Waarom blokkeren sommige Parkinson patiënten tijdens het lopen?

Background:
Freezing of gait (FOG) is common in Parkinson’s disease (PD). The underlying mechanism of FOG is however unknown. It was hypothesized that PD patients with FOG are unable to keep different tasks (motor or cognitive) on-line and can not flexibly shift between response sets. Whether shifting impairments underlie the mechanism of motor freezing has never been investigated.
Impairments in set-shifting have been associated with a reduced activation in the fronto-striatal circuits in PD. Thus, if impairments in shifting between response sets underlie motor freezing there may be a close inter-relationship between the fronto-striatal circuitry disturbances underlying both shifting impairments and motor freezing.

Treatment options are insufficient to relieve FOG in PD. Recently, Methylphenidate (MPH) has been introduced as a treatment option. No randomized, clinical controlled trial has been performed to investigate the efficacy of MPH for FOG in PD.
Furthermore, there is no understanding of the neural mechanism by which MPH ameliorates cognition and gait in PD. Studies suggest that the neural effects of MPH vary according to task requirements. In healthy controls MPH modulated the striatal activity when response shifting was required.



Objectives:
To investigate whether impairments of shifting between response sets underlie motor freezing in PD and to investigate the efficacy and the neural mechanism by which MPH improves gait and cognition in PD patients with FOG.

Parkinson's disease patients with Freezing of Gait show impairments shifting between response sets and a reduced activation in brain areas involved in shifting between response sets, relative to Parkinson's disease patients without Freezing of Gait.



Methylphenidate improves gait and the ability to shift between response sets and will lead to a relative increase of activation in the brain areas involved in shifting between response sets in Parkinson's disease patients with Freezing of Gait, compared to a placebo.

Pilot study: 6 months;

Data collection: 1.5 years;

Data analysis and publication: 1 year.

1. Parkinson's disease patients with Freezing of Gait, Parkinson's disease patients without Freezing of Gait and healthy controls will be assessed with a set-shifting task in a behavioral setting and during functional Magnetic Resonance Imaging with simultaneous Electromyography (fMRI-EMG). In addition, gait characteristics will be assessed;

2. Parkinson's disease patients with Freezing of Gait will be treated with Methylphenidate or placebo for three months with a dosage of 1 mg/kg/day. Methylphenidate or placebo will be randomly assigned (50/50);

3. After three months the assessment of gait characteristics and set-shifting in a behavioral setting and during fMRI-EMG will be repeated in Parkinson's disease patients with Freezing of Gait.