Long-term success of low-frequency subthalamic nucleus stimulation for Parkinson’s disease depends on tremor severity and symptom duration

Abstract

Patients with Parkinson’s disease can develop axial symptoms including speech, gait and balance difficulties. Chronic high frequency (>100 Hz) deep brain stimulation can contribute to these impairments while lower frequency stimulation (<100 Hz,) may improve symptoms but only in some individuals. Factors predicting which patients benefit from low frequency stimulation in the long term remain unclear. This study aims to confirm that low frequency stimulation improves axial symptoms, and to go further to also explore which factors predict the durability of its effects. We recruited patients who developed axial motor symptoms while using high frequency stimulation and objectively assessed the short-term impact of low frequency stimulation on axial symptoms, other aspects of motor function, and quality of life. A retrospective chart review was then conducted on a larger cohort to identify which patient characteristics were associated with not only the need to trial low frequency stimulation, but also those which predicted its sustained use. Among 20 prospective patients, low frequency stimulation objectively improved mean motor and axial symptom severity and quality of life in the short term. Among a retrospective cohort of 168 patients, those with less severe tremor and those in whom axial symptoms had emerged sooner after subthalamic nucleus deep brain stimulation were more likely to be switched to and remain on long term low frequency stimulation. These data suggest that low frequency stimulation results in objective mean improvements in overall motor function and axial symptoms among a group of patients, while individual patient characteristics can predict sustained long-term benefits. Longer follow up in the context of a larger, controlled double blinded study would be required to provide definitive evidence of the role of Low frequency Deep brain stimulation.

Long-Term Effects of Subthalamic Stimulation on Motor Symptoms and Quality of Life in Patients with Parkinson’s Disease

“…Additionally, with disease progression, levodopa-resistant symptoms, such as axial motor symptoms, might have developed with the longer follow-up period. A previous study demonstrated that treatment with STN-DBS switching from high- to low-frequency stimulation reduced patients’ axial impairments, such as gait, postural stability, and speech, as well as UPDRS motor scores [ 51 ]. Since low-frequency stimulation offers less beneficial effects for tremor than high-frequency stimulation, we did not use lower-frequency STN-DBS for improving axial symptoms.…”

How Does Deep Brain Stimulation Change the Course of Parkinson's Disease?

“…88 For patients already under DBS, strategies to improve outcomes are also being investigated. One example are axial motor symptoms such as gait impairment and freezing of gait for which low frequency stimulation, 89,90 drugs (eg, rivastigmine), 91 or physiotherapy may provide relief.…”

Neuroscience fundamentals relevant to neuromodulation: Neurobiology of deep brain stimulation in Parkinson's disease

“…PD involves a state of exaggerated synchrony, and therefore it follows that high-frequency (i.e., 130 ​Hz) DBS could disrupt this synchrony to alleviate cardinal symptoms, while very-low frequency (i.e., 10 ​Hz) can actually increase pathological synchrony and worsen symptoms [ 53 ]. Intriguingly, stimulation at 60 ​Hz (which many refer to as ‘low frequency stimulation’) may offer superior relief of freezing of gait and other axial symptoms compared to traditional high-frequency stimulation [ 54 , 55 ]. Theories for the different therapeutic effect of 60 ​Hz stimulation include reduced current spread to the nearby pedunculopontine nucleus area, or alternatively, by boosting prokinetic gamma oscillations [ 56 ].…”