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Tactile threshold detection in leprosy patients with an electronic algometer
Journal of Neuroscience Methods 179 (2009) 319–322
Contents lists available at ScienceDirect
Journal of Neuroscience Methods journal homepage: www.elsevier.com/locate/jneumeth
Tactile threshold detection in leprosy patients with an electronic algometer Fernanda Guzzo Gomes a , Wilson Marques Jr. b , Norma Tiraboschi Foss c , Luísiane de Ávila Santana a , Marco Andrey Cipriani Frade a,c,∗ a Interunit of Bioengineering (School of Engineering of São Carlos – Institute of Chemistry of São Carlos – Faculty of Medicine of Ribeirão Preto), University of São Paulo (USP), SãoCarlos, SP, Brazil b Department of Neurology, Psychiatry and Medical Psychology, Faculty of Medicine of Ribeirão Preto, Brazil c Dermatology Division, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Brazil
a r t i c l e
i n f o
Article history: Received 29 September 2008 Received in revised form 28 January 2009 Accepted 30 January 2009 Keywords: Leprosy Electronic esthesiometer Semmes-Weinstein monofilaments Sensitivity alteration
a b s t r a c t 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. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Leprosy is still considered to be a public health problem in many countries, including Brazil (WHO, 2006). The etiological agent of leprosy, M. leprae, is an obligatory intracellular bacillus with a preferential habitat in macrophages and Schwann cells (Foss, 1997; Rambukkana, 2001; Rotberg and Bechelli, 1944). When invading Schwann cells, the bacillus can demyelinate them, transform them into a safe niche for its growth and multiplication, an event that defines the first and determinant stage of the occurrence of neural damage (Rambukkana, 2001; Rambukkana et al., 2002). The involvement of peripheral nerves in leprosy can range from damage to intradermal nerves in cutaneous regions to more severe injuries in neural trunks (Sajid and Malaviya, 2007). Von Frey was the first to use esthesiometry in order to measure the sensation of touch by the application of filaments consisting of horse hairs of varying caliber (Fruhstorfer et al., 2001; Malaviya,
∗ Corresponding author at: Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, CEP 14.049.900, Brazil. Tel.: +55 1636022447; fax: +55 1636330236. E-mail address: [email protected] (M.A.C. Frade). 0165-0270/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2009.01.030
2003). Even today, one of the ways of monitoring the neural damage of leprosy patients is to evaluate tactile threshold using a similar methodology with Semmes-Weinstein monofilaments. The monofilaments vary in thickness, with a different value in grams for each one, and the inability to perceive the touch of one of them represents an absence of tactile sensitivity to that given pressure (Ministério da Saúde, 2001, 2002). The monofilaments are applied to points recommended by the Health Ministry, 7 on each hand (Fig. 1A) and 10 on each foot (Fig. 1B). In 2004, 30 leprosy patients were evaluated with SemmesWeinstein monofilaments at the University Hospital of the Faculty of Medicine of Ribeirão Preto in order to characterize them in terms of degree and symmetry of neural involvement at hand and foot points. The authors concluded that, even though they represent a semiquantitative method for the evaluation of tactile threshold, monofilaments are of help for the diagnosis and monitoring of neural damage (Leite et al., unpublished data). In an attempt to improve and better quantify the sensitivity test, the von Frey hand-held electronic device is currently being used, based on the monofilament test in rats. This device consists of a monitor that records the mass applied in grams by means of a transducer to which a fine tip (0.5 mm2 ) is coupled (Möller et al., 1998; Vivancos et al., 2004). Although positive results have
320
F.G. Gomes et al. / Journal of Neuroscience Methods 179 (2009) 319–322
Fig. 1. Schematic drawing of spots for sensitivity evaluation on the hands and the feet according the Brazilian Health Ministry.
been obtained in animals using the electronic pressure algometer, no such evaluation has been carried out in humans. Based on the animal studies, the objective of the present study was to assess an electronic method to evaluate tactile threshold in humans, especially leprosy patients, using the Semmes-Weinstein monofilaments as a methodological reference. 2. Materials and methods Thirty leprosy patients, either previously treated or currently undergoing treatment at the Leprosy Outpatient Clinic of HCFMRPUSP were selected at random for inclusion in the study after informed consent (protocol n◦ 1015/2006). The patients were consecutively evaluated by the two esthesiometric methods under study, being their own controls.
