Many of the motor symptoms of Parkinson disease (PD) can be preceded, sometimes for several years, by non-motor symptoms that include hyposmia, sleep disorders, depression and constipation. These non-motor features appear across the spectrum of patients with PD, including individuals with genetic causes of PD. The neuroanatomical and neuropharmacological bases of non-motor abnormalities in PD remain largely undefined. Here, we discuss recent advances that have helped to establish the presence, severity and effect on the quality of life of non-motor symptoms in PD, and the neuroanatomical and neuropharmacological mechanisms involved. We also discuss the potential for the non-motor features to define a prodrome that may enable the early diagnosis of PD.

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Non-motor features of Parkinson disease.

Patients suffering from Parkinson's disease (PD) will typically experience a range of motor and nonmotor symptoms during the course of their illness, each of which will affect a particular individual to varying degrees. However, patients' perceptions of troublesome symptoms often differ from the clinician's view, and these discrepancies can hamper effective management of PD. In this study, we have assessed 265 consecutive PD patients by asking them to rank their three most troublesome symptoms in the last 6 months, so to gain further insight from the impact of illness on patients' quality of life. Patients were divided into early ( /=6 years) from symptom onset. The division at 6 years was based on the mean time from symptom onset to the development of motor complications. In the early PD group, the 5 most prevalent complaints (ranked in descending order) are slowness, tremor, stiffness, pain, and loss of smell and/or taste. In the advanced PD group, fluctuating response to their medication (most common: wearing-off phenomenon followed by dyskinesia), mood changes, drooling, sleep problems (most common: middle and late night insomnia followed by daytime sleepiness), and tremor were the top 5. Our findings provide further evidence for the diversity of experience in PD and suggest that as the disease advances the most troublesome issues that patients perceive are the lack of response to medication and the nonmotor aspects of the disease, highlighting the importance of assessment and patient-centered management in the follow-up of these patients.

Parkinson's Disease Symptoms: The Patient's Perspective

Changes in sensory function that have been described in patients with Parkinson disease (PD) can be either 'pure' disorders of conscious perception such as elevations in sensory threshold, or disorders of sensorimotor integration, in which the interaction between sensory input and motor output is altered. In this article, we review the extensive evidence for disrupted tactile, nociceptive, thermal and proprioceptive sensations in PD, as well as the influences exerted on these sensations by dopaminergic therapy and deep brain stimulation. We argue that abnormal spatial and temporal processing of sensory information produces incorrect signals for the preparation and execution of voluntary movement. Sensory deficits are likely to be a consequence of the dopaminergic denervation of the basal ganglia that is the hallmark of PD. A possible mechanism to account for somatosensory deficits is one in which disease-related dopaminergic denervation leads to a loss of response specificity, resulting in transmission of noisier and less-differentiated information to cortical regions. Changes in pain perception might have a different explanation, possibly involving disease-related effects outside the basal ganglia, including involvement of peripheral pain receptors, as well as structures such as the periaqueductal grey matter and non-dopaminergic neurotransmitter systems.

Pathophysiology of somatosensory abnormalities in Parkinson disease

Differences in the expression of non-motor symptoms (NMS) by Parkinson's disease (PD) patients may have important implications for their management and prognosis. Gender is a basic epidemiological variable that could influence such expression. The present study evaluated the prevalence and severity of NMS by gender in an international sample of 951 PD patients, 62.63% males, using the non-motor symptoms scale (NMSS). Assessments for motor impairment and complications, global severity, and health state were also applied. All disease stages were included. No significant gender differences were found for demographic and clinical characteristics. For the entire sample, the most prevalent symptoms were Nocturia (64.88%) and Fatigue (62.78%) and the most prevalent affected domains were Sleep/Fatigue (84.02%) and Miscellaneous (82.44%). Fatigue, feelings of nervousness, feelings of sadness, constipation, restless legs, and pain were more common and severe in women. On the contrary, daytime sleepiness, dribbling saliva, interest in sex, and problems having sex were more prevalent and severe in men. Regarding the NMSS domains, Mood/Apathy and Miscellaneous problems (pain, loss of taste or smell, weight change, and excessive sweating) were predominantly affected in women and Sexual dysfunction in men. No other significant differences by gender were observed. To conclude, in this study significant differences between men and women in prevalence and severity of fatigue, mood, sexual and digestive problems, pain, restless legs, and daytime sleepiness were found. Gender-related patterns of NMS involvement may be relevant for clinical trials in PD.

Gender-related differences in the burden of non-motor symptoms in Parkinson's disease.

Chronic pain is a frequent component of many neurological disorders, affecting 20-40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.

Neurological diseases and pain.

Parkinson’s disease is a chronic, progressive, incurable neurodegenerative disease. As the disease progresses, motor disturbances and non-motor symptoms represent considerable illness burdens. Symptom relief is the goal for the treatment. Pain is frequently observed in patients with Parkinson’s disease, but its prevalence, characteristics and associations with Parkinson’s disease are poorly documented. These were investigated in 176 home-living PD patients. They underwent a neurological examination and a structured interview for registration of pain characteristics in addition to responding to standardised questionnaires. Pain was reported by 146 (83%) patients. Compared to the general population, the Parkinson’s disease patients experienced significantly more pain as measured by SF-36 Bodily Pain Scale. The average pain during the last 24 h measured by the Brief Pain Inventory was 2.85. Fifty-three percent of the patients reported one, 24% reported two and 5% reported three pain types. Musculoskeletal pain was reported by 70%, dystonic pain by 40%, radicular-neuropathic pain by 20% and central neuropathic pain by 10%. Thirty-four percent were on analgesic medication. Pain was not associated with age, disease duration or severity of the disease; female gender was the only significant predictor of pain. Pain is frequent and disabling, independent of demographic and clinical variables except for female gender, and is significantly more common in Parkinson’s patients compared to the general population. A minority of the Parkinson’s disease patients with pain received analgesic medication. The findings call for improved attention to assessment and treatment of pain in the follow-up of Parkinson’s disease patients.

A. Rønningen

Papers

Pain in Parkinson's disease: Prevalence and characteristics.