Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms.
The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots).
CIDP is closely related to Guillain–Barré syndrome and is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.
Signs and symptoms In its traditional manifestation, chronic inflammatory demyelinating polyneuropathy is characterized by symmetric, progressive limb weakness and sensory loss, which typically starts in the legs. Patients report having trouble getting out of a chair, walking, climbing stairs, and falling. Problems with gripping objects, tying shoe laces, and using utensils can all be brought on by upper limb involvement. Proximal limb weakness is a fundamental clinical characteristic that sets apart chronic inflammatory demyelinating polyneuropathy from the vast majority of distal polyneuropathies, which are far more common. Proprioception impairment, distal paresthesias, loss of feeling, and poor balance are all brought on by sensory involvement. Only a small percentage of cases involve neuropathic pain.
Fatigue has been identified as common in CIDP patients, but it is unclear how much this is due to primary (due to the disease action on the body) or secondary effects (impacts on the whole person of being ill with CIDP).
Numerous reports have outlined a range of clinical patterns that are thought to be chronic inflammatory demyelinating polyneuropathy variations. Different variations include ataxic, pure motor, and pure sensory patterns; additionally, there are multifocal patterns in which the distributions of specific nerve territories experience weakness and sensory loss.
Causes
Chronic inflammatory demyelinating polyneuropathy (or polyradiculoneuropathy) is considered an autoimmune disorder destroying myelin, the protective covering of the nerves. Typical early symptoms are "tingling" (sort of electrified vibration or paresthesia) or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations, "vibration" feelings, loss of balance, general muscle cramping and nerve pain. CIDP is extremely rare but under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is favoured in preventing irreversible axonal loss and improving functional recovery.
There is a lack of awareness and treatment of CIDP. Although there are stringent research criteria for selecting patients for clinical trials, there are no generally agreed-upon clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often misses the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.
Risk factors HIV infection is a factor in the occurrence of CIDP. At every stage of HIV infection, distinct patterns of CIDP, whether progressive or relapsing, have been noted. Increased protein content is linked to CSF pleocytosis in the majority of HIV-CIDP cases. Pregnancy has been linked to a significantly greater risk of relapse.
Triggers In one study, 31% (29 out of 92) CIDP patients had a history of infection or vaccination within 6 weeks of the onset of neurological symptoms, with the majority of events being non-specific infections such as upper respiratory tract, Gastroenteritis, or Cystitis according to Table 3 of the cited article. A different study showed that 30% (3 out of 10) CIDP patients had an infectious event according to Table 1 of the cited article.
Genetics There is no known genetic predisposition to chronic inflammatory demyelinating polyneuropathy.
Variants with paranodal autoantibodies
Some variants of CIDP present autoimmunity against proteins of the node of Ranvier. These variants comprise a subgroup of inflammatory neuropathies with IgG4 autoantibodies against the paranodal proteins neurofascin-155, contactin-1 and caspr-1.
These cases are special not only because of their pathology, but also because they are non-responsive to the standard treatment. They are responsive to Rituximab instead.
Also some cases of combined central and peripheral demyelination (CCPD) could be produced by neurofascins.
Autoantibodies of the IgG3 Subclass in CIDP
Autoantibodies to components of the Ranvier nodes, specially autoantibodies the Contactin-associated protein 1 (CASPR), cause a form of CIDP with an acute "Guillain-Barre-like" phase, followed by a chronic phase with progressive symptoms. Different IgG subclasses are associated with the different phases of the disease. IgG3 Caspr autoantibodies were found during the acute GBS-like phase, while IgG4 Caspr autoantibodies were present during the chronic phase of disease.
Mechanism In the local tissue compartment of peripheral nerves, the immune system is carefully regulated by a normal, balanced collection of immunocompetent cells as well as soluble factors, maintaining the integrity of the system. Maintaining self-tolerance requires defense against immune reactions to autoantigens. Chronic inflammatory demyelinating polyneuropathy disrupts self-tolerance and activates autoreactive T and B cells, which are normally suppressed immune cells. This leads to the organ-specific damage typical of autoimmune disease. Molecular mimicry may be particularly relevant to the tolerance breakdown linked to autoimmune neuropathies. The process known as "molecular mimicry" occurs when an infectious organism that shares epitopes from its host's afflicted tissue triggers an immune response in the host. However, only a small number of convincingly identified specific targets for such a response have been found in chronic inflammatory demyelinating polyneuropathy.
Individuals with chronic inflammatory demyelinating polyneuropathy have evidence of activation of T cells in the systemic immune compartment; however, antigen specificity is still largely unknown.
It was proposed more than 20 years ago that autoantibodies play a role in the development of chronic inflammatory demyelinating polyneuropathy. This was supported by the detection of oligoclonal IgG bands in the cerebrospinal fluid and immunoglobulin as well as complement deposition on myelinated nerve fibers.
Target antigens may also include gangliosides and related glycolipids. There is serologic evidence of recent Campylobacter jejuni infection in a small number of individuals with chronic inflammatory demyelinating polyneuropathy. Because carbohydrate epitopes are expressed in both microbial lipopolysaccharides and nerve glycolipids, this discovery may, in rare cases, point to molecular mimicry as the root cause of chronic inflammatory demyelinating polyneuropathy.
Apart from myelin-directed antibodies, other serum components that can cause demyelination as well as conduction block include complement, cytokines, and other inflammatory mediators. Individuals with chronic inflammatory demyelinating polyneuropathy have a low frequency of specific antibodies, which suggests that different antibodies and different mechanisms are involved in each patient.
Diagnosis When a patient presents with a non-length-dependent demyelinating polyneuropathy which either develops chronically over several months or progresses over more than a month, CIDP may be diagnosed. There may be a secondary progressive course along with a progressive course that follows, or it may be relapsing and remitting. Pathological investigations and electrophysiological studies, if necessary, show the underlying demyelinating process.
The primary basis for diagnosing CIDP is the electrophysiological studies that depict an asymmetric demyelinating process. Comparison of the proximal and distal latencies of equivalent segments of two nerves in the same limb reveals that these patients with acquired demyelinating neuropathy frequently have a differential slowing of conduction velocity. There is always a noticeable difference in the compound muscle action potential's dispersion, and conduction block is commonly experienced.
An MRI can show proximal nerve or root enlargement and gadolinium enhancement, which indicate active inflammation as well as demyelination in the brachial plexus or cauda equina.
Classification Clinically, CIDP is divided into "typical" and "atypical" cases. A typical case of CIDP is a symmetrical polyneuropathy that affects the proximal and distal muscles equally. Atypical cases of CIDP include multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), Lewis-Sumner syndrome (LSS), and distal acquired demyelinating symmetric (DADS). DADS is a sensory or sensorimotor neuropathy that is symmetrical and length-dependent. It is frequently linked to an IgM paraprotein and noticeably longer distal motor latencies. The characteristics are typical of demyelinating neuropathy with antimyelin-associated glycoprotein (MAG) antibodies; however, anti-MAG neuropathy is not included in the CIDP criteria according to the EFNS/PNS criteria, primarily due to the presence of a particular antibody and a different response to treatment. LSS exhibits a multifocal distribution, with conduction block serving as the disease's electrophysiological hallmark. Furthermore, there have been reports of pure motor and sensory CIDP variants, with the latter occasionally limited to sensory nerve roots (chronic immune sensory polyradiculopathy). The acronym CANOMAD refers to a rare chronic ataxic neuropathy linked to disialosyl (ganglioside) antibodies, IgM paraprotein, ophthalmoplegia, and cold agglutinins.
Differential diagnosis CIDP variants are among several types of immune-mediated neuropathies recognised. These include: Chronic inflammatory demyelinating polyneuropathy (CIDP) with subtypes: Classical CIDP CIDP with diabetes CIDP/monoclonal gammopathy of undetermined significance Sensory CIDP Multifocal motor neuropathy Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome) Multifocal acquired sensory and motor neuropathy Distal acquired demyelinating sensory neuropathy Guillain–Barré syndrome with subtypes: Acute inflammatory demyelinating polyradiculoneuropathy Acute motor axonal neuropathy Acute motor and sensory axonal neuropathy Acute pandysautonomia Miller Fisher syndrome IgM monoclonal gammopathies with subtypes: Waldenström's macroglobulinemia Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS)
Other possible diagnoses are Bickerstaff brainstem encephalitis Fisher syndrome Guillain–Barré syndrome
For this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations. The diagnosis is usually provisionally made through a clinical neurological examination.
Tests Typical diagnostic tests include: Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include: a reduction in nerve conduction velocities; the presence of conduction block or abnormal temporal dispersion in at least one motor nerve; prolonged distal latencies in at least two nerves;