Parkinsonism and Related Disorders 21 (2015) 1005e1007
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Thalamic deep brain stimulation for orthostatic tremor: Clinical and neurophysiological correlates
Keywords: Orthostatic tremor Deep brain stimulation Microelectrode recordings
Orthostatic tremor (OT) is characterized by progressive unsteadiness during stance, due to fine-amplitude leg tremor with a 13e18 Hz frequency, leading to limited ability to stand or walk and impaired functioning. Medication is often ineffective. Bilateral deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius medialis (Vim) has been reported in only five patients so far [1e5]. A 70-years-old lady complained of progressive bilateral postural hand tremor and unsteadiness during stance and walking since 20 years. She could stand without support only for a few seconds, could not walk longer than 10 min and had difficulties in many activities including writing and cooking. Clonazepam (6 mg/day) and other benzodiazepines, gabapentin, and pramipexole were ineffective. Her medical history included Meniere's disease, vitrectomy for macula pucker, and gynecological surgeries. Neurological and surface EMG evaluations revealed a 16 Hz leg tremor, which appeared immediately after the patient stood and necessitated her sitting after about 30 s (Video 1, Fig. 1 panel A). A postural arm tremor, downbeat nystagmus, and brisk stretch reflexes were observed, though neither ataxia nor parkinsonism was. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.06.008. Her older sister had EMG-confirmed OT since the age of 67, accompanied by saccadic eye-movements, hyperreflexia and bilateral Babinski sign, with normal MRI. Stereotactic surgery was performed without sedation or medication. Based on test-stimulation and intra-operative microelectrode recordings (MER) performed at several sites, DBS electrodes (3389®; Medtronic, Minneapolis, MN) were bilaterally implanted and connected to two single-channel Soletra® pulse generators (Medtronic). Intra-operative leg EMG during isometric contraction showed burst-like activity with frequency ranging from 14 to 22 Hz. There was no relevant coherence between the leg EMG and MER of the Vim (Supplementary Fig. 1). http://dx.doi.org/10.1016/j.parkreldis.2015.06.008 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
Early postoperative imaging showed a correct electrode position (Supplementary Fig. 2). After surgery, off stimulation, there was marked symptomatic improvement which gradually decreased thereafter. Switching on stimulation produced additional benefit, both on leg and arm tremor. The patient reported a relevant prolongation of the ability to stand and walk without feeling the tremor (Video 2) EMG recordings showed markedly lower amplitude of tremor bursts, a more homogeneous frequency spectrum with shift in peak frequency to 14 Hz, and a slightly increased latency from standing to tremor onset (Fig. 1 panel D). Eight months postoperatively, the ETRS part-C score decreased to 1/16, and she had resumed her activities including professional cooking, biking, and rowing. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.06.008. One year after surgery, the patient underwent surgical replacement of non-flexible wires for flexible ones, because of persistent pain along the extension wires. Afterwards, the efficacy of stimulation on tremor decreased and did not improve with parameter adjustments. A CT scan showed an upward displacement of both electrodes (Supplementary Fig. 2) Stereotactic repositioning of both electrodes restored the therapeutic effect, which lasted an additional two years, i.e., four years following the original surgery. Over time, tremor slowly worsened and at last follow-up (5 years after surgery) stimulation, although still effective, could not produce optimal clinical improvement. Additional electrodes placement (e.g. in the Vop), which has anecdotally been reported as effective for other forms of tremor, was not considered at the time. Bilateral Vim DBS can be effective for disabling, medicationresistant OT. Electrode displacement resulted in a loss of effect in our patient, while stereotactic repositioning restored the original benefit, confirming the therapeutic effect of Vim stimulation. Nystagmus, brisk reflexes and positive family history could suggest a secondary form, although known genetic cerebellar disorders were excluded, and familial primary OT has been reported. The difficulty in walking was likely related to OT, considering that it disappeared completely after surgery with tremor suppression. A possible association with essential tremor could be considered, as reported in the literature [6]. Only five patients who underwent bilateral Vim DBS have been reported so far. In all these cases tremor severity was reduced, but long-term follow-up was not available [1e5]. During surgery, isometric contraction of the leg muscles did not induce the 15e16 Hz tremor although burst-like activity with frequency ranging from 14 to 22 Hz was seen in the tibialis anterior
1006
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1005e1007
Fig. 1. Neurophysiological findings EMG of the right tibialis anterior (TA) muscle while standing and corresponding power spectrum. A): Before surgery. EMG recordings show a 16 Hz tremor. B) Two months after surgery with stimulator off. EMG recordings show a 16 Hz tremor with slightly reduced amplitude and slightly increased latency from standing as compared to before surgery. C) Nine months after surgery with stimulator off and D) with stimulation on. With stimulation on, EMG recordings show tremor bursts with markedly reduced amplitude and increased latency as compared to before surgery. Notably the frequency spectrum is more homogeneous and hardly shows any peak around 14 Hz.
muscle (Supplementary Fig. 1), which showed no clear coherence with MER of the Vim. MER have not been documented in OT patients before; future studies might provide more insight into the relationship between thalamic oscillators and OT. The clinical benefit was reflected by markedly lower amplitude of the postoperative EMG bursts, while a disruption of the spectrum was observed, as reported in one previous patient [4]. We conclude that bilateral Vim stimulation can provide long-lasting relief of symptoms in patients with medication-resistant orthostatic tremor.
2. Manuscript: A. Writing of the first draft, B. Review and Critique, C. Final approval of the submitted version. MF Contarino: 1A, 1B, 1C, 2A, 2C. LJ Bour: 1B, 1C, 2B, 2C. PR Schuurman: 1B, 2B, 2C. E.R. Blok: 1C, 2B, 2C. V. Odekerken: 1B, 2B, 2C. P van den Munckhof: 1B, 2B, 2C. R.M.A. de Bie: 1A, 2B, 2C. AF van Rootselaar: 1A, 1B, 1C, 2B, 2C.
Conflict of interests Acknowledgements The DBS team of the AMC received unrestricted research grants from Medtronic and received financial compensation for teaching courses for the European Continue Medical Training program. M.F. Contarino: Advisory board: Medtronic, Boston Scientific. Is co-inventor on a patent application relevant to Deep Brain Stimulation. Speaking fees: Abbvie, Medtronic, Boston Scientific, ECMT. L.J. Bour: acts as independent advisor for Medtronic. Is coinventor on a patent application relevant to Deep Brain Stimulation. P.R. Schuurman: acts as independent advisor for Medtronic and Elekta. E. Blok, V. Odekerken, P. van den Munckhof, R.M.A. de Bie, and A.F. van Rootselaar have nothing to disclose. Author contributions 1. Case study: A. Conception, B. Execution, C. Analysis and interpretation of data;
The authors wish to thank Prof. Dr. J. Stam for referring the patient for surgery.
Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.parkreldis.2015.06.008. References [1] J. Guridi, M.C. Rodriguez-Oroz, J. Arbizu, M. Alegre, E. Prieto, I. Landecho, M. Manrique, J. Artieda, J.A. Obeso, Successful thalamic deep brain stimulation for orthostatic tremor, Mov. Disord. 23 (2008) 1808e1811. [2] A.J. Espay, A.P. Duker, R. Chen, M.S. Okun, E.T. Barrett, J. Devoto, P. Zeilman, M. Gartner, N. Burton, H.A. Miranda, G.T. Mandybur, T.A. Zesiewicz,
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1005e1007
[3] [4]
[5]
[6]
K.D. Foote, F.J. Revilla, Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observations, Mov. Disord. 23 (2008) 2357e2362. T.C. Yaltho, W.G. Ondo, Thalamic deep brain stimulation for orthostatic tremor, Tremor Other Hyperkinet Mov. (N Y ) 1 (2011). M.K. Lyons, M. Behbahani, O.K. Boucher, J.N. Caviness, V.G. Evidente, Orthostatic tremor responds to bilateral thalamic deep brain stimulation, Tremor Other Hyperkinet Mov. (N Y ) 2 (2012). C. Magarinos-Ascone, F.M. Ruiz, A.S. Millan, E. Montes, I. Regidor, P.M. del Alamo de, R. Figueiras-Mendez, Electrophysiological evaluation of thalamic DBS for orthostatic tremor, Mov. Disord. 25 (2010) 2476e2477. P.M. FitzGerald, J. Jankovic, Orthostatic tremor: an association with essential tremor, Mov. Disord. 6 (1) (1991) 60e64.
Maria Fiorella Contarino* Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Department of Neurology, Haga Teaching Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands
1007
Vincent J.J. Odekerken Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Pepijn van den Munckhof Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Rob M.A. de Bie Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Anne-Fleur van Rootselaar Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands *
Lo J. Bour Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Corresponding author. Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands E-mail address: [email protected] (M.F. Contarino).
