By Claire Henchcliffe, MD, PhD

Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College

Dr. Henchcliffe reports she is a consultant and on the speakers bureau for Acadia Pharmaceuticals, Impax Pharmaceuticals, and Allergan, and is a consultant for US WorldMeds and Gerson Lehman Group.

SYNOPSIS: A comparison of ambulatory blood pressure monitoring with tilt-table testing in 23 patients with multiple system atrophy, 18 with Parkinson’s disease and autonomic dysfunction, and 33 with Parkinson’s disease alone demonstrated 82% sensitivity and 100% specificity in detecting orthostatic hypotension. This suggests ambulatory monitoring provides valuable information on these patients’ function.

SOURCE: Vichayanrat E, Low DA, Iodice V, et al. Twenty-four-hour ambulatory blood pressure and heart rate profiles in diagnosing orthostatic hypotension in Parkinson’s disease and multiple system atrophy. Eur J Neurol 2017;24: 90-97.

This observational study included patients referred to a specialist autonomic testing unit for evaluation of orthostatic symptoms from 2004-2013. The patients enrolled comprised three groups: multiple system atrophy (MSA); Parkinson’s disease with autonomic failure (PDAF), in whom autonomic failure was defined on the basis of blood pressure (BP) and heart rate (HR) responses to orthostasis, Valsalva, and deep breathing; and Parkinson’s disease without autonomic failure (PD). A total of 74 patients were included (MSA: 23; PDAF: 18; PD: 33). Mean age was higher in the PDAF group (72 ± 7 years vs. 62 ± 9 years for MSA and 64 ± 10 years for PD; P < 0.05). Median disease duration (IQR: inter-quartile range) was 4 (3-6) years, 7 (4-10) years, and 6 (2-10) years for the MSA, PDAF, and PD groups, respectively. All patients underwent tilt-table testing with BP and HR recording while off anti-PD medication. For comparison, each was then fitted with an ambulatory BP monitoring (ABPM) device, that provided BP and HR measures every 20 minutes during the day and every 60 minutes at night for a 24-hour period. Furthermore, patients performed a five-minute standing test at four pre-specified times during the day. Diaries were also completed, recording symptoms and activities. ABPM was able to detect orthostatic hypotension ( 20 mm systolic BP drop during the standing tests) with 82% sensitivity and 100% specificity compared to the “gold standard” tilt-table testing. Diastolic BP measures performed less well, with sensitivity and specificity of 57% and 94%, respectively, when comparing ABPM to tilt testing. In contrast to tilt-table testing, ABPM provided a longer period of monitoring, including information on circadian patterns in each group. Although the normal pattern is a nighttime “dip” in BP, abnormal BP circadian rhythm was noted in all 96% MSA, 78% PDAF, and 48% PD. Of these, 57% MSA, 56% PDAF, and 15% PD demonstrated a reversed circadian BP pattern.

COMMENTARY

BP management of individuals with PD and MSA in the clinic is often challenging. BP control is affected not only by the disease process itself, but also by dopaminergic medications, comorbidities in a generally older population, and many of the drugs taken to manage those comorbidities. Vichayanrat et al attempted to minimize the effects of medications and comorbidities using careful inclusion/exclusion criteria. In practical terms, the study suggests that diagnosing orthostatic hypotension by ambulatory monitoring is highly accurate when compared with in-clinic tilt testing. Orthostatic hypotension is under-recognized in PD, and may present with non-specific or unexpected complaints such as a “coat hanger” pain. Therefore, broader use of this relatively straightforward testing modality could improve patient care. Moreover, the study provides a valuable description of cardiac autonomic dysfunction in MSA and PD/PDAF, albeit in a small number of clinically diagnosed individuals. It highlights how fairly simple ambulatory monitoring can significantly augment information from the clinic, particularly in a situation in which motivated subjects will follow a stand-testing protocol and complete diaries.

However, the report raises some questions. It is unclear whether feasibility and level of accuracy will be matched in the neurology clinic, as opposed to an academic center with highly motivated patients with specialist referrals. There is no information on other forms of autonomic function, nor a description of other clinical features associated with the three categories of patients. And although the authors discussed mechanism and possible involvement of the hypothalamic suprachiasmatic nucleus, lack of information on sleep disruption, level of physical activity, and other factors make this highly speculative. Finally, use of continuous monitoring outside of the clinic may augment the “snapshot” of traditional in-clinic evaluation. Establishing how well such monitoring performs in regular clinical care will take more work, but in the meantime ABPM may be considered to support diagnosing and treating important non-motor manifestations of PD and MSA.