Longitudinal accumulation of glial activation measured by TSPO-PET predicts later brain atrophy in multiple sclerosis.

In multiple sclerosis (MS), accumulation of disability is driven by CNS-compartmentalized inflammation. This inflammatory process involves activated microglia and astrocytes, which contribute to neuroaxonal damage which in turn accelerates disease progression. Activated glial cells express 18-kDa translocator protein (TSPO), and TSPO-binding radioligands and positron emission tomography (PET) imaging can be used to quantitate glial activation in vivo.

Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain.

Background: Serum glial fibrillary acidic protein (sGFAP) is a promising biomarker for multiple sclerosis (MS) disease progression. Elevated sGFAP levels are considered to reflect ongoing astrocyte-related pathology in the central nervous system.

Objectives: To study whether sGFAP levels associate with 18 kDa translocator protein (TSPO) availability in MS brain.

Multiple sclerosis: 2024 update.

Multiple sclerosis (MS) is a complex immune-mediated disease that leads to neurological disability, with ongoing challenges in understanding its initiation, predicting progression, and optimizing personalized treatment. This review article summarizes key research findings from 2024, covering advances in diagnostic criteria, understanding of pathophysiology, and treatment strategies. New studies reinforce the strong link between Epstein-Barr virus (EBV) and MS, while recent data point towards a role of genetics in MS disease progression.

Synaptic Density in Multiple Sclerosis: An In Vivo Study Using [C]UCB-J-PET Imaging.

Background And Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease coupled with neurodegenerative processes affecting both the white matter and gray matter (GM) in the CNS. Several histopathologic studies have reported a reduction in synaptic density in various areas of the brain. However, this pathologic feature is yet an unexplored entity among people with MS (pwMS).

Hemispheric asymmetry of [C](PK11195 binding to translocator protein 18 kDa (TSPO) in normal brain.

Many positron emission tomography (PET) imaging studies in health and disease of the translocator protein 18 kDa (TSPO) using different radioligands have been published, however, only few separately reported left and right regions of interest in the brain. Thus, TSPO binding in healthy brains using [C]()PK11195 datasets of 76 participants from two PET sites was assessed for symmetry. Structural MRI scans were used for brain segmentation and to define six regions of interest (thalamus, putamen, temporal, frontal, parietal, and occipital cortex) with a probabilistic brain atlas.

The role of microglia in multiple sclerosis: implications for treatment with Bruton's tyrosine kinase inhibitors.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS), characterized by inflammation and neurodegeneration. The pathophysiology of MS, especially its progressive forms, involves various cellular components, including microglia, the primary resident immune cells of the CNS. This review discusses the role of microglia in neuroinflammation, tissue repair, and neural homeostasis, as well as their involvement in MS and explores potential therapeutic strategies targeting microglial function.

Plasma CHI3L1 associates with brain volume loss and glial activation in multiple sclerosis.

Background: Multiple sclerosis (MS) progression independent of relapses is driven by brain innate immune cell activation. The aim of this study was to evaluate the association between chitinase-3-like protein 1 (CHI3L1), expressed in brain by astrocytes and microglia, measured from blood and smouldering inflammation measured using 18 kDa translocator protein (TSPO) positron emission tomography (PET) in patients with MS.

Methods: The study cohort included 55 patients with MS (25 progressive MS (PMS) and 30 relapsing remitting MS (RRMS)) and 17 healthy controls (HC).

Microglia positron emission tomography and progression in multiple sclerosis: thalamus on fire.

Increased innate immune activity promotes neurodegeneration and contributes to progression in multiple sclerosis. This prospective case-control study aims to investigate thalamic microglia density on 18kDa translocator protein PET in patients with multiple sclerosis using a third-generation radioligand, C-ER176, and investigate the associations of C-ER176 PET uptake with imaging and clinical measures of progression in multiple sclerosis. Patients with multiple sclerosis ( = 50) and controls ( = 55) were prospectively enrolled and they underwent C-ER176 PET and MRI including diffusion MRI with neurite orientation dispersion and density imaging.

Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis.

Current multiple sclerosis (MS) treatments reduce relapse activity but have limited impact on disease progression. Clinical trials targeting progression often fail because of insufficient understanding of its underlying mechanisms. This study analyzed a clinically well-characterized MS autopsy cohort from the Netherland Brain Bank (186 individuals) from which we selected donors exhibiting opposite disease trajectories of slow versus rapid progression.

Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis.

Background: Predicting disease progression in multiple sclerosis (MS) remains challenging. PET imaging with 18 kDa translocator protein (TSPO) radioligands can detect microglial and astrocyte activation beyond MRI-visible lesions, which has been shown to be highly predictive of disease progression. We previously demonstrated that nuclear magnetic resonance (NMR)-based metabolomics could accurately distinguish between relapsing-remitting (RRMS) and secondary progressive MS (SPMS).

Generics, Biosimilars and Follow-On Non-Biologic Complex Drugs for Multiple Sclerosis: A Narrative Review of the Regulatory and Clinical Implications for European Neurologists.

Background: Multiple sclerosis (MS) places substantial socioeconomic burden on patients due to its early onset and progressive nature, but healthcare systems are also impacted by the high costs of disease-modifying treatments (DMTs). The use of generics (for conventional drugs), biosimilars (for biologics) or follow-on versions of non-biologic complex drugs (NBCDs) can help to reduce the cost of MS care and improve patient access. This review describes the European regulatory processes for these DMT 'copies' and the available data in people with MS.

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.