Thalamic deep brain stimulation for acquired dystonia in children and young adults: a phase 1 clinical trial

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  • 1 Department of Neurology, Weill Institute for Neurosciences, and
  • 3 Department of Neurological Surgery, University of California, San Francisco, California; and
  • 2 Department of Neurology, Division of Child Neurology, Washington University in St. Louis, Missouri
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OBJECTIVE

The aim of this study was to evaluate the feasibility and preliminary efficacy and safety of combined bilateral ventralis oralis posterior/ventralis intermedius (Vop/Vim) deep brain stimulation (DBS) for the treatment of acquired dystonia in children and young adults. Pallidal DBS is efficacious for severe, medication-refractory isolated dystonia, providing 50%–60% long-term improvement. Unfortunately, pallidal stimulation response rates in acquired dystonia are modest and unpredictable, with frequent nonresponders. Acquired dystonia, most commonly caused by cerebral palsy, is more common than isolated dystonia in pediatric populations and is more recalcitrant to standard treatments. Given the limitations of pallidal DBS in acquired dystonia, there is a need to explore alternative brain targets. Preliminary evidence has suggested that thalamic stimulation may be efficacious for acquired dystonia.

METHODS

Four participants, 3 with perinatal brain injuries and 1 with postencephalitic symptomatic dystonia, underwent bilateral Vop/Vim DBS and bimonthly evaluations for 12 months. The primary efficacy outcome was the change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Barry-Albright Dystonia Scale (BADS) scores between the baseline and 12-month assessments. Video documentation was used for blinded ratings. Secondary outcomes included evaluation of spasticity (Modified Ashworth Scale score), quality of life (Pediatric Quality of Life Inventory [PedsQL] and modified Unified Parkinson’s Disease Rating Scale Part II [UPDRS-II] scores), and neuropsychological assessments. Adverse events were monitored for safety.

RESULTS

All participants tolerated the procedure well, and there were no safety concerns or serious adverse events. There was an average improvement of 21.5% in the BFMDRS motor subscale score, but the improvement was only 1.6% according to the BADS score. Following blinded video review, dystonia severity ratings were even more modest. Secondary outcomes, however, were more encouraging, with the BFMDRS disability subscale score improving by 15.7%, the PedsQL total score by 27%, and the modified UPDRS-II score by 19.3%. Neuropsychological assessment findings were unchanged 1 year after surgery.

CONCLUSIONS

Bilateral thalamic neuromodulation by DBS for severe, medication-refractory acquired dystonia was well tolerated. Primary and secondary outcomes showed highly variable treatment effect sizes comparable to those of pallidal stimulation in this population. As previously described, improvements in quality of life and disability were not reflected in dystonia severity scales, suggesting a need for the development of scales specifically for acquired dystonia.

Clinical trial registration no.: NCT03078816 (clinicaltrials.gov)

ABBREVIATIONS AC-PC = anterior commissure–posterior commissure; BADS = Barry-Albright Dystonia Scale; BFMDRS = Burke-Fahn-Marsden Dystonia Rating Scale; DBS = deep brain stimulation; GPi = globus pallidus pars interna; PedsQL = Pediatric Quality of Life Inventory; UCSF = University of California, San Francisco; UPDRS-II = Unified Parkinson’s Disease Rating Scale Part II; Vim = ventralis intermedius; Vop = ventralis oralis posterior.

Supplementary Materials

    • Supplementary Table (PDF 384 KB)

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Contributor Notes

Correspondence Marta San Luciano: Weill Institute for Neurosciences, University of California, San Francisco, CA. marta.sanlucianopalenzuela@ucsf.edu.

INCLUDE WHEN CITING Published online November 27, 2020; DOI: 10.3171/2020.7.PEDS20348.

M.S.L. and A.R.V. share first authorship of this work.

Disclosures Dr. San Luiciano: consultant for Boston Scientific. Dr. Bledsoe: consultant for Boston Scientific. Dr. Starr: support of non–study-related clinical or research effort from Medtronic and Boston Scientific. Dr. Ostrem: consultant for Abbot and support of non–study-related clinical or research effort from Medtronic and Boston Scienfic.

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