CSF Diagnostics: A Potentially Valuable Tool in Neurodegenerative and Inflammatory Disorders Involving Motor Neurons: A Review

Abstract

Cerebrospinal fluid (CSF) diagnostics has emerged as a valid tool for a variety of neurological diseases. However, CSF diagnostics has been playing a subordinate role in the diagnosis of many neurological conditions. Thus, in the multitude of neuromuscular diseases in which motor neurons are affected, a CSF sample is rarely taken routinely. However, CSF diagnostics has the potential to specify the diagnosis and monitor the treatment of neuromuscular disorders. In this review, we therefore focused on a variety of neuromuscular diseases, among them amyotrophic lateral sclerosis (ALS), peripheral neuropathies, and spinal muscular atrophy (SMA), for which CSF diagnostics has emerged as a promising option for determining the disease itself and its progression. We focus on potentially valuable biomarkers among different disorders, such as neurofilaments, cytokines, other proteins, and lipids to determine their suitability, differentiating between different neurological disorders and their potential to determine early disease onset, disease progression, and treatment outcome. We further recommend novel approaches, e.g., the use of mass spectrometry as a promising alternative techniques to standard ELISA assays, potentially enhancing biomarker significance in clinical applications.

Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model

“…Samples without a given protein were excluded from analysis for that protein. Key proteins identified as biomarkers in ALS were selected for further analysis [1,2,6,[23][24][25][26][27]. Differences in abundances between groups were calculated using Welch's t-test.…”

“…We analyzed the proteome of the CSF from patients with ALS, characterized the changes in composition after filtration, and tested the effect of ALS-CSF on mouse motor activity. Proteomics identified over 1,600 proteins in the CSF, of which 58 were selected as key proteins implicated in the disease [1,2,6,[23][24][25][26][27]. This even results in the filtration of other proteins (mentioned in Table in appendices).…”

“…Of these, 58 were identified as key proteins for further analysis. [1,2,6,[23][24][25][26][27]. The average abundances and number of samples containing each protein in the unfiltered and filtered CSF can be found in Figure 1.…”

Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy

“…6,7 The intrathecal administration of nusinersen, requiring the removal of cerebrospinal fluid (CSF) before injecting the medication, has led to the emerging field of CSF biomarker studies in SMA. 8,9 Ever since the US Food and Drug Administration (FDA) approved nusinersen in 2016, numerous studies attempting to identify biomarkers of clinical significance have been published. [10][11][12][13][14][15][16] The CSF protein composition is unique: while most plasma proteins are excluded by the blood-CSF barrier, the choroid plexus and the brain parenchyma comprise an exclusive source for certain proteins, such as transthyretin, tau, NSE, S-100B, cystatin, and more.…”

“…The intrathecal administration of nusinersen, requiring the removal of cerebrospinal fluid (CSF) before injecting the medication, has led to the emerging field of CSF biomarker studies in SMA 8,9 . Ever since the US Food and Drug Administration (FDA) approved nusinersen in 2016, numerous studies attempting to identify biomarkers of clinical significance have been published 10–16 .…”