Peripheral neuropathy

    Last updated date: 09-May-2023

    Originally Written in English

    Peripheral neuropathy

    Peripheral neuropathy


    Peripheral neuropathy affects around 2.4 percent of the population. In senior groups, the frequency rises to 8%. Peripheral neuropathy can be a symptom of a variety of illnesses that need additional assessment and/or treatment. Furthermore, peripheral neuropathies must be treated before they cause problems, such as falls that result in hip fractures or pedal infections that need amputation.

    Interprofessional team members must detect and assess peripheral neuropathy in order to address any underlying cause and prevent complications, hence improving patient outcomes.


    Peripheral neuropathy definition

    Peripheral neuropathies are abnormalities of peripheral nerve cells and fibers that appear as a result of a variety of illnesses. These nerves comprise cranial nerves, spinal nerve roots and ganglia, nerve trunks and divisions, and autonomic nervous system nerves.

    Peripheral neuropathies are classified using a variety of approaches, including mono-neuropathies, multifocal neuropathies, and poly-neuropathies. Further subclassifications can be created to distinguish peripheral neuropathies as axonal, demyelinating, or mixed, which is important for therapy and management.

    Numbness and paresthesia are the most common signs of peripheral neuropathy; pain, weakness, and loss of deep tendon reflexes may accompany these symptoms. Peripheral neuropathies often develop over months to years, while some may develop more quickly and be progressive. Peripheral neuropathies can impact motor, sensory, and autonomic fibers, resulting in a wide spectrum of severity and clinical symptoms.



    nerve fiber function

    Neuropathies are defined by the gradual loss of nerve fiber function. Diabetic peripheral neuropathy is defined as "the existence of symptoms and/or indications of peripheral nerve damage in patients with diabetes when alternative causes have been ruled out.

    Neuropathy is the most prevalent consequence of diabetes mellitus (DM), affecting up to 50% of type 1 and type 2 DM patients. Distal polyneuropathy in type 1 diabetes mellitus usually develops symptomatic after several years of chronic persistent hyperglycemia. Individuals with type 2 diabetes mellitus, on the other hand, may develop distal polyneuropathy after just a few years of recognized poor glycemic management; in some cases, these patients already have neuropathy at the time of diagnosis.

    Neuropathies have a significant impact on patients' quality of life. Furthermore, while the basic symptoms of neuropathy might be excruciating, the secondary problems (e.g., falls, foot ulcers, cardiac arrhythmias, and ileus) are even more significant and can result in fractures, amputations, and even death in diabetic patients.

    Because diabetic neuropathy can cause a wide range of sensory, motor, and autonomic symptoms, a standardized list of symptoms can be used to evaluate all diabetes patients for neuropathy. Patients with suspected distal sensory motor or focal neuropathies should have a physical examination that includes tests for peripheral and autonomic neuropathy.

    Multiple consensus committees propose that electrophysiologic testing be included in the assessment of diabetic neuropathy. An suitable battery of electrodiagnostic tests comprises nerve conduction testing as well as needle EMG of the most distal muscles that are often affected.

    Diabetic neuropathy should be managed from the time diabetes is diagnosed. The primary care physician must be on the lookout for the onset of neuropathy, as well as its existence at the time of diabetes diagnosis, because failing to recognize diabetic polyneuropathy can result in catastrophic repercussions such as incapacity and amputation. Furthermore, the primary care physician is in charge of teaching patients about the acute and chronic problems of diabetes.

    Diabetic peripheral neuropathy patients require more frequent follow-up, with a focus on foot examination to underline the importance of regular self-care.

    Tight and steady glycemic control is probably the most significant therapy for decreasing the progression of neuropathy. Many drugs are available to treat diabetic neuropathic pain, albeit the majority of them have not been expressly authorized for this use by the US Food and Drug Administration. Rehabilitation, which may include physical, occupational, speech, and recreational therapy, is an example of nonpharmacologic treatment. 



    Understanding the categorization of diabetic peripheral neuropathy can be aided by a review of the anatomy of the peripheral nerve system. Peripheral neurons are classified as motor, sensory, or autonomic.

    Motor neurons originate in the central nervous system (CNS) and extend to the spinal cord's anterior horn. They exit the spinal cord (through ventral roots) from the anterior horn and join with other fibers in the brachial or lumbar plexuses to innervate their target organs via peripheral nerves.

    Sensory neurons, like motor neurons, originate in the dorsal root ganglia (which are located outside the spinal cord). Sensory neurons are classified according to the sensory modality they communicate.

    Sympathetic and parasympathetic neurons make up autonomic neurons. Preganglionic fibers exit the CNS and synapse with postganglionic neurons in the sympathetic chain or sympathetic ganglia in the periphery. In DM, the smaller fibers are the first to be impacted. The bigger fibers are harmed as a result of continuous hyperglycemia exposure. Different forms of sensation are mediated by fibers of varying sizes.



    Peripheral nerve problems affect around 2.4 percent of the population; in older populations, the frequency rises to 8.0 percent. Diabetic neuropathy affects almost half of people with chronic type 1 and type 2 diabetes. Leprosy is still a prevalent cause of peripheral neuropathy worldwide, with the highest frequency in South East Asia.

    Charcot-Marie-Tooth disease, especially type 1a, is the most prevalent genetic sensorimotor polyneuropathy. Carpal tunnel syndrome is the most prevalent kind of mononeuropathy.



    Peripheral neuropathies can be caused by a number of factors, including metabolic, systemic, and toxic factors. Consider the following underlying etiologies:

    • Diabetes mellitus
    • Chronic alcoholism
    • Nutritional deficiencies (e.g., B1,B6, B12, vitamin E)
    • Inflammatory conditions (e.g., vasculitis)
    • Hypothyroidism
    • Autoimmune disease (e.g., Sjogren syndrome, lupus, rheumatoid arthritis)
    • Infections (e.g.,  Lyme disease, Epstein-Barr virus, hepatitis C, shingles, leprosy, HIV)
    • Guillain-Barre syndrome
    • Toxins (heavy metals, chemicals)
    • Chemotherapy agents
    • Medications (antibiotics, cardiovascular medications)
    • Tumors (secondary to compression or associated paraneoplastic syndromes)
    • Inherited conditions (e.g., Charcot-Marie-Tooth disease, familial amyloidosis)
    • Trauma/injury
    • Multiple myeloma and its treatments
    • Monoclonal gammopathy of undetermined significance (MGUS)

    In some cases, a direct cause may not be apparent.



    Pathophysiology of Peripheral Neuropathy

    The pathogenesis of peripheral neuropathy varies depending on the underlying condition. Although a diverse range of disorders can eventually lead to peripheral neuropathies, the methods by which peripheral nerves are injured follow a similar pattern. Segmental demyelination, as well as Wallerian and axonal degeneration, are examples of these responses.

    • Segmental Demyelination: This process refers to the degradation of the myelin sheath while the nerve axon is spared. This sort of response can occur in mononeuropathies, sensory neuropathies, and, most notably, motor neuropathies. These are frequently inflammatory and, in some cases, immune-mediated. Damage to the myelin accounts for around 20% of symmetrical peripheral neuropathies. Charcot-Marie-Tooth disease and neuropathy linked with monoclonal gammopathy of unknown significance are two examples.
    • Wallerian Degeneration: When a nerve axon degenerates as a result of a lesion or physical compression, the section distal to the axon wastes away passively, most likely owing to a lack of nutrition from the cell body. This response causes a focal mononeuropathy as a result of nerve damage or infarction.
    • Axonal Degeneration, also known as the dying-back phenomenon: This form of degeneration typically appears as symmetrical polyneuropathy (about 80%) and causes weakness, most notably weakness in dorsiflexion of the ankles and foot, with trophic alterations to muscle. The axon degenerates in a pattern that begins distal and advances proximally, which is assumed to be because the most distal region of the axon is most susceptible due to its distance from the cell body, which provides metabolic support. A suggested mechanism is that nerve injury impairs the supply of local axonal survival factors, resulting in a rise in intra-axonal calcium levels and a calcium-dependent cytoskeletal breakdown. Diabetes, HIV, HCV, and Guillain-Barre syndrome are examples of disorders that cause axonal degeneration.


    Clinical presentation 

    Peripheral neuropathy's clinical appearance

    Peripheral neuropathy's clinical appearance varies greatly depending on the underlying disease process. Patients may experience sensations that begin in their fingers and spread to their proximal limbs. Symptoms include sensory alterations, weakening, atrophy, discomfort, numbness, and even autonomic abnormalities. Clinically, these symptoms may be similar to those of myelopathies, radiculopathies, autoimmune illnesses, and muscular disorders.

    Deep tendon reflexes may be decreased or absent in advanced illness, as well as sensory loss in the stocking-glove pattern, muscular atrophy, and weakening. Obtaining a comprehensive history is critical in determining the root cause of the neuropathy. Aside from a thorough assessment of the patient's past medical history, doctors should question about toxic exposures, current and previous drugs, trauma, food and nutritional deficits, and alcohol use.


