A prospective, controlled study of non-motor effects of subthalamic stimulation in Parkinson’s disease: results at the 36-month follow-up

Objective To examine 36-month effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS) compared with standard-of-care medical treatment (MED) in Parkinson’s disease (PD). Methods Here we report the 36-month follow-up of a prospective, observational, controlled, international multicentre study of the NILS cohort. Assessments included NMSScale (NMSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). Propensity score matching resulted in a pseudo-randomised sub-cohort balancing baseline demographic and clinical characteristics between the STN-DBS and MED groups. Within-group longitudinal outcome changes were analysed using Wilcoxon signed-rank and between-group differences of change scores with Mann-Whitney U test. Strength of clinical responses was quantified with Cohen’s effect size. In addition, bivariate correlations of change scores were explored. Results Propensity score matching applied on the cohort of 151 patients (STN-DBS n=67, MED n=84) resulted in a well-balanced sub-cohort including 38 patients per group. After 36 months, STN-DBS significantly improved NMSS, PDQ-8, SCOPA-motor examination and -complications and reduced LEDD. Significant between-group differences, all favouring STN-DBS, were found for NMSS, SCOPA-motor complications, LEDD (large effects), motor examination and PDQ-8 (moderate effects). Furthermore, significant differences were found for the sleep/fatigue, urinary (large effects) and miscellaneous NMSS domains (moderate effects). NMSS total and PDQ-8 change scores correlated significantly. Conclusions This study provides Class IIb evidence for beneficial effects of STN-DBS on NMS at 36-month follow-up which also correlated with quality of life improvements. This highlights the importance of NMS for DBS outcomes assessments.

[1]  V. Visser-Vandewalle,et al.  Beneficial effect of 24-month bilateral subthalamic stimulation on quality of sleep in Parkinson’s disease , 2020, Journal of Neurology.

[2]  Marios Politis,et al.  Non-motor outcomes depend on location of neurostimulation in Parkinson's disease. , 2019, Brain : a journal of neurology.

[3]  S. Paek,et al.  Long-term effects of bilateral subthalamic nucleus stimulation on sleep in patients with Parkinson’s disease , 2019, PloS one.

[4]  G. Fink,et al.  EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease , 2019, Movement disorders : official journal of the Movement Disorder Society.

[5]  G. Fink,et al.  Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease , 2018, European journal of neurology.

[6]  S. Kuwabara,et al.  Urinary symptoms are correlated with quality of life after deep brain stimulation in Parkinson's disease , 2018, Brain and behavior.

[7]  V. Visser-Vandewalle,et al.  Subthalamic Stimulation Improves Quality of Life of Patients Aged 61 Years or Older With Short Duration of Parkinson's Disease , 2018, Neuromodulation : journal of the International Neuromodulation Society.

[8]  V. Visser-Vandewalle,et al.  Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease , 2018, Brain Stimulation.

[9]  G. Fink,et al.  Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts , 2018, Brain Stimulation.

[10]  E. Fonoff,et al.  Effects of Subthalamic Stimulation on Olfactory Function in Parkinson Disease. , 2018, World neurosurgery.

[11]  V. Visser-Vandewalle,et al.  Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease , 2018, Movement disorders : official journal of the Movement Disorder Society.

[12]  P. Kaňovský,et al.  Bilateral subthalamic deep brain stimulation initial impact on nonmotor and motor symptoms in Parkinson's disease , 2018, Medicine.

[13]  G. Fink,et al.  Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age , 2018, Movement disorders : official journal of the Movement Disorder Society.

[14]  A. Engel,et al.  Adverse events in deep brain stimulation: A retrospective long-term analysis of neurological, psychiatric and other occurrences , 2017, PloS one.

[15]  M. Kurtis,et al.  The effect of deep brain stimulation on the non-motor symptoms of Parkinson’s disease: a critical review of the current evidence , 2017, npj Parkinson's Disease.

[16]  J. S. Onge,et al.  Effects of Minority Status and Perceived Discrimination on Mental Health , 2016, Population Research and Policy Review.

[17]  I. Dalen,et al.  The long‐term development of non‐motor problems after STN‐DBS , 2015, Acta neurologica Scandinavica.

