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Pallidal Deep Brain Stimulation

Bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi).


Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been established as an effective and safe treatment for dystonia.

Pallidal Deep Brain Stimulation for the Treatment of Levodopa Responsive Juvenile Dystonia and Parkinsonism Secondary to SPG11 Mutation 1).

GPi and subthalamic nucleus (STN) DBS improve motor function and activities of daily living for Parkinson's disease (PD) patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long-term observations on therapeutic effects are needed 2).

Mirzadeh et al prospectively examined all consecutive patients with advanced Parkinson's disease (PD) who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented.

Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. CONCLUSIONS Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after surgery 3).

Side effects

Globus pallidus internus deep brain stimulation induces tremor in Parkinson's disease: A paradoxical phenomenon 4).

Findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease 5).

The success of deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) depends on accurately placing the electrode into the GPi motor territory. Direct targeting can be difficult as GPi laminar borders are not always clearly identifiable on MRI.

Stimulation-induced hypokinetic gait disorders with freezing of gait (FOG) have been reported as adverse effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with dystonia.

Wolf et al., prospectively performed computerized gait analysis in ten consecutive patients (mean age 57.8+/-14.3 years) with segmental dystonia but without involvement of lower trunk or legs who were treated with bilateral GPi DBS. Using pressure sensitive insoles, several parameters were measured preoperatively (pre-OP) and at a median of 7 months postoperatively.

The mean step length significantly decreased from 60.0+/-6.9cm pre-OP to 54.3+/-6.4cm with GPi DBS (p<0.01). Due to only small changes of walking distance and gait velocity, the cadence correspondingly increased from 105.6+/-9.2 steps/min to 111.3+/-11.4 steps/min (p<0.05). More importantly, the variance of several gait parameters significantly decreased postoperatively.

In patients with segmental dystonia, chronic DBS of the posteroventral lateral GPi is associated with only mild hypokinesia of gait, but with a relevant decrease in gait variability. Given other recently reported hypokinetic effects of GPi DBS for dystonia and recent results of electrophysiological coherence studies, these findings support the hypothesis of a general alteration of neuronal activity in striato-pallido-thalamo-cortical motor pathways following chronic stimulation of the posteroventral lateral GPi 6).

Case series

Thirty-nine patients with dystonia treated with bilateral Pallidal Deep Brain Stimulation in Sweden at 2 Swedish DBS centers from 2005 to 2015 were included. Different pulse widths (PW) paradigms were used at the 2 centers, 60-90 µs (short PWs) and 450 µs (long PW), respectively. The frequency of IPG replacements, pulse effective voltage (PEV), IPG model, pre-/postoperative imaging, and clinical outcome based on the clinical global impression (CGI) scale were collected from the medical charts and compared between the 2 groups.

Results: The average IPG longevity was extended for the short PWs (1,129 ± 50 days) compared to the long PW (925 ± 32 days; χ2 = 12.31, p = 0.0005, log-rank test). IPG longevity correlated inversely with PEV (Pearson's r = -0.667, p < 0.0001). IPG longevities did not differ between Kinetra® and Activa® PC in the short (p = 0.319) or long PW group (p = 0.858). Electrode distances to the central sensorimotor region of the GPi did not differ between the short or long PW groups (p = 0.595). Pre- and postoperative CGI did not differ between groups.

Short PWs were associated with decreased energy consumption and increased IPG longevity. These effects were not dependent on the IPG model or the anatomic location of the electrodes. PWs did not correlate with symptom severities or clinical outcomes. The results suggest that the use of short PWs might be more energy efficient and could therefore be preferred initially when programming patients with GPi DBS for dystonia 7).

Case reports

Nombela et al., from Hospital Clínico San Carlos, Toronto Western Hospital, reported a Parkinson's disease (PD) patient diagnosed with mild cognitive impairment who underwent DBS surgery targeting the Globus pallidus internus (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere.

Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation.

This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead 8).

Kilbane et al. report the long-term clinical outcomes of 3 patients treated at our center.

All patients presented with medication refractory dystonia and parkinsonism. They were followed prospectively. Clinical evaluations included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS). Adverse events were recorded.

