent STN DBS, because this tract has been implicated in speech deterioration.METHODSSpontaneous speech samples were obtained with STN DBS in both on and off modes in 35 patients with PD and assessed across multiple domains. Diffusion tensor imaging tractography seeded from the therapeutic DBS contacts was performed to identify the fiber tracts involved and, specifically, the DRTt. The position of active electrode contacts was assessed relative to that of the STN.RESULTSFifteen patients with akinetic-rigid (AR) PD and 20 with tremor-dominant (TD) PD subtypes were identified. In the AR-PD subgroup of patients, in whom there was DRTt involvement, 71% demonstrated much better overall speech and largely improved or unchanged fluency in the DBS-off condition. In patients with TD PD with DRTt involvement, 50% demonstrated better overall speech in the off condition, and equivocal results regarding improved or worsened fluency were found. When there was minimal DRTt involvement, 75% of patients with AR PD had better overall speech in the DBS-on condition and better or minimal fluency changes. Similarly, 83% of patients with TD PD with minimal DRTt involvement had better or minimal overall speech and fluency changes in the on condition. More medially placed left electrode contacts were associated with more DRTt involvement in 77% of patients (10 of 13).CONCLUSIONSTo the authors' knowledge, this is the first study to have investigated a specific fiber tract involved in STN DBS in different subtypes of PD relative to its impact on spontaneous speech. At optimal therapeutic programming of STN DBS, overall spontaneous speech and fluency were affected more negatively in patients with AR PD than in those with TD PD when there was DRTt involvement. After fiber tract analysis and modeling, it was found that medially positioned left electrode contacts more often involved fibers of the DRTt. If possible, avoidance of the DRTt by using active electrode contacts that are positioned less medially, specifically in patients with AR PD, might result in less speech deterioration.

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