After a lapse of 11 years, the European Society of Neurology/Peripheral Neurology has updated its guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy!

The EFNS/PNS consensus guidelines on the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) were first published in 2005 and revised in 2010
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This revision is the second revision, according to GRADE (Grading of Recommendations Assessment) to update the 2010 guidelines
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During the update process, 17 disease experts, one patient representative and two Cochrane methodologists constructed 12 population/intervention/comparison/outcome (PICO) questions about diagnosis and treatment to guide the literature search
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This article briefly summarizes the relevant points of the guide
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Compilation: Compilation and sorting of Reflection Wuhen Yimaitong, please do not reprint without authorization
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 CIDP diagnostic criteria 01 Clinical Criteria Working Group (Task Force, TF) divides CIDP into "typical CIDP" and "CIDP variants" for definition (Table 1, Figure 1)
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(1) Typical CIDP The most common manifestation of typical CIDP is paresthesia and weakness starting from the distal extremities and difficulty walking
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Clinical examination revealed progressive symmetrical proximal and distal muscle weakness, loss of sensation, and diminished or disappeared deep reflexes
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The course of the disease progressed more than 8 weeks, but relapse-remission can be achieved
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Typical CIDP is more common in men and can occur at any age, but it is most common in 40-60 years of age, and it may also develop in infancy and childhood
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Up to 13% of patients may have an acute attack (acute-onset CIDP [A-CIDP]), which progresses rapidly within 4 weeks, and may initially be diagnosed with Guillain-Barré syndrome (GBS)
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Therefore, it is difficult to distinguish between A-CIDP and GBS, because 5% of patients who were initially diagnosed with GBS were later reclassified as A-CIDP
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In contrast to GBS patients, A-CIDP patients continue to worsen for more than 8 weeks after the onset or relapse at least 3 times after the initial improvement
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Patients with A-CIDP are usually still able to walk independently, are less likely to have facial weakness, respiratory or autonomic nervous system involvement, and are more likely to have sensory signs
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Although these features may help the diagnosis of A-CIDP, there are no specific clinical features or laboratory tests that can distinguish GBS from A-CIDP in the acute phase of the disease
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 (2) CIDP variants The clinical manifestations of CIDP variants are different from typical CIDP, but they have common features of demyelination and response to immunotherapy
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The identification of CIPD variants is very important, because the diagnostic process and differential diagnosis may be different from typical CIDP
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➤Distal CIDP (also known as distal acquired demyelinating symmetry neuropathy): It is manifested by loss of sensation and gait instability in the distal upper and lower limbs; weakness may occur, and the distal end of the lower limb is usually more severe than the upper limb.
Stand out
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Approximately two-thirds of patients have IgM paraproteinemic neuropathy and have anti-myelin-associated glycoprotein (MAG) antibodies
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Distal neuropathy with IgM paraprotein and anti-MAG antibody, that is, anti-MAG neuropathy, is considered not to belong to the CIDP category, because most patients have specific electrophysiological and pathological results, and it is against intravenous immunoglobulin (IVIg) Or no response to corticosteroids
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➤Multifocal CIDP (also known as: multifocal demyelinating neuropathy with persistent conduction block, Lewis-Sumner syndrome [LSS]; multifocal acquired sensory and motor demyelinating neuropathy [MADSAM ]; Multifocal inflammatory demyelinating neuropathy): Usually the upper limbs are affected first, and the lower limbs may be affected later or sometimes from the beginning of the onset
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Cranial nerves (including the oculomotor nerve, trigeminal nerve, facial nerve, vagus nerve, and hypoglossal nerve) may be more commonly affected than other CIDP types
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➤Focal CIDP: It is rare, usually involving the brachial plexus or lumbosacral plexus, but also affects a single peripheral nerve
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➤Sports CIDP: It is characterized by relatively symmetrical proximal and distal weakness, but it feels normal clinically and electrophysiologically.
