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Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis
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Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis
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Literature review current through: Sep 2017. | This topic last updated: May 19, 2017.

INTRODUCTION — Chronic inflammatory demyelinating polyneuropathy (CIDP, also known as chronic inflammatory demyelinating polyradiculoneuropathy) is an acquired disorder of peripheral nerves and nerve roots. There have been descriptions of patients with disorders that would now be considered CIDP for over 75 years, and the landmark report of Austin in 1958 described two patients with relapsing disease and glucocorticoid response [1].

The concept of CIDP as a distinct entity was introduced in 1975 when a review of the clinical, electrodiagnostic, and pathologic findings of 53 patients was presented [2]. While that publication did not include "demyelinating" in the title, subsequent reports have included it, and demyelination is now recognized as a cardinal feature of the disorder.

The classification, etiology, clinical features, and diagnosis of CIDP will be reviewed here. Treatment and prognosis of this disorder are discussed separately. (See "Chronic inflammatory demyelinating polyneuropathy: Treatment and prognosis".)

CLASSIFICATION — Whether CIDP is a disease or a syndrome remains controversial. The following neuropathies all have chronicity, demyelination, inflammation, or immune-mediation in common:

CIDP

Multifocal motor neuropathy (MMN) (see "Multifocal motor neuropathy")

Lewis-Sumner syndrome, also known as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)

Distal demyelinating neuropathy with IgM paraprotein, with or without anti-myelin associated glycoprotein (anti-MAG)

Demyelinating neuropathy with IgG or IgA paraprotein (the terms paraprotein and monoclonal gammopathy of undetermined significance [MGUS] are used synonymously in this setting)

POEMS syndrome (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) (see "POEMS syndrome")

Sensory predominant demyelinating neuropathy

Demyelinating neuropathy with central nervous system demyelination

Demyelinating neuropathy associated with systemic disorders, including:

Hepatitis B or C

HIV infection

Lymphoma

Diabetes mellitus

Systemic lupus erythematosus or other collagen vascular disorders

Thyrotoxicosis

Organ or bone marrow transplants

Inherited neuropathies

Nephrotic syndrome

Inflammatory bowel disease

While there is no established consensus regarding the classification of all these neuropathies, there is general agreement that MMN, POEMS, and the MAG-related neuropathies are distinct from CIDP and the other neuropathies on the basis of clinical, electrodiagnostic, and therapeutic differences.

Most investigators consider the remaining disorders to be variants of CIDP since they have many common clinical and electrodiagnostic features and treatment response with immunotherapy appears to be similar. The classification of inflammatory demyelinating neuropathies will continue to evolve as specific immune mechanisms are elucidated.

Temporal continuum — There is a temporal continuum between acute inflammatory demyelinating polyneuropathy (AIDP), which is the demyelinating form of Guillain-Barré syndrome (GBS), and CIDP.

AIDP is a monophasic subacute illness that reaches its nadir within three to four weeks

CIDP continues to progress or has relapses for greater than eight weeks

Subacute inflammatory demyelinating polyneuropathy (SIDP) is the term used by some authors for disease that reaches its nadir between four and eight weeks [3,4]

This arbitrary temporal delineation of inflammatory demyelinating polyneuropathy can occasionally be difficult to ascertain in practice. Only observation of the patient over time can clarify whether the clinical course is that of AIDP or CIDP [5], and therapeutic interventions are likely to be initiated before a patient reaches a specific time point that distinguishes between these entities. As an example, some patients with CIDP have a subacute onset resembling that seen in GBS, and CIDP is recognized only after relapses or progression occur over the ensuing few months.

In addition to chronicity, other features may be useful to distinguish GBS (including AIDP) from CIDP.

The onset of GBS is usually easily identified, while the precise onset of CIDP is typically less clear. (See "Guillain-Barré syndrome in adults: Clinical features and diagnosis".)

Antecedent events are more frequent with GBS than in CIDP. Approximately 70 percent of AIDP cases are preceded by an infectious illness, vaccination, or surgery by three to four weeks prior to the onset of clinical symptoms. In contrast, most studies have found an antecedent event prior to CIDP in no more than 30 percent of patients. (See "Guillain-Barré syndrome: Pathogenesis", section on 'Antecedent events'.)

Prominent sensory signs (ie, sensory ataxia and impaired vibration and pinprick sensation) favor CIDP [6].

The need for ventilator support favors GBS [6].

Progression or relapse beyond eight weeks from onset suggests acute onset CIDP rather than GBS [7].

PATHOGENESIS — Although the cause of CIDP and its variants is unknown, there is evidence to support the hypotheses that the disorder(s) are immunologically based and have multiple triggers. Both the cellular and humoral components of the immune system appear to be involved in the pathogenesis of CIDP and its variants [8-11].

Cellular immunity involvement is supported by evidence of T-cell activation, crossing of the blood-nerve barrier by activated T-cells, and by expression of cytokines, tumor necrosis factor, interferons, and interleukins.

Humoral immunity is implicated by the demonstration of immunoglobulin and complement deposition on myelinated nerve fibers, and by passive transfer experiments that induce conduction block and demyelination by injecting serum or purified IgG from CIDP patients into rats.

