Abstracts

Factors influencing the blood pressure response to salt loading in patients with posturally related syncope

Cerebrovascular changes during vasovagal syncope

V.L. Wight, R. Hainsworth

Divisions of 1Medicine for the Elderly and 2Medical Physics, University of Leicester, United Kingdom

Institute for Cardiovascular Research, University of Leeds, Leeds, United Kingdom

B.J. Carey, 1 P.J. Eames, 1 R.B. Panerai, 2 J.F. Potter ~

Background: [t is unclear whether cerebral autoreguladon Although salt loading may be an effective treatment for posturally related syncope [1], there is the possibility that it may sometimes lead to hypertension [2]. We determined the effects of salt loading in patients with demonstrated poor orthostatic tolerance and examined whether there were any factors which could predict those who would develop increases in blood pressure (BP). We studied 168 patients referred due to attacks of unexplained syncope with no apparent cardiovascular or neurological cause and who were not taking relevant medication. Orthostatic tolerance was assessed as time to presyncope in a test of head-up tilt and lower body suction [3]. Sodium excretion was determined from a 24-h urine collection, Multiple regression analysis on the baseline data revealed significant correlations between systolic and diastolic BP and age and between diastolic BP and sodium excretion. There was no correlation between orthostatic tolerance and salt excretion. Ninety-one patients with iower than predicted[3] orrhostatic tolerance, baseline salt excretion <170 mmol/day, and supine BP <140/90 m m Hg were treated with slow sodium (15 m m o l ' k g - l ' d -1) and reassessed after 2-3 months. After salt loading, 65 (71%) patients had improved orthostatic tolerance. Changes in supine BP were variable and not significant; systolic changed by +2.4 (SD • 12.1) m m Hg and diastolic by +1.5 (SD • 8.9) m m Hg. Multiple regression analysis revealed that the change in BP was significantly correlated with age (p <0.05) and inversely with the baseline BP (p <0.005). There was, however, no correlation with baseline salt excretion or with the change in orthostatic tolerance. These results confirm the benefits of salt for treating unexplained orthostatic intolerance. Over a 2-3 month period, the salt had little overall effect on BP. However, some patients did show increases, and we would recommend discontinuation of salt for those showing no benefit and regular BP checks for those continuing on long-term treatment.

(CA) is impaired prior to VVS, with some authors reporting a paradoxical increase in cerebrovascular resistance (CVR) prior to VVS and others reporting appropriate cerebral vasodilation, Critical closing pressure (CrCP) refers to the pressure below which blood flow in a vessel ceases. Resistance-area product (RAP) is an index of CVR that takes CrCP into account. This study clarifies the cerebral hemodynamics of VVS by using the concepts of CrCP and RAP. Methods: Sixty-five normal subjects and 15 patients with recurrent VVS were subjected to 30 minutes of 70 ~ head-up tilt. Bilateral middle cerebral artery (MCA) blood flow velocities (CBFV) were measured using transcranial Doppler ultrasound. MCA pressure was estimated by using the Finapres device at heart level and adjusting values for the height difference. Heart rate and end-tidal and transcutaneous carbon dioxide (CO2) concentrations were monitored simultaneously. Results: All 15 patients and 13 normal subjects developed VVS. During presyncope, mean CBFV declined in tandem with the decline in MCA pressure, bu~ diasmIic CBFV declined to a greater extent than systolic CBFV (43% vs 7%, p >0.0001). CO 2 levels and RAP decreased during presyncope. CrCP increased prior to syncope to levels approaching MCA diastolic pressure and then decreased precipitously on syncope. Changes in CBFV, MCA pressure, RAP, and CrCP were identical in the presyncopal period in patients and normal subjects. Condusions- The fall in CBFV during presyncope suggests that CA is impaired during this period, despite a fall in RAP and, hence, in CVR. The rise in CrCP during presyncope is probably due to hypocapnia and may account for the selective fall in diastolic CBFV during presyncope. Rises in CrCP, therefore, offset the fall in RAP leading to impaired CA prior to NMS.

Reflex responses from carotid baroreceptors and chemoreceptors in dogs on high-salt diet A. Knill, O.A. Sofola, M. Drinkhill, R. H a i n s w o r t h Institute for Cardiovascular Research, University of Leeds, United Kingdom

References 1. EI-Sayed HM, Hainsworth H. Heart 1996; 75:24-50. 2. Intersalt co-operative research group. Br Med J 1998; 297:319328. 3. Hainsworth R, EI-Bedawi KM. Clin Auton Res 1994; 4:239244.

Several epidemiological studies have indicated an association between dietary salt intake and the level of arterial blood pressure. The mechanism responsible for the higher blood pressure is partly due to altered responsiveness of the 0959-9851 9 2000 Lippincott Williams & Wilkins

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CARS/EFAS Joint Meeting vascular smooth muscle, but an additional possibility is that cardiovascular reflexes may be changed. Evidence in support of this is our finding that salt loading of patients with syncope tends to reduce sensitivity of the baroreceptorheart rate reflex [1]. The study reported here was designed to examine the affects of dietary salt on the blood pressure responses to two reflexes: carotid baroreceptors, an inhibitory reflex, and carotid baroreceptors, an excitatory reflex. Dogs were maintained for 1 month on diets containing either 0.4 or 6 mmol/kg sodium chloride per day. They were then anesthetized with chloralose (100 mg/kg) and both carotid sinus regions vascularly isolated and perfused with blood at controlled pressures. Baroreceptors were stimulated by stepwise increases in carotid sinus pressure from 60 to 210 m m Hg. Chemoreceptors were stimulated either by changing the perfusate from arterial (Po~, 113 _+5 m m Hg; P c o , 36 + 2 m m Hg; p H 7.43 -+ 0.01) to venous blood (Po2, ~9 -+ 2 m m Hg; Pco2, 41 _+ 1 m m Hg; pH, 7.40 _+ 0.01) or by a bolus injection of nicotine bitartrate (40 lag). At low carotid pressures, the dogs on high-salt diets (n = 5) had higher blood pressures than the low-salt dogs (n = 5), and the stimulus response curves were to the right; ie, responses obtained to higher carotid pressures. The sensitivity of the reflex, measured as the peak slope of the curve, however, did not change. In the same dogs, stimulation of chemoreceptors with venous blood caused an increase in blood pressure of 8.9 _+ 5.0 and 3.8 + 1.6 m m Hg in the high- and low-salt groups, respectively. The corresponding responses to nicotine were 10.0 + 6.7 and 2.3 _+5.0 m m Hg. These results demonstrate that following salt-loading baroreceptors are reset to higher pressures and that the responses to chemoreceptor stimulation are enhanced. Both of these effects could contribute to the development of hypertension.

Reference 1. EI-Sayed H, Hainsworth R. Clin Sci 1995; 88:463-470.

Observations on recurrent syncope and presyncope in 641 patients: tertiary autonomic referral center experience C.J. Mathias, 1 K. Deguchi, 1 I. Schatz 1'2

1Autonomic Unit, National Hospital for Neurology and Neurosurgery, Institute of Neurology, University College London, and Neurovascular Medicine Unit, Imperial College School of Medicine at St. Mary's, London, United Kingdom; 2University of Hawaii at Manoa, Department of Medicine, Honolulu, Hawaii, USA Syncope is a relatively common disorder that can be potentially disabling in young and particularly in older subjects. Once neurological, cardiological, and metabolic causes have been excluded, there still remains a large group in which the diagnosis is unclear; some may have an autonomic basis. We therefore performed a retrospective study on consecutive patients referred to our tertiary referral autonomic centers between 1992 and 1998 with recurrent syncope and presyncope, in whom nonautonomic causes, prior to referral, had been sought and excluded. The object was to determine if autonomic investigation (screening and additional testing if relevant) contributed to diagnosis. 150

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Data from case notes and from the autonomic database were analyzed. Syncopal patients with a known or provisional diagnosis of autonomic failure were excluded from analysis. The role of screening autonomic tests in either establishing or excluding autonomic failure was assessed. Response to different autonomic tests (such as head-up tilt with or without venepuncture, and food challenge and exercise) was documented. Some patients underwent further additional testing if nonautonomic neurological, psychiatric, and other disorders were considered. Screening autonomic function tests indicated orthostatic hypotension and confirmed chronic autonomic failure in 31 (4.8%). Neurally mediated syncope, an intermittent autonomic abnormality in the absence of autonomic failure, was diagnosed in 279 (43.5%) on the basis of clinical features and autonomic testing. The majority had vasovagal syncope (81%); other causes included carotid sinus hypersensitivity (13.3%) and, in a group of 15 (5.4%), rarer causes, such as micturition, swallowing, and coughing. Miscellaneous cardiovascular causes (systemic hypotension, arrhythmias) or drugs contributed to syncope in 53 (8.3%). Nonautonomic neurological causes included vestibular dysfunction (32; 5%) and epilepsy (11; 1.7%). In 56 (8.7%), a psychiatric cause was thought to be contributory. In 179 (27.9%), despite investigation, no abnormalities were found and the final diagnosis was syncope of unknown etiology, Referral to an autonomic center led to a diagnosis of an autonomic disorder (either chronic or intermittent) in nearly half the patients. The majority had vasovagal syncope while other diagnoses included chronic autonomic failure, carotid sinus hypersensitivity, or rarer causes of neurally mediated syncope. Some observations from autonomic screening tests (such as a low basal blood pressure, orthostatic hypotension without evidence of neurogenic failure, or arrhythmias) contributed to diagnosis. The lack of an autonomic nervous system abnormality was of importance in the 52% without an autonomic disorder, and further testing led to diagnosis of associated disorders, ranging from neurological deficits to psychiatric or morbidity. In 28%, although a definitive diagnosis could not be made, autonomic failure was excluded and an autonomic cause of syncope was thought unlikely. In patients with syncope in whom neurological, cardiological, and metabolic causes have been excluded, autonomic investigation is of value in confirming or excluding diagnoses and, thus, in aiding management.

Myocardial endothelial dysfunction complicates cardiac sympathetic dysinnervation in diabetic autonomic neuropathy M. Stevens, R. Pop-Busui, I. Kirkwood, D. Wieland, J. Corbett, D. Raffel

Ann Arbor, Michigan, USA Regional cardiac sympathetic hyperactivity predisposes to malignant arrhythmias in nondiabetic cardiac disease. Conversely, cardiac sympathetic denervation predicts increased morbidity and mortality in severe diabetic autonomic neuropathy (DAN). We propose that, in diabetes, regional cardiac denervation may elsewhere induce regional sympathetic

CARS/EFASJoint Meeting hyperactivity and ischemia, which may in turn act as a focus for chemical and electrical instability. We have previously used positron emission tomography (PET) and [11C]hydroxyephedrine to explore regional changes in cardiac sympathetic neuronal density and [13N]ammonia to measure regional changes in myocardial coronary flow reserve (CFR) in DAN patients. These studies identified islands of left ventricular (LV) sympathetic hyperinnervation that exhibited impaired CFR. Since diabetes is characterized by endothelial dysfunction, we hypothesized that these hyperinnervated regions would also demonstrate paradoxical vasoconstriction on sympathetic activation. Therefore, regional changes in LV myocardial blood flow (MBF) were studied in response to cold-pressor testing in type 1 diabetic patients with DAN (DAN+; n = 7) and age-, sex-, and diabetes duration-matched type 1 diabetic subjects without DAN (DAN-; n = 7). In response to sympathetic activation, MBF in the proximal innervated regions decreased to 0.85 + 0.07% of resting values (p <0.05) in DAN+ subjects, compared to a 1.2 + 0.12% (p <0.05) increase in flow in the DAN- subjects (p <0.05 vs DAN+). In contrast, MBF remained unchanged in the distal denervated segments (CFR 0.96 _+ 0.06) of the DAN+ subjects, compared to a 1.47 _+0.14 (p <0.01)fold increase in the DAN- subjects. Diabetes may result in LV sympathetic dysinnervation. In DAN+ subjects, the proximal innervated segments demonstrate impaired CFR and paradoxical vasoconstriction on sympathetic activation consistent with microangiopathy and endothelial dysfunction, respectively. This combination could result in potentially life-threatening myocardial electrical and chemical instability.

