Search

In angiosperms, a decrease in fruit production towards the apex of individual inflorescences is usually observed. Orchids are thought to be primarily pollination‐limited species, and non‐uniform pollination could cause this decrease pattern in several species. Fruit production was investigated in relation to flower position and floral display size in Orchis militaris (Orchidaceae), a deceptive species.Over 2 years, eight populations of O. militaris were studied and fruit position along the inflorescence was recorded. Generalised linear models were performed to examine the effect of population, year, flower position and floral display size on fruit production.The dominant pattern was characterised by a higher fruit set in the middle part of the inflorescence (parabolic pattern). A non‐directional pattern of fruit production was also detected in some populations. Within a given population, patterns were generally consistent among years. In one of the two study years and in one of the eight populations specifically, the proximal‐to‐distal decrease in fruit production was dramatic in plants with a large floral display but weak or absent in small displays.Our study demonstrates the intraspecific diversity of fruit distribution patterns in O. militaris. Non‐uniform pollination along the inflorescence is likely to be responsible for the parabolic pattern, while irregular visitation could explain the non‐directional pattern of fruit production. Pattern variation among years and between populations could arise from spatiotemporal variation in pollinator assemblages. Resource competition effects could explain the interaction effect between display size and flower position. [ABSTRACT FROM AUTHOR]

The congeners Rhinanthus angustifolius and Rhinanthus minor, two annual hemiparasites pollinated by bumblebees, are known to hybridise in the wild. Both species are self-compatible, but the capacity for autonomous selfing is higher in R. minor. This suggests a difference in realized outcrossing rates, which have not been determined before in these species. Using microsatellites, both species turned out to have mixed mating systems, but with a much lower multilocus outcrossing rate (0.13) for R. minor compared to R. angustifolius (0.76). We hypothesised that a higher outcrossing rate should lead to a higher chance of heterospecific pollination, and we therefore determined the rate of hybrid formation on each species in an artificial mixed population. Hybrid seeds were produced at low frequency (4.5%), and no significant difference was found between the species. It is therefore likely that post-pollination processes influence hybrid seed formation to counteract the expected difference in heterospecific pollen deposition. We checked fruit set, seed set and the rate of autonomous selfing in controlled crosses in the greenhouse in 2 years, and found that fruit set (2003) or seed set (2010) were lower in R. angustifolius × R. minor crosses relative to the reciprocal cross. Hybrid seeds produced on R. angustifolius also had a much lower germination rate, so most of the established F1 hybrid plants have the R. minor cytoplasm. The formation of advanced hybrids depends on pollinator preference, which is biased towards R. angustifolius if present in sufficient numbers, because it offers more rewards. [ABSTRACT FROM AUTHOR]

Fifteen polymorphic microsatellite loci were developed from an enriched genomic library of the annual plant Rhinanthus angustifolius and characterized using 36 individuals. These markers provided high polymorphism ranging from two to 15 alleles per locus. Four loci showed significant departure from Hardy–Weinberg equilibrium, probably because of the occurrence of null alleles. No significant linkage disequilibrium was detected between pairs of loci. Tests of cross-species transferability were performed on four congeners with a success rate of 100% in Rhinanthus minor, 93% in R. mediterraneus and R. glacialis, and 80% in R. alectorolophus. These microsatellite loci will be useful tools to study mating system, gene flow and hybridization in the genus Rhinanthus. [ABSTRACT FROM AUTHOR]

