Nonmotor fluctuations in Parkinson disease Severity and correlation with motor complications

From the Department of Neurology, Division of Neurodegenerative Diseases (A.S., C.B.S., M.W., Y.S.), Department of Medical Informatics and Biometry (R.K.), and Department of Neurology (H.R.), Dresden University of Technology, Dresden
Neurology (Impact Factor: 8.29). 01/2013; 80(9). DOI: 10.1212/WNL.0b013e318285c0ed
Source: PubMed


To evaluate frequency, severity, and correlation of nonmotor symptoms (NMS) with motor complications in fluctuating Parkinson disease (PD).

The Multicenter NonMotor Fluctuations in PD cross-sectional study used clinical examination of 10 NMS (dysphagia, anxiety, depression, fatigue, excessive sweating, inner restlessness, pain, concentration/attention, dizziness, bladder urgency) quantified using a visual analogue scale (VAS) in motor-defined on (NMS(On)) and off state (NMS(Off)) combined with motor assessments and self-ratings at home in 100 patients with advanced PD.

All NMS except dysphagia, excessive sweating, and bladder urgency fluctuated in conjunction to motor fluctuations with more frequent and severe symptoms in off compared to on state. The proportions of patients experiencing autonomic/sensory NMS in both motor states were similar to those with these NMS exclusively in off state (ratios 0.4-1.3), while for mental/psychic NMS the proportions with exclusive manifestation in off state were higher (ratios 1.8-3.1). Demographic and clinical characteristics correlated neither with NMS frequency patterns and severities nor with ΔNMS(On/Off) severities (defined as the differences of VAS scores between on and off). Severities of NMS(on), NMS(Off), and ΔNMS(On/Off) did not correlate with motor function. Presence of anxiety, depression, fatigue, and pain had negative impact on health-related quality of life (HRQOL) measured by Parkinson's Disease Questionnaire-8 scoring independent of their occurrence with respect to motor state. Fluctuations of these NMS but not of fatigue deteriorated HRQOL.

Patterns of NMS fluctuations are heterogeneous and complex, but psychic NMS fluctuate more frequently and severely. Demographic parameters and motor function do not correlate with NMS or nonmotor fluctuation severities in fluctuating PD.

Download full-text


Available from: Wolfgang H Jost, Jan 08, 2015
62 Reads
    • "A comprehensive assessment of NMF seems not only important for future development of evidence-based treatments of NMF, but also for the management of NMF in clinical practice. In contrast to NMF-VAS, NMSS covers a broader range of NMS and it does not measure effective NMS present at the moment of examination, but assesses NMF for a time period of 4 weeks (Storch et al. 2013). However, based on the present findings, an adjustment of NMSS items can be considered for the design of a more specific instrument to measure NMF. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Data on frequency, severity and correlations of NMS with motor complications are only available for a limited number of NMS. The NMS Scale (NMSS) is a validated tool to assess a broad range of NMS, which has not been used in NMS fluctuations. We assessed fluctuations of a broad range of non-motor symptom (NMS) for a 1-month time period in fluctuating Parkinson's disease (PD) in a multicenter cross-sectional study using the NMSS assessing NMS in motor On (NMSSOn) and Off state (NMSSOff) combined with clinical NMS and motor function scoring in 100 fluctuating PD patients. ΔNMSSOn/Off was defined as the differences of NMSS scores between On and Off. Complete NMSS datasets were available from 73 patients (53 % men; age: 68.2 ± 9.7 years) with mean total NMSS score in On state of 41.5 ± 37.6 and in Off state of 75.6 ± 42.3 (P < 0.001). Scores were higher in Off compared to On state for all domains except for domain "perceptual problems/hallucinations" (P = 0.608). Clinimetric properties of the NMSS were similar to those reported previously for NMS assessments independent of motor oscillations. NMSSOn, NMSSOff and ΔNMSSOn/Off showed weak to moderate correlations with demographics, indicators of motor symptom severity as well as with other measures of NMS, depression and quality of life. Correlations of NMSS items/domains with independent measures of related constructs were weak to moderate. In conclusion, when assessed with the NMSS, a broad range of NMS fluctuate with motor oscillations, but these fluctuations do neither correlate with motor function nor with measures of disease progression.
    Journal of Neural Transmission 08/2015; DOI:10.1007/s00702-015-1437-x · 2.40 Impact Factor
  • Source
    • "Cognitive decline, falls and gait problems such as freezing may counteract beneficial responses. However, cognitive issues such as clouding of consciousness, concentration impairment as a manifestation of non-motor fluctuation and freezing may occur during 'off' periods and should be treatable by device-aided therapies [13]. Cognitive assessment should be conducted ideally at 'on' and 'off' stages before initiating device-aided therapy, recognizing that even marked cognitive impairment may be a consequence of a patient's current treatment. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS. Copyright © 2015. Published by Elsevier Ltd.
    Parkinsonism & Related Disorders 07/2015; DOI:10.1016/j.parkreldis.2015.07.020 · 3.97 Impact Factor
  • Source
    • "There was a significant improvement in total NMSS score (27% and 29% reduction) at M6 and M12, respectively, which is consistent with the concept that specific non-motor features can be ameliorated by optimizing dopaminergic delivery [23]. Indeed, Storch and colleagues have recently shown that a majority of PD patients with motor fluctuations report greater prevalence of a variety of non-motor symptoms when in the " Off " as compared to the " On " state and also had greater non-motor symptom severity in the " Off " versus " On " state [24]. Improvement in the NMSS does not allow us to establish precisely whether this is linked to " Off " time reduction, but the observation that this was driven by items such as sleep/fatigue and urinary problems supports sensitivity of these domains to dopaminergic therapy [12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Intermittent oral delivery of levodopa is a major contributing factor for motor complications in Parkinson's disease (PD). Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) into the jejunum using a portable pump via percutaneous endoscopic gastrostomy (PEG) improves motor complications and quality of life (QoL). Objectives: To record long-term effectiveness of advanced PD patients undergoing LCIG infusion in routine care, by Unified Parkinson's Disease Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), PDQ-8 and EQ-5D questionnaires. Methods: Overall, 375 patients from 75 movement disorder centers in 18 countries were enrolled in this prospective non-interventional study. The 12-month interim outcomes of the first 172 included patients are presented here. Results: There were reductions of mean daily "Off" time from baseline (BL) (7.1 +/- 3.5 h) and "On" time with dyskinesias (5.2 +/- 4.5 h) at month 12 (M12) of -4.7 +/- 3.4 and -1.7 +/- 5.0 h respectively (p < 0.0001; p = 0.0228). UPDRS II and III "On" scores decreased from BL to M12 (p = 0.0107 and p = 0.0128). Total NMSS and PDQ-8 scores improved at M12 (p = 0.0014 and p = 0.0100). Mean LCIG dose administered through PEG at first visit (day after implantation) was 1304 +/- 618 mg/day and remained stable through M12. Continuous LCIG infusion tolerability and adverse drug reactions were consistent with the known safety profile of previous studies. Conclusions: This observational, routine-care study supports long-term safety and efficacy of LCIG infusion in advanced PD including motor, non-motor and QoL improvements. (C) 2015 AbbVie Inc. employs authors Yegin, Preda, and Bergmann. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (
    Parkinsonism & Related Disorders 12/2014; 21(3). DOI:10.1016/j.parkreldis.2014.12.012 · 3.97 Impact Factor
Show more