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Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
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2018 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, no 7, p. 710-716Article in journal (Refereed) Published
Abstract [en]

Background: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD).

Method: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.

Results: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups.

Conclusion: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018. Vol. 89, no 7, p. 710-716
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-150375DOI: 10.1136/jnnp-2017-317219ISI: 000438044100010PubMedID: 29386253Scopus ID: 2-s2.0-85050267457OAI: oai:DiVA.org:umu-150375DiVA, id: diva2:1237337
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2023-11-13Bibliographically approved
In thesis
1. Deep brain stimulation targeting the caudal zona incerta as a treatment for parkinsonian and essential tremor
Open this publication in new window or tab >>Deep brain stimulation targeting the caudal zona incerta as a treatment for parkinsonian and essential tremor
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Deep brain stimulation (DBS) is used as a treatment for Parkinson’s disease (PD) and Essential tremor (ET) when medications are insufficient. The most common DBS-targets for PD and ET, the subthalamic nucleus (STN) and the ventral intermediate nucleus of the thalamus (Vim) respectively, have certain side effects and limitations. In the early 2000s, the posterior subthalamic area (PSA) was introduced as an alternative DBS-target with good results on PD and ET in non-blinded, non-randomised, short-term studies. Different structures in the PSA, such as the caudal zona incerta (cZi), have been used as targets but an optimal target within this area has not been established. Furthermore, there has been an increased interest in asleep DBS surgery but with a paucity of results of asleep surgery for ET, as the Vim is not visible on conventional MRI.

Aims: To evaluate DBS targeting the cZi for PD in a blinded, randomised manner. To spatially map the effects of DBS within the PSA. To evaluate the long-term effects of cZi-DBS on PD tremor and ET. To analyse the outcome of awake and asleep cZi-DBS surgery for ET. 

Method: The thesis is based on five studies. Bilateral cZi-DBS was compared to Best Medical Treatment for PD in a randomised blinded trial. The long-term effects of unilateral cZi-DBS on PD tremor were evaluated retrospectively. Prospectively collected data on cZi-DBS for ET were used to evaluate long-term effects and compare awake and asleep surgery. The effects of cZi-DBS were spatially mapped within the PSA using electric field simulations and contact location in relation to the STN.

Results: Bilateral cZi-DBS improved motor symptoms and quality of life in patients with PD in both blinded and non-blinded evaluations with a pronounced effect on tremor (90%) and a modest on bradykinesia (25-40%). The effects of unilateral cZi-DBS on PD tremor remained undiminished at a mean of five years after surgery. cZi-DBS significantly improved ET 10 years after surgery with a slight deterioration over time. Asleep surgery had similar effects and side effects as awake surgery for patients with ET. Electric field simulations did not reveal an optimal target but together with contact location analyses consistently found that the stimulation was concentrated within the PSA, overlapping the cZi and the cerebellothalamic tract. 

Conclusion: DBS targeting the cZi reliably achieved a pronounced effect on PD tremor and ET up to at least five and ten years after surgery respectively. In addition, cZi-DBS had a modest effect on bradykinesia and improved quality of life in patients with PD. Finally, targeting the cZi enabled asleep surgery with seemingly similar efficacy as awake surgery for ET.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2023. p. 140
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2267
Keywords
movement disorders, parkinson's disease, tremor, essential tremor, deep brain stimulation, zona incerta, posterior subthalamic area
National Category
Neurology Neurosciences
Research subject
Neurology; Neurosurgery
Identifiers
urn:nbn:se:umu:diva-216408 (URN)978-91-8070-208-9 (ISBN)978-91-8070-209-6 (ISBN)
Public defence
2023-12-08, Hörsal B, målpunkt T, by 1D, plan 9,, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council
Available from: 2023-11-17 Created: 2023-11-13 Last updated: 2023-11-15Bibliographically approved

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Blomstedt, PatricStenmark Persson, RasmusHariz, Gun-MarieLinder, JanFredricks, AnnaHäggström, BjörnPhilipson, JohannaForsgren, LarsHariz, Marwan

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