16ournal ofNeurology, Neurosurgery, and Psychiaty 1993;56:1096-1102

Cardiovascular and sweating dysfunction inpatients with Holmes-Adie syndrome

P J Bacon, S E Smith

AbstractA cross-sectional study is reported inwhich 53 patients with Holmes-Adie syn-drome have been subjected to a batteryof tests of autonomic nervous functionreferable to the cardiovascular system, totwo objective tests of sweating function,and to subjective assessment of sweatingby application of quinizarin powder fol-lowed by body heating. The majority ofpatients were consecutive referrals; nonewas selected because of clinical indica-tions of autonomic dysfunction. Eightythree per cent of these patients had atleast one, 57% at least two, and 40% atleast three objective test abnormalities,as defined by values lying outside 95 per-centiles of healthy subjects who wwerematched for age and subjected to thesame tests. In the context of multipletesting, the probability of finding outsidevalues was such that a minimum of 3 wasrequired to define abnormality. On thisbasis 40% of patients were found to havesignificant evidence of autonomicdysfunction. The most frequent abnor-malities were impaired digital vaso-constriction to cold (23%), -a reducedheart rate response to the Valsalvamanoeuvre (17%), and excessive vari-ability in sweating between test sites (inone of the tests, 43%MO) which is consistentwith patchy loss. Abnormal quinizarintest appearances were seen in 10 patientsand in a further five patients the appear-ances were thought to be suggestive ofabnormality. Though assessment of theresults of this test are subjective, theobservations are consistent with the find-ings obtained from the objective testswhich were applied. Cardiovascular andsweating abnormality did not concur sig-nificantly and only the former was foundto increase progressively with knownduration of the pupillotonia. It is con-cluded that Holmes-Adie syndrome iscommonly accompanied by progressivemild but widespread autonomic involve-ment but rarely is this symptomatic. Ifsymptoms suggestive of autonomic neu-ropathy are found in a patient with tonicpupils, a careful search for some othergeneralised disorder is recommended.

(JNeurol Neurosurg Psychiatry 1993;56:1096-1 102)

Holmes-Adie syndrome is widely recognisedas comprising unilateral or bilateral tonicpupils with light-near dissociation togetherwith tendon areflexia. Though the conditionis almost always benign, a number of patientshave been reported in whom disturbances ofautonomic function occurred who couldshare the same unidentified aetiology. Thus,orthostatic hypotension," cough syncope,'and impairment of cardiac vagal reflexes67 aredocumented, suggesting that sympathetic andparasympathetic lesions may at least occa-sionally accompany this condition.Alternatively, as suggested by several authors,a putative lesion may lie within afferent fibres.Two patients with orthostatic hypotensiondescribed by Johnson et al3 were found tohave afferent baroreceptor blockade, which isconsistent with this hypothesis. Such a find-ing may be analogous to the disturbanceobserved in H reflex function.8

Disturbance of sweating was first observedby Ross.9 He reported the case of a 32 yearold patient with Holmes-Adie syndrome who,in suffering from selective progressive sudo-motor loss, readily developed heat intoler-ance. The association with Holmes-Adiesyndrome he considered to be fortuitous buta number of further reports followed."l"The occurrence of orthostatic hypotension inat least one of these cases2 suggests that thesweating disorder is determined by damage tothe controlling sympathetic nerve supply,though we know of no direct evidence thatestablishes this with certainty. Progressivehypohidrosis is likely to present clinically inone of two ways. Firstly, the affected skinareas may develop signs of drying. Secondly,if the anhidrotic area becomes very extensive,then hyperhidrosis will develop in the unaf-fected areas, particularly in hot climatesand/or in response to exercise and body heat-ing. Such hyperhidrosis is, however, likely tobe a late manifestation of a progressive disor-der of this type and it is therefore possiblethat lesser degrees of sweating disturbancemay exist undetected in this condition.

