INTERNATIONAL JOURNAL OF LEPROSY^ Volume 51, Number 3

Printed in the U.S.I.

Autonomic Neuropathy in Leprosy'Michael K. Kyriakidis, Costas G. Noutsis, Christine A. Robinson-Kyriakidis,

Panayiotis J. Venetsianos, Gregory P. Vyssoulis, Pavlos C. Toutouzas,Nicolas G. Parissis, and Dimitris G. Avgoustakis 2

In autonomic neuropathy cardiovascularreflexes may be impaired. The integrity ofthe autonomic control of the heart can bestudied by observing the heart rate duringsimple tests which can easily be performedat the bedside (• 4 . 5 '")).

Leprosy is known to damage both so-matic and autonomic nerves (" 2). Howeverthe effect of leprosy on the autonomic con-trol of the cardiovascular system has notbeen described in detail.

The present study was initiated to assessthe extent of autonomic impairment ofcardiovascular reflexes in 21 patients withlong-standing lepromatous leprosy regular-ly attending the Leprosy Clinic, InfectiousDiseases Hospital, Athens, Greece.

MATERIALS AND METHODSWe studied 21 patients (8 men and 13

women) with leprosy, and 10 normal people(4 men and 6 women). The patients weredrawn from the population attending theLeprosy Clinic, Infectious Diseases Hospi-tal, Athens, and the control group consistedof healthy medical staff. The leprosy pa-tients ranged in age from 39-81 (mean 55years) and the control group from 28-62(mean 47 years).

All 21 patients had the lepromatous typeof leprosy with a characteristic early historyof disseminated nodules and infiltratedplaques on the face, trunk and extremities.

' Received for publication on 19 April 1982: ac-cepted for publication in revised form on 30 March1983.

= M. K. Kyriakidis, M.D., Registrar; Christine A.Robinson-Kyriakidis, M.D., M.R.C.P., Research Fel-low; G. P. Vyssoulis, M.D., Research Fellow; P. C.Toutouzas, M.D., Associate Professor of Cardiology,and D. G. Avgoustakis, M.D., Professor of Cardiology,Department of Cardiology, University of Athens, Hip-pokration Hospital, Athens, Greece. C. G. Noutsis,M.D., Registrar; P. J. Venetsianos, M.D., Registrar,and N. G. Parissis, M.D., Consultant Dermatologist,Department of Dermatology, Infectious Diseases Hos-pital, Athens, Greece.

Eyebrow and eyelash loss, leonine facies andpendulous earlobes were noted in somecases. All 21 patients developed leprosy atleast two years before chemotherapy wasstarted. Thirteen of them remained withouttreatment for a period ranging from 5-17years after the onset of symptoms. In somecases, therapy was discontinued intermit-tently because of poor patient compliance.

Criteria for inclusion in the study in thelepromatous patients were: a) the presenceof leprosy for more than five years; b) theabsence of lepra reactions during the study,and c) the ability to walk with no majormalformations. Inclusion criteria for bothgroups were: d) no history of ischemic heartdisease, normal resting ECG; c) the absenceof other causes of autonomic neuropathysuch as diabetes mellitus, amyloidosis, por-phyria and syphilis as shown by relevantinvestigations; 0 no drugs taken which werelikely to affect autonomic nervous systemfunction, and g) willingness to give in-formed consent.

ProceduresThe subjects rested supine for at least 20

min before the investigation. Standard 12lead electrocardiograms were performed andlead II strips recorded for measurement ofheart rate.

The following non-invasive tests of auto-nomic cardiovascular control were per-formed:

Heart rate variability during deep breath-ing.Response to mental stress, consisting ofrapid performance of subtraction testsaloud under mild harassment.Carotid sinus pressure. Firm pressure wasapplied for 15 sec each carotid sinus inturn.Valsalva maneuver. Patients blew into amodified mercury sphygmomanometer.A pressure of 40 mm Hg was reached assoon as possible and maintained for 10

331

332^ International Journal of Leprosy

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sec. Pressure was then released abruptlyand recordings were continued for at leastanother 20 sec.Tilting. Patients were tilted to vertical for3 min.Between the above tests the patients rest-

ed in the supine position for 15 min. Thepulse rate had returned to control levels be-fore the next test. Statistical analysis wasperformed using Student's t test, White'sSum of Ranks, the non-parametric t test,and non-parametric rank correlation.

