What is Chronic Inflammatory Demyelinating Polyneuropathy?
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a type of acquired immune-mediated inflammatory condition affecting the peripheral nervous system. It is characterized by a progressive weakness as well as compromised sensory function in legs and arms. It occurs when the myelin sheath, a fatty covering that protects the nerve fibers of peripheral nerves is damaged.
CIDP is closely associated with Guillain-Barré syndrome and is believed to be the chronic form of that acute disorder. Its symptoms are similar to that of progressive inflammatory neuropathy. CIDP is also sometimes referred to as chronic relapsing polyneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy due to its involvement with the nerve roots.
Chronic Inflammatory Demyelinating Polyneuropathy Epidemiology
CIDP is a rare disorder. The estimated prevalence in populations from Japan, Australia, UK, Italy and Norway is around 0.8 to 7.7 in per 100000 individuals.
Chronic Inflammatory Demyelinating Polyneuropathy Variants
CIDP has a number of clinical variants which are identified by their distinct characteristic features. These include:
Lewis-Sumner syndrome, also referred to as the multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), is characterized by a striking multifocal picture that is indistinguishable from the other types of mononeuropathy multiplex, along with motor and/or sensory symptoms in the individual nerve distributions. Chronic immune sensory polyradiculopathy or CISP is a similar disease of sensory ataxia caused by inflammations that are confined to dorsal roots.
Sensory-predominant CIDP is marked by sensory symptoms along with signs associated with pain, balance problems, dysesthesias and paresthesias. Although there is no weakness, studies carried out on nerve conduction demonstrate significant slowing of motor conduction as well as other demyelinating features.
Distal acquired demyelinating sensory neuropathy
Distal acquired demyelinating sensory neuropathy (DADS) is normally more slow-progressing than the typical CIDP. It is also frequently linked with IgM paraprotein. Both variations of DADS with and without the participation of IgM paraprotein exist.
CIDP with involvement of the central nervous system (CNS)
CIDP is sometimes connected with CNS involvement, along with hyperreflexia, optic nerve disorders, Babinski signs, as well as MRI abnormalities of central nervous system demyelination. However, it is not clear whether the combined signs indicate associated diseases or coincidental happenings of unrelated diseases.
Chronic Inflammatory Demyelinating Polyneuropathy Causes
The exact factors responsible for causing CIDP are not known, although it is believed to be an autoimmune disorder. In a healthy individual, the immune system of the body provides protection against diseases by making antibodies that fight off infections that are caused by bacteria and viruses. However, for some unknown cause, the immunity system perceives the myelin sheath as something foreign and therefore attacks it. Sometimes abnormal proteins in the blood may trigger the damage, although the exact procedure as to how that happens is not known.
Chronic Inflammatory Demyelinating Polyneuropathy Symptoms
CIDP normally starts insidiously and then evolves slowly, either in a slow progressive or in a relapsing manner. Complete or partial recovery is observed between recurrences, with periods of improvement or worsening that lasts for several weeks or months. The majority of experts believe that the symptoms should persist for 8 weeks or more in order for the diagnosis to be conclusive. The most common symptoms of CIDP include the following:
- Fasciculations or twitching
- Infrequent preceding infections
- Atrophy or shrinkage of muscles
- Loss of the deep tendon reflexes
- Usually predominant motor symptoms
- Initial limb weakness, both distal and proximal
- Sensory symptoms, such as numbness and tingling felt in the hands and feet
- A comparatively acute or sub-acute onset of symptoms in around 16% of cases
- Usually a rather precipitous beginning of symptoms observed in children
- Symptoms related to autonomic system dysfunction, such as orthostatic dizziness
There might be pertinent physical findings that are limited to nervous system, except those times when CIDP is associated with some other disorders. Such findings might include the following:
- Gait abnormalities
- Impaired coordination
- Absent or diminished deep tendon reflexes
- Sensory deficits normally seen in stocking-glove distribution
- Signs of CN (cranial nerve) involvement, such as diplopia or facial muscle paralysis
- Motor deficits, such as symmetric weakening of both distal and proximal muscles in the upper and the lower extremities
Patients may additionally have fainting spells while trying to stand up or experience burning pain in the extremities. Some patients might suddenly experience pain in the back or neck which radiates down the extremities. This pain is generally diagnosed as a radicular pain and its symptoms are generally progressive and might be intermittent. Dysfunction of the peripheral nerves or a single cranial nerve can be observed. Autonomic system dysfunction might occur in some cases. In such instances, patients might complain of problems with the bowel and the bladder functions, orthostatic dizziness, and cardiac problems as well.
