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ARTICLES: C. Moreau, L. Defebvre, A. Destée, S. Bleuse, F. Clement, J. L. Blatt, P. Krystkowiak, and D. Devos STN-DBS frequency effects on freezing of gait in advanced Parkinson disease Neurology 2008; 71: 80-84 [Abstract] [Full text] [PDF]

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STN-DBS frequency effects on freezing of gait in advanced Parkinson disease

Hana Brozova, Isabelle Barnaure, Ron L. Alterman, and Michele Tagliati   (26 June 2008)

Reply from the authors

Caroline Moreau, Luc Defebvre, Alain Destée, Séverine Bleuse, Frédérik Clement, Jean-Louis Blatt, Pierre Krystkowiak and David Devos   (26 June 2008)

STN-DBS frequency effects on freezing of gait in advanced Parkinson disease 26 June 2008
Hana Brozova, Mount Sinai School of Medicine 5 East 98th Street, Box 1139, New York, NY 10029, Isabelle Barnaure, Ron L. Alterman, and Michele Tagliati Send Correspondence to journal: Re: STN-DBS frequency effects on freezing of gait in advanced Parkinson disease hana.brozova{at}lf1.cuni.cz Hana Brozova, et al.	We read with interest the article by Moreau et al. describing a new treatment for severe freezing of gait (FOG) in advanced Parkinson’s disease (PD) by using 60 Hz STN-DBS. [1] We reported that stimulation of the STN with lower frequencies produced a positive effect on gait and speech but symptoms insufficiently improved or even worsened after several years of high frequency (HF) STN-DBS. [2] We switched 12 PD patients with persistent gait difficulties to 60Hz stimulation after a mean 4.3 years (range 2-8) of bilateral HF STN-DBS. Seven patients had FOG, six had postural instability and seven experienced falls. Three patients could not acutely tolerate the change in settings because of increased tremor (one), rigidity (one) and gait worsening (one). The remaining nine subjects (three women, six men) were followed open label. These nine subjects had a mean age of 66.8 (9.6 SD) years and a mean PD duration of 16.6 (5.0 SD) years. ON-medication UPDRS scores were collected 8-12 weeks after switching to 60 Hz and compared to ON-medication scores obtained at higher stimulation frequencies. Significant average improvements were observed for the UPDRS-II subscale (3.9 points; p<0.05), UPDRS-II sub-items relative to speech, falling and walking (p<0.05), and UPDRS-III sub- items relative to speech and gait (p<0.05). Postural instability and gait (items 27-30) worsened in two patients. An average voltage increase of 1.3 volts (range 0.7-2.5) was required bilaterally in seven patients for beneficial maintenance of other PD symptoms. The conflicting responses observed with regard to frequency suggests that lower frequency STN stimulation may not be the solution to all gait problems in advanced PD. In our limited experience, we failed to find distinguishing features between responders and non-responders. The selection of proper candidates will be a challenge to the widespread use of 60 Hz STN- DBS. There was also dramatic speech improvement in some of our patients, as well as in some described by Moreau et al. [1] Therapeutic current spreading to the pedunculo-pontine nucleus may explain the beneficial effect of lower stimulation frequencies on gait, [1] but this mechanism would not underlie speech improvement. As very low frequency STN stimulation improves verbal fluency [3], it is possible that in addition to new targets of stimulation, alternative programming strategies may be needed to optimize control of the complex symptoms of PD. References 1. Moreau C, Defebvre L, Destée A, et al. STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 2008; Epub April 16. 2. Krack P, Batir A, Van Blercom N, et al. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 2003;349:1925-1934. 3. Vojtecki L, Timmermann L, Jörgens S, et al. Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation. Arch Neurol 2006;63:1273-1276. Disclosure: The authors report no disclosures.
Reply from the authors 26 June 2008
Caroline Moreau, Department of Neurology and Movement Disorders, EA2683, IFR 114, University of Lille 2 Clinique Neurologique, Hôpital R. Salengro, CHU, F-59037 LILLE cedex FRANCE, Luc Defebvre, Alain Destée, Séverine Bleuse, Frédérik Clement, Jean-Louis Blatt, Pierre Krystkowiak and David Devos Send Correspondence to journal: Re: Reply from the authors c-moreau{at}chru-lille.fr Caroline Moreau, et al.	We thank Dr. Brozova and colleagues for their comments on our article and their findings which underline the utility of investigating modulation of STN DBS parameters in general and the stimulation frequency in particular. The idea of increasing voltage in order to obtain a better efficacy is partially true and somewhat limited. The effects of DBS remain unclear and inconsistent. [4] It is evident that the neurodegeneration and disease progression modify the various brain structures involved [5] and thus their activity. This has led to the concept of different disease phenotypes within PD. These phenotypes could be associated with different patterns of noisy basal ganglia signals that disrupt both local and remote functions. [5] In addition to the hypothetical diffusion of current to the PPN, it has been suggested that different DBS frequencies may suppress or override the various noisy signals in the basal ganglia-cortical loop (i.e. in the beta band, < 30 Hz). [6] Or, they may boost disease-impaired local activity in these structures (i.e. in the gamma band, 60-90 Hz). The clinical results confirm fundamental studies suggesting that DBS not only suppresses the abnormal pattern of basal ganglia activity but also drives activity that mimics normal gamma band patterns (60 Hz). The current challenge is to define the various frequency effects for different phenotypes and candidates. This is in progress for gait disorders but speech disturbances and cognitive functions require further investigation. Our initial results suggest that good candidates for 60Hz STN DBS may be PD patients with: long disease duration; severe gait disorders with freezing of gait; and predominant but partially dopa-responsive axial signs. However, these findings need further confirmation. Finally, to improve the benefit of 60Hz STN DBS, it may be necessary to increase the voltage at 60 Hz within a range that could vary among patients. Voltage should be assessed stepwise in each patient from 4 to 5.5V. In addition, the range could be higher than the previously reported increase of 1.3 V (range: 0.7- 2.5). With 60 Hz and a 60 µs pulse width, we observed a greater improvement in gait at 5V than at 4V. [1] References 4. Brown and Eusebio. Paradoxes of Functional Neurosurgery: clues from basal ganglia recordings. Mov Disorders 2008;23:12-20. 5. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004;318:121-134. 6. Devos D, Szurhaj W, Reyns N et al Predominance of the contralateral movement-related activity in the subthalamo-cortical loop. Clinical Neurophysiology 2006;117 :2315-2327. Disclosure: The authors report no conflicts of interest.