served tactile sensitivity. The tip of the transducer was then placed against the region to be evaluated with gradually increasing force. The patient, in the resting condition and blindfolded, reported the moment when he “felt” the tip touching his skin. In order to minimize errors or simulations, the patient was asked to mention the site where he felt the touch and the measurement was considered only when the correct site was mentioned. The measurements were made 5 times at each site and the mean of the 3 close values was then calculated. As proposed by Vivancos et al. (2004), the investigator was trained in applying a uniform force with the transducer in order to obtain the least possible variation and to guarantee a slowly increasing application. The two tests were carried out in a double-blind manner by the two workers, each of whom was unaware of the other’s results. 2.2. Statistical analysis
2.1. Sensitivity evaluation Standard monofilament esthesiometry was applied by a nurse of the hospital according to routine methodology using the points for hand and foot tactile sensitivity evaluation recommended by the Brazilian Health Ministry according to Fig. 1. The electronic esthesiometry test was carried out by a researcher using a digital analgesimeter produced by the Insight Pesquisa e Ensino Company, Ribeirão Preto (SP) Brazil applied to the same points as the monofilaments (Fig. 2). The digital analgesimeter consists of a pressure transducer adapted with a cable to a digital counter with 0.1 g precision which records the weight (grams/force, gf) applied. In order to demonstrate the sensation elicited by the touch of the device, the patients were first tested on the trunk at points of pre-
In order to reach the objective of the study and to understand the device proposed, the Kappa coefficient was used, which measures the degree of agreement between evaluators when the variables are categorical. In order to transform the variables into categorical ones, we decided to divide the results into altered and non-altered tactile sensitivity. Values of more than 0.2 g on the hands and of 2.0 g on the feet were considered to represent altered tactile sensitivity (Brakel et al., 2005). Data were analyzed statistically using the SAS® software and the “proc freq” procedure. The intraclass correlation coefficient (ICC) was used to determine the correlation between the 3 measurements made with the electronic pressure algometer and used to calculate the mean. The ICC determines the degree of correlation between measurements within each class and is calculated from a table of analysis of variance (ANOVA) (Snedecor and Cochran, 1972). The closer to 1 the ICC value, the better the agreement between the values studied. 3. Results
Fig. 2. Digital analgesimeter® .
Strong agreement was observed between the three measurements made at a single point with the electronic device in both the groups with altered and non-altered tactile sensitivity (Table 1) by the concordance analysis (95% confidence interval). This demonstrated the reproducibility of the measurements and the reliability of the electronic test. A variety of values was obtained with the electronic pressure algometer within intervals defined by the categorical variables established with the standard monofilaments (0.05, 0.2, 2.0, 4.0, 10, and 300 g). Thus, the number of points detected by the electronic method within these intervals was calculated, as shown in Table 2. The results showed that of the 7 points evaluated on the right hand as 4.0 g, 6 (85.7%) yielded values within the 2.0–4.0 gf interval with the electronic algometer. Of the 6 points on the left
F.G. Gomes et al. / Journal of Neuroscience Methods 179 (2009) 319–322 Table 1 Concordance analysis between the 3 measurements obtained by electronic algometer for the group with altered sensitivity. Site
Point
ICC*
95% Confidence interval Upper limit
Right hand
1 2 3 4 5 6 7
0.726 0.522 0.853 0.996 0.940 0.917 0.998
0.424 0.041 0.657 0.990 0.854 0.819 0.997
1.000 1.000 1.000 1.000 1.000 1.000 1.000
Left hand
1 2 3 4 5 6 7
0.740 0.761 0.972 0.999 0.982 0.965 0.723
0.450 0.418 0.928 0.998 0.956 0.919 0.472
1.000 1.000 1.000 1.000 1.000 1.000 1.000
Right foot
1 2 3 4 5 6 7 8 9 10
0.970 0.951 0.954 0.971 0.986 0.933 0.983 0.964 0.922 0.942
0.946 0.912 0.918 0.949 0.975 0.885 0.969 0.938 0.869 0.893
0.994 0.990 0.991 0.993 0.996 0.982 0.997 0.991 0.976 0.990
Left foot
1 2 3 4 5 6 7 8 9 10
0.966 0.950 0.986 0.910 0.980 0.975 0.960 0.974 0.984 0.987
0.940 0.913 0.974 0.846 0.967 0.957 0.928 0.954 0.973 0.976
0.992 0.986 0.997 0.974 0.994 0.993 0.991 0.993 0.995 0.998
*
Table 3 Kappa coefficient for the measurements made at specific points using the standard method and the electronic method, with the 95% confidence interval. Site
Lower limit
321
Point
Kappa coefficient
95% Confidence interval Lower limit
Upper limit
Right hand
1 2 3 4 5 6 7
0.44 0.53 0.38 0.29 0.39 0.66 0.30
0.06 0.20 −0.03 −0.06 0.02 0.35 −0.04
0.82 0.85 0.78 0.63 0.75 0.97 0.63
Left hand
1 2 3 4 5 6 7
0.40 0.52 0.45 0.53 0.26 0.25 0.15
0.05 0.11 0.10 0.22 −0.13 −0.14 −0.21
0.75 0.93 0.81 0.85 0.64 0.65 0.52
Right foot
1 2 3 4 5 6 7 8 9 10
0.49 0.74 0.61 0.48 0.50 0.55 0.42 0.36 0.38 0.45
0.20 0.51 0.36 0.19 0.24 0.29 0.13 0.05 0.07 0.15
0.77 0.97 0.87 0.76 0.76 0.81 0.70 0.66 0.70 0.75
Left foot
1 2 3 4 5 6 7 8 9 10
0.30 0.36 0.42 0.38 0.22 0.13 0.30 0.24 0.23 0.53
0.01 0.05 0.11 0.10 −0.03 −0.20 0.00 −0.01 −0.03 0.25
0.60 0.66 0.72 0.65 0.46 0.47 0.60 0.48 0.49 0.82
Intraclass correlation coefficient.
