Accepted Manuscript Simultaneous Improvement of Tics and Parkinsonism after Pallidal DBS Neepa Patel , MD Joohi Jimenez-Shahed , MD PII:
S1353-8020(14)00198-9
DOI:
10.1016/j.parkreldis.2014.05.009
Reference:
PRD 2348
To appear in:
Parkinsonism and Related Disorders
Received Date: 26 March 2014 Revised Date:
13 May 2014
Accepted Date: 18 May 2014
Please cite this article as: Patel N, Jimenez-Shahed J, Simultaneous Improvement of Tics and Parkinsonism after Pallidal DBS, Parkinsonism and Related Disorders (2014), doi: 10.1016/ j.parkreldis.2014.05.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Patel et al.| 1
Simultaneous Improvement of Tics and Parkinsonism after Pallidal DBS Neepa Patel, MD1 and Joohi Jimenez-Shahed, MD2 Clinical Center for Movement Disorders, Department of Neurology and Neurotherapeutics,
RI PT
1
University of Texas- Southwestern Dallas, TX 2
Parkinson’s Disease Center and Movement Disorders Clinic
SC
Department of Neurology, Baylor College of Medicine Houston, TX
Brain Stimulation
M AN U
Keywords: Basal Ganglia, Parkinson’s disease/Parkinsonism, Tourette syndrome, Tics, Deep
Short title: Simultaneous Improvement of Tics & Parkinsonism Word count: 789
TE D
Supplementary data: 2 videos
Please address correspondence to:
EP
Joohi Jimenez-Shahed, MD
Parkinson’s Disease Center and
AC C
Movement Disorders Clinic Department of Neurology
Baylor College of Medicine
6550 Fannin Street Suite 1801 Houston, TX 77030 USA (713) 798-7438 [email protected]
ACCEPTED MANUSCRIPT Patel et al.| 2
Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a widely accepted treatment for Parkinson’s disease (PD), a disorder resulting in downstream disinhibition of the GPi due to loss of dopamine producing cells in the substantia nigra[1]. We and others[2] have reported
RI PT
efficacy of GPi DBS in the treatment of refractory Tourette syndrome (TS). Prior to considering DBS, patients with TS should have failed therapy with dopamine receptor blockers or depletors (amongst other therapies) for tic suppression and/or treatment of psychiatric co-morbidities.
SC
These medications can cause drug induced parkinsonism (DIP) through increased post-synaptic receptor blockade or presynaptic dopamine depletion and chronic use my result in tardive
M AN U
disorders. Although others [3] have reported improvement in tardive dyskinesia and dystonia (TDD) following pallidal stimulation, there are no known reports of DIP treated with DBS. We describe a patient with malignant TS treated with GPi DBS who developed acute recurrent symptoms of drug-induced parkinsonism (DIP) when her DBS was turned off. DIP improved
TE D
after stimulation was reinstated.
