Nonmotor PD Symptoms Are Many and Deserve Attention

"Nonmotor symptoms of Parkinson disease [PD] are diverse and include sleep disorders, depression, and pain," reported Carlo Colosimo, MD, assistant professor of neurology at La Sapienza University in Rome. He noted that a screening tool is needed.

During a symposium on nonmotor symptoms of PD at the Annual Meeting of the American Academy of Neurology (AAN) in early May, Colosimo presented unpublished data from the ongoing, 2-year, longitudinal, observational Parkinson and Non-motor Symptoms (PRIAMO) study showing that mood and sleep disorders are at the top of a list of common nonmotor symptoms seen among patients with PD. Mood disorders-primarily depression and anxiety-were diagnosed in a full 67% of the study cohort (1072 patients from 58 centers throughout Italy). Sleep disorders were diagnosed in 64%. Both pain and GI problems were diagnosed in 61%, followed by fatigue in 58%, and urinary tract disorders in 57%. Apathy, attention and memory deficits, respiratory disorders, postural instability, and psychotic disorders also were in the mix.

Colosimo noted that on average, study participants had 5.5 nonmotor symptoms. The most frequently reported at disease onset were pain, 28%; anxiety, 25%; and fatigue, 24%. Depression was diagnosed in 22% of the study population. It also was observed that the frequency of nonmotor symptoms increased with disease severity and motor disability.

Other speakers during the AAN symposium tackled specific nonmotor symptoms of concern in PD: hallucinations, apathy, and visual impairment.

HALLUCINATIONS

Christopher Goetz, MD, professor and associate chairman of the Department of Neurological Sciences at Rush University Medical Center in Chicago, stressed the importance of treating mild hallucinations in patients with PD. "Visual hallucinations become chronic and disabling," he told the audience. Indeed, he and colleagues demonstrated, in a study published in Archives of Neurology in 2006, that so-called benign hallucinations often progress to thought disorders whereby the patient loses insight about hallucination symptoms. This symptom can then progress to frank psychosis.¹ (For a synopsis, see Mental Note: Malignancy of "Benign" Hallucinations Exposed, Applied Neurology, June 2006, page 14.)

Goetz noted that neuroleptics were the drug of choice for managing hallucinations in this patient group but some clinicians are reluctant to use them for fear that the agents might incite seizure activity. He reassured his audience that the benefits outweigh the risks.

Goetz reported on a study conducted by him and his team that included 64 patients who experienced hallucinations secondary to PD therapy. Thirty-one of these patients were taking neuroleptic agents to control hallucinations. PD drug therapy dose was reduced in an additional 13 patients, and the remaining 20 patients did not receive intervention for hallucinations but were observed.

Median follow-up was 27 months. Those patients who were taking neuroleptics, especially if they began neuroleptic therapy in the early stages of symptom onset, were significantly protected from progression to thought disorder. "Median time to conversion to thought disorder greater than grade 2 [Table] was 39 months for treated patients compared with 12 months for untreated patients," reported Goetz.

APATHY

Apathy is another relatively common nonmotor symptom of PD. Although it is thought to be an aspect of depression or dementia, which are common comorbidities in persons with PD, Lindsey Kirsch-Darrow, MS, a graduate student in the Department of Clinical Health and Psychology at the University of Florida in Gainesville, and colleagues have demonstrated that to a significant degree, apathy occurs as an independent symptom in patients with PD and may be intrinsic to it.

The team got some press in 2006 when their study on apathy and depression was published in Neurology.² In examining the incidence of apathy and depression in 80 patients with PD and in 20 patients with dystonia, the researchers found a significantly higher degree of apathy in patients with PD than in patients with dystonia (51% vs 20%). Furthermore, apathy specifically manifested as a symptom of depression in patients with dystonia (no patient had apathy in the absence of depression), whereas 28.8% of patients with PD and apathy did not meet the criteria for depression. The research team concluded that apathy might be an independent symptom of PD.

Continuing along this line, the team's most recent study, reported at the AAN meeting, looked at the incidence of apathy in 38 nondemented patients with idiopathic PD. The study results confirmed the earlier findings. Forty-two percent of the study participants met criteria for apathy. Twenty-nine percent of those who met criteria for apathy also met criteria for depression; 32% met criteria for depression alone.

VISUAL IMPAIRMENT

Impairment of visual perception and visual cognition (or the ability to apprehend "where" and "what") also are common nonmotor symptoms of PD. In an article published in Neurology in 2005,³ Ergun Y. Uc, MD, assistant professor of neurology at the University of Iowa Carver College of Medicine in Iowa City, and colleagues demonstrated that visual perception and cognition often are impaired in nondemented persons with even mild PD.

In the earlier, published study, Uc and colleagues evaluated basic visuosensory functions, visual acuity, contrast sensitivity, visual speed of processing and attention, and other parameters related to visuospatial perception and cognitive functions in 76 nondemented persons with mild to moderate PD and 161 healthy seniors. Patients with PD consistently and significantly had poorer scores on tests related to visual perception and cognition, cognition itself, mood, and motor skills compared with controls. Indeed, deficits in visuosensory functions and perception correlated with deficits in cognition, suggesting that perceptual and cognitive visual deficits contribute to intellectual decline.

In evaluating the driving ability of patients with mild to moderate PD, Uc and colleagues confirmed their earlier findings and also sent a message about the implications of visual impairment in PD. Uc entertained the AAN symposium audience with video clips of simulated driving under low-visual contrast conditions (ie, fog or night) by a healthy older adult (control), a patient with sound cognitive perception but impaired visual perception, and a patient with adequate visual perception but impaired cognitive perception. The challenge of the simulated driving exercise was to brake in time to avoid smashing into a car at an approaching intersection.

The control braked in time to avoid an accident. The perceptually visually impaired patient reacted but braked too late. The cognitively visually impaired patient, who was also quite sleepy and driving at a constant speed of 15 mph, showed no reaction in demeanor or reflexes when he plowed into the simulated car in his path.

The clips were samples from a study that Uc and colleagues conducted involving 67 active drivers who had mild to moderate PD and 51 elderly controls. The simulation depicted foggy conditions on a 2-lane rural road in which, within 4 seconds of the driver's approach to an intersection, a car illegally proceeds into the driver's path.

A significantly larger proportion of drivers with PD crashed than did controls (76.1% vs 37.3%). Reaction time was slower among patients with PD, which not only correlated with poor motor performance scores but with poor performance on tests of visual perception and memory, visuospatial awareness, and cognition. Furthermore, severity of motor disability was not predictive of motor accident risk, whereas delayed reaction and less-than-stellar performances on tests of contrast sensitivity, perception of structure from motion, visual speed in processing and attention, and visuospatial perception was.

Uc recommended that patients with PD and visual impairment refrain from driving under low-contrast lighting conditions.

References:

REFERENCES1. Goetz CG, Fan W, Leurgans S, et al. The malignant course of "benign hallucinations" in Parkinson disease. Arch Neurol. 2006;63:713-716.
2. Kirsch-Darrow L, Fernandez HH, Marsiske M, et al. Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67:33-38.
3. Uc EY, Rizzo M, Anderson SW, et al. Visual dysfunction in Parkinson disease without dementia. Neurology. 2005;65:1907-1913.