Effects of hemodialysis and autonomic dysfunction on QT interval in patients with renal failure S. Maule, 1 M. Veglio, 2 F. Mecca, 1 C. Calvo, 1 R. Quadri, ~ M. Marangella, 3 P. C a v a l l o Perin ~

1Department of Internal Medicine, University of Turin, Turin, Italy; 2Endocrinology Unit and 3Nephrology Unit, Mauriziano Hospital, Turin, Italy

Background: Q T interval prolongation is related to autonomic nervous activity; it predicts cardiovascular death in the general population and is associated with a poor prognosis in various diseases. Patients with end-stage renal disease show a high incidence of ventricular arrhythmias and cardiovascular sudden death and may have impaired autonomic nervous function and prolonged Q T interval. Aim of the study: To assess the effects of hemodialysis and autonomic nervous dysfunction on corrected Q T interval and dispersion in end-stage renal failure patients. Patients and methods: Twenty-two patients on maintenance hemodialysis (mean age, 67 + 10 y; 7 with diabetic nephropathy) were studied. A 12-lead electrocardiogram was recorded before and after a single hemodialysis session. Q T interval was measured manually and corrected according to Bazett's formula (QTc), and QTc dispersion was calculated. The degree of autonomic impairment was assessed with a battery of standard cardiovascular tests (deep breathing, lying to standing, cough test, and postural blood

pressure). Patients with two or more abnormal results in the cardiovascular tests were considered to be affected by autonomic neuropathy. Results: Seven of 22 (31.8%) patients were affected by autonomic neuropathy, 3 (42.8%) of whom were diabetic. Basal QTc interval was 429 _+22 ms and rose to 456 + 33 ms after the dialysis session (p = 0.003). Basal QTc dispersion was 38 + 17 ms and remained unchanged after the dialysis session (33 -+ 17 ms; p = 0.44). In the patients with (A) and without (N) autonomic neuropathy, basal QTc was similar (A: 433 + 27 ms; N: 427 + 21 ms; p = 0.59), and no difference was observed in the QTc increase after the dialysis (A: 5.6 -+ 5.1% change; N: 5.5 + 8.0% change; p = 0.97). Conduslons: Hemodialysis increases QTc interval but not QTc dispersion in patients with end-stage renal disease. Though in a limited number of patients, our preliminary results suggest that autonomic neuropathy might not contribute to Q T interval variation in such patients.

Cardiac MIBG uptake in the differential diagnosis of parkinsonian syndromes with autonomic failuremwhere do we stand? S. Braune

Neurologische Universit~its!dinik Freiburg, Freiburg, Germany Scintigraphy with [123]metaiodobenzylguanidine (MIGB) enables the quantification of postganglionic sympathetic cardiac innervation. MIBG has a biochemical structure similar to noradrenaline, but no pharmacological activity. It is incorporated into adrenergic cells by the same active uptake mechanism as norepinephrine and stored in granules. Therefore, the concentration of MIBG not only reflects the localization of postganglionic adrenergic neurons in organs but also serves as an index of their integrity and function. Unequivocal evidence has accumulated from several groups with a total of more than 130 patients that cardiac MIBG uptake is grossly reduced in idiopathic Parkinson's disease (IPD), indicting an involvement of postganglionic sympathetic neurons. More than 40 patients with MSA were investigated up to now, with MIBG scintigraphy showing normal uptake in nearly all patients. Three cases, reported from a Japanese group, with undoubtedly probable MSA and impaired cardiac MIBG uptake, were taking droxidopa. This substance is also known as L-threo~3,4-dihydroxyphenylserine, which is a precursor of norepinephrine, increases norepinephrine plasma levels, and, therefore, reduces cardiac MIBG uptake. Otherwise, all patients were correctly assigned to their clinical diagnosis based on the MIBG results. This was possible independent of parldnsonian medication, duration of disease, and clinical evidence of autonomic failure. In comparison with MRI, PET, and SPECT techniques, MIBG scintigraphy is more widely available, is cheaper, and appears to be more accurate than previously reported techniques. To obtain reliable results, imaging has to be performed 4 hours after injection of MIBG, and a number of substances need to be avoided that can interfere with neuronal uptake of MIBG. Clinical Autonomic Research 2000, Vol 10 No 3

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Daily variations of cortisol secretion in patients with multiple system atrophy with nocturnal decrease of vasopressin secretion into plasma T. O z a w a , 1 Y. S o m a , 1 N. Y o s h i m u r a , z N. F u k u h a r a , 3 S. Tsuji 1

1Department of Neurology, Brain Research Institute, Niigata University, Niigata; 2Takeda General Hospital; 3National Saigata Hospital, Japan We recently reported a nocturnal decrease in vasopressin secretion into the plasma in patients with multiple system atrophy (MSA) [1], which could explain the mechanism involved in the nocturnal polyuria reported in patients with MSA and autonomic failure by Mathias et al, [2]. Neurodegeneration of the suprachiasmatic nucleus (SCN) in the hypothalamus, reported previously [3], is considered to be responsible for the nocturnal decrease of vasopressin secretion in patients with MSA. These clinical results necessitate further investigations of cortisol secretion, which is also regulated by the SCN. With this background, we measured the plasma cortisol concentrations in 18 patients with MSA every 4 hours during a 24-hour period to determine whether the pattern of diurnal and nocturnal cortisol secretion is aberrant in these patients. The results showed that the plasma concentrations of cortisol in these patients were the highest during the night, indicating a discrepancy from the circadian rhythm of cortisol secretion in healthy people. This raises the possibility that the system responsible for light-mediated regulation of the rate of cortisol secretion [4] is affected in patients with MSA. These results support the hypothesis that the SCN is affected in patients with MSA.

References 1. Ozawa T, Tanaka H, Nakano R, et al. J Neurol Neurosurg Psychiatry 1999; 67:542-545. 2. Mathias C J, Fosbraey P, de Costa DF, et al. BMJ 1986; 293:353354. 3. Ozawa T, Oyanagi K, Tanaka H, et al. J Neurol Sci 1998; 154:116121. 4. Buijs RM, Wortel J, van Heerikhuize J J, et al. Eur J Neurosci 1999; 11:1535-1544.

Investigation into cardiovascular dysautonomia in Parkinson's disease and reported excess mortality with selegiline therapy using autonomic function tests and heat rate variability analysis K.F. B h a t t a c h a r y a , R. H o o p e r , L. Nashef, K.R. C h a u d h u r i

Movement Disorders Unit, Department of Neurology, King's College Hospital, London, United Kingdom

Background" Mortality in Parkinson's disease (PD) continues to be raised in the postlevodopa era. Concerns have been raised 'over the use of the monoamine oxidase inhibitor selegiline in combination with levodopa after links with excess mortality reported by the PDRG UK. It has been suggested that postural hypotension in both PD itself and selegiline therapy is linked to excess mortality. Objectives: Using a standard battery of autonomic function tests (AFTs) in conjunction with power spectral analysis (PSA) of heart rate variability (HRV), we aimed to investigate further cardiovascular reflexes in PD with particular emphasis on the cardiovascular side effects of selegiline. 152

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Methods: The four patient groups were as follows: group 1, levodopa and selegiline therapy (n = 13); group 2, levodopa therapy (n = 11); group 3, drug-naive patients (n = 13); and group 4, normal controls (n = 10). Groups 1, 2, and 3 were matched for age, and groups 1 and 2 were matched for disease severity and duration. All patients underwent a clinical examination, UPDRS assessment, autonomic questionnaire, a battery of AFTs, and a 24-hour Holter recording. The AFTs were modified for concurrent Holter recording. Heart rate (HR) and blood pressure (BP) responses were measured after 5 minutes supine, sitting and standing, 2 minutes isometric handgrip (IHG), and 30 minutes headup tilt at 60 ~ Statistical group comparison of HR, BP re-sponses and HF/LF ratios (high frequency/low frequency) was performed using repeated measures of analysis and oneway ANOVA. Results: Six patients in group 1 and three patients in group 2 reported orthostatic symptoms. Two patients in group 1 had documented previous cardiac arryhthmias. During head-up tilt, one patient in group 2 only experienced presyncopal symptoms toward the end of the tilt period. Systolic BP (SBP) response to standing and head-up tilt showed a clear trend toward greater fall in SBP in group 1 > group 2 > group 3 > group 4. This was significant on repeated measures of analysis between groups 1 and 4 in response to standing (p <0.05) and between groups 1, 3, and 4 during head-up tilt (p <0.01 and 0.05, respectively). There was neither a significant group difference for HR, diastolic blood pressure (DBP), and SBP while supine and after 2 minutes IHG nor in HR and DBP during standing and head-up tilt. Conclusion: Our results to date show that selegiline causes a greater fall in systolic blood pressure in response to orthostatic stress when compared to other treated and untreated PD groups. This supports previous data sitting reduced cardiovascular reflexes with selegiline therapy. HRV PSA findings in response to AFT's will be presented in conjunction with the raw autonomic data.

Task-independent and -dependent differences in regional brain activity in pure autonomic failure and healthy subjects H.D. Critchley, 1'2 R.J. Dolan, 2 C.J. M a t h i a s 1,3

1Autonomic Unit, NHNN, and Institute of Neurology; 2Wellcome Department of Cognitive Neurology, Institute of Neurology, UCL, London, United Kingdom; 3Neurovascular Medicine Unit, Imperial College School of Medicine at St. Mary's, London, United Kingdom Subjects with pure autonomic failure (PAF) have normal brains but fail to generate states of autonomic arousal during stress as a result of peripheral denervation of the autonomic nervous system [1]. Consequently, in PAF, peripheral autonomic responses are uncoupled from cerebral control, and there is no integrated afferent feedback of autonomic changes accompanying behavior. Thus, PAF provides a lesion/deficit model to investigate the influence of autonomic states of arousal on regional brain activity. Healthy controls and subjects with PAF were scanned using H2150 positron emission tomography (PET) during effortful exercise and mental stress tests

CARS/EFAS Joint Meeting and effortless control conditions, during which mean arterial blood pressure (MAP) and heart rate (HR) were measured. Data were analyzed using statistica[ parametric mapping (SPM99) [2]. Separate analyses identified betweengroup differences in regional brain activity (1) independent of task and (2) corresponding to the interaction between diagnosis and task effort. PAF subjects had significantly (p <0.05, corrected) greater activity in dorsal pons independent of task, significantly (p <0.001, uncorrected) greater activity in right cingulate and insula, and reduced activity in posterior cingulate/medial parietal lobe when performing effortful, compared to effortless, tasks (diagnosis-by-task interaction). Our findings clarify the functional neuroanatomy underlying autonomic control. Moreover, our findings support a recent theoretical model [3] that proposes a firstorder (context-independent autoregulatory) representation of bodily states at the level of dorsal pons and a secondorder mapping of bodily state to behavioral context, subserved by cingulate, insula, and medial parietal cortices. References

1. Mathias C J, Bannister R. Investigation of autonomic disorders. In: Autonomic failure: a textbook of clinical disorders of the autonomic nervous system. 4th ed. Mathias CJ, Bannister R, eds. Oxford: Oxford University Press; 1999. pp. 169-195. 2. http://www.fil.ion.ucl.ac.uk/spm/spm99.html 3. Damasio AR. The feeling of what happens. New York: Harcourt Brace; 1999.

Impaired afferent baroreflex response in patients with stenosis of the internal carotid artery S. Braune, A. Hertzel, B. G u s c h i b a u e r , C.H. L{icking

Neurologische Universit~itsklinik, Freiburg, Germany Atherosclerosis of the internal carotid artery (ICA) can potentially impair baroreflex responses. Ten patients with a unilateral ICA stenosis of more than 70% and 17 agematched healthy volunteers underwent a protocol with measurement of blood pressure, heart rate, end-expiratory CO2 partial pressure during supine rest, 70 ~ head-up tilt, and Valsalva maneuver under normocapnic and hypercapnic conditions. Hypercapnia induces a centrally generated sympathomimetic effect in cardiovascular regulation [1]. Increase in CO 2 values was induced by rebreathing room air, which was enriched with 7% CO 2. The differences to baseline of blood pressure values after 30 s in 70 ~ upright position and in phases II, IIe, III, and IV of the Valsalva maneuver were significantly lower in patients, compared with controls, under normocapnic and hypercapnic conditions. During hypercapnia in supine rest, increases in blood pressure were similar in both groups, indicating similar efferent sympathetic activity following central sympathetic stimulation. These findings underline that baroreflexmediated blood pressure regulation can be impaired in patients with ICA stenosis and that this is caused by,changes in the afferent baroreceptor pathway. Reference 1. Braune S, Hertzel A, Prasse A, Dohms K, Guschibauer B, LOcking CH. Stimulation of sympathetic activity by carbon dioxide in patients with autonomic failure compared to healthy subjects. Clin Auton Res 1997; 7:327-332.

Baroreceptor function during carotid endarterectomy with contralateral occlusion D. Sigaudo-RousseL, D.H. Evans, A.R. Naylor, R.B. Panerai, N.L. L o n d o n , P. Bell, M.E. G a u n t

Departments of Medical Physics and Surgery, Leicester, United Kingdom Blood pressure instability after carotid endarterectomy (CEA) has been associated with disturbance of the baroreflex control mechanism caused by the surgery on the carotid sinus region. This study aimed to investigate the mechanism by which CEA affects baroreceptor function. Methods: Fifty patients underwent a CEA. During the operation, heart rate (HR) and intra-arterial blood pressure (BP) were constantly monitored and recorded. During analysis, the following surgical maneuvers were investigated for their effects on baroreceptor function: dissection, clamping of the common carotid artery, restoration of cerebral blood flow through a bypass shunt, stroke test-stimulation of the intra-arterial carotid sinus area (carotid plaque in situ), removal of atheromatous plaque, repeat stroke test (plaque removed), clamping of the shunt, and restoration of blood flow through the carotid sinus area. Results: Patients with a contralateral occlusion (CO) were separated from the others (NCO). The CO patients had a lower BP and HR than the NCO patients until the plaque was removed. For both groups, the baroreflex was functioning before the endarterectomy, shown by the BP increase and decrease in response to clamping and to the first stroke test (with the plaque in place), respectively. The major result is a quicker and greater BP response for the CO patients, compared to the NCO before the endarterectomy. However, after the plaque was removed, the repeat stroke test was associated with an attenuated BP response and baroreceptor functionality, which persisted throughout the rest of the operation for both groups. Moreover, the endarterectomy induced a significant increase in BP and HR for both groups, but there is a more dramatic BP increase for the CO group, resulting in a similar BP trace for both patient groups. Conclusions: These results suggest that the carotid baroreceptor function may be altered by a carotid occlusion, which would then cause an inability to compensate a baroreflex disruption occurring on the other side.

Aim:

Autonomic studies in a hypertensive patient with unusual sexual dysfunction: response to reserpine K.K. D e e p a k , ~ B. B h a r g a v a , 2 R. Narang, 2 B.H. Paudel, 1 P.K. Rai, 1 S. S a x e n a 3

Departments of 1Physiology,2Cardiology, and 3Psychiatry,India Institute of Medical Sciences, New Delhi, India A 48-year-old male presented with hypertension (6 years) and history of erections and ejaculations on cold exposure and confrontation with fear situation (20 years). The patient had satisfactory sexual life and had 3 children. Exposure of foot to cold (10~ water) induced ejaculation in 10 Clinical Autonomic Research 2000, Vol 10 No 3

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CARS/EFASJoint Meeting sec. The study of cardiovascular autonomic function revealed increased sympathetic reactivity, normal parasympathetic reactivity, and normal sympathetic and parasympathetic tone. Earlier, he was prescribed a calcium channel blocker and b-blocker, which resulted in mild to moderate control of hypertension, without any improvement in ejaculatory function. We prescribed prazosin (1 mg followed by 2 mg over 2 weeks), which controlled the blood pressure but did not affect the episodes of ejaculations. We measured autonomic reactivity (by five standard tests) and activity (tone) while patient underwent therapy with prazosin, reserpine, and a combination of the two. Treatment with reserpine resulted in gradual reduction in blood pressure to normal, subjective improvement, gradual increment in latency of ejaculation, marked decline in volume of ejaculate, and reduction in sympathetic tone.

Baroreflex sensitivity in severe or mild essential hypertension and secondary hypertension M. Hanna, ~ V. Esko,1 H. Juha, 2 I. Risto,2 L. Tomi,~ L. Marrkku, 2 L. Esko 2

1Department of Clinical Physiology and Nuclear Medicine and 2Department of Medicine, Kuopio University Hospital and University of Kuopio, Finland Blood pressure variation is transmitted by arterial baroreceptors causing reflex changes in heart rate and vascular resistance, targeting the normalization of blood pressure. When blood pressure elevates, baroreceptor reflex regulation resets toward higher blood pressure range and operates with reduced sensitivity. The aim of this study was to evaluate the role of BRS in patients with different severity of essential hypertension and in patients with secondary hypertension. We compared patients in whom long-lasting high blood pressure was caused primarily by altered blood pressure regulation and patients in whom high blood pressure was secondary to renovascular disease. Fourteen patients with renovascular hypertension (RVHT), 36 patients with severe essential hypertension (SEHT), and 29 with mild essential hypertension (MEHT), as well as healthy age- and sex-matched control subjects, were studied. BRS was measured with the phenylephine method. BRS was reduced in the RVHT (3.7 +- 0.6 vs 8.5 _+1.6 ms/ram Hg; p = 0.004) and in the SEHT groups (7.6 _+ 0.8 vs 13.3 -+ 1.6 ms/mm Hg; p = 0.006), compared to corresponding control groups. However, BRS in the M E H T group did not differ from the control subjects (8.5 _+ 1.2 vs 90 -+ 1.0 ms/ram Hg). In the RVHT group, we found a negative association between BVRS and age and a positive association between BRS and SDNN, RMSSD, LF power, and HF power of HRV. In the SEHT group, BRS was associated inversely with age and systolic office blood pressure and positively with SDNN, total power, and LF power. In the M E H T group, BRS did not correlate significantly with any of the parameters. In conclusion, our study suggests that the impairment of BRS reflects the severity of long-lasting hypertension, rather than the initial pathophysiology leading to hypertension. 154

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Baroreflex failure induces orthostatic hypotension in familial dysautonomia M. Duetsch, 1 M.J. Hilz, 1'2 U. Rauhut, 1 B. Neund6rfer, ~ F.B. Axelrod 2

1Department of Neurology, University of Erlangen-Nuremberg, Germany; 2Departmem of Neurology, New York University, New York, USA Orthostatic hypotension (OH) in familial dysautonomia (FD) is attributed to sympathetic denervation of peripheral blood vessels. The clinical observation that blood pressure (BP) decreases and heart rate (HR) increases insufficiently with standing up suggests that baroreflex dysfunction contributes to O H in FD. In this study, we evaluated cardiovascular autonomic function and baroreflex sensitivity in FD. We monitored H R and systolic BP (Pilot) in 8 FD patients and 8 age- and sex-matched controls. We calculated mean HR, BP, and normalized low-frequency (LF; 0,040.15 Hz) and high-frequency (HF; 0.15-0.5 Hz) power during 85 s in sitting and standing position (HRView). As a measure of baroreflex sensitivity, we determined the LF transfer function gain between systolic BP and HR for coherence values above 0.5. After standing up, BP fell significantly in the FD patients (110.0 _+22.5 mm Hgvs 74,6 _+22.8 mm Hg; p <0.05) but not in the controls (116.4 _+ 10.5 mm Hg vs 120.8 +_ 12.5 mm Hg; p >0,05). H R did not change in the FD patients (80.0 _+4.0 bpm vs 83.4 +_3.9 bpm; p >0.05) but increased in the controls (72.9 -+ 3.5 bpm vs 84,5 _+ 4.3 bpm; p <0.05). LF power of systolic BP did not increase in FD (0.21 + 0.09 vs 0.26 _+ 0.12; p >0.05) but did in controls (0.35 -+ 0.08 vs 0.51 + 0.14; p <0.05). The LF transfer function gain decreased in the FD patients (1.65 -+ 1.00 vs 0.55 -+ 0.11; p <0.05) and remained stable in the controls (1.21 + 0.46 vs 1.05 _+ 0.42; p >0.05). Our findings confirm that standing up induces O H without compensatory tachycardia in FD patients and that there is inadequate sympathetic activation. The inadequate change of LF transfer function gain shows that impaired baroreflex function contributes to the pathophysiology of O H in FD.

Autonomic cardiovascular disturbances in Parkinson's disease and multiple system atrophy G. Wasner, J. Schattschneider, G. Deuschl, R. Baron

Klinik ftir Neurologie der CAU Kiel, Germany

Introduction" Autonomic disturbances are common features in Parkinson's disease (PD) and multiple system atrophy (MSA). It is still unclear to what extent different functional autonomic channels are involved. The aim of this study was to investigate cardiovascular reflexes using four different tests to differentiate the involvement of separate autonomic pathways in both diseases. For this, the skin vasoconstrictor test was applied as a new test to investigate cutaneous sympathetic outflow. Methods- The study was performed on 10 patients with PD and on 7 patients with MSA. All patients underwent four different autonomic tests: (1) head-up tilt testing was ap-

CARS/EFASJoint Meeting plied as a marker for sympathetic muscle vasoconstrictor outflow; (2) heart rate variability was measured to investigate mainly cardiac autonomic innervation; (3) skin temperature of the hands was measured (infrared thermometer), as it was suggested to be a marker for thermoregulatory disturbances [1]; and (4) skin vasoconstrictor test was performed to investigate cutaneous sympathetic activity--skin blood flow was measured with laser Doppler flowmetry during deep inspiratory gasps, leading to a vasoconstriction due to sympathetic vasoconstrictor neurons. Results: Eighty percent of PD and 100% of MSA patients had autonomic disturbances. However, autonomic failure was much more severe in MSA. Concerning the different tests, head-up tilt test showed orthostatic hypotension in only 20% of PD but in 100% of MSA patients; heart variability was disturbed in 80% of PD and in 86% of MSA patients; the "cold-hand sign" was observed in 10% of PD and in 40% of MSA patients; skin vasoconstrictor test was abnormal in 30% of PD but in 71% of MSA patients. Conclusions: The leading autonomic symptom in PD was autonomic cardiac dysfunction, while other sympathetic involvement was mild. In MSA, separate sympathetic pathways were severely disturbed. The skin vasoconstrictor test seems to be useful to investigate involvement of cutaneous sympathetic outflow. Supported by the Wilhelm Sander-Stiftung and the Deutsche Forschungsgemeinschaft (DFG Ba 1921/1-1).

Reference 1. Klein C, Brown R, Wenning G, Quinn N. Mov Disord 1997; 4:514518.

Elevated endogenous endothelin is a predictor for vasovagal syncope C. Magerkurth, S. Braune, R. Schnitzer

Department of Neurology, University of Freiburg, Freiburg, Germany The pathophysiology of vasovagal syncope is still poorly understood. We studied changes in blood pressure, heart rate, norepinephrine, epinephrine, endothelin, atrial natriuretic peptide (ANP), cortisol, and cGMP during 30 minutes in supine position and after 10 minutes in 70 ~ head-up tilt in 40 persons (20 men, 20 women). All subjects were investigated twice on different days. Seven subjects developed symptoms of a vasovagal syncope on one day with a typical drop in blood pressure and heart rate. Endothelin levels on both examination days were significantly higher during rest and head-up tilt, and norepinephrine increase was significantly lower in syncope patients. Variance analysis of the cardiovascular parameters showed a significant elevation of systolic blood pressure during rest and head-up tilt for the syncope patients on their examination day, without syncope. There were no differences for epinephrine, ANP, cortisol, and cGMP by comparing both groups. The results point to a permanent pituitary activation with an augmented endothelin release in persons with the tendency for vasovagal syncope independent of existing symptoms.

Effects of various simulated activities on arterial blood pressure in healthy subjects M.S. Pitt, R. Hainsworth Institute for Cardiovascular Research, University of Leeds, United Kingdom

Background: Orthostatic tolerance is usually assessed by determining responses to head-up tilting, lower body suction, or a combination of the two. However, although these tests are often of diagnostic value, they do not relate very closely to a person's normal daily activities. Objective: We used a continuous ambulatory blood pressure monitor (Portapres, TNO, The Netherlands) to record blood pressure fluctuations in subjects during various maneuvers designed to simulate the stresses likely to be encountered during typical activities. Method: Eighteen healthy subjects (12 men; mean age, 33.6; age range, 22-61 y) undertook the following maneuvers: (1) passive head-up tilt for 5 rain; (2) sitting at rest for 5 min, followed by standing (2 rain); (3) lying supine for 5 min, followed by standing for 2 min; (4) crouching for 1 min, followed by standing and stretching up (2 min); (5) treadmill walking, followed by standing still for 2 min; (6) isometric work, holding a weight at 25% MCV for 1 min; and (7) walking up a flight of stairs, then standing for 2 rain. Subjects then consumed a high carbohydrate "meal," and, after 15 min, tests 3, 4, and 7 were repeated. Results: All maneuvers caused perturbations of blood pressure. The largest change occurred during the crouch and subsequent stand, which increased blood pressure by 9.8 +1.8 mm Hg, followed by a decrease of 38 -+ 3 mm Hg. The duration of the fall from 50% of the maximum change to 50% recovery was 13.2 _+2.0 s. After the "meal," the pressure changes during the crouch and the level of the fall in pressure were significantly increased (p <0.01 and p <0.05, respectively). Conclusion: We propose that these maneuvers and the reference values provided by normal subjects may be of value in assessing patients with suspected deficient blood pressure control.

Influence of focus laterality on autonomic heart rate modulation in temporal lobe epilepsy B. Neund6rfer, Y. Saleh, A. Kirchner, E. Pauli, H. Stefan,

M.J. Hilz Department of Neurology, University of Erlangen-Nuremberg, Germany Epileptic activity modulates autonomic cardiovascular control. There are reports suggesting hemispheric lateralization of sympathetic and parasympathetic activity [1]. So far, there is no clinical correlation between heart rate (HR) changes and epileptic focus lateralization. This study evaluated whether seizure-related HR changes depend on the lateralization of the focus. In 27 epilepsy patients with seizure onset in the right (n = 16) and left (n = 11) temporal lobe, we studied HR changes in an interval from 1 min prior to 1 min after seizure onset using simultaneous video monitoring of seizures, HR, and electroencephalographic activity. We averClinical Autonomic Research 2000, Vol 10 No 3

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CARS/EFASJoint Meeting aged 5-sec HR intervals and analyzed changes of these average values before and during seizure onset in relation to the focus side by means of analysis of variance for repeated measures. Before seizure onset, HR of patients with lefr-sided focus increased slightly from 72.9 to 74.3 bpm (p >0.05), while patients with right-sided focus showed a significant increase from 72.5 to 80.9 bpm (p <0.05). After seizure onset, HR increased significantly in patients with left-sided focus from 85 to 109.5 bpm and with right-sided focus from 94 to 118 bpm (p <0.05), and the increase no longer differed between groups. The results confirm that there is a hemispheric lateralization of HR modulation with predominance of sympathetic activation in the right hemisphere. The findings might be relevant for the pathophysiology of cardiovascular complications and sudden unexplained death in epilepsy patients.

in CRPS I depends on spontaneous sympathetic activity. Taking this into consideration, skin temperature differences are capable of reliably distinguishing CRPS I from other extremity pain syndromes with high sensitivity and specificity. Supported by the Wilhelm Sander-Stifrung and the Deutsche Forschungsgemeinschaft (DFG Ba 1921/1-1). Reference 1. Tahmoush AJ, Malley J, dennings JR. Neurology 1983; 33:14831486.

Symptoms of autonomic failure in patients with Parkinson's disease (IPD) C. Magerkurth, S. Braune, R. Schnitzer

Department of Neurology, Universityof Freiburg, Freiburg, Germany

Reference 1. Hilz MJ, Devinsky O, Duetsch M, Perrine K, Rauhut U, Nelson PK. Ann Neuro11998; 44:449.

Validity of vascular disturbances in reflex sympathetic dystrophy G. Wasner, J. Schattschneider, R. Baron

Klinik fiir Neurologie der CAU Kid, Germany Introduction" Reflex sympathetic dystrophy (newer classi-

fication: complex regional pain syndrome type I [CRPS I]) is a chronic, painful disease of one extremity. It is clinically characterized by sensory, motor, and autonomic symptoms. Autonomic symptoms include differences in skin temperature between the affected and the unaffected limb due to disturbed unilateral perfusion that is suggested to be caused by sympathetic dysregulation. However, validity of autonomic symptoms is estimated to be low [1]. In this study, we investigated the sensitivity and specificity of unilateral vascular disturbances in CRPS in consideration of the sympathetic activity. Methods" Controlled thermoregulation was performed to change cutaneous sympathetic vasoconstrictor activity by the use of a thermal suit: skin sympathetic vasoconstrictor neurons were activated by whole-body cooling, and nerve activity was abolished by whole-body warming. Skin temperature (infrared thermometer) was continuously monitored at the affected and unaffected limb. Twenty-five patients with CRPS I were studied. Fifteen patients with painful limbs of other origin and 20 healthy individuals served as controls. Results" Absolute values of temperature side differences between the extremities changed dynamically in CRPS patients with highest values during a middle degree of sympathetic outflow. Vascular disturbances were less pronounced when sympathetic activity was low. In both control groups, there were only minor side differences in temperature. During controlled alteration of sympathetic activity, unilateral vascular abnormalities had a sensitivity of 76% and a specificity of 94%. Under resting conditions, sensitivity was only 32% and specificity was 100%. Discussion: The degree of unilateral vascular disturbances 156

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Since the first description of Parkinson's disease, symptoms of autonomic dysregulation have been part of the disease. Their frequency and impact on quality of life have been discussed controversially. One hundred forty-one patients with IPD were asked for symptoms of autonomic failure and their influence on quality of life, following a semistructured questionnaire and performance of a standardized cardiovascular reflect test. We investigated the frequency of symptoms in the overall group as well as comparing the group with cardiovascular autonomic dysfunction (32%) with the grouP2with normal cardiovascular reflex (68%) by using the X test. In the overall group, 48% reported dizziness; 45% reported bladder dysfunction; 30% reported bowel dysfunction, mainly constipation; 64% reported erectile dysfunction; 38% reported sleeping disorders; and 46% reported changes in hidrosis, exclusive of hyperhidrosis. The presence of dizziness (60% vs 41%), bladder dysfunction (60% vs 39%), constipation (60% vs 29%), and erectile dysfunction (82% vs 53%) was significantly more frequent in the group with cardiovascular autonomic dysfunction. In this group, Hoehn and Yahr stage and the L-dopa doses were higher, independent of the duration of disease. There was no correlation between the L-dopa dosage and blood pressure, either at rest or during active or passive tilt. In our study, cardiovascular autonomic dysfunction was found in one third of the patients with IPD and was already present in parkinsonian patients with disease duration of less than 5 years. Autonomic dysfunction in patients with IDP compromises their quality of life, which underlines the necessity to diagnosis and treat these nondopaminergic symptoms.

Neuropathy is a major cause of erectile dysfunction in diabetes M.J. Hecht, B. Neund6rfer, M.J. Hilz

Department of Neurology, Universityof Erlangen-Nuremberg, Germany Erectile dysfunction (ED) in diabetes is multifactorial. So far, the impact of neuropathy has not been well-determined.

