This page contains a Flash digital edition of a book.
Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease


this review reported results six months after surgery, but there were some studies with follow-up of up to 12 months. Overall, PIGD symptoms significantly improved with both STN and GPi stimulation in both the medication ‘off’ state and ‘on’ state, but more so in the medication ‘off’ state. Both STN and GPi stimulation improved timed tests of PIGD as well as gait and balance performance on quantitative gait analysis and posturography.


These results seem to contradict the results of a recent blinded controlled trial of DBS in PD,110


which reported six-month outcomes


of 255 patients randomized to DBS or best medical therapy. While PIGD symptoms were not specifically examined and reported, the motor portion of the Unified Parkinson’s Disease Rating Scale (UPDRS) improved significantly and patients had more ‘on’ time with DBS. Despite this, subjects in the DBS arm of this trial had more falls and gait disturbances in the first three months after receiving surgery than subjects in the best medical therapy group. At six months, there were no differences in the percentage of subjects experiencing gait disturbance between the two groups, but falls remained more prominent in the DBS group. In a separate article reporting 24-month outcomes of these subjects after randomization to STN or GPi stimulation,111


the number of patients with


falls or gait disturbance at 24 months did not differ significantly between the two different targets.


It is unclear why PIGD scores improve with DBS yet patients undergoing DBS seem to have more falls, at least initially after DBS surgery. The improvement in PIGD scores could simply result from improvement in bradykinesia and rigidity which previously affected gait and balance. Such improved motor function could cause patients to engage in activities that they previously avoided, resulting in more falls. It is also well known that increasing stimulation can transiently worsen dyskinesia, especially with STN stimulation.112


Transient increased dyskinesias may


also impact gait and contribute to falls in the short term. There are many other contributors to gait and posture other than bradykinesia, rigidity, and dyskinesia. Such systems, such as the complex network responsible for postural control described earlier, could be directly affected by DBS as well.


Deep Brain Stimulation for Parkinson’s Disease— Long-term Studies on Gait and Balance


A common theme in long-term studies of DBS in PD is the sustained control of cardinal symptoms such as bradykinesia, tremor, and rigidity.112–116


An equally common finding in these long-term studies, however, is worsening gait function. One recent study, for example, reported 10-year outcomes of bilateral STN DBS in PD.117


Although


improvements in tremor and bradykinesia were sustained, axial motor scores showed progressive deterioration over time (–53.6 % at five years and –101.8 % at 10 years). Posture also significantly deteriorated over time (–80 % both at five and 10 years). This phenomenon seems to occur with both STN and GPi stimulation, and in long-term studies has been attributed to the progression of dopamine-resistant symptoms. A relevant question, however, is whether DBS site placement has differential long-term effects on gait function. Direct comparisons are difficult because most centers typically implant primarily in one site, with more centers choosing the STN. A recently published meta-regression analysis of long-term studies of bilateral DBS addresses


US NEUROLOGY 0 2468 10 -0.5


Figure 4: Change in Axial Signs Over Time in Long-term Studies of Subthalamic Nucleus Deep Brain Stimulation


1.5


1


0.5


-1


Schupbach et al., 2005 Wider et al., 2008


Years


Piboolnurak et al., 2007 Castrioto et al., 2011


Studies reporting axial motor scores with at least five years of follow-up were included in this figure. The graph shows the standardized difference between axial motor scores recorded at various time-points after surgery in the medication ‘on’ and stimulation ‘on’ state. The standardized change score was the difference between the axial motor score at the assessment time after surgery and the baseline score, divided by the average standard deviation of each score. A change score <0 indicates improvement, while a change score >0 indicates worsening.


potential differences in progression of PIGD features in patients receiving STN versus GPi DBS.118


There were sustained improvements in tremor,


bradykinesia, and rigidity in both STN and GPi DBS with minimal deterioration over time. Progression of balance and gait deficits, however, apparently varied with DBS site selection. In the ‘on’ medication state, balance and gait initially improved with DBS but by two years were worse than the pre-operative ‘on’ medication state in the STN group, whereas there was no deterioration in postural stability and gait in the GPi group.


These results suggest that the long-term progression of PIGD features may be different with GPi stimulation than with STN stimulation and that GPi is a better target for patients with significant balance and gait problems. The reasons for this discrepancy are not clear, but medications are typically reduced more with STN DBS compared with GPi DBS.111


It is


possible that sustained higher levels of dopaminergic medications over time in GPi patients lead to less progression of PIGD symptoms. It may be that there is adaptation to commonly used stimulation settings over time, and that patients receiving STN DBS experience such adaptation over time. A recent study on the 10-year outcome of bilateral STN DBS in PD reported that, although improvements in tremor and bradykinesia were sustained, axial motor scores showed the most progressive deterioration over time (–53.6 % at five years and –101.8 % at 10 years).117


Posture also


deteriorated significantly over time. These findings suggest a lack of neuroprotective effects of DBS on PD progression (see Figure 4).


Another group examined whether modifying DBS frequency in patients with STN DBS could improve gait and freezing episodes developing several years after surgery.119


The rationale for this intervention was the 105


Worsening – improvement in axial signs


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108