A Review of Cognitive Outcomes Across Movement Disorder Patients Undergoing Deep Brain Stimulation

Abstract

Introduction: Although the benefit in motor symptoms for well-selected patients with deep brain stimulation (DBS) has been established, cognitive declines associated with DBS can produce suboptimal clinical responses. Small decrements in cognition can lead to profound effects on quality of life. The growth of indications, the expansion of surgical targets, the increasing complexity of devices, and recent changes in stimulation paradigms have all collectively drawn attention to the need for re-evaluation of DBS related cognitive outcomes. Methods: To address the impact of cognitive changes following DBS, we performed a literature review using PubMed. We searched for articles focused on DBS and cognition. We extracted information about the disease, target, number of patients, assessment of time points, cognitive battery, and clinical outcomes. Diseases included were dystonia, Tourette syndrome (TS), essential tremor (ET), and Parkinson's disease (PD). Results: DBS was associated with mild cognitive issues even when rigorous patient selection was employed. Dystonia studies reported stable or improved cognitive scores, however one study using reliable change indices indicated decrements in sustained attention. Additionally, DBS outcomes were convoluted with changes in medication dose, alleviation of motor symptoms, and learning effects. In the largest, prospective TS study, an improvement in attentional skills was noted, whereas smaller studies reported variable declines across several cognitive domains. Although, most studies reported stable cognitive outcomes. ET studies largely demonstrated deficits in verbal fluency, which had variable responses depending on stimulation setting. Recently, studies have focused beyond the ventral intermediate nucleus, including the post-subthalamic area and zona incerta. For PD, the cognitive results were heterogeneous, although deficits in verbal fluency were consistent and related to the micro-lesion effect. Conclusion: Post-DBS cognitive issues can impact both motor and quality of life outcomes. The underlying pathophysiology of cognitive changes post-DBS and the identification of pathways underpinning declines will require further investigation. Future studies should employ careful methodological designs. Patient specific analyses will be helpful to differentiate the effects of medications, DBS and the underlying disease state, including disease progression. Disease progression is often an underappreciated factor that is important to post-DBS cognitive issues.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC)

“…Svenningsson et al, 2012;Duncan et al, 2014;Manza et al, 2017). Medical treatments fail to improve cognitive symptoms in many patients (Svenningsson et al, 2012), and cognitive outcomes following conventional high-frequency DBS are mixed (Okun et al, 2009;Combs et al, 2015;Wang et al, 2016), with a recent meta-analysis finding that STN-DBS patients experienced decrements in multiple cognitive domains compared to medically-treated controls (Cernera et al, 2019). Ideally, nextgeneration therapies would address both motor and cognitive aspects of the disease, but will likely require alternative patterns of stimulation.…”

“…Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) and other movement disorders (Deuschl et al, 2006;Starr et al, 2006;Baizabal-Carvallo et al, 2014). However, standard DBS is not generally considered effective for the cognitive impairments associated with PD (Cernera et al, 2019), which can be a source of overwhelming disability (Duncan et al, 2014). A small number of studies have suggested that novel DBS paradigms may address this issue in PD and other diseases.…”

Advantages and Recent Developments of Autologous Cell Therapy for Parkinson’s Disease Patients

“…In addition to the high initial surgical cost, patients require battery replacements every 3-5 years (Dang et al, 2019) and anticipating battery failure is also a critical clinical issue since it can result in a subacute worsening of symptoms (Montuno et al, 2013). Additionally, there is a risk that the DBS can result in cognitive sideeffects if not implanted properly (Fields and Troster, 2000;Cernera et al, 2019).…”

Paediatric deep brain stimulation: ethical considerations in malignant Tourette syndrome

“…4 Cognitive decline has neither reliably nor consistently been associated with DBS in patients with TS. 20 Long-term prospective data on paediatric patients who have received DBS for TS are lacking. Studies exist suggesting long-term utilisation of DBS for treatment of Parkinson's disease and dystonia may result in unwanted neural reorganisation.…”