Clinical Features

Parkinsonism is a general term used to define a syndrome of bradykinesia (slowness of voluntary movements) with rigidity and/or tremor (Table 186-1 Clinical Features of Parkinson's Disease); it has a wide differential diagnosis (Table 186-2 Differential Diagnosis of Parkinsonism). Parkinson's disease (PD) is idiopathic parkinsonism without evidence of more widespread neurologic involvement. PD afflicts >1 million individuals in the United States. Mean age of onset is about 60 years; course progressive over 10-25 years. Tremor (“pill rolling” of hands) at rest (4-6 Hz). Presentation with tremor confined to one limb or one side of body is common. Other findings: rigidity (“cogwheeling”-increased ratchet-like resistance to passive limb movements), bradykinesia, fixed expressionless face (facial masking) with reduced frequency of blinking, hypophonic voice, drooling, impaired rapid alternating movements, micrographia (small handwriting), reduced arm swing, and flexed “stooped” posture with walking, shuffling gait, difficulty initiating or stopping walking, en-bloc turning (multiple small steps required to turn), retropulsion (tendency to fall backwards). Nonmotor aspects of PD include depression and anxiety, cognitive impairment, sleep disturbances, sensation of inner restlessness, loss of smell (anosmia), and disturbances of autonomic function. Normal muscular strength, deep tendon reflexes, and sensory examination. Diagnosis based on history and examination; neuroimaging, EEG, and CSF studies usually normal for age.

Pathophysiology

Most PD cases occur sporadically. Degeneration of pigmented pars compacta neurons of the substantia nigra in the midbrain resulting in lack of dopaminergic input to striatum; accumulation of cytoplasmic intraneural inclusion granules (Lewy bodies). Cause of cell death is unknown, but may result from generation of free radicals and oxidative stress, inflammation, or mitochondrial dysfunction; no environmental factor has yet been conclusively determined to cause typical PD. Genetic forms of parkinsonism exist (5-15% of cases); most common are mutations in glucocerebrosidase, LRRK2, α-synuclein or parkin genes. Early age of onset suggests a possible genetic cause of PD, although LLRK2 mutations cause PD in the same age range as sporadic.

Differential Diagnosis

Atypical parkinsonism refers to a group of neurodegenerative conditions usually associated with more widespread neurodegeneration than is found in PD including multiple-system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal ganglionic degeneration (CBGD), and frontotemporal dementia (FTD). Secondary parkinsonism can be associated with drugs (neuroleptics as well as GI medications such as metoclopramide, all of which block dopamine), infection, or exposure to toxins such as carbon monoxide or manganese. Some features to suggest that parkinsonism might be due to a condition other than PD are shown in Table 186-3 Features Suggesting an Atypical or Secondary Cause of Parkinsonism.