Sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma.

BACKGROUND: Leprosy (Hansen's disease) is a chronic granulomatous infection caused by Mycobacterium leprae with peripheral neuropathy as cutaneous and neurological manifestations. Peripheral nerve regeneration may be stimulated by vascular endothelial growth factor and other growth factors (GFs) that have important roles in extracellular matrix regeneration. All of those GFs can be found in platelet-rich plasma (PRP) preparation. The effect of PRP injection in leprosy peripheral neuropathy has never been reported. MATERIALS AND METHODS: A double-blind, randomized, control clinical trial was conducted among 60 patients with leprosy peripheral neuropathy. They were randomized to receive either a 1-ml injection of PRP as treatment or a 1-ml injection of platelet-poor plasma (PPP) as control. Skin sensibilities were measured by two-point discrimination test (TPDT) and visual analog scale (VAS), which were taken before and two weeks after treatment. RESULTS: Perineural injection of PRP was shown to be significantly more effective than PPP (P < 0.05) either in VAS or TPDT measurements. In both groups, the patients had a tingling sensation at the time of injection that disappeared shortly after. CONCLUSION: This study shows that perineural PRP injection could promote improvement of peripheral neuropathy sensibility in patients with leprosy. More research is needed to better determine the effects of PRP in nerve regeneration.

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration.

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers-Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases.

Effect of corticosteroid usage combined with multidrug therapy on nerve damage assessed using nerve conduction studies: a prospective cohort study of 365 untreated multibacillary leprosy patients.

The purpose of this study is to determine the extent of nerve involvement and to study the effect of corticosteroids combined with multidrug therapy on nerve damage in leprosy patients using sensory and motor nerve conduction studies. A cohort of 365 untreated multibacillary leprosy patients were prospectively studied using sensory and motor nerve conduction studies on upper and lower limb nerves. They were subgrouped as those to be treated with 12-week regimen of corticosteroids for reaction and/or neuritis or silent neuropathy of <6 months duration along with 12-month multidrug therapy (group A), and those with no reaction were treated with multidrug therapy only (group B). Analysis was performed using SPSS version 10.0. Significance of association was tested using chi(2) test. At registration, abnormality by nerve conduction studies was seen in 92% of patients and majority (65%) showing involvement of more than five sensory and motor nerves. Sensory nerve abnormalities were higher (52%) than motor (37%) (P < 0.001). Affection of sensory and motor nerves was higher in group A (P < 0.001). Notably, 40% nerves in group B also showed impairment at 0 month. This implies that almost all patients showed abnormal nerve conduction studies at onset regardless of reaction, proving nerve damage is more widespread than envisaged. At 18 months, overall percentile deterioration (23%) of nerves was higher than improvement (9%) (P < 0.001) indicating that corticosteroids combined with multidrug therapy failed to significantly improve the nerve status. Sensory nerve (57%) affection was significantly higher than motor (46%) (P < 0.001). Moreover, percentile deterioration of sensory nerves was higher in group A (P < 0.001) implying corticosteroids is not very efficacious in the prevention or reversal of nerve damage. Electrophysiological tests provide valuable information for detecting nerve function impairment and evaluating appropriate therapeutic regimens.

Leprosy: report of a case with severe peripheral neuropathy.

Leprosy (Hansen's disease) is a chronic granulomatous infectious disease, caused by Mycobacterium leprae, with cutaneous and neurological manifestations. Leprosy is very rare in Europe but some cases are reported, especially among people coming from endemic areas. Here, we report a case of Hansen's disease and emphasize the importance of a prompt diagnosis and treatment also in non-endemic areas.

Charcot's arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation.

Neuropathic arthropathy (Charcot's arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot's arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot's arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot's arthropathy secondary to herpetic encephalitis.

Tactile threshold detection in leprosy patients with an electronic algometer.

OBJECTIVE: To propose an electronic method for sensitivity evaluation in leprosy and to compare it to the Semmes-Weinstein monofilaments. METHODS: Thirty patients attending the Dermatology outpatient clinic of HCFMRP-USP were consecutively evaluated by both the electronic aesthesiometer and Semmes-Weinstein monofilaments on hand and foot test points. The intraclass correlation coefficient (ICC) was calculated to determine the variability of the electronic measures and the Kappa coefficient was calculated to determine the agreement between methods according to their categories (altered and non-altered tactile sensitivity). RESULTS: The ICC was approximately 1, demonstrating repeatability. The Kappa coefficient showed more than 75 and 63% agreement on the hand and foot points, respectively. The mean agreement between the 2 methods for the 7 points of the right and left hand was 77.14 and 75.71%, respectively. The mean agreement for all 10 points was 74.33 and 63.66% on the right and left foot, respectively. In cases of disagreement the detection of altered tactile sensitivity by the electronic esthesiometer on the right and left foot was 90.91 and 84.25%, respectively, with no detection by the monofilaments. CONCLUSION: The results suggest that the electronic esthesiometer is a reliable and easy application, capable of evaluating alterations of tactile sensitivity in leprosy patients.