The immunologic cause(s) of most forms of CIDP remain unclear, since specific provoking antigens have not previously been identified [10]. However, antibodies to neurofascin-155 or to contactin were detected in small numbers of patients with CIDP who had severe disease, in some cases associated with tremor [12,13]. Neurofascin and contactin are critical structural elements of the paranodal loop attachment to the axolemma. The antibodies identified are in the IgG4 subclass. These antibodies appear to target paranodal proteins and may disrupt the axonal-glial junctions, leading to nerve conduction slowing [14-16]. (See 'Neurofascin antibody-mediated CIDP' below and 'Contactin 1 antibody-mediated CIDP' below.)

As seen in another IgG4-mediated neuromuscular disorder, MuSK antibody myasthenia gravis, these CIDP cases were not responsive to intravenous immunoglobulin and glucocorticoids but were responsive to B cell depletion treatment with rituximab [17].

EPIDEMIOLOGY — The estimated prevalence of CIDP in populations from the United Kingdom, Australia, Italy, Japan, and the United States is 0.8 to 8.9 per 100,000 [18-23]. CIDP can affect all ages but is more common in older males. It is thought that the disease is more likely to be progressive in the older age group and relapsing-remitting in younger patients.

No specific predisposing factors for CIDP have been identified. There have been conflicting studies on human leukocyte antigen (HLA) type associations, but no clear genetic predisposition has been found. In several case reports, treatment with tumor necrosis factor-alpha inhibitors has been associated with the subsequent development of chronic demyelinating neuropathies [24].

CLINICAL MANIFESTATIONS — The initial description of CIDP in 1975 pointed out the major cardinal features of the disorder [2]. The classic form of CIDP is fairly symmetric and motor involvement is greater than sensory. Weakness is present in both proximal and distal muscles, and this pattern is a hallmark of acquired demyelinating polyneuropathy [5]. Cranial nerve and bulbar involvement occur in 10 to 20 percent of patients. Tremor has been reported as a common symptom in several studies [25,26].

Most patients with CIDP also have sensory involvement and globally diminished or absent reflexes [2,27]. Sensory impairment in CIDP is usually greater for vibration and position sense than for pain and temperature sense, reflecting the involvement of larger myelinated fibers. Unlike the motor involvement, the sensory involvement tends to follow a distal to proximal gradient, although finger involvement is frequently seen as early as toe and foot involvement. Painful dysesthesias can occur. Back pain may also be present. Symptoms of lumbar spinal stenosis and cauda equina syndrome can occur rarely if there is marked nerve root hypertrophy, and these problems may require surgical intervention.

Autonomic involvement in CIDP is generally mild and limited in distribution [28]. Constipation and urinary retention are not usually early symptoms of CIDP, but may occur in more severe cases.

Most patients with CIDP exhibit a slowly progressive course, but a relapsing-remitting course is noted in at least one-third, and may be more common in younger patients [27]. The advent of early treatment for CIDP has made the temporal progression of the disease more difficult to characterize, since remissions may be related to therapy rather than to the natural course of the disease. (See "Chronic inflammatory demyelinating polyneuropathy: Treatment and prognosis", section on 'Prognosis'.)

Variants of CIDP — The clinical variants of CIDP are distinguished by their presentation and include the Lewis-Sumner syndrome, sensory-predominant CIDP, distal acquired demyelinating symmetric neuropathy, and CIDP with central nervous system (CNS) involvement.

Lewis-Sumner syndrome — The Lewis-Sumner syndrome, also known as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), presents with a much more striking multifocal picture, indistinguishable from other forms of mononeuropathy multiplex, involving sensory and/or motor symptoms in individual nerve distributions [29,30]. A similar disorder of sensory ataxia due to inflammation confined to the dorsal roots known as chronic immune sensory polyradiculopathy (CISP) may be a restricted form of CIDP [31,32].

Sensory-predominant CIDP — The sensory-predominant form of CIDP is characterized clinically by sensory symptoms and signs with balance problems, pain, paresthesias, and dysesthesias. Despite the lack of weakness, the nerve conduction studies demonstrate significant motor conduction slowing and other demyelinating features [33].

Distal acquired demyelinating symmetric neuropathy — Distal acquired demyelinating symmetric neuropathy (DADS) is usually more slowly progressive than typical CIDP, and is frequently associated with an IgM paraprotein [5,34].

DADS with IgM paraprotein, whether or not associated with anti-myelin associated glycoprotein (anti-MAG), is usually considered to be distinct from CIDP because it tends to be resistant to the standard immunomodulatory therapies for CIDP. Approximately one-half of patients with DADS and IgM paraprotein also have anti-myelin associated glycoprotein (anti-MAG) antibodies, but it is unclear whether presence or absence of these antibodies alters the clinical features of this disorder.

DADS without IgM paraprotein is generally considered to be variant of CIDP because it may respond to treatment with immunomodulatory therapies.

Pure motor CIDP — A pure motor variant of CIDP has been reported in a small number of cases [35,36]. Involvement of motor nerves and sparing of sensory fibers is present on clinical and electrodiagnostic evaluations.