A 21 year old right handed woman with long-standing malignant TS experienced self-injurious motor and vocal tics including severe whiplash tics, arm flailing, leg extension, punching and
EP
kicking walls, self-cutting, partial word repetition, loud sounds and coprolalia. She had
AC C
comorbid obsessive-compulsive behaviors (OCB), attention deficit-hyperactivity disorder (ADHD) and depression. Past medication trials included tetrabenazine 150mg/day, fluphenazine 3mg/day, ziprasidone 20mg, topiramate 225mg/ day, baclofen, metaxalone, benzodiazepines, clonidine, and guanfacine, various serotonin reuptake inhibitors, methylphenidate and vocal cord botulinum toxin injections for coprolalia. Medication management was limited by side effects of parkinsonism, sedation and persistent malignant tics. In 2011, after consensus review, the patient underwent bilateral GPi DBS. At the time of implantation, Yale Global Tic Severity
ACCEPTED MANUSCRIPT Patel et al.| 3
Score (YGTSS) was 89 (39 severity, 50 impairment) and neuroleptic treatment included tetrabenazine 112.5mg/day, aripiprazole 4mg/day, and fluphenazine 3mg/day. She had mild,
RI PT
non-impairing parkinsonism (subtle bradykinesia and rigidity). After implantation, stimulation was gradually adjusted to left GPi: C+2-, 5.5V, 110µs, 150 Hz and right GPi: C+10-, 5.5V, 90µs, 150Hz. At 6 month follow-up, tics were reduced by 47%
SC
(YGTSS 42; 22 severity, 20 impairment). Neuroleptics were gradually reduced to tetrabenazine 64.5mg/day and aripiprazole 5mg/day after marked reduction in tic severity and mood
M AN U
symptoms. During follow-up, she became intermittently compliant with medications due to psychosocial stressors, and rapidly resumed regular doses of her neuroleptics. 14 months after implantation, she experienced sharp shock-like pains overlying her abdominal pulse generator. She was advised to discontinue stimulation due to concerns of hardware malfunction. Six days after discontinuation of stimulation, examination revealed marked parkinsonism with 4+
TE D
hypomimia, 3+ global bradykinesia, generalized rigidity and abnormal gait and balance with MDS-UPDRS part 3 score of 37 (Video 1), in addition to exacerbation of complex motor and vocal tics (clapping, head jerking, leg extension, hitting head with fist, coprolalia and other
EP
sounds). Electrode and therapy impedances were normal and stimulation was reinstated at the
AC C
same polarity with frequency of 150Hz, and bilateral pulse with of 90 µsec. During amplitude re-titration, parkinsonism gradually improved until a final setting of 5.5V bilaterally. MDS-UPDRS part 3 score was 12, ten minutes after adjustment (Video 2). In the following days, a herpes zoster rash overlying the battery site emerged, explaining her pain. One month later, tic control was re-captured with additional improvement in parkinsonism (MDSUPDRS part 3= 3), despite an increase in apripiprazole to 10mg/day for depression.
ACCEPTED MANUSCRIPT Patel et al.| 4
This patient’s recurrent parkinsonism is likely secondary to rapid re-titration of neuroleptics, but its emergence and regression according to DBS condition (off vs. on) parallels the pattern seen in idiopathic PD treated with DBS. The management of DIP is best achieved through medication
RI PT
adjustment, however to our knowledge this is the first case of DIP reported to improve with bilateral GPi DBS, furthering the spectrum of tardive disorders amenable to DBS. Pallidal DBS is a mainstay of PD and dystonia therapy, but is increasingly considered for management of other
M AN U
DIP improved quite rapidly in our patients.
SC
hyperkinetic movement disorders[1]. Additionally, similar to some reported cases of TDD [3],
Our case demonstrates simultaneous improvement in hyperkinetic (tic) and hypokinetic (parkinsonian) movements with GPi stimulation. Improvement in tics and PD with subthalamic nucleus (STN) DBS has previously been described[4]. While there is no known STN pathology in TS, irregular and reduced neuronal firing of GPi neurons has been observed[5]. By contrast,
TE D
an increase in oscillatory bursts and synchrony of GPi neurons is found in low dopamine states such as PD[6]. The simultaneous improvement of tics and parkinsonism observed in our patient therefore supports theories that the beneficial effects of high frequency stimulation are
EP
attributable to normalization of firing patterns within dysfunctional circuits[6]. GPi may be a
AC C
particularly suitable target to treat co-existing hyper- and hypo-kinetic disorders, due to its direct downstream influence on thalamocortical pathways. Acknowledgements:
Dr. Patel was involved in the conception, design and preparation of the first draft of the manuscript.
ACCEPTED MANUSCRIPT Patel et al.| 5
Dr. Jimenez-Shahed was involved in the conception, design and critical revision of the manuscript for important intellectual content.
RI PT
Financial Disclosures: Dr. Patel has received honorarium as a consultant for USWorldMed.
