Climate change and disorders of the nervous system.

Anthropogenic climate change is affecting people's health, including those with neurological and psychiatric diseases. Currently, making inferences about the effect of climate change on neurological and psychiatric diseases is challenging because of an overall sparsity of data, differing study methods, paucity of detail regarding disease subtypes, little consideration of the effect of individual and population genetics, and widely differing geographical locations with the potential for regional influences. However, evidence suggests that the incidence, prevalence, and severity of many nervous system conditions (eg, stroke, neurological infections, and some mental health disorders) can be affected by climate change. The data show broad and complex adverse effects, especially of temperature extremes to which people are unaccustomed and wide diurnal temperature fluctuations. Protective measures might be possible through local forecasting. Few studies project the future effects of climate change on brain health, hindering policy developments. Robust studies on the threats from changing climate for people who have, or are at risk of developing, disorders of the nervous system are urgently needed.

Social environment-based opportunity costs dictate when people leave social interactions.

There is an ever-increasing understanding of the cognitive mechanisms underlying how we process others' behaviours during social interactions. However, little is known about how people decide when to leave an interaction. Are these decisions shaped by alternatives in the environment - the opportunity-costs of connecting to other people? Here, participants chose when to leave partners who treated them with varying degrees of fairness, and connect to others, in social environments with different opportunity-costs. Across four studies we find people leave partners more quickly when opportunity-costs are high, both the average fairness of people in the environment and the effort required to connect to another partner. People's leaving times were accounted for by a fairness-adapted evidence accumulation model, and modulated by depression and loneliness scores. These findings demonstrate the computational processes underlying decisions to leave, and highlight atypical social time allocations as a marker of poor mental health.

Differences in Cardiovascular Health at the Intersection of Race, Ethnicity, and Sexual Identity.

Importance: An understanding of the intersectional effect of sexual identity, race, and ethnicity on disparities in cardiovascular health (CVH) has been limited. Objective: To evaluate differences in CVH at the intersection of race, ethnicity, and sexual identity using the American Heart Association's Life's Essential 8 measure. Design, Setting, and Participants: This cross-sectional study was conducted from July 27 to September 6, 2023, using National Health and Nutrition Examination Survey data from 2007 to 2016. Participants were noninstitutionalized, nonpregnant adults (aged 18-59 years) without cardiovascular disease or stroke. Exposures: Self-reported sexual identity, categorized as heterosexual or sexual minority (SM; lesbian, gay, bisexual, or "something else"), and self-reported race and ethnicity, categorized as non-Hispanic Black (hereafter, Black), Hispanic, non-Hispanic White (hereafter, White), and other (Asian, multiracial, or any other race and ethnicity). Main Outcome and Measures: The primary outcome was overall CVH score, which is the unweighted mean of 8 CVH metrics, assessed from questionnaire, dietary, and physical examination data. Regression models stratified by sex, race, and ethnicity were developed for the overall CVH score and individual CVH metrics, adjusting for age, survey year, and socioeconomic status (SES) factors. Results: The sample included 12 180 adults (mean [SD] age, 39.6 [11.7] years; 6147 [50.5%] male, 2464 [20.2%] Black, 3288 [27.0%] Hispanic, 5122 [42.1%] White, and 1306 [10.7%] other race and ethnicity). After adjusting for age, survey year, and SES, Black (ß, -3.2; 95% CI, -5.8 to -0.6), Hispanic (ß, -5.9; 95% CI, -10.3 to -1.5), and White (ß, -3.3; 95% CI, -6.2 to -0.4) SM female adults had lower overall CVH scores compared with their heterosexual counterparts. There were no statistically significant differences for female adults of other race and ethnicity (ß, -2.8; 95% CI, -9.3 to 3.7) and for SM male adults of any race and ethnicity compared with their heterosexual counterparts (Black: ß, 2.2 [95% CI, -1.2 to 5.7]; Hispanic: ß, -0.9 [95% CI, -6.3 to 4.6]; White: ß, 1.5 [95% CI, -2.2 to 5.2]; other race and ethnicity: ß, -2.2 [95% CI, -8.2 to 3.8]). Conclusions and Relevance: In this cross-sectional study, CVH differed across race and ethnicity categories in SM females, suggesting that different communities within the larger SM population require tailored interventions to improve CVH. Longitudinal studies are needed to identify the causes of CVH disparities, particularly in Black and Hispanic SM females and inclusive of other racial and ethnic identities.

