Chronic inflammatory demyelinating polyneuropathy
Encyclopedia
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. 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.
sheath (the fatty covering that insulates and protects nerve
fibers) of the peripheral nerves.
Chronic inflammatory demyelinating polyneuropathy is believed to be due to immune cells, cells which normally protect the body from foreign infection, but here begin 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.
. 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.
On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy
(shrinkage) of muscles, fasciculation
s (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.
In usual CIDP, the nerve conduction studies show demyelination.
These findings include:
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.
), 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. Ciclosporin
has also been used in CIDP but with less frequency as it is a newer approach. Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.
Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine
(Imuran) 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.
Physical therapy
may improve muscle strength, function and mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.
, 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.
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
. The disorder is sometimes called chronic relapsing polyneuropathy. CIDP is closely related to Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
and it is considered the chronic counterpart of that acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
disease. Its symptoms are also similar to progressive inflammatory neuropathy
Progressive inflammatory neuropathy
Progressive inflammatory neuropathy is a disease that was identified in a report, released on January 31, 2008, by the Centers for Disease Control and Prevention. The first known outbreak of this neuropathy was in southeastern Minnesota in the United States. The disease was reported among pig...
. An asymmetrical variant of CIDP is known as Lewis-Sumner syndrome.
Overview
The pathologic hallmark of the disease is loss of the myelinMyelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheath (the fatty covering that insulates and protects nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
fibers) of the peripheral nerves.
Chronic inflammatory demyelinating polyneuropathy is believed to be due to immune cells, cells which normally protect the body from foreign infection, but here begin 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.
Diagnosis
Diagnosis is usually made through a clinical neurological examinationNeurological examination
A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired...
. 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
Radicular pain
Radicular pain, or radiculitis, is pain "radiated" along the dermatome of a nerve due to inflammation or other irritation of the nerve root at its connection to the spinal column...
. These symptoms are usually progressive and may be intermittent.
On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
(shrinkage) of muscles, fasciculation
Fasciculation
A fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
s (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
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
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.
- Electrodiagnostics - electromyographyElectromyographyElectromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
(EMG) and nerve conduction studyNerve conduction studyA nerve conduction study is a test commonly used to evaluate the function, especially the ability of electrical conduction, of the motor and sensory nerves of the human body.Nerve conduction velocity is a common measurement made during this test...
(NCS).
In usual CIDP, the nerve conduction studies show demyelination.
These findings include:
- a reduction in nerve conduction velocities b;
- 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 waveF waveIn neuroscience, an F wave is the second of two voltage changes observed after electrical stimulation is applied to the skin surface above the distal region of a nerve...
s 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.
- Spinal tapLumbar punctureA lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
and serum test for Anti-ganglioside antibodiesAnti-ganglioside antibodiesAnti-ganglioside antibodies that react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells...
, which are one branch of the CIDP diseases, as anti-GM1 anti-GD1a anti-GQ1b.
- Sural nerve biopsyBiopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
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.
Treatment
First-line treatment for CIDP includes corticosteroids (e.g. prednisonePrednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
), plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
(plasma exchange) and intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG) which may be prescribed alone or in combination with an immunosuppressant drug
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
.
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
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status for this drug for the treatment of CIDP.
Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including Rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
(Rituxan) which targets B Cells, and cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, a drug which reduces the function of the immune system. Ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
has also been used in CIDP but with less frequency as it is a newer approach. Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.
Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
(Imuran) and mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
(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
Anti-thymocyte globulin
Anti-thymocyte globulin is an infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia.-Uses:...
(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.
Physical therapy
Physical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
may improve muscle strength, function and mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.
Prognosis
As in multiple sclerosisMultiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, 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
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
.
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.
External links
- CIDP information and booklets from the Guillain-Barré Syndrome Support Group (UK and Ireland)
- The Neuropathy Association
- CIDP information from the GBS/CIDP Foundation
- Specialised reference centre for rare neuropathies