Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease

Abstract

L-DOPA is still the most effective pharmacological therapy for the treatment of motor symptoms in Parkinson's disease (PD) almost four decades after it was first used. Deep brain stimulation (DBS) is a safe and highly effective treatment option in patients with PD. Even though a clear understanding of the mechanisms of both treatment methods is yet to be obtained, the combination of both treatments is the most effective standard evidenced-based therapy to date. Recent studies have demonstrated that DBS is a therapy option even in the early course of the disease, when first complications arise despite a rigorous adjustment of the pharmacological treatment. The unique feature of this therapeutic approach is the ability to preferentially modulate specific brain networks through the choice of stimulation site. The clinical effects have been unequivocally confirmed in recent studies; however, the impact of DBS and the supplementary effect of L-DOPA on the neuronal network are not yet fully understood. In this review, we present emerging data on the presumable mechanisms of DBS in patients with PD and discuss the pathophysiological similarities and differences in the effects of DBS in comparison to dopaminergic medication. Targeted, selective modulation of brain networks by DBS and pharmacodynamic effects of L-DOPA therapy on the central nervous system are presented. Moreover, we outline the perioperative algorithms for PD patients before and directly after the implantation of DBS electrodes and strategies for the reduction of side effects and optimization of motor and non-motor symptoms.

A comparison of indirect and direct targeted STN DBS in the treatment of Parkinson’s disease—surgical method and clinical outcome over 15-year timespan

“…It also has the highest betaband-activity, the socalled sweet spot [10]. Though the effect of STN DBS with regard to antiparkinsonian medication is well-documented [1], still the combined effect of STN DBS and levodopa and the neural mechanism of action remain unclear [17].…”

The Role of Inflammation in Amyloid Diseases

“…Although great results were seen in mouse models, in AD patients, clinical trial using nonsteroidal anti-inflammatory drugs (NSAID) were unsuccessful to prevent or treat the disease, but these drugs only account for a small part of inflammatory pathways dependent on cyclooxygenases (COX) and have diverse side effects. For PD, treatment using drugs is aimed at enhancing cholinergic and dopaminergic transmissions and hence decreasing motor and gut-related symptoms, such as tremors and constipation [91]. Deep-brain stimulation is a surgical treatment available for PD and can also decrease motor symptoms [91].…”

“…For PD, treatment using drugs is aimed at enhancing cholinergic and dopaminergic transmissions and hence decreasing motor and gut-related symptoms, such as tremors and constipation [91]. Deep-brain stimulation is a surgical treatment available for PD and can also decrease motor symptoms [91]. Most treatments, as the ones described above, are aimed at treating the consequence of amyloid accumulation rather than treating the amyloid accumulation itself or the inflammatory components of these many amyloid diseases.…”

The advances of Deep Brain Stimulation (DBS) for treatment of Parkinson s disease (PD)

“…Patients should be made fully aware that DBS is not able to cure the disease but it is able to optimize the motor symptoms, henceforth, the quality of life. Second Muthuraman et al 22 , the detailed initial evaluation is needed preferably in a movement disorder center. This support determines whether the patient will benefit from DBS.…”

“…Khabarova et al 63 [21][22][23][24][25][26][27][28][29][30][31] in those with prior pallidotomy (p < 0.01), and by 37.5%, from 48.8 ± 12.6 (range, 35-65) to 29.8 ± 13.6 (range, in those with prior thalamotomy (p < 0.01). This study indicates that bilateral STN-DBS is effective and can be used in patients with PD with prior unilateral stereotactic destructive operations on subcortical structures.…”