Chronic Inflammatory Demyelinating Polyneuropathy – Associated Disorders
Numerous health disorders are commonly associated with CIDP. Often the symptoms include signs of CIDP as well as certain other disorders that occur alongside it. The disorders which most frequently occur along with CIDP include:
- HIV infections
- Diabetes mellitus
- Multiple sclerosis
- Hodgkin lymphoma
- Systemic lupus erythematosus
- Chronic active hepatitis (B or C)
- Inflammatory bowel disease (IBD)
- Vasculitis or vasculitic neuropathies
- Paraproteinemias and plasma cell dyscrasias
- Side effects of treatment with TNF-alpha blockers
Pregnancy can exacerbate the symptoms of CIDP. The condition worsens especially during the 3rd trimester or in postpartum period.
Chronic Inflammatory Demyelinating Polyneuropathy Diagnosis
The diagnosis for this disorder should be considered for patients having asymmetric or symmetric polyneuropathy who have progressive or a relapsing-remitting course for 2 months or more, especially if the clinical aspects include:
- Proximal weakness
- Positive sensory symptoms
- Areflexia without wasting, and/or
- Selective loss of joint position sense or vibration
While the initial diagnosis of CIDP is primarily clinical, the diagnosis can be confirmed by tests such as:
- Spinal tap
- Nerve biopsies
- Electromyography (EMG)
- Cerebrospinal fluid analysis
- Nerve conduction study (NCS)
- Evaluation for the inherited neuropathies
- Serum tests for anti-ganglioside antibodies
- MRI of the brachial plexus, spinal roots and lumbosacral plexus
- Serum tests to exclude the possibilities of other autoimmune disorders
A treatment trial can be carried out if diagnosis remains inconclusive despite a complete evaluation, as a positive reaction to immunotherapy might add credible evidence to diagnosis of CIDP.
Nerve biopsies are mostly carried out with the sural nerve. However, other candidate nerves for biopsies include the superficial radial, superficial peroneal, and the gracilis motor nerve. A teased fiber analysis and electron microscopy inspection of the nerve biopsy samples are highly recommended. The supportive features that indicate CIDP on a nerve biopsy include:
- Endoneurial edema
- Onion bulb formation
- Variation between fascicles
- Macrophage-associated demyelination
- Endoneurial mononuclear cell infiltration
- Remyelinated and demyelinated nerve fibers
A number of tests that can be helpful to diagnose diseases that are closely associated with CIDP. These include:
- HIV antibody
- Hepatitis profiles
- Chest radiograph
- C reactive protein
- Liver function tests
- Renal function tests
- Glycated hemoglobin
- Complete blood count
- Antinuclear antibodies
- Thyroid function studies
- Borrelia burgdorferi serology
- Angiotensin converting enzyme
- Extractable nuclear antigen antibodies
- Skeletal survey, if traces of paraprotein are found
- Fasting serum glucose or oral glucose tolerance test
- Serum and urine immunofixation electrophoresis to detect paraprotein
Nerve conduction studies exhibit signs of demyelination in usual CIDP. The general findings include:
- A reduction in the nerve conduction velocities
- Prolonged distal latencies found in at least two nerves
- The presence of abnormal temporal dispersion or conduction block in at least one motor nerve
- Absent F waves or signs of prolonged minimum F wave latencies observed in at least two motor nerves. The EMG/NCV can lie within normal range in some cases.
Chronic Inflammatory Demyelinating Polyneuropathy Diagnostic Criteria
According to a general agreement, the following criteria indicate a conclusive diagnosis for the classical form of CIDP:
- Reduced deep tendon reflexes
- Progression for a minimum of 2 months
- Symmetric involvement of legs and arms
- Weakness more than the general sensory symptoms
- Involvement of both proximal as well as distal muscles
- Nerve conduction as evidence of demyelinating neuropathy
- Increased levels of cerebrospinal fluid protein without any pleocytosis
- Nerve biopsies bearing indications of segmental demyelination along with or without inflammations
It is important to note that the above mentioned criteria are not the gold standard for diagnosing CIPD. Two other well known sets of criteria, namely, the Koski criteria and EFNS/PNS criteria are also in use alongside the above diagnostic criteria.
