Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review.

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort's genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.

Central Retinal Artery Visualization with Cone-Beam CT Angiography.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

King-Devick Test Performance and Cognitive Dysfunction after Concussion: A Pilot Eye Movement Study.

(1) Background: The King-Devick (KD) rapid number naming test is sensitive for concussion diagnosis, with increased test time from baseline as the outcome measure. Eye tracking during KD performance in concussed individuals shows an association between inter-saccadic interval (ISI) (the time between saccades) prolongation and prolonged testing time. This pilot study retrospectively assesses the relation between ISI prolongation during KD testing and cognitive performance in persistently-symptomatic individuals post-concussion. (2) Results: Fourteen participants (median age 34 years; 6 women) with prior neuropsychological assessment and KD testing with eye tracking were included. KD test times (72.6 ± 20.7 s) and median ISI (379.1 ± 199.1 msec) were prolonged compared to published normative values. Greater ISI prolongation was associated with lower scores for processing speed (WAIS-IV Coding, r = 0.72, p = 0.0017), attention/working memory (Trails Making A, r = -0.65, p = 0.006) (Digit Span Forward, r = 0.57, p = -0.017) (Digit Span Backward, r= -0.55, p = 0.021) (Digit Span Total, r = -0.74, p = 0.001), and executive function (Stroop Color Word Interference, r = -0.8, p = 0.0003). (3) Conclusions: This pilot study provides preliminary evidence suggesting that cognitive dysfunction may be associated with prolonged ISI and KD test times in concussion.

Neuro-ophthalmologic complications of coronavirus disease 2019 (COVID-19).

Multiple neuro-ophthalmological manifestations have been described in association with COVID-19. These symptoms and signs may be the result of a range of pathophysiological mechanisms throughout the course from acute illness to recovery phase. Optic nerve dysfunction, eye movement abnormalities and visual field defects have been described.

Binocular Diplopia Caused by an Epiretinal Membrane With Foveal Displacement.

A 73-year-old woman presented with 3 years of monocular visual distortion and progressive binocular diplopia. She was found to have a comitant left hypertropia due to an epiretinal membrane causing inferior foveal drag. Displacement of the fovea from an epiretinal membrane is a likely under-recognized cause ocular cause of a comitant binocular diplopia.

Subtypes of type I IFN differentially enhance cytokine expression by suboptimally stimulated CD4(+) T cells.

Human type I interferons (IFNs) include IFN-ß and 12 subtypes of IFN-α. During viral infection, infiltrating memory CD4(+) T cells are exposed to IFNs, but their impact on memory T-cell function is poorly understood. To address this, we pretreated PBMCs with different IFNs for 16 h before stimulation with Staphylococcus aureus enterotoxin B and measured cytokine expression by flow cytometry. IFN-α8 and -α10 most potently enhanced expression of IFN-γ, IL-2, and IL-4. Potency among the subtypes differed most at doses between 10 and 100 U/mL. While enhancement of IL-2 and IL-4 correlated with the time of preincubation with type I IFN, IFN-γ production was enhanced best when IFN-α was added immediately preceding or simultaneously with T-cell stimulation. Comparison of T-cell responses to multiple doses of Staphylococcus aureus enterotoxin B and to peptide libraries from RSV or CMV demonstrated that IFN-α best enhanced cytokine expression when CD4(+) T cells were suboptimally stimulated. We conclude that type I IFNs enhance Th1 and Th2 function with dose dependency and subtype specificity, and best when T-cell stimulation is suboptimal. While type I IFNs may beneficially enhance CD4(+) T-cell memory responses to vaccines or viral pathogens, they may also enhance the function of resident Th2 cells and exacerbate allergic inflammation.