Sex and stroke risk factors: A review of differences and impact.

OBJECTIVES: There is an increase in stroke incidence risk over the lifetime of women, given their longer life expectancy. However, an alarming trend for sex disparities, particularly in certain stroke risk factors, shows a concerning need for focus on sex differences in stroke prevention and treatment for women. In this article, we are addressing sex differences in both traditional and sex-specific stroke risk factors. METHODS: We searched PubMed from inception to December 2022 for articles related to sex differences and risk factors for stroke. We reviewed full-text articles for relevance and ultimately included 152 articles for this focused review. RESULTS: Women are at increased risk for stroke from both traditional and non-traditional stroke risk factors. As women age, they have a higher disease burden of atrial fibrillation, increased risk of stroke related to diabetes, worsening lipid profiles, and higher prevalence of hypertension and obesity compared to men. Further, women carry sex hormone-specific risk factors for stroke, including the age of menarche, menopause, pregnancy, and its complications, as well as hormonal therapy. Men have a higher prevalence of tobacco use and atrial fibrillation, as well as an increased risk for stroke related to hyperlipidemia. Additionally, men have sex-specific risks related to low testosterone levels. CONCLUSIONS: By identifying biological sex-specific risk factors for stroke, developing robust collaborations, researching, and applying the knowledge for risk reduction strategies, we can begin to tailor prevention and reduce the global burden of stroke morbidity and mortality.

Leptomeningeal Carcinomatosis Mimicking Reversible Cerebral Vasoconstriction Syndrome.

Leptomeningeal carcinomatosis is the result of metastatic infiltration of the leptomeninges by malignant cells originating from an extra-meningeal primary tumor site. We describe a patient with active breast cancer who presented with thunderclap headaches (THs) and imaging showing multi-segment irregular arterial narrowing of intracranial vasculature. A 58-year-old Caucasian woman with active stage IV estrogen receptor-positive breast adenocarcinoma and migraine presented with THs. Computed tomography and brain magnetic resonance imaging (MRI) without contrast were unremarkable. Over a period of one week, she had recurrent THs. Interval vessel imaging showed multi-segment irregular arterial narrowing. Treatment with verapamil was initiated for suspected reversible cerebral vasoconstriction syndrome (RCVS). She subsequently had two discrete episodes of confusion with aphasia and left upper extremity numbness. Repeat gadolinium-enhanced MRI showed nodular leptomeningeal enhancement. Lumbar puncture revealed malignant cells in the cerebrospinal fluid consistent with leptomeningeal carcinomatosis. She subsequently underwent whole brain radiation treatment and intrathecal chemotherapy and had no further episodes of TH. Our case emphasizes the importance of considering leptomeningeal carcinomatosis in the differential diagnosis of THs and reversible cerebral vasculopathy, especially in patients with known underlying active cancer. The illustration also proves the importance of a complete work-up in patients with known malignancy in the setting of suspected RCVS.

Endovascular thrombectomy for acute ischemic stroke in patients with cancer: a propensity-matched analysis.

BACKGROUND: There is a paucity of data and a belief that endovascular thrombectomy (EVT) has low efficacy for acute ischemic stroke (AIS) in patients with cancer. We aimed to critically compare the clinical outcomes of EVT for AIS in patients with and without cancer. METHODS: Records of all patients undergoing EVT for AIS between January 2015 and 2020 were screened for cancer at the time of EVT. Active cancer was defined as patients who were diagnosed with cancer and were undergoing or refused treatment for that cancer. Baseline modified Rankin Scale (mRS), age and sex were used in a 1:5 propensity score matching ratio. After matching we evaluated for any change in the National Institutes of Health Stroke Scale (NIHSS) from baseline to discharge, hemorrhagic transformation (HT), and 90-day mRS and mortality. RESULTS: There were 19 patients with cancer and 95 matched controls. The mean±SD age was 70.89±11.16 years, and 17 (89.47%) were female. The baseline NIHSS was 22±7.5 and baseline mRS was 1 (IQR 1). There was no significant difference in change in baseline to discharge NIHSS, 90-day mRS or mortality; 90-day mRS 0-2 was 45.2% in the non-cancer group versus 46.7% in cancer group (p=0.54). HT was significantly higher in patients with cancer (57.89% vs 6.49%, p<0.001). CONCLUSIONS: In propensity matched analysis of patients undergoing EVT for AIS with and without cancer, 90-day functional outcomes and mortality were similar. However, there was a significantly higher rate of HT in cancer patients.

Acute Ischemic Stroke and COVID-19: Experience From a Comprehensive Stroke Center in Midwest US.

Background: COVID-19 has been associated with increased risk of venous and arterial thromboembolism including ischemic stroke. We report on patients with acute ischemic stroke and concomitant COVID-19 in a diverse patient population. Methods: This is a retrospective analysis of patients hospitalized with acute ischemic stroke (AIS) and COVID-19 to our comprehensive stroke center in Chicago, IL, between March 1, 2020, and April 30, 2020. We reviewed stroke characteristics, etiologies, and composite outcomes. We then compared our cohort with historic patients with AIS without COVID-19 admitted in the same time frame in 2019 and 2020. Results: Out of 13 patients with AIS and COVID-19, Latinos and African-Americans compromised the majority of our cohort (76.8%), with age ranging from 31-80 years. Most strokes were cortical (84.6%) and more than 50% of patients had no identifiable source, and were categorized as embolic stroke of unknown source (ESUS). A trend toward less alteplase administration was noted in the COVID-19 stroke patients compared to the non-COVID group from 2020 and 2019 (7.1 vs. 20.7% p 0.435 and 7.1 vs. 27.2% p 0.178). Endovascular thrombectomy was performed in 3 (23%) patients. Systemic thrombotic complications occurred in 3 (23%) COVID-19 AIS patients. Median National Institutes of Health Stroke Scale and modified Rankin Scale at discharge were 11 (IQR 4-23) and 4 (IQR 3-4), respectively. In the logistic regression model corrected for age and sex, COVID-19 was associated with discharge to mRS > 2 (p 0.046, OR 3.82, CI 1.02-14.3). Eight patients (63.8%) were discharged home or to acute rehabilitation, and two deceased from COVID-19 complications. Conclusion: AIS in the setting of COVID-19 is associated with worse outcomes, especially among African-American and Latino populations. Large vessel disease with ESUS was common suggesting an increased risk of coagulopathy and endothelial dysfunction as a potential etiology.

Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline.

OBJECTIVE: To report neurological manifestations seen in patients hospitalized with Coronavirus disease 2019 (COVID-19) from a large academic medical center in Chicago, Illinois. METHODS: We retrospectively reviewed data records of 50 patients with COVID-19 who were evaluated by the neurology services from March 1, 2020 - April 30, 2020. Patients were categorized into 2 groups based on timing of developing neurological manifestations: the "Neuro first" group had neurological manifestations upon initial assessment, and the "COVID first" group developed neurological symptoms greater than 24 h after hospitalization. The demographics, comorbidities, disease severity and neurological symptoms and diagnoses of both groups were analyzed. Statistical analysis was performed to compare the two groups. RESULTS: A total of 50 patients (48% African American and 24% Latino) were included in the analysis. Most common neurological manifestations observed were encephalopathy (n = 30), cerebrovascular disease (n = 20), cognitive impairment (n = 13), seizures (n = 13), hypoxic brain injury (n = 7), dysgeusia (n = 5), and extraocular movement abnormalities (n = 5). The "COVID-19 first" group had more evidence of physiologic disturbances on arrival with a more severe/critical disease course (83.3% vs 53.8%, p 0.025). CONCLUSION: Neurologic manifestations of COVID-19 are highly variable and can occur prior to the diagnosis of or as a complication of the viral infection. Despite similar baseline comorbidities and demographics, the COVID-19 patients who developed neurologic symptoms later in hospitalization had more severe disease courses. Differently from previous studies, we noted a high percentage of African American and Latino individuals in both groups.

Cerebral Vasculopathy and Spinal Arachnoiditis: Two Rare Complications of Ventriculitis Post Subarachnoid Hemorrhage.

This report describes a case of subarachnoid hemorrhage complicated by ventriculitis and subsequent delayed cerebral vasospasm, severe chronic spinal arachnoiditis, and Froin syndrome. A 60-year-old woman presented with diffuse aneurysmal subarachnoid hemorrhage and underwent successful coil embolization of ruptured left anterior cerebral artery aneurysm. Her course was complicated by bacterial ventriculitis and acute hydrocephalus necessitating ventriculoperitoneal shunt placement. She returned ten weeks later with recurrent headaches; CT angiography showed diffuse cerebral vasospasm. Spine magnetic resonance imaging ordered due to concern for mass or other obstruction of the cerebrospinal fluid obstruction based on lumbar puncture results showed leptomeningeal enhancement with loculated cerebrospinal fluid collections along the spinal canal concerning for spinal arachnoiditis and septal adhesions. Lumbar puncture was consistent with Froin syndrome. She was treated with calcium-channel blockers. Follow up imaging showed resolution of vasospasm, but progression of the arachnoiditis. No surgical intervention was pursued as the patient had no symptoms concerning myelopathy. Aneurysmal subarachnoid hemorrhage and ventriculitis may lead to delayed reversible vasculopathy as well as arachnoiditis, with "dry tap" and Froin-like syndrome picture. Workup should be initiated in patients who develop persistent headaches or myelopathic changes to investigate these possibilities.