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common complication of chimeric antigen receptor (CAR) T-cell therapy. Current practice guidelines recommend the immune effector cell-associated encephalopathy (ICE) score for the assessment and monitoring of ICANS., Objective: To demonstrate modifications to ICE score to patients with vision and hearing impairments or who are who are from non-native-speaking backgrounds., Methods: We discuss five cases and the modifications made to adapt the ICE score to meet patients' needs., Results: Modifications to ICE score was feasible and it assisted with CAR T cell therapy outcome monitoring., Discussion: These cases highlight the need for flexible and patient-tailored strategies and the importance of collaboration between multidisciplinary teams and patients' families/caregivers when monitoring patients for ICANS after CAR T-cell therapy., Competing Interests: CK has no competing interests to declare. TS has received conference travel support and speaker fees from Gilead. CA has received conference travel support and speaker fees from Gilead. MW has no competing interests to declare. NS has received conference fee sponsorship from Roche. TH-LT has received speaker honoraria from Eisai and travel support from Biogen. RW has no competing interests to declare. KK has no competing interests to declare. SMW has no competing interests to declare. SI has no competing interests to declare. CT has received honoraria from AbbVie, BeiGene, Janssen, AstraZeneca, Novartis and Lilly. SF has no competing interests to declare. TJO’B has received research funding from Eisai, UCB Pharma, LivaNova, ES Therapeutics and Kinoxis Therapeutics. He has also received competitive grant funding from the NHMRC, MRFF, NINDS and the DoD. RA has no competing interests to declare. AS has no competing interests to declare. CM has received conference travel support and/or speaker fees from Merck, Novartis, and Biogen. He has received research support from the National Health and Medical Research Council, Multiple Sclerosis Research Australia, The University of Melbourne, The Royal Melbourne Hospital Neuroscience Foundation, and Dementia Australia. MM has served on the advisory board for Merck and Novartis, and has received speaker honoraria from Merck, Biogen and Novartis. Her institution receives funding from Merck, Australian National Health Medical Research Council, Brain Foundation and MS Research Australia., (Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system. There were 33 335 people with MS in Australia in 2021 and 2917 in New Zealand in 2006 and the prevalence and incidence are increasing with time. Although new treatments have substantially improved outcomes in recent decades, the treatment landscape has become increasingly complex due to the expanding number of disease-modifying therapies (DMTs) and associated safety considerations., Main Recommendations: A total of 80 consensus recommendations were developed on the current best-practice management of MS in Australia and New Zealand. Part 1 of these guidelines outlines the consensus recommendations covering domains including DMT counselling and selection, pre-DMT assessments, monitoring disease activity on DMT, switching DMT, and discontinuing DMT. The remaining recommendations are outlined in Part 2, encompassing risk mitigation strategies during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures, acute MS relapses, and symptomatic treatments for MS., Changes in Management as a Result of the Guidelines: This two-part position statement provides a practical resource for clinicians on current best-practice consensus recommendations for managing adults (≥ 18 years old) with MS in the Australian and New Zealand health care settings. It outlines the 14 DMTs currently available through the Australian Pharmaceutical Benefits Scheme and eight through the New Zealand Pharmaceutical Schedule, including the unique efficacy, safety and monitoring considerations of each. Through these guidelines, we aim to support safe, timely and effective management of patients with MS in Australia and New Zealand., (© 2025 AMPCo Pty Ltd.)

Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system with rapidly evolving treatment options and strategies. An iterative modified Delphi process was used to develop 80 consensus recommendations for the management of MS in Australia and New Zealand. Part 1 of these guidelines includes recommendations related to selection of initial disease-modifying therapy (DMT) for MS, assessments before commencing DMT, monitoring disease activity on DMT, switching DMT, and discontinuing DMT., Main Recommendations: This article, Part 2, covers recommendations related to risk mitigation during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures for MS, acute MS relapses, and symptomatic treatments., Changes in Management as a Result of the Guidelines: Together with Part 1, this consensus statement provides practical guidance for clinicians involved in the care of adults (≥ 18 years old) with MS in Australia and New Zealand. A safe, effective and comprehensive approach to managing MS is crucial for improving long term outcomes and quality of life in individuals affected by MS., (© 2025 AMPCo Pty Ltd.)

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact on the P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ 'non-classical' monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis., Competing Interests: Declaration of competing interest, (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: Autoimmune encephalitis (AE) is often associated with clinically significant memory impairment. This study aimed to evaluate memory in a cross-sectional prospective AE cohort using multiple memory paradigms., Methods: 52 patients (50% seropositive) meeting Graus criteria for possible AE were prospectively recruited between October 2019 and August 202. A comprehensive examination of memory was performed, including tests of supraspan verbal memory (list learning), logicosemantic memory (story learning), figural memory (learning of geometric designs), and verbal associative learning (verbal paired associates). Memory scores were compared to demographically adjusted normative data. Pattern analysis was conducted to assist in the identification of patterns in memory performances., Results: Mean memory scores were not significantly below the normative mean. At an individual patient level, over 20% of the cohort exhibited impaired delayed figural memory, supraspan verbal memory learning and recall. Observed performances were significantly below expected performance for story learning (p = 0.017) and recall (p = 0.003), figural recall (p < 0.0001), initial acquisition (p < 0.001) and final acquisition of a list (p < 0.001) and all delayed recall measures of the list (p < 0.00001). 54.76% of patients exhibited intact psychometrics, and 16 distinct patterns of impairment emerged, indicating variability in memory outcomes., Discussion: While statistical evidence for memory impairment did not emerge at an aggregate level, a proportion of patients present with evidence of abnormal memory performance on psychometrics. Variability in impaired memory measures argues for an individualised patient-focused approach to clinical assessment in AE. Future research should validate these findings with a larger sample size and explore the relationships between memory profiles and other cognitive functions., (© 2024. The Author(s).)

