Targeting noradrenergic system combats gait freezing in Parkinson’s patients

By Eleanor McDermid

Methylphenidate may be a useful treatment for patients with advanced Parkinson's disease receiving subthalamic nucleus (STN) stimulation who experience gait hypokinesia and freezing, show findings from a randomized trial.

"These problems are often evident after several years of STN deep brain stimulation and are difficult to manage," say David Devos (Lille Nord de France University) and team.

After 90 days of treatment, the 33 patients assigned to take methylphenidate 1 mg/kg per day completed a median of 33 steps in the stand-walk-sit test without levadopa. The 32 patients who took placebo completed a median of 31 steps, which was a significant difference from the active treatment group. Both groups completed a median of 33 steps at baseline.

The time needed to complete the test off levadopa decreased in the methylphenidate but not the placebo group. Also, the number of gait freezing episodes during a gait trajectory test (which includes multiple freezing triggers) fell from six to four off levadopa, and from five to three on levadopa among patients in the methylphenidate group. The placebo group did not improve.

"The positive short-term risk-benefit balance we note here has yet to be assessed in the long term," the researchers caution in The Lancet Neurology.

Methylphenidate is generally used to treat attention deficit/hyperactivity disorder, and Devos et al believe it aids Parkinson's patients by combating the effects of lesions within the noradrenergic system, which develop as Parkinson's disease progresses and are not affected by levadopa.

But they add that "the effects we report apply to only a selected population of patients with Parkinson's disease receiving STN stimulation. Further work is needed to establish whether other patients without previous surgery or in less advanced disease stages might also benefit."

Adverse events occurred more often in the methylphenidate than placebo groups; nausea, vomiting, and gastritis accounted for most of the difference, occurring in 10 versus two patients. Average heart rate rose in the methylphenidate group, from 70 to 74 beats per min, but remained stable in the placebo group. Weight also remained constant in the placebo group, but decreased from an average of 79 to 76 kg in the methylphenidate group.

Methylphenidate treatment also had positive effects on the Epworth sleepiness scale, reducing daytime sleepiness without worsening sleep quality.

"This is important, because sleepiness affects up to 50% of patients and worsens with dopaminergic treatments," say Devos et al.

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