Chronic Inflammatory Demyelinating Polyneuropathy Differential Diagnosis
The symptoms of numerous disorders overlap with those of CIDP. Hence, while determining the diagnosis of this condition, it is necessary to differentiate it from such similar diseases in order to come up with the optimum treatment plan. The differential diagnoses of CIDP include isolating its symptoms from those of health conditions such as:
- Toxic Neuropathy
- Myasthenia Gravis
- Uremic Neuropathy
- Cervical Myelopathy
- Polyarteritis Nodosa
- Diabetic Neuropathy
- Metabolic Myopathies
- Vasculitic Neuropathy
- Nutritional Neuropathy
- Inclusion Body Myositis
- Wegener Granulomatosis
- Tropical Myeloneuropathies
- Sarcoidosis and Neuropathy
- Amyotrophic Lateral Sclerosis
- Systemic Lupus Erythematosus
- Limb-Girdle Muscular Dystrophy
- Lambert-Eaton Myasthenic Syndrome
- Guillain-Barre Syndrome in Childhood
- HIV-1 associated progressive polyradiculopathy
- Cauda Equina and Conus Medullaris Syndromes
- Neuromuscular and Myopathic Complications of HIV
- Multifocal motor neuropathy with conduction blocks
- Acute inflammatory demyelinating polyradiculoneuropathy
- Hereditary Neuropathies of the Charcot-Marie-Tooth Disease Type
- HIV-1 Associated Acute/Chronic Inflammatory Demyelinating Polyneuropathy
Chronic Inflammatory Demyelinating Polyneuropathy Treatment
The first-line treatment for this disorder includes corticosteroid medications such as prednisone, plasma exchange or plasmapheresis and application of intravenous immunoglobulin (IVIG). IVIG might be administered alone or alongside an immunosuppressant drug.
Plasmapheresis and IVIG have proven beneficial in double-blind, randomized, placebo-controlled trials. Although having less definitive published record of efficacy, corticosteroid medications are considered to be standard among therapies due to their prolonged history of usage as well as their cost effectiveness. Although IVIG is quite effective in managing this condition, it is extremely expensive.
The immunosuppressant drugs that are commonly in use generally belong to the cytotoxic or chemotherapy class. Examples of such drugs include rituximab (Rituxan) which primarily targets the B Cells. Cyclophosphamide is a drug that minimizes the functionality of immune system. Another drug that is used in association with CIDP even though only sparingly is Cyclosporin. This drug is believed to bind itself to the immunocompetent lymphocytes, especially the T-lymphocytes.
Non-cytotoxic immunosuppressive medications generally include anti-rejection transplant drugs mycophenolate mofetil (Cellcept) and azathioprine (Imuran). In the U.S., these drugs are employed as “off-label” medications for CIDP, which means that although their use is approved by the FDA, their use in CIDP management is not explicitly approved or indicated in drug literature. Before taking azathioprine, a patient should go through a blood test to make sure its use is safe.
Anti-thymocyte globulin (ATG) is an immunosuppressive drug that selectively destroys the T-lymphocytes. Its use in managing CIDP is currently being studied by medical experts. ATG can be classified as a polyclonal antibody that is a gamma globulin fraction of anti-serum from animals that has been immunized against the human thymocytes.
Although immunosuppressive and chemotherapeutic agents have proven their effectiveness in managing CIDP, adequate evidence is lacking primarily due to the heterogeneous nature of the disease as well as the lack of properly controlled trials.
Patients should also be given physical therapy as this may help in increasing muscle strength, mobility and function as well as minimize shrinkage of tendons and muscles and distortions of joints.
Chronic Inflammatory Demyelinating Polyneuropathy Complications
Breathing and swallowing functions of a patient might get affected if the disorder becomes severe. Other complications that might emerge include:
- Respiratory failure
- Aspiration pneumonia
- Orthostatic hypotension
- Cardiac conduction defects
Bladder functions and GI motility can be abnormal if autonomic functions are involved. Complications might also result from treatment procedures.
Chronic Inflammatory Demyelinating Polyneuropathy Prognosis
It is difficult to accurately predict how CIDP will affect a person in future. The patterns of relapses and the remissions vary greatly between one patient and another. A relapse can prove to be very disturbing. However, more than 70% of all sufferers manage to recover considerably from these relapses.
If the condition is diagnosed early, early treatment should be aimed at preventing the loss of the nerve axons. However, many patients are left with weakness, residual numbness, fatigue, tremors and other symptoms that might result in long term morbidity and a reduced quality of life.
Some patients fail to respond to usual treatments and therefore accumulate significant disability. Others might become treatment dependent after a certain period of time. The CIDP activity status or CDAS is a model by which the clinical status of the patients can be evaluated.
Chronic Inflammatory Demyelinating Polyneuropathy Pictures
The images here show the loss of myelin sheath of the affected peripheral nerves.
Picture 1 – Chronic Inflammatory Demyelinating Polyneuropathy
Picture 2 – Chronic Inflammatory Demyelinating Polyneuropathy Image