Review: Exploring the electrocardiogram as a potential tool to screen for premotor PD

Movement Disorders
Volume 25, Issue 14, 2010, pages 2296-2303, 30 October 2010

Authors: Ruksana Azhu Valappil PhD[1], Jed E. Black MD[2], Meredith J. Broderick MD[3], Oscar Carrillo RPSGT[2], Eric Frenette MD, FRCP(C)[4], Shannon S. Sullivan MD[2], Samuel M. Goldman MD, MPH[1], Caroline M. Tanner MD, PhD[1], James W. Langston MD[1]*

1 Clinical Research Department, The Parkinson's Institute and Clinical Center, Sunnyvale, California, USA
2 Department of Psychiatry and Behavioral Sciences, Stanford University, Redwood City, California, USA
3 Sleep Medicine, Minor & James Medical, Seattle, Washington, USA
4 Department of Neurology, University of Sherbrooke, Sherbrooke, Quebec, Canada

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The aim of this study was to test the hypothesis that patients with REM sleep behavior disorder, many of whom will develop Parkinson's disease (PD) or a related synucleinopathy, will demonstrate decreased heart rate variability (HRV) compared with a group of age-matched controls as measured by an electrocardiogram during wakefulness. We compared HRV in 11 untreated idiopathic REM sleep behavior disorder patients (9 men and 2 women; mean age, 63.3 years; SD, 7.5 years) and 11 control subjects with idiopathic insomnia without REM sleep behavior disorder (7 men and 4 women; mean age, 59.5 years; SD, 8.7 years). Subjects with other causes of reduced HRV were excluded. HRV was determined from 5-minute presleep segments of a single channel electrocardiogram recorded during polysomnographic evaluations, using R-R intervals during wakefulness. Time domain, geometric measures, and spectral analysis of the R-R intervals were significantly different between cases and controls. A discriminant function analysis correctly classified 95.5% of subjects (overall model fit, P = 0.016). Leave-one-out cross-validation correctly classified 77.3% of subjects. HRV during wakefulness is significantly decreased in patients with idiopathic REM sleep behavior disorder compared with control subjects, suggesting abnormalities of both sympathetic and parasympathetic function. Patients with RBD may later develop motor and cognitive features of a Lewy body disorder, such as PD. Cardiac autonomic dysfunction is also impaired in PD, suggesting that impaired HRV may be an early sign of PD. HRV measured by routine electrocardiograms could be used to screen for Lewy body disorders such as PD.

© 2010 Movement Disorder Society

Summary and review by Dr. Laura Silveira-Moriyama, MD, PhD, UCL, Institute of Neurology, Queen Square, London

The article chosen by the Web Editorial Board this month is called "Exploring the Electrocardiogram as a Potential tool to Screen for Premotor Parkinson's Disease". This retrospective study from Ruksana Valappil and associates looked at heart rate (HR) variability in a group of 11 patients with untreated idiopathic REM sleep behaviour disorder (iRBD) and compared this with 11 control subjects who had idiopathic insomnia without REM sleep behaviour disorder. REM sleep behavioural disorder is considered a harbinger for Parkinson's disease and this experiment was conducted to explore the idea that early dysautonomia might be an early marker for Parkinson's disease.

They used previously recorded single channel electrocardiograms selected from the records of patients who underwent polysomnography at the Stanford Sleep Medicine Center. They selected 11 patients with a diagnosis of iRBD according to the International Classification of Sleep Disorders. Due to the fact that there was no polysomnography for healthy controls, they used 11 subjects with primary insomnia. This condition is not associated with neurodegeneration or dysautonomia.

From the recorded electrocardiogram they extracted the heart rate variability from a short period of 5 minutes under stable conditions (stable breathing and no leg movements) during the 15 minutes recording performed routinely before the patients fall asleep. The RR interval was processed by a software which calculated common parameters used in heart rate variability analysis including time and frequency domain measures, as well as geometric and non-linear measures. Time-domain measures describe the variability of the RR interval. Frequency-domain measures relate mostly to respiration and parasympathetically mediated changes in heart rate. Geometric and non-linear measures are related to the complex interactions that make up the autonomic system regulation on physiological circumstances, including hemodynamic, endocrinologic and other factors.

The mean age of subjects with iRBD was 63.3 years, and nine of the eleven were men. Mean age of the controls with idiopathic insomnia was 59.5 years and seven were men. Most of the measurements of HR variability were lower in subjects with iRBD than in the controls. The measurements were then used as factors in a discriminant function analysis creating a significantly fitting model which was able to correctly classify 95.5% of the subjects in the iRBD or control groups.

The authors interpret their findings as evidence that both sympathetic and parasympathetic influences on cardiac function are decreased in patients with iRBD when compared with controls. They add that there are other evidences that patients with iRBD have disturbance in the autonomic innervation of the heart, including decreased HR variability during REM sleep and sympathetic denervation on MIBG. They speculate that this is yet another evidence that iRBD might be part of a spectrum that includes Parkinson's disease and Lewy body dementia, and in particular that iRBD could be part of a constellation of symptoms that happen in pre-motor Parkinson's disease. Currently there is not enough prospective evidence to understand what percentage of people with such non-motor features will indeed develop PD. Nevertheless, given that electrocardiograms are a cheap and accessible tool, if pre-motor screening of PD becomes clinically useful, EKG is a potential tool for routine use. The small number of subjects in this trial precludes any definite conclusions about the accuracy of the test in discriminating controls from iRBD, but the high accuracy found encourages further studies.

The main take-home message of this featured article is that HR variability is significantly decreased in iRBD and that further studies in this area are warranted.

About Dr. Laura Silveira-Moriyama

Dr. Laura Silveira Moriyama graduated and trained in Neurology at the University of São Paulo, Brazil. She worked with Prof. Egberto Barbosa until 2004, when she moved to London to work in Queen Square under Prof. Andrew Lees' supervision, at the Reta Lila Weston Institute of Neurological Studies (RLWI). In 2009 she completed a PhD on the subject of olfaction in Parkinson’s disease and published a series of articles demonstrating that smell tests could be helpful in the differential diagnosis of parkinsonism and tremor, and that olfaction was impaired in various clinical manifestations of Lewy body disorders including pure autonomic failure and LRRK2 gene mutation carriers who present with parkinsonism. Currently she is a postgraduate fellow in Movement Disorders at the RLWI and continues to work with Prof. Andrew Lees teaming up with various international collaborators.