The measurement of fluid biomarkers such as phosphorylated tau at threonine 181 (pTAU181), amyloid-β 40 (Aβ40), and Aβ42 is a routine medical examination that contributes to achieving an accurate diagnosis within the Alzheimer's disease (AD) clinical continuum. The aim of this study is to compare the concentration of these biomarkers in CSF and plasma and determine their relationship with the patients' clinical variant and profile. Patients were diagnosed following the NIA-AA criteria. Plasma and CSF were obtained from healthy controls (HC), mild cognitive impairment (MCI non-AD), MCI displaying positive AD markers (MCI-AD), and AD patients. Biomarker levels were assessed using the LUMIPULSE® G600II instrument (Fujirebio, Japan). Data showed a significant increase in pTAU181 concentration, specifically in the progression from MCI non-AD to AD conditions. The opposite trend was observed for Aβ42 and Aβ42/Aβ40. Furthermore, these biomarker trends appeared to change consistently with variations in the MMSE score, highlighting the relevance of plasma in detecting changes in patients' cognitive function. Considering the clinical variant, atypical patients displayed the highest pTAU181 and lowest Aβ42 levels, consistent with their lower MMSE scores. Lastly, the posterior cortical atrophy (PCA) profile showed higher pTAU181 and lower Aβ42 levels when compared to other profiles. Nevertheless, these last results are to be cautiously interpreted given the limited number of samples included in the analysis. Hence, further analyses on larger cohorts are needed to better define the role of these biomarkers in distinguishing between patients' clinical variants.

BACKGROUND AND OBJECTIVES:Autoantibodies against contactin-associated protein-like 2 (CASPR2-IgG) and leucine-rich glioma inactivated 1 protein (LGI1-IgG) identify a subgroup of autoimmune encephalitis (AE). Up to 65% of patients with LGI1/CASPR2 AE show cognitive sequelae that are unpredictable at onset. We aimed to assess the clinical relevance of serum autoantibody titers and neurofilament light chain (NfL) levels as biomarkers in CASPR2/LGI1 AE. METHODS:We selected consecutive CASPR2/LGI1-IgG-positive patients with at least 2 longitudinal serum samples obtained more than 60 days apart. Samples were defined as acute (first diagnostic evaluation after onset or relapse and before immunotherapy) and remission (>2 months from attack). CASPR2/LGI1-IgG was titered with a live cell-based assay. Functional outcome was measured using modified Rankin Scale and Clinical Assessment Scale in AE and cognitive impairment using Montreal Cognitive Assessment (MoCA). RESULTS:We included 23 patients (LGI1 = 15, CASPR2 = 7, CASPR2/LGI1 = 1) with 130 serum samples (acute = 32; remission = 98). Serum titers in the acute phase were higher than in remission and decreased over time and after immunosuppressive treatment. In 9 of 10 patients, relapses occurred with seropositive samples, and in 4 of 5 patients, these occurred with increased titers. Onset titers did not correlate with functional/cognitive outcome at follow-up.Serum NfL median levels in both patients with LGI1 AE (35.3 pg/mL, range: 5.4-164) and CASPR2 AE (31.4 pg/mL, range: 9.11-120) were higher than in age/sex-matched controls (14.55, range: 5.4-56.8, p = 0.004 and p < 0.001, respectively). Acute-phase samples had higher NfL median levels (47.2, range: 9.11-120) compared with remission (31.2 pg/mL; range, 5.4-114, p = 0.02). NfL levels at onset predicted lower MoCA scores at follow-up in univariate linear regression analysis (B = -3.881, p = 0.0256). NfL levels decreased over time, but at the last follow-up remained higher than those in controls (p = 0.02). DISCUSSION:Measuring LGI1 and CASPR2-IgG titers in AE could help to confirm the disease stage and define relapses but has no prognostic implications. Serum NfL at onset could be used to identify patients at higher risk of cognitive sequelae that might deserve tailored management.

BACKGROUND AND OBJECTIVES:Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum. METHODS:We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments. RESULTS:PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement (p = 0.01), and in patients with MS (12/42), more frequently with atypical features (p < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores (p < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, p < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested. DISCUSSION:Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.