Neurofascin antibody-mediated CIDP — Immunoglobulin G4 (IgG4) autoantibodies to neurofascin-155 (NF155) are found in some patients with CIDP [13,37,38]. Compared with antibody-negative CIDP, patients with neurofascin antibody-mediated CIDP have a younger mean age at onset, and are more likely to have sensory ataxia and prominent tremor. The symptoms can cause severe dysfunction. Limited data suggest the condition is often responsive to B cell depletion therapy (eg, rituximab) but is less likely to improve with intravenous immune globulin therapy [17,38].

Contactin 1 antibody-mediated CIDP — Autoantibodies of the IgG4 class to contactin 1 are found in a small subset of patients with CIDP [12,16,39]. The clinical phenotype is not fully established but is often severe and predominantly motor with early axonal involvement. As with neurofascin antibody-mediated CIDP, this condition may be responsive to B cell depletion therapy (eg, rituximab) and refractory to intravenous immune globulin therapy.

CIDP with CNS involvement — CIDP is occasionally associated with CNS involvement, including optic nerve disorders, hyperreflexia, Babinski signs, and MRI abnormalities of CNS demyelination. However, it is unclear whether these combined signs represent associated disease entities or coincidental occurrences of unrelated diseases [40].

Electrophysiology — Peripheral nerve demyelination underlies the characteristic electrophysiologic features of CIDP, which are as follows:

Partial conduction block

Conduction velocity slowing:

Prolonged distal motor latencies

Delay or disappearance of F waves

Dispersion and distance dependent reduction of compound motor action potential (CMAP) amplitude

Pathology — The characteristic pathologic features of CIDP include segmental demyelination and remyelination, and onion bulb formation [2]. The term "onion-bulb formation" refers to the appearance of affected nerves when viewed under the microscope in transverse section. As a result of repeated episodes of demyelination and remyelination, such nerves are enlarged due to whorls of overlapping and proliferating Schwann cell processes encircling bare axons. Some degree of axonal degeneration is usually present as well [41].

Varying degrees of interstitial edema and endoneurial inflammatory cell infiltrates, including lymphocytes and macrophages, are additional pathologic features of CIDP. The macrophages are thought to initiate the demyelination by unraveling and degrading the myelin [42]. Unfortunately, this is not commonly found on most biopsy specimens.

While the exact mechanism of axonal degeneration in CIDP is not known, it has been considered to be a secondary bystander product of the inflammatory demyelinating process.

EVALUATION AND DIAGNOSIS — The diagnosis of CIDP should be considered in patients with symmetric or asymmetric polyneuropathy who have a progressive or relapsing-remitting clinical course for more than two months, particularly if the clinical features include positive sensory symptoms, proximal weakness, or areflexia [43].

While the initial diagnosis of CIDP is clinical, the diagnosis is confirmed by evidence of peripheral nerve demyelination, which must be demonstrated by either electrodiagnostic findings or by nerve biopsy.

We suggest utilizing one of the published sets of diagnostic criteria for CIDP to improve diagnostic accuracy and avoid misdiagnosis [44]. We prefer the EFNS/PNS criteria for this purpose. (See 'Diagnostic criteria' below and 'EFNS/PNS criteria' below.)

Patients with atypical features or diagnostic uncertainty should be referred to a neuromuscular specialist with expertise in the diagnosis of peripheral nerve disorders. The GBS/CIDP Foundation International has selected clinical Centers of Excellence in the United States, Argentina, and Europe that specialize in the diagnosis and treatment of Guillain-Barré syndrome and CIDP.

Electrodiagnostic testing is recommended for all patients with suspected CIDP [43,45]. Additional studies that may be indicated in select patients include:

Cerebrospinal fluid (CSF) analysis

Nerve biopsy

MRI of spinal roots, brachial plexus, and lumbosacral plexus

Laboratory studies

Evaluation for inherited neuropathies

A treatment trial may be indicated if the diagnosis remains unclear despite a thorough evaluation, since an objective, positive response to immunotherapy may add supportive evidence to the diagnosis of CIDP. (See "Chronic inflammatory demyelinating polyneuropathy: Treatment and prognosis".)

Electrodiagnostic testing — A critical component of the CIDP evaluation, electrodiagnostic testing is used to determine if there is demyelination, which causes reduced conduction velocity, prolonged distal motor latencies, dispersion and distance-dependent reduction of compound motor action potential (CMAP) amplitude [46], and delay or disappearance of F waves.

The overwhelming majority of patients with CIDP will have electrodiagnostic evidence of primary demyelination [47]. However, other focal or generalized nerve diseases (eg, diabetic neuropathy) can also result in slow conduction velocities or apparent block in neural conduction. It may be difficult to determine conduction slowing in patients who have severe axonal loss. Evaluating nerves that supply more proximal and less severely denervated muscles may be helpful in finding the conduction abnormalities. As already mentioned, various sets of electrodiagnostic criteria for demyelinating neuropathy have been established to address this problem (table 1). While these criteria can be helpful to the clinician, none have ideal sensitivity and specificity [47].

Extensive studies of the upper limbs or all four limbs, rather than unilateral or lower limb studies, may improve the electrodiagnostic yield [48].

