ENFD

Arkana Laboratories offers Epidermal Nerve Fiber Density (ENFD) Testing. ENFD testing is widely used by neurologists in the United States and Europe to evaluate for small fiber neuropathy.

epidermal nerve fiber density image showing small fiber neuropathy

What is small fiber neuropathy (SFN)?

Small fiber neuropathy, or SFN, is a sensory neuropathy that preferentially involves thinly myelinated A-delta and unmyelinated C sensory fibers involved in the perception of pain and temperature. They are typically length-dependent and symmetrical.

Symptoms of SFN

Less commonly, patients may have non-length-dependent, focal, or multifocal symptoms. As SFN does not involve large motor and sensory fibers, patients typically present with burning pain and paresthesias beginning in the feet and progressing upwards, with normal EMG and NCS, and abnormal Quantitative Sensory Testing (QST).

What does ENFD testing evaluate?

ENFD testing quantitatively evaluates the degree of small nerve fiber loss in 3mm punch biopsies of skin. The nerve fibers are made visible by PGP9.5 antibody staining performed on 50um thick frozen sections of Zamboni-fixed biopsy tissue. Samples from the ankle (10cm proximal to the lateral malleolus) and at least one more proximal site (proximal thigh and/or distal thigh) are typically taken to demonstrate the length-dependent nature that is characteristic of most small fiber neuropathies (SFN).

Why perform skin punch biopsy for ENFD?

1) Evaluate possible cause(s) of painful neuropathy
2) Establish the diagnosis of SFN
3) Monitor response to treatment

Skin Biopsy Specimen Collection

Biopsy of proximal and distal sites allows for assessment of length-dependent processes. Alternative biopsy sites are best evaluated by also submitting a punch biopsy from a similar location in the opposite non-affected limb to serve as a reference control.

Distal lower leg 10.0 cm above the lateral malleolus (most common site)
Distal Thigh 7.0 cm above the knee, lateral
Proximal Thigh 20.0 cm below the anterior iliac spine, upper lateral thigh

Causes of small fiber neuropathy include: 

  • Idiopathic/unknown (up to 50% of cases)
  • Diabetes Mellitus, pre-diabetes/impaired glucose intolerance
  • Connective tissue disorders
  • Vitamin B12 deficiency
  • Chemotherapy

 

Biopsy Handling Protocol For ENFD Testing:

  1. Clean the biopsy site with alcohol swabs and numb the area(s) with local anesthesia (for example 1% lidocaine or 1% lidocaine with epinephrine).
  2. Use provided 3.0 mm biopsy punch; rotate with light pressure to 2/3 of its depth (2 to 3 mm).
  3. Use forceps and scissors to carefully remove the biopsy specimen (do not grasp or pinch the epidermis when removing the punch biopsy as this will crush the small nerves we are measuring).
  4. Immediately place the removed biopsy into the appropriate labeled specimen vial containing Zamboni’s fixative and tightly close the lid.
  5. Label specimen containers with biopsy site and two patient identifiers (e.g. name and date of birth).

 

Specimen Handling & Transport

It is essential that skin biopsy is immediately-fixed in the provided fixative (Zamboni’s) for evaluation. Please only transport specimens Monday-Thursday. Optimal results are obtained when the specimen is not fixed for more than 24 hours. Results are final within 3-5 days.

ENFD Testing Forms