Apheresis therapies for NMOSD attacks A retrospective study of 207 therapeutic interventions

Objective To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). Methods This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. Results Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04-144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89-0.99, p = 0.014), the presence of AQP4-abantibodies (OR 33.34, 95% CI: 1.76-631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03-21.62, p = 0.046). Conclusion: s Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques

Chitinase 3-like 1: prognostic biomarker in clinically isolated syndromes

Prognostic molecular biomarkers for the conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS) are lacking. In a prospective longitudinal study of 813 individuals with CIS, Cantó et al. validate elevated CSF levels of chitinase 3-like 1 as a biomarker for conversion to MS and development of disabilit

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders

Background: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. Objective: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). Methods: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. Results: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%;p40years. Conclusion: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients

Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis.

BACKGROUND: Oligoclonal bands (OCB) are the most widely used CSF test to support the diagnosis of MS and to predict conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS). Since OCB tests are based on non-quantitative and difficult to standardise techniques, measurement of immunoglobulin kappa free light chains (KFLC) may represent an easier to use quantitative test. METHODS: KFLC were measured in CSF and serum of 211 patients using ELISA. These include patients without any inflammatory central nervous system reaction (NIND, n = 77), MS (n = 20), viral CNS infections (V-CNS-I, n = 10), neuroborreliosis (NB, n = 17) and other bacterial CNS infections (B-CNS-I, n = 10). Furthermore a cohort of 77 patients with CIS, including 39 patients that remained CIS over follow-up of two years (CIS-CIS) and 38 patients that developed MS over the same follow-up time (CIS-MS). RESULTS: CSF-serum ratio of KFLC (Q KFLC) was elevated in all patients with MS, 86.8% of patients with CIS-MS and 61.5% of patients with CIS-CIS. It was significantly elevated in CIS with presence of OCB (p<0.001). Q KFLC significantly correlated with other CSF variables such as CSF leukocyte count (p<0.001, R = 0.46), CSF CXCL13 levels (p<0.001, R = 0.64) and also intrathecal IgG synthesis (p<0.001, R = 0.74) as determined by nephelometry and quotient diagram. OCB were detected in 66.7% of CIS-CIS and in 92.1% of CIS-MS. CONCLUSIONS: Although the measurement of CSF KFLC is a rapid and quantitative easy to standardize tool, it is almost equal but not superior to OCB with regard to diagnostic sensitivity and specificity in patients with early MS

KFLC in CSF and serum.

<p>Immunoglobulin kappa free light chain (KFLC) in CSF and serum of patients with MS, CIS, pathogen-related diseases and NIND (for abbreviations see legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-t001" target="_blank">table 1</a>). Q KFLC: CSF- serum ratio of KFLC. Data are shown as the median and IQR.</p

Demographic data and basic cerebrospinal fluid findings.

<p>Data are shown as the median and IQR. Abbreviations: B-CNS-I bacterial central nervous system infections, CIS clinically isolated syndrome, CSF cerebrospinal fluid, MS multiple sclerosis, NB neuroborreliosis, NIND non-inflammatory neurological diseases, OCB oligoclonal IgG bands, V-CNS-I viral central nervous system infections.</p

CSF-serum ratio of KFLC (Q KFLC) was elevated in patients with positive oligoclonal IgG (OCB). Q KFLC of 77 CIS patients are shown.

<p>Dashed line indicates the approximately upper reference value of Q KFLC, described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002" target="_blank">figure 2</a>. Black rhomb indicate positive OCBs, white rhomb indicate negative OCBs.</p

Sensitivity, specificity, positive and negative predictive value for elevated KFLC, MRI parameters and OCB regarding conversion of clinically isolate syndrome to definite multiple sclerosis.

<p>Data are shown as percent and 95% confidence interval. Q KFLC = CSF-serum ratio of KFLC above the approximately upper reference value described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone-0088680-g002" target="_blank">figure 2</a>. OCB = cerebrospinal fluid oligoclonal bands of IgG class not detectable in serum. Intrathecal IgG- Synthesis according to Reiber quotients diagrams. IgG- Index = CSF/serum IgG:CSF/serum albumin >0.7. Barkhof = 3 of 4 Barkhof criteria <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Barkhof1" target="_blank">[21]</a> fulfilled.</p

CSF-serum ratio of KFLC (Q KFLC) among different oligoclonal IgG band patterns.

<p>There are five classic patterns of oligoclonal bands <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088680#pone.0088680-Andersson1" target="_blank">[48]</a> (type 1, no bands in CSF and serum; type 2, oligoclonal IgG bands in CSF but not in serum, indicative of intrathecal IgG synthesis; type 3, oligoclonal bands in CSF plus identical oligoclonal bands in serum and CSF, indicative of intrathecal IgG synthesis; type 4, identical pattern of oligoclonal bands in CSF and serum. There was no patient with type 5 (identical patterns of monoclonal bands in CSF and serum) in the study. Horizontal solid line indicates median, Kruskal-Wallis test among groups revealed a significant difference (p<0.001), significant P-values for pairwise comparisons (Mann-Whitney U test) are displayed.</p