Cerebrospinal fluid analysis — A lumbar puncture is supportive of the diagnosis of CIDP when the CSF protein is elevated (>45 mg/dL) and the CSF white cell count is normal (ie, the classic albuminocytologic dissociation). This finding is present in over 80 percent of patients with CIDP [49-51]. In most cases, the elevated CSF protein level is >100 mg/dL, though CSF protein elevations as high as 10 times the upper limits of normal are occasionally seen in patients with CIDP

An increased CSF white cell count of >10 cells/mm3 should suggest a diagnosis other than CIDP. An exception to this general rule is that patients with HIV infection may have a cerebrospinal fluid pleocytosis, although the CSF white cell count in patients with CIDP and HIV infection is generally <50/mm3 [52].

Nerve biopsy — The diagnostic utility of nerve biopsy (typically of the sural nerve) for suspected CIDP is controversial [53-55]. Nerve biopsy is used mainly when other studies fail to clearly establish the diagnosis of CIDP, particularly when electrophysiologic criteria for demyelination are not met.

A major limitation of nerve biopsy is suboptimal sensitivity and specificity [43,45]. CIDP is a multifocal disorder, and motor nerve fibers tend to be more affected than sensory nerves (the usual nerves used for biopsy). As a result, the biopsy sample may not demonstrate the demyelination. In addition, the inflammatory component of CIDP may not be prominent and thus may not be apparent on biopsy.

Despite these drawbacks, nerve biopsy can provide solid evidence of demyelination. In addition, biopsy occasionally reveals other neuropathies that mimic CIDP, such as those due to amyloidosis [56], sarcoidosis, and vasculitis. (See "Overview of amyloidosis", section on 'Neurologic abnormalities' and "Neurologic sarcoidosis" and "Clinical manifestations of vasculitic neuropathy" and "Diagnosis and treatment of vasculitic neuropathy".)

The nerve selected for biopsy should be one that is clinically and electrophysiologically affected by the disorder [45]. However, care should be taken to choose a nerve that has either electrophysiologic or clinical evidence of functionality, as completely devastated nerves usually convey limited information. Typically, the sural nerve is biopsied, but other candidate nerves include the superficial peroneal, superficial radial, and gracilis motor nerve. Electron microscopy and teased fiber analysis of nerve biopsy specimens is highly desirable [45].

Supportive features for CIDP on nerve biopsy include the following [45]:

Endoneurial edema

Macrophage-associated demyelination

Demyelinated and remyelinated nerve fibers

Onion bulb formation (see 'Pathology' above)

Endoneurial mononuclear cell infiltration

Variation between fascicles

MRI — MRI with gadolinium of the spinal roots, cauda equina, brachial plexus, lumbosacral plexus, and other nerve regions can be used to look for enlarged or enhancing nerves. MRI abnormalities are useful as supportive criteria for CIDP in the EFNS/PNS guideline [45]. The MRI results can also guide selection of abnormal nerves for biopsy [43].

Laboratory studies — There are no laboratory test findings that specifically point to CIDP. However, a number of studies are useful to look for disorders that are either associated with or mimic CIDP [45]. These include:

Fasting serum glucose and/or oral glucose tolerance test

Glycated hemoglobin

Thyroid function studies

Hepatitis profiles

HIV antibody

Serum and urine immunofixation electrophoresis to detect paraprotein

Complete blood count

Renal function tests

Liver function tests

Borrelia burgdorferi serology

C-reactive protein

Antinuclear antibodies

Extractable nuclear antigen antibodies

Angiotensin converting enzyme

Chest radiograph

Skeletal survey, if a paraprotein is found

Diagnostic criteria — There is general agreement that the following criteria support the diagnosis of the classic form of CIDP:

Progression over at least two months

Weakness more than sensory symptoms

Symmetric involvement of arms and legs

Proximal muscles involved along with distal muscles

Reduced deep tendon reflexes throughout

Increased cerebrospinal fluid protein without pleocytosis

Nerve conduction evidence of a demyelinating neuropathy

Nerve biopsy evidence of segmental demyelination with or without inflammation

However, there is still no gold standard set of diagnostic criteria for the electrophysiologic identification of demyelination, or for the clinical diagnosis of CIDP and its variants, even though multiple sets of diagnostic criteria have been published since 1989 [5,43,45-47,49,52,57-62]. Differences between these sets are related to definitions of the clinical picture, the requirements for nerve biopsy, electrodiagnostic criteria for demyelination, and the number of features required to make the diagnosis. The plethora of criteria sets for CIDP illustrate the difficulty of developing precise standards for problems that have multiple variations. Two sets of criteria – the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria (see 'EFNS/PNS criteria' below) and the Koski criteria (see 'Koski criteria' below) – deserve special mention.

While the Koski classification is an interesting and valuable approach, we believe that the CIDP guideline from the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS), published in 2006 and updated in 2010 (table 1), is the most useful for clinical practice and patient care [43,45]. When independently validated in a retrospective study, the 2006 EFNS/PNS criteria had a sensitivity and specificity of 81 and 97 percent, whereas the Koski criteria had a sensitivity and specificity of 63 and 99 percent [63]. The lower sensitivity of the Koski criteria was primarily due to problems detecting atypical cases of CIDP such as multifocal variants. Another retrospective study that compared 15 sets of criteria for CIDP found that the 2010 EFNS/PNS criteria ranked in the top three for sensitivity, and had the highest specificity among the three most sensitive criteria [64].

