Peripheral Neuropathies

The nervous system consists of two components: the central nervous system, consisting of the brain and spinal cord, and the peripheral nervous system made ​​up of nerves that connect the central nervous system (CNS) to the muscles, skin and internal organs. The Peripheral neuropathies are a heterogeneous group of disorders that affect the peripheral nerve fibers.
The basic unit of the peripheral nervous system is the nerve cell or neuron. Each neuron consists of a cell body and a long extension, called axon, leading pulses between the cell body and the periphery, where it comes into contact with the receptors, specialized structures, present in the muscles, in the skin and internal organs. Many axons are surrounded by a membrane, the myelin sheath, which allows electrical impulses to be transmitted more quickly and efficiently. The axons traveling together united in nerve trunks, that go through the human body such as cables of a complex electric circuit. Then the task of neuron is to send information from one part of the body through electrical impulses.

We can distinguish three types of nerves depending on the type of fibers which contain:

  • Motors – They are responsible of voluntary movements
  • Sensory – They allow us to feel pain, vibration, touch, to recognize the shapes of objects just by touching them, and to know the location of parts of our body in space
  • Vegetative or autonomic – They controls involuntary functions (ie not under the control of the will), such as breathing, heartbeat, blood pressure, digestive and sexual functions. They work always, independently, both when we wake and when we sleep

Many neuropathies affect, in several degrees, all three types of nerve fibers, but in some cases only one or two types of fibers are interested in so we distinguish a purely or predominantly motor neuropathy, sensory or autonomic.


The neuropathies can be classified into:

  • Mononeuropathies – They affect individual peripheral nerves in well-defined areas and are often a result of a traumatic injury, a local compression, with compression of the nerve, or inflammatory or ischemic events. The symptoms are, therefore, localized and restricted to the innervation territory of the injured nerve. Examples of mononeuropathies are the entrapment neuropathies (eg, Carpal tunnel Syndrome), and Bell’s palsy, a disorder of cranial nerve VII (the facial nerve), which contains motor fibers to the facial muscles of the face and vegetative fibers. In most cases you do not know the cause of this disorder, which is manifested by asymmetry of the lips (you have “crooked mouth”) and difficulty to close the eye on the same side. They can sometimes be associated with hearing disorders (hyperacusis) and taste disorders. In most cases the deficit recovers spontaneously in more or less long periods (from one to five months or more) depending on whether the damage has affected only the myelin sheath or even the axon.
  • Multiple mononeuropathy – If the symptoms affecting simultaneously or at different times two or more nerves in separate areas. This occurs, generally, in the course of systemic diseases, such as diabetes or rheumatological diseases.
  • Polyneuropathies – They represent the majority of peripheral neuropathies, and refers to a bilateral and symmetrical involvement of peripheral nerves, that is affects, in a similar manner both sides of the body. Generally disorders begin in the hands and feet. Depending on which nerves are affected (motor, sensory or both), it is called motor neuropathy, sensory, or mixed.

Causes and Symptoms

The causes of neuropathy are varied. Depending on the origin, neuropathies can be classified as:

  • Hereditary – They are caused by genetic abnormalities
  • Acquired – They constitute the majority of neuropathies and are due to diseases acquired in the course of life, metabolic factors, oxidative stress of nervous tissue, trauma, infection and inflammation.
  • Idiopathic – When the cause of the neuropathy is unknown. Depending of its manifestations, also the idiopathic neuropathy can be sensory, motor, or mixed.

