Parkinson disease: Not just a movement disorder
ABSTRACTNonmotor symptoms are common in Parkinson disease and can significantly worsen the health and quality of life of the patient and family members. These symptoms can be broadly categorized as sensory, autonomic, cognitive-behavioral, and sleep-related. Clinicians can improve the care of these patients by recognizing and addressing these problems.
KEY POINTS
- Nonmotor symptoms can be due to the disease itself, to its treatment, or to on-off fluctuations in motor status as doses of medication wear off.
- 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.
- Orthostatic hypotension, sedation, psychosis, confusion, and impulsiveness may be adverse effects of medical therapy or may worsen with it.
- Depression occurs in up to 50% of patients with Parkinson disease, although it may be difficult to recognize because many of its physical features can also be manifestations of Parkinson disease itself.
Cold limbs, sweating
Complaints related to temperature regulation include cold limbs and excessive sweating. Off-period drenching sweats occur as an endof- dose symptom thought to be related to subtherapeutic plasma dopamine levels and may respond to dopaminergic therapy aimed at reducing motor fluctuations and off periods.22
Gastrointestinal symptoms
Dysphagia (difficulty swallowing), sialorrhea (excessive salivation), nausea, constipation, and defecatory dysfunction are more common in patients with Parkinson disease than in agematched controls, even after controlling for factors such as drugs, autonomic dysfunction, diet, and exercise.23 These problems can cause malnutrition (necessitating a gastrostomy tube), aspiration pneumonia, and difficulty in swallowing and retaining pills,24 all of which can lead to problems that are even more serious. Although gastrointestinal symptoms occur in all stages of Parkinson disease, patients with advanced disease are at greater risk.
Dysphagia. James Parkinson described dysphagia and sialorrhea in his original 1816 monograph.25 The prevalence of dysphagia increases with severity of disease.23 Dysphagia is usually due to altered pharyngeal contraction, resulting in difficulty propelling food into the pharynx and retention of food in the pyriform sinuses and valleculae, but esophageal dilatation and dysmotility, spasms, gastroesophageal reflux, and increased transit time also contribute.24,26,27
Constipation may affect more than half of patients.28 One study reported a higher risk of developing Parkinson disease in men with infrequent bowel movements.29
Constipation and defecatory dysfunction can be severe enough to result in colonic dilatation and pseudo-obstruction.30 Altered gastrointestinal transit time may contribute to erratic absorption of medications.
Causes of constipation include slow colonic transit, weak abdominal muscles, decreased phasic contraction, and a paradoxical increase in puborectalis muscle and anal sphincter activity with straining, consistent with pelvic muscle dystonia.31
Treatment includes reducing off periods, limiting anticholinergic agents, prescribing a proper bowel regimen, and encouraging fluids and exercise. In addition, daily stool softeners, fiber, and polyethylene glycol are effective. Botulinum toxin injection into the puborectalis muscle may improve outlet obstruction.32
Risk of aspiration. Dysphagia, in association with respiratory symptoms, should prompt an evaluation for aspiration. Thickening liquids and early referral to a swallowing specialist may lessen the risk of aspiration.
Drooling is bothersome and embarrassing for many patients. Treatment historically included antimuscarinic agents, but these can cause constipation and confusion in patients with advanced disease. More recently, botulinum toxin injections into the parotid and submandibular glands have been shown to be effective in patients with excessive drooling.33
Urinary problems
Urologic abnormalities can be divided into dysfunction of the bladder, dysfunction of the urethral sphincter, and other causes of outflow obstruction such as prostate enlargement in men. The most common complaint is nocturia, followed by frequency and urgency.34
Nocturnal polyuria and urinary hesitancy and urgency are embarrassing but treatable. Urinary incontinence is a common reason for nursing home placement, and nocturia is a common cause of falls, as patients attempt to get up to urinate.35,36
Treatment of urinary incontinence should begin with an assessment for urinary tract infection, stress incontinence in women, and prostate enlargement in men. Urinary urgency due to detrusor hyperreflexia or spastic bladder can improve with anticholinergic antispasmodic agents. However, these should be used with caution in patients who are experiencing hallucinations or cognitive problems.
Sexual dysfunction
Sexual dysfunction, including decreased libido and erectile dysfunction, is in part related to autonomic dysfunction.
Treatment is complex, as these problems are multifactorial. Contributing factors include physical disability, the stress of living with a progressive illness, drug effects, depression, pain, difficulty in communication, caregiver stress, and impact on intimacy. The phosphodiesterase inhibitor sildenafil (Viagra) can improve erectile dysfunction, but must be used cautiously in patients with orthostatic hypotension.37 Other drugs of this class are available but have not been tested in this population.
COGNITIVE-BEHAVIORAL PROBLEMS
Neuropsychiatric disorders are common in Parkinson disease and at times can be more distressing to the patient and family than the motor symptoms. These include mood disorders, apathy, anxiety, impulse control disorders, psychosis, and dementia.
Dopaminergic medications used to treat movement can precipitate or exacerbate these neuropsychiatric problems. Therefore, treatment requires a balance between motor and neuropsychiatric benefits, with close dialogue with the patient and family about primary goals of treatment.
Depression
Depression is among the most common neuropsychiatric symptoms in Parkinson disease, occurring to some degree in up to 50% of patients.38 Diagnosing it is critical, because it can worsen physical symptoms, cognitive status, quality of life, and caregiver distress.39
However, depression can be difficult to recognize, because many of its features (eg, fatigue, psychomotor slowing, flattened affect, sleep difficulties) can also be manifestations of Parkinson disease. One should specifically ascertain whether the patient has a depressed mood or loss of interest in pleasurable activities. The Beck Depression Inventory is sensitive for depression in Parkinson disease and thus may be a reasonable screening tool.40
Treatment. Psychotherapy may help and may even be a first-line treatment in patients who cannot tolerate antidepressant drugs. Practical recommendations include relaxation techniques, a sleep hygiene regimen, engaging in meaningful activities to achieve a sense of purpose, and caregiver education.41
We have little evidence-based guidance on drug treatment of depression in patients with Parkinson disease. A recent meta-analysis found only two placebo-controlled studies in the past 40 years that monitored outcome based on a standardized rating scale of depression in patients with Parkinson disease.42
In preliminary studies, dopamine agonists have shown some efficacy in treating depression without Parkinson disease.43 However, the antidepressant contributions of anti-Parkinson drugs have not been well established.
Selective serotonin reuptake inhibitors (SSRIs) appear to be safe and well tolerated.44 Venlafaxine (Effexor) and mirtazapine (Remeron) are also reasonable initial options. Tricyclic antidepressants should be used with caution because they can cause anticholinergic side effects, especially confusion, in this population.
All serotonergic agents should be used with caution when given in combination with monoamine oxidase inhibitors, which are often used to treat motor symptoms in Parkinson disease, because of the risk of serotonin syndrome, which is characterized by fever, altered mental status, myoclonus, tremor, hyperreflexia, and diaphoresis and may be fatal.
Electroconvulsive therapy can be reserved for the treatment of severe refractory depression in patients with Parkinson disease without complex medical issues.45