P. Richard Schuurman Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
16 March 2015
Erik R. Blok Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Thalamic deep brain stimulation for orthostatic tremor: Clinical and neurophysiological correlates
Keywords: Orthostatic tremor Deep brain stimulation Microelectrode recordings
Orthostatic tremor (OT) is characterized by progressive unsteadiness during stance, due to fine-amplitude leg tremor with a 13e18 Hz frequency, leading to limited ability to stand or walk and impaired functioning. Medication is often ineffective. Bilateral deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius medialis (Vim) has been reported in only five patients so far [1e5]. A 70-years-old lady complained of progressive bilateral postural hand tremor and unsteadiness during stance and walking since 20 years. She could stand without support only for a few seconds, could not walk longer than 10 min and had difficulties in many activities including writing and cooking. Clonazepam (6 mg/day) and other benzodiazepines, gabapentin, and pramipexole were ineffective. Her medical history included Meniere's disease, vitrectomy for macula pucker, and gynecological surgeries. Neurological and surface EMG evaluations revealed a 16 Hz leg tremor, which appeared immediately after the patient stood and necessitated her sitting after about 30 s (Video 1, Fig. 1 panel A). A postural arm tremor, downbeat nystagmus, and brisk stretch reflexes were observed, though neither ataxia nor parkinsonism was. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.06.008. Her older sister had EMG-confirmed OT since the age of 67, accompanied by saccadic eye-movements, hyperreflexia and bilateral Babinski sign, with normal MRI. Stereotactic surgery was performed without sedation or medication. Based on test-stimulation and intra-operative microelectrode recordings (MER) performed at several sites, DBS electrodes (3389®; Medtronic, Minneapolis, MN) were bilaterally implanted and connected to two single-channel Soletra® pulse generators (Medtronic). Intra-operative leg EMG during isometric contraction showed burst-like activity with frequency ranging from 14 to 22 Hz. There was no relevant coherence between the leg EMG and MER of the Vim (Supplementary Fig. 1). http://dx.doi.org/10.1016/j.parkreldis.2015.06.008 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
Early postoperative imaging showed a correct electrode position (Supplementary Fig. 2). After surgery, off stimulation, there was marked symptomatic improvement which gradually decreased thereafter. Switching on stimulation produced additional benefit, both on leg and arm tremor. The patient reported a relevant prolongation of the ability to stand and walk without feeling the tremor (Video 2) EMG recordings showed markedly lower amplitude of tremor bursts, a more homogeneous frequency spectrum with shift in peak frequency to 14 Hz, and a slightly increased latency from standing to tremor onset (Fig. 1 panel D). Eight months postoperatively, the ETRS part-C score decreased to 1/16, and she had resumed her activities including professional cooking, biking, and rowing. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.06.008. One year after surgery, the patient underwent surgical replacement of non-flexible wires for flexible ones, because of persistent pain along the extension wires. Afterwards, the efficacy of stimulation on tremor decreased and did not improve with parameter adjustments. A CT scan showed an upward displacement of both electrodes (Supplementary Fig. 2) Stereotactic repositioning of both electrodes restored the therapeutic effect, which lasted an additional two years, i.e., four years following the original surgery. Over time, tremor slowly worsened and at last follow-up (5 years after surgery) stimulation, although still effective, could not produce optimal clinical improvement. Additional electrodes placement (e.g. in the Vop), which has anecdotally been reported as effective for other forms of tremor, was not considered at the time. Bilateral Vim DBS can be effective for disabling, medicationresistant OT. Electrode displacement resulted in a loss of effect in our patient, while stereotactic repositioning restored the original benefit, confirming the therapeutic effect of Vim stimulation. Nystagmus, brisk reflexes and positive family history could suggest a secondary form, although known genetic cerebellar disorders were excluded, and familial primary OT has been reported. The difficulty in walking was likely related to OT, considering that it disappeared completely after surgery with tremor suppression. A possible association with essential tremor could be considered, as reported in the literature [6]. Only five patients who underwent bilateral Vim DBS have been reported so far. In all these cases tremor severity was reduced, but long-term follow-up was not available [1e5]. During surgery, isometric contraction of the leg muscles did not induce the 15e16 Hz tremor although burst-like activity with frequency ranging from 14 to 22 Hz was seen in the tibialis anterior
1006
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1005e1007
Fig. 1. Neurophysiological findings EMG of the right tibialis anterior (TA) muscle while standing and corresponding power spectrum. A): Before surgery. EMG recordings show a 16 Hz tremor. B) Two months after surgery with stimulator off. EMG recordings show a 16 Hz tremor with slightly reduced amplitude and slightly increased latency from standing as compared to before surgery. C) Nine months after surgery with stimulator off and D) with stimulation on. With stimulation on, EMG recordings show tremor bursts with markedly reduced amplitude and increased latency as compared to before surgery. Notably the frequency spectrum is more homogeneous and hardly shows any peak around 14 Hz.