hand tested as 300 g with the monofilaments, 3 (50%) were detected with values within the 10–300 gf range with the electronic pressure algometer. On the feet, of the 33 points on the right foot and of the 35 points on the left foot characterized as 300 g with the standard method, 21 (63.6%) and 18 (51.4%) were detected with values within the 10–300 gf range, respectively. It should be pointed out that the interval values obtained by the electronic method are not measured by the standard monofilament test. Table 3 presents the values of the Kappa coefficients, which show that agreement among the cases was mild in 47.06% of cases, moderate in 38.23%, and substantial in 8.82%. Based on the cases evaluated as “altered and non-altered tactile sensitivity” by the Kappa coefficient, the percentage of agreement Table 2 Measurements obtained by standard esthesiometry and the values given by electronic esthesiometry to the corresponding categorical intervals. Method of evaluation
Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry
Measurements
0.05–0.2 g 0.2 g 0.2–2.0 g 2.0 g 2.0–4.0 g 4.0 g 4.0–10.0 g 10.0 g 10.0–300 g 300 g
Number of points R hand
L hand
R foot
L foot
0 30 2 41 6 7 1 2 0 4
0 26 4 44 0 9 – – 3 6
1 47 6 88 1 21 5 39 21 33
0 30 8 108 2 18 2 39 18 35
between cases was calculated. For the 7 points on the right hand there was an agreement between the two methods, resulting in a mean agreement (sum of the percentage of concordant values for each point divided by the number of points) of 77.14% of cases. Among the discordant cases, at 3 of 7 points there was equivalent disagreement, i.e., the number of cases in which the electronic algometer recorded altered tactile sensitivity and the monofilaments recorded non-altered tactile sensitivity was equal to the number of cases in which the opposite result was recorded (nonaltered electronic and altered monofilament). Only at point 7 we observed a larger number (70%) of recordings of altered tactile threshold with the electronic method than with the monofilaments, with most of the latter recording non-altered tactile threshold. For the left hand, mean agreement between the cases was 75.71%. Interestingly, the discordant cases behaved in the same manner as those of the right hand also regarding point 7, with 54.5% of them being recorded as having altered tactile threshold with the electronic algometer and non-altered tactile threshold with the monofilaments. Regarding foot evaluation, the following values were obtained: at the 10 points on the right foot the mean agreement in the evaluation of altered and non-altered tactile sensitivity was 74.33%. Among the discordant cases there was predominance (90.91% on average) of detection of altered tactile sensitivity with the electronic pressure algometer which was not detected by the monofilaments. At the 10 points on the left foot, the average agreement of evaluation was 63.66%. Among the discordant cases there was predominance (84.25% on average) of detection of altered tactile sensitivity with the electronic algometer which was
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not detected by the monofilaments. In the end, for the same cases the monofilaments recorded non-altered, i.e., normal sensitivity. 4. Discussion and conclusion The use of nylon monofilaments for evaluation of tactile sensitivity in leprosy patients is a validated method. However the method is subjective since the influence of filament thickness on the force applied by the observer or the perception of the subject is not considered. Earlier, Möller et al. (1998) demonstrated that the electronic algometer is a useful instrument for the evaluation of sensitivity in rats since a tip of a standard diameter can be used for all evaluations, thus eliminating the interference of filament thickness in this type of measurement. The same authors stated that the calculation of the mean of the measured values reduced the possibility of error of the device, a procedure adopted in the present study. In the present study, the three measurements made with the electronic algometer at a given point for each leprosy patient (cases) were reproducible, as demonstrated by the ICC. This suggests the reliability of both the proposed device and of the researcher’s technique. Based on the values obtained with the electronic pressure algometer within the intervals not measured by the monofilaments, it was observed that, the greater the interval, as in the case of 10–300 g, the greater the probability that the real esthesiometric value was between these extremes. This impairs the follow-up of the patient, who is evaluated as having higher sensitivity than the recorded one (overestimated), with a consequent difficulty in the detection of prognostic improvement and in the encouragement of patient compliance with treatment and with preventive measures. Although this was less common in the present study, if the sensitivity value is underestimated this would also be harmful because the degree of nerve damage would also be underestimated. The Kappa coefficient was used to determine the agreement between digital esthesiometry and the Semmes-Weinstein monofilaments, revealing agreement in 94.1% of cases. This means that in most cases, when a method yielded values that represented altered or non-altered sensitivity, the other method also did so, even though the absolute values were different. This demonstrates the reliability of the proposed method, since