Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease

Abstract

Background: Therapeutic management of gait disorders in patients with advanced Parkinson's disease (PD) can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related parkinsonian signs than for gait disorders. Gait disorders could also be partly related to norepinephrine system impairment, and the pharmacological modulation of both dopamine and norepinephrine pathways could potentially improve the symptomatology. Aim: To assess the clinical value of chronic, high doses of methylphenidate (MPD) in patients with PD having gait disorders, despite their use of optimal dopaminergic doses and STN stimulation parameters. Methods: Efficacy was blindly assessed on video for 17 patients in the absence of L-dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using a Stand-Walk-Sit (SWS) Test, the Tinetti Scale, the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and the Dyskinesia Rating Scale. Results: An improvement was observed in the number of steps and time in the SWS Test, the number of freezing episodes, the Tinetti Scale score and the UPDRS part III score in the absence of L-dopa after 3 months of taking MPD. The L-dopa-induced improvement in these various scores was also stronger after the 3-month course of MPD than before. The Epworth Sleepiness Scale score fell dramatically in all patients. No significant induction of adverse effects was found. Interpretation: Chronic, high doses of MPD improved gait and motor symptoms in the absence of L-dopa and increased the intensity of response of these symptoms to L-dopa in a population with advanced PD.

Association of exceptional parental longevity and physical function in aging

“…Based on footfalls recorded on the walkway, the software automatically computes gait parameters such as gait speed (cm/s). The GAITRite system is widely used in clinical and research settings, and excellent reliability has been reported in our and other centers (Devos et al 2007;Verghese et al 2007a;Verghese et al 2007b). Research assistants also measured time in seconds to climb up three steps, a quick and valid clinical measure for assessing risk of functional decline (Oh-Park et al 2012).…”

Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease

“…Some small, open-label pilot studies suggested that a low dose methylphenidate may improve gait, and especially freezing, in patients with severe PD, without the need for exogenous levodopa. [99][100][101] This result was not confirmed by other trials 102,103 A recent randomized, placebo-controlled, double-blind 6-month trial showed that methylphenidate in doses up to 80 mg per day did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life. 104 Atomoxetine is a selective inhibitor of norepinephrine uptake and a small study failed to find significant benefits in gait and balance scores in PD.…”

Novel therapeutic strategies in Parkinson’s disease

“…The effects of MPH on motor deficits are somewhat controversial. Some small, open, pilot studies demonstrated that a low dose may improve gait, and especially freezing, in patients with severe PD, without the need for exogenous levodopa [33][34][35]. However, this was not confirmed by other trials [36,37], including one set up in 2007.…”