It is different from typical CIDP (paresthesia) and multifocal motor neuropathy (MMN, where weakness is often asymmetric and mainly Involve the upper extremities) in contrast
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If there is abnormal sensory nerve conduction in clinical sports CIDP, it is diagnosed as sports-based CIDP
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Patients with sports CIDP may get worse after using corticosteroids
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➤Sensory CIDP: Usually characterized by gait ataxia, impaired vibration and position perception, and changes in skin sensation, usually without muscle weakness
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If there is motor nerve conduction slowdown or motor block, the diagnosis is sensory-based CIDP
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Long-term follow-up studies have shown that sensory CIDP is usually a short clinical stage, and approximately 70% of patients appear before weakness
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 (3) Diseases not classified as CIDP ➤ Chronic immune sensory polyneuropathy (CISP): It is suspected clinically that it is sensory CIDP, but patients with normal motor and sensory nerve conduction tests may have CISP
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There may be no somatosensory evoked potentials or only a very proximal slowdown in CISP because the sensory axons near the dorsal root ganglia are involved
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Because the sensory neurons in the dorsal root ganglia remain intact, standard sensory nerve conduction tests are often normal
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Although CISP is most likely to be immune-mediated and responsive to immunotherapy, there is insufficient evidence to determine whether CISP is altered in demyelination or is related to sensory CIDP and therefore is not included in CIDP variants
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➤Autoimmune Langfei's disease: A small group of patients who met the 2010 EFNS/PNS CIDP criteria were found to target node-paranodal cell adhesion molecules (CNTN1, NF155, Caspr1) and neurofascin (NF140/186) Of antibodies
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Patients with these antibodies usually have specific clinical characteristics
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CIDP patients with CNTN1 antibody positive have acute or subacute onset, motor dysfunction or ataxia, and have no response or poor response to IVIg treatment
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CIDP patients with positive NF155 antibodies have a younger age of onset, and have a subacute or chronic course, distal weakness, ataxia, tremor, and no response or poor response to IVIg treatment
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Caspr1 antibody-positive patients present with acute/subacute neuropathy, usually accompanied by ataxia, neuropathic pain, cranial nerve involvement, and poor response to IVIg
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The fascin antibody-positive patients will have a severe phenotype, especially IgG3 antibody
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TF proposed to name these diseases "autoimmune nodular diseases" instead of treating them as CIDP variants because they have unique clinical features, no obvious inflammation or macrophage-mediated myelination, and The poor response to CIDP treatment, especially IVIg
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However, rituximab may be effective
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➤CIDP is related to many diseases (such as diabetes, IgG or IgA monoclonal gammopathy of unknown significance [MGUS], MAG antibody negative IgM monoclonal gammopathy, HIV infection, malignant tumors)
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There is insufficient evidence that CIDP associated with these diseases is different from idiopathic CIDP
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In most published reports, there is no difference in treatment from idiopathic CIDP
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 02 Electrophysiological diagnosis standard TF strongly recommends electrophysiological diagnosis (nerve conduction examination) to support the clinical diagnosis of typical CIDP and CIDP variants (Tables 2 and 3)
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TF reduced the level of certainty of electrophysiological diagnosis used in the 2010 EFNS/PNS guidelines from three (determined, probable, and probable CIDP) to two (determined, probable, and probable CIDP)
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(1) Recommendation 1-Typical CIDP➤ At least two motor nerves have abnormal motor conduction to confirm the clinical diagnosis of typical CIDP
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If only one nerve is abnormal, the diagnosis is a probable typical CIDP
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➤At least two nerves have sensory conduction abnormalities
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➤For patients suspected of typical CIDP, because they meet the clinical criteria but do not meet the minimum electrophysiological diagnostic criteria, if they are objectively improved after receiving IVIg, corticosteroids or plasma exchange treatment, and if there is at least one additional support standard, they can Diagnosed as possible typical CIDP
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(2) Recommendation 2-Distal CIDP➤ At least two upper limb nerves meet the motor conduction standards to confirm the clinical diagnosis of distal CIDP
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The amplitude of the negative phase wave of the remote CMAP should be at least 1mV
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When two lower limb nerves meet the criteria but the upper limb nerves do not meet the criteria, or only one upper limb nerve meets the criteria, at most the diagnosis is possible distal CIDP
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➤At least two nerves have sensory conduction abnormalities
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(3) Recommendation 3-Multifocal and focal CIDP ➤ At least two nerves in at least one limb meet the motor conduction standard to confirm the clinical diagnosis of multifocal CIDP; at least two nerves in one limb meet the motor conduction standard In order to confirm the clinical diagnosis of focal CIDP; when only one nerve meets the criteria, at most the diagnosis is possible multifocal or focal CIDP
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➤The presence of sensory conduction abnormalities in at least two nerves of the affected limb can confirm the clinical diagnosis of multifocal or focal CIDP, while the presence of sensory conduction abnormalities in one nerve of the affected limb is diagnosed as possible focal CIDP
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(4) Recommendation 4-Sports CIDP (and exercise-based CIDP) ➤At least two nerves meet the motor conduction standard, and at least four nerves (median nerve, ulnar nerve, radial nerve and peroneal nerve) have normal sensory conduction.