it agrees with the standard method used to evaluate sensitivity i.e., the monofilaments. Similar results were obtained for the right and left hand both in terms of concordant and discordant cases. The detection of tactile threshold by the two methods was similar for the hands. An exception was at point 7 at which most of the discordant cases were evaluated by the algometer as having altered tactile sensitivity while the monofilaments recorded non-altered tactile sensitivity. Probably, this fact is related to different characteristics of dorsal structure of hand with thinner skin and subcutaneous where others receptors can have been stimulated beyond tactile receptors by electronic device. Although there was a general agreement between the 2 methods in detecting tactile sensitivity in the feet, the discordant cases are of interest. In more than 80.0% of the discordant cases the electronic algometer was able to “perceive” altered tactile sensitivity, whereas for the same cases the monofilaments recorded non-altered/normal, tactile sensitivity at these sites. The results obtained are indicative of the difficulty in recording alterations of tactile sensitivity on the feet by the monofilament method used in leprosy services for disability prevention. The observations are suggestive of the need for caution especially since the feet are known to be important sites of complications during the course of leprosy. We cannot state which method correctly recorded the alteration or
not of sensitivity, but the coinciding and similar fact occurring in both methods shows coherence of the values obtained. Although the methods agreed regarding altered or non-altered tactile sensitivity, the electronic method recorded absolute values differing from those obtained with the monofilaments in cases of altered tactile sensitivity. These differences between methods may be attributed to the characteristics of each, such as (a) maintenance of the same thickness in the electronic evaluation as opposed to varying thickness in the monofilament evaluation, (b) the possibility of controlling the force applied by the hand of the examiner through the digital monitor of the electronic esthesiometer, which cannot be done with the monofilaments, and (c) numerical values obtained with the electronic method which allows quantification of the altered sensitivity while the monofilaments use categorical variables. In conclusion, the electronic esthesiometer proved to be a quantitative method of easy clinical application that can evaluate the alterations of tactile sensitivity in leprosy patients, providing objective results both for the diagnosis and follow-up of these patients. In addition, the method can minimize the variables interference and/or quantify them, permitting a smaller error on its application, in contrast to the use of Semmes-Weinstein monofilaments. Acknowledgments Financial research supported by CAPES; FAEPA-HCFMRP-USP; CNPq/DECIT (Process number: 401061/2005-1), BRAZIL. We are indebted to Anand Iyer from Academic Medical Center—University of Amsterdam for English editing. References Brakel WHV, Nicholls PG, Das L, et al. The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India. Leprosy Review 2005;76:14–34. Foss, NT. Aspectos imunológicos da hanseníase. Medicina, Ribeirão Preto, v.30, Ribeirão Preto, 1997, p. 335–339. Fruhstorfer H, Gross W, Selbmann O. Von Frey hairs: new materials for a new design. European Journal of Pain, Marburg 2001;5:341–2. Leite, SN; Frade MAC; Barros, ARSB. et al. Avaliac¸ão estesiométrica de mãos e pés de pacientes hansenianos em servic¸o de fisioterapia de hospital terciário. Revista Brasileira de Fisioterapia. Paper accepted for publication on 07/27/2008. Malaviya GN. Review sensory perception in leprosy-neurophysiological correlates. International Journal of Leprosy and Other Mycobacterial Diseases, Washington 2003;71(2):119–24, India. Ministério da Saúde. 2002. Guia para o controle da hanseníase. Cadernos de Atenc¸ão Básica. Ministério da Saúde. 2001, Hanseníase–Atividades de Controle e Manual de Procedimentos. Brasília: Fundac¸ão Nacional de Saúde, p.15–28. Möller KA, Johanson B, Berge OG. Assessing mechanical allodynia in the rat paw with a new electronic algometer. Journal of Neuroscience Methods, Sweden 1998;84:41–7. Rambukkana A. Molecular basis for the peripheral nerve predilection of Mycobacterium leprae. Current Opinion in Microbiology New York 2001;4:21–7. Rambukkana A, Zanazzi G, Tapinos N, Salzer JL. Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells. Science New York 2002;296(5569):927–31. Rotberg and Bechelli, Rotberg, A.; Bechelli, LM. Micobacterium leprae. In: TRATADO de leprologia - etiopatogenia e anatomia patológica. Ministério da Educac¸ão e Saúde; Servic¸o Nacional da Lepra; Ministério da Educac¸ão. Rio de Janeiro, 1944, v.2, cap.1, p.3-26. Sajid H, Malaviya GN. Early nerve damage in leprosy: an electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits. Neurology India, India 2007;55(1):22–6. Snedecor GW, Cochran WG. Statistical methods. 6th ed. Lowa: The Lowa State University Press; 1972. Vivancos GG, Verri Jr WA, Cunha TM, et al. An electronic pressure-meter nociception paw test for rats. Brazilian Journal of Medical and Biological Research 2004;37:391–9. WOLRD HEALTH ORGANIZATION - Estratégia Global para Aliviar a Carga da Hanseníase e Manter as Atividades de Controle da Hanseníase, p. 1-27. who.int/lep/Reports/GlobalStrategy-PDF. 2006.