Sensitivity and specificity of nerve palpation, monofilament testing and voluntary muscle testing in detecting peripheral nerve abnormality, using nerve conduction studies as gold standard; a study in 357 patients.

OBJECTIVE: To determine sensitivity and specificity of clinical tools viz. nerve palpation (NP), monofilament (MF), and voluntary muscle testing (VMT), for assessing peripheral nerve function impairment (NFI) in leprosy, using nerve conduction studies (NCS) as gold standard. STUDY POPULATION AND METHODS: 357 untreated multibacillary (MB) leprosy patients were assessed using above tests. The nerves assessed were left and right ulnar, median, radial cutaneous, sural, common peroneal and posterior tibial. The concordance between the clinical and NCS tests was done for each nerve. The sensitivity and specificity of clinical tests for detecting nerve impairment was determined, using NCS as gold standard. Analysis was performed using SPSS version 10.0. RESULTS: The sensitivity of NP ranged between 71% to 88% for all nerves, except the median (43%) and sural (59%) nerves. Specificity was > 60% for all, but low for ulnar (34%) and common peroneal (40%) nerves. The specificity of MF testing was > 80% and of VMT assessment was >90% for all nerves. The sensitivity of MF testing ranged between 35-44%, while of VMT assessment was very low i.e. 4-5%, the maximum was for the ulnar nerve (25%). Detection sensitivity of MF testing and VMT assessment improved two fold when combined with NP and was closely comparable to NCS test findings. CONCLUSIONS: Both MF testing and VMT assessment showed good specificity, but moderate to low sensitivity. NP was less specific but more sensitive than MF testing and VMT assessment. Combining NP with MF testing and VMT assessment gives a two fold improvement in the sensitivity for assessing nerve damage and could therefore serve as the most useful clinical tools for diagnosis of leprosy and detecting nerve damage at field level.

Intra- and inter-tester reliability of sensibility testing in leprosy.

We conducted an intra- and inter-tester agreement study of three sensory screening tests used in nerve function assessment of leprosy patients: the Semmes-Weinstein monofilament (SWM) test, moving 2-point discrimination (M2PD), and the pin prick test. The weighted kappa (Kw) statistic was used as the reliability coefficient. The SWM had intra-observer Kws ranging from 0.83 to 0.92 and inter-observer Kws ranging from 0.76 to 0.89. The M2PD had intra- and inter-tester Kws ranging from 0.75 to 0.82 and 0.54 to 0.82, respectively. Inter-tester agreement for the pin prick test ranged from 0.45 to 0.85. There was evidence that the main source of variability between testers was testing skill and experience. Among the experienced physiotechnicians there was no significant difference between intra- and inter-tester reliability. We conclude that reliability of the SWM test was very good, closely followed by the M2PD test. Reliability of the pin prick test was less good than that of the SWM and M2PD, making it less suitable for serial testing.

Effect of hand soaking on sensory testing.

This study investigates the effect of hand soaking on sensory testing scores in 58 patients with leprosy. Sensation was tested with Semmes-Weinstein monofilaments and scored. Patients were tested before and after soaking their hands in water for 30 minutes. A statistically significant improvement in sensory testing scores for individual nerve territories was noted. The importance of these findings should be considered when using sensory testing as an evaluative tool for nerve damage in leprosy.

Substrato anatômico da sensibilidade tátil na hanseníase / anatomic substratum of tactile sensibility in hanseniasis

Proposta de uma melhor avaliaçäo, com bases anatômicas e métodos clínicos de fácil execuçäo, da sensibilidade tátil na hanseníase

[Peripheral nerve lesions of experimental leprosy in monkeys. V. Histopathological finding of cutaneous nerves and cutaneous sensory organs].