Some peripheral neuropathies begin quite suddenly, others gradually over years. The symptoms depend on the type of nerve fibers affected and by their localization and are constituted by a general motor disability of patients, but in most cases occur with:

  • Muscle weakness and fatigue – These symptoms are due to an alteration of the motor nerves. Depending of the involvement of lower or upper limbs, may occur easily fatigued and feeling of “heaviness” in the limbs.
  • Numbness, tingling, pain – A lesion of the sensory nerves can cause symptoms very different. There may be paraesthesias, which include numbness, tingling, pins and needles sensation, or pinching, itching, burning, cold, sharp and profound pains, and deep electric shock. These disorders often worsen at night. You can also have unpleasant sensations triggered by tactile stimuli (dysesthesia) or decrease (hypoesthesia) and disappearance (anesthesia) of sensation, which may mean that you cut or scald without realizing it.
  • Absence of the sense of position – In presence of this disorder, you are not sure where are exactly your feet and can occur incoordination and insecurity in walking. You can see that the way of walking has changed, you can drag your feet, or the gear widens in an unconscious attempt to maintain balance.
  • Feeling of “gloves” and “socks” – You feel like you’re wearing gloves, socks or slippers, while instead hands and feet are completely bare.
  • Symptoms of damage to the autonomic fibers – A lesion of the autonomic fibers may cause dizziness when you are standing, constipation, diarrhea, sexual dysfunction, and thinning of the skin, easy to bruise and difficulty in wound healing.

Neuropathic pain is pathological as it is characterized by an amplification process of nociceptive messages that can occur in both the peripheral and central nervous system. Unlike somatic pain, which comes from nerve endings and pain receptors located in the skin that is felt through tissue damage, neuropathic pain comes directly from nerve dysfunction and does not imply a damage in progress. Neuropathic pain is associated with several types of sensors, signs and symptoms that may occur alone or in conjunction with other specific manifestations. Among the various pathogenetic mechanisms postulated and demonstrated at the base of the signs and symptoms of peripheral neuropathies mechanical, may include alteration of sodium channels (diabetic neuropathy), hyperexcitability of neurons, sudden changes in the spinal connectivity, high oxidative stress of nervous tissue. Also the mediators of inflammatory processes appear to have a specific role in the onset of degenerative and inflammatory neuropathies. In summary, the causes of painful symptoms of upper and lower limbs are numerous and of various origins, and may be of interest to orthopedic (myalgia, compressive or traumatic neuropathies). In fact, a significant percentage of these pain syndromes of the limbs are due to a mechanical compression, of different origin, acting on a nerve root (radiculopathy by irritation or compression), as regards cervical area in the case of the upper limbs (cervical brachial pain), and lumbosacral as regards the lower extremities (low back pain), the most common cause of which is represented by slipped disc.


From a diagnostic point of view, it is important to perform a careful clinical examination of the patient and investigate, through specific questionnaires in detail the type of symptoms, previous and/or concomitant diseases of patient, search for possible causal factors traumatic, occupational, outcomes of surgical interventions, nutritional deficiency (vitamin B1, B6, B12), toxic, ischemic, paraneoplastic factors. Other tests useful for diagnosis are represented by laboratory tests and electrophysiological investigations such as electromyography (EMG) for the study of conduction sensory/motor nerve fibers and to search for signs of denervation. The CT scan and MRI are also able to confirm the diagnostic suspects in cases of low back pain and cervical brachial pain, also the presence of osteophytes and/or arthritic alterations in the joints or vertebral bodies. The nerve biopsy can sometimes provide important information on the type and cause of the neuropathy. You can see, in fact, if the nerve shows signs of vasculitis, inflammation or amyloid deposition.
A lumbar puncture may be useful to detect the presence of infection or inflammation, and some analysis of blood and urine tests can help to identify underlying diseases or genetic defects that cause neuropathy.

Acquired neuropathies

Entrapment Neuropathies

Hereditary Neuropathies

The hereditary neuropathies are caused by genetic defects that are transmitted from generation to generation. For many of these, the genetic defect is known and diagnostic tests are available.

  • HSMN (Hereditary Sensory Motor Neuropathy) or Charcot-Marie-Tooth Disease (CMT)
    They are the most common hereditary neuropathies. Once they were defined Charcot-Marie-Tooth disease, but have recently been reclassified as HSMN (Hereditary Sensory Motor Neuropathy). We distinguish different subtypes based on clinical features and genetic alterations. La HSMN type 1 is the most common. It is a demyelinating neuropathy in slow evolution, often associated with abnormalities of the foot (pes cavus).
  • Amyloidotic family Neuropathy
    The amyloidotic family neuropathy presents with sensory disturbances and autonomic nervous system alterations (diarrhea, impotence, etc.). It is due to a mutation in a protein called transthyretin. The abnormal protein is deposited as amyloid in the peripheral nerves, causing damage.
  • Neuropathies during porphyria
    The porphyria (an inherited disease by altered porphyrin metabolism) is associated with peripheral neuropathy, predominantly motor.

Treatment of Neuropathies

The primary aims of treatment are two: eliminate the cause of the disease and reduce symptoms. For example, a vitamin deficiency can be corrected with oral or parenteral administration of vitamin deficit. Infections are treated with antibiotics or anti-viral agents. Autoimmune diseases often respond to plasmapheresis, immunosuppressive or immunomodulatory therapies (corticosteroids, intravenous immunoglobulin or chemotherapy). In paraneoplastic neuropathies (which are associated and sometimes precede the appearance of a cancer), treatment is aimed to eliminate the underlying cancer. The toxic or drug-induced neuropathies are treated by removing the causative agent. In diabetes, a careful control of hyperglycemia helps to slow the progression of neuropathy. Depending on the cause of the neuropathy, therapy can alleviate, slow down or cure the neuropathy. Once the damage is blocked, the nerve can regenerate. The degree of recovery depends on how severe the damage was. Minor damage was, the better is the recovery. It is therefore extremely important an early diagnosis, which allows a rapid start of treatment .
For the reduction of the symptoms of neuropathy, it is important to reduce pain and muscle weakness. Physical therapy and their supports may help in maintaining muscle strength and improve the “motor performance”. Generally, although the neuropathic pain responds poorly to treatment with NSAIDs or analgesics, these classes of drugs are however equally and widely used in these diseases. The most correct approach, which results from various studies and clinical research, seems to be that multidisciplinary which provides a therapy with anti-inflammatory drugs, analgesics, or SSNRI o SSRI antidepressants, anticonvulsants. Some drugs (antidepressants SSNRI, weak opioids, tricyclic antidepressants) may be used as first-line therapy, then following, as second-line drugs, anticonvulsants, antidepressants, topical agents, opioids, and nutritional supplements. Among other medications used, anti-epileptics have been shown to reduce neuronal hyperexcitability through various mechanisms that interfere with the excitatory neurotransmitter activity. The therapy also includes the use of neuroprotective drugs, such as alpha-lipoic acid, which have an antioxidant activity, so as to improve nerve conduction velocity and endoneural blood flow, thereby reducing the pain and hypo-dysesthesia. The involvement of the oxidation processes (ROS, Reactive Oxygen Species) in the onset and worsening of neuropathic pain has been demonstrated in numerous studies that have confirmed that oxidative stress is an important determinant of degenerative and painful pathological conditions of peripheral nerves. Infact the various oxidative reactions seem involved in nociceptive painful and sensitization signaling cascade typical of neuropathic pain. In view of these findings, the role of alpha-lipoic acid lies in its strong antioxidant activity able to neutralize the oxidative reactions and to reduce the oxidized forms resulting from other factors; among its features it is interesting to note that the alpha-lipoic acid is soluble in both water and lipid, which makes it unique among antioxidants. Numerous clinical studies have demonstrated the efficacy of alpha-lipoic acid on improving the parameters of signal conduction of peripheral nerves involved in neuropathies, with an increase in nerve function. Other studies have demonstrated efficacy in patients with peripheral neuropathies, in which it has significantly improved the painful symptoms.

RSS Journal of Orthopedic Trauma