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Neurodegenerative Disease Parkinson’s Disease

finding that low-frequency stimulation of the PPN may improve gait disorders in PD. Freezing seemed to improve with high-voltage 60 Hz stimulation compared with standard or high-voltage 130 Hz stimulation. Brozova et al. found that, of the 12 patients who were switched to 60 Hz stimulation, three could not tolerate the change because of worsened parkinsonian symptoms.120

This suggests that lower-frequency stimulation

may not be the answer for everyone who has gait problems after STN DBS. More studies are clearly needed to determine the appropriate patients for low-frequency STN DBS.

Pedunculopontine Nucleus Deep Brain Stimulation for Gait and Balance Dysfunction in Parkinson’s Disease

Because of progressive decline in gait and balance functions in PD patients who have undergone DBS, there has been recent interest in other brain targets to address features not helped by STN or GPi DBS. The most promising target is the PPN. Evidence that PPN degeneration/dysfunction occurs in PD and the important role of the PPN in gait and postural stability, coupled with the fact that stimulation of the PPN in animal models increases locomotor activity,74,121,122 interest in PPN stimulation for gait dysfunction in PD.

led to

The first two case series of low-frequency PPN stimulation in patients with PD reported both significant improvement in gait and posture and improved UPDRS total motor scores.123,124 unfortunately, are not as impressive.125–127

Subsequent reports, Moro et al. reported six patients

with PD who underwent low-frequency unilateral PPN stimulation and demonstrated improvements in falls and freezing of gait at three months compared with the baseline ‘off medication’ state.126

There were, however,

no improvements in the UPDRS total motor or in gait/posture scores. Ferraye et al. reported an open-label study of bilateral PPN stimulation in six PD patients who had previously undergone STN DBS but with gait and postural problems unresponsive to STN DBS.125

A critical review of the literature by Kwakkel et al. noted that the effects of physical therapy are task- and context-specific and have limited long-term carry-over effects in PD patients’ home environments.131

Kwakkel et al. There was significant

improvement in freezing of gait and falls at one year compared with baseline, but blinded ‘on’ and ‘off’ stimulation comparisons at one year failed to demonstrate any difference in gait or posture.

Several possibilities may explain the variability in results of PPN stimulation in PD. First, the PPN is a difficult structure to pin down anatomically in humans and the PPN is difficult to visualize on traditional magnetic resonance sequences.67,128

The regions targeted in recent

studies are somewhat different and differential targeting may explain discrepant results. Another factor is the difficulty of finding a suitable stimulation site within the PPN when severe degeneration, such as in PD fallers, has already occurred.73

investigated unilateral PPN stimulation only, while other studies reported patients with both bilateral STN and PPN stimulation.124,125

to how many different targets are being stimulated. For example, Moro et al.126


The studies by Ferraye et al. and Moro et al. suggest that patients with freezing of gait and falls related to freezing may benefit more from PPN stimulation than patients with postural instability only.125,126 It is clear that further studies are needed to better characterize PPN targeting, patient selection, and efficacy of PPN stimulation and stimulation of other targets on gait and balance dysfunction in PD.

recent study reports significant improvement in axial motor scores when DBS of the PPN is combined with stimulation of the caudal zone incerta in patients with PD.129


emphasize the need for long-term treatment programs for PD patients. In this respect, exercise programs that can be maintained in the home situation would be preferred. A large body of empiric evidence suggests that exercise programs may be an effective strategy to delay or reverse functional decline for people with PD.132,133

concluded that exercise is beneficial with regard to physical functioning, health-related quality of life, strength, balance, and gait speed for people with PD, but caution that good-quality research is needed.132,133

A recent meta-analysis of the effects of exercise and motor training on balance and falls in PD conclude a significant but small benefit on balance-related performance measures.134

However, there was no

beneficial effect on falls in PD. These findings indicate that it remains unclear whether exercise and motor training alone can effectively reduce falls in PD.

There may also be differences related

Novel physical therapy and exercise interventions may also be useful. Recent controlled clinical trials show gait improvements with treadmill exercise.135,136

Alternative treatment modalities, such as tai chi,137 have

shown modest improvements in gait and balance in PD. Although evidence remains anecdotal, bicycling exercise may be of particular benefit in patients with PD and freezing of gait.37

Further research is needed to

demonstrate the efficacy and safety of cycling in more advanced PD. It is interesting to note that changes in executive functions occur after acute bouts of passive cycling in PD, suggesting a striatocortically mediated process.138

Combinations of novel pharmacotherapies and novel physical therapy and/or exercise interventions may be useful in delaying or ameliorating gait and balance problems in PD.


Physical Therapy and Exercise in the Management of Gait and Balance Problems in Parkinson’s Disease

Physical therapy management of gait disorders in people with PD has three key elements.130

The first element is teaching the person how to

move more easily and to maintain postural stability by using cognitive strategies. This is known as ‘strategy training’ and targets the primary motor control deficit in the basal ganglia, brainstem, and motor cortex. The second element of physical therapy is the management of secondary sequelae affecting the musculoskeletal and cardiorespiratory systems that occur as a result of deconditioning, reduced physical activity, advanced age, and comorbid conditions. The third element is the promotion of physical activities that assist the person in making lifelong changes in exercise and physical activity habits as well as preventing falls.

Current approaches with physical therapy interventions have significant limitations. The strategy training approach depends considerably on patient commitment and intact cognitive capacities. As described above, cognitive impairments may be an important contributor to impaired gait and balance function in PD. The PD patients most in need of rehabilitation of their gait and balance problems may be least able to participate in this therapeutic modality. This is particularly true for patients with more advanced PD, where the prevalence of cognitive impairment, including overt dementia, is high.

Recent reviews have

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