Relationships of Hematocrit With Chronic Covert and Acute Symptomatic Lacunar Ischemic Lesions.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. METHODS: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. RESULTS: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient ß = 0.020; SE = 0.009; p = 0.03). DISCUSSION: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

Plateauing atrial fibrillation burden in acute ischemic stroke admissions in the United States from 2010 to 2020.

BACKGROUND: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade. METHODS: We used data contained in the 2010-2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time. RESULTS: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010-2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8-1.7%). Joinpoint regression showed that prevalence increased in the period 2010-2015 (APC: 2.8%, 95% CI: 1.9-3.9%) but remained stable in the period 2015-2020 (APC: -0.3%, 95% CI: -1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18-39 years (APC: 4.0%, 95% CI: 0.2-7.9%), men 40-59 years (APC: 3.4%, 95% CI: 1.9-4.9%) and women 40-59 years (APC: 4.4%, 95% CI: 2.0-6.8%). In contrast, prevalence declined in hospitalizations in women 60-79 (APC: -1.0%, 95% CI: -0.5 to -1.5%) and women ⩾ 80 years over the period 2015-2020 but plateaued in hospitalizations in similar-aged men over the same period. CONCLUSION: AF prevalence in AIS hospitalizations in the United States increased over the period 2010-2015, then plateaued over the period 2015-2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years.

Demographic Disparities in the Incidence, Clinical Characteristics, and Outcome of Posterior Reversible Encephalopathy Syndrome in the United States.

OBJECTIVES: To estimate age-specific, sex-specific, and race-specific incidence of posterior reversible encephalopathy syndrome (PRES) in the United States. METHODS: We conducted a retrospective cohort study using the State Inpatient Database of Florida (2016-2019), Maryland (2016-2019), and New York (2016-2018). All new cases of PRES in adults (18 years or older) were combined with Census data to compute incidence. We evaluated the generalizability of incident estimates to the entire country using the 2016-2019 National Readmissions Database (NRD). RESULTS: Across the study period, there were 3,716 incident hospitalizations for PRES in the selected states. The age-standardized and sex-standardized incidence of PRES was 2.7 (95% CI 2.5-2.8) cases/100,000/y. Incidence in female patients was >2 times that of male patients (3.7 vs 1.6 cases/100,000/y, p < 0.001). Incidence increased with age in both sexes (p-trend <0.001). Similar demographic distribution of first hospitalization for PRES was also noted in the entire country using the NRD. Age-standardized and sex-standardized PRES incidence in Black patients (4.2/100,000/y) was significantly greater than in Non-Hispanic White (2.7/100,000/y) and Hispanic patients (1.2/100,000/y) (p < 0.001 for pairwise comparisons). DISCUSSION: The incidence of PRES in the United States is approximately 3/100,000/y, but incidence in female patients is >2 times that of male patients. PRES incidence is higher in Black compared with non-Hispanic White and Hispanic patients.

Duration of Heightened Risk of Acute Ischemic Stroke After Hospitalization for Acute Systolic Heart Failure.

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008-2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30-day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1-2.7]) and without AF (HR, 4.6 [95% CI, 4.0-5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2-1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7-2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays in ICU Admitted Patients.

