Accepted Manuscript Dopamine agonist withdrawal syndrome in Parkinson's disease
Paolo Solla, Alfonso Fasano, Antonino Cannas, Francesco Marrosu PII: DOI: Reference:
S0022-510X(17)33761-9 doi: 10.1016/j.jns.2017.08.3263 JNS 15541
To appear in:
Journal of the Neurological Sciences
Received date: Accepted date:
4 August 2017 30 August 2017
Please cite this article as: Paolo Solla, Alfonso Fasano, Antonino Cannas, Francesco Marrosu , Dopamine agonist withdrawal syndrome in Parkinson's disease. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jns(2017), doi: 10.1016/j.jns.2017.08.3263
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ACCEPTED MANUSCRIPT DOPAMINE AGONIST WITHDRAWAL SYNDROME IN PARKINSON’S DISEASE
Paolo Solla1,*
[email protected],
Alfonso Fasano2,3 , Antonino Cannas 1 and Francesco
Marrosu1 Movement
Disorders of
Institute
Neurology,
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Department
of
University
of
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Cagliari, Italy 2
Neurology, Cagliari,
Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in
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Parkinson’s
Western
UHN,
Division
Toronto, Ontario, Canada
Disease, Hospital,
of
Neurology,
of
Toronto,
Research
Institute,
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Krembil
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University
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Toronto
3
Center,
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1
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Toronto, Ontario, Canada
Keywords: DAWS, Parkinson’s disease Conflicts of Interest and Source of Funding: None of the authors has any competing interests.
*
Corresponding author at: Movement Disorders Center Department of Neurology University of Cagliari SS 554 Bivio per Sestu 09042 Monserrato (Cagliari) – ITALY
ACCEPTED MANUSCRIPT Dear Editor, we read with interest the review written by Yu and Fernandez [1] with the purpose of providing a comprehensive account on the current knowledge of dopamine agonist withdrawal syndrome (DAWS) and offering expert insights into the management of this severe, stereotyped cluster of physical and psychological symptoms, as firstly described by Rabinak and Niremberg in 2010 [2],
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and subsequentely by Pondal and colleagues [3]. This review appears surely valuable because, in spite of the significant disabling impact of DAWS
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in patients affected by Parkinson’s disease (PD) [1], there is little understanding of DAWS
authors [4], the literature on this topic remains scarce.
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pathogenesis. Furthermore, with the exception of the recent original study of the same group of
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However, in this comprehensive review, we have noted that four significant papers addressing this
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issue were not quoted, papers that could have strengthen Authors’ conclusions. First at all, although Authors state that emerging data suggest that DAWS ‘in the setting of history
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of deep brain stimulation (DBS) may also be a risk’, this statement is not adequately accompanied by the necessary citation of the two relevant references that previously treated this relation [5,6]. In
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the first of these papers, Thobois and colleagues clearly described the occurrence of a drug withdrawal state precipitated by the rapid tapering of dopaminergic medications (especially
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dopamine agonists) after DBS surgery for PD and correlated this syndrome with the mesolimbic dopaminergic denervation on neuroimaging studies. This seminal article was subsequently commented by the letter by Nirenberg [6] who suggested that subjects who undergo DBS are generally at high risk for DAWS. Moreover, Authors statement that ‘emerging data show that ICD may not be an absolute requirement, but rather a significant risk factor for the development of DAWS in PD patients’, was not adequately accompanied by the necessary citation of a previous relevant research which clearly evidenced this result. In fact, Limotai and colleagues [7] retrospectively investigated the presence of DAWS in a large single-center PD cohort acquired over 9 years revealing a strong relationship
ACCEPTED MANUSCRIPT between DAWS and ICD. From this cohort of 1,040 patients, 26 subjects (2.5%) met the criteria for DAWS, but only 34.6% of DAWS patients were associated with ICDs, in contrast with Rabinak and Nirenberg [2] who reported the association with ICD in 100% of their DAWS cases. Finally, in this analysis of DAWS risk factors, we were surprised that the authors did not refer to our previous publication on DAWS appearance after the introduction of levodopa-carbidopa
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intestinal gel infusion (LCIG) [8]. In this paper, we described for the first time the occurrence of DAWS symptoms in advanced PD patients after the rapid withdrawal of dopamine agonists after
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LCIG introduction and we noted that only a single patient was previously affected by DDS, while
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no other disorders evocative of ICD were registered [8].
