Cerebrospinal fluid biomarkers in patients with neurological symptoms but without neurological diseases

Abstract

Background Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF‐L] and total tau protein [t‐tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. Aims To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. Methods Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. Results Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty‐eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9‐65.1) years. Age‐adjusted CSF‐NF‐L, CSF‐t‐tau, and CSF‐GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. Conclusion In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF‐L, t‐tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations.

Biomarkers of demyelination and axonal damage are decreased after autologous hematopoietic stem cell transplantation for multiple sclerosis

“…It has consistently been reported that MS patients have increased levels of GFAp in CSF (Momtazmanesh et al, 2021). Several reports have also claimed that GFAp is a biomarker for progressive MS, but this is likely confounded by the strong correlation between GFAp and age (Constantinescu et al, 2019). The CSF concentrations of GFAp were somewhat higher in MS patients in comparison to the controls, most likely reflecting reactive astrocytes and astrogliosis rather than tissue damage.…”

Functional brain activity constrained by structural connectivity reveals cohort-specific features for serum neurofilament light chain

“…Changes in NfL levels have also been linked to aging 9,17 and regional atrophy in cortical brain areas 15,18 and are therefore relatable to brain atrophy in aging among people without a recognizable neurological disease. While existing studies provide convincing evidence that serum NfL level is a promising biomarker to detect neurodegeneration in a broad range of clinical applications, the interpretation of these results has been limited by focusing analysis only on detecting the abnormal increase in serum NfL levels and by a lack of studies aimed at identifying the relevant underlying features associated with serum NfL levels 6,19 . For instance, the fundamental mechanism that links aging with serum NfL levels, even among healthy subjects, is unknown 6 .…”

“…For instance, the fundamental mechanism that links aging with serum NfL levels, even among healthy subjects, is unknown 6 . Moreover, while serum NfL levels have been studied in controlled groups in the context of various neurological disorders, insight into the relationship between serum NfL levels and the onset of common neurological symptoms in a healthy group is still lacking 19 . Therefore, it is relevant to search for underlying features that can help ongoing neurological studies model the variance in serum NfL levels among healthy controls and thereby provide a better understanding of both baseline serum NfL levels and how abnormal variation in these levels is mechanistically linked to neurodegenerative disease through these features.…”