Natural history of non-polyglutamine CACNA1A disease in Austria.

BACKGROUND AND OBJECTIVES: Non-polyglutamine CACNA1A variants underlie an extremely variable phenotypic spectrum encompassing developmental delay, hemiplegic migraine, epilepsy, psychiatric symptoms, episodic and chronic cerebellar signs. We provide our experience with the long-term follow-up of CACNA1A patients and their response to interval therapy. METHODS: Patients with genetically confirmed non-polyglutamine CACNA1A disease were prospectively followed at the Center for Rare Movement Disorders of the Medical University of Innsbruck from 2004 to 2024. RESULTS: We recruited 41 subjects with non-polyglutamine CACNA1A disease, of which 38 (93%) familial cases. The mean age at the first examination was 35 ± 22 years. Disease onset was in the childhood/adolescence in 31/41 patients (76%). Developmental delay and episodic symptoms were the first disease manifestation in 9/41 (22%) and 32/41 (78%) patients respectively. Chronic neurological signs encompassed a cerebellar syndrome in 35/41 (85%), which showed almost no progression during the observation period, as well as cognitive deficits in 9/20 (45%, MOCA test score < 26), psychiatric and behavioral symptoms in 11/41(27%). Seizures occurred in two patients concomitant to severe hemiplegic migraine. At the last visit, 27/41 patients (66%) required an interval prophylaxis (including acetazolamide, flunarizine, 4-aminopyridine, topiramate), which was efficacious in reducing the frequency and severity of episodic symptoms in all cases. In one patient in his 70ies with progressively therapy resistant hemiplegic migraine, treatment with the anti-CGRP antibody galcanezumab successfully reduced the frequency of migraine days from 4 to 1/month. CONCLUSIONS: Non-polyglutamine CACNA1A disease show an evolving age-dependent presentation. Interval prophylaxis is effective in reducing the burden of episodic symptoms.

High-Sensitivity Cardiac Troponin T and Cardiovascular Risk After Ischemic Stroke or Transient Ischemic Attack.

Background: High-sensitivity cardiac troponin T (hs-cTnT) is associated with cardiovascular disease (CVD) risk in general and various high-risk populations. Objectives: The purpose of this study was to precisely characterize the association of hs-cTnT with CVD risk in patients following acute ischemic stroke or transient ischemic attack. Methods: We conducted post hoc analyses of data from the STROKE-CARD trial (NCT02156778), a pragmatic randomized controlled trial of a disease management program in patients with acute ischemic stroke or transient ischemic attack (ABCD2 score ≥3). We measured hs-cTnT on admission (Roche Elecsys, detection limit 5 ng/L) and quantified HRs for a composite CVD outcome (ie, stroke, myocardial infarction, CVD death) adjusted for age, sex, prior coronary heart disease, prior heart failure, diabetes, smoking, systolic blood pressure, and low- and high-density-lipoprotein cholesterol. Results: Among 1,687 patients (mean age, 69.3 ± 13.7 years; 40.7% female), hs-cTnT was detectable in 80.7%. Median hs-cTnT was 10 ng/L (IQR: 6-18 ng/L). Over a median follow-up of 12.1 months, 110 patients had a CVD event. The association of hs-cTnT level with CVD risk was of log-linear shape, with a multivariable-adjusted HR of 1.40 (95% CI: 1.15-1.70; P < 0.001) per 1-SD higher log-transformed hs-cTnT value. The strength of association was similar when further adjusted for other potential confounders and across clinically relevant subgroups. Corresponding outcome-specific HRs were 1.33 (95% CI: 1.06-1.68; P = 0.016) for stroke, 1.28 (95% CI: 0.69-2.37; P = 0.430) for myocardial infarction, 1.98 (95% CI: 1.43-2.73; P < 0.001) for CVD death, and 1.93 (95% CI: 1.54-2.41; P < 0.001) for all-cause death. Conclusions: High hs-cTnT is associated with increased CVD risk in ischemic stroke and transient ischemic attack patients.

Pain in Multiple System Atrophy: A Community-Based Survey.

