Oral health-related quality of life is more strongly correlated with mental health than with oral health in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young and middle-aged populations, associated with substantial burden of illness. Because a growing literature now shows that this burden extends to poorer oral health, oral health-related quality of life (OHRQoL) may be reduced as well. OBJECTIVES: To test whether people with relapsing-remitting MS (RRMS) have poorer OHRQoL than demographically matched controls, and to establish which variables are associated with worse OHRQoL. MATERIALS AND METHODS: In total, 64 people with RRMS and 69 demographically matched controls participated. Both groups completed the Oral Health Impact Profile (OHIP-14), a validated measure of OHRQoL, as well as an objective oral health examination performed by a qualified dentist, a measure of dental-related functionality and a measure of mental health. RESULTS: OHRQoL was significantly poorer in the RRMS relative to the control group. However, although poorer OHRQoL in the RRMS group was moderately associated with objectively assessed oral health (r = .30), it was more strongly associated with mental health (r = .61). For the control group, the reverse pattern of association was evident, with OHRQoL more strongly associated with oral health (r = .48) relative to mental health (r = .20). CONCLUSION: People with RRMS report poorer OHRQoL than demographically matched controls, but these appraisals are more strongly linked to mental health than to objective oral health indicators.

Analysing triggers for anti-NMDA-receptor encephalitis including herpes simplex virus encephalitis and ovarian teratoma: results from the Queensland Autoimmune Encephalitis cohort.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (anti-NMDA-R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies have demonstrated that anti-NMDA-R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE). AIM: To present details from a Queensland cohort analysing triggering events in patients with anti-NMDA-R encephalitis in an Australian context. METHODOLOGY: The authors identified patients with anti-NMDA-R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements. RESULTS: Thirty-one cases of anti-NMDA-R encephalitis were included in the study. Three cases of anti-NMDA-R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti-NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti-NMDA-R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups. CONCLUSION: In this cohort, the number of cases of anti-NMDA-R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti-NMDA-R encephalitis had no identifiable trigger or associated disease process.

Cognitive function and oral health in relapsing-remitting multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is often associated with reduced cognitive function, and there is also emerging evidence of a heightened vulnerability to oral health problems. However, although links between cognitive function and oral health have been identified in other special populations, it remains to be established whether this relationship is also evident for people with MS. The aim of this study was to provide the first empirical test of whether there is a relationship between cognitive function and oral health in people diagnosed with relapsing-remitting multiple sclerosis (RRMS). METHODS: One hundred and eleven individuals were evaluated: 56 people diagnosed with RRMS and 55 demographically matched healthy controls. All participants completed an objective oral health assessment as well as a standardized battery that assessed six distinct neurocognitive domains. RESULTS: Relative to controls, people with RRMS presented with higher rates of decayed teeth and mild gingivitis, and also performed more poorly in three of the six neurocognitive domains assessed (language, complex attention, and executive function). However, for the RRMS group, no associations emerged between oral health with performance on any of the six neurocognitive domains. CONCLUSIONS: These data cross-validate previous research which shows people with RRMS are more likely to present with both reduced cognitive function and poorer oral health, but also extends this literature in a meaningful way by additionally showing for the first time that these clinical features are unrelated in RRMS. CLINICAL RELEVANCE: The findings emphasize the need for early assessment of both oral health and cognitive function in people with RRMS so that appropriate interventions and support can be put in place for each of these clinical symptoms.

Psychiatric management of anti-NMDAR encephalitis: a cohort analysis.

BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches. METHODS: All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared. RESULTS: The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics. CONCLUSIONS: Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.

Voltage-gated potassium channel blanket testing in first-episode psychosis: Diagnostic nihilism?

OBJECTIVE: Voltage-gated potassium channel antibodies are implicated in limbic encephalitis and currently included in first-episode psychosis organic screening guidelines. Individuals with high-positive voltage-gated potassium channel titres most commonly present with neurological symptoms as well as sleep, cognitive, behaviour, psychosis and mood disturbance. The significance of low-positive voltage-gated potassium channel antibody titres in psychiatric patients is unclear and has not been previously examined. We aim to describe a statewide cohort of psychiatric patients with low- and high-positive voltage-gated potassium channel titres and explore if this finding influenced clinical management and patient outcomes. METHODS: A retrospective review of all voltage-gated potassium channel antibodies testing performed in public psychiatric services in Queensland, Australia, with comparison of the clinical presentation and long-term outcomes of low- and high-positive voltage-gated potassium channel titre cases. Specific antigen targets (leucine-rich glioma-inactivated protein 1 and contactin-associated protein 2 antibodies) were also assessed. RESULTS: The overall prevalence of voltage-gated potassium channel antibody positivity in Queensland, public, psychiatric service testing was 0.3% (14/4098), with 12 cases of low-positive voltage-gated potassium channel titre, 2 cases of high-positive (leucine-rich glioma-inactivated protein 1 antibody positive) cases and a voltage-gated potassium channel negative contactin-associated protein 2 antibody positive case. No low-positive case developed neurological abnormalities or had abnormal paraclinical investigations. In comparison, both high-positive voltage-gated potassium channel/leucine-rich glioma-inactivated protein 1 cases and the contactin-associated protein 2 antibody positive case rapidly developed neurological symptoms, had abnormal paraclinical testing and improved only with immunotherapy. There was no later development of encephalitic symptoms in the low-positive cases over an average of 1067 days follow-up. CONCLUSION: Voltage-gated potassium channel antibody-associated limbic encephalitis was rare, and always associated with high antibody titres. Low-positive titres were not associated with the development of encephalitis over a long period of follow-up. The value of universal voltage-gated potassium channel antibody screening is unclear, and further prospective studies in first-episode psychosis populations are required.

