Background Individuals with Fragile X syndrome (FXS) and autism spectrum disorder (ASD) exhibit an array of symptoms, including sociability deficits, increased anxiety, hyperactivity, and sensory hyperexcitability. It is unclear how endocannabinoid (eCB) modulation can be targeted to alleviate neurophysiological abnormalities in FXS as behavioral research reveals benefits to inhibiting cannabinoid (CB) receptor activation and increasing endocannabinoid ligand levels. Here, we hypothesize that enhancement of 2-arachidonoyl-sn-glycerol (2-AG) in Fragile X mental retardation 1 gene knock-out (Fmr1 KO) mice may reduce cortical hyperexcitability and behavioral abnormalities observed in FXS. Methods To test whether an increase in 2-AG levels normalized cortical responses in a mouse model of FXS, animals were subjected to electroencephalography (EEG) recording and behavioral assessment following treatment with JZL-184, an irreversible inhibitor of monoacylglycerol lipase (MAGL). Assessment of 2-AG was performed using lipidomic analysis in conjunction with various doses and time points post-administration of JZL-184. Baseline electrocortical activity and evoked responses to sound stimuli were measured using a 30-channel multielectrode array (MEA) in adult male mice before, 4 h, and 1 day post-intraperitoneal injection of JZL-184 or vehicle. Behavior assessment was done using the open field and elevated plus maze 4 h post-treatment. Results Lipidomic analysis showed that 8 mg/kg JZL-184 significantly increased the levels of 2-AG in the auditory cortex of both Fmr1 KO and WT mice 4 h post-treatment compared to vehicle controls. EEG recordings revealed a reduction in the abnormally enhanced baseline gamma-band power in Fmr1 KO mice and significantly improved evoked synchronization to auditory stimuli in the gamma-band range post-JZL-184 treatment. JZL-184 treatment also ameliorated anxiety-like and hyperactivity phenotypes in Fmr1 KO mice. Conclusions Overall, these results indicate that increasing 2-AG levels may serve as a potential therapeutic approach to normalize cortical responses and improve behavioral outcomes in FXS and possibly other ASDs.

Background: The novel severe acute respiratory syndrome coronavirus 2 is responsible for over 83 million cases of infection and over 1.8 million deaths since the emergence of the COVID-19 pandemic. Because COVID-19 infection is associated with a devastating mortality rate and myriad complications, it is critical that clinicians better understand its pathophysiology to develop effective treatment. Cumulative evidence is suggestive of cerebral aneurysms being intertwined with the hyperinflammatory state and hypercytokinemia observed in severe COVID-19 infections. Case Description: In case example 1, the patient presents with chills, a mild cough, and sore throat. The patient develops high-grade fever of 39.8° C, decreased oxygen saturation of 93% on room air, and an extensive spontaneous subarachnoid hemorrhage (SAH) in the basal cisterns from a ruptured left posterior communicating artery aneurysm. In case example 2, the patient presents with a positive PCR test for COVID-19 2 weeks prior with spontaneous SAH and found to have a large multilobulated bulbous ruptured aneurysm of the anterior communicating artery. Both patients’ symptoms and high-grade fever are consistent with hypercytokinemia and a hyperinflammatory state, with elevated granulocyte colony-stimulating factor, inducible protein-10, monocyte chemoattractant protein-1, M1P1A, and tumor necrosis factor-α inflammatory mediators found to be elevated in COVID-19 intensive care unit admissions. Conclusion: COVID-19 effect on cerebral aneurysms requires future studies to clearly delineate correlation, however, hypercytokinemia and a hyperinflammatory state are strongly implicated to cause degenerative vascular changes that may predispose patients to cerebral aneurysm formation, change in size or morphology, and resultant aneurysm rupture.

Introduction: Liver disease affects approximately 3% of pregnant women and is associated with increased morbidity and mortality. This is worsened by the increased incidence of liver disease in pregnancy with COVID-19 infection. As incidence for these diseases rises, the importance of studying these conditions must also. We present a case of a patient with acute COVID-19 infection and HELLP syndrome as well as a summary of the associated literature. A 26-year-old G1P0 female at 32 weeks gestation with medical history of asthma, obesity, gestational DM, and HTN, presented to the ED for evaluation of general malaise. She had COVID-19 infection 2 weeks prior to presentation with symptoms of fever, chills, and dyspnea. Three days after admission, there was an acute drop in platelets and hemoglobin, elevated LDH, hypertension, and elevated LFTs, highly suggestive of HELLP syndrome. She underwent emergency cesarean delivery with rapid resolution of jaundice and LFT elevation. Methods: We gathered relevant published articles through a PubMed search from March 2020 to May 2022 using the keywords: HELLP, COVID-19, SARS-CoV-2, liver injury in pregnancy. No case-control or cohort studies on the relationship between COVID-19 and HELLP syndrome identified. A total of 5 similar case reports/ series were identified, compiling a total of 8 peripartum women who developed HELLP syndrome and tested positive for COVID-19. We then performed a literature review of these cases alongside our case. Results: The age of the patients ranged from 23-41 years (mean 29.2). 5 primigravida patients. The mean gestational age was 30.4 weeks. 6 patients diagnosed with COVID-19 on admission, 3 tested positive prior to admission. 6 patients presented to the hospital within 7 days of symptom onset, 3 within 10 days of symptom onset. Ground-glass opacities seen in 7 patients. 7 patients had undergone emergency cesarean section due to complications of HELLP syndrome. Outcomes included 6 living fetuses, 2 stillborn, 1 IUFD, and 1 maternal fatality. 6 of the patients had postoperative complications, including preeclampsia/eclampsia, hypertensive emergency, AHRF, ARF, acute blood loss anemia, sepsis, and CVA. (Table)Conclusion: There is a paucity of literature detailing a possible correlation between COVID-19 infection and the development and progression of HELLP syndrome. This case report and review should remain hypothesis-generating and prompt larger, multi-center studies to better describe and elucidate the interplay between these two conditions.