angina pectoris with normal coronary arteries in shy

Journal ofNeurology, Neurosurgery, and Psychiatry, 1979, 42, 910-913

Angina pectoris with normal coronary arteries inShy-Drager syndromeRUTH SILVERBERG, YAAKOV NAPARSTEK,BASIL S. LEWIS , AND MICHA LEVY

From the Departments of Neurology, Medicine A, and Cardiology,Hadassah University Hospital, Jerusalem, Israel

SUMMARY A patient with Shy-Drager syndrome who presented with severe angina pectoris isdescribed. Special investigations of his autonomic nervous system showed sympathetic and para-sympathetic dysfunction with supersensitive end-organ response. Sympathetic dysfunctionmanifested as labile hypertension, severe postural hypotension, and inadequate heart rateresponse to atropine and the Valsalva manoeuvre. These changes in blood pressure were

accompanied by severe disabling angina pectoris. Selective coronary angiography showed normalcoronary arteries. It is suggested that angina pectoris resulted from the inadequate circulatoryresponse and is another clinical manifestation of the Shy-Drager syndrome.

The combination of extrapyramidal signs andautonomic system dysfunction is the hallmark ofthe syndrome described by Shy and Drager (1960).Autonomic dysfunction includes orthostatic hypo-tension, anhidrosis, iris atrophy, impotence, atonicbladder, and loss of rectal sphincter tone. Inade-quate circulatory responses to the Valsalvamanoeuvre, exercise, hyperventilation, and super-sensitivity to infusion of catecholamines arecharacteristic of the syndrome (DeJong, 1970;Klutzow et al., 1975; Davies et al., 1978).We describe a patient with the Shy-Drager

syndrome suffering from severe angina pectorisin whom selective coronary angiography showednormal coronary arteries. We suggest that theangina pectoris was caused by changes in bloodpressure as a result of autonomic nervous systemdysfunction and is another clinical manifestationof the syndrome.

Case report

A 61 year old man had a two year history of re-current episodes of syncope, progressive im-potence, urinary incontinence and, during thethree months before admission to hospital, severeangina pectoris related to changes of posture and

Address for reprint requests: Dr Yaakov Naparstek, Department ofMedicine A, Hadassah University Hospital, PO Box 499, Jerusalem,Israel.Accepted 27 February 1979

mild physical exertion. In addition he had slow-ness of movement, a resting tremor in the upperlimbs, and disturbances of gait. On examination,the pulse rate was regular, 68 per minute, bloodpressure 160/85 mmHg in the supine position.Immediately upon standing, the blood pressuredropped to 75/60 mmHg with no compensatoryrise in the pulse rate, and the patient complainedof anginal pain. There were no signs of heartfailure. Hypomimia, as well as a mild restingtremor, increased muscle tone, inco-ordinationof limbs, and an unsteady gait were noted.Routine blood tests including complete blood

count, serum electrolytes, blood urea nitrogen,glucose, liver function tests, calcium, phosphorus,acid phosphatase, cholesterol, triglycerides, serumcortisol, vitamin B12, folic acid, VDRL, andglucose tolerance tests were normal. Urinaryexcretion of 17-hydroxy- and keto-steroids werenormal. The electrocardiogram was normal atrest and showed minor flattening of the T wavein leads V5 and V6 during chest pain. A treadmilltest had to be discontinued after three minutesbecause of weakness, dizziness, and chest dis-comfort with a fall in blood pressure from100/80 mmHg to 80/60 mmHg. The heart rate atthis time was 126 beats/min. Skull and chestradiographs, and intravenous pyelograms, includ-ing post-voiding films, were normal. Electro-encephalogram and computerised tomography ofthe brain were also normal.

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Angina pectoris with normal coronary arteries in Shy-Drager syndrome

Cardiac catheterisation and coronary angio-graphy were performed for detailed study of theautonomic nervous system and to investigatefurther the cause of the severe angina pectoris.The following interventions were performed: (1)to test the baroreceptors, change of body position,carotid sinus massage and Valsalva manoeuvrewere used; (2) to test central integration of thepathways and sympathetic outflow, the Valsalvamanoeuvre and intravenous injection of atropine(2.5 mg) were used; (3) to test the end-organresponse, ephedrine (25 mg) was given orally.

Result of special studies

There was marked postural hypotension withouta compensatory rise in heart rate on standing(Table). Carotid massage produced bradycardiawith a decrease in heart rate from 75 to 52 beats/min, indicating a normal vagal response. Theresponse to the Valsalva manoeuvre was abnormal(Fig. 1). There was virtually no change in heartrate in response to the hypotension which occurredin phase 3, and there was no overshoot in bloodpressure nor reflex bradycardia in phase 4. Ahypertensive response was observed after ingestionof 25 mg ephedrine-the blood pressure rose from110/70 to 180/100 mmHg while the pulse rateshowed almost no change. Intravenous injectionof atropine produced very little change in heartrate, and after 2.5 mg (given in 0.5 mg bolusesevery three minutes) the heart rate increased from90 to 110 beats/min. These abnormalities indicateinadequate sympathetic function and exaggeratedend-organ response.Coronary angiography, performed in multiple

oblique views using the Judkin's technique andfilming at 25 and 50 frames/second with a 4.5 inchimage intensifier, showed normal coronary arteries(Fig. 2). Left ventriculography showed that the

Table Results of autonomic nervous system studies

Intervention Before intervention After inter} ention

Heart Blood Heart Bloodrate pressure rate pressurebeats/min mmHg beats/min mmHg

Standing 68 168/85 68 75/60(supine)

Carotid massage 75 215/70 52 210/80Valsalva manoeuvre

Phase 1 87 215/70 80 255/130Phase 2 87 215/70 88 165/115Phase 3 87 215/70 88 120/75Phase 4 87 215/70 82 190/80

Ephedrine 25 mg 75 110/70 78 180/100orallyAtropine 2.5 mg 90 100/70 110 110/75intravenouslyTreadmill effort test 88 100/80 126 80/60

left ventricle was normal in size and contractedwell.

