Can Past Psychedelic Use Mitigate the Severity of Opioid Use Disorder?: Case Report of a Musician.

Little is known about the association between psychedelic use and substance abuse in the general population. We present a case of an award winning musician with an extensive history of hallucinogen use during his early life and how this impacted his overall wellbeing and opioid experience.

mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.

BACKGROUND: Mutations in the gene MTARC1 (mitochondrial amidoxime-reducing component 1) protect carriers from metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MTARC1 encodes the mARC1 enzyme, which is localized to the mitochondria and has no known MASH-relevant molecular function. Our studies aimed to expand on the published human genetic mARC1 data and to observe the molecular effects of mARC1 modulation in preclinical MASH models. METHODS AND RESULTS: We identified a novel human structural variant deletion in MTARC1, which is associated with various biomarkers of liver health, including alanine aminotransferase levels. Phenome-wide Mendelian Randomization analyses additionally identified novel putatively causal associations between MTARC1 expression, and esophageal varices and cardiorespiratory traits. We observed that protective MTARC1 variants decreased protein accumulation in in vitro overexpression systems and used genetic tools to study mARC1 depletion in relevant human and mouse systems. Hepatocyte mARC1 knockdown in murine MASH models reduced body weight, liver steatosis, oxidative stress, cell death, and fibrogenesis markers. mARC1 siRNA treatment and overexpression modulated lipid accumulation and cell death consistently in primary human hepatocytes, hepatocyte cell lines, and primary human adipocytes. mARC1 depletion affected the accumulation of distinct lipid species and the expression of inflammatory and mitochondrial pathway genes/proteins in both in vitro and in vivo models. CONCLUSIONS: Depleting hepatocyte mARC1 improved metabolic dysfunction-associated steatotic liver disease-related outcomes. Given the functional role of mARC1 in human adipocyte lipid accumulation, systemic targeting of mARC1 should be considered when designing mARC1 therapies. Our data point to plasma lipid biomarkers predictive of mARC1 abundance, such as Ceramide 22:1. We propose future areas of study to describe the precise molecular function of mARC1, including lipid trafficking and subcellular location within or around the mitochondria and endoplasmic reticulum.

Black Americans have worse stroke outcome compared with non-Hispanic whites.

INTRODUCTION: We studied racial differences in post-stroke outcomes using a prospective, population-based cohort of stroke survivors as part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. METHODS: Neurologic (NIHSS, range of 0-42, higher scores are worse), functional (ADLs/IADLs, range 1-4, higher scores are worse), and cognitive (3MSE, range 0-100, higher scores are better) outcomes were measured 90 days after stroke. Cox proportional hazards and negative binomial linear regression models were used to examine the associations between race and 90-day all-cause mortality and NIHSS, respectively, whereas linear regression was used for ADLs/IADLs and 3MSE scores. Covariates included demographics, initial NIHSS, comorbidities, prior stroke history, tPA treatment status, pre-stroke disability, and pre-stroke cognition. The mortality model was also adjusted for DNR status. RESULTS: At 90 days post-stroke, Black American individuals (BAs) (n = 122) had a median (IQR) NIHSS of 2 (1,6) compared to NIHSS of 1 (0,3) in non-Hispanic White American individuals (NHWs) (n = 795). BAs had a median (IQR) ADL/IADL score of 2.41 (1.50, 3.39) compared to 2.00 (1.27, 2.95) in NHWs. BAs scored a median of 84 (75, 92) on the 3MSE compared to NHWs' score of 91.5 (83, 96). Death occurred in 23 (8%) of BAs and 268 (15%) of NHWs within 90 days among those who participated in baseline. After adjustment for covariates, functional outcomes at 90 days were worse in BAs compared to NHWs, with 15.8% (95% CI=5.2, 26.4) greater limitations in ADLs/IADLs and 43.9% (95% CI=12.0, 84.9) greater severity of stroke symptoms. Cognition at 90 days was 6.5% (95% CI=2.4, 10.6) lower in BAs compared to NHWs. BAs had a 35.4% lower (95% CI=-9.8, 61.9) hazard rate of mortality than NHWs. CONCLUSIONS: In this prospective, population-based community sample, BAs had worse neurologic, functional and cognitive outcomes at 90 days compared to NHWs. Future research should investigate how social determinants of health including structural racism, neighborhood factors and access to preventive and recovery services influences these racial disparities.

