Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that still lacks reliable diagnostic biomarkers. This study aims to evaluate the diagnostic and prognostic potential of CSF total Tau (t-Tau), phospho-Tau (p-Tau) and p-Tau/t-Tau ratio in ALS patients using CSF neurofilament light (NFL) as the reference biomarker. METHODS: Eighty-five incident ALS, 30 ALS-mimicking (AM) diseases and 51 other non-neurodegenerative diseases (ONND) were included in the study. RESULTS: ALS patients had higher levels of CSF t-Tau and lower p-Tau/t-Tau ratio than AM (p = 0.005 and p = 0.006) and ONND (p < 0.001). CSF t-Tau levels discriminated ALS from AM with a sensitivity of 69% and specificity of 60%, and from ONND with a sensitivity of 88% and specificity of 51%. These values were lower than the accuracy of CSF NFL in ALS (sensitivity 86% and specificity 87% in distinguishing ALS from AM and sensitivity 83% and specificity 75% from ONND); CSF t-Tau correlated with progression rate and SNIP. CSF p-Tau did not show relation with any ALS clinical features. CSF NFL significantly correlated with all considered clinical parameters. High levels of CSF t-Tau and NFL were related to poor survival. CONCLUSION: CSF t-Tau showed no reliable diagnostic significance but the relation between the high levels of CSF t-Tau and short survival suggests the potential prognostic role of this biomarker in ALS. However, CSF NFL was confirmed to be the most reliable and efficient tool for diagnosis and prediction of clinical progression and survival in ALS patients.

Cerebrospinal fluid analysis and the determination of oligoclonal bands.

This document presents the guidelines for the cerebrospinal fluid (CSF) analysis and the determination of oligoclonal bands (OCBs) as pivotal tests in neuroinflammatory pathologies of the central nervous system. The guidelines have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on the pathologies in which the CSF analysis is indicated, and, particularly, on those characterized by the presence of OCBs in the intrathecal compartment, indications and limits of CSF analysis and OCB determination, instructions for result interpretation, and agreed laboratory protocols (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of the neuromyelitis optica spectrum disorders (NMOSD).

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes.

In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP, p=0.02) and primary progressive (PP, p=0.01) MS than short disease duration (SDD) relapsing-remitting (RR) MS, but not different from the healthy control (HC) group. Whereas the MMP-9/TIMP-1 ratio in serum showed higher (p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (p=0.006) or from the magnetic resonance imaging (MRI, p<0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes. These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease.