- Email: [email protected]
Alternating deep brain stimulation frequencies in Parkinson's disease
Journal of the Neurological Sciences 371 (2016) 32–33
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Alternating deep brain stimulation frequencies in Parkinson's disease Keywords: Deep brain stimulation Low frequency stimulation Parkinson's disease
Dear Editor: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy to improve the motor symptoms of Parkinson's disease (PD). Most patients with PD are treated with current frequencies at or above 100 Hz; however, there is evidence that stimulation frequencies below 100 Hz can provide benefit in some patients with PD whose symptoms are unresponsive to high frequency stimulation [1, 2]. However, the benefit of STN stimulation at frequencies below 100 Hz is not always sustained, with some reports showing a wearing-off effect [3,4]. Here we report a patient with PD showing immediate benefit in her motor symptoms using 50 and 80 Hz stimulation frequencies, but who suffered rapid wearing-off using any of these frequencies, requiring alternating between them, in order to obtain a sustained benefit of the DBS. The patient was videotaped in the levodopa “off” state, and DBS “on” at 130, 50 and 80 Hz unaware of the stimulation frequency. Written informed consent was provided by the patient to be presented in a scientific journal. (See Table 1.)
on the left hemisphere provided the greatest benefit. Initial settings were as it follows: frequency at 130 Hz, pulse width of 60 μs and progressively higher voltage. The patient had mild benefit in her rigidity and bradykinesia but no improvement in her gait with persistent left leg dragging, “off” dystonia and diphasic dyskinesia despite multiple voltage adjustments (Video 1); for this reason, we tried lower frequencies, in a 10 Hz steps from 120 to 20 Hz, observing the greatest improvement in her gait, “off” dystonia and diphasic dyskinesia with 50 Hz (Video 2) (table) without compromising appendicular rigidity and bradykinesia. Less benefit was observed with 80 Hz, without improvement with other frequencies. Interestingly, the symptomatic benefit at 50 Hz wore off almost completely in about 72 h; this phenomenon was corroborated three times in the medication “off” state. However, the benefit in her gait, “off” dystonia and diphasic dyskinesia was regained after switching from 50 to 80 Hz (Video 3); but the benefit at 80 Hz also wore off consistently in less than 24 h. For this reason, we alternated frequencies between 50 and 80 Hz, the latter was provided every 40 h for 8 h overnight, without side effects or trade-off compared to 130 Hz stimulation; with this strategy, we were able to maintain a prolonged daytime benefit of the stimulation within the last eleven months avoiding a wearing-off and loss of the antiparkinsonian effect. The total electrical energy delivered (TEED) was not adjusted increasing voltage as the patient complained of gait deterioration and poor equilibrium with stimulation currents above 2.8 V. Current pharmacological treatment includes levodopa/carbidopa/entacapone 150/37.5/200 mg three times a day and amantadine 100 mg twice a day, these medications were used between assessments.
2. Discussion 1. Case presentation This is a 59-year-old, right-handed woman, who came for evaluation of a nine-year history of PD manifested chiefly by upper limb tremor, generalized moderate rigidity, bradykinesia, slow gait, with left leg dragging. The patient received treatment with levodopa up to 200 mg three times a day, amantadine 100 mg twice a day and rotigotine 4–8 mg/day, but despite dose adjustments, she developed motor fluctuations with left-sided “off” dystonia, bilateral peak-dose and diphasic dyskinesia, besides of poor tolerance to levodopa due to gastric upset and nausea. A Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) of 48 in the medication “off” state and of 17 in the medication “on” state was recorded preoperatively. She underwent bilateral STN electrode implantation on May 2015 without complications. Correct placement of the electrodes into the STN was supported by effective intraoperative macrostimulation, microelectrode recordings signaling STN activity and post-operative T2-weighted MRI. She had a microlesion effect with some benefit in her rigidity and bradykinesia within the first 3 weeks following surgery. Baseline DBS programming was carried out with bilateral bipolar stimulation, electrodes model 3389 (Medtronic Corporation; Fridley, MN) contacts 2 (−), 3 (+) on the right hemisphere and 9 (−), 10 (+)
http://dx.doi.org/10.1016/j.jns.2016.10.013 0022-510X/© 2016 Published by Elsevier B.V.
