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.

Keywords: ELISA; Guillain-Barré syndrome; amyotrophic lateral sclerosis; biomarker; cerebrospinal fluid; motor neurons; peripheral neuropathies; spinal muscular atrophy.

Figure 1

Potential workflow for a mass spectrometric analysis of CSF samples obtained from SMA patients. CSF samples of SMA patients are obtained in the context of intrathecal nusinersen treatment. After collection, proteins and cells contained in the CSF samples are separated via centrifugation and separately prepared for mass spectrometric analyses. The used schematics in this figure were partly provided by Servier Medical art (https://smart.servier.com/, accessed date: 17 November 2020). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.