muscle (Supplementary Fig. 1), which showed no clear coherence with MER of the Vim. MER have not been documented in OT patients before; future studies might provide more insight into the relationship between thalamic oscillators and OT. The clinical benefit was reflected by markedly lower amplitude of the postoperative EMG bursts, while a disruption of the spectrum was observed, as reported in one previous patient [4]. We conclude that bilateral Vim stimulation can provide long-lasting relief of symptoms in patients with medication-resistant orthostatic tremor.
2. Manuscript: A. Writing of the first draft, B. Review and Critique, C. Final approval of the submitted version. MF Contarino: 1A, 1B, 1C, 2A, 2C. LJ Bour: 1B, 1C, 2B, 2C. PR Schuurman: 1B, 2B, 2C. E.R. Blok: 1C, 2B, 2C. V. Odekerken: 1B, 2B, 2C. P van den Munckhof: 1B, 2B, 2C. R.M.A. de Bie: 1A, 2B, 2C. AF van Rootselaar: 1A, 1B, 1C, 2B, 2C.
Conflict of interests Acknowledgements The DBS team of the AMC received unrestricted research grants from Medtronic and received financial compensation for teaching courses for the European Continue Medical Training program. M.F. Contarino: Advisory board: Medtronic, Boston Scientific. Is co-inventor on a patent application relevant to Deep Brain Stimulation. Speaking fees: Abbvie, Medtronic, Boston Scientific, ECMT. L.J. Bour: acts as independent advisor for Medtronic. Is coinventor on a patent application relevant to Deep Brain Stimulation. P.R. Schuurman: acts as independent advisor for Medtronic and Elekta. E. Blok, V. Odekerken, P. van den Munckhof, R.M.A. de Bie, and A.F. van Rootselaar have nothing to disclose. Author contributions 1. Case study: A. Conception, B. Execution, C. Analysis and interpretation of data;
The authors wish to thank Prof. Dr. J. Stam for referring the patient for surgery.
Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.parkreldis.2015.06.008. References [1] J. Guridi, M.C. Rodriguez-Oroz, J. Arbizu, M. Alegre, E. Prieto, I. Landecho, M. Manrique, J. Artieda, J.A. Obeso, Successful thalamic deep brain stimulation for orthostatic tremor, Mov. Disord. 23 (2008) 1808e1811. [2] A.J. Espay, A.P. Duker, R. Chen, M.S. Okun, E.T. Barrett, J. Devoto, P. Zeilman, M. Gartner, N. Burton, H.A. Miranda, G.T. Mandybur, T.A. Zesiewicz,
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1005e1007
[3] [4]
[5]
[6]
K.D. Foote, F.J. Revilla, Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observations, Mov. Disord. 23 (2008) 2357e2362. T.C. Yaltho, W.G. Ondo, Thalamic deep brain stimulation for orthostatic tremor, Tremor Other Hyperkinet Mov. (N Y ) 1 (2011). M.K. Lyons, M. Behbahani, O.K. Boucher, J.N. Caviness, V.G. Evidente, Orthostatic tremor responds to bilateral thalamic deep brain stimulation, Tremor Other Hyperkinet Mov. (N Y ) 2 (2012). C. Magarinos-Ascone, F.M. Ruiz, A.S. Millan, E. Montes, I. Regidor, P.M. del Alamo de, R. Figueiras-Mendez, Electrophysiological evaluation of thalamic DBS for orthostatic tremor, Mov. Disord. 25 (2010) 2476e2477. P.M. FitzGerald, J. Jankovic, Orthostatic tremor: an association with essential tremor, Mov. Disord. 6 (1) (1991) 60e64.
Maria Fiorella Contarino* Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Department of Neurology, Haga Teaching Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands
1007
Vincent J.J. Odekerken Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Pepijn van den Munckhof Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Rob M.A. de Bie Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Anne-Fleur van Rootselaar Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands *
Lo J. Bour Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
Corresponding author. Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands E-mail address: [email protected] (M.F. Contarino).
P. Richard Schuurman Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
16 March 2015
Erik R. Blok Department of Neurology/Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
