Study of patients presenting with symptoms of peripheral neuropathy and thickened greater auricular nerve.

OBJECTIVE: To analyze symptoms and make a clinical diagnosis of leprosy in patients presenting with symptoms of peripheral neuropathy and found to have thickened greater auricular nerve. DESIGN: Cross-sectional study. SETTING: Kathmandu Medical College Teaching Hospital, Sinamangal, Kathmandu. Patients attending the medical out-patient department of this hospital were taken in the study. MATERIALS AND METHODS: 40 patients presenting with symptoms of peripheral neuropathy and are found to have thickened greater auricular nerve were included. RESULTS: Thickened greater auricular nerve and sensory symptoms showed male predominance (97.5%). Mean age of involvement was 28.65 years. The symptom most frequently complained of was chest pain (75%), followed by pins and needle sensation 67.5%, burning of the upper extremities, nape of the neck and chest 57.5%, palpitation 45%, disturbed sleep mostly said to be due to burning 35%, sweating 20%, dizziness 17.5%, shortness of breath 7.5%, and numbness of the limbs in 2.5%. None of the patients had somatic neuropathy. Autonomic neuropathy was present in 42.5 %. CONCLUSIONS: 1. In endemic areas patients with thickened peripheral nerve and sensory symptoms should be diagnosed clinically as primary neuritic leprosy. 2. In absence of objective loss of somatic sensation autonomic neuropathy may be the only early indicator of neuritis. 3. Close follow up of these patients is necessary.

Correlation of quantitative tests of nerve and target organ dysfunction with skin immunohistology in leprosy.

Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attributed to early invasion by Mycobacterium leprae of Schwann cells related to unmyelinated nerve fibres. We have studied skin lesions and contralateral clinically unaffected skin in 28 patients across the leprosy spectrum with a range of selective quantitative sensory and autonomic tests, prior to biopsy of both sites. Unaffected sites showed normal skin innervation, when antibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were used, with the exception of intraepidermal fibres which were not detected in the majority of cases. Elevation of thermal thresholds and reduced sensory axon-reflex flare responses in affected skin correlated with decreased nerve fibres in the subepidermis, e.g. axon-reflex flux units (means+/-SEM) for no detectable innervation; decreased innervation; and clinically unaffected skin, were 23+/-3.1; 41.2+/-7.3; and 84.5+/-4.0, respectively. Reduced nicotine-induced axon-reflex sweating was correlated with decreased innervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of sweat gland structure. This study demonstrates a correlation between selective nerve dysfunction on clinical tests and morphological changes in skin, irrespective of the type of leprosy, and is the first to show that loss of sweating in leprosy may result either from decreased innervation and/or involvement of the sweat glands. The findings have implications for the selection and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.

Peripheral autonomic nerve dysfunction in asymptomatic leprosy contacts.

In endemic areas, subclinical autonomic nerve dysfunction may be a manifestation of infection with M. leprae and possibly allow detection before progression to clinical disease. Vasomotor reflex (VMR) testing was performed in 36 asymptomatic leprosy contacts (24 household contacts, 12 hospital contacts) and 47 age- and sex-matched controls in Pokhara, Nepal. Mean age was 30 years, two thirds were male. A Moor instruments DRT4 laser doppler monitor was used for velocimetry of microvascular blood flow. The flow reduction following an inspiratory gasp was recorded from finger and toe tips. Mean percent reduction was 57.8 (standard deviation 14.6) among household contacts, 61.9 (17.5) among hospital contacts and 66.8 (7.8) among controls (p=0.001 by analysis of variance). The prevalence of abnormal test results was 54% among household contacts, 42% among hospital contacts and 15% among controls (p=0.0005 by chi-square test for trend). Subclinical autonomic neuropathy is common among healthy contacts of leprosy patients. Prospective studies are now needed to clarify to what extent abnormal VMR tests predict the risk of progression to clinical disease.

Electrophysiological evaluation of peripheral autonomic function in leprosy patients, leprosy contacts and controls.

