BRIEF
Nonmotor Symptoms in Subjects Without Evidence of Dopaminergic Deficits Fabienne S. Sprenger, MD,1 Klaus Seppi, MD,1 Atbin Djamshidian, MD,1 Eva Reiter, MD,1 Michael Nocker, MD,1 Katherina Mair, MD,1 €bel, MD,2 and Werner Poewe, MD1* Georg Go 1
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria 2Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria
ABSTRACT Background: A subgroup of patients initially diagnosed with Parkinson’s disease (PD) turn out to have normal dopamine transporter single-photon emission computed tomography imaging and have been labeled as subjects without evidence of dopaminergic deficit (SWEDDs). In this study, we sought to further characterize these patients and have analyzed the frequency of nonmotor symptoms (NMS) in SWEDDs, PD patients, and healthy controls. Methods: We analyzed the baseline clinical data of 412 PD patients, 184 controls, and 62 SWEDDs included in the Parkinson’s Progression Marker Initiative study on a variety of different NMS questionnaires. Results: Both PD patients and SWEDDs had greater frequency of NMS than healthy controls. Furthermore, some NMS, such as orthostatic hypotension as well as cardiovascular and thermoregulatory dysfunction were even more commonly reported in SWEDDs than in PD patients, whereas hyposmia was more common in PD, compared to SWEDDs. Conclusion: NMS are more frequent in SWEDDs than in controls, and autonomic dysfunction and orthostatic hypotension were even more common than in PD patients. These findings support the notion that SWEDDS represent a group of patients with still poorly C 2015 International Parunderstood pathophysiology. V kinson and Movement Disorder Society
-----------------------------------------------------------*Correspondence to: Prof. Werner Poewe, Department of Neurology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria; [email protected] Funding agencies: The study was sponsored by the PPMI. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 5 August 2014; Revised: 5 February 2015; Accepted: 8 February 2015 Published online 15 March 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26204
976
Movement Disorders, Vol. 30, No. 7, 2015
REPORTS
Key Words: Parkinson’s disease; SWEDDs; nonmotor symptoms
Around 4%–15% of patients clinically diagnosed with Parkinson’s disease (PD) have normal dopamine transporter (DAT) single-photon emission computed tomography (SPECT) imaging1,2 and are referred to as having scans without evidence of dopaminergic deficit (SWEDDs). Whereas it seems possible that such subjects may be in an early stage of PD, current evidence suggests that these patients likely suffer from non-PD conditions with different prognosis and treatment requirement.3 Failure to respond to levodopa,4 absent or minimal clinical progression,5 the lack of midbrain hyperechogenicity in transcranial ultrasound studies,6 and consistently normal DAT scans after follow-up7 all suggest alternate diagnoses, including essential tremor, adult-onset dystonic tremor, depression, vascular-, psychogenic- or drug-induced parkinsonism.6,8-11 Whereas nonmotor symptoms (NMS) are common in PD, their frequency is unknown in SWEDDs. In this study, we analyzed the baseline clinical data on NMS of SWEDDs, PD, and healthy controls (HCs) who were included in the Parkinson’s Progression Marker Initiative (PPMI) study.12
Patients and Methods This study used data from patients with newly diagnosed, untreated PD, SWEDDs, and HCs enrolled in the PPMI study. PPMI is an observational, international, multicentre study designed to identify PD progression biomarkers. The study was launched in June 2010, and the data analyzed here were obtained from the PPMI database (http://www.ppmi-info.org/accessed October, 2013). All DAT scans were analyzed centrally by the Institute for Neurodegenerative Disorders (New Haven, CT). Those patients who were clinically diagnosed as PD, but had a DAT-SPECT showing no evidence of DAT deficit at screening, were referred to as SWEDDs in our study. Further details regarding inclusion and exclusion criteria of the PPMI cohort can be found on http://clinicaltrials.gov/show/NCT01141023.
