Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common form of autoimmune polyneuropathy. It is a chronic disease and may be monophasic, progressive or recurrent with exacerbations and incomplete remissions, causing accumulating disability. In recent years, there has been rapid progress in understanding the background of CIDP, which allowed us to distinguish specific phenotypes of this disease. This in turn allowed us to better understand the mechanism of response or non-response to various forms of therapy. On the basis of a review of the relevant literature, the authors present the current state of knowledge concerning the pathophysiology of the different clinical phenotypes of CIDP as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of CIDP.

The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case–Control Study

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort.Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis.Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P < 0.01). The QALB stratification analysis showed that the ranges of 10 < QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB > 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P < 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P < 0.01).Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.

Difficult-to-Treat Polyradiculoneuropathy

A 51-year-old healthy man sought care for a 6-month history of progressive, distal, lower extremity weakness, imbalance, and numbness in the feet. Neurologic examination showed a steppage gait, upper and lower extremity weakness, distal greater than proximal, absent tendon reflexes, and large fiber–predominant sensation loss in the feet. Nerve conduction studies showed marked temporal dispersion and slowed conductions. Cerebrospinal fluid analysis showed an increased protein concentration, 1 white blood cell/µL, and normal glucose level. Lumbar spine magnetic resonance imaging showed enlargement and enhancement of the nerve roots in the cauda equina, along with hypointensity in lumbar vertebral bodies. He underwent right sural nerve biopsy that showed an inflammatory demyelinating process. The patient was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and started on intravenous immunoglobulin. He was markedly worse at 12-week follow-up, with severe proximal and distal weakness and requiring the use of a walker. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was revisited. Lumbar spine magnetic resonance imaging again showed enhancement of the nerve roots. Because of concern for neurolymphomatosis, a proximal fascicular nerve biopsy of the right sciatic nerve was performed. It showed the hallmark pathologic features of chronic inflammatory demyelinating polyradiculoneuropathy: endoneurial inflammation and signs of long-standing demyelination and remyelination with stacks on Schwann cell processes. The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy was confirmed. Intravenous immunoglobulin was stopped, and the patient was started on an aggressive plasma exchange regimen. He had modest improvement. Azathioprine was also started. The patient continued to improve. He remained on this regimen for 2 years. Over the next year, the intravenous methylprednisolone dose was reduced. He was weaned off plasma exchange and intravenous methylprednisolone. At the last follow-up the disease was still in remission. Chronic inflammatory demyelinating polyradiculoneuropathy was described and named in 1975. It is a fairly symmetric peripheral neuropathy that usually presents with proximal and distal weakness, imbalance, and large fiber sensory dysfunction. Cerebrospinal fluid analysis shows albuminocytologic dissociation in 80% to 95% of those with typical chronic inflammatory demyelinating polyradiculoneuropathy.

P.055 Clinical and Electrophysiological characteristics of anti-nodal/paranodal antibodies in chronic inflammatory demyelinating polyradiculoneuropathy patients

Background: CIDP is an autoimmune polyneuropathy. Antibodies against the Node of Ranvier have been described, NF155,NF140/186 and contactin-1. Methods: A retrospective review of patients with CIDP who tested positive for anti-nodal/paranodal antibodies via Western blot were evaluated. We have included 20 sero-negative CIDP patients. All patients met definite or probable EFNS criteria. clinical, electrophysiological data and response to treatment were obtained. Results: Forty-five patients tested positive for the antibodies. Sixteen were positive for NF155, 11 for NF140, 5 for CNTN1,11 were double positive for NF155 and NF140, and 3 were triple positive for NF155, NF140 and CNTN1. Age of onset was similar in both seronegative (53.9 ± 3.1 yrs.) versus seropositive (52.3 ± 2.4 yrs.). Chronic presentation manifested in 85% of seronegative, 80% of seropositive patients.Intrestingly,all triple-positive patients presented with a more acute presentation (i.e,<8 wks.) 7/20 seronegative (35%),1/16 NF155, 6/11 NF140,1/5 contactin, 2/11 of double-positive, 3/3 of triple-positive (28%,13/46) responded to IVIg. Conclusions: No major clinical or electrophysiological differences between groups. triple-positive patients showed 100% response to IVIg.These results cast doubt on the specificity of the Western blot as a clinico-electrophysiologic discriminator. Future testing with cell-based assays will likely provide a robust measure that will guide treatment decision.