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Thalamic deep brain stimulation for drug-induced tremor
Parkinsonism and Related Disorders 21 (2015) 1369e1370
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 drug-induced tremor
Keywords: Deep brain stimulation Tremor Drug-induced
Tremor is a common side effect of many medications, including antipsychotics [1]. Drug-induced tremors typically have a temporal relation to the start of an offending agent and a dose-dependent response. They are best treated by removal of the offending drug, but in patients with psychiatric disease, withdrawal of antipsychotic medications is not always possible. Thalamic ventralis intermedialis (VIM) nucleus deep brain stimulation (DBS) is an established treatment for essential tremor (ET) and Parkinsonian tremor, but may also be effective for other tremor conditions [2]. To our knowledge, DBS for drug-induced tremor has not been described. This 70-year-old right-handed woman had been treated with antipsychotics for major depressive disorder with psychotic features since age 34. She was initially started on haloperidol and developed an action tremor of her hands while on this medication. Haloperidol was weaned off, but she experienced increased paranoia and was subsequently transitioned to risperidone. She continued to have an unstable mood resulting in multiple hospitalizations and multiple medication trials. After transitioning to lamotrigine and aripiprazole 15 mg daily in 2009, her psychiatric symptoms stabilized. Low dose antipsychotics were deemed necessary by her treating psychiatrist to prevent recurrence of paranoia. Hand tremor persisted throughout all of her medication changes but did not interfere with activities until 2011. Writing, applying makeup and eating/drinking became problematic. Tremor became socially embarrassing when head and voice tremor developed in 2012. Mild bradykinesia with activities of daily living also started at this time. There was a positive family history of tremor in her mother and sister, and mild improvement of the tremor with alcohol. Both the patient and her psychiatrist did not want to discontinue aripiprazole given the difficulty of her mood stabilization, so medications were added to try and control tremor. Unfortunately, propranolol (120 mg/day), primidone (250 mg/day), topiramate (200 mg/day), clonazepam (4 mg/day), gabapentin (900 mg/ day), and trihexyphenidyl were either ineffective or caused intolerable side effects. http://dx.doi.org/10.1016/j.parkreldis.2015.08.033 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
She presented for a multidisciplinary DBS evaluation in September 2013. Exam at the time showed mild facial hypomimia. She had an intermittent head tremor, mild amplitude rest tremor in both hands, mild amplitude postural tremor in the left hand, and a moderate to severe amplitude postural tremor in the right hand. Rigidity was present in the left wrist and she had decreased amplitude with finger tapping and hand opening-closing bilaterally, worse on the right. She had minimal arm swing bilaterally on gait examination (see Video). Detailed neuropsychological evaluation showed no dementia, and her psychiatrist felt that her mood was well controlled and stable. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.08.033. Frame-based left VIM-DBS surgery was performed using standard stereotactic surgical techniques, including microelectrode recording for localization [3]. Microstimulation revealed good stimulation of the hand area at target. The DBS electrode was then placed, tested intraoperatively, and showed suppression of right hand tremor. Lead placement was followed a month later by implantation of an ActivaSC stimulator (Medtronic, Inc.). Right hand tremor control was achieved with monopolar stimulation, amplitude 1.7 V, pulse width 60 ms, frequency 130 Hz. She was able to resume her daily activities without difficulty and continues to have absence of right hand tremor 12 months post-operatively (see Video). Her depression remained well-controlled. Our patient had a long psychiatric history and there was a clear temporal relation between the initiation of haloperidol and onset of her hand tremor, suggesting drug-induced tremor. Tremor persisted despite being transitioned to risperidone and later, aripiprazole. Because her psychiatric disorder had been difficult to control, she could not be weaned off aripiprazole. After failing multiple medications, she underwent left VIM-DBS, which successfully controlled her right hand tremor. We cannot completely rule out a diagnosis of underlying ET, given the distribution of her tremor, the family history and mild response of her tremor to alcohol. It would be difficult though, to establish a diagnosis of ET in the setting of an agent known to cause tremors. Furthermore, her tremor started and worsened after being on antipsychotic treatment. She also later developed mild parkinsonism on these agents, which would support a drug-induced etiology, though the development of parkinsonism secondary to dopaminergic denervation is also possible. A DaTscan to look for dopaminergic denervation was not performed, but would not have changed the DBS target given that tremor was her most bothersome symptom. DBS for drug-induced tremor has not been described in the literature to date. This is partly because active psychiatric disease is a
1370
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1369e1370
general contraindication for DBS and partly because subthalamic nucleus DBS may worsen mood in Parkinson patients [4,5]. Detrimental effects on mood, however, do not seem to occur with targets other than the STN [6]. Our patient continues to have wellcontrolled depression 12 months after VIM-DBS. VIM-DBS is effective in treating multiple types of tremor, including ET and Parkinsonian tremor [2]. Our case demonstrates that it may also help in the presence of drugs that induce tremor. While discontinuation of the offending agent should always be attempted or considered in patients with drug-induced tremor, VIM-DBS may be a possible alternative when the offending agent cannot be removed. Financial disclosure related to research covered in this article The authors report no conflicts of interest related to the research covered in this article. Acknowledgements Dr. Rodrigues has no financial disclosures. Dr. Patil receives research support from the Coulter Foundation, the A. Alfred Taubman Medical Institute, and St. Jude Medical Inc. He receives royalties from Demos Health for his book Deep Brain Stimulation; A New Life for People with Parkinson's, Dystonia, and Essential Tremor, and serves as a consultant for Medtronic, Inc. and Monteris, Inc. Dr. Chou has received grants from the National Institutes of Health (grants NS044504-08, NS091856-01), Michael J. Fox Foundation (N012137 through a University Health Network subgrant e PI Marras), and Huntington Study Group (site PI for 2CARE), has served as a consultant for Medtronic, Inc. and Accordant and receives royalties from UpToDate and Demos Health.
