Theresa Zesiewicz Discusses New Guideline on Treatment of Nonmotor Symptoms of Parkinson's Disease

March 15, 2010

A new AAN guideline, "Treatment of Nonmotor Symptoms of Parkinson Disease," has been published in the print issue of Neurology® (2010;74:924-931). Theresa Zesiewicz, MD, FAAN, professor of neurology in the Department of Neurology at the University of South Florida, Tampa, Florida, and lead author of the review, spoke with José G. Merino, MD, Science Editor of AAN.com, about the guideline and the need for further studies in the field.

AAN.com: What are the most common nonmotor symptoms of Parkinson's disease (PD)? How prevalent are they?

Zesiewicz: The most common nonmotor symptoms are sleep disorders (which occur in approximately 90 percent of PD patients) and hyposmia, or impaired sense of smell. However, other nonmotor symptoms occur frequently in PD patients as well. For example, it is estimated that 45 to 50 percent of PD patients suffer from depression, and at least 40 percent of patients experience dementia. Fatigue, constipation, and urinary incontinence are also commonly experienced.

AAN.com: How was this practice parameter developed?

Zesiewicz: In the past decade, it became clear that nonmotor symptoms in PD were frequently experienced by PD patients, although there were often undertreated and underrecognized. It was realized that these symptoms significantly interfered with patients' quality of life. The Quality Standards Subcommittee (QSS) of the AAN voted to approve an evidence-based guideline of nonmotor symptoms of PD to formally examine the treatment of these symptoms in PD, and to form recommendations to better help health care providers treat PD patients who suffer from these symptoms.

In April of 2005, an expert panel of investigators from the United States and Europe was selected to formulate this guideline. In November 2006, a literature search was performed to identify potential therapies for nonmotor symptoms of PD. Each abstract was reviewed by at least two members of the panel for relevance for further review. Articles that evaluated treatment of a nonmotor symptom in patients with PD were considered relevant. These articles were reviewed in detail, and data were extracted. The articles were classified for quality of evidence based on the AAN therapeutic classification scheme, and recommendations were based on class of evidence. The final evidence-based guideline was approved in 2009 after extensive research and discussion.

AAN.com: Which nonmotor symptoms of PD are the focus of this practice parameter?

Zesiewicz: Articles that evaluated treatment of any nonmotor symptom in patients with PD were considered relevant, with the exception of cognitive or mood disorders in PD or treatment of sialorrhea with botulinum toxin (these treatments were already reviewed in previous parameters). The nonmotor symptoms include psychiatric symptoms, sleep disorders, sensory symptoms, and autonomic symptoms such as gastrointestinal dysfunction, and others including fatigue, double-blind, and seborrhea.

AAN.com: For each of the nonmotor symptoms of PD addressed in the guidelines, can you summarize the key treatment interventions supported by evidence?

Zesiewicz: For sexual dysfunction, sildenafil citrate is possibly efficacious in the treatment of erectile dysfunction (ED) in PD and may be considered to treat ED (Level C). However, a complete medical evaluation should determine whether other treatable causes of ED may be present, including other medical conditions or side effects of medications.

For constipation, isosmotic macrogol (polyethylene glycol) possibly improves constipation in PD and may be considered to treat constipation in patients with PD (Level C).

The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements and should be considered to treat periodic limb movements of sleep inpatients with PD (Level B).

For excessive daytime sleepiness (EDS), modafinil should be considered to improve patients' subjective perception of EDS, but it was ineffective in objectively improving EDS. This is important, because a PD patient may feel less fatigued, but, by objective measures, may not be improved.

AAN.com: What studies are required to strengthen the recommendations?

Zesiewicz: There are few dedicated, controlled drug trials to treat nonmotor symptoms in PD. Such trials are urgently required. These symptoms include urinary incontinence, orthostatic hypotension, excessive daytime sleepiness, and anxiety.

AAN.com: Can clinicians predict which patents will develop these nonmotor symptoms?

Zesiewicz: The vast majority of PD patients will experience some form of sleep dysfunction and will suffer from hyposmia. There are some risk factors for other nonmotor symptoms as well. For example, age at onset, duration of PD, akinetic-rigid syndrome, and an early occurrence of psychosis may be risk factors of dementia in PD. For other nonmotor symptoms, it is more difficult to predict.

AAN.com: How often should clinicians caring for patients with PD screen for these nonmotor symptoms? Are there scales that can be used routinely in the evaluation of these patients?

Zesiewicz: Clinicians should be aware of the prevalence of nonmotor symptoms in patients with PD. Two scales have recently been published that should help clinicians in the screening and early detection of these symptoms. The NMS Quest study established a valid and reliable questionnaire to identify nonmotor symptoms in PD. In addition, a revised version of the Unified Parkinson's Disease Rating Scale (UPDRS) will include an expanded section to assess nonmotor symptoms. Other screening tools for nonmotor symptoms in PD include the Epworth Sleepiness Scale (ES), Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale, Beck Depression Scale, Montgomery-Asberg Depression Scale, Hospital Anxiety and Depression Scale, Parkinson's Disease Fatigue Scale, Fatigue Severity Scale, Mini-Mental State Examination (MMSE), Parkinson Psychosis Rating Scale, and the Cambridge Cognitive Examination Scale.

AAN.com: At which stage of the disease do the nonmotor symptoms of PD develop? Do these symptoms correlate with changes in specific neurotransmitters? What are the neuropathologic changes underlying these symptoms?

Zesiewicz: Some nonmotor symptoms actually precede the onset of the motor symptoms of PD by many years, including depression and constipation. Hyposmia is being investigated as a "biomarker" for the development of PD.

However, the treatment of PD may contribute to the development of other nonmotor symptoms. For example, dopaminergic therapy may contribute to sleep dysfunction and psychosis.

Abnormalities in the dopaminergic pathway may contribute to some of the nonmotor symptoms of PD. However, because many of the symptoms do not respond to dopaminergic therapy or alteration, it is probable that other neurotransmitters are involved in the development of nonmotor symptoms as well. Serotonergic, noradrenergic, cholinergic, and dopaminergic mechanisms probably play a role in several of the nonmotor symptoms.

AAN.com: What is the effect of these nonmotor symptoms on quality of life?

Zesiewicz: Nonmotor symptoms significantly interfere with quality of life in PD patients. Depression clearly reduces patients' quality of life. The presence of dementia is a predictor of nursing-home placement and short survival in PD patients. It's important to identify these symptoms and offer treatment, when appropriate.

Related Resources

• Guideline
• Clinician Summary

Author Disclosure

Dr. Merino performed a one-time consultation with staff from Bell, Falla and Associates.

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