EFNS/PNS criteria — The EFNS/PNS guideline defines CIDP as typical (ie, classic) or atypical [45]. Atypical CIDP encompasses variants of CIDP (see 'Variants of CIDP' above) with predominantly distal weakness such as distal acquired demyelinating symmetric neuropathy (DADS), and variants with pure motor or pure sensory presentations. The diagnosis of CIDP is based upon clinical, electrodiagnostic (mandatory), and supportive criteria:

Clinical inclusion criteria for typical CIDP require both of the following:

Chronically progressive, stepwise, or recurrent symmetric proximal and distal weakness and sensory dysfunction of all extremities, developing over at least two months; cranial nerves may be affected

Absent or reduced tendon reflexes in all extremities

Clinical inclusion criteria for atypical CIDP require one of the following, but otherwise as in typical CIDP (tendon reflexes may be normal in unaffected limbs):

Predominantly distal (distal acquired demyelinating symmetric neuropathy, DADS) or

Asymmetric (multifocal acquired demyelinating sensory and motor neuropathy [MADSAM], Lewis-Sumner syndrome) or

Focal (eg, involvement of the brachial or lumbosacral plexus or of one or more peripheral nerves in one upper or lower limb) or

Pure motor or

Pure sensory (including chronic immune sensory polyradiculopathy affecting the central process of the primary sensory neuron)

Clinical exclusion criteria:

Neuropathy probably caused by Borrelia burgdorferi infection (Lyme disease), diphtheria, drug or toxin exposure

Hereditary demyelinating neuropathy

Prominent sphincter disturbance

Diagnosis of multifocal motor neuropathy

IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein

Other causes for a demyelinating neuropathy including POEMS syndrome, osteosclerotic myeloma, diabetic and nondiabetic lumbosacral radiculoplexus neuropathy; peripheral nervous system lymphoma and amyloidosis may occasionally have demyelinating features

Supportive criteria:

Elevated cerebrospinal fluid protein with leukocyte count <10/mm3

MRI showing gadolinium enhancement and/or hypertrophy of the cauda equina, lumbosacral or cervical nerve roots, or the brachial or lumbosacral plexuses

Abnormal sensory electrophysiology in at least one nerve:

-Normal sural with abnormal median (excluding median neuropathy at the wrist from carpal tunnel syndrome) or radial sensory nerve action potential (SNAP) amplitudes; or

-Conduction velocity <80 percent of lower limit of normal (<70 percent if SNAP amplitude <80 percent of lower limit of normal); or

-Delayed somatosensory evoked potentials without central nervous system disease

Objective clinical improvement following immunomodulatory treatment

Nerve biopsy showing unequivocal evidence of demyelination and/or remyelination by electron microscopy or teased fiber analysis

The EFNS/PNS diagnostic categories (ie, degrees of certainty) are determined by the combination of clinical, electrodiagnostic (table 1), and supportive criteria as follows [45]:

Definite CIDP:

Typical or atypical CIDP by clinical inclusion criteria, no clinical exclusion criteria, and definite CIDP by electrodiagnostic criteria (table 1); or

Probable CIDP plus at least one supportive criterion; or

Possible CIDP plus at least two supportive criteria

Probable CIDP

Typical or atypical CIDP by clinical inclusion criteria, no clinical exclusion criteria, and probable CIDP by electrodiagnostic criteria (table 1); or

Possible CIDP plus at least one supportive criterion

Possible CIDP

Typical or atypical CIDP by clinical inclusion criteria, no clinical exclusion criteria, and possible CIDP by electrodiagnostic criteria (table 1)

CIDP (definite, probable, or possible) associated with concomitant diseases

Koski criteria — The Koski criteria were derived by predictive modeling of the clinical data of 150 patients who were diagnosed by expert consensus as having CIDP or other polyneuropathies [58]. For the diagnosis of idiopathic CIDP, the Koski criteria require the following:

Chronic polyneuropathy, progressive for at least eight weeks

No serum paraprotein and no genetic abnormality, and either:

Recordable compound muscle action potentials in at least 75 percent of motor nerves and either abnormal distal latency or abnormal motor conduction velocity or abnormal F wave latency in >50 percent of motor nerves or

Symmetric onset or symmetric exam and weakness in all four limbs and proximal weakness in at least one limb

Of note, while the Koski criteria combine clinical presentation and electrophysiologic abnormalities, either is sufficient to establish the diagnosis. One of the striking features of this classification method is that patients who have symmetric proximal and distal weakness are so likely to have CIDP that nerve conduction studies are primarily confirmatory.

Diagnostic pitfalls — Both clinical experience and data from retrospective studies suggest that the over-diagnosis of CIDP is common, involving one-third to nearly one-half of patients so labelled [44,65]. Furthermore, many of those with an erroneous diagnosis of CIDP receive long-term treatment with immunosuppressants [44,65].

