Chronic inflammatory demyelinating polyradiculoneuropathy: clinical guidelines

List of Abbreviations

Terms and Definitions

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a group of chronic dysimmune neuropathies, heterogeneous in clinical presentation, characterized by a progressive generalized involvement of the proximal and distal segments of large sensory and motor nerve fibers lasting for more than 8 weeks.

First-line pathogenetic therapy for CIDP is the treatment received by a patient for the first time after diagnosis establishment. First-line pathogenetic therapy for CIDP involves treatment with first-line drugs and methods: GCs, HDIVIG, or PE.

Maintenance pathogenetic therapy for CIDP is treatment received by a patient to maintain a stable condition, remission, and prevent relapse. First- and/or second-line drugs and methods are prescribed as part of maintenance therapy.

Glucocorticoids (GCs) are synthetic drugs (analogs of endogenous hormones produced by the adrenal cortex) that exert anti-inflammatory, desensitizing, immunosuppressive, anti-shock, and antitoxic effects. GCs are a first-line pharmacological method of pathogenetic therapy for CIDP. High-dose GC therapy involves oral administration of drugs at a dose of 1 mg/kg of the patient's weight daily or every other day for 1–2 months, followed by a gradual dose reduction to the minimum maintenance dose or complete drug withdrawal.

High-volume therapeutic plasmapheresis (PE) is an extracorporeal method of first-line pathogenetic therapy for CIDP. High-volume plasmapheresis involves the removal of a total plasma volume of at least 140 ml/kg of the patient's weight per course.

High-dose intravenous immunotherapy (HDIVIG) is a first-line pharmacological method of pathogenetic therapy for CIDP, in which normal human intravenous immunoglobulin (IVIG) preparations with a class G immunoglobulin content of at least 95% are prescribed. HDIVIG involves the administration of the drug at a total course dose of 2 grams per kilogram of the patient's body weight. Maintenance IVIG immunotherapy is carried out with doses selected individually for each patient (from 0.4 to 2 grams per kilogram of the patient's body weight), with a variable administration regimen.

Monoclonal gammopathy of undetermined significance (MGUS) is a condition frequently associated with CIDP, characterized by paraprotein secretion in the absence of clinical and laboratory features of hemoblastosis.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a group of clinically heterogeneous, acquired, dysimmune neuropathies characterized by a progressive course lasting more than 8 weeks or a relapsing course, featuring electrophysiological and pathomorphological signs of peripheral nerve demyelination, and responding to immunosuppressive or immunomodulating therapy [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

To date, the exact mechanisms, causes of development, and trigger factors of the disease have not been fully elucidated; however, the dysimmune genesis of CIDP is beyond doubt. A number of experimental studies on animal models, as well as the response to immunosuppressive and immunomodulating therapy, indicate the undeniable participation of both cell-mediated and humoral immunity in the pathogenesis of the disease [2, 3]. The involvement of cellular immunity is confirmed by the presence of inflammatory infiltrates in sural nerve biopsies, represented by CD8+ T cells, CD4+ T cells, and macrophages; changes in the activity of the T-cell arm of immunity; and an increase in the expression of cytokines and other pro-inflammatory mediators in the blood and CSF of CIDP patients [4–6]. The involvement of humoral immunity in pathogenesis is confirmed by the detection of complement and immunoglobulin deposits on the surface of Schwann cells and in the compact layer of myelin in sural nerve biopsies, the presence of antibodies in patient sera, the creation of experimental models with active immunization of various nerve structures, and the efficacy of PE [7–9].

Over the past 5 years, antibodies associated with CIDP directed against nodal and paranodal proteins—neurofascin-140, 155, and 186 (NF-140, NF-155, NF-186), contactin-1 (CNTN1), contactin-associated protein 1 (Caspr1), and nodal isoforms of neurofascin—have been discovered. These antibodies are frequently associated with a severe disease course, early secondary axonal damage, and a poor response to GCs and IVIG [10–12]. The proportion of CIDP patients with antibodies to paranodal proteins is approximately 10% [10–14].

1.3 Epidemiology of the Disease or Condition

The global prevalence of CIDP ranges from 1 to 9 per 100,000 population [9, 15, 16]. CIDP is included in the List of Rare (Orphan) Diseases of the Russian Ministry of Health (dated February 25, 2020). The average age at disease onset is about 50 years, but the disease can be diagnosed at any age [17]. The male-to-female ratio is 2:1 [9, 15, 16]. According to N.A. Suponeva, the prevalence of CIDP in the Russian Federation ranges between 1 and 3 per 100,000 population [18]. According to the research results of E.A. Kantimirova (using ZATO Zheleznogorsk, Krasnoyarsk Krai, as an example), the prevalence of CIDP, including the sensory variant of the disease, was 25.5 per 100,000 adult population [17]. No large-scale epidemiological studies on the prevalence of CIDP have been conducted in the Russian Federation.

1.4 Features of Coding the Disease or Condition

G61.8 – Other inflammatory polyneuropathies

G61.9 – Inflammatory polyneuropathy, unspecified

G62.8 – Other specified polyneuropathies

G62.9 – Polyneuropathy, unspecified

1.5 Classification of the disease or condition

Distinguishing clinical variants of CIDP (typical and others) is important due to significant variability in the clinical and electrophysiological picture, immunopathogenesis, and response to various types of pathogenetic therapy (Table 1) [1, 8, 9, 15, 19, 20].

Table 1. Typical and variant forms of CIDP [1, 8, 9, 15, 19, 20].

1.6 Clinical presentation of the disease or condition

The most common form is typical CIDP, the clinical presentation of which is characterized by [1, 8, 9, 19, 20]:

• symmetric flaccid tetraparesis with uniform involvement of the distal and proximal segments of the limbs;

• superficial and deep sensory disturbances of polyneuritic pattern ("glove and stocking" distribution);

• sensory ataxia, hand tremor;

• decreased or absent tendon reflexes.

Extremely rarely, involvement of the respiratory muscles and cranial nerves (most commonly the facial nerve) is observed. Muscle hypotrophy may develop in the late stages of the disease. Motor impairments are usually more pronounced than sensory ones. Autonomic disturbances and neuropathic pain syndrome are not typical for classic CIDP. There are no signs of CNS and pelvic organ dysfunction. The degree of neurological deficit can vary from mild, without significant limitation of mobility and self-care, to severe, with complete dependence on outside assistance [1, 8, 9, 19, 20].

The second most common variant of CIDP is multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), also known as Lewis-Sumner syndrome. In contrast to classic CIDP, the clinical presentation is characterized by asymmetry of impairments and a multiple mononeuropathy pattern. Predominant involvement of the upper extremities is typical. In some patients, as the disease progresses, symptoms may transition into classic symmetric CIDP [1, 8, 9, 19-21].

The sensory variant of CIDP, which frequently debuts with lower extremity involvement, accounts for up to 5–35% of all disease variants. Sensory ataxia and a polyneuritic pattern of sensory impairments are characteristic. Muscle weakness is absent. Upon detection of neurophysiological signs of motor nerve fiber involvement according to nerve conduction studies (NCS) of one or more nerves, a diagnosis of "predominantly sensory CIDP variant" is established. Long-term studies have demonstrated that the sensory variant of CIDP is often a transient clinical stage of the disease that precedes the onset of muscle weakness in approximately 70% of patients [1, 8, 9, 19, 20, 22].

Distal acquired demyelinating symmetric neuropathy (DADS) is a variant of CIDP with predominant or isolated involvement of the distal extremities (hands and feet), presenting with a typical pattern of symmetric polyneuritic sensorimotor impairment [1, 8, 9, 19, 20, 23, 24]. Diagnosis of this variant is complicated by the similarity of clinical manifestations to hereditary motor and sensory neuropathy, paraproteinemic demyelinating neuropathies, as well as polyneuropathies of other origins (Appendix A3).

The motor variant of the disease is found in 4–10% of patients with CIDP. It is characterized by minimal severity (predominantly motor CIDP) or absence of sensory deficit, symmetric flaccid tetraparesis involving both proximal and distal segments, as well as an inadequate response to 1st-line pathogenetic therapy: GCS and plasmapheresis [1, 20, 25].

In the focal variant of CIDP, the pathological process involves the brachial or lumbosacral plexus, or peripheral nerves of 1–3 segments unilaterally; even more rarely, symptoms present as mononeuropathy. The focal variant of CIDP is considered by some authors to be a form of Lewis-Sumner syndrome. Over time, generalization of the pathological process and transformation of the clinical picture into classic symmetric or multifocal asymmetric CIDP variants are possible [1, 8, 9, 19, 20].

In classic CIDP and its variants, neurological impairments overwhelmingly progress steadily, or a relapsing-remitting chronic course is observed with symptom progression lasting longer than 8 weeks. Up to 16% of CIDP cases may have an acute onset and at presentation do not differ in their clinical, anamnestical, and neurophysiological characteristics from acute inflammatory demyelinating polyneuropathy (AIDP). There are no reliable instrumental and laboratory methods for differential diagnosis between acute-onset CIDP and AIDP at disease onset. The diagnosis of CIDP in the presence of acute symptom development is established if impairments progress for more than 8 weeks or if there are 3 episodes of deterioration despite ongoing pathogenetic therapy [1, 8, 9, 18, 19, 20].

Currently, chronic immune sensory polyradiculopathy and CIDP associated with antibodies to nodal and paranodal antigens are considered separately (not within the framework of CIDP variants). The symptom complex in chronic immune sensory polyradiculopathy is represented by pronounced sensory ataxia and sensory polyneuritic impairments; diagnosis can be significantly challenging because NCS findings reveal no pathological changes due to involvement of sensory roots at the preganglionic level and intactness of motor fibers. CIDP associated with IgG4 antibodies against neurofascin-155 and contactin-1 is characterized by an earlier age of disease onset, sensory ataxia, pronounced limb tremor, and central nervous system involvement in a number of patients; an aggressive disease course and early secondary axonal involvement of peripheral nerves are possible [1, 10-14, 19, 20, 26].

CIDP may also develop in conditions and diseases such as diabetes mellitus, monoclonal gammopathy of undetermined significance (IgG or IgA MGUS), IgM monoclonal gammopathy without anti-MAG antibodies, HIV infection, and malignancies. However, currently there is no convincing evidence of a direct relationship between CIDP and these conditions. In some cases, CIDP may be triggered by medications or biological agents [1, 10-14, 19, 20].

The differential diagnosis for classic CIDP and its variants is presented in Appendix A3.

2. Diagnostics, medical indications and contraindications for diagnostic methods

2.1 Complaints and Anamnesis

Comment: patients complain of weakness in the muscles of the hands and predominantly the legs, gait changes, difficulty running and climbing stairs; numbness, and decreased sensation in the hands and feet. In some cases, gait instability is a concern. Complaints of neuropathic pain, visual disturbances, swallowing or breathing difficulties, and pelvic organ dysfunction are not typical. During the interview, attention should be paid to the duration of symptom progression, presence of comorbid somatic diseases, premorbid background, and family history of neuromuscular disorders.

2.2 Physical Examination

2.3 Laboratory Diagnostics

Comment: the differential diagnosis is presented in Appendix A.3. If necessary, the list of additional laboratory diagnostic tests can be expanded and supplemented with assays such as determination of antibodies in the blood against Borrelia burgdorferi sensu lato group pathogens of tick-borne borreliosis, rheumatoid factor, C-reactive protein, antinuclear antibodies to Sm antigen, antibodies to extractable nuclear antigens in the blood, native DNA antibodies, cyclic citrullinated peptide antibodies (anti-CCP), antineutrophil cytoplasmic antibodies in the blood; blood test for antineuronal antibodies; peripheral nerve ganglioside antibodies, cryoglobulins, molecular genetic testing, and others.

Comment: diagnostic lumbar puncture is not recommended if there is full compliance with the clinical and electrodiagnostic criteria for CIDP [1]. In CIDP, the CSF protein level is elevated in 83–95% of cases with normal cell count <10/mm³. The normal CSF protein range should be adjusted for age (>0.5 g/L up to 50 years and >0.6 g/L after 50 years) [1, 32-34]. A normal CSF protein level does not rule out the diagnosis of CIDP. If pleocytosis >50/mm³ is detected, other causes of neurological impairment (neuroinfections, neurosarcoidosis, malignant lymphoproliferative disorders, etc.) must be ruled out [19, 35-36].

