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Stenmark Persson, Rasmus
Publications (9 of 9) Show all publications
Blomstedt, Y., Stenmark Persson, R., Awad, A., Hariz, G.-M., Philipson, J., Hariz, M., . . . Blomstedt, P. (2023). 10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor. Movement Disorders Clinical Practice, 10(5), 783-793
Open this publication in new window or tab >>10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor
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2023 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 10, no 5, p. 783-793Article in journal (Refereed) Published
Abstract [en]

Background: Long-term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). Objectives: The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery.

Methods: Thirty-four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS).

Results: One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1–9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow-up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11–14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off-stimulation scores did not differ between year 1 and 10, this 20% deterioration of on-DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year.

Conclusions: This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
DBS, essential tremor, long-term follow-up, posterior subthalamic area, zona incerta
National Category
Neurology Surgery
Identifiers
urn:nbn:se:umu:diva-206764 (URN)10.1002/mdc3.13729 (DOI)000961376000001 ()2-s2.0-85151937204 (Scopus ID)
Funder
Swedish Research Council, 2018-00618
Available from: 2023-04-28 Created: 2023-04-28 Last updated: 2023-11-13Bibliographically approved
Stenmark Persson, R. (2023). Deep brain stimulation targeting the caudal zona incerta as a treatment for parkinsonian and essential tremor. (Doctoral dissertation). Umeå: Umeå University
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
Stenmark Persson, R., Fytagoridis, A., Ryzhkov, M., Hariz, M. & Blomstedt, P. (2023). Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor. Stereotactic and Functional Neurosurgery, 101(6), 369-379
Open this publication in new window or tab >>Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor
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2023 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 101, no 6, p. 369-379Article in journal (Refereed) 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. 

Place, publisher, year, edition, pages
S. Karger, 2023
Keywords
Deep brain stimulation, Parkinson’s disease, Zona incerta, Tremor, Volume of tissue activated
National Category
Neurology Neurosciences
Research subject
Neurology; Neurosurgery
Identifiers
urn:nbn:se:umu:diva-216406 (URN)10.1159/000533793 (DOI)37879313 (PubMedID)2-s2.0-85178594623 (Scopus ID)
Funder
Umeå UniversityParkinsonfonden
Available from: 2023-11-10 Created: 2023-11-10 Last updated: 2023-12-15Bibliographically approved
Stenmark Persson, R., Nordin, T., Hariz, G.-M., Wårdell, K., Forsgren, L., Hariz, M. & Blomstedt, P. (2022). Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations. Neuromodulation, 25(6), 935-944
Open this publication in new window or tab >>Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations
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2022 (English)In: Neuromodulation, ISSN 1094-7159, E-ISSN 1525-1403, Vol. 25, no 6, p. 935-944Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Deep brain stimulation, electric field simulation, improvement maps, Parkinson's disease, quality of life, zona incerta
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-187193 (URN)10.1111/ner.13500 (DOI)000679040500001 ()34313376 (PubMedID)2-s2.0-85111082159 (Scopus ID)
Available from: 2021-09-13 Created: 2021-09-13 Last updated: 2023-11-13Bibliographically approved
Hariz, G.-M., Fredricks, A., Stenmark Persson, R., Hariz, M., Forsgren, L. & Blomstedt, P. (2021). Blinded Versus Unblinded Evaluations of Motor Scores in Patients with Parkinson's Disease Randomized to Deep Brain Stimulation or Best Medical Therapy [Letter to the editor]. Movement Disorders Clinical Practice, 8(2), 285-287
Open this publication in new window or tab >>Blinded Versus Unblinded Evaluations of Motor Scores in Patients with Parkinson's Disease Randomized to Deep Brain Stimulation or Best Medical Therapy
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2021 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 8, no 2, p. 285-287Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2021
Keywords
Parkinson's disease, blinded trial, randomization, deep brain stimulation, UPDRS
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-179502 (URN)10.1002/mdc3.13141 (DOI)000607212300001 ()2-s2.0-85099384415 (Scopus ID)
Available from: 2021-02-05 Created: 2021-02-05 Last updated: 2023-03-24Bibliographically approved
Philipson, J., Blomstedt, P., Fredricks, A., Hariz, M., Stenmark Persson, R. & Jahanshahi, M. (2021). Short- and long-term cognitive effects of deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease. Journal of Neurosurgery, 134(2), 357-365
Open this publication in new window or tab >>Short- and long-term cognitive effects of deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease
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2021 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, no 2, p. 357-365Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: A growing number of studies are showing positive effects of deep brain stimulation (DBS) in the caudal zona incerta (cZi) in various tremor disorders, as well as motor symptoms of Parkinson’s disease (PD). The focus of the present study was to evaluate short- and long-term cognitive effects of bilateral cZi DBS in patients with PD.