A review of histopathologic and radiologic features of non-atherosclerotic pathologies of the extracranial carotid arteries.

Diseases of the carotid arteries can be classified into different categories based on their origin. Atherosclerotic carotid disease remains the most encountered arterial wall pathology. However, other less-common non-atherosclerotic diseases can have detrimental clinical consequences if not appropriately recognized. The underlying histological features of each disease process may result in imaging findings that possess features that are obvious of the disease. However, some carotid disease processes may have histological characteristics that manifest as non-specific radiologic findings. The purpose of this manuscript is to review various non-atherosclerotic causes of carotid artery disease as well as their histologic-radiologic characteristics to aid in the appropriate recognition of these less-commonly encountered pathologies.

A Randomized Clinical Trial of Catheter Ablation and Antiarrhythmic Drug Therapy for Suppression of Ventricular Tachycardia in Ischemic Cardiomyopathy: The VANISH2 Trial.

Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT. The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques. The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction. Clinicaltrials.gov registration NCT02830360.

Final phase I substudy results of ivosidenib in patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome.

Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor and has shown efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in front-line and relapsed/refractory (R/R) mIDH1 AML populations. We report final data from a phase I single-arm substudy (NCT02074839) of patients with R/R mIDH1 MDS following failure of standard-of-care therapies. Oral ivosidenib was taken once daily on days 1-28 in 28-day cycles. Primary objectives were to determine safety, tolerability, and clinical activity. The primary efficacy endpoint was the complete remission + partial remission (CR+PR) rate. Nineteen patients were enrolled; 18 were included in the efficacy analysis. Treatment-related adverse events occurred in eight (42.1%) patients, including a grade 1 QT interval prolongation in one (5.3%) patient and grade 2 differentiation syndrome in two (10.5%) patients. Rates of CR+PR and objective response (CR +PR+marrow CR) were 38.9% (95% confidence interval [CI]: 17.3, 64.3) and 83.3% (95% CI: 58.6, 96.4), respectively. Kaplan-Meier estimates showed a 68.6% probability of patients in CR achieving a remission duration of >=5 years, and a median OS of 35.7 months. Of note, 71.4% and 75.0% baseline red blood cell (RBC) and platelet transfusion-dependent patients, respectively, became transfusion independent (TI; no transfusion >=56 days); 81.8% and 100% of baseline RBC and platelet TI patients, respectively, remained TI. One (5.3%) patient proceeded to a hematopoietic stem cell transplant by data cut-off. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in patients with mIDH1 R/R MDS.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Lipid clinic experience with bempedoic acid in three UK centres.

OBJECTIVE: Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid. METHODS: This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres - a university hospital (n = 77) and two district general hospitals (n = 106 and 33). Cardiovascular disease (CVD) risk factors, prescription qualification criteria, efficacy and adverse effects were assessed. RESULTS: The population was aged 65.9 ± 11.0 years, 42% were male, 25% had type 2 diabetes, and 31% had familial hypercholesterolaemia. CVD was present in 19% and multibed vascular disease in 8%. Statin intolerance was reported in 92%. Bempedoic acid reduced total cholesterol by 1.58 ± 1.44 mmol/L (20%), LDL-C by 1.37 ± 1.31 mmol/L (27%), triglycerides by 0.22 mmol/L (2%) with an 0.06 mmol/L (1%) increase in HDL-C after 22 ± 9 months follow-up. An LDL-C <2.5 mmol/L was achieved in 40% and <2 mmol/L in 20%. Efficacy (r2 = .33) was predicted by baseline LDL-C (ß = .54; p <.001). No significant changes were seen in transaminases, creatinine, creatine kinase, urate or HbA1c. Treatment was discontinued by 33% of patients and occurred due to myalgia (43%), lack of efficacy (16%) and gastrointestinal adverse effects (15%). No cases of gout were observed. In a logistic regression only the number of previous drug classes not tolerated (ß = 1.60; p = .009) was a contributing factor to discontinuation. CONCLUSION: This audit suggests that bempedoic acid therapy is effective but that adverse effects and discontinuation are common. This suggests nocebo effects might be generalizable to all lipid-lowering drug therapies in susceptible individuals.

Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice.

The localization, number, and function of postsynaptic AMPA-type glutamate receptors (AMPARs) are crucial for synaptic plasticity, a cellular correlate for learning and memory. The Hippo pathway member WWC1 is an important component of AMPAR-containing protein complexes. However, the availability of WWC1 is constrained by its interaction with the Hippo pathway kinases LATS1 and LATS2 (LATS1/2). Here, we explored the biochemical regulation of this interaction and found that it is pharmacologically targetable in vivo. In primary hippocampal neurons, phosphorylation of LATS1/2 by the upstream kinases MST1 and MST2 (MST1/2) enhanced the interaction between WWC1 and LATS1/2, which sequestered WWC1. Pharmacologically inhibiting MST1/2 in male mice and in human brain-derived organoids promoted the dissociation of WWC1 from LATS1/2, leading to an increase in WWC1 in AMPAR-containing complexes. MST1/2 inhibition enhanced synaptic transmission in mouse hippocampal brain slices and improved cognition in healthy male mice and in male mouse models of Alzheimer's disease and aging. Thus, compounds that disrupt the interaction between WWC1 and LATS1/2 might be explored for development as cognitive enhancers.

Does Inter-Residue Hydrogen Bonding in ß-(1→4)-Linked Disaccharides Influence Linkage Conformation in Aqueous Solution?

Two disaccharides, methyl ß-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl ß-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective 13C-enrichment to allow measurement of six trans-O-glycosidic J-couplings (2JCOC, 3JCOCH, and 3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J-couplings to either ϕ or ψ. MA'AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5' of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-µs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3-14%) and could not be validated by MA'AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ/ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3.

Decision making capacity for treatment in psychiatric inpatients: a systematic review and meta-analysis.

Decision-making capacity (DMC) among psychiatric inpatients is a pivotal clinical concern. A review by Okai et al. (2007) suggested that most psychiatric inpatients have DMC for treatment, and its assessment is reliable. Nevertheless, the high heterogeneity and mixed results from other studies mean there is considerable uncertainty around this topic. This study aimed to update Okai's research by conducting a systematic review with meta-analysis to address heterogeneity. We performed a systematic search across four databases, yielding 5351 results. We extracted data from 20 eligible studies on adult psychiatric inpatients, covering DMC assessments from 2006 to May 2022. A meta-analysis was conducted on 11 papers, and a quality assessment was performed. The study protocol was registered on PROSPERO (ID: CRD42022330074). The proportion of patients with DMC for treatment varied widely based on treatment setting, the specific decision and assessment methods. Reliable capacity assessment was feasible. The Mini-Mental State Examination (MMSE), Global Assessment of Function (GAF), and Brief Psychiatric Rating Scale (BPRS) predicted clinical judgments of capacity. Schizophrenia and bipolar mania were linked to the highest incapacity rates, while depression and anxiety symptoms were associated with better capacity and insight. Unemployment was the only sociodemographic factor correlated with incapacity. Assessing mental capacity is replicable, with most psychiatric inpatients able to make treatment decisions. However, this capacity varies with admission stage, formal status (involuntary or voluntary), and information provided. The severity of psychopathology is linked to mental capacity, though detailed psychopathological data are limited.

MA'AT Analysis: Unbiased Multi-State Conformational Modeling of Exocyclic Hydroxymethyl Group Conformation in Methyl Aldohexopyranosides.

