Abstract
Objective
To assess autonomic function by infrared dynamic pupillometry in patients with ANCA-vasculitis (AAV) in correlation to autonomic symptoms, disease specific clinical parameters and cardiovascular reflex tests.
Methods
Patients with AAV and healthy controls underwent pupillometry at rest and after sympathetic stimulation (cold pressor test). Three parasympathetic parameters (amplitude, relative amplitude, maximum constriction velocity) and one sympathetic parameter (late dilatation velocity) were assessed. Results were correlated with clinical parameters, symptoms of autonomic dysfunction (COMPASS31 questionnaire), heart rate variability during deep breathing test and blood pressure response to pain.
Results
23 patients and 18 age-matched controls were enrolled. Patients had a smaller amplitude (1.44 vs. 1.70 mm; p = 0.009) and a slower constriction velocity (4.15 vs. 4.71 mm/s; p = 0.028) at baseline and after sympathetic stimulation (1.47 vs. 1.81 mm, p = 0.001; 4.38 vs. 5.19 mm/s, p = 0.006, respectively). Relative amplitude was significantly smaller in patients after sympathetic stimulation (28.6 vs. 32.5%; p = 0.043), but not at baseline. There was no difference in sympathetic pupillary response between the groups. In patients, parasympathetic pupil response was correlated negatively with age and positively with parasympathetic cardiac response. After adjusting for age, no significant correlation was observed with clinical parameters. However, there was a trend towards a negative correlation with disease duration, vasculitis damage index and CRP.
Conclusion
Patients with AAV exhibit parasympathetic pupillary autonomic dysfunction. Although correlations were weak and not significant, pupillary autonomic dysfunction is rather linked to chronic damage than to active inflammation or symptoms of autonomic dysfunction.
Similar content being viewed by others
References
Agarwal SK, Norby FL, Whitsel EA, Soliman EZ, Chen LY, Loehr LR, Fuster V, Heiss G, Coresh J, Alonso A (2017) Cardiac autonomic dysfunction and incidence of atrial fibrillation: results from 20 years follow-up. J Am Coll Cardiol 69:291–299
Barendregt PJ, van der Heijde GL, Breedveld FC, Markusse HM (1996) Parasympathetic dysfunction in rheumatoid arthritis patients with ocular dryness. Ann Rheum Dis 55:612–615
Basu N, Jones GT, Fluck N, MacDonald AG, Pang D, Dospinescu P, Reid DM, Macfarlane GJ (2010) Fatigue: a principal contributor to impaired quality of life in ANCA-associated vasculitis. Rheumatology (Oxford) 49:1383–1390
Bertinotti L, Pietrini U, Del Rosso A, Casale R, Colangelo N, Zoppi M, Matucci-Cerinic M (2002) The use of pupillometry in joint and connective tissue diseases. Ann N Y Acad Sci 966:446–455
Binkley PF, Nunziata E, Haas GJ, Nelson SD, Cody RJ (1991) Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. J Am Coll Cardiol 18:464–472
Bremner F, Smith S (2006) Pupil findings in a consecutive series of 150 patients with generalised autonomic neuropathy. J Neurol Neurosurg Psychiatry 77:1163–1168
Bremner FD, Smith SE (2006) Pupil abnormalities in selected autonomic neuropathies. J Neuroophthalmol 26:209–219
Cohen Tervaert JW (2013) Cardiovascular disease due to accelerated atherosclerosis in systemic vasculitides. Best Pract Res Clin Rheumatol 27:33–44
Faurschou M, Mellemkjaer L, Sorensen IJ, Svalgaard Thomsen B, Dreyer L, Baslund B (2009) Increased morbidity from ischemic heart disease in patients with Wegener’s granulomatosis. Arthritis Rheum 60:1187–1192