Longitudinal Assessment of Sleep Apnea in the Year After Stroke in a Population-Based Study.

BACKGROUND: The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project. METHODS: First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors. RESULTS: Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (P=0.35) but obstructive apnea index increased over time (P<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (P=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons. CONCLUSIONS: Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.

Outcomes in the Year After First-Ever Ischemic Stroke in a Bi-Ethnic Population.

OBJECTIVE: To investigate stroke outcomes at 3, 6, and 12 months post-stroke overall and by ethnicity in a population-based, longitudinal study. METHODS: First-ever ischemic strokes (2014-2019, n = 1,332) among Mexican American persons (n = 807) and non-Hispanic white persons (n = 525) were identified from the Brain Attack Surveillance in Corpus Christi Project. Data were collected from patient or proxy interviews (baseline, 3, 6, and 12 months post-stroke) and medical records, including functional (activities of daily living/instrumental activities of daily living score), neurological (National Institutes of Health Stroke Scale), cognitive (Modified Mini-Mental State Examination), and quality of life (QOL) outcomes (12-domain Stroke-specific Quality of Life scale). Outcome trajectories were analyzed using multivariable adjusted linear models, with generalized estimating equations to account for within-subject correlations; interactions between ethnicity and time were included to investigate ethnic differences in outcomes. RESULTS: The median age was 67 years (interquartile range 58,78), 48.5% were women, and 60.6% were Mexican American persons. For all outcomes, significant improvement was seen between 3 and 6 months (p < 0.05 for all), with stability between 6 and 12 months. Mexican American persons had significantly worse outcomes compared with non-Hispanic white persons at all time points (3, 6, and 12 months), with the exception of the National Institutes of Health Stroke Scale, which did not differ by ethnicity at 6 and 12 months, and the average change in outcomes did not vary significantly by ethnicity. INTERPRETATION: Outcomes were at their worst at 3 months post-stroke, and ethnic disparities were already present, suggesting the need for early assessment and strategies to improve outcomes and possibly reduce disparities. ANN NEUROL 2023;93:348-356.

CD8 Encephalitis: A Diagnostic Dilemma.

CD8+ encephalitis is a subacute encephalopathy associated with HIV infection. Pathophysiology is thought to be auto-reactive CD8+ cells attacking on HIV infected CD4+ cells and 'viral escape' phenomena (replication of CD8+ cells in CSF). We present a case of a 45-year-old man with well controlled HIV who developed CD8 encephalitis following Herpes simplex encephalitis. He had persistent encephalopathy for several weeks with status epilepticus and agitated delirium, and diagnosis remained elusive until a brain biopsy confirmed the diagnosis.

Hunger Training as a Self-regulation Strategy in a Comprehensive Weight Loss Program for Breast Cancer Prevention: A Randomized Feasibility Study.

Weight losses >10% favorably modulate biomarkers of breast cancer risk but are not typically achieved by comprehensive weight loss programs, including the Diabetes Prevention Program (DPP). Combining the DPP with hunger training (HT), an evidence-based self-regulation strategy that uses self-monitored glucose levels to guide meal timing, has potential to enhance weight losses and cancer-related biomarkers, if proven feasible. This two-arm randomized controlled trial examined the feasibility of adding HT to the DPP and explored effects on weight and metabolic and breast cancer risk biomarkers. Fifty postmenopausal women [body mass index (BMI) >27 kg/m2)] at risk of breast cancer were randomized to the DPP+HT or DPP-only arm. Both arms followed a 16-week version of the DPP delivered weekly by a trained registered dietitian. Those in the DPP+HT also wore a continuous glucose monitor during weeks 4-6 of the program. Feasibility criteria were accrual rates >50%, retention rates >80%, and adherence to the HT protocol >75%. All a priori feasibility criteria were achieved. The accrual rate was 67%, retention rate was 81%, and adherence to HT was 90%. Weight losses and BMI reductions were significant over time as were changes in metabolic and breast cancer risk biomarkers but did not vary by group. This trial demonstrated that HT was feasible to add to comprehensive weight management program targeted toward postmenopausal women at high risk of breast cancer, though upon preliminary examination it does not appear to enhance weight loss or metabolic changes. PREVENTION RELEVANCE: This study found that it was feasible to add a short glucose-guided eating intervention to a comprehensive weight management program targeting postmenopausal women at high risk of breast cancer. However, further development of this novel intervention as a cancer prevention strategy is needed.