BACKGROUND: Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. OBJECTIVE: This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. METHODS: A community-based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. RESULTS: We included 190 persons with MSA and 114 caregivers. Eighty-seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27-32.08], P = 0.025) and low-income groups (OR: 5.02 [95% CI: 1.32-19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92-12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54-6.82], P = 0.002). Seventy-six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti-inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. CONCLUSIONS: Pain is more prevalent than previously reported in MSA and particularly affects women and low-income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non-motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Trends in Sex Differences of Functional Outcome after Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies - including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR) - detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. AIMS: To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. METHODS: We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. RESULTS: Among 11840 patients receiving IVT, 2489/5503 (45.4%) women achieved favorable functional outcome compared to 3787/6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjOR 0.87, 95%CI 0.79-0.96, p=0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) 1.04, 95%CI 1.02-1.06, p<0.001) but not in women (adjOR (per year) 1.01, 95%CI 0.99-1.03, p=0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction and longer door-to-needle times were significantly associated with outcome only in women. CONCLUSIONS: Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future.Data access statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (DM), access inquiries have to be addressed to the registry's academic review board.

Objective and subjective cognitive outcomes one year after COVID-19.

OBJECTIVE: This study aimed to evaluate subjective cognitive, physical, and mental health symptoms as well as objective cognitive deficits in COVID-19 patients 1 year after infection. METHODS: This was a cross-sectional study. Seventy-four patients, who contracted a SARS-CoV-2 infection in 2020, underwent an in-person neuropsychological assessment in 2021. This included standardized tests of memory, attention, and executive functions. In addition, participants also responded to scales on subjective attention deficits, mental health symptoms, and fatigue. Patients' scores were compared to published norms. RESULTS: Patients (N = 74) had a median age of 56 years (42% female). According to the initial disease severity, they were classified as mild (outpatients, 32%), moderate (hospitalized, non-ICU-admitted, 45%), or severe (ICU-admitted, 23%). Hospitalized patients were more often affected than outpatients. In general, deficits were most common in attention (23%), followed by memory (15%) and executive functions (3%). Patients reported increased levels of fatigue (51%), anxiety (30%), distractibility in everyday situations (20%), and depression (15%). An additional analysis suggested an association between lower scores in an attention task and hyperferritinemia. As indicated by a hierarchical regression analysis, subjective distractibility was significantly predicted by current anxiety and fatigue symptoms but not by objective attention performance (final model, adj-R2 = 0.588, P < 0.001). INTERPRETATION: One year after infection, COVID-19 patients can have frequent attention deficits and can complain about symptoms such as fatigue, anxiety, and distractibility. Anxiety and fatigue, more than objective cognitive deficits, have an impact on the patients' experienced impairments in everyday life.

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents.

Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction. Oligodendrocyte lineage cells and astrocytes range among the most transcriptionally perturbed populations and exhibit infarction- and subtype-specific molecular signatures. Specifically, we find infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and reactive astrocytes, exhibiting transcriptional commonalities in response to ischemic injury. OPCs and reactive astrocytes are involved in a shared immuno-glial cross talk with stroke-specific myeloid cells. Within the perilesional zone, osteopontin positive myeloid cells accumulate in close proximity to CD44+ proliferating OPCs and reactive astrocytes. In vitro, osteopontin increases the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition of acutely infarcted brain tissue.

Relationship of Suboptimal and Disordered Sleep with Cardiovascular Disease and Its Risk Factors - A Narrative Review.

BACKGROUND: Cardiovascular disease (CVD), including coronary heart disease and cerebrovascular disease, is already amongst the leading causes of morbidity and mortality worldwide, but its burden continues to rise. Over time, relevant risk factors for CVD have been identified, many of which are modifiable. More recently, the relationship of sleep and CVD has been of interest, specifically increased rates of disrupted and disordered sleep, which have been found to be associated with CVD. Longitudinal studies have linked sleep difficulties to a predisposition of vascular risk factors, suggesting a potential role for sleep improvement in primary and secondary CVD. SUMMARY: In the present narrative review article, we summarize the current body of research linking suboptimal sleep (e.g., short/long sleep, fragmented sleep) as well as nonbreathing-related sleep disorders (i.e., insomnia, restless legs syndrome/peripheral leg movements of sleep, narcolepsy) to modifiable CVD risk factors and CVD outcomes (morbidity and mortality).

A narrative review on cervical artery dissection-related cranial nerve palsies.

Introduction: This study aimed to emphasize the importance of cranial nerve (CN) palsies in spontaneous cervical artery dissection (sCeAD). Methods: A search term-based literature review was conducted on "cervical artery dissection" and "cranial nerve palsy." English and German articles published until October 2023 were considered. Results: Cranial nerve (CN) palsy in sCeAD is evident in approximately 10% of cases. In the literature, isolated palsies of CN II, III, VII, IX, X, and XII have been reported, while CN XI palsy only occurs in combination with other lower cranial nerve palsies. Dissection type and mural hematoma localization are specific to affected CN as CN palsies of II or III are solely evident in those with steno-occlusive vessel pathologies located at more proximal segments of ICA, while those with CN palsies of IX, X, XI, and XII occur in expansive sCeAD at more distal segments. This dichotomization emphasizes the hypothesis of a different pathomechanism in CN palsy associated with sCeAD, one being hypoperfusion or microembolism (CN II, III, and VII) and the other being a local mass effect on surrounding tissue (CN IX, X, XI, and XII). Clinically, the distinction between peripheral palsies and those caused by brainstem infarction is difficult. This differentiation is key, as, according to the reviewed cases, peripheral cranial nerve palsies in sCeAD patients mostly resolve completely over time, while those due to brainstem stroke do not, making cerebrovascular imaging appraisal essential. Discussion: It is important to consider dissections as a potential cause of peripheral CN palsies and to be aware of the appropriate diagnostic pathways. This awareness can help clinicians make an early diagnosis, offering the opportunity for primary stroke prevention.

Long-Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. OBJECTIVE: To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. METHODS: We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. RESULTS: In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. CONCLUSION: In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.

Peripheral inflammatory response in people after acute ischaemic stroke and isolated spontaneous cervical artery dissection.

The systemic inflammatory response following acute ischaemic stroke remains incompletely understood. We characterised the circulating inflammatory profile in 173 acute ischaemic stroke patients by measuring 65 cytokines and chemokines in plasma. Participants were grouped based on their inflammatory response, determined by high-sensitivity C-reactive protein levels in the acute phase. We compared stroke patients' profiles with 42 people experiencing spontaneous cervical artery dissection without stroke. Furthermore, variations in cytokine levels among stroke aetiologies were analysed. Follow-up samples were collected in a subgroup of ischaemic stroke patients at three and twelve months. Ischaemic stroke patients had elevated plasma levels of HGF and SDF-1α, and lower IL-4 levels, compared to spontaneous cervical artery dissection patients without stroke. Aetiology-subgroup analysis revealed reduced levels of nine cytokines/chemokines (HGF, SDF-1α, IL-2R, CD30, TNF-RII, IL-16, MIF, APRIL, SCF), and elevated levels of IL-4 and MIP-1ß, in spontaneous cervical artery dissection (with or without ischaemic stroke as levels were comparable between both groups) compared to other aetiologies. The majority of cytokine/chemokine levels remained stable across the study period. Our research indicates that stroke due to large artery atherosclerosis, cardioembolism, and small vessel occlusion triggers a stronger inflammatory response than spontaneous cervical artery dissection.

Genetic Determined Iron Starvation Signature in Friedreich's Ataxia.

BACKGROUND: Early studies in cellular models suggested an iron accumulation in Friedreich's ataxia (FA), yet findings from patients are lacking. OBJECTIVES: The objective is to characterize systemic iron metabolism, body iron storages, and intracellular iron regulation in FA patients. METHODS: In FA patients and matched healthy controls, we assessed serum iron parameters, regulatory hormones as well as the expression of regulatory proteins and iron distribution in peripheral blood mononuclear cells (PBMCs). We applied magnetic resonance imaging with R2*-relaxometry to quantify iron storages in the liver, spleen, and pancreas. Across all evaluations, we assessed the influence of the genetic severity as expressed by the length of the shorter GAA-expansion (GAA1). RESULTS: We recruited 40 FA patients (19 women). Compared to controls, FA patients displayed lower serum iron and transferrin saturation. Serum ferritin, hepcidin, mean corpuscular hemoglobin and mean corpuscular volume in FA inversely correlated with the GAA1-repeat length, indicating iron deficiency and restricted availability for erythropoiesis with increasing genetic severity. R2*-relaxometry revealed a reduction of splenic and hepatic iron stores in FA. Liver and spleen R2* values inversely correlated with the GAA1-repeat length. FA PBMCs displayed downregulation of ferritin and upregulation of transferrin receptor and divalent metal transporter-1 mRNA, particularly in patients with >500 GAA1-repeats. In FA PBMCs, intracellular iron was not increased, but shifted toward mitochondria. CONCLUSIONS: We provide evidence for a previously unrecognized iron starvation signature at systemic and cellular levels in FA patients, which is related to the underlying genetic severity. These findings challenge the use of systemic iron lowering therapies in FA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sex-related differences in the clinical presentation of multiple system atrophy.

PURPOSE: To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. METHODS: The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis. RESULTS: The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004). CONCLUSION: The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.

Case report: Dissolving carotid plaque associated to Lorlatinib-related dyslipidemia.

We present a case with prolonged Lorlatinib-related dyslipidemia causing internal carotid artery stenosis, putting the patient at risk of cerebrovascular events. Through intensified lipid-lowering treatment and dose reduction of Lorlatinib, LDL-C levels decreased markedly. Surprisingly, the left sided internal carotid artery stenosis dissolved accordingly. Due to the high efficacy of the new selective tyrosine kinase inhibitors and resulting long-term treatment, it is essential to carefully follow-up and include drug specific side effect monitoring. This case emphasizes that Loraltinib-related dyslipidemia has to be taken seriously and treatment should be initiated as promptly as possible. We conclude that in cases were lipid dysregulation remains and Lorlatinib treatment has to be continued, cerebrovascular appraisal through ultrasound should be considered and, if stenosis is evident, intensified treatment regimen of dyslipidemia or dose reduction of Lorlatinib should be discussed in an interdisciplinary setting.

Cervical artery tortuosity-a reliable semi-automated magnetic resonance-based method.

Background: Assessments of subclinical connective tissue disorders depend on complex approaches, emphasizing the need for more accessible methods applicable to clinical routine. Therefore, we aimed to establish a reliable approach assessing cervical vessel tortuosity, which is known to be associated with such disorders. Methods: Magnetic resonance angiography (MRA) images of ReSect study participants [single-center prospective cohort of spontaneous cervical artery dissection (sCeAD) patients] were used. Each patient underwent the same magnetic resonance imaging (MRI) protocol. The segmentation procedure was done using MATrix LABoratory 9.4 [up-sampling of raw MRA images, distance metric (DM) calculation], ITK-SNAP [region of interest (ROI) determination, vessel segmentation] and Vascular Modelling ToolKit (centerline determination). To assess inter-user variability and validity, we (I) had two blinded independent users segment all arteries and we (II) compared the results of our method to visual appraisal of vessel tortuosity done by two blinded expert neuro-radiologists. Results: A total of 526 extracranial cervical arteries were available for analysis. The inter-user variability of our method users was below 0.5% throughout. Overall, our method outperformed the visual tortuosity appraisal, as the visual grading underestimated the DM in 38.8% subjects when tasked to assess overall cervical artery tortuosity (both vertebral and internal carotid arteries) and in 16.6% and 33.3% respectively if tasked to grade anterior or posterior circulation separately. Conclusions: We present a reliable method to assess cervical artery tortuosity derived from MRA images applicable in clinical routine and future research investigating the potential correlation of sCeAD and connective tissue disorder.

Generation of the human induced pluripotent stem cell line (IBKMOLi003-A) from PBMCs of a vascular Ehlers-Danlos syndrome (vEDS) patient carrying the heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene.

Ehlers-Danlos syndrome (EDS) belongs to a spectrum of rare heritable connective tissue disorders and is characterised by hyperextensibility, joint hypermobility and tissue fragility. Peripheral blood mononuclear cells (PBMCs) from a vascular EDS (vEDS) patient, known as the rarest EDS subtype, carrying a heterozygous nonsense mutation c.430C > T (p.Q105*) in the COL3A1 gene, which is essential for type III collagen synthesis, were reprogrammed into induced pluripotent stem cells (iPSCs). The generated iPSCs exhibit high expression of pluripotency-associated markers, possess trilineage differentiation capacity and reveal a normal karyotype. This novel patient-specific cell line enables in-depth pathophysiological studies of vEDS.

Association between dysphagia and symptoms of depression and anxiety after ischemic stroke.

BACKGROUND AND PURPOSE: Dysphagia is associated with poor outcome, higher mortality, reduced quality of life, and social isolation. We investigate the relationship between swallowing impairment and symptoms of anxiety and depression after ischemic stroke. METHODS: Consecutive patients with ischemic stroke participating in the prospective STROKE-CARD Registry study from 2020 to 2022 were assessed for dysphagia on hospital admission (clinical swallowing assessment) and for persistence until discharge and 3-month follow-up (SINGER Independency Index). Anxiety and depression symptoms were recorded using Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS) at 3-month follow-up. RESULTS: Of 648 patients, 19.3% had dysphagia on admission, persisting in 14.8% at discharge and 6.8% at 3-month follow-up. With the presence or duration of dysphagia (no dysphagia, dysphagia at baseline, at discharge, at 3 months), score (mean ± SD) increased on the BDI (7.9 ± 6.7, 12.5 ± 8.7, 13.5 ± 9.0, 16.5 ± 10.2), HADS-D (4.4 ± 3.7, 7.1 ± 4.2, 7.7 ± 4.4, 9.8 ± 4.3), and HADS-A (4.4 ± 3.5, 5.4 ± 3.6, 6.0 ± 3.6, 7.0 ± 3.6). In linear regression analysis adjusting for age, sex, diabetes, dementia, and either functional disability or stroke severity, BDI and HADS-D scores were significantly higher in patients with dysphagia across all points in time (admission, discharge, 3-month follow-up). An independent association with HADS-A scores was only evident in patients with persisting dysphagia after 3 months. Patients with dysphagia were more likely to receive antidepressants, antipsychotics, or benzodiazepines at discharge and 3-month follow-up. CONCLUSIONS: Dysphagia after stroke is common and severely affects psychosocial functioning of individuals. Our results highlight swallowing impairment as an independent predictor for poststroke depressive and, to a lesser extent, anxiety symptoms.

