Effect of steriod therapy on parameters of peripheral autonomic dysfunction in leprosy patients with acute neuritis

International Journal of Leprosy and Other Mycobacterial Diseases, Mar 1997 by Annelies Wilder-Smith, Einar Wilder-Smith

Effect of Steroid Therapy on Parameters of Peripheral Autonomic Dysfunction in Leprosy Patients with Acute Neuritis1

Nerve damage is the major cause of longterm disability in leprosy (6 Il). Consequently, the primary prevention of longterm disabilities in leprosy will only be achieved by early detection and adequate treatment of neural impairment. The benefits of steroid treatment of leprosy reactions and neuropathy have been recognized for several decades (18). Studies assessing the outcome of antineuritis treatment have used motor and/or sensory functions as parameters (I3.25, 27).

The effect of steroid therapy on the parameters of autonomic function is unknown. Since autonomic nerve dysfunction may be the earliest and most reversible component of neuropathies (8, 10), sequential electrophysiological studies of autonomic function may prove important for monitoring the treatment of neuropathy in leprosy.

Recent studies on peripheral dysautonomia in leprosy were based on vasomotor reflex (VMR) testing ( 3.29, 30) and the sympathetic skin response (SSR) (28, 31). VMR measures the reduction in fingertip skin blood flow in response to a test stimulus and is an index of peripheral autonomic function ("4. 5). SSR is a simple autonomic test measuring the changes in skin voltage in response to exosomatic stimuli with sweat glands as effectors (2 16, 19, 23), A high prevalence of impaired VMR and SSR was found in leprosy patients (1,3,29). It remains to be established whether these lesions are permanent or reversible.

The aims of this pilot study were to describe the short-term effects of steroid treatment on two parameters of peripheral autonomic function (VMR and SSR) in comparison with motor and sensory nerve functions.

STUDY PARTICIPANTS AND METHODS

Patients

A prospective pilot study was carried out at the Green Pastures Hospital (GPH) in Pokhara, West Nepal, between April and June 1995. All leprosy patients [confirmed according to World Health Organization (WHO) criteria] attending the GPH neuritis clinic were included in the study if they fulfilled the inclusion criteria: age range between 10 and 55 years, voluntary participation after informed consent, current treatment with standard WHO-recommended multidrug therapy (WHO/MDT), and a course of steroid treatment for neuritis due to leprosy. The diagnosis of neuritis was made by three experienced medical doctors at the neuritis clinic and was based on the following criteria: a) Skin = redness and swelling of skin lesions and tenderness of the lesions. b) Peripheral nerves = swelling on palpation, and/or spontaneous pain, and/or tenderness on palpation, and/or paresthesia and/or nerve function impairment [as tested by touch sensibility test (TST) and voluntary muscle test (VMT), see below]. c) General = sometimes edema of hands, feet or face, occasionally fever.

The skin signs were obligatory, the nerve signs and general signs optional. Patients with erythema nodosum leprosum (ENL) were not included.

Corticosteroid treatment was given in the following way: Prednisolone 40 mg initially, tapering approximately 5 mg every 2 weeks, depending on the progress of the patient as judged by serial TST and VMT measurements. Depending on the clinical severity of neuritis and steroid side effects, individual dose adjustments could be undertaken.

Exclusion criteria were ulcers on or reabsorption of more than one fingertip, more than one missing digit, and patients suffering from alcoholism or diabetes mellitus.

Controls

Healthy Nepali volunteers between the ages of 10 and 55 were recruited from the Pokhara Red Cross Organization. In addition, some of the Nepali hospital staff recruited friends. All controls had no known contact with leprosy patients. All patients and controls were recruited by an independent investigator.

The study was approved by the local ethical committee in Berne, Switzerland, and in Pokhara, Nepal.

Measurement of autonomic reflexes All subjects were allowed to equilibrate at an ambient temperature of 28-34C in a quiet room. The procedure was explained to them in Nepali by a translator. The neurophysiological tests were performed by a consultant in neurology or were performed under his direct supervision. Repeat examinations were conducted at an interval of between 10 to 40 days for leprosy patients and 3 to 40 days for controls.

Vasomotor reflex (VMR). A laserDoppler flow-temperature monitor (Model DRT4; Moor Instruments, Axminster, England) with machine settings of band width 10 KHz, time constant 1 sec, gain control and zeroing automatic was used to measure fingertip blood flow. Low, et al.'s guidelines ('5) were used. Double-sided adhesive disk secured attachment of the combined laserDoppler to the skin. Fingertip blood flow was taken as the mean of the laser-Doppler measured red blood cell flux value during a 3-min observation period. An inspiratory gasp was used to induce the VMR. Subjects were asked to practice to "take the quickest and deepest breath you can and hold it for 10 seconds." The largest response elicited from three gasps was used for subsequent analysis. For each subject, 12 recordings were made (10 fingers, 2 big toes). The onset of each inspiratory gasp was marked with an event marker, and the resultant maximal reduction in skin blood flow recorded and expressed as a percentage of the resting skin blood flow. VMR testing was not begun until the inspiratory gasp was satisfactorily mastered and a stable baseline blood flow was recorded. A more complete description of VMR testing is presented elsewhere (15,29),