Temporal Trends in Ischemic Stroke Rates by Ethnicity, Sex, and Age (2000-2017): The Brain Attack Surveillance in Corpus Christi Project.

OBJECTIVE: To compare 18-year (2000-2017) temporal trends in ischemic stroke rates by ethnicity, sex, and age. METHODS: Data are from a population-based stroke surveillance study conducted in Nueces County, Texas, a geographically isolated, biethnic, urban community. Active (screening hospital admission logs, hospital wards, intensive care units) and passive (screening inpatient/emergency department discharge diagnosis codes) surveillance were used to identify cases aged ≥45 (n = 4,875) validated by stroke physicians using a consistent stroke definition over time. Ischemic stroke rates were derived from Poisson regression using annual population counts from the US Census to estimate the at-risk population. RESULTS: In those aged 45-59 years, rates increased in non-Hispanic Whites (104.3% relative increase; p < 0.001) but decreased in Mexican Americans (-21.9%; p = 0.03) such that rates were significantly higher in non-Hispanic Whites in 2016-2017 (p for ethnicity-time interaction < 0.001). In those age 60-74, rates declined in both groups but more so in Mexican Americans (non-Hispanic Whites -18.2%, p = 0.05; Mexican Americans -40.1%, p = 0.002), resulting in similar rates for the 2 groups in 2016-2017 (p for ethnicity-time interaction = 0.06). In those aged ≥75, trends did not vary by ethnicity, with declines noted in both groups (non-Hispanic Whites -33.7%, p = 0.002; Mexican Americans -26.9%, p = 0.02). Decreases in rates were observed in men (age 60-74, -25.7%, p = 0.009; age ≥75, -39.2%, p = 0.002) and women (age 60-74, -34.3%, p = 0.007; age ≥75, -24.0%, p = 0.02) in the 2 older age groups, while rates did not change in either sex in those age 45-59. CONCLUSION: Previously documented ethnic stroke incidence disparities have ended as a result of declining rates in Mexican Americans and increasing rates in non-Hispanic Whites, most notably in midlife.

The Ethic of Access: An AIDS Activist Won Public Access to Experimental Therapies, and This Must Now Extend to Psychedelics for Mental Illness.

If patients with mental illnesses are to be treated fairly in comparison with other categories of patients, they must be given access to promising experimental therapies, including psychedelics. The right of early access to promising therapies was advanced as an ethical principle by activist Larry Kramer during the AIDS pandemic, and has now largely been adopted by the medical establishment. Patients are regularly granted access to experimental drugs for many illness categories, such as cancer and infectious diseases. The need for expanded access is especially relevant during evolving crises like the AIDS and the coronavirus pandemics. In contrast to non-psychiatric branches of medicine, psychiatry has failed to expedite access to promising drugs in the face of public health emergencies, psychological crises, the wishes of many patients, and the needs of the community. Psychiatry must catch up to the rest of medicine and allow the preferences of patients for access to guide policy and law regarding unapproved medications like psychedelics.

Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Differences in acute ischemic stroke (AIS) treatment by cognitive status are unclear, but some studies have found patients with preexisting dementia get less treatment. We compared AIS care by preexisting cognitive status. METHODS: Cross-sectional analysis of prospectively obtained data on 836 adults ≥45 with AIS from the population-based Brain Attack Surveillance in Corpus Christi project from 2008 to 2013. We compared receipt of a composite quality measure representing the percentage of 7 treatments/procedures received (ordinal scale; values, <0.75, 0.75-0.99, and 1.0), a binary defect-free quality score, and individual treatments after AIS between patients with preexisting dementia (Informant Questionnaire on Cognitive Decline in the Elderly score ≥3.44), mild cognitive impairment (MCI, score 3.1-3.43), and normal cognition (score ≤3). RESULTS: Among patients with AIS, 42% had normal cognition (47% women; median age [interquartile range], 65 [56-76]), 32% had MCI (54% women; median age, 70 [60-78]), 26% had dementia (56% women; median age, 78 [64-85]). After AIS, 44% of patients with preexisting dementia and 55% of patients with preexisting MCI or normal cognition received defect-free care. Compared with cognitively normal patients, patients with preexisting MCI had similar cumulative odds (unadjusted cumulative odds ratio =0.99, P=0.92), and patients with preexisting dementia had 36% lower cumulative odds of receiving the composite quality measure (unadjusted cumulative odds ratio [OR]=0.64, P=0.005). However, the dementia-quality association became nonsignificant after adjusting for patient factors, namely sex, comorbidity, and body mass index (adjusted cumulative OR [acOR]=0.79, P=0.19). Independent of patient factors, preexisting MCI was negatively associated with receipt of IV tPA (intravenous tissue-type plasminogen activator; acOR=0.36, P=0.04), rehabilitation assessment (acOR=0.28, P=0.016), and echocardiogram (acOR=0.48, P<0.001). Preexisting dementia was negatively associated with receipt of antithrombotic by day 2 (acOR=0.39, P=0.04) and echocardiogram (acOR=0.42, P<0.001). CONCLUSIONS: Patients with preexisting MCI and dementia, compared with cognitively normal patients, may receive less frequently some treatments and procedures, but not the composite quality measure, after AIS.

Tissue-Based Stroke Definition Impacts Stroke Incidence but not Ethnic Differences.

OBJECTIVES: We explored how the new, tissue-based stroke definition impacted incidence estimates, including an ethnic comparison, in a population-based study. METHODS: Stroke patients, May, 2014-May, 2016 in Nueces County, Texas were ascertained and validated using source documentation. Overall, ethnic-specific and age-specific Poisson regression models were used to compare first-ever ischemic stroke and intracerebral hemorrhage (ICH) incidence between old and new stroke definitions, adjusting for age, ethnicity, sex, and National Institutes of Health Stroke Scale score. RESULTS: Among 1308 subjects, 1245 (95%) were defined as stroke by the old definition and 63 additional cases (5%) according to the new. There were 12 cases of parenchymal hematoma (PH1 or PH2) that were reclassified from ischemic stroke to ICH. Overall, incidence of ischemic stroke was slightly higher under the new compared to the old definition (RR 1.07; 95% CI 0.99-1.16); similarly higher in both Mexican Americans (RR 1.06; 95% CI 1.00-1.12) and Non Hispanic whites (RR 1.09, 95% CI 0.97-1.22), p(ethnic difference)=0.36. Overall, incidence of ICH was higher under the new definition compared to old definition (RR 1.16; 95% CI 1.05-1.29), similarly higher among both Mexican Americans (RR 1.14; 95% CI 1.06-1.23) and Non Hispanic whites (RR 1.20, 95% CI 1.03-1.39), p(ethnic difference)=0.25. CONCLUSION: Modest increases in ischemic stroke and ICH incidence occurred using the new compared with old stroke definition. There were no differences between Mexican Americans and non Hispanic whites. These estimates provide stroke burden estimates for public health planning.

Stroke Quality Measures in Mexican Americans and Non-Hispanic Whites.

Mexican Americans (MAs) have been shown to have worse outcomes after stroke than non-Hispanic Whites (NHWs), but it is unknown if ethnic differences in stroke quality of care may contribute to these worse outcomes. We investigated ethnic differences in the quality of inpatient stroke care between MAs and NHWs within the population-based prospective Brain Attack Surveillance in Corpus Christi (BASIC) Project (February 2009- June 2012). Quality measures for inpatient stroke care, based on the 2008 Joint Commission Primary Stroke Center definitions were assessed from the medical record by a trained abstractor. Two summary measure of overall quality were also created (binary measure of defect-free care and the proportion of measures achieved for which the patient was eligible). 757 individuals were included (480 MAs and 277 NHWs). MAs were younger, more likely to have hypertension and diabetes, and less likely to have atrial fibrillation than NHWs. MAs were less likely than NHWs to receive tPA (RR: 0.72, 95% confidence interval (CI) 0.52, 0.98), and MAs with atrial fibrillation were less likely to receive anticoagulant medications at discharge than NHWs (RR 0.73, 95% CI 0.58, 0.94). There were no ethnic differences in the other individual quality measures, or in the two summary measures assessing overall quality. In conclusion, there were no ethnic differences in the overall quality of stroke care between MAs and NHWs, though ethnic differences were seen in the proportion of patients who received tPA and anticoagulant at discharge for atrial fibrillation.

