Utility of the 2023 international MOGAD panel proposed criteria in clinical practice: An institutional cohort.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently defined demyelinating disorder with a rapidly evolving clinical spectrum. Recently, consensus criteria have been proposed (Banwell et al., 2023) to help with disease diagnosis.

Predicting the final clinical phenotype after the first attack of optic neuritis.

Background And Objectives: To evaluate the factors determining the final clinical phenotype after an initial isolated attack of optic neuritis (ON). ON could be an isolated event or the initial presentation of a chronic neuroimmunological condition.

Methods: This was a retrospective analysis of patients presenting to University Hospitals Cleveland Medical Center for an initial, isolated attack of ON.

Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD.

Background And Objectives: Ocrelizumab and rituximab are monoclonal antibodies targeting the CD20 marker on B lymphocytes. The enhanced efficacy of B lymphocyte depleting therapies poses a greater risk of decreased immunoglobulin (Ig) levels. The rate and risk factors of hypogammaglobulinemia in MS and NMOSD patients treated with anti-CD20 therapies are unknown.

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry.

Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method.

Small Extracellular Vesicles Secreted by Nigrostriatal Astrocytes Rescue Cell Death and Preserve Mitochondrial Function in Parkinson's Disease.

Extracellular vesicles (EVs) are emerging as powerful players in cell-to-cell communication both in healthy and diseased brain. In Parkinson's disease (PD)-characterized by selective dopaminergic neuron death in ventral midbrain (VMB) and degeneration of their terminals in striatum (STR)-astrocytes exert dual harmful/protective functions, with mechanisms not fully elucidated. Here, this study shows that astrocytes from the VMB-, STR-, and VMB/STR-depleted brains release a population of small EVs  in a region-specific manner.

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

Background: Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown.

Objective: To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic.

The humoral response to SARS-COV-2 vaccines in MS patients: A case series exploring the impact of DMT, lymphocyte count, immunoglobulins, and vaccine type.

Background & Objectives: Certain disease modifying therapies may negatively impact the humoral response to SARS-CoV-2 vaccines. Many MS related clinical, demographic, and immunological characteristics can also affect vaccine response but those have not been fully explored. This study aimed to investigate potential correlations between clinical, demographic, and immunological variables in MS patients to post-vaccination spike protein antibody positivity rates and levels.

Residual symptoms and long-term outcomes after all-cause autoimmune encephalitis in adults.

Background And Objectives: To evaluate residual symptoms after all-cause autoimmune encephalitis in a real-life outpatient setting and compare long-term outcome measures. A secondary objective was to identify correlates of poor outcomes.

Methods: We analyzed patients referred to the Neuroimmunology clinic for evaluation of autoimmune encephalitis for whom standardized data were collected.

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination.

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time.

The pressing questions in multiple sclerosis Care in the era of COVID-19.

• MS patients should continue their disease modifying therapy during the pandemic. • Newly diagnosed patients should start disease modifying therapy without delay. • The effect on COVID-19 infection and future vaccination should be considered.

Current and emerging therapeutics for neuromyelitis optica spectrum disorder: Relevance to the COVID-19 pandemic.

Neuromyelitis optica spectrum disorder (NMOSD) can lead to immobility and bulbar weakness. This, in addition to the older age of onset and the higher rate of hospitalization compared to multiple sclerosis, makes this patient group a potential target for complicated COVID-19 infection. Moreover, many of the commonly used preventive therapies for NMOSD are cell-depleting immunouppsressants with increased risk of viral and bacterial infections.

A model-based study of internuclear ophthalmoparesis and ocular-motor fatigue in multiple sclerosis.

Internuclear ophthalmoparesis (INO) in multiple sclerosis (MS) is due to demyelination of the medial longitudinal fasciculus (MLF). INO is typically modeled as an increased peak-velocity and peak-acceleration ratio of abducting to adducting eye (pulse-size ratio, PSR). PSR can be affected by fatigue during prolonged ocular-motor tasks (ocular-motor fatigue).

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment.

Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients' disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease.

Neuromodulation in multiple sclerosis.

Neuromodulation, or the utilization of advanced technology for targeted electrical or chemical neuronal stimulation or inhibition, has been expanding in several neurological subspecialties. In the past decades, immune-modulating therapy has been the main focus of multiple sclerosis (MS) research with little attention to neuromodulation. However, with the recent advances in disease-modifying therapies, it is time to shift the focus of MS research to neuromodulation and restoration of function as with other neurological subspecialties.

T Lymphocytes Influence the Mineralization Process of Bone.

Bone is a unique organ able to regenerate itself after injuries. This regeneration requires the local interplay between different biological systems such as inflammation and matrix formation. Structural reconstitution is initiated by an inflammatory response orchestrated by the host immune system.

Macrophages in bone fracture healing: Their essential role in endochondral ossification.

In fracture healing, skeletal and immune system are closely interacting through common cell precursors and molecular mediators. It is thought that the initial inflammatory reaction, which involves migration of macrophages into the fracture area, has a major impact on the long term outcome of bone repair. Interestingly, macrophages reside during all stages of fracture healing.

Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory.

In the bone marrow, a population of memory T cells has been described that promotes efficient secondary immune responses and has been considered to be preactivated, owing to its expression of CD69 and CD25. Here we show that human bone marrow professional memory T cells are not activated but are resting in terms of proliferation, transcription, and mobility. They are in the G0 phase of the cell cycle, and their transcriptome is that of resting T cells.

Improvement of internuclear ophthalmoparesis in multiple sclerosis with dalfampridine.

Internuclear ophthalmoparesis (INO) in multiple sclerosis (MS) is due to demyelination of the medial longitudinal fasciculus (MLF) and provides an accessible model for studying consequences of raised body temperature and fatigue on central demyelination. Prompted by one of our patient’s report of vision improvement after initiating dalfampridine, a potassium channel blocker prescribed for gait impairment, we measured this drug's effects on 3 patients with MS with bilateral INO. All showed changes in horizontal saccadic conjugacy consistent with improved transmission of the neural pulse responsible for adducting movements.

T and B cells participate in bone repair by infiltrating the fracture callus in a two-wave fashion.

Fracture healing is a regenerative process in which bone is restored without scar tissue formation. The healing cascade initiates with a cycle of inflammation, cell migration, proliferation and differentiation. Immune cells invade the fracture site immediately upon bone damage and contribute to the initial phase of the healing process by recruiting accessory cells to the injury site.

Ocular-motor profile and effects of memantine in a familial form of adult cerebellar ataxia with slow saccades and square wave saccadic intrusions.

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading.

Dimethyl fumarate for relapsing MS.

Dimethyl fumarate (DMF) is the latest oral therapy approved for relapsing-remitting multiple sclerosis (RRMS). In 2 placebo-controlled phase III trials, twice daily DMF demonstrated a 44%-53% reduction in annualized relapse rate and 71%-90% reduction in new MRI lesions. In one trial, DMF slowed the accumulation of disability, but not in the other trial.