In conclusion, we strongly agree with the Authors’ belief that current knowledge of DAWS remains
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incomplete at this time and this consideration suggests the importance to closely monitor for
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withdrawal symptoms PD patients undergoing dopamine agonist discontinuation. Also in agreement with Authors’ observations, we retain that prospective large studies finalized to
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the prompt recognition and treatment of DAWS are needed.
ACCEPTED MANUSCRIPT Acknowledgements
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or
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not-for-profit sectors.
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Conflicts of interest: none.
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Disclosures
P. Solla has received honoraria from serving on Advisory board of Abbvie, has received
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institutional research funding from the University of Cagliari, received funding from the
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Fondazione Banco di Sardegna, and received research grant from the Dystonia Europe. A. Fasano has given expert testimony for Medtronic, has received honoraria from serving on
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scientific boards of Abbvie and UCB Pharma, has received honoraria from Lundbeck, UCB Pharma, Medtronic, Abbvie, Allergan, and Chiesi Farmaceutici, and has received has received
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institutional research funding from the University of Toronto and received funding for expert testimony from BioMarin Neureca–Onlus, Milan, AFaR Roma.
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A. Cannas reports no disclosures relevant to the manuscript. F. Marrosu reports no disclosures relevant to the manuscript.
ACCEPTED MANUSCRIPT References [1] Yu XX, Fernandez HH. Dopamine agonist withdrawal syndrome: A comprehensivereview. J Neurol Sci. 2017 Mar 15;374:53-55. [2] Rabinak CA, Nirenberg MJ. Dopamine agonist withdrawal syndrome in Parkinson disease. Arch Neurol 2010;67:58e63
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[3] Pondal M, Marras C, Miyasaki J, Moro E, Armstrong MJ, Strafella AP, Shah BB, Fox S, Prashanth LK, Phielipp N, Lang AE. Clinical features of dopamine agonist withdrawal syndrome in
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a movement disorders clinic. J Neurol Neurosurg Psychiatry. 2013 Feb;84(2):130-5.
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[4] Patel S, Garcia X, Mohammad ME, Yu XX, Vlastaris K, O'Donnell K, Sutton K,Fernandez HH. Dopamine agonist withdrawal syndrome (DAWS) in a tertiary Parkinsondisease treatment center. J
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Neurol Sci. 2017 Aug 15;379:308-311.
surgery
for
Parkinson’s
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[5] Thobois S, Ardouin C, Lhommee E, et al. Non-motor dopamine withdrawal syndrome after disease: predictors and
Brain
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2010;133:1111e27.
underlying mesolimbic denervation.
[6] Nirenberg MJ. Dopamine agonist withdrawal syndrome and non-motor symptoms after
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Parkinson's disease surgery. Brain. 2010 Nov;133(11):e155; author replye156. [7] Limotai N, Oyama G, Go C, Bernal O, Ong T, Moum SJ, Bhidayasiri R, Foote KD, Bowers D,
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Ward H, Okun MS. Addiction-like manifestations and Parkinson's disease: a large single center 9year experience. Int J Neurosci. 2012 Mar;122(3):145-53. [8] Solla P, Fasano A, Cannas A, Mulas CS, Marrosu MG, Lang AE, Marrosu F. Dopamine agonist withdrawal syndrome (DAWS) symptoms in Parkinson's disease patients treated with levodopacarbidopa intestinal gel infusion. Parkinsonism Relat Disord. 2015 Aug;21(8):968-71.