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Deep brain stimulation of the posterior subthalamic area in the treatment of movement disorders
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The posterior subthalamic area (PSA) is essentially composed of the caudal Zona incerta and the prelemniscal radiation. Subthalamotomy in the PSA was renowned for its effectiveness in alleviating movement disorders and particularly tremor. The modern literature on DBS of this area is limited, but promising results have been presented for Parkinson’s disease (PD), essential tremor (ET) and other movement disorders.  

Aim: To evaluate the safety of PSA DBS with emphasis on the panorama of side effects, the distribution of stimulation-induced side effects and the effects of PSA DBS on verbal fluency. To evaluate the therapeutic effect of PSA DBS on less common forms of tremor, tremor-dominant PD, and concerning the long-term results in ET.

Method: 40 patients were evaluated regarding side effects of the procedure. 28 patients with ET were analyzed for stimulation-induced side effects in a standardized manner. The locations of the contacts that caused stimulation-induced side effects were plotted on atlas slides. A 3-D model of the area was created based on these slides. Verbal fluency was analyzed in 17 patients with ET before surgery, after 3 days and finally after 1 year. Five patients with less common forms of tremor and 18 with ET were evaluated according to the ETRS at baseline and one year or 3-5 years after surgery, respectively. 14 patients with mainly unilateral tremor-dominant PD were evaluated a mean of 18 months after surgery according to the motor part of UPDRS.

Results: PSA DBS was associated with few serious side-effects, but a transient and mild postoperative dysphasia was found in 22.5% of the patients. There was a slight transient decline in the performance on verbal fluency tests immediately after surgery. Visualization of the contacts causing stimulation-induced side effects showed that identical responses can be elicited from various points in the PSA and its vicinity. The effect on the less common forms of tremor was excellent except for neuropathic tremor where the effect was moderate. A pronounced and sustained microlesional effect was seen for some of the patients. After a mean of 4 years with unilateral PSA DBS the total ETRS score was improved by 52.4%, tremor by 91.8% and hand function by 78.0% in the patients with ET. There was no increase in the stimulation strength over time. In PD, the scores improved 47.7% for contralateral UPDRS III. Contralateral tremor, rigidity, and bradykinesia improved by 82.2%, 34.3%, and 26.7%, respectively.

Conclusions: PSA DBS generally seem to be a safe procedure, but it may be associated with transient declines of verbal fluency. There was no clear somatotopic pattern with regard to stimulation-induced side effects in the PSA. PSA DBS can alleviate tremor regardless of the etiology. The long-term effects in ET were favorable when compared to our previous results of Vim DBS. The effect on Parkinsonian tremor was satisfying, however, the reductions of rigidity and bradykinesia were less compared to previous studies of PSA DBS for PD.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2012. , 64 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1464
Keyword [en]
Deep brain stimulation, Movement disorders, Posterior subthalamic area, Zona incerta, Prelemniscal radiations, Tremor, Essential tremor, Parkinson's disease
National Category
Neurology
Research subject
Neurosurgery
Identifiers
URN: urn:nbn:se:umu:diva-51785ISBN: 978-91-7459-328-0 (print)OAI: oai:DiVA.org:umu-51785DiVA: diva2:488625
Public defence
2012-02-24, Sal E04, byggnad 6E, Norrlands Universitetssjukhus, Umeå, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2012-02-03 Created: 2012-02-01 Last updated: 2012-06-04Bibliographically approved
List of papers
1. Complications and side effects of deep brain stimulation in the posterior subthalamic area.
Open this publication in new window or tab >>Complications and side effects of deep brain stimulation in the posterior subthalamic area.
2010 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, no 2, 88-93 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The posterior subthalamic area (PSA), including the zona incerta and prelemniscal radiation (Raprl), has recently been presented in number of publications as a promising target for deep brain stimulation (DBS) in the treatment of various movement disorders. In order to evaluate the safety of the procedure, we analyzed our initial 40 patients for complications and side effects. METHODS: 40 patients treated with PSA DBS for Parkinson's disease, essential tremor and other forms of tremor were included. RESULTS: The most severe complication was 1 transient mild hemiparesis and 1 infection. Minor complications and side effects were relatively frequent, including mild transient dysphasia in 22.5% of the patients. CONCLUSIONS: Few serious complications were encountered, and we consider the PSA to be a safe target for DBS.

Place, publisher, year, edition, pages
Karger, 2010
Keyword
Deep brain stimulation, Posterior subthalamic area, Zona incerta, Prelemniscal radiation, Parkinson’s disease, Complications, Essential tremor
National Category
Surgery
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-35529 (URN)10.1159/000271824 (DOI)20068384 (PubMedID)
Available from: 2010-08-23 Created: 2010-08-23 Last updated: 2017-12-12Bibliographically approved
2. Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization
Open this publication in new window or tab >>Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization
2013 (English)In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, no 1, 65-71 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area.

Methods: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created.

Results: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern.

Conclusion: Stimulation-induced side effects in the PSA and its vicinity were difficult to attribute to certain anatomical areas as the same response was induced from various locations. Therefore, this study could not provide a meaningful somatotopic map with regard to stimulation-induced side effects in the PSA.

Place, publisher, year, edition, pages
Elsevier, 2013
Keyword
Deep brain stimulation, Posterior subthalamic area, Zona incerta, Prelemniscal radiation, Essential tremor, Side effects, Contact location
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-51866 (URN)10.1016/j.clineuro.2012.04.015 (DOI)
Note

Originally included in thesis in manuscript form

Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved
3. Effects of deep brain stimulation in the caudal Zona incerta on verbal fluency
Open this publication in new window or tab >>Effects of deep brain stimulation in the caudal Zona incerta on verbal fluency
Show others...
2013 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, 24-29 p.Article in journal (Refereed) Published
Abstract [en]

Background: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a relatively unexplored and promising treatment in patients with severe essential tremor (ET). Preliminary data further indicate that the ability to produce language may be slightly affected by the treatment.

Objective: To evaluate the effects on verbal fluency following cZi DBS in patients with ET.

Method: Seventeen consecutive patients who had undergone DBS of the cZi for ET were tested regarding verbal fluency before surgery, 3 days after surgery and after 1 year. Ten patients were also evaluated by comparing performance on versus off stimulation after 1 year.

Results: The total verbal fluency score decreased slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD = 7.5) 3 days after surgery (p = 0.036). After 1 year the score was nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no detectable difference between stimulation on and off after 1 year.

Conclusion: There was a tendency of an immediate and mostly transient postoperative decline in verbal fluency following cZi DBS for ET. In some of the patients this reduction was, however, more pronounced and also sustained over time.

Place, publisher, year, edition, pages
S. Karger, 2013
Keyword
Deep brain stimulation, Verbal fluency, Essential tremor, Zona incerta, Posterior subthalamic area
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-51870 (URN)10.1159/000342497 (DOI)
Note

Originally included in thesis in manuscript form

Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved
4. Deep brain stimulation of the posterior subthalamic area in the treatment of tremor
Open this publication in new window or tab >>Deep brain stimulation of the posterior subthalamic area in the treatment of tremor
2009 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, no 1, 31-36 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Several studies have described lesional therapy in the posterior subthalamic area (PSA) in the treatment of various movement disorders. Recently, some publications have illustrated the effect of deep brain stimulation (DBS) in this area in patients with Parkinson's disease, essential tremor, MS-tremor, and other forms of tremor. Even though the clinical series is small, the reported benefits prompted us to explore DBS in this area in the treatment of tremor.

METHOD: Five patients with tremor were operated using unilateral DBS of the PSA. Two patients had dystonic tremor, one primary writing tremor, one cerebellar tremor and the other neuropathic tremor. All patients were assessed before and 1 year after surgery using items 5 and 6 (tremor of the upper extremity), 11-14 (hand function), and when appropriate item 10 (handwriting) from the essential tremor rating scale.

FINDINGS: The mean improvement on stimulation after 1 year was 87%. A pronounced and sustained microlesional effect was seen in several of the patients, and while the mean improvement off stimulation was 56% the reduction in the three patients with the most pronounced effect was 89%. The two patients with dystonic tremor did also become free of the dystonic symptoms and pain in the treated arm. No severe complication occurred.

CONCLUSIONS: DBS of the PSA in this small group of patients had an excellent effect on the different forms of tremor, except for the neuropathic tremor where the effect was moderate. These preliminary results suggest PSA to be an effective target for the treatment of various forms of tremor. Further studies concerning indications, safety and efficacy of DBS in the posterior subthalamic area are required.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-51855 (URN)10.1007/s00701-008-0163-7 (DOI)19093072 (PubMedID)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved
5. Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor
Open this publication in new window or tab >>Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor
Show others...
2012 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 3, 258-262 p.Article in journal (Refereed) Published
Abstract [en]

Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS.

Methods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5±10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated.

Results A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time.

Conclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-51856 (URN)10.1136/jnnp-2011-300765 (DOI)22205676 (PubMedID)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved
6. Unilateral caudal Zona incerta deep brain stimulation for Parkinsonian tremor
Open this publication in new window or tab >>Unilateral caudal Zona incerta deep brain stimulation for Parkinsonian tremor
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2012 (English)In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, no 10, 1062-1066 p.Article in journal (Other academic) Published
Abstract [en]

Background: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.

Methods: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.

Results: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.

Conclusion: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsoniantremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-51873 (URN)10.1016/j.parkreldis.2012.05.024 (DOI)
Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08Bibliographically approved

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