Dr. Jimenez-Shahed received research support from Avid Radiopharmaceutical, Inc., Siena
SC
Biotech SPA, Phytopharm, Acadia Pharmaceuticals, NeuroSearch Sweden AB, and ScheringPlough. She is a member of the speakers’ bureau for Teva, Allergan, and Lundbeck.
M AN U
There are no funding sources for this case report. Video Legend:
Video 1: A 21 year-old female with Tourette syndrome and parkinsonism has tics and marked parkinsonism (MDS-UDPRS=37) with bilateral GPi DBS off for 6 days.
TE D
Video 2: The same patient is shown after re-instating bilateral GPi DBS for 10minutes with marked improvement of parkinsonism (MDS-UPDRS= 12). Consent for publication of videotape
AC C
EP
was obtained from the patient with an IRB approved institutional form.
ACCEPTED MANUSCRIPT Patel et al.| 6
References: [1]
Welter ML, Grabli D, Vidailhet M. Deep brain stimulation for hyperkinetics disorders:
dystonia, tardive dyskinesia, and tics. Curr Opin Neurol 2010;23:420-5. Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J. Deep brain
RI PT
[2]
stimulation for tourette syndrome: target selection. Stereotact Funct Neurosurg 2012; 90:213-4. [3]
Spindler MA, Galifianakis NB, Wilkinson JR, Duda JE. Globus pallidus interna deep
SC
brain stimulation fro tardive dyskinesia: case report and review of the literature. Parkinsonism Relat Disord 2013;19:141-7.
Martinez-Torres I, Hariz MI, Zrinzo L, Foltynie T, Limousin P. Improvement of tics after
M AN U
[4]
subthalamic nucleus deep brain stimulation. Neurology 2009;72:1787-9. [5]
Zhuang P, Hallett M, Zhang X, Li J, Zhang Y, Li Y. Neuronal activity in the globus
pallidus internus in patients with tics. J Neurol Neurosurg Psychiatry 2009;80:1075-81.
AC C
EP
TE D
[6] Wichmann T, Delong MR. Deep-Brain Stimulation for Basal Ganglia Disorders Basal Ganglia 2011;1:65-77.
S1353-8020(14)00198-9
DOI:
10.1016/j.parkreldis.2014.05.009
Reference:
PRD 2348
To appear in:
Parkinsonism and Related Disorders
Received Date: 26 March 2014 Revised Date:
13 May 2014
Accepted Date: 18 May 2014
Please cite this article as: Patel N, Jimenez-Shahed J, Simultaneous Improvement of Tics and Parkinsonism after Pallidal DBS, Parkinsonism and Related Disorders (2014), doi: 10.1016/ j.parkreldis.2014.05.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Patel et al.| 1
Simultaneous Improvement of Tics and Parkinsonism after Pallidal DBS Neepa Patel, MD1 and Joohi Jimenez-Shahed, MD2 Clinical Center for Movement Disorders, Department of Neurology and Neurotherapeutics,
RI PT
1
University of Texas- Southwestern Dallas, TX 2
Parkinson’s Disease Center and Movement Disorders Clinic
SC
Department of Neurology, Baylor College of Medicine Houston, TX
Brain Stimulation
M AN U
Keywords: Basal Ganglia, Parkinson’s disease/Parkinsonism, Tourette syndrome, Tics, Deep
Short title: Simultaneous Improvement of Tics & Parkinsonism Word count: 789
TE D
Supplementary data: 2 videos
Please address correspondence to:
EP
Joohi Jimenez-Shahed, MD
Parkinson’s Disease Center and
AC C
Movement Disorders Clinic Department of Neurology
Baylor College of Medicine
6550 Fannin Street Suite 1801 Houston, TX 77030 USA (713) 798-7438 [email protected]
ACCEPTED MANUSCRIPT Patel et al.| 2
Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a widely accepted treatment for Parkinson’s disease (PD), a disorder resulting in downstream disinhibition of the GPi due to loss of dopamine producing cells in the substantia nigra[1]. We and others[2] have reported
RI PT
efficacy of GPi DBS in the treatment of refractory Tourette syndrome (TS). Prior to considering DBS, patients with TS should have failed therapy with dopamine receptor blockers or depletors (amongst other therapies) for tic suppression and/or treatment of psychiatric co-morbidities.
