Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

Schneider, Ruth; Bellenberg, Barbara; Gisevius, Barbara; Hirschberg, Sarah; Sankowski, Roman; Prinz, Marco; Gold, Ralf; Lukas, Carsten; Haghikia, Aiden

doi:10.1212/nxi.0000000000000906

Cited by 26 publications

(37 citation statements)

References 37 publications

(59 reference statements)

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“…Interestingly, we observed that the presence of monocytes/macrophages was associated with conversion to CDMS. This underlines findings on Chitinase 3like 1 (CHI3L1), a glycoprotein secreted by macrophages (41), which was determined as a biomarker in MS (42)(43)(44) and which was also associated with the conversion from CIS to CDMS (45).…”

Section: Discussionsupporting

confidence: 76%

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

et al. 2021

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BackgroundReports on typical routine cerebrospinal fluid (CSF) findings are outdated owing to novel reference limits (RL) and revised diagnostic criteria of Multiple Sclerosis (MS).ObjectiveTo assess routine CSF parameters in MS patients and the frequency of pathologic findings by applying novel RL.MethodsCSF white blood cells (WBC), CSF total protein (CSF-TP), CSF/serum albumin quotient (Qalb), intrathecal synthesis of immunoglobulins (Ig) A, M and G, oligoclonal IgG bands (OCB) were determined in patients with clinically isolated syndrome (CIS) and MS.ResultsOf 541 patients 54% showed CSF pleocytosis with a WBC count up to 40/μl. CSF cytology revealed lymphocytes, monocytes and neutrophils in 99%, 41% and 9% of patients. CSF-TP and Qalb were increased in 19% and 7% applying age-corrected RL as opposed to 34% and 26% with conventional RL. Quantitative intrathecal IgG, IgA and IgM synthesis were present in 65%, 14% and 21%; OCB in 95% of patients. WBC were higher in relapsing than progressive MS and predicted, together with monocytes, the conversion from CIS to clinically definite MS. Intrathecal IgG fraction was highest in secondary progressive MS.ConclusionsCSF profile in MS varies across disease courses. Blood-CSF-barrier dysfunction and intrathecal IgA/IgM synthesis are less frequent when the novel RL are applied.

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Section: Discussionsupporting

confidence: 76%

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

et al. 2021

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“…Similarly, being in remission or in relapse does not influence the CSF levels of RRMS patients [ 144 ]. In contrast, higher levels were associated with increased numbers of T2 and Gd+ enhancing lesions on MRI scans and faster disability progression, fulminant disease course [ 149 ] and hastened spinal cord atrophy [ 150 , 151 , 152 , 153 , 154 , 155 , 156 ]. Furthermore, CHI3L1 proved to be a reliable marker for distinguishing between RR and progressive phenotype and forecasting disability progression when measured together with the neurofilament light chain (NFL) [ 157 ].…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

“…Natalizumab, fingolimod and mitoxantrone were found to reduce CSF levels of CHI3LI1 in RRMS patients, while for interferon-beta, the same was true only for treatment responders [ 153 , 158 , 159 ]. On the other hand, glatiramer acetate [ 156 ] and dimethyl fumarate (at least in patients with progressive disease [ 158 ]) did not influence CHI3L1 levels.…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

“…Some assessments examining NfL levels in MS compared to HCs found no correlation between age and CSF NfL in MS, but strengthened the association mentioned above with age in HCs [ 274 , 285 , 286 ]. On the other hand, different studies documented a significant relationship between age and CSF, serum, and plasma NfL in MS [ 40 , 156 , 278 , 287 ]. The association between NfL and gender is also controversial; most studies found no relationship between CSF and serum NfL and sex [ 40 , 271 , 287 , 288 ].…”

Section: Fluid Biomarkers Of Multiple Sclerosismentioning

confidence: 99%

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Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Biernacki

Kokas

Sandi

et al. 2022

IJMS

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Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient’s health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

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“…A recent study examining the value of cNfL and CHI3L1 concluded that CHI3L1 levels were associated with spinal cord volume loss but not with brain gray matter atrophy. In contrast, cNfL was associated with brain but not with spinal cord volumes ( Schneider et al, 2021 ). The combined measurement of CHI3L1 + cNfL could therefore provide complementary information on the location of atrophy in pwMS.…”

Section: The Known Unknownsmentioning

confidence: 99%

The Evolution of Neurofilament Light Chain in Multiple Sclerosis

et al. 2021

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Multiple sclerosis (MS) is an autoimmune, inflammatory neurodegenerative disease of the central nervous system characterized by demyelination and axonal damage. Diagnosis and prognosis are mainly assessed through clinical examination and neuroimaging. However, more sensitive biomarkers are needed to measure disease activity and guide treatment decisions in MS. Prompt and individualized management can reduce inflammatory activity and delay disease progression. Neurofilament Light chain (NfL), a neuron-specific cytoskeletal protein that is released into the extracellular fluid following axonal injury, has been identified as a biomarker of disease activity in MS. Measurement of NfL levels can capture the extent of neuroaxonal damage, especially in early stages of the disease. A growing body of evidence has shown that NfL in cerebrospinal fluid (CSF) and serum can be used as reliable indicators of prognosis and treatment response. More recently, NfL has been shown to facilitate individualized treatment decisions for individuals with MS. In this review, we discuss the characteristics that make NfL a highly informative biomarker and depict the available technologies used for its measurement. We further discuss the growing role of serum and CSF NfL in MS research and clinical settings. Finally, we address some of the current topics of debate regarding the use of NfL in clinical practice and examine the possible directions that this biomarker may take in the future.

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Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

Cited by 26 publications

References 37 publications

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Cerebrospinal Fluid Findings in 541 Patients With Clinically Isolated Syndrome and Multiple Sclerosis: A Monocentric Study

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

The Evolution of Neurofilament Light Chain in Multiple Sclerosis

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