Chapter 17 - The challenge of non-motor symptoms in Parkinson’s disease
Introduction
Non-motor symptoms (NMS) in Parkinson’s disease (PD) are common across all stages of PD but often receive little attention as NMS-related issues are often overshadowed by the motor symptoms. In spite of their importance there have been only two ‘holistic’ prevalence studies of NMS in PD, the NMSQuest study in 2007 and the PRIAMO study in 2009, both indicating the importance of NMS and its presence across all stages of common PD (Barone et al., 2009, Martinez-Martin et al., 2007). These NMS significantly impair quality of life and may precipitate hospitalization and strongly contribute to the cost of care for PD. NMS create a significant burden for people with PD and caregivers, and studies suggest that NMS are a greater determinant of quality of life than motor features. (Martinez-Martin et al., 2009). Some NMS, such as depression, dementia, dysautonomia, and sleep problems, are well established but others such as dysphagia, dribbling of saliva, weight changes, sexual problems, and diplopia are poorly recognized. In recent years, a self-completed NMS questionnaire and NMS scale has been validated specifically for use in PD and a recent international survey showed that up to 62% of NMS in PD might remain undeclared to healthcare professionals because patients may be unaware that the symptoms are linked to PD. (Chaudhuri et al., 2010).
In addition to the disease itself, some NMS can be precipitated by dopaminergic treatment of PD. Finally, non-motor fluctuations frequently complicate treatment, the symptoms occurring when there is low level of central dopaminergic stimulation (Muzerengi et al., 2007).
Section snippets
Pathogenesis
It is clear that several NMS have a relatively poor response to dopaminergic therapy, and other pathways including the serotonergic and noradrenergic ones are involved (Zgaljardic et al., 2004). Braak et al. have introduced the concept of a six-stage pathological process, beginning at induction sites with degeneration of the olfactory bulb and the anterior olfactory nucleus (clinically manifest as olfactory dysfunction) at stage 1, while stage 2 reflects progression of the pathological process
Non-motor symptoms can predict the emergence of motor symptoms of PD
It is well established that NMS of PD can present at any stage of the disease including a “pre-motor stage”. Prospective data suggest that at least four distinct NMS of PD such as olfactory problems, rapid eye movement behavior disorder (RBD), constipation, and depression may predate the motor signs (Abbot et al 2001; Berendse, 2006, Boeve et al., 2001, Chaudhuri et al., 2006a). Other symptoms include visual disturbances such as color vision disturbances and impairment in contrast sensitivity,
Prevalence of non-motor symptoms of PD
A recent international study validating a self-completed non-motor questionnaire (NMSQuest) by Chaudhuri and colleagues revealed that NMS are highly prevalent in PD patients compared with age-matched controls, and a typical patient reported 10–12 NMS (Chaudhuri et al., 2006b). This study also showed that NMS can occur in all disease stages and the number of symptoms correlates with disease duration and severity (Chaudhuri et al., 2006b). The NMS complex of PD is frequently unrecognized by
Non-motor fluctuations
Traditionally fluctuation of response to therapy in PD is recognized as motor fluctuations. However, non-motor fluctuations are prevalent and common and are arbitrarily subclassified as cognitive (clouding of thoughts, depression, apathy, panic), autonomic (sweating, lightheadedness), and sensory (pain, parasthesae) (Chaudhuri and Schapira, 2009). Therapies aimed at continuous drug delivery such as long-acting dopamine agonists, apomorphine infusion, intra-jejunal levodopa infusion may improve
Non-recognition of NMS
In a prospective study of PD patients followed up for 20 years, Hely et al. reported that non-levodopa-responsive NMS were the most disabling, ahead of levodopa-induced dyskinesias in the Sydney multicenter study (Hely et al., 2008). Subsequently, although both NMSQuest and PRIAMO study have indicated the importance of the overall burden of NMS in PD, the NMS of PD are not well recognized in clinical practice. A clinic-based US study showed that existing depression, anxiety, and fatigue are not
Self-declaration of NMS and empowering patients
Stacy et al. reported that NMS were common even in patients within 5 years of (motor) disease onset, and the use of a patient-completed questionnaire facilitated detection of these problems rather than routine clinic appraisal which is heavily biased towards motor symptoms. Recent studies using the non-motor questionnaire for PD (NMSQuest) have highlighted the significant occurrence of a range of 30 different NMS in PD in comparison with an age-matched control group (Fig. 1). These occurred
Management of NMS
Robust controlled studies are virtually nonexistent for the treatment of NMS in PD. However, there is some evidence from a handful of controlled trials for the treatment of certain NMS in PD, in particular depression, cognitive decline, psychosis, and EDS. Moreover, the effect of these treatments on quality of life in PD is lacking, and many trials include only small numbers of patients. Dopaminergic treatment has some effect on depressive symptoms. Pramipexole has been investigated for its
Conclusions
Delayed detection of NMS may lead to disability and poor quality of life, increasing the cost of care of PD in the society. NMS such as visual hallucinations, dementia, and falls are a major source of hospitalization and institutionalization. Recognition of NMS is therefore essential for the holistic management of PD and the importance of a multidisciplinary approach, including support for carers, cannot be overemphasized (Global Parkinson’s disease Survey Steering Committee, 2002).
Future perspective
In future, it is anticipated that there will be a focus on development of pre-symptomatic tests in asymptomatic individuals who are at increased risk of PD although this raises ethical issues if robust neuroprotective strategies are not available. The development of the NMS-orientated PD-specific tools such as the SCOPA instruments, the NMSQuest and NMS Scale, and the modified UPDRS suggest a growing interest in recognition and awareness of NMS complex of PD among clinicians and researchers and
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