Beneficial Effects of Bilateral Subthalamic Stimulation on Non-Motor Symptoms in Parkinson's Disease

doi:10.1016/j.brs.2015.08.005

Brain Stimulation

Volume 9, Issue 1, January–February 2016, Pages 78-85

https://doi.org/10.1016/j.brs.2015.08.005 Get rights and content

Highlights

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Investigated bilateral STN-DBS motor, non-motor and quality of life effects in 60 patients with PD.
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Significant improvement of quality of life, non-motor and motor symptoms on 6 months follow-up.
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Significant non-motor benefit on sleep/fatigue, miscellaneous, perceptual problems, urinary domain.

Abstract

Background

STN-DBS is well established to improve motor symptoms and quality of life in patients with PD. While non-motor symptoms are crucial for quality of life in these patients, only neuropsychiatric and neuropsychological symptoms have been systematically studied in a longitudinal design so far. However, these are only a part of the non-motor symptoms spectrum.

Hypothesis

We hypothesized that STN-DBS is associated with a beneficial effect on a range of non-motor symptoms.

Methods

In this multicenter, open, prospective, international study (EuroInf-study, UKCRN10084/DRKS00006735) we investigated non-motor effects of STN-DBS in “real-life” use. We evaluated Non-motor Symptom Scale, and Questionnaire, PD Questionnaire-8, Scales for Outcomes of PD motor examination and complications, and activities of daily living preoperatively and at 6 months follow-up in 60 consecutive patients (35 male, mean age: 61.6 ± 7.8 years, mean disease duration: 10.4 ± 4.2 years).

Results

All outcomes improved significantly at 6 months follow-up (PD Questionaire-8, p = 0.006; activities of daily living, p = 0.012; all others, p < 0.001; Wilcoxon signed-rank, respectively paired t-test; Bonferroni-correction). Post-hoc analyses of Non-motor Symptom Scale domains showed a significant reduction of sleep/fatigue and miscellaneous domains (p ≤ 0.001), perceptual problems/hallucinations (p = 0.036), and urinary (p = 0.018) scores. Effect sizes were “moderate” for Non-motor Symptom Scale, and motor complications, “large” for motor examination, and “small” for other outcomes.

Conclusions

This study provides evidence that bilateral STN-DBS improves non-motor burden in patients with PD and opens the door to a more balanced evaluation of DBS outcomes. Further randomized studies are needed to confirm these findings and compare DBS non-motor effects to other invasive therapies of advanced PD.

Introduction

Subthalamic nucleus (STN) deep brain stimulation (DBS) is well established for the symptomatic treatment of Parkinson's disease (PD) improving motor symptoms, activities of daily living (ADL), and quality of life (QoL) [1], [2], [3]. Non-motor symptoms (NMS) play a crucial role for QoL in patients with PD [4], [5]. Long-term effects of DBS on neuropsychological [6], [7] and neuropsychiatric symptoms [8], [9] have been studied. However, these symptoms contribute only to a part of NMS in patients with PD. Previously published studies on a wider range of NMS have methodological limitations due to a lack of objective clinician-based [10], patient-based [11], [12] or any validated assessment at all [12], and small cohort sizes of only 10 [13], [14] or 11 subjects followed up on 6 month [12].

In this study, we therefore investigated prospective data using validated non-motor clinician-based and self-assessment outcome measures collected on 6 months follow-up (6MFU) of a multicenter registry trial. We hypothesized that STN-DBS is associated with a reduction of NMS burden in patients with PD.

Furthermore, to investigate the relationship between changes of NMS, motor and QoL outcomes from baseline, an exploratory aim of our study was to analyze their correlation.

Section snippets

Design

This was a multicenter, open, prospective, European registry study (Cologne, London, and Manchester) of a subgroup of the “Non Motor Symptoms study group” of the “International Parkinson's disease and Movement Disorders Society” with a longitudinal follow-up (EuroInf-study). The “Non Motor Symptoms study group” has previously published results of two other arms of the EuroInf-study (subcutaneous apomorphine and intrajejunal levodopa infusion therapies) [15].

For the third arm, centers were

Results

Here we present data of 60 consecutive patients (35 male) aged 61.64 years (±7.84) with long histories of PD (10.45 ± 4.22 years) and moderate to high LEDD (1073.55 ± 475.93) at baseline. The median Hoehn & Yahr score was 2.75 (interquartile range: 2–3).

