What Is Neuropathy?
Neuropathy is a general term for any disorders of the central and peripheral nervous system. It encompasses the conditions of
- Polyneuropathy: In which the same process affects many nerves, especially peripheral nerves;
- Mononeuropathy: Which is isolated involvement of a single nerve due to trauma, compression, or entrapment (e.g., carpal tunnel syndrome);
- Mononeuropathy multiplex: Referring to more than one nerve trunk involvement, usually due to compression or an inflammatory vascular cause.
Diseases of the central nervous system (malignancy, stroke, or spinal lesion) can present with similar symptoms, making diagnosis difficult.
Causes of Neuropathy
- Kidney disease (uremia)
- HIV infection
- Vitamin deficiencies (B12, folate)
- Lyme disease
- Autoimmune diseases (Guillain-Barré Syndrome)
- Toxicity (alcohol, chemotherapy, metals)
- Hereditary (Charcot-Marie-Tooth disease
- Mechanical injury (vibration-induced, e.g., construction jack-hammers, etc.)
- Prolonged cold exposure
Signs and Symptoms
Signs and symptoms of neuropathy include sensory loss, usually distally–hands, feet, fingers, toes, and burning sensation, pain, or weakness. Weakness and sensory loss can occur simultaneously when the nerves involve have mixed motor and sensory functions. In many neuropathies, the longer nerves are affected first, which is why nerves of the feet may offer the first presentation of neuropathy. The neuropathy related to the longest nerves can present as a “stocking and glove” distribution pattern, which can then extend when severe.
Depending on the cause, neuropathy can stabilize and even improve, but typically progresses slowly over years. Acute neuropathy from toxic exposure can worsen over a few weeks, stabilize, and then recover slowly over months.
The speed of conduction of some nerves depends on an insulating coating (myelin), and when a neuropathy involves destruction of this coating, nerves for movement are mostly involved, presenting as weakness. Chronic injury related to length of the nerves, such as in diabetes, will present with sensory loss and paresthesia (tingling, numbness, burning) first, then motor symptoms of weakness.
How Is Neuropathy Diagnosed?
The diagnosis of neuropathy is based on an in-depth history and a thorough physical exam, including a neurological exam, blood tests, and electrodiagnostic testing. The more obvious the cause, the less necessary are extensive diagnostic procedures. For example, a diabetic patient with foot pain neuropathy may not require a full evaluation that includes nerve conduction studies or electromyography (EMG).
Pertinent Medical History
The onset, progress, nature, and distribution of neuropathy, reported by the patient, can classify the complaints as to the type of neuropathy that is present. Family history can indicate a possible hereditary influence that predisposes an individual. Most importantly, the history is crucial to tell apart the polyneuropathy syndromes (same illness affecting many nerves) from mononeuropathy multiplex (multiple compressions of unrelated nerves). If neuropathic symptoms are from higher up, i.e., the central nervous system, a history can distinguish signs and symptoms of a stroke.
The history also can highlight suspicions of toxicities that cause neuropathy, such as drugs (both prescribed and illicit abuse) and environmental causes (work-related chemical exposure). During the medical history, illnesses that figure prominently in neuropathy are all reviewed, from diabetes to Lyme disease.
The difference between signs and symptoms is that signs are objective observations, such as blood pressure or pulse, whereas symptoms are subjective complaints from the patient, such as tingling. For the diagnosis of neuropathy, the signs are more reliable than symptoms, unless there are many of them that cluster about a common syndrome. Isolated symptoms are not particularly helpful.
Signs during a physical exam, however, take advantage of the fact that the human body is generally symmetric and, with the exception of one’s dominant hand, is generally balanced as to strength. Even taking a dominant hand into account, reflexes and sensitivity to tactile stimuli (pinprick, vibration, temperature, feather, etc.) can easily indicate when one side or one part is weak, hypersensitive, or has decreased sensitivity. These techniques are part of a neurological evaluation during the physical exam.
