Elsevier

The Lancet Neurology

Volume 5, Issue 3, March 2006, Pages 235-245
The Lancet Neurology

Review
Non-motor symptoms of Parkinson's disease: diagnosis and management

https://doi.org/10.1016/S1474-4422(06)70373-8Get rights and content

Summary

The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.

Introduction

James Parkinson1 accurately described the motor problems of patients but also noted several non-motor features. The motor disorder of Parkinson's disease has been extensively researched resulting in improved diagnostic accuracy and development of robust rating scales and treatment startegies.2, 3 Despite this emphasis on motor symptomatology, several studies have shown that the non-motor symptoms of Parkinson's disease, such as depression, psychosis, falls, and sleep disturbance, have greater significance when assessed by quality-of-life measures, institutionalisation rates, or health economics.4, 5, 6, 7, 8, 9, 10, 11

Section snippets

The scale of the problem

Non-motor symptoms correlate with advancing age and disease severity, although some non-motor symptoms, such as olfactory problems, constipation, depression, and rapid eye movement disorder, can occur early in the disease (panel 1).12 As the average age and life expectancy of the population increases, the non-motor features of Parkinson's disease become increasingly important.12, 13 The prevalence of non-motor symptoms as a whole is inadequately documented because there are insufficient

Pathophysiology of the non-motor symptom complex and the Braak hypothesis

Our understanding of the sequence and distribution of pathological changes in Parkinson's disease continues to evolve with non-dopaminergic-cell dysfunction being thought to play a major part in the development of the non-motor symptom complex.15, 16 The neuroanatomical and neurochemical substrates for much of the non-motor symptom complex in Parkinson's disease are unknown. A substantial part of the discussion in relation to pathophysiology of non-motor symptoms, therefore, remains

Nocturnal non-motor symptoms

Virtually all patients with Parkinson's disease have sleep disruption and studies show that this usually starts early in the disease course.27, 28 The causes of sleep disturbance are multifactorial, but pathological degeneration of central sleep regulation centres in the brainstem and thalamocortical pathways is probably important. The pedunculopontine nucleus, the locus coeruleus, and the retrorubral nucleus affect normal REM atonia and phasic generator circuitry and, as discussed previously,

Recognition of non-motor symptoms

The non-motor-symptom complex of Parkinson's disease is frequently overlooked. In a prospective study of 101 patients, neurologists did not discuss important symptoms such as depression, anxiety, fatigue, and sleep disturbance with more than 50% of their patients.115 This finding could be a result of limited consultation time, perception of the patient and the carer that their symptoms are unrelated to the disease (eg, visual hallucinations or diplopia), or non-awareness of the physician who

Non-motor rating scales

Panel 3 lists some of the existing non-motor scales in Parkinson's disease. Most scales address individual non-motor symptoms such as sleep, excessive daytime sleepiness, dysautonomia, fatigue, psychosocial aspects and depression, and quality of life.116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 An integrated instrument that addresses the whole and diverse range of non-motor symptoms is not available to date, although some are in preparation

Burden of non-motor symptoms

Parkinson's disease decreases quality of life for patients and imposes a significant economic burden on society comparable with other chronic diseases, such as congestive heart failure, diabetes, and stroke.136, 137 The health economics in relation to hospital versus community-based management of non-motor symptoms is poorly evaluated, although individual symptoms such as visual hallucinations, dementia, and falls are a major source of hospitalisation and institutionalisation. A UK based cost

Is there a role for dopaminergic treatment?

A comprehensive description of the treatment strategies for the non-motor symptom complex of Parkinson's disease is beyond the scope of this review and we recommend a series of recent excellent reviews that focus on individual non-motor symptoms of the disease.28, 46, 48, 79, 86, 105 However, the evidence base for treatment of the non-motor symptom complex is poor and a review of the pharmacological and surgical treatments of the disease by the Movement Disorders Society Task Force highlighted

Conclusion

Early recognition of non-motor symptoms is essential for the care of patients with Parkinson's disease and the importance of a multidisciplinary approach, including support for carers, cannot be overemphasised.5 Poor recognition of non-motor symptoms affects cost of care of patients with the disease in society; the development of integrated methods to measure non-motor symptoms will help identification and the development of better treatment strategies in the future.

Search strategy and selection criteria

The review was based on information obtained from papers identified by searches of PubMed and Google with the terms “non motor”, “Parkinson's disease”, and “cognitive” as the main keywords, between 1960 and September 2005. Information was also obtained from perusal of abstract supplements of the Movement Disorders journal based on international congress proceedings. Articles were cited on the basis of importance in relation to non-motor aspects of Parkinson's disease, ease of access, and

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