Autonomic involvement in Holmes-Adiesyndrome has been reviewed by Johnson.'8Though it is clear that autonomic functionmay be disturbed, we cannot find docu-mented evidence to indicate the prevalence ofsuch disturbances in this condition. The pre-sent study has been undertaken to investigatethe prevalence of cardiovascular reflex and

Department ofClinicalPharmacology, UnitedMedical and DentalSchools ofGuy's andSt Thomas's Hospitals(St Thomas'sCampus), London,UKP J BaconS E SmithCorrespondence to:Professor SE Smith,16 Dorchester Drive,London SE24 ODQ.Received 14 July 1992and in revised form5 January 1993.Accepted 14 January 1993

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Autonomic disorder in Adie's syndrome

sweating disturbance in patients withHolmes-Adie syndrome, as judged byresponses to a battery of tests.

MethodsPATIENTS AND HEALTHY SUBJECTSFifty three patients were recruited to thestudy; 43 were consecutive referrals from StThomas' Hospital, Moorfields Eye Hospital,and the National Hospital for Neurology andNeurosurgery, London. Ten further patients,whose names were on a diagnostic register,were studied at the Iowa State UniversityHospital, Iowa City, USA. None was selectedor referred because of known abnormalities ofthe autonomic nervous system other thanpupillotonia and none had symptoms indica-tive of cardiovascular autonomic abnormalityas revealed by direct questioning. Onepatient, a 39 year old man, reported a six yearprogressive history of excess sweating on theleft side of the body sufficient on occasion toproduce marks of salt deposition on thattrouser leg and shoe; much of his right sidehe described as excessively dry. This patientundoubtedly had Ross's syndrome. No otherpatient admitted to a sweating abnormality.

Cohorts of a parallel group of 71 healthysubjects of approximately matching age andsex distribution were studied for comparison;the numbers studied are provided in theResults section. None of the patients orhealthy subjects was taking drugs which hadaction on the autonomic nervous system.Characteristics of both groups are given intable 1.

All subjects gave written consent to partici-pation and the study was approved by theethics committee of West Lambeth HealthAuthority.

DIAGNOSISThe diagnosis of Holmes-Adie syndrome wasbased on unilateral or bilateral pupillotonia asrecorded by a Whittaker infrared televisionpupillometer, on light-near dissociation and,where light reflex response remained, on seg-mental iris palsy. Seventeen patients hadbilateral involvement. Tendon jerk hypore-flexia was present in all but four patients.Each subject had a normal fasting bloodsugar and glucose tolerance test, negativeVDRL, normal peripheral vibration sense (as

Table 1 Characteristics of healthy subjects and patientswith Holmes-Adie syndrome

Healthy Holmes-Adie

n 71 53Sex (M/F) 34/37 13/40Age:

(median) 43 42(range) 20-84 25-80

Systolic BP (mm Hg)* 126 (24) 118 (21)Diastolic BP (mm Hg)* 72 (12) 69 (9)Heart rate (bpm)* 67 (11) 66 (10)Pupillotonia:Known duration (years)

median - 9range - 0-5-42

Unilateral/bilateral - 36/17

*Mean (standard deviation).

recorded by biothesiometer), and was freefrom other neurological, orbital, or oculardisease.

INVESTIGATIONSSix tests of cardiovascular autonomic func-tion were applied as follows. Resting cardiacsinus arrhythmia and the response to deepbreathing and a Valsalva manoeuvre wererecorded with a microcomputer linkedECG.'9 Systolic and diastolic blood pressureand heart rate responses to slow passive head-up 70° tilt were measured by sphygmo-manometry and ECG respectively. Theresponse to sustained hand grip to 30% ofmaximum voluntary contraction was mea-sured similarly.20 The digital blood flowresponse to opposite hand immersion in ice-cold water was recorded by plethysmography(Vasculab SPG16) with the strain gaugeapplied to the middle phalanx of the leftindex finger. The response was calculated asproportional reduction in flow.

