Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age- and BMI-Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response.

Objective: Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy.

Methods: Observational cohort study including the first serum sample of participants after the start of fingolimod therapy.

Stellate Ganglion Block for Management of Nicolau's Syndrome Following Intravenous Ibuprofen Injection: a Case Report and Literature Review.

Purpose Of The Review: Nicolau's syndrome (NS) is a rare but serious drug reaction that occurs after administration of many drugs through various routes, with a broad spectrum of manifestations ranging from severe pain up to skin necrosis. In this review, we reported a case of advanced-grade NS following intravenous injection of ibuprofen. Moreover, we reviewed the existing knowledge and current practice to present in-depth any possible pathogeneses involved in this condition and highlight the specific pharmacological properties of the offending drugs that may play a role in the development of this syndrome.

Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.

Background And Objectives: Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).

The role of serum neurofilament light (sNfL) as a biomarker in multiple sclerosis: insights from a systematic review.

Objective: This systematic literature review (SLR) was conducted to explore the role of serum neurofilament light chain (sNfL) as a biomarker in multiple sclerosis (MS) disease management.

Methods: The review was conducted in accordance with the recommendation laid by the Cochrane Handbook for Systematic Reviews. A comprehensive literature search was performed in key biomedical databases (EMBASE, MEDLINE, MEDLINE-In-Process, and all Evidence-Based Medicine [EBM] Reviews databases) to retrieve studies reporting the association between sNfL and disease activity in patients with MS.

Markers of axonal injury in blood and tissue triggered by acute and chronic demyelination.

Neuroaxonal injury is a major driver of irreversible disability in demyelinating conditions. Accurate assessment of the association between demyelination and axonal pathology is critical for evaluating and developing effective therapeutic approaches. Measuring neurofilament light chain (NfL) in the blood could putatively allow longitudinal monitoring of neuroaxonal injury at 'single protein resolution' with high pathological specificity.

Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults.

Objective: Vitamin B12 (B12) plays a critical role in fatty- and amino-acid metabolism and nucleotide synthesis. While the association between B12 deficiency and neurological dysfunction is well-known, the exact threshold for adequacy remains undefined in terms of functional impairment and evidence of injury. The objective was to assess whether B12 levels within the current normal range in a cohort of healthy older adults may be associated with measurable evidence of neurological injury or dysfunction.

Multifaceted Biomarkers Suggest a Similar Profile of CNS Pathology in Relapsing and Progressive MS.

Background: Relapsing-remitting (RR) and primary progressive (PP) multiple sclerosis (MS) have distinct clinical courses, but underlying pathophysiological differences remain unclear. We compared pathological components between RRMS, PPMS, and other inflammatory and neurodegenerative disorders, leveraging soluble biomarkers and post-mortem pathology.

Methods: Serum and cerebrospinal fluid (CSF) of people diagnosed with (pw) PPMS (n = 104), RRMS (n = 38), Alzheimer's disease (AD, n = 22), neuromyelitis optica spectrum disorder (NMOSD, n = 10), and myelin oligodendrocyte glycoprotein-associated disease (MOGAD, n = 10) were collected.

Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis.

Background And Objective: The impact of menopause on the brain is not well understood. Hormonal changes, including puberty and pregnancy, influence the onset and course of multiple sclerosis (MS). After menopause, a worsening of MS disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some, but not all, studies.

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis.

Background And Objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

Background And Objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).

Targeting complement C3a receptor resolves mitochondrial hyperfusion and subretinal microglial activation in progranulin-deficient frontotemporal dementia.

Mutations in progranulin ( ) cause frontotemporal dementia ( -FTD) due to deficiency of the pleiotropic protein progranulin. -FTD exhibits diverse pathologies including lysosome dysfunction, lipofuscinosis, microgliosis, and neuroinflammation. Yet, how progranulin loss causes disease remains unresolved.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies.

Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS.

Patient-reported outcome parameters and disability worsening in progressive multiple sclerosis.

Objectives: Detection and prediction of disability progression is a significant unmet need in people with progressive multiple sclerosis (PwPMS). Government and health agencies have deemed the use of patient-reported outcomes measurements (PROMs) in clinical practice and clinical trials a major strategic priority. Nevertheless, data documenting the clinical utility of PROMs in neurological diseases is scarce.

Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis.

Importance: Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting.

Objective: To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW).

Remyelination protects neurons from DLK-mediated neurodegeneration.

Chronic demyelination and oligodendrocyte loss deprive neurons of crucial support. It is the degeneration of neurons and their connections that drives progressive disability in demyelinating disease. However, whether chronic demyelination triggers neurodegeneration and how it may do so remain unclear.

Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study.

Background: Neurological conditions represent an important driver of paediatric disability burden worldwide. Measurement of serum neurofilament light chain (sNfL) concentrations, a specific marker of neuroaxonal injury, has the potential to contribute to the management of children with such conditions. In this context, the European Medicines Agency recently declared age-adjusted reference values for sNfL a top research priority.