Anatomy and Neuroscience - Research Publications
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ItemPsychometric deficits in autoimmune encephalitis: A retrospective study from the Australian Autoimmune Encephalitis Consortium(WILEY, 2022-08)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.
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ItemSeizures in autoimmune encephalitis: Kindling the fire(WILEY, 2020-06)Epilepsy is a common neurological disorder that increases the risk of morbidity and mortality. Autoimmune epilepsy is a subset of epilepsy that occurs in the setting of autoimmunity, such as in autoimmune encephalitis (AIE). AIE is an autoimmune disorder characterized by immune-mediated neuroinflammation resulting in a variety of neurological symptoms, including psychiatric disturbance, cognitive dysfunction, and seizures. Seizures in AIE are thought to be a result of antibodies directed against neuronal cell-surface proteins involved in synaptic transmission. The role of blood-brain barrier dysfunction, myeloid cell infiltration, and the initiation of proinflammatory cascades in epileptogenesis has been shown to be important in animal models and human patients with epilepsy. Epileptogenesis in AIE is likely to arise from the synergistic effect of both innately driven neuroinflammation and antibody-induced hyperexcitability. Together, these processes produce persistent drug-resistant seizures that contribute to the morbidity seen in AIE. Understanding the proinflammatory pathways involved in this process may improve diagnostics and provide alternative treatment targets in AIE.
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ItemNo Preview AvailablePatient Preferences for Time and Location of Infusible Therapies in Multiple Sclerosis and Neuroimmunologic Disorders.(Consortium of Multiple Sclerosis Centers, 2021)BACKGROUND: People with multiple sclerosis and neuroimmunologic disorders (herein referred to as patients) are increasingly treated with infusible monoclonal antibodies. This rise in demand has placed increased loads on current infusion services and mandates careful strategic planning. This study examined patient preferences for the timing and location of infusions and their association with demographic and disease variables to facilitate patient-focused strategic planning. METHODS: Ninety-one patients receiving an infusible therapy at an infusion service during March 2019 were asked to complete a questionnaire exploring eight domains, including preferences for time of infusions and location of infusion centers. Potential access to home-based treatment was included as an option. Unstructured (free-text) feedback on current service was also obtained. RESULTS: Eighty-three patients completed the survey (mean age, 42 years; 75% women). Infusions were predominantly natalizumab (66%) and ocrelizumab (25%). Of these patients, 71% were engaged in some form of work or study, and 83% of this group had to arrange time off from work or study to attend treatment. Seventy percent of patients would prefer their infusion before noon, and 60% would consider home-based infusions. Most used a car as their transport to the infusion service. CONCLUSIONS: These results suggest that patients are more likely to prefer infusible treatment in the morning and are open to home-based infusions. This study provides information for health services to target service delivery at peak preference times and consider alternate ways of delivering infusible treatments.
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ItemNo Preview AvailableFast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic(ELSEVIER SCI LTD, 2021-01)BACKGROUND: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients. OBJECTIVE: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic. METHODS: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed. RESULTS: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive. CONCLUSION: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.
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ItemPrognosis in autoimmune encephalitis: Database(ELSEVIER SCIENCE BV, 2018-12)Autoimmune encephalitis is a rare and debilitating disease. An important question in clinical neurology is what factors may be correlated with outcomes in autoimmune encephalitis. There is observational data describing statistical analyses on such variables, but there are no review articles that collaborate and interpret this information. This data in brief article represents the data collection for such a review (Broadley et al., 2018). Herein we summarize clinical information from 44 research articles, in particular pertaining to outcomes and prognostic variables.
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ItemCharacterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination(BMC, 2019-09-03)Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples). MOG extracellular domain was also immobilized to determine the affinity of MOG Ab. MOG Ab response was of immunoglobulin G1 isotype, and was of peripheral rather than intrathecal origin. High affinity MOG Ab were detected in 15% paediatric and 18% adult sera. More than 75% of paediatric and adult MOG Ab targeted a dominant extracellular antigenic region around Proline42. MOG Ab titers fluctuated over the progression of disease, but affinity and reactivity to Proline42 remained stable. Adults with a relapsing course intrinsically presented with a reduced immunoreactivity to Proline42 and had a more diverse MOG Ab response, a feature that may be harnessed for predicting relapse. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. Loss of MOG Ab seropositivity was observed upon conformational changes to MOG, and this greatly impacted the sensitivity of the detection of relapsing disorders, largely considered as more severe. Careful consideration of the binding characteristics of autoantigens should be taken into account when detecting disease-relevant autoantibodies.
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ItemVitamin D status in an Australian patient population: a large retrospective case series focusing on factors associated with variations in serum 25(OH)D(BMJ Journals, 2020-03-01)OBJECTIVES: To investigate whether sex, age, medical specialty and seasonal variations in serum concentration of 25-hydroxy vitamin D (25(OH)D) are evident among an Australian patient population. DESIGN: Retrospective study analysing the results of serum 25(OH)D lab tests and vitamin D supplementation from Royal Melbourne Hospital (RMH) between 2014 and 2017. SETTING: Tertiary healthcare centre in Victoria, Australia. PARTICIPANTS: 30 023 patients (inpatient and outpatient) who had their serum 25(OH)D levels measured at RMH between 2014 and 2017. MAIN OUTCOME MEASURES: Serum 25(OH)D levels stratified according to patients' sex, age and medical specialty admitted to, as well as the season and year (2014 to 2017) 25(OH)D level was measured. RESULTS: Mean serum 25(OH)D level of study population was 69.9 nmol/L (95% CI 69.5 to 70.2). Only 40.2% patients in this cohort were sufficient in vitamin D (>75 nmol/L). On average, 25(OH)D levels in male patients were 6.1 units (95% CI 5.4 to 6.9) lower than in females. Linear regression analysis found that 25(OH)D levels increased by 0.16 unit (95% CI 0.14 to 0.18) for every year increase in age. One-way analysis of variance showed patients from neurology had the highest average 25(OH)D level, 76.8 nmol/L (95% CI 74.2 to 79.3) compared with other medical specialties. Mean 25(OH)D level during winter, 64.9 nmol/L (95% CI 64.2 to 65.6) was significantly lower compared with other seasons despite supplementation. Average 25(OH)D level measured in 2014, 71.5 nmol/L (95 CI% 70.8 to 72.2) was significantly higher than levels measured in 2016-2017. CONCLUSIONS: There is a sex, age, medical specialty, seasonal and yearly variation in vitamin D status in an Australian patient population. The association between low vitamin D status and winter despite supplementation suggests other interventions are required to boost serum 25(OH)D levels.
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ItemInnate Immunity in the Central Nervous System: A Missing Piece of the Autoimmune Encephalitis Puzzle?(FRONTIERS MEDIA SA, 2019-09-10)The autoimmune encephalitides are a group of autoimmune conditions targeting the central nervous system and causing severe clinical symptoms including drug-resistant seizures, cognitive dysfunction and psychiatric disturbance. Although these disorders appear to be antibody mediated, the role of innate immune responses needs further clarification. Infiltrating monocytes and microglial proliferation at the site of pathology could contribute to the pathogenesis of the disease with resultant blood brain barrier dysfunction, and subsequent activation of adaptive immune response. Both innate and adaptive immune cells can produce pro-inflammatory molecules which can perpetuate ongoing neuroinflammation and drive ongoing seizure activity. Ultimately neurodegenerative changes can ensue with resultant long-term neurological sequelae that can impact on ongoing patient morbidity and quality of life, providing a potential target for future translational research.