Three tests of sweating were applied to 51of the patients (two declined to be tested) inthe following order. Skin resistance wasrecorded with surface electrodes applied tothe first digit of each limb, using a microam-meter linked to a BBC B computer.Measurements (in kohms) were taken fromall four sites at rest (baseline) and in responseto a single deep breath (psychogalvanicresponse). The latter was recorded as per-centage change in resistance. Baseline valuesfor the four sites were averaged and expressedas a mean value and the variability betweensites as the coefficient of variation (CV%= SD x 100/mean). The psychogalvanicresponses were expressed in the same way.The numbers of active sweat glands at twosites (1 cm diameter) on the volar aspect ofeach forearm were recorded with a plasticimpression technique.2' The proximal sitewas at the junction of the upper and middlethirds, the distal site at the junction of themiddle and lower thirds. Measurements weretaken from all four sites at rest (baseline) andfollowing intradermal injection of carbachol(2 x 10-5M; 0-183 ,ug in 0-05 ml). As withresistance measurements, the results wereexpressed as mean and CV%. Finally, bodysweating was assessed subjectively followingdusting the skin of the trunk, shoulders, andupper limbs with quinizarin red powder andraising of core temperature by 1 °C by immer-sion of both legs to knee level for 20 minutesin a water bath maintained at 43°C. Theresults were graded as abnormal if there wasasymmetric patchy loss, and doubtful if thereappeared to be symmetric patchy loss.

STATISTICAL ANALYSISAll test results on patients were comparedwith age-related normal values previouslypublished (cardiac sinus arrhythmia, deepbreathing, and Valsalva responses) or withvalues obtained on the healthy subjects stud-ied here. Where appropriate, these were cal-culated as deviations from, or as ratios to, theexpected values. Abnormal test results were

l1097

Bacon, Smith

Table 2 Cardiovascular function test results (mean and SEM) in healthy subjects andpatients with Holmes-Adiesyndrome

Healthy subjects Holmes-Adie patients DifferenceMean 95% Mean No abnormal between groups

Measurement n (SEM) CI n (SEM) (high) (low) t test p value

Sinus arrhythmia and related:Mean RR interval (ms) 898 655-1141 52 908(19) 3 1 0-520 0-605SD of RR interval

(O/E)* 1.0 0-41-2-44 52 0-86 (0.05) 0 1 -2-768 0-008Deep breathing

difference (O/E)* 1-0 0-38-2-61 52 1-14 (0.07) 2 1 1-890 0-064Valsalva ratio (O/E)* 1-0 0-36-2-77 52 0-79 (0.08) 1 9 -2-670 0-010

Hand grip changes:Diastolic BP (mm Hg) 37 21-8 (1-3) 5-38 52 20-6 (1-3) 2 3 -0-630 0-530Heart rate (bpm) 37 14-9 (1-2) 0-30 51 18-0 (1-5) 6 2 1-480 0-142

Digital blood flow:Proportional reduction 32 0 59 (0 03) 0-24-0-93 51 0.47 (0.04) 0 12 -2-213 0-030

Tilt test changes:Systolic BP (mm Hg)

(O/E)* 65 0 (-)20-20 43 1-0 (1-7) 2 1 0-604 0-549Diastolic BP (mm Hg)

(O/E)* 65 0 (-)15-15 43 -2-7 (1-0) 0 3 -2-620 0-012Heart rate (bpm)

(O/E)* 65 0 (-)12-12 42 3-6 (1-2) 6 0 2-882 0-006

*0 = observed; E = expected (age-dependent); 95% confidence intervals are approximate.

defined as values lying outside 95 percentilesin the normal range.

Grouped deviations from the expected val-ues and differences between patient andhealthy groups were tested by Student'sunpaired t tests. Relationships between testresults and known duration of pupillotoniawere examined by linear regression analysisusing standard methods.

