Polyneuropathy

Myelin dysfunction (demyelinating) polyneuropathies most often result from a parainfectious immune response triggered by encapsulated bacteria (eg, Campylobacter Campylobacter and Related Infections Campylobacter infections typically cause self-limited diarrhea but occasionally cause bacteremia, with consequent endocarditis, osteomyelitis, or septic arthritis. Diagnosis is by culture... read more sp), viruses (eg, enteric or influenza viruses Influenza Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those... read more , HIV Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more ), or vaccines (eg, influenza vaccine Influenza Vaccine Based on recommendations by the World Health Organization and the Centers for Disease Control and Prevention (CDC), vaccines for influenza are modified annually to include the most prevalent... read more ). Presumably, antigens in these agents cross-react with antigens in the peripheral nervous system, causing an immune response (cellular, humoral, or both) that culminates in varying degrees of myelin dysfunction.

In acute cases (eg, in Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more ), rapidly progressive weakness and respiratory failure may develop. In chronic inflammatory demyelinating polyneuropathy Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Chronic inflammatory demyelinating polyneuropathy is an immune-mediated polyneuropathy characterized by symmetric weakness of proximal and distal muscles and by progression continuing > 2 months... read more (CIDP), symptoms may recur or progress over months and years.

Myelin dysfunction usually results in large-fiber sensory disturbances (paresthesias), significant muscle weakness greater than expected for degree of atrophy, and greatly diminished reflexes. Trunk musculature and cranial nerves may be involved. Demyelination typically occurs along the entire length of a nerve, causing proximal and distal symptoms. There may be side-to-side asymmetries, and the upper body may be affected before the lower body, or vice versa. Muscle bulk and tone are relatively preserved.

Chronic arteriosclerotic ischemia, vasculitis, infections, and hypercoagulable states can compromise the vascular supply to nerves, causing nerve infarction.

Usually, small-fiber sensory and motor dysfunction occurs first. Patients typically have painful, often burning sensory disturbances. Pain and temperature sensation are deficient.

Vasa nervorum involvement (eg, caused by vasculitis or infections) can begin as multiple mononeuropathies, which, when many nerves are affected bilaterally, can look like polyneuropathy. Abnormalities tend to be asymmetric early in the disorder and rarely affect the proximal one third of the limb or trunk muscles. Cranial nerve involvement is rare, except in diabetes, which commonly affects the 3rd cranial (oculomotor) nerve and, slightly less commonly, the 6th cranial (abducens) nerve. Later, if nerve lesions coalesce, symptoms and signs may appear symmetric.

Dysautonomia and skin changes (eg, atrophic, shiny skin) sometimes occur.

Muscle weakness tends to be proportional to atrophy, and reflexes are rarely lost completely.

Axonopathies tend to be distal; they may be symmetric or asymmetric.

Symmetric axonopathies result most often from toxic-metabolic disorders. Common causes include the following:

Axonopathy may result from nutritional deficiencies (most commonly, of thiamin Thiamin Deficiency Thiamin deficiency (causing beriberi) is most common among people subsisting on white rice or highly refined carbohydrates in countries with high rates of food insecurity and among people with... read more , vitamin B6 Vitamin B6 Deficiency and Dependency Because vitamin B6 is present in most foods, dietary deficiency is rare. Secondary deficiency may result from various conditions. Symptoms can include peripheral neuropathy, a pellagra-like... read more , vitamin B12 Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more , or vitamin E Vitamin E Deficiency Dietary vitamin E deficiency is common in countries with high rates of food insecurity; deficiency among adults in other countries is uncommon and usually due to fat malabsorption. The main... read more ) or from excess intake of vitamin B6 Vitamin B6 Toxicity The ingestion of megadoses (> 500 mg/day) of pyridoxine may cause peripheral neuropathy. Vitamin B6 includes a group of closely related compounds: pyridoxine, pyridoxal, and pyridoxamine... read more or alcohol Alcohol Toxicity and Withdrawal Alcohol (ethanol) is a central nervous system depressant. Large amounts consumed rapidly can cause respiratory depression, coma, and death. Large amounts chronically consumed damage the liver... read more . Less common metabolic causes include hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more , porphyria Acute Porphyrias Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and... read more , sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , and amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more . Other causes include certain infections (eg, Lyme disease Lyme Disease Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early symptoms include an erythema migrans rash, which may be followed weeks to months later by... read more ), drugs (eg, nitrous oxide), and exposure to certain chemicals (eg, Agent Orange, n-hexane) or heavy metals (eg, lead Lead Poisoning Lead poisoning often causes minimal symptoms at first but can cause acute encephalopathy or irreversible organ damage, commonly resulting in cognitive deficits in children. Diagnosis is by whole... read more , arsenic, mercury).