Background and Objective: Autoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups., Methods: Fifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence-Second Edition. The results were standardised with normative data., Results: The mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004)., Discussion: While, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial., (© 2024. The Author(s).)

Objective: New-onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%-50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well-phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers., Methods: Well-characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005-2019. Treating epileptologists reported on post-NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post-discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome., Results: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow-up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes., Significance: Among survivors of cryptogenic NORSE, longer-term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: In Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible., Objective: To analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery., Methods: We undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented., Results: Of the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04)., Conclusion: Tixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location., Competing Interests: Competing interests: AvdW served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche She has received speaker’s honoraria and travel support from Novartis, Roche and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. MM has served on advisory board for Merck, has received speaker honoraria from Merck and Biogen. Her institution receives funding from Merck, Australian National Health Medical Research Council, Brain Foundation, Charles and Sylvia Viertel Foundation, Bethlehem Griffith Foundation and MS Research Australia. WZY has received speaker honoraria from Merck & Novartis. LR served on advisory boards from Biogen, Merck and Roche She has received speaker’s honoraria and travel support from Biogen, Novartis, Roche and Merck. HB has received compensation for consulting, talks, advisory/steering board activities from Biogen, Merck, Novartis, Genzyme, Alfred Health; research support from Novartis, Biogen, Roche, Merck, NHMRC, Pennycook Foundation, MSRA; received compensation for same activities from Oxford Health Policy Forum, Merck, Biogen, Novartis. OS received travel support, speaker honoraria for Biogen, Merck, Genzyme and Novartis and served on scientific advisory board of Merck and Biogen. RW has received travel support from Merck, Roche and Honoraria from Biogen. MZ has received conference support from Roche. CN has no conflicts of interest. AR has no conflicts of interest. FB has received travel support from Biogen. NS has received conference support from Roche. TT has no conflicts of interest. YF has received travel support from Biogen., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injuries (TBIs) and concussions are prevalent in collision sports, and there is evidence that levels of exposure to such sports may increase the risk of neurological abnormalities. Elevated levels of fluid-based biomarkers have been observed after concussions or among athletes with a history of participating in collision sports, and certain biomarkers exhibit sensitivity toward neurodegeneration. This study investigated a cohort of 28 male amateur athletes competing in "Masters" competitions for persons >35 years of age. The primary objective of this study was to compare the levels of blood and saliva biomarkers associated with brain injury, inflammation, aging, and neurodegeneration between athletes with an extensive history of collision sport participation (i.e., median = 27 years; interquartile range = 18-44, minimum = 8) and those with no history. Plasma proteins associated with neural damage and neurodegeneration were measured using Simoa ® assays, and saliva was analyzed for markers associated with inflammation and telomere length using quantitative real-time polymerase chain reaction. There were no significant differences between collision and non-collision sport athletes for plasma levels of glial fibrillary acidic protein, neurofilament light, ubiquitin C-terminal hydrolase L1, tau, tau phosphorylated at threonine 181, and brain-derived neurotrophic factor. Moreover, salivary levels of genes associated with inflammation and telomere length were similar between groups. There were no significant differences between groups in symptom frequency or severity on the Sport Concussion Assessment Tool-5th Edition. Overall, these findings provide preliminary evidence that biomarkers associated with neural tissue damage, neurodegeneration, and inflammation may not exhibit significant alterations in asymptomatic amateur athletes with an extensive history of amateur collision sport participation., Competing Interests: No competing financial interests exist., (© Lauren P. Giesler et al., 2024; Published by Mary Ann Liebert, Inc.)

