Maternal vs Fetal Origin of Placental Intervillous Thrombi.

OBJECTIVES: To determine maternal vs fetal origin for blood in placental intervillous thrombi (IVTs). METHODS: We used comparative analysis of microsatellites (short tandem repeats [STRs]), sex chromosome fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for fetal (ɑ-fetoprotein [AFP]) and maternal (immunoglobulin M [IgM]) serum proteins to distinguish the origin of IVTs. Using an informatics approach, we tested the association between IVTs and fetomaternal hemorrhage (FMH). RESULTS: In 9 of 10 cases, the preponderance of evidence showed that the thrombus was mostly or entirely maternal in origin. In 1 case, the thrombus was of mixed origins. STR testing was prone to contamination by entrapped fetal villi. FISH was useful but limited only to cases with male fetuses. IgM showed stronger staining than AFP in 9 cases, supporting maternal origin. By informatics, we found no association between IVTs and FMH. CONCLUSIONS: Evidence supports a maternal origin for blood in IVTs. IHC for IgM and AFP may be clinically useful in determining maternal vs fetal contribution to IVTs.

Concomitant cervical spine fractures are the primary driver of disability after traumatic vertebral artery dissection: A Case series of 123 patients.

Background: Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. Aims and Objectives: To characterize the tVAD population and identify factors associated with clinical outcomes. Materials and Methods: We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Results: Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p<0.0007), were more likely to smoke (OR 3.0 [1.2178, 7.4028], p=0.0202), be male (OR 7.125 [3.0181, 16.8236], p<0.0001), and have mRS≥3 at discharge (OR 3.0545 [1.0937, 8.5752], p=0.0449). On multivariable regression, only fracture independently predicted mRS≥3 at discharge (OR 5.6898 [1.5067, 21.4876], p=0.010). Conclusion: tVADs may be associated with stroke and/or cervical fracture. Presenting symptoms predict stroke, but baseline demographic and clinical characteristics do not. Comorbid cervical fractures, not stroke, drive negative outcomes.

Traumatic and Spontaneous Vertebral Artery Dissections: An Analysis of Tertiary-Center 310 Patient Cohort.

BACKGROUND: Vertebral artery dissections (VADs) are rare yet potentially devastating events. While the etiology of these events is either traumatic or spontaneous, there is a paucity of quantitative literature comparing the two. OBJECTIVE: To identify differences in predisposing factors, event characteristics, and clinical outcomes between traumatic VADs (tVADs) and spontaneous VADs (sVADs). METHODS: We retrospectively identified patients with VADs presenting to our institution at VAD onset with at least a 3-mo follow-up. Demographics, event characteristics, treatment details, and neurological outcomes as modified Rankin scale (mRS) scores were collected. RESULTS: Of the 310 patients sustaining 366 VADs total, 187 (60.3%) patients experienced a total of 221 (60.4%) sVADs and 123 (39.7%) patients experienced a total of 145 (39.6%) tVADs. sVADs were more likely to occur in the intracranial course of the artery (P = .042) and have a lower mRS at discharge, 3-month, and last clinical follow-up (P = 003, .002, and .001, respectively). tVADs were more likely associated with concomitant fractures (P < .001). CONCLUSION: Despite similar patient populations, tVADs are associated with higher mRS scores at all time points. Although further study is needed, this may suggest other concomitant trauma rather than the VAD itself is contributing to worse neurological status in patients with tVADs.

Clinical Characteristics, Course, and Outcomes of Vertebral Artery Dissections in the Postpartum Period.