Serum and CSF Anti-NMDAR Antibody Testing in Psychiatry.

OBJECTIVE: The authors examined and compared the clinical presentation of CSF positive and negative N-methyl-d-aspartate receptor (NMDAR) antibody. METHODS: The investigators performed a retrospective chart review of NMDAR-antibody-positive cases (serum or CSF) involving patients presenting to psychiatric services from 2010 to 2018 in Queensland, Australia. Presentation, progress, investigations, and efficacy of treatment are detailed. RESULTS: There were 24 serum or CSF NMDAR-antibody-positive cases and three equivocal serum results. High rates of prodromal cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity were observed in the 16 CSF NMDAR-antibody-positive case patients and two CSF NMDAR-antibody-negative case patients, all evident before neurological deterioration with seizures, movement disorder, and autonomic disturbance occurring in the weeks following admission. The majority of these patients (N=17) were treated successfully with immunomodulatory therapy. The nine remaining patients, who were CSF NMDAR antibody negative or equivocal, did not demonstrate any of these features and improved with psychiatric care alone. CONCLUSIONS: These findings suggest that traditional psychiatric care may be appropriate for patients with isolated psychiatric symptoms who have positive serum NMDAR testing when CSF is negative and there are no key clinical features such as cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity. However, if these key features are present, a trial of immunomodulatory treatment should be considered with repeated examination of CSF for neuronal antibodies.

A case of immune-mediated encephalitis related to daclizumab therapy.

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Episodic foresight in multiple sclerosis.

OBJECTIVE: Episodic foresight refers to the ability to imagine future scenarios and to then use this imaginative capacity to guide future-directed behavior. Multiple sclerosis (MS) is associated with deficits generating the phenomenological characteristics of future events (the imaginative component of episodic foresight), but no study to date has tested whether MS is also associated with deficits using episodic foresight to appropriately guide future-directed behavior. METHOD: Forty people with relapsing-remitting MS (RRMS) and 40 demographically matched healthy participants completed a validated measure that met strict criteria for assessing the functional application of episodic foresight, Virtual-Week Foresight (VW-Foresight). RESULTS: Overall, people with RRMS did not differ significantly relative to comparison participants in how likely they were to spontaneously acquire items that would later allow a problem to be solved and were also just as likely to subsequently use these items to solve the problem. However, the latter group difference was large in magnitude and just failed to attain significance. Higher levels of depression were significantly related to performance on this same "use" component of foresight in the RRMS group, and depressed RRMS participants were significantly impaired in this aspect of foresight relative to both healthy participants and nondepressed RRMS participants. The depressed MS subgroup also differed from the nondepressed subgroup in their ability to perform instrumental activities of daily living. CONCLUSIONS: People with RRMS who present with heightened levels of depressive symptomatology also appear to be at greater risk of experiencing specific problems with episodic foresight. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Correlations between macrophage/microglial activation marker sTREM-2 and measures of T-cell activation, neuroaxonal damage and disease severity in multiple sclerosis.

BACKGROUND: Soluble triggering receptor expressed on myeloid cells-2 (sTREM-2) is a marker of macrophage and microglial activation and is increased in the cerebrospinal fluid (CSF) in multiple sclerosis (MS). OBJECTIVE: To determine the relationships among sTREM-2, T cell activation, neuroaxonal damage and clinical features of MS. METHODS: Enzyme-linked immunosorbent assays were used to measure the levels of sTREM-2, soluble CD27 (sCD27, a marker of T cell activation), neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) in the CSF of 42 patients with MS (including nine with clinically isolated syndrome) and 15 patients with other neurological diseases (OND) and in the serum of 164 patients with MS, 87 patients with OND and 62 healthy controls. RESULTS: sTREM-2 was significantly elevated in the CSF (p = 0.012), but not in the serum, in MS compared to OND. In MS, CSF sTREM-2 correlated positively with CSF sCD27 (p = 0.005), CSF NfL (p = 0.0001), CSF pNfH (p = 0.0006), Expanded Disability Status Scale (EDSS) score (p = 0.0079) and MS Severity Score (MSSS) (p = 0.0006). CONCLUSION: In MS the level of sTREM-2 in the CSF is related to measures of T cell activation (sCD27), neuroaxonal damage (NfL and pNfH), disability (EDSS) and disease severity (MSSS).