METHODS: Twenty-five nondemented patients with advanced PD were recruited to participate in a randomized trial of cZi DBS versus best medical treatment (BMT). The patients in the BMT group were offered surgery after 6 months. Neuropsychological evaluations focusing on assessing verbal and visuospatial memory, attention, and executive function were conducted at baseline and at 6 and 24 months after surgery. Self-reported measures of depression, anxiety, and change in "frontal" behaviors were also completed at all assessment points.

RESULTS: Bilateral cZi DBS in patients with PD generated few adverse cognitive effects. At the short-term follow-up after 6 months, no differences were found between patients randomized to BMT and patients randomized to DBS with regard to most of the cognitive domains assessed. A transient improvement in anxiety was, however, found in the surgical group. At the long-term follow-up 24 months after cZi DBS, no major changes in global cognitive functioning were found, although a decline in attention and self-reported executive function was noted.

CONCLUSIONS: With the exception of a decline in attention and self-reported executive function, bilateral cZi DBS for PD in appropriately screened patients appears to be generally safe with regard to cognitive function, both in the short- and long-term perspective.

Place, publisher, year, edition, pages
American Association of Neurological Surgeons (AANS), 2021
Keywords
zona incerta, Parkinson's disease, deep brain stimulation, neuropsychology, cognition, functional neurosurgery
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-170467 (URN)10.3171/2019.12.JNS192654 (DOI)000646422100005 ()32032954 (PubMedID)2-s2.0-85100240654 (Scopus ID)
Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2023-05-03Bibliographically approved
af Bjerkén, S., Stenmark Persson, R., Barkander, A., Karalija, N., Pelegrina-Hidalgo, N., Gerhardt, G. A., . . . Strömberg, I. (2019). Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance. Neurochemistry International, 131, Article ID 104551.
Open this publication in new window or tab >>Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance
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2019 (English)In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 131, article id 104551Article in journal (Refereed) Published
Abstract [en]

In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
DSP4, Dopamine, In vivo amperometry, In vivo chronoamperometry, Noradrenaline, Parkinson's disease
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-163942 (URN)10.1016/j.neuint.2019.104551 (DOI)000498755800021 ()31542295 (PubMedID)2-s2.0-85072404826 (Scopus ID)
Funder
Swedish Research Council, 9917Västerbotten County CouncilLars Hierta Memorial Foundation
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2021-04-16Bibliographically approved
Blomstedt, P., Stenmark Persson, R., Hariz, G.-M., Linder, J., Fredricks, A., Häggström, B., . . . Hariz, M. (2018). Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation. Journal of Neurology, Neurosurgery and Psychiatry, 89(7), 710-716
Open this publication in new window or tab >>Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation
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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
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-150375 (URN)10.1136/jnnp-2017-317219 (DOI)000438044100010 ()29386253 (PubMedID)2-s2.0-85050267457 (Scopus ID)
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2023-11-13Bibliographically approved
Stenmark Persson, R., Blomstedt, Y., Fytagoridis, A., Hariz, M. & Blomstedt, P.Awake and asleep deep brain stimulation targeting the caudal zona incerta for essential tremor.
Open this publication in new window or tab >>Awake and asleep deep brain stimulation targeting the caudal zona incerta for essential tremor
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(English)Manuscript (preprint) (Other academic)
National Category
Neurology Neurosciences
Research subject
Neurology; Neurosurgery
Identifiers
urn:nbn:se:umu:diva-216407 (URN)
Available from: 2023-11-10 Created: 2023-11-10 Last updated: 2023-11-14
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