Problems leading to a misdiagnosis of CIDP in these reports included the following [44,65,66]:

Failure to focus on symptoms and signs that characterize CIDP

Technically inadequate or misinterpreted electrodiagnostic studies (eg, a lax electrodiagnostic interpretation of demyelination)

Failure to adhere to diagnostic criteria

Over-emphasis on the importance of minimally elevated cerebrospinal fluid protein levels (ie, mild to moderate cytoalbuminologic dissociation)

Excessive reliance on subjective measures of patient-reported treatment response

As an example, in a report of 59 consecutive patients referred to an expert center with a diagnosis of CIDP made elsewhere, the proportion who failed to meet EFNS/PNS criteria was 47 percent [44]. The correct diagnoses in these cases were heterogeneous and included diabetic polyneuropathy, multifactorial neuropathy, multifocal motor neuropathy, and hereditary neuropathy, but a number of patients had non-neuropathic disorders such as amyotrophic lateral sclerosis and fibromyalgia.

Of note, none of the patients in this report who were misdiagnosed with CIDP satisfied the EFNS/PNS inclusion criteria for typical CIDP, while 44 percent fulfilled the clinical inclusion criteria for atypical CIDP without meeting electrodiagnostic criteria [44]. This finding suggests that the diagnosis of atypical CIDP is particularly challenging and requires astute interpretation of electrodiagnostic and laboratory data, as well as rigorous adherence to diagnostic criteria.

Differential diagnosis — The clinical features that distinguish CIDP from chronic length-dependent (ie, axonal) peripheral neuropathies are the prominence of muscle weakness and the involvement of upper extremity and proximal muscles, as well as distal muscles. In contrast, axonal polyneuropathies are characterized by predominantly distal weakness. Furthermore, deep tendon reflexes are globally reduced or absent in CIDP, whereas only the ankle reflexes are diminished in typical axonal polyneuropathies. The features of CIDP point to the multifocal or generalized nature of the disease even at early stages of the illness.

To confirm the diagnosis of CIDP, the clinician must be sure that the patient has a clinical picture that is consistent with the diagnosis and that the electrophysiology and/or other studies (cerebrospinal fluid analysis, nerve biopsy, MRI) have features suggesting a demyelinating neuropathy.

Genetic considerations — Certain genetic disorders of peripheral nerve myelin have characteristics that can mimic the clinical or electrodiagnostic features of CIDP or its variants. These include:

Charcot-Marie-Tooth (CMT) disease, particularly CMT1A, adult-onset CMT1B, CMT1X, and recessive cases such as CMT4 (eg, CMT4C due to SH3TC2 gene mutations being the most common) can cause multi-focal, non-uniform slowing and conduction block. (See "Hereditary primary motor sensory neuropathies, including Charcot-Marie-Tooth disease".)

Hereditary neuropathy with liability to pressure palsies, which causes conduction slowing at compression sites. (See "Overview of hereditary neuropathies", section on 'Hereditary neuropathy with liability to pressure palsy'.)

A careful family history and examination of parents and siblings is important if these disorders are a consideration [45]. Appropriate genetic testing should be considered in select patients, particularly for PMP22 gene duplication or deletion and connexin 32 mutations.

SUMMARY AND RECOMMENDATIONS

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired disorder of peripheral nerves and nerve roots. Whether CIDP is a disease or a syndrome remains controversial. (See 'Classification' above.)

There is a temporal continuum between acute inflammatory demyelinating polyneuropathy (AIDP), the demyelinating form of Guillain-Barré syndrome, and CIDP. (See 'Temporal continuum' above.)

Both the cellular and humoral components of the immune system appear to be involved in the pathogenesis of CIDP and its variants. The precise cause is unclear in most cases. However, the findings of antibodies directed against neurofascin and contactin in some severe cases of CIDP may shed new light on the pathophysiology of CIDP. (See 'Pathogenesis' above.)

The classic form of CIDP is fairly symmetric and motor involvement is greater than sensory. Weakness is present in both proximal and distal muscles. Most patients also have sensory involvement and globally diminished or absent reflexes. Sensory impairment in CIDP is usually greater for vibration and position sense than for pain and temperature sense. Cranial nerve and bulbar involvement occur in a minority. Most patients have a slowly progressive course, but a relapsing-remitting course is noted in at least one-third. (See 'Clinical manifestations' above.)

Major clinical variants of CIDP include (see 'Variants of CIDP' above):

Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), also known as Lewis-Sumner syndrome

A sensory-predominant form of CIDP

Distal acquired demyelinating symmetric neuropathy (DADS)

The diagnosis of CIDP should be considered in patients with symmetric or asymmetric polyneuropathy who have a progressive or relapsing-remitting clinical course for more than two months, particularly if the clinical features include positive sensory symptoms, proximal weakness, or areflexia. While the initial diagnosis of CIDP is clinical, the diagnosis is confirmed by evidence of peripheral nerve demyelination, which must be demonstrated by either electrodiagnostic findings or by nerve biopsy. Patients with atypical features or diagnostic uncertainty should be referred to a neuromuscular specialist with expertise in the diagnosis of peripheral nerve disorders. (See 'Evaluation and diagnosis' above.)

