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  • 1.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Tisch, Stephen
    Department of Neurology, St Vincent's Hospital, University of New South Wales, Sydney, Australia.
    The posterior subthalamic area in the treatment of movement disorders: past, present, and future2009In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 64, no 6, p. 1029-1038Article in journal (Refereed)
    Abstract [en]

    The introduction of thalamotomy in 1954 led naturally to exploration of the underlying subthalamic area, with the development of such procedures as campotomy and subthalamotomy in the posterior subthalamic area. The most popular of these procedures was the subthalamotomy, which was performed in thousands of patients for various movement disorders. Today, in the deep brain stimulation (DBS) era, subthalamic nucleus DBS is the treatment of choice for Parkinson's disease, whereas thalamic and pallidal DBS are mainly used for nonparkinsonian tremor and dystonia, respectively. The interest in DBS in the posterior subthalamic area has been quite limited, however, with a total of 95 patients presented in 14 articles. During recent years, interest has increased, and promising results have been published concerning both Parkinson's disease and nonparkinsonian tremor. We reviewed the literature to investigate the development of surgery in the posterior subthalamic area from the lesional era to the present.

  • 2.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan
    UCL Insitute of Neurology, Queen Square, London, Uk.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor2011In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, no 8, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

  • 3.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Fredricks, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor2011In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 153, no 12, p. 2329-2335Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET). Currently the ventrolateral thalamus is the target of choice, but the posterior subthalamic area (PSA), including the caudal zona incerta (cZi), has demonstrated promising results, and the subthalamic nucleus (STN) has been suggested as a third alternative. The objective of the current study was to evaluate the effect of STN DBS in ET and to compare this to cZi DBS.

    Methods: Four patients with ET were implanted with two ipsilateral electrodes, one in the STN and one in the cZi. All contacts were evaluated concerning the acute effect on tremor, and the effect of chronic DBS in either target was analyzed.

    Results: STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was more efficient, since the same degree of tremor reduction could here be achieved at lower energy consumption. Three patients became tremor-free in the treated hand with either STN or cZi DBS, while the fourth had a minor residual tremor after stimulation in either target.

    Conclusion: In this limited material, STN DBS was demonstrated to be an efficient treatment for ET, even though cZi DBS was more efficient. The STN may be an alternative target in the treatment of ET, pending further investigations to decide on the relative merits of the different targets.

  • 4.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Tisch, Stephen
    Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor2010In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 25, no 10, p. 1350-1356Article in journal (Refereed)
    Abstract [en]

    To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty-one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor.

  • 5.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Åström, Mattias
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor2012In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 3, p. 258-262Article in journal (Refereed)
    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.

  • 6.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Stereotactic functional procedures in the treatment of essential tremor2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Essential tremor (ET) is the most common movement disorder. In cases resistant to pharmacological treatment, functional stereotactic neurosurgery can be an alternative. Lesional surgery has largely been replaced by deep brain stimulation (DBS). The current target of choice is the ventrolateral thalamus (Vim). Vim DBS has generally shown good results, but in some cases it is associated with a suboptimal effect as well as side effects. DBS in the posterior subthalamic area/caudal zona incerta (PSA/cZi) has recently shown promising effects. Recently the role of lesional therapy in selected cases has been discussed.

    Aim: The aim is to evaluate stereotactic functional procedures in the treatment of ET, with special emphasis on PSA DBS. Further the effects of DBS in the PSA are evaluated. The optimal target is also assessed by evaluating the effect of Vim and PSA DBS in relation to the position of the electrode. An attempt to identify patient-specific factors of prognostic importance for the outcome after DBS will be made. The quality of life (QoL) of patients treated with PSA DBS for ET will be assessed. Finally, the aim is also to analyze retrospectively the long-term outcome of lesional procedures (thalamotomies).

    Method: The thesis consists of five studies. The optimal electrode location is evaluated in a study analyzing the location of the electrode contact yielding the best effect in Vim DBS and PSA DBS groups. The efficacy of PSA DBS in 21 patients is evaluated in a prospective study. The correlation between outcome, age, tremor grade and gender is established in a prospective study consisting of 68 patients. Finally, the degree of improvement in QoL is determined in 16 patients operated on in the PSA. The very long-term effect of lesional surgery has been investigated in a retrospective study of nine patients who have undergone thalamotomy.

    Results: In the study of PSA DBS the total score on the Essential Tremor Rating Scale (ETRS) was reduced by 60% compared to the baseline value. Tremor of the arm was improved by 95%. The study evaluating the optimal contact location showed that the best effect was in the PSA in 54% and in the Vim in 12%. The efficacy of DBS was not related to age, gender, or the severity of tremor with regard to the percentage reduction of tremor on stimulation. In patients with a more severe tremor at baseline, a higher degree of residual tremor on stimulation was seen. With regard to QoL, the activities of daily living (ADL) according to the ETRS score were significantly improved, as well as according to the ADL and psychosocial subscores on the Questionnaire for Essential Tremor (QUEST) scale. No significant changes were found on the generic Short Form (SF-36) QoL scale. Thalamotomy had some positive effects, but also a significant amount of side effects that might be attributed to the surgery.

    Conclusions: The effect of PSA DBS was very satisfying and compares well with the results from Vim DBS. When both Vim and PSA DBS are considered, the optimal target seems to be located in the PSA. PSA DBS shows good results in improving ADL, but the results have been difficult to demonstrate on QoL scales. The efficacy of DBS could not be shown to be associated with gender or age. Nor was it associated with the severity of tremor regarding the percentage of tremor reduction on stimulation. The preoperative severity of tremor was the most important factor regarding outcome following DBS. With regard to thalamotomies, some possible remaining benefit of the surgery could be seen along with some severe side effects.

  • 7.
    Sandvik, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Quality of life following DBS in the caudal zona incerta in patients with essential tremor2012In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 3, p. 495-499Article in journal (Refereed)
    Abstract [en]

    Background: Essential tremor (ET) is the most common movement disorder and oftenaffects the quality of life. There are only a few studies evaluating the quality of life after deepbrain stimulation (DBS).

    Findings: This is a prospective study of 16 patients undergoing deep brain stimulation in thecaudal Zona incerta (cZi). The quality of life was assessed with Quality of Life in EssentialTremor Questionnaire (QUEST) and SF-36 scores and the tremor was evaluated using theessential tremor rating scale (ETRS).

    Results: In the tremor rating hand tremor on the treated side improved by 95%, hand functionby 78% and activities of daily living improved by 74%. The QUEST score showedstatistically significant improvements in the psychosocial and activities of daily livingsubscores. The SF-36 score did not show any significant improvement.

    Conclusions: Although very good tremor reduction was achieved, the improvement in thequality of life scores was more modest. This could partly be explained by the quality of lifebeing affected by other factors than the tremor itself.

  • 8.
    Sandvik, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamic and subthalamic DBS for essential tremor: where is the optimal target?2012In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 70, no 4, p. 840-846Article in journal (Refereed)
    Abstract [en]

    Background: The ventrolateral thalamus (Vim, ventral intermediate nucleus) is the traditional target for neurosurgical treatment of essential tremor (ET). The target has, however, varied substantially among different neurosurgeons.

    Objective: To evaluate the effect of deep brain stimulation (DBS) in the thalamus and posterior subthalamic area (PSA) in relation to electrode location.

    Methods: 36 (17Vim / 19 PSA) patients, with 44 DBS electrodes, were included in this retrospective study. The effect of stimulation was evaluated with standardized settings for each contact using items from the essential tremor rating scale (ETRS).

    Results: When each contact was evaluated regarding the treated hand with standardized stimulation, the electrode contact providing the best effect in the individual patient was in 54% located in the zona incerta (Zi) or radiation prelemniscalis (raprl) and in 12 % the Vim. 40 contacts provided a tremor reduction of >90%. Of these, 43% were located in the PSA and 18% in the Vim according to the Schaltenbrandt atlas. 37 of these 40 contacts were found in the PSA group.

    Conclusion: More contacts yielding an optimal effect were found in the PSA group than in the Vim. Many patients operated upon in the Vim got the best effect in a contact located in the PSA. This might suggest that the PSA is a more efficient target than the Vim.

  • 9.
    Sandvik, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamic and subthalamic deep brain stimulation for essential tremor: where is the optimal target?2012In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 70, no 4, p. 840-845Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The ventrolateral thalamus (ventral intermediate nucleus [ Vim]) is the traditional target for neurosurgical treatment of essential tremor. The target, however, has varied substantially among different neurosurgeons.

    OBJECTIVE: To evaluate the effect of deep brain stimulation in the thalamus and posterior subthalamic area (PSA) in relation to electrode location.

    METHODS: Thirty-six (17 Vim/19 PSA) patients with 44 deep brain stimulation electrodes were included in this retrospective study. The effect of stimulation was evaluated with standardized settings for each contact using items from the Essential Tremor Rating Scale.

    RESULTS: When each contact was evaluated in terms of the treated hand with standardized stimulation, the electrode contact providing the best effect in the individual patient was located in the zona incerta or radiation prelemniscalis in 54% and the Vim in 12%. Forty contacts provided a tremor reduction of > 90%. Of these, 43% were located in the PSA and 18% in the Vim according to the Schaltenbrand atlas. Of these 40 contacts, 37 were found in the PSA group.

    CONCLUSION: More contacts yielding an optimal effect were found in the PSA group than in the Vim. Many patients operated on in the Vim got the best effect from a contact located in the PSA. This might suggest that the PSA is a more efficient target than the Vim.

  • 10.
    Sandvik, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Rosendal, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    van Doorn, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamotomy for essential tremor: a very long-term follow-upManuscript (preprint) (Other academic)
    Abstract [en]

    Background: DBS (deep brain stimulation) is currently the golden standard in the surgical treatment of ET (essential tremor). Despite the benefits of DBS, there remain situations where lesional surgery may provide an alternative.

    Objective: To perform a very long-term retrospective evaluation of thalamotomies for ET.

    Methods: Nine patients who underwent thalamotomy for ET during 1972–1999 (follow-up period 20.8 ± 5.2 years) were assessed with regard to tremor scores, side effects, and quality of life, as well as lesion size and location.

    Results: All patients had tremor recurrence, although hand function remained slightly better on the treated side than on the non-treated side. Side effects that could be attributed to the procedure were frequent and did in some cases result in a disability for the patient. Quality of life was poorer in this group than in an age-adjusted healthy population. No correlation between lesion size, location, and long-term outcome could be established.

    Conclusions: In this study population the benefits of thalamotomies were limited, while complications were frequent.

  • 11.
    Sandvik, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rosendal, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    van Doorn, Janis
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Speech and Language Therapy.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamotomy for essential tremor: a very long-term follow-up2012In: The Open Neurosurgery Journal, ISSN 1876-5297, Vol. 5, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Lesional procedures in the thalamus (thalamotomies)were introduced in 1954 by Hassler in the treatment of Parkinsoniantremor and were later also used for ET [1]. After theintroduction of Deep Brain Stimulation (DBS) by Benabid in1987, this technique has gradually replaced lesional surgeryand DBS is at present the treatment of choice for ET [2].DBS is considered to be a reversible technique with fewerrisks, especially in bilateral procedures [3]. Disadvantages ofDBS includehardware related complications, the high cost ofthe procedure, and the more cumbersome life-long follow-up[4]. The American Academy of Neurology gives thalamotomyevidence class C (probably effective) in a recent guidelineupdate [5].For these reasons lesional surgery has recentlybeen discussed as an alternative to DBS in certainselected cases [4].We have therefore decided to review thelong-term results of thalamotomies performed at our departmentby scoring the present symptoms and describing thepresence of persistent neurological deficits which might beattributed to the procedure.

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