Blink reflex, H-reflex and nerve-conduction alterations in leprosy patients.

Peripheral nerve lesions are the most important cause of disability in leprosy patients. Electrophysiological studies are used in the diagnosis and prognosis of neuropathy. Nerve conduction is the most frequently used electrophysiological test method to detect neuropathy, although it evaluates only a part of the peripheral nervous system. Blink reflex and H-reflex are electrophysiological tests which evaluate facial and trigeminal nerve function. This study determined the frequencies of blink reflex, H-reflex and motor and sensory nerve conduction alterations in twenty five heterogeneous, clinic patients with lepromatous leprosy and a control group of 20 healthy subjects. Study results showed a decrease in motor and sensory nerve conduction in 40% and 30%, respectively. In blink reflex (BR), right R1 was altered in latency in 20% of patients, left R1 in 20%, right ipsilateral R2 in 16%, left ipsilateral R2 in 20%, and right and left contralateral R2 were altered in 32% of patients. There was an absence of H-reflex in 16% (n = 4) and prolonged latency in 4% (n = 1).

Cyclosporine A treatment of leprosy patients with chronic neuritis is associated with pain control and reduction in antibodies against nerve growth factor.

OBJECTIVES: Chronic neuritis (CN) is still a major problem in leprosy and is difficult to manage in patients who do not respond well to prednisone. In this study we (i) evaluate the efficacy of cyclosporine A (CyA) in controlling CN patients, and (ii) analyse the presence of anti-NGF antibodies in the sera of leprosy patients, and their behaviour during CyA treatment. DESIGN: This was an open, prospective, non-comparative study. Sixty-seven leprosy patients in three different institutions in Pará, Brazil were studied from January, 2001 to January, 2004. Of these, 47 had no CN and 20 were leprosy patients suffering from CN and taking at least 40 mg/day prednisone to control nerve impairment and pain. Patients received 12 months reducing course CyA starting at 5 mg/kg per day. The outcome measure was sensory impairment, assessed using Semmes-Weinstein monofilament examination (SWME), muscular force and spontaneous or palpation-related pain. RESULTS: Antibodies against NGF were detected in the sera of leprosy patients, which may explain the depletion of NGF in leprosy contributing to neuritis, inflammation and loss of cutaneous nociception. The levels of these antibodies in CN patients were slightly lower than in patients with no CN. However, anti-NGF titres in CN patients treated with CyA were lowered to levels similar to those in the normal subjects. There was also improvement in sensory impairment, muscular force and pain. CONCLUSIONS: These data suggest that anti-NGF antibodies are present in the sera of leprosy patients and may influence the outcome of neuritis, and that CyA might be a useful drug in controlling nerve impairment and pain in leprosy patients.

Evaluación neurológica completa en la neuropatía Hanseniana / Complete neurological assessment in Hansen's disease

Dada la importancia de la afectación neurológica de la Enfermedad de Hansen, los autores intentan recoger en este artículo como se realiza una exploración neurológica completa. Dentro de esta exploración nos centramos en los puntos fundamentales como son la palpación y búsqueda de los nervios periféricos engrosados, el estudio de la sensibilidad superficial y profunda, la exploración de la motilidad voluntaria, el examen de los reflejos y la valoración de los procesos neurotróficos secundarios al daño. Debemos resaltar que en la mayoría de las ocasiones para el diagnóstico de la enfermedad y fundamentalmente en el trabajo de campo, realizaremos una exploración basada en todos estos puntos, pero mucho más simplificada. Como anexo del artículo expondremos los resultados obtenidos tras la exploración neurológica en 71 pacientes controlados en el Sanatorio de Fontilles (AU)

Skin and muscle vasomotor reflexes in detecting autonomic dysfunction in leprosy.

There are few tests to assess the function of small unmyelinated nerve fibers. One established test is the skin vasomotor reflex (SVMR), which uses laser doppler flow velocimetry. The SVMR has the disadvantages of being susceptible to interference (from change of temperature and alerting stimuli) and of requiring expensive equipment. An ultrasound doppler method, which is less expensive, can be used to detect muscle vasomotor reflex (MVMR) activity. We sought to compare the efficacy of these two methods in detecting dysfunction of small unmyelinated nerve fibers in patients with leprosy. SVMR was shown to be less sensitive (P < 0.01) and specific (P < 0.001) than MVMR. The favorable results of MVMR may be attributed to its lesser susceptibility to interfering sympathetic vasoconstriction from alerting stimuli. MVMR also reflects larger areas of blood vessel innervation than the laser doppler method. In leprosy, nerve damage is typically patchy and may be missed by the smaller sampling of the laser method.

Do nerve growth factor-related mechanisms contribute to loss of cutaneous nociception in leprosy?

