Optic nerve assessment identifies biomarkers of axonal pathology in multiple sclerosis

Abstract

Our aim was to identify possible correlations between physical disabilities assessed by expanded disability status score (EDSS) and neurodegenerative process measured by retinal nerve fibers thickness, and also with demyelization process measured by visual evoked potential with P100 wave latency at optic nerve level on patients diagnosed with multiple sclerosis (MS). This study aimed to find a structural biomarker at central nerve system (CNS) level which could correlate with clinical disability. The optic nerve is an accessible structure of CNS easy to investigate. We analyzed a population of 111 patients diagnosed with different clinical forms of multiple sclerosis based on 2005 revised Mc Donald criteria, for whom we assessed clinical disability by EDSS, and by different subscales of multiple sclerosis composite (MSFC) as timed to walk 25 foot (TW25F) and nine hole peg test (9HPT). Optic nerve involvement was assessed for each eye measuring visual acuity (VA) (Snellen chart), P100 wave latency by visual evoked potential (VEP) and retinal nerve fiber layer thickness (RNFL) by optical coherence tomography (OCT). The medium age of our population was 38.09 and the medium EDSS was 3.3. – 76 out of 111 were women. 79 patients were diagnosed with relapsing remitting (RR) MS, 7 with clinically isolated syndrome (CIS), the other were diagnosed with progressive form of MS: 7 with primary progressive MS and one with primary progressive with relapse MS. We obtained positive correlations, and statistically significant between EDSS and 9HPT for dominant hand (r=0.58, p = 0.0001) and also for non dominant hand (r = 0.66, p = 0.0001) using Pearson correlation. EDSS score correlates statistically significant with P100 wave latency and visual acuity for both eyes using Pearson correlation, so we obtained negative correlation between EDSS and VA for right eye (r = -0.45, p = 0.0001), and for left eye (r = -0.49, p = 0.0001). We also observed statistically significant positive correlation between EDSS and P100 wave latency for right eye (r = 0.405, p = 0.0001), and left eye (r = 0.400, p = 0.0001). RNFL doesn’t correlate with EDSS, VA or P100 wave latency. Using chi square correlation between EDSS score (we choose a cut of value of 3) and pathological value of RNFL by OCT we didn’t obtain a statistical significant result. The results were : for right eye phi = 0.01, p = 0.9), and for left eye (phi = -0.1, p = 0.3). Similar results were obtained for EDSS of 4.0. The results were: for right eye (phi=-0.009, p= 0.9), and for left eye (phi = 0.017, p = 0.8). In conclusion, in order to understand the pathology of multiple sclerosis the anterior optic nerve pathway offers an attractive model. Optic nerve assessment can be realized through non-invasive complementary methods. Functional and structural data of optic nerve can be obtained by VA measurement, VEP and OCT assessments. Our study showed that axonal pathology of the optic nerve (part of CNS exclusively composed by white matter) correlates with clinical disability measured by EDSS, suggesting that P100 latency is a functional biomarker of the disease. A prospective study to validate such a marker of the progression of the disease is needed.

Keywords

• optic nerve
• axonal pathology
• multiple sclerosis