Search

Background: Non-relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (nr-MOGAD) is an inflammatory demyelinating disorder of the central nervous system that frequently affects younger populations. The longitudinal impact of nr-MOGAD on cognitive function remains poorly characterized., Objectives: To investigate cognitive profiles and longitudinal cognitive changes in patients with nr-MOGAD compared to individuals with Relapsing-Remitting Multiple Sclerosis (pwRRMS) and healthy controls (HCs)., Methods: A cohort of 8 nr-MOGAD patients, 32 pwRRMS patients, and 22 HCs underwent a baseline and a 12-month follow-up assessment with the Brief Repeatable Battery of Neuropsychological Tests (BRBN) and Stroop test., Results: At baseline, nr-MOGAD patients exhibited moderate cognitive deficits, particularly in verbal memory and processing speed domains, with scores intermediate between pwRRMS and HCs. At follow-up, nr-MOGAD patients, especially those with pediatric-onset, showed significant cognitive recovery, contrasting with the stable impairments observed in pwRRMS., Conclusions: Cognitive impairment patterns in nr-MOGAD are distinct from those observed in pwRRMS and, particularly in younger patients, show a frequent reversal unlike pwRRMS, in which persistently impaired cognitive performances are much more common., Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients., Methods: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed., Results: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689)., Conclusion: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon., Competing Interests: Declaration of competing interest Yin Yin Tan: No conflicts of interests to disclose. Seyed Ehsan Saffari: No conflicts of interests to disclose. Janis Siew Noi Tye: No conflicts of interests to disclose. Xuejuan Peng: No conflicts of interests to disclose. Min Jie Koh: No conflicts of interests to disclose. Abu Bakar Shakran Bin Mahmood: No conflicts of interests to disclose. Jeanne May May Tan: JMM Tan has received honoraria from Merck for speaker's fees and research grants from the National Neuroscience Institute (Singapore). Kevin Tan: K Tan has received travel grants and compensation from Novartis, Merck, Sanofi, Eisai, Roche, and Terumo BCT for consulting services and education activities. Tianrong Yeo: T Yeo has received honoraria from ASNA, Edanz Pharma, Euroimmun AG, Merck, Novartis, Terumo BCT for consulting services and speaker's fees, and research grants from the National Medical Research Council (NMRC Singapore) and Roche. He has also received travel grants and awards from PACTRIMS, ACTRIMS, ECTRIMS, Orebro University, UCB, and Merck., (Copyright © 2024. Published by Elsevier B.V.)

Aim: To: (1) provide greater insight into the psychological and social impact of a range of demyelinating disorders, (2) explore differences between disorders, and (3) provide direction for future research., Method: Studies were identified by searching online databases. Studies that explored the psychological, emotional, or social impact of a range of demyelinating disorders in childhood, including acute disseminated encephalomyelitis (ADEM), optic neuritis, transverse myelitis, and multiple sclerosis, were included and screened independently by three authors. Data on the design, sample characteristics, psychosocial measures, key findings, and methodological strengths and limitations were extracted. Twenty-five studies were included in the narrative synthesis., Results: Demyelinating disorders are associated with lower quality of life, affecting young people's emotional, social, school, and behavioural functioning. There is a high prevalence of psychiatric disorders and fatigue, particularly in multiple sclerosis. Subtle differences exist in the psychological presentation between different demyelinating disorders, with clear gaps in the research for the long-term psychosocial impact of monophasic conditions., Interpretation: The difference between the impact of monophasic and relapsing demyelinating disorders on psychosocial functioning is unclear. Future research should aim to identify the psychosocial impact across disorders and over time, ensure that services are capturing those patients who may benefit from tailored interventions., What This Paper Adds: Prevalence of psychiatric diagnoses in paediatric demyelinating disorders is higher than controls. Depression and emotional concerns are elevated in paediatric demyelinating disorders. Demyelinating disorders impact children's quality of life across school, social, and physical functioning., (© 2020 Mac Keith Press.)

Introduction: The profile of psychiatric disorders associated with multiple sclerosis (MS) may differ in children. We aimed to assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa., Patients and Methods: We analyzed linked English Hospital Episode Statistics, and mortality data, 1999-2011. Cohorts were constructed of children admitted with MS and other central nervous system (CNS) demyelinating diseases. We searched for any subsequent episode of care with psychiatric disorders in these cohorts and compared to a reference cohort., Results: Children with CNS demyelinating diseases had an increased rate of psychotic disorders (rate ratio (RR) = 5.77 (95% confidence interval (CI) = 2.48-11.41)); anxiety, stress-related, and somatoform disorders (RR = 2.38 (1.39-3.81)); intellectual disability (RR = 6.56 (3.66-10.84)); and other behavioral disorders (RR = 8.99 (5.13-14.62)). In analysis of the pediatric MS cohort as the exposure, there were elevated rates of psychotic disorders (RR = 10.76 (2.93-27.63)), mood disorders (RR = 2.57 (1.03-5.31)), and intellectual disability (RR = 6.08 (1.25-17.80)). In reverse analyses, there were elevated rates of a recorded hospital episode with CNS demyelinating disease after a previous recorded episode with anxiety, stress-related, and somatoform disorders; attention-deficit hyperactivity disorder (ADHD); autism; intellectual disability; and other behavioral disorders., Conclusion: This analysis of a national diagnostic database provides strong evidence for an association between pediatric CNS demyelinating diseases and psychiatric disorders, and highlights a need for early involvement of mental health professionals.