In order to confirm the clinical diagnosis of sports CIDP; if only one motor nerve meets the criteria, it is diagnosed as possible sports CIDP
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➤Sport-based CIDP with abnormal sensory conduction in two nerves is diagnosed as motor-based CIDP
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(5) Recommendation 5-Sensory CIDP (and sensory-based CIDP) ➤ The sensory conduction standards must be met, and the motor conduction of at least 4 nerves (median, ulnar, peroneal, and tibial nerves) must be normal for confirmation The clinical diagnosis of sensory CIDP
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➤A sensory CIDP whose nerve meets the motor conduction criteria is diagnosed as a possible sensory-based CIDP
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If the two nerves meet the motor conduction criteria, it is diagnosed as sensory-based CIDP
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03 Support criteria Therapeutic response, imaging, cerebrospinal fluid (CSF) or nerve biopsy may provide support for meeting the clinical criteria of CIDP while electrophysiological diagnosis is possible
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Since sensory nerve conduction testing is now part of the diagnostic criteria for electrophysiology, it has been removed from the supporting criteria
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(1) Treatment response ➤TF believes that the objective response to treatment with immunomodulators (IVIg, plasma exchange, corticosteroids) supports the clinical diagnosis of CIDP that is diagnosed as possible by clinical, electrophysiological and other supporting criteria
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➤The objective response to treatment needs to be improved on at least one disability and one injury scale
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Lack of improvement after treatment does not exclude CIDP, and positive reactions are not unique to CIDP
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 (2) Imaging ➤ Ultrasound: TF recommends the use of ultrasound in adult patients to support the diagnosis of possible CIDP
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If the proximal median nerve and/or brachial plexus nerves are enlarged in at least two parts (the median nerve forearm horizontal cross-sectional area>10mm2, upper arm level>13mm2, interscaler level>9mm2 or nerve root level>12mm2) , It is more likely to be diagnosed as CIDP; there is currently no evidence to support ultrasound examinations in pediatric patients
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➤MRI: TF recommends not to use MRI in adult patients to help the diagnosis of CIDP, unless the patient only meets the criteria for possible CIDP but does not meet the criteria for definite CIPD
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If the T2-weighted MRI sequence shows enlarged nerve roots and/or increased signal strength, CIDP is more likely to be diagnosed; there is currently no evidence to support MRI in pediatric patients
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 (3) CSF➤ If the diagnostic criteria have been met, TF recommends not to perform cerebrospinal fluid analysis
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➤CSF analysis should be considered to exclude other diagnoses or to support the diagnosis of CIDP in the following situations: meet the criteria for possible CIDP but not the established criteria for CIDP; acute or subacute attacks; when infectious or malignant causes are suspected or may be present; Elevated CSF protein should be interpreted with caution in the presence of diabetes; in view of the higher normal value of CSF protein in individuals over 50 years of age, higher levels are needed to support the diagnosis of CIDP; so far there has not been enough research to determine a strict cut-off value
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 (4) Nerve biopsy ➤TF recommends not to use nerve biopsy as a routine procedure for diagnosing CIDP, but it is limited to the following specific situations: when CIDP is suspected but cannot be confirmed by clinical, laboratory, imaging and electrophysiological diagnostic tests; In the case of suspected CIDP but little or no response to treatment, alternative diagnoses such as CMT, amyloidosis, sarcoidosis, or schwannoma/neurofibromatosis can be considered
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➤Nerve biopsy should be considered only in the following situations: you have skilled (neurological) surgeons and neuropathologists, as well as professional and experienced pathology laboratory facilities; the symptoms are severe enough to offset the potential complications of the nerve biopsy; Before the tissue examination, the patient is fully aware of the low accuracy of the test
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➤When performing nerve biopsy: The current expert consensus on the minimum standards for handling and evaluating nerve biopsy should be followed; the sural nerve or superficial peroneal nerve is most commonly used for biopsy, but biopsy of clinically affected nerves is more likely to provide useful information
