P2X -receptor binding in new-onset and secondary progressive MS - a [C]SMW139 PET study.

Background: PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at 'smoldering' lesion rims have been implicated as drivers of disability progression. The P2X R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.

A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis.

Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation.

Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals.

Background: Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.

Objective: We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.

Methods: The study cohort consisted of 102 MS patients (mean (SD) age 45.

Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

Key unmet needs in multiple sclerosis (MS) include detection of early pathology, disability worsening independent of relapses, and accurate monitoring of treatment response. Collaborative approaches to address these unmet needs have been driven in part by industry-academic networks and initiatives such as the Grant for Multiple Sclerosis Innovation (GMSI) and Multiple Sclerosis Leadership and Innovation Network (MS-LINK) programs. We review the application of recent advances, supported by the GMSI and MS-LINK programs, in neuroimaging technology to quantify pathology related to central pathology and disease worsening, and potential for their translation into clinical practice/trials.

Adenosine A receptor availability in cerebral gray and white matter of patients with Parkinson's disease.

Objective: Atrophic changes in cerebral gray matter of patients with PD have been reported extensively. There is evidence suggesting an association between cortical gyrification changes and white matter abnormalities. Adenosine A receptors have been shown to be upregulated in cerebral white matter and on reactive astrocytes in preclinical models of neurodegenerative diseases.

TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis.

Background And Objectives: In the multiple sclerosis (MS) brain, chronic active lesions can be detected using MRI- and PET-based methods. In this study, we investigated whether the frequency of TSPO-PET-detectable chronic active lesions associates with disease progression measured using the Expanded Disability Status Scale (EDSS) at 5-year follow-up.

Methods: Chronic lesion-associated innate immune cell activation was evaluated using TSPO-PET in 82 patients with MS.

Association of serum neurofilament light with microglial activation in multiple sclerosis.

Background: Translocator protein (TSPO)-PET and neurofilament light (NfL) both report on brain pathology, but their potential association has not yet been studied in multiple sclerosis (MS) in vivo. We aimed to evaluate the association between serum NfL (sNfL) and TSPO-PET-measurable microglial activation in the brain of patients with MS.

Methods: Microglial activation was detected using PET and the TSPO-binding radioligand [C]PK11195.

PET-measurable innate immune cell activation reduction in chronic active lesions in PPMS brain after rituximab treatment: a case report.

Objectives: To evaluate the effects of rituximab treatment on innate immune cell activation in primary progressive multiple sclerosis (PPMS).

Methods: A 48-year-old woman with PPMS was started on rituximab shortly after diagnosis. [C]PK11195 PET imaging was employed to assess innate immune cell activation with special interest in the white matter around chronic lesions.

Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in.

It has been over a year since people with multiple sclerosis (pwMS) have been receiving vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a negligible number of cases in which vaccination led to a relapse or new onset MS, experts around the world agree that the potential consequences of COVID-19 in pwMS by far outweigh the risks of vaccination. This article reviews the currently available types of anti-SARS-CoV-2 vaccines and the immune responses they elicit in pwMS treated with different DMTs.

Using personalized prognosis in the treatment of relapsing multiple sclerosis: A practical guide.

The clinical course of multiple sclerosis (MS) is highly variable among patients, thus creating important challenges for the neurologist to appropriately treat and monitor patient progress. Despite some patients having apparently similar symptom severity at MS disease onset, their prognoses may differ greatly. To this end, we believe that a proactive disposition on the part of the neurologist to identify prognostic "red flags" early in the disease course can lead to much better long-term outcomes for the patient in terms of reduced disability and improved quality of life.

Diagnosis and treatment of progressive multiple sclerosis: A position paper.

Background And Purpose: Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians.

Adenosine A receptor availability in patients with early- and moderate-stage Parkinson's disease.

Introduction: Adenosine 2A (A) receptors co-localize with dopamine Dreceptors in striatopallidal medium spiny neurons of the indirect pathway. A receptor activation in the striatum or pallidum decreases Dsignaling. In contrast, A receptor antagonism may help potentiate it.

