INTRODUCTION — First described by James Parkinson in his classic 1817 monograph, "An Essay on the Shaking Palsy" [1], Parkinson disease (PD; also known as paralysis agitans) is a progressive neurodegenerative disease that affects between 100 and 200 per 100,000 people over 40, and over 1 million people in North America alone [2,3]. PD is uncommon in people younger than 40, and the incidence of the disease increases rapidly over 60 years, with a mean age at diagnosis of 70.5 years [4].
While PD has traditionally been considered a motor system disorder, it is now recognized to be a complex condition with diverse clinical features that include neuropsychiatric and other nonmotor manifestations in addition to its motor symptomatology [5]. An accurate diagnosis of PD rests on the clinician's ability to recognize its characteristic signs and associated symptoms, especially in the early stages.
This topic will review the clinical manifestations of PD. The diagnosis and treatment of PD are discussed separately. (See "Diagnosis and differential diagnosis of Parkinson disease" and "Initial pharmacologic treatment of Parkinson disease" and "Nonpharmacologic management of Parkinson disease" and "Management of nonmotor symptoms in Parkinson disease".)
EPIDEMIOLOGY — The epidemiology of PD is reviewed in detail elsewhere. (See "Epidemiology, pathogenesis, and genetics of Parkinson disease", section on 'Epidemiology'.)
CARDINAL FEATURES — The cardinal features of PD are tremor, bradykinesia, and rigidity. A fourth feature, postural instability, is commonly mentioned, although it does not generally occur until much later in the course of the disease and is thus not included in any published diagnostic criteria for PD [6-9]. The severity of motor symptoms appears to be an independent predictor of mortality in patients with PD [10].
Tremor — The tremor in PD, typically described as "pill-rolling," is a rest tremor, meaning that it is most noticeable when the tremulous body part is supported by gravity and not engaged in purposeful activities. Tremors in other conditions, such as essential tremor or multiple sclerosis, are typically action tremors, in which the tremor occurs when the affected limb is being used. (See "Overview of tremor".)
It is not unusual for a parkinsonian tremor to be present with postural maneuvers or with action, but in such cases, the tremor is typically much more severe at rest. Because parkinsonian tremor decreases with purposeful action, it is usually the least disabling of the cardinal manifestations. However, when the tremor is severe, it can be difficult to distinguish a primary resting tremor from a primary action tremor. Some patients with PD may have a re-emergent tremor: a postural tremor that manifests after a latency of several seconds and has a frequency typical of the rest tremor in PD [11,12]. This distinction is important, as patients with PD who have a re-emergent postural tremor may be misdiagnosed as having essential tremor [13].
The tremor of early PD is most often intermittent, and may not be noticeable to others. In fact, approximately half of patients with PD report a sensation of internal tremulousness in the limbs or body that is unrelated to the presence of observable tremor [14]. However, as the disease progresses, tremor usually becomes evident.
In the clinical setting, tremor in the limbs can be seen when the patient is relaxed with the hands resting quietly on the lap. Distracting the patient by asking him or her to perform mental calculations or voluntary repetitive movements of the contralateral limb often accentuates a mild tremor and may uncover a latent tremor. A resting hand tremor may be present only during the gait evaluation.
The frequency of the tremor in PD is between 3 and 7 Hz, and most often is between 4 and 5 Hz [15]. Tremor is the presenting symptom in approximately 70 to 80 percent of patients with PD [16,17], and the percentage of patients with tremor at some point in the course of the disease is high, ranging from 79 to 100 percent [16,18-21]. Tremor usually starts unilaterally in the hand, and then spreads contralaterally several years after the onset of symptoms [22]. The side that is initially affected tends to be the more affected side throughout the course of the disease.
The tremor of PD can also involve the legs, lips, jaw, and tongue, but rarely involves the head [15,23]. Anxiety, emotional excitement, or stressful situations can exacerbate the tremor.
Bradykinesia — Bradykinesia is a generalized slowness of movement, and is present at onset of PD in approximately 80 percent of patients [17]. It is arguably the major cause of disability in PD and is eventually seen in almost all patients. While it is the most common feature in PD, it is also the most difficult symptom for patients to describe. "Weakness," "incoordination," and "tiredness" are often used to describe the decreased ability to initiate voluntary movement.
