Effect of low versus high frequency stimulation on freezing of gait and other axial symptoms in Parkinson patients with bilateral STN DBS: a mini-review

Abstract

Some studies have shown that low frequency stimulation (LFS, most commonly 60 Hz), compared to high frequency stimulation (HFS, most commonly 130 Hz), has beneficial effects, short-term or even long-term, on improving freezing of gait (FOG) and other axial symptoms, including speech and swallowing function, in Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN DBS). However, other studies failed to confirm this. It seems not clear what determines the difference in response to LFS. Differences in study design, such as presence or absence of FOG, exact LFS used (60 Hz versus 80 Hz), study size, open label versus randomized double blind assessment, retrospective versus prospective evaluation, medication On or Off state, total electric energy delivered maintained or not with the change in frequency, and the location of active contacts could all potentially affect the results. This mini-review goes over the literature with the aforementioned factors in mind, focusing on the effect of LFS versus HFS on FOG and other axial symptoms in PD with bilateral STN DBS, in an effort to extract the essential data to guide our clinical management of axial symptoms and explore the potential underlying mechanisms as well. Overall, LFS of 60 Hz seems to be consistently effective in patients with FOG at the usual HFS in regards to improving FOG, speech, swallowing function and other axial symptoms, though LFS could reduce tremor control in some patients. Whether LFS simply addresses the axial symptoms in the context of HFS or has other beneficial effects requires further studies, along with the mechanism.

Short Versus Conventional Pulse‐Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison

“…Optimization of programming parameters to reduce these stimulation‐related side effects have so far largely focused on voltage and frequency modulations, with beneficial effects reported for speech, gait, and freezing . The pulse width (PW) is another parameter that may be altered in an attempt to reduce stimulation‐induced side effects.…”

Long-term effect of low frequency stimulation of STN on dysphagia, freezing of gait and other motor symptoms in PD

“…As suggested by our recent review, patients with FOG under routine HFS almost always benefit from the LFS 8. Almost all the studies with patients exhibiting FOG at HFS on examination showed a good response to LFS,9 10 13 14 18 23 regardless of medication off9 14 or on state,10 13 18 23 with9 14 23 24 or without adjusting the TEED 10 11 18 23 24.…”

“…Hence, 60 Hz probably would be more likely to produce a beneficial effect on FOG. It makes sense that ventral contacts, which are closer to PPNr, could be more likely to benefit from LFS,9 12 13 though this is not always the case 8. Overriding antikinetic neuronal oscillations in the beta band and enhancing the prokinetic gamma band activity by 60 Hz stimulation could also play a role in the beneficial effect of LFS 38 39.…”

An update on adaptive deep brain stimulation in Parkinson's disease

“…Three recent reviews on low‐frequency STN‐DBS described beneficial effects on freezing of gait, speech, and swallowing that did not respond to, or were caused by, high‐frequency DBS. However, beneficial effects could not always be reproduced, and low‐frequency stimulation sometimes led to worsening of cardinal PD symptoms . The effect of variable frequency stimulation, a paradigm interleaving high‐ and low‐frequency DBS, will be explored soon …”

“…However, beneficial effects could not always be reproduced, and low-frequency stimulation sometimes led to worsening of cardinal PD symptoms. [87][88][89] The effect of variable frequency stimulation, a paradigm interleaving high-and low-frequency DBS, 90 will be explored soon. 91 Also, pulse-width modulation might provide clinical benefit in certain situations.…”