Caroline Tilikete

Recent revisions to multiple sclerosis (MS) diagnostic criteria include the optic nerve as a site of dissemination in space, enabling this diagnosis in patients with acute optic neuritis (ON) and a single additional MS-typical location on MRI if dissemination in time (DIT) is demonstrated. We aimed to assess the frequency of non-MS diagnoses in this context. We retrospectively analyzed consecutive patients with inaugural acute ON and at least 1 MS-typical lesion in a single brain location on baseline MRI across 3 French centers. All patients met DIT criteria and underwent aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing. Final diagnoses were based on clinical, radiologic, and follow-up data. Among 96 patients (mean age 35.8 years; 70.8% female), 73 (76.0%) were diagnosed with MS and 23 (24.0%) with MOG antibody-associated disease (n = 18) or neuromyelitis optica spectrum disorder. Longitudinally extensive lesions, bilateral involvement, chiasmal enhancement, or optic perineuritis were observed in 100% of non-MS patients and 24.6% of patients with MS (difference 75.4%, 95% CI: 64.3-86.6; p < 0.001). All patients without these patterns were ultimately diagnosed with MS. AQP4 and MOG antibody testing, along with careful orbital MRI interpretation, is recommended in patients with ON meeting minimal new MS criteria.

Background: Impaired vestibulo-ocular reflex (VOR) can be compensated by catch-up saccades and/or increased residual VOR. Prediction and intention seem able to potentiate both responses, but how do these effects combine, particularly in individuals with bilateral vestibulopathy (BVP), remains largely unknown. Objective: To compare the impact of passive, predictive and voluntary conditions of head impulse tests (HIT) on global oculomotor compensatory responses in individual with BVP. Methods: HIT were performed in Passive(P)-Random, Passive(P)-Cued and Active head movement conditions. VOR gain and latency and gain of the 1 ^st catch up saccades were calculated for the 32 tested ears. Among the 1 ^st catch up saccade, a separate analysis of covert saccades was performed. Results: Latency of covert saccades was shorter in the Active compared to P-Random and P-Cued. First saccades showed shorter latency and greater gain in the P-Cued condition versus P-Random. VOR gain was significantly higher in the Active condition compared to P-Random and P-Cued. Most individuals enhanced catch-up saccades and VOR gain simultaneously while others either boosted VOR gain while reducing saccade efficiency, or enhanced saccade efficiency while decreasing VOR gain. Conclusions: Prediction and intention improve gaze during HIT in individuals with BVP by optimising existent oculomotor responses. During active movements, these effects combined according to subjects’ individual strategies.

The identification of the RFC1 homozygous intronic expansion in cerebellar ataxia neuropathy and vestibular areflexia syndrome (CANVAS) highlighted that genetically determined CANVAS patients exhibit a wide range of clinical presentations and natural course. Previous studies suggested a link between disease severity and the size of the intronic expansion. The aim of our study was to obtain quantitative data related to vestibular and cerebellar impairments using oculomotor recordings to provide further evidence of a link between RFC1 intronic expansion size and the phenotype. This study recruited 26 genetically determined CANVAS patients in whom the size of the pathological intronic expansion was measured on both alleles. In addition to clinical data, we also recorded the Overall Neuropathy Limitation Scale (ONLS) and conducted objective oculomotor testing. According to the median expansion length on one allele, the patients were divided in a longer intronic repeat subgroup and a shorter intronic repeat subgroup. Given the homozygous nature of this disease, this analysis was carried out for the smallest and for the longest allele. We found for the smallest allele that vestibular deficit and cerebellar impairment were significantly more frequent and mean ONLS, smooth pursuit, pendular visually enhanced vestibulo-ocular reflex, and head impulse vestibulo-ocular reflex gains were significantly more impaired in the subgroup of patients with the long intronic repeat. This work provides objective evidence for a functional impact of the pathological intronic expansion size in CANVAS and highlights the interest of oculomotor assessment in research and clinical practice both for diagnostic and potentially prognostic purposes.

Higher-order visual symptoms of patients with posterior cortical atrophy (PCA) are not well recognized in routine ophthalmological examination. More specifically, vision as assessed by the Snellen or Monoyer chart may not be sensitive enough. We hypothesized increased visual difficulties related to 1) visual crowding and to 2) short distances/larger stimuli. We therefore aimed at comparing 1) far visual acuity measures using the Monoyer (each line is presented separately) and the ETDRS charts (all lines are presented at the same time), as well as 2) far and closer visual acuity using the ETDRS chart (at 4 and at 2 meters). These tests were performed in a group of patients with PCA (PCA-AD) and a group of typical amnesic form (T-AD as a control group) of Alzheimer disease (AD) without any ophthalmologic pathology. While the Monoyer chart did not allow to distinguish between the two groups, the PCA-AD group specifically displayed a decrease of visual acuity when the ETDRS chart, rather than the Monoyer chart, was tested at 4 meters (effect of visual crowding), and another decrease when the ETDRS chart was tested at 2 meters, rather than at 4 meters (effect of stimulus size/distance). This uncommon decrease of visual acuity with closer distance correlated with a score of higher-order visual symptoms (Q-ACP). The present study incites ophthalmologists to pay attention to the possible discrepancy between different conditions of visual acuity assessment and preconizes to combine these conditions for a better evaluation.

To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability. This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system. Data comparisons and statistical analyses between cytokine levels and clinical outcomes were performed. Eighty-eight patients with MOGAD and 32 patients with MS were included. Patients with MOGAD showed higher IL6 (p = 0.036), IL8 (p = 0.012), and IL18 (p = 0.026) baseline levels compared with those with MS, in non-optic neuritis (ON) presentations. BAFF values increased over time, especially in patients with MOGAD treated with anti-CD20 (p = 0.002). Baseline BAFF, CXCL10, IL10, and IL8 levels correlated with disease severity at MOGAD onset (all p < 0.05). Finally, higher baseline BAFF levels predicted lower risk of relapses (hazard ratio 0.41 [0.19; 0.89], p = 0.024). This study suggests a proinflammatory Th17-dominant profile in non-ON MOGAD patients, with a novel finding of a potential protective role of BAFF on relapses. These results shed new light on the pathogenesis of MOGAD, potentially guiding therapeutic decisions.