SC
These medications can cause drug induced parkinsonism (DIP) through increased post-synaptic receptor blockade or presynaptic dopamine depletion and chronic use my result in tardive
M AN U
disorders. Although others [3] have reported improvement in tardive dyskinesia and dystonia (TDD) following pallidal stimulation, there are no known reports of DIP treated with DBS. We describe a patient with malignant TS treated with GPi DBS who developed acute recurrent symptoms of drug-induced parkinsonism (DIP) when her DBS was turned off. DIP improved
TE D
after stimulation was reinstated.
A 21 year old right handed woman with long-standing malignant TS experienced self-injurious motor and vocal tics including severe whiplash tics, arm flailing, leg extension, punching and
EP
kicking walls, self-cutting, partial word repetition, loud sounds and coprolalia. She had
AC C
comorbid obsessive-compulsive behaviors (OCB), attention deficit-hyperactivity disorder (ADHD) and depression. Past medication trials included tetrabenazine 150mg/day, fluphenazine 3mg/day, ziprasidone 20mg, topiramate 225mg/ day, baclofen, metaxalone, benzodiazepines, clonidine, and guanfacine, various serotonin reuptake inhibitors, methylphenidate and vocal cord botulinum toxin injections for coprolalia. Medication management was limited by side effects of parkinsonism, sedation and persistent malignant tics. In 2011, after consensus review, the patient underwent bilateral GPi DBS. At the time of implantation, Yale Global Tic Severity
ACCEPTED MANUSCRIPT Patel et al.| 3
Score (YGTSS) was 89 (39 severity, 50 impairment) and neuroleptic treatment included tetrabenazine 112.5mg/day, aripiprazole 4mg/day, and fluphenazine 3mg/day. She had mild,
RI PT
non-impairing parkinsonism (subtle bradykinesia and rigidity). After implantation, stimulation was gradually adjusted to left GPi: C+2-, 5.5V, 110µs, 150 Hz and right GPi: C+10-, 5.5V, 90µs, 150Hz. At 6 month follow-up, tics were reduced by 47%
SC
(YGTSS 42; 22 severity, 20 impairment). Neuroleptics were gradually reduced to tetrabenazine 64.5mg/day and aripiprazole 5mg/day after marked reduction in tic severity and mood
M AN U
symptoms. During follow-up, she became intermittently compliant with medications due to psychosocial stressors, and rapidly resumed regular doses of her neuroleptics. 14 months after implantation, she experienced sharp shock-like pains overlying her abdominal pulse generator. She was advised to discontinue stimulation due to concerns of hardware malfunction. Six days after discontinuation of stimulation, examination revealed marked parkinsonism with 4+
TE D
hypomimia, 3+ global bradykinesia, generalized rigidity and abnormal gait and balance with MDS-UPDRS part 3 score of 37 (Video 1), in addition to exacerbation of complex motor and vocal tics (clapping, head jerking, leg extension, hitting head with fist, coprolalia and other
EP
sounds). Electrode and therapy impedances were normal and stimulation was reinstated at the
AC C
same polarity with frequency of 150Hz, and bilateral pulse with of 90 µsec. During amplitude re-titration, parkinsonism gradually improved until a final setting of 5.5V bilaterally. MDS-UPDRS part 3 score was 12, ten minutes after adjustment (Video 2). In the following days, a herpes zoster rash overlying the battery site emerged, explaining her pain. One month later, tic control was re-captured with additional improvement in parkinsonism (MDSUPDRS part 3= 3), despite an increase in apripiprazole to 10mg/day for depression.