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➤The factors that may support the diagnosis of CIDP may include: thin sheathed axons and onion globular degeneration; combing of thin fiber internodes or demyelination; accumulation of macrophages around blood vessels; electron microscopy supports demyelination 04 immunological examination standards (1 ) Monoclonal gammopathy test: TF strongly recommends serum monoclonal protein test for adult patients who are clinically suspected of CIDP; it should include serum protein electrophoresis and immunofixation, light chain (Bence Jones protein) urine immunofixation; for distal type CIDP, if no IgM paraprotein or negative anti-MAG antibody test is found, repeat the test should be considered; when POEMS syndrome is suspected, the serum vascular endothelial growth factor test is suitable for the CIDP phenotype of distal pain
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 (2) Antibody testing: TF recommends that all patients with clinical suspicion of CIDP be considered for Langfei’s knot and paranodal antibody testing; it is recommended to perform Langfei’s knot and paranodal antibody testing for CIDP patients with the following characteristics (for IVIg and corticosteroid therapy Poor response; acute or subacute aggressive attack, and previously diagnosed as GBS or A-CIDP; low-frequency tremor, disproportionate sensory involvement, ataxia, other cerebellar features or distal weakness, mainly; respiratory failure and cranial nerve involvement ; With nephrotic syndrome; very high levels of cerebrospinal fluid protein)
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 05CIDP Diagnosis Process The diagnosis process of CIDP is shown in Figure 1
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CIDP should be considered for patients with progressive symmetrical or multifocal polyneuropathy who have a clinical course of relapse and remission or who have progressed for more than 8 weeks, especially if they have sensory symptoms, proximal weakness, loss of reflexes but no muscle atrophy or The sense of vibration or joint position is first lost
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 Treatment of CIDP 1.
Corticosteroid TF strongly recommends the use of corticosteroid therapy; the best corticosteroid regimen is unclear; because patients with exercise CIDP may worsen after corticosteroids, IVIg should be regarded as the first-line treatment for exercise CIDP
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 2.
Immunoglobulin TF strongly recommends the use of IVIg for treatment
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(1) Induction therapy: IVIg usually has a total dose of 2g/kg, divided into 2-5 days; because not all patients respond to the first course of treatment, it may be necessary to repeat 1g/kg IVIg 2-5 times every 3 weeks , And then the patient can get better or it can be determined that IVIg is invalid
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In addition, clinical experience has shown that 2g/kg in the second course of treatment a few weeks after the first course of treatment may be sufficient to determine whether IVIg is ineffective
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(2) Maintenance treatment: Most patients require IVIg maintenance treatment
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The optimal IVIg maintenance dose and time are not yet known
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The most commonly used IVIg maintenance regimen in clinical trials is to give 1g/kg every 3 weeks, but in clinical practice, you should consider reducing the dose and extending the treatment interval to maintain the maximum continuous improvement (such as 0.
4-1g/kg given every 2-6 weeks) ); The deterioration of the objective dose end before the next IVIg infusion should be minimized.
If it occurs, the IVIg dose can be increased or the infusion interval can be shortened
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If the patient's clinical condition is stable, it is recommended to regularly check whether the IVIg dose can be reduced (for example, 25% each time), extend the treatment interval or stop treatment
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According to clinical experience, it can be performed every 6-12 months in the first 2-3 years of treatment, and then the frequency is reduced (such as every 1-2 years)
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 3.
Comparison of IVIg and corticosteroids IVIg and oral or intravenous corticosteroids are both first-line treatments for CIDP
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According to the level of evidence, TF has no tendency to recommend the two; the choice of the two should consider short-term and long-term effectiveness, risk, ease of implementation and cost, if short-term treatment is needed or there is a (relative) contraindication to corticosteroids , IVIg may be preferable
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In addition, studies have shown that corticosteroid pulse therapy may be more effective for long-term treatment
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 4.