Ocrelizumab is an anti-CD20 monoclonal antibody (mAb) that has been shown in phase 3 clinical trials to reduce relapses and disease progression in multiple sclerosis (MS) patients. Prior to the approval of ocrelizumab, rituximab, a chimeric anti-CD20 mAb was used to treat MS. Rituximab is still used to treat MS in many countries outside of Australia and remains mainstay of treatment of many non-MS neuroimmunological and systemic inflammatory diseases. Rituximab is currently used in neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis, in addition to its widespread usage in hematological malignancies and systemic inflammatory diseases. Ocrelizumab is currently approved in Australia for treatment of relapsing-remitting MS (RRMS). Neutropaenia is a rare complication of both ocrelizumab and rituximab treatment. This case series reports 12 patients who have experienced neutropaenia following ocrelizumab or rituximab treatment and aims to characterize the clinical parameters of neutropaenia experienced by these patients, including the severity and duration of neutropaenia, length of hospital admission, the types of subsequent infections experienced and types of treatment necessary before patients reached count recovery. The unpredictability of neutropaenia and potential for serious infections highlight the need for continued hematological monitoring for patients on B-cell depleting therapies and calls for careful patient counselling to provide guidance on whether to continue such therapies in patients who have experienced related neutropaenia., Competing Interests: Declaration of Competing Interest NS has received conference fee sponsorship from Roche. HB's institution receives funding from Biogen, Roche, Merck and Novartis for speaker engagements, study steering and advisory committee service. He is on the editorial board of Multiple Sclerosis and Related Disorders and the Steering committee of the Brain Health Initiative (Oxford Health Policy Forum). MM has served on advisory board for Merck, has received speaker honoraria from Merck, Biogen and Novartis. Her institution receives funding from Merck, Australian National Health Medical Research Council, Brain Foundation, Charles and Sylvia Viertel Foundation, and MS Research Australia., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study uses the Wechsler intelligence and memory scales to characterize the cognitive function of patients with autoimmune encephalitis (AE) in the chronic stage of the disease. AE is a group of neuroinflammatory disorders, and cognitive impairment is a significant source of chronic morbidity in these patients., Methods: Fifty patients with an average disease duration of 3.2 years after diagnosis were prospectively recruited from four hospitals. They underwent a comprehensive cognitive examination using the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Summary statistics were computed, and single-sample and independent-samples t tests were used to compare the cohort to normative data., Results: The results revealed significantly reduced performances in perceptual reasoning, processing speed, and working memory among AE patients. Seropositive AE patients exhibited below-norm processing speed, while the seronegative group showed reduced working memory and processing speed. Delayed memory performance was significantly below expectations only in seronegative patients. Pattern analysis indicated that intact cognition was the most observed outcome after AE, but significant heterogeneity was observed among the impaired patients., Conclusions: The study identified deficits in perceptual reasoning, processing speed, and working memory among chronic AE patients. Pattern analysis highlighted positive long-term cognitive outcomes for many but varied outcomes for those with ongoing difficulties. Although severely cognitively impaired patients were not included, the findings apply to  AE cohorts who attend outpatient clinical neuropsychology consultations emphasizing the need for thorough cognitive assessment. The results suggest a need for further research targeting other cognitive domains, including executive functions., (© 2023. The Author(s).)

Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware. The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease. Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain-Barré syndrome, and cerebrovascular disease. Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease. Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19. The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance., (© 2023 The Author. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration., (© 2023 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Objective: To examine the utility of neuroimaging characteristics as biomarkers of prognosis in seropositive autoimmune encephalitis (AE)., Methods: In this multi-center study, we retrospectively analyzed 66 cases of seropositive AE. The MRI and PET imaging was assessed by independent visual inspection. Whole brain and regional volumes were imputed by IcoMetrix, an automated volumetric assessment package. The modified Rankin Scale (mRS) was utilized to assess the patients' follow-up disability. Other outcomes were mortality, first line treatment failure, medial temporal lobe (MTL) atrophy, and clinical relapse. Univariate and multivariable regression analysis was performed., Results: Abnormalities on MRI were detected in 35.1% of patients, while PET was abnormal in 46.4%. Initial median whole brain and hippocampal volumes were below the 5th and 20th percentile respectively compared to an age-matched healthy database. After a median follow-up of 715 days, 85.2% had good functional outcome (mRS ≤ 2). Nine patients developed MTL atrophy during follow-up. On multivariable analysis, inflammatory MTL changes were associated with development of MTL atrophy (HR 19.6, p = 0.007) and initial hippocampal volume had an inverse relationship with mortality (HR 0.04, p = 0.011). Patients who developed MTL atrophy had a reduced chance of good final mRS (HR 0.16, p = 0.015)., Conclusions: Neuroimaging on initial hospital admission may be provide important diagnostic and prognostic information. This study demonstrates that structural and inflammatory changes of the MTL may have importance in clinical and radiological prognosis in seropositive AE., (© 2022. Fondazione Società Italiana di Neurologia.)