OBJECTIVES: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU. DESIGN: Observational cohort study and separate in vitro laboratory study. SETTING: Multicenter tertiary referral ICUs. PATIENTS: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory study was performed utilizing ICH patient blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Relationships between baseline hemoglobin and ROTEM/TEG results were separately assessed across patient cohorts using Spearman correlations and linear regression models. A separate in vitro study assessed ROTEM tracing changes after serial hemoglobin modifications from ICH patient blood samples. In both our ROTEM (n = 34) and TEG (n = 239) ICH cohorts, hemoglobin concentrations directly correlated with coagulation kinetics (ROTEM r: 0.46; p = 0.01; TEG r: 0.49; p < 0.0001) and inversely correlated with clot strength (ROTEM r: -0.52, p = 0.002; TEG r: -0.40, p < 0.0001). Similar relationships were identified in perioperative ICU admitted patients (n = 121). We continued to identify these relationships in linear regression models. When manipulating ICH patient blood samples to achieve lower hemoglobin concentrations in vitro, we similarly identified that lower hemoglobin concentrations resulted in progressively faster coagulation kinetics and greater clot strength on ROTEM tracings. CONCLUSIONS: Lower hemoglobin concentrations have a consistent, measurable impact on ROTEM/TEG testing in ICU admitted patients, which appear to be artifactual. It is possible that patients with low hemoglobin may appear to have normal viscoelastic parameters when, in fact, they have a mild hypocoagulable state. Further work is required to determine if these tests should be corrected for a patient's hemoglobin concentration.

Transcirculation Embolization to New Territory During Mechanical Thrombectomy for Acute Ischemic Stroke.

Embolization in new territories (ENT) is a known complication of mechanical thrombectomy with incidence dependent upon a variety of procedural factors. We present 2 cases of anterior circulation to posterior circulation ENT. These cases were managed with manual aspiration thrombectomy with excellent radiographic and clinical outcome. We present the available literature involving ENT along with our experience in management.

Breakthrough Seizure Associated With Kratom Use in Patients With Epilepsy.

PURPOSE OF REVIEW: Kratom (mitragynine) is a commercially available herbal supplement that is gaining popularity in the United States. Kratom is associated with a variety of neurologic effects. This review will discuss kratom's association with seizure through 3 cases and highlight what neurologists should know about kratom's clinical effects and legal status. RECENT FINDINGS: Kratom is currently commercially available, unscheduled by the US Drug Enforcement Administration, and a topic of regulatory debate in the United States. Large poison center reviews have suggested that kratom use is associated with seizure. There have been limited case studies to corroborate this finding. We present 3 cases in which seizures were associated with kratom use in patients treated for epilepsy. SUMMARY: Since 2008, kratom use is rising in prevalence in the United States aided by lack of regulation. Neurologists need to be aware of its association with seizure and other neurologic side effects.

Bruxism in Acute Neurologic Illness.

PURPOSE OF REVIEW: While traditionally encountered in ambulatory settings, bruxism occurs in patients with a variety of acute neurologic illnesses including encephalitis, intracerebral hemorrhage, traumatic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke. Untreated bruxism in acute neurologic illness can lead to tooth loss, difficulty in mouth care resulting in recurrent aspiration pneumonia, endotracheal tube dislodgement, and even tongue laceration or amputation. Inpatient clinicians should be aware of the etiologies and management strategies for bruxism secondary to acute neurologic illness. RECENT FINDINGS: Management strategies for bruxism are varied and include pharmacologic and non-pharmacologic therapies in addition to onabotulinumtoxinA (BoNT-A). Bruxism impacts patients with a variety of acute neurologic illnesses, and emerging evidence suggests successful and safe treatment strategies.

Cavernous Thrombophlebitis Secondary to Cavernous Internal Carotid Mycotic Aneurysm.

We report a case of a 22-year-old male with a history of intravenous drug use presenting with cavernous sinus syndrome secondary to cavernous thrombophlebitis. The source of the thrombophlebitis was from a mycotic aneurysm in the setting of fungal endocarditis. With antifungal therapy and aortic valve replacement, the patient had full resolution of cranial nerve deficits. Descriptions of mycotic aneurysms of the cavernous portion of the internal carotid artery are limited to case reports and case series. Most have been nonendocarditic in etiology with poor prognosis. We present a unique case with endocarditic etiology and an excellent prognosis.

OnabotulinumtoxinA wear-off in chronic migraine, observational cohort study.

