Chronic inflammatory demyelinating polyneuropathy
|Chronic inflammatory demyelinating polyneuropathy|
|Classification and external resources|
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots). CIDP is closely related to Guillain-Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. An asymmetrical variant of CIDP is known as Lewis-Sumner syndrome.
Chronic inflammatory demyelinating polyneuropathy is believed to be due to immune cells, which normally protect the body from foreign infection, incorrectly attacking the nerves in the body instead. As a result, the affected nerves fail to respond, or respond only weakly, to stimuli, causing numbing, tingling, pain, progressive muscle weakness, loss of deep tendon reflexes (areflexia), fatigue, and abnormal sensations. The likelihood of progression of the disease is high.
CIDP is under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is important in preventing irreversible axonal loss and improving functional recovery.
Lack of awareness and treatment of CIDP is also due to limitations of clinical trials. Although there are stringent research criteria for selecting patients to clinical trials, there are no generally agreed-on clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often miss the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.
In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.
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Diagnosis is usually made through a clinical neurological examination. Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking. They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.
Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.
On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have Multi-Focal Motor neuropathy, as they have no sensory loss.
Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.
Typical diagnostic tests include:
- Electrodiagnostics - electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include:
- a reduction in nerve conduction velocities;
- the presence of conduction block or abnormal temporal dispersion in at least one motor nerve;
- prolonged distal latencies in at least two nerves;
- absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).
- Serum test to exclude other autoimmune diseases.
- Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b.
- Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.
First-line treatment for CIDP includes corticosteroids (e.g. prednisone), plasmapheresis (plasma exchange) and intravenous immunoglobulin (IVIG) which may be prescribed alone or in combination with an immunosuppressant drug.
IVIG and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. IVIG is probably the first-line CIDP treatment, but is extremely expensive (in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $8,000, just for the immunoglobulin, not including other charges such as nurse administration). Gamunex brand IVIG is the only U.S. FDA approved treatment for CIDP, as in 2008 Talecris, the maker of Gamunex, received orphan drug status for this drug for the treatment of CIDP.
Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including rituximab (Rituxan) which targets B Cells, and cyclophosphamide, a drug which reduces the function of the immune system. Cyclosporin has also been used in CIDP but with less frequency as it is a newer approach. Cyclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.
Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In the U.S., these drugs are used as "off-label" treatments for CIDP, meaning that their use here is accepted by the FDA, but that CIDP treatment is not explicitly indicated or approved in the drug literature. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used.
Anti-thymocyte globulin (ATG), an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody.
Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials.
As in multiple sclerosis, another demyelinating condition, it is not possible to predict with certainty how CIDP is going to affect an individual in the future. The pattern of relapses and remissions varies greatly with each patient. A period of relapse can be very disturbing, but many patients make significant recoveries.
If diagnosed early, initiation of early treatment to prevent loss of nerve axons is recommended. However, many individuals are left with residual numbness, weakness, tremors, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life.
It is important to build a good relationship with doctors, both primary care and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of the variability in severity and progression of the disease, doctors will not be able to give a definite prognosis. A period of experimentation with different treatment regimes is likely to be necessary in order to discover the most appropriate treatment regimen for a given patient.
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- CIDP at NINDS
- CIDP information and booklets from the Guillain-Barré Syndrome Support Group (UK and Ireland)
- The Neuropathy Association
- The Inflammatory Neuropathy Support Group of Victoria Inc.
- GBS/CIDP Foundation International