Chronic inflammatory demyelinating polyneuropathy is a neuroinflammatory disorder with considerable variation in clinical phenotype, disease progression and therapy response among patients. Recently, paranodal antibodies associated with poor response to intravenous immunoglobulin therapy and more aggressive disease course have been described in small subsets of patients, but reliable serum-based prognostic biomarkers are not yet available for the general population. In current retrospective longitudinal study, we utilized logistic regression models to investigate the associations of serum neurofilament light chain levels with 1-year disease progression and therapy response during follow-up in chronic inflammatory demyelinating polyneuropathy. 1-year disease progression was defined as a decrease of four or more points (the minimal clinically important difference) on an 80-point Medical Research Council sum-score scale one year after sampling. Patients who, compared to treatment received at time of sampling, required therapy switch during follow-up due to insufficient effect were classified as non-responders. Serum neurofilament light chain was measured by electrochemiluminescence assay in clinical residual serum samples of 76 patients diagnosed with probable (13 patients) or definite (63 patients) chronic inflammatory demyelinating polyneuropathy according to European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria. 11 (15%) patients were female, and mean (standard deviation) cohort age was 61.5 (11.7) years. In both univariate and multivariable (including demographics) models, elevated serum neurofilament light chain harbored increased odds for 1-year disease progression (respectively odds ratio (OR), 1.049; 95% confidence interval (95%CI), 1.022—1.084 and OR, 1.097; 95%CI, 1.045—1.169; both P = 0.001). Patients with levels above the median cohort neurofilament light chain level (28.3 pg/mL) had largely increased odds of 1-year disease progression (univariate: OR, 5.597; 95%CI, 1.590—26.457; P = 0.01; multivariable: OR, 6.572; 95%CI, 1.495—39.702; P = 0.02) and of insufficient treatment response (univariate: OR, 4.800; 95%CI, 1.622—16.442; P = 0.007; multivariable: OR, 6.441; 95%CI, 1.749—29.357; P = 0.009). In a combined approach analysis, patients with levels above median cohort serum neurofilament light chain level reported strongly increased odds of demonstrating 1-year disease progression and/or therapy non-response during follow-up (univariate: OR, 6.337; 95%CI, 2.276—19.469; P<0.001; multivariable: OR, 10.138; 95%CI, 2.801—46.404; P = 0.001). These results show that in various logistic regression models, serum neurofilament light chain was associated with both 1-year disease progression and therapy response during follow-up in chronic inflammatory demyelinating polyneuropathy. Hence, our findings warrant further prospective research regarding the value of neurofilament light chain as potential prognostic biomarker in chronic inflammatory demyelinating polyneuropathy.

Screening for paraneoplastic antibodies is often performed by means of indirect immunofluorescence on primate cerebellar slices. However, atypical immunofluorescence patterns, i.e. patterns that are not specifically related to paraneoplastic antibodies, are often reported. The clinical significance of these patterns is not clear. Therefore, the purpose of this study was to determine the significance and diagnostic value-in terms of a paraneoplastic neurological syndrome or other neurological disease being diagnosed in the patient-of such atypical immunofluorescence screening patterns on primate cerebellum. Methods: This study is a retrospective single center study including atypical indirect immunofluorescence screening patterns of patients with a negative or absent typing assay for intraneuronal and anti-amphiphysin paraneoplastic antibodies. Patients with a positive typing assay or without final diagnosis were excluded. Included patients were grouped according to (i) reported immunofluorescence pattern and (ii) established diagnosis, after which contingency table analyses were performed to investigate an interrelation between reported pattern and diagnostic group. Results: In 3.7% of cases, patients with an atypical pattern obtained a final diagnosis of a paraneoplastic neurological syndrome. The presence of atypical patterns was more prominent in patients with epilepsy or peripheral neuropathies (p Monte Carlo simulation = 0.026), without, however, adding any diagnostic information. Conclusions: An atypical indirect immunofluorescence pattern on primate cerebellum in the screening for paraneoplastic antibodies has only very minor relevance with respect to paraneoplastic neurological syndromes or any other neurological disease, recommending clinicians to interpret the results of positive screening assays for such antibodies with care.