By Heather Baer, M.D., University of Colorado Denver
Deep brain stimulation surgery (DBS) is a powerful tool in the treatment of both Parkinson disease (PD) and essential tremor (ET). DBS has been shown to be very helpful for the management of tremor (in ET) and for tremor, rigidity and slowness of movement (in PD). However, it is more challenging to interpret the literature with regard to the effect of DBS on gait (overground walking) and balance (the ability to maintain control over one’s center of gravity) for persons living with ET or PD. A main reason for this is that DBS has differential effects upon various aspects of gait and balance control. Other factors influencing interpretation of studies include variations in study design, differences in degree of pre-surgical gait and balance impairments between study participants, effects of different aspects and degrees of cognitive impairment, effects of medications, choice of surgical targets, lead placement and programming techniques.
EFFECTS OF ET AND PD ON GAIT AND BALANCE:
In order to understand the effects of DBS on gait and balance it is important to first appreciate the complexity of normal functioning, as well as the effects that ET and PD have on these activities. Walking is an activity that requires adequate strength, vision, proprioception (sensation of where the body is in space) and motor planning. Similarly, balance control depends upon the proper functioning of the inner ear (vestibular apparatus), vision, proprioception, cerebellar function, cognitive function and motor strength.
Proper functioning of multiple neurotransmitter systems (brain chemicals) is part of this equation.
Unfortunately, balance generally declines with aging, even in the absence of a neurodegenerative disorder. In addition, PD and ET are associated with deterioration of gait and balance over time. ET has been associated with changes in gait and balance which might only be recognized through specific testing in the clinic or in an instrumented gait laboratory. ET related gait and balance problems include impaired tandem gait (as in the road side sobriety testing), wide based gait (legs spread apart to increase the base of support), reduced gait speed, an increased number of near falls (stumbles) and other subtle abnormalities. These gait and balance impairments are thought to be related to dysfunction in cerebellar pathways. Interestingly, the severity of the tremor does not clearly predict the severity of the balance problem.
PD is well known to adversely effect gait and balance, although these problems may vary across a given day depending upon medication state, fatigue and other factors. Gait deviations seen in PD include short steps, poor foot clearance, slowness, decreased arm swing, asymmetric steps, freezing of gait and start hesitations (trouble with initiation of gait).
PD-related balance impairment is often expressed by the term “postural instability”, which is a problem in maintaining control of one’s center of gravity in response to an external perturbation. In addition, it has become increasingly clear that cognitive or behavioral impairments (e,g, confusion and impulsivity) can adversely effects motor planning and gait safety.
EFFECT OF MEDICATIONS/NEUROTRANSMITTER SYSTEMS:
Medications used in the treatment of ET and PD may have variable effects on gait and balance. This is due in part to medication side effects and to the effect of medications on various neurotransmitter systems that impact balance and gait control. Those given for tremor in ET can cause confusion, dizziness and sedation. PD medications have a more complex effect upon gait and balance. On the positive side, dopamine replacement therapy (e.g. levodopa and dopamine agonists) can lead to improvements in stooped posture, longer and more even steps, better arm swing, less freezing and a faster gait speed. Unfortunately, PD medications can also lead to dizziness, confusion, impulsivity and dyskinesias, all of which can undermine gait and balance.
In general, it is thought that the effect of dopamine replacement therapy on PD-related symptoms is predictive of the response of those symptoms to DBS. For the most part, this seems to be true, although there appear to be exceptions. For example, it is well established that individuals with PD or ET who have medication resistant tremors are still extremely likely to benefit from DBS. The correlation between responsiveness to medications and response of PD-related gait and balance problems to DBS is a little harder to describe. For example, freezing of gait that occurs predominantly in the OFF medication state, is likely to get better with DBS, but may continue to be a problem after DBS (although possibly to a lesser extent).
DBS FOR ET:
Thalamic (VIM) DBS for ET is associated with mixed effects upon gait and balance. Some researchers have found improvements in overground walking and tandem gait. However, there are more reports of deterioration in gait and balance, particularly when DBS leads are placed on both sides of the brain (bilateral DBS). Predictors for worsened gait and balance after VIM DBS include older age and the severity of pre-DBS balance problems.
DBS FOR PD:
Positive effects of subthalamic nucleus (STN) DBS on gait and balance have included increased gait speed, improved arm and leg swing, improved stride lengths, decreased stooped posture (which puts the center of gravity too far forward) and improved preparations for step initiation. Unfortunately, post-DBS worsening has been reported to occur soon enough after surgery to suggest that it is due to DBS and not just due to further disease progression. Post-surgical problems have included increased falls, increased freezing of gait and worsened gait mechanics. There are also studies that show a negative effect on preparation to take a step (gait initiation). Explanations for worsening after STN DBS have included the severity of pre-DBS balance impairments, problems with electrode placement, stimulation parameters, impulsivity, cognitive worsening and lowering of dopaminergic drugs. In addition, it is thought that non-dopaminergic systems (those not amenable to DBS at the current targets that are used) play an important role in control of gait and balance.
Mixed results have also been reported in studies of DBS targeting the globus pallidus internus (GPi). Positive effects have included increased gait velocity, improvements in preparatory postural adjustments for gait initiation and improved responses to small balance perturbations. Conversely, other authors have reported declines in aspects of gait initiation and no improvements in response to external perturbations. It should be noted, however, that there is much less information available about the effects of GPi stimulation on gait and balance.
When GPI and STN stimulation are directly compared for outcomes on gait and balance, GPi stimulation has seemed to be better in terms of balance confidence (which has been shown to reflect the risk of falling), rate of severe falls (which were fewer after GPi), automatic postural responses, step velocity and response to external perturbations. Other studies have found no difference between STN and GPi for balance and gait outcomes.
Movement disorders specialists are now well aware that the current applications of DBS for PD do not adequately address gait and balance problems. Current efforts to remedy this situation include trials aimed at combining the use of specific medications and DBS, studies of different brain targets for DBS (particularly the pedunculopontine nucleus), and the use of new imaging techniques to try to learn how to individualize DBS to be tailored to the particular brain anatomy of each individual person.
Gait and balance control is complex. Normal aging, ET and PD can all contribute to impairments in both gait and balance. Medications used in the treatment of ET and PD also can impact these activities. Understanding of the effect of DBS on gait and balance control in ET and PD requires an understanding of the underlying factors that control normal functioning, the impact of the neurodegenerative disorders on these activities and an appreciation for the complexity of study designs currently used to help elucidate these effects. Further research is needed to help differentiate the effects of multiple variables (including surgical targets, programming techniques, medication choices and patient-related factors) in order to arrive at better predictive models that can be used to help counsel patients with regard to the likely outcome of DBS surgery upon gait and balance.