These nonmotor symptoms—sensory, autonomic, and behavioral—are important to recognize, as they can lead to even more serious complications and impair quality of life.
COMMON, TROUBLESOME, AND UNDERDIAGNOSED
Nonmotor symptoms are very common. In fact, up to 60% of patients suffer from more than one nonmotor symptom, and 25% have four or more,1 including autonomic dysfunction, sensory symptoms, and cognitive and behavioral problems.2
Nonmotor symptoms can be primary complaints and, for some patients and family members, can cause greater disability than motor symptoms.3,4 For instance, depression and cognitive problems contribute to a decline in quality of life regardless of the degree of motor impairment.
Yet these symptoms are often underdiagnosed. 5 A delay in diagnosis may reflect the tendency of clinicians, patients, and family members to focus on the more apparent motor features of Parkinson disease, a lack of awareness of the nonmotor symptoms, or both. Consequently, patient education is essential. Identifying and treating these symptoms requires a multidisciplinary clinical team approach and an ongoing dialogue with the patient and family.
VARIOUS SYMPTOMS, VARIOUS CAUSES
Some nonmotor symptoms (eg, impaired sense of smell, depression, anxiety, fatigue, and constipation) can precede the motor symptoms of Parkinson disease and may be symptoms of the disease itself. Perhaps accounting for these observations, recent pathologic studies described diffuse Lewy body deposition in areas outside of nigral dopaminergic neurons,6,7 and the olfactory bulb, medulla, and pontine tegmentum may be involved before the substantia nigra.
Other symptoms, such as orthostatic hypotension, sedation, psychosis, confusion, and impulsiveness, may be adverse effects of medical therapy or may worsen with it.
Nonmotor symptoms can also emerge as a “wearing-off” phenomenon with standard treatment.2,8 The “off period” is a term primarily used to describe the reemergence of motor symptoms as a dose of levodopa wears off and before the patient receives the next dose. However, nonmotor symptoms, in particular depression and anxiety, can also occur in this period.
To treat nonmotor symptoms, one needs to identify and treat the primary symptom or the comorbid illnesses that may worsen it (eg, confusion in the setting of dehydration and infection), assess the possibility of adverse drug effects (a particular problem with many anti-Parkinson drugs), and try to reduce off periods with changes in dopaminergic therapy.
Off-period pain, paresthesia
Pain that cannot be attributed to muscle spasms, dystonia, somatic disease, autonomic dysfunction, or peripheral nerve disease occurs in up to 38% of patients with Parkinson disease.9,10 The pain is often diffuse and aching. Paresthesia-like complaints include numbness, tingling, and change in temperature.
Some sensory symptoms occur mostly during off periods and may respond to dopaminergic therapy. Examples are limb paresthesia, truncal pain, trigeminal neuralgia-like pain, and vaginal or perineal pain.9–11
Impaired sense of smell, vision
Impaired sense of smell can precede motor symptoms and is being investigated as a possible screening symptom for early diagnosis.12,13
Altered vision is a less recognized symptom of Parkinson disease. Many patients have difficulty reading even if they have normal visual acuity. Part of their difficulty stems from oculomotor defects such as impairment in visual saccadic movements and muscle rigidity.14 Visual pathways can be affected, as evidenced by abnormal visual evoked potentials that correlate with disease severity and by impairment in contrast sensitivity, color perception, and judgment of line orientation.15
It is unclear how these visual abnormalities contribute to everyday symptoms in Parkinson disease. Certainly, visual scanning activities such as reading are impaired.
Patients also suffer from drug-induced visual illusions and hallucinations, which are often colorful. Diederich et al16 found that contrast discrimination and color perception were significantly more impaired in Parkinson patients who have visual hallucinations, which suggests that it is important to correct visual abnormalities.
In general, autonomic problems increase with age, disease severity, medication use, postural instability, cognitive decline, and visual hallucinations.17,18
Almost half of patients with Parkinson disease have orthostatic hypotension.19 Of concern, patients with postural instability are at greater risk of orthostatic hypotension, thereby further increasing their risk of falling and injuring themselves.20
Postprandial hypotension is more common in Parkinson disease and is more often associated with midday meals, perhaps owing to a higher carbohydrate content and its effect on insulin release21 (many patients reserve high-protein meals for the evening and eat a greater proportion of carbohydrates during the day).
Home blood pressure monitoring is especially helpful, since blood pressure can fluctuate significantly and office readings may not reveal the problem.
Orthostatic hypotension can be both a drug side effect and a manifestation of the disease. Although all dopaminergic drugs can worsen orthostatic hypotension, the motor benefits of these drugs should be reviewed in relation to this risk. Dopaminergic agonists and amantadine (Symmetrel) should be used with caution in patients with significant orthostatic hypotension.
Treatment should include fluids, a highsalt diet, elastic stockings, fludrocortisone (Florinef), pyridostigmine (Mestinon), and perhaps the selective alpha 1 agonist midodrine (Proamatine). However, midodrine can cause supine hypertension and must be used cautiously in patients with advanced disease who take daytime naps because of fatigue. If postprandial hypotension is a problem, altering the patient's diet to include smaller but more frequent meals may help.