In a paraneoplastic syndrome Paraneoplastic syndromes Lung carcinoma is the leading cause of cancer-related death in men and women worldwide. About 85% of cases are related to cigarette smoking. Symptoms can include cough, chest discomfort or pain... read more associated with small-cell lung cancer, loss of dorsal root ganglia and their sensory axons results in subacute sensory neuropathy.

Primary axon dysfunction may begin with symptoms of large- or small-fiber dysfunction or both. Usually, the resulting neuropathy has a distal symmetric, stocking-glove distribution; it evenly affects the lower extremities before the upper extremities and progresses symmetrically from distal to proximal areas.

Asymmetric axonopathy can result from parainfectious or vascular disorders.

Regardless of clinical findings, electromyography (EMG) and nerve conduction studies are necessary to classify the type of neuropathy and help clinicians tailor laboratory tests based on possible causes. At a minimum, EMG of both lower extremities should be done to assess for asymmetry and full extent of axon loss.

Because nerve conduction studies assess primarily large myelinated fibers in distal limb segments, they may be normal, except for prolonged F wave responses,in patients with proximal myelin dysfunction (eg, early in Guillain-Barré syndrome) and in patients with primarily small-fiber dysfunction. In such cases, quantitative sensory or autonomic testing, done at specialized testing centers, or skin punch biopsy may be done depending on the presenting symptoms.

Baseline laboratory tests for all patients include

Some clinicians include serum protein electrophoresis, especially if patients have a painful sensory neuropathy not explained by diabetes. The need for other tests is determined by polyneuropathy subtype (large- or small-fiber). When electrodiagnostic tests and clinical differentiation are inconclusive, tests for all subtypes may be necessary.

For acute myelin dysfunction neuropathies, the approach is the same as that for Guillain-Barré syndrome Diagnosis Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more ; forced vital capacity is measured to check for incipient respiratory failure. In acute or chronic myelin dysfunction, tests for infectious disorders and immune dysfunction, including tests for hepatitis and HIV and serum protein electrophoresis, are done. A lumbar puncture Lumbar Puncture (Spinal Tap) Lumbar puncture is used to do the following: Evaluate intracranial pressure and cerebrospinal fluid (CSF) composition (see table Cerebrospinal Fluid Abnormalities in Various Disorders) Therapeutically... read more should also be done; myelin dysfunction due to an autoimmune response often causes albuminocytologic dissociation: increased cerebrospinal fluid protein (> 45 mg%) but normal white blood cell count (≤ 5/mcL).

For vasa nervorum compromise or asymmetric axonal polyneuropathies, tests for hypercoagulable states and parainfectious or autoimmune vasculitis, particularly if suggested by clinical findings, should be done; the minimum is

CK may be elevated when rapid onset of disease results in muscle injury.

Other tests depend on the suspected cause:

An affected sural nerve is usually biopsied. A muscle adjacent to the biopsied sural nerve or a quadriceps, biceps brachii, or deltoid muscle may be biopsied. The muscle should be one with moderate weakness that has not been tested by needle EMG (to avoid misinterpretation of needle artifacts). An abnormality is more often detected when the contralateral muscle has EMG abnormalities, particularly when the neuropathy is somewhat symmetric. Nerve biopsies are useful in symmetric and asymmetric polyneuropathies but are particularly useful in asymmetric axonopathies.

If initial tests do not identify the cause of distal symmetric axonopathies, blood levels may be measured or a 24-hour urine collection may be done to check for heavy metals. Hairs or nails may be tested and may confirm heavy metals as the cause.

Whether tests for other causes are needed depends on history and physical examination findings.