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In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12–22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not., Luijten et al. report that patients with Guillain-Barré syndrome (GBS) after SARS-CoV-2 infection share uniform neurological features, similar to those previously described in other cases of post-viral GBS. They conclude that SARS-CoV-2 infection may be an occasional trigger for GBS, but that a strong association is unlikely.

ObjectiveTo compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses.MethodsFrom the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared those treated with one IVIg course to those treated with two IVIg courses. The primary endpoint, the GBS disability scale at 4 weeks, was assessed with multivariable ordinal regression.ResultsOf 237 eligible patients, 199 patients received a single IVIg course. Twenty patients received an ‘early’ second IVIg course (1–2 weeks after start of the first IVIg course) and 18 patients a ‘late’ second IVIg course (2–4 weeks after start of IVIg). At baseline and 1 week, those receiving two IVIg courses were more disabled than those receiving one course. Compared with the one course group, the adjusted OR for a better GBS disability score at 4 weeks was 0.70 (95%CI 0.16 to 3.04) for the early group and 0.66 (95%CI 0.18 to 2.50) for the late group. The secondary endpoints were not in favour of a second IVIg course.ConclusionsThis observational study did not show better outcomes after a second IVIg course in GBS with poor prognosis. The study was limited by small numbers and baseline imbalances. Lack of improvement was likely an incentive to start a second IVIg course. A prospective randomised trial is needed to evaluate whether a second IVIg course improves outcome in GBS.

ObjectiveTo compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only.MethodsWe selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis.ResultsOf 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms.ConclusionIn patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.

The SYNERGORS Final Project Report is available at: https://eng.ox.ac.uk/synergors/publications/ Executive Summary: The SYNERGORS project (“A systems approach to synergistic utilisation of secondary organic streams”) was funded by the UKRI Natural Environment Research Council (NERC), running from 2018 to 2021. The project aimed to develop new systems approaches for promoting resource recovery from secondary organic waste streams including food waste, residual biomass and municipal solid waste. The project received support from more than 10 UK and international organisations, including academia, industry and policymakers, to provide multidisciplinary expertise to address the global challenges in resources and waste management. The formation of the core team was greatly assisted by the British Council / Newton Fund Researcher Links workshops, with collaboration between the British, Malaysian, Mexican and Brazilian academics. The SYNERGORS project has led to substantial impacts beyond academia, resulting in 9 academic publications, new experimental studies with Anaero Technology, a number of engagement activities and international visits (including case studies in Malaysia, Brazil and Mexico), and the creation of the Society of Circular, Regenerative and Sustainable Systems (CRES) which aims to promote systems thinking and circular economy. SYNERGORS’s research spans three themes: Theme 1: Strategic analysis for sustainable organic resources and waste management to achieve circular economy and net zero Theme. 2: Development of novel resource recovery and valorisation technology concept Theme. 3: Development of innovative biorefinery system design. Key Recommendations from SYNERGORS 1. Waste and recycling industries should move away from a treatment-oriented waste management approach and adopt a more transformative and innovative resource recovery approach to achieve a more circular economy. 2. A systems approach to addressing waste management is needed to promote collaboration among different groups of stakeholders (e.g. government, local authorities, waste and recycling industries, commercial sector, public etc.) 3. Resources embedded in organic waste streams should be exploited for value-added products such 4 as chemicals and hydrogen. This requires significant revamp on existing waste treatment facilities. Further research is needed to improve system efficiency and achieve greater cost reduction. This work was supported by the UKRI Natural Environment Research Council (NE/R012938/1) through the UKRI/NERC Industrial Innovation Fellowship Programme.

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.

OBJECTIVE: To determine the frequency and significance of concurrent glial (glial-Ab) or neuronal-surface (NS-Ab) antibodies in patients with anti-NMDA receptor (NMDAR) encephalitis. METHODS: Patients were identified during initial routine screening of a cohort (C1) of 646 patients consecutively diagnosed with anti-NMDAR encephalitis and another cohort (C2) of 200 patients systematically rescreened. Antibodies were determined with rat brain immunostaining and cell-based assays. RESULTS: Concurrent antibodies were identified in 42 patients (4% from C1 and 7.5% from C2): 30 (71%) with glial-Ab and 12 (29%) with NS-Ab. Glial-Ab included myelin oligodendrocyte glycoprotein (MOG) (57%), glial fibrillary acidic protein (GFAP) (33%), and aquaporin 4 (AQP4) (10%). NS-Ab included AMPA receptor (AMPAR) (50%), GABAa receptor (GABAaR) (42%), and GABAb receptor (8%). In 39 (95%) of 41 patients, concurrent antibodies were detected in CSF, and in 17 (41%), concurrent antibodies were undetectable in serum. On routine clinical-immunologic studies, the presence of MOG-Ab and AQP4-Ab was suggested by previous episodes of encephalitis or demyelinating disorders (8, 27%), current clinical-radiologic features (e.g., optic neuritis, white matter changes), or standard rat brain immunohistochemistry (e.g., AQP4 reactivity). GFAP-Ab did not associate with distinct clinical-radiologic features. NS-Ab were suggested by MRI findings (e.g., medial temporal lobe changes [AMPAR-Ab], or multifocal cortico-subcortical abnormalities [GABAaR-Ab]), uncommon comorbid conditions (e.g., recent herpesvirus encephalitis), atypical tumors (e.g., breast cancer, neuroblastoma), or rat brain immunostaining. Patients with NS-Ab were less likely to have substantial recovery than those with glial-Ab (5 of 10 [50%] vs 17 of 19 [89%], p = 0.03). CONCLUSIONS: Between 4% and 7.5% of patients with anti-NMDAR encephalitis have concurrent glial-Ab or NS-Ab. Some of these antibodies (MOG-Ab, AQP4-Ab, NS-Ab) confer additional clinical-radiologic features and may influence prognosis.

©. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in [Endodoncia].

BACKGROUND: Rebound of multiple sclerosis (MS) activity has been described after the withdrawal of high-efficacy drugs, but its impact during pregnancy is less known. We describe a series of cases of rebound syndrome after the cessation of fingolimod due to pregnancy planning. METHODS: The clinical and radiological data of 7 MS patients who discontinued fingolimod therapy between May 2012 and March 2018 to plan a pregnancy was analysed. RESULTS: Three (42.8%) of the 7 patients experienced a rebound effect, all of whom became pregnant. During pregnancy, the 3 patients had a mean (SD) of 5.3 (1.3) relapses, and 13 of the 15 relapses were treated with intravenous steroids and/or immunoglobulin. These patients experienced a median increase of 3 points in the Expanded Disability Status Scale (range, 2-4), as well as a median increase of 27 new gadolinium-enhancing lesions (range, 9-40) and 38 new T2 lesions in a post-partum MRI (range, 21-70). The 3 pregnancies resulted in the delivery of healthy babies. A strong correlation was found between the lymphocyte count at fingolimod onset and the annual relapse rate in the period without therapy (r= -0.84, p?=?0.005). The time to first relapse was shorter in patients who had

To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe).

Malaysia has a plethora of biomass that can be utilized in a sustainable manner to produce bio-products for circular green economy. At the 15th Conference of Parties in Copenhagen, Malaysia stated to voluntarily reduce its emissions intensity of gross domestic product by upto 40% by 2020 from 2005 level. Natural resources e.g. forestry and agricultural resources will attribute in achieving these goals. This paper investigates optimum bio-based systems, such as bioenergy and biorefinery, and their prospects in sustainable development in Malaysia, while analyzing comparable cases globally. Palm oil industry will continue to play a major role in deriving products and contributing to gross national income in Malaysia. Based on the current processing capacity, one tonne of crude palm oil (CPO) production is associated with nine tonnes of biomass generation. Local businesses tend to focus on products with low-risk that enjoy subsidies, e.g. Feed-in-Tariff, such as bioenergy, biogas, etc. CPO biomass is utilized to produce biogas, pellets, dried long fibre and bio-fertilizer and recycle water. It is envisaged that co-production of bio-based products, food and pharmaceutical ingredients, fine, specialty and platform chemicals, polymers, alongside biofuel and bioenergy from biomass is possible to achieve overall sustainability by the replacement of fossil resources. Inception of process integration gives prominent innovative biorefinery configurations, an example demonstrated recently, via extraction of recyclable, metal, high value chemical (levulinic acid), fuel, electricity and bio-fertilizer from municipal solid waste or urban waste. Levulinic acid yield by only 5 weight% of waste feedstock gives 1.5 fold increase in profitability and eliminates the need for subsidies such as gate fees paid by local authority to waste processor. Unsustainable practices include consumable food wastage, end-of-pipe cleaning and linear economy that must be replaced by sustainable production and consumption, source segregation and process integration, and product longevity and circular economy.

