Nonmotor Symptoms of Parkinson’s Disease

A 68-year-old man presents to his primary care physician with a 3-year history of progressive constipation, reduced sense of smell, and increasing anxiety. He reports excessive daytime fatigue and lightheadedness when standing. He does report increasing insomnia over the past 6 months, which he has attributed to increasing nocturia. He has no significant weakness or sensory loss. He still enjoys his hobbies but has been more reluctant to do activities because he is more anxious. He has lost about 10 lb in the past year which he attributes to eating less because food doesn’t taste as good. He has noticed a decreased sense of smell for the past few years.What is the most likely diagnosis? A. Depression B. Panic disorder C. Sleep apnea D. Parkinson’s disease E. Pancreatic cancerA nonmotor presentation of Parkinson’s disease fits this set of symptoms best. For some patients, nonmotor symptoms predate the diagnosis of Parkinson’s disease by years. Decreased sense of smell occurs in most patients with Parkinson’s disease (> 90%) and often occurs before other symptoms. Anosmia in patients who develop Parkinson’s disease is also associated with more frequent autonomic failure, especially the symptom of orthostasis. Douglas S. Paauw, MDFatigue is also a common symptom in patients with Parkinson’s disease (50%), and as is often the case with fatigue in all patients, it can be multifactorial. This patient’s nocturia may also be related to Parkinson’s disease. Urinary dysfunction in Parkinson’s disease includes nocturia and increased frequency and urgency of micturition, which are associated with detrusor hyperreflexia. Diaconu and colleagues studied the prevalence of nocturia in a cohort of Parkinson’s patients and found it in 86% of patients. This patient also has anxiety, which has been described as a prodromal symptom associated with Parkinson’s disease.Sleep disorders are extremely common in patients with Parkinson’s disease, occurring in 90% of patients, with insomnia being the most common, occurring in up to 80% of patients. REM sleep disorder is common in patients with Parkinson’s disorder, and the presence of isolated REM sleep disorder is much more common in patients who end up manifesting a neurodegenerative disease. Postuma et al reported that the overall conversion rate from idiopathic REM sleep disorder to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. Constipation is common in patients with Parkinson’s disease (50%) and is an important, prodromal symptom and may predate the onset of the classical motor symptoms by decades. Adams-Carr and colleagues did a meta-analysis of studies looking at constipation as a prodromal symptom of Parkinson’s disease. They found that those with constipation had a pooled odds ratio of 2.27 (95% CI, 2.09-2.46) for developing subsequent Parkinson’s disease compared with those without constipation. In a study of prediagnostic presentations of symptoms in primary care that were more common in eventual Parkinson’s patients, at 10 years before diagnosis, the incidence of constipation (risk ratio, 2.01) was higher in those who went on to develop Parkinson’s disease than in controls.Pearl: Several common primary care symptoms such as fatigue, anxiety, constipation, and nocturia are seen in the prodrome of a Parkinson’s disease diagnosis. Anosmia can also be a prodromal symptom, and as it is less common, is a more specific symptom.