Freezing of Gait During Crawling: The Role of Four-Limb Coordination?

Abstract

Full financial disclosures and author roles may be found in the online version of this article.

Freezing of gait (FOG) is a disabling motor feature of Parkinson's disease (PD) that frequently leads to falls.¹ Similar motor blocks can also affect the upper limbs, swallowing, or speech.² Many patients can mitigate FOG by using compensatory strategies, such as external cues.¹ We describe a unique case of a patient with PD experiencing FOG in all four limbs while crawling.

The patient, a 64-year-old man, had a 26-year history of PD, which began at age 38 with slowness in his right arm. A decade later, he developed FOG, particularly when initiating gait. Sixteen years into his illness, he underwent subthalamic deep brain stimulation (STN-DBS) to manage severe levodopa (l-dopa)-related motor fluctuations and dyskinesias (l-dopa equivalent daily dosage of 950 mg/day). l-dopa provided partial relief of FOG (Unified Parkinson's Disease Rating Scale [UPDRS] item 2.13 off/on l-dopa = 2/1) without falls. Postsurgery, his motor symptoms (UPDRS Part III) improved by 45% with STN-DBS alone, with both electrodes accurately placed bilaterally within the STN. FOG showed partial improvement (item 2.13 ON DBS = 1). Over the next 10 years, his FOG progressively worsened (item 2.13 ON DBS = 3), becoming unresponsive to both STN-DBS adjustments and dopaminergic medication, resulting in frequent falls (Video 1, segment 1). He has no dementia (Mattis Dementia Rating Scale = 133). In daily life, he relied on a broom as an external visual cue, stepping over it to initiate walking (Video 1, segment 2). Although this enabled him to take a few steps, FOG quickly recurred. At home, he occasionally resorted to crawling, which initially triggered leg movements but was also impaired by freezing affecting all four limbs (Video 1, segment 3). External visual cues directed at hand movements temporarily alleviated his crawling-related freezing (Video 1, segment 4).

This is the first report of freezing during crawling in PD, with freezing involving both upper and lower limbs in a quadrupedal position. Crawling, initially adopted as compensatory strategy by the patient, involves diagonal coordination of the forelimbs and hind limbs (trotlike gait) in approximately half of adults.³ This coordination pattern was also evident in our patient (Video 1, segment 5). However, discoordination between all four limbs obstructed his ability to crawl, leading to freezing (segment 5). This observation underscores the importance of coordinated four-limb movement in human locomotion and suggests that dysfunction in this coordination may be a contributing mechanism underlying FOG. In mammals, spinal central pattern generators (CPGs)⁴ and ascending proprioceptive signals regulate the rhythmic coordination of quadrupedal limb movements. However, the role of CPGs in human locomotion remains incompletely understood. In our patient, the temporary relief from freezing during crawling through external cueing, which restored interlimb coordination, suggests involvement of supraspinal neural centers. At the supraspinal level, the basal ganglia, mesencephalic locomotor region,⁵ and reticulospinal pathways contribute to coordination of arm and leg movements during walking. Arm movement, in turn, helps optimize the cyclic movement of the legs.⁶ Lesions in these neural structures have been associated with FOG in PD. Dysfunction of interlimb coordination might also explain why patients with PD often find swimming with just their legs easier than using all four limbs simultaneously.⁷ This case indicates that therapeutic approaches that focus on improving four-limb coordination could be effective to manage gait deficits and FOG.

Conception: M.-L. Welter and J.-C. Corvol; acquisition, analysis, and interpretation of data: M.-L. Welter, J.-C. Corvol, M. Romanato, B. Lau, C. Karachi, J. Nonnekes, and B.R. Bloem; manuscript preparation, draft, review, and critique: M.-L. Welter, J.-C. Corvol, M. Romanato, B. Lau, C. Karachi, J. Nonnekes, and B.R. Bloem.

M.-L. Welter has served in advisory boards for Boston Scientific and has received grants from Medtronic, Boston Scientific, and Fondation France Parkinson outside of this work. J.-C. Corvol has served in advisory boards for Alzprotect, Bayer, Ferrer, iRegene, Prevail Therapeutic, Roche, Servier, and UCB, and has received grants from Biogen and The Michael J. Fox Foundation outside of this work. C. Karachi has served in advisory boards for Medtronic and Boston Scientific and has received grants from Boston Scientific outside of this work. J. Nonnekes received funding from ZonMW, The Michael J. Fox Foundation, Gossweiler Foundation, International Parkinson and Movement Disorders Society, European Reference Network for Rare Neurological Disease, and a consultancy fee from Cue2Walk. B.R. Bloem serves as the Co-Editor in Chief for the Journal of Parkinson's Disease; serves on the editorial board of Practical Neurology and Digital Biomarkers; has received fees from serving on the scientific advisory board for the Critical Path Institute, Gyenno Science, MedRhythms, UCB, Kyowa Kirin, and Zambon (paid to the Institute); has received fees for speaking at conferences from AbbVie, Bial, Biogen, GE Healthcare, Oruen, Roche, UCB, and Zambon (paid to the Institute); and has received research support from Biogen, Cure Parkinson's, Davis Phinney Foundation, Edmond J. Safra Foundation, Fred Foundation, Gatsby Foundation, Hersenstichting Nederland, Horizon 2020, IRLAB Therapeutics, Maag Lever Darm Stichting, The Michael J. Fox Foundation, Ministry of Agriculture, Ministry of Economic Affairs & Climate Policy, Ministry of Health, Welfare and Sport, Netherlands Organization for Scientific Research (ZonMw), Not Impossible, Parkinson Vereniging, Parkinson's Foundation, Parkinson's UK, Stichting Alkemade-Keuls, Stichting Parkinson NL, Stichting Woelse Waard, Health Holland/Topsector Life Sciences and Health, UCB, Verily Life Sciences, Roche, and Zambon.