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Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
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2022 (Engelska)Ingår i: Neuromodulation, ISSN 1094-7159, E-ISSN 1525-1403, Vol. 25, nr 6, s. 935-944Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: To evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.

Materials and Methods: We report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III, and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for creation of improvement maps and anatomical evaluation.

Results: Median UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change but the subdomains activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29% respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.

Conclusions: Bilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.

Ort, förlag, år, upplaga, sidor
Elsevier, 2022. Vol. 25, nr 6, s. 935-944
Nyckelord [en]
Deep brain stimulation, electric field simulation, improvement maps, Parkinson's disease, quality of life, zona incerta
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-187193DOI: 10.1111/ner.13500ISI: 000679040500001PubMedID: 34313376Scopus ID: 2-s2.0-85111082159OAI: oai:DiVA.org:umu-187193DiVA, id: diva2:1593673
Tillgänglig från: 2021-09-13 Skapad: 2021-09-13 Senast uppdaterad: 2023-11-13Bibliografiskt granskad
Ingår i avhandling
1. Deep brain stimulation targeting the caudal zona incerta as a treatment for parkinsonian and essential tremor
Öppna denna publikation i ny flik eller fönster >>Deep brain stimulation targeting the caudal zona incerta as a treatment for parkinsonian and essential tremor
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2023. s. 140
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2267
Nyckelord
movement disorders, parkinson's disease, tremor, essential tremor, deep brain stimulation, zona incerta, posterior subthalamic area
Nationell ämneskategori
Neurologi Neurovetenskaper
Forskningsämne
neurologi; neurokirurgi
Identifikatorer
urn:nbn:se:umu:diva-216408 (URN)978-91-8070-208-9 (ISBN)978-91-8070-209-6 (ISBN)
Disputation
2023-12-08, Hörsal B, målpunkt T, by 1D, plan 9,, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Forskningsfinansiär
Vetenskapsrådet
Tillgänglig från: 2023-11-17 Skapad: 2023-11-13 Senast uppdaterad: 2023-11-15Bibliografiskt granskad

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