The assumption of normal distribution was violated for PDQ-8 Summary Index (p = 0.015), and SPES/SCOPA motor examination (p = 0.019), ADL (p = 0.006) and motor complications scores (p = 0.006), but not for NMSS total score (p = 0.066), and NMSQ

Discussion

This multicenter, open label European study provides evidence that bilateral STN-DBS improves NMS burden in patients with PD as has been suggested from single-center studies in small cohorts. Also, in accordance to previous studies investigating changes from baseline to 6MFU, in our cohort STN-DBS significantly improved motor outcomes and QoL [1], [32]. Studies investigating changes of motor examination from baseline MedON to 6MFU MedON/StimON report comparable results for motor examination

Conclusions

To conclude, STN-DBS ameliorates NMS burden in a range of aspects of NMS. In our cohort around 40% of patients treated with DBS improved their NMS. Number needed to treat results was consistent with relative change and effect size results for all outcome parameters. Reports of these parameters are needed to better understand responses to different treatment strategies like, e.g., DBS, conventional pharmacotherapy, and subcutaneous apomorphine and intrajejunal levodopa infusion therapies.

Acknowledgments

The authors wish to express their gratitude to patients for their consent and cooperation in this study.

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Cited by (82)

Utility of Postoperative Imaging Software for Deep Brain Stimulation Targeting in Patients with Movement Disorders
2022, World Neurosurgery
Citation Excerpt :
Deep brain stimulation (DBS) is an established therapy for different movement disorders when they are refractory to medical treatment, including Parkinson disease (PD), essential tremor (ET), and dystonia.1 Subthalamic nucleus (STN)-DBS has been shown to be effective in improving both motor and nonmotor symptoms, and the quality-of-life (QoL) of PD patients.2-5 Thalamic DBS in the ventral intermediate nucleus (Vim) is effective in achieving symptomatic control of the tremor associated with different movement disorders.6,7
The objective of this study was to evaluate the accuracy of the SureTune3 postoperative imaging software in determining the location of a deep brain stimulation (DBS) electrode based on clinical outcomes and the adverse effects (AEs) observed.
Twenty-six consecutive patients with Parkinson disease (n = 17), essential tremor (n = 8), and dystonia (n = 1) who underwent bilateral DBS surgery (52 electrodes) were included in this study. Presurgical assessments were performed in all patients prior to surgery and at 3 and 6 months after surgery, using quality-of-life and clinical scales in each case. The SureTune3 software was used to evaluate the anatomical positioning of the DBS electrodes.
Following DBS surgery, motor and quality-of-life improvement was observed in all patients. Different AEs were detected in 12 patients, in 10 of whom (83.3%) SureTune3 related the symptoms to the positioning of an electrode. A clinical association was observed with SureTune3 for 48 of 52 (92.3%) electrodes, whereas no association was found between the AEs or clinical outcomes and the SureTune3 reconstructions for 4 of 52 electrodes (7.7%) from 4 different patients. In 2 patients, the contact chosen was modified based on the SureTune3 data, and in 2 cases, the software helped determine that second electrode replacement surgery was necessary.
The anatomical position of electrodes analyzed with SureTune3 software was strongly correlated with both the AEs and clinical outcomes. Thus, SureTune3 may be useful in clinical practice, and it could help improve stimulation parameters and influence decisions to undertake electrode replacement surgery.
Non-motor symptoms in a cohort of patients submitted deep bilateral stimulation of the subthalamic nucleus
2022, Neurologia Argentina
La estimulación cerebral profunda (ECP) ha demostrado ser una terapia eficaz en el tratamiento de la enfermedad de Parkinson avanzada (EPA), aunque no está claramente establecido su efecto sobre la sintomatología no motora (SNM).
Analizar la prevalencia de la SNM post-ECP y evaluar posibles factores relacionados.
Se reclutaron pacientes intervenidos en nuestro centro entre los años 2005 y 2019, y se les aplicaron las siguientes escalas: del sueño de la enfermedad de Parkinson (PDSS), evaluación cognitiva de Montreal (MoCA), inventario de depresión de Beck, escala de severidad de hiposmia y dolor y un cuestionario de sintomatología disautonómica.
Se analizaron 32 pacientes, obteniéndose una puntuación media de 83,56 ± 30,3 en la PDSS, de 18,48 ± 7,4 en la MoCA y de 18,53 ± 8,8 en el inventario de Beck. El 93,7% de los pacientes presentaban tanto hiposmia como dolor, y todos ellos, algún síntoma disautonómico. El análisis estadístico reveló que tanto ser mujer (OR: 0,072; IC 95%: 0,007-0,713; p = 0,025), como un menor tiempo de enfermedad (0R: 0,834; IC 95%: 0,692-0,999; p = 0,05), se asociaban a una mejor calidad del sueño. Los peores resultados en la MoCA se relacionaron en el análisis bivariante con el tiempo de enfermedad (OR: 3,741; IC 95%: 3,7-12,5; p = 0,01), perdiéndose dicha asociación en el multivariante. La presencia de síntomas premotores se asoció en el análisis univariante con una peor puntuación en el inventario de Beck (OR: 4,81; IC 95%: 1,001-25,65; p = 0,05).
Los pacientes con EPA presentan importante SNM, a pesar de que hayan sido sometidos a ECP.
Deep brain stimulation (DBS) has proven to be an effective therapy in the treatment of advanced Parkinson's disease (APD), although its effect on non-motor symptomatology (NMS) is not clearly established.
