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Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
Department of Clinical Neuroscience, Neurosurgery, Karolinska Institute, Stockholm.
Cranial & Spinal Technologies, Medtronic, Lafayette, USA .
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. UCL Queen Square Instituteof Neurology, London, UK.ORCID-id: 0000-0001-5930-6037
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2023 (Engelska)Ingår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 101, nr 6, s. 369-379Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus (Vim) is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located postero-medial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant Parkinson’s disease.

Methods: Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1-2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term).

Results: At short-term follow-up DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone.

Conclusions: Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia. 

Ort, förlag, år, upplaga, sidor
S. Karger, 2023. Vol. 101, nr 6, s. 369-379
Nyckelord [en]
Deep brain stimulation, Parkinson’s disease, Zona incerta, Tremor, Volume of tissue activated
Nationell ämneskategori
Neurologi Neurovetenskaper
Forskningsämne
neurologi; neurokirurgi
Identifikatorer
URN: urn:nbn:se:umu:diva-216406DOI: 10.1159/000533793PubMedID: 37879313Scopus ID: 2-s2.0-85178594623OAI: oai:DiVA.org:umu-216406DiVA, id: diva2:1811183
Forskningsfinansiär
Umeå universitetParkinsonfondenTillgänglig från: 2023-11-10 Skapad: 2023-11-10 Senast uppdaterad: 2023-12-15Bibliografiskt 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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