The skin samples of each palm side and dorsum side of finger, nose and peripheral nerves running under the finger skin at the area between proximal phalanx and distal phalanx of mangabey monkey A022 and rhesus monkey A125 were studied by histopathological methods (semithin section and light microscopic findings). Results found about this study were as follows. 1. In spite of the existence of a large amount of leprosy bacilli at the areas of corium and subcutis, some of Meissner's corpuscles, Vater-Pacinian corpuscles (or Golgi-Mazzoni's corpuscles) and Krauze's end bulbs-like structures were observed. 2. Occasionally, several intracytoplasmic foamy structures containing a large amount of leprosy bacilli were observed at the shallow and deep layers of stratum papillare of corium, where leprosy bacilli were not so remarkable as shown on Figure 4. So, it was thought that the affinity of leprosy bacilli to free nerve endings should be exist there. 3. Some of M. arrector pili were kept in good condition in spite of the existence of multiplying leprosy bacilli around the hair follicles. 4. It was thought that the histopathological findings of the fascicles of cutaneous nerves were classified to 4 patterns. The first pattern of histopathological finding of the cutaneous nerve was shown as A on Figure 25. In this pattern observed in almost of all the fascicles locating at the subcutis, no leprosy bacillus was observed inside the fascicles, and the nerve fibers were kept in good condition. The second pattern observed in almost of all the fascicles located at the corium, was shown as B on Figure 25. In this pattern, a large amount of leprosy bacilli were observed inside the fascicles, and the nerve fibers were often kept in good condition. The third pattern observed in almost of all the fascicles located at the deep layer of corium and subcutis, was shown as C on Figure 25. In this pattern, not only multiplying leprosy bacilli but also remarkable fibrosis were found inside one fascicle, and many nerve fibers disappeared by the existence of the bacilli and fibrosis. The final pattern observed in almost of all the fascicles located at the deep layer of corium and subcutis, was shown as D on Figure 25. In this pattern, remarkable fibrosis was observed inside the fascicles, and the nerve fibers often disappeared by the existence of fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Lack of wrinkle formation in the fingertips of patients with Hansen's disease. Confirmation of previous observations.

Immersion of a hand in water at 38-40 degrees C for half an hour was performed in two phases with a one year interval in 38 patients with Hansen's disease and 20 controls. In all 20 controls wrinkles were produced. However, 32 of the 38 patients failed to show wrinkles in the fingertips. In 12, who participated in both phases, results of the second test confirmed those of the first. This may be an indication of irreversible damage. Due to the small number of individuals tested, no conclusions may be drawn in reference to groups and types of the disease. Provided that these results can be confirmed in larger groups of patients, this method could prove to be a tool in the diagnosis of Hansen's disease. Since the test is very easy to perform, it would be of great value in areas far from specialized medical centers.

Lack of wrinkle formation in the fingertips of patients with Hansen's disease. Confirmation of previous observations.

Em uma experiencia, realizada em duas etapas com intervalo de um ano, manteve-se imersa uma das maos de 38 hansenianos e de 20 individuos, que formaram o grupo controle, em agua a temperatura de 38 a 40o.C, durante meia hora. Em todos os 20 componentes do grupo controle, observou-se a formacao de rugas nas pontas dos dedos.Contudo, em 32 dos 38 portadores de hanseniase, nao ocorreu a formacao de rugas. Em 12 destes pacientes, que participaram das duas fases, os resultados do segundo teste confirmaram os do primeiro, sugerindo danos irreversiveis. Porem, nao de pode obter nenhuma conclusao com relacao a grupos e tipos da doenca devido ao pequeno numero de individuos testados. Por outro lado, devido a sua facil aplicacao, esse metodo podera tornar-se em um meio de diagnostico de hanseniase

Some aspects of the pathogenesis and pathomorphology of leprosy.

The results of bacteriological and histological examinations of the organs of mice infected in the footpad with human leprosy bacilli by the Shepard method are summarized. The periods of observation ranged from a few days to 2 years. The disease developed in mice as a chronic infection with a lengthy "incubation" period of 3-4 months or more without symptoms. Usually about 2 years after inoculation, or in some cases after a shorter interval, the disease became generalized. Different types of tissue reaction occurred: simple inflammatory infiltration, tuberculoid granuloma, and leproma-like granuloma, similar to the clinical types of leprosy in man. When the infection became general, cells resembling lepra cells formed in the internal organs and at the site of infection. These cells contained massive intracellular aggregations of mycobacteria and compact globi with lipids and a vacuolized protoplasm, similar in origin and morphology to the lepra cells in human lesions. Changes were found in the neuroreceptor apparatus of the skin of the mice, with groups of leprosy bacilli in the endoneurium, the Schwann cells, and the perineural spaces. The length of the experiments and the histological examination of material from the sacrificed mice at different stages of the infective process revealed biological parallels with human leprosy and threw light on a number of aspects of the pathogenesis of leprosy.