CARS/EFAS Joint Meeting This study was performed to assess the contribution of neuropathy to diabetic ED. Forty-nine men with ED were examined by historytaking, a questionnaire focusing on autonomic symptoms other than ED, clinical examination, nerve conduction studies (NCS), sphincter ani electromyography (EMG), heart rate variability testing (HRV), and quantitative sensory testing (QST) of vibratory (V), cold (C), and warm (W) sensation. Vascular function was assessed by intracavernosal prostaglandin E1 (PGE1) injection test. We classified ED as diabetic (history of diabetes, no other neuropathy), neuropathic (~>2 abnormal results with the above mentioned tests, no diabetes), or of other origin. The frequency of abnormal results in diabetic and neuropathic patients was compared by X2 test. The percentage of the men who fulfilled the criteria of diabetic ED was 26.6; 42.9% had neuropathic ED. Vascular function was abnormal in only one patient with diabetic ED and three patients with neuropathic ED. Both groups had similar frequencies of autonomic symptoms other than ED (64% in diabetic vs 64% in neuropathic patients), abnormal EMG (33 vs 40%), and abnormal QST (V, 83 vs 84%; C, 9 vs 19%; W, 42 vs 43%). Abnormal clinical findings (50 vs 33%), NCS (75 vs 50%), and HRV (39 vs 25%) occurred slightly, but not significantly, more often in men with diabetic ED than neuropathic ED. To summarize, the tests indicating neuropathy showed abnormalities in men with diabetic ED as frequently as in men with neuropathic ED. Some tests suggested neuropathy even more often in diabetic than in neuropathic ED. The findings support the conclusion that neuropathy contributes significantly to the pathophysiology of ED in diabetes mellitus.

The effect of erythropoietin treatment on supine and standing blood pressure in patients with diabetic autonomic neuropathy A.S. Winkler, S. Landau, K.R. Chaudhuri, P.J. Watkins

Diabetes Centre, King's College Hospital, London, United Kingdom

Background: We have previously shown that some insulindependent diabetic patients with severe autonomic neuropathy (IDDM-DAN), including postural hypotension, can present with a normochromic anemia associated with etythropoietin (EPO) deficiency, which responds impressively to treatment with EPO. In this study, we investigated the effect of EPO treatment on the postural hypotension in these patients. Methods: Four anemic IDDM-DAN patients with significant postural hypotension and at least one other symptom of diabetic autonomic neuropathy were treated with EPO, After a l-month control period, EPO was injected subcutaneously thrice weekly in a dose of 25 IU/kg for 3 months. Blood pressure (BP) was recorded four times daily (morning, lunch, evening, and night), three times weekly, with a semiautomatic BP device. Supine mean BP was compared to the lowest corresponding standing BP within 5 minutes. Results. Daily standing mean BP in the individual patients increased significantly by 2.6 to 10.5 mm Hg (p <0.01) during treatment with EPO. In three patients, there was a

concomitant significant increase in daily supine mean BP, ranging from 2.8 to 14.8 mm Hg (p <0.001). Standing mean BP at different times of day showed a significant increase in the morning in all four patients (maximum difference between EPO on and off: 4.9 to 16.7 mm Hg; p <0.04) and a less uniform BP increase throughout the rest of the day. Conclusion: IDDM-DAN patients with postural hypotension may respond to treatment with EPO.

Brain activity relating to generation and representation of sympathetic skin responses in man: an fMRI study H.D. Critchley, 1'2 C.J. Mathias, 1'3 R.J. Dolan 2

1Autonomic Unit, NHNN, and Institute of Neurology; 2Wellcome Department of Cognitive Neurology, Institute of Neurology, UCL, London, United Kingdom; 3Neurovascular Medicine Unit, Imperial College School of Medicine at St. Mary's, London, United Kingdom Afferent cerebral feedback of states of autonomic arousal influences motivational behavior [1]. The sympathetic skin response (SSR) is one index of autonomic arousal. The precise functional neuroanatomy underlying generation and representation of SSR during motivational behavior is undetermined, though it is impaired by discrete brain lesions to ventromedial prefrontal cortex, anterior cingulate, and parietal lobe [2]. We used functional magnetic resonance imaging and continuous monitoring of SSR in healthy subjects to study brain activity associated with fluctuations in SSR, and activity corresponding to generation and afferent representation of discrete SSR events. Functional data were analyzed using statistical parametric mapping (SPM99) [3], first by examining brain activity covarying with SSR activity over the scanning period, and second using event-related methods to examine neural activity preceding and following discrete SSR peaks. Regions that covaried with increased SSR included right orbitofrontal cortex, right anterior insula, left lingual gyrus, right frusiform gyrus, and left cerebellum (p <0.05, corrected), and, at a less stringent level of significance (p <0.0001, uncorrected), bilateral medial prefrontal cortex and right inferior parietal lobule. Generation of discrete SSR events was associated with significant activity (p <0.05) in left medial prefrontal cortex, bilateral extrastriate visual cortices, and cerebellum, whereas activity in right medial prefrontal cortex related to afferent representation of SSR events and varied parametrically with SSR amplitude. Our results suggest that areas implicated in emotion and attention are differentially involved in generation and representation of peripheral SSR responses. We propose that this functional arrangement enables integration of adaptive bodily responses with ongoing emotional and attentional states.

References 1. Damasio AR. Descartes' error. New York: Putnam; 1994. 2. Tranel D, Damasio H. Neuroanatomical correlates of electrodermal skin conductance responses. Psychophysiology 1994; 31:427-438. 3. http://www.fil.ion.ucl.ac.uk/spm/spm99.html Clinical Autonomic Research 2000, Vol 10 No 3

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Baroreflex is impaired in familial dysautonomia B. Stemper, 1 M.J. Hilz, ~,2 L. Bernardi, 3 G. Welsch, 1 C. Passino, 3 M. Duetsch, 2 T. Haendl, ~ F.B. Axelrod ~

1Department of Neurology, New York University, New York, New York, USA; 2Department of Neurology, University of Erlangen-Nuremberg, Germany; 31RCCS S. Matteo, University of Pavia, Italy Familial dysautonomia (FD) patients have impaired blood pressure (BP) control with orthostatic hypotension (OH) and supine hypertension. Baroreflex is essential for shortterm BP control and interacts with other systems of cardiovascular regulation. Baroreflex failure may account for cardiovascular emergencies seen in FD. To further pursue this hypothesis, we evaluated baroreflex function in FD patients. Twenty-one FD patients (mean age, 24.7 + 11.2 y; 11 men, 10 women) and 22 controls (mean age, 26.0 + 10.4 y; 12 men, 10 women) underwent 3 rain of passive head-up tilt (HUT) and baroreceptor stimulation by means of sinusoidal neck suction (NS; 0 to -30 m m Hg). NS was performed with 0.1 Hz (LF) to test the effect of sympathetic modulation on the vessels and the heart and with 0.2 Hz (HF) to test the effect of parasympathetic stimulation on the heart. Respiration was maintained constant during NS at 15 cycles/min; ie, 0.25 Hz. We monitored electrocardiogram R-R intervals (RRI), systolic BP (Colin), and respiration. NS-induced changes of RRI and BP were determined by spectral analysis. The increase in NS-induced fluctuations, compared to baseline recordings, is an indicator for the effect of baroreceptor stimulation. H U T showed O H without compensatory tachycardia in FD patients (systolic BP, -33.2 m m Hg; diastolic BP, -20.3 m m Hg; RRI, +17.8 ms) but not in controls (systolic BP, +8.8 m m Hg; diastolic BP, +13.8 m m Hg; RRI, -89.3 ms). LF NS increased LF power of RRI and BP in controls (LF RRI, from 548.8 + 512.4 to 1,628.8 + 1,063.9; LF BP, from 2.7 _+ 3.5 to 9.5 + 18.4; p <0.05) but not in FD patients (LF RRI, from 160.4 _+ 154.7 to 199.4 _+262.7; LF BP, from 0.6 + 0.8 to 0.6 _+0.9; p >0.05), indicating lack of sympathetic modulation by arterial baroreflex in FD. HF NS increased HF power of RRI in controls (from 0 to 588.5 + 674.9) but not in FD (from 0 to 0), indicating lack of vagal modulation by arterial baroreflex in FD. We conclude that barorecept0r failure contributes significantly to orthostatic hypotension in FD. Absence of syncope, despite baroreceptor failure, suggests other compensatory mechanisms of orthostatic hypotension. Dr. Stemper was supported by a grant from the Deutsche Akademie fuer Naturfoscher Leopoldina.

Na*, K*, adenosine triphosphatase (ATPase) and burning feet/burning hands at altitude J. Gamboa, R. Caceda, M. Vargas, A, Gamboa, P.K. Thomas, O. Appenzeller

We reported on the widespread complaint of burning feet/ burning hands (BF/BH) in Cerro de Pasco (CP), 4,338 m above sea level in Peru, and on the remission of these symptoms at sea level [1]. We studied 13 CP-native males who underwent sural nerve biopsy. There were 3 controls with158

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out BF/BH and 3 controls with BF/BH. Four patients with chronic mountain sickness (CMS) and hypoxemia inappropriate for altitude were biopsied in CP and three in Lima (sea level) after their BF/BH had disappeared (biopsies carried out 8, 61, and 84 hours later). BF/BH was assigned a symptom score (SS; 0 = no BF/BH; 1 = BH; 2 = BF). All subjects were rated using standard CMS scores based on cardiovascular, neurologic, and hematologic parameters. Sural nerves were assayed for ATPase and cytochrome oxidase (CO) by standard methods. Mean (_+ SD) age: controls (C) = 36 + 6.7; CMS = 41 + 5.5, NS. SS: C = 1.3 _+ 0.5; CMS = 2.87 + 0.5, p <0.0001. Hematocrit: C = 50.5 + 5.7; CMS = 68.4 + 3.5, p <0.0004. CMS score (normal up to 12): C = 6.8 + 4.4; CMS = 20.1 _+ 3.1, p <0.0001. Using univariate and multivariate procedures, we found CO was age dependent but not related to any other parameters. Low ATPase was strongly related to SS but not to any other parameters. Patients with CMS biopsied in Lima with an SS of 0 but unchanged CMS score had ATPase levels NS different from C with SS of 0 biopsied in CP. We show that BF/BH is associated with hypoxia at altitude and low ATPase in sensory nerves. Normoxia leads to disappearance of BF/BH and restoration of ATPase levels within hours. ATPase is associated with axolemmal function and, if reduced, may lower axolemmal resting potential, leading to ectopic impulse generation. BF/BH may be a symptom in small fiber neuropathies associated with autonomic failure, as in some diabetic neuropathies. Low ATPase levels have been found in experimental diabetic neuropathy, and hypoxia of nerves has been implicated in the pathogenesis. Support: N M H E M C Research Foundation, USA; Laboratorio de Transporte de Oxigeno, Departamento de Ciencias Fisiol6gicas, Universidad Peruana Cayetano Heredia, Peril.

