Biomarkers of Multiple Sclerosis

Introduction: Scleroderma is a rare heterogeneous multisystem autoimmune disease. The disease is characterized by structural abnormalities of the small blood vessels. Scleroderma affects all organs of the body. Skin manifestations are commonly reported, but peripheral nervous system (PNS) and central nervous system (CNS) involvement has been less frequently reported. Neurological manifestations are broad, and it is challenging for clinicians to confirm a diagnosis of scleroderma. Case Presentation: In our case, a 53-year-old white woman had extensive clinical presentations: skin rashes and symptoms from internal organs, CNS, and PNS during the previous 11 years. She had not undergone any specific treatment because diagnosis has not been made in the early stages. Conclusion: It is important to make the diagnosis as early as possible and start treatment with immunomodulatory and immunosuppressant medication, as it affects the patient's disease progression, quality of life, and mortality. A detailed medical history, physical examination, and laboratory and radiology findings help us to identify and diagnose scleroderma. But unfortunately, it was late, and the patient died. This case guides us to be more careful and make the diagnosis of scleroderma earlier in the future.

Background and Objectives: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system. The disease can manifest and progress with both physical and cognitive symptoms, affecting the patient’s daily activities. The aim of our study was to investigate the correlation between functional status, cognitive functions, and neurofilament light chain levels in plasma in MS patients. Materials and Methods: In a cross-sectional study, MS patients with a relapsing–remitting course (according to McDonald’s criteria, 2017) (n = 42) from Riga East University Hospital and a control group (n = 42) were included. In the MS group, the functional status was determined using the Expanded Disability Status Scale (EDSS), and neurofilament light chain levels in plasma (pNfL) were detected using single molecule array (Simoa) technology. The symbol digit modalities test (SDMT), brief visuospatial memory test—revised (BVMT-R), and the nine-hole peg test (9-HPT) were performed on the MS and control groups, dividing the groups by education level. Results: On the SDMT spreading speed, the MS group performed worse than the control group. The median score for the control group was 94.0, and for the MS group, it was 81.3. Slower performance on the SDMT also correlated with a higher EDSS in the MS group. Cognitive processing speed and memory were better in the control group and among individuals with higher education in both groups. For the BVMT-R, we found no difference between the two groups; both groups were able to learn the task equally well, but we found a weak correlation between age and learning in both groups, which could be related to the normal aging process. Execution reaction speed on the 9-HPT with the dominant hand was slower in the MS group (24.1 s) than in the control group (19.4 s). In the MS group, we observed a trend between SDMT performance and pNfL levels: higher pNfL levels were found in individuals who performed more slowly on the SDMT. Conclusions: Cognitive and fine motor dysfunction correlates with neurological impairment and plasma neurofilament light chain levels in MS patients.

Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a rare subtype of autoimmune encephalitis, often presenting with early-onset, disease-specific neuropsychiatric symptoms. This case report describes a female patient with relapsing-remitting multiple sclerosis (RRMS) who developed anti-NMDA receptor encephalitis while receiving disease-modifying treatment. She exhibited neurocognitive symptoms and atypical magnetic resonance findings. Clinical and laboratory findings, including lumbar puncture, confirmed the presence of IgG antibodies against the GluN1 subunit of the NMDA receptor, establishing the diagnosis. First-line therapy with methylprednisolone and plasma exchange proved refractory, and immunoglobulin therapy yielded only a suboptimal response. Rituximab achieved the optimal therapeutic effect; however, therapy was followed by recurrent COVID-19 infection in this previously unvaccinated patient. This report highlights the complexities of diagnosis, differential considerations, therapeutic strategies and the detrimental impact of anti-NMDA receptor encephalitis and RRMS on the patient’s quality of life.

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL.

Background/Objectives: Multiple sclerosis (MS) remains challenging to diagnose due to clinical and radiological overlap with mimicking conditions. The 2024 revisions of the McDonald criteria have incorporated the central vein sign (CVS) and paramagnetic rim lesions (PRLs) as magnetic resonance imaging (MRI) biomarkers to improve diagnostic specificity. This study assessed the prevalence and anatomical distribution of CVS and PRLs in patients with relapsing–remitting MS (RRMS). Methods: This cross-sectional study included 91 patients with RRMS diagnosed according to the 2017 McDonald criteria. MRI scans were obtained using 3T scanners, and T2-FLAIR and susceptibility-weighted angiography (SWAN) sequences were analyzed. CVS and PRLs were identified using established criteria. Patients were stratified by lesion count (<5, 5–9, ≥10), and lesions were categorized by anatomical location. Descriptive statistics, chi-square tests, and multivariable logistic regression adjusted for covariates were performed. Results: CVS was present in 69.2% of patients, while PRLs were identified in 29.7%. Both markers were more frequent in patients with higher lesion burden in univariate analysis. CVS prevalence increased significantly with lesion count (p < 0.001) and remained an independent predictor in multivariable logistic regression. PRL presence was associated with lesion count in univariate analysis but not after adjustment. Most CVS- and PRL-positive lesions were supratentorial and predominantly periventricular. No significant association was observed between CVS and PRL presence. Conclusions: CVS is a highly prevalent MRI feature in RRMS and independently associated with lesion burden, supporting its role as a diagnostically relevant imaging marker. PRLs were less prevalent and showed weaker independent associations.