What Is Chronic Inflammatory Demyelinating Polyneuropathy?

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune motor sensory peripheral neuropathy with chronic demyelinating peripheral nerves as the main lesion. It belongs to chronic acquired demyelinating polyneuropathy ( ADP), the most common type of CADP, presents a chronic progression or remission-relapse course. Most patients respond well to immunotherapy.

Basic Information

English name

Chronic inflammatory demyelinating polyneuropathy, CIDP

Visiting department

Neurology

Multiple groups

40 to 60 years old

Common locations

Chronic peripheral demyelination

Common causes

Upper respiratory tract infections and gastrointestinal inflammatory diseases

Common symptoms

Muscle weakness, numbness of the limbs, some with pain, weakened or disappeared tendon reflexes, etc.

Causes of chronic inflammatory demyelinating polyneuropathy

The cause of the disease is unclear. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is currently associated with infectious precursor diseases, the most common of which are upper respiratory infections (viral or bacterial) and gastrointestinal inflammatory diseases (Campylobacter jejuni) However, the etiology of CIDP has not suggested a relationship with precursor infection. The detection rate of virus-related bacteria in CIDP patients is also low. Of course, this may also be due to the insidious onset of CIDP, it is difficult to determine whether the precursor infection is related to the time of symptoms, or because the incidence of CIDP is much lower than AIDP and the diagnosis is difficult, and relatively few epidemiological data are insufficient to confirm the precursor disease. Relationship with CIDP.

Clinical manifestations of chronic inflammatory demyelinating polyneuropathy

The disease can be mainly seen in adults, and children can also be affected. The peak age of onset is 40 to 60 years. The onset is relatively insidious or subacute, and there are few precursor infections before the disease. The natural course includes three forms of stepwise progression, stable progression, and remission-relapse. The progression period is from several months to several years, with an average of 3 months. There is no obvious improvement within 6 months of onset. The progression process is more than 8 weeks, which can be distinguished from GBS.

1.CIDP Classic

Found in all ages, more common in 40 to 60 years old, male and female incidence rate is similar. Fewer definite prodromal infections. Chronic onset, symptoms progress more than 8 weeks, but 16% of patients have subacute onset, symptoms progress rapidly, peaked in 4-8 weeks, and are sensitive to glucocorticoid response, these patients are currently Still tends to be classified as CIDP rather than AIDP. CIDP symptoms are limited to the peripheral nervous system and are mainly manifested as:

(1) Facial paralysis or ophthalmoplegia may occur in a small number of patients with abnormal cerebral nerves. The cerebral nerves that dominate the bulbar muscles may be involved, and dysphonia may occur, making it difficult to swallow.

(2) Most patients with myasthenia gravis appear myasthenia gravis, which can affect both the proximal and distal ends of the limbs, but are characterized by proximal muscle weakness. Typical weakness is symmetry of weakness in the proximal and distal limbs, which usually starts from both lower limbs and progress from the distal to the proximal end; respiratory muscle involvement is rare.

(3) Most patients with sensory disorders show numbness in their limbs and some with pain. May have gloves, sock-like acupuncture sensations, and deep sensations, severe cases of sensory ataxia. However, the sensory disturbance of objective physical examination is generally not prominent.

(4) Abnormal tendon reflexes The tendon reflexes weaken or disappear, and even those with normal muscle strength weaken or disappear.

(5) Autonomic dysfunction can be manifested as orthostatic hypotension, sphincter dysfunction, and arrhythmia. A few patients developed Horner sign, impotence, urinary incontinence, disc edema, and decreased vision. About 5% of patients with CIDP can have central nervous system damage at the same time. Demyelinating lesions can be found in the brain and cerebellum, similar to multiple sclerosis. Central immune system symptoms and brain imaging changes can disappear after immunotherapy.

2.CIDP variant

(1) Pure exercise type selectively involves motor fibers, conduction block is more common, and response to intravenous immunoglobulin is better than hormones.

(2) CIDP or chronic sensory demyelinating neuropathy begins with sensory disturbance at the extremities, and even sensory ataxia appears. Although there are only sensory symptoms, electrophysiology suggests that the nerve conduction velocity has typical CIDP motor fiber damage. As the disease progresses, symptoms of exercise involvement may occur.

(3) Mild muscle strength is usually normal. Symptoms include distal numbness, tingling, or weakness, which can progress with prolonged disease.

(4) Multifocal (multifocal acquired demyelinating sensorimotor neuropathy) clinical manifestations are multifocal neuropathy, affected nerves have conduction block, there is evidence of sensory damage, and hormone response is good.

(5) Distal type (distal acquired demyelinating symmetrical neuropathy). The proximal muscle strength is not affected, no monoclonal protein is found, and the treatment response is similar to the classic CIDP.

(6) The clinical manifestations of chronic immune sensory polyradiculopathy are sensory ataxia and large fibrous sensory loss. Electrophysiological examination of somatosensory evoked potentials indicates that sensory nerve roots are involved, but nerve conduction velocity is normal. Its histological model is similar to CIDP. ^[1]

Examination of chronic inflammatory demyelinating polyneuropathy

Electrophysiological examination

Motor nerve conduction measurements suggest the presence of demyelinating lesions in peripheral nerves. Conduction blocks or discrete waveform discontinuities at non-embedded sites are more valuable in diagnosing demyelinating lesions. The median nerve, ulnar nerve, tibial nerve, and common peroneal nerve are usually selected for measurement. The results of neuroelectrophysiological tests must be consistent with clinical manifestations. The electrophysiological diagnostic criteria are:

(1) At least two nerves in the motor nerve must have at least one of the following parameters: The latency of the distal end is extended by more than 50% from the upper limit of the normal value; The velocity of the motor nerve is reduced by more than 30% from the lower limit of the normal value ; F-wave latency is longer than the upper limit of normal value by more than 20% [When the distal composite muscle action potential (CMAP) negative-phase wave amplitude decreases by more than 20% from the lower limit of normal value, the F-wave latency is required to be extended by more than 50%] or cannot be derived F wave; partial conduction block of the motor nerve: compared with the proximal end of the peripheral nerve conventional segment, the amplitude of CMAP negative phase wave decreased by more than 50%; abnormal waveform dispersion: compared with the proximal end of the conventional peripheral segment of the peripheral nerve, CAMP Negative-phase wave duration is widened by more than 30%. When the amplitude of CMAP negative phase wave is less than 20% of the lower limit of the normal value, the reliability of detecting conduction block decreases.

(2) Sensory nerve conduction may have a decrease in sensory nerve conduction speed and / or a decrease in amplitude.

(3) The needle electrode electromyogram is usually normal, and abnormal autogenous potentials, widening of the time limit and amplitude of the motor unit potential, and loss of the motor unit may occur during secondary axonal damage.

2. Cerebrospinal fluid examination

Typical cerebrospinal fluid changes are protein-cell separation and increased protein content, while the cell count is normal or only slightly increased, and the protein content fluctuates greatly, usually in the range of 0.75 to 2.0 g / L. Some patients may have positive oligoclonal bands. In 24 hours, intrathecal IgG synthesis rate increased.

3. Nerve biopsy

When the disease is suspected but the results of the electrophysiological examination are inconsistent with the clinic, a nerve biopsy is required. The main pathological changes of the gastrocnemius nerve biopsy include segmental demyelination of myelinated nerve fibers, axonal degeneration, Schwann cell proliferation and formation of onion skin-like structures, and monocyte infiltration. This change is not a CIDP-specific marker. Vascular inflammatory peripheral neuropathy and hereditary peripheral neuropathy can also be excluded. The nerve biopsy is also because the sural nerve and superficial peroneal nerve biopsy are distal sensory nerves, and the most prominent lesions of CIDP are located in the nerve root and proximal motor fibers. Therefore, the positive diagnosis of CIDP in peripheral nerve biopsy is 60%. about.

4.MRI examination

MRI can detect thickening of the proximal nerve or nerve root, and enhancement can help find active lesions. ^[2]

Diagnosis of chronic inflammatory demyelinating polyneuropathy

The diagnosis of CIDP is mainly based on the patient's clinical manifestations and neuroelectrophysiological changes, cerebrospinal fluid changes, and nerve biopsy consistent with demyelinating lesions. Demyelination and myelin regeneration suggest this diagnosis. Typical CIDP responds well to corticosteroid treatment with curative effects. Observations can also be used for differential diagnosis.

According to the "China 2010 Guidelines for the Diagnosis and Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy", the diagnosis of CIDP is still an exclusion diagnosis, and the disease can be considered if it meets the following conditions:

1. Symptoms progress more than 8 weeks, chronic progress or remission-relapse;

2. Clinical manifestations: different degrees of limb weakness, most of which are symmetrical, and a few are asymmetric, which can be involved at the proximal and distal ends, and the tendon reflexes of the limbs are reduced or disappeared, with deep and shallow paresthesia;

3. Cerebrospinal fluid: protein-cell separation;

4. Electrophysiological examination: slowing of nerve conduction speed, conduction block or abnormal waveform dispersion;

5. Nerve biopsy: peripheral neuropathy caused by other reasons;

6. Glucocorticoid treatment is effective.

Differential diagnosis of chronic inflammatory demyelinating polyneuropathy

1. Multifocal motor neuropathy (MMN)

MMN is a demyelinating peripheral neuropathy that only affects the motor nerves. It is mainly manifested as asymmetric weakness starting from the distal limb muscles, mainly in the upper limbs, without sensory decline. In some patients, serum GM1 antibodies increased, cerebrospinal fluid protein levels and Cell counts are usually normal; electrophysiology is incomplete motor conduction block at multiple non-embedded sites. MMN is generally ineffective for corticosteroids and can be treated with immunoglobulins and cyclophosphamide.

2. Recurrent GBS

Rarely, it progresses to a peak within 1 month, and the average CIDP is 3 months. In addition, relapsed GBS has a history of precursor infection, common facial paralysis and respiratory muscle involvement, and CIDP is rare.

3.POEMS syndrome

Mainly manifested as demyelinating peripheral neuropathy and M protein (usually IgG type, increased lambda light chain) positive, and may also have organ enlargement (such as liver, spleen, lymph nodes, etc.), endocrine abnormalities (such as diabetes, Hypothyroidism, etc.) and skin changes (darker skin tone).

4. Unknown monoclonal gamma globulin disease (MGUS)

MGUS is accompanied by prominent sensory symptoms of peripheral neuropathy, and the distal involvement is more obvious. The most common type is IgM. Immunoprotein fixation electrophoresis found that M protein is the key to the diagnosis of MGUS. The disease responds well to gamma globulin, and some patients can progress to multiple Myeloma.

5. Paraneoplastic neuropathy

Most of them are pure sensory or sensorimotor, with obvious sensory symptoms and progressive course of the disease. Tumor-related autoantibodies can be detected in the serum of some patients, and peripheral nerve damage can occur before, at the same time or after the appearance of cancer.

6. Hereditary motor sensory neuropathy (HSMN)

Based on family history, the combination of signs such as retinitis pigmentosa, ichthyosis, and arcuate feet can help identify, and the diagnosis depends on nerve biopsy.

7. Other

CIDP also needs to identify chronic multiple peripheral neuropathy caused by various reasons, such as HIV infection, hepatitis C virus, connective tissue disease, lymphoma, leukemia, diabetes and other metabolic diseases, toxicity, drugs and so on.

