Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), or chronic Grimballi syndrome, is an immune-mediated motor-sensory peripheral neuropathy. The course of the disease is chronic progression or relapse in remission; cerebrospinal fluid protein-cell separation; slowed peripheral nerve conduction velocity, conduction block, and abnormal waveform dispersion; and pathology with multifocal demyelination of myelinated fibers, endoneurial edema, and inflammatory cell infiltration. The disease responds well to immunotherapy.
Clinical manifestations
I. Classic CIDP.
Age of onset 40-60 years, similar ratio of males and females; less history of antecedent infection. It can be divided into 2 types: chronic progressive type and remitting relapsing type; generally chronic onset with symptoms >8 weeks; 16% of patients have subacute onset with symptoms peaking at 4-8 weeks. Specific manifestations are as follows.
(i) cerebral nerve abnormalities: <10% present with facial palsy, oculomotor palsy, and true globe palsy.
(ii) muscle weakness: proximal and distal weakness of the extremities, with the former prominent.
③Sensory impairment: numbness and pain in the extremities, glove and glove-like hyperalgesia, and sensory ataxia.
④Tendon reflexes are diminished or absent.
⑤ Autonomic dysfunction: postural hypotension, sphincter dysfunction, and cardiac arrhythmia may occur.
II. Variant CIDP.
1, pure motor type: 10-11%, only limb weakness, no sensory symptoms.
2, pure sensory type: 8-17%, only sensory symptoms (such as sensory ataxia, numbness, pain, etc.), later may appear motor involvement.
3, distal acquired demyelinating symmetric neuropathy (DADS): weakness, sensory impairment is limited to the distal limb, slow progress. It is further divided into 2 types as follows.
a. with IgM monoclonal gamma globulinemia, which is monoclonal to gammaglobulinemia (MGUS) and is ineffective to hormonal therapy.
b. without monoclonal gamma globulinemia, sensitive to immunotherapy.
4, multifocal acquired demyelinating sensory and motor neuropathy (MADSAM): asymmetric sensory-motor peripheral neuropathy of the extremities, similar to multifocal motor neuropathy, but with sensory deficits and no anti-ganglioside Elevated GM1 antibody titers.
Ancillary tests
I. Neurophysiology: Generally, the median, ulnar, tibial and common peroneal nerves were selected for examination
1. Motor nerve conduction: at least 2 nerves must have at least 1 of the following parameters abnormal: (1) distal latency is more than 50% longer than the upper limit of normal value; (2) motor nerve conduction velocity is more than 30% lower than the lower limit of normal value; (3) F-wave latency is more than 20% longer than the upper limit of normal value [when the distal compound muscle action potential (CMAP) F-wave latency is required to be extended by more than 50% when the negative phase wave amplitude of the distal compound muscle action potential (CMAP) decreases by more than 20% compared with the lower limit of the normal value] or the F-wave cannot be elicited; ④ partial motor nerve conduction block: the negative phase wave amplitude of CMAP decreases by more than 50% compared with the distal end of the conventional peripheral nerve segment; ⑤ abnormal waveform dispersion: the negative phase wave time of CAMP widens by more than 30% compared with the distal end of the conventional peripheral nerve segment The time frame of the negative phase wave was widened by more than 30%. When the CMAP negative phase wave amplitude is less than 20% of the lower limit of normal value, the reliability of detecting conduction block is reduced.
2.Sensory nerve conduction: there may be a decrease in conduction velocity and/or a decrease in wave amplitude.
3. Needle electrode electromyography: normal, but abnormal spontaneous potentials, broadened time frame and increased wave amplitude of motor unit potentials, and loss of motor units may occur secondary to axonal damage.
I. Cerebrospinal fluid examination
Cerebrospinal fluid protein-cell separation is seen in 80-90% of patients, with protein mostly in the range of 0.75-2.00 g/L.
II. Peroneal nerve biopsy
When the disease is suspected but the electrophysiological findings are not clinically consistent, a peroneal nerve biopsy is required. The characteristic changes are
Myelinated nerve fibers segmental demyelination, axonal degeneration, Schwann cell proliferation and formation of onion skin-like structures, mononuclear cell infiltration, etc.
Diagnosis
The disease is considered when the following conditions are met.
(1) Progression of symptoms >8 weeks, chronic progression or remission relapse.
(2) Varying degrees of limb weakness, mostly symmetrical, a few asymmetrical (e.g., MADSAM), with both proximal and distal involvement, and decreased or absent tendon reflexes in the extremities with abnormalities of deep and superficial sensation.
(3) Cerebrospinal fluid protein-cell separation.
(4) Electrophysiological examination suggesting slowed peripheral nerve conduction velocity, conduction block, or abnormal waveform dispersion.
(5) Excluding other causes of peripheral neuropathy.
(6) Glucocorticoids are effective.
Differential diagnosis
POEMS syndrome.
Present with multiple peripheral neuropathies, organomegaly, endocrine abnormalities, M protein, and skin changes. Plasmacytosis or myeloma seen on bone aspiration. Positive urine Ben-Peripheral protein.
Carcinomatous peripheral neuropathy.
Non-metastatic peripheral nerve damage caused by cancer. Peripheral nerve damage may precede cancer, or may occur simultaneously or later. It is mostly seen in middle-aged and elderly people, has progressive development, and is poorly treated with immunotherapy. The diagnosis is confirmed and differentiated mainly by a thorough examination of the cancer.
MGUS with peripheral neuropathy.
Sensory symptoms are more important than motor symptoms, and distal involvement is more pronounced; about 50% of patients are positive for anti-myelin-associated glycoprotein (MAG) antibodies. Poor response to immunosuppressive or immunomodulator therapy, but may be effective with rituximab therapy. Occasionally, IgG or IgA MGUS may also be associated with CADP, which has similar clinical and electrophysiological features to CIDP. The discovery of M protein by immunofixation electrophoresis is key to the diagnosis of MGUS with peripheral neuropathy.
Multifocal motor neuropathy (MMN).
MMN is an asymmetric CADP involving only motor nerves. it is more common in adult males; the onset of the disease is initially asymmetric distal upper extremity weakness, which gradually involves the proximal upper extremity and lower extremity, and may also start in the lower extremity. The distribution of affected muscles shows the characteristics of most mononeuropathies.
The neurophysiological examination shows a multifocal distribution of motor conduction block. MMN is very similar to the typical MADSAM, and the distinction between the two is
a. The former has no sensory symptoms, and IgM-type anti-ganglioside GM antibodies are detectable in the serum. Intravenous immunoglobulln (IVlg) or cyclophosphamide (CTX) treatment is effective, while glucocorticoid treatment is ineffective.
b. The latter with sensory symptoms, no anti-ganglioside GM1 antibodies in the serum, and effective glucocorticoid therapy.
Refsum’s disease: a hereditary motor-sensory peripheral neuropathy. The disease is diagnosed by a significant increase in plasma phytanic acid.
Treatment
Immunotherapy.
1.Glucocorticoid: preferred
(1) methylprednisolone 500-1000mg/d, 3-5 days, tapered, or prednisone l mg. kg-1?d-1, early morning dose, maintained for 1-2 months and then tapered.
(ii) Dexamethasone 10-20 mg/d for 7 days, followed by prednisone l mg. kg-1. d-1 in the morning and tapered after 1-2 months.
(3) Prednisone l mg. kg-1. d-1 early in the morning, maintained for 1-2 months and then tapered.
The above-mentioned prednisone is reduced to the minimum (5-10 mg) for more than six months.
Note: Calcium, potassium, and protection of gastric mucosa.
2. Gammaglobulin.
The dose is 400 mg?kg-1?d-1, intravenous drip, for 3-5 d for a course of treatment. Repeat once a month for 3 months, the application can be extended for several months if necessary.
3. Plasma exchange.
Each course of treatment 3-5 times with 2-3 d interval, each exchange volume is 30 ml/kg, 1 course of treatment per month. It should be noted that plasma exchange should not be performed within 3 weeks after the application of IVIg.
4. Other immunosuppressive agents.
Azathioprine, CTX, cyclosporine, methotrexate and other immunosuppressive agents. The more common clinical use is azathioprine, the use of 1-3 mg?kg-1?d-1, divided into 2-3 oral doses, the use of the process need to follow up liver and kidney function and blood routine, etc.
Neurotrophy.
B vitamin therapy, including B1, B12, B6, etc.
Allopathic treatment.
Carbamazepine, amitriptyline, tramadol, gabapentin, pregabalin for neuralgia.
Rehabilitative treatment.
Prevention of disuse muscle atrophy and joint contractures.
Prognosis
The prognosis is better in the remitting relapsing form than in the chronic progressive form; 70-80% of patients respond well to immunotherapy, with a small proportion not responding or becoming dependent after a short period of effectiveness.