In the arms, bradykinesia typically starts distally with decreased manual dexterity of the fingers. Patients often complain of difficulty performing simple tasks, such as buttoning clothes, tying shoelaces, double clicking a computer mouse, typing, or lifting coins from a pocket or purse.
In the legs, common complaints related to bradykinesia when walking include dragging the legs, shorter (shuffling) steps, or a feeling of unsteadiness. Patients may also have difficulty standing up from a chair or getting out of a car. As the disease progresses, gait freezing and festination may develop. James Parkinson defined festination as "an irresistible impulse to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace" [1].
Clinical examination of bradykinesia includes evaluation of limb movements on each side of the body. The speed, amplitude, and rhythm of finger tapping, hand opening-closing, pronation-supination hand movements, and heel or toe tapping should be carefully observed. In mild PD, these tasks usually show some slowing and decreased amplitude when observed for more than a few seconds. As the disease progresses, movements become less coordinated, with frequent hesitations and/or arrests.
Rigidity — Rigidity is an increased resistance to passive movement about a joint and occurs in approximately 75 to 90 percent of patients with PD [16-20]. Rigidity, like tremor and bradykinesia, often begins unilaterally, and typically on the same side as the tremor if one is present. Rigidity eventually progresses to the contralateral side, and remains asymmetric throughout the disease [22].
Cogwheel rigidity can be seen in PD, and the term refers to a ratchety pattern of resistance and relaxation as the examiner moves the limb through its full range of motion [24]. This phenomenon is thought to be a manifestation of tremor superimposed on increased tone [25]. However, not all patients with PD have cogwheel rigidity; many instead will have lead-pipe rigidity, a tonic resistance that is smooth throughout the entire range of passive movement.
Rigidity can affect any part of the body, and may contribute to complaints of stiffness and pain. Features, such as the striatal hand (extension of the proximal and distal interphalangeal joints with flexion at the metacarpophalangeal joints), decreased arm swing with walking, and the typical stooped posture, result, at least in part, from rigidity.
At the bedside, rigidity is tested by passively manipulating the limbs. It can be brought out by having the patient perform repetitive maneuvers using the contralateral limb or by performing mental arithmetic.
Postural instability — Postural instability is an impairment of centrally mediated postural reflexes that cause a feeling of imbalance and a tendency to fall with a significant risk of injury. Because postural instability usually does not appear until later in the course of PD, patients with parkinsonian signs who fall early in the course of the illness most likely have another parkinsonian syndrome, such as progressive supranuclear palsy or multiple system atrophy (MSA). (See "Diagnosis and differential diagnosis of Parkinson disease", section on 'Differential diagnosis'.)
Postural instability is tested clinically with the "pull" test, where the examiner stands behind the patient and firmly pulls the patient by the shoulders. Patients with normal postural reflexes should be able to maintain balance and retropulse (step backward) no more than one step. Patients with PD and postural instability, on the other hand, are likely to fall or take multiple steps backwards.
Initially, a positive pull test may be the only sign of balance impairment. However, as postural instability progresses, the gait may show signs of festination. Once postural reflexes are lost, patients generally require a wheelchair for safety.
Among the primary motor features of PD, postural instability is the least responsive to dopaminergic therapies [26]. In addition, postural instability and gait difficulty are major contributors to disability in patients with PD [27].
CLINICAL SUBTYPES — Some investigators have postulated that the rate of disease progression in PD varies for certain clinically defined subgroups or subtypes of PD [28-30].
The major subtypes are as follows:
●Tremor-dominant
●Akinetic-rigid
●Postural instability and gait difficulty
Several studies have compared the tremor-dominant subtype with either the akinetic-rigid or the postural instability and gait difficulty subtypes, and most have found that the tremor-dominant subtype was associated with slower progression and less neuropsychologic impairment than the other two groups [31-37].
While some clinicians may find these groupings useful, clinical PD progression is highly variable among individuals, and assignment of patients to subtypes can change as the disease progresses [37,38]. Thus, there are currently no symptoms or signs in idiopathic PD that allow a practitioner to accurately predict the future course of PD for any given individual.