BACKGROUND: Postpartum vertebral artery dissections (ppVADs) are rare but potentially morbid conditions that occur in otherwise healthy patients. OBJECTIVE: To evaluate clinical characteristics of ppVADs. METHODS: Demographic, clinical, treatment, and outcome data were collected on ppVADs and are presented in a case series of 12 patients and compared to the general cohort. RESULTS: In total, 12 patients had ppVADs in our cohort of 310 patients with vertebral artery dissections (VADs). They occurred 11.27 days (95% CI, -0.85 to 23.39) postdelivery. Of these, there were 5 (42%) with a hypertensive disorder of pregnancy, and 4 (33%) who had migraines. A total of 3 (25%) had ischemic strokes and 1 (8%) had a subarachnoid hemorrhage. In total, 2 patients (17%) had unfavorable modified Rankin Scale (mRS, 2-6) at discharge from hospital. Patients with ppVADs more often had bilateral VADs (42% vs 17%, P = .03), had pseudoaneurysms (50% vs 18%, P = .0068), were younger (33.83 years vs 44.32 years, P = .018), and had lower Charlson Comorbidity Index (CCI = 0 vs 0.99, P = .0038). Anticoagulant treatment was used in a similar percentage of patients. Multivariate analysis revealed 3 factors were predictive of change in mRS: CCI (OR = 1.09, 95% CI, 1.02-1.15), stroke (OR = 0.78, 95% CI, 0.65-0.95), and mRS at hospital discharge (OR = 0.80, 95% CI, 0.74-0.87). CONCLUSION: There are only 15 isolated ppVADs reported in the literature; this study adds 12 patients with 17 ppVADs. Postpartum VADs occur in younger, healthier patients than in the general cohort, raising questions about mechanism of injury. The majority of ppVADs have good neurological outcomes.

Chiropractic associated vertebral artery dissection: An analysis of 34 patients amongst a cohort of 310.

BACKGROUND: Vertebral artery dissections (VAD) are a rare but important cause of ischemic stroke, especially in younger patients. Many etiologies have been identified, including MVAs, cervical fractures, falls, physical exercise, and cervical chiropractic manipulation. The goal of this study was to investigate the subgroup of patients who suffered a chiropractor-associated injury and determine how their prognosis compared to other-cause VAD. METHODS: We conducted a retrospective chart review of 310 patients with vertebral artery dissections who presented at our institution between January 2004 and December 2018. Variables included demographic data, event characteristics, treatment, radiographic outcomes, and clinical outcomes measured using the modified Rankin Scale. FINDINGS: Overall, 34 out of our 310 patients suffered a chiropractor-associated injury. These patients tended to be younger (p = 0.01), female (p = 0.003), and have fewer comorbidities (p = 0.005) compared to patients with other-cause VADs. The characteristics of the injuries were similar, but chiropractor-associated injuries appeared to be milder at discharge and at follow-up. A higher proportion of the chiropractor-associated group had injuries in the 0-2 mRS range at discharge and at 3 months (p = 0.05, p = 0.04) and no patients suffered severe long-term neurologic consequences or death (0% vs. 9.8%, p = 0.05). However, when a multivariate binomial regression was performed, these effects dissipated and the only independent predictor of a worse injury at discharge was the presence of a cervical spine fracture (p < 0.001). INTERPRETATION: Chiropractor-associated injuries are similar to VADs of other causes, and apparent differences in the severity of the injury are likely due to demographic differences between the two populations.

Characteristics and Predictors of Outcome of Pseudoaneurysms Associated With Vertebral Artery Dissections: A 310-Patient Case Series.

BACKGROUND: Vertebral artery dissections (VADs) are a common cause of stroke in young patients and can result in various secondary effects, including pseudoaneurysm formation. OBJECTIVE: To identify differences in predisposing factors and outcomes for VADs with and without concomitant pseudoaneurysms. METHODS: We retrospective chart reviewed patients who presented to our institution at the time of VAD with at least a 3-mo clinical follow-up. Demographics, VAD characteristics, treatment, and outcomes represented as modified Rankin scale (mRS) scores were collected. RESULTS: Of 310 patients with a VAD included in this study, 301 patients had an identified pseudoaneurysm status, with 54 pseudoaneurysm-associated VADs and 247 VADs not associated with pseudoaneurysm. VAD patients with associated pseudoaneurysms were more likely to be female (P < .004), have bilateral VADs (P < .001), and have fewer vertebral artery segments affected (P = .018), and less likely to have stroke (P < .008) or occlusion of the vertebral artery (P < .001). There was no difference in the proportion of patients treated with antiplatelet agents (P = .12) or anticoagulants (P = .27) between the groups. VAD patients with associated pseudoaneurysms were more likely to have a higher mRS at 3-mo follow-up (P = .044) but not discharge (P = .18) or last follow-up (P = .05). VAD patients with pseudoaneurysms were equally likely to have resolution of occlusion (P = .40) and stenosis (P = .19). CONCLUSION: Demographics and clinical and radiological characteristics of VADs associated with pseudoaneurysms are different from those without associated pseudoaneurysms. Vertebral artery dissections with concomitant pseudoaneurysms are neither associated with worse functional nor radiographic outcomes.

