Safety and Tolerability of Burst-Cycling Deep Brain Stimulation for Freezing of Gait in Parkinson’s Disease

Abstract

Background: Freezing of gait (FOG) is a common symptom in Parkinson’s disease (PD) and can be difficult to treat with dopaminergic medications or with deep brain stimulation (DBS). Novel stimulation paradigms have been proposed to address suboptimal responses to conventional DBS programming methods. Burst-cycling deep brain stimulation (BCDBS) delivers current in various frequencies of bursts (e.g., 4, 10, or 15 Hz), while maintaining an intra-burst frequency identical to conventional DBS.Objective: To evaluate the safety and tolerability of BCDBS in PD patients with FOG.Methods: Ten PD subjects with STN or GPi DBS and complaints of FOG were recruited for this single center, single blinded within-subject crossover study. For each subject, we compared 4, 10, and 15 Hz BCDBS to conventional DBS during the PD medication-OFF state.Results: There were no serious adverse events with BCDBS. It was feasible and straightforward to program BCDBS in the clinic setting. The benefit was comparable to conventional DBS in measures of FOG, functional mobility and in PD motor symptoms. BCDBS had lower battery consumption when compared to conventional DBS.Conclusions: BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy.

Alternative patterns of deep brain stimulation in neurologic and neuropsychiatric disorders

“…A later study found that the implementation of a cycling stimulation pattern improved FOG in one PD patient who had developed tolerance to DBS ( Dayal et al, 2021 ). On the other hand, Wong et al (2021) did not find significant differences between cycling and conventional HFS in the treatment of FOG in patients with PD. Montgomery et al found that continuous HFS of the STN provided greater symptom relief than burst cycling, showing a linear relationship between cycling interval and motor performance, with increasing efficacy of cycling from 0.1 to 0.5 s, both of which were inferior to continuous HFS.…”

“…Of the excluded studies, five were reviews, three did not use ILS, one was in silico (i.e., no human subjects), one was a video, and one was not in English. For burst cycling, the search found 32 studies, of which 14 were included ( Montgomery, 2005 ; Velasco et al, 2007 ; Tai et al, 2011 ; Kuncel et al, 2012 ; Min et al, 2013 ; Boongird et al, 2016 ; Huang et al, 2019 ; Enatsu et al, 2020 ; Kaufmann et al, 2020 ; Dayal et al, 2021 ; Vázquez-Barrón et al, 2021 ; Wong et al, 2021 ; Dalic et al, 2022 ; Loeffler et al, 2022 ). Of the excluded studies, five did not report clinical outcomes (e.g., imaging study with fMRI), four did not use burst cycling, four did not use DBS, three were reviews, one was a conceptual study with no human subjects, and one combined VNS and DBS.…”

“…Continuous TBS appears to improve motor PD symptoms, although the therapeutic threshold is higher with low intraburst frequencies (∼50 Hz vs. 100 Hz) ( Horn et al, 2020 ). The impact of burst cycling on battery longevity has been directly investigated, and one of the main motivations for using burst cycling stimulation over conventional continuous HFS has been to conserve device battery and decrease the frequency of IPG replacements ( Kuncel et al, 2012 ; Wong et al, 2021 ). In the case of TOPS and aDBS battery life is conserved in a more indirect approach, using computational modeling or biomarker-driven auto-regulating systems, respectively, which ultimately leads to more efficient energy consumption.…”

Past, Present, and Future of Deep Brain Stimulation: Hardware, Software, Imaging, Physiology and Novel Approaches

“…Efforts have been made to bring such therapeutic paradigms to DBS programming ( 163 ), but current evidence is preliminary and based on in-clinic observations and may require further testing to address the neuroplasticity effects and long-term observations during chronic stimulation. Additional studies in this area also seek to investigate different burst frequencies for axial symptoms with significantly less battery consumption and fewer side effects ( 164 ). However, it is also important to note that not all brain targets benefit from cycling.…”

Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus

“…An alternative theory is that DBS entrains neural activity 8 , which interferes with individual neuronsʼ ability to respond to synaptic inputs and thereby creates an informational lesion 19 that disrupts pathological network patterns. The effects of DBS on network dynamics have inspired the exploration of stimulation pulse patterns that may better engage plasticity mechanisms 20 , 21 , and the development of closed-loop DBS systems that target network-level pathological electrical field features in epilepsy 2 , 21 and Parkinson’s disease 5 , 6 , 22 , 23 . Recent long-term clinical studies reported an impressive reduction of seizure frequency by closed-loop responsive neurostimulation that targeted subject-specific abnormal intracranial electroencephalogram patterns in epilepsy patients 24 , 25 .…”