Brenda L. Jordan Parkinson disease (PD) is a slowly progressive neurodegenerative disease with an insidious onset of the cardinal features of asymmetric resting tremor, bradykinesia, and rigidity, commonly with postural changes. The prevalence of PD is thought to be 0.3% in the general population and 1% in those older than 60 years. Worldwide, approximately 5 million people have PD; the incidence is 8 to 18.6 new cases per 100,000 person-years.1 Mean age at diagnosis is 70.5 years, with a rapid increase in incidence after the age of 65 years. PD is uncommon in those younger than 40 years. Studies show 50% more men with PD than women.2 The risk for development of PD appears to double if a first-degree relative has PD compared with people in the general population (Box 200-1).1,2 Traditionally considered a motor system disorder, PD is now recognized to be a complex disorder with diverse features. Those who develop PD may be affected by neuropsychiatric and other nonmotor manifestations in addition to the cardinal motor features.3 The specific mechanisms of the neurodegeneration of PD are not understood. It is most likely caused by a cascade of events between genetics and environmental factors,4,5 with abnormalities in protein processing,6 oxidative stress,7 mitochondrial dysfunction,8 inflammation and immune regulation, and other mechanisms. Purely genetic Parkinson varieties probably affect a small minority of people with the parkin gene on chromosome 6.4 PD develops after widespread depletion of dopamine in the substantia nigra and the nigrostriatal pathway to the caudate and putamen. Depigmentation, neuronal loss, and gliosis are most significant in the substantia nigra pars compacta and the pontine locus ceruleus. This dopamine depletion ultimately results in increased inhibition of the thalamus and reduced excitatory input to the motor cortex, which results in the cardinal features of PD: tremor at rest, rigidity, bradykinesia, and postural instability. Compensatory mechanisms, including the large number of acetylcholine-secreting neurons with excitatory signals that remain active in the presymptomatic phase of PD, mask the deleterious effects of dopamine depletion.16 The clinical features most suggestive of PD are asymmetric or unilateral tremor, rigidity, bradykinesia with freezing, and flexed posture with loss of postural reflexes. Some investigators have postulated that there are clinically defined subgroups or subtypes that may affect the rate of progression of PD. The subtypes are tremor dominant, akinetic-rigid, and postural instability and gait difficulty. The tremor dominant subtype is associated with slower progression and less neuropsychiatric impairment than in the other two groups.17 Rest tremor in PD is present at rest, is usually unilateral at first, and characteristically disappears with action. Rest tremor of the hands, described as “pill rolling,” increases with walking and may be an early sign when others are not yet present. Most often, patients with PD exhibit a slow, coarse tremor with a rate varying from two to five oscillations per second, usually averaging four or five oscillations per second when the hand is motionless and decreasing with postural changes. There is a clear distinction from essential or intention tremors, which appear only or primarily with deliberate, willed movement.18 Another classic sign is rigidity, an increased resistance to passive movement at a joint, which occurs in 90% of patients with PD. The increased resistance to passive movement is equal in all directions and usually manifests with a ratcheting or “cogwheeling” during the movement. Rigidity of the passive limb increases when another limb is engaged in voluntary active movement.19 The patient with PD often has a uniquely flexed posture involving the entire body. The head is bowed; the trunk is bent forward; the back is kyphotic; the hands are held in front of the body; and the elbows, hips, and knees are flexed. Deformities of the hands and feet may also be apparent. Lateral tilting of the trunk is common.19 Other features of PD are associated with slowness of movement (hypokinesia), loss of automatic movement (bradykinesia), and difficulty initiating movement (freezing) or an irresistible impulse to take much quicker and shorter steps, which creates an almost running pace (festination). Shuffling gait with a decrease in arm swing may be evident. Masked facies (a reduction in spontaneous facial expression) and decreased frequency of blinking are prevalent. Speech becomes soft (hypophonia), and the voice often has a monotonous tone with lack of inflection (aprosody of speech). Some patients are not able to enunciate clearly (dysarthria) or may experience repetition of syllables (palilalia). All of these features clearly respond to treatment with levodopa, which is considered both diagnostic and therapeutic.19 Postural reflexes can be tested by giving a sudden, firm pull on the shoulders from behind, but the health care provider should be prepared to catch the patient. Rigidity, demonstrated by cogwheeling, may be tested by grasping the patient’s elbow at the antecubital region and slowly flexing and extending the elbow or pronating-supinating the forearm. Walking can also be marked by festination, whereby the patient walks faster and faster with short steps, trying to move the feet forward under the flexed body’s center of gravity.19 The freezing phenomenon, a motor block, is a transient inability to perform active movements. It most often affects the legs but can involve eyelid opening, speaking, and writing. The feet may appear to be glued to the ground. Because patients with PD exhibit an increased ability to perform intentional or conscious movement as opposed to automatic movement, freezing can be overcome by having patients intentionally raise their legs as if stepping over objects or cycling. Despite severe bradykinesia with marked immobility, patients with PD may rise suddenly and move normally for a short burst of motor activity when physically cued (kinesia paradoxa).19 Diagnostic studies are usually not indicated. There are no physiologic tests or blood tests, and neuroimaging is most helpful in differentiation of PD from other neurodegenerative disorders but requires specific neuroimaging best identified by neurologic specialists. The “gold standard” for diagnosis is postmortem neuropathologic examination, especially noting midbrain Lewy bodies. Diagnosis of idiopathic PD is based on the clinical presentation and physical examination findings, with two of the three cardinal manifestations (tremor, bradykinesia, rigidity) present. A rest tremor with unilateral onset and excellent response to dopaminergic therapy are important criteria for the diagnosis of idiopathic PD.20,21 According to the 2006 American Academy of Neurology (AAN) systematic review and practice parameter, a number of clinical features in early-stage PD are probably useful in distinguishing other forms of parkinsonism from PD.22 The signs and symptoms of idiopathic PD can occur in other neurodegenerative disorders, including dementia with Lewy bodies, corticobasal degeneration, multiple system atrophy, and progressive supranuclear palsy. Secondary parkinsonism is seen in the presence of drug reactions (neuroleptics), infections (postencephalitic), metabolic disorders (parathyroid disorders), post-traumatic conditions, neoplastic disorders, toxicity (carbon monoxide), and vascular disorders. As previously noted, the diagnosis of PD and other forms of parkinsonism is often based on the response to levodopa, although this is no longer recommended.21 Bradykinesia and rigidity respond best, but lack of improvement does not exclude the diagnosis of PD. Tremor may never respond satisfactorily. Signs and symptoms that can be useful in identifying patients with parkinsonism other than PD are falls at presentation and early in the disease, poor response to levodopa, symmetry with onset of tremor, rapid progression of symptoms, lack of tremor, and dysautonomia.20,21
Parkinson Disease
Definition and Epidemiology
Pathophysiology
Clinical Presentation
Physical Examination
Diagnostics
Differential Diagnosis
Parkinson Disease
Chapter 200