2.4 Instrumental Diagnostics

Comments: ENMG in CIDP patients reveals a generalized, predominantly symmetrical, sensorimotor neural lesion of primarily demyelinating type, characterized by a significant decrease in motor nerve conduction velocity (NCV), increased distal motor latency, increased minimum F-wave latency, presence of motor conduction blocks (reduction of proximal M-wave amplitude relative to distal by 30% or more), or pathological temporal dispersion (polyphasia and an increase in proximal motor response duration by >30% relative to distal) [1, 37-40]. Appendix A.3 (electrodiagnostic criteria for CIDP) specifies the recommended scope of the neurophysiological study. During ENMG, skin temperature must be maintained at no less than 33 °C over the palm and no less than 30 °C over the lateral malleolus [1].

Comments: Ultrasound of peripheral nerves and brachial plexus trunks is included in the supportive diagnostic criteria for CIDP (Appendix A.3). In CIDP, 40–80% of cases show an increased cross-sectional area of spinal nerves, brachial plexus trunks, and peripheral nerves outside tunnel zones, as well as intraneural sonographic changes (enlargement of individual fascicles, alternation of hypoechoic and hyperechoic enlarged fascicles). Appendix A.3 specifies the recommended minimum scope of the sonographic study. Peripheral nerve ultrasound findings do not correlate with the severity of clinical manifestations, and the absence of changes does not rule out the diagnosis of CIDP [45-50].

Comments: Plexus MRI is included in the supportive diagnostic criteria for CIDP (Appendix A.3). Increased signal intensity from the trunks of the brachial or lumbosacral plexuses in T2-STIR and DTI modes and/or hypertrophy (thickening) of spinal nerves and plexus trunks is detected in 44–82% of patients with CIDP. The absence of changes on MRI does not rule out the diagnosis of CIDP [4-44].

Comment: nerve morphological study is included in the supportive diagnostic criteria for CIDP (Appendix A.3). A sensory nerve biopsy is performed (most commonly the sural nerve) [52-54]. CIDP is characterized by the following morphological changes: onion-bulb formations, signs of perivascular inflammation, segmental macrophage-induced demyelination, axonal degeneration, remyelination [9, 19, 52-55].

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. First-line pathogenetic therapy

Comment: the aforementioned pathogenetic treatment methods have an equivalent short-term therapeutic effect [1, 9, 19]. If monotherapy is insufficiently effective or side effects occur, switching from one first-line therapy to another is possible. Combinations of GCs and IVIG, or GCs and PE, are permitted; intravenous normal human immunoglobulin administration is possible upon completion of a PE course.

Comment: in cases of a stable, non-progressive disease course and minimal neurological deficit (INCAT <2), initiating pathogenetic therapy is not recommended, leaving the patient under dynamic observation. Pathogenetic therapy is indicated for patients with CIDP in case of disease progression or relapse, acute onset, or the presence of neurological deficit that impairs mobility and self-care.

3.1.1 High-dose intravenous immunotherapy (HDIVIG)

Comment: severe anaphylactic reactions to IVIG are extremely rare. They most commonly develop in patients with IgA deficiency caused by the presence of antibodies (IgG or, less commonly, IgE) which, by interacting with IgA in the IVIG preparation, can trigger an anaphylactic reaction. The IgA level defining an IgA immunodeficiency is typically <7 mg/dL (0.07 g/L; 5–10 mg/dL). With IgA levels above 7 mg/dL, but 2 times lower than normal values, the condition may be considered partial IgA deficiency. The risk of adverse effects associated with IgA deficiency should not be regarded as an absolute contraindication to therapy. In such cases, premedication is administered; normal human immunoglobulin** preparations containing the lowest possible amount of IgA are infused intravenously; and the infusion rate recommended in the product instructions must not be exceeded.

Comments: the initial intravenous infusion of normal human immunoglobulin is performed in an inpatient setting (round-the-clock hospital) via daily infusions at a dose of 0.4 g/kg/day for 5 days (total course dose of 2 grams of the drug per kg of the patient's weight) [1, 70].

Comments: in the maintenance regimen for CIDP, IVIG can be administered in a round-the-clock or day hospital setting according to the following schedules [1, 9, 19, 70]:

• total dose of 0.4 g/kg, administration over 1 day, frequency – 1–2 times a week;

• total dose of 1 g/kg, administration over 2–3 days, frequency – every 3–4 weeks;

• total dose of 2 g/kg, administration over 3–5 days, frequency – every 4–6 weeks.

If the patient's condition remains stable for 6–12 months, achieved and maintained with regular repeated IVIG infusions, a gradual dose reduction and/or an increase in the interval between infusions is recommended. In cases of IVIG dependence—where remission is maintained by regular IVIG therapy, but deterioration occurs if the regimen is disrupted—IVIG administration should be continued for as long as possible [1, 9, 19, 59, 63-70]

3.1.2 Subcutaneous administration of normal human immunoglobulin

Comments: in the maintenance regimen for CIDP, subcutaneous immunoglobulin can be administered in a hospital setting, out-patient clinic, or at home according to the schedule [1, 9, 19, 67]: total dose 0.4 g/kg, administration over 1 day, frequency – once a week. If this regimen is ineffective, it is recommended to increase the dose and/or reduce the administration frequency.

3.1.3 Glucocorticoids (GCs)

Comments: the following GCS drugs and administration regimens are used in the treatment of CIDP [1, 74, 78]:

• #prednisolone** orally at a dose of 1–2 mg/kg/day daily or on an alternating schedule alternating "high" (1–2 mg/kg) and "low" (0.5–1 mg/kg) doses for 4–6 weeks. Upon achieving a clinical effect, the GCS dose is slowly tapered (on average, by 5–10 mg of #prednisolone** per week) over several months to the minimum maintenance dose or complete discontinuation [62, 89];

• intravenous administration of #methylprednisolone** at a dose of 1 g daily for 3–5 days (total course dose of 3–5 g) followed by a transition to intravenous #methylprednisolone** at 1 g once a week for 1 month, or to oral GCS according to the above schedule [62, 90];

• #dexamethasone** orally at 40 mg daily for 4 days once a month for six months [91].

Comment: monitoring of complete blood count (CBC) and general clinical blood chemistry, blood potassium and sodium levels is required twice in the first month of therapy, and monthly thereafter. Every 6 months (or as clinically indicated), the following investigations are performed: dual-energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur, EGD, consultations with a general physician (therapist), ophthalmologist, and endocrinologist. For the entire duration of GCS intake, it is necessary to prescribe: potassium supplements; proton pump inhibitors; calcium supplements in combination with vitamin D. Strict adherence to a diet (Pevzner diet Table 9), regular body weight measurement, and peripheral blood pressure monitoring are required while taking GCS.

Comment: in the motor form of CIDP, GCS therapy may worsen the condition; IVIG or #rituximab** administration is preferred [1, 25, 93, 94].

3.1.4 High-volume therapeutic plasmapheresis (PE)

Comments: continuous centrifugal or membrane (filtration) methods are used. TPE sessions are performed every 1–2 days, 3–5 procedures in total. The effect of plasmapheresis usually manifests quite quickly, but its duration is short-lived (2–4 weeks). TPE is preferred in cases of acute disease onset or rapid disease progression.

Comments: GCS or IVIG are prescribed according to the aforementioned regimens upon completion of the initial TPE course. As maintenance therapy, TPE sessions are performed once every 2–4 weeks with a total removed plasma volume of at least 140 ml/kg for six months, followed by a further individual increase in the interval between sessions (up to once every 3–6 months).

Comment: monitoring the patient's condition dynamics during therapy should be carried out using objective assessment methods (Appendix A3): neurological examination using rating scales (e.g., Neuropathy Impairment Score/NIS, Inflammatory Neuropathy Cause And Treatment/INCAT, Medical Research Council sum score/MRCss, and Inflammatory Rasch-built Overall Disability Scale/I-RODS (Appendix G1-G5). The assessment is performed at 4, 8, and 12 weeks after the initiation of therapy; based on the results – a conclusion is made regarding the efficacy of the ongoing treatment, and the adjustment of management tactics is considered. In the complete absence of effect or insufficient efficacy of a single first-line pathogenetic therapy method, one should switch to another method or combine two methods. If all first-line pathogenetic therapy methods (glucocorticosteroids, IVIG, plasma exchange) are ineffective, the diagnosis should be reconsidered; CIDP-like polyneuropathies should be ruled out if this has not been done previously (see Appendix A3), first- and second-line methods should be combined, and a switch to second-line therapy should be made.

3.2 Second-line pathogenetic therapy

Comments: clinical studies in CIDP have been conducted for the following drugs: azathioprine**, cyclosporine**, cyclophosphamide**, methotrexate**, rituximab**, mycophenolate mofetil**, interferon beta-1a**. At the time of developing these guidelines, there are no studies with a sufficient level of evidence to recommend one specific drug. The choice of a 2nd-line drug is individual [1, 104, 105].

There is convincing evidence of the efficacy of #rituximab** in the treatment of refractory forms of CIDP [97], however, controlled trials have not been conducted to date.

#Rituximab: intravenous administration according to the following regimens: 375 mg/m² once a week for 4 weeks; or at a dose of 1 g/m² once every 2 weeks, 2 doses; or 375 mg/m² once every 6 months. The drug is administered in a hospital setting; premedication must be performed 30 minutes before the infusion: intramuscular administration of #diphenhydramine, intramuscular administration of #dexamethasone**, #paracetamol** orally, according to the drug prescribing information. Adverse events: infusion reactions, cytopenia, allergic reactions, infections [93, 94, 107-109].

3.3 Symptomatic therapy

Comments: for nociceptive pain, patients with CIDP are prescribed non-steroidal anti-inflammatory and antirheumatic drugs and/or other analgesics and antipyretics according to the drug prescribing information. The presence of neuropathic pain syndrome in a patient with suspected CIDP requires differential diagnosis with neuropathies of other genesis (Appendix A3). In accordance with the EFNS guidelines for the management of neuropathic pain, a first-line drug is prescribed (monotherapy or combination): non-selective monoamine reuptake inhibitors, antiepileptic drugs (gabapentin), other antidepressants (duloxetine) [113].

3.4 Non-pharmacological therapy

Comments: prevention of pressure ulcers, hypostatic pneumonia, contractures, secondary infectious complications, deep vein thrombosis, and pulmonary embolism is necessary.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comment: a comprehensive approach is required, combining exercise therapy (physiotherapy exercises) using apparatus and exercise equipment for peripheral nervous system diseases, physical therapy, macroenvironment adaptation procedures and clinical-psychological adaptation in accordance with the patient's functional deficit, the use of assistive devices and technical aids (orthoses, additional support, etc.), and psychological support. The rehabilitation process for patients with CIDP should be continuous in a maintenance mode.

Comments: exercise therapy sessions are conducted under the supervision of a physical therapy instructor in the following mode – 60 minutes 3 times a week for at least 12 weeks.

Comments: aerobic exercises are performed for 20-30 minutes 3 times a week for at least 12 weeks. Strength exercises are performed under the supervision of a physical therapy instructor with a weight comfortable for the patient, working the major muscle groups according to the scheme: 3 sets of 12 repetitions 3 times a week for at least 12 weeks.

4.1 Sanatorium-resort treatment and medical rehabilitation methods based on natural therapeutic factors

Methods of sanatorium-resort treatment for CIDP have not been developed [1,9]. In accordance with Order of the Russian Ministry of Health No. 557n dated May 31, 2021, "On approval of the classification of natural therapeutic resources, medical indications and contraindications for their use for therapeutic and prophylactic purposes," the use of natural therapeutic resources for CIDP is not indicated [125]. If the sanatorium-resort organization has a license for medical rehabilitation:

Comment: a comprehensive approach is required, combining exercise therapy (physiotherapy exercises) using apparatus and exercise equipment for peripheral nervous system diseases, physical therapy, macroenvironment adaptation procedures and clinical-psychological adaptation in accordance with the patient's functional deficit, the use of assistive devices and technical aids (orthoses, additional support, etc.), and psychological support.

5. Prevention and Dispensary Observation

Methods for preventing the development of CIDP have not been developed [1, 9, 113].

Comment: for patients receiving pathogenetic therapy, visits to a neurologist are necessary every 1-3 months for the entire duration of therapy in order to adjust it and monitor adverse events. In case of a stable condition (remission), visits to a neurologist are possible once every six months or as needed.

