Long-term outcomes of deep brain stimulation in Parkinson disease

Abstract

| The efficacy of deep brain stimulation (DBS) for Parkinson disease (PD) is well established for up to 1 or 2 years, but long-term outcome data are still limited. In this Review, we critically discuss the evidence on the long-term outcomes of DBS and consider the clinical implications. Although many patients are lost to follow-up, the evidence indicates that subthalamic nucleus DBS improves motor function for up to 10 years, although the magnitude of improvement tends to decline over time. Functional scores recorded during onmedication periods worsen faster than those recorded in off periods, consistent with the degeneration of non-dopaminergic pathways. Dyskinesia, motor fluctuations and activities of daily living in off periods remain improved at 5 years, but quality of life scores have usually fallen below pre-operative levels.The incidence and severity of dementia among patients receiving DBS are comparable to those among patients who receive medical treatment. Severe adverse events are rare, but adverse events such as dysarthria are common and probably under-reported. Long-term data on the outcomes of globus pallidus interna DBS are limited and mostly confirm the efficacy for dyskinesia. A trend towards offering DBS in the earlier stages of PD creates a need to identify factors that predict long-term outcomes and to discuss realistic expectations with patients pre-operatively.

Mapping heritability of obesity by brain cell types

“…Despite these limitations, several lines of evidence suggest that the cell types identified herein to be enriched for BMI GWAS signal are relevant to human obesity. First, weight gain is the most pronounced side effect of subthalamic nucleus deep brain stimulation used to treat Parkinson patients 55 , an adverse side effect that may involve the DEINH3 cell type thought to reside in the subthalamic nucleus. Second, lorcaserin (Belviq), one of the few FDA-approved anti-obesity drugs, acts on the 5-HTR2C receptor to enhance serotonin signaling.…”

Gene Therapy for Aromatic L-Amino Acid Decarboxylase Deficiency by MR-Guided Direct Delivery of AAV2-AADC to Midbrain Dopaminergic Neurons

“…The symptom diary was completed twice during the period between the Screening and Baseline visits, each over a consecutive 7day period at least 1 month apart. Follow-up observations for 7-day periods were recorded at Week 6 and Months 3,6,12,18 and 24 after surgery.…”

“…A number of surgical strategies have been used to treat adult patients with Parkinson's disease (PD), a neurodegenerative disorder in which brain AADC activity is progressively lost due to disease progression or cell death. These include placement of deep brain stimulation electrodes 6 , cell transplants 7 , and gene therapy 8 . Most clinical trials evaluating the e cacy of gene therapy for PD have utilized an adeno-associated virus type 2 (AAV2), encoding a neurotrophic factor 9,10 or the DDC gene (hAADC), delivered by a direct surgical procedure to the putamen 11,12 .…”

Current Directions in Deep Brain Stimulation for Parkinson’s Disease—Directing Current to Maximize Clinical Benefit

“…Over the last three decades, the long-term efficacy of deep brain stimulation (DBS) in the management of Parkinson disease (PD) has been well established, with 60% improvement of levodopa-related motor complications [1,2], 40-60% amelioration in quality of life [3], and a significant increase in quality-adjusted life expectancy [4]. Despite these remarkable results, not all patients experience maximal benefit from DBS.…”