Vertebral Artery Dissections With Concurrent Intracranial Hemorrhage: A Case Series of 13 Patients Among a Cohort of 301.

BACKGROUND: Vertebral artery dissections (VADs) are a rare cause of ischemic stroke that can occasionally lead to intracranial hemorrhage (ICH). This study aims to identify differences in predisposing factors, event characteristics, and outcomes between patients with only a VAD and patients with VAD and concomitant ICH. METHODS: We conducted a retrospective chart review of 301 patients who presented with VADs at our institution from 2004-2018. A total of 13 patients were identified with VAD and concomitant ICH. Data were collected on demographics, event characteristics, treatments, and neurologic outcomes, measured using the modified Rankin Scale (mRS). RESULTS: VAD+ICH and VAD-only groups were similar in terms of age, sex, and recorded comorbidities. Additionally, etiology of the dissections did not seem to vary between groups (P = 0.6), even when selecting for traumatic causes such as motor vehicle accidents (P = 0.22) and violence (P = 0.25). Concomitant strokes and aneurysms/pseudoaneurysms occurred in similar proportions as well, but cervical fractures were more common in the VAD+ICH group (P = 0.003). Using the mRS as a measure of neurological outcome, we found that the VAD+ICH group had worse neurologic function at discharge, 3-month follow-up, and last follow-up (P < 0.001). CONCLUSIONS: Patients who experienced an ICH in addition to a VAD did not have any identifiable risk factors. Cervical spine fractures were more common in patients with VAD and ICH. VAD patients with a concomitant ICH have worse neurologic outcomes than patients with only a VAD.

Vertebral artery dissections with and without cervical spine fractures: Analysis of 291 patients.

OBJECTIVES: Vertebral artery dissections occur when tears in the intimal layer of the vertebral artery and are associated with trauma, infection, and spontaneous etiologies. We aimed to identify differences in predisposing factors and outcomes in vertebral artery dissections associated with cervical spine fractures compared to those not associated with cervical spine fractures. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with vertebral artery dissections who presented to our institution at the time of dissection and had a minimum of 3 month follow-up and collected data on demographics, event characteristics, treatments, and outcomes in the form of modified Rankin scale scores. RESULTS: In total, 291 patients with VAD were included in this study. Thirty-nine patients with VADs had associated fracture, while 252 patients had VADs without fracture. VAD patients with associated cervical fractures were more likely to be male (p < 0.001), have a greater number of comorbid conditions (p < 0.01), be smokers (p = 0.045), or have violence (p < 0.001) or motor vehicle accidents (p < 0.001) as the cause of their VADs. VAD patients with associated cervical fractures were less likely to have associated aneurysms or pseudoaneurysms (p = 0.002). VAD patients with associated cervical fractures were more likely to have higher mRS at discharge from the hospital (p < 0.001), 3 month follow-up (p < 0.001), and last follow-up (p < 0.001). CONCLUSION: Cervical spine fracture is likely the primary driver of poor neurological outcomes following vertebral artery dissection with associated cervical spine fracture.

Placental pathology in COVID-19.

OBJECTIVES: To describe histopathologic findings in the placentas of women with COVID-19 during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020 and May 5, 2020 were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: 16 placentas from patients with SARS-CoV-2 were examined (15 with live birth in the 3rd trimester 1 delivered in the 2nd trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), including abnormal or injured maternal vessels, as well as delayed villous maturation, chorangiosis, and intervillous thrombi. Rates of acute and chronic inflammation were not increased. The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of features of maternal vascular malperfusion (MVM), a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

Placental Pathology in COVID-19.

OBJECTIVES: To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy. METHODS: Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma. RESULTS: Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma. CONCLUSIONS: Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.

Vascular type 1 angiotensin receptors control blood pressure by augmenting peripheral vascular resistance in female mice.

Angiotensin II (ANG II) is a major mediator of hypertension pathogenesis. In addition, there are well-documented differences in expression of the renin-angiotensin system (RAS) components and ANG II responses between males and females, which may explain sex differences in blood pressure (BP) and hypertension epidemiology. We previously showed that type 1A angiotensin (AT1A) receptors in vascular smooth muscle cells (VSMCs) play a critical role in BP regulation and hypertension pathogenesis, but these studies were carried out in male mice. Therefore, the major goal of the current studies was to examine the impact of VSMC AT1A receptors on BP and hypertension pathogenesis in female mