High-Resolution Ultrasonography (HRUS) in Leprosy - Notes

1. Background / Rationale

• Diagnosis of leprosy classically relies on skin lesion examination and palpation of peripheral nerves (clinical assessment), but palpation is highly subjective with wide intra- and inter-observer variability.
• Invasive tests (slit skin smear, skin/nerve biopsy) have declined in use due to risk of transmitting HIV, Hepatitis B, and HCV.
• Electrophysiological studies (nerve conduction studies, EMG) assess nerve function but give no spatial/anatomical information about the nerve and surrounding structures.
• USG and MRI have emerged as imaging tools to study structural changes in peripheral nerves.
  • MRI: excellent soft tissue resolution but time-consuming, expensive, stationary equipment, and difficult for tracing superficial nerve course.
  • HRUS: more sensitive, efficient, economical, portable, real-time — preferred over MRI for tracing peripheral nerves along their course.

2. Technique of HRUS

• Uses high-frequency broadband linear array transducers + color Doppler (CD).
  • HRUS frequency: 10-14 MHz (worldwide use); ideally ≥12 MHz, preferably 15-18 MHz.
  • CD broadband frequency: 6-18 MHz.
• Provides real-time examination of soft tissue in static and dynamic states.
• Nerves examined bilaterally, in both cross-sectional (transverse) and longitudinal planes.
• Four key nerves studied (found to yield maximum diagnostic results):
  1. Ulnar nerve (UN) — at elbow, proximal to medial epicondyle (~3-4 cm above elbow in leprosy)
  2. Median nerve (MN) — at wrist and forearm
  3. Lateral popliteal nerve (LP) — at fibular head
  4. Posterior tibial nerve (PT) — at ankle, proximal to medial malleolus
• If a nerve shows thickening, adjacent cutaneous nerves should also be imaged to assess extent of spread.

3. Normal Nerve Appearance on HRUS

• Characteristic "honeycomb" / fascicular pattern:
  • Longitudinal view: tubular structure with multiple discontinuous hypoechoic linear areas separated by hyperechoic bands (like "bundles of straw").
  • Transverse view: multiple rounded hypoechoic areas (fascicles) in a homogeneous hyperechoic background.

4. Five Main Pathological Changes Detectable by Nerve Sonography

1. Nerve enlargement
2. Increased hypo-echogenicity or hyperechogenicity
3. Enlarged fascicles
4. Increased thickness of epineurium
5. Increased endo- or epineural blood flow

a) Nerve Enlargement

• Assessed by measuring cross-sectional area (CSA) — taken from the area within the inner margin of the hyperechoic rim, at the point of maximum thickness.
• Compared against reference/normal values.
• Example CSA comparisons (healthy vs leprosy subjects):
  • Ulnar: ~6 mm² (healthy) vs ~23 mm² (leprosy)
  • Median: ~6 mm² vs ~16 mm²
  • Lateral popliteal: ~6 mm² vs ~56 mm²
  • Posterior tibial: ~7 mm² vs ~14 mm²

b) Echogenicity

• Graded as:
  • Mild = some hypoechogenicity
  • Moderate = obvious hypoechogenicity
  • Severe = absence of any fascicular pattern
• Computerized gray-scale analysis can standardize/quantify this.
• Increased hypoechoic areas also seen in diabetic neuropathy, carpal tunnel syndrome, ulnar neuropathy at elbow (likely due to intraneural edema) — so echogenicity helps discriminate normal vs pathological nerves, not leprosy-specific alone.

c) Fascicle Size

• Hypoechoic areas on USG correspond histologically to neuronal fascicles.
• Enlarged fascicles reported in leprosy, CIDP (chronic inflammatory demyelinating polyneuropathy), and Charcot-Marie-Tooth disease.

d) Epineurium Thickness

• Measured in transverse plane.
• Epineurium of ulnar nerve is often strikingly thickened in leprosy when involved.

e) Vascularization (Color Doppler / Power Doppler)

• Assesses epineural/endoneural blood vessels.
• Presence of flow signals in epineural plexus or intrafascicular vessels = hypervascularity, seen with local inflammation (e.g., in reactions — Type I and Type II).
• Normal physiological blood flow usually not visible on CD; only increased flow (pathological) is detectable.