The average length of follow-up was 45.7 months. No serious adverse events occurred. All patients experienced an immediate and sustained improvement in dystonia. Mean percentage improvement in motor subscores of BFMDRS was 63.5% at the last follow-up visit. Parkinsonism was less responsive to neuromodulation, with a mean improvement in UPDRS-III of 39.5%. Standard pallidal stimulation parameters were used. Freezing of gait developed after DBS therapy in 2 patients, stimulation-induced in one and due to disease progression in the other.

Bilateral pallidal DBS resulted in significant and sustained improvement in dystonia and moderate improvement in parkinsonism. Pallidal DBS represents an important treatment option for XPD for the management of motor symptoms 9).


Ramirez-Zamora A, Gee L, Youn Y, Shin DS, Pilitsis JG. Pallidal Deep Brain Stimulation for the Treatment of Levodopa-Responsive Juvenile Dystonia and Parkinsonism Secondary to SPG11 Mutation. JAMA Neurol. 2016 Nov 7. doi: 10.1001/jamaneurol.2016.4297. [Epub ahead of print] PubMed PMID: 27820618.
Liu Y, Li W, Tan C, Liu X, Wang X, Gui Y, Qin L, Deng F, Hu C, Chen L. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease. J Neurosurg. 2014 Sep;121(3):709-18. doi: 10.3171/2014.4.JNS131711. Epub 2014 Jun 6. PubMed PMID: 24905564.
Mirzadeh Z, Chapple K, Lambert M, Evidente VG, Mahant P, Ospina MC, Samanta J, Moguel-Cobos G, Salins N, Lieberman A, Tröster AI, Dhall R, Ponce FA. Parkinson's disease outcomes after intraoperative CT-guided “asleep” deep brain stimulation in the globus pallidus internus. J Neurosurg. 2016 Apr;124(4):902-7. doi: 10.3171/2015.4.JNS1550. Epub 2015 Oct 9. PubMed PMID: 26452116.
Hu W, Eisinger R, Hess C, Foote K, Okun M, Wagle Shukla A. Globus pallidus internus deep brain stimulation induces tremor in Parkinson's disease: A paradoxical phenomenon. J Neurol Sci. 2018 Jul 10;392:102-104. doi: 10.1016/j.jns.2018.07.005. [Epub ahead of print] PubMed PMID: 30036780.
Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC, Beute GN, van Vugt JP, Lenders MW, Contarino MF, Mink MS, Bour LJ, van den Munckhof P, Schmand BA, de Haan RJ, Schuurman PR, de Bie RM. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 2013 Jan;12(1):37-44. doi: 10.1016/S1474-4422(12)70264-8. Epub 2012 Nov 16. PubMed PMID: 23168021.
Wolf ME, Capelle HH, Bäzner H, Hennerici MG, Krauss JK, Blahak C. Hypokinetic gait changes induced by bilateral pallidal deep brain stimulation for segmental dystonia. Gait Posture. 2016 Jul 29;49:358-363. doi: 10.1016/j.gaitpost.2016.07.301. [Epub ahead of print] PubMed PMID: 27491053.
Ågren R, Bartek J Jr, Johansson A, Blomstedt P, Fytagoridis A. Pulse Width and Implantable Pulse Generator Longevity in Pallidal Deep Brain Stimulation for Dystonia: A Population-Based Comparative Effectiveness Study [published online ahead of print, 2020 Jul 15]. Stereotact Funct Neurosurg. 2020;1-6. doi:10.1159/000508794
Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019 Jan 10;47(1-2):19-28. doi: 10.1159/000493094. [Epub ahead of print] PubMed PMID: 30630160.
Kilbane C, Witt J, Galifianakis NB, Glass GA, Volz M, Heath S, Starr PA, Ostrem JL. Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism. Stereotact Funct Neurosurg. 2018 Nov 27;96(5). doi: 10.1159/000492823. [Epub ahead of print] PubMed PMID: 30481788.
pallidal_deep_brain_stimulation.txt · Last modified: 2020/07/16 07:28 by administrador