We present a case with robust improvement in her parkinsonian gait, “off” dystonia and diphasic dyskinesia with 50 Hz stimulation; this observation has been previously reported by other authors using 60 and 80 Hz [1,2,5]. However, the main finding in this case was the rapid wearing-off effect of such low frequency, with the benefit completely disappearing within 72 h; for this reason, we decided to cycle the stimulation frequencies between 50 Hz and 80 Hz, maintaining the improvement provided by the DBS in the levodopa “on” and “off” state. The time for cycling the stimulation frequencies was chosen to avoid a wearing-off effect, and the 80 Hz frequency which provided less benefit in her gait was used overnight instead of turning the DBS off, allowing normal motor behavior if the patient was active during the night. A study in which stimulation frequencies were customized to provide benefit within the oscillatory gamma activity (30–100 Hz) into the STN showed improvement of parkinsonian symptoms [6]. However, it is unclear why in some cases; stimulation frequencies below 100 Hz improve mainly axial symptoms such as gait and swallowing [2]. It has been hypothesized that reciprocal connections between the STN and the pedunculopontine nucleus may have a role on this effect [7,8]. It is unclear why our patient had a wearing-off effect of the stimulation
Postoperative scores were average from 3 evaluations. Composite axial subscore was derived from items 3.9–3.13 (arising from chair, posture, gait and postural stability. Scores were obtained 30 min following changes in settings. a Using 250 mg of levodopa. b Postoperative scores carried out 5 weeks following electrode implantation. c Using 150 mg of levodopa.
0 0 4 12 0 5 0 21 0 0 4 11 0 4 0 19 0 0 2 11 0 3 0 16 0 0 6 9 1 1 0 17 Speech (item 3.1) Facial expression (item 3.2) Rigidity (item 3.3) Bradykinesia (items 3.4–3.8) Tremor (items: 3.15–3.18) Axial subscore (items 3.9–3.13) Global spontaneity of movements (item 3.14) Total score
0 2 11 20 3 10 2 48
0 1 10 19 2 9 1 42
0 0 2 12 0 4 0 18
0 1 10 19 2 10 2 44
Postoperative: med off/DBS “on” (80 Hz) Postoperative: med on/DBS “on” (50 Hz)c Postoperative: med off/DBS “on” (130 Hz)b Preoperative medication “on”a Preoperative medication “off”
Table 1 Summary of the MDS-UPDRS motor score in different “on” and “off” conditions.
Postoperative: med off/DBS “on” (50 Hz)
Postoperative: med off/ DBS “on” (50 Hz) “Wearing-off”
Postoperative: med on/DBS “on” (80 Hz)3
Letter to the Editor
33
suggesting a switch from a prokinetic oscillatory activity (i.e. gamma) to an antikinetic one (i.e. beta) in the basal ganglia [7]; and what time it takes a change in the stimulation frequency to reset the system, topics that requires further research. There is also a question whether TEED should be adjusted in patients treated with low frequency [7], although this was limited in our patient due to gait worsening. In conclusion, we show a strategy to improve gait, “off” dystonia and diphasic dyskinesia in a patient suffering PD with benefit but rapid wearing-off effect using relative low stimulation frequencies. We suggest trying individualized low frequencies in patients unresponsive to standard stimulation frequencies above 100 Hz. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2016.10.013. Financial disclosure/conflict of interest concerning the research related to the manuscript None for all authors. Acknowledgment None. References [1] C. Moreau, L. Defebvre, A. Destée, S. Bleuse, F. Clement, J.L. Blatt, et al., STN-DBS frequency effects on freezing of gait in advanced Parkinson disease, Neurology 71 (2008) 80–84. [2] T. Xie, J. Vigil, E. MacCracken, A. Gasparaitis, J. Young, W. Kang, et al., Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD, Neurology 84 (2015) 415–420. [3] V. Ricchi, M. Zibetti, S. Angrisano, A. Merola, N. Arduino, C.A. Artusi, et al., Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: a 15 months follow-up study, Brain Stimul. 5 (2012) 388–392. [4] C. Sidiropoulos, R. Walsh, C. Meaney, Y.Y. Poon, M. Fallis, E. Moro, Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease, J. Neurol. 260 (2013) 2306–2311. [5] A. Merola, M. Zibetti, C.A. Artusi, L. Rizzi, S. Angrisano, M. Lanotte, et al., 80 Hz versus 130 Hz subthalamic nucleus deep brain stimulation: effects on involuntary movements, Parkinsonism Relat. Disord. 19 (2013) 453–456. [6] E.W. Tsang, C. Hamani, E. Moro, F. Mazzella, U. Saha, A.M. Lozano, et al., Subthalamic deep brain stimulation at individualized frequencies for Parkinson disease, Neurology 78 (2012) 1930–1938. [7] J.F. Baizabal-Carvallo, M. Alonso-Juarez, Low-frequency deep brain stimulation for movement disorders, Parkinsonism Relat. Disord. 10 (2016) 14–22. [8] M.J. Birdno, W.M. Grill, Mechanisms of deep brain stimulation in movement disorders as revealed by changes in stimulus frequency, Neurotherapeutics 5 (2008) 14–25.
José Fidel Baizabal-Carvallo, M.D., M.Sc. Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA Corresponding author at: Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, 7200 Cambridge, Suite 9A, MS: BCM 609, Houston, TX 77030-4202, USA. E-mail address: [email protected]. Marlene Alonso-Juarez, M.D. National Polytechnic Institute, Mexico City, Mexico 5 June 2016 Available online 11 October 2016
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Alternating deep brain stimulation frequencies in Parkinson's disease Keywords: Deep brain stimulation Low frequency stimulation Parkinson's disease
Dear Editor: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy to improve the motor symptoms of Parkinson's disease (PD). Most patients with PD are treated with current frequencies at or above 100 Hz; however, there is evidence that stimulation frequencies below 100 Hz can provide benefit in some patients with PD whose symptoms are unresponsive to high frequency stimulation [1, 2]. However, the benefit of STN stimulation at frequencies below 100 Hz is not always sustained, with some reports showing a wearing-off effect [3,4]. Here we report a patient with PD showing immediate benefit in her motor symptoms using 50 and 80 Hz stimulation frequencies, but who suffered rapid wearing-off using any of these frequencies, requiring alternating between them, in order to obtain a sustained benefit of the DBS. The patient was videotaped in the levodopa “off” state, and DBS “on” at 130, 50 and 80 Hz unaware of the stimulation frequency. Written informed consent was provided by the patient to be presented in a scientific journal. (See Table 1.)
