Introduction
Inflammatory and neurodegenerative pathological features lead to cognitive impairment in 50–70% of multiple sclerosis patients. Biomarkers of axonal damage in multiple sclerosis include macular ganglion cell layer and retinal nerve fiber layer and its thickness may be associated with brain atrophy and cognitive impairment. Multiple sclerosis involves presence of oligoclonal bands in the cerebrospinal fluid (CSF) or an elevated immunoglobulin G index in up to 95% of patients.
Study Design
A prospective, single-center, observational cohort study.
Objective
To evaluate the effect of neurodegenerative markers such as retinal nerve fiber layer (RNFL) thickness and brain atrophy on cognitive decline of multiple sclerosis (MS) patients. The role of inflammatory biomarkers including intrathecal oligoclonal bands (OCBs) and immunoglobulin G (IgG) index was also assessed over a 5-year follow-up period.
Patient Population
49 MS patients (aged 18-60 years) diagnosed with relapsing-remitting MS being treated with stable-disease-modifying therapy at least for 3 months were enrolled in the study.
Patients with presence of primary or secondary progressive MS, neurological disorders other than MS, any vision or hearing problems influencing performance on the tests and optic neuritis during the observation period were excluded from the study.
Assessment Parameters
- Physical and neurological examinations: Expanded Disability Status Scale (EDSS)
- Neuropsychological assessment: Brief International Cognitive Assessment for MS (BICAMS)
- Ophthalmological examination: OCT for RNFL thickness and papillomacular bundle (PMB) thickness
- Brain MRI for brain atrophy, the Huckman index, third ventricle width and bicaudate ratio (BCR)
All evaluations were repeated 5 years (±14 days) later.
Results
- 63.3% of patients had positive OCBs and 59.2% had elevated IgG indices in the CSF.
- Positive OCBs and elevated IgG indices were similar, irrespective of gender, age and disease duration.
- The change in EDSS scores did not differ between patients with positive and negative OCBs. Similar results were found in patients with elevated and lower than normal IgG indices.
- The incidence of positive OCBs and elevated IgG indices was 63.3 and 59.2%, respectively, in patients.
- No relationship between positive OCBs and elevated IgG indices was observed.
- Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test Revised (BVMTR) scores were lower during the follow-up assessment compared to baseline.
- California Verbal Learning Test, Second Edition (CVLT-II) scores were unchanged.
- Overall RNFL thickness and individual RNFL thickness in the temporal, nasal, inferotemporal and inferonasal segments were lower in both eyes at the follow-up assessment.
- The average thickness of the PMB was lower in the right eye while in the left eye, the thickness of the superotemporal segment was lower.
- Huckman index and third ventricle width were significantly lower during the follow-up period.
- BCR remained unchanged during the follow-up assessments.
- In patients with relapsing MS, decline in information processing speed over 5 years was due to RNFL thickness in the temporal segment or PMB in both eyes and the CSF-OCBs.
Conclusion
Thinning of the RNFL and the presence of CSF-OCBs were found to be feasible biomarkers for cognitive decline in multiple sclerosis patients.