References [1] J.C. Morgan, K.D. Sethi, Drug-induced tremors, Lancet Neurol. 4 (12) (2005 Dec) 866e876. [2] A. Barbey, J. Bloch, F.J. Vingerhoets, DBS in dystonia and other hyperkinetic movement disorders, Curr. Treat. Options Neurol. 17 (9) (2015 Sep) 373. [3] I.M. Garonzik, S.E. Hua, S. Ohara, F.A. Lenz, Intraoperative microelectrode and semi-microelectrode recording during the physiological localization of the thalamic nucleus ventral intermediate, Mov. Disord. 17 (Suppl. 3) (2002) S135eS144. [4] K.A. Follett, F.M. Weaver, M. Stern, K. Hur, C.L. Harris, P. Luo, et al., Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease, N. Engl. J. Med. 362 (22) (2010 Jun 3) 2077e2091. [5] M.S. Okun, H.H. Fernandez, S.S. Wu, L. Kirsch-Darrow, D. Bowers, F. Bova, et al., Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial, Ann. Neurol. 65 (5) (2009 May) 586e595. [6] P. Damier, S. Thobois, T. Witjas, E. Cuny, P. Derost, S. Raoul, et al., Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia, Arch. General Psychiatry 64 (2) (2007 Feb) 170e176.
Bernardo Rodrigues Department of Neurology, University of Michigan, Ann Arbor, MI, USA Parag G. Patil, Kelvin L. Chou* Department of Neurology, University of Michigan, Ann Arbor, MI, USA Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA *
Corresponding author. Surgical Therapies Improving Movement (STIM) Program, University of Michigan Medical School, 2301 Commonwealth Blvd., Ann Arbor, MI 48105-2945, USA. E-mail address: [email protected] (K.L. Chou). 15 July 2015
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 drug-induced tremor
Keywords: Deep brain stimulation Tremor Drug-induced
Tremor is a common side effect of many medications, including antipsychotics [1]. Drug-induced tremors typically have a temporal relation to the start of an offending agent and a dose-dependent response. They are best treated by removal of the offending drug, but in patients with psychiatric disease, withdrawal of antipsychotic medications is not always possible. Thalamic ventralis intermedialis (VIM) nucleus deep brain stimulation (DBS) is an established treatment for essential tremor (ET) and Parkinsonian tremor, but may also be effective for other tremor conditions [2]. To our knowledge, DBS for drug-induced tremor has not been described. This 70-year-old right-handed woman had been treated with antipsychotics for major depressive disorder with psychotic features since age 34. She was initially started on haloperidol and developed an action tremor of her hands while on this medication. Haloperidol was weaned off, but she experienced increased paranoia and was subsequently transitioned to risperidone. She continued to have an unstable mood resulting in multiple hospitalizations and multiple medication trials. After transitioning to lamotrigine and aripiprazole 15 mg daily in 2009, her psychiatric symptoms stabilized. Low dose antipsychotics were deemed necessary by her treating psychiatrist to prevent recurrence of paranoia. Hand tremor persisted throughout all of her medication changes but did not interfere with activities until 2011. Writing, applying makeup and eating/drinking became problematic. Tremor became socially embarrassing when head and voice tremor developed in 2012. Mild bradykinesia with activities of daily living also started at this time. There was a positive family history of tremor in her mother and sister, and mild improvement of the tremor with alcohol. Both the patient and her psychiatrist did not want to discontinue aripiprazole given the difficulty of her mood stabilization, so medications were added to try and control tremor. Unfortunately, propranolol (120 mg/day), primidone (250 mg/day), topiramate (200 mg/day), clonazepam (4 mg/day), gabapentin (900 mg/ day), and trihexyphenidyl were either ineffective or caused intolerable side effects. http://dx.doi.org/10.1016/j.parkreldis.2015.08.033 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
She presented for a multidisciplinary DBS evaluation in September 2013. Exam at the time showed mild facial hypomimia. She had an intermittent head tremor, mild amplitude rest tremor in both hands, mild amplitude postural tremor in the left hand, and a moderate to severe amplitude postural tremor in the right hand. Rigidity was present in the left wrist and she had decreased amplitude with finger tapping and hand opening-closing bilaterally, worse on the right. She had minimal arm swing bilaterally on gait examination (see Video). Detailed neuropsychological evaluation showed no dementia, and her psychiatrist felt that her mood was well controlled and stable. Supplementary video related to this article can be found at http://dx.doi.org/10.1016/j.parkreldis.2015.08.033. Frame-based left VIM-DBS surgery was performed using standard stereotactic surgical techniques, including microelectrode recording for localization [3]. Microstimulation revealed good stimulation of the hand area at target. The DBS electrode was then placed, tested intraoperatively, and