Deep Brain Stimulation to Alleviate Freezing of Gait and Cognitive Dysfunction in Parkinson's Disease: Update on Current Research and Future Perspectives.

Chuyi Huang,Heling Chu,Xiaoping Wang,Yan Zhang

doi:10.3389/fnins.2018.00029

Chuyi Huang, Heling Chu + Show 2 more

Open Access

https://doi.org/10.3389/fnins.2018.00029

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Abstract

Freezing of gait (FOG) is a gait disorder featured by recurrent episodes of temporary gait halting and mainly found in advanced Parkinson's disease (PD). FOG has a severe impact on the quality of life of patients with PD. The pathogenesis of FOG is unclear and considered to be related to several brain areas and neural circuits. Its close connection with cognitive disorder has been proposed and some researchers explain the pathogenesis using the cognitive model theory. FOG occurs concurrently with cognitive disorder in some PD patients, who are poorly responsive to medication therapy. Deep brain stimulation (DBS) proves effective for FOG in PD patients. Cognitive impairment plays a role in the formation of FOG. Therefore, if DBS works by improving the cognitive function, both two challenging conditions can be ameliorated by DBS. We reviewed the clinical studies related to DBS for FOG in PD patients over the past decade. In spite of the varying stimulation parameters used in different studies, DBS of either subthalamic nucleus (STN) or pedunculopontine nucleus (PPN) alone or in combination can improve the symptoms of FOG. Moreover, the treatment efficacy can last for 1–2 years and DBS is generally safe. Although few studies have been conducted concerning the use of DBS for cognitive disorder in FOG patients, the existing studies seem to indicate that PPN is a potential therapeutic target to both FOG and cognitive disorder. However, most of the studies have a small sample size and involve sporadic cases, so it remains uncertain which nucleus is the optimal target of stimulation. Prospective clinical trials with a larger sample size are needed to systematically assess the efficacy of DBS for FOG and cognitive disorder.

Highlights

Freezing of gait (FOG) is a gait disorder featured by recurrent transient gait retardation and interruption
Gliadi et al established the freezing of gait questionnaire (FOG-Q) in 2000, which is highly reliable in clinically assessing FOG (Giladi et al, 2000)
As glutamate and gamma-amino butyric acid (GABA) are closely related to the memory function in Parkinson’s disease (PD) patients (Buchanan et al, 2014), it suggests subthalamic nucleus (STN)-Deep brain stimulation (DBS) may influence the basal ganglia networks which are associated with cognitive functions

Summary

INTRODUCTION

Freezing of gait (FOG) is a gait disorder featured by recurrent transient gait retardation and interruption. FOG is defined as “an episodic inability (lasting seconds) to generate effective stepping in the absence of any known cause other than parkinsonism or high-level gait disorders. It is most commonly experienced during turning and step initiation and when faced with spatial constraint, stress, and distraction. The risk of FOG is higher if the PD patients present with abnormal gait but no tremor at an early stage (Macht et al, 2007); (2) FOG symptoms occur suddenly, with a sense of having the feet stuck to the floor in spite of the inclination of the trunk to move forwards. FOG usually happens unexpectedly, which leads to falls or injuries (Fasano and Bloem, 2013)

Evaluation of FOG

60 Hz non-blind

60 Hz review

20–40 Hz 5–130 Hz

25 Hz analysis

CONCLUSIONS AND FUTURE PERSPECTIVES