5. Indications / Uses of HRUS in Leprosy

1. Patients with signs/symptoms of peripheral neuropathy but no visible skin lesions (primary/pure neuritic leprosy).
2. Patients with skin patches showing normal sensation but peripheral neuropathy symptoms.
3. Established leprosy patients with no nerve pain/tenderness but signs of peripheral neuropathy ("silent nerve paralysis").
4. All proven leprosy patients — to assess degree of nerve thickening and risk of impending nerve damage, regardless of neuropathy presence.
5. Follow-up during reactions/neuritis — to confirm reaction and support early intervention (e.g., starting corticosteroids).
6. Differentiating ulnar nerve entrapment (UNE) from leprous neuritis:
   • UNE: enlargement at/just above the elbow sulcus.
   • Leprosy: enlargement more proximal, 3-4 cm above the elbow.
7. Differentiating pure neuritic leprosy (PNL) from other neuropathies (avoids need for nerve biopsy/FNAC in some cases) — PNL accounts for ~5-10% of leprosy cases, presents without skin lesions, and carries the highest risk of deformity.

6. Clinical Correlation / Key Study Findings

• HRUS can detect nerve thickening before nerve function impairment (NFI) is clinically apparent or seen on nerve conduction studies (e.g., in a study of 21 patients, 3 had normal nerve conduction but focal ulnar thickening on sonography).
• Case-control study (20 leprosy patients): nerve enlargement found in median 59%, ulnar 44%, tibial 33%, lateral popliteal 47%.
• Significant correlation between clinical parameters (grade of thickening, sensory loss, muscle weakness) and sonographic findings (CSA, echotexture, endoneural flow).
• Increased vascularity on CD seen not just in nerve trunks near inflamed skin lesions but also in contralateral and distant nerve trunks during reactions — suggesting more widespread nerve involvement than skin involvement suggests.
• Epineural thickening of ulnar nerve correlates with CSA but not with increased blood flow.
• HRUS can detect early hemodynamic changes even before clinical signs (pain/tenderness) of reaction develop — potentially useful as an early warning sign to start steroid therapy (once standardized).
• Classification based on imaging appearance:
  • Group I: Normal
  • Group II: Enlarged with fascicular abnormalities
  • Group III: No fascicular structure at all

7. Interpretation Checklist (Summary of HRUS Report Components)

1. Maximum cross-sectional area (CSA) of the nerve
2. Length of nerve enlargement
3. Nerve echotexture analysis
4. Identification of nerve compression within osteo-fibrous tunnels
5. Detection of endo- and epineural color flow (Doppler) signals

8. Advantages of HRUS

• Noninvasive, real-time, cost-effective, portable
• Provides objective (vs subjective palpation) assessment of nerve thickening
• Can study nerves in deeper planes (under muscle fascicles/retinacula) not accessible to palpation
• Can visualize entire nerve course, not just sites of predilection (elbow, fibular head)
• Useful for follow-up/monitoring disease progression and treatment response
• Increasingly learnable by dermatologists, neurologists, and leprologists with basic training in nerve anatomy

9. Limitations Noted

• No standardized national/international guidelines yet for HRUS use in leprosy.
• Spatial resolution of color Doppler is not yet high enough to visualize normal physiological endoneural/epineural blood flow (only increased/pathological flow is detected).
• Nerve thickening alone (on palpation) is not always a reliable indicator of nerve function impairment — hence the value of combining HRUS with clinical/electrophysiological tests.

10. Documentation

• A standard proforma is used to record clinical and HRUS findings (patient demographics, classification, MDT status, reactions, VMT/sensory testing, and nerve-by-nerre findings for ulnar, median, LP, PT, radial cutaneous nerve — recording enlargement, pain, tenderness, VMT).