POSTED: 10/28/2022

Peripheral Neuropathy

Friday, October 28, 2022

What is peripheral neuropathy?

The nervous system is divided into two main sections, central and peripheral. The central nervous system encompasses the brain and spinal cord. From the spinal cord emerge spinal nerve roots. These form bundles of nerves referred to as the plexus which in turn gives rise to the peripheral nerves of the limbs. The peripheral nervous system encompasses the roots, plexus, and peripheral nerves. These nerves travel throughout the limbs and provide sensory input to the brain for interpretation and carry motor commands from the brain/spine to the limbs.

Peripheral neuropathy is a broad term that refers to dysfunction of the peripheral nerves. It does not imply a particular disease or etiology. And though the peripheral system starts at the root level, peripheral neuropathy typically implies dysfunction of the nerve endings rather then plexus or root. Disease of the plexus is referred to as plexopathy and disease of the nerve root is referred to as radiculopathy.

What are the types of peripheral neuropathy?

There are a variety of ways to approach the classification of peripheral neuropathy. To understand the most common classification scheme, a brief overview of the peripheral nerve anatomy is needed. On some level, nerves are like electrical wires. A wire has a metal core that conducts the electricity and a plastic insulation that surrounds the core. In a somewhat but not identical fashion, the nerve has a core referred to as the “axon” which carries electrical impulses. This axon is surrounded by a fatty insulating substance referred to as “myelin”. Unlike an electrical wire, the insulation of the nerve is not continuous and has breaks in it to allow for faster conduction of electricity. Thus, a neuropathy can be axonal, referring to damage of the nerve core, demyelinating referring to damage of the insulation, or mixed referring to damage of both the axon and myelin.

Another classification method employs the division of the nerve that’s involved. If the neuropathy damages primarily motor nerves, it is referred to as a motor neuropathy. Similarly, if it damages primarily the sensory fibers, it is called a sensory neuropathy. And if both are involved, the neuropathy is referred to as a sensorimotor neuropathy. Seldom, there is involvement of the autonomic nerves, nerves that we have no voluntary control over. These nerves handle functions such as blood pressure, heart rate, pupillary size, hair movement in the skin, sweating, satiety, erection, and ejaculation. This can be in isolation or in combination with motor or sensory neuropathy.

One third way to classify a neuropathy is by the nerve fiber type that’s damaged. Two main nerve fibers exist: small and large. The small fibers tend to be less insulated, transmit impulses slowly, and primarily handle sensation of pain and temperature. The large fibers on the other hand are heavily myelinated, transmit impulses faster, and handle fine touch, vibration, and proprioception. As such, a neuropathy can be a small fiber, large fiber, or a mixed small and large fiber polyneuropathy.

In clinical practice however, a combination of these classifications is frequently employed. For instance, a neurologist may refer to a neuropathy as a sensorimotor axonal or demyelinating polyneuropathy. The classification is not only descriptive, but can aid in isolating causes of neuropathy as some diseases affect the axon while other affect the myelin primarily.

What are the symptoms of neuropathy?

The symptoms of neuropathy can be classified as positive or negative. Positive symptoms in a way refer to excessive sensation such as tingling, burning, prickling, pain, sensitivity to touch/temperature, and cramping. Negative symptoms refer more to loss of function of the nerves such as numbness or weakness. Generally speaking, when treating neuropathy, positive symptoms respond favorably to medications, but negative symptoms respond very little if any at all. For instance, treating a patient experiencing primarily tingling is likely to be more successful than treating someone with numbness primarily.

What are the causes of neuropathy?

There are numerous causes of neuropathy. Some causes of neuropathy may be reversible while others result in permanent nerve damage. Causes of neuropathy also distinguish themselves in how rapidly they progress. Some neuropathies can develop over 1-2 weeks and can be life threatening while other can develop over years and be slowly progressive. As such, diagnosing the underlying etiology of the neuropathy is important to ensure the proper treatment is issued.

An oversimplification of the causes of neuropathy is the rule of thirds. One third of worldwide neuropathies are due to diabetes. Another third includes a variety of other causes reversible and otherwise. And a third of the time, a particular etiology is not found and this is referred as idiopathic neuropathy. In this category however, about half of those patients end up having an inherited neuropathy.

Diabetic neuropathy is by far the most common and typically develops after years of having diabetes, especially when poorly controlled. Rarely however, peripheral neuropathy onset can precede the diagnosis of diabetes. Another rare form of diabetes related neuropathy is referred to as insulin neuritis and typically occurs when someone’s long standing high blood glucose levels are rapidly corrected. Most of the time, the diabetic neuropathy is axonal as prolonged high blood glucose states result in axonal toxicity. Typically, a diabetic neuropathy is length dependent and therefore involves the toes first with onset of hand symptoms when the lower extremity involvement reaches the knees. Diabetic neuropathy can involve the autonomic nervous system which results in lightheadedness with standing, passing out, changes in sweating, early satiety, and erectile dysfunction to name a few.  

The following will be a non-comprehensive list of other causes of neuropathy. Certain cancers, lung in particular, can activate in the immune system strongly to where it also attacks the nerves of the body resulting in neuropathy referred to as a paraneoplastic neuropathy. Various nutritional deficiencies can cause neuropathy including but not limited to vitamin B12, folic acid, niacin, B6 (Pyridoxine), and copper. Increased levels of B6 can also cause neuropathy. Thyroid dysfunction and renal failure can cause neuropathy as well. Various infections, both sexually and non-sexually transmitted diseases, can cause neuropathy including but not limited to hepatitis C, HIV, syphilis, and leprosy. Various inflammatory conditions of the human body can cause neuropathy such rheumatoid arthritis, sarcoidosis, amyloidosis, and lupus.

Various blood line malignancies including multiple myeloma can directly injure nerves and cause neuropathy. One important cause to mention is medications, particularly chemotherapies and antibiotics, which can directly injure the nerve axon causing symptoms of neuropathy.

Lastly, genetic mutations can be passed on generation to generation and cause peripheral neuropathy though either poorly formed myelin, destruction of myelin, or poorly formed nerve axons. One common syndrome that comes to mind that is prevalent among French Canadians is Charcot Marie Tooth which is now referred as inherited sensorimotor neuropathy. Inherited neuropathies typically begin in childhood, are very slowly progressive, do not often include positive symptoms or pain, and are characteristically associated high arches, hammertoe deformities, and joint deformities.

Diagnosis and treatment?

Much like most neurological diseases, the diagnosis of neuropathy rests on the history and physical exam findings. However, a useful tool in not only confirming the diagnosis but classifying the neuropathy is a test called Electromyography and Nerve Conduction Study (EMG/NCS). This two-portion exam involves conducting the nerves to study the velocity of electrical impulse transmission as well as electromyography which is a study of the muscle activation in response to nerve signals. Other additional and at times helpful tests include skin/nerve biopsy and genetic testing.

The treatment of neuropathy begins with obtaining the correct diagnosis. Depending on the underlying etiology, the treatment of the neuropathy may simply be management of symptoms or more involved including chemotherapy, immunotherapy, or in some instance surgery. The first line symptomatic treatment is a class of medications referred to as Gabapentinoids such as Gabapentin and Pregabalin. Various antidepressants can be used in the treatment of neuropathy such as Amitriptyline and Duloxetine. Other used oral agents include antiseizure medications such as Oxcarbazepine, alpha lipoic acid, and rarely opioids. In addition to oral agents, topical creams can be used in isolation or in conjunction.


Oliver Achi, MD
 Medical Director of Neurology Services

Iberia Medical Center