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People.

BACKGROUND: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. METHODS AND RESULTS: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. CONCLUSIONS: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Risk of stroke in patients with prior VKA or DOAC: A population-based real-world registry analysis.

INTRODUCTION: To date, risk assessment of suffering ischemic and hemorrhagic stroke in individuals under oral anticoagulation (OAC) is limited to hospital-based cohorts and patients with atrial fibrillation. PATIENTS AND METHODS: Through the combination of three individual datasets, (1) the population-based Tyrolean Stroke Pathway database, prospectively documenting all (unselected) stroke patients in the entire federal state of the Tyrol and (2) nation-wide prescription data, detailing each reimbursed prescription in Austria as well as (3) the Austrian Stroke Unit Registry, a nation-wide registry comprising data on all patients admitted to any of the 38 stroke units in Austria, we assessed risk of stroke in patients with prior oral anticoagulation and compared characteristics of patients taking direct oral anticoagulants and Vitamin-K-Antagonists. RESULTS: In Austria, oral anticoagulant prescription reimbursements increased from 292,475 in 2015 to 389,407 in 2021. In the Tyrol, prior oral anticoagulation treatment was evident in 586 of 3861 (15.2%) patients with ischemic and 131 of 523 (25.0%) with hemorrhagic stroke, with 20% and 35% of those stroke patients respectively having prior oral anticoagulation due to other indications than non-valvular atrial fibrillation. Considering prescription rates, treatment with direct oral anticoagulants was associated with a reduced stroke risk compared to Vitamin-K-Antagonists, especially in ischemic (1.05% vs 0.62%; RR 0.59, p < 0.001) but also in hemorrhagic stroke, even if less pronounced (0.21% vs 0.14%; RR 0.68, p = 0.06). In Austria, prior intake of direct oral anticoagulants was associated with lower risk of suffering acute large vessel occlusion stroke (RR 0.79, p = 0.003). DISCUSSION AND CONCLUSIONS: One in seven patients suffering ischemic and one in four suffering hemorrhagic stroke had prior oral anticoagulation treatment. Both ischemic and hemorrhagic strokes are less frequent in those with direct oral anticoagulant intake compared to those taking Vitamin-K-Antagonists. Establishment of clear standard operating procedures on how to best care for acute stroke patients with oral anticoagulation is essential.

Sex differences in acute stroke metrics and outcome dependent on COVID status.

BACKGROUND AND PURPOSE: Biological sex is known to have an impact on quality metrics of acute stroke. We aimed to determine whether COVID positivity accentuates this effect and constitutes worse outcome. METHODS: The present analysis was based on the Global COVID-19 Stroke Registry, a retrospective, international, cohort study of consecutive ischemic stroke patients receiving intravenous thrombolysis and/or endovascular thrombectomy between 1 March 2020 and 30 June 2021. We investigated differences between the sexes in patient characteristics, acute stroke metrics as well as post-stroke outcome in COVID-positive and COVID-negative stroke patients undergoing acute revascularization procedures. RESULTS: A total of 15,128 patients from 106 centers were recorded in the Global COVID-19 Stroke Registry, 853 (5.6%) of whom were COVID-positive. Overall, COVID-positive individuals were treated significantly slower according to every acute stroke metric compared to COVID-negative patients. We were able to show that key quality indicators in acute stroke treatment were unfavorable for COVID-negative women compared to men (last-seen-well-to-door time + 11 min in women). Furthermore, COVID-negative women had worse 3-month outcomes (3-month modified Rankin Scale score [interquartile range] 3.0 [4.0] vs. 2.0 [3.0]; p < 0.01), even after adjusting for confounders. In COVID-positive individuals no such difference between the sexes, either in acute management metrics or in 3-month outcome, was seen. CONCLUSION: Known sex-related differences in acute stroke management exist and extend to times of crisis. Nevertheless, if patients were COVID-19-positive at stroke onset, women and men were treated the same, which could be attributed to structured treatment pathways.