ResultsThe mean results of all the tests applied tohealthy subjects and Holmes-Adie patientsare given in tables 2 and 3. The differencesbetween groups are presented as unpaired ttests and the numbers of patients lying out-side the normal confidence limits are pro-vided.

SINUS ARRHYTHMIA AND RELATED TESTS

All but two of the patients had resting heartrates within the normal range. These two,women aged 44 and 58 years, had no otherabnormal results. One patient, a 66 year oldman known to have had pupillotonia for 17years, had reduced sinus arrhythmia at restand on forced deep breathing, as well as an

abnormally low Valsalva ratio. Eight furtherpatients (one man, seven women) had abnor-mally low Valsalva ratios (fig 1). As a group

the patients yielded significantly lower valuesof resting sinus arrhythmia (0-86 vs 1-00, p =

0008) and of the Valsalva ratio (079 vs 1 00,p = 0010).

HAND GRIP CHANGESThe responses of the patients to sustainedhand grip did not differ significantly fromthose of the healthy subjects. Five patientsshowed diastolic BP changes outside the nor-

mal range, two above and three below, andseven patients had heart rate changes outsidethe normal range, five above and two below.Such a distribution pattern is of doubtful sig-nificance.

DIGITAL BLOOD FLOWThe patients with Holmes-Adie syndromehad a significantly reduced response of digitalblood flow to ice-cold hand immersion bycomparison with the healthy subjects (047 vs

059, p = 0030). Twelve of the patients(three men, nine women) showed responsesbelow the normal range (fig 1).

TILT TEST CHANGESThe responses of the patients to passive head-up tilt differed marginally from those of thehealthy subjects. Systolic BP changes did notdiffer, but diastolic BP fell slightly more (-2-7mm Hg, p = 0012) and the heart rate rose

Table 3 Sweat test results (mean and SEM) in healthy subjects and patients with Holmes-Adie syndrome

Healthy subjects Holmes-Adie Patients DifferenceMean 95% Mean No abnormal between groups

Measurement n (SEM) CI n (SEM) (high) (low) t test p value

Skin resistance (kohms)Mean baseline 35 513 (58) 0-1200 48 816 (128) 6 0 1-920 0-058CV%* baseline 35 14-1 (1-6) 0-32-5 48 27-0 (3 5) 15 0 2-996 0 004Mean psychogalvanic

response 35 5-5 (0 8) 0-15 48 5*9 (0 6) 2 0 0 397 0-692CV% psychogalvanic

response 35 30-4 (2 8) 0-64 47 49 7 (4 8) 14 0 3-181 0-002No of active sweat

glandsMean baseline 31 5-1 (0 5) 0-11.1 47 9-8 (2 5) 7 0 1-488 0-141CV% baseline 31 66-0 (5-5) 4-3-127-8 47 66-6 (5-0) 3 0 0 077 0 939Mean carbachol

stimulated 31 89-9 (5 5) 28-4-151-5 47 87-9 (5-0) 3 0 0-267 0-790CV% carbachol 31 28-3 (2-0) 5-8-50-8 47 38-6 (2-6) 10 0 2-839 0-006

stimulated

CV% = coefficient of variation.

1098

Autonomic disorder in Adie's syndrome

Figure I The Valsalvaratio (A), expressed inrelation to the age-relatednormal value,'9 and theproportional reduction indigital bloodflow inducedby cold water immersion ofthe opposite hand (B) inpatients with Holmes-Adiesyndrome in relation tO age.Continuous lines indicatemean values in healthysubjects. Broken linesindicate the upper andlower 95 percentiles of thenormal range.

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slightly more (3-6 bpm, p = 0-006) thanexpected. Six patients (four men, and twowomen) had heart rate changes above thenormal range.