To analyze the prevalence of post-DBS NMS and evaluate possible related factors.
Patients underwent surgery at our center between 2005 and 2019 were recruited and the following scales were applied: Parkinson's disease sleep scale (PDSS), MoCA (Montreal Cognitive Assessment), Beck Depression Inventory, severity scale of hyposmia and pain and questionnaire of dysautonomic symptomatology.
Thirty-two patients were analyzed, obtaining a median of 86.56±30.3 in the PDSS, 18.48±7.4 in the MoCA and 18.53±8.8 in the Beck inventory. 93.7% of the patients presented both hyposmia and pain, and all of them, some dysautonomic symptom. Statistical analysis revealed that both being a woman [0.072 95% CI (0.007-0.713), P=.025], and a shorter illness time [0.834, 95% CI (0.692–0.999), P=.05], were related to better sleep quality. The worst results in the MoCA were related in the bivariate analysis with the time of illness [3741 (95% CI 3.7-12.5), P=.01), however, in the multivariate the association was lost. The presence of premotor symptoms was associated only in the univariate analysis with a worse score in Beck's inventory [OR: 4.81, 95% CI (1.001-25.65), P=.05].
Patients with APD present important NM symptoms, despite having undergone DBS.
Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational, prospective study
2021, Parkinsonism and Related Disorders
Several studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study.
Forty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test.
The following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006).
We observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.
Subthalamic nucleus deep brain stimulation induces sustained neurorestoration in the mesolimbic dopaminergic system in a Parkinson's disease model
2021, Neurobiology of Disease
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapeutic principle in Parkinson's disease, but the underlying mechanisms, particularly mediating non-motor actions, remain largely enigmatic.
The delayed onset of neuropsychiatric actions in conjunction with first experimental evidence that STN-DBS causes disease-modifying effects prompted our investigation on how cellular plasticity in midbrain dopaminergic systems is affected by STN-DBS.
We applied unilateral or bilateral STN-DBS in two independent cohorts of 6-hydroxydopamine hemiparkinsonian rats four to eight weeks after dopaminergic lesioning to allow for the development of a stable dopaminergic dysfunction prior to DBS electrode implantation.
After 5 weeks of STN-DBS, stimulated animals had significantly more TH⁺ dopaminergic neurons and fibres in both the nigrostriatal and the mesolimbic systems compared to sham controls with large effect sizes of g_Hedges = 1.9–3.4. DBS of the entopeduncular nucleus as the homologue of the human Globus pallidus internus did not alter the dopaminergic systems. STN-DBS effects on mesolimbic dopaminergic neurons were largely confirmed in an independent animal cohort with unilateral STN stimulation for 6 weeks or for 3 weeks followed by a 3 weeks washout period. The latter subgroup even demonstrated persistent mesolimbic dopaminergic plasticity after washout. Pilot behavioural testing showed that augmentative dopaminergic effects on the mesolimbic system by STN-DBS might translate into improvement of sensorimotor neglect.
Our data support sustained neurorestorative effects of STN-DBS not only in the nigrostriatal but also in the mesolimbic system as a potential factor mediating long-latency neuropsychiatric effects of STN-DBS in Parkinson's disease.
Deep brain stimulation effects on lower urinary tract function: Systematic review and meta-analysis
2020, Parkinsonism and Related Disorders
Citation Excerpt :
Out of these 29 studies, 9 reported on urodynamic parameters in DBS ON versus DBS OFF and were used for the quantitative analysis. Of the 29 included studies, 25 were prospective cohort studies [9,14–37], two were retrospective cohort studies [38,39], and two were case reports [40,41]. Overall, the 29 included studies enrolled a total of 1293 patients: 429 women (33%), 805 men (62%), and 59 patients (5%) for whom the gender was not reported.
While efficacy of deep brain stimulation for motor symptoms of neurological disorders is well accepted, its effects on the autonomic system remain controversial. We aimed to systematically assess all available evidence of deep brain stimulation effects on lower urinary tract function.
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science (last search July 12, 2019) and by screening of reference lists and reviews.
After screening 577 articles, we included 29 studies enrolling a total of 1293 patients. Deep brain stimulation of the globus pallidus internus (GPi), pedunculopontine nucleus (PPN), and subthalamic nucleus (STN) had an inhibitory effect on detrusor function, while deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) showed an excitatory effect. In the meta-analysis, deep brain stimulation of the STN led to a significant increase in maximum bladder capacity (mean difference 124 mL, 95% confidence interval 60–187 mL, p = 0.0001) but had no clinically relevant effects on other urodynamic parameters. Adverse events (reported in thirteen studies) were most commonly respiratory issues, postural instability, and dysphagia. Risk of bias and confounding was relatively low.
Deep brain stimulation does not impair lower urinary tract function and might even have beneficial effects. This needs to be considered in the deep brain stimulation decision-making process helping to encourage and to reassure prospective patients.
Efficacy of deep brain stimulation of the subthalamic nucleus versus globus pallidus internus on sensory complaints
2024, npj Parkinson's Disease