Reference 1. Thomas PK, Muddle JR, King RHM, GamboaJ, Tapia R, Vargas M, et al. Neurology 1998; 50(suppl 4):A345,

Impaired parasympathetic function in open-angle and normal-pressure glaucoma C.M. Brown, 1 M. Tutaj, 3 M. Brys, 3 H. Marthol, 1 G. Michelson, 2 M.J. Hilz 1

Departments of 1Neurology and 2Ophthalmology, University of Erlangen-Nuremberg, Germany; 3Department of Neurology, Jagiellonian University, Cracow, Poland Pathophysiology of normal-pressure glaucoma is as yet unclear. There is some evidence that autonomic neuropathy contributes to both open-angle andnormal-tension glaucoma. So far, sympathetic and parasympathetic function have not been studied in detail in either disease. In this study, we assessed autonomic function in primary open-angle glaucoma (OAG) and normal-pressure glaucoma (NPG). In 14 patients with OAG (age, 54 • 9.9 y), 13 with N P G (age, 58 -+ 14.3 y), and 20 controls (age, 55 -+ 12.5 y) we evaluated responses to sinusoidal neck suction (NS; 0-30 m m Hg) applied at 0.1 Hz (LF) to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz (HF) to assess the effect of parasympathetic stimulation on the heart. Respiration was maintained at 0.25 Hz.

CARS/EFASJoint Meeting Changes in electrocardiogram R-R intervals (RRI) and in systolic blood pressure (BP) were determined by spectral analysis, and the effect of baroreceptor stimulation was assessed as the increase in NS-induced LF and HF fluctuations compared to baseline. Baseline recordings showed no significant differences among the three groups. During 0.1-Hz NS, LF modulation of RRI increased in controls (4.22 _+ 0.24 to 5.67 -+ 0.25 In ms2), N P G patients (3.68 _+ 0.29 to 4.86 + 0.35 In ms2), and OAG patients (3.62 + 0.23 to 5.31 -+ 0.30 In ms2). NS at 0.1 Hz also increased LF modulation of BP in controls (0.36 + 0.23 to 0.55 -+ 0.27 In m m Hg2), N P G patients (-0.29 _+ 0.26 to 0.84 _+ 0.26 In mm Hg2), and OAG patients (-0.07 + 0.21 to 0.46 _+ 0.33 In m m Hg2). The LF RRI or LF BP responses to 0.1-Hz NS did not differ among any of the groups. NS at 0.2 Hz increased the HF modulation of RRI in all three groups. The response in the control group (0 + 0 to 2.76 _+0.32 In ms ) was slgmficantly greater than that of the N P G patients (0 _+0 to 1.74 + 0.37 In ms 2) and the OAG patients (0 + 0 to 1.58 -+ 0.35 In ms2; p <0.05, ANOVA). These results indicate that the vagal control of the heart is impaired in patients with glaucoma. The findings suggest that parasympathetic dysfunction may contribute to the pathogenesis of both open-angle and normal-pressure glaucoma. 2

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Influence of caloric vestibular stimulation on cardiovascular and cerebrovascular modulation M.J. Hilz, 1,2 T. Haendl, 2 B. Sternper, 2 H. Marthol, 1 F.B. Axelrod, 2 B. Neund6rfer 1

1Department of Neurology, University Erlangen-Nuremberg, Germany; 2Department of Neurology, New York University, New York, New York, USA Vestibular stimulation influences autonomic cardiovascular and cerebrovascular modulation and orthostatic regulation, but autonomic responses are inconclusive [1,2]. In this study, we evaluated the effects of caloric vestibular stimulation on cardiovascular and cerebrovascular autonomic control in healthy persons. Twenty-one volunteers (age range, 22-44 y; mean age, 26.2 _+ 5.8 y) underwent vestibular stimulation by means of 44~ warm- and 27~ cold-water irrigation (440 ml within 30 s) of the right and left external ear canal. At rest and during stimulation, we monitored heart rate (HR), noninvasive radial artery blood pressure (BP; Colin), respiration (Respitrace), skin blood flow (SBF) at the right index finger pulp (Perimed-laser Doppler), and middle cerebral artery blood flow velocity (CBFV; M u l t i d o p X4transcranial Doppler). We assessed low- (LF; 0.04-0.15 Hz) and high- (HF; 0.15-0.5 Hz) frequency power spectra of H R and BP. During the first caloric stimulation, effects were most pronounced. BPsys increased from 127.5 + 16.4 to 132.6 _+ 17.9 m m Hg; BPdia increased from 71.1 + 9.9 to 75.7 -+ 10.4 m m Hg; H R accelerated from 67.2 _+ 11.4 to 69.9 _+ 11.3 bpm; CBFV increased from 65.3 -+ 6.1 to 69.2 + 8.8 cm/s; SBF decreased from 216 _+ 160.2 to 182.5 _+ 148.3 PU; sympathetic LF power of blood pressure increased from 3.3 + 1.8 to 4.4 + 2.7 m m Hg 2 (Wilcoxon, p <0.05).

Respiration and LF and HF power of heart rate did not change. Caloric stimulation increases sympathetic cardiovascular activity. Our findings confirm the results of previous studies suggesting connections between vestibular and autonomic brainstem centers [2]. Further studies are needed to determine the influence of vestibular and autonomic system interactions on orthostatic regulation.

References 1. Kaufmann H, Biaggioni I, Voustianiouk A, Diedrich A, Costa F, Clark R, et al. Clin Auton Res 1999;9:214. 2. Biaggioni I, Costa F, Kaufmann H. J Vestib Res 1998;8:35-41.

Kinematic analysis of prehension movements in C R P S patients J. Schattschneider, R. Wenzelburger, K. L6ffler, G. Wasner, R. Baron, G. Deuschl

Klinik ftir Neurologie der CAU, Kid, Germany

Introduction: Complex regional pain syndrome (CRPS) is characterized by the presence of sensory and autonomic symptoms following a noxious event. Furthermore, the occurrence of motor disturbances like tremor, dystonia, spasms, weakness, or involuntary movements are common findings in the patients. Nevertheless, the knowledge about motor performance in CRPS patients is still poor. The aim of the present study was to analyze and quantify possible motor deficits using a kinematic paradigm. Methods: The kinematic of prehension movements was analyzed in five patients with CRPS of the upper limb. The subjects repeatedly reached out for a cylindrical target object and grasped it with a precise grip. The trajectory of the reaching hand and the finger aperture were monitored by optoelectronic motion analysis. The kinematic data were compared with data collected from 11 healthy volunteers. To estimate the effect of pain on motor performance, we examined 4 healthy volunteers with and without experimental muscle pain due to the injection of 0.15 ml 5.8% saline into the abductor minimi muscle. Results: (1) In comparison with the healthy volunteers, CRPS patients showed a significantly prolonged movement time on the affected side. (2) A closer analysis showed that the prolongation was the result of an extended acceleration and target perception phase. (3) It seems that, in volunteers with experimental muscle pain, the acceleration phase is prolonged, whereas the duration of the deceleration and target perception phase is decreased. Conclusion: The prolonged total movement time could indicate a changed movement pattern. The extended acceleration and target perception phase suggested a disturbed kinematic performance in proximal and distal joints of the affected limb. To what extent these changes are due to central or peripheral sensorimotor processes can not be judged clearly. It should be taken into account that unspecific factors, like pain, also affect the kinematic performance. This work was supported by the Wilhelm SanderStiftung and the Deutsche Forschungsgemeinschaft (BA 1921/1-1). Clinical Autonomic Research 2000, Vol 10 No 3

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CARS/EFAS Joint Meeting Adaptation of sympathetic skin responses in man: effects of repeated electrical stimulation of peripheral nerves on duration, latency, and amplitude P. Cariga, 1'2 M. Catley, ~ C.J. Mathias, 2 P.H. E l l a w a y ~

1Department of Sensorimotor Systems, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London; 2Neurovascular Medicine Unit, Imperial College School of Medicine at St. Mary's, London, United Kingdom The effect of repeating electrical peripheral nerve stimulation on the variability in latency, duration, and amplitude of the sympathetic skin response (SSR) was studied in 15 normal subjects, who participated with informed consent. The study had ethical approval. SSRs were elicited in all four limbs by electrical stimulation of either the median or peroneal nerve, using an intensity of 1.5 times the motor threshold. In 10 subjects, 20 stimuli were applied at random time intervals of 15 to 20 seconds. The mean (+ SE) amplitude of right hand response to left peroneal nerve stimulation decreased from 5.05 -+ 0.76 mV at the first stimulus to 1.23 + 0.42 mV at the 20th stimulus (p <0.001), as previously reported [1]. The latency of onset of SSR did not change significantly (1,473 _+82 to 1,550 _+90 ms; p = 0.1). The latency of the first negative peak (2,132 _+98 to 2,609 + 245 ms; p <0.001) and of the following positive peak (3,345 + 379 to 4,720 + 753 ms; p <0.001) increased significantly. Stimulation and recording at other sites showed similar trends. In five subjects tested with the same protocol, switching the stimulation site every 10 or 5 stimuli without warning, changing the site of stimulation had no reversing effect on the adaptation process of the SSR in terms of amplitude and duration, despite the modification of the sensory and central components of the reflex. These findings suggest that habituation in SSR is not only the result of changes in the central polysynaptic pathway [2] but may be determined in part by activity of peripheral sweat glands activated by efferent sympathetic fibers. This work was supported by the International Spinal Research Trust. References 1. Shahani BT, Halperin J J, Boulu P, Cohen J. J Neurol Neurosurg Psychiatry 1984; 47:536-542. 2. Toyokura M, Murakami K. Muscle Nerve 1996; 19:1481-1483.

Pathophysiological basis of a paroxysmal episodic central thermoregulatory failure F. Magnifico, 1 G. Pierangeli, 1 G. Barletta, ~ C. C a n d e l a , 1 G. B o n a v i n a , ~ P. Cortelli 2

1Institute of Neurology, University of Bologna, Italy; 2Institute of Neurology, University of Modena and Reggio Emilia, Italy Abnormal sweating may occur as a compensatory reaction to the loss of thermoregulatory sweating on the denervated side (Harlequin syndrome), or it may be associated with poikilothermia and agenesis of the corpus callosum (Shapiro syndrome). We evaluated the pathophysiological basis of a possible new syndrome characterized by unilateral crisis of sweating with hypothermia. A 51-year-old male, with 2-month history of paroxysmal prolonged attacks (>60 min160

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utes) of unilateral sweating over the left side of upper body and face following an aspecific flu infection, was studied. This crisis occurred when getting up in the morning or, less frequently, after a meal. Microbiologic, biochemical, and endocrinological studies were normal. The corpus callosum on brain MRI was normal. EMG, sympathetic skin response, and cardiovascular autonomic function tests in the interictal state were performed, along with thermoregulatory sweat test (TST). The study of circadian rhythm of body core temperature (CRT~ by continuous monitoring (every 2 min) of rectal temperature (rT~ and skin temperature (left side, L-sT~ right side, R-sT~ by mini-logger) were evaluated for 4 days. During body heating, when the rectal temperature rose by I~ (from a low baseline 34.82~ to 36.15~ sweating on the left side of the face, neck, and upper body, including the hand, occurred, while the right side and lower legs remained almost dry. The onset of sweating was accompanied by a fall in rectal temperature by 1~ (from 36 to 35~ A spontaneous sweating episode recorded during standing up was characterized by a slight increase in BP and H R and by noradrenaline increase from a baseline level of 728 pg/ml to 1,012 pg/ml, with adrenaline in a normal range. The continuous recording of rT ~ showed that the onset of sweating "crisis" was immediately followed by a progressive fall in rectal temperature, taking about 85 minutes (from 37.27~ to a nadir of 33.9~ as well as a fall in right (from 36.04~ to 31.67~ and left (35.45~ to 30.90~ skin temperature. At this stage, the unilateral upper sweating stopped, while the hypothermia (33.9~ lasted about 2 hours and corresponded clinically to the severe weakness, shivering, and confusion phase. Then, in about 2 hours, the rectal and skin temperatures returned slowly to baseline values (rT ~ = 36.5~ R-sT ~ = 35.6~ L-sT ~ = 35.45~ In our patient, a sympathetic noradrenergic storm of unknown origin determined the fall in cutaneous and rectal temperature, leading to a severe episodic hypothermia. The normal response to the TST indicated a normal function of the heat-loss mechanisms. However, the spontaneous sweating "crisis" leading to hypothermia indicates an abnormal downward shift of the thermoregulatory set-point and a delay in the effect of those mechanisms blocking the heat dissipation. Clinical and laboratory findings make the diagnosis of Shapiro syndrome and Harlequin syndrome unlikely. References 1. Fellow L, Benoit J, Schondorf R. Neurology 1999; 52(suppl 2):A340. 2. Drummond PD, Lance JW. Ann Neuro11993; 34:814-819.