SKIN RESISTANCE (FIG 2)In the healthy subjects, there were no signifi-cant differences in mean resistance or psy-chogalvanic response between the four testsites used. The mean baseline skin resistancein the patients was marginally higher (p =0-058) than in the healthy subjects and this

was subject to significantly greater variabilityas indicated by the CV% (p = 0-004). Themean psychogalvanic response of the patientsdid not differ from that of the healthy sub-jects, but it was subject to significantly greatervariability (p = 0-002). In both cases, thegreater variability is indicative of patchy func-tional differences.

FOREARM SWEAT GLAND COUNTS (FIG 3)In the healthy subjects, there were signifi-cantly greater numbers of active sweat glandsat the distal than at the proximal forearm testsites, both at baseline (5-9 vs 4-3, p = 0-009)and after carbachol stimulation (103-8 vs76-1, p < 0-001), but there were no signifi-cant side to side differences in either mea-surement. The mean number of active sweatglands in the patients did not differ from thatin the healthy subjects at baseline (p = 0-141)nor after carbachol stimulation (p = 0-790).The numbers of sweat glands activated bycarbachol was, however, subject to signifi-cantly greater variability as indicated by theCV% (p = 0-006). In this case, the greatervariability is indicative of a patchy functionaldifference.

QUINIZARIN TESTSTen patients showed evidence of patchyasymmetric sweating loss; this group includedthe one patient who had symptomaticlocalised hyperhidrosis as described in theMethods section. Five further patients alsoappeared to have patchy loss but in thesecases the loss was symmetrical and to thatextent it must therefore be regarded as uncer-tain.

PATIENTS WITH ABNORMAL RESPONSESIn the tests performed 44/53 patients (83%)had at least one abnormal result, 30 patients

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Figure 2 Mean skin resistance, its percentage change with deep respiration, and their variability between test sites (CV)in patients with Holmes-Adie syndrome. Symbols as in figure 1.

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Figure 3 Mean numberof active sweat glands atbaseline, after carbacholstimulation, and theirvariability between testsites (CV) in patients withHolmes-Adie syndrome.Symbols as in figure 1.

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(57%) had at least two, and 21 patients(40%) at least three abnormal results. Twopatients, a 28 year old woman and a 55 yearold woman, each had five abnormalities, one40 year old man had six, and one 80 year oldman seven abnormal test results. Assuming abinomial distribution of test abnormalities,the probability of these findings occurringsolely from multiple testing is p < 0-001 (X2 =256-00). With the number of tests applied inthis study, however, the overall probabilitythat results outside the normal 95 percentileswill be found is such that only a minimum ofthree or more such results in the individualpatient can be taken as evidence of his or herabnormality. On this basis 21 patients (40%)have evidence of autonomic dysfinction.There was no sex bias in the occurrence ofabnormal test results.The commonest abnormal findings were

(a) a reduced Valsalva response; (b) reduced

Table 4 Cardiovascular and sweating tests results in patients with Holmes-Adiesyndrome. Relationship with known duration ofpupillotonia (n = 41)

SlopeMeasurement (per 10 years) t test p Value

Sinus arrhythmia and related:Mean RR interval (ms) -30-5 - 1-468 0-150SD ofRR interval (O/E) - 0-02 - 0-365 0-717Deep breathing difference (O/E) -0-03 -0-317 0-753Valsalva ratio (O/E) -0-14 -1-800 0-080

Hand grip changes:Diastolic BP (mm Hg) - 1-22 -0-903 0-372Heart rate (bpm) -4-11 -2-399 0-022

Digital blood flow:Proportional reduction -0-12 -2-971 0-005

Tilt test changes:Systolic BP (mm Hg) (O/E) -2-3 -1-389 0-175Diastolic BP (mm Hg) (OLE) - 1-2 -0-990 0-330Heart rate (bpm) (O/E) -2-2 -1-532 0-137

Skin resistance:Mean 140-5 2-389 0-023CV% 9-1 2-197 0035Mean respiratory change -0-73 -1-080 0-288CV% respiratory change -1-8 -0-382 0-705

