Syphilis can present with diverse ocular manifestations, including optic nerve and retinal involvement, often mimicking inflammatory or demyelinating disorders. In patients with pre-existing demyelinating conditions, new visual symptoms are frequently attributed to demyelination, which may delay recognition of coexisting syphilitic eye disease. We report a man in his 40s with relapsing-remitting multiple sclerosis who developed sequential central scotomas without pain on eye movements or dyschromatopsia. Examination revealed bilateral vitreous cells, and optical coherence tomography (OCT) showed ellipsoid zone disruption. Serologic testing demonstrated a reactive rapid plasma reagin titre of 1:64, confirming syphilitic chorioretinopathy. Treatment with intravenous penicillin led to marked visual improvement and restoration of the ellipsoid zone on OCT. This underscores the need to consider syphilis in the differential diagnosis of optic neuritis, even in patients with known demyelinating disease, and highlights the value of thorough ophthalmic evaluation and OCT imaging in such presentations.

Background/Objectives: To evaluate changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with multiple sclerosis (MS) and healthy controls over a 15-year period. Methods: This is a retrospective, observational, longitudinal, case-control study. The study included 53 patients with relapsing-remitting MS and 44 age-matched healthy controls. pRNFL thickness was measured using optical coherence tomography (OCT) at baseline (2010) and 15 years later (2025) across 12 peripapillary sectors. Eyes were categorized into three groups: healthy control eyes (Control), eyes from MS patients without a history of optic neuritis (MSnoON), and eyes from MS patients with a history of optic neuritis (MS+ON). Median and interquartile range (IQR) were used for descriptive statistics. Non-parametric tests were applied for statistical analysis. Results: At baseline, the median pRNFL thickness was 94.8 µm in Control eyes, 86.3 µm in MSnoON eyes, and 69.5 µm in MS+ON eyes. After 15 years, the values were 88.5 µm, 80.8 µm, and 59.5 µm, respectively. Intragroup comparisons between 2010 and 2025 showed statistically significant reductions in pRNFL thickness across all three groups (Wilcoxon test, p < 0.05). Intergroup comparisons revealed significant differences among the three groups at both time points (Mann-Whitney test, p < 0.05). In all cases, Control eyes exhibited the greatest pRNFL thickness, followed by MSnoON eyes, and then MS+ON eyes. pRNFL thinning was not uniform across all peripapillary sectors. In MSnoON eyes, the temporo-superior and infero-nasal sectors appeared more resistant to fiber loss, whereas in MS+ON eyes, all sectors demonstrated significant thinning. Conclusions: Significant pRNFL thinning occurs over time in both MS and healthy eyes. Eyes from MS patients, regardless of a history of optic neuritis, exhibited greater loss than healthy controls. Sectoral analysis suggests differential vulnerability among peripapillary regions. The relative differences between Control, MSnoON, and MS+ON eyes were maintained over a 15-year period.

Concurrent headache and visual symptoms pose a diagnostic challenge across specialties, ranging from benign to life-threatening etiologies. Overlapping manifestations and terminological confusion often lead to misdiagnosis and delayed care. This narrative review searched eight databases from inception to May 5th, 2026, for articles on headache and visual symptoms. Extracted data were synthesized into a structured diagnostic framework. Key benchmarks were clarified across seven categories. Retinal migraine and migraine with aura are distinguished by monocular/binocular involvement, duration, and stroke risk. Visual snow syndrome is confirmed as a persistent disorder distinct from migraine aura. Life-threatening vascular emergencies-including giant cell arteritis, posterior reversible encephalopathy syndrome, subarachnoid hemorrhage, cerebral venous sinus thrombosis, and arterial dissection-exhibit unique red-flag patterns and imaging features. Intracranial pressure disorders present with pressure-dependent headaches. Optic neuritis subtypes (MS-associated, MOGAD, NMOSD) differ significantly in visual impairment, imaging lesions, treatment response, and prognosis. Occipital lobe epilepsy is differentiated by ultra-short visual hallucinations with ictal activity. Additional ophthalmic, structural, and infectious etiologies further broaden the differential spectrum. This evidence-based framework standardizes clinical differentiation of headache with visual symptoms. Emphasizing key historical features, red-flag signs, advanced imaging biomarkers, and antibody testing enables accurate classification, timely intervention, prevents irreversible vision loss and fatal complications, and optimizes long-term prognosis.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are inflammatory disorders of the CNS with distinct immunopathologic mechanisms and treatment responses and partially overlapping clinical phenotypes. The identification of aquaporin-4 (AQP4)-IgG and MOG-IgG has transformed disease classification and diagnosis, enabled a classification of antibody-defined subgroups, and facilitated the development of targeted therapies. However, optimal use of these biomarkers in clinical practice requires careful interpretation within the appropriate clinical and radiologic context. This review synthesizes current evidence on established and emerging fluid biomarkers in NMOSD and MOGAD, with emphasis on analytical performance, biological relevance, and clinical utility. We review antibody detection using cell-based assays, highlighting differences between live and fixed platforms and the impact of antigen conformation on sensitivity and specificity, particularly for MOG-IgG. Common causes of false-positive and false-negative results are discussed, including low-titer reactivity, testing in low pretest probability populations, treatment-related antibody titer reduction, and assay-specific limitations. The diagnostic challenges posed by indiscriminate testing in adult cohorts with multiple sclerosis, in whom disease prevalence markedly exceeds that of MOGAD, are emphasized. We also discuss the role of repeat testing during acute attacks and paired serum-CSF analysis in improving diagnostic confidence when results are equivocal or discordant. Beyond disease-defining antibodies, we examine biomarkers of tissue injury and immune activation. Serum and CSF neurofilament light chain and glial fibrillary acidic protein provide complementary measures of neuroaxonal and astrocytic damage and show associations with attack severity, disease activity, relapse risk, and long-term disability. Cytokines, chemokines, and complement components reflect inflammatory pathways, including IL-6-driven immune activation in NMOSD and MOGAD and complement-mediated astrocytopathy in NMOSD, and may support mechanistic stratification and treatment monitoring in both conditions. We further review the contribution of CSF analysis, neuropathology, genetics, and antigen discovery platforms to refine disease classification, particularly in seronegative or atypical presentations. Finally, we outline priorities for future research, including assay harmonization, standardized sampling protocols, longitudinal biomarker profiling, and integrative multiomic approaches. Collectively, advances in biomarker science have the potential to improve diagnostic precision, guide individualized therapeutic strategies, and support de-escalation decisions in NMOSD and MOGAD.

Eculizumab, a humanized monoclonal antibody targeting the complement protein C5, is highly efficient in paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. However, recent reports have highlighted a subset of patients who show inadequate treatment response, prompting dose escalation or interval shortening. The serum concentration required for sustained inhibition of the complement lytic pathway remains uncertain, and the commonly cited 50-100 µg/ml range is not grounded in robust pharmacokinetic-pharmacodynamic data. Using publicly available clinical data digitized from four rare indications, we trained machine-learning supervised classifiers to predict complete C5 inhibition as a function of serum eculizumab concentration, identifying logistic regression on log-transformed concentration as the best and mechanistically appropriate model on real data. We then examined whether augmenting the real training data with high-fidelity synthetic data improves the resulting estimate. Although augmentation did not significantly change balanced accuracy, it reduced the confidence interval for the effective concentration by roughly 12-fold (a 92% reduction). The augmentation-stabilized estimate of the concentration associated with complete C5 inhibition was approximately 310.8-335.2 µg/ml (real-data-only estimate 338 µg/ml, 95% CI 275-454). These data-driven, hypothesis-generating results indicate that current maintenance targets aimed at near-complete C5 suppression may be substantially underestimated and that faithful synthetic augmentation can improve the precision of model-based pharmacological estimates in rare diseases; prospective validation in independent cohorts is required before any clinical application.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare multifocal inflammatory disease that primarily affects the optic nerve and spinal cord, leading to visual loss and paralysis. Although current research has identified numerous biomarker changes in the cerebrospinal fluid (CSF), the causal relationships between these changes and NMOSD are not yet fully understood, and they are susceptible to confounding factors. In this study, Mendelian randomization (MR) analyses were conducted to estimate the role of CSF metabolites in aquaporin-4 (AQP4)-IgG positive and AQP4-IgG negative NMOSD. We strictly adhered to the 3 principles of MR when selecting instrumental variables, effectively reducing the impact of confounding variables. Additionally, we conducted a comprehensive and meticulous sensitivity analysis to ensure the robustness of positive outcomes. We have elucidated the roles of several CSF metabolites in NMOSD, with specific glycerophosphocholine species showing risk associations in AQP4-IgG positive and AQP4-IgG negative subtypes, while ascorbate and N-acetylhexosamines demonstrate protective effects across both subtypes, thereby providing valuable insights. No evidence of heterogeneity or horizontal pleiotropy was observed in MR analyses. These metabolites hold the potential to inform pathogenesis and guide the development of therapeutic strategies for these conditions.