Explainable time-to-progression predictions in multiple sclerosis.

Background: Prognostic machine learning research in multiple sclerosis has been mainly focusing on black-box models predicting whether a patients' disability will progress in a fixed number of years. However, as this is a binary yes/no question, it cannot take individual disease severity into account. Therefore, in this work we propose to model the time to disease progression instead.

Consensus recommendations on multiple sclerosis management in Australia and New Zealand: part 2.

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.

Consensus recommendations on multiple sclerosis management in Australia and New Zealand: part 1.

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.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy.

TREX1 mutations underlie a variety of human diseases, including retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S), a catastrophic adult-onset vasculopathy that is often confused with multiple sclerosis, systemic vasculitis, or systemic lupus erythematosus. Patients with RVCL develop brain, retinal, liver, and kidney disease around age 35-55, leading to premature death in 100% of patients expressing an autosomal dominant C-terminally truncated form of TREX1. We previously demonstrated that RVCL is characterized by high levels of DNA damage, premature cellular senescence, and risk of early-onset breast cancer before age 45.

Cognitive behavioural therapy for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

Background: Treatment of fatigue is important for many patients with multiple sclerosis (MS). While pharmacological options have not shown consistent benefit, psychological interventions offer another avenue of treatment. Cognitive behavioural therapy (CBT) involves strategies to change maladaptive cognition and illness behaviours that modulate how patients with MS respond to fatigue.

Induction cyclophosphamide with maintenance immunosuppression in high-risk myasthenia gravis: long-term follow-up and safety profile.

Background: Patients with refractory or high-risk myasthenia gravis (MG) respond poorly to conventional immunosuppressive therapy, requiring rescue therapies and often experiencing treatment toxicity. Rescue and injectable therapies do not induce remission and require repetitive administration leading to significant constraints on patients and the healthcare system. This long-term follow-up study demonstrates cyclophosphamide as a rapidly effective and safe treatment in patients with refractory or high-risk MG.

The neurocognitive and neuropsychiatric manifestations of Susac syndrome: a brief review of the literature and future directions.

Encephalopathy is part of the clinical triad of Susac syndrome, but a detailed understanding of the neurocognitive and neuropsychiatric profile of this condition is lacking. Existing literature indicates that cognitive deficits range in severity from subtle to profound. Executive function and short-term recall are affected frequently.

A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.

Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted.

CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis.

Background: There is a need for biomarkers of disease progression and therapeutic response in multiple sclerosis (MS). This study aimed to identify cerebrospinal fluid (CSF) lipids that differentiate MS from other neuroinflammatory conditions and correlate with Expanded Disability Status Scale (EDSS) scores, gadolinium-enhancing lesions or inflammatory mediators.

Methods: Lipids and inflammatory cytokines/chemokines were quantified with liquid chromatography-tandem mass spectrometry and multiplex ELISA, respectively, in CSF from people with untreated MS, neuromyelitis optica spectrum disorder (NMOSD), other inflammatory neurological diseases and non-inflammatory neurological diseases (NIND).

Peripheral oedema as an adverse effect of treatment of secondary progressive multiple sclerosis with siponimod: A case series.

Siponimod is a sphingosine 1-phosphate receptor (S1P) modulator used to treat secondary progressive multiple sclerosis (SPMS). We report 3 SPMS patients treated with siponimod who developed new or worsening peripheral oedema soon after commencing treatment. In one case, peripheral oedema resulted in immobility.

Clinical and radiological characteristics and outcomes of patients with recurrent or relapsing tumefactive demyelination.

Background: Relapsing or recurrent tumefactive demyelination is rare and has not been studied beyond individual case reports.

Objective: We examined the clinical course, neuroimaging, cerebrospinal fluid (CSF), treatment and outcomes of patients with recurrent tumefactive demyelinating lesions (TDLs).

Methods: We used PubMed to identify reports of recurrent TDLs and included the details of an additional, unpublished patient.

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown.

The Impact of Relapses on Pain and Quality of Life in Patients with Multiple Sclerosis Treated with Corticosteroids.

Background: We assessed the prevalence and risks associated with pain during and after a multiple sclerosis (MS) relapse, and the impact of pain on quality of life (QoL), in MS patients.

Methods: 117 patients suffering an acute MS relapse were evaluated with clinician- and patient-reported outcomes, including the expanded disability status scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), and MS Walking scale-12 (MSWS-12). Relapse-related pain was assessed via the short-form 36 (SF-36) questionnaire upon first visit (relapse onset) and at 6 weeks after treatment with intravenous methylprednisolone (follow-up visit).

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.

Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS.

Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'.

Sex differences in Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy and experimental autoimmune neuritis.

Guillain Barré syndrome (GBS) and its variants, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP and its variants, are regarded as immune mediated neuropathies. Unlike in many autoimmune disorders, GBS and CIDP are more common in males than females. Sex is not a clear predictor of outcome.