ACCEPTED MANUSCRIPT Patel et al.| 4
This patient’s recurrent parkinsonism is likely secondary to rapid re-titration of neuroleptics, but its emergence and regression according to DBS condition (off vs. on) parallels the pattern seen in idiopathic PD treated with DBS. The management of DIP is best achieved through medication
RI PT
adjustment, however to our knowledge this is the first case of DIP reported to improve with bilateral GPi DBS, furthering the spectrum of tardive disorders amenable to DBS. Pallidal DBS is a mainstay of PD and dystonia therapy, but is increasingly considered for management of other
M AN U
DIP improved quite rapidly in our patients.
SC
hyperkinetic movement disorders[1]. Additionally, similar to some reported cases of TDD [3],
Our case demonstrates simultaneous improvement in hyperkinetic (tic) and hypokinetic (parkinsonian) movements with GPi stimulation. Improvement in tics and PD with subthalamic nucleus (STN) DBS has previously been described[4]. While there is no known STN pathology in TS, irregular and reduced neuronal firing of GPi neurons has been observed[5]. By contrast,
TE D
an increase in oscillatory bursts and synchrony of GPi neurons is found in low dopamine states such as PD[6]. The simultaneous improvement of tics and parkinsonism observed in our patient therefore supports theories that the beneficial effects of high frequency stimulation are
EP
attributable to normalization of firing patterns within dysfunctional circuits[6]. GPi may be a
AC C
particularly suitable target to treat co-existing hyper- and hypo-kinetic disorders, due to its direct downstream influence on thalamocortical pathways. Acknowledgements:
Dr. Patel was involved in the conception, design and preparation of the first draft of the manuscript.
ACCEPTED MANUSCRIPT Patel et al.| 5
Dr. Jimenez-Shahed was involved in the conception, design and critical revision of the manuscript for important intellectual content.
RI PT
Financial Disclosures: Dr. Patel has received honorarium as a consultant for USWorldMed.
Dr. Jimenez-Shahed received research support from Avid Radiopharmaceutical, Inc., Siena
SC
Biotech SPA, Phytopharm, Acadia Pharmaceuticals, NeuroSearch Sweden AB, and ScheringPlough. She is a member of the speakers’ bureau for Teva, Allergan, and Lundbeck.
M AN U
There are no funding sources for this case report. Video Legend:
Video 1: A 21 year-old female with Tourette syndrome and parkinsonism has tics and marked parkinsonism (MDS-UDPRS=37) with bilateral GPi DBS off for 6 days.
TE D
Video 2: The same patient is shown after re-instating bilateral GPi DBS for 10minutes with marked improvement of parkinsonism (MDS-UPDRS= 12). Consent for publication of videotape
AC C
EP
was obtained from the patient with an IRB approved institutional form.
ACCEPTED MANUSCRIPT Patel et al.| 6
References: [1]
Welter ML, Grabli D, Vidailhet M. Deep brain stimulation for hyperkinetics disorders:
dystonia, tardive dyskinesia, and tics. Curr Opin Neurol 2010;23:420-5. Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J. Deep brain
RI PT
[2]
stimulation for tourette syndrome: target selection. Stereotact Funct Neurosurg 2012; 90:213-4. [3]
Spindler MA, Galifianakis NB, Wilkinson JR, Duda JE. Globus pallidus interna deep
SC
brain stimulation fro tardive dyskinesia: case report and review of the literature. Parkinsonism Relat Disord 2013;19:141-7.
Martinez-Torres I, Hariz MI, Zrinzo L, Foltynie T, Limousin P. Improvement of tics after
M AN U
[4]
subthalamic nucleus deep brain stimulation. Neurology 2009;72:1787-9. [5]
Zhuang P, Hallett M, Zhang X, Li J, Zhang Y, Li Y. Neuronal activity in the globus
pallidus internus in patients with tics. J Neurol Neurosurg Psychiatry 2009;80:1075-81.
AC C
EP
TE D
[6] Wichmann T, Delong MR. Deep-Brain Stimulation for Basal Ganglia Disorders Basal Ganglia 2011;1:65-77.
