DSPN Predictive Biomarkers

According to the ADA, assessment should include a careful history and either temperatures or pinprick sensation (small-fiber function) and vibration sensation using a 128-Hz tuning fork (large-fiber function). The DND provides objective results that are easier to understand than current screening methods. A study in the 2009 Annals of Family Medicine entitled, Accuracy of Monofilament Testing to Diagnose Peripheral Neuropathy: A Systematic Review; concluded that they did not recommend the sole use of monofilament testing to diagnose peripheral neuropathy. Adding the Diabetic Neuropathy Device™ to any diabetes foot screening or fall-risk assessment meets the newest screening and diagnosis recommendations by the American Diabetes Association (ADA) by using temperatures and vibrations to measure a patients' level risk for neuropathy.

Pathophysiology and Etiology. Peripheral neuropathy results from damage to the cell body, nerve fiber, or the surrounding myelin sheath of peripheral nerves. The majority of peripheral neuropathy cases are glove-and-stocking peripheral neuropathy, which affects the distal portions of the extremities. Causes of peripheral neuropathy with symmetrical distal sensory loss and weakness include the metabolic disorder of diabetes mellitus, impaired glucose intolerance, compromising alcohol, heavy metals, medications, vitamin B deficiencies, hereditary conditions, including Charcot-Marie-Tooth disease. Other causes of neuropathies, such as localized trauma and tumors, tend to result in asymmetric peripheral neuropathy.

An axon or nerve fiber is a long, slender projection of a nerve cell or neuron invertebrates that typically conducts electrical impulses known as action potentials away from the nerve cell body. Screening is a process for evaluating a particular problem's possible presence, and the outcome is usually a simple yes or no. An assessment is a process for defining the nature of that problem, determining a diagnosis, and developing specific treatment recommendations for addressing the issue or diagnosis. Anesthesiologists, in particular, have long observed that surgical anesthetic blocks tend to progress from smaller nerves to larger diameter nerves. A nerve block moves from the loss of temperature with cold before heat, pain, touch, vibration, and proprioception. Restoration of these sensations usually occurs in reverse order as patients recover from a block. Nerve fibers divide into:

• Aα fibers are large myelinated fibers in charge of motor functions and muscle control.

• Aβ fibers are large myelinated fibers with sensory functions such as perception to touch, vibration, and position.

• Aδ fibers are small myelinated fibers in charge of pain stimuli and cold perception.

• C fibers can be myelinated or unmyelinated and have sensory (warm perception and pain) and autonomic functions (blood pressure and heart rate regulation, sweating, etc.).

Skin is the largest organ of the body and helps regulate body temperatures and permits touch, heat, and cold sensations. The mechanism in identifying nerve fibers may be performed by testing the autonomic nervous system's sudomotor function using the sympathetic skin response (SSR). The SSR specifically tests sudomotor skin fibers that do not participate in thermoregulatory sweating. This methodology is currently performed using monofilaments and tuning forks and is recognized by the American Diabetes Association (ADA) to diagnose autonomic dysfunction in polyneuropathies. Small fiber peripheral neuropathy primarily or exclusively affects the body, such as the skin and those that mediate pain and thermal sensation. These nerve fibers also help regulate the body's largely unconscious functions, such as heart rate and digestion.

The SSR is defined as the momentary change of the skin's electrical potential, which may be spontaneous or reflexively evoked by a variety of internal or the more common, externally applied arousal stimuli. Over the last 20-years, the SSR has been advocated by several studies as a simple means of assessing sympathetic sudomotor outflow in central and peripheral nervous system disorders. The science of sensation and touch is based on the relative minimum difference discrimination principle, discovered by German physician Ernst Heinrich Weber in the 19th century. Doctor Weber showed that control subjects do not sense absolute weight differences but relative ones like a patient’s ability to discriminate temperature and vibration stimuli.

The SSR is a simple, reproducible, and non-invasive test based on modifying the skin potential of peripheral nerves. SSR has been used to diagnose polyneuropathy, erectile dysfunction, central degenerative diseases, multiple sclerosis, brain infarction, reflex sympathetic dystrophies, spinal, and peripheral nerve lesions. The Diabetic Neuropathy Device™ is a modern tool that uses the SSR to help patients discriminate against variable temperature and vibration stimuli.

It is imperative that we use our ability to measure quantitatively the different types of defects that occur in the disorder, so that appropriate therapies can be targeted to specific nerve fiber types.