Contents lists available at ScienceDirect
Journal of Neuroscience Methods journal homepage: www.elsevier.com/locate/jneumeth
Tactile threshold detection in leprosy patients with an electronic algometer Fernanda Guzzo Gomes a , Wilson Marques Jr. b , Norma Tiraboschi Foss c , Luísiane de Ávila Santana a , Marco Andrey Cipriani Frade a,c,∗ a Interunit of Bioengineering (School of Engineering of São Carlos – Institute of Chemistry of São Carlos – Faculty of Medicine of Ribeirão Preto), University of São Paulo (USP), SãoCarlos, SP, Brazil b Department of Neurology, Psychiatry and Medical Psychology, Faculty of Medicine of Ribeirão Preto, Brazil c Dermatology Division, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Brazil
a r t i c l e
i n f o
Article history: Received 29 September 2008 Received in revised form 28 January 2009 Accepted 30 January 2009 Keywords: Leprosy Electronic esthesiometer Semmes-Weinstein monofilaments Sensitivity alteration
a b s t r a c t 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. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Leprosy is still considered to be a public health problem in many countries, including Brazil (WHO, 2006). The etiological agent of leprosy, M. leprae, is an obligatory intracellular bacillus with a preferential habitat in macrophages and Schwann cells (Foss, 1997; Rambukkana, 2001; Rotberg and Bechelli, 1944). When invading Schwann cells, the bacillus can demyelinate them, transform them into a safe niche for its growth and multiplication, an event that defines the first and determinant stage of the occurrence of neural damage (Rambukkana, 2001; Rambukkana et al., 2002). The involvement of peripheral nerves in leprosy can range from damage to intradermal nerves in cutaneous regions to more severe injuries in neural trunks (Sajid and Malaviya, 2007). Von Frey was the first to use esthesiometry in order to measure the sensation of touch by the application of filaments consisting of horse hairs of varying caliber (Fruhstorfer et al., 2001; Malaviya,
∗ Corresponding author at: Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, CEP 14.049.900, Brazil. Tel.: +55 1636022447; fax: +55 1636330236. E-mail address: [email protected] (M.A.C. Frade). 0165-0270/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2009.01.030
2003). Even today, one of the ways of monitoring the neural damage of leprosy patients is to evaluate tactile threshold using a similar methodology with Semmes-Weinstein monofilaments. The monofilaments vary in thickness, with a different value in grams for each one, and the inability to perceive the touch of one of them represents an absence of tactile sensitivity to that given pressure (Ministério da Saúde, 2001, 2002). The monofilaments are applied to points recommended by the Health Ministry, 7 on each hand (Fig. 1A) and 10 on each foot (Fig. 1B). In 2004, 30 leprosy patients were evaluated with SemmesWeinstein monofilaments at the University Hospital of the Faculty of Medicine of Ribeirão Preto in order to characterize them in terms of degree and symmetry of neural involvement at hand and foot points. The authors concluded that, even though they represent a semiquantitative method for the evaluation of tactile threshold, monofilaments are of help for the diagnosis and monitoring of neural damage (Leite et al., unpublished data). In an attempt to improve and better quantify the sensitivity test, the von Frey hand-held electronic device is currently being used, based on the monofilament test in rats. This device consists of a monitor that records the mass applied in grams by means of a transducer to which a fine tip (0.5 mm2 ) is coupled (Möller et al., 1998; Vivancos et al., 2004). Although positive results have
320
F.G. Gomes et al. / Journal of Neuroscience Methods 179 (2009) 319–322
Fig. 1. Schematic drawing of spots for sensitivity evaluation on the hands and the feet according the Brazilian Health Ministry.
been obtained in animals using the electronic pressure algometer, no such evaluation has been carried out in humans. Based on the animal studies, the objective of the present study was to assess an electronic method to evaluate tactile threshold in humans, especially leprosy patients, using the Semmes-Weinstein monofilaments as a methodological reference. 2. Materials and methods Thirty leprosy patients, either previously treated or currently undergoing treatment at the Leprosy Outpatient Clinic of HCFMRPUSP were selected at random for inclusion in the study after informed consent (protocol n◦ 1015/2006). The patients were consecutively evaluated by the two esthesiometric methods under study, being their own controls.
