Future Therapeutic Strategies for Freezing of Gait in Parkinson’s Disease

Abstract

Freezing of gait (FOG) is a common and challenging clinical symptom in Parkinson’s disease. In this review, we summarise the recent insights into freezing of gait and highlight the strategies that should be considered to improve future treatment. There is a need to develop individualised and on-demand therapies, through improved detection and wearable technologies. Whilst there already exist a number of pharmacological (e.g., dopaminergic and beyond dopamine), non-pharmacological (physiotherapy and cueing, cognitive training, and non-invasive brain stimulation) and surgical approaches to freezing (i.e., dual-site deep brain stimulation, closed-loop programming), an integrated collaborative approach to future research in this complex area will be necessary to systematically investigate new therapeutic avenues. A review of the literature suggests standardising how gait freezing is measured, enriching patient cohorts for preventative studies, and harnessing the power of existing data, could help lead to more effective treatments for freezing of gait and offer relief to many patients.

Genetic architecture of Parkinson’s disease subtypes – Review of the literature

“…In patients with the GD subtype, an improvement on levodopa alone is often not satisfactory, and additional medications are given to improve gait and balance. In clinical settings, amantadine and rivastigmine are most often used ( Cui and Lewis, 2021 ). Patients with advanced PD, motor fluctuations, and levodopa-induced dyskinesia are good candidates for DBS and infusional therapies.…”

Botulinum Toxin Treatment of Motor Disorders in Parkinson Disease—A Systematic Review

“…3- Generic exercises including physical therapy for general physical and mental benefits. Furthermore, Cui and Lewis [ 45 ] listed other therapeutic courses of action for treatment of FOG. FOG can be reduced successfully by deep brain stimulation (DBS) of the subthalamic nucleus [ 46 , 47 , 48 ].…”

How resistant are levodopa‐resistant axial symptoms? Response of freezing, posture, and voice to increasing levodopa intestinal infusion rates in Parkinson disease

“…Despite these clinically derived concepts of FoG pathophysiology, studies aiming to systematically evaluate FoG response to progressively increasing levodopa doses are lacking [9,10]. Similarly, other axial symptoms like postural abnormalities and speech impairment have an uncertain response to levodopa that current literature does not help to clarify [4,5,9,11,12].…”

“…According to the response to levodopa, four different FoG conditions have been clinically described: “OFF‐FoG,” relieved by dopaminergic medications; “pseudo‐ON‐FoG,” appearing during a seemingly optimal ON state but improved by higher dopaminergic supply; “unresponsive‐FoG,” present in both OFF and ON states, independently from changes in dopaminergic medication; and “ON‐FoG,” a rare type of FoG induced by dopaminergic medications [ 7 , 8 ]. Despite these clinically derived concepts of FoG pathophysiology, studies aiming to systematically evaluate FoG response to progressively increasing levodopa doses are lacking [ 9 , 10 ]. Similarly, other axial symptoms like postural abnormalities and speech impairment have an uncertain response to levodopa that current literature does not help to clarify [ 4 , 5 , 9 , 11 , 12 ].…”