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: 8.3). 01/2013; 80(9). DOI: 10.1212/WNL.0b013e318285c0ed
Source: PubMed

ABSTRACT OBJECTIVE: To evaluate frequency, severity, and correlation of nonmotor symptoms (NMS) with motor complications in fluctuating Parkinson disease (PD). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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    ABSTRACT: Editor's comment: Levodopa-carbidopa intestinal gel (LCIG) is a gel suspension of levodopa/carbidopa administered by continuous delivery via portable pump via PEG to a patients who typically have advanced PD. Although an expensive option, the effectiveness of this mode of treatment is confirmed by Antonini et al.'s long term study, which demonstrated a number of positive findings at 12 months, including almost 5 hours less off time, a 20% improvement in motor UPDRS, and worthwhile reductions in non-motor symptoms. 5% of patients had an adverse drug reaction leading to LCIG discontinuation, and the commonest side effects included loss of weight and abdominal pain (5.6 and 3.1% respectively). A particular concern is that of polyneuropathy (noted in 3%), and until the origin of this has been clarified, vitamin B12 supplementation is recommended. Global long-term study on motor and non-motor symptoms and safety of levodopa-carbidopa intestinal gel in routine care of advanced Parkinson's disease patients; 12-month interim outcomes Keywords: Advanced Parkinson's disease Duodenal levodopa-carbidopa infusion Motor symptoms Non-motor symptoms Quality of life Routine patient care a b s t r a c t Introduction: Intermittent oral delivery of levodopa is a major contributing factor for motor complica-tions 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 com-plications 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 À4.7 ± 3.4 and À1.7 ± 5.0 h respectively (p < 0.0001; p ¼ 0.0228). UPDRS II and III " On " scores decreased from BL to M12 (p ¼ 0.0107 and p ¼ 0.0128). Total NMSS and PDQ-8 scores improved at M12 (p ¼ 0.0014 and p ¼ 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.
    Parkinsonism & Related Disorders 12/2014; 21(3). DOI:10.1016/j.parkreldis.2014.12.012 · 4.13 Impact Factor
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    ABSTRACT: The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.
    Frontiers in Neurology 12/2014; 5:242. DOI:10.3389/fneur.2014.00242
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    ABSTRACT: Background The Mini-BESTest is a clinical balance test that has shown a high sensitivity in detecting balance impairments in elderly with Parkinson's disease (PD). However, its reproducibility between different raters and between test occasions has yet to be investigated in a clinical context. Moreover, no one has investigated the reproducibility of the Mini-BESTest's subcomponents (i.e. anticipatory postural adjustments; postural responses; sensory orientation and dynamic gait).We aimed to investigate the inter-rater and test-retest reproducibility (reliability as well as agreement) of the Mini-BESTest, as well as its subcomponents, in elderly with mild to moderate PD, performed under conditions assimilating clinical practice.Method This was an observational measurement study with a test-retest design.Twenty-seven individuals with idiopathic PD (66 - 80 years, mean age: 73; Hoehn & Yahr: 2-3; 1-15 years since diagnosis) were included. Two test administrators, having different experiences with the Mini-BESTest, administered the test individually, in separate rooms in a hospital setting. For the test-retest assessment, all participants returned 7 days after the first test session to perform the Mini-BESTest under similar conditions. Intra-class correlation coefficients (ICC2.1), standard error of measurement (SEMagreement), and smallest real difference (SRD) were analyzed.ResultsThe Mini-BESTest showed good reliability for both inter-rater and test-retest reproducibility (ICC = 0.72 and 0.80). Regarding agreement, the measurement error (SRD) was found to be 4.1 points (accounting for 15% of the maximal total score) for inter-rater reproducibility and 3.4 points (12% of the maximal total score) for test-retest reproducibility. The investigation of the Mini-BESTest's subcomponents showed a similar pattern for both inter-rater and test-retest reproducibility, where postural responses had the largest proportional measurement error, and sensory orientation showed the highest agreement.Conclusions Our findings indicate that the Mini-BESTest is able to distinguish between individuals with mild to moderate PD; however, when used in clinical balance assessments, the large measurement error needs to be accounted for.
    BMC Neurology 12/2014; 14(1):235. DOI:10.1186/s12883-014-0235-7 · 2.49 Impact Factor


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