La Rovere MT, Bigger JT, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (autonomic tone and reflexes after myocardial infarction) investigators. Lancet 351:478–484
Lock G, Straub RH, Zeuner M, Antoniou E, Holstege A, Schölmerich J, Lang B (1998) Association of autonomic nervous dysfunction and esophageal dysmotility in systemic sclerosis. J Rheumatol 25:1330–1335
Louthrenoo W, Ruttanaumpawan P, Aramrattana A, Sukitawut W (1999) Cardiovascular autonomic nervous system dysfunction in patients with rheumatoid arthritis and systemic lupus erythematosus. QJM 92:97–102
Mandl T, Granberg V, Apelqvist J, Wollmer P, Manthorpe R, Jacobsson LT (2008) Autonomic nervous symptoms in primary Sjogren’s syndrome. Rheumatology (Oxford) 47:914–919
Moog P, Eren O, Witt M, Rauschel V, Kossegg S, Straube A, Grunke M, Schulze-Koops H (2016) Assessment of autonomic function in a cohort of patients with ANCA-associated vasculitis. Clin Auton Res 26:279–285
Muppidi S, Adams-Huet B, Tajzoy E, Scribner M, Blazek P, Spaeth EB, Frohman E, Davis S, Vernino S (2013) Dynamic pupillometry as an autonomic testing tool. Clin Auton Res 23:297–303
Newton JL, Frith J, Powell D, Hackett K, Wilton K, Bowman S, Price E, Pease C, Andrews J, Emery P, Hunter J, Gupta M, Vadivelu S, Giles I, Isenberg D, Lanyon P, Jones A, Regan M, Cooper A, Moots R, Sutcliffe N, Bombardieri M, Pitzalis C, McLaren J, Young-Min S, Dasgupta B, Griffiths B, Lendrem D, Mitchell S, Ng WF (2012) Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjogren’s syndrome. Ann Rheum Dis 71:1973–1979
Nishino H, Rubino FA, DeRemee RA, Swanson JW, Parisi JE (1993) Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 33:4–9
Nomura A, Kishimoto M, Takahashi O, Deshpande GA, Yamaguchi K, Okada M (2014) Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus. Rheumatol Int 34(5):643–647
Pop-Busui R, Cleary PA, Braffett BH, Martin CL, Herman WH, Low PA, Lima JA, Bluemke DA (2013) Association between cardiovascular autonomic neuropathy and left ventricular dysfunction: DCCT/EDIC study (diabetes control and complications trial/epidemiology of diabetes interventions and complications). J Am Coll Cardiol 61:447–454
Schwemmer S, Beer P, Schölmerich J, Fleck M, Straub RH (2006) Cardiovascular and pupillary autonomic nervous dysfunction in patients with rheumatoid arthritis—a cross-sectional and longitudinal study. Clin Exp Rheumatol 24:683–689
Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W (2012) COMPASS 31: a refined and abbreviated composite autonomic symptom score. Mayo Clin Proc 87:1196–1201
Stojanovich L (2009) Autonomic dysfunction in autoimmune rheumatic disease. Autoimmun Rev 8:569–572
Straub RH, Glück T, Zeuner M, Schölmerich J, Lang B (1998) Association of pupillary parasympathetic hyperreflexia and systemic inflammation in patients with systemic lupus erythematosus. Br J Rheumatol 37:665–670
Straub RH, Zeuner M, Lock G, Rath H, Hein R, Schölmerich J, Lang B (1996) Autonomic and sensorimotor neuropathy in patients with systemic lupus erythematosus and systemic sclerosis. J Rheumatol 23:87–92
Zafrir B, Azencot M, Dobrecky-Mery I, Lewis BS, Flugelman MY, Halon DA (2016) Resting heart rate and measures of effort-related cardiac autonomic dysfunction predict cardiovascular events in asymptomatic type 2 diabetes. Eur J Prev Cardiol 23:1298–1306
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Moog, P., Eren, O., Kossegg, S. et al. Pupillary autonomic dysfunction in patients with ANCA-associated vasculitis. Clin Auton Res 27, 385–392 (2017). https://doi.org/10.1007/s10286-017-0463-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10286-017-0463-1