Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune Encephalomyelitis.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Characterized by pathogenic immunoglobulin G (IgG) antibodies against MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG levels, e.g., by interference with the IgG recycling pathway mediated by the neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Our objective was to investigate effects of a monoclonal anti-FcRn antibody in murine MOG-IgG-associated experimental autoimmune encephalomyelitis (EAE). METHODS: We induced active MOG35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were assessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by immunofluorescence. RESULTS: In MOG-IgG-augmented MOG35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89-54.15]; isotype IgG [n = 24], 66.75 [59.54-73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and complement deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48-0.55] to 0.50 [0.48-0.58]; isotype IgG [n = 17], 0.50 [0.49-0.54] to 0.45 [0.39-0.51]). DISCUSSION: We show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.

Management of postoperative internal carotid artery intimal flap after carotid endarterectomy: a cohort study and systematic review.

OBJECTIVE: Postoperative internal carotid artery (ICA) intimal flap (IF) is a potential complication after carotid endarterectomy (CEA) for carotid artery stenosis. There are no clear recommendations in the current literature on the management of this condition due to sparse evidence. Some authors advocate carotid stent placement or reoperation, while others suggest watchful waiting. The aim of this study was to analyze incidence and management strategies of postoperative ICA-IF, and moreover, to put these findings into context with a systematic literature review. METHODS: The authors retrospectively reviewed all consecutive CEA cases performed at the University Hospital of Bern over a decade (January 2008 to December 2018). The incidence of postoperative ICA-IF, risk factors, management strategies, and outcomes were analyzed. These results were put into context with a systematic review following the PRISMA guidelines. RESULTS: A total of 725 CEAs were performed between January 2008 and December 2018. Postoperative ICA-IF was detected by routine duplex neurovascular ultrasound (NVUS) in 13 patients, corresponding to an incidence rate of 1.8% (95% CI 1.0%-3.1%). There were no associated intraluminal thrombi on the detected IF. Intraoperative shunt placement was used in 5.6% and one or more intima tack sutures were performed in 42.5% of the 725 cases. There was no significant association between intraoperative shunt placement and the occurrence of an IF (p > 0.99). Two patients (15.4%) with IF experienced a transient postoperative neurological deficit (transient ischemic attack). In these cases, the symptoms resolved spontaneously without any interventions or change in the antiplatelet regimen. All other cases (84.6%) with IF were asymptomatic. In 1 patient (7.7%) with IF, the antiplatelet treatment was switched from a mono- to a dual-antiaggregating regimen because the IF led to a stenosis > 70%; this patient remained asymptomatic. All cases of IFs were managed conservatively with close radiological follow-up evaluations, without reoperation or stenting of the ICA. All 13 IFs vanished spontaneously after a mean duration of 6.9 months (median 1.5 months, range 0.5-48 months). A systematic literature review revealed a postoperative ICA-IF incidence of 3.0% (95% CI 2.1%-4.1%) with relatively heterogenous management strategies. CONCLUSIONS: Postoperative ICA-IF is a rare finding after CEA. Conservative therapy with close NVUS follow-up evaluations appears to be an acceptable and safe management strategy for asymptomatic IFs without associated intraluminal thrombi.