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:
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:
The causes of neuropathy are varied. Depending on the origin, neuropathies can be classified as:
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:
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.
It is one of the most common causes of neuropathy, characterized by damage to the peripheral nervous system somatic or vegetative and is related to biochemical disorders caused by diabetes. The predominant symptoms are represented by pain, burning-pain symptoms, paresthesia and hypoesthesia, especially in the foot. The sensory symptoms predominate on the motor, appearing in more distal portions of the limbs and progressing proximally according to a “glove” or “sock” distribution. In any case the clinical symptoms are related to the type of nerve fiber involved. The pathogenesis of diabetic neuropathy is multifactorial, in agreement with the multiplicity of metabolic abnormalities that characterize diabetes, and therefore it is possible to formulate a series of hypotheses at the same time responsible for the clinical manifestations.Deficiency Neuropathy
They are caused by nutritional deficiency, eg. Vitamin B12, B1 (thiamin), B6 (pyridoxine) and vitamin E that determine polyneuropathy with axonal degeneration. The vitamin deficiency may be due to an inadequate diet or a problem of malabsorption in the stomach or intestine. Even excesses of vitamin B6 can cause neuropathy.Immune-mediated Neuropathies
The role of the immune system is to protect the body against infectious agents. Sometimes, however, for unknown reasons, the immune system attacks parts of the body causing the onset of autoimmune diseases. If the peripheral nerves are “attacked”, may develop immune-mediated neuropathies (ie caused by an alteration of the immune system). Among these are:
The alcohol abuse is a common cause of neuropathy. Other toxic substances that can damage the nerves are: Lead (motor neuropathy); arsenic, mercury (sensory neuropathy) ; organic solvents and insecticides.Neuropathies in course of systemic diseases
In addition to diabetes, many systemic conditions may be associated with neuropathy. Among these, chronic renal failure, liver disease, endocrine abnormalities (eg. hypothyroidism). Neuropathies may also occur in patients who are in intensive care units.Neuropathy by cancer
A neuropathy can result from a direct infiltration of nerves by cancer cells or by an indirect effect, at a distance, of the cancer (in the latter case it is called “paraneoplastic syndrome” and the neuropathy is associated with antibodies against the Hu protein). In patients with cancer, neuropathy can also be caused by local irradiation or be caused by drugs such as vincristine and cisplatin (“iatrogenic” neuropathies).Amyloidosis
The amyloid is a substance that is deposited in the peripheral nerves interfering with their function. The disease is called amyloidosis, and we can distinguish different types. In primary amyloidosis (which is often associated with monoclonal gammopathy or myeloma) amyloid deposits are composed of fragments of monoclonal antibodies, while in family amyloidosis (an hereditary neuropathies) amyloid deposits contain an abnormal form of a protein called transthyretin.Neuropathies by Infectious agents
Viruses or bacteria can cause neuropathies. Among the viruses that cause neuropathies there is Herpes Zoster virus; the AIDS virus (HIV-I), which cause different forms of neuropathy, including painful sensory neuropathies; cytomegalovirus, associated with poly-root neuritis quickly worsening, especially in immunocompromised individuals; also hepatitis B and C are sometimes associated with neuropathy. Among the bacterial infections that cause neuropathy include: borreliosis (or Lyme disease) caused by a spirochete; leprosy, which causes a sensory neuropathy; diphtheria, which causes a rapidly progressive paralytic neuropathy; and trypanosomiasis, caused by a parasite (there are, however, rare in our region).Neuropathies by Drugs
A number of drugs can cause neuropathy. Among these vincristine and cisplatin, used in anti-cancer therapy; nitrofurantoin, used in some chronic kidney diseases; amiodarone, used in cardiac arrhythmias; disulfiram, used in alcoholism; and dapsone, which is used in the treatment of leprosy.Neuropathies by trauma or compression/entrapment
Localized neuropathies can result from trauma or from external compression by tendons or other surrounding tissues. The most famous are the Carpal tunnel Syndrome, which results from compression of the median nerve at the wrist; the cervical and lumbosacral radiculopathy (low back pain) due to compression of the nerve roots at their exit point at the level of the spine. Other areas of frequent nerve compression are the elbow, armpit and the back of the knee.
It consists of the compression on the median nerve by the transverse carpal ligament or thickened by the structures contained therein. The pathogenesis involves a thickening of the tunnel by hypertrophy and/or calcification of the transverse carpal ligament, reducing the capacity of the container, or a tenosynovitis of the flexor tendons with increase in the “content” (chronic inflammatory rheumatism). The compression of the nerve may be secondary to overuse of the wrist or inflammatory processes; sometimes there are underlying conditions such as diabetes, rheumatoid arthritis, acromegaly. The symptomatology consists of a painful burning syndrome, paresthesia, hypoesthesia, until anesthesia of one or all the first three fingers of the hand.Guyon’s canal Syndrome
This is the compression/entrapment of the ulnar nerve in the bony-fibrous and neurovascular Guyon’canal, the tunnel that the ulnar nerve crosses to pass from the forearm to the hand (wrist). The Guyon’s canal has a floor formed by the bones of the wrist and the top made by a ligament, and in addition to the ulnar nerve, it contain the ulnar artery and vein. Coming out of the Guyon’s canal, the ulnar nerve divides into two branches that carry the stimulus for the movement of most of the muscles of the hand and provide the sensitivity to the little and ring fingers. In its passage through this canal, the nerve can be compressed.
The pathogenesis involves a compression by neoplastic growths or cysts, structural alterations of the vessels or vascular abnormalities, direct trauma, employment microtrauma, anatomical abnormalities, as well as inflammatory and degenerative changes of the closer synovial sheaths. The clinical picture is characterized by widespread pain in the wrist and in ulnar innervation territory, tingling sensation, numbness and decreased sensitivity of the ring and little fingers. In more advanced cases there is an aspect of a clawed hand and you can also detect a deep flexion deficit of the fourth and fifth fingers, for compromised of the abductor muscle of the little finger.
The ulnar nerve is compressed in the epitrochlear-oleocranon canal or cubital tunnel (elbow). Among the various causes, may include also the recurrent subluxation of the ulnar nerve during flexion-extension of the elbow, elbow osteoarthritis, rheumatism, elbow valgus and direct trauma or repetitive and frequent microtrauma. Clinically this syndrome has two phases. The first phase is characterized by paresthesias in the ulnar territory of innervation to the hand, the fourth and the fifth fingers. In the second phase there is a worsening of the tingling that becomes persistent and muscle disorders also occur with weakening until the paresis of the interosseous muscles and aggravation of sensory disorders, up to a real painful-thermo and tactile anesthesia in the sensory area of ulnar nerve. In advanced stages, the damage of the motor component also leads to a deficiency of abduction of the thumb, of the flexor carpi ulnaris and flexor digitorum profundus of the fourth and fifth fingers. The clinical evident sign is the cubital maneuvering positive, or the onset of pain and paresthesias in the ulnar innervation territory to the forced flexion of the elbow.Tarsal tunnel Syndrome
It is a compression of the posterior tibial nerve in the medial tarsal tunnel The syndrome is established for an alteration of the ratio content/containing this passage. It can be a result of fracture or dislocation of the ankle bone resulting in bony irregularities and/or perineural fibrosis and calcification, or sprain traumas of the ankle, with thickening or scar retraction of the fascial or ligamentous structures. It may be related to the presence of static functional abnormalities and dysmorphic foot, such as calcaneal varus and acquired flat foot, or to vascular abnormalities in this area, such as pseudo-aneurysm of the tibial artery or venous varicosities. It should also be reminded of the possible correlation with inflammatory diseases of the flexor hallucis longus and of the fingers tendons and the association with rheumatoid arthritis and connective tissue disorders. Secondary forms may be due to various subcutaneous neoformations such as, lipomas, tenosynovial and bony cysts, paresthesie of the ankle and sole of the foot medial side, exacerbated by standing and running and with a possible deficiency of flexion of the basal phalanx of the fingers.
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.
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.