DBS, but Not Medications, Seen to Ease Gait Changes Tied to Fall Risk
Gait variability, or changes in stride while walking that associate with a greater risk of falls in people with Parkinson’s disease, significantly eased with patients’ use of deep brain stimulation (DBS) but not dopamine-increasing medications, a study showed.
“We found that … DBS reduced step-to-step variability in a range of lower limb gait parameters in [Parkinson’s], whereas dopaminergic medication had no significant effect,” the researchers wrote.
These findings suggest that gait variability may not be driven by dopamine-dependent mechanisms, with the scientists proposing that a specific group of nerve cells, which DBS can modulate, are involved instead.
Parkinson’s is characterized by the progressive loss of motor abilities and other non-motor symptoms arising from the degeneration of dopamine-producing nerve cells in the brain. Levodopa, a dopamine precursor that is found naturally in the body, and other dopamine-enhancing medications are often used to treat patients.
Deep brain stimulation (DBS) is sometimes also used alone or in combination with dopaminergic medications. DBS involves the delivery of electrical pulses to the brain’s subthalamic nucleus, which has been implicated in Parkinson’s. These pulses are thought to disrupt abnormal nerve signaling and restore more normal nerve firing.
The greater the gait variability, or stride-by-stride fluctuations, in people Parkinson’s, the greater is their likelihood of postural instability and falls. While the effects of levodopa or DBS on other gait features, like speed, are well-established, their effects on gait variability remain unknown.
Researchers, largely in the U.K., evaluated several gait measures in 26 Parkinson’s patients while both on and off treatment with dopaminergic medications or DBS. Participants were recruited through the Oxford Quantification in Parkinsonism study (NCT04139551) at the John Radcliffe Hospital in Oxford.
Among those with Parkinson’s, 15 used dopaminergic medications only and 11 had underwent DBS. Of note, 10 of the 11 people using DBS were also on dopaminergic medications, which remained in use throughout the study.
All participants wore a device called an inertial measurements unit (IMU) — with synchronized sensors positioned on both wrists and feet, the trunk, and lumbar area of the lower spine — and performed a walking test during on- and off-therapy phases. For patients using DBS, this meant they performed the test either when the stimulator was turned on or 30 minutes after it was turned off. For those on medication only, the test was performed one hour after taking medication and again at least 12 hours after a last dose.
The study also included 42 age-matched healthy volunteers, who were used to calculate age-matched normal ranges for the gait analysis.
Patients’ mean age in the DBS group was 58.9 years, and their average disease duration was 10.7 years. Among the dopaminergic-medication group, the mean age was 64.9 and the disease duration was 8.8 years.
Participants were asked to walk for two minutes along an uncarpeted 15-meter (almost 50-foot) corridor.
Results generally showed that DBS use, but not dopaminergic medications, led to a lesser gait variability in a number of lower limb gait measures, including toe-out angle and single-limb support.
“We found that STN [subthalamic nucleus] DBS reduced step-to-step variability in a range of lower limb gait parameters in PD, whereas dopaminergic medication had no significant effect,” the researchers wrote.
Dopaminergic medication did, however, lead to significant improvements in other lower and upper limb features, including a more normal stride length and foot strike angle — the angle at which the foot hits the ground during a step. Benefits were also seen in a better range of motion of the arms and trunk.
DBS also led to significant improvements in foot strike angle.
The findings overall suggest that while dopaminergic medication may improve some features of gait, “STN stimulation, but not dopaminergic medication, modulates the [nerve] circuits that control gait rhythm,” the researchers wrote.
It has been suggested that gait rhythm disturbances may not be caused by dopamine dysfunction, but instead by the degeneration of cells that produce a neurochemical called acetylcholine in the brain’s pedunculopontine nucleus (PPN). The subthalamic nucleus communicates with the PPN, and thus DBS could indirectly target these cells, the researchers suggested.
“Because the proposed mechanism is cholinergic [involving acetylcholine], this is something that dopaminergic medication should not do,” they added, which could explain the observed lack of effect of medication on gait variability.
While DBS, by lowering gait variability overall, may be helpful in preventing falls in Parkinson’s patients, it cannot be determined that gait variability alone causes such falls, the researchers pointed out. Further assessments are needed to “know if the difference in the effect of DBS and medication on gait variability is large enough to be clinically important.”
Researchers also noted that “the lack of effect of medication” on gait variability seen in this study “is at odds with previous literature,” which they suggested could be due to differences in “the way in which variability is being measured.”
Results in tests of patients under DBS, however, “back the conclusion of an earlier work,” the team added.