Toward Precision Phenotyping of Multiple Sclerosis.

The classification of multiple sclerosis (MS) has been established by Lublin in 1996 and revised in 2013. The revision includes clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive MS, and has added activity (i.e.

The White Matter Rounds experience: The importance of a multidisciplinary network to accelerate the diagnostic process for adult patients with rare white matter disorders.

Introduction: Adult genetic leukoencephalopathies are rare neurological disorders that present unique diagnostic challenges due to their clinical and radiological overlap with more common white matter diseases, notably multiple sclerosis (MS). In this context, a strong collaborative multidisciplinary network is beneficial for shortening the diagnostic odyssey of these patients and preventing misdiagnosis. The White Matter Rounds (WM Rounds) are multidisciplinary international online meetings attended by more than 30 physicians and scientists from 15 participating sites that gather every month to discuss patients with atypical white matter disorders.

Establishment of a human induced pluripotent stem cell line (TAUi008-A) derived from a multiple sclerosis patient.

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system where the main pathogenetic events include demyelination and axonal degeneration. Here, we generated a human induced pluripotent stem cell (hiPSC) line from peripheral blood mononuclear cells of an MS patient utilizing Sendai virus reprogramming. The produced hiPSC line expressed pluripotency markers, differentiated into three germ layers, showed a normal karyotype and was free of virus vectors, transgenes and mycoplasma.

Microglia in multiple sclerosis - pathogenesis and imaging.

Purpose Of Review: Microglia normally protects the central nervous system (CNS) against insults. However, their persistent activation in multiple sclerosis (MS) contributes to injury. Here, we review microglia activation in MS and their detection using positron emission tomography (PET).

Innate Immune Cell-Related Pathology in the Thalamus Signals a Risk for Disability Progression in Multiple Sclerosis.

Background And Objectives: Our aim was to investigate whether 18-kDa translocator protein (TSPO) radioligand binding in gray matter (GM) predicts later disability progression in multiple sclerosis (MS).

Methods: In this prospective imaging study, innate immune cells were investigated in the MS patient brain using PET imaging. The distribution volume ratio (DVR) of the TSPO-binding radioligand [C]PK11195 was determined in 5 GM regions: thalamus, caudate, putamen, pallidum, and cortical GM.

Association between microglial activation and serum kynurenine pathway metabolites in multiple sclerosis patients.

Background: Microglial activation associates with MS progression but it is unclear what drives their persistent pro-inflammatory state. Metabolites of the kynurenine pathway (KP), the main metabolism route of tryptophan, can influence the function of brain innate immune cells.

Objective: To investigate whether tryptophan metabolites in blood associate with TSPO-PET measurable microglial activation in MS brain.

Phenotyping of multiple sclerosis lesions according to innate immune cell activation using 18 kDa translocator protein-PET.

Chronic active lesions are promotors of neurodegeneration and disease progression in multiple sclerosis. They harbour a dense rim of activated innate immune cells at the lesion edge, which promotes lesion growth and thereby induces damage. Conventional MRI is of limited help in identifying the chronic active lesions, so alternative imaging modalities are needed.

Synaptic Loss in Multiple Sclerosis: A Systematic Review of Human Post-mortem Studies.

Gray matter pathology plays a central role in the progression of multiple sclerosis (MS). The occurrence of synaptic loss appears to be important but, to date, still poorly investigated aspect of MS pathology. In this systematic review, we drew from the recent knowledge about synaptic loss in human post-mortem studies.

Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: An international consensus statement.

In this consensus statement, we provide updated recommendations on multiple sclerosis (MS) management during the COVID-19 crisis and the post-pandemic period applicable to neurology services around the world. Statements/recommendations were generated based on available literature and the experience of 13 MS expert panelists using a modified Delphi approach online. The statements/recommendations give advice regarding implementation of telemedicine; use of disease-modifying therapies and management of MS relapses; management of people with MS at highest risk from COVID-19; management of radiological monitoring; use of remote pharmacovigilance; impact on MS research; implications for lowest income settings, and other key issues.