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CIDP is an "organ specific immune-mediated disorder emerging from a synergistic interaction of cell mediated and hummoral immune responses directed against incompletely characterized peripheral nerve antigens" (Koller et al 2005:1348). The classic presentation of CIDP includes sensory and motor symptoms in the distal and proximal segments of the four limbs and related areflexia evolving over eight weeks (Vallat 2010). The pathological and clinical variability of CIDP make diagnosing this condition problematic (Said 2006) and this is highlighted in the numerous different diagnostic criteria used to diagnose CIDP. In a study by Koski et al (2009) they compared and evaluated the differing diagnostic criteria available for CIDP and came up with a diagnostic rule which is summarized in table 1 below:
Table 1: Adapted from Koski et al (2009) Criteria for diagnosing CIDP
Chronic non genetic polyneuropathy progressive for at least eight weeks
Recordable compound muscle action potentials in >75% of nerves
Distal latency in >50% of nerves
Abnormal motor conduction velocity in >50% of nerves
Abnormal F wave latency in >50% of nerves
Symmetric onset of weakness of four limbs
Proximal weakness in one or more limbs
There is no diagnostic biological marker or lab test for CIDP so the diagnosis of is based on the recognition of a characteristic history and examination supported by evidence of peripheral nerve demyelination from nerve conduction studies. Further nerve biopsy albumino-cytological dissociation in the cerebrospinal fluid (CSF) and lab tests to exclude other potential etiologies of peripheral nerve disorders are used to strengthen the diagnosis (Koski et al 2009).
Prevalence studies for CIDP show varied results, with Rajabally et al (2009) estimating that 1.97 per 100,000 in a sub group of people in the United Kingdom suffer from CIDP while a study by Mygland & Monstad (2001) found this to be much higher in northern Norway with a figure of 7.7 per 100,000 inhabitants estimated. Such discrepancies in figures could be down to the differing inclusion criteria used in diagnosing CIDP but also due to difficulty in diagnosing atypical cases (Vallat et al 2010) with twenty percent of idiopathic neuropathy estimated to comprise of undiagnosed CIDP (Latov 2002).
Aetiology and Pathophysiology of CIDP
While the exact aetiology of CIDP is unknown there are a number of theories hypothesized on its initiation. A history of recent infection has been raised as a possible causative factor, with an analysis by Said (2006) finding that in 100 patients, 16% had experienced an infectious event six weeks prior to the first neurological episode. One of the specific infections mentioned is Campylobacter jejuni. Given the shared expression of carbohydrate epitopes in nerve glycolipids and microbial lipopolysaccharides of this and CIDP the idea of molecular mimicry has been suggested as a causative factor (Koller 2005). This refers to a process in which the host generates an immune response to an inciting factor, most commonly a harmful organism which shares epitopes with the hosts affected tissue (Koller 2005). However the specific inciting factor is yet to be ascertained.
There is also evidence of a genetic disposition to CIDP with factors implicated in the early control of T-cell activation important (Vallat 2010). It has been shown (Notturno et al 2008) that there is a significant link between a homozygous genotype for a low repeat number of tandem GA in the SH2D2A gene coding for T-cell specific adapter protein. This may result in faulty control and eradication of autoreactive T-cells (Vallat 2010).
CIDP has also been associated with concomitant disease including autoimmune disorders such as: systemic lupus errythematosus, thyroid disease, rheumatoid arthritis, sjorgen's syndrome, sarcoidosis and other medical illness such as diabetes and renal insufficiency (Gorson 1999). While CIDP occurs seldom in association with cancer there is also a possible link between CIDP and melanoma. This is because both melanoma and schwaan cells derive from neural crest tissue and share antigens (Koller 2005) with cases of CIDP developing with the disease noted (Weiss et al 1998).
Cellular Immune Response
While the disorder appears to be heterogeneous in terms of how it presents and immunopathogeneis, one of the hypothesized methods of action of CIDP involves a cellular immune response. Evidence of T-cell activation in the systemic immune compartment in CIDP exists through increased systemic concentrations of tumor necrosis factor and interleukin-2 (Misawa et al 2001) although the antigen responsible for this remains unknown (Dalakas 1999). For inflammatory lesions to be generated in the peripheral nervous system, these stimulated T-cells must cross the blood-nerve barrier which involves adhesion, transmigration and homing (Gold et al 1999). Evidence which suggests damage to this barrier in people with CIDP can be found with an increase in adhesion molecules, matrix metalloproteinase and chemokines present in CSF (Mahad et al 2002), also a decreased amount of tight junction proteins claudin 5 and ZO-1 might be evidenced in sural nerve biopsy specimens (Kanda et al 2004). Activated T-cells have the ability to invade peripheral nerve cells and the T-cell masses responsible for this belong to both the CD4 and CD8 subgroups (Illes et al 2004). Once inside the peripheral nervous system the T-cells may undergo clonal expansion and secrete cytokines such as tumor necrosis and interleukin-2 (Gold et al 1999). As a result of this process T-cells activate endoneurial macrophages which exonerate oxygen radicals, nitric oxide and arachidonic acid metabolites which cause an attack on myelin and the schwaan cells leading to the characteristic trait of demyelination evidenced in CIDP (Koller et al 2005). This demyelinating process can also lead to concomitant axonal loss (Dalakas 1999) which is important as the long term prognosis depends on the level of damage to the axon rather than on the level of demyelination (Koller 2005).
Hummoral Immune Response
Another hypothesized method of action of CIDP is the pathological contribution of autoantibodies. This was suggested on the basis of immunoglobulin and complement deposition present on myelinated nerve fibers and oligoclonal IgG bands in the CSF (Dalakas & Engel 1980). Passive transfer experiments have shown that purified IgG from CIDP affected patients resulted in conduction block and demyelination in rat nerves leading experts to believe it could play a part in the pathophysiology of CIDP in humans (Yan et al 2000). However this method of action was only identified in a small set of patients and its significance remains unclear (Tagawa et al 2000). Also the low frequency of specific antibodies observed in CIDP cases suggests that various antibodies and separate mechanisms are involved in individual cases making the exact pathophysiology difficult to clarify.