Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis

Barro, Christian; Healy, Brian C.; Liu, Yanqing; Saxena, Shrishti; Paul, Anu; Polgar‐Turcsanyi, Mariann; Bakshi, Rohit; Kropshofer, Harald; Weiner, Howard L.; Chitnis, Tanuja

doi:10.1212/nxi.0000000000200052

Cited by 85 publications

(52 citation statements)

References 56 publications

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“…Patients were also required to have SDMT data available ± 2 years from the baseline visit (Table 1), notably the majority of patients (66/94, 70%) had the SDMT assessed within 6 months from the sample time point. Consistently with our previous work, 16 we identified active and nonactive patients based on their clinical and radiological activity status in the brain and spinal cord, briefly: (1) patients with a relapse or new MRI lesion in 2 years after baseline; (2) patients with relapses in 2 years prior to baseline; (3) patients with a relapse or new lesion in 2 years prior to baseline; and (4) patients with a relapse or new lesion in 2 years prior or after the baseline visit.…”

Section: Methodssupporting

confidence: 94%

“…Serum samples were collected with standardized procedures 16 and frozen at −80°C until analysis. The baseline levels of sNfL and sGFAP were quantified on a single-molecule array platform with the Neurology 4-plex A at Quanterix (Billerica, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Considering the strong association between sNfL and acute disease activity, 4 we additionally performed the predictive analyses stratifying the patients in active and nonactive (Table 2) utilizing previously adopted definitions of activity status. 16 Due to the low number of individuals per each subgroup, the analysis was limited to unadjusted estimates. Here, sNfL was associated with the change in SDMT in active but not in nonactive patients.…”

Section: Association Of Snfl and Sgfap With Cognitive Declinementioning

confidence: 99%

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Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients

et al. 2022

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Background: Cognitive decline is inadequately captured by the standard neurological examination. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are biomarkers of neuronal damage and astrocytic reactivity that may offer an accessible measure of the multiple sclerosis (MS) pathology linked to cognitive decline. Objective: To investigate the association of sNfL and sGFAP with cognitive decline in MS patients at high risk for progressive pathology. Methods: We included 94 MS patients with sustained Expanded Disability Status Score (EDSS) ⩾ 3, available serum samples and cognitive assessment performed by symbol digit modalities test (SDMT) over a median of 3.1 years. The visit for sGFAP/sNfL quantification was at confirmed EDSS ⩾ 3. Linear regression analysis on log-transformed sGFAP/sNfL assessed the association with current and future SDMT. Analyses were adjusted for age, sex, EDSS, treatment group, and recent relapse. Results: sNfL was significantly associated with concurrent SDMT (adjusted change in mean SDMT = −4.5; 95% confidence interval (CI): −8.7, −0.2; p = 0.039) and predicted decline in SDMT (adjusted change in slope: −1.14; 95% CI: −1.83, −0.44; p = 0.001), particularly in active patients. sGFAP was not associated with concurrent or future SDMT. Conclusions: Higher levels of sNfL were associated with cognitive impairment and predicted cognitive decline in MS patients at high risk for having an underlying progressive pathology.

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Section: Methodssupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Association Of Snfl and Sgfap With Cognitive Declinementioning

confidence: 99%

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Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients

et al. 2022

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“…Beyond AD, a rise in GFAP levels in frontotemporal dementia may indicate the late presymptomatic stage, as well as the severity of the disease [26,27 ▪ ]. Plasma GFAP is also increased in neuroinflammatory conditions, including multiple sclerosis, and is a top biomarker candidate for the progressive form of the disease [52,53].…”

Section: Diagnostic and Prognostic Performances Suggesting That Blood...mentioning

confidence: 99%

Plasma biomarkers for neurodegenerative disorders: ready for prime time?

Balogun

Zetterberg

Blennow

et al. 2023

Current Opinion in Psychiatry

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Purpose of reviewSeveral plasma biomarkers for Alzheimer's disease and related disorders (ADRD) have demonstrated clinical and technical robustness. However, are they ready for clinical implementation? This review critically appraises current evidence for and against the immediate use of plasma biomarkers in clinical care. Recent findingsPlasma biomarkers have significantly improved our understanding of ADRD time-course, risk factors, diagnosis and prognosis. These advances are accelerating the development and in-human testing of therapeutic candidates, and the selection of individuals with subtle biological evidence of disease who fit the criteria for early therapeutic targeting. However, standardized tests and well validated cut-off values are lacking. Moreover, some assays (e.g., plasma Ab methods) have poor robustness to withstand inevitable day-to-day technical variations. Additionally, recent reports suggest that common comorbidities of aging (e.g., kidney disease, diabetes, hypertension) can erroneously affect plasma biomarker levels, clinical utility and generalizability. Furthermore, it is unclear if health disparities can explain reported racial/ethnic differences in biomarker levels and functions. Finally, current clinically approved plasma methods are more expensive than CSF assays, questioning their cost effectiveness.

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“…In NMOSD, astrocyte damage is pronounced and serum GFAP levels are increased during relapses (141). In MS, increased GFAP is seen with progressive disease (145).…”

Section: Biomarkers and Therapeutic Mechanismsmentioning

confidence: 99%

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease

Corbali

Chitnis

2023

Front. Neurol.

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Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is a spectrum of diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cerebral cortical encephalitis. In addition to distinct clinical, radiological, and immunological features, the infectious prodrome is more commonly reported in MOGAD (37–70%) than NMOSD (15–35%). Interestingly, pediatric MOGAD is not more aggressive than adult-onset MOGAD, unlike in multiple sclerosis (MS), where annualized relapse rates are three times higher in pediatric-onset MS. MOGAD pathophysiology is driven by acute attacks during which T cells and MOG antibodies cross blood brain barrier (BBB). MOGAD lesions show a perivenous confluent pattern around the small veins, lacking the radiological central vein sign. Initial activation of T cells in the periphery is followed by reactivation in the subarachnoid/perivascular spaces by MOG-laden antigen-presenting cells and inflammatory CSF milieu, which enables T cells to infiltrate CNS parenchyma. CD4+ T cells, unlike CD8+ T cells in MS, are the dominant T cell type found in lesion histology. Granulocytes, macrophages/microglia, and activated complement are also found in the lesions, which could contribute to demyelination during acute relapses. MOG antibodies potentially contribute to pathology by opsonizing MOG, complement activation, and antibody-dependent cellular cytotoxicity. Stimulation of peripheral MOG-specific B cells through TLR stimulation or T follicular helper cells might help differentiate MOG antibody-producing plasma cells in the peripheral blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) in MOGAD support that most axonal damage happens in the initial attack, whereas relapses are associated with increased myelin damage.

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Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis

Cited by 85 publications

References 56 publications

Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients

Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients

Plasma biomarkers for neurodegenerative disorders: ready for prime time?

Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease

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