Medical treatment of freezing of gait

Abstract

Freezing of gait (FOG) is frequently considered as one of the dopamine-resistant motor symptoms of Parkinsonism. Recent studies have clearly demonstrated that the Off-related FOG is improved by levodopa (L-dopa) or entacapone treatment. L-dopa can decrease duration of each FOG episode as well as its frequency. On-related FOGs are not common and difficult to diagnose. Only in the most advanced stages of the disease, FOGs are resistant to treatment as many other symptoms. Off-related FOGs are likely to be improved by dopamine agonists (DAs), but this has never been looked at systematically. In contrast, DA treatment might provoke FOG, and in two pivotal studies when DAs were compared to L-dopa in early stages of Parkinson's disease, the DA-treated arms experienced more FOGs. MAO-B inhibitors (selegiline and rasagiline) can decrease FOG frequency or severity, but its clinical significance is still unknown. L-Threo-DOPS has been reported to have a symptomatic beneficial effect in patients with pure freezing syndrome, but small-scale, controlled trials in Parkinson's disease could not support those early observations. Botulinum toxin injected into the calf muscles has been suggested to have a symptomatic benefit. However, double-blind, prospective studies could not support that early observation and increased fall risk in the injected patients has put this direction of treatment on hold. The potential benefit of amantadine, antidepressive drugs, acetylcholine esterase inhibitors, and methylphenidate on FOG has been studied in small-scale studies, and there is a need for prospective studies to understand the future role of those drugs.