Short communicationAutonomic insufficiency in pupillary and cardiovascular systems in Parkinson’s disease☆
Introduction
Parkinson’s disease (PD) neuropathology suggests neurodegenerative changes involve neurons in autonomic pathways affecting multiple organ systems [1] which may lead to widespread changes in autonomic physiology which if quantified may serve as non-motor markers of PD. Such markers could allow earlier diagnosis and better treatment of PD as non-motor features of PD occur earlier and contribute more to the burden of disease than do motor features [2]. Both the pupillary and cardiovascular systems may provide such physiological markers.
The pupil can provide a unique window into brain function as it integrates inputs from both cortical and subcortical structures which influence its autonomic function – parasympathetic constriction or sympathetic dilation. Pupillary measures include pupillary unrest, constriction velocity and redilation velocity. Pupillary unrest refers to spontaneous fluctuations in autonomic tone which lead to changes in pupil diameter in darkness. It is positively associated with arousal related symptoms such as sleepiness which are common in PD [3]. The cardiovascular system is also of clinical significance, as evidenced by the high prevalence of orthostatic hypotension in PD [2]. Cardiac measures include respiratory sinus arrythmia with deep breathing, resting heart rate variability, the Valsalva ratio and orthostatic blood pressure and heart rate. Cardiac measures in PD have been reported, but mostly in isolation without taking account of how other autonomic end-organs are functioning. Our objective in this exploratory study is to simultaneously acquire measures in the pupillary and cardiovascular systems, allowing correlations of autonomic function between the two systems. Results of such analyses would reveal information on hierarchically higher centers of autonomic integration in elderly controls and how such systems may be affected in PD [4].
Section snippets
Methods
All participants were recruited from the University of Pittsburgh Medical Center. The IRB gave ethical approval and the participants signed informed consent. PD participants fulfilled the UK PD Society Brain Bank Clinical Criteria, scoring Hoehn and Yahr Stage (HY) < 5, taking either no anti-parkinsonian medication, carbidopa/levodopa or dopamine agonists. As a group, controls were age and sex matched to PD participants. Exclusion criteria included: pyramidal and/or cerebellar signs, any other
Results
Characteristics of PD and control groups are summarized in Table 1. Pupillary unrest was higher in PD and four of the six cardiovascular measures were lower in PD compared to controls. Medications in the first five participants were not withheld and included: no medications in the first participant; selegiline 5 mg/day and levodopa 800 mg/day in the second; amantadine 200 mg/day and ropinirole 12 mg/day in the third; levodopa 600 mg/day in the fourth; and levodopa 300 mg/day in the fifth. There
Discussion
Simultaneous recordings of pupillary and cardiovascular autonomic measures in PD have not been previously reported. We observed lower HRV in both low and high frequency bands, greater decreases in supine to standing (orthostatic) systolic blood pressure and higher pupillary unrest in PD relative to controls. This represents lower sympathetic and parasympathetic cardiac function, as well as higher autonomic variability in pupillary function in PD.
Given the known association of pupillary unrest
Acknowledgments
NIH grants KL2 RR024154, KMH082998, MH55762, P30 AG-024826, UL1 RR024153, Dept. of Veterans Affairs, and the American Parkinson’s Disease Association Center for Advanced Research at the University of Pittsburgh.
References (12)
- et al.
Non-motor symptoms of Parkinson’s disease: diagnosis and management
Lancet Neurology
(2006 Mar) - et al.
Mathematical procedures in data recording and processing of pupillary fatigue waves
Vision Research
(1998) - et al.
Correlations between the autonomic modulation of heart rate, blood pressure and the pupillary light reflex in healthy subjects
Journal of the Neurological Sciences
(2009 Apr 15) - et al.
Pupillometric findings in patients with Parkinson’s disease and cognitive disorder
International Journal of Psychophysiology
(2009 May) - et al.
Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders
Acta Neuropathologica
(2010) The pupil: anatomy, physiology, and clinical applications
(1993)
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2021, Journal of Biomedical InformaticsCitation Excerpt :They were also sub grouped by region of pupillary signal, short-term characteristics (transient) of the contraction phase and longer duration characteristics (sustained) measured in the dilation phase. In addition to the characteristics presented, there were others that were sometimes considered in the studies: (1) Spontaneous fluctuations in pupil size, also called Hippus [108] or pupillary unrest [109] or Spontaneous Pupillary Fluctuation [110] or Pupil Oscillation Frequency (POF) [67] - which are spontaneous variations in pupillary size when it is not being stimulated. ( 2) Anisocoria of contraction - which occurs when the stimulated pupil (direct reflex) contracts more than the pupil that is not being illuminated (consensual reflex).
The pupillary light reflex for predicting the risk of hypotension after spinal anaesthesia for elective caesarean section
2018, Anaesthesia Critical Care and Pain MedicineCitation Excerpt :The surface diameter of the pupil therefore reflects these interactions between the sympathetic and parasympathetic systems. Pupillometry has been adopted in a growing number of medical fields (obstructive sleep apnoea syndrome [23], congenital central hypoventilation syndrome [24], Parkinson's disease [25], schizophrenia [26], diabetic polyneuropathy [27], heart failure [28], bronchial hyperactivity [29] and migraine headaches [30]) and various studies have used this device to highlight autonomic nervous system dysfunction. Its low cost, safety profile, measurement reproducibility, speed and ease of use make it an ideal tool for use during CS.
Differences of sympathetic and parasympathetic modulation in major depression
2017, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :The pupillary unrest index (PUI) is mainly used to quantify temporal changes of pupil size (Lüdtke et al., 1998). Alterations of pupillary fluctuations were described in patients suffering from Parkinson's disease, multiple sclerosis or epilepsy (Centeno et al., 2011; Egg et al., 2002; Jain et al., 2011a,b). The objective of this study was the assessment of autonomic function in a more comprehensive way, using HRV, baroreflex sensitivity, pupillary function, electrodermal activity and respiration.
Management of the aging risk factor for Parkinson's disease
2014, Neurobiology of AgingCitation Excerpt :When endogenous defenses can no longer resist these stresses, neuropathologic changes may accumulate, notably in dopamine neurons, which are rendered especially susceptible to the combined effects of energy deficit and oxidative stress by the catechol structure and metabolism of dopamine (Cohen, 1994; Kristal et al., 2001; Lamensdorf et al., 2000; Marchitti et al., 2007). Abnormalities in PD also occur outside the central dopaminergic pathways, as there is evidence of widespread dysfunction (shown by biochemical change, gene underexpression, pathology, and functional deficit) in other non-dopamine central neurons, autonomic and sensory pathways, and peripheral structures including nonneural tissue (Beach et al., 2010; Braak et al., 2003; Gibson et al., 2003; Halliday, 2009; Hargreaves et al., 2008; Harris et al., 1992; Hindle, 2010; Jain et al., 2011; Jellinger, 1999; Mytilineou et al.,1994; Zheng et al., 2010), and many patients later develop cortical pathology (Braak et al., 2003) and dementia (Hindle, 2010). Some of the changes in the central nervous system associated with PD are also found, in less severe form, in normal aging tissue.
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The review of this paper was entirely handled by an Associate Editor, R. L. Rodnitzkyi.