Axonal damage in patients with early multiple sclerosis: disease stage related changes of Tau protein level in cerebrospinal fluid

Axonal damage has been proposed as the major substrate of permanent clinical disability in multiple sclerosis. Tau protein, a microtubule-associated protein localised in neuronal axons, may serve as a biochemical surrogate marker to evaluate axonal damage in vivo.We intended to determine the extent of axonal damage in different stages and clinical subtypes of MS by investigating cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in 35 patients with relapsing—remitting MS, eight patients with secondary progressive MS, nine patients with primary progressive MS, 50 patients with clinically isolated syndrome suggestive of early MS and 46 normal controls. Cerebrospinal fluid tau was significantly elevated in MS compared with normal controls (median 206.0 pg/mL versus152.0 pg/mL;P=0.002). No significant difference among different subtypes of MS could be detected, although highest levels were found in very early disease stages. There was a significant elevation of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic resonance imaging (P=0.02) and a tendency towards higher CSF tau levels in patients with pronounced intrathecal IgG synthesis, supporting the notion that axonal damage is influenced by inflammatory activity.

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Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319190 ◽

2019 ◽

Vol 90 (9) ◽

pp. 1059-1067 ◽

Cited By ~ 14

Author(s):

Sarah-Jane Martin ◽

Sarah McGlasson ◽

David Hunt ◽

James Overell

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Light Chain ◽

Meta Analysis ◽

Grey Literature ◽

Case Control ◽

Disease Stage ◽

Case Control Studies ◽

Neurofilament Light Chain ◽

Neurofilament Light

ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

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Increased Cerebrospinal Fluid Tau Protein in Multiple Sclerosis

European Neurology ◽

10.1159/000008181 ◽

2000 ◽

Vol 43 (4) ◽

pp. 228-232 ◽

Cited By ~ 54

Author(s):

Elisabeth Kapaki ◽

George P. Paraskevas ◽

Maria Michalopoulou ◽

Konstantinos Kilidireas

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Tau Protein

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

Multiple Sclerosis Journal ◽

10.1177/1352458517699874 ◽

2017 ◽

Vol 24 (4) ◽

pp. 472-480 ◽

Cited By ~ 10

Author(s):

Cyra E Leurs ◽

Petar Podlesniy ◽

Ramon Trullas ◽

Lisanne Balk ◽

Martijn D Steenwijk ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Disease Progression ◽

Progressive Multiple Sclerosis ◽

Neurologic Disease ◽

Brain Volumes ◽

Multiple Sclerosis Disease ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis ◽

Digital Polymerase Chain Reaction

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. To explore the effect of disease-modifying therapies on mtDNA levels in the CSF. Methods: CSF mtDNA was measured using a digital polymerase chain reaction (PCR) CSF mtDNA in two independent MS cohorts. The cohorts included 92 relapsing-remitting multiple sclerosis (RRMS) patients, 40 progressive multiple sclerosis (PMS) patients (27 secondary progressive and 13 primary progressive), 50 various neurologic disease controls, and 5 healthy controls. Results: Patients with PMS showed a significant increase in CSF mtDNA compared to non-inflammatory neurologic disease controls. Patients with higher T2 lesion volumes and lower normalized brain volumes showed increased concentration of mtDNA. Patients treated with fingolimod had significantly lower mtDNA copy levels at follow-up compared to baseline. Conclusion: Our results showed a non-specific elevation of concentration of mtDNA in PMS patients. mtDNA concentrations respond to fingolimod and may be used to monitor biological effect of this treatment.

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