Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

Predictive value of brain atrophy, serum biomarkers and information processing speed for early disease progression in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance. Methods: This prospective study included patients with MS diagnosed up to 1 year before recruitment. We analyzed serum biomarkers such as CXCL13, CHI3L1, OPN, IL-6, and GFAP and neurofilament light chains (NfLs); brain MRI parameters of linear atrophy such as bicaudate ratio (BCR), third ventricle width (TVW); and information processing speed were measured using the Symbol Digit Modalities Test (SDMT) during the 2 years follow-up. Results: The study included a total of 50 patients recruited shortly after the diagnosis of MS diagnosis (median 0 months; range 0-11 months), and the mean time of observation was 28 months (SD = 4.75). We observed a statistically significant increase in the EDSS score (Wilcoxon test: Z = 3.06, p = 0.002), BCR (Wilcoxon test: Z = 4.66, p < 0.001), and TVW (Wilcoxon test: Z = 2.84, p = 0.005) after 2 years of disease. Patients who had a significantly higher baseline level of NfL suffered from a more severe disease course as per the EDSS score (Mann-Whitney U-test: U = 107, Z = -2,74, p = 0.006) and presence of relapse (Mann-Whitney U-test: U = 188, Z = -2.01, p = 0.044). In the logistic regression model, none of the parameters was a significant predictor for the achieving of no evidence of disease activity status (NEDA). In the model considering all assessed parameters, only the level of NfL had a significant impact on disease progression, measured as the increase in EDSS (logistic regression: ß = 0.002, p = 0.017). Conclusion: We confirmed that NfL levels in serum are associated with more active disease. Moreover, we found that TVW at the time of diagnosis was associated with an impairment in cognitive function measured by information processing speed at the end of the 2-year observation. The inclusion of serum NfL and TVW assessment early in the disease may be a good predictor of disease progression independent of NEDA.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement.

BACKGROUND: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). METHODS: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. RESULTS: The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. CONCLUSIONS: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

Cognitive impairment in NMOSD-More questions than answers.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a type of central nervous system antibody-mediated disease which affects mainly optic nerves and spinal cord, but may also present with acute brainstem syndrome, acute diencephalic syndrome, and cerebral syndrome with typical brain lesions. One of the most disabling symptoms, diagnosed in 29%-67% of cases, is cognitive dysfunction, with such processes as memory, processing speed, executive function, attention, and verbal fluency being predominantly affected. However, description of cognition in NMOSD patients is still a relatively new area of research. METHODS: A systematic MEDLINE search was performed to retrieve all studies that investigated cognitive impairment and its clinical correlates in patients with NMOSD. RESULTS: We summarize the current knowledge on cognitive impairment profile, neuropsychological tests used to examine NMOSD patients, clinical and demographical variables affecting cognition, and magnetic resonance imaging correlates. We provide a comparison of cognitive profile of patients with multiple sclerosis and NMOSD. CONCLUSION: Patients with NMOSD are at significant risk of cognitive deficits. However, the knowledge of cognitive symptoms in NMOSD and potential modifying interventions is still scarce. Further accumulation of clinical data may facilitate effective therapeutic interventions.

The Role of Optical Coherence Tomography in Differential Diagnosis of Multiple Sclerosis and Autoimmune Connective Tissue Diseases with CNS Involvement.

The purpose of this study was to examine whether application of optical coherence tomography (OCT) measurements can provide a useful biomarker for distinguishing central nervous system (CNS) involvement in autoimmune connective tissue diseases (CTD) from multiple sclerosis (MS). An observational study included non-optic neuritis eyes of 121 individuals: 59 patients with MS, 30 patients with CNS involvement in CTD, and 32 healthy controls. OCT examination was performed in all subjects to measure retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, ganglion cell layer-inner plexiform layer (GCIPL) thickness, and volume of the macula. There was a significant group effect with regard to superior optic disc RNFL, macular RNFL, GCC, and GCIPL thickness, and macular volume. Post-hoc analysis revealed that MS patients have significantly smaller macular volume and thinner superior optic disc RNFL, macular RNFL, GCC, and GCIPL compared to healthy controls. CTD patients have significantly smaller superior optic disc RNFL, GCIPL, and GCC thickness compared to healthy controls. However, no significant group differences were observed between the patient groups (MS vs. CTD) on any outcome. Although a prominent retinal thinning may be a useful biomarker in MS patients, in a general population of individuals with a confirmed CNS involvement the use of OCT is not specific enough to discriminate between MS and autoimmune CTD.

Cognitive Dysfunction in the Early Stages of Multiple Sclerosis-How Much and How Important?

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that mainly affects young adults and that is one of the leading causes of disability in this age group, with cognitive impairment occurring early in the course of the disease. This article summarizes the current knowledge about cognitive dysfunction in the early phase of MS, including biomarkers, MRI correlates, and its value as a prognostic marker. RECENT FINDINGS: New sets of neuropsychological tests have been established to screen for cognitive dysfunction more easily and accurately. Moreover, structural changes detected by brain MRI and several biomarkers found in cerebrospinal fluid and blood serum have been recently correlated with decreased cognitive performance. Additionally, factors influencing cognition in MS, such as disease-modifying therapy, mood disorders, and lifestyle, are better described. Cognitive impairment early in the course of MS is suggested as a prognostic factor for disease progression. However, clear-cut definitions of the early stage of MS as well as unified criteria for the diagnosis of cognitive impairment are still lacking. New and more reliable tools for evaluating cognition in MS patients should be developed and introduced into everyday practice to facilitate the implementation of effective disease-modifying therapy, cognitive rehabilitation, and lifestyle management.