Since there is immunocytochemical evidence that the initial damage in leprosy is directed at distal, small, unmyelinated nerve fibers, we investigated several electrophysiological methods for their potential value in detecting peripheral autonomic dysfunction in leprosy contacts and leprosy patients. Fingertip blood flow velocity and its control by vasomotor reflexes (VMR) with a laser Doppler flowmeter, fingertip skin temperature, and the sympathetic skin response (SSR) to exosomatic stimuli were studied in 89 leprosy patients, 36 leprosy contacts and 47 normal subjects. Whereas there were no significant differences between the groups in fingertip skin temperature and resting blood flow velocity measurements, there were significant differences in the prevalence of impaired fingertip VMR and absent SSR. The prevalence of absent SSR in leprosy patients was 60.9%, in contacts 13.8%, in controls 6.3%. The prevalence of abnormal VMR in leprosy patients was 61.2%, in contacts 34.7% and in controls 10.6%. VMR testing is a more sensitive test method for autonomic dysfunction compared with the SSR. The implication of impairment in vasomotor and sudomotor function in leprosy contacts needs yet to be determined. However, we propose this to be a response to exposure to Mycobacterium leprae, which represents either ongoing nerve damage or nonprogressive residual autonomic nerve damage. We suggest that VMR testing and SSR are valuable methods to evaluate early leprous neuropathy.

Impairment of vasomotor reflexes in the fingertips of leprosy patients.

A method is described for eliciting fingertip vasomotor reflexes by inspiratory gasp and contralateral hand cold challenge. The results of the two tests are reproducible on replicate testing and, when taken together, have proved reliable for detection of impairment of autonomic reflexes in 10 newly registered leprosy patients who did not have any obvious deformity. Similar, but less severe, impairment of vasomotor reflexes was noted in a group of 10 fully treated, apparently cured ex-leprosy patients, none of whom showed clinically obvious neuropathy. Both the new patients and the ex-patients were significantly different from healthy contacts and from healthy Europeans, who were indistinguishable by this test. Evidence is presented suggesting that impairment of these vasomotor reflexes is mainly due to damage to the efferent pathway in the peripheral nerves. The method might prove valuable for investigation of early nerve damage in new patients or during reversal reactions in leprosy at a stage before irreversible damage is done.

Intraocular pressure and iris denervation in Hansen's disease.

We retrospectively analyzed 255 Hansen's disease patients and found low intraocular pressure (less than 7 mm Hg) in 12% of them. We showed a correlation between low intraocular pressure and avascular keratitis and iritis. We also found that patients with low intraocular pressures had abnormally large postural changes in intraocular pressure. We speculate that abnormalities in the autonomic innervation of the anterior segment of the eye may be related to the intraocular pressure abnormalities. Further investigations along this line may increase our understanding not only of the pathophysiology of Hansen's disease but also of the mechanisms regulating homeostasis of intraocular pressure.

Cardiovascular dysautonomia in patients with lepromatous leprosy.

Autonomic functions were studied by six standard tests in 65 patients with lepromatous leprosy and 25 healthy controls. Dysautonomia was observed in 22 patients, all having the disease for more than five years. Associated peripheral neuropathy, judged clinically, was present in all, except one patient. Of the 22 dysautonomic patients, 9 each had mild or moderate dysantonomia and 4 had severe dysautonomia as per the scoring schedule devised by us. Syncope, gustatory sweating and impotence were the symptoms suggestive of dysautonomia. But not all affected patients reported these symptoms. Involvement of the sympathetic system was more frequent than that of the parasympathetic system. Statistically significant abnormality was seen with Atropine ratio, standing 30:15 beat ratio, postural hypotension and sustained hand grip test. Sustained hand grip test was the one which consistently gave abnormal results in all the 22 dysautonomic patients.

Autonomic neuropathy in leprosy.

21 patients of borderline lepromatous and lepromatous leprosy of both sexes were taken for study after exclusion of autonomic disorders. Autonomic functions pertaining to cardiovascular and genital system were carried out. Five healthy volunteers served as controls. Autonomic function tests indicate definite involvement of cardiovascular and genital system. The incidence of autonomic neuropathy in 21 patients studied was ranging from 14.3 to 57% for various tests. There is involvement of parasympathetic system (vagus nerve) which occurred early and more common than sympathetic. The sympathetic damage is always associated with parasympathetic damage. The severity of autonomic neuropathy is found to be high in leprosy of longer duration. Autonomic neuropathy widely occurs in leprosy as in diabetes mellitus.