[18]  S. Paek,et al.  An 8-Year Follow-up on the Effect of Subthalamic Nucleus Deep Brain Stimulation on Pain in Parkinson Disease. , 2015, JAMA neurology.

[19]  P. Derost,et al.  Central pain modulation after subthalamic nucleus stimulation , 2013, Neurology.

[20]  G. Deuschl,et al.  Neurostimulation for Parkinson's disease with early motor complications. , 2013, The New England journal of medicine.

[21]  K. Burchiel,et al.  Randomized trial of deep brain stimulation for Parkinson disease , 2012, Neurology.

[22]  Felix Thoemmes,et al.  Propensity score matching in SPSS , 2012, 1201.6385.

[23]  J. Marinus,et al.  SPES/SCOPA and MDS-UPDRS: formulas for converting scores of two motor scales in Parkinson's disease. , 2011, Parkinsonism & related disorders.

[24]  K. Chaudhuri,et al.  The impact of non‐motor symptoms on health‐related quality of life of patients with Parkinson's disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[25]  C. Clarke,et al.  Systematic review of levodopa dose equivalency reporting in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[26]  M. Eckman,et al.  Early versus delayed bilateral subthalamic deep brain stimulation for parkinson's disease: A decision analysis , 2010, Movement disorders : official journal of the Movement Disorder Society.

[27]  Marco Sassi,et al.  Deep brain stimulation and cognitive functions in Parkinson's disease: A three‐year controlled study , 2009, Movement disorders : official journal of the Movement Disorder Society.

[28]  T. Morioka,et al.  Subthalamic Nucleus Stimulation Does Not Cause Deterioration of Preexisting Hallucinations in Parkinson’s Disease Patients , 2009, Stereotactic and Functional Neurosurgery.

[29]  Lorenzo Moreno,et al.  Propensity Score Matching , 2008 .

[30]  S. Morris Estimating Effect Sizes From Pretest-Posttest-Control Group Designs , 2008 .

[31]  Paolo Barone,et al.  The metric properties of a novel non‐motor symptoms scale for Parkinson's disease: Results from an international pilot study , 2007, Movement disorders : official journal of the Movement Disorder Society.

[32]  M. Lanotte,et al.  Motor and Nonmotor Symptom Follow-Up in Parkinsonian Patients after Deep Brain Stimulation of the Subthalamic Nucleus , 2007, European Neurology.

[33]  Donald B. Rubin,et al.  BEST PRACTICES IN QUASI- EXPERIMENTAL DESIGNS Matching Methods for Causal Inference , 2007 .

[34]  G. Deuschl,et al.  Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease. , 2006, Brain : a journal of neurology.

[35]  W Poewe,et al.  Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society‐European Section (MDS‐ES). Part II: late (complicated) Parkinson's disease , 2006, European journal of neurology.

[36]  G. Deuschl,et al.  A randomized trial of deep-brain stimulation for Parkinson's disease. , 2006, The New England journal of medicine.

[37]  M. Elam,et al.  Bilateral stimulation of nucleus subthalamicus in advanced Parkinson's disease: No effects on, and of, autonomic dysfunction , 2005, Movement disorders : official journal of the Movement Disorder Society.

[38]  J. Benito-León,et al.  The SCOPA-Motor Scale for assessment of Parkinson's disease is a consistent and valid measure. , 2005, Journal of clinical epidemiology.

[39]  L Lopiano,et al.  Sexual well being in parkinsonian patients after deep brain stimulation of the subthalamic nucleus , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[40]  A. Benabid,et al.  Long term effects of bilateral subthalamic nucleus stimulation on cognitive function, mood, and behaviour in Parkinson’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[41]  A M Stiggelbout,et al.  A short scale for the assessment of motor impairments and disabilities in Parkinson’s disease: the SPES/SCOPA , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[42]  R. Hauser,et al.  Sleep Attacks and Dopamine Agonists for Parkinson’s Disease , 2003, CNS drugs.

[43]  R. Fitzpatrick,et al.  The PDQ-8: Development and validation of a short-form parkinson's disease questionnaire , 1997 .

[44]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.