    Diabetic Neuropathy

    Diabetic neuropathy is the most prevalent consequence of diabetes mellitus (DM), affecting up to 50% of type 1 and type 2 DM patients. Diabetic peripheral neuropathy is defined as the existence of symptoms or evidence of peripheral nerve damage in diabetics after all other plausible causes have been ruled out. In certain circumstances, patients are sick for a long time before a basic clinical examination identifies abnormalities. Tight and steady glycemic control is probably the most significant therapy for decreasing the progression of neuropathy.


    Signs and symptoms of diabetic neuropathy

    Distal polyneuropathy in type 1 DM often manifests after several years of chronic protracted hyperglycemia, however in type 2, it may manifest after only a few years of recognized poor glycemic management, or even upon diagnosis. Among the symptoms are the following:

    • Sensory – Negative or positive, diffuse or localized; generally insidious in start and characterized by a stocking-and-glove distribution in the distal extremities.
    • Motor – Distal, proximal, or more focal weakness, sometimes occurring along with sensory neuropathy
    • Autonomic – Neuropathy affecting the cardiovascular, gastrointestinal, and genitourinary systems, as well as the sweat glands


    Physical examination should include the following assessments:

    • Peripheral neuropathy testing – Vibrational sense; deep tendon reflexes; strength testing and muscle atrophy; dorsal pedal and posterior tibial pulses; skin evaluation Tinel testing is a type of cranial nerve testing.
    • Autonomic neuropathy testing – Objective assessment of cardiovagal, adrenergic, and sudomotor function in a dedicated autonomic laboratory; may be preceded by bedside screening to check supine and upright blood pressure and heart rate, with sinus arrhythmia ratio measurement.



    Diagnosis of Peripheral Neuropathy

    A complete history and physical examination, as well as a review of current and previous medicines, are required when evaluating individuals with neuropathy. Although there are no standard laboratory or imaging investigations to screen for peripheral neuropathies, the following studies may aid in the diagnosis and help narrow down the underlying etiology (e.g., inflammatory, infectious, or metabolic) of the neuropathy:

    • Complete Blood Count: Macrocytic anemia may indicate a vitamin B12 or folate deficit, or even alcoholism.
    • HbA1c Testing (Diabetes is a common cause of neuropathy)
    • Testing for vitamin and mineral deficiencies, including copper, thiamine, pyridoxine, folate, B12, and vitamin E, all of which play important roles in nervous system development and maintenance.
    • Heavy metal toxicities such as mercury, lead, arsenic are known to cause peripheral nerve toxicities along with CNS disturbances. 
    • Infectious workup for Lyme disease, Epstein-Barr virus, hepatitis C, HIV, and syphilis as a long-standing disease may manifest with peripheral neuropathies and paresthesias. 
    • Thyroid function testing. 
    • Anti-body testing for specific autoimmune diseases known to cause peripheral neuropathies such as Sjogren syndrome, lupus, rheumatoid arthritis. 
    • Nerve conduction study and electromyography (EMG)
    • MRI or CT scans in cases where compression of the nerve is of concern
    • Nerve biopsy
    • Genetic testing (for inherited neuropathies)
    • Urine Test (looking for Bence-Jones proteins as multiple myeloma and its treatments can cause peripheral neuropathy)



    The therapy of peripheral neuropathies should focus on the underlying illness mechanism. For example, in diabetic neuropathy, glucose management is important, as is abstaining from alcohol in alcoholic neuropathy. Nutritional deficiencies can be treated by supplementing deficient vitamins or minerals. Regrettably, not all peripheral neuropathies can be reversed.

    Physical and occupational therapy may be initiated to improve a patient's overall strength and function. Chronic inflammatory demyelinating neuropathy is first treated with corticosteroids, although it can also be treated with intravenous immunoglobulin, plasma exchange, and other immunosuppressive drugs.

    Patients suffering from neuropathic pain may benefit from a referral to a pain expert. Simple analgesics do not usually relieve neuropathic pain, especially in people with small-fiber neuropathies. Instead, membrane stabilizers, some anti-epileptics, and tricyclic antidepressants can be used to alleviate pain associated with peripheral neuropathies. Transcutaneous electrical nerve stimulation (TENS) is another noninvasive pain treatment alternative. 


