Chronic inflammatory demyelinating polyneuropathy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6]

Synonyms and keywords:

Overview

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system but often can have central nervous system involvement. The disorder is sometimes called chronic relapsing polyneuropathy. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart of that acute disease.

The pathologic hallmark of the disease is loss of the myelin sheath (the fatty covering that wraps around and protects nerve fibers) of the peripheral nerves.

Chronic inflammatory demyelinating polyneuropathy is disease believed to be due to immune cells, cells which normally protect the body, but are now attacking the nerves in the body. 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.[1]

Under-recognized and under-treated 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.[2]

In some cases electrophysiological studies fail to show any evidence of demyelination, though conventional electrophysiological diagnostic criteria are not filled the patient may respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical justifying fully investigations including sural nerve biopsy.[3]

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Chronic Inflammatory Demyelinating Polyneuropathy from other Diseases

Epidemiology and Demographics

Age

Gender

Race

Risk Factors

Natural History, Complications and Prognosis

It is not possible to predict with certainty how CIDP is going to affect an individual in the future just like as in Multiple Sclerosis or any other autoimmune disease. The pattern of relapses and remissions varies greatly from person to person. A period of relapse can be very disturbing but many patients make a good recovery. The course of CIDP varies widely among individuals. Some may have a bout of CIDP followed by spontaneous recovery, while others may have many bouts with partial recovery in between relapses.

If diagnosed early the disease is usually a treatable cause of acquired neuropathy and initiation of early treatment to prevent loss of nerve axons is recommended. However, many individuals are left with residual numbness, weakness, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life. [4]

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, the doctor will not be able to give you a definite prognosis.

Although there is not one single overall treatment for CIDP, there is much that your doctor can do to help. Each person responds in different ways to different treatments. A period of experimentation with different treatment regimes is likely to be necessary in order to discover the regime which is most appropriate for you.

Diagnosis

Diagnostic Criteria

Symptoms

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 come and go.

Physical Examination

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.

The patient may present with a single cranial nerve or peripheral nerve dysfunction.

Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems with bowel and bladder functions, and cardiac problems.

Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.

Laboratory Findings

Imaging Findings

In usual CIDP, the nerve conduction studies show demyelination . These findings include: (a) a reduction in nerve conduction velocities b; (b) the presence of conduction block or abnormal temporal dispersion in at least one motor nerve; (c) prolonged distal latencies in at least two nerves; (d) absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).

Other Diagnostic Studies

Biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (eg, hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.

Treatment

Medical Therapy

First line treatment for CIDP includes corticosteroids such as 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.

Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including Rituximab (Rixutan) which targets B Cells, and cyclophosphamide, a drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach.[5] Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.

Non-cytotoxic immunosuppressive treatments usually include imuran and cellcept.

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.

Physiotherapy may improve muscle strength, function and mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.

Surgery

Prevention

Prognosis

References

  1. [1]Toothaker TB, Brannagan TH 3rd. "Chronic inflammatory demyelinating polyneuropathies: current treatment strategies." Curr Neurol Neurosci Rep. 2007 Jan;7(1):63-70
  2. [2]Latov N. "Diagnosis of CIDP." Neurology. 2002 Dec 24;59(12 Suppl 6):S2-6.
  3. [3]Azulay JP. "The diagnosis of chronic axonal polyneuropathy: the poorly understood chronic polyradiculoneuritides". Rev Neurol (Paris). 2006 Dec;162(12):1292-5.
  4. [4]Kissel JT. "The treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Semin Neurol." 2003 Jun;23(2):169-80.
  5. [5]Odaka M, Tatsumoto M, Susuki K, Hirata K, Yuki N. "Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin"J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1115-20.

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