Evaluation of Patients with High National Institutes of Health Stroke Scale as Thrombectomy Candidates Using the Kentucky Appalachian Stroke Registry.

INTRODUCTION: Mechanical thrombectomy has become standard of care for emergent large vessel occlusive stroke. Estimates of incidence for thrombectomy eligibility vary significantly. National Institutes of Health Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥10 to determine patient characteristics among that group along with effects and needs in thrombectomy utilization. METHODS: Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome. RESULTS: Between 2010 and 2016, 1,510 patients were admitted with NIHSS ≥10. 87.2% had high blood pressure, 69.6% had dyslipidemia, and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥10 with females being older on average and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016, but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010-2014, the 2015-2016 period had higher rates of obesity and tobacco abuse. CONCLUSION: Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.

Effect of Known Atrial Fibrillation and Anticoagulation Status on the Prehospital Identification of Large Vessel Occlusion.

INTRODUCTION: The Cincinnati Prehospital Stroke Severity scale (C-STAT), Los Angeles Motor Scale (LAMS), Rapid Arterial Occlusion Evaluation (RACE) score, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scales were designed to aid emergency responder identification of patients with stroke related to large vessel occlusion (LVO). We hypothesized that the addition of a known history of atrial fibrillation (AF) without anticoagulation to currently used scales would improve LVO detection. METHODS: Medical records of patients admitted to a Comprehensive Stroke Center with acute ischemic stroke in 2014-2015 were reviewed. LVO identification using the C-STAT, LAMS, RACE, and FAST-ED scores and the AF variable were compared using univariable analyses. The areas under the receiver operating curves (AUCs) were then compared for each score, the AF variable, and each score with the addition of the AF variable. RESULTS: The sample included 233 patients without and 188 patients with an LVO. A history of known AF, history of AF with no anticoagulation, and the C-STAT, LAMS, RACE, and FAST-ED scores were each associated with LVO in univariable analyses. The AUCs for C-STAT, LAMS, RACE, and FAST-ED were similar. The addition of the known AF and no anticoagulation variable did not appreciably change these AUCs. CONCLUSION: Although known AF with no anticoagulation was associated with LVO in patients with acute ischemic stroke, this historic feature did not improve the accuracy of existing LVO detection scales.

When Headache Warns of Homeostatic Threat: the Metabolic Headaches.

Headache attributable to disorders of homeostasis represents a diverse diagnostic category in which external (i.e., high-altitude) or internal (i.e., fasting) demands exceed homeostatic capacity, resulting in symptomatic headaches. Metabolic headaches, especially fasting headache, have been observed to be common in the general population. In many cases, a history of migraine is a risk factor, consistent with the hypothesis of an adaptive, evolutionary role of headache to warn against environmental and physiological threats. Because many exposures may also be interpreted as migraine triggers, some authors have considered certain disorders in this category to more accurately represent primary headache disorders. Nonetheless, these disorders not only represent important clinical entities, recognition of which may prevent medical morbidity, but also interesting exposure-response models to further our understanding regarding headache pathophysiology.

Reduced effect of stimulation of AMPA receptors on cerebral O2 consumption in a rat model of autism.

Previous work demonstrated that basal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activity did not contribute to the elevated regional cerebral O2 consumption in the brains of Eker rat (an autism-tuberous sclerosis model). We tested the hypothesis that increased stimulation of AMPA receptors also would not augment cerebral O2 consumption in the Eker rat. Three cortical sites were prepared for administration of saline, 10⁻4 and 10⁻³ M AMPA in young (4 weeks) male control Long Evans and Eker rats (70-100 g). Cerebral blood flow (¹4C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. Receptor levels were studied through Western analysis of the GLuR1 subunit of the AMPA receptor. We found significantly increased cortical O2 consumption (+33%) after 10⁻4 M AMPA in control rats. The higher dose of AMPA did not further increase consumption. In the Eker rats, neither dose led to a significant increase in cortical O2 consumption. Regional blood flow followed a similar pattern to oxygen consumption but cortical O2 extraction did not differ. Cortical AMPA receptor protein levels were significantly reduced (-21%) in the Eker compared to control rats. Both O2 consumption and blood flow were significantly elevated in the pons of the Eker rats compared to control. These data demonstrate a reduced importance of AMPA receptors in the control of cortical metabolism, related to reduced AMPA receptor protein, in the Eker rat. This suggests that increasing AMPA receptor activity may not be an effective treatment for children with autism spectrum disorders as they also have reduced AMPA receptor number.