Standard Protocol Approvals, Registrations, and Patient Consents Each participating PPMI site received approval from an ethical standards committee on human
Female Male
ESS 10 points GDS 5 points RBDSQ 5 points UPSIT
Nonmotor Symptoms in Subjects Without Evidence of Dopaminergic Deficits Fabienne S. Sprenger, MD,1 Klaus Seppi, MD,1 Atbin Djamshidian, MD,1 Eva Reiter, MD,1 Michael Nocker, MD,1 Katherina Mair, MD,1 €bel, MD,2 and Werner Poewe, MD1* Georg Go 1
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria 2Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria
ABSTRACT Background: A subgroup of patients initially diagnosed with Parkinson’s disease (PD) turn out to have normal dopamine transporter single-photon emission computed tomography imaging and have been labeled as subjects without evidence of dopaminergic deficit (SWEDDs). In this study, we sought to further characterize these patients and have analyzed the frequency of nonmotor symptoms (NMS) in SWEDDs, PD patients, and healthy controls. Methods: We analyzed the baseline clinical data of 412 PD patients, 184 controls, and 62 SWEDDs included in the Parkinson’s Progression Marker Initiative study on a variety of different NMS questionnaires. Results: Both PD patients and SWEDDs had greater frequency of NMS than healthy controls. Furthermore, some NMS, such as orthostatic hypotension as well as cardiovascular and thermoregulatory dysfunction were even more commonly reported in SWEDDs than in PD patients, whereas hyposmia was more common in PD, compared to SWEDDs. Conclusion: NMS are more frequent in SWEDDs than in controls, and autonomic dysfunction and orthostatic hypotension were even more common than in PD patients. These findings support the notion that SWEDDS represent a group of patients with still poorly C 2015 International Parunderstood pathophysiology. V kinson and Movement Disorder Society
-----------------------------------------------------------*Correspondence to: Prof. Werner Poewe, Department of Neurology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria; [email protected] Funding agencies: The study was sponsored by the PPMI. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 5 August 2014; Revised: 5 February 2015; Accepted: 8 February 2015 Published online 15 March 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26204
976
Movement Disorders, Vol. 30, No. 7, 2015
REPORTS
Key Words: Parkinson’s disease; SWEDDs; nonmotor symptoms
Around 4%–15% of patients clinically diagnosed with Parkinson’s disease (PD) have normal dopamine transporter (DAT) single-photon emission computed tomography (SPECT) imaging1,2 and are referred to as having scans without evidence of dopaminergic deficit (SWEDDs). Whereas it seems possible that such subjects may be in an early stage of PD, current evidence suggests that these patients likely suffer from non-PD conditions with different prognosis and treatment requirement.3 Failure to respond to levodopa,4 absent or minimal clinical progression,5 the lack of midbrain hyperechogenicity in transcranial ultrasound studies,6 and consistently normal DAT scans after follow-up7 all suggest alternate diagnoses, including essential tremor, adult-onset dystonic tremor, depression, vascular-, psychogenic- or drug-induced parkinsonism.6,8-11 Whereas nonmotor symptoms (NMS) are common in PD, their frequency is unknown in SWEDDs. In this study, we analyzed the baseline clinical data on NMS of SWEDDs, PD, and healthy controls (HCs) who were included in the Parkinson’s Progression Marker Initiative (PPMI) study.12
Patients and Methods This study used data from patients with newly diagnosed, untreated PD, SWEDDs, and HCs enrolled in the PPMI study. PPMI is an observational, international, multicentre study designed to identify PD progression biomarkers. The study was launched in June 2010, and the data analyzed here were obtained from the PPMI database (http://www.ppmi-info.org/accessed October, 2013). All DAT scans were analyzed centrally by the Institute for Neurodegenerative Disorders (New Haven, CT). Those patients who were clinically diagnosed as PD, but had a DAT-SPECT showing no evidence of DAT deficit at screening, were referred to as SWEDDs in our study. Further details regarding inclusion and exclusion criteria of the PPMI cohort can be found on http://clinicaltrials.gov/show/NCT01141023.
Standard Protocol Approvals, Registrations, and Patient Consents Each participating PPMI site received approval from an ethical standards committee on human
Female Male
ESS 10 points GDS 5 points RBDSQ 5 points UPSIT