served tactile sensitivity. The tip of the transducer was then placed against the region to be evaluated with gradually increasing force. The patient, in the resting condition and blindfolded, reported the moment when he “felt” the tip touching his skin. In order to minimize errors or simulations, the patient was asked to mention the site where he felt the touch and the measurement was considered only when the correct site was mentioned. The measurements were made 5 times at each site and the mean of the 3 close values was then calculated. As proposed by Vivancos et al. (2004), the investigator was trained in applying a uniform force with the transducer in order to obtain the least possible variation and to guarantee a slowly increasing application. The two tests were carried out in a double-blind manner by the two workers, each of whom was unaware of the other’s results. 2.2. Statistical analysis
2.1. Sensitivity evaluation Standard monofilament esthesiometry was applied by a nurse of the hospital according to routine methodology using the points for hand and foot tactile sensitivity evaluation recommended by the Brazilian Health Ministry according to Fig. 1. The electronic esthesiometry test was carried out by a researcher using a digital analgesimeter produced by the Insight Pesquisa e Ensino Company, Ribeirão Preto (SP) Brazil applied to the same points as the monofilaments (Fig. 2). The digital analgesimeter consists of a pressure transducer adapted with a cable to a digital counter with 0.1 g precision which records the weight (grams/force, gf) applied. In order to demonstrate the sensation elicited by the touch of the device, the patients were first tested on the trunk at points of pre-
In order to reach the objective of the study and to understand the device proposed, the Kappa coefficient was used, which measures the degree of agreement between evaluators when the variables are categorical. In order to transform the variables into categorical ones, we decided to divide the results into altered and non-altered tactile sensitivity. Values of more than 0.2 g on the hands and of 2.0 g on the feet were considered to represent altered tactile sensitivity (Brakel et al., 2005). Data were analyzed statistically using the SAS® software and the “proc freq” procedure. The intraclass correlation coefficient (ICC) was used to determine the correlation between the 3 measurements made with the electronic pressure algometer and used to calculate the mean. The ICC determines the degree of correlation between measurements within each class and is calculated from a table of analysis of variance (ANOVA) (Snedecor and Cochran, 1972). The closer to 1 the ICC value, the better the agreement between the values studied. 3. Results
Fig. 2. Digital analgesimeter® .
Strong agreement was observed between the three measurements made at a single point with the electronic device in both the groups with altered and non-altered tactile sensitivity (Table 1) by the concordance analysis (95% confidence interval). This demonstrated the reproducibility of the measurements and the reliability of the electronic test. A variety of values was obtained with the electronic pressure algometer within intervals defined by the categorical variables established with the standard monofilaments (0.05, 0.2, 2.0, 4.0, 10, and 300 g). Thus, the number of points detected by the electronic method within these intervals was calculated, as shown in Table 2. The results showed that of the 7 points evaluated on the right hand as 4.0 g, 6 (85.7%) yielded values within the 2.0–4.0 gf interval with the electronic algometer. Of the 6 points on the left
F.G. Gomes et al. / Journal of Neuroscience Methods 179 (2009) 319–322 Table 1 Concordance analysis between the 3 measurements obtained by electronic algometer for the group with altered sensitivity. Site
Point
ICC*
95% Confidence interval Upper limit
Right hand
1 2 3 4 5 6 7
0.726 0.522 0.853 0.996 0.940 0.917 0.998
0.424 0.041 0.657 0.990 0.854 0.819 0.997
1.000 1.000 1.000 1.000 1.000 1.000 1.000
Left hand
1 2 3 4 5 6 7
0.740 0.761 0.972 0.999 0.982 0.965 0.723
0.450 0.418 0.928 0.998 0.956 0.919 0.472
1.000 1.000 1.000 1.000 1.000 1.000 1.000
Right foot
1 2 3 4 5 6 7 8 9 10
0.970 0.951 0.954 0.971 0.986 0.933 0.983 0.964 0.922 0.942
0.946 0.912 0.918 0.949 0.975 0.885 0.969 0.938 0.869 0.893
0.994 0.990 0.991 0.993 0.996 0.982 0.997 0.991 0.976 0.990
Left foot
1 2 3 4 5 6 7 8 9 10
0.966 0.950 0.986 0.910 0.980 0.975 0.960 0.974 0.984 0.987
0.940 0.913 0.974 0.846 0.967 0.957 0.928 0.954 0.973 0.976
0.992 0.986 0.997 0.974 0.994 0.993 0.991 0.993 0.995 0.998
*
Table 3 Kappa coefficient for the measurements made at specific points using the standard method and the electronic method, with the 95% confidence interval. Site
Lower limit
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Point
Kappa coefficient
95% Confidence interval Lower limit
Upper limit
Right hand
1 2 3 4 5 6 7
0.44 0.53 0.38 0.29 0.39 0.66 0.30
0.06 0.20 −0.03 −0.06 0.02 0.35 −0.04
0.82 0.85 0.78 0.63 0.75 0.97 0.63
Left hand
1 2 3 4 5 6 7
0.40 0.52 0.45 0.53 0.26 0.25 0.15
0.05 0.11 0.10 0.22 −0.13 −0.14 −0.21
0.75 0.93 0.81 0.85 0.64 0.65 0.52
Right foot
1 2 3 4 5 6 7 8 9 10
0.49 0.74 0.61 0.48 0.50 0.55 0.42 0.36 0.38 0.45
0.20 0.51 0.36 0.19 0.24 0.29 0.13 0.05 0.07 0.15
0.77 0.97 0.87 0.76 0.76 0.81 0.70 0.66 0.70 0.75
Left foot
1 2 3 4 5 6 7 8 9 10
0.30 0.36 0.42 0.38 0.22 0.13 0.30 0.24 0.23 0.53
0.01 0.05 0.11 0.10 −0.03 −0.20 0.00 −0.01 −0.03 0.25
0.60 0.66 0.72 0.65 0.46 0.47 0.60 0.48 0.49 0.82
Intraclass correlation coefficient.