While sensory loss in leprosy skin is the consequence of invasion by M. leprae of Schwann cells related to unmyelinated fibres, early loss of cutaneous pain sensation, even in the presence of nerve fibres and inflammation, is a hallmark of leprosy, and requires explanation. In normal skin, nerve growth factor (NGF) is produced by basal keratinocytes, and acts via its high affinity receptor (trk A) on nociceptor nerve fibres to increase their sensitivity, particularly in inflammation. We have therefore studied NGF- and trk A-like immunoreactivity in affected skin and mirror-site clinically-unaffected skin from patients with leprosy, and compared these with non-leprosy, control skin, following quantitative sensory testing at each site. Sensory tests were within normal limits in clinically-unaffected leprosy skin, but markedly abnormal in affected skin. Sub-epidermal PGP 9.5- and trk A- positive nerve fibres were reduced only in affected leprosy skin, with fewer fibres contacting keratinocytes. However, NGF-immunoreactivity in basal keratinocytes, and intra-epidermal PGP 9.5-positive nerve fibres, were reduced in both sites compared to non-leprosy controls, as were nerve fibres positive for the sensory neurone specific sodium channel SNS/PN3, which is regulated by NGF, and may mediate inflammation-induced hypersensitivity. Keratinocyte trk A expression (which mediates an autocrine role for NGF) was increased in clinically affected and unaffected skin, suggesting a compensatory mechanism secondary to reduced NGF secretion at both sites. We conclude that decreased NGF- and SNS/PN3-immunoreactivity, and loss of intra-epidermal innervation, may be found without sensory loss on quantitative testing in clinically-unaffected skin in leprosy; this appears to be a sub-clinical change, and may explain the lack of cutaneous pain with inflammation. Sensory loss occurred with reduced sub-epidermal nerve fibres in affected skin, but these still showed trk A-staining, suggesting NGF treatment may restore pain sensation.

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.

Sympathetic vasomotor dysfunction in leprosy patients: comparison with electrophysiological measurement and qualitative sensation testing.

Testing of skin vasomotor reflexes (VRs) by laser Doppler flowmetry (LDF) is now a recognised method of measuring peripheral dysautonomia. To assess its specificity as an indicator of impairment to unmyelinated autonomic fibres, VR testing at the fingerpulp was compared with standard qualitative sensation (QST) and with sensory electrophysiological (SNVC) measurements in 39 Iranian leprosy patients. There was a significant relationship between VR and SNCV values (but not QST): these were jointly measurable in 38.5% of fingers, and jointly absent in 35.3% of fingers which also showed significantly reduced LDF perfusion and skin temperatures. However, in 10.3% of fingers, predominantly index and otherwise apparently healthy, VRs were absent but SNCV present, suggesting early sub-clinical autonomic impairment. In a further 16% of fingers, predominantly ulnar and with poor microcirculation, intact (though impaired) VRs could be recorded despite the absence of SNCV responses, suggesting sparing or regeneration of these fibres. This evidence suggests that where there is heterogeneity of nerve damage a combination of VR and electrophysiological testing can indicate the functional status of distinct fibre types.

Vasomotor reflexes in the fingertip skin of patients with type 1 diabetes mellitus and leprosy.

Fingertip skin blood flow was measured by laser Doppler flowmetry (as LDflux) under environmental conditions promoting vasodilation in Scottish patients with diabetes mellitus and Indian patients with leprosy. The reflex control of fingertip blood flow was assessed by measuring the reduction in LDflux induced by deep inspiratory gasp (IG) and cold challenge (CC) of immersing the contralateral hand in cold water. The uncomplicated diabetic patients showed normal vasomotor reflexes and an increased, though non significant, LDflux level (p < 0.06). The patients with diabetic neuropathy had resting LDflux levels significantly less than the uncomplicated group and also had substantial impairment of both IG and CC reflexes. Those with retinopathy (but no clinically apparent neuropathy) had LDflux within the normal range, but they showed minor evidence of impairment of the vasomotor reflexes. The uncomplicated newly registered leprosy patients had reduced LDflux and substantial impairment of CC reflexes. These changes were more marked in newly registered leprosy patients with clinical evidence of neuropathy. Leprosy patients with long-standing neuropathy requiring orthopaedic treatment had LDfluxes so greatly reduced that measurement of vasomotor reflexes was not practicable. The CC reflex was more severely affected than the IG reflex and more frequently absent in leprosy patients, possibly because of associated sensory neuropathy affecting the afferent limb of this response. Thus laser Doppler flowmetry can detect impairment of reflex control of fingertip blood flow in both diabetes mellitus and leprosy, but there are functional differences in the pattern of autonomic impairment between the diseases, suggesting differences in the pathogenesis of nerve damage.