Pallidal Deep Brain Stimulation for dystonia

Pallidal Deep Brain Stimulation is the primary surgical treatment. 1).

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

Pallidal Deep Brain Stimulation for the Treatment of Levodopa Responsive Juvenile Dystonia and Parkinsonism Secondary to SPG11 Mutation 2).

Response is better for primary dystonias, e.g. tardive dystonias than for secondary dystonias such as postanoxic, postencephalitic, perinatal, and poststroke dystonia 3). (other targets need to be assessed). For primary dystonias, the globus pallidus internus (GPi) is the most common primary target.

Pallidal DBS can yield marked and long-lasting improvement in patients with Dystonia who underwent both pallidotomy and selective peripheral denervation earlier. Therefore, such patients, in general, should not be excluded from DBS 4).

Good results have also been reported with STN DBS. Dyskinetic cerebral palsy in children may also be treated with pallidal stimulation 5).

Stereotactic thalamotomy or dentatotomy: Useful for unilateral dystonia, but cannot be used for bilateral dystonia as bilateral lesions would be required which jeopardizes speech, cognition… Effective only for dystonia distal to shoulders or hips, and should not be used if the condition is rapidly progressive

Evidence from case series or uncontrolled study suggests that it may lead in some patients to specific parkinsonian symptoms such as freezing of gait, micrographia, and bradykinesia.

Mahlknecht et al. investigated parkinsonian signs using the Movement Disorder Society Unified Parkinson Disease Rating Scale by means of observer-blinded video ratings in a group of 29 patients treated with pallidal Deep Brain Stimulation and a non-surgical control group of 22 patients, both with predominant cervical dystonia. Additional assessments included MRI-based models of volume of neural tissue activated to investigate areas of stimulation related to dystonic symptom control and those likely to induce parkinsonian signs as well as an EMG analysis to investigate functional vicinity of stimulation fields to the pyramidal tract. Compared with controls, stimulated patients had significantly higher motor scores (median, 25th-75th percentile: 14.0, 8.0-19.5 versus 3.0, 2.0-8.0; P < 0.0001), as well as bradykinesia (8.0, 6.0-14.0 versus 2.0, 0.0-3.0; P < 0.0001) and axial motor subscores (2.0, 1.0-4.0 versus 0.0, 0.0-1.0; P = 0.0002), while rigidity and tremor subscores were not different between groups. Parkinsonian signs were partially reversible upon switching stimulation off for a median of 90 min in a subset of 19 patients tolerating this condition. Furthermore, the stimulation group reported more features of freezing of gait on a questionnaire basis. Quality of life was better in stimulated patients compared with control patients, but parkinsonian signs were negatively associated with quality of life. In the descriptive imaging analysis maximum efficacy for dystonia improvement projected to the posteroventrolateral internal pallidum with overlapping clusters driving severity of bradykinesia and axial motor symptoms. The severities of parkinsonian signs were not correlated with functional vicinity to the pyramidal tract as assessed by EMG. In conclusion, parkinsonian signs, particularly bradykinesia and axial motor signs, due to pallidal stimulation in dystonic patients are frequent and negatively impact on motor functioning and quality of life. Therefore, patients with pallidal stimulation should be monitored closely for such signs both in clinical routine and future clinical trials. Spread of current outside the internal pallidum is an unlikely explanation for this phenomenon, which seems to be caused by stimulation of neural elements within the stimulation target volume 6).

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).

Retrospective chart review of 22 consecutive PGD patients, ≤21 years of age treated by one DBS team over an 8-year period. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate symptom severity and functional disability, pre- and post-operatively. Adverse events and medication changes were also noted.

Results: The median follow-up was 2 years (range, 1-8 years). All 22 patients reached 1-year follow-up; 14 reached 2 years, and 11 reached 3 years. The BFMDRS motor subscores were improved 84%, 93%, and 94% (median) at these time points. These motor responses were matched by equivalent improvements in function, and the response to DBS resulted in significant reductions in oral and intrathecal medication requirements after 12 and 24 months of stimulation. There were no hemorrhages or neurological complications related to surgery and no adverse effects from stimulation. Significant hardware-related complications were noted, in particular, infection (14%), which delayed clinical improvement.

Pallidal DBS is a safe and effective treatment for PGD in patients <21 years of age. The improvement appears durable. Improvement in device design should reduce hardware-related complications over time 8).

1) , 3)
Awan NR, Lozano A, Hamani C. Deep brain stimulation: current and future perspectives. Neurosurg Focus. 2009; 27. DOI: 10.3171/2009.4.FOCUS0982
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.
Saryyeva A, Capelle HH, Kinfe TM, Schrader C, Krauss JK. Pallidal Deep Brain Stimulation in Patients with Prior Bilateral Pallidotomy and Selective Peripheral Denervation for Treatment of Dystonia. Stereotact Funct Neurosurg. 2020 Oct 20:1-5. doi: 10.1159/000509822. Epub ahead of print. PMID: 33080617.
Keen JR, Przekop A, Olaya JE, et al. Deep brain stimulation for the treatment of childhood dystonic cerebral palsy. J Neurosurg Pediatr. 2014; 14: 585–593
Mahlknecht P, Georgiev D, Akram H, Brugger F, Vinke S, Zrinzo L, Hariz M, Bhatia KP, Hariz GM, Willeit P, Rothwell JC, Foltynie T, Limousin P. Parkinsonian signs in patients with cervical dystonia treated with pallidal deep brain stimulation. Brain. 2018 Aug 24. doi: 10.1093/brain/awy217. [Epub ahead of print] PubMed PMID: 30165511.
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
Haridas A, Tagliati M, Osborn I, et al. Pallidal deep brain stimulation for primary dystonia in children. Neurosurgery. 2011;68(3):738-743. doi:10.1227/NEU.0b013e3182077396
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