OTHER MOTOR FEATURES — In addition to the cardinal manifestations just discussed, there are a number of other motor features seen in PD (table 1):
●Craniofacial
•Hypomimia (masked facial expression)
•Decreased spontaneous eye blink rate
•Speech impairment, including hypokinetic dysarthria, hypophonia, and palilalia (repetition of a phrase or word with increasing rapidity)
•Dysphagia
•Sialorrhea
●Visual
•Blurred vision
•Impaired contrast sensitivity
•Hypometric saccades
•Impaired vestibuloocular reflex
•Impaired upward gaze and convergence
•Eyelid-opening apraxia
●Musculoskeletal
•Micrographia
•Dystonia
•Myoclonus
•Stooped posture
•Camptocormia (severe anterior flexion of the thoracolumbar spine) [39]
•Pisa syndrome (subacute axial dystonia with lateral flexion of the trunk, head, and neck) [40-42]
•Kyphosis
•Scoliosis
•Difficulty turning in bed
●Gait
•Shuffling, short-stepped gait
•Freezing
•Festination
Most of these features result from one or more of the cardinal manifestations. As examples, decreases in spontaneous associated movements, such as loss of gestures during conversation, decreased eye blinking, or facial masking, probably result from a combination of bradykinesia and rigidity. Dysphagia is due to bradykinesia of the pharyngeal musculature, which can lead to pooling of saliva in the mouth and drooling (sialorrhea) [43].
NONMOTOR SYMPTOMS — PD has traditionally been considered a motor system disorder, but it is now widely recognized to be a complex disorder with diverse clinical features that include neuropsychiatric and nonmotor manifestations in addition to its motor symptomatology [44-48]. These features include the following:
●Cognitive dysfunction and dementia
●Psychosis and hallucinations
●Mood disorders including depression, anxiety, and apathy/abulia
●Sleep disturbances
●Fatigue
●Autonomic dysfunction
●Olfactory dysfunction
●Gastrointestinal dysfunction
●Pain and sensory disturbances
●Dermatologic findings
In a multicenter survey of over 1000 patients with PD, virtually all (97 percent) patients reported nonmotor symptoms, with each patient experiencing an average of approximately eight nonmotor symptoms [45]. Nonmotor symptoms in the psychiatric domain occurred most frequently. Psychiatric symptoms such as psychosis or dementia may cause more disability than the motor features and may be more difficult to treat. In a single-center survey of 265 patients with PD, pain, mood disorders, and sleep problems were the most troublesome nonmotor symptoms occurring in both early- and late-stage PD [49].
In some patients, certain nonmotor features of PD (eg, olfactory dysfunction, constipation, depression, and rapid eye movement [REM] sleep behavior disorder [RBD]) may present before the motor ones [5]. The most clinically relevant nonmotor manifestations of PD will be reviewed here individually.
The management of nonmotor symptoms of PD is discussed separately. (See "Management of nonmotor symptoms in Parkinson disease".)
Cognitive dysfunction and dementia — Cognitive dysfunction and dementia are common in PD, and the presence of dementia appears to be an independent predictor of mortality in PD [10]. In community-based studies, the prevalence of dementia in PD is as high as 41 percent, and in longitudinal studies, the cumulative incidence of dementia in PD is as high as 78 percent. Older age and severity of PD motor symptoms are consistently associated with an increased risk of developing dementia in prevalence and incidence studies. Later age of onset of PD, longer duration of PD symptoms, the presence of hallucinations, depressive symptoms, and a family history of dementia may also be risk factors for dementia. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Epidemiology'.)
The dementia of PD is classically considered a subcortical dementia, with psychomotor retardation, memory difficulty, and altered personality. Patients with PD typically report problems with executive function (decision-making or multitasking), memory retrieval, and visuospatial misperception. Deficits in executive functioning are often the earliest indicators of disturbed cognition. This is in contrast to Alzheimer disease (AD), the prototypical cortical dementia, with features of aphasia and apraxia. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Clinical features'.)
