Deep Brain Stimulation in the Treatment of Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a common progressive neurodegenerative movement disorder. The cardinal feature of Parkinson's is neuronal degeneration causing a dopamine deficit in the brain which leads to a host of clinical features in the patient. However, consensus over specific clinical criteria for diagnosis remains to be established. Parkinson's does not have a cure yet, but a variety of diagnostic and treatment protocols have been developed over the years with a primary focus on pharmacological therapy. Anti-parkinsonian drugs such as levodopa lose their efficacy over time and are needed in higher doses as the disease inevitably progresses. An alternative to pharmacological therapy is deep brain stimulation (DBS). Deep brain stimulation involves transcranial placement of unilateral or bilateral leads (wires) most commonly in the sub-thalamic nucleus or the globus pallidus interna of the brain by stereotactic surgery. Given the multiple hypotheses explaining the different effects of DBS with sometimes conflicting mechanisms, it is difficult to pinpoint the exact way in which DBS operates. Nevertheless, it has proven to be significantly effective. DBS, although being a cost-effective treatment measure for Parkinson's patients, is not without limitations. A careful selection of patients is required preoperatively that determines the response and tolerance to the therapy in patients. This review aims to summarize the current literature on DBS in Parkinson's with a focus on the hypothesized mechanisms, selection criteria, advantages and its limitations.

Personalizing Deep Brain Stimulation Therapy for Parkinson’s Disease With Whole-Brain MRI Radiomics and Machine Learning

“…The levodopa challenge, which is the most used preoperative test for DBS patient selection worldwide, showed that individual patient improvement after the therapy was inaccurately predicted with a large range of up to 30 UPDRSIII points [11]. A machine learning algorithm that could identify/predict which patients will benefit the most from DBS surgery would pave the way not only to a more cost-effective selection of candidate patients but also give confidence to potentially consider cohorts of older people [12] and those with comorbidities [13] who are for now discouraged on risk-benefit assessment. Our results can be interpreted as a proof-of-concept machine learning patient selection tool produced by an easy-to-implement imaging analysis pipeline.…”

“…To summarise, PD is characterised by neuronal loss not only in the substantia nigra but throughout the brain [26]. Although there are several hypotheses with regard to the mechanism of DBS [13], there is no doubt that its effects are not only local around the electrode but also remote, throughout the basal ganglia circuitry and cortex. This hypothesis requires a functional connectivity between these areas.…”

Premature drug reduction after subthalamic nucleus deep brain stimulation leading to worse depression in patients with Parkinson's disease

“…If there is a clear response to stim, even a partial response, medication can be gradually reduced. If there is not a response to stimulation because the stimulation parameters are still being determined, medication should not be reduced ( 21 ). However, the current drug reduction strategy only relies on clinical response and doctor experience, which has some limitations.…”