An Australian State-Based Cohort Study of Autoimmune Encephalitis Cases Detailing Clinical Presentation, Investigation Results, and Response to Therapy.

Introduction: Autoimmune encephalitis is a disorder associated with antibodies directed against central nervous system proteins with variable clinical features. This study aims to add to knowledge of the disease by reporting the details of a cohort of patients with autoimmune encephalitis in Queensland, Australia. Methodology: We surveyed patients with autoimmune encephalitis diagnosed and managed through public hospitals in Queensland, Australia between 2010 and the end of 2019. Cases were identified via case detection through a centralized diagnostic neuroimmunology laboratory (Division of Immunology, HSQ Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia) and a survey of neurologists. Data including demographic details, clinical presentation, investigation results, treatments including immune therapy and outcomes was collected. Results: Sixty cases of antibody positive autoimmune encephalitis were identified. Twenty-eight were of anti-NMDA-receptor encephalitis with other cases associated with antibodies against LGi1, Caspr2, glycine receptor, DPPX, GABAB receptor, IgLON5, GFAP, and SOX1. The number of diagnosed cases, especially of anti-NMDA-receptor encephalitis has markedly increased over the period 2017 to 2019. Clinical presentations were marked by heterogeneous symptom complexes and prolonged hospital admissions. Imaging studies were largely normal or non-specific. There was a response to immune therapy and a low mortality rate. Most cases affected by this disorder were left with ongoing symptoms associated with mild disability. Conclusion: Autoimmune encephalitis in Queensland, Australia is an increasingly common but complex clinical entity marked by heterogeneous presentations, response to immune therapy and outcome results marked by low mortality and incomplete recovery.

Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein-Barr Virus-Specific T Cell Therapy.

Background: Increasing evidence indicates a role for Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment. Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy. Methods: We assessed participants 2 and 3 years after completion of T cell therapy. Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product. Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

Synergy and sustainability in rural procedural medicine: views from the coalface.

OBJECTIVE: The practice of rural and remote medicine in Australia entails many challenges, including a broad casemix and the remoteness of specialist support. Many rural practitioners employ advanced procedural skills in anaesthetics, surgery, obstetrics and emergency medicine, but the use of these skills has been declining over the last 20 years. This study explored the perceptions of rural general practitioners (GPs) on the current and future situation of procedural medicine. DESIGN: The qualitative results of data from a mixed-method design are reported. Free-response survey comments and semistructured interview transcripts were analysed by a framework analysis for major themes. SETTING: General practices in rural and remote Queensland. PARTICIPANTS: Rural GPs in Rural and Remote Metropolitan Classification 4-7 areas of Queensland. MAIN OUTCOME MEASURE: The perceptions of rural GPs on the current and future situation of rural procedural medicine. RESULTS: Major concerns from the survey focused on closure of facilities and downgrading of services, cost and time to keep up skills, increasing litigation issues and changing attitudes of the public. Interviews designed to draw out solutions to help rectify the perceived circumstances highlighted two major themes: 'synergy' between the support from medical teams and community in ensuring 'sustainability' of services. CONCLUSIONS: This article presents a model of rural procedural practice where synergy between staff, resources and support networks represents the optimal way to deliver a non-metropolitan procedural service. The findings serve to remind educators and policy-makers that future planning for sustainability of rural procedural services must be broad-based and comprehensive.

Screening for anti-NMDAR encephalitis in psychiatry.

Anti-NMDAR encephalitis most commonly presents to psychiatric services, so early identification of this disorder is essential. We aim to validate the two screening criteria (Scott et al. and Herken and Pruss) which have been proposed to identify first episode psychosis patients who should have anti-NMDAR antibody testing. The performance of the screening criteria were assessed using anti-NMDAR encephalitis cases published in the literature, and antibody positive and negative cases from a state-wide cohort (Queensland, Australia). Sensitivity, specificity and area under receiver operator characteristic curve analysis was performed. There were 258 anti-NMDAR encephalitis cases and 103 control cases, which demonstrated high performance of both Scott et al. "screening recommended" criteria (sensitivity 97.3%, specificity 85.4%, AUC 0.914) and Herken and Pruss "yellow flags" criteria (sensitivity 91.5%, specificity 83.5%, AUC 0.875). These criteria remained accurate when neurological variables were excluded, and in cases without psychosis. The Scott et al. "screening not recommended", and Herken and Pruss "red flags" criteria did not demonstrate clinical utility for first episode psychosis case screening. The screening criteria with good performance identify an atypical picture of psychiatric presentation with increased risk of anti-NMDAR positivity prior to overt neurological symptoms or investigations and may be beneficial to include in the routine psychiatric assessment process.

Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.

BACKGROUND: Increasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy. METHODS: An open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses. RESULTS: Of the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (P = 0.033, Fisher's exact test). CONCLUSION: EBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000422527. FUNDING: MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.