Mycobacterium leprae causes leprosy and can impair peripheral nerves. If nerve function is damaged and is not treated immediately and effectively, it can cause disability. Hence, early detection of peripheral neuropathy is critical. Toronto Clinical Scoring System (TCSS) is a simple neuropathy assessment instrument for diabetic neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus neuropathy. Therefore, TCSS is expected to be an alternative tool for diagnosing leprosy neuropathy. This study aims to determine the diagnostic value of TCSS in leprosy neuropathy. This is a cross-sectional observational study with 40 participants. The TCSS and Semmes–Weinstein Monofilament tests were used to assess neuropathy. The diagnostic analysis showed that the sensitivity was 85.7%, specificity was 84.2%, positive predictive value was 85.7%, negative predictive value was 84.2%, positive likelihood ratio (LR+) was 5.42, negative (LR-) was 0.17, accuracy was by 85%, and area under curve value of 93.2%. The optimal cut-off point score of TCSS is ≥6. It can be concluded that TCSS is an alternative diagnostic tool with a high accuracy value and can be used as a routine examination for the early detection of leprosy neuropathy.
Keywords: Diagnostic tool, leprosy, neuropathy, Semmes-Weinstein monofilament test, Toronto clinical scoring system
| Introduction|| |
Peripheral neuropathy is a disorder that occurs in the structure of the peripheral nerves. Leprosy, which causes autonomic, sensory, and motor neuropathy, is among the most common causes of peripheral neuropathy., The posterior tibial nerve is the most commonly afflicted peripheral nerve in leprosy, followed by the ulnar, median, lateral popliteal, and facial nerves. Common nerve involvement in leprosy was in colder and superficial predilection, where there was also prone to trauma. Early diagnosis of leprosy neuropathy can reduce the number of leprosy defects.
Clinical examination can be challenging in detecting early nerve damage. Nerve damage in leprosy can be seen with further examination, such as electroneuromyography (ENMG) and Semmes-Weinstein Monofilament (SWM) tests. ENMG is the gold standard diagnosis for neuropathy, but because of the significant cost and time required to train employees, ENMG is not available in all health facilities. The SWM test has been widely used to assess neuropathy in leprosy. Nevertheless, it is not available in all health facilities and requires a certain level of expertise to use it, a quiet examination place, and a lot of time. Thus, a new diagnostic tool is needed that is accurate and simple in diagnosing leprosy neuropathy.,
The TCSS, also known as Toronto Clinical Neuropathy Score (TCNS), is a simple neuropathy scoring system based on neurological history and physical examination approaches. It is intended to be simple and useful for clinicians. This evaluation includes symptom, reflex, and sensory scores.,,,, Modified TCNS (mTCNS) is a modification of TCSS and it has been used in diabetic neuropathy but none in leprosy neuropathy. The study by Basuki found the sensitivity, specificity, accuracy, and area under curve (AUC) values of mTCNS were 63%, 75%, 66%, and 81.9%, whereas TCSS were 72%, 80%, 74%, and 84.5% at the cut-off point 8 in diabetic neuropathy.
Several diagnostic test studies indicate that TCCS has proven superior in diagnosing and assessing the severity of diabetic neuropathy, Chemotherapy-induced peripheral neuropathy (CIPN), and HIV neuropathy.,,, Toronto Clinical Scoring System is expected to be an alternative leprosy neuropathy diagnostic tool that is accurate, simple, and less expensive to be used in all health facilities.,,,,
| Methods|| |
An observational study with a cross-sectional design was conducted. Forty participants were diagnosed with leprosy at Universitas Sumatera Utara Hospital, Dr. Pirngadi Hospital, and H. Adam Malik Hospital, between January and July 2021, who were ≤18 years old and signed informed consent, were included in this study. Patients with stroke, limb amputation, diabetes, hypothyroidism, alcoholism, HIV, and chemotherapy were excluded. According to the WHO, leprosy is diagnosed clinically when a person exhibits one or more of three cardinal signs: (i) loss of certain sensation in pale (hypopigmented) or reddish skin; (ii) thickening of the peripheral nerve; or (iii) the presence of acid-fast bacilli in skin scraping. This study has been reviewed by the ethics committee in the Faculty of Medicine at Universitas Sumatera Utara/H. Adam Malik General Hospital (approval number 366/KEP/USU/2021).
Leprosy neuropathy was examined in the study participants using the SWM test and TCSS score. SWM was applied to the hands (7 areas) and the feet (8 areas) until they were bent in the form of a “C” curve for 1.5 s, then slowly released and repeated three times on the same area. The examination starts with the thinnest monofilament (green). If the patient cannot feel the monofilament, thicker monofilaments proceed. The test is declared correct if the patient can point to the stimulated area within a range of 2 cm at least two times. The neuropathy diagnosis can be made when the monofilament threshold increases by three or more levels at one site. The monofilament threshold increases by two levels at one site and one level at the other site or when the monofilament threshold increases by one level at three sites.
The TCSS symptom score was assessed by asking for pain, numbness, tingling, weakness in the legs, ataxia, and symptoms in the upper limbs. In addition, a reflex score examination was performed using the neurological reflex hammer on the patella and Achilles tendon, a sensory pinprick score was served with a toothpick on the big toe, and the temperature was measured with a test tube containing warm and cold water on the big toe, touch was measured with cotton on the big toe, the vibration was measured with a tuning fork 128 Hz on the medial malleolus, and position was determined by moving the index toe. No neuropathy is indicated by a score of ≤5. A score of >5 was interpreted as neuropathy; a score of 6-8 indicates mild neuropathy, moderate neuropathy is indicated by a score of 9–11, and 12–19 shows severe neuropathy [Appendix].
Data from the study were statistically analyzed with statistical analyzing software to assess sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, LR-, accuracy, and AUC value of the TCSS compared to the SWM test. The characteristic data, if normally distributed, the mean and standard deviation (SD) were calculated using the Student's t-test. Finally, the categorical data were examined using Fisher's exact test.
| Results|| |
Participant characteristics data are presented in [Table 1]. Using the SWM test for the established Leprosy Neuropathy diagnosis, this study group was divided into Leprosy-Neuropathy and Leprosy-No Neuropathy; 21 participants (52.5%) were thus allocated to the Leprosy-Neuropathy and 19 participants (47.5%) to the Leprosy-No Neuropathy group. The majority of the participants were male, 31 participants (77.5%), middle-aged (mean ± SD age, 36.12 ± 14.21), and had the MB type of leprosy, 37 participants (92.5%). In terms of sex, age, and kind of leprosy, there was no significant difference between the Leprosy-Neuropathy and Leprosy-No Neuropathy groups. In this study, from 40 participants examined with TCSS, 21 participants with leprosy neuropathy were then assessed for the severity of the neuropathy. The majority of the neuropathy was mild, with 11 participants (52.4%).
|Table 1: Characteristics of the patient in leprosy-neuropathy and leprosy-no neuropathy|
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Cross-tabulation of the TCSS score is shown in [Table 2]. Based on the table, TCSS sensitivity value is 85.7%, specificity is 84.2%, PPV is 85.7%, NPV is 84.2%, LR + is 5, 42, LR- is 0.17, and the accuracy is 85%. The diagnostic value of TCSS using the receiver operating curve (ROC) is shown in [Figure 1]. The AUC value of TCSS was 93.2% (95% confidence interval [CI] 86%–100%), with P < 0.001. The optimal cut-off point, a score ≥6, is determined using the value acquired from the ROC curve [Figure 2].
|Figure 1: ROC Analysis Result for TCSS Score. ROC: Receiver operating curve, TCSS: Toronto clinical scoring system.|
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|Figure 2: Optimal Cut-off Point Sensitivity and Specificity of TCSS Score. TCSS: Toronto clinical scoring system.|
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| Discussion|| |
This study found that most neuropathy that occurred in the study participants was mildly based on the TCSS examination. Novriansyah et al. found that the prevalence of CIPN was mild, 22 participants (64.7%). Purbasari et al. reported that most study participants had mild and moderate degrees of HIV neuropathy, with 17 people (21%) each. No other studies use TCSS as a diagnostic tool to assess the severity of leprosy neuropathy. A clinician should be aware of three clinical presentations of leprosy neuropathy because this is related to the treatment and prognosis of the patient, namely acute, chronic, and recurrent neuropathy. Acute neuropathy is neuropathy that lasts less than 6 months. This neuropathy often occurs at leprosy reaction and is very responsive to neuropathy treatment. If neuropathy lasts more than 6 months, it is called chronic neuropathy, and this condition does not respond to treatment. Recurrent neuropathy is a recurrent episode of neuropathy that occurs at least 3 months after the previous neuropathic condition and has a poor prognosis. Participants in this study were newly diagnosed with neuropathy or not at the time of sampling, so it was not possible to determine whether they had acute or chronic neuropathy.
In this study, the sensitivity value of TCSS was 85.7%, specificity was 84.2%, and an accuracy of 85%. From the ROC technique yielded an AUC value of 93.2% (95% CI 86%–100%), with P < 0.001. The ROC curve found that TCSS has an excellent diagnostic value because the ROC curve is distant from the 50% line and near 100%. The AUC value of 93.2% is statistically excellent. The AUC value of 93.2% means that if the TCSS score is used to diagnose neuropathy in 100 leprosy patients, the correct conclusion will be obtained in 93 patients. Based on the calculation results produced from the tug of war between sensitivity and specificity, the optimal cut-off point value is 5.5 or a score is ≥6 that has a sensitivity of 85.7% and a specificity of 84.2% [Figure 2].
The TCSS diagnostic test result on leprosy neuropathy is in coherent with the previous study. Supriyanta found sensitivity, specificity, and accuracy of TCSS in diabetic patients were 86.6%, 94.1%, 88%, and the optimal cut-off point score of TCSS is ≥6. It can be concluded that TCSS has a good diagnostic value for the early detection of leprosy neuropathy.
ENMG, a gold standard diagnostic tool for neuropathy, was not used in this study because of the scarce availability in health-care facilities. In our study, we use SWM tests as a diagnostic tool for neuropathy in leprosy because of its validity and accessibility.
Financial support and sponsorship
The authors are responsible for all of the study funding without the involvement of a grant or any external source of funding.
Conflicts of interest
There are no conflicts of interest.
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Dina Arwina Dalimunthe,
Jl. DR. Mansyur No. 5, Medan, Sumatera Utara, Medan
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2]