Polyneuropathy

Polyneuropathy is a condition of the peripheral nerves that is not limited to the distribution of a single nerve or limb and is usually bilaterally symmetrical. Electrodiagnostic tests must always be carried out in order to classify the nerve structures impacted, as well as the location and severity of symptoms, and to aid in the identification of the cause. The goal of treatment is to eliminate the source of the problem.

Polyneuropathies that primarily affect motor fibers are known as polyneuropathies. They include the following:

• Immune-mediated illnesses such as Guillain-Barré syndrome and multifocal motor

• Lead toxicity

• Dapsone use

• Tick bite

• Porphyria

• Spinal muscular atrophy

Others mostly affect sensory fibers. They include the following:

• Dorsal root ganglions of cancer
• Leprosy
• AIDS
• Diabetes mellitus
• Chronic pyridoxine intoxication

The cranial nerves can be affected by a variety of conditions. They include the following:

• Guillain-Barré syndrome
• Lyme disease
• Diabetes
• Diphtheria

Polyneuropathy Symptoms and Signs

Depending on the etiology, polyneuropathy symptoms may occur quickly or grow slowly and become chronic. Polyneuropathies are frequently categorized by area of dysfunction because pathophysiology and symptoms are linked:

• Myelin
• Vasa nervorum
• Axon

Polyneuropathies can be inherited or acquired.

Myelin dysfunction

The most common cause of myelin dysfunction (demyelinating) polyneuropathies is a parainfectious immune response triggered by encapsulated bacteria (e.g., Campylobacter sp. ), viruses (e.g., enteric or influenza viruses, HIV), or vaccinations (eg, influenza vaccine). Antigens in these compounds are thought to cross-react with antigens in the peripheral nervous system, resulting in an immunological response (cellular, humoral, or both) and variable degrees of myelin damage.

Rapidly escalating paralysis and respiratory failure can occur in acute cases (e.g., Guillain-Barré syndrome). Symptoms of chronic inflammatory demyelinating polyneuropathy (CIDP) might recur or worsen over months or even years.

Large-fiber sensory abnormalities (paresthesias), severe muscle weakness higher than predicted for the degree of atrophy, and greatly reduced reflexes are all symptoms of myelin malfunction. It’s possible that the trunk musculature and cranial nerves are implicated. Demyelination affects the entire length of a nerve, resulting in both proximal and distal symptoms. There may be side-to-side asymmetries, with the upper body being affected first, and the lower body second. Muscle mass and tone have been preserved to a large extent.

Vasa nervorum compromise

Nerve infarction can be caused by chronic arteriosclerotic ischemia, vasculitis, infections, and hypercoagulable conditions that damage the blood supply to nerves.

Small-fiber sensory and motor impairment usually comes first. Sensory abnormalities are common in patients, and they are often unpleasant and burning. There is a lack of pain and temperature sensation.

Vasa nervorum involvement can begin as many mononeuropathies, which can look like polyneuropathy when many nerves are afflicted bilaterally. Early on in the condition, abnormalities are asymmetric and rarely impact the proximal one-third of the limb or trunk muscles. Except in diabetes, which affects the 3rd cranial (oculomotor) nerve and, slightly less commonly, the 6th cranial (abducens) nerve, cranial nerve involvement is uncommon. Symptoms and signs may become symmetrical later if nerve lesions consolidate.

Dysautonomia and skin changes (e.g., atrophic, glossy skin) are occasionally seen.
Muscle atrophy is usually proportional to muscle weakness, and reflexes are rarely lost totally.

Axonopathy

Axonopathies are distal in nature and can be symmetric or asymmetric.

Toxic-metabolic diseases are the most common cause of symmetric axonopathies. The following are some of the most common causes:

• Diabetes mellitus
• Chronic renal insufficiency
• Adverse effects of chemotherapy drugs

Nutritional deficiencies (most typically thiamin, vitamin B6, vitamin B12, or vitamin E) or excessive ingestion of vitamin B6 or alcohol can cause axonopathy. Hypothyroidism, porphyria, sarcoidosis, and amyloidosis are some of the less prevalent metabolic reasons. Other factors include diseases (e.g., Lyme disease), medications (e.g., nitrous oxide), and chemical (e.g., Agent Orange, n-hexane) or heavy metal exposure (e.g., Agent Orange) (eg, lead, arsenic, mercury).

Subacute sensory neuropathy is caused by the loss of dorsal root ganglia and their sensory axons in a paraneoplastic condition linked with small-cell lung cancer.

