Shervin Rahimpour1, Wendy Gaztanaga2, Amol P Yadav3,4, Stephano J Chang2, Max O Krucoff5,6, Iahn Cajigas2, Dennis A Turner1,7, Doris D Wang8. 1. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. 2. Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA. 3. Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. 5. Department of Neurosurgery, Medical College of Wisconsin, Wauwatosa, WI, USA. 6. Department of Biomedical Engineering, Marquette University & Medical College of Wisconsin, Milwaukee, WI, USA. 7. Departments of Neurobiology and Biomedical Engineering, Duke University, Durham, NC, USA. 8. Department of Neurological Surgery, University of California, San Francisco, CA, USA.
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.
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.
Authors: Won Hyuk Chang; Min Soo Kim; Eunhee Park; Jin Whan Cho; Jinyoung Youn; Yun Kwan Kim; Yun-Hee Kim Journal: Arch Phys Med Rehabil Date: 2017-02-11 Impact factor: 3.966
Authors: Maxwell B Santana; Pär Halje; Hougelle Simplício; Ulrike Richter; Marco Aurelio M Freire; Per Petersson; Romulo Fuentes; Miguel A L Nicolelis Journal: Neuron Date: 2014-10-30 Impact factor: 17.173
Authors: Lukas Jaeger; Laura Marchal-Crespo; Peter Wolf; Robert Riener; Lars Michels; Spyros Kollias Journal: Front Hum Neurosci Date: 2014-10-28 Impact factor: 3.169
Authors: V Caggiano; R Leiras; H Goñi-Erro; D Masini; C Bellardita; J Bouvier; V Caldeira; G Fisone; O Kiehn Journal: Nature Date: 2018-01-17 Impact factor: 49.962
Authors: Nicoló G Pozzi; Chiara Palmisano; Martin M Reich; Philip Capetian; Claudio Pacchetti; Jens Volkmann; Ioannis U Isaias Journal: Front Hum Neurosci Date: 2022-05-16 Impact factor: 3.473
Authors: Alice Barra; Martin Rosenfelder; Sepehr Mortaheb; Manon Carrière; Geraldine Martens; Yelena G Bodien; Leon Morales-Quezada; Andreas Bender; Steven Laureys; Aurore Thibaut; Felipe Fregni Journal: Brain Sci Date: 2022-03-24
Authors: Stephano J Chang; Iahn Cajigas; James D Guest; Brian R Noga; Eva Widerström-Noga; Ihtsham Haq; Letitia Fisher; Corneliu C Luca; Jonathan R Jagid Journal: Front Hum Neurosci Date: 2021-06-08 Impact factor: 3.169