Freezing of Gait in Parkinson’s Disease: Invasive and Noninvasive Neuromodulation

Abstract

Introduction: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.Materials and Methods: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders. Conclusion:Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.

Gait-Related Brain Activation During Motor Imagery of Complex and Simple Ambulation in Parkinson's Disease With Freezing of Gait

“…However, the increased activation in the CLR, MLR, and SLR in PD FOG might not sustain adequately to stop the ongoing freezing all the time, and FOG might breach the compensation intermittently throughout the course of walking (Gratsch et al, 2019 ). Furthermore, Mori et al demonstrated that stimulation of the CLR can independently induce locomotion in decerebrate cats (Mori et al, 1999 ; Rahimpour et al, 2021 ). However, although stimulation of the SLR or MLR also could evoke locomotion in decerebrate cats, the coordination of the limbs was greatly disrupted and extensor rigidity was elicited (Orlovskii, 1970 ; Rahimpour et al, 2021 ).…”

“…Furthermore, Mori et al demonstrated that stimulation of the CLR can independently induce locomotion in decerebrate cats (Mori et al, 1999 ; Rahimpour et al, 2021 ). However, although stimulation of the SLR or MLR also could evoke locomotion in decerebrate cats, the coordination of the limbs was greatly disrupted and extensor rigidity was elicited (Orlovskii, 1970 ; Rahimpour et al, 2021 ). These findings suggest that the CLR may play a pivotal role in coordinating SLR and MLR for generating and monitoring locomotion (Rahimpour et al, 2021 ).…”

“…However, although stimulation of the SLR or MLR also could evoke locomotion in decerebrate cats, the coordination of the limbs was greatly disrupted and extensor rigidity was elicited (Orlovskii, 1970 ; Rahimpour et al, 2021 ). These findings suggest that the CLR may play a pivotal role in coordinating SLR and MLR for generating and monitoring locomotion (Rahimpour et al, 2021 ). The current findings of no significant difference between the PD FOG and normal subjects in MLR and SLR activities as what we saw in CLR also strengthen the notion.…”

Comparing the Clinical and Neuropsychological Characteristics of Parkinson’s Disease With and Without Freezing of Gait

“…FOG is one of the most common walking problems in advanced Parkinson's disease (PD) (Ortelli et al, 2019). It not only increases patients' risk of falls and injuries, but also leads to emotional disorders and poor quality of life (Morrist et al, 2020;Rahimpour et al, 2020). Although some pharmacological and physical interventions are used to alleviate FOG in PD patients, the results are still far from satisfactory (Onder and Ozyurek, 2020).…”

MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson’s Disease Patient With Levodopa-Resistant Freezing of Gait

“…Freezing of gait (FOG) is one of the most debilitating of these deficits, and is described as the sudden and paroxysmal inability to generate effective stepping, despite the intention to do so ( Giladi and Nieuwboer, 2008 ). It is a poorly understood phenomenon without a single unifying pathology and may represent a heterogeneous collection of circuitopathies affecting nodes along the locomotor control network ( Rahimpour et al, 2020 ). Perhaps consequently, the management of FOG is complicated by its variable response to dopaminergic therapy—while some patients improve with medication, others have freezing that is refractory to levodopa ( Nonnekes et al, 2015 ).…”