on the left hemisphere provided the greatest benefit. Initial settings were as it follows: frequency at 130 Hz, pulse width of 60 μs and progressively higher voltage. The patient had mild benefit in her rigidity and bradykinesia but no improvement in her gait with persistent left leg dragging, “off” dystonia and diphasic dyskinesia despite multiple voltage adjustments (Video 1); for this reason, we tried lower frequencies, in a 10 Hz steps from 120 to 20 Hz, observing the greatest improvement in her gait, “off” dystonia and diphasic dyskinesia with 50 Hz (Video 2) (table) without compromising appendicular rigidity and bradykinesia. Less benefit was observed with 80 Hz, without improvement with other frequencies. Interestingly, the symptomatic benefit at 50 Hz wore off almost completely in about 72 h; this phenomenon was corroborated three times in the medication “off” state. However, the benefit in her gait, “off” dystonia and diphasic dyskinesia was regained after switching from 50 to 80 Hz (Video 3); but the benefit at 80 Hz also wore off consistently in less than 24 h. For this reason, we alternated frequencies between 50 and 80 Hz, the latter was provided every 40 h for 8 h overnight, without side effects or trade-off compared to 130 Hz stimulation; with this strategy, we were able to maintain a prolonged daytime benefit of the stimulation within the last eleven months avoiding a wearing-off and loss of the antiparkinsonian effect. The total electrical energy delivered (TEED) was not adjusted increasing voltage as the patient complained of gait deterioration and poor equilibrium with stimulation currents above 2.8 V. Current pharmacological treatment includes levodopa/carbidopa/entacapone 150/37.5/200 mg three times a day and amantadine 100 mg twice a day, these medications were used between assessments.
2. Discussion 1. Case presentation This is a 59-year-old, right-handed woman, who came for evaluation of a nine-year history of PD manifested chiefly by upper limb tremor, generalized moderate rigidity, bradykinesia, slow gait, with left leg dragging. The patient received treatment with levodopa up to 200 mg three times a day, amantadine 100 mg twice a day and rotigotine 4–8 mg/day, but despite dose adjustments, she developed motor fluctuations with left-sided “off” dystonia, bilateral peak-dose and diphasic dyskinesia, besides of poor tolerance to levodopa due to gastric upset and nausea. A Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) of 48 in the medication “off” state and of 17 in the medication “on” state was recorded preoperatively. She underwent bilateral STN electrode implantation on May 2015 without complications. Correct placement of the electrodes into the STN was supported by effective intraoperative macrostimulation, microelectrode recordings signaling STN activity and post-operative T2-weighted MRI. She had a microlesion effect with some benefit in her rigidity and bradykinesia within the first 3 weeks following surgery. Baseline DBS programming was carried out with bilateral bipolar stimulation, electrodes model 3389 (Medtronic Corporation; Fridley, MN) contacts 2 (−), 3 (+) on the right hemisphere and 9 (−), 10 (+)
http://dx.doi.org/10.1016/j.jns.2016.10.013 0022-510X/© 2016 Published by Elsevier B.V.
We present a case with robust improvement in her parkinsonian gait, “off” dystonia and diphasic dyskinesia with 50 Hz stimulation; this observation has been previously reported by other authors using 60 and 80 Hz [1,2,5]. However, the main finding in this case was the rapid wearing-off effect of such low frequency, with the benefit completely disappearing within 72 h; for this reason, we decided to cycle the stimulation frequencies between 50 Hz and 80 Hz, maintaining the improvement provided by the DBS in the levodopa “on” and “off” state. The time for cycling the stimulation frequencies was chosen to avoid a wearing-off effect, and the 80 Hz frequency which provided less benefit in her gait was used overnight instead of turning the DBS off, allowing normal motor behavior if the patient was active during the night. A study in which stimulation frequencies were customized to provide benefit within the oscillatory gamma activity (30–100 Hz) into the STN showed improvement of parkinsonian symptoms [6]. However, it is unclear why in some cases; stimulation frequencies below 100 Hz improve mainly axial symptoms such as gait and swallowing [2]. It has been hypothesized that reciprocal connections between the STN and the pedunculopontine nucleus may have a role on this effect [7,8]. It is unclear why our patient had a wearing-off effect of the stimulation
Postoperative scores were average from 3 evaluations. Composite axial subscore was derived from items 3.9–3.13 (arising from chair, posture, gait and postural stability. Scores were obtained 30 min following changes in settings. a Using 250 mg of levodopa. b Postoperative scores carried out 5 weeks following electrode implantation. c Using 150 mg of levodopa.