View all citing articles on Scopus

: Funding sources for study: This paper presents independent research funded by the German Research Foundation (Clinical Research Group 219), the National Institute of Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London. Additionally an unrestricted peer reviewed educational grant was provided to support coordination of the UK dataset from Medtronic. This study was supported by the Koeln Fortune Program.

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Beneficial Effects of Bilateral Subthalamic Stimulation on Non-Motor Symptoms in Parkinson's Disease

Highlights

Abstract

Background

Hypothesis

Methods

Results

Conclusions

Introduction

Section snippets

Design

Results

Discussion

Conclusions

Acknowledgments

Lancet Neurol

Parkinsonism Relat Disord

Parkinsonism Relat Disord

Basal Ganglia

J Clin Epidemiol

Parkinsonism Relat Disord

Parkinsonism Relat Disord

Clin Neurol Neurosurg

J Neurol Sci

A randomized trial of deep-brain stimulation for Parkinson's disease

N Engl J Med

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease

N Engl J Med

Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial

JAMA

The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease

Mov Disord

The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease

Mov Disord

Reversing cognitive-motor impairments in Parkinson's disease patients using a computational modelling approach to deep brain stimulation programming

Brain

The impact of deep brain stimulation on executive function in Parkinson's disease

Brain

Chronic deep brain stimulation of the subthalamic nucleus for Parkinson's disease: effects on cognition, mood, anxiety and personality traits

Eur Neurol

Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease

Neurology

Effect of deep brain stimulation on Parkinson's nonmotor symptoms following unilateral DBS: a pilot study

Parkinsons Dis

EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease

Mov Disord

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases

J Neurol Neurosurg Psychiatry

Chronic subcutaneous infusion therapy with apomorphine in advanced Parkinson's disease compared to conventional therapy: a real life study of non motor effect

J Parkinsons Dis

Intrajejunal levodopa versus conventional therapy in Parkinson disease: motor and nonmotor effects

Clin Neuropharmacol

The metric properties of a novel non-motor symptoms scale for Parkinson's disease: results from an international pilot study

Mov Disord

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study

Mov Disord

A short scale for the assessment of motor impairments and disabilities in Parkinson's disease: the SPES/SCOPA

J Neurol Neurosurg Psychiatry