6. Organization of Medical Care

As clinically indicated at any stage of the disease, an expert assessment (examination) regarding the loss of professional and general working capacity is recommended to establish a disability group.

Indications for hospitalization of a patient with CIDP in a medical organization:

1. Emergency hospitalization (24-hour inpatient facility) is indicated for all patients with CIDP presenting with an acute or subacute onset for differential diagnosis with other polyneuropathies of similar course (Guillain-Barré syndrome, porphyric neuropathy, etc.) and pathogenetic therapy (plasma exchange, glucocorticosteroids, IVIG); upon the appearance of signs of respiratory failure, bulbar dysfunction, or rapid progression in patients with a previously or newly established diagnosis;

2. Elective hospitalization (24-hour inpatient facility) is indicated for all patients to perform differential diagnosis with CIDP-like neuropathies, lumbar puncture, initiation or maintenance of first-line pathogenetic therapy (IVIG or glucocorticosteroid pulse therapy), parenteral second-line pathogenetic therapy in an ICU setting to prevent exacerbation and disease progression, rehabilitation measures, and symptomatic therapy.

Comments: first-line maintenance pathogenetic therapy, symptomatic therapy, and rehabilitation in the acute period (или при обострении) can also be carried out in a day hospital if the patient has no impairment of vital functions and no severe motor deficit (wheelchair-bound, walks with support no more than 10 m). Rehabilitation and symptomatic therapy, as well as maintenance GC therapy, can be performed in an outpatient setting.

Indications for discharging a patient from a medical organization:

1. Discharge of a patient from a medical organization during emergency hospitalization is possible provided that all necessary diagnostic, therapeutic, and rehabilitation measures from items 2–4 of these clinical guidelines are performed in full; the patient is in a stable satisfactory condition with preserved vital functions.

2. Discharge of a patient from a medical organization during elective hospitalization is possible provided that planned therapy and rehabilitation measures are performed in full; the patient is in a stable satisfactory condition with preserved vital functions.

Indications for medical rehabilitation in sanatorium-resort organizations:

1. If the sanatorium-resort organization has a license for medical rehabilitation, medical care for patients with CIDP is organized in accordance with Order of the Ministry of Health of the Russian Federation No. 788n dated July 31, 2020, "On Approval of the Procedure for Organizing Medical Rehabilitation for Adults" [127].

7. Additional Information

• Individual studies have shown that the most significant factors influencing the outcome of CIDP are morphological signs of active demyelination of a large number of nerve fibers and their axonal degeneration, which underlies disability [122].

• Early diagnosis and initiation of pathogenetic therapy according to recommended regimens prevent the development of axonal degeneration and are thus associated with less disability [123–125].

• Severe neurological deficit and progressive course, concomitant somatic disorders and coexisting CNS diseases, and older age at CIDP onset are unfavorable prognostic factors [122], whereas subacute onset, symmetry of changes, absence of muscle atrophy, response to GC therapy at CIDP onset, and a predominantly distal pattern of peripheral nerve involvement according to ENMG at disease onset are associated with a favorable 5-year prognosis [123–125].

• More than 70–80% of patients respond to first-line pathogenetic therapy [1, 9, 19, 59], and sustained drug-induced remission can be achieved in many cases; however, upon long-term follow-up, varying degrees of disability are possible in the majority of cases, with 28% of patients requiring assistive mobility devices [123].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Piradov Mikhail Aleksandrovich – Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Director of the Research Center of Neurology (Moscow);

2. Gusev Evgeny Ivanovich – Neurologist, Academician of the RAS, Doctor of Medical Sciences, Professor, Head of the Department of Neurology, Neurosurgery, and Medical Genetics, Pirogov Russian National Research Medical University of the Russian Ministry of Health. Chairman of the All-Russian Society of Neurologists;

3. Suponeva Natalia Aleksandrovna – Neurologist, Functional Diagnostics Physician, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, Director of the Institute of Neurorehabilitation and Restorative Technologies of the Research Center of Neurology, Scientific Consultant of the Peripheral Nervous System Disorders Center of the Research Center of Neurology (Moscow);

4. Nikitin Sergey Sergeevich – Neurologist, Functional Diagnostics Physician, Doctor of Medical Sciences, Professor, Chairman of the NGO "Association of Neuromuscular Disease Specialists" (Moscow), Head of the Department of Genetics of Neurological Diseases at the Research Centre for Medical Genetics named after Academician N.P. Bochkov;

5. Grishina Daria Aleksandrovna – Neurologist, Functional Diagnostics Physician, Candidate of Medical Sciences, Senior Research Fellow at the Laboratory of Clinical Neurophysiology, Head of the Center for Peripheral Nervous System Disorders of the Research Center of Neurology (Moscow);

6. Devlikamova Farida Ildusovna – Neurologist, Doctor of Medical Sciences, Professor at the Department of Neurology, Kazan State Medical Academy – a branch of the Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, Honored Doctor of the Republic of Tatarstan, Accredited Expert of the Federal Service for Surveillance in Healthcare in Neurology (Kazan);

7. Zinovyeva Olga Evgenyevna – Neurologist, Doctor of Medical Sciences, Professor at the Department of Nervous System Diseases and Neurosurgery, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Moscow);

8. Kurenkov Alexey Lvovich – Neurologist, Functional Diagnostics Physician, Doctor of Medical Sciences, Head of the Laboratory of Nervous System Diseases in Children at the National Medical Research Center for Children's Health of the Russian Ministry of Health (Moscow);

9. Rachin Andrey Petrovich – Neurologist, Doctor of Medical Sciences, Professor, Deputy Director for Research, Head of the Department of Neurorehabilitation and Clinical Psychology at the National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health (Moscow);

10. Prokopenko Semyon Vladimirovich – Neurologist, Physical and Rehabilitation Medicine Physician, Doctor of Medical Sciences, Professor, Head of the Department of Nervous Diseases at KrasSMU, Chief Neurorehabilitation Specialist of the Siberian Federal District, Scientific Director of the Neurology and Neurorehabilitation Service at the Federal Siberian Research and Clinical Center of the Federal Medical-Biological Agency, Neurologist;

11. Ivanova Galina Evgenyevna – Physical and Rehabilitation Medicine Physician, Professor, Doctor of Medical Sciences. Chairperson of the All-Russian Public Organization for the Promotion of Medical Rehabilitation Development "Union of Rehabilitation Specialists of Russia". Chief Specialist in Medical Rehabilitation of the Russian Ministry of Health. Head of the Department of Medical and Social Stroke Rehabilitation at the Research Institute of Cerebrovascular Pathology and Stroke. Head of the Department of Medical Rehabilitation at the Faculty of Additional Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health;

12. Martynov Mikhail Yuryevich – Doctor of Medical Sciences, Professor, Corresponding Member of the RAS, Professor at the Department of Neurology, Neurosurgery, and Medical Genetics, Senior Research Fellow at the Research Laboratory of Vascular Brain Diseases, Head of the Directorate for the Implementation of Functions of the National Medical Research Center for Neurology, Chief Freelance Neurologist of the Ministry of Health of the Russian Federation;

13. Belova Natalia Vyacheslavovna – Neurologist, Functional Diagnostics Physician, Candidate of Medical Sciences, Research Fellow at the Research Center of Neurology, Deputy Head of the Center for Peripheral Nervous System Disorders of the Research Center of Neurology;

14. Bardakov Sergey Nikolaevich – Neurologist, Candidate of Medical Sciences, Military Medical Academy named after S.M. Kirov.

Conflict of interest: none among all members of the working group

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Neurologists;

2. Functional diagnostics physicians;

3. General practitioners;

4. General practitioners (family physicians);

5. Physiotherapists.

Methods used for evidence collection/selection: the working group reviewed all publications on the definition, diagnosis, and treatment of CIDP from 1982 to 2020. All systematic reviews on randomized controlled trials regarding CIDP treatment were selected, and the levels of evidence (LE) and grades of recommendation (GR) were assessed. The assessment of LE and GR was carried out in accordance with the scales provided in tables 1-3 of Appendix A2. Literature searches were performed in Medline, the Cochrane Library, the eLIBRARY.ru scientific electronic library, Google Scholar, and PubMed. To minimize potential errors, each study was evaluated independently.

Table 1. Scale for grading levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for grading levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading the grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Order of the Ministry of Health of the Russian Federation dated December 24, 2012, No. 1537n "On Approval of the Standard of Specialized Medical Care for Chronic Inflammatory Demyelinating Polyneuropathy" (Registered with the Ministry of Justice of Russia on April 1, 2013, No. 27954).

Diagnostic criteria for CIDP

Title in Russian: "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"

Original title (if available): "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"

Source (developers' official website, validation publication): Van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA, Attarian S, Blomkwist-Markens PH, Cornblath DR, Eftimov F, Goedee HS, Harbo T, Kuwabara S, Lewis RA, Lunn MP, Nobile-Orazio E, Querol L, Rajabally YA, Sommer C, Topaloglu HA. 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. doi: 10.1111/jns.12455. Epub 2021 Jul 30. PMID: 34085743.

Type (underline):

rating scale

index

questionnaire

other (specify): diagnostic criteria

CIDP DIAGNOSTIC CATEGORIES

Differential diagnosis of CIDP with paraproteinemic demyelinating neuropathies

Paraproteinemic demyelinating neuropathies are a heterogeneous group of disorders in which the clinical presentation of CIDP is combined with paraprotein secretion. Up to 30% of CIDP cases are accompanied by monoclonal secretion, and up to 50% of these turn out to be malignant lymphoproliferative disorders, in which neurological symptoms may be the first or only clinical manifestations.

1. Definition

Monoclonal gammopathy (paraproteinemia, M-protein secretion, M-gradient) is the pathological secretion of one of the immunoglobulin classes by B-lymphoid cells.

2. Classification

A. Monoclonal gammopathy of undetermined significance (MGUS):

a) IgA, IgG paraprotein secretion

b) IgM paraprotein secretion:

• with antibodies against myelin-associated glycoprotein (anti-MAG) – classified as a separate nosological entity, not included in the list of CIDP variants;

• without antibodies against myelin-associated glycoprotein (anti-MAG);

B. Lymphoproliferative disorders:

a) Multiple myeloma, plasmacytoma, malignant lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, heavy chain disease, primary amyloidosis;

b) POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes);

c) CANOMAD syndrome – chronic ataxic neuropathy with ophthalmoplegia, IgM-associated monoclonal gammopathy, cold agglutinins, and anti-disialoganglioside antibodies (IgM antibodies to GD1b/GQ1b).

3. Clinical presentation

A. Meets the clinical criteria for CIDP (EAN/PNS, 2021);

B. May have the following features:

a) Predominance of sensory symptoms;

b) Marked sensory ataxia, limb tremor;

c) Predominantly distal distribution of muscle weakness;

d) Slow, steady progression without remissions.

4. Instrumental and laboratory diagnostics

A. ENMG: compliance with electrodiagnostic criteria for CIDP (EAN/PNS, 2021) in the "definite/probable" category;

B. Laboratory methods:

a) Serum and urine protein electrophoresis with immunofixation;

b) Blood testing for antibodies to myelin antigens (if paraprotein secretion is IgM);

c) Testing for vascular endothelial growth factor (VEGF) levels if POEMS syndrome is suspected;

d) Testing for antibodies to peripheral nerve gangliosides (GQ1b, GM1, GD1a, GD1b, SGPG) (advisable when CANOMAD and IgM paraproteinemia without anti-MAG antibody secretion are suspected).

C. Additional workup aimed at clarifying the type of hemoblastosis:

a) Computed tomography of the chest and abdominopelvic organs,

b) Radiography of the ribs, sternum, and scapula,

c) CT-guided trephine bone marrow biopsy of the pelvic bones / sternal puncture,

d) Ultrasound of lymph nodes with needle biopsy as indicated,

e) Consultation with an oncologist or hematologist based on the examination results.

5. Treatment and monitoring

A. Monitoring:

a) Blood paraprotein levels; urine test for Bence-Jones protein;

b) Blood immunoglobulin levels;

c) Complete blood count, erythrocyte sedimentation rate;

d) Blood creatinine, total and ionized calcium, and beta-2-microglobulin levels;

For MGUS, tests are performed once a year; in cases of high risk of malignant transformation, once every 3–6 months.

B. Treatment:

1. For established CIDP associated with monoclonal gammopathy of undetermined significance (IgA, IgG, IgM secretion without anti-MAG antibodies): treatment regimens do not differ from those for CIDP without paraproteinemia;

2. For established IgM-paraproteinemic demyelinating polyneuropathy with anti-MAG antibodies:

• first-line therapy is #Rituximab at standard therapeutic doses;

• in Waldenström macroglobulinemia with hyperviscosity syndrome, high-volume plasmapheresis is advisable prior to initiating #Rituximab therapy.

3. For an established lymphoproliferative disorder, treatment is managed by an oncologist or hematologist; the neurologist acts as a consultant, with symptomatic therapy for neuropathic pain and rehabilitation measures prescribed as necessary.

Differential diagnosis of CIDP variants

Differential diagnosis of CIDP with polyneuropathies of other genesis

Note: CIDP – chronic inflammatory demyelinating polyradiculoneuropathy with acute onset; AIDP – acute inflammatory demyelinating polyneuropathy; MMN – multifocal motor neuropathy; CB – conduction block; M-wave – motor response; MCV – motor conduction velocity.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Definition and Epidemiology

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare chronic peripheral nerve disease. The global prevalence of CIDP averages 8–9 cases per 100,000 population. Men are affected more frequently than women. CIDP can develop at any age, but the peak incidence occurs in working-age adults (40–50 years).

Etiology

The disease is based on an immune response disorder. The patient's patient immune system mistakenly attacks the myelin sheath of their own peripheral nerves, impairing their function, which manifests as a loss of sensation and strength in the arms and legs. The exact cause triggering the immune response and the development of CIDP remains unknown. CIDP is a non-hereditary and non-contagious disease. There are no clear triggers or risk factors for developing the disease.

Clinical presentation

Symptoms develop slowly, over more than 2 months. The disease typically begins in the feet and spreads in an ascending pattern to the thighs, trunk, and arms. Facial muscles and vital functions (respiration) are rarely involved. Symptoms of CIDP usually present as relatively symmetrical limb involvement and include:

• weakness in the legs and arms, decreased muscle tone;

• gait disturbance; instability and impaired motor coordination;

• decreased sensitivity, numbness, or tingling in the hands and feet.

Pain syndrome is not characteristic. The course of the disease can be variable:

• the majority of patients experience relapses of the disease; maintenance therapy is required;

• in some cases, primary therapy achieves stable, long-term (more than 1 year) remission;

• isolated cases are distinguished by resistance to applied treatment methods, and the disease progresses.

Diagnostics

To establish a diagnosis of CIDP, the physician thoroughly studies the medical history, performs an examination, and orders additional diagnostic tests:

• general (clinical) blood and urine tests;

• ENMG – a highly informative instrumental method for studying peripheral nerve function.

During the diagnostic process, it is important to exclude other nervous system diseases and polyneuropathies of a different genesis that present under the "mask" of CIDP. If the diagnosis cannot be established using the aforementioned examination methods, more advanced studies are prescribed:

• ultrasound examination (US) of peripheral nerves and plexuses;

• magnetic resonance imaging (MRI) of nerve plexuses;

• lumbar puncture;

• sural nerve biopsy.

The definitive diagnosis of "CIDP" is established based on the criteria proposed by the European Federation of Neurological Societies in 2010.

Treatment

Treatment of this disease requires an integrated approach consisting of both pharmacotherapy and non-pharmacotherapeutic therapy (physical and psychological rehabilitation). Pathogenetic therapy has been developed for CIDP—treatment aimed at controlling the pathological immune attack. Pathogenetic therapy includes three main methods:

• Glucocorticoids (GC) are prescribed in tablet and/or infusion form. The duration of administration and dose size depend on the severity of symptoms. Despite proven efficacy and relatively low cost, GC treatment is associated with a number of side effects, the frequency and severity of which are individual—weight gain, nausea, insomnia, irritability, exacerbation of peptic ulcer disease, elevated blood pressure and blood sugar levels, decreased bone mineral density (osteopenia, osteoporosis), etc. Regular monitoring and timely prevention of therapy-related side effects are required.

• Intravenous human immunoglobulin (IVIG) preparations are highly effective and safe. Treatment consists of monthly course-based intravenous administration of the drug. Subsequently, the frequency of intravenous administration of normal human immunoglobulin can vary depending on its efficacy. It is important to correctly select the preparation—only IVIG containing 95% IgG immunoglobulin is used to treat CIDP. Before starting treatment, screening for blood IgA levels is necessary to reduce the risk of IVIG side effects.

• High-volume plasmapheresis is a procedure for removing pathogenic antibodies from blood plasma and replacing them with sterile solutions, protein solutions, and/or donor plasma. The procedure includes 3 to 5 sessions. The therapeutic effect lasts no longer than 2–4 weeks. This method of therapy is not used for long-term treatment, but is useful in cases of rapid and/or severe exacerbation, or as an adjunct treatment method to the main therapy (glucocorticoids, etc.).

In some patients, despite timely and adequate treatment, the disease may progress and remain refractory to control. In such cases, immunosuppressants (mycophenolate mofetil, azathioprine, cyclosporine, cyclophosphamide, etc.) or a monoclonal antibody preparation (rituximab) are prescribed.

None of the currently known drugs cures CIDP, but they reduce disease activity and prevent further deterioration or exacerbation. Each treatment method has its pros and cons, which are discussed with the physician, taking into account all the features of the case.

General Recommendations

• Avoid excessive emotional and physical stress, maintain a proper work-rest balance;

• Insolation and thermal procedures should be dosed;

• Limit alcohol intake and any other neurotoxic medications;

• Follow the neurologist's prescriptions;

• Adhere to the principles of continuous rehabilitation.

The life expectancy of patients with CIDP does not differ from that of individuals without this disease. Timely prescription of treatment, careful monitoring of the patient, and the effect of ongoing therapy are extremely important for the prognosis.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Medical Research Council (MRC) Sum Score for muscle strength

Russian title: Medical Research Council sum score.

Original title: Medical Research Council sum score (MRCss)

Source (official developer website, validation publication): https://www.researchgate.net/profile/Martin_Posch/publication/23484750_Reliability_and_Validity_of_the_Medical_Research_Council_MRC_Scale_and_a_Modified_Scale_for_Testing_Muscle_Strength_in_Patients_with_Radial_Palsy/links/0c96051f8cd6db8174000000/Reliability-and-Validity-of-the-Medical-Research-Council-MRC-Scale-and-a-Modified-Scale-for-Testing-Muscle-Strength-in-Patients-with-Radial-Palsy.pdf

Type (underline):

- rating scale

- index

- questionnaire

- other (specify).

