Cerebrospinal Fluid Level of Phosphorylated Neurofilament Heavy Chain is Higher in Converting Clinically Isolated Syndrome and Correlates with CAMP Response Element‑Binding Protein Concentration

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Gencer M., Koral G., Şanlı E. , Çırak S., Akbayır E., Yüceer H. , ...More

NEUROLOGICAL SCIENCES AND NEUROPHYSIOLOGY, vol.38, no.4, pp.256-261, 2021 (Journal Indexed in SCI Expanded)

  • Publication Type: Article / Article
  • Volume: 38 Issue: 4
  • Publication Date: 2021
  • Doi Number: 10.4103/nsn.nsn_144_21
  • Page Numbers: pp.256-261


Introduction: Prevision of conversion from clinically isolated syndrome (CIS) to

multiple sclerosis (MS) is required to avoid unnecessary use of immunomodulating

agents and to recognize patients with high disease activity. Our aim was to

evaluate the value of phosphorylated neurofilament heavy chain (pNFH, a marker

for neuroaxonal degeneration) and Cyclic adenosine monophosphate response

element‑binding protein (cAMP response element‑binding protein [CREB], a

marker for neuroregeneration) levels in the prediction of conversion from CIS to

MS. Methods: Twenty‑three consecutively recruited treatment‑naïve CIS patients

were followed for 36 months. pNFH and CREB levels were measured in the first

episode cerebrospinal fluid (CSF) and the serum of 12 converting (CIS‑MS) and

11 nonconverting CIS patients (CIS‑CIS) by enzyme‑linked immunosorbent assay.

Results: Baseline CSF but not serum samples of CIS‑CIS patients displayed

significantly lower pNFH levels compared to patients with CIS‑MS. The analysis

of receiver operating characteristic curve presented a high specificity for the

prediction of MS conversion for the CSF pNFH cut‑off level of 730.9 pg/ml. CSF

pNFH levels significantly correlated with serum and CSF CREB levels. Higher

baseline CSF pNFH and CREB levels were associated with more rapid progression

to MS or increased disability scores. Conclusion: CSF pNFH measurement may

potentially determine MS patients with unfavorable clinical progression after the

first attack. pNFH and CREB appear to be increased in parallel in CSF of CIS

patients with higher disease activity. These results suggest that neurofilaments are

not only indicators of axonal degeneration but also partly a marker of neuronal

differentiation and new axon regeneration mediated by CREB signaling pathway.