Systolic failure of myocardial and cardiovascular reflex tests in patients with diabetes mellitus and autonomic neuropathy B. Milovanovic, M. Krotin, A. Milovanovic, V. Bisenic, D. Vidric, A. Veljovic, S. Markovic, I. Jovancic, M. Babic, C.H.C.B. K o s a

Department of Cardiology, Neurocardiological Laboratory, University of Belgrade, Yugoslavia Insufficiency of heart is followed by autonomic dysfunction, relatively to mainly increased function of sympathicus. Au-

CARS/EFASJoint Meeting tonomic dysfunction appears in diabetics because of autonomic neuropathy, which is diagnosed by cardiovascular reflex tests. However, these tests are used in examinations of functions of cardiovascular system. Aim: To examine the correlation between systolic heart insufficiency in diabetics with autonomic neuropathy and results of cardiovascular reflex tests (after Ewing). Methodology: We examined 100 (62 M, 38 F) diabetics, who were divided into 2 groups toward EF of left ventricle: (1) diabetics without systolic insufficiency (s.i.; n = 67; 36 M, 31 F; EF >40%) and (2) diabetics with systolic insufficiency (n = 33; 26 M, 7 F; EF <40%; Acuson 128). All diabetics had cardiovascular reflex tests after Ewing: Valsalva maneuver (VM), deep breathing test (DBT), heart rate response to standing test (HRRT; for vagus), blood pressure response to standing test (BPRT), and hand grip test (HG; for sympathicus). Peripheral neuropathy was diagnosed by neurological examination. Results: VM was positive in 3 (50%) diabetics (D) with s.i. and in 14 (29.78%) D without s.i. (p >0.05). D B T was positive in 10 (45.45%) and borderline in 9 (40.90%) D with s.i., in comparison to D without s.i., whereas it was positive in 18 (35.29%) and borderline in 10 (19.60%) cases (p <0.05). H R R T was positive in 11 (50%) D with s.i. and 32 (62.74%) without s.i. (p >0.05). BPRT was positive in 5 (22.72%) D with s.i. and 9 (17.64%) D without s.i. (p >0.05). H G was positive in 12 (59.54%) D with s.i. and 34 (66.66%) D without s.i. (p >0.05). There was not statistical difference between systolic failure and autonomic neuropathy. Condusions: Valsalva maneuver and especially test of deep breathing are more often positive in diabetics with systolic heart insufficiency. Diabetics with systolic insufficiency have more often peripheral and autonomic neuropathy (denervation of vagus), but without statistically important difference.

The 24-hour oscillation of blood pressure and heart rate in Parkinson's disease (PD): circadian and sleep influences G. Pierangeli, ~ G. Barletta, ~ F. Magnifico, ~ G. Bonavina, 1 S. Cevoli, 1 P. Montagna, 1 P. Cortelli2 1Institute of Neurology, University of Bologna, Italy; 2Institute of Neurology, University of Modena and Reggio Emilia, Italy

Abnormal circadian rhythms have been reported in extrapyramidal syndromes. This study aimed to evaluate sleep and circadian influences on autonomic pathways controlling blood pressure and heart rate 24-hour oscillations in PD. We evaluated eight patients with PD (six men; mean age, 58 _+ 12 y) and three controls (CN; two men; mean age, 58 _+ 8 y). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored for 48 hours by a Portapres model II. Sleep-wake cycle was simultaneously monitored with an ambulant polygraphic recorder (Oxford Medilog 9200; parameters recorded: EEG, EOG, ECG, EMG). The patients during the study lived in a temperature-controlled room, lying in bed, except for eating six times per day (1800 Kcal) in a fixed light-dark schedule. The sleep stages were scored according to the criteria suggested by Rechtschaffen and Kales, considering epochs of 30

s. Mean SBP, DBP, and H R were evaluated during the same 30-s periods. Circadian rhythmicity of SBP, DBP, and H R was analyzed on the different 24-hour recordings according to the single cosinor method. Mean SBP, DBP, and H R during wakefulness and deep, light, and REM sleep were evaluated. To date, we have analyzed data from three PD patients and three controls. In these patients, the 24-hour oscillation of SBP, DBP, and H R was preserved, and the physiological nocturnal fall of these parameters was present. Mean + SD SBP/DBP during wakefulness was PD = 141 _+ 16/78 _+4, CN = 127 + 8/73 + 3 m m Hg; during phase 1-2, PD = 129 + 14/71 _+ 7, CN = 118 _+ 9/67 -+ 3 m m Hg; during phase 3-4, PD = 127 _+ 18/69 + 9, CN = 115 + 7/64 _+4 m m Hg; and during REM, PD = 137 -+ 19/76 -+ 8, CN = 124 _+ 19/68 + 6 m m Hg. Mean _+SD H R during wakefulness was PD = 60 _+ 12, CN = 74 _+ 13 b/m; during phase 1-2 NREM, PD = 50 _+9, CN = 64 + 12 b/m; during phase 3-4 NREM, PD = 50 + 11, CN = 64 + 12 b/m; and during REM, PD = 52 _+ 10, C N = 66 + 10 b/m. The complete analysis of the data will be presented at the meeting.

Oral mucosal blood flow following dry ice stimulation in humans J.G. Heckmann, 1 S.M. Heckmann, 2 T. Hummel, 3 M. Popp, 2 H. Marthol, 1 B. Neund6rfer, 1 M.J. Hilz ~

Departments of 1Neurology and 2prosthodontics, University of Erlangen-Nuremberg; 3Department of Otorhinolaryngology, University of Dresden, Germany Blood flow of the oral mucosa seems to be altered in various autonomic diseases. So far, there are no data on blood flow responses of the oral mucosa to external stimuli. This study evaluated blood flow changes of the oral mucosa after local cold stimulation in healthy volunteers. In 13 healthy, nonsmoking volunteers (1 man, 12 women; mean age, 64.7 y; SD 8.1), we assessed mucosal blood flow (mBF) at the hard palate, tip of the tongue, midline of the vestibulum otis, and the lower lip using a Perimed-Laser Doppler. Measurements were taken at rest and over 2 min following 10 sec of dry ice application to the tested sites with a pencil-like device. We also monitored heart rate (HR), radial artery beat-to-beat blood pressure (BP; Colin Pilot), peripheral skin blood flow, and transcutaneous p C O 2 and pO 2 (Radiometer). After cold stimulation, mBF increased significantly to a peak flow within 0.5-1.5 min at all sites (p <0.0001) and returned toward baseline after 1.5-2 min. Responses were lowest at the tongue (p <0.05). HR, BP, pCO2, pO2, and peripheral skin blood flow remained stable during stimulation. To conclude, dry ice stimulation effectively evaluates the adaptability of mucosal perfusion to external stimuli. The smaller response of tongue mucosa might be due to the different anatomical tissue with papillae dampening cold stimuli. Mucosal blood flow regulation depends on the integrity of the vasculature and its supplying nervous reflex arc. The stability of HR, BP, pCO2, and pO 2 demonstrates that mBF changes are a local response to the cold stimulus. In contrast to cold face stimulation, mucosal stimulation does not seem to induce systemic cardiovascular responses. Clinical Autonomic Research 2000, Vol 10 No 3

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Cerebral autoregulation of healthy persons remains intact during external counterpulsation H. Marthol, 1 M.J. Hilz, 1 D. Werner, 2 S. Horn, 1 B. Neund~Srfer, ~ W.G. Daniel 2

Departments of 1Neurologyand 2Cardiology, University of Erlangen-Nuremberg, Germany External counterpulsation (PECP) increases organ perfusion in patients with coronary artery disease or impaired cerebral perfusion and augments diastolic blood flow volume in large peripheral arteries. This study was performed to evaluate whether PECP induces changes of cerebral perfusion and impairs cerebral autoregulation. We performed PECP over 5 rain in 23 healthy persons (mean age, 27.9 -+ 4 y) and monitored heart rate, beat-tobeat radial artery mean blood pressure (BP. . . . . Colin Pilot, San Antonio, TX, USA), respiration (Respitrace, Ambulatory Monitoring, Ardsley, NY, USA), and middle cerebral artery blood flow velocity (CBFV) by means of transcranial Doppler sonography (MultiDop X4, DWL, Sipplingen, Germany). During PECP, impulses of 300 mm Hg external pressure were applied to the lower body area. Compressions were HR-triggered during the each cardiac diastole (Vasomedical Inc., Westbury, USA). Signals were compared to 5-min baseline data by Wilcoxon test. During PECP, BP. . . . (86.2 + 9.8 mm Hg) and heart rate (75.6 -+8.6 bpm) were significantly higher than baseline BP. . . . (83.5 _+ 10.2 mm Hg) and heart rate (72.7 + 9.0 bpm; p <0.05). In contrast, mean CBFV was lower during PECP (50.1 + 0.13 cm/s) than at baseline (55.0 -+ 18.5 cm/s; p <0.001). Respiration did not change significantly. To conclude, cerebral blood flow velocity of healthy persons decreases during PEeP and thus counter-regulates passively increased heart rate and blood pressure. The CBFV response shows intact cerebral autoregulation during PECP. The result supports further studies intended to evaluate whether PECP can be applied in patients with coronary artery disease and cerebral angiopathy without compromising cerebral autoregulation.

Orthostatic dizziness in chronic atrial fibrillation: autonomic function analysis as a target for therapeutical intervention B. G o m e s Pinto, M.J. Bettencourt, L. Silva-Carvalho, J. S i l v a - C a r v a l h o

Laboratoiro Moniz de Bettencourt, Instituto de Fisiologia, Lisbon Medical School, Lisbon University,Portugal Introduction: In previous studies, we found an important autonomic dysfunction in asymptomatic (ASY) subjects with chronic atrial fibrillation (CAF) characterized by a peculiar a
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ance and sphygomanometry, we evaluated thoracic fluid index, inotropic index, heart rate, peripheral vascular and resistance, besides other hemodynamic variables. Measurements were obtained in CLINO, 15 min after rest, in adaptation period, and 1 to 2 rain after abrupt ORTHO. CAF OD group data were compared to those from control series-normal (N) [3] and ASY CAF. Subgroups of OD patients were arranged according to the eventual abnormal parametric evolution detected, and a subsequent therapeutical autonomic modulation (ie, alpha and/or beta agonists or antagonists, M2 antagonists) was attempted. Two to four weeks after starting this treatment, we proceeded with a clinical and O R T H O test re-evaluation. Results: In comparison with N and ASY CAR, 89.2% of the OD patients presented a significant (p <0.01) CRH alteration in O R T H O in at least one parameter. So, we recognized in CAT OD 9 dysfunction types: brady (I) or tachy (II) disrythmic, inotropic status failure (III) or hyperactivity (IV), vasodepressor (V) or vasopressor (VI), central hypovolemic (VII) or hypervolemic (VIII), and mixed types (IX). The individual pharmacological autonomic adjustment has induced a clinical and CRH improvement in all OD-patient subgroups. Discussion and conclusions: These data indicate an independent autonomic control for each one of the cardiac performance determinants. The reflex response threshold of the pulmonary venous and cardiac atrial (A and B) receptors is probably involved in CRH mechanisms disorders [4-6]; in synthesis, our study in CAF OD suggests (1) various types of autonomic control derangement; (2) clinical and hemodynamic benefits induced by selective pharmacological autonomic modulation; and (3) the interest for an algorithm for therapeutical decision proposed by the AA. References 1. Gomes Pinto B, Bettencourt MJ, Fresta M, Rocha L, Silva Carvalho L, Silva Carvalho J. Rev Port Cardio11994; 13(suppl 1):18. 2. Gomes Pinto B, Bettencourt MJ, Silva Carvalho L, Silva Carvalho J. Clin Auton Res 1995; 5:107-108. 3. Bettencourt MJ, Gomes Pinto B, Infante de Oliveira E, Sirva Carvalho L, Silva Carvalho J. Rev Port Cardiol 1998;17:875-879. 4. Bettencourt MJ, Gomes Pinto B, Silva Carvalho L, Silva Carvalho J. Clin Auton Res 1996; 6:60. 5. Gomes Pinto B, Bettencourt MJ, Infante de Oliveira E, Silva Carvalho L, Silva Carvalho, J. Bol Soc Port Hemooreologia c Microcircula H#o 1998; 13:37. 6. Bettencourt MJ, Gomes Pinto B, Infante de Oliveira E, Silva Carvalho L, Silva Carvalho J. Clin Auton Res 1999; 9:40-41.

Age-dependent autonomic prevalence assessed by electroautonomography (EAG) E. Eerner, E. v a n Zanten, D. B e e k i n k

Lerner Medical Technology Ltd., Amsterdam, The Netherlands Introduction: A previous study to determine the autonomic prevalence in a healthy population group (n = 400; age 18-32 years) revealed a normal distribution pattern [1]. Based on the averaged outcome of 10 autonomic function tests, 43% _+ 3 (-+ standard deviation) of the subjects were categorized as balanced, 24% _+ 7 were parasympathetic, and 32% _+6 were sympathetic prevalence& respectively. Similar outcomes (92% correlation between the two methods) were found using the electroautonomograph to determine the autonomic prevalence, a method based on skin potential amplitude analysis. The presently described study was assessed to determine if the found distribution

CARS/EFASJoint Meeting pattern is consistent with age. The autonomic prevalence of children and elderly people was determined using both the averaged outcome of 10 autonomic function tests and the electroautonomograph. Methods and materials: Similar to the previous study performed on 400 healthy adolescents, the autonomic prevalence was determined of a group of 60 children aged 8-9 years and a group of 42 elderly people aged 60-72 years. Each subject group was divided into the following categories of autonomic prevalence: parasympathetic, balanced, or sympathetic, based on the averaged outcome of 10 standard autonomic function tests and amplitude analysis results of the electroautonomograph. Statistical comparison of the different groups was performed using a standard Student t test (el = 0.05) for comparison of group averages. Results: For the group of 60 children, 58% -+ 13 were categorized as parasympathetic prevalenced, 25% -+ 8 were balanced, and 17% -+ 7 were sympathetic prevalenced according to the averaged outcome of the 10 standard autonomic function tests. Electroautonomography test results showed a similar categorization (88% correlation of results). In the elderly people's group (42 subjects), the following percentages were found: 24% _+ 16 parasympathetic prevalenced, 24% _+ 9 balanced, and 52% +- 21 sympathetic prevalenced. Again, the electroautonomograph was capable of showing similar results: 86% of the categorization was correlated. The percentage of parasympathetic prevalenced subjects was significantly higher (p <0.05) in the children's group than in the adolescent group, while the percentage of sympathetic prevalenced subjects was significantly higher in the elderly people's group (p <0.05), compared to the adolescent group. Conclusions: With age, autonomic prevalence shifts from a predominance of parasympathetic prevalence in children (age 8-9 years) to a normal distribution in adolescents (age 18-32 years) to a predominance of sympathetic prevalence in elderly people (age 60-72 years). The electroautonomograph can be used as a simple method to show autonomic prevalence instead of the averaged outcome of 10 standard autonomic function tests.

Reference 1. kerner EN. Electroautonomography: a non-invasive apparatus to assess autonomic nervous system function. Clin Auton Res 1999; 9:42.

Clinicopathological study on autonomic failure with Parkinson's disease T. leda, 1 M. Y o s h i d a , 2 Y. Arahata, 1 Y. Niimi, 3 H. Ito, 1 M. H i r a y a m a , 4 Y. H a s e g a w a , 5 Y. Koike, e A. T a k a h a s h i , 7 G. S o b u e ~

1Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan; 2Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan; 3Department of Autonomic Neuroscience, Division of Higher Nervous Control, the Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; 4LaboratoryMedicine, Nagoya University School of Medicine, Nagoya, Japan; 5Department of Neurology, Nagoya City Higashi General Hospital, Nagoya, Japan; 6Department of Health Sciences, Nagoya University School of Medicine, Nagoya, Japan; 7Tohkai Central Hospital, Kakamigahara,Japan

Background: Autonomic failure with Parkinson's disease (AFPD) was first reported in 1965; however, the whole

clinical entity remains incompletely delineated. At the last EFAS meeting, we presented clinical features, PET manifestations, and EEG findings in patients with AFPD. Also, outline of pathological study on a patient with AFPD was discussed. In this study, we made further pathological analysis in detail. Case presentation: A 74-year-old man was admitted for syncope. Neurological examination revealed parkinsonism and orthostatic hypotension. A series of autonomic function tests showed primary autonomic failure with postganglionic lesions. We diagnosed him as AFPD according to our clinical criteria for AFPD. When he was 77 years old, he had a second admission because of psychosis and hyperthermia. The symptoms deteriorated after the episode, and he died 10 years after the onset of parkinsonism. At autopsy, marked cell loss and Lewy bodies were observed in the substantia nigra. Lewy bodies were also detected in the sympathetic ganglia. Though there were a few Lewy bodies, alpha-synuclein-positive Lewy neurites were found in the neocortex. Pathological study confirmed our clinical diagnosis. Condusions: The primary lesion of autonomic failure in AFPD is considered to be the sympathetic ganglia. Not only Lewy bodies but also Lewy neurites may be responsible for dementia and psychosis in patients with AFPD.

Autonomic dysfunction in long-standing cases of Parkinson's disease Y. Niimi, 1 K. Mano, 2 M. Hirayama, 3 T. leda, 4 R. Nishimura, 4 H. Ito, 4 H. W a t a n a b e , 2 G. Sobue, 1 Y. Koike s

1Department of Autonomic Neuroscience, Division of Higher Nervous Control, the Research Institute of Environmental Medicine, Nagoya University; 2Department of Neurology, Nagoya Daiichi Red Cross Hospital; 3LaboratoryMedicine, Nagoya University School of Medicine; 4Department of Neurology, Nagoya University School of Medicine; 5Department of Health Sciences, Nagoya University School of Medicine, Nagoya, Japan

Introduction: Recently, some patients with long-standing cases of idiopathic Parkinson's disease (IPD) who do not suffer from autonomic failure (AF) have been reported to have subclinical orthostatic hypotension with advancing age or their disease, though few patients with Parkinson's disease (PD) generally show AF. In this study, we evaluate autonomic function in long-standing IPD patients and AF with PD (AFPD), in which prominent AF develops even in the early stage of disease. Patients and methods. Ten patients with IPD (age, 72 + 5 years; duration, 14 _+years) satisfied UK PD Society Brain Bank clinical diagnostic criteria for PD, and seven patients with AFPD (age, 70 -+ 4 years; duration, 7 + 2 years) fulfilled our clinical criteria for AFPD were enrolled into the study. We assessed blood pressure (BP), heart rate (HR), plasma norepinephrine (NE), and arginine vasopressin (AVP) levels before and after head-up tilting (HUT). NE infusion tests were also performed in order to estimate denervation supersensitivity. Results and discussion: In IPD, HR increased and BP decreased with HUT, but less than AFPD. The increments of NE with HUT were preserved in IPD, but not in AFPD. Clinical Autonomic Research 2000, Vol 10 No 3

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CARS/EFASJoint Meeting In contrast, plasma AVP increased with HUT in both groups. After NE infusion tests, BP elevation was observed to have denervation supersensitivity in both groups, but was marked in AFPD. In conclusion, long-standing PD patients have subclinical autonomic dysfunction, the lesion of which is considered to be ganglionic or postganglionic sympathetic neurons, as shown in AFPD.

Cardiac uptake 12al-metaiodobenzylguanidine (MIBG) differentiates dementia with Lewy bodies from Alzheimer disease H. Watanabe, 1 T. leda, 1 T. K a t a y a m a , 2 A. Takeda, I. Aiba, 2 M. Doyu, 1 G. S o b u e ~

1Department of Neurology, Nagoya University School of" Medicine, Nagoya, Japan; 2Department of Neurology, Higashi Nagoya National Hospital, Nagoya, Japan

Objectives: The aim of this study is to investigate subclinical autonomic dysfunction in demented patients using 123IMIBG myocardial scintigraphy.

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Patients and methods: Ten patients with dementia with Lewy bodies (DLB) (age 69 + 8 years) and six patients with Alzheimer disease (AD) (age 74 + 7 years) were enrolled in the study. The patients with DLB fulfilled the consensus criteria for the clinical diagnosis of DLB, and the patients with AD satisfied the NINCDS-ADRDA clinical diagnosis of AD. All patients were examined by neurologists for neurological examination and by cardiologists for cardiac function. None of them had orthostatic hypotension and cardiac dysfunction. Results: In all patients with DLB, the heart/mediastinum ratio (H/M ratio) of MIBG uptake was dramatically decreased, though they had normal autonomic manifestation. On the other hand, H/M ratio in patients with AD was within normal range. Then, the mean H/M ratio of the DLB group was significantly lower than that of the AD group (p <0.001). Conclusions: 123I-MIBG myocardial scintigraphy may detect subclinical postganglionic lesions in patients with DLB. It is one of the practical methods for differential diagnosis between DLB and AD.