Stroke Performance Measures Do Not Predict Functional Outcome.

BACKGROUND AND PURPOSE: Poststroke functional outcome is critical to stroke survivors. We sought to determine whether adherence to current stroke performance measures is associated with better functional outcome 90 days after an ischemic stroke. METHODS: Utilizing the Brain Attack Surveillance in Corpus Christi cohort, we examined adherence to 7 ischemic stroke performance measures from February 2009 to June 2012. Adherence to the measures was analyzed in aggregate using a binary defect-free score and an opportunity score, representing the proportion of eligible measures met. The opportunity score ranges from 0 to 1, with values closer to 1 implying better adherence. Functional outcome, defined by an activities of daily living and instrumental activities of daily living (ADL/IADL) score (range 1-4, higher scores worse), was ascertained at 90 days poststroke. Tobit regression models were fitted to examine the associations between the performance measures and functional outcome, adjusting for demographic and clinical characteristics, including stroke severity. RESULTS: There were 565 patients with ischemic stroke included in the analysis. The median ADL/IADL score was 2.32 (interquartile range [IQR]: 1.41-3.41). The median opportunity score was 1 (IQR: 0.8-1), and 58.4% of the patients received defect-free care. After adjustment, the opportunity score (P = .67) and defect-free care (P = .92) were not associated with functional outcome. CONCLUSION: In this population, adherence to a composite of current stroke performance measures was not associated with poststroke functional outcome after adjustment for other factors. Performance measures that are associated with improved functional outcome should be developed and incorporated into stroke quality measures.

Sex Disparity in Stroke Quality of Care in a Community-Based Study.

BACKGROUND: Studies have suggested that women may receive lower stroke quality of care (QOC) than men, although population-based studies at nonacademic centers are limited. We investigated sex disparities in stroke QOC in the Brain Attack Surveillance in Corpus Christi Project. METHODS: All ischemic stroke patients admitted to 1 of 6 Nueces County nonacademic hospitals between February 2009 and June 2012 were prospectively identified. Data regarding compliance with 7 performance measures (PMs) were extracted from the medical records. Two overall quality metrics were calculated: a composite score of QOC representing the number of achieved PMs over all patient-appropriate PMs, and a binary measure of defect-free care. Multivariable models with generalized estimating equations assessed the association between sex and individual PMs and between sex and overall quality metrics. RESULTS: A total of 757 patients (51.6% female) were included in our analysis. After adjustment, women were less likely to receive deep vein thrombosis prophylaxis at 48 hours (relative risk [RR] = .945; 95% CI, .896-.996), an antithrombotic by 48 hours (RR = .952; 95% CI, .939-.965), and to be discharged on an antithrombotic (RR = .953; 95% CI, .925-.982). Women had a lower composite score (mean difference -.030, 95% CI -.057 to -.003) and were less likely to receive defect-free care than men (RR = .914; 95% CI, .843-.991). CONCLUSIONS: Women had lower overall stroke QOC than men, although absolute differences in most individual PMs were small. Further investigation into the factors contributing to the sex disparity in guideline-concordant stroke care should be pursued.

Emerging temporal trends in tissue plasminogen activator use: Results from the BASIC project.