showed suppression of right hand tremor. Lead placement was followed a month later by implantation of an ActivaSC stimulator (Medtronic, Inc.). Right hand tremor control was achieved with monopolar stimulation, amplitude 1.7 V, pulse width 60 ms, frequency 130 Hz. She was able to resume her daily activities without difficulty and continues to have absence of right hand tremor 12 months post-operatively (see Video). Her depression remained well-controlled. Our patient had a long psychiatric history and there was a clear temporal relation between the initiation of haloperidol and onset of her hand tremor, suggesting drug-induced tremor. Tremor persisted despite being transitioned to risperidone and later, aripiprazole. Because her psychiatric disorder had been difficult to control, she could not be weaned off aripiprazole. After failing multiple medications, she underwent left VIM-DBS, which successfully controlled her right hand tremor. We cannot completely rule out a diagnosis of underlying ET, given the distribution of her tremor, the family history and mild response of her tremor to alcohol. It would be difficult though, to establish a diagnosis of ET in the setting of an agent known to cause tremors. Furthermore, her tremor started and worsened after being on antipsychotic treatment. She also later developed mild parkinsonism on these agents, which would support a drug-induced etiology, though the development of parkinsonism secondary to dopaminergic denervation is also possible. A DaTscan to look for dopaminergic denervation was not performed, but would not have changed the DBS target given that tremor was her most bothersome symptom. DBS for drug-induced tremor has not been described in the literature to date. This is partly because active psychiatric disease is a
1370
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1369e1370
general contraindication for DBS and partly because subthalamic nucleus DBS may worsen mood in Parkinson patients [4,5]. Detrimental effects on mood, however, do not seem to occur with targets other than the STN [6]. Our patient continues to have wellcontrolled depression 12 months after VIM-DBS. VIM-DBS is effective in treating multiple types of tremor, including ET and Parkinsonian tremor [2]. Our case demonstrates that it may also help in the presence of drugs that induce tremor. While discontinuation of the offending agent should always be attempted or considered in patients with drug-induced tremor, VIM-DBS may be a possible alternative when the offending agent cannot be removed. Financial disclosure related to research covered in this article The authors report no conflicts of interest related to the research covered in this article. Acknowledgements Dr. Rodrigues has no financial disclosures. Dr. Patil receives research support from the Coulter Foundation, the A. Alfred Taubman Medical Institute, and St. Jude Medical Inc. He receives royalties from Demos Health for his book Deep Brain Stimulation; A New Life for People with Parkinson's, Dystonia, and Essential Tremor, and serves as a consultant for Medtronic, Inc. and Monteris, Inc. Dr. Chou has received grants from the National Institutes of Health (grants NS044504-08, NS091856-01), Michael J. Fox Foundation (N012137 through a University Health Network subgrant e PI Marras), and Huntington Study Group (site PI for 2CARE), has served as a consultant for Medtronic, Inc. and Accordant and receives royalties from UpToDate and Demos Health.
References [1] J.C. Morgan, K.D. Sethi, Drug-induced tremors, Lancet Neurol. 4 (12) (2005 Dec) 866e876. [2] A. Barbey, J. Bloch, F.J. Vingerhoets, DBS in dystonia and other hyperkinetic movement disorders, Curr. Treat. Options Neurol. 17 (9) (2015 Sep) 373. [3] I.M. Garonzik, S.E. Hua, S. Ohara, F.A. Lenz, Intraoperative microelectrode and semi-microelectrode recording during the physiological localization of the thalamic nucleus ventral intermediate, Mov. Disord. 17 (Suppl. 3) (2002) S135eS144. [4] K.A. Follett, F.M. Weaver, M. Stern, K. Hur, C.L. Harris, P. Luo, et al., Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease, N. Engl. J. Med. 362 (22) (2010 Jun 3) 2077e2091. [5] M.S. Okun, H.H. Fernandez, S.S. Wu, L. Kirsch-Darrow, D. Bowers, F. Bova, et al., Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial, Ann. Neurol. 65 (5) (2009 May) 586e595. [6] P. Damier, S. Thobois, T. Witjas, E. Cuny, P. Derost, S. Raoul, et al., Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia, Arch. General Psychiatry 64 (2) (2007 Feb) 170e176.
Bernardo Rodrigues Department of Neurology, University of Michigan, Ann Arbor, MI, USA Parag G. Patil, Kelvin L. Chou* Department of Neurology, University of Michigan, Ann Arbor, MI, USA Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA *
Corresponding author. Surgical Therapies Improving Movement (STIM) Program, University of Michigan Medical School, 2301 Commonwealth Blvd., Ann Arbor, MI 48105-2945, USA. E-mail address: [email protected] (K.L. Chou). 15 July 2015