Objectives: Multiple sclerosis is a degenerative disease of the CNS with a pathology consistent with immunological mediation. Although its cause is unknown, multiple factors are thought to influence both the onset and exacerbation of the disease, including both genetic background as well as environmental factors., Methods: We are interested in the effect of psychological stress on the onset and exacerbation of Theiler's virus-induced demyelinating disease (TVID), a murine model of MS in which viral persistence facilitates demyelination. In the current study, we determined whether chronic restraint stress (RS)-induced immunosuppression could result in the establishment of a persistent CNS infection in the normally TVID-resistant C57BL/6 mouse strain, resulting in demyelination., Results: Our data indicated that RS repeated over the course of 7 days was not sufficient to cause decreases in virus-specific adaptive immunity, and did not significantly alter CNS viral levels. Furthermore, chronic repeated RS lasting until 4 weeks after infection altered neither the development of virus-specific IgG nor motor function determined by Rotarod analysis. In addition, histological analysis of the CNS of stressed mice indicated no inflammation or demyelination on day 193 after infection., Conclusion: These results suggest that stress alone is not sufficient to overcome genetic resistance to TVID in the C57BL/6 mouse strain., (Copyright 2009 S. Karger AG, Basel.)

Causes and pathogenesis of psychiatric disorders is poorly understood. Infections by viruses or other agents may disturb neurotransmitters and elicit behavioral abnormalities, and induce long lasting immune reactions, referred to as mild encephalitis (ME). New findings (pathology, biochemistry, imaging) in schizophrenia and bipolar psychoses are compatible with ME hypothesis. In Chorea Sydenham and PANDAS syndrome autoimmune ME seems to explain anxiety-compulsive-hyperactivity symptoms. Add-on-therapy with Cox-II-blockers or valacyclovir improved acute schizophrenia, CSF filtration some cases of therapy resistant psychoses.

Chronic restraint stress, administered during early infection with Theiler's virus, was found to exacerbate the acute central nervous system (CNS) viral infection and the subsequent demyelinating phase of disease (an animal model of Multiple Sclerosis (MS)) in SJL male and female mice. During early infection, stressed mice displayed decreased body weights and spontaneous activity; while increased behavioral signs of illness and plasma corticosterone (CORT) levels. During the subsequent chronic demyelinating phase of disease, previously stressed mice had greater behavioral signs of the chronic phase, worsened rotarod performance, and increased inflammatory lesions of the spinal cord. In addition, mice developed autoantibodies to myelin basic protein (MBP), proteolipid protein peptide (PLP139-151), and myelin oligodendrocyte glycoprotein peptide (MOG33-55)., (Copyright 2004 Elsevier B.V.)

Infectious diseases can cause an array of symptoms, including psychiatric symptoms. Psychiatrists serving the medically ill need to be aware not only of classic infectious diseases (e.g., neurosyphilis and HIV), but also of less commonly discussed infectious diseases (e.g., NCC, PANDAS, and Lyme disease). These examples represent an internationally endemic disease (e.g., NCC), a probable immunogenetic disease (e.g., PANDAS), and a frequently overdiagnosed and overtreated disease (Lyme disease).

Adenovirus-mediated gene transfer of interferon gamma (AdIFN) elicits rejection of intracerebral Lewis lung carcinoma. In this system, gene transfer into brain parenchymal cells is both necessary and sufficient to generate the antitumor response. Despite persistent parenchymal inflammation and demyelination, wild-type mice injected intracerebrally with either AdIFN or beta-galactosidase adenovirus (AdBGAL) perform as well as non-injected animals in behavioral, memory, and motor tests. Both AdIFN and AdBGAL elicit demyelination whose incidence rises sharply when the lowest effective dose of AdIFN is exceeded. Therefore, transfer of interferon gamma into brain parenchyma does not seem to elicit detectable cognitive, behavioral or motor deficits. Furthermore, gene transfer into the brain, by adenoviral vectors currently in clinical trials, is associated with a narrow therapeutic window where the incidence of demyelination rises sharply soon after the effective dose is achieved. Gene Therapy (2000) 7, 2094-2098.