Anatomy and Neuroscience - Research Publications

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    Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic
    Rath, L ; Bui, MV ; Ellis, J ; Carey, J ; Baker, J ; Taylor, L ; Fernando, H ; Taylor, N ; Savage, P ; Richards, J ; Zhong, M ; Kalincik, T ; Skibina, O ; Wesselingh, R ; Nguyen, A-L ; Monif, M ; Butzkueven, H ; van der Walt, A (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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    Evaluating the perspective of patients with MS and related conditions on their DMT in relation to the COVID-19 pandemic in one MS centre in Australia
    Seery, N ; Li, V ; Nguyen, A-L ; Roos, I ; Buzzard, KA ; Atvars, R ; Taylor, N ; Tunnell, K ; Carey, J ; Dwyer, C ; Taylor, HFL ; Baker, J ; Marriott, MP ; Kilpatrick, TJ ; Kalincik, T ; Monif, M (ELSEVIER SCI LTD, 2020-11-01)
    Objective: Patients with Multiple Sclerosis (MS) and on disease modifying therapies (DMTs) that can be immunosuppressive or immunomodulatory form a special group where risk of continuation of DMT needs to be taken into account with risk of contracting Covid-19. This concept can pose a degree of anxiety for patients as well as neurologists. We aimed to evaluate patient perspectives regarding the use of Natalizumab and anti-CD20 therapies (Rituximab and Ocrelizumab) in the context of the COVID-19 pandemic. Methods: cross-sectional study conducted via voluntary survey filled in by patients with MS and related disorders receiving their infusional treatment in one MS centre in Australia, exploring their concerns regarding their therapy, their therapy and COVID-19, precautions undertaken in response to the pandemic, and factors impacting their decision-making. Results: 170 patients completed the survey. Of patients on Natalizumab, the majority had either no or mild concern regarding their DMT and COVID-19, and of patients on B-cell depleting therapies, again, the majority had no or mild concern, though a slightly higher proportion had a moderate level of concern. Asked to delineate their concerns, an increased risk of contracting COVID-19 was more commonly conveyed than MS-specific factors or poor outcomes pertaining to COVID-19 if contracted, by patients in both groups. Conversely, being invited to specifically consider the possibility of contracting COVID-19 or experience a relapse of MS, almost half of the cohort rated both of equal of concern. More than half of the cohort were self-isolating more stringently than general government advice and government-related resources followed by information provided by patient's neurologist where the commonest means of information to guide decision making. Conclusions: Whilst a large proportion of patients had some concern regarding the impact of their DMT on COVID-19, whether on their risk of contracting COVID-19 or a theoretical risk for more severe disease, the overall level of concern in most cases was at most mild. Patients on B-cell depleting therapies were more inclined to express a higher level of concern. A similar concern was ascribed to a risk of a relapse or worsening MS symptoms compared to the risk of contracting COVID-19. Such attitudes may underscore a willingness of patients to continue their DMT where benefits outweigh risks during future phases of the COVID-19 pandemic.
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    Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination
    Tea, F ; Lopez, JA ; Ramanathan, S ; Merheb, V ; Lee, FXZ ; Zou, A ; Pilli, D ; Patrick, E ; van der Walt, A ; Monif, M ; Tantsis, EM ; Yiu, EM ; Vucic, S ; Henderson, APD ; Fok, A ; Fraser, CL ; Lechner-Scott, J ; Reddel, SW ; Broadley, S ; Barnett, MH ; Brown, DA ; Lunemann, JD ; Dale, RC ; Brilot, F ; Sinclair, A ; Kermode, AG ; Kornberg, A ; Bye, A ; McGettigan, B ; Trewin, B ; Brew, B ; Taylor, B ; Bundell, C ; Miteff, C ; Troedson, C ; Pridmore, C ; Spooner, C ; Yiannikas, C ; O'Gorman, C ; Clark, D ; Suan, D ; Jones, D ; Kilfoyle, D ; Gill, D ; Wakefield, D ; Hofmann, D ; Mathey, E ; O'Grady, G ; Jones, HF ; Beadnall, H ; Butzkueven, H ; Joshi, H ; Andrews, I ; Sutton, I ; MacIntyre, J ; Sandbach, JM ; Freeman, J ; King, J ; O'Neill, JH ; Parratt, J ; Barton, J ; Garber, J ; Ahmad, K ; Riney, K ; Buzzard, K ; Kothur, K ; Cantrill, LC ; Menezes, MP ; Paine, MA ; Marriot, M ; Ghadiri, M ; Boggild, M ; Lawlor, M ; Badve, M ; Ryan, M ; Aaqib, M ; Shuey, N ; Jordan, N ; Urriola, N ; Lawn, N ; White, O ; McCombe, P ; Patel, R ; Leventer, R ; Webster, R ; Smith, R ; Gupta, S ; Mohammad, SS ; Pillai, S ; Hawke, S ; Simon, S ; Calvert, S ; Blum, S ; Malone, S ; Hodgkinson, S ; Nguyen, TK ; Hardy, TA ; Kalincik, T ; Ware, T ; Fung, VSC ; Huynh, W (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 (nā€‰=ā€‰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.