Treatment of chronic inflammatory demyelinating polyneuropathy

Immunotherapy for patients with CIDP can relieve or control the disease in most patients. Immunotherapy includes corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange (PE), and immunosuppressants. Immunotherapy can stop the autoimmune response and inflammatory demyelination and prevent secondary axonal mutation. Patients who are effective in treatment must adhere to the treatment until the condition is improved or stabilized to the greatest extent, and then maintenance treatment is performed to prevent recurrence and progression. CIDP is a chronic disease. The treatment plan is individualized and selected based on the patient's weakness, cost, convenience, systemic disease, side effects, etc.

Corticosteroid

The preferred treatment for CIDP. Commonly used drugs are methylprednisolone, prednisone, and dexamethasone. During the use of hormones, pay attention to calcium, potassium and protect the gastric mucosa.

2.IVIG

More than 50% of patients are effective with IVIG. Some patients are relieved after the initial treatment, and most patients need to continue treatment. Relapse treatment or maintenance treatment is recommended once a month and gradually reduced. In order to improve the condition continuously, a small dose of prednisone or other immunosuppressive agents such as cyclophosphamide can be added orally.

3.PE

Can clear immune complexes and related antibodies to reduce the inflammatory destruction of peripheral neurons. Nearly half of CIDP patients respond well to PE. Most patients have a transient response and need to receive regular PE treatment multiple times. PE treatment is not recommended for 3 weeks after IVIG application.

4. Immunosuppressive drugs

Immunosuppressive therapy is usually given when other treatments fail. Commonly used drugs include cyclophosphamide, azathioprine, and cyclosporin A.

5. Immunomodulators

Patients with poor response to corticosteroids, PE, or IVIG can be treated with alpha-interferon.

6. Other treatments

B-vitamin nutrition neurotherapy can be applied, such as vitamin B ₁ , B ₁₂ , B ₆ etc .; those with severe neuralgia can not be treated with carbamazepine, gabapentin, pregabalin, etc .; early neurological rehabilitation exercise prevention Muscle atrophy and joint contractures. ^[3]

Prognosis of chronic inflammatory demyelinating polyneuropathy

Remission-Relapsed patients with CIDP have a better prognosis than patients with continuous progression. Studies have shown that the long-term prognosis of patients with CIDP depends on the patient's age of onset, clinical manifestations, and response to treatment. Young patients with subacute onset or one-way disease have better treatment outcomes. Elderly people older than 64 years of age are less likely to recover completely after treatment than patients younger than 64 years of age. CIDP patients with proximal weakness have a higher remission rate than distal weakness and have a better prognosis. In short, the long-term prognosis of patients with CIDP is generally better, especially in patients with one-way or remission-type disease; in addition, experience suggests that the time from onset to initiation of treatment is the key to prognosis, but further research is needed to confirm it.

Prevention of chronic inflammatory demyelinating polyneuropathy

Because the direct etiology and initiating factors of CIDP are not clear, there is no clear primary prevention recommendation, and there are no preventive measures and preventive drugs. Although CIDP has not been confirmed to have a clear relationship with a precursor infection event or vaccination, the recurrence or exacerbation of some patients with CIDP is related to the infection. Therefore, it is recommended to avoid infection in patients with CIDP, especially respiratory and digestive infections. In addition, the recurrence of some young female patients is accompanied by pregnancy, suggesting an increased risk during pregnancy, and attention should be paid to changes in neurological symptoms during pregnancy.

References

1. Chinese Medical Association Neurology Branch Neuromuscular Group, Chinese Medical Association Neurology Branch Electromyography and Clinical Neuroelectrophysiology, Chinese Medical Association Neurology Branch Neuroimmunology Group. Guidelines for diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy in China: Chinese Journal of Neurology, 2010: 43: 586-588.

2. JeanMV, ClaudiaS, LaurentM. Chronicinflammatorydemyelinatingpolyradiculoneuropaty: diagnosticandtherapeuticchallegesforatreatablecondition: LancetNeurol, 2010: 9: 402-12.

3. KamakshiP, MinalB, SurajAM. Manegementstrageiesinchronicinflammatorydemyelinatingpolyradiculoneuropathy: NeurolIndia, 2010: 58: 351.