Stroke severity mediates the effect of socioeconomic disadvantage on poor outcomes among patients with intracerebral hemorrhage

BackgroundSocioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes.MethodsElectronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4–6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1–4), moderate (5–15), moderate–severe (16–20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling.ResultsA total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06–2.23]; p = 0.024), severe CSVD (2.14 [1.42–3.21]; p < 0.001), moderate (8.03 [2.76–17.15]; p < 0.001), moderate–severe (32.79 [11.52–93.29]; p < 0.001), and severe stroke (104.19 [37.66–288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75–6.69]; p < 0.001) and moderate (5.84 [2.27–15.01], p < 0.001), moderate–severe (27.59 [7.34–103.69], p < 0.001), and severe stroke (36.41 [9.90–133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation’s effect on severe disability or death (p = 0.005), while CSVD accounted for 4.9% (p = 0.524).ConclusionCSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes

MTHFR Gene Mutations Correlate with White Matter Disease Burden and Predict Cerebrovascular Disease and Dementia

The incidence of dementia is on the rise and expected to continue to increase in the foreseeable future. Two of the most common subtypes of dementia are Alzheimer’s subtype and vascular dementia. Hyperhomocysteinemia has been shown to serve as a risk factor for dementia due to an associated blood–brain barrier dysfunction and subsequent small-vessel disease pathology. There are varying causes for hyperhomocysteinemia, including genetic and dietary, among others. We highlight the importance of identifying hyperhomocysteinemia as a potential etiologic and therapeutic target for the most common subtypes of dementia

Delirium Leads to Poor In‐Hospital and 90‐Day Outcomes Among Patients With Acute Ischemic Stroke With and Without Intravenous Thrombolysis or Intraarterial Therapy

Background Delirium experienced poststroke is known to be associated with poor prognosis; however, the outcomes and functional consequences among patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis (intravenous tissue plasminogen activator) or intraarterial therapy are not well characterized. Methods Using data from 7 stroke centers with standardized delirium screening protocols, delirium was determined by a positive modified “Arousal, Attention, Abbreviated Mental‐Test, Acute Change Test” or Confusion Assessment Method for the Intensive Care Unit screen including diagnosis codes. Multivariable models were fit to estimate likelihoods of in‐hospital mortality, unfavorable discharge disposition, and longer length of stay among delirious patients with AIS, reported as adjusted odds ratios (aORs), adjusted incident rate ratios, and 95% CIs. A subset of patients with AIS with 90‐day modified Rankin scale (mRS) including those receiving intravenous tissue plasminogen activator or intraarterial therapy were analyzed for shifts in mRS scores associated with delirium, via ordinal logistic regression models. Results Between May 2016 and June 2021, AIS was the primary diagnosis in 12 409 hospitalization encounters representing 10 874 unique patients. Delirium was documented in 41.6% of AIS encounters, compared with 26.5% of age and mild cognitive impairment– or dementia‐matched non‐AIS encounters. Delirious (versus nondelirious) patients with AIS were older (median: 75 years versus 65 years), more frequently women (53.3% versus 48.7%), with a higher comorbidity burden (median Charlson Comorbidity Index: 7 versus 5). Delirious patients with AIS had higher odds of in‐hospital mortality (aOR, 2.66; [95% CI, 1.62–4.49]), unfavorable discharge disposition (aOR, 3.68; [95% CI, 3.15–4.30]), and longer length of stay (adjusted incidence rate ratio, 1.67; CI, 1.61–1.73). In the cohort of 2784 patients with treated and untreated AIS with 90‐day mRS, adjusted models indicated lower mRS (aOR, 0.54; CI, 0.46–0.63) associated with treatment, and higher mRS for delirious patients with AIS (aOR, 3.09; CI, 2.58–3.71). Among the subcohort of 948 patients with treated AIS, delirium remained significantly associated with higher mRS (aOR, 2.82; CI, 2.08–3.83). Conclusion Delirium is common among patients with AIS including those receiving intravenous tissue plasminogen activator or undergoing intraarterial therapy and prognosticates poor in‐hospital and 90‐day outcomes. Active screening and management of delirium may lead to improved stroke outcomes

Gene-Environment Interactions for Metals

It has become increasingly clear that the individual genetic background influences susceptibility to metal toxicity. Genetic variation in genes that regulate metal toxicokinetics and toxicodynamics influence the degree of metal accumulation and retention in the body, as well as toxic effects. Moreover, factors that regulate gene expression, so-called epigenetic factors, have been identified as targets for metal toxicity. This chapter addresses what is currently known about such gene-environment interactions. The picture that emerges for most metals is that the genetic influence is probably not attributed to a single gene for each metal; rather it is polygenic, with some genes having a stronger effect than others. The presence of variants of the human leukocyte antigen system and the risk of beryllium-related pulmonary disease was one of the first and maybe the strongest example of a gene-environment interaction. There are also clear gene-environment interactions for arsenic and lead. Evidence is rapidly growing for epigenetic effects of metals, e.g. for arsenic, cadmium, and lead, which may explain the association between metal exposure early in life and toxic effects later in life, as well as metal carcinogenicity

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded (<1%). Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681