Damien Biotti

BACKGROUND AND PURPOSE: Microvascular ischemic neuropathy is a common cause of third nerve palsy (TNP) in adults. Gadolinium enhancement of the intracavernous segment of the third cranial nerve (CNIII) has been previously reported in this context. Given the high spatial resolution of the 3D CISS sequence for analyzing the cavernous sinus, our objective was to evaluate the diagnostic accuracy of intracavernous third nerve changes on 3D contrast-enhanced CISS in differentiating microvascular ischemic TNP from other etiologies. MATERIALS AND METHODS: We conducted a single-center retrospective case-control study involving patients presenting with isolated TNP at the emergency department between 2018 and 2022, where all of whom underwent 3T MRI, including a 3D contrast-enhanced CISS sequence. Based on clinical examination and paraclinical investigations, a neurologist and an ophthalmologist jointly established the etiology of TNP during the initial patient care. Patients diagnosed with microvascular ischemic TNP were matched with a control group of TNP from other etiologies. Two radiologists independently assessed contrast enhancement and thickening of the intracavernous third nerve on the 3D contrast-enhanced CISS without knowledge of the etiological diagnosis. Sensitivity and specificity for diagnosing microvascular ischemic TNP were calculated. RESULTS: Fifty-four patients were included: 27 with microvascular ischemic TNP and 27 controls (59% men, mean age 72 years). The control group comprised TNP of inflammatory (18%), infectious (18%), aneurysmal (16%), tumoral (11%), stroke-related (22%), and undetermined (15%) origins. Contrast enhancement and thickening of the intracavernous third nerve were more frequent in microischemic TNP compared with the control group (78% versus 52%, P = .046, and 67% versus 27%, P = .003, respectively). The combination of contrast enhancement and nerve thickening demonstrated a sensitivity of 67% and a specificity of 74% for diagnosing microvascular ischemic TNP. CONCLUSIONS: Detection of contrast enhancement and thickening of the intracavernous third nerve by using the 3D contrast-enhanced CISS sequence on 3T MRI is significantly more frequent in microvascular ischemic TNP than in TNP from other etiologies. Though not specific, these findings may support this diagnosis when accompanied by supportive clinical features. Graphical Abstract

Background: Retrospective studies did not show strong evidence of higher risk of adverse neonatal or pregnancy outcomes in women with multiple sclerosis (MS) compared to general population, but there are contradictory data on prematurity, cesarean section, and small birthweight for gestational age (SGA). Methods: We compared pregnancy and birth outcomes in MS women included in RESPONSE, a French prospective cohort, with a recent survey (Enquête Nationale Périnatale (ENP)) describing leading indicators in perinatal epidemiology in France. Results: On 7 April 2023, 476 pregnancies (461 MS women, 482 expected newborns) from RESPONSE were available. The ENP study reported 12,723 women and 12,939 expected newborns in March 2021. MS patients were older (mean age 32.6 ± 4.4 vs. 30.9 ± 5.3 years, p < 0.001), with similar rate of cesarean (23.8% vs. 21.4%, p = 0.115) and use of locoregional analgesia (86.6% vs. 85.1%, p = 0.51). Preterm birth was less frequent (4.0% vs. 7.0%, p = 0.001). Birthweight of children from MS mothers was similar to general population (3240 ± 477.2 vs. 3264.5 ± 552.9 g, p = 0.22), with slightly more children with SGA (13.4% vs. 9.8%, p = 0.04). Conclusion: This prospective and contemporary comparison of pregnancy in MS women and the French population provides reassuring results. In the future, we need to assess the impact of disease-modifying treatment exposure during conception.

Optic Atrophy (OA) can be associated with the development of microcystic macular edema (MME) in the perifoveal retinal inner nuclear layer (INL). We aimed here to retrospectively determine the prevalence of MME in patients with non-glaucomatous OA in our tertiary ophthalmology department between 2015 and 2020. We then examined how MME affected the thicknesses of the different retinal layers and the differences in demographic and clinical characteristics between those patients who developed MME and those who did not. A total of 643 eyes (429 patients) were included (mean age 45.9 ± 17.8 years, 52% female). MME developed in 95 (15%) eyes and across all etiologies of OA except for toxic/nutritional causes, but the prevalence of MME varied between the different etiologies. The development of MME was associated with thinning of the ganglion cell layer (11.0 vs. 9.6 μm; p = 0.001) and the retinal nerve fiber layer (10.1 vs. 9.15 μm; p = 0.024), with INL thickening in the 3- and 6-mm diameter areas of the central fovea. Patients developing MME had significantly worse distance best-corrected visual acuity than those not developing MME (0.62 vs. 0.38 logMAR; p = 0.002). Overall, the presence of MME in OA cannot be used to guide the diagnostic work-up of OA.

Background: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021. Objectives: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022. Methods: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity. Results: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave ( p < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25–1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51–2.67]), obesity (OR = 2.36, 95% CI = [1.52–3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46–3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43–3.06] for EDSS 3–5.5 and OR = 4.53, 95% CI = [3.04–6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85–3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60–0.69]) or off (RR = 0.32, 95% CI = [0.30–0.33]) anti-CD20. Discussion: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status.

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12–17) years) treated with RTX/OCR with 6 month standard-interval dosing ( n = 9) or early extended-interval dosing ( n = 12, median (range) interval 18 months (12–25)). Within a median (range) follow-up of 31 (12–63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS.