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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 4  |  Page : 230-235

Role of high-resolution sonography and doppler imaging in detecting nerve damage in leprosy patients


Department of Radiodiagnosis and Imageology, Kurnool Medical College and Government General Hospital, Kurnool, Andhra Pradesh, India

Date of Submission15-Dec-2019
Date of Acceptance20-Apr-2020
Date of Web Publication6-Jan-2021

Correspondence Address:
Dr. N Bhavana
Department of Radiodiagnosis, Kurnool Medical College, Kurnool -518 002, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_123_19

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  Abstract 


Leprosy is the chronic infectious disease-causing peripheral nerve damage leading to functional impairment of limbs, ulcer formation, and deformities. Pathological findings of leprosy are nerve enlargement and inflammation, with the help of high-resolution sonography and color Doppler (CD) imaging to demonstrate nerve enlargement and inflammation.
Aims: To assess the role of high-resolution sonography in detecting nerve damage in leprosy patients.
Methods and Materials: The study group of 30 cases of leprosy performed on e Soate My lab 40 and evaluated bilateral US of the ulnar (UN), lateral popliteal (LP), and posterior tibial (PT) nerves compared this with the sonographic findings in 30 healthy controls.
Results and Conclusions: The nerves were significantly thicker in the leprosy patients as compared with healthy controls (P < 0.001 for each nerve). Increased neural vascularity was present in 47 of 158 examined nerves (3%). A significant correlation observed between clinical parameters of the grade of thickening, sensory loss and muscle weakness, and US abnormalities of nerve echotexture, endoneurial flow, and cross-sectional area. Studies have reported that clinical examination of enlarged nerves in leprosy patients is subjective and inaccurate, whereas ultrasonography (USG) provides an objective measure of nerve damage.

Keywords: Color doppler, high-resolution ultrasonography, leprosy


How to cite this article:
Ontedddoo JR, Bhavana N, Abdul GJ, Suresh B, Padmalatha M, Harinath D. Role of high-resolution sonography and doppler imaging in detecting nerve damage in leprosy patients. J NTR Univ Health Sci 2020;9:230-5

How to cite this URL:
Ontedddoo JR, Bhavana N, Abdul GJ, Suresh B, Padmalatha M, Harinath D. Role of high-resolution sonography and doppler imaging in detecting nerve damage in leprosy patients. J NTR Univ Health Sci [serial online] 2020 [cited 2021 Jan 18];9:230-5. Available from: https://www.jdrntruhs.org/text.asp?2020/9/4/230/306119




  Introduction Top


Leprosy (Hansen disease) is a chronic infectious disease caused by Mycobacterium leprae, in it is many and various clinical forms primarily involve the skin and nerves. The initial symptom of nerve involvement is a sensory loss, which increases the frequency of minor trauma, leading to infections and eventually to mutilating injuries and blindness. Sensory abnormalities usually precede paralysis. Clinically, leprosy patients grouped into two polar forms, TT tuberculoid and LL lepromatous, between which borderline forms show an intermediate spectrum of phenotypes.[1] In TT leprosy, there is an intense immune response, which limits the proliferation of bacilli: aggressive infiltration of epithelioid and lymphoid cells into the nerve causes thickening of the epi- and perineurium and destruction of fascicles. In LL leprosy, the immune response is an indolent and active proliferation of bacilli occurs: this form shows better preservation of the nerve architecture than the high-resistance disease. Patients with TT or LL forms are usually stable, while those with intermediate forms are not stable because of alterations between the level of immunity and the number of bacteria over time. Shifting toward the LL pole may either be part of the natural history of leprosy or the result of inappropriate therapy. A transition toward a higher-resistance form of leprosy is a favorable sign, but nerve deficit may be precipitated during episodes of acute neuritis, and primarily type 1 (reversal reaction (RR)) and type 2 (erythemanodosum leprosum (ENL)) reactions. In these phases, a nerve segment may become intensely painful and tender, and, as the disease progresses, each subsequent episode of neuritis adds to the deficit until the affected nerve may become completely paralyzed. The nerve involvement by leprosy reactions, if recognized and to be treated with steroids and nerve release surgery, can be reversible.[2],[3],[4],[5]

Currently, nerve assessment in leprosy relies mainly on clinical assessment and electrical testing. The accuracy of these techniques has, however, limitations both in confirming the anatomic extent of involvement and in serving as an index of response to treatment. High-frequency ultrasonography (US) has increasingly been used for the noninvasive assessment of peripheral nerve diseases. Although the increased size and superficial course of the involved nerves in leprosy lend themselves to a detailed depiction with these radiologic modalities. Accordingly, we prospectively studied the spectrum of US findings of 158 nerves in 30 leprosy patients with clinical correlates, to determine the role of imaging in these patients.


  Subjects and Methods Top


The study group of 30 patients with leprosy (5 women and 25 men; age range 1872 years, mean 44 years). The study group included in and out-patients referred from dermatology [Table 1]. Patients with coexisting conditions with diabetes, hypothyroidism are excluded. History of any trauma-related peripheral nerve disease patients excluded from the study.
Table 1: Profile of Leprosy Patients Included in Study

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The diagnosis of leprosy is based on established clinical, bacteriologic, and histopathologic criteria. According to Ridley and Jopling, sixteen patients classified as borderline tuberculoid (BT), four as borderline lepromatous (BL), one with lepromatous and nine cases of pure neuritic leprosy.

Imaging findings compared with those obtained in 30 control subjects (15 women and 15 men; age range 17-58 years, mean 33 years) who were free of obvious peripheral neuropathies – informed consent obtained from all patients and controls. A total of 158 nerves, including 50 ulnar (UNs), 54 lateral popliteal nerves (MNs), 54 posterior tibial nervess (PTNs) nerves examined. UN, MNs, and PTNs were clinically graded after palpation as follows. Grade 0 was defined as a nerve not thicker than the contralateral nerve and with normal sensation; Grade 1 occurred when the affected nerve was thicker than the contralateral nerve; Grade 2 was a thickening of the affected nerve which felt rope-like; Grade 3 was a thickened nerve which felt beaded or nodular.

All peripheral nerves imaged with high-frequency linear transducer 7-12 MHz linear array transducer. UN at the elbow and proximal to the medial epicondyle, LP at the fibula head and PT nerves at the ankle and proximal to the medial malleolus. We examined, and the length of abnormality of the nerve was determined by the presence of abnormal size and echo reflectivity of the nerves bilaterally. All nerves measured on transverse sections at a point where the nerve thickness was maximum in the visualized segment of the nerve. On transverse scans, the cross-sectional area of the nerve was determined from that area by one within the hyperechoic rim surrounding the nerve. The echo reflectivity of the nerves assessed on imaging was arbitrarily graded as follows: mild = some hypo-reflectivity, moderate = obvious hypo-reflectivity, and severe = absence of any fascicular pattern. Color Doppler (CD) settings chosen with Pulse repetition frequency set of 1 KHZ, and Doppler gains adjusted to the maximum level that thus not produce any clutter to optimize the identification of weak signals from vessels with slow velocity. Visibility of blood flow signals in the intrafascicular vessels indicated hypervascularity of the nerve during CD imaging.

Ethical Clearance

Ethical approval for this study (Ethical Committee ECR/1397/Inst/AP/2020) was provided by the Institutional Ethics Committee, Kurnool Medical College & Government General Hospital, Kurnool, on 04 November 2007.


  Results Top


In controls, on palpation, all the nerve trunks were of normal size (grade 0) and not tender. On ultrasonography (USG), the peripheral nerves appeared as round to oval, giving a 'honeycomb pattern' in transverse scans [Figure 1], and as hypoechoic tubular structures with parallel linear internal echoes suggestive of 'bundles of straw' in longitudinal scans[Figure 2]. The epineurium and perineurium were uniformly hyperechoic, with an absence of endo and epineural blood flow signals on CD imaging. The mean cross-sectional area for all three nerves showed no age or gender-related differences (P > 0.1). The UN showed the highest mean cross-sectional area as compared with the other nerves [Table 2].
Figure 1: Transverse scan of ulnar nerve from a healthy subject as denoted by dotted ellipse (CSA = 5.5 mm2) showing hypoechoic fascicles separated by hyperechoic areas in a ‘honeycomb’ like pattern with absence of blood flow signals

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Figure 2: Longitudinal ultra sonogram of ulnar nerve from a healthy subject (dotted lines) with hyperechogenic bands in a linear pattern appearing as bundles of straw

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Table 2: Cross Sectional Area (mm2) of Major Peripheral Nerve Trunks of Upper and Lower Limbs of Healthy Subjects and Leprosy Patients

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Clinical thickening ranging from grade 1 to 3, observed in 76 nerves of the total 158, examined nerves (42%). An increased cross-sectional area was observed 58% of all nerves [Figure 3]. In cases of no nerve thickening clinically, the CSA was above the upper limit of normal. When the sonographic findings and the clinical characteristics analyzed, significant differences observed in the mean CSA for clinical grades 0 versus grades 1, 2, and 3. In the 44 nerves for which clinical thickening was not observed (6UN, 18 LP, and 20 PTN) by palpation (grade 0), the CSA was above the upper limit of normal in 12 nerves (4 LP and 8 PT). On the contrary, 29 of the 56 clinically thickened nerves (13 UN, 19 LP, and 24 PT) did not show a sonographic enlargement. UN did not show sonographic enlargement for any situation in which clinical thickening was not observed.
Figure 3: Transverse sonogram showing bilateral Enlarged ulnar nerves with enlarged fascicles measuring CSA (r) 31 mm2 and (l) 28 mm2 and hypervascularity noted in BT leprosy with type 1 reaction patient

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In our Study, CD flow signals observed most frequently in the UN. The most significant thickening of the UN was observed proximal segment of the UN above the medial epicondyle. CD flow signals observed in 2 of the 26 clinically nonthickened nerves of the UN. Increases CD flow signals noted in the 24 nerves out of 92 thickened nerves. In the 32 nerves of 10 patients with sensory loss [Table 3], the nerve supplying the area of sensory loss was sonographically enlarged in 26 nerves (17%). In the 40 nerves of 15 patients presenting with motor weakness, thickening was observed sonographically in 24 nerves (62.5%), and in the 16 nerves of patients with both motor and sensory loss, 11 nerves (68.75%) were sonographically enlarged. A significant correlation was observed between clinical parameters of the grade of thickening, sensory loss, and muscle weakness, and US abnormalities of CSA, echotexture, endoneurial flow.
Table 3: Clinical and Sonographic Findings of Major Peripheral Nerves in Leprosy Patients

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Sonographic characteristics: echotexture and CD flow. Of the 158 nerves examined in the leprosy patients, 41.7% of the nerves showed normal echo patterns. In the remainder, moderate or severe reduced echo reflectivity, indicative of partial to total loss of fascicle structure. The most extended lengths were measured in the UN. Mild, moderate, and severe echo reflectivity changes were observed respectively in 53% [Figure 4], 33% [Figure 5], and 5% [Figure 6] of the nerves examined. All the nerves with neural vascularity were from the 24 patients who had associated leprosy reactions [Figure 7].
Figure 4: Transverse scan of LP nerve from a pure neuritic leprosy as denoted by dotted ellipse (CSA = 21 mm2) showing mild hyporeflectivity in absence of blood flow signals

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Figure 5: Transverse scan of posterior tibial (PT) nerve from BT leprosy as denoted by dotted ellipse (CSA = 11.5 mm2) showing moderate hyporeflectivity in absence of blood flow signals

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Figure 6: Transverse sonogram showing enlarged UN with severe hyporeflectivity of fascicles

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Figure 7: Transverse sonogram with CD showing mixed echogenic lesion and increased vascularity of right UN

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  Discussion Top


This study demonstrates the usefulness of US in detecting nerve damage in leprosy. Our findings may have clinical and therapeutical consequences. Peripheral nerves are often enlarged in leprosy, and these are more accurately assessed by the US than by clinical palpation. UN is the most commonly involved nerve. Nerve enlargement is more often present in patients with type 1 or types two reaction and the nerves of these patients often showed increased vascularity in both the clinically involved nerves and nerves far distant from those clinically affected. There is a growing interest in the US as a diagnostic tool for diseases of the peripheral nervous system including mononeuropathies, polyneuropathies, and peripheral nerve tumors. USG is noninvasive, amenable to studying structural changes in nerve sites that cannot be biopsied for histopathology and is more cost-effective than magnetic resonance imaging. Moreover, with the US, the nerve can be probed for a longer length than MRI examination, which is limited to defined segments. Technical developments leading to improved image quality and reduced sizes of US equipment, together with a reduction in price, will make it possible for the US to become a tool that can be used in countries where leprosy is still endemic.