Purpose: assessment of the strength of tested muscles at the time of examination.

Content (template): the strength of tested muscle groups is scored from 0 (no muscle contraction) to 5 (normal).

Key (interpretation): the higher the score, the greater the muscle strength; a score sum of 0 (minimum) corresponds to tetraplegia; a score sum of 60 (maximum) corresponds to normal.

Medical Research Council Sum Score

Strength is assessed in 6 muscle groups bilaterally:

Appendix G2. Inflammatory Neuropathy Cause and Treatment (INCAT) scale

Russian name: Inflammatory Neuropathy Cause and Treatment scale.

Original name: Inflammatory Neuropathy Cause and Treatment (INCAT)

Source (official website of the developers, validation publication):

1) https://n.neurology.org/content/54/4/943

2) https://nmb.abvpress.ru/jour/article/view/466/307

Type (underline):

- rating scale

- index

- questionnaire

- other (specify).

Purpose: assessment of the degree of disability in patients with chronic inflammatory demyelinating polyneuropathy.

Content (template): The INCAT disability scale allows assessing the degree of activity limitation based on a series of questions asked by the physician to the patient. Impairment in the arms and legs is scored from 0 to 5 based on the patient's selection of the severity of impairment.

Key (interpretation): sum of scores for upper and lower limb impairments.

Upper limb score:

• 0 – no impairment;

• 1 – symptoms in one or both hands that do not affect the execution of any of the following activities: fastening all zippers and buttons; washing hair or combing hair; simultaneous use of a knife and fork; handling small coins;

• 2 – symptoms in one or both hands that impair the execution of any of the listed activities, but do not prevent it;

• 3 – symptoms in one or both hands that prevent the execution of one or two of the listed activities;

• 4 – symptoms in one or both hands that prevent the execution of three or all of the listed activities;

• 5 – purposeful hand movements are impossible.

Lower limb score:

• 0 – gait is not impaired;

• 1 – gait is impaired, independent outdoor ambulation is possible;

• 2 – unilateral support (cane, crutch, support from another person) is required for outdoor ambulation;

• 3 – bilateral support (two canes, crutches, support from two people) is required for outdoor ambulation;

• 4 – a wheelchair is required for outdoor mobility; the ability to stand up and take a few steps with outside assistance is retained;

• 5 – wheelchair-bound; the patient is unable to stand up and take a few steps with outside assistance.

Inflammatory Neuropathy Cause and Treatment scale

Appendix G3. Neuropathy Impairment Score

Russian name: Neuropathy Impairment Score

Original name: Neuropathy Impairment Score (NIS)

Source (official website of the developers, validation publication):

https://onlinelibrary.wiley.com/doi/10.1002/ana.410080608

Official validated version, published in print

Type (underline):

- rating scale

- index

- questionnaire

- other (specify).

Purpose: to provide a general assessment of neuropathic deficit, as well as an assessment of specific parameters: cranial nerves, muscle weakness, reflexes, and sensory disturbances. Impairments are identified during a neurological examination that assesses all these functions.

Content (template): The NIS disability scale allows assessing the severity of neuropathic impairments compared to the norm, depending on the evaluation method, localization, age, sex, height, body weight, and physical fitness. Impairment scores are determined based on the results of a neurological examination. Tactile, pain, and vibration sensitivity are assessed on the dorsal side of the distal phalanx of the index finger and the great toe in the periungual area. Tactile sensitivity is assessed using a long cotton wisp. Pain sensitivity is assessed using a needle pinprick. Vibration sensitivity is assessed using a 165 Hz tuning fork. Joint position sense is assessed by moving the distal phalanx of the index finger and the great toes.

Key (interpretation):

For patients aged 50–69 years, absent Achilles reflexes are scored as 1 point, while diminished Achilles reflexes are scored as 0 points. For patients over 70 years of age, absent Achilles reflexes are scored as 0 points.

Neuropathy Impairment Score (NIS)

Appendix G4. Disability Rating Scale for Patients with Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Polyneuropathy Associated with Monoclonal Gammopathy of Undetermined Significance

Russian name: Disability Rating Scale for Patients with Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Polyneuropathy Associated with Monoclonal Gammopathy of Undetermined Significance.

Original name: Inflammatory Rasch-built Overall Disability Scale (I-RODS)

Source (official developers' website, validation publication):

https://n.neurology.org/content/76/4/337.long

Official validated version, published in print

Type (underline):

- rating scale

- index

- questionnaire

- other (specify).

Purpose: to assess the relationship between health status and daily activity, and to evaluate the impact of polyneuropathy on the performance of daily activities at home and in society.

Content (template): the patient independently answers questions regarding the degree of limitation in daily activities and household tasks due to polyneuropathy. The answer is recorded by marking a single option with a cross in the corresponding column.

Key (interpretation): the result is scored in points: the higher the score, the fewer limitations the patient experiences in daily activities.

Disability Rating Scale for Patients with Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Polyneuropathy Associated with Monoclonal Gammopathy of Undetermined Significance.

Original name: Inflammatory Rasch-built Overall Disability Scale (I-RODS)

Appendix G5. CIDP Disease Activity Status scale

Russian title: Chronic Inflammatory Demyelinating Polyneuropathy Disease Activity Status

Original title: Chronic inflammatory demyelinating polyneuropathy Disease Activity Status (CDAS)

Source (official website of the developers, validation publication):

https://onlinelibrary.wiley.com/doi/10.1111/j.1529-8027.2010.00284.x

Type (underline):

- rating scale

- index

- questionnaire

- other (specify): disease activity classification

Purpose: assessment of CIDP disease activity

Content (template): the CDAS classification is based on a clinical assessment performed by the attending physician, taking into account disease duration, clinical response to therapy, neurological examination findings, and treatment duration.

Key (interpretation): based on the clinical assessment, a disease activity status is assigned: cured, remission, stable active disease, improvement, or unstable active disease.

Chronic Inflammatory Demyelinating Polyneuropathy Disease Activity Status (CDAS)

*5B and 5C refer to patients who were refractory to previous therapy or experienced deterioration despite ongoing treatment.