Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis.

Background And Objectives: To investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab.

Methods: Patients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, the Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation.

Tissue Transglutaminase Expression Associates With Progression of Multiple Sclerosis.

Objective: The clinical course of multiple sclerosis (MS) is variable and largely unpredictable pointing to an urgent need for markers to monitor disease activity and progression. Recent evidence revealed that tissue transglutaminase (TG2) is altered in patient-derived monocytes. We hypothesize that blood cell-derived TG2 messenger RNA (mRNA) can potentially be used as biomarker in patients with MS.

Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.

Background: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS).

Objective: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients.

Methods: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included.

Dynamic functional connectivity as a neural correlate of fatigue in multiple sclerosis.

Background: More than 80% of multiple sclerosis (MS) patients experience symptoms of fatigue. MS-related fatigue is only partly explained by structural (lesions and atrophy) and functional (brain activation and conventional static functional connectivity) brain properties.

Objectives: To investigate the relationship of dynamic functional connectivity (dFC) with fatigue in MS patients and to compare dFC with commonly used clinical and MRI parameters.

Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma.

Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by . We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.

Blood platelet RNA enables the detection of multiple sclerosis.

Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.

Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation.

Plasma proteome in multiple sclerosis disease progression.

Background: The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression.

Methods: We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma.

Long-term disease activity and disability progression in relapsing-remitting multiple sclerosis patients on natalizumab.

Background: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited.

Objective: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab.

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS).

Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples.

Acid sphingomyelinase: No potential as a biomarker for multiple sclerosis.

Background: Multiple sclerosis (MS) lacks reliable biomarkers that reflect disease activity. Recent evidence suggests that an altered sphingolipid metabolism is associated with MS pathogenesis.

Objective: To explore acid sphingomyelinase (ASM) activity and altered sphingolipid metabolism as potential biomarkers in serum of MS patients, to predict active and progressive disease, and response to disease modifying therapy (DMT).

No Plasmatic Proteomic Signature at Clinical Disease Onset Associated With 11 Year Clinical, Cognitive and MRI Outcomes in Relapsing-Remitting Multiple Sclerosis Patients.

The clinical course of relapsing-remitting multiple sclerosis (RRMS) is highly heterogeneous and prognostic biomarkers at time of diagnosis are lacking. We investigated the predictive value of the plasma proteome at time of diagnosis in RRMS patients. The plasma proteome was interrogated using a novel aptamer-based proteomics platform, which allows to measure the levels of a predefined set of 1310 proteins.

Information processing speed in multiple sclerosis: Relevance of default mode network dynamics.

Objective: To explore the added value of dynamic functional connectivity (dFC) of the default mode network (DMN) during resting-state (RS), during an information processing speed (IPS) task, and the within-subject difference between these conditions, on top of conventional brain measures in explaining IPS in people with multiple sclerosis (pwMS).

Methods: In 29 pwMS and 18 healthy controls, IPS was assessed with the Letter Digit Substitution Test and Stroop Card I and combined into an IPS-composite score. White matter (WM), grey matter (GM) and lesion volume were measured using 3 T MRI.

Progression of regional grey matter atrophy in multiple sclerosis.

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood.

Disease activity following pregnancy-related discontinuation of natalizumab in MS.

Objective: To investigate disease activity and disability progression following pregnancy-related discontinuation of natalizumab (NTZ) in patients with relapsing-remitting MS.

Methods: A retrospective cohort study of clinical and radiologic data in patients who discontinued NTZ for pregnancy-related reasons.

Results: Twenty-two pregnancy-related NTZ discontinuations in 17 patients were evaluated.

Deep gray matter volume loss drives disability worsening in multiple sclerosis.

Objective: Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.

Methods: We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.

Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients.

Background: Natalizumab is an effective treatment in relapsing-remitting multiple sclerosis (MS). Mainly because of the risk of progressive multifocal leukoencephalopathy (PML), a substantial proportion of John Cunningham (JC) virus-positive patients switch to fingolimod. Previous reports show a clear benefit when the duration of a washout (WO) period of natalizumab is 0-3 months in comparison to longer WO periods.

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.

John Cunningham virus conversion in relation to natalizumab concentration in multiple sclerosis patients.

Background And Purpose: Infection with the John Cunningham virus (JCV) is required for the development of progressive multifocal leukoencephalopathy, the feared complication of natalizumab treatment in multiple sclerosis patients. The JCV seroconversion rate seems higher in natalizumab treated patients than in the normal population, with an unknown cause.

Methods: Natalizumab concentration was correlated to JCV antibody status and seroconversion in a large cohort of multiple sclerosis patients.

The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing.

Background: Natalizumab is efficacious in the treatment of relapsing-remitting multiple sclerosis. All patients receive the same treatment regimen of 300 mg every 4 weeks, despite differences in pharmacokinetics between individual patients.

Objective: To give neurologists insight into natalizumab concentrations at time of re-dosing, we investigated longitudinal natalizumab concentrations in 80 patients in relation to disease activity, with possible influencing factors.

Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment.

Background: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response.

Objectives: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes.

Natalizumab-associated progressive multifocal leukoencephalopathy is not preceded by elevated drug concentrations.

Background: In recent years, a small but increasing number of neurologists choose to extend dose intervals of natalizumab with the aim of reducing the risk of progressive multifocal leukoencephalopathy (PML). This idea is based on the hypothesis that high drug concentrations increase the risk of PML.

Objective: We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML.