Peripheral nerve ultrasound in Hansen's disease

by Glauber Voltan

Post-Graduate Program, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Ultrasonography (USG) can be used as a complementary diagnostic method in Hansen's disease (HD) to identify neuropathy. HD is the only condition in which assessment of neural hypertrophy is central to its diagnosis,1 and is proposed by the World Health Organization as one of the three criteria for case definition of the disease.2 Simplified neurological physical examination, including palpation of the peripheral nerves, aids in the diagnosis of neural thickening and neuritis but is subjective even for well-trained professionals.3 HD is a neural disease and may or may not have cutaneous manifestations.4–10 Cases of peripheral neuropathy accompanied by neural thickening, with or without cutaneous manifestations, should lead the clinician to suspect the diagnosis of HD.11

High Resolution USG

High-resolution USG (HRUS) two-dimensional and Doppler modes make it possible to:

  • evaluate the entire extent of superficial and deep peripheral nerves

  • assess and quantify the cross-sectional area (CSA) and the diameter of the epineurium and perineurium in various neural segments

  • characterize fascicular patterns and echogenicity

  • identify the presence or absence of endoneural or perineural vascularization.12

HRUS is able to identify a greater number of altered nerves and a greater extent of alterations, even in areas inaccessible to palpation or when clinical examination of palpation of peripheral nerves leaves the examiner in doubt as to presence of thickening. Being accurate and objective, it can bring new parameters to the diagnosis of HD and the early recognition of neuritis, especially in the reaction phases of the disease.13–15 HRUS is more cost-effective than magnetic resonance imaging,17 and is a complementary method to electrophysiology.

Anatomical aspects of peripheral nerves

Peripheral nerves are made up of axons held together by a thin endoneurium (inner layer), grouped into fascicles covered by the perineurium and reunited into the nerve, which is surrounded by the epineurium (outer layer) (Figure 1). Echographic images show the nerves as hypoechoic structures with a fine fascicular pattern. In the longitudinal axis, these appear as hypoechoic tubular structures interspersed by hyperechoic lines and externally lined by a hyperechoic line (cord or rope pattern) (Figure 1). On the transverse axis, they appear rounded or oval, with multiple rounded hypoechoic images (neural fascicles) inside located on a hyperechoic background (epineurium + perineurium), an appearance described as "honeycomb" or connective fascicular (Figure 1).18–20

Figure 1: Images of peripheral nerves from healthy people, honeycomb pattern (1-A: right common fibular nerve, cross-section at fibular head and proximal; 1-B: right ulnar nerve, cross-section at cubital tunnel and proximal; 1-C schematic representation of normal peripheral nerve; 1-D left ulnar nerve, longitudinal section).

Morphological aspects of Hansen's disease neuropathy seen by high-resolution USG

USG of peripheral nerves should verify the CSA, analyze the presence or absence of Doppler and be done bilaterally. This method presents high sensitivity and specificity to diagnose, locate and evaluate peripheral nerve thickening when compared to clinical neurological examination and other imaging methods. In general, it is performed in the following nerves: median in the carpal and forearm tunnels; ulnar in the cubital and proximal tunnels, common fibular in the fibular head and proximal, tibial in the popliteal fossa and/or tarsal tunnel; sural in the leg and ankle; and radial in the radial groove of the arm.

In HD, we observe greater thickening of the neural trunks represented by increased CSA, together with morphological alterations of echogenicity, fascicular pattern, perineuro and vascularization in peripheral nerves. More severe thickening is noted above the medial epicondyle in the ulnar nerve, the median nerve proximal to the carpal tunnel, the common fibular nerve at the fibular head and the tibial nerve at the medial malleolus, features which should be included in routine sonographic evaluation (Figure 2).9,13

Besides the parameters of the absolute values of the CSA measurements, other authors have suggested that asymmetry of peripheral nerve thickening is a characteristic of HD patients, regardless of their classification in multibacillary or paucibacillary, and that the asymmetry index [∆CSA = (>CSA right or left) - (< CSA right or left)] between the right and left peripheral nerves has high sensitivity and specificity in the differentiation of nerves from healthy individuals and nerves from HD patients.9,15

Focal thickening of the ulnar nerve begins at the ulnar sulcus and reaches its maximum four centimeters above the medial epicondyle.15,21 This characteristic finding may help mainly in the diagnosis of primary or pure neural HD (PNHD), in which skin lesions are absent, and also in differentiating HD from other neuropathies in which diffuse nerve enlargement may occur.

The absence of neural thickening or other peripheral nerve changes does not exclude the diagnosis of HD because the lesion may be in the neural ramus and not in the nerve trunks. On the other hand, the identification of neural thickening does not confirm the diagnosis of HD, and a thorough investigation of the clinical, bacteriological and electrophysiological aspects of the disease is required.

Figure 2: Sonographic images and representative schemes of peripheral nerves in patients diagnosed with HD (2-A thickening of the epineurium seen by HRUS: upper = ulnar nerve, cross-section, cubital tunnel / lower = ulnar nerve, cross-section, cubital post-tunnel; 2-B several nerves with altered morphological pattern - loss of fascicular pattern; 2-C neural hypertrophy and loss of fascicular pattern of common tibial and fibular nerves in the distal third of the thigh; 2-D positive Doppler signal, endoneural or neuritis of the tibia in the left medial malleolus).

Figure 3: Ultrasound images of bilateral peripheral nerves at major neural points of the same patient diagnosed with HD showing thickening and morphological change corresponding to ulnar neuropathy hypertrophic (CSA > normal), asymmetric (∆CSA > normal), and focal (∆TPT > normal) types.


1. Donaghy, M. Enlarged Peripheral Nerves. Pract. Neurol. 3, 40 (2003).

2. WHO. Guidelines for the Diagnosis, Treatment and Prevention of Leprosy. (2017).

3. van Brakel, W. H. et al. International workshop on neuropathology in leprosy - Consensus report. Lepr. Rev. 78, 416–433 (2007).

4. Alemu Belachew, W. & Naafs, B. Position statement: LEPROSY: Diagnosis, treatment and follow-up. J. Eur. Acad. Dermatol. Venereol. 33, 1205–1213 (2019).

5. Scollard, D. M., Truman, R. W. & Ebenezer, G. J. Mechanisms of nerve injury in leprosy. Clin. Dermatol. 33, 46–54 (2015).

6. Garbino, J. A. et al. Primary neural leprosy: Systematic review | Hanseníase neural primária: Revisão sistemática. Arq. Neuropsiquiatr. 71, 397–404 (2013).

7. Filho, F. B. et al. Evidence of hidden leprosy in a supposedly low endemic area of Brazil. Mem. Inst. Oswaldo Cruz 112, 822–828 (2017).

8. Lugão, H. B., Frade, M. A. C., Marques-Jr, W., Foss, N. T. & Nogueira-Barbosa, M. H. Ultrasonography of Leprosy Neuropathy: A Longitudinal Prospective Study. PLoS Negl. Trop. Dis. 10, e0005111 (2016).

9. Frade, M. A. C. et al. New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy. Mem. Inst. Oswaldo Cruz 108, 257–262 (2013).

10. Leprosy as a neurological disease. Lancet Neurol. 8, 217 (2009).

11. El Gency, H. I., Ghanema, M., Hussein, S. A., Almaghraby, O. S. & Rashad, W. Peripheral neuropathy is not the end but the beginning. Lepr. Rev. 88, 574–582 (2017).

12. Peer, S. & Gruber, H. Atlas of peripheral nerve ultrasound: with anatomic and MRI correlation. (Springer, 2013).

13. Jain, S. et al. High-Resolution Sonography : A New Technique to Detect Nerve Damage in Leprosy. PLoS Negl. Trop. Dis. 3, 1–7 (2009).

14. Gupta, S., Bhatt, S., Bhargava, S. K., Singal, A. & Bhargava, S. High resolution sonographic examination: a newer technique to study ulnar nerve neuropathy in leprosy. Lepr. Rev. 87, 464–475 (2016).

15. Lugão, H. B., Nogueira-Barbosa, M. H., Marques, W., Foss, N. T. & Frade, M. A. C. Asymmetric Nerve Enlargement: A Characteristic of Leprosy Neuropathy Demonstrated by Ultrasonography. PLoS Negl. Trop. Dis. 9, e0004276 (2015).

16. Elias, J. et al. Role of Ulnar Nerve Sonography in Leprosy Neuropathy With ENMG correlation. 1201–1209 (2009).

17. Martinoli, C. et al. US and MR imaging of peripheral nerves in leprosy. Skeletal Radiol. 29, 142–150 (2000).

18. Graif, M., Seton, A., Nerubai, J., Horoszowski, H. & Itzchak, Y. Sciatic nerve: sonographic evaluation and anatomic-pathologic considerations. Radiology 181, 405–408 (1991).

19. Martinoli, C. et al. Ultrasonography of peripheral nerves. J. Peripher. Nerv. Syst. JPNS 1, 169–178 (1996).

20. Wortsman, X. & Jemec, G. B. E. Dermatologic ultrasound with clinical and histologic correlations. (Springer, 2013).

21. Bathala, L. et al. Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a characteristic sign in Hansen’s neuropathy. PLoS Negl. Trop. Dis. 11, 1–10 (2017).