Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Sep 10:2019:9320791.
doi: 10.1155/2019/9320791. eCollection 2019.

Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients

Massimiliano Castellazzi  1   2   3 , Giuseppe Lamberti  4 , Maria Vittoria Resi  5 , Eleonora Baldi  2   3 , Luisa Maria Caniatti  2   3 , Giuditta Galante  1 , Paolo Perri  1   4 , Maura Pugliatti  1   2   3
Affiliations

Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients

Massimiliano Castellazzi et al. Dis Markers. .

Abstract

Background: Multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the central nervous system, typically features immune-mediated focal demyelination and secondary axonal degeneration. Cerebral hypoperfusion of the normal-appearing white matter (NAWM) has been reported in MS patients and may be mediated by elevated levels of endothelin-1 (ET-1), a most potent vasoconstrictive peptide released from reactive astrocytes in MS focal lesions. Optic neuritis (ON) is one of the most frequent manifestations of MS and also shows peripapillary vascular hypoperfusion in combination with disc swelling.

Aims: We aimed to compare serum and cerebrospinal fluid (CSF) levels of ET-1 as a potential prognostic marker of MS-ON in two groups of patients differing for severity of MS-ON clinical presentation.

Materials and methods: A cross-sectional study to compare serum and CSF levels of ET-1 between patients with clinically aggressive MS-ON (A-MS-ON) and nonaggressive MS-ON (NA-MS-ON) according to conventional ophthalmological criteria, including optical coherence tomography. CSF and serum concentrations of ET-1 were measured using a commercially available ELISA method.

Results: Sixteen patients consecutively referred to the Units of Neurology for visual disturbances attributable to MS were recruited, 11 (69%) patients with A-MS-ON and 5 (31%) with NA-MS-ON. Median CSF ET-1 levels and CSF/serum ET-1 quotient were significantly higher in patients with A-MS-ON (0.30 vs. 0.56 ng/ml) as compared to NA-MS-ON (0.16 vs. 0.16).

Conclusions: Severity and failure in the recovery from ON in MS patients may depend from vascular hypoperfusion of the optic nerve induced by high intrathecally produced ET-1, a potential prognostic marker of ON recovery in MS. The detection of CSF ET-1 levels may allow identifying groups of ON patients potentially benefitting from treatment with ET-1 antagonists (e.g., bosentan).

PubMed Disclaimer

Conflict of interest statement

All authors have no conflicting interests related to the topic.

References

    1. Adhya S., Johnson G., Herbert J., et al. Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. NeuroImage. 2006;33(4):1029–1035. doi: 10.1016/j.neuroimage.2006.08.008. - DOI - PMC - PubMed
    1. Law M., Saindane A. M., Ge Y., et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004;231(3):645–652. doi: 10.1148/radiol.2313030996. - DOI - PubMed
    1. D'haeseleer M., Hostenbach S., Peeters I., et al. Cerebral hypoperfusion: a new pathophysiologic concept in multiple sclerosis? Journal of Cerebral Blood Flow and Metabolism. 2015;35(9):1406–1410. doi: 10.1038/jcbfm.2015.131. - DOI - PMC - PubMed
    1. Aliev G., Smith M. A., Obrenovich M. E., de la Torre J. C., Perry G. Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Alzheimer disease. Neurotoxicity Research. 2003;5(7):491–504. doi: 10.1007/BF03033159. - DOI - PubMed
    1. Marshall O., Lu H., Brisset J. C., et al. Impaired cerebrovascular reactivity in multiple sclerosis. JAMA Neurology. 2014;71(10):1275–1281. doi: 10.1001/jamaneurol.2014.1668. - DOI - PMC - PubMed

MeSH terms