Treatment

The patient received 9-fluoro-cortisone acetate0.2 mg daily and wore elastic stockings withoutany effect on the blood pressure. Ephedrine(25 mg daily) resulted in a rise of the supineblood pressure from 110/60 mmHg to 180/100mmHg, but did not relieve the orthostatic hypo-tension (70/55 mmHg). An antigravity suit wasused at a pressure of 40 mmHg. This preventedthe fall in blood pressure as well as the sympto-matology of angina pectoris and dizziness onchange of body position. However, the suit wasimpractical for everyday use and was rejectedby the patient. Dipyridamole (75 mg threetimes daily), isosorbide dinitrate (10 mg threetimes daily), and nitroglycerine (2.6 mg three timesdaily) did not relieve the angina but seemed toaggravate it.

Discussion

Our patient presented with the typical picture ofthe Shy-Drager syndrome including autonomicand extrapyramidal dysfunction. Sympathetic dis-orders manifested as orthostatic hypotension,impaired response to the Valsalva manoeuvre,inadequate response to atropine as well as hypo-tension on physical exertion. Nonetheless thepatient was able to achieve a moderate increasein heart rate during effort testing. The blood vesselswere found to be supersensitive to smallquantities of ephedrine, consistent with thedenervation supersensitivity observed in the Shy-Drager syndrome (Meyer et al., 1973). In ourpatient ephedrine did not prevent orthostatichypotension. Although treatment with sym-pathomimetic drugs is sometimes successful inpreventing orthostatic hypotension, this is oftena.chieved at the expense of supine hypertensionand tachycardia (Davies et al., 1978). The pressuresuit did succeed in preventing orthostatic hypo-tension, but was too cumbersome to be practical.Impotence was the main feature of para-sympathetic dysfunction. The patient also suf-fered from severe urgency, often accompanied byurinary incontinence. Nevertheless, his bladderwas of normal size and there was no residue onvoiding. This picture is not compatible with aparasympathetic lesion but seems to fall into thecategory of "disinhibited bladder" (DeJong,1970).The distinguishing feature of this patient was

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Fig. 1 Intra-arterial pressure recording from the ascending aorta (A,) during theValsalva manoeuvre. The arrows indicate the onset and end of the manoeuvre. Thereis a normal increase in pressure in phase 1 and a normal decrease in pressure duringphases 2 and 3, but reflex tachycardia does not occur. After release of the Valsalvamanoeuvre overshoot hypertension and bradycardia do not occur (phase 4.)

Fig. 2 Selective coronary arteriogram. (A) Right coronary artery (RCA) is normal (left anterior obliqueview). (B) Left coronary arteriogram (right anterior oblique view) shows a normal left main stem andvirtually normal left anterior descending (LAD) and circumflex (Cx) branches with trivial, nonobstructiveatheroma in the circumflex system.

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Angina pectoris with normal coronary arteries in Shy-Drager syndrome

the severe angina pectoris which appeared onchange of body position or minimal exertion inthe presence of normal coronary arteries. Al-though 9% of patients with angina pectoris havenormal coronary arteriograms (Schlant, 1974), itis likely that in the present case, angina wasrelated to the hypotension which appeared onstanding or during physical exertion. Moreover,vasodilators such as dipyridamole and isosorbidedinitrate which normally alleviate the chest painof coronary artery disease were ineffective andaggravated his condition. We suggest that anginapectoris may be another symptom of the inade-quate circulatory response in the Shy-Dragersyndrome.

We thank Dr Bentwich for referring the patientand Ms G. Obstfeld for technical assistance.

References

Davies, B., Bannister, R., and Sever, P. (1978).Pressor amines and monoamine oxidase inhibitorsfor treatment of postural hypotension in autonomicfailure. Lancet, 1, 172-175.

DeJong, R. N. (1970). The Neurologic Examination,third edition, pp. 730-731. Harper and Row: NewYork.

Klutzow, F. W., Earle, K. M., and Webster, D. D.(1975). Disorders of autonomic function. MilitaryMedicine, 140, 338-344.

Meyer, J. S., Shinazu, K., Fukuuchi, Y., Ohachi, T.,Okanoto, S., Koto, A., and Ericsson, A. D. (1973).Central dysautoregulation in central neurogenichypotension (Shy-Drager syndrome). Neurology(Minneapolis), 23, 262-273.

Schlant, R. C. (1974). Altered cardiovascularphysiology of coronary atherosclerotic heart disease.In Heart, Arteries and Veins, pp. 1022. Edited byJ. W. Hurst. McGraw-Hill Kogakuaha Ltd: Tokyo.

Shy, G. M., and Drager, G. A. (1960). A neurologicalsyndrome associated with orthostatic hypotension.Archives of Neurology (Chicago), 2, 511-527.

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