Polyneuropathy is a neurological disorder that occurs when many 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 numerous conditions that can cause polyneuropathy.
Polyneuropathies can be classified in different ways, such as by cause, by speed of progression, or by the parts of the body involved. Classes of polyneuropathy are also distinguished by 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 neurons to metabolic or toxic disturbances, and 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 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. People 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), and 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 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 have 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 present within the family and what diseases the patient may 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), and 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.
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. Transthyretin amyloidogenesis is established to cause polyneuropathy in the case of inherited mutations and it could be that wild type transthyretin amyloidogenesis, which is established to cause cardiomyopathy, could also lead to peripheral neuropathy, as transthyretin amyloid diseases can present as either a prominent cardiomyopathy, a peripheral neuropathy, or both.
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.
If possible, treatment focuses on the underlying disease. Further, pain medications may be given and physical therapy is used to retain muscle function. Vyndaqel or Tafamidis is a European Medicines Agency approved drug for the treatment of familial amyloid polyneuropathy caused by transthyretin amyloisis.
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.
- ↑ 1.0 1.1 Polyneuropathy, Merck Manual
- ↑ Andrade C (1952). A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain : a journal of neurology 75: 408–27.
- ↑ Coelho T (1996). Familial amyloid polyneuropathy: new developments in genetics and treatment. Current opinion in neurology 9 (5): 355–9.
- ↑ Westermark P., Sletten K., Johansson B., Cornwell G. G. (1990). Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proceedings of the National Academy of Sciences of the United States of America 87 (7): 2843–5.
- ↑ Jacobson D. R., Pastore R. D., Yaghoubian R., Kane I., Gallo G., Buck F. S., Buxbaum J. N. (1997). Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. The New England Journal of Medicine 336 (7): 466–73.
- ↑ D. Gaist (2002). Statins and risk of polyneuropathy – A case-control study. Neurology 58 (9): 1333–1337.
- ↑ Chronic renal failure, Medline Plus
|Nervous system pathology, primarily PNS (G50-G99, 350-359)|
|Nerve, nerve root
and plexus disorders
cranial nerve: V (Trigeminal neuralgia) - VII (Facial nerve paralysis, Bell's palsy, Melkersson-Rosenthal syndrome, Central seven) - XI (Accessory nerve disorder)
nerve root and plexus: Brachial plexus lesion - Thoracic outlet syndrome - Phantom limb
mononeuropathy: Carpal tunnel syndrome - Ulnar nerve entrapment - Radial neuropathy - Causalgia - Meralgia paraesthetica - Tarsal tunnel syndrome - Morton's neuroma - Mononeuritis multiplex
and other disorders of the PNS
Hereditary and idiopathic (Charcot-Marie-Tooth disease, Dejerine Sottas syndrome, Refsum's disease, Morvan's syndrome) - Guillain-Barré syndrome - Alcoholic polyneuropathy - Neuropathy
|Diseases of myoneural junction
Myasthenia gravis - Primary disorders of muscles (Muscular dystrophy, Myotonic dystrophy, Myotonia congenita, Thomsen disease, Neuromyotonia, Paramyotonia congenita, Centronuclear myopathy, Nemaline myopathy, Mitochondrial myopathy) - Myopathy - Periodic paralysis (Hypokalemic, Hyperkalemic) - Lambert-Eaton myasthenic syndrome
Familial dysautonomia - Horner's syndrome - Multiple system atrophy (Shy-Drager syndrome, Olivopontocerebellar atrophy)