Since late syphilis results in both central and peripheral neuropathy, a screening test for it is indicated when there are problems with walking; the false positives in the screening can be eliminated with definitive testing for its specific antigen. Hepatitis B and C antigens can be identified. Chronic inflammatory states can be identified by tests for inflammation such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Measurements of heavy metals can be done by testing the blood, as can antibodies associated with neuropathy (hepatitis C, herpes) and vitamin levels. Blood tests are also useful in identifying systemic disease that correlate with neuropathy. Besides the obvious glucose measurements used in diabetes, tests for uremia (kidney illness) can be useful in identifying such a cause or in ruling it out.
Electrodiagnostic testing is indicated when there is suspicion of polyneuropathy, there is no reliable cause elicited from the history and physical exam, or when signs and symptoms progress rapidly or become severe. It is also useful when there is obvious asymmetry or predominantly motor abnormalities (as opposed to sensory). Nerve conduction studies and electromyography can determine conduction speeds of the nerves and can identify partial or complete blocks of the transmission signals.
Management of Neuropathy
Management of neuropathy centers on treating the underlying process, when one is identified.
Diabetes: if the cause is diabetes, strict glycemic control and maintaining a target hemoglobin A1c level (<7%) will not only control hyperglycemia which impacts the nerves directly and indirectly (by affecting blood supply to the nerves–vasculitis), but will also control symptoms and delay or prevent progression of the neuropathy.
Demyelination disease: immunological conditions such as multiple myeloma and cranial nerve loss of the insulation around nerves (“demyelination”), which decreases the speed of conduction, can be treated with immunologic therapy, which includes anti-inflammatories (corticosteroids) and intravenous immune globulin.
Toxic exposure: treatment relies on removal of the individual from the toxin, be it a suspect medication or an environmental (work-related) danger. In cases of heavy metal toxicity, using chelating agents (chemicals that bind metals in the blood for excretion) may be used.
Neuropathy due to infections which cross-react with peripheral nerves (e.g., Guillain-Barré syndrome) can be treated, when severe enough to cause neuromuscular respiratory failure, with plasma exchange and immunoglobulins. Support for ventilation, when the neuropathy is severe, may be necessary.
Nerve injury resulting in neuropathy is treated by inhibiting the transmission of signals from the damaged nerve. Anticonvulsants, primarily gabapentin and pregabalin, are used to decrease the conduction of pain signals from damaged nerves. Antidepressants can both subjectively lessen a person’s sensitivity to the perceived pain of neuropathy, but also directly impact the pain by adjusting the level of neurotransmitters that are involved (serotonin and norepinephrine). Anti-inflammatories (NSAIDs) are used if chronic inflammation contributes to the neuropathy.
Nerve compression initially can be treated by steroid injections to reduce inflammation, which may be the cause of the swelling creating the compression. More mechanical compressions, such as disc disease and bone displacement, can only be reversed by mechanical means, i.e, surgery to repair the anatomical distortion.
Asymmetric weakness can be addressed with the use of physical therapy, which not only strengthens the weak side of a unilateral weakness, but is used as an educational device to train patients in ways to move and position themselves to maintain the gains made during therapy.
Prevention of Neuropathy
Prevention of neuropathy depends on optimal management of predisposing conditions, such as diabetes. Once neuropathy emerges as part of a predisposing illness, management of that underlying cause can prevent advancement of the disease or mitigate its severity.
Pain is a large component of neuropathy, and its prevention is a cardinal feature of neuropathic management. For patients with neuropathic pain, pain can be prevented with anticonvulsants such as gabapentin and pregabalin. Antidepressants that impact the re-uptake of pain-related neurotransmitters, serotonin and norepinephrine, can be used as adjuncts. Narcotic agonist/antagonists (e.g., tramadol), low dose narcotics, or NSAIDs can be available for those who have breakthrough spikes of pain.
Interventional injections of anesthetic or steroids can prevent continued symptoms of neuropathy from compressive inflammation syndromes. When these fail, or if the compression is a mechanical distortion of the bone anatomy, a therapeutic or pre-emptive decompression via surgery can both eliminate the compression as well as prevent further damage to the nerves already involved.
For patients who do not benefit from the more conservative remedies that medical management or physical therapy hope to achieve, or who require multiple injections, nerve ablation via radiofrequency (thermal) destruction is useful if the nerves are purely sensory. (Destruction of motor nerve components may cause damage that cannot be healed or undone.)
The diagnostics used for neuropathy can be repeated serially to identify the severity of disease in hopes of preventing its progression.