Symptoms of large- or small-fiber dysfunction, or both, may precede primary axon malfunction. The resulting neuropathy usually has a distal symmetric, stocking-glove distribution, affecting the lower extremities first and progressing symmetrically from distal to proximal locations.

Parainfectious or vascular diseases can cause asymmetric axonopathy.

Polyneuropathy Diagnosis

Patients with diffuse or multifocal sensory impairments, weakness without hyperreflexia, or both are suspected of having polyneuropathy. Multiple mononeuropathy could be the explanation if the symptoms are widespread yet started asymmetrically. Clinicians must obtain a detailed description of the beginning of symptoms from patients in order to identify whether symptoms began symmetrically or asymmetrically. Patients should be asked whether symptoms first emerged in one foot, then one hand, then the other foot (symmetrically) or whether symptoms first appeared in one foot, then one hand, then the other foot (asymmetrically).

Clinical data, notably the onset time, aid clinicians in diagnosing and determining the origin of polyneuropathy, as shown below:

Vasculitis is indicated by asymmetric neuropathies.

Distal neuropathies that are symmetrical point to a toxic or metabolic etiology.

Chronic neuropathies are slow-progressing neuropathies that can be hereditary or caused by long-term chemical exposure or metabolic abnormalities.

Acute neuropathies could be caused by an autoimmune condition, vasculitis, a toxin, an infection, or a postinfectious condition, as well as a drug or cancer.

In individuals with asymmetric axonal neuropathy, rashes, skin ulcers, and Raynaud syndrome reflect a hypercoagulable condition or parainfectious or autoimmune vasculitis.

A tumor or paraneoplastic syndrome is indicated by weight loss, fever, lymphadenopathy, and mass lesions.

Axonopathies should be considered in all polyneuropathy patients.

Electrodiagnostic tests

Electromyography (EMG) and nerve conduction studies are required regardless of clinical findings to diagnose the kind of neuropathy and assist clinicians in tailoring laboratory testing depending on suspected causes. EMG of both lower limbs should be performed at the very least to check for asymmetry and the whole amount of axon loss.

Nerve conduction investigations may be normal in patients with proximal myelin dysfunction (eg, early in Guillain-Barré syndrome) and in individuals with largely small-fiber dysfunction, save for prolonged F wave responses, because they assess mostly big myelinated fibers in distal limb segments. Depending on the presenting symptoms, quantitative sensory or autonomic testing or skin punch biopsies may be performed at specialized testing institutes.

Laboratory tests

For all patients, baseline laboratory testing include

• Complete blood count
• Electrolytes
• Renal function tests
• Rapid plasma reagin test
• Fasting plasma glucose, glycosylated hemoglobin (HbA1C), and sometimes a 2-hour glucose tolerance test are all used to diagnose diabetes.
• Vitamin B12 and folate levels
• Thyroid-stimulating hormone (TSH) level

Serum protein electrophoresis is used by certain practitioners, especially if a patient has a painful sensory neuropathy that is not caused by diabetes. The requirement for additional tests is decided on the type of polyneuropathy (large- or small-fiber). Tests for all subtypes may be required if EMG and clinical distinction are unclear.

The technique is the same for acute myelin dysfunction neuropathies as it is for Guillain-Barré syndrome; forced vital capacity is tested to rule out incipient respiratory failure. In the case of acute or chronic myelin failure, tests for viral illnesses and immunological dysfunction are performed, including hepatitis and HIV tests, as well as serum protein electrophoresis. A lumbar puncture is also recommended because myelin dysfunction caused by an autoimmune response frequently results in albuminocytologic dissociation, which is defined as an increase in cerebrospinal fluid protein (> 45 mg%) but a normal white blood cell count (less than 5/mcL).

Treatment of Polyneuropathy

When possible, polyneuropathy treatment focuses on eliminating the reasons, such as a causative drug or toxin, or treating a dietary deficiency. While these measures may reduce the advancement of the disease and alleviate symptoms, recovery is difficult and may be incomplete.

Treatment focuses on limiting impairment and discomfort if the cause cannot be remedied. Occupational and physical therapists can prescribe helpful assistive equipment. Neuropathic pain can be relieved with tricyclic antidepressants like amitriptyline or antiseizure medicines like gabapentin (eg, diabetic burning feet).

Immune system–modifying therapies are commonly utilized for myelin malfunctioning polyneuropathies:

For acute myelin impairment, plasma exchange or IV immune globulin are used.

For persistent myelin impairment, plasma exchange or IV immune globulin, corticosteroids, and/or antimetabolite medications may be used.

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