The anatomic and pathologic basis of PD dementia (PDD) is not fully understood. Neuropathologic studies have shown that patients with PD and dementia have a mixture of cortical neuronal Lewy inclusion bodies filled with alpha-synuclein and the signature amyloid plaques and neurofibrillary tangles of AD. However, the degree of Lewy body pathology (Lewy bodies and Lewy neurites) correlates better with cognitive decline and dementia than does the degree of Alzheimer pathology, which is relatively modest in these patients. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Neuropathology'.)
Dementia usually occurs late in the course of PD. Complicating the diagnosis of dementia in PD is the entity of dementia with Lewy bodies (DLB). This illness is characterized primarily by dementia, but it also has parkinsonian features, visual hallucinations, and fluctuating cognition. Because of the overlapping clinical as well as pathological similarities (Lewy bodies in the limbic cortex and neocortex) between DLB and PD with dementia, many experts believe the two conditions may be two ends of the same disorder. (See "Clinical features and diagnosis of dementia with Lewy bodies" and "Epidemiology, pathology, and pathogenesis of dementia with Lewy bodies".)
Clinically, patients are diagnosed with PDD if their illness begins with PD and they develop dementia at least a year after the onset of parkinsonian motor symptoms. (See "Cognitive impairment and dementia in Parkinson disease", section on 'Evaluation'.)
When dementia begins before or concurrently with parkinsonian motor symptoms, DLB is the more likely diagnosis. (See "Clinical features and diagnosis of dementia with Lewy bodies", section on 'Evaluation and diagnosis'.)
Psychosis and hallucinations — Psychosis occurs in 20 to 40 percent of drug-treated patients with PD, and visual hallucinations are the most common psychotic symptom [50-52]. Auditory, olfactory, and tactile hallucinations also occur in PD, although less frequently, and generally in conjunction with visual hallucinations [50,53]. The prevalence and severity of hallucinations increase over time in patients with PD [54]. (See "Approach to the patient with visual hallucinations", section on 'Neurodegenerative disease'.)
When psychosis occurs, it is attributable to the underlying Lewy body disease, to antiparkinson drug therapy, or to a combination of the two. All antiparkinsonian medications have been reported to induce psychosis [55,56], yet certain drugs are more likely than others to cause psychotic symptoms. For example, large trials of dopamine agonists have demonstrated that visual hallucinations are more likely to result from these agents than levodopa [57,58]. Psychotic symptoms may persist but generally resolve when PD medications are discontinued [59]. However, the duration or dose of antiparkinsonian drug therapy correlates poorly with the severity of psychosis [60].
Delusions can also be a prominent feature of psychosis in PD, and are usually paranoid in nature. Common delusions include spousal infidelity, people stealing money, intruders living in the house, or nurses planning harmful plots. Many patients with PD who have psychotic symptoms nevertheless retain the insight that their hallucinations are not real. However, patients with PD can also have delirium or dementia and manifest psychosis as a result. The patients in this latter category tend to be less responsive to treatment.
Studies have shown that psychosis, not motor dysfunction, is the single greatest risk factor for nursing home placement in patients with PD [61,62]. Psychosis is also associated with increased caregiver burden [63] and an increased risk of mortality [10,64]. Commonly reported risk factors for psychosis in PD include the use of high doses of antiparkinson drugs, the presence of dementia, advancing age, impaired vision, depression, presence of sleep disorders, high comorbid disease burden, and longer disease duration [51,60,65,66].
Mood disorders — Depression, anxiety, and abulia or apathy are mood disorders that occur most often in patients with PD. As noted above, mood disorders were ranked among the most troublesome nonmotor symptoms in a survey of patients with both early- and late-stage PD [49].
Depression — Depression is the most common psychiatric disturbance seen in PD [67]. Though generally mild to moderate in severity, depressive symptoms in PD are associated with a negative impact on motor disability and decreased quality of life [68-70].
Estimates for the prevalence of depression in PD vary, but up to 50 percent of patients have depressive symptoms, occasionally as a presenting complaint [67,70-72]. The rates for major depressive disorder in PD are less, ranging from less than 10 percent in community studies [71,73], to more than 20 percent in specialty movement disorder clinics [74-76]. Despite the high prevalence, however, depression in PD remains undertreated [70,74,77].
