Patient B

The following is adapted from a case presented in the Clinical Crossroads Series in the Journal of the American Medical Association (JAMA).
JAMA (2009) "A 52-Year-Old Woman with Disabling Peripheral Neuropathy" 302 (13): 1451-1458.  Quotes from the text of the paper are presented in yellow blocks; questions are presented in the blue blocks.

This patient was initially diagnosed and treated for plantar fasciitis, an inflammation of connective tissue on the sole of the foot. When the pain spread to both feet, the podiatrist suspected a more generalized problem and referred her for neurological tests.

In a nerve conduction study, the axons in a peripheral nerve are stimulated with a voltage that will trigger an action potential in every axon of the nerve. Then, at some distance from the stimulating electrode, the resulting signal is measured. (In these tests, both the stimulating electrode and the recording electrode are extracellular; the recording electrode is actually measuring small changes in voltage that occur in the extracellular fluid near a neuron when it fires an action potential.)  The electrical signal recorded will be the summed activity of all the axons in the nerve adjacent to the recording electrode.  Two things are looked at:  the latency (time between stimulus and arrival of the signal at the recording electrode) and the amplitude of the signal.  Electromyography (EMG) is another type of test in which a nerve is stimulated and the electrical response is recorded from the muscle.   

Neuropathy is the term that refers to disease or dysfunction of neurons.  Usually, when clinicians use the term neuropathy, they are talking about peripheral neuropathy, which is damage or dysfunction in peripheral nerves.  Peripheral neuropathy can occur due to problems with myelin (demyelinating peripheral neuropathy), or it can be due to neuronal degeneration (axonal peripheral neuropathy), or it can be a combination of the two.  Polyneuropathy is when the disorder is generalized, affecting multiple nerves.

The diagnosis for Ms. Q is diabetic neuropathy, which is considered an axonal neuropathy. The most common pattern seen with diabetic neuropathy is a diffuse polyneuropathy in which there is generalized symmetric dysfunction, primarily affecting distal sites (the hands and feet), because the longest axons are affected first.  For this reason, the symptoms of diabetic neuropathy are said to have a "glove and stocking" distribution.

The pathogenesis of diabetic neuropathy is complicated and not entirely understood. In diabetes mellitus there is chronic hyperglycemia due either to a lack of insulin or decreased insulin action.  Hyperglycemia causes various biochemical changes that are toxic for cells. Peripheral nerve fibers that innervate the hands and the feet seem to be particularly vulnerable because the nerve terminals are quite distant from the neuronal cell bodies. Hyperglycemia also damages the circulatory system. So poor blood flow to distal axons and nerve terminals could also be a factor that contributes to diabetic neuropathy.

Numbness is due to loss of touch sensitive afferent neurons. Abnormal sensations such as tingling and burning are called paresthesias.  Another phenomenon that is common with diabetic peripheral neuropathy is allodynia.  Allodynia is when a normally non-painful stimulus, such as touch, is felt as painful.

Hemoglobin A1c (HbA1c) is a test that measures glycated hemoglobin.  Glycation is the nonenzymatic addition of sugar to proteins, which is greatly increased with the hyperglycemia that occurs in diabetes mellitus.  Testing of HbA1c is used to monitor glucose control in diabetics, and is also now used to diagnose diabetes.  The target HbA1c for a diabetic should be closer to 7%.  A normal value is less than 6%.

Here, "reflexes" refers to testing of the stretch reflex. "2+" is considered normal, while "trace" means a weak or absent reflex. "No Babinski signs" means there is not a positive Babinski sign.

The neurological examination reveals that Ms. Q has neuropathy primarily affecting sensory (afferent) neurons. Pinprick and cold are sensations that would be detected by A-delta and C fibers, which are the smallest diameter axons.  But vibration sense is also affected.  Vibration sense is tested by touching the handle of a vibrating tuning fork to the bone and counting how long it takes before the patient can no longer feel the vibration.

Because there is an effect on the stretch reflex at the ankles, other tests are done to see whether proprioception is affected in the patient.  Joint position sense is tested by having the patient look away and then determining whether she can tell which direction a toe is being moved.  Romberg's sign is when a patient becomes unsteady while standing with the feet together and the eyes closed.  A Romberg sign (unsteady with eyes closed) means a loss of proprioception.

Diabetic neuropathy is treated with various drugs to control symptoms of pain.  As well, it is very important to treat the diabetes effectively, to reduce hyperglycemia and slow the progression of nerve damage.  Although there is the potential for repair and regeneration in the peripheral nervous system, unfortunately there usually is very little recovery in patients with diabetic neuropathy.  This is probably because the disorder also leads to central nervous system changes in pain pathways.