Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis

Abstract

The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.

Upper reference limits for cerebrospinal fluid total protein and albumin quotient based on a large cohort of control patients: implications for increased clinical specificity

“…These patients were screened applying the following criteria: sample processing within 24 h after withdrawal, RBC count < 1500/3 [8], WBC count < 30/3 (unit "/3" is explained below), CSF TP < 1 g/L and lack of intrathecal immunoglobulin synthesis according to Reiber hyperbolic formula [9]. Medical records of the remaining patients were studied, and patients who did not have objective clinical or paraclinical findings to define a specific neurological disease at the time of sampling were included, fulfilling the criteria for "symptomatic control" group according to the guidelines by the BioMS consortium ( Figure 1) [10]. These patients were subdivided by their diagnoses according to the consortium's proposal [10].…”

“…Medical records of the remaining patients were studied, and patients who did not have objective clinical or paraclinical findings to define a specific neurological disease at the time of sampling were included, fulfilling the criteria for "symptomatic control" group according to the guidelines by the BioMS consortium ( Figure 1) [10]. These patients were subdivided by their diagnoses according to the consortium's proposal [10]. Serum samples were collected by venous puncture.…”

Inflammatory molecules in Frontotemporal Dementia: Cerebrospinal fluid signature of progranulin mutation carriers

“…Of these, seven people underwent LP in suspicion of pathologies of the Central Nervous System (CNS) and were discharged with no evidence of CNS involvement. Therefore, we considered them as non-inflammatory disease controls, according to recently proposed guidelines (Teunissen et al, 2013). In four cases, biomarkers were evaluated and were normal (details in the Supplementary Table).…”

CSF-PR 2.0: An Interactive Literature Guide to Quantitative Cerebrospinal Fluid Mass Spectrometry Data from Neurodegenerative Disorders

“…Consensus guidelines are available (52,53), but there is still a large variety in the names and definitions used when describing disease and control groups in CSF biomarker studies. This represents a problem when attempting to group and compare data across studies, especially if limited information is provided regarding the individual patients in the groups.…”