Peripheral neuropathies encompass disorders of peripheral nerve cells and fibers which manifest secondary to a wide range of pathologies. These nerves include cranial nerves, spinal nerve roots & ganglia, nerve trunks & division, along with nerves of the autonomic nervous system. There are several methods used to classify peripheral neuropathies including categorizing them as mono-neuropathies, multifocal neuropathies, and poly-neuropathies. Further subclassifications can be made separating peripheral neuropathies as axonal, demyelinating, or mixed, which is essential for treatment and management purposes. The most frequently encountered symptoms of peripheral neuropathy include numbness and paresthesias; pain, weakness, and loss of deep tendon reflexes may accompany these symptoms. Peripheral neuropathies usually develop over months to years, while some may develop more rapidly and be progressive in nature. Peripheral neuropathies have a broad range of severity and clinical manifestations as they can affect motor, sensory, and autonomic fibers.
Peripheral neuropathies stem from a variety of origins including metabolic, systemic, and toxic causes. Underlying etiologies to consider include:
In some cases, a direct cause may not be apparent.
About 2.4% of the population is affected by peripheral nerve disorders; the prevalence increases to 8.0% in older populations. Diabetic neuropathy occurs in approximately half of individuals with chronic type 1 and type 2 diabetes. Globally, leprosy remains a common cause of peripheral neuropathy, with the highest prevalence in South East Asia.
The most common genetic sensorimotor polyneuropathy is Charcot-Marie-Tooth disease, specifically, type 1a. The most common mononeuropathy is carpal tunnel syndrome.
The exact pathophysiology of peripheral neuropathy is contingent on the underlying disease. Although a wide assortment of distinct diseases can ultimately lead to peripheral neuropathies, the mechanisms in which peripheral nerves suffer injury exhibit similar patterns. These reactions include segmental demyelination, along with Wallerian and axonal degeneration.
The clinical presentation of peripheral neuropathy widely varies depending on the underlying disease process. Patients may complain of symptoms initially starting in their digits, progressing to their proximal limbs. Symptoms range and include changes in sensation, weakness, atrophy, pain, numbness, and even autonomic disturbances. Clinically, these symptoms may resemble that of myelopathies, radiculopathies, autoimmune disease, and diseases of muscles. Advanced disease may progress to reduced or absent deep tendon reflexes, stocking-glove pattern sensory loss, muscle wasting, and weakness. Obtaining a thorough history is vital in helping to uncover the primary cause of the neuropathy. Aside from a meticulous review of past medical history, providers should inquire about toxic exposures, present and past medications, trauma, dietary and nutritional deficiencies, and alcohol use.
Evaluating patients with neuropathy involves a detailed history and physical including a review of current and past medications. Although there are no standard laboratory or imaging studies to test for peripheral neuropathies, the following studies may aid in the diagnosis and help narrow down the underlying cause of the neuropathy (e.g., inflammatory, infectious, metabolic):
Treatment of peripheral neuropathies should focus on the treatment of the underlying disease process. For example, glucose control in diabetic neuropathy, alcohol cessation in alcoholic neuropathy. Nutritional deficiencies can have therapy with supplementation of the depleted vitamins or minerals. Unfortunately, not all peripheral neuropathies are reversible. Physical therapy and occupational therapy can be initiated to aid in the improvement of a patient's overall strength and function. Chronic inflammatory demyelinating neuropathy is treated using corticosteroids initially, but can also be treated using intravenous immunoglobulin, plasma exchange, and some immunosuppressant drugs.
A referral to a pain specialist can be beneficial for those patients who are suffering from neuropathic pain. Neuropathic pain, particularly in those suffering from small-fiber neuropathies, do not typically respond to simple analgesics. Instead, effective treatment for pain associated with peripheral neuropathies can be with membrane stabilizers, certain anti-epileptics, and tricyclic antidepressants. Transcutaneous electrical nerve stimulation (TENS) is also an option as a noninvasive intervention for pain relief.
Differentials to consider greatly vary depending on clinical presentation. Symptoms of peripheral neuropathies may resemble that of myelopathies, radiculopathies, autoimmune disease, and diseases of muscles.
In those diseases where peripheral nerves suffer damage through Wallerian or axonal degeneration, the prognosis is poorer, as the recovery of the nerve is more challenging. For clinical improvement to take place, the axon must regenerate itself, and reinnervate the affected muscle or organ. The prognosis of diseases which occur secondary to segmental demyelination is more favorable because remyelination is achieved more quickly, allowing the return of function of the axon.
Complications of peripheral neuropathies include pain, altered sensation, muscle atrophy, and weakness. Diabetic peripheral neuropathy is infamous for complications including foot ulcers which can lead to gangrenous digits and limbs, sometimes progressing to amputation.
Consultations and referrals to consider for patients suffering from peripheral neuropathy include:
Patients require education on the signs and symptoms of peripheral neuropathy. Patients should be made aware that they have an increased risk of injury due to loss of sensation, they should be conscious of any new cuts or damage to their skin as wound healing can be delayed, and risk for infection increases. Recommend always wearing socks with closed-toed shoes to decrease the risk of infection. Patients should take caution when exposing themselves to hot or cold environments to avoid burns and frostbite. Patients with diabetes should receive counseling on managing their diabetes appropriately. Patients with alcohol-induced neuropathy should get information on cessation.
Demyelinating neuropathies are commonly inflammatory in nature and often treatable
Neurophysiological tests can differentiate axonal from demyelinating neuropathies
Peripheral neuropathy can be into divided into mono-neuropathies, multifocal neuropathies, and poly-neuropathies, with further subclassifications into axonal, demyelinating, or mixed type.
A wide range of disease processes can lead to peripheral neuropathies, which routinely requires a multidisciplinary team approach to diagnosis and treatment. This team should include physicians, specialists, specialty-trained nurses, and when necessary, pharmacists, all working collaboratively to achieve optimal patient care and outcomes. [Level V] Neuropathies can be both painful and debilitating for patients. Thus it is vital to acquire a prompt diagnosis of the underlying condition followed by the initiation of appropriate treatment(s) to reverse, slow, or stop the progression of the disease. Identifying patients most at risk for neuropathies and implementing a preventative approach to their care can undoubtedly improve outcomes for patients, as seen in the case of diabetic neuropathy. As primary care providers and nurse practitioner are often the first to work-up these patients, it is imperative that they are familiar with the full range of etiologies that play a role in the development of peripheral neuropathies, including testing and referrals to the appropriate specialists.
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