Comparison of IVIg and plasma exchange Although the evidence from the study is limited, compared with plasma exchange, TF weakly recommends IVIg therapy, mainly based on the ease of administration of IVIg; in some patients with good vascular access, plasma exchange may be An acceptable option for chronic treatment
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5.
SCIgTF strongly recommends the use of SCIg in CIDP for maintenance treatment; TF has no tendency to recommend IVIg or SCIg for maintenance treatment of CIDP; during follow-up, the dose should be adjusted according to individual treatment response; TF is weak and recommends not to use SCIg in CIDP Induction therapy
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 6.
Plasma exchange TF strongly recommends plasma exchange treatment; initial treatment may start with 5 exchanges within 2 weeks, after which the plasma exchange interval should be individualized; if possible, peripheral veins should be used
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 7.
Other treatment methods: TF is weak; it is recommended not to use methotrexate; TF strongly recommends not to use interferon β-1a; TF is weak; fingolimod is not recommended; although there is only very low certainty evidence, TF recommends the use of sulfur Alemtrine, cyclophosphamide, cyclosporine, mycophenolate mofetil, and rituximab (used after first-line drugs are ineffective or as a combination therapy); TF recommends not to use alemtuzumab, bortezomib, etanercept Plasma, Fampridine, Fludarabine, Immunoadsorption, Interferon Alpha, Abatacept, Natalizumab, and Tacrolimus; Azathioprine, Mycophenolate Mofetil, or Cyclosporine can be considered Immunoglobulin or corticosteroid exemption agent for CIDP patients using immunoglobulin or corticosteroids as maintenance therapy; cyclophosphamide, cyclosporine or rituximab may be considered for first-line treatment (IVIg, corticosteroids and Plasma exchange) ineffective patients
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 8.
Pharmacological treatment of pain (1) TF recommends evaluation and treatment of pain in CIDP
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(2) Assess the cause of pain; consider alternative diagnoses that mimic CIDP (such as POEMS, vasculitis, diabetes, amyloidosis, CMT1B).
Neuropathic pain may be more common in these diseases
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(3) For neuropathic pain or sensory disorders, please consider treatment according to published guidelines, including tricyclic antidepressants, pregabalin, gabapentin or serotonin-norepinephrine reuptake inhibitor (dulo Xetine or venlafaxine) as first-line treatment
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 Summary 1.
CIDP diagnostic criteria (Figure 1) Figure 1 (1) Clinical diagnosis: typical CIDP and CIDP variants (Table 1) Table 1 CIDP clinical criteria (2) Electrophysiological diagnostic criteria: strong and weak support for demyelination (Table 2 and Table 3) Table 2 Motor nerve conduction standards Table 3 Sensory nerve conduction standards (3) Supporting standards: CSF, imaging, nerve biopsy and treatment response
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(4) Diagnostic certainty: confirmed CIDP and possible CIDP (Table 4)
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Table 4 Diagnostic classification 2.
Induction therapy (1) In the typical CIDP and CIDP variants with disabling symptoms, IVIg or corticosteroids should be considered (strongly recommended)
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Plasma exchange is equally effective (strongly recommended), but may be less tolerated and more difficult to manage
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(2) If the objective response is insufficient or the maintenance dose of the initial treatment (IVIg, corticosteroid or plasma exchange) causes obvious side effects, other first-line treatment options should be tried before considering the combination therapy (strongly recommended)
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You can consider adding immunosuppressants or immunomodulatory drugs, but there is not enough evidence to recommend any specific drugs
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(3) In sports CIDP, IVIg should be regarded as the initial treatment
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3.
Maintenance treatment (1) If the first-line treatment is effective, consider continuing to use it until the maximum benefit is achieved (strongly recommended), and then reduce the dose or increase the interval to find the lowest effective maintenance dose
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(2) Both SCIg and IVIg can be used as maintenance treatment for patients with active IVIg disease
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(3) Neuropathic pain should be treated with drugs in accordance with the published guidelines for the treatment of neuropathic pain
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(4) Recommendations on foot care, exercise, diet, driving and life>
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According to the needs of the patient, the use of orthotics, physical therapy, occupational therapy, psychological support and referral to a rehabilitation specialist should be considered
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 Original index: European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision.
J Peripher Nerv Syst.
2021 Sep;26(3):242-268.