BACKGROUND:Alzheimer's disease (AD) molecular hallmarks are the accumulation of β-amyloid (Aβ) peptides and phosphorylated tau proteins in the patients' cerebral cortex. For this reason, the measurement of cerebrospinal fluid (CSF) levels of phosphorylated tau at threonine 181 (pTAU181), Aβ40, and Aβ42 is a routine clinical evaluation that, together with other diagnostic tools, helps providing a correct diagnosis. However, CSF collection is an invasive procedure. Hence, this study aims to compare these biomarkers concentration in CSF and plasma, assess their diagnostic accuracy within AD clinical continuum and determine the clinical variant and profile effect on their concentrations. METHOD:Patients were assigned to a specific diagnosis, variant (typical vs atypical AD) and clinical profile (single or multidomain) following the NIA-AA criteria. Plasma samples were collected from a total of 85 healthy control (HC), 17 mild-cognitive impairment (MCI non-AD), 14 MCI presenting positive AD markers (MCI-AD) and 51 AD patients. CSF was obtained from 10 MCI non-AD, 12 MCI-AD and 42 AD dementia cases. APOE genotype was assessed using TaqMan™ SNP Genotyping Assay (Applied Biosystems, USA). Both plasma and CSF biomarkers measurements were performed using the LUMIPULSE® G600II instrument (Fujirebio, Japan) with relative kits. RESULT:Plasma concentrations of the three biomarkers and relative ratios followed a trend confirmed both by CSF measurements and by literature. Furthermore, both biofluid biomarker levels appeared to change coherently with the change in patients' MMSE score, further supporting that cognitive function impairment is mirrored by a variation in CSF and most importantly blood biomarker levels. Considering the clinical variant, atypical patients displayed higher pTAU181 and lower Aβ42 concentrations, reflecting their lower MMSE score. As for the clinical profile, the Posterior Cortical Atrophy (PCA) one appeared to deviate from the others, showing higher pTAU181 and lower Aβ42 levels. Lastly, pTAU181 and Aβ42 were observed to be the best AD predictors. CONCLUSION:pTAU181, Aβ42, and the Aβ42/Aβ40 ratio were confirmed to be good indicators of AD pathology. Although further analyses are needed to accurately define the role of these biomarkers in distinguishing between the clinical variants, data hints at a possible difference between AD typical and atypical form.

BACKGROUND:Cerebrospinal fluid (CSF) oligoclonal IgM bands (OCMBs) have been suggested as prognostic biomarkers in MS, but serum OCMBs meaning is still uncertain. OBJECTIVES:We aimed to assess frequency and clinical relevance of all OCMB patterns. METHODS:In this retrospective cohort study, 136 paired sera-CSF from consecutive persons with MS (pwMS) were tested in 2 centers for OCMBs using isoelectric focusing-immunoblotting. Active disease was defined as clinical or radiological relapse occurring during two-year follow-up. Predictors of active disease were analyzed with logistic regressions and Kaplan-Meier survival curves. RESULTS:OCMBs were found in 6.6 % of pwMS as unique-to-CSF (pattern #2), and in 20.6 % as identical in serum-CSF (pattern #4), without between-cohort difference. Active disease was more frequent in those with pattern #2 (88.9 %) and #4 (64.3 %) than in those OCMB-negative (33.3 %, p < 0.001). In multivariate analysis, pattern #2 (OR: 15.9; 95 % CI [1.8-136]), and pattern #4 (OR: 3.3 95 % CI [1.3-8.3]) were independent predictors of active disease. In survival analysis, pattern #2 (p < 0.001) and #4 (p = 0.017) predicted radiological relapses. CONCLUSIONS:Our data confirm that CSF OCMB marks poor prognosis in MS. However, both OCMB pattern #4 and pattern #2, with different strength prediction, might be useful to stratify pwMS deserving more aggressive treatments, although the stratification could be achieved in the near future with more standardized and easily measurable biomarkers (e.g., serum neurofilaments).

Alzheimer's disease (AD) molecular hallmarks are the accumulation of β-amyloid (Aβ) peptides and phosphorylated tau proteins in the patients’ cerebral cortex. For this reason, the measurement of cerebrospinal fluid (CSF) levels of phosphorylated tau at threonine 181 (pTAU181), Aβ40, and Aβ42 is a routine clinical evaluation that, together with other diagnostic tools, helps providing a correct diagnosis. However, CSF collection is an invasive procedure. Hence, this study aims to compare these biomarkers concentration in CSF and plasma, assess their diagnostic accuracy within AD clinical continuum and determine the clinical variant and profile effect on their concentrations. Patients were assigned to a specific diagnosis, variant (typical vs atypical AD) and clinical profile (single or multidomain) following the NIA-AA criteria. Plasma samples were collected from a total of 85 healthy control (HC), 17 mild-cognitive impairment (MCI non-AD), 14 MCI presenting positive AD markers (MCI-AD) and 51 AD patients. CSF was obtained from 10 MCI non-AD, 12 MCI-AD and 42 AD dementia cases. APOE genotype was assessed using TaqMan™ SNP Genotyping Assay (Applied Biosystems, USA). Both plasma and CSF biomarkers measurements were performed using the LUMIPULSE® G600II instrument (Fujirebio, Japan) with relative kits. Plasma concentrations of the three biomarkers and relative ratios followed a trend confirmed both by CSF measurements and by literature. Furthermore, both biofluid biomarker levels appeared to change coherently with the change in patients’ MMSE score, further supporting that cognitive function impairment is mirrored by a variation in CSF and most importantly blood biomarker levels. Considering the clinical variant, atypical patients displayed higher pTAU181 and lower Aβ42 concentrations, reflecting their lower MMSE score. As for the clinical profile, the Posterior Cortical Atrophy (PCA) one appeared to deviate from the others, showing higher pTAU181 and lower Aβ42 levels. Lastly, pTAU181 and Aβ42 were observed to be the best AD predictors. pTAU181, Aβ42, and the Aβ42/Aβ40 ratio were confirmed to be good indicators of AD pathology. Although further analyses are needed to accurately define the role of these biomarkers in distinguishing between the clinical variants, data hints at a possible difference between AD typical and atypical form.

APOE ɛ4 allele is the major genetic risk factor for Alzheimer's Disease (AD). Furthermore, APOE methylation pattern has been described to be associated with the disease and to follow a bimodal pattern, with a hypermethylated CpG island and a hypomethylated promoter region. However, little is known about the methylation levels in the APOE 5'UTR region. Here, the methylation of two regions (R1 and R2) within APOE 5'UTR was investigated in both peripheral blood mononuclear cells (PBMCs) and hippocampus (HIC) samples to identify differentially methylated CpG sites and to associate clinical, genetic features and cerebrospinal fluid (CSF) biomarkers levels. DNA was extracted from PBMCs of 20 AD and 20 healthy controls (HC) and from 6 AD and 3 HC HIC samples. The methylation analysis was carried out by means of pyrosequencing. In AD PBMCs we found that R1 region displayed a higher methylation level, while the opposite trend was observed in R2. The presence of ɛ4 allele highlighted a marked increase in R1 methylation level and a decrease in R2. In AD PBMCs and HIC, age progression resulted to be associated with an increase in the methylation level of R1. Lastly, the methylation of a CpG site in R2 was found to be related to CSF biomarkers. Despite the lack of a statistical significance, the outcome from this exploratory analysis highlighted the presence of a difference in methylation in APOE 5'UTR in PBMCs of AD patients which seemed to be associated also with APOE genotype, age and CSF biomarkers level.

BackgroundCerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS).MethodsWe retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF− and ITS+/ITS− patients.ResultsMOG-IgG were found in 55/960 patients (5.7%; serum+/CSF−: 58.2%, serum+/CSF+: 34.5%; serum−/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI −0.46 to –0.65), p=0.65). There were no clinical–paraclinical differences between MOG-IgG CSF+ vs CSF− patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOGcorrelated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01).ConclusionsConsistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

23Na in the prefused rat mandibular salivary gland was measured by spin-echo double quantum filter 23Na-NMR spectroscopy at 8.45 T. Resonances due to the intracellular 23Na and the interstitial 23Na were observed in the perfused gland at 25°C. The resonance due to intracellular 23Na consisted of two Lorentzian signals stemming from the |12〉〈−12| coherence (sharp resonance) and the |−12〉〈−32| and |32〉〈12| coherences (broad resonance). The transverse relaxation rate constant corresponding to the |12〉〈−12| coherence was 95 ± 4 s−1 and that corresponding to the |−12〉〈−32| and |32〉〈12| coherences was 1360 ± 75 s−1 (ean ± S.E., n = 5). The resonance due to the interstitial 32Na had longer relaxation rate constants, and disappeared upon administration of dysprosium triethylenetetramine-N,N′,N″,N‴,N‴-hexaacetic acid.

Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder with unknown etiology. A selective depletion of aquaporin 4 (AQP4) has been shown in iNPH patients. We collected serum and cerebrospinal fluid (CSF) from 43 iNPH patients and 35 with other neurodegenerative conditions, and serum from 43 healthy subjects. All samples were tested for AQP4-IgG/IgA/IgM antibodies using a live cell-based assay. No patients or controls had serum/CSF AQP4-IgG/IgA. One/43 iNPH patient and 0/43 controls tested positive for serum AQP4-IgM. The AQP4-IgM-positive iNPH patient had no clinico-radiological distinctive features. AQP4 antibodies are unlikely to play a role in iNPH pathogenesis.

Background: Neuroimmunology has impressively expanded in the past decade. Novel assays, especially cell-based assays (CBAs) can detect conformational antibodies (Abs) recognizing antigens in their native conformation. Generally, the availability of in-house and of commercial tests has improved the diagnostics, but introduced demanding laboratory tasks. Hence, standardization and quality controls represent a key step to promote accuracy. We report on the results of the 2018 external quality assessment program (EQAP) organized by the Italian Neuroimmunology Association. Methods: EQAP regarded 10 schemes, including oligoclonal bands (OCBs), intracellular-neuronal (ICN)-Abs, neuronal-surface (NS)-Abs, aquaporin-4 (AQP4)-Abs, myelin oligodendrocyte glycoprotein (MOG)-Abs, myelin-associated glycoprotein (MAG)-Abs, ganglioside-Abs, acetylcholine-receptor (AChR)-Abs, and muscle-specific-kinase (MuSK)-Abs, and 34 laboratories. Assays were classified as tissue-based assays (TBAs), solid-phase assays (SPAs), liquid-phase assays (LPAs), and CBAs. Thirty-three samples were provided. Results: Three-quarter of the tests were commercial. Median accuracy for the laboratories was 75% (range 50-100). In 8/10 schemes, at least one sample provided discrepant results. Inter-laboratory "substantial agreement" was found in 6/10 schemes (AChR, MuSK, MAG, AQP4, MOG, and NS-Abs), whereas the worst agreements regarded OCBs and ganglioside-Abs. Both commercial and in-house assays performed better in experienced laboratories. Conclusions: Assays could be divided in (a) robust commercial tests with substantial inter-laboratory agreement (MAG-Abs; AChR- and MuSK-Abs); commercial/"in-house" tests with (b) partial inter-laboratory agreement (AQP4-Abs, MOG-Abs, NS-Abs, ICN-Abs), and (c) with large inter-laboratory disagreement (OCBs, ganglioside-Abs). This real-life snapshot of the neuroimmunology test performances highlights shortcomings attributable to technician-dependent performances, assay structural limitations, and errors in test interpretations.

The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Consecutive sera from 204 patients with ‘possible MOGAD’ (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgGH+L), and a live-CBA for IgG1 (LCBA-IgG1). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgGFcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgGFcγ). Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8–95.9) and specificity 93.3% (CI:88.0–96.7) for LCBA-IgGH+L, and 74.6% (CI:61.0–85.3) and 100% (CI:97.6–100) for LCBA-IgG1. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG1); of these, three with ‘possible MOGAD’ showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG2, whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 ‘possible MOGAD’, 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1–98.4) and specificity 97.0% (CI:83.8–99.9) for LCBA-IgGFcγ, and 87.2% (CI:72.6–95.7) and 97.0% (CI:83.8–99.9) for FCBA-IgGFcγ. LCBA-IgG1 showed the highest specificity but can miss MOG-IgG2 reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgGH+L/ IgGFcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgGFcγ yielded the highest accuracy, and FCBA-IgGFcγ good specificity, but it was at risk of false-negative results.

Objective To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role. Methods Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay. Results Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex. Conclusions Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. Classification of evidence This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).

Background Anti-ganglioside antibodies are currently used in the differential diagnosis of suspected immune-mediated neuropathies. In-house and increasingly used commercial assays seem to perform suboptimally, and comparative information on their analytical performance are essentially lacking. Born within the frame of guidelines and standardization activities by the Italian Association of Neuroimmunology, this external quality assessment scheme (EQAS) is a real-life snapshot of the laboratory diagnostics in this field. Methods The EQAS consisted of five surplus, anonymized serum samples from patients with clinically-defined neuropathies and two serum samples from healthy blood donors. Eight laboratories used commercial line-/dot-blots, seven in-house/commercial ELISAs (in addition, 13 laboratories tested a recently released ELISA by Bühlmann). Only high anti-ganglioside antibody reactivities were considered, in accordance with consolidated recommendations. Results Large variations in anti-ganglioside antibody profiles were observed, even, although to a lesser extent, within homogeneous classes of assays. Concordance between the profiles and clinical phenotypes was also partial. Conclusions Although conducted on a relatively small, but representative number of Italian laboratories, this EQAS shows a critical between-laboratory disagreement in the test results of anti-ganglioside antibodies. Also considering the trend for using certified assays in generalist laboratories, strong efforts toward standardization and the identification of the best method(s) for their determinations are compellingly needed.

Journal of the Peripheral Nervous SystemVolume 23, Issue 1 p. 70-72 LETTER TO THE EDITOR Cerebrospinal fluid total protein determination in acute and chronic inflammatory demyelinating polyneuropathies: a critical reappraisal Diego Franciotta, Corresponding Author Diego Franciotta diego.franciotta@mondino.it Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, ItalyAddress correspondence to: Diego Franciotta, IRCCS Mondino Foundation, via Mondino 2, I-27100 Pavia, Italy. Tel: +(39)0382-380365; Fax: +(39)0382-380286; E-mail: diego.franciotta@mondino.itSearch for more papers by this authorMatteo Gastaldi, Matteo Gastaldi Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalySearch for more papers by this authorElisabetta Zardini, Elisabetta Zardini Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalySearch for more papers by this authorEduardo Nobile-Orazio, Eduardo Nobile-Orazio Neuromuscular and Neuroimmunology Service, Department of Medical Biotechnology and Translational Medicine, Humanitas Clinical and Research Institute, Milan University, Milan, ItalySearch for more papers by this author Diego Franciotta, Corresponding Author Diego Franciotta diego.franciotta@mondino.it Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, ItalyAddress correspondence to: Diego Franciotta, IRCCS Mondino Foundation, via Mondino 2, I-27100 Pavia, Italy. Tel: +(39)0382-380365; Fax: +(39)0382-380286; E-mail: diego.franciotta@mondino.itSearch for more papers by this authorMatteo Gastaldi, Matteo Gastaldi Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalySearch for more papers by this authorElisabetta Zardini, Elisabetta Zardini Laboratory of Neuroimmunology, IRCCS Mondino Foundation, Pavia, Italy Department of Brain and Behavioral Sciences, University of Pavia, Pavia, ItalySearch for more papers by this authorEduardo Nobile-Orazio, Eduardo Nobile-Orazio Neuromuscular and Neuroimmunology Service, Department of Medical Biotechnology and Translational Medicine, Humanitas Clinical and Research Institute, Milan University, Milan, ItalySearch for more papers by this author First published: 18 February 2018 https://doi.org/10.1111/jns.12253Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume23, Issue1March 2018Pages 70-72 RelatedInformation

This document presents the guidelines for anti-ganglioside antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Main clinical information on dysimmune peripheral neuropathies, indications and limits of anti-ganglioside antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

This document presents the guidelines for onconeural antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on paraneoplastic neurological syndromes, indications and limits of onconeural antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Background: Transverse myelitis (TM) is an inflammatory disorder that can be idiopathic or associated with central nervous system autoimmune/dysimmune inflammatory diseases, connective tissue autoimmune diseases, or post-infectious neurological syndromes. Prognosis of initial TM presentations is uncertain. Objective: To identify outcome predictors in TM. Methods: Retrospective study on isolated TM at onset. Scores ⩾3 on the modified Rankin scale (mRS) marked high disability. Results: A total of 159 patients were identified. TM was classified as follows: idiopathic (I-TM, n = 53), post-infectious (PI-TM, n = 48), associated with multiple sclerosis (MS-TM, n = 51), or neuromyelitis optica spectrum disorders/connective tissue autoimmune diseases/neurosarcoidosis ( n = 7). At follow-up (median, 55 months; interquartile range, 32–80), 42 patients were severely disabled, and patients with I-TM or PI-TM showed the worst outcomes. Predictors of disability were infectious antecedents, sphincter and pyramidal symptoms, high mRS scores, blood–cerebrospinal fluid barrier damage, lumbar magnetic resonance imaging (MRI) lesions on univariate analysis, and older age (odds ratio (OR), 1.1; 95% confidence interval (CI), 1.0–1.1), overt/subclinical involvement of the peripheral nervous system (PNS) (OR, 9.4; 95% CI, 2.2–41.0), complete TM (OR, 10.8; 95% CI, 3.4–34.5) on multivariate analysis. Conclusion: Our findings help define prognosis and therapies in TM at onset. Infectious antecedents and PNS involvement associate with severe prognosis. Nerve conduction studies and lumbar MRI could improve the prognostic assessment of this condition.