0 0 4 12 0 5 0 21 0 0 4 11 0 4 0 19 0 0 2 11 0 3 0 16 0 0 6 9 1 1 0 17 Speech (item 3.1) Facial expression (item 3.2) Rigidity (item 3.3) Bradykinesia (items 3.4–3.8) Tremor (items: 3.15–3.18) Axial subscore (items 3.9–3.13) Global spontaneity of movements (item 3.14) Total score
0 2 11 20 3 10 2 48
0 1 10 19 2 9 1 42
0 0 2 12 0 4 0 18
0 1 10 19 2 10 2 44
Postoperative: med off/DBS “on” (80 Hz) Postoperative: med on/DBS “on” (50 Hz)c Postoperative: med off/DBS “on” (130 Hz)b Preoperative medication “on”a Preoperative medication “off”
Table 1 Summary of the MDS-UPDRS motor score in different “on” and “off” conditions.
Postoperative: med off/DBS “on” (50 Hz)
Postoperative: med off/ DBS “on” (50 Hz) “Wearing-off”
Postoperative: med on/DBS “on” (80 Hz)3
Letter to the Editor
33
suggesting a switch from a prokinetic oscillatory activity (i.e. gamma) to an antikinetic one (i.e. beta) in the basal ganglia [7]; and what time it takes a change in the stimulation frequency to reset the system, topics that requires further research. There is also a question whether TEED should be adjusted in patients treated with low frequency [7], although this was limited in our patient due to gait worsening. In conclusion, we show a strategy to improve gait, “off” dystonia and diphasic dyskinesia in a patient suffering PD with benefit but rapid wearing-off effect using relative low stimulation frequencies. We suggest trying individualized low frequencies in patients unresponsive to standard stimulation frequencies above 100 Hz. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.jns.2016.10.013. Financial disclosure/conflict of interest concerning the research related to the manuscript None for all authors. Acknowledgment None. References [1] C. Moreau, L. Defebvre, A. Destée, S. Bleuse, F. Clement, J.L. Blatt, et al., STN-DBS frequency effects on freezing of gait in advanced Parkinson disease, Neurology 71 (2008) 80–84. [2] T. Xie, J. Vigil, E. MacCracken, A. Gasparaitis, J. Young, W. Kang, et al., Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD, Neurology 84 (2015) 415–420. [3] V. Ricchi, M. Zibetti, S. Angrisano, A. Merola, N. Arduino, C.A. Artusi, et al., Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: a 15 months follow-up study, Brain Stimul. 5 (2012) 388–392. [4] C. Sidiropoulos, R. Walsh, C. Meaney, Y.Y. Poon, M. Fallis, E. Moro, Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease, J. Neurol. 260 (2013) 2306–2311. [5] A. Merola, M. Zibetti, C.A. Artusi, L. Rizzi, S. Angrisano, M. Lanotte, et al., 80 Hz versus 130 Hz subthalamic nucleus deep brain stimulation: effects on involuntary movements, Parkinsonism Relat. Disord. 19 (2013) 453–456. [6] E.W. Tsang, C. Hamani, E. Moro, F. Mazzella, U. Saha, A.M. Lozano, et al., Subthalamic deep brain stimulation at individualized frequencies for Parkinson disease, Neurology 78 (2012) 1930–1938. [7] J.F. Baizabal-Carvallo, M. Alonso-Juarez, Low-frequency deep brain stimulation for movement disorders, Parkinsonism Relat. Disord. 10 (2016) 14–22. [8] M.J. Birdno, W.M. Grill, Mechanisms of deep brain stimulation in movement disorders as revealed by changes in stimulus frequency, Neurotherapeutics 5 (2008) 14–25.
José Fidel Baizabal-Carvallo, M.D., M.Sc. Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA Corresponding author at: Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Department of Neurology, 7200 Cambridge, Suite 9A, MS: BCM 609, Houston, TX 77030-4202, USA. E-mail address: [email protected]. Marlene Alonso-Juarez, M.D. National Polytechnic Institute, Mexico City, Mexico 5 June 2016 Available online 11 October 2016