OBJECTIVE: To describe the clinical features of late-onset (=50 years) neuromyelitis optica spectrum disorder (LO-NMOSD), to compare the outcome with that of early-onset (EO-NMOSD), and to identify predictors of disability. METHODS: A retrospective, multicenter study of 238 patients with NMOSD identified by the 2015 criteria. Clinical and immunologic features of patients with LO-NMOSD were compared with those with EO-NMOSD. All patients were evaluated for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies. RESULTS: Sixty-nine (29%) patients had LO-NMOSD. Demographic features, initial disease presentation, annualized relapse rate, and frequency of AQP4-IgG and MOG-IgG did not differ between patients with LO-NMOSD and EO-NMOSD. Among patients with AQP4-IgG or double seronegativity, those with LO-NMOSD had a higher risk to require a cane to walk (hazard ratio [HR], 2.10, 95% CI 1.3-3.54, p = 0.003 for AQP4-IgG, and HR, 13.0, 95% CI 2.8-59.7, p = 0.001, for double seronegative). No differences in outcome were observed between patients with MOG-IgG and LO-NMOSD or EO-NMOSD. Older age at onset (for every 10-year increase, HR 1.63, 95% CI 1.35-1.92 p < 0.001) in NMOSD, and higher disability after the first attack (HR 1.68, 95% CI 1.32-2.14, p < 0.001), and double seronegativity (HR 3.74, 95% CI 1.03-13.6, p = 0.045) in LO-NMOSD were the main independent predictors of worse outcome. CONCLUSIONS: Patients with LO-NMOSD have similar clinical presentation but worse outcome than EO-NMOSD when they are double seronegative or AQP4-IgG positive. Serostatus and residual disability after first attack are the main predictors of LO-NMOSD outcome.

OBJECTIVE: To determine the frequency and clinical relevance of immunoglobulin (Ig)G, IgA, and IgM N-methyl-d-aspartate receptor (NMDAR) antibodies in several diseases, and whether the IgG antibodies occur in disorders other than anti-NMDAR encephalitis. METHODS: Evaluation of IgG, IgA, and IgM NMDAR antibodies in serum of 300 patients with anti-NMDAR encephalitis, stroke, dementia, schizophrenia, or seronegative autoimmune encephalitis. Antibodies and their effect on cultured neurons were examined with cell-based assays and brain and live neuronal immunostaining. Retrospective analysis of the clinical diagnoses of a cohort of 1,147 patients with IgG NMDAR antibodies identified since 2005. RESULTS: Among the 300 patients studied, IgG NMDAR antibodies were only identified in those with anti-NMDAR encephalitis and all reacted with brain and live neurons. By cell-based assay, IgA or IgM antibodies were detected in 22 of 300 patients (7%) with different diseases, but only 10 (3%) reacted with brain and 7 (2%) with live neurons. In cultured neurons, IgG but not IgA or IgM antibodies caused a decrease of synaptic and extrasynaptic NMDAR. Among the cohort of 1,147 patients with IgG NMDAR antibodies, 1,015 (88.5%) had anti-NMDAR encephalitis, 45 (3.9%) a limited form of the disease, 41 (3.6%) autoimmune post-herpes simplex encephalitis, 37 (3.2%) overlapping syndromes (anti-NMDAR encephalitis and demyelinating disease), and 9 (0.8%) atypical encephalitic syndromes; none had schizophrenia. CONCLUSIONS: IgG NMDAR antibodies are highly specific for anti-NMDAR encephalitis and cause a decrease of the levels of NMDAR. In contrast, IgA or IgM antibodies occur infrequently and nonspecifically in other diseases and do not alter the receptor levels.

Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: 'Europe/Americas', 'Asia' (without Bangladesh), and 'Bangladesh'. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome.

At the local scale, interconnected production, consumption, waste management and other man-made technological components interact with local ecosystem components to form a local production system. The purpose of this work is to develop a framework for the conceptual characterization and mathematical modelling of a local production system to support the assessment of process and component options that potentially create symbiosis between industry and ecosystem. This framework has been applied to a case study to assess options for the establishment of a local energy production system that involves a heathland ecosystem, bioenergy production and wastewater treatment. We found that the framework is useful to analyze the two-way interactions between these components in order to obtain insight into the behavior and performance of the bioenergy production system. In particular, the framework enables exploring the levels of the ecosystem states that allow continuous provisioning of resources in order to establish a sustainable techno-ecological system.

IMPORTANCE Most studies on opsoclonus-myoclonus syndrome (OMS) in adults are based on small case series before the era of neuronal cell surface antibody discovery. OBJECTIVE To report the clinical and immunological features of idiopathic OMS (I-OMS) and paraneoplastic OMS (P-OMS), the occurrence of antibodies to cell surface antigens, and the discovery of a novel cell surface epitope. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study and laboratory investigations of 114 adult patients with OMS at a center for autoimmune neurological disorders done between January 2013 and September 2015. MAIN OUTCOMES AND MEASURES Review of clinical records. Immunohistochemistry on rat brain and cultured neurons as well as cell-based assays were used to identify known autoantibodies. Immunoprecipitation and mass spectrometry were used to characterize novel antigens. RESULTS Of the 114 patients (62 [54%] female; median age, 45 years; interquartile range, 32-60 years), 45 (39%) had P-OMS and 69 (61%) had I-OMS. In patients with P-OMS, the associated tumors included lung cancer (n = 19), breast cancer (n = 10), other cancers (n = 5), and ovarian teratoma (n = 8); 3 additional patients without detectable cancer were considered to have P-OMS because they had positive results for onconeuronal antibodies. Patients with I-OMS, compared with those who had P-OMS, were younger (median age, 38 [interquartile range, 31-50] vs 54 [interquartile range, 45-65] years; P < .001), presented more often with prodromal symptoms or active infection (33% vs 13%; P = .02), less frequently had encephalopathy (10% vs 29%; P = .01), and had better outcome (defined by a modified Rankin Scale score

The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.

