Small-Fiber Neuropathies: Etiologies, Diagnostic Tests, and Treatments
An estimated 40 million Americans are affected by peripheral neuropathies, most of which are thought to involve both small and large fibers.
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LAS VEGAS — During the 2018 PAINWeek conference, held September 4-8, Charles E. Argoff, MD, professor of neurology at Albany Medical College, Albany, New York, presented an overview of diagnostic tests and available treatments for small-fiber polyneuropathies.
An estimated 40 million Americans are affected by peripheral neuropathies, most of which are thought to involve both small (ie, myelinated Aδ fibers and unmyelinated C fibers) and large fibers. Neuropathic pain, which results from conditions that affect the somatosensory system, can be graded as "definite," "probable," or "possible" and is known to result from a number of conditions ranging from diabetic peripheral neuropathy, postherpetic neuralgia, spinal cord injury, and trigeminal neuralgia — all conditions that can be treated with US Food and Drug Administration-approved drugs — as well as phantom limb pain and pain resulting from stroke, among other conditions.
Symptoms, functional changes, and diagnostic tests are distinct for small- and large-fiber neuropathies, which co-occur in mixed polyneuropathies. For example, large-fiber neuropathies are characterized by paresthesias (eg, numbness, sensations of "pins and needles," and "tingling"); balance may also be affected. Small-fiber neuropathies may manifest by sensations of burning, of electric shocks, as well as stabbing pain and numbness, often starting distally.
Conditions that have been associated with small-fiber polyneuropathies include diabetes, thyroid dysfunction, metabolic syndrome, rheumatoid arthritis, sodium channelopathies, and Sjögren syndrome. Patients with small-fiber neuropathies often have close to normal physical and neurologic exams, with the exception in some cases of reduced sensation to pin prick or thermal stimuli, as well as hyperalgesia and dry skin, rendering the conduct of a thorough history and additional testing essential to reach a diagnosis.
Diagnostic tests for large-fiber neuropathies should include electromyogram combined with nerve conduction velocity and a biopsy of the sural nerve, and those for small-fiber neuropathies may include blood tests (for metabolic functions: fasting blood sugar, thyroid function; nutritional profile: complete blood count, hepatic profile, vitamins B1 and B12; infectious status: Lyme disease, HIV, hepatitis C virus; autoimmune disorders: antinuclear antibodies, erythrocyte sedimentation rate, antineutrophile cytoplasmic antibodies); x-rays, computed tomography, or magnetic resonance imaging; electromyography (EMG); nerve conduction velocity (NCV); quantitative sensory testing; and skin punch biopsy to assess the density of intraepidermal fibers. Still, EMG and NCV may not be sensitive to acute insult and may not detect an involvement of small fibers. In addition, normal results on these 2 tests are not sufficient to rule out neuropathic pain. Other tests that may be useful in diagnosing small-fiber neuropathies include the Neuropathic Pain Symptom Inventory, Quantitative Sudomotor Axon Reflex testing, nociceptive evoked potentials, and peripheral nerve ultrasound. When an autoimmune or inflammatory etiology is suspected, a lumbar puncture may be carried out.
"Treat the treatable!" admonished Dr Argoff. "If an underlying cause of small fiber neuropathy can be determined, optimal treatment of the causative condition may lessen the symptoms." The European Federation of Neurological Societies, the Canadian Pain Society, and the International Association for the Study of Pain (IASP) all recommend tricyclic antidepressants and gabapentin/pregabalin as first-line treatment for neuropathic pain, with European Federation of Neurologic Societies and International Association for the Study of Pain (IASP) guidelines also including lidocaine 5%, and IASP adding serotonin-norepinephrine reuptake inhibitors (SNRIs) and opioids (in specific cases) as first-line options. Recommended second-line treatments include opioids, SNRIs, tramadol, and third-line options, opioids, bupropion, and N-methyl-D-aspartate antagonists.
"Recognizing small fiber neuropathy and its existence in perhaps more conditions than previously recognized may lead to improved treatment approaches," concluded Dr Argoff.
Argoff CE. Big news in small fiber neuropathies. Presented at: PAINWeek 2018; September 4-8, 2018; Las Vegas, NV. Presentation NRO-03.
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