hand tested as 300 g with the monofilaments, 3 (50%) were detected with values within the 10–300 gf range with the electronic pressure algometer. On the feet, of the 33 points on the right foot and of the 35 points on the left foot characterized as 300 g with the standard method, 21 (63.6%) and 18 (51.4%) were detected with values within the 10–300 gf range, respectively. It should be pointed out that the interval values obtained by the electronic method are not measured by the standard monofilament test. Table 3 presents the values of the Kappa coefficients, which show that agreement among the cases was mild in 47.06% of cases, moderate in 38.23%, and substantial in 8.82%. Based on the cases evaluated as “altered and non-altered tactile sensitivity” by the Kappa coefficient, the percentage of agreement Table 2 Measurements obtained by standard esthesiometry and the values given by electronic esthesiometry to the corresponding categorical intervals. Method of evaluation
Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry Electronic esthesiometry Standard esthesiometry
Measurements
0.05–0.2 g 0.2 g 0.2–2.0 g 2.0 g 2.0–4.0 g 4.0 g 4.0–10.0 g 10.0 g 10.0–300 g 300 g
Number of points R hand
L hand
R foot
L foot
0 30 2 41 6 7 1 2 0 4
0 26 4 44 0 9 – – 3 6
1 47 6 88 1 21 5 39 21 33
0 30 8 108 2 18 2 39 18 35
between cases was calculated. For the 7 points on the right hand there was an agreement between the two methods, resulting in a mean agreement (sum of the percentage of concordant values for each point divided by the number of points) of 77.14% of cases. Among the discordant cases, at 3 of 7 points there was equivalent disagreement, i.e., the number of cases in which the electronic algometer recorded altered tactile sensitivity and the monofilaments recorded non-altered tactile sensitivity was equal to the number of cases in which the opposite result was recorded (nonaltered electronic and altered monofilament). Only at point 7 we observed a larger number (70%) of recordings of altered tactile threshold with the electronic method than with the monofilaments, with most of the latter recording non-altered tactile threshold. For the left hand, mean agreement between the cases was 75.71%. Interestingly, the discordant cases behaved in the same manner as those of the right hand also regarding point 7, with 54.5% of them being recorded as having altered tactile threshold with the electronic algometer and non-altered tactile threshold with the monofilaments. Regarding foot evaluation, the following values were obtained: at the 10 points on the right foot the mean agreement in the evaluation of altered and non-altered tactile sensitivity was 74.33%. Among the discordant cases there was predominance (90.91% on average) of detection of altered tactile sensitivity with the electronic pressure algometer which was not detected by the monofilaments. At the 10 points on the left foot, the average agreement of evaluation was 63.66%. Among the discordant cases there was predominance (84.25% on average) of detection of altered tactile sensitivity with the electronic algometer which was
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not detected by the monofilaments. In the end, for the same cases the monofilaments recorded non-altered, i.e., normal sensitivity. 4. Discussion and conclusion The use of nylon monofilaments for evaluation of tactile sensitivity in leprosy patients is a validated method. However the method is subjective since the influence of filament thickness on the force applied by the observer or the perception of the subject is not considered. Earlier, Möller et al. (1998) demonstrated that the electronic algometer is a useful instrument for the evaluation of sensitivity in rats since a tip of a standard diameter can be used for all evaluations, thus eliminating the interference of filament thickness in this type of measurement. The same authors stated that the calculation of the mean of the measured values reduced the possibility of error of the device, a procedure adopted in the present study. In the present study, the three measurements made with the electronic algometer at a given point for each leprosy patient (cases) were reproducible, as demonstrated by the ICC. This suggests the reliability of both the proposed device and of the researcher’s technique. Based on the values obtained with the electronic pressure algometer within the intervals not measured by the monofilaments, it was observed that, the greater the interval, as in the case of 10–300 g, the greater the probability that the real esthesiometric value was between these extremes. This impairs the follow-up of the patient, who is evaluated as having higher sensitivity than the recorded one (overestimated), with a consequent difficulty in the detection of prognostic improvement and in the encouragement of patient compliance with treatment and with preventive measures. Although this was less common in the present study, if the sensitivity value is underestimated this would also be harmful because the degree of nerve damage would also be underestimated. The Kappa coefficient was used to determine the agreement between digital esthesiometry and the Semmes-Weinstein monofilaments, revealing agreement in 94.1% of cases. This means that in most cases, when a method yielded values that represented altered or non-altered sensitivity, the other method also did so, even though the absolute values were different. This demonstrates the reliability