RESULTSThe results are illustrated in Tables 1, 2,

and 3.Heart rate variability. There were no sig-

nificant changes in heart rate during deepbreathing in the lepromatous patients. Themean minimum heart rate was 82.1 beatsper minute and the maximum was 84.3. Incontrast there were significant changes inthe normal group (p < 0.02) with meanminimum heart rate of 83.0 and maximumof 104.4 beats per minute. The mean per-centage heart rate change during deepbreathing was 2.7 in the lepromatous pa-tients and 26.0 in the control group (p <0.0001).

Mental stress. Mental stress did not affectthe heart rate significantly in either group.The mean heart rate was 70.7 beats perminute at rest and 70.2 after mental stressin the lepromatous patients, and 75.3 at restand 87.4 after mental stress in the controlgroup. However the mean percentage heartrate change was significantly higher in thecontrol group (p < 0.005).

Carotid sinus pressure. There were nochanges in heart rate with carotid sinus pres-sure in the lepromatous patients, but therewere significant changes in the control group.In the lepromatous patients the mean rest-ing heart rate was 67.3 beats per minutebefore pressure was applied to the right ca-rotid artery, and 68.1 during right carotidpressure. The mean resting heart rate was67.3 beats per minute before pressure wasapplied to the left carotid artery and 68.2during left carotid pressure. In the controlgroup the mean resting heart rate was 75.3beats per minute before pressure was ap-plied to the right carotid artery and 62.8beats per minute during right carotid pres-

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51, 3^Kyriakidis, et al.: Autonomic Neuropathi in Leprosy^333

TABLE 2. Mean heart rates at rest and after test situations in leprosy patients and thecontrol group.

Leprosy patients Control group

Mean HR^

Significance^Mean HK^Significance

Deep breathing inill`\min

Rest^ 70.7Mental stress^70.0

Rest^ 67.3R carotid pressure^68.1

Rest^ 67.3I. carotid pressure^68.2Rest^ 68.0Valsalva maneuver^72.6

Rest^ 68.7Tilting at 15th beat^85.8

Rest^ 68.7Tilting at 30th beat^84.5

N.S.

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p < 0.001

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sure (p < 0.05). The mean resting heart ratewas 74.9 beats per minute before pressurewas applied to the left carotid artery and60.3 beats per minute during left carotidpressure (p < 0.025). The mean percentheart rate changes during carotid pressurewere significantly greater (p < 0.0001) forthe control group than for the lepromatouspatients.

Valsalva maneuver. In the lepromatouspatients the mean heart rate changed from68.0 beats per minute at rest to 72.6 beatsper minute with the Valsalva maneuver (p <0.01). Only three patients showed reflexbradycardia. All the people in the controlgroup showed reflex bradycardia except forone in whom the heart rate did not change.The mean heart rate in this group changedfrom 72.2 beats per minute at rest to 65.4beats per minute with the Valsalva maneu-ver.

Tilting. All patients responded to stand-ing with a significant tachycardia at about10 seconds which persisted in most casesuntil after 20-30 seconds. The mean restingheart rate was 68.7 beats per minute andincreased to 85.8 beats per minute after tilt-ing (p < 0.001). The mean 30:15 beat ratio(length of R-R interval at beat 30 dividedby length of R-R interval at beat 15) (') was1.01. In the control group the mean restingheart rate was 75.5 beats per minute andincreased to 107.4 beats per minute aftertilting (p < 0.005), and the 30:15 beat ratiowas 1.24. This was significantly different(p < 0.0005) from that of the patient group.

DISCUSSIONThe results indicate that these patients

with long-standing lepromatous leprosyhave defective autonomic control of theheart. Impairment of vagal function was

TABLE 3. Mean percent heart rate changes from rest and alter test situations in leprosypatients and the control group.

Leprosypatients

Controlgroup Sign ificance

HR min/max (deep breathing) 2.70 26.07 <0.0001"bid HR rest/mental stress -0.16 16.32 <0.0005')/0.A HR rest/R carotid pressure 1.07 21.80 <0.0001%A I^rest/L carotid pressure 0.02 25.89 <0.0001To..1 HR rest/Valsalva maneuver 7.28 10.76 N.S.%A I IR rest/tilting (15th beat) 25.52 44.25 <0.01(Y0A FIR rest/tilting (30th beat) 23.28 16.16 N.S.ToA R-R interval 30th/15th beat (tilting) 1.01 1.24 <0.0005

334^ International Journal of Leprosy^ 1983

easily demonstrated by the different tests.Sympathetic impairment was less consis-tently demonstrated.

