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Prevention of acute allograft dysfunction is the principal focus in the immediate post-transplant period. However, many immune-modulating agents have been associated with posterior reversible encephalopathy syndrome (PRES). We describe a complex case of extended critical illness triggered by PRES in the immediate post-transplant period, leading to super-refractory status epilepticus of unclear etiology and acute rejection of the 2 transplanted organs. Brain autopsy showed findings of multifocal necrotizing leukoencephalopathy (MNL). Our patient differed from previously described cases of PRES after heart transplantation in that our patient did not receive calcineurin inhibitors and had a fatal outcome. A delicate balance must be maintained between the risk of acute rejection in a high-risk patient with inadequate immunosuppression vs the risk of PRES from the use of aggressive immunosuppression. Furthermore, several antiseizure medications interfere with the metabolism of immunosuppressive medications and these potential interactions must be carefully considered to reduce morbidity and prevent mortality. Lastly, our case suggests that perhaps MNL should be considered in the differential diagnosis for refractory seizures in the setting of established risk factors, such as immunosuppression and sepsis.

Introduction: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals., Objective: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology., Methods: After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells., Results: We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis., Discussion: NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lopez-Rivera, Castano-Jaramillo, Yamazaki-Nakashimada, Ramirez Uribe, Corcuera Delgado, Ignorosa-Arellano, Medina-Torres, Berrón Ruiz, Espinosa-Padilla, Scheffler-Mendoza, López-Velázquez, Cruz-Munoz and Lugo Reyes.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan-McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3 +/- mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3 +/- mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light-dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3 +/- mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N -methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3 +/- animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3 +/- mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alamilla, Ramiro-Cortés, Mejía-López, Chavez, Rivera, Felipe and Aguilar-Roblero.)