Centralised production of essential products and services based on fossil fuels and large scale distribution infrastructures have contributed to a plethora of issues such as deterioration of ecosystems, social-economic injustice and depletion of resources. The establishment of localised production systems can potentially reduce unsustainable resource consumption and bring socioeconomic and environmental benefits. The main objective of this work is to develop engineering tools for the rational design of such systems. Production of products and services is characterised as inter-linked subsystems (e.g. food, energy, water and waste). A sequential design approach is developed to design subsystems in turn, with necessary iterations. The process is illustrated through the co-design of energy, water and food production for a case study locale based on a developing eco-town in the UK. This design approach suggested an integrated system based primarily on locally available resources and allowed greater insight into the drivers and constraints on local resource use.

IMPORTANCE Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment. OBJECTIVE To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study. MAIN OUTCOMES AND MEASURES Analysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals. RESULTS Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against gamma-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff- person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor. CONCLUSIONS AND RELEVANCE Patients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.

Objective Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a frequent autoimmune neuropathy with a heterogeneous clinical spectrum. Clinical and experimental evidence suggests that autoantibodies may be involved in its pathogenesis, but the target antigens are unknown. Axoglial junction proteins have been proposed as candidate antigens. We examined the reactivity of CIDP patients' sera against neuronal antigens and used immunoprecipitation for antigen unraveling. Methods Primary cultures of hippocampal neurons were used to select patients' sera that showed robust reactivity with the cell surface of neurons. The identity of the antigens was established by immunoprecipitation and mass spectrometry, and subsequently confirmed with cell-based assays, immunohistochemistry with teased rat sciatic nerve, and immunoabsorption experiments. Results Four of 46 sera from patients with CIDP reacted strongly against hippocampal neurons (8.6%) and paranodal structures on peripheral nerve. Two patients' sera precipitated contactin-1 (CNTN1), and 1 precipitated both CNTN1 and contactin-associated protein 1 (CASPR1). Reactivity against CNTN1 was confirmed in 2 cases, whereas the third reacted only when CNTN1 and CASPR1 were cotransfected. No other CIDP patient or any of the 104 controls with other neurological diseases tested positive. All 3 patients shared common clinical features, including advanced age, predominantly motor involvement, aggressive symptom onset, early axonal involvement, and poor response to intravenous immunoglobulin. Interpretation Antibodies against the CNTN1/CASPR1 complex occur in a subset of patients with CIDP who share common clinical features. The finding of this biomarker may help to explain the symptoms of these patients and the heterogeneous response to therapy in CIDP. ANN NEUROL 2013;73:370380

Background Reactivity against terminal NeuNAc(alpha 2-3) Gal, common to several gangliosides such as GD1a, GT1b and GM3, has rarely been reported. The authors recently described a patient with a clinical picture of acute relapsing sensory ataxic neuropathy and bulbar involvement in whom they demonstrated concomitant reactivity against NeuNAc(alpha 2-3) Gal and disialosyl epitopes. The authors suggested a correlation between NeuNAc(alpha 2-3) Gal reactivity and bulbar involvement. Aim To determine the frequency of reactivity against terminal NeuNAc(alpha 2-3) Gal in acute and chronic immune-mediated disorders, and its possible correlation with bulbar involvement. Methods The authors retrospectively reviewed reactivity in the serum of more than 3000 consecutive patients with acute and chronic disorders in which antiganglioside antibodies were studied. The authors selected those patients who were simultaneously positive, by ELISA or thin-layer chromatography, for IgG or IgM antibodies anti-GM3, GD1a and GT1b, and reviewed their clinical features. Results Reactivity against NeuNAc(alpha 2-3) Gal, shared by GM3, GD1a and GT1b gangliosides, was detected in 10 patients: isolated in one patient, and concomitant with reactivity against other gangliosides in the remaining patients. Reactivity against NeuNAc(alpha 2-3) Gal was frequently associated (8/10) with symptoms suggestive of bulbar involvement, such as dysphagia, dysarthria or dysphonia. Severe respiratory failure requiring mechanical ventilation was observed in four patients. Conclusions Reactivity against the NeuNAc(alpha 2-3) Gal epitope is rare and is generally found in association with reactivity against the disialosyl epitope. It can be detected in patients with acute or chronic disorders and could be a serological marker of clinical bulbar involvement and, to a lesser extent, associated with the development of severe respiratory failure.