Painful Feet: Small Fiber Neuropathies
By Marc Treihaft, MD, FAAN

Peripheral neuropathies involve different populations of nerve fibers. Patients with disorders of the large nerve fibers present with numbness, tingling, weakness, and abnormal clinical and electrophysiologic examinations (electromyography and nerve conduction studies). A more enigmatic group of patients presents with severe pain and few findings on clinical examination and electrophysiologic studies. These individuals have small fiber neuropathies. The extreme pain described by these patients and the absence of objective signs on examination sometimes lead to an erroneous diagnosis of psychogenic (arising from mental or emotional processes) pain. Patients with these syndromes are difficult to treat; consequently, prompt evaluation and accurate identification of these syndromes is important.

The nerves of the peripheral nervous system carry information to and from the brain similar to the wires or “twisted pair” of the telephone system. Sensory information from the limbs, such as the position of the fingers or the heat of the stovetop, is conveyed to the brain. Information leaves the brain and spinal cord and is directed to the muscles of the limbs, allowing us to move away from pain or obstacles. The incoming wires or nerves are of different sizes and carry specific information. The large fibers carry information regarding position and vibration from the skin receptors. Patients with strictly large fiber neuropathies due to disorders such as diabetes and hereditary sensory motor neuropathies complain of numbness without pain. Weakness results from involvement of the motor nerves innervating the muscles. Examination may reveal diminished deep tendon reflexes, reduced vibratory and position sense, and weakness. The clinical impression is confirmed by abnormalities on the electromyogram (EMG) and nerve conduction studies such as slowed motor and sensory conduction velocities, reduced motor and sensory action potentials, and denervation.

In contrast, small fibers carry information regarding pain and temperature. Abnormalities affecting these nerves cause alteration of pain and temperature perception and severe pain. Because of the difficulty characterizing the discomfort, orthopedists, podiatrists, and rheumatologists may initially evaluate patients for arthritic disorders. Pain is described as burning, prickling, stabbing, jabbing, or tight band-like pressure. The pain is initially localized to the toes but may spread to the legs and even the arms and hands. The examination may be normal or reveal a “stocking-glove” distribution sensory loss. Rarely, patients present with a more widespread or diffuse pain syndrome.

Small fiber disorders are associated with systemic conditions, most commonly diabetes. Also associated are amyloid, autoimmune or collagen vascular disorders; HIV; chemotherapy (such as antiretroviral therapy); alcohol; or they may be hereditary, associated with disorders such as Fabry’s or hereditary sensory autonomic neuropathy. In many patients, no specific cause is identified and the syndrome is termed “idiopathic.” Evaluation for a suspected small fiber neuropathy includes a thorough history and examination with review of medical conditions, family history, medications, and toxic exposures such as heavy metals.

Initial laboratory screens should include but are not limited to blood counts, blood urea and nitrogen, creatinine, electrolytes, liver enzymes, thyroid function studies, fasting glucose, B12, Erythrocyte Sedimentation Rate (ESR), Antinuclear Antibody (ANA), protein, and immunoglobulin electrophoretic patterns. The neuropathy of diabetes or glucose intolerance may antecede the diagnosis and a glucose tolerance test is frequently recommended. Early identification and treatment have a definitive effect on the neuropathy and the impact on other end organs. If appropriate, Fluorescent treponemal antibody (FTA) and human immunodeficiency virus studies may be required. The electrodiagnostic studies—electromyography and nerve conduction studies—evaluate large fiber function and are normal in the pure small fiber syndromes. They are still an important part of the evaluation and may identify co-involvement of large fibers. Specialized testing for thermal sensitivity and autonomic function (i.e. sweating, heart rate) may also be performed.

In our clinic, the skin biopsy for epidermal fiber density has proven a beneficial diagnostic tool. Prior to this technique, the diagnosis was one of exclusion based only on the clinical presentation. The lack of a diagnostic test obviously led to problems for many patients. In 1868, Langerhans identified the nerves in the skin or epidermal nerve fibers as terminal fibers of the dorsal root or sensory nerves. Attempts to quantify these small fibers were limited on sural nerve biopsy and by staining techniques. A new technique was developed in the late 1990s, utilizing skin biopsy and a neuronal antibody protein stain. This technique is relatively painless and noninvasive, and is performed in most neuromuscular clinics. Newer techniques allow examination of the nerve receptors in the skin without biopsy.

Treatment options for neuropathic pain include anticonvulsants, antidepressants, mexiletine, opioids, and topical agents such as lidocaine and capsaicin. Adverse effects, such as drowsiness, confusion, and anorexia, limit the effective doses of many of these medications. In our experience, a combination of medications, or “cocktail,” is required, initializing therapy with an anticonvulsant, followed by addition of an antidepressant, analgesic, and a topical agent.

In conclusion, many patients suffer from burning feet due to small fiber neuropathies. Clinical awareness and the development of staining of small epidermal fibers have facilitated the care of individuals with these disorders. The early identification of these syndromes is important to direct the evaluation and initiate adequate pain management. Research into diabetic neuropathy causes and small fiber syndromes may ultimately provide more effective therapies.

Marc Treihaft, MD

Dr. Marc Treihaft is Medical Director, CNI Neuromuscular and Peripheral Nerve Disorders Center and professor of Neurology, University of Colorado Health Sciences Center. Dr. Treihaft is also medical advisor for The Denver Chapter of The Neuropathy Association.


All active news articles

Home / Contact UsPeripheral Neuropathy Site Map / Disclaimer
© 2015 The Neuropathy Association / 110 W. 40th Street, Suite 1804 / New York, NY 10018 / 212-692-0662


- +