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

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.

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.

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.