OBJECTIVE: To explore temporal trends in tissue plasminogen activator (tPA) administration for acute ischemic stroke (AIS) in a biethnic community without an academic medical center and variation in trends by age, sex, ethnicity, and stroke severity. METHODS: Cases of AIS were identified from 7 hospitals in the Brain Attack Surveillance in Corpus Christi (BASIC) project, a population-based surveillance study between January 1, 2000, and June 30, 2012. tPA, demographics, and stroke severity as assessed by the NIH Stroke Scale (NIHSS) were ascertained from medical records. Temporal trends were explored using generalized estimating equations, and adjustment made for age, sex, ethnicity, and NIHSS. Interaction terms were included to test for effect modification. RESULTS: There were 5,277 AIS cases identified from 4,589 unique individuals. tPA use was steady at 2% and began increasing in 2006, reaching 11% in subsequent years. Stroke severity modified temporal trends (p = 0.003) such that cases in the highest severity quartile (NIHSS > 8) had larger increases in tPA use than those in lower severity quartiles. Although ethnicity did not modify the temporal trend, Mexican Americans (MAs) were less likely to receive tPA than non-Hispanic whites (NHWs) due to emerging ethnic differences in later years. CONCLUSIONS: Dramatic increases in tPA use were apparent in this community without an academic medical center. Primary stroke center certification likely contributed to this rise. Results suggest that increases in tPA use were greater in higher severity patients compared to lower severity patients, and a gap between MAs and NHWs in tPA administration may be emerging.

Thrombus burden is associated with clinical outcome after intra-arterial therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Studies have established a relation between recanalization and improved clinical outcome in acute ischemic stroke patients; however, intra-arterial clot size has not been routinely assessed. The aim of the study was to determine the impact of intra-arterial thrombus burden on intra-arterial treatment (IAT) and clinical outcome. METHODS: A retrospective review of our IAT stroke database included procedure time, recanalization, symptomatic intracranial hemorrhage, poor outcome (modified Rankin Scale score >/=4 at discharge), and mortality. The modified Thrombolysis in Myocardial Infarction thrombus grade was dichotomized into grades 0 to 3 (no clot or moderate thrombus, <2 vessel diameters) versus grade 4 (large thrombus, >2 vessel diameters). RESULTS: Data were collected on 135 patients with thrombus grading. The baseline median National Institutes of Health Stroke Scale score was higher in patients of grade 4 compared with grades 0 to 3 (19 vs 17, P=0.012). Grade 4 thrombi required longer (median, range) times for IAT (113, 37 to 415 minutes vs 74, 22 to 215 minutes, respectively; P<0.001) and higher rates of mechanical clot disruption (wire, angioplasty, snare, stent, or Merci retriever) compared with grades 0 to 3 (76% vs 53%, P=0.005). There were no differences in rates of symptomatic intracranial hemorrhage (6.6% vs 4.1%, P=0.701) or recanalization (50% vs 61%, P=0.216) in grade 4 versus grades 0 to 3. Multivariate analysis adjusted for age, baseline National Institutes of Health Stroke Scale score, and artery of involvement showed that grade 4 thrombi were independently associated with poor outcome (odds ratio=2.4; 95% CI, 1.06 to 5.57; P=0.036) and mortality (odds ratio=4.0; 95% CI, 1.2 to 13.2; P=0.023). CONCLUSIONS: High thrombus grade as measured by the modified Thrombolysis in Myocardial Infarction criteria may be a risk factor that contributes to poor clinical outcome.

Is intra-arterial thrombolysis safe after full-dose intravenous recombinant tissue plasminogen activator for acute ischemic stroke?

BACKGROUND AND PURPOSE: The optimal approach for acute ischemic stroke patients who do not respond to intravenous recombinant tissue plasminogen activator (IV rt-PA) is uncertain. This study evaluated the safety and response to intra-arterial thrombolytics (IATs) in patients unresponsive to full-dose IV rt-PA. METHODS: A case series from a prospectively collected database on consecutive acute ischemic stroke patients treated with IATs after 0.9 mg/kg IV rt-PA during a 7-year interval was collected. Primary outcome measures included symptomatic intracranial hemorrhage and mortality. As indicators of response, secondary outcome measures were recanalization and discharge disposition. RESULTS: Sixty-nine patients (mean+/-SD age, 60+/-13 years; range, 26 to 85 years; 55% male) with a median pretreatment National Institutes of Health Stroke Scale score of 18 (range, 6 to 39) were included. IV rt-PA was started at 124+/-32 minutes (median, 120 minutes) and IAT, at 288+/-57 minutes (median, 285 minutes). IATs consisted of reteplase (n=56), alteplase (n=7), and urokinase (n=6), with an average total dosage of 2.8 U, 8.6 mg, and 700 000 U, respectively. Symptomatic intracranial hemorrhage occurred in 4 of 69 (5.8%) patients; 3 cases were fatal. Recanalization was achieved in 50 (72.5%) and a favorable outcome (home or inpatient rehabilitation) in 38 (55%). CONCLUSIONS: IAT therapy after full-dose IV rt-PA in patients with persisting occlusion and/or lack of clinical improvement appears safe compared with IV rt-PA alone or low-dose IV rt-PA followed by IAT. A high rate of recanalization and favorable outcome can be achieved.