The following general criteria support the diagnosis of the classic form of CIDP (see 'Diagnostic criteria' above):

Progression over at least two months

Weakness more than sensory symptoms

Symmetric involvement of arms and legs

Proximal muscles involved along with distal muscles

Reduced deep tendon reflexes throughout

Increased cerebrospinal fluid protein without pleocytosis

Nerve conduction evidence of a demyelinating neuropathy

Nerve biopsy evidence of segmental demyelination with or without inflammation

To improve diagnostic accuracy and avoid misdiagnosis, we suggest utilizing one of the published sets of diagnostic criteria for CIDP; we prefer the EFNS/PNS criteria for this purpose. (See 'Diagnostic criteria' above and 'EFNS/PNS criteria' above.)

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REFERENCES

  1. AUSTIN JH. Recurrent polyneuropathies and their corticosteroid treatment; with five-year observations of a placebo-controlled case treated with corticotrophin, cortisone, and prednisone. Brain 1958; 81:157.
  2. Dyck PJ, Lais AC, Ohta M, et al. Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc 1975; 50:621.
  3. Hughes R, Sanders E, Hall S, et al. Subacute idiopathic demyelinating polyradiculoneuropathy. Arch Neurol 1992; 49:612.
  4. Oh SJ, Kurokawa K, de Almeida DF, et al. Subacute inflammatory demyelinating polyneuropathy. Neurology 2003; 61:1507.
  5. Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve 2001; 24:311.
  6. Dionne A, Nicolle MW, Hahn AF. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy. Muscle Nerve 2010; 41:202.
  7. Ruts L, van Koningsveld R, van Doorn PA. Distinguishing acute-onset CIDP from Guillain-Barré syndrome with treatment related fluctuations. Neurology 2005; 65:138.
  8. Dalakas MC, Medscape. Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol 2011; 7:507.
  9. Schneider-Hohendorf T, Schwab N, Uçeyler N, et al. CD8+ T-cell immunity in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 2012; 78:402.
  10. Peltier AC, Donofrio PD. Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside. Semin Neurol 2012; 32:187.
  11. Mathey EK, Park SB, Hughes RA, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry 2015; 86:973.
  12. Querol L, Nogales-Gadea G, Rojas-Garcia R, et al. Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. Ann Neurol 2013; 73:370.
  13. Querol L, Nogales-Gadea G, Rojas-Garcia R, et al. Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg. Neurology 2014; 82:879.
  14. Vallat JM, Yuki N, Sekiguchi K, et al. Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-Neurofascin 155 antibodies. Neuromuscul Disord 2017; 27:290.
  15. Koike H, Kadoya M, Kaida KI, et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies. J Neurol Neurosurg Psychiatry 2017; 88:465.
  16. Doppler K, Appeltshauser L, Wilhelmi K, et al. Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies. J Neurol Neurosurg Psychiatry 2015; 86:720.
  17. Querol L, Rojas-García R, Diaz-Manera J, et al. Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. Neurol Neuroimmunol Neuroinflamm 2015; 2:e149.
  18. Lunn MP, Manji H, Choudhary PP, et al. Chronic inflammatory demyelinating polyradiculoneuropathy: a prevalence study in south east England. J Neurol Neurosurg Psychiatry 1999; 66:677.
  19. McLeod JG, Pollard JD, Macaskill P, et al. Prevalence of chronic inflammatory demyelinating polyneuropathy in New South Wales, Australia. Ann Neurol 1999; 46:910.
  20. Chiò A, Cocito D, Bottacchi E, et al. Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy. J Neurol Neurosurg Psychiatry 2007; 78:1349.
  21. Iijima M, Koike H, Hattori N, et al. Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population. J Neurol Neurosurg Psychiatry 2008; 79:1040.
  22. Rajabally YA, Simpson BS, Beri S, et al. Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population. Muscle Nerve 2009; 39:432.
  23. Laughlin RS, Dyck PJ, Melton LJ 3rd, et al. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology 2009; 73:39.
  24. Lozeron P, Denier C, Lacroix C, Adams D. Long-term course of demyelinating neuropathies occurring during tumor necrosis factor-alpha-blocker therapy. Arch Neurol 2009; 66:490.
  25. Saifee TA, Schwingenschuh P, Reilly MM, et al. Tremor in inflammatory neuropathies. J Neurol Neurosurg Psychiatry 2013; 84:1282.
  26. Cao Y, Menon P, Ching-Fen Chang F, et al. Postural tremor and chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2017; 55:338.
  27. McCombe PA, Pollard JD, McLeod JG. Chronic inflammatory demyelinating polyradiculoneuropathy. A clinical and electrophysiological study of 92 cases. Brain 1987; 110 ( Pt 6):1617.
  28. Figueroa JJ, Dyck PJ, Laughlin RS, et al. Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 2012; 78:702.
  29. Lewis RA, Sumner AJ, Brown MJ, Asbury AK. Multifocal demyelinating neuropathy with persistent conduction block. Neurology 1982; 32:958.
  30. Rajabally YA, Chavada G. Lewis-sumner syndrome of pure upper-limb onset: diagnostic, prognostic, and therapeutic features. Muscle Nerve 2009; 39:206.
  31. Sinnreich M, Klein CJ, Daube JR, et al. Chronic immune sensory polyradiculopathy: a possibly treatable sensory ataxia. Neurology 2004; 63:1662.
