Objective: We review the state-of-the-art for deep brain stimulation (DBS) in Parkinson’s disease (PD) management, and present a case-series to evaluate the potential of DBS prior to levodopa (L-Dopa) in improving Quality-of-life (QoL), challenging the current paradigms of delivery of DBS therapy.

Background: Management of Parkinson’s disease (PD) consists of primarily pharmacological therapy, which are pivotal for controlling both motor and non-motor symptoms. Deep brain stimulation (DBS) is indicated as disease progresses and motor complications arise. Recent data on DBS feasibility in populations with short (7.3±3.1 yrs.)[1] and very short (>6 months but <2 yrs.)[2] disease duration reveals the superiority of DBS to medical treatment alone and compared to later interventions[3]. Nonetheless, to date no paradigms for the optimal DBS timely intervention exist.

Method: Eight patients, (50 to 67 years old) with at least 5 years of PD symptoms and without initiation of L-Dopa therapy, received subthalamic nucleus (STN) DBS implantation. In the 8 PD cases, indication for DBS was not driven by motor complications, as supported by current guidelines, but by relevant QoL impairment and patient’s reluctance to initiate L-Dopa treatment. We present data on clinical manifestation, decision finding during early indication to DBS and trajectories after DBS.

Results: All patients treated with STN-DBS prior to L-Dopa presented improvement in motor and non-motor symptoms and significant improvement of their QoL (46%, 18.2 points in PDQ-39). All patients reduced the intake of dopamine agonists and five are currently free from L-Dopa medication, with no reported adverse events. When compared to QoL outcomes in [1] and [2] our results suggest higher responsiveness to DBS when no L-Dopa has been administered.

Conclusion: Here, we introduce a multicenter observational study to investigate whether early DBS treatment may affect the natural course of PD. Early application of DBS instead of L-Dopa administration could rely on the ability of DBS to properly modulate the brain structural and functional network topology[4, 5] and be prompted by a significant incline on QoL through disease progression; however the clinical value of this proposed paradigm shift should be addressed in clinical trials aimed at modulate the natural course of PD.

References: 1. Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson’s disease with early motor complications. New Engl J Med 2013;368:610-622. 2. Charles D, Konrad PE, Neimat JS, et al. Subthalamic nucleus deep brain stimulation in early stage Parkinson’s disease. Parkinsonism & related disorders 2014;20:731-737. 3. Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology 2018;91:e463-e471. 4. Muthuraman M, Deuschl G, Koirala N, Riedel C, Volkmann J, Groppa S. Effects of DBS in parkinsonian patients depend on the structural integrity of frontal cortex. Scientific reports 2017;7:43571. 5. Koirala N, Fleischer V, Glaser M, et al. Frontal Lobe Connectivity and Network Community Characteristics are Associated with the Outcome of Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson’s Disease. Brain topography 2018;31:311-321.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pre-dopa-dbs-is-early-deep-brain-stimulation-able-to-modify-the-natural-course-of-parkinsons-disease/