Autonomic neuropathy in leprosy.

21 patients of borderline lepromatous and lepromatous leprosy of both sexes were taken for study after exclusion of autonomic disorders. Autonomic functions pertaining to cardiovascular and genital system were carried out. Five healthy volunteers served as controls. Autonomic function tests indicate definite involvement of cardiovascular and genital system. The incidence of autonomic neuropathy in 21 patients studied was ranging from 14.3 to 57% for various tests. There is involvement of parasympathetic system (vagus nerve) which occurred early and more common than sympathetic. The sympathetic damage is always associated with parasympathetic damage. The severity of automatic neuropathy is found to be high in leprosy of longer duration. Autonomic neuropathy widely occurs in leprosy as in diabetes mellitus.

Effect of one year clofazimine therapy on autonomic functions in lepromatous leprosy with lepra (ENL) reaction.

Twenty patients of either sex of Lepromatous leprosy with frequent type II (ENL) reactions were selected for the study after exclusion of autonomic disorders. ANS functions were evaluated before and after Clofazimine therapy at an interval of two months for one year. Sweat function test, valsalva manoeuvre, Histamine triple response, cold pressor test and Homatropine instillation were carried out in twenty normal healthy volunteers (controls) and the (ENL) patients. Clofazimine was administered initially 100 mg three times daily for one month and then gradually reduced to a dose of 100 mg biweekly for the last three months. Before the clofazimine therapy, eighteen patients had abnormal sweat functions, five patients had abnormal valsalva score, five patients had abnormal cold pressor response and all the eighteen patients had abnormal histamine triple response test. Homatropine instillation test was normal in all the patients. ANS functions did not improve significantly with Clofazimine therapy, except in one patients with abnormal cold pressor response who showed slight improvement in pressor response which, however, did not reach the normal value. ANS function tests indicate complete involvement of local axon reflex and hyporeactivity of sympathetic system and cardiac regulatory mechanisms in these patients. Parasympathetic system seems to be normal as seen from Homatropine instillation test.

Assessment of cutaneous autonomic nerve functions in leprosy.

31 cases of established leprosy were studied for sweat response to acetylcholine and adrenaline injected intradermally and compared with normal areas of skin on the contralateral side in a total of 40 lesions. Sweating was measured by counting the number of blue dots which appeared on the yellow back ground of a filter paper soaked in 1% Bromophenol blue solution which represented sweat pores, whereas there was decreased, or absent sweat response in 31 lesions, there was an increased response in to acetylcholine in 7 lesions, and normal response in 2 lesions. Sweat response to adrenaline was obtained in 29 lesions. It was increased in 13 lesions all of which were anaesthetic or analgesic. Adrenergic sweating in these cases is probably a result of direct effect of adrenaline on sweat glands. Biopsy sections of 20 cases were reviewed for the histological appearance of the nerves. It was found that out of the cases who showed increased sweat response 1 had partially destroyed nerves while 2 others had intact nerves. Sweat function tests are of limited value in the diagnosis of leprosy and some autonomic function may continue in leprosy despite loss of somatic nerve function.

A study of autonomic functions in leprosy.

The two groups of leprosy patients were compared with normal for the evaluation of the functional status of the autonomic nervous system, with the aid of several established procedures. Our findings reveal that in the leprosy patients the adrenergic system is hypo-functional as compared to the cholinergic. Further, in maculoanaesthetic group, there appears to be a physiological Dale's vasomoter reversal when adrenaline was used.

A study of autonomic functions in leprosy

The two groups of leprosy patients were compared with normal for the evaluation of the functional status of the autonomic nervous system, with the aid of several established procedures. Our findings reveal that in the leprosy patients the adrenergic system is hypo-functional as compared to the cholinergic. Further, in maculoanaesthetic group, there appears to be a physiological Dale's vasomoter reversal when adrenaline was used.