Active sweat glands:Mean unstimulated 5-4 1-671 0-104CV% unstimulated 9-3 1-589 0-122Mean stimulated -17-5 -3-236 0-003CV% stimulated 5-3 1-773 0-085

digital vasoconstriction in response to cold;and (c) exaggerated variabilities in three ofthe sweating tests. An abnormal Valsalvaresponse occurred in 8/21 patients who hadat least three abnormal test results and inonly 1/32 patients who had fewer. As a pre-dictor of multiple abnormality indicatingautonomic dysfunction as defined above, thistest has sensitivity of 38-1% and specificity of96-9%. Similarly, the digital blood flow testshowed sensitivity of 38- 1% and specificity of87-5%. Variation in baseline skin resistanceshowed sensitivity of 61-9% and specificity of93.7%An abnormal appearance on quinizarin

testing occurred in 11/21 patients who had atleast three abnormal objective test results andin only 4/30 patients who had fewer. As a

predictor of multiple abnormality, this testhas sensitivity of 52-4% and specificity of86-7%.The duration of pupillotonia was known in

41 patients, there being borderline associa-tion between increased duration and involve-.ment of the second eye (Spearman r = 0-313,p = 0-046). Increased duration was associ-ated marginally-with a decline in the Valsalvaratio (p = 0-080), and with a fall in heart rateresponse to hand grip (p = 0-022), a fall indigital vasoconstriction to cold (p = 0-005),an increase in resting skin resistance (p =0-023) and its variability (p = 0-035), a

decrease in the response of sweat glands tocarbachol stimulation (p = 0-003), and a bor-derline increase in its variability (p = 0-085)(table 4). The prevalence of all test abnormal-ities increased with increasing duration of thecondition (Spearman r = 0-331, p = 0-034),though this relationship was found only withthe cardiovascular tests (r = 0-364, p =

0-0 19) and not with the sweating tests (r =-0-170, p = 0-287). Overall, the prevalence ofcardiovascular abnormalities did not correlatesignificantly with that of sweating abnormali-ties (r = 0-214, p = 0-131).

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Autonomic disorder in Adie's syndrome

DiscussionThe observations reported here indicate thatdisturbance in autonomic function asrevealed by a battery of cardiovascular andsweating test responses is common in patientswith Holmes-Adie syndrome. Thus, we foundin this cross-sectional study that 83% showedat least one, 57% at least two, and 40% atleast three test abnormalities. This highprevalence of abnormal test results must,however, be interpreted in the knowledge thatwith multiple tests (normal range defined asthe mean with 2 SDs), the probability ofobtaining outlying results is very high. Takingthis into account, we conclude that 40% ofthe subjects show evidence of abnormality.The most frequent such abnormalitiesinvolved impaired peripheral vasoconstrictionin response to cold, a reduced heart rateresponse to the Valsalva manoeuvre, andexcessive variability in sweating tests. Overall,approximately equal numbers of subjects hadevidence of cardiovascular and sweating dis-order. Our findings are therefore consistentwith the few existing published clinicalreports of autonomic dysfunction in this con-dition, though they indicate that the underly-ing abnormalities are probably more frequentthan previously supposed.We failed, however, to observe a clear dis-

tinctive pattern of disorder which- could per-mit localisation to a particular part of theautonomic nervous system. Failure of periph-eral vasoconstriction and abnormal sweatgland responses imply that the sympatheticsystem is involved; failure to slow the heartduring the recovery phase of the Valsalvamanoeuvre, as previously reported,6 impliesparasympathetic involvement. We found anabnormally low Valsalva ratio in nine (17%)of our patients, which is consistent withimpaired parasympathetic function, and in afew other patients exaggerated heart rateresponses to hand grip and passive upright tiltwhich are also possible consequences of dis-turbed parasympathetic function. Such con-siderations suggest that on the efferent sideboth divisions of the autonomic nervous sys-tem may be involved in Holmes-Adie syn-drome, though the integrated and interactivenature of their function in normal physiologymakes this deduction uncertain. The disorderwould also appear to be consistent with anabnormality lying within autonomic afferents,to which reference was made earlier, thoughour observations do not help to distinguishthis possibility.The prevalence of cardiovascular abnor-

