Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease?

BACKGROUND Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome. OBJECTIVE To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres. METHODS Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson's Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded. RESULTS At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time. CONCLUSIONS Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.

[1]  G. Halliday,et al.  Dementia in Parkinson's disease: a 20-year neuropsychological study (Sydney Multicentre Study) , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[2]  P. Perozzo,et al.  Deep brain stimulation of the subthalamic nucleus: Clinical effectiveness and safety , 2001, Neurology.

[3]  A. Benabid,et al.  Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation. , 2002, Brain : a journal of neurology.

[4]  M Tagliati,et al.  Subthalamic deep brain stimulation and impulse control in Parkinson’s disease , 2009, European journal of neurology.

[5]  Y. Agid,et al.  Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation , 2006, Movement disorders : official journal of the Movement Disorder Society.

[6]  J. Obeso,et al.  Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. , 2005, Brain : a journal of neurology.

[7]  Thomas Foltynie,et al.  The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. , 2009, Brain : a journal of neurology.

[8]  A. Bentivoglio,et al.  Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants , 2010 .

[9]  J. Jankovic,et al.  Variable expression of Parkinson's disease , 1990, Neurology.

[10]  M. Lanotte,et al.  Probable REM sleep behaviour disorder and STN-DBS outcome in Parkinson's Disease. , 2010, Parkinsonism & related disorders.

[11]  S. Houle,et al.  Stimulation of the subthalamic nucleus and impulsivity: Release your horses , 2009, Annals of neurology.

[12]  M. Rizzone,et al.  Beyond nine years of continuous subthalamic nucleus deep brain stimulation in Parkinson's disease , 2011, Movement disorders : official journal of the Movement Disorder Society.

[13]  J. Dostrovsky,et al.  Levodopa response in long‐term bilateral subthalamic stimulation for Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[14]  P. House Ten-Year Outcome of Subthalamic Stimulation in Parkinson Disease: A Blinded Evaluation , 2012 .

[15]  M. Hely,et al.  Sydney multicenter study of Parkinson's disease: Non‐L‐dopa–responsive problems dominate at 15 years , 2005, Movement disorders : official journal of the Movement Disorder Society.

[16]  P. Remy,et al.  Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT‐PD) , 1999, Movement disorders : official journal of the Movement Disorder Society.

[17]  Yasin Temel,et al.  Impulse control and related disorders in Parkinson's disease patients treated with bilateral subthalamic nucleus stimulation: a review. , 2011, Parkinsonism & related disorders.

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

[19]  A. Dinçer,et al.  Brainstem 1H-MR spectroscopy in patients with Parkinson's disease with REM sleep behavior disorder and IPD patients without dream enactment behavior , 2006, Clinical Neurology and Neurosurgery.

[20]  S. Fahn Unified Parkinson's Disease Rating Scale , 1987 .

[21]  M. Rizzone,et al.  Subthalamic nucleus deep brain stimulation outcome in young onset Parkinson's disease: a role for age at disease onset? , 2011, Journal of Neurology, Neurosurgery & Psychiatry.

[22]  J. L. Del Pozo,et al.  Neurostimulation for Parkinson's disease with early motor complications. , 2013, The New England journal of medicine.

[23]  Keith Wheatley,et al.  Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial , 2010, The Lancet Neurology.

[24]  R. Barker,et al.  The heterogeneity of idiopathic Parkinson's disease , 2002, Journal of Neurology.

[25]  Angelo Antonini,et al.  Behavioural Adverse Effects of Dopaminergic Treatments in Parkinson’s Disease , 2009, Drug safety.

[26]  E. Tolosa,et al.  Clinical diagnostic criteria for dementia associated with Parkinson's disease , 2007, Movement disorders : official journal of the Movement Disorder Society.

[27]  N. Quinn,et al.  Young‐onset Parkinson's disease revisited—clinical features, natural history, and mortality , 1998, Movement disorders : official journal of the Movement Disorder Society.

[28]  A L Benabid,et al.  Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: A consecutive series of 62 patients , 1999, Annals of neurology.

[29]  G. Wooten,et al.  UPDRS activity of daily living score as a marker of Parkinson's disease progression , 2009, Movement disorders : official journal of the Movement Disorder Society.

[30]  A. Benabid,et al.  Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 2003, The New England journal of medicine.

[31]  Y Mizuno,et al.  [Clinical subtypes of Parkinson's disease]. , 1993, No to shinkei = Brain and nerve.

[32]  E. Moro,et al.  Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease , 1999, Neurology.