Prognostic Value of Cerebrospinal Fluid Immunoglobulin Free Light Chains in Patients With Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, usually presenting as clinically isolated syndrome (CIS). The course of MS following first symptoms is unpredictable, as approximately 30% of patients with MS have a benign course and don't develop significant disability while another 20-30% progress to severe disability within a relatively short time period. In this context, it is difficult to counsel an individual patient and choose the best treatment option at time of diagnosis. For these reasons, prognostic markers that could be used to predict future disease course are extremely useful.

The only cerebrospinal fluid (CSF) prognostic biomarker currently used in clinical practice are oligoclonal bands (OCB) that can predict conversion from CIS to clinically definite MS, although this observation is not consistent. However, OCB analyses are qualitative with issues in reproducibility and a limited dynamic range. CSF immunoglobulin (Ig) free light chains (FLC) are a quantitative measure of humoral response in CSF that has showed greater sensitivity and specificity than OCB for confirming diagnosis of MS. Moreover, in few recent studies they seem to have also a prognostic value, predicting conversion from CIS to clinically definite MS and correlating with the Expanded Disability Status Scale (EDSS).

Optic Neuritis (ON) can be a first clinical relapse of MS and is particularly interesting because it may constitute a suitable clinical model for neuroprotection studies, as visual function can be measured with quantitative methods, including Visual Evoked Potential (VEP) and Optical Coherence Tomography (OCT).

The investigators aim to better explore the utility of CSF Ig FLC as potential prognostic biomarker for MS, and to predict the recovery of visual function after ON, as model of MS relapse.

The investigators will study its potential correlation with MS relapses, with changes in several functional outcome scores, exploring physical disability, fatigue, behavior, cognition, upper and lower extremity function, and with MRI disease activity. For a subgroup of patient, the investigators aim to explore its potential correlation with in vivo measures of demyelination and neuronal and axonal loss after ON, as model of potential recovery after MS relapse. The investigators aim also to compare the prognostic value of Ig FLC with Neurofilament light chain (NfL), a potential prognostic biomarker wider studied in MS.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, usually presenting as clinically isolated syndrome (CIS). The course of MS following first symptoms is unpredictable, as approximately 30% of patients with MS have a benign course and don't develop significant disability while another 20-30% progress to severe disability within a relatively short time period. In this context, it is difficult to counsel an individual patient and choose the best treatment option at the time of diagnosis. For these reasons, prognostic markers that could be used to predict future disease course are extremely useful.

The only cerebrospinal fluid (CSF) prognostic biomarker currently used in clinical practice are oligoclonal bands (OCB), that can predict the conversion from CIS to clinically definite MS, although this observation is not consistent. However, OCB analyses are qualitative, with issues in reproducibility and a limited dynamic range.

CSF immunoglobulin (Ig) free light chains (FLC) are a quantitative measure of humoral response in CSF that had shown greater sensitivity and specificity than OCB for confirming diagnosis of MS. Moreover, in few recent studies, they showed to have also a potential prognostic value, predicting conversion from CIS to clinically definite MS and correlating with the Expanded Disability Status Scale (EDSS), a scale widely used in clinical practice as marker of MS disability. However, this scale counts very close to ambulation abilities and poorly correlates with other frequent MS symptoms, such as upper extremity disability, fatigue, cognitive and neuropsychiatric symptoms.

One of the most currently studied biomarkers of disease activity and treatment response in MS, not yet widely available in clinical practice, is represented by Neurofilament light chain (NfL). Elevated CSF and blood concentrations of NfL were found to correlate with an increase in the number of relapses, disability worsening, MRI disease activity, and brain volume loss in MS. Blood NfL was shown to strongly correlate with NfL in the CSF of patients with MS and has been proposed as an easily accessible biomarker of treatment response.

Optic Neuritis (ON) can be a first clinical manifestation of MS and is particularly interesting since it may constitute a suitable clinical model for neuroprotection studies. First, visual function can be measured with quantitative methods, including low-contrast acuity, visual fields, and color discrimination. Secondly, Visual Evoked Potential (VEP) with the evaluation of P100 latency, and Optical Coherence Tomography (OCT) with the evaluation of Ganglion Cell Layer (GCL) and Retinal Nerve Fiber Layer (RNFL) thickness, represent in-vivo measures of demyelination, and neuronal and axonal loss secondary to ON, respectively. The investigators aim to better explore the utility of CSF Ig FLC as potential prognostic biomarker of disease activity, disability worsening, and treatment response in patients with MS, and as potential predictor of visual recovery after ON as model of MS relapse. To investigate the prognostic value of CSF Ig FLC, the investigators evaluate the correlation of CSF Ig FLC at the time of MS diagnosis with clinical relapse, with changes in several functional outcome scores, exploring physical disability, fatigue, behavior, cognition, upper and lower extremity functions, and with MRI disease activity. For a subgroup of patient, the investigators aim to explore the correlation of CSF Ig FLC with in vivo measures of demyelination, neuronal and axonal loss after ON, as model of potential recovery after MS relapse. The investigators aim also to compare the prognostic value of Ig FLC with Neurofilament light chain (NfL) concentrations in CSF and blood.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 at the time of enrollment
* Diagnosis of multiple sclerosis according to 2017 McDonald diagnostic criteria or optic neuritis (fulfilling or not criteria for multiple sclerosis, i.e. clinically isolated syndrome)
* Receiving both lumbar puncture and brain MRI for the routine diagnostic work-up

Exclusion Criteria:

• None