of the proposed method, since it agrees with the standard method used to evaluate sensitivity i.e., the monofilaments. Similar results were obtained for the right and left hand both in terms of concordant and discordant cases. The detection of tactile threshold by the two methods was similar for the hands. An exception was at point 7 at which most of the discordant cases were evaluated by the algometer as having altered tactile sensitivity while the monofilaments recorded non-altered tactile sensitivity. Probably, this fact is related to different characteristics of dorsal structure of hand with thinner skin and subcutaneous where others receptors can have been stimulated beyond tactile receptors by electronic device. Although there was a general agreement between the 2 methods in detecting tactile sensitivity in the feet, the discordant cases are of interest. In more than 80.0% of the discordant cases the electronic algometer was able to “perceive” altered tactile sensitivity, whereas for the same cases the monofilaments recorded non-altered/normal, tactile sensitivity at these sites. The results obtained are indicative of the difficulty in recording alterations of tactile sensitivity on the feet by the monofilament method used in leprosy services for disability prevention. The observations are suggestive of the need for caution especially since the feet are known to be important sites of complications during the course of leprosy. We cannot state which method correctly recorded the alteration or
not of sensitivity, but the coinciding and similar fact occurring in both methods shows coherence of the values obtained. Although the methods agreed regarding altered or non-altered tactile sensitivity, the electronic method recorded absolute values differing from those obtained with the monofilaments in cases of altered tactile sensitivity. These differences between methods may be attributed to the characteristics of each, such as (a) maintenance of the same thickness in the electronic evaluation as opposed to varying thickness in the monofilament evaluation, (b) the possibility of controlling the force applied by the hand of the examiner through the digital monitor of the electronic esthesiometer, which cannot be done with the monofilaments, and (c) numerical values obtained with the electronic method which allows quantification of the altered sensitivity while the monofilaments use categorical variables. In conclusion, the electronic esthesiometer proved to be a quantitative method of easy clinical application that can evaluate the alterations of tactile sensitivity in leprosy patients, providing objective results both for the diagnosis and follow-up of these patients. In addition, the method can minimize the variables interference and/or quantify them, permitting a smaller error on its application, in contrast to the use of Semmes-Weinstein monofilaments. Acknowledgments Financial research supported by CAPES; FAEPA-HCFMRP-USP; CNPq/DECIT (Process number: 401061/2005-1), BRAZIL. We are indebted to Anand Iyer from Academic Medical Center—University of Amsterdam for English editing. References Brakel WHV, Nicholls PG, Das L, et al. The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India. Leprosy Review 2005;76:14–34. Foss, NT. Aspectos imunológicos da hanseníase. Medicina, Ribeirão Preto, v.30, Ribeirão Preto, 1997, p. 335–339. Fruhstorfer H, Gross W, Selbmann O. Von Frey hairs: new materials for a new design. European Journal of Pain, Marburg 2001;5:341–2. Leite, SN; Frade MAC; Barros, ARSB. et al. Avaliac¸ão estesiométrica de mãos e pés de pacientes hansenianos em servic¸o de fisioterapia de hospital terciário. Revista Brasileira de Fisioterapia. Paper accepted for publication on 07/27/2008. Malaviya GN. Review sensory perception in leprosy-neurophysiological correlates. International Journal of Leprosy and Other Mycobacterial Diseases, Washington 2003;71(2):119–24, India. Ministério da Saúde. 2002. Guia para o controle da hanseníase. Cadernos de Atenc¸ão Básica. Ministério da Saúde. 2001, Hanseníase–Atividades de Controle e Manual de Procedimentos. Brasília: Fundac¸ão Nacional de Saúde, p.15–28. Möller KA, Johanson B, Berge OG. Assessing mechanical allodynia in the rat paw with a new electronic algometer. Journal of Neuroscience Methods, Sweden 1998;84:41–7. Rambukkana A. Molecular basis for the peripheral nerve predilection of Mycobacterium leprae. Current Opinion in Microbiology New York 2001;4:21–7. Rambukkana A, Zanazzi G, Tapinos N, Salzer JL. Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells. Science New York 2002;296(5569):927–31. Rotberg and Bechelli, Rotberg, A.; Bechelli, LM. Micobacterium leprae. In: TRATADO de leprologia - etiopatogenia e anatomia patológica. Ministério da Educac¸ão e Saúde; Servic¸o Nacional da Lepra; Ministério da Educac¸ão. Rio de Janeiro, 1944, v.2, cap.1, p.3-26. Sajid H, Malaviya GN. Early nerve damage in leprosy: an electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits. Neurology India, India 2007;55(1):22–6. Snedecor GW, Cochran WG. Statistical methods. 6th ed. Lowa: The Lowa State University Press; 1972. Vivancos GG, Verri Jr WA, Cunha TM, et al. An electronic pressure-meter nociception paw test for rats. Brazilian Journal of Medical and Biological Research 2004;37:391–9. WOLRD HEALTH ORGANIZATION - Estratégia Global para Aliviar a Carga da Hanseníase e Manter as Atividades de Controle da Hanseníase, p. 1-27. who.int/lep/Reports/GlobalStrategy-PDF. 2006.