Analysis of emboli during carotid stenting with distal protection device.

BACKGROUND: The newly developed multi-frequency transcranial Doppler (TCD) is able to differentiate gaseous from solid emboli. Our goal was to apply this technology to initially characterize emboli detected during carotid stenting with distal protection. METHODS: Patients undergoing carotid angiography and stenting were monitored with 2-2.5 MHz TCD (Embo-Dop, DWL) over the middle cerebral artery unilateral to stent deployment. Sonographers insured optimal signal recordings during the procedures. Automated emboli detection and classification software (MultiXLab version 2.0) was applied for offline count and analysis. Monitoring using the Filter Wire EX (Boston Scientific) and ACCUNET system (Guidant Corporation) was performed. RESULTS: A total of 9,649 embolic signals were detected during 11 angiographic and 10 stenting procedures. An observer confirmed the signals using the International Consensus definition. Automated software classified these events into 5,900 gaseous and 3,749 solid emboli. During contrast injections without the protection device, 1,013 emboli were detected with 28% of these being solid. With deployment of the distal protection device, 8,636 emboli were found with 40% being solid (p < 0.001). During stenting and angioplasty with the protection device, 7,395 emboli with 42% solids were detected (p < 0.001). Finally injection of contrast after the procedure, with the protection device still deployed, yielded 1,241 emboli with 31% solids (NS). Only 1 patient developed transient hemiparesthesia during ballooning that reduced the flow velocity to zero for 14 s. Neither gaseous nor solid emboli resulted in a mean flow velocity decrease or clinical symptoms. CONCLUSIONS: Microembolization frequently occurs during stenting even with deployment of the distal protection device. More solid emboli are seen during manipulations associated with lesion crossing. Although novel TCD methods yield a high frequency of embolic signals, further validation of this technique to determine the true nature, size, and number of emboli is needed.

Yield and accuracy of urgent combined carotid/transcranial ultrasound testing in acute cerebral ischemia.

BACKGROUND AND PURPOSE: We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). METHODS: NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, > or =50% stenoses or thrombus in the symptomatic artery. RESULTS: One hundred and fifty patients (70 women, mean age 66+/-15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS > or =10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P<0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. CONCLUSIONS: Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

Aggressive mechanical clot disruption: a safe adjunct to thrombolytic therapy in acute stroke?

BACKGROUND AND PURPOSE: This study evaluated the safety and efficacy of aggressive mechanical clot disruption (AMCD) in acute stroke patients with persisting middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion after thrombolytic therapy. METHODS: Retrospective case series were used from a prospectively collected stroke database on consecutive acute ischemic stroke patients treated with intra-arterial (IA) thrombolytics and mechanical clot disruption during a 5-year interval. Thrombolytic dosage, endovascular techniques, immediate and final recanalization rates, symptomatic hemorrhage, mortality, and outcome were determined. RESULTS: Thirty-two patients received AMCD. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 18, and median time to initiation of IA treatment was 261 minutes from symptom onset. ICA occlusion was noted in 16 patients and MCA occlusion in 16 patients: 22 received combined IV/IA thrombolytics, 3 received IV thrombolytics, 6 received IA thrombolytics, and 1 patient received no thrombolytics before AMCD. No immediate periprocedural complications were noted. Immediate recanalization was achieved in 38% (50% MCA, 25% ICA) and final recanalization in 75% (88% MCA, 63% ICA) of patients. Favorable outcome occurred in 19 (59%) patients, symptomatic cerebral hemorrhage in 3 (9.4%) patients, and mortality in 4 (12.5%) patients. CONCLUSIONS: AMCD can be performed safely with comparable intracerebral hemorrhage and mortality rates to other IA therapies even after use of intravenous thrombolytics in selected patients. Early deployment of this technique leads to immediate recanalization in one third of patients. AMCD may potentially shorten the time to flow restoration and improve overall recanalization rates achieved with IA therapy.