| 1. |
- Blomstedt, Patric, et al.
(författare)
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Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease : a randomised blinded evaluation
- 2018
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 89:7, s. 710-716
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Blomstedt, Yulia, et al.
(författare)
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10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor
- 2023
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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:5, s. 783-793
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Fazel, Seena, et al.
(författare)
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Neurological disorders and violence : a systematic review and meta-analysis with a focus on epilepsy and traumatic brain injury
- 2009
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 256:10, s. 1591-1602
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Forskningsöversikt (refereegranskat)abstract
- The objectives of this study were to systematically review and meta-analyze the research literature on the association of common neurological disorders and violence. Keywords relating to neurological disorders and violence were searched between 1966 and August 2008. Case-control and cohort studies were selected. Odds ratios of violence risk in particular disorders compared with controls were combined using fixed-effects meta-analysis with the data presented in forest plots. Sensitivity analyses were conducted to identify possible differences in risk estimates across surveys. Information on risk factors for violence was extracted if replicated in more than one study. Nine studies were identified that compared the risk of violence in epilepsy or traumatic brain injury compared with unaffected controls. For the epilepsy studies, the overall pooled odds ratio for violent outcomes was 0.67 [95% confidence interval (CI) 0.46-0.96]. For traumatic brain injury, the odds ratio was 1.66 (95% CI 1.12-2.31). An additional 11 case-control studies investigated factors associated with violence in epilepsy and traumatic brain injury. It was not possible to meta-analyze these data. Comorbid psychopathology was associated with violence. Data on other neurological conditions was limited and unreplicated. In conclusion, although the evidence was limited and methodological quality varied, epilepsy and traumatic brain injury appeared to differ in their risk of violence compared with control populations. Longitudinal studies are required to replicate this review's provisional findings that epilepsy is inversely associated with violence and that brain injury modestly increases the risk, and further research is needed to provide information on a broader range of risk factors.
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| 4. |
- Philipson, Johanna, 1975-
(författare)
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Cognitive effects of deep brain stimulation : focus on caudal zona incerta for essential tremor and Parkinson´s disease, and on bed nucleus of stria terminalis for obsessive compulsive disorder
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preserved cognition is an important determinant for perceived Quality of Life (QoL) and has been found to be essential in order to translate improvements in primary symptoms following Deep Brain Stimulation (DBS) into activities of daily living that drive QoL. Therefore, it is important to evaluate not only the clinical improvement, but also the cognitive impact of DBS.The aim of this thesis was to evaluate the cognitive effects of DBS in a new target, the caudal Zona incerta (cZi), which has shown promising results in patients with both Parkinson’s Disease (PD) and Essential Tremor (ET). Given that this is a novel target, the effects on cognition were lacking in the literature. In the same manner, the cognitive effects in patients with Obsessive-Compulsive Disorder (OCD) receiving DBS in the Bed Nucleus of Stria Terminalis (BNST) lacked long-term follow-up.The main findings from the studies included in this thesis, suggest that DBS in the cZi in patients with PD and ET, and in the BNST in patients with OCD, does not generate any major cognitive effects and can be considered safe from a cognitive perspective.However, subtle effects involving aspects of executive function may be present following cZi DBS in patients with PD. Significant results concerned primarily a decrease in selective attention and aspects of inhibition. cZi DBS in patients with ET generated fewer cognitive effects, including a decrease in semantic verbal fluency 12 months after DBS in the cZi. fMRI results evaluating the effects of cZi DBS on brain activity during a working memory task, did not show any significant changes when DBS was ON or OFF. This study also revealed a significant Task-x-DBS interaction, with faster response times during DBS ON relative to DBS OFF for the more cognitively demanding “manipulation” task. In OCD patients with BNST DBS, improved results on the Color-Word Inhibition/switching subtest were found, indicating a possible improvement in cognitive flexibility. However, there was a decrease of performance in visuo-spatial learning at 12 months after surgery.The studies in patients with PD and ET were the first to report comprehensive neuropsychological data regarding cZi DBS. The fMRI study was the first in patients with ET treated with cZi DBS, focusing on cognitive effects during a working memory task in on/off DBS conditions. The OCD study was the first to report long-term data on cognitive effects after BNST DBS. By showing that DBS in these targets does not produce any major cognitive side effects, valuable knowledge in terms of safety has been added. This will hopefully contribute to increased treatment options in DBS.
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| 5. |
- Philipson, Johanna, et al.
(författare)
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Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive–compulsive disorder: effects on cognition after 12 months
- 2023
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165:5, s. 1201-1214
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive–Compulsive Disorder (OCD).Methods: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure.Results: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25–34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility.Conclusions: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.
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| 6. |
- Philipson, Johanna, et al.
(författare)
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Deep brain stimulation in the caudal zona incerta in patients with essential tremor : effects on cognition 1 year after surgery
- 2021
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons (AANS). - 0022-3085 .- 1933-0693. ; 134:1, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The ventral intermediate nucleus (VIM) of the thalamus is currently the established target in the use of deep brain stimulation (DBS) to treat essential tremor (ET). In recent years, the caudal zona incerta (cZi), a brain target commonly used during the lesional era, has been revived as the primary target in a number of DBS studies that show evidence of the efficacy of cZi targeting in DBS treatment for controlling the symptoms of ET. The authors sought to obtain comprehensive neuropsychological data and thoroughly investigate the cognitive effects of cZi targeting in patients with ET treated with DBS.METHODS: Twenty-six consecutive patients with ET who received DBS with cZi as the target at our department from December 2012 to February 2017 were included in this study. All patients were assessed using a comprehensive neuropsychological test battery covering the major cognitive domains both preoperatively and 12 months postoperatively.RESULTS: The results show no major adverse effects on patient performance on the tests of cognitive function other than a slight decline of semantic verbal fluency.CONCLUSIONS: This study indicates that the cZi is a safe target from a cognitive perspective in the treatment of ET with DBS.
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| 7. |
- Philipson, Johanna, et al.
(författare)
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Evaluation of the effects of DBS in the caudal Zona incerta on brain activity during a working memory task in patients with essential tremor
- 2023
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Ingår i: Neuroimage: Reports. - : Elsevier. - 2666-9560. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Essential tremor (ET) is characterized by bilateral upper limb postural and/or kinetic tremor, but also cognitive deficits. Tremor in ET, as well as aspects of cognitive deficits associated with ET, have been suggested to be linked to dysfunction in the cerebello-thalamo-cerebral circuit. In ET patients with disabling and medically intractable motor symptoms, Deep Brain Stimulation (DBS) is effective in reducing tremor. DBS in the caudal Zona incerta (cZi) has been shown to modulate the activity of the sensorimotor cerebello-cerebral circuit during motor tasks. Whether the activity in the cerebello-cerebral circuit is modulated by DBS during tasks involving working memory is unknown. The present study therefore aimed to investigate the possible effects of cZi DBS on working-memory processing in ET patients by means of task-based blood oxygen level-dependent (BOLD) fMRI.Thirteen ET patients completed a working-memory task during DBS OFF and ON conditions. The task involved three conditions: maintenance, manipulation, and control. Behaviorally, there was no significant effect from DBS on accuracy, but a marginally significant Task x DBS interaction was detected for response times (RTs). However, post hoc comparisons for each condition failed to reach statistical significance. FMRI analyses revealed that DBS did not alter BOLD signal in regions of interest (lateral prefrontal cortex, parietal cortex, and the cerebellum), or in a complementary whole-brain analysis.The present study indicates that DBS in the cZi in patients with ET has at most marginal effects on working memory, which is consistent with the results of pre- and post-DBS neuropsychological assessment showing minimal cognitive effects of surgery.
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| 8. |
- Philipson, Johanna, et al.
(författare)
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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
- 2021
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons (AANS). - 0022-3085 .- 1933-0693. ; 134:2, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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