Suman Jain et al.[1] performed high-resolution ultrasonography bilateral USG of the UN, LPNs, and PTNs in 30 leprosy patients and compared this with the clinical findings in these patients and with the sonographic findings in 30 healthy Indian controls. The nerves were significantly thicker in the leprosy patients as compared to healthy controls (P < 0.0001 for each nerve) and observed significant correlation was observed between clinical parameters of the grade of thickening, sensory loss and muscle weakness and USG abnormalities of nerve echotexture, endoneurial flow and cross-sectional area (P < 0.001)[Table 4] and [Figure 8]. Martinoli et al. examined the median, ulnar, and posterior tibial nerve in 23 leprosy patients (58 nerves), both with sonography and MRI. However, their main finding was that nerves that showed a reversal reaction toward a more intense immune response had a hypervascular pattern demonstrated by Doppler studies (or by a marked T2 intensity and increased gadolinium enhancement on MRI). That study had some limitations. It took the authors 3.5 years to examine 23 consecutive patients, but more importantly, the patients had a mean disease duration of 15 years compared with 24.7 months in our study. Moreover, only affected clinical nerves were examined by sonography or MRI, while we examined the UN, LPNs, and PTNs systematically in all leprosy patients. Finally, they did not compare the imaging results with clinical findings.
Figure 8: Bar diagram showing comarision with previous study

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Table 4: Comparison to Previous Study Reports

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One of the three vital signs of leprosy is the presence of enlarged nerves. Ascertaining the presence of enlarged nerves can be difficult, and for some nerves, this is impossible because of their location. Additionally, it is impossible to assess the length of nerve abnormality by palpation. There is considerable interobserver variability in assessing the presence of enlarged nerves by palpation. In contrast, the US imaging with the interobserver agreement between sonographic measurements is excellent. We conclude that clinical examination of enlarged nerves is subjective and inaccurate, whereas sonography provides an objective measure of the nerve dimensions in addition to revealing structural changes over a longer length of the nerve. Besides enlargement, nerves in leprosy patients exhibited varying degrees of structural abnormalities such as fusiform enlargement or loss of fascicles, edema, and increased neural vascularity. Nerves that showed increased blood flow signals in the endo/perineurium belonged to patients with leprosy reactions, as Jain et al.[1] also demonstrated. As compared with the nerve size or echotexture, the above feature discriminates leprosy reactions from non-reaction leprosy. However, in the present study, sonography was unable to discriminate between reversal and ENL reactions, although multiple nerve involvement was seen more often in ENL reactions. We also found that the more enlarged the nerve, the more often CD flow signals were present.

The increased neural vascularity taken together with interfascicular edema may reflect immune-mediated inflammation known to occur during leprosy reactions. Increased CSA and abnormal echotexture may reflect chronic, long term effects of leprosy. We believe that using sonography, these processes, and progressive nerve damage can be followed, and a follow-up study is ongoing to assess the long-term value of the US in leprosy.

Acknowledgements

Nil.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jain S, Visser LH, Praveen TL, Rao PN, Surekha T, Ellanti R, et al. High-resolution sonography: A new technique to detect nerve damage in leprosy. PLoS Negl Trop Dis 2009;3:e498.  Back to cited text no. 1
    
2.
Martinoli C, Derchi LE, Bertolotto M, Gandolfo N, Bianchi S, Fiallo P, et al. US and MR imaging of peripheral nerves in leprosy. Skeletal Radiol 2000;29:142-50.  Back to cited text no. 2
    
3.
Visser LH, Jain S, Lokesh B, Suneetha S, Subbanna J. Morphological changes of the epineurium in leprosy: A new finding detected by high-resolution sonography. Muscle Nerve 2012;46:38-41.  Back to cited text no. 3
    
4.
Goedee HS, Brekelmans GJ, van Asseldonk JT, Beekman R, Mess WH, Visser LH. High-resolution sonography in the evaluation of the peripheral nervous system in polyneuropathy-a review of the literature. EurJNeurol 2013;20:1342-51.  Back to cited text no. 4
    
5.
Bathala L, Kumar K, Pathapati R, Jain S, Visser LH. Ulnar neuropathy in Hansen disease: Clinical, high-resolution ultrasound, and electrophysiologic correlations. J Clin Neurophysiol 2012;29:190-3.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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