MA'AT analysis (J. Chem. Inf. Model. 2022, 62, 3135-3141) has been applied to model exocyclic hydroxymethyl group conformation in methyl ß-D-glucopyranoside (ßGlcOMe), methyl ß-D-galactopyranoside (ßGalOMe), and methyl ß-D-mannopyranoside (ßManOMe) in an unbiased manner. Using up to eight NMR J-couplings sensitive to rotation about the C5-C6 bond (torsion angle ω), two-state models of ω were obtained that are qualitatively consistent with the relative populations of the gg, gt, and tg rotamers reported previously. MA'AT analysis gave consistent unbiased gt ⇌ tg models of ω in ßGalOMe, with gt more populated than tg and mean values of ω for each population similar to those obtained from aqueous 1-µs MD simulation. Using different combinations of J-couplings had little effect on the ßGalOMe model in terms of the mean values of ω and circular standard deviations (CSDs). In contrast, MA'AT analysis of ω in ßGlcOMe and ßManOMe produced more than one two-state model independent of the ensemble of J-values used in the analyses. These models were characterized by gg ⇌ gt conformer exchange as expected, but the mean values of ω in both conformers varied significantly in the different fits, especially for the gg rotamer. Constrained (biased) MA'AT analyses in which only staggered geometries about ω were allowed gave RMSDs slightly larger than those obtained from the unbiased fits, precluding an assignment of an unbiased model. It is unclear why MA'AT analysis gives consistent and predictable unbiased models of ω in ßGalOMe but not in ßGlcOMe and ßManOMe. One possibility is that the distribution of ω in one or both of the gg and gt conformers in the latter does not conform to a von Mises function (i.e., is not Gaussian-like), but rather to a broad and/or flat distribution that cannot be fit by the current version of MA'AT. Nevertheless, the results of this study provide new evidence of the ability of MA'AT analysis to treat multi-state conformational exchange using only experimental NMR data, extending recent MA'AT applications to furanosyl ring pseudorotation (Biochemistry 2022, 61, 239-251).

Validation of the familial chylomicronaemia syndrome (FCS) score in an ethnically diverse cohort from UK FCS registry: Implications for diagnosis and differentiation from multifactorial chylomicronaemia syndrome (MCS).

BACKGROUND AND AIMS: Prognosis and management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it. METHODS: A retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis. RESULTS: At the recommended FCS score threshold ≥10 points, the sensitivity and specificity of the score in the UK population were 96% and 75%, respectively. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.88 (95% CI 0.83-0.94, p < 0.001). This study identified non-European (predominantly South Asian) ethnicity, parental consanguinity, body mass index (BMI) < 25 kg/m2, and recurrent pancreatitis as additional positive predictors, while BMI >30 kg/m2 was found to be a negative predictor for FCS. However, inclusion of additional FCS predictors had no significant impact on performance of standard FCS score. CONCLUSIONS: Our study validates the FCS score in the UK population to distinguish FCS from MCS. While additional FCS predictors were identified, they did not improve further the score diagnostic performance.

Etiological Factors and Symptom Triggers in Functional Motor Symptoms and Functional Seizures: A Pilot Investigation.

OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.

Heterogeneity of State Stroke Center Certification and Designation Processes.

BACKGROUND: Stroke centers are critical for the timely diagnosis and treatment of acute stroke and have been associated with improved treatment and outcomes; however, variability exists in the definitions and processes used to certify and designate these centers. Our study categorizes state stroke center certification and designation processes and provides examples of state processes across the United States, specifically in states with independent designation processes that do not rely on national certification. METHODS: In this cross-sectional study from September 2022 to April 2023, we used peer-reviewed literature, primary source documents from states, and communication with state officials in all 50 states to capture each state's process for stroke center certification and designation. We categorized this information and outlined examples of processes in each category. RESULTS: Our cross-sectional study of state-level stroke center certification and designation processes across states reveals significant heterogeneity in the terminology used to describe state processes and the processes themselves. We identify 3 main categories of state processes: No State Certification or Designation Process (category A; n=12), State Designation Reliant on National Certification Only (category B; n=24), and State Has Option for Self-Certification or Independent Designation (category C; n=14). Furthermore, we describe 3 subcategories of self-certification or independent state designation processes: State Relies on Self-Certification or Independent Designation for Acute Stroke Ready Hospital or Equivalent (category C1; n=3), State Has Hybrid Model for Acute Stroke Ready Hospital or Equivalent (category C2; n=5), and State Has Hybrid Model for Primary Stroke Center and Above (category C3; n=6). CONCLUSIONS: Our study found significant heterogeneity in state-level processes. A better understanding of how these differences may impact the rigor of each process and clinical performance of stroke centers is worthy of further investigation.