    Management of diabetic neuropathy

    Management of diabetic neuropathy

    Key components of the management of diabetic neuropathy include the following:

    • Foot care, including regular follow-up, patient education, and referral if needed
    • Glycemic control that is tight and consistent (most important for slowing progression of neuropathy)
    • Pain control (eg, with pregabalin, gabapentin, sodium valproate, dextromethorphan, morphine sulfate, tramadol, oxycodone, duloxetine, topical capsaicin, transdermal lidocaine)
    • Diabetic gastroparesis management (eg, with erythromycin, cisapride [not available in the United States], metoclopramide, polyethylene glycol 3350, tegaserod [currently available only on an emergency basis])
    • Experimental treatments include aldose reductase inhibitors, alpha-lipoic acid, actovegin, and spinal cord stimulators.


    Treatment of autonomic dysfunction must address the following:

    • Erectile dysfunction
    • Orthostatic hypotension
    • Gustatory sweating


    Surgical treatment may be considered as follows:

    • For intractable foot necrosis or infection, aggressive debridement or amputation may be required.
    • Intractable gastroparesis requires a jejunostomy.
    • Implantation of a penile prosthesis to treat persistent impotence
    • Bracing, special footwear, or, in certain circumstances, surgery are all options for Charcot foot.
    • Diabetic patients with end-stage renal failure may benefit from pancreatic transplantation.



    When peripheral nerves are damaged due to Wallerian or axonal degeneration, the prognosis is poor since nerve repair is more difficult. In order for clinical improvement to occur, the axon must regenerate and reinnervate the afflicted muscle or organ. The prognosis of disorders caused by segmental demyelination is better because remyelination occurs more quickly, enabling the axon to resume function.

    People with untreated or improperly managed diabetes have greater rates of morbidity and complication from neuropathy than patients with carefully controlled diabetes. Repetitive trauma to afflicted regions can result in skin breakdown, ulceration, and infection. Amputations and death are possible outcomes.

    Diabetic neuropathy treatment is a demanding endeavor for both the physician and the patient. The majority of the medications listed in the Medication section do not provide complete symptom relief. Clinical trials are being conducted to aid in the discovery of novel methods of treating symptoms and delaying disease development.

    People with cardiovascular autonomic neuropathy have a higher mortality rate (CAN). Over a 10-year period, the total death rate in individuals with DM and CAN found was 27%, compared to a 5% mortality rate in those without evidence of CAN. Foot ulceration and lower-extremity amputation cause morbidity. In Western nations, these two problems are the most prevalent reasons for hospitalization among patients with diabetes. Severe pain, disorientation, diarrhea, and impotence are frequent symptoms that reduce a diabetic patient's quality of life. The prognosis for diabetic peripheral neuropathy is excellent, although the patient's quality of life is diminished.



    Pain, impaired sensation, muscular atrophy, and weakness are all complications of peripheral neuropathies. Diabetic peripheral neuropathy is notorious for consequences such as foot ulcers, which can lead to gangrenous digits and limbs and, in severe cases, amputation.


    How can I help prevent diabetic neuropathy?

    The following steps may help to prevent or slow the worsening of diabetic neuropathy:

    • Control diabetes by attempting to maintain blood sugar levels normal.
    • Maintain appropriate blood pressure levels.
    • Exercise on a regular basis, as directed by your healthcare physician.
    • Quit smoking.
    • Limit your alcohol consumption since too much alcohol might cause or worsen neuropathy.
    • Maintain a healthy weight by eating a nutritious food and avoiding high triglyceride levels in the blood.
    • Maintain follow-up appointments with your healthcare practitioner.



    Neuropathies may be very painful and incapacitating for individuals. As a result, it is critical to obtain an early diagnosis of the underlying ailment, followed by the beginning of suitable treatment(s) to reverse, delay, or stop the disease's course. As evidenced in the instance of diabetic neuropathy, identifying individuals at high risk for neuropathies and taking a preventative strategy to their care will surely enhance patient outcomes. Because primary care providers and nurse practitioners are frequently the first to work up these patients, it is critical that they are familiar with the full range of etiologies that can contribute to the development of peripheral neuropathies, including testing and referrals to appropriate specialists.


    Patients must be educated about the symptoms and indicators of peripheral neuropathy. Patients should be informed that they are at a higher risk of harm owing to lack of feeling, and they should be aware of any new wounds or damage to their skin since wound healing can be delayed and infection risk increases. To reduce the risk of infection, always wear socks with closed-toed shoes.

    To avoid burns and frostbite, patients should exercise caution while exposing themselves to hot or cold settings. Diabetes patients should get adequate diabetes management guidance. Patients suffering from alcohol-induced neuropathy should seek advice about quitting.