INTRODUCTION: The current standard-of-care protocol for OnabotulinumtoxinA (BoNTA) injections consists of fixed-site injections every 12 weeks. This pattern is based on clinical practice and extrapolated from BoNTA injections for other, non-migraine-related indications. It is unclear if this protocol is optimal for chronic migraine. In clinical practice, migraine patients frequently describe a period of increased headache frequency and intensity in the few weeks preceding their next injections. In order to evaluate the duration of the clinical effect of BoNTA injections in chronic migraine, we studied the variation in headache frequency on a weekly basis during the 12-week period following treatment in a cohort of migraine patients. METHOD: 38 consecutive subjects were enrolled from an outpatient headache clinic, and asked to keep daily headache journals. 24 completed headache journals were analyzed. Headache frequency, duration and severity, as well as intake of symptomatic headache medications were recorded and compared among the different weeks. RESULTS: The time-response plot following BoNTA injection was roughly U-shaped, with 3 distinct phases: an induction phase, a maximum efficacy phase, and a wear-off phase. The time-response plot revealed that the wear-off commenced around the eighth week post injection. The mean difference in the number of headache days per week between the first and the eighth week was 1.8 (95% CI [0.670-2.830], p = 0.003). CONCLUSION: The effect of BoNTA injections on chronic migraines was not uniform throughout a 12-week period. A window of vulnerability to migraine attacks exist in the beginning and end of each cycle.

Extensive meningeal enhancement in acute central nervous system Lyme: Case series and review of literature.

INTRODUCTION: Clinical presentation of the central nervous system Lyme disease is nonspecific and therefore brain imaging and disease-specific serological testing is generally pursued to assist with diagnosis. Brain imaging findings are, however, rare and often unspecific. CASE DESCRIPTION: In the current report, we are presenting a rare magnetic resonance imaging (MRI) finding of extensive meningeal enhancement in two patients with acute Lyme disease. DISCUSSION: We discussed clinical implications and reviewed the relevant literature.

Seeing Is Believing: Headway27 as a Highly Visible and Versatile Microcatheter with Ideal Dimensions for Stroke Thrombectomy.

INTRODUCTION: Microcatheter selection is an infrequent focus of stroke thrombectomy technique evaluation. The Headway27 microcatheter strikes an excellent balance of microcatheter dimensions (156 cm length, 2.6 Fr distal OD, ID 0.027 inches) and visibility, making it ideal for stroke thrombectomy. METHODS: We evaluated a prospectively maintained acute stroke thrombectomy database containing 50 consecutive cases using the Headway27 microcatheter. From the database, patient demographics, clinical and angiographic information as well as procedural technical details and complications were extracted. RESULTS: Manual aspiration thrombectomy (MAT) was performed alone in 72% of cases, stentriever-assisted MAT was performed in 6% of cases, and a combination was used in 22% of cases. Median groin puncture to final recanalization time was 27 min and mTICI 2B/3 recanalization was achieved in 94% of cases. There were 2 intra-procedural complications, neither related to the microcatheter. In all cases, the Headway27 reached the intended target vessel: M1 (n = 4), M2 (n = 26), M3 (n = 13), P2 (n = 3), P3 (n = 1), and basilar artery (n = 3). There were no cases requiring usage of an additional or alternative microcatheter. In 45/47 cases of MAT, the reperfusion catheter tracked over the Headway to the clot/intended target; in two cases, the microcatheter was used to deploy a stentriever that then allowed the reperfusion catheter to track to the clot. CONCLUSION: The Headway27 microcatheter reliably facilitated rapid clot access in anterior and posterior circulation acute large vessel occlusions with no microcatheter-associated complications.

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration.

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-derived superoxide production. Both peroxidase- and lipase-deficient mutant forms of Prdx6 (Prdx6 C47S and S32A, respectively) failed to bind to or stabilize Nox1 components or support Nox1-mediated superoxide generation. Furthermore, the transition-state substrate analogue inhibitor of Prdx6 phospholipase A2 activity (MJ-33) was shown to suppress Nox1 activity, suggesting Nox1 activity is regulated by the phospholipase activity of Prdx6. Finally, wild type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which this antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing.