Cardiac autonomic function was studied in 23 alcohol dependent men by standard tests of autonomic function and measurement of 24 hour heart rate variability. In all there was peripheral or central nervous system damage or both. Standard tests of autonomic function showed vagal neuropathy in seven. The remainder had normal autonomic function tests. Twenty four hour heart rate variability was measured as the standard deviation of the successive differences between RR intervals from an ambulatory electrocardiogram recording. Twenty four hour heart rate variability was significantly lower in both alcohol dependent groups than in controls, but the results in the two alcohol dependent groups were not significantly different from each other. The results of standard tests of autonomic function did not distinguish between the alcohol dependent men with normal autonomic function and controls. The differences in heart rate variability between this group and the controls may have been the result of the ability of this method to detect small changes in autonomic integrity. Cardiomyopathy may also account for some of these differences and such abnormalities should be excluded before results are to be regarded as a reflection of vagal function. Twenty four hour measurement of heart rate variability may be a more useful index of cardiac vagal neuropathy than currently available tests of autonomic function. activity but this does not take into account that inputs of different frequencies produce the change in heart rate; those at lower frequencies are not necessarily autonomic in origin such as reflex mechanisms involved with continuing haemodynamic changes. Tests of autonomic function also tend to classify patients merely on the basis of the presence of neuropathy and give little scope for grading its severity.5 Measurement of short term (5 min) heart rate variability has been advocated as an indicator of autonomic neuropathy6; however, there is disagreement about whether the recording should be performed with the patient standing, sitting, or lying and about the best index for measuring heart rate variability.7 Ambulatory electrocardiographic (Holter) monitoring of heart rate variability may provide a more sensitive index of autonomic function than is currently available8 because it makes a large number of RR intervals available for the calculation of heart rate variability. Monitoring over 24 hours also provides an opportunity to examine autonomic function during normal daily activities without interference from investigators. It may enable disease progression in alcohol dependent patients to be monitored. Ewing and colleagues reported that heart rate variability was reduced in diabetic patients who had normal standard autonomic function tests.8 The present study was conducted to test whether similar results apply to alcohol dependent patients and whether 24 hour measurement of heart rate variability is a useful method for assessing cardiac autonomic changes in alcohol dependent patients.

SUMMARY Parasympathetic innervation of the pupil was studied in 30 alcoholics. Twelve alcoholics had cardiac vagal neuropathy. The resting pupillary diameters in this group were larger, and pupil reponses to methacholine were greater, than in control subjects or alcoholics without vagal neuropathy. These observations imply that lesions in the parasympathetic supply to the pupil may occur in alcoholics with other evidence of autonomic neuropathy involving the parasympathetic system.Parasympathetic neuropathy involving the vagus nerve was reported in 1974 from neuropathological studies of four alcoholic patients. ' We have recently shown' that evidence of vagal neuropathy may also be obtained during life and that this is not uncommon in alcoholic subjects with other evidence of moderate to severe nervous damage. However, a study of the parasympathetic supply to the pupil in alcoholic subjects showed no evidence of denervation, with 8% each of alcoholics' and control subjects showing pupillary constriction of 1 mm or greater with methacholine.' Patients in that study had relatively mild nervous damage. with only 40% having peripheral neuropathy and no patients having vagal neuropathy as determined from the heart rate responses to Valsalva's manoeuvre. It remained to be determined whether, in alcoholics with vagal neuropathy, the third cranial nerve may also be affected. This was the purpose of the present study. Parasympathetic denervation of the pupil was tested by measuring the resting pupil diameter and by examining the supersensitivity of the pupil to topical administration of dilute methacholine. Photographic studies A 2% solution of methacholine in normal saline ("Mecholyl", acetyl-f3-methylcholine) was used for the pupillary test. The solution was freshly prepared monthly by the Wellington Hospital Pharmacy, sterilised by the method of filtration and kept stored at 4°C. The study was carried out in a photographic studio under standard lighting conditions. The ambient light was kept moderate and constant. A studio flash unit (timing 1/60th second, exposure f 11-0) was positioned at a far corner of the room. The subject sat behind a head-rest on which he rested his chin to obtain constant and reproducible positions. Photographs were taken of the eyes with a vertical scale (ruled in centimetres) positioned close to and in the plane of the eyes. The camera used was a Nikon F2 35 mm single lens reflex camera with a 105 mm lens. Two drops of 2% methacholine were instilled in both eyes which then were closed for 30 seconds, during which time a gentle pressure was applied on the lacrimal duct to delay drainage of fluid. Twenty minutes after instillation of the drug, photographs were again taken of the eyes. Enlarged prints of the eyes and the scale were made from the exposures. The pupil diameters (measured in the horizontal plane) were measured blind by three observers using the centimetre scale on the prints, with an accuracy of ±0-1 mm. The three readings for each pupil were averaged. The constriction of a pupil...

ZealandSUMMARY A patient with peripheral neuropathy and orthostatic hypotension was found to have pernicious anaemia. Symptoms improved after vitamin B,2 replacement therapy. Insulin toler-ance testing showed that the patient lacked catecholamine, heart rate, and sweating responses to hypoglycaemia. This indicates that pernicious anaemia may cause orthostatic hypotension owing to failure of noradrenaline release.Pernicious anaemia is frequently accompanied by numerous CNS and peripheral nervous system abnormalities. These include pyramidal tract and posterior column dysfunction, optic neuropathy, and distal symmetric polyneuropathy with spinal cord involvement."' Other disturbances include impotence, constipation, urinary retention and postural hypotension.24 The causes of these have not been established, but could be due to autonomic neuropathy. We report a case of pernicious anaemia in which the presenting symptom was orthostatic hypotension. We have examined the pathophysiological basis of the orthostatic hypotension in this patient by measuring catecholamine and vasopressin responses to insulin-induced hypoglycaemia. Case historyThe patient was a 79-year-old male who complained of coldness and pins and needles sensations in the hands and feet, and dizziness on standing. He had fainting spells and occasionally broke out in a hot sweat. For six months these symptoms had progressively worsened, necessitating his admission to hospital. The patient complained that he had trouble initiating micturition and, after admission to hospital, constipation became a problem. The patient had given up smoking 10 years earlier, and was a light drinker.On examination, no abnormalities were found in mental state or in the cranial nerves. His complexion was pale, with a lemon-yellow tinge. Supine blood pressure and pulse rate were 130/50 mmHg and 60/min, respectively. Loss of sensation for pinprick was present to a clearly defined level above the knees in both legs, and above the wrists in both hands. The loss was bilaterally symmetrical. Decreased vibration sense in both legs was also apparent. A cervical spine radiograph revealed gross degenerative changes involving virtually all levels, with bony ankylosis between C4 and C5, and narrowing of the spinal canal. Motor conduction velocities were normal in the right radial and median and lateral popliteal nerves. The ulnar median and sural sensory potentials were of low magnitude. On assumption of upright posture, blood pressure dropped from 130/50 to 92/44 mmHg at three minutes in the standing position, at which time the subject developed palor, dizziness and said he was going to faint. The heart rate responses to standing (increase of 22/min) and to atropine (increase of 20/min) were normal. An insulin tolerance test was carried out, with blood samples collected at 20, 30, 35, 40, 45 and 60 min after intravenous injection of 0-1 unit/kg insulin. Samples were analysed for glucose, catecholamines and vasopressin. Catecholamines were measured using a radioenzymatic assay, as desc...