Recognizing depressive features in PD is a challenge. The psychomotor slowing and blunted affect commonly seen with depression often resemble the bradykinesia and masked facial expression seen in PD. Furthermore, somatic features of depression, such as decreased appetite, difficulty with concentration, and sleep disturbances, are commonly seen in patients with PD who do not have depression.
Patients with PD who develop depression usually present with sadness, anhedonia, and decreased interest in activities. Guilt and feelings of worthlessness may occur less frequently in PD-related depression [78]. Suicide occurs at approximately the same rate in PD as in the general population [79], but suicide rates may be increased after deep brain stimulation. (See "Device-assisted and lesioning procedures for Parkinson disease", section on 'Complications and adverse effects'.)
Anxiety — Anxiety is the next most frequent psychiatric disturbance in PD [67] and is estimated to occur in approximately 30 to 40 percent of patients [76,80]. All types of anxiety disorders have been reported in PD, though generalized anxiety disorder and social phobia appear to be the most common [80-82]. Depression and anxiety are often comorbid conditions in PD [83]; they are also associated with "on-off" fluctuations, with worsened mood and anxiety during "off" periods, and with improvement when in the "on" state [84-86].
Apathy and abulia — Apathy has been defined as a primary loss of motivation, characterized by diminished speech, motor activity, and emotional expression [87]. This definition of apathy is essentially synonymous with that of abulia, which has been defined as a loss of the impulse, will, or motivation to think, speak, and act. Diminished motivation is the key concept in both apathy and abulia. The neurologic basis of apathy and abulia is most commonly ascribed to frontal lobe and limbic system dysfunction [88-90].
While apathy frequently accompanies depression, it can occur in patients with PD who do not have depression [91,92]. A potentially useful discriminating characteristic is mood, which is neutral in apathy and negative in depression [87]. In a systematic review and meta-analysis of 23 studies with over 5300 subjects with PD, the following observations were made [93]:
●The pooled prevalence of apathy was 40 percent, but ranged from 17 to 62 percent due to heterogeneity of studies
●Apathy was associated with older age, cognitive impairment, depression, increased motor symptoms, and more severe disability
●Among patients with apathy, coexisting depression was present in 58 percent
●The prevalence of apathy among those without depression or cognitive impairment was 23 percent; this finding supports the view that apathy is a separate clinical feature of PD
●Apathy was less prevalent in patients with higher levodopa equivalent dose (mainly dopamine agonists), suggesting that dopamine agonists are a possible therapy
The presence of apathy has a negative impact on quality of life in patients with PD [45]. Apathy may coexist with impulse control disorders, which also have detrimental effects on quality of life [76]. (See "Initial pharmacologic treatment of Parkinson disease", section on 'Impulse control disorders'.)
Sleep disorders — Sleep disorders including insomnia, daytime sleepiness with sleep attacks, restless legs syndrome (RLS), and REM sleep behavior disorder (RBD) affect between 55 and 80 percent of patients with PD [94,95]. As noted above, sleep difficulty was ranked as one of the most troublesome nonmotor symptoms in a survey of patients with both early- and late-stage PD [49]. The most common sleep disturbances in PD are sleep fragmentation (frequent awakening throughout the night) and early morning awakening.
●In a prospective eight-year longitudinal cohort study, insomnia (including sleep initiation problems, sleep fragmentation, or early awakening) was reported by 54 to 60 percent of patients with PD [96]. On multivariate analysis, insomnia was associated with depressive symptoms, female sex, and disease duration.
●It is estimated that approximately 40 percent of patients with PD take medications for sleep, significantly more than is taken in the general older adult population [94,96].
There are many potential causes of frequent awakenings in PD, but the most common are nocturia, difficulty turning over in bed, cramps, vivid dreams or nightmares, and pain (especially in the neck or back) [96-100]. Tremor may also contribute to sleep fragmentation. The rest tremor in PD disappears with REM sleep, but recurs during light sleep and may awaken the patient as a result [101]. Some patients may have painful dystonia, especially of the legs, which typically occurs in the early morning and disrupts sleep. Depression is also commonly associated with poor sleep efficiency, decreased sleep time, and early morning awakening [102].
Symptoms of RLS are often reported in PD. RLS is a movement disorder characterized by an urge to move the limbs, associated with an unpleasant sensation that occurs mainly or exclusively at night, emerges or worsens with rest, and improves with movement, especially walking. The prevalence of RLS in patients with PD is uncertain, as data are inconsistent. Furthermore, the prevalence of RLS in PD is difficult to assess because of overlapping clinical features between RLS and PD, such as "wearing off" symptoms related to levodopa therapy and akathisia (a state of motor restlessness characterized by the inability to sit or lie still). These issues are reviewed separately. (See "Clinical features and diagnosis of restless legs syndrome and periodic limb movement disorder in adults", section on 'Parkinson disease'.)
Periodic limb movements of sleep (PLMS) are frequently but not always associated with RLS. The symptoms of PLMS are typically slow rhythmic movements of the legs, consisting of dorsal flexion of the foot and great toe [103]. In some patients, flexion of the knee and hip may also occur. Estimates of the prevalence of PLMS in patients with PD range from 30 to 80 percent [104].
RBD is another nocturnal disorder commonly seen in patients with PD [105]. This disorder is characterized by vigorous movements that are related to increased muscle tone during REM sleep [106]. Patients with RBD often act out their dreams and exhibit vocalizations as well as flailing, kicking, and punching motions of the limbs. Some patients may injure themselves or their bed partners. Behaviors related to RBD are reported to occur in 15 to 47 percent of patients with PD [105,107,108], and over three-quarters of spontaneous RBD cases eventually develop PD or other alpha-synucleinopathies, often years after the onset of RBD. (See "Rapid eye movement sleep behavior disorder".)
Excessive daytime sleepiness — Excessive daytime sleepiness (EDS) has long been recognized as a problem in PD [65,109,110]. The prevalence of EDS in PD varies according to study methodology, but estimates range from 33 to 76 percent [111-114]. Some patients may just be sleepy, while others have additional unintended sleep episodes or sudden sleep "attacks" [115]. EDS and sudden somnolence can be a hazard for patients with PD who drive [116].
EDS in PD is likely multifactorial. Possible risk factors include difficulty sleeping at night, depression, dementia, dopaminergic treatment, high comorbid disease burden, and male sex [66,117-121]. It has also been argued that EDS may be intrinsic to the disease process [122].
Fatigue — Fatigue is a common problem in patients with PD, with prevalence rates of 33 to 58 percent [110,123-129]. In a population-based longitudinal cohort study of fatigue in 233 patients with PD, the following observations were reported [128]:
●The proportion of patients with PD who had mental fatigue increased from 36 to 56 percent over eight years of follow-up
●Fatigue was significantly related to PD progression, depression, and EDS
●The prevalence of fatigue remained high (32 to 39 percent over the study period) even in patients without depression and EDS
●When present in patients with PD, fatigue was persistent in 56 percent and intermittent in 44 percent
Although fatigue is associated with depression and EDS, several studies have found that patients with PD who do not have depression or EDS nonetheless have a high prevalence of fatigue [124,125,128]. These data support the hypothesis that fatigue is an independent symptom of PD that overlaps with, but is not causally related to, depression and EDS. The pathophysiology of fatigue in PD is not understood.
Autonomic dysfunction — Autonomic problems in PD include orthostasis, constipation, dysphagia, diaphoresis, urinary difficulties, and sexual dysfunction [130,131]. These problems are also present in multiple system atrophy (MSA), making it difficult to distinguish between the two disorders. The autonomic symptoms in MSA, however, are generally more severe than in PD. Furthermore, MSA tends to be less responsive to levodopa as the disease progresses, and MSA is often associated with cerebellar and pyramidal findings. (See "Multiple system atrophy: Clinical features and diagnosis".)
Orthostatic hypotension is very common in patients with PD, even relatively early in the course of disease, with a cumulative prevalence of approximately 60 percent [131-133]. Risk factors include older age, cognitive dysfunction, and longer disease duration [133]. In addition to the disease itself, orthostatic hypotension can be aggravated or caused by antiparkinsonian agents including levodopa, dopamine agonists, and monoamine oxidase type B (MAO B) inhibitors, and other drugs, particularly alpha-adrenergic blockers such as tamsulosin for prostatism.