Background and Objectives: Autoimmune encephalitis (AE) is an inflammatory disease of the central nervous system which can result in long-term seizures and cognitive dysfunction despite treatment with immunotherapy. The role of the innate immune system in AE is not well established. To investigate the contribution of innate immunity to AE and its long-term outcomes we evaluated peripheral monocytes and serum cytokines in the periphery of patients with AE., Methods and Results: We recruited 40 patients with previously diagnosed AE and 28 healthy volunteers to our cross-sectional observation study and evaluated their peripheral blood monocytes via flow cytometry and serum cytokines (CCL-2, CCL-17, G-CSF, GM-CSF, IFNγ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα) via ELISA.Compared with controls the AE cohort had expansion of the 'pro-inflammatory' CD14 + CD16 + monocyte sub-population (7.13% vs 5.46%, p < 0.01) with higher levels of serum IL-6 (2.34 pg/mL vs 0.54 pg/mL, p < 0.001). These changes were most significant in anti-LGI-1 antibody mediated AE, an AE subtype with poor long-term cognitive outcomes., Conclusion: Expansion of the peripheral CD14 + CD16 + monocyte population and increased serum IL-6 in AE is reflective of changes seen in other systemic inflammatory and neurodegenerative conditions. These changes may indicate a persistent pro-inflammatory state in AE and may contribute to poor long-term outcomes., Competing Interests: Declaration of competing interest Prof Helmut Butzkueven's institution receives funding from Biogen, Roche, Merck and Novartis for speaker engagements, study steering and advisory committee service. He is on the editorial board of Multiple Sclerosis and Related Disorders and the Steering committee of the Brain Health Initiative (Oxford Health Policy Forum). Prof Terence J. O'Brien receives research funding from Biogen, UCB Pharma, Eisai Pharma, Anavex Pharmaceuticals, Zynerba Pharmaceuticals, and serves on the scientific advisory boards for UCB Pharma, Eisai Pharmaceuticals, Zynerba Pharmaceuticals, ESTherapeutics, Seqirus Pharmaceuticals. Dr Mastura Monif's has served on advisory board for Merck and has received speaker honoraria from Merck and Biogen. Her institution receives funding from Merck, Australian.National Health Medical Research Council, Brain Foundation, Charles and Sylvia.Viertel Foundation, and MS Research Australia. The remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Purpose: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes., Methods: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes., Results: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty-nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome., Conclusions: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes., (© 2022 European Academy of Neurology.)

Objective: To evaluate the prevalence and biomarkers of drug-resistant epilepsy (DRE) in patients with autoimmune encephalitis (AIE)., Methods: Sixty-nine patients with AIE were recruited retrospectively and electroencephalographies (EEGs) were reviewed using a standard reporting proforma. Associations between EEG biomarkers and DRE development at 12 months were examined using logistic regression modeling and were utilized to create a DRE risk score., Results: Sixteen percent of patients with AIE developed DRE at 12-month follow-up. The presence of status epilepticus (SE) (OR 11.50, 95% CI [2.81, 51.86], p-value <0.001), temporal lobe focality (OR 9.90, 95% CI [2.60, 50.71], p-value 0.001) and periodic discharges (OR 19.12, 95% CI [3.79, 191.10], p-value 0.001) on the admission EEG were associated with the development of DRE at 12 months. These variables were utilized to create a clinically applicable risk score for the prediction of DRE development., Conclusions: Drug-resistant epilepsy is an infrequent complication of AIE. Electroencephalography changes during the acute illness can predict the risk of DRE at 12 months post-acute AIE., Significance: The identified EEG biomarkers provide the basis to generate a clinically applicable prediction tool which could be used to inform treatment, prognosis, and select patients for acute treatment trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)