Observational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia.
Dystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an established treatment for severe isolated dystonia but long-term data are sparse.
We considered 36 consecutive patients with isolated generalized (n = 14) and cervical/segmental (n = 22) dystonia operated at Charité-University Hospital between 2000 and 2007 in a retrospective analysis for long-term outcome of pallidal DBS. In 19 of these patients, we could analyze dystonic symptoms and disability rated by the Burke–Fahn–Marsden Dystonia Rating scale (BFMDRS) at baseline, short-term (ST-FU, range 3–36 months) and long-term follow-up (LT-FU, range 93–197 months). Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires.
Patients reached an improvement in motor symptoms of 63.8 ± 5.7% (mean ± SE) at ST-FU and 67.9 ± 6.1% at LT-FU. Moreover, a significant and stable reduction in disability was shown following DBS (54.2 ± 9.4% at ST-FU and 53.8 ± 9.2% at LT-FU). BDI and SF36 had improved by 40% and 23%, respectively, at LT-FU (n = 14). Stimulation-induced adverse events included swallowing difficulties, dysarthria, and bradykinesia. Pulse generator (n = 3) and electrodes (n = 5) were revised in seven patients due to infection.
Pallidal DBS is a safe and efficacious long-term treatment for dystonia with sustained effects on motor impairment and disability, accompanied by a robust improvement in mood and quality of life.
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The study was supported by a grant of the German Research Foundation (DFG) Grant KFO 247 and the Federal Ministry of Education and research (BMBF) with the network for rare diseases DYSTRACT 01GM1514D. This study has been approved by the local ethics committee and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Conflicts of interest
AAK received speaker´s honoraria or consultancies and travel grants from Medtronic, Boston Scientific and Abbott. P. Krause received speaker´s honoraria from Medtronic. S. Völzmann: None. S. Ewert: None. A. Kupsch belongs to the Advisory Board ´Medtronic USA´ and received honoraria from Allergan, Boehringer Ingelheim, Ipsen Pharma, Lundbeck, Medtronic, Merck, Merz Pharmaceuticals, Orion, St. Jude UCB. G.H. Schneider received speaker´s honoraria from Medtronic, Boston Scientific and Abbott.
This study has been approved by the local ethics committee of the Charité, University Medicine Berlin and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
All patients gave their written informed consent for long-term followup.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary file1 Suppl. Table 1: Demographic characteristics and clinical data (mean ± standard error) of the DBS patients with generalized dystonia (1-10) and cervical/segmental dystonia (11-19). None of the patients had any structural brain abnormalities in individual MRI. Note the complete withdrawal of medication after DBS in 10 of 19 patients. BFMDRS Burke–Fahn–Marsden Dystonia Scale for motor impairment (M) and degree of disability (D) at baseline (BL), short-term follow-up (ST-FU) and last long-term follow-up (LT-FU). p.d.: per day; i.r.: if required; *indicates patients that had been included in the national dystonia trial [7, 40] (DOCX 19 kb)
Supplementary file2 Suppl. Table 2: Stimulation parameters of all patients at short-term and long-term follow-up. Patient numbers given here match table 1 with demographic data of all patients. Patient 18 initially was stimulated quadripolar (Vim and Gpi). After lack of benefit of thalamic stimulation, only bilateral pallidal stimulation was selected (DOCX 20 kb)
Supplementary file3 Suppl. Table 3: Overview of the Drop Outs (n=17; 13 CD/SD versus 4 GD patients) and their individual preoperative and short-term (post DBS) scoresavailable retrospectively (range of ST-FU: 3-60months). * Indicate patients with THAP1 gene mutation. Maximum Value in points for TWSTRS=35,TSUI=25, BFMDRS=120. n. a. = not available (DOCX 20 kb)
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Krause, P., Völzmann, S., Ewert, S. et al. Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16 years. J Neurol 267, 1622–1631 (2020). https://doi.org/10.1007/s00415-020-09745-z
- Pallidal DBS
- Long-term effects
- DBS and quality of life