  32. Trip SA, Saifee T, Honan W, et al. Chronic immune sensory polyradiculopathy with cranial and peripheral nerve involvement. J Neurol 2012; 259:1238.
  33. Oh SJ, Joy JL, Kuruoglu R. "Chronic sensory demyelinating neuropathy": chronic inflammatory demyelinating polyneuropathy presenting as a pure sensory neuropathy. J Neurol Neurosurg Psychiatry 1992; 55:677.
  34. Katz JS, Saperstein DS, Gronseth G, et al. Distal acquired demyelinating symmetric neuropathy. Neurology 2000; 54:615.
  35. Donaghy M, Mills KR, Boniface SJ, et al. Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin. J Neurol Neurosurg Psychiatry 1994; 57:778.
  36. Sabatelli M, Madia F, Mignogna T, et al. Pure motor chronic inflammatory demyelinating polyneuropathy. J Neurol 2001; 248:772.
  37. Ng JK, Malotka J, Kawakami N, et al. Neurofascin as a target for autoantibodies in peripheral neuropathies. Neurology 2012; 79:2241.
  38. Devaux JJ, Miura Y, Fukami Y, et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 2016; 86:800.
  39. Miura Y, Devaux JJ, Fukami Y, et al. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. Brain 2015; 138:1484.
  40. Feasby TE, Hahn AF, Koopman WJ, Lee DH. Central lesions in chronic inflammatory demyelinating polyneuropathy: an MRI study. Neurology 1990; 40:476.
  41. Harbo T, Andersen H, Jakobsen J. Length-dependent weakness and electrophysiological signs of secondary axonal loss in chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2008; 38:1036.
  42. Prineas JW. Demyelination and remyelination in recurrent idiopathic polyneuropathy. An electron microscope study. Acta Neuropathol 1971; 18:34.
  43. Hughes RA, Bouche P, Cornblath DR, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2006; 13:326.
  44. Allen JA, Lewis RA. CIDP diagnostic pitfalls and perception of treatment benefit. Neurology 2015; 85:498.
  45. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--First Revision. J Peripher Nerv Syst 2010; 15:1.
  46. Thaisetthawatkul P, Logigian EL, Herrmann DN. Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy. Neurology 2002; 59:1526.
  47. Van den Bergh PY, Piéret F. Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2004; 29:565.
  48. Rajabally YA, Jacob S, Hbahbih M. Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases. J Peripher Nerv Syst 2005; 10:282.
  49. Barohn RJ, Kissel JT, Warmolts JR, Mendell JR. Chronic inflammatory demyelinating polyradiculoneuropathy. Clinical characteristics, course, and recommendations for diagnostic criteria. Arch Neurol 1989; 46:878.
  50. Gorson KC, Allam G, Ropper AH. Chronic inflammatory demyelinating polyneuropathy: clinical features and response to treatment in 67 consecutive patients with and without a monoclonal gammopathy. Neurology 1997; 48:321.
  51. Gorson KC, Katz J. Chronic inflammatory demyelinating polyneuropathy. Neurol Clin 2013; 31:511.
  52. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Report from an Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Neurology 1991; 41:617.
  53. Molenaar DS, Vermeulen M, de Haan R. Diagnostic value of sural nerve biopsy in chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry 1998; 64:84.
  54. Bosboom WM, van den Berg LH, Franssen H, et al. Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy. Brain 2001; 124:2427.
  55. Vallat JM, Tabaraud F, Magy L, et al. Diagnostic value of nerve biopsy for atypical chronic inflammatory demyelinating polyneuropathy: evaluation of eight cases. Muscle Nerve 2003; 27:478.
  56. Mathis S, Magy L, Diallo L, et al. Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2012; 45:26.
  57. Hughes R, Bensa S, Willison H, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 2001; 50:195.
  58. Koski CL, Baumgarten M, Magder LS, et al. Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy. J Neurol Sci 2009; 277:1.
  59. Magda P, Latov N, Brannagan TH 3rd, et al. Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy. Arch Neurol 2003; 60:1755.
  60. Berger AR, Bradley WG, Brannagan TH, et al. Guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy. J Peripher Nerv Syst 2003; 8:282.
  61. Nicolas G, Maisonobe T, Le Forestier N, et al. Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 2002; 25:26.
  62. Albers JW, Kelly JJ Jr. Acquired inflammatory demyelinating polyneuropathies: clinical and electrodiagnostic features. Muscle Nerve 1989; 12:435.
  63. Rajabally YA, Nicolas G, Piéret F, et al. Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study. J Neurol Neurosurg Psychiatry 2009; 80:1364.
  64. Breiner A, Brannagan TH 3rd. Comparison of sensitivity and specificity among 15 criteria for chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2014; 50:40.
  65. Cornblath DR, Gorson KC, Hughes RA, Merkies IS. Observations on chronic inflammatory demyelinating polyneuropathy: A plea for a rigorous approach to diagnosis and treatment. J Neurol Sci 2013; 330:2.
  66. Gorson KC, Gooch CL. The (mis)diagnosis of CIDP: The high price of missing the mark. Neurology 2015; 85:488.
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