malities observed, collectively and in someindividual tests, was found to increase withincreasing known duration of pupillotonia.Thus, among the 10 patients who wereknown to have had the condition for 15 yearsor more, nine of them had at least one, andfive had at least two test abnormalities. Thissuggests that involvement of the autonomicnervous system is progressive. Despite thisgeneral picture, however, not one of thepatients had symptoms referable to thisinvolvement. If the disturbances observed are

indicative of an autonomic neuropathicprocess analogous to that affecting the ciliaryganglia, it must be one which is characterisedby very slow progress. It can be concludedthat cardiovascular reflexes are frequentlyimpaired in Holmes-Adie syndrome, which issuggestive of progressive autonomic dysfunc-tion in this condition. The impairment, how-ever, rarely results in clinical disturbance. Itfollows that, if symptoms indicative of auto-nomic neuropathy are found in a patient withtonic pupils, a careful search for a generalisedcause must be instituted.The observations reported here indicate

that disturbance of sweating as revealed bymeasurement of skin resistance and countingof active sweat glands is also common inpatients with Holmes-Adie syndrome. Thus,we found in this cross-sectional study that61% showed at least one and 37% at leasttwo such test abnormalities. Skin resistancehas long been employed as a measure ofsweating but is prone to great inter and intra-subject variation. As expected, therefore, ourobserved normal ranges for baseline resis-tance and for the psychogalvanic responsewere wide. In each case the 95% confidenceintervals embraced zero, making it impossibleto detect reduced resistance-that is, hyper-hidrosis, with this test. Six patients, however,had increased baseline resistance, indicatingareas of hypohidrosis, and larger numbersshowed exceptionally wide variations insweating between the various test sites, bothat baseline and in the psychogalvanicresponse, which is consistent with patchysweating loss. Similar, though opposite, con-straints affect the usefulness of testing thenumbers of active sweat glands within dis-crete areas of forearm skin. Nevertheless, sixpatients showed exaggerated responses to thistest, four of them by a substantial margin (fig3). As expected, larger numbers showedexceptionally wide variations in sweatingbetween the various test sites, which is consis-tent with patchy involvement of the sudomo-tor system.

These findings are consistent with theappearances obtained when these patientswere subjected to quinizarin testing, theassessment of which is less objective. Wewere indeed surprised that as many as 10 ofthe patients had obvious asymmetric, and afurther five less obvious symmetrical, sweat-ing loss. In the analysis, however, this servedto confirm the objective evaluations whichindicate a remarkably high prevalence ofsweating impairment in this condition.

It has been suggested that sweating loss inRoss's syndrome is caused by autonomicnerve dysfunction.2 On this basis we hadanticipated that the occurrence of sweatingloss in these patients would coincide withautonomic dysfunction affecting the cardio-vascular system and furthermore that it wouldbe related to the duration of pupillotonia. Nosuch association was apparent in the analysisand there is therefore no present basis for theassumption that the sweating and cardiovas-cular abnormalities are necessarily manifesta-

1 101

1102

tions of the same general disturbance. It canbe concluded that sweating is frequentlyimpaired in Holmes-Adie syndrome, thoughthe development of symptomatic hypohidro-sis as first described by Ross9 must still beregarded as a rarity.

We are grateful to the Research (Endowments) Committee ofSt Thomas' Hospital for financial support. We thank the con-sultant neurologists and ophthalmologists of St Thomas'Hospital, Moorfields Eye Hospital, the National Hospital forNeurology and Neurosurgery, and Iowa State UniversityHospital for kindly allowing us to study their patients.

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