The variation-in heart rate (sinus arrhyth-mia) which depends on the vagal innerva-tion of the heart ( 7 '47) was abolished. Therewas no significant diRrence in the lepro-matous patients between the maximum andminimum heart rate during deep breathing(Table 2). In contrast the control groupshowed a significant difference in this pa-rameter (p < 0.02) and the mean percentheart rate changes occurring from rest toafter deep breathing were significantly dif-ferent for the two groups (p < 0.0001). Thistest is probably the most sensitive for as-sessment of vagal function ( 2 . 15 ).

Mental stress causes tachycardia which ismediated by sympathetic mechanisms(1.10.11 , .) In the present study there were nosignificant changes in heart rate in bothgroups after significant stress was applied.In the lepromatous patients the mean heartrate at rest was 70.7 beats per minute andafter mental arithmetic under mild harass-ment was still 70 beats per minute. In thenormal group the mean resting heart ratewas 75.3 beats per minute, and after thesame mental stress was 87.4 beats per min-ute. The mean percent heart rate changesfrom rest to after mental stress in these twogroups were statistically significant (p <0.0005) indicating greater changes in thecontrol group and probably impairment ofsympathetic function in the lepromatousgroup.

The response to carotid sinus pressure,although sometimes erratic ( 3), is a usefultest of vagal function. Carotid sinus pres-sure slows the pulse by six or more beatsper minute, in over 50% of normal people,particularly in the elderly (' 4). In the patientswith lepromatous leprosy there was nochange in heart rate with carotid sinus pres-sure on either side. In the control group thecarotid sinus pressure on either side pro-duced significant bradycardia. These find-ings indicate defective vagal function in thelepromatous patients.

Valsalva rate responses are particularlyuseful in assessment of autonomic nervousfunction ( 5). The early strain bradycardiawhich is the normal response ( 7) and is usu-ally 10% lower than the resting heart rate

( 13) did not occur in our patients with lep-romatous leprosy who had statistically sig-nificant tachycardia (Table 2). In contrastthe control group presented with early bra-dycardia with heart rates 9% lower than theresting heart rate (Table 2). These findingsindicate vagal impairment in the leproma-tous patients

The lepromatous patients also showed astatistically significant increase in heart rateimmediately after standing which, unlikethat in normals ( 44 ), persisted for quite along time. Ewing, et al. (4) showed that inpeople with normal autonomic control thereis a rapid increase in heart rate with the firstfew beats after standing, followed by a pla-teau for a further 5-10 beats, and then arelative bradycardia which is maximal atabout the 30th beat. The same investigatorsshowed that the heart rate in diabetics withautonomic neuropathy increases slowly andcontinuously over the 30 beat period. Theirdrug studies showed that this response ismediated through the vagus. They foundthat the 30:15 beat ratio gives a simple nu-merical value that reflects the presence orabsence of the relative bradycardia. Theirpatients with a 30:15 beat ratio of 1.00 orless had vagal damage. In patients with nor-mal autonomic function the 30:15 beat ratiowas 1.03 or more. Our patients with lep-romatous leprosy had a 30:15 beat ratio of1.01 and our control group a 30:15 beatratio of 1.24. These findings also indicatevagal impairment in the lepromatous pa-tients.

SUMNIARYThe integrity of the autonomic control of

the cardiovascular system was studied in 21patients with lepromatous leprosy and inten normal people using several simple testsbased on cardiovascular reflexes.

Inipairment of both parasympathetic andsympathetic function was demonstrated inthe lepromatous patients.

RESUMENSe estudia la integridad del control autonOmico del

sistema cardiovascular en 21 pacientes con lepra le-promatosa y en 10 personas sanas usando pruebas sim-ples basadas en los reflejos cardiovasculares.

Se demostrO una alteraciOn en las funciones sim-patica y parasimpatica en los pacientes lepromatosos.

5 1 , 3^Ki'riakidis, et al.: Autonomic Neuropathv in Leprosy^335

RESUME

On a cu recours a plusicurs epreuves simples, bastessur Its reflexes cardio-vasculaires, pour etudier, l'in-

tegrite du controle autonomique du systeme cardio-vasculaire chez 21 =lades atteints de lepre lepro-

mateuse et chez 10 personnes normales.On a pu demontrer clue les fonctions parasympa-

tiques etaient tomes deux endommagees chez les ma-

lades lepromateux.

Acknowledgment. We thank Mrs. Bernadette Kefa-

kis, Professor of Statistics, for help with the statistics.

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J. R., HOSKING, D. J. and Ri000r, P. A. Assess-ment of vagal control of the heart in diabetes.

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