Common urinary symptoms indicative of autonomic dysfunction in patients with PD include frequency, urgency, and urge incontinence [134,135]. The most common abnormality on urodynamic evaluation is reduced bladder capacity because of involuntary detrusor muscle contractions at early stages of bladder filling [136].
Sexual dysfunction can range from underactivity to hypersexuality and may affect up to 25 percent of patients with PD [137]. Underactive sexual behavior in PD commonly manifests as decreased interest and drive [138,139] and can be due to depression [140], axial rigidity, bradykinesia, or dissatisfaction with relationships [141]. Male patients may have the inability to achieve or maintain an erection, while female patients with PD often report vaginal tightness, dryness, an inability to achieve orgasm, or involuntary micturition during sex [139,142,143].
A separate issue is that hypersexuality can be associated with antiparkinsonian therapies, both pharmacologic and surgical. (See "Device-assisted and lesioning procedures for Parkinson disease", section on 'Deep brain stimulation' and "Initial pharmacologic treatment of Parkinson disease", section on 'Impulse control disorders'.)
Olfactory dysfunction — Olfactory dysfunction is very common in PD and can manifest as deficits in odor identification, discrimination, and detection [144]. Loss of smell often goes unnoticed by patients, even when dysfunction is present on smell testing. These deficits in olfaction may precede motor symptoms or occur relatively early in the course of PD [135,145,146]. Although nonspecific, olfactory dysfunction on smell testing in community-dwelling older adults is associated with an increased risk of incident PD over 5 to 10 years of follow-up [145-149].
Pain — Painful sensory symptoms are reported in up to 46 percent of patients with PD [150]. As noted above, pain was ranked as one of the most troublesome nonmotor symptoms in a survey of patients with both early- and late-stage PD [49]. The pain can be lancinating, burning, or tingling, and can be generalized or localized to different areas of the body, including the face, abdomen, genitals, and joints [150-152].
Painful sensations in PD tend to correlate with motor fluctuations. Dystonia, which is often painful, is a common symptom in PD. It can occur spontaneously in early PD, or it can occur when levodopa wears off. Morning dystonia affecting the foot is a common "off" response to abstinence from levodopa during sleep. [153]. However, levodopa-induced dyskinesia can be dystonic and painful as well. (See "Medical management of motor fluctuations and dyskinesia in Parkinson disease".)
Dermatologic findings — Seborrheic dermatitis is a common, well-recognized skin disorder that affects 20 to 60 percent of patients with PD, often as an early symptom [135,154]. It is unclear why it occurs so frequently in PD. Manifestations include scaly erythematous patches in areas of the skin rich with sebaceous glands, such as the scalp, face, and chest [155]. Other dermatologic changes include hyperhidrosis and dermatophytosis [135].
Melanoma occurs with a higher frequency in PD than in the general population. Based on a meta-analysis of 24 observational studies in a total of over 290,000 individuals, the risk of melanoma is nearly twofold higher in patients with PD (odds ratio [OR] 1.83, 95% CI 1.46-2.30) [156]. The exact relationship between PD and melanoma has not been fully elucidated. Although case reports have suggested an association between melanoma and levodopa therapy due to a shared dopamine biochemical pathway, a review of large cohort studies found that the risk of melanoma is elevated even before exposure to levodopa therapy [157].
DISEASE PROGRESSION AND PROGNOSIS — As noted above, progression in PD is variable, and there currently are no symptoms or signs in idiopathic PD that allow a practitioner to accurately predict the future course of PD for any given individual. (See 'Clinical subtypes' above.)
However, several observations provide insight into the general rate of disease progression in PD.
●In an early landmark study of patients with PD seen from 1949 to 1964, the proportion who were severely disabled or dead within five years of disease onset was approximately 25 percent [16]. This increased to 67 percent at five to nine years, and 80 percent at 10 to 14 years. A small group of atypical patients had slow disease progression, maintaining balance and postural stability for ≥10 years, and lacking severe disability even at ≥20 years. Results were similar in a later study of 142 patients with PD followed from 2000 to 2012, with approximately 77 percent having a poor outcome (ie, death, dementia, or postural instability) at 10 years after diagnosis [35].
●A report of 618 patients with PD found that the transition from disease impairment to disability occurred generally between three and seven years after the onset of PD [158]. Impairment was defined by difficulty with daily activities without loss of independent function, while disability was defined by loss of independent function.
●Most studies suggest that mortality is only modestly increased for patients with PD compared with age-matched controls [35,159-163]. A systematic review and meta-analysis found that mortality ratios varied widely among included studies, but nearly all showed increased mortality in PD, with a pooled mortality ratio 1.5 [164]. Median survival ranged from 6 to 22 years. Increasing age and presence of dementia were associated with an increased risk of mortality.
●The prevalence of dementia in PD is approximately 40 percent, and increases with age and disease duration. (See 'Cognitive dysfunction and dementia' above and "Cognitive impairment and dementia in Parkinson disease", section on 'Epidemiology'.)
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Parkinson disease (The Basics)")
●Beyond the Basics topics (see "Patient education: Parkinson disease symptoms and diagnosis (Beyond the Basics)")
PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Parkinson disease".)
SUMMARY AND RECOMMENDATIONS
●Cardinal features – The cardinal features of Parkinson disease (PD) are tremor, bradykinesia, and rigidity. Symptoms often begin unilaterally and later spread to involve both sides of the body. Postural instability is another key feature, but it generally occurs later in the course of the disease and is not included in the diagnostic criteria for PD.
•Tremor – The tremor of PD is typically described as "pill-rolling" because of the way the thumb and the fingers appear to be rolling a small object between them. It is most noticeable when the affected limb is relaxed or "at rest." Tremor can also involve the legs, lips, and jaw but rarely the head. (See 'Tremor' above.)
•Bradykinesia – Bradykinesia is a generalized slowness of movement. In the arms, bradykinesia typically starts distally with decreased manual dexterity of the fingers. In the legs, it manifests as dragging of the feet and shortened, shuffling steps. (See 'Bradykinesia' above.)
•Rigidity – Rigidity is an increased resistance to passive movement. In PD, rigidity may have a cogwheel or ratchety quality as the limb is moved through its full range of motion. In other patients, there is tonic resistance that is smooth throughout the entire range (lead-pipe rigidity). (See 'Rigidity' above.)
●Other motor features – In addition to the cardinal manifestations, other motor features of PD include craniofacial (eg, masked facial expression, hypophonia), visual (eg, hypometric saccades, eyelid-opening apraxia), musculoskeletal (eg, micrographia, stooped posture), and gait (eg, shuffling, short-stepped gait, freezing) abnormalities (table 1). (See 'Other motor features' above.)
●Nonmotor features – PD is a complex disorder with diverse clinical features that include nonmotor manifestations (table 2) in addition to motor symptomatology. These features include the following (see 'Nonmotor symptoms' above):
•Cognitive dysfunction, most commonly problems with executive function (decision-making or multitasking), memory retrieval, and visuospatial misperception (see 'Cognitive dysfunction and dementia' above)
•Psychosis, most commonly visual hallucinations (see 'Psychosis and hallucinations' above)
•Mood disorders including depression, anxiety, and apathy/abulia (see 'Mood disorders' above)
•Sleep disturbances, including frequent awakenings, restless legs syndrome (RLS), and rapid eye movement (REM) sleep behavior disorder (RBD) (see 'Sleep disorders' above)
•Excessive daytime sleepiness (EDS) and fatigue (see 'Excessive daytime sleepiness' above and 'Fatigue' above)
•Autonomic dysfunction, including orthostasis, constipation, dysphagia, diaphoresis, urinary dysfunction, and sexual dysfunction (see 'Autonomic dysfunction' above)
•Olfactory dysfunction (see 'Olfactory dysfunction' above)
•Pain and sensory disturbances (see 'Pain' above)
•Dermatologic findings, most commonly seborrheic dermatitis (see 'Dermatologic findings' above)
●Patient perspective – A patient perspective on the clinical manifestations of PD is provided separately. (See "Patient perspective: Parkinson disease".)
