Contrast-induced encephalopathy (CIE) is an adverse event associated with diagnostic and therapeutic endovascular procedures. Decades of animal and human research support a mechanistic role for pathological blood-brain barrier dysfunction (BBBd). Here, we describe an institutional case series and review the literature supporting a mechanistic role for BBBd in CIE.

A literature review was conducted by searching MEDLINE, Web of Science, Embase, CINAHL and Cochrane databases from inception to January 31, 2022. We searched our institutional neurovascular database for cases of CIE following endovascular treatment of cerebrovascular disease during a 6-month period. Informed consent was obtained in all cases.

Review of the literature revealed risk factors for BBBd and CIE, including microvascular disease, pathological neuroinflammation, severe procedural hypertension, iodinated contrast load and altered cerebral blood flow dynamics. In our institutional series, 6 of 52 (11.5%) of patients undergoing therapeutic neuroendovascular procedures developed CIE during the study period. Four patients were treated for ischemic stroke and two patients for recurrent cerebral aneurysms. Mechanical stenting or thrombectomy were utilized in all cases.

In this institutional case series and literature review of animal and human data, we identified numerous shared risk factors for CIE and BBBd, including microvascular disease, increased procedure length, large contrast volumes, severe intraoperative hypertension and use of mechanical devices that may induce iatrogenic endothelial injury.

Many individuals with COVID-19 develop mild to moderate physical symptoms that can last days to months. In addition to physical symptoms, individuals with COVID-19 have reported depressive symptoms and cognitive decline, posing a long-term threat to mental health and functional outcomes. Few studies have examined the presence of co-occurring depression and subjective cognitive decline in individuals who tested positive for COVID-19. The current study examined whether having COVID-19 is subsequently associated with greater depressive symptoms and subjective cognitive decline when compared to healthy individuals. Our study also examined differential associations between symptoms of depression and subjective cognitive decline between individuals who have and have never had COVID-19.

Adults (N = 104; mean age = 37 years, 69% female) were recruited online from Ontario and British Columbia, Canada. Participants were categorized into two groups: (1) persons who tested positive for COVID-19 at least three months prior, had been symptomatic, and had not been ventilated (N = 50); and (2) persons who have never been suspected of having COVID-19 (N = 54). The Center for Epidemiological Studies Depression Scale (CES-D) and the Subjective Cognitive Decline Questionnaire (SCD-Q) were administered to both groups as part of a larger clinical neuropsychological evaluation. Two separate linear regression analyses were conducted to examine the association of COVID-19 with depressive symptoms and subjective cognitive decline. A moderation analysis was performed to examine whether depressive symptoms were associated with subjective cognitive decline and the extent to which this differed by group (COVID-19 and controls). Participants’ age, self-reported sex, and history of depression were included as covariates.

The first regression model explained 17.2% of the variance in CES-D scores. It was found that the COVID-19 group had significantly higher CES-D scores (ß = .20, p = .03). The second regression model explained 35.9% of the variance in SCD-Q scores. Similar to the previous model, it was found that the COVID-19 group had significantly higher SCD-Q scores compared to healthy controls (ß = .22 p = .01). Lastly, the moderation model indicated that higher CES-D scores were associated with higher SCD-Q scores (ß = .43, p < .01), but there was no statistically significant group X CES-D score interaction.

These findings suggest that individuals who previously experienced a mild to moderate symptomatic COVID-19 infection report greater depressive symptom severity as well as greater subjective cognitive decline. Additionally, while more severe depressive symptoms predicted greater subjective cognitive decline in our sample, the magnitude of this association did not vary between those with and without a previous COVID-19 infection. While the underlying neurobiological and social mechanisms of cognitive difficulties and depressive symptoms in persons who have had COVID-19 have yet to be fully elucidated, our findings highlight treatment for depression and cognitive rehabilitation as potentially useful intervention targets for the post COVID-19 condition.

The Rare and Atypical DIAbetes NeTwork (RADIANT) aims to discover the underlying pathoetiology of atypical diabetes by conducting both genotyping and non-genetic deep phenotyping. While the return of genetic test results in research settings has been investigated, the return of non-genetic results (RoR-NG) has received less attention. We explore the RoR-NG with RADIANT investigators and participants.

We conducted one-on-one interviews with 10 adult RADIANT participants and 10 RADIANT investigators. Participants also completed two health literacy screening tools and a survey on perspectives regarding return of results (RoR). Investigators completed one survey on experience and confidence in explaining clinical tests utilized in the RADIANT study and another survey on perspectives regarding RoR.

Most participants were non-Hispanic White. All participants had high scores on health literacy screens. Both RADIANT participants and investigators expressed strong support for RoR-NG. RADIANT participants and investigators acknowledged the different roles and responsibilities between research and clinical care for interpreting and acting on non-genetic results. However, the lines between clinical care and research in returning and acting on results were often blurred by both participants and investigators.

Our study provides important insight into how both investigators and participants simultaneously distinguish and blur clinical and research roles and responsibilities when discussing non-genetic research results and the return of these results. Further study should engage individuals from diverse racial and ethnic backgrounds and with varying levels of health literacy to understand how best to support all participants when returning research results.