Polyneuropathy

Polyneuropathy is a neurological disorder that occurs when many peripheral nerves throughout the body malfunction simultaneously. It may be acute and appear without warning, or chronic and develop gradually over a longer period of time. Many polyneuropathies have both motor and sensory involvement; some also involve dysfunction of the autonomic nervous system. These disorders are often symmetric and frequently affect the feet and hands, causing weakness, loss of sensation, pins-and-needle sensations or burning pain. There are quite a few conditions that can cause polyneuropathy.

Classification
Polyneuropathies can be classified in many different ways, such as by cause, by speed of progression, or by the parts of the body involved. It is also important to distinguish between classes of polyneuropathy according to which part of the nerve cell is mainly affected: the axon, the myelin sheath, or the cell body.
 * Distal axonopathy, or "dying-back neuropathy", is the result of some metabolic or toxic derangement of neurons. It is the most common response of neurones to metabolic or toxic disturbances, and as such may be caused by metabolic diseases such as diabetes, renal failure, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs such as chemotherapy. They can be further divided according to the type of axon affected: large-fiber, small-fiber, or both. The most distal portions of axons are usually the first to degenerate, and axonal atrophy advances slowly towards the nerve's cell body. If the cause is removed, regeneration is possible, though the prognosis depends on the duration and severity of the stimulus. Those with distal axonopathies usually present with sensorimotor disturbances that have a symmetrical "stocking and glove" distribution. Deep tendon reflexes and autonomic nervous system functions are also lost or diminished in affected areas.
 * Myelinopathy, or "demyelinating polyneuropathy", is due to a loss of myelin (or of the Schwann cells that make and contain it). This demyelination slows down or completely blocks the conduction of action potentials through the axon of the nerve cell. The most common cause is acute inflammatory demyelinating polyneuropathy (AIDP, the most common form of Guillain-Barré syndrome), though other causes include chronic inflammatory demyelinating polyneuropathy (CIDP), genetic metabolic disorders (e.g., leukodystrophy), or toxins.
 * Neuronopathy is the result of destruction of peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies (e.g., Herpes zoster), toxins or autonomic dysfunction. Neurotoxins may cause neuronopathies, such as the chemotherapy agent vincristine.

Evaluation
Evaluation and classification of polyneuropathies begins with a history and physical exam in order to document what the pattern of the disease process is (arms, legs, distal, proximal, symmetric), when they started, how long they've lasted, if they fluctuate, and what deficits and pain are involved. If pain is a factor, and it often is, determining where and how long the pain has been present is important.

One also needs to know what disorders are already present within the family and what diseases the patient may currently have. This is vital in forming a differential diagnosis.

Although often diseases are suggested by the physical exam and history alone, testing is still a large part of the diagnosis. Tests which may be employed include: electrodiagnostic testing using electromyography, muscle biopsy, serum creatine kinase (CK), antibody testing. Nerve biopsy is not used much, but is helpful in determining small fiber neuropathy. Other tests may be used, especially tests for specific disorders associated with polyneuropathies.

Causes
Acute polyneuropathy can have various causes, including infections, autoimmune reactions, toxins, certain drugs, and cancer.

Chronic polyneuropathy is often caused by diabetes mellitus or by the excessive use of alcohol (alcoholic polyneuropathy), but a variety of other less common causes are known, including nutritional deficiencies, and liver or kidney failure.

One Danish study in 2002 suggested a link between long term exposure to statins and increased risk of polyneuropathy, although other studies have not confirmed this finding.

Treatment
If possible, treatment focuses on the underlying disease. Further, pain medications may be given and physical therapy is used to retain muscle function.

Differential
There is a large differential for polyneuropathies: vitamin deficiency, cancer, toxins, infections (ex. Guillain-Barré Syndrome, Lyme Disease), liver disease, endocrine disease (including diabetes with diabetic and pre-diabetic neuropathy), amyloidosis, genetic disorders, motor neuron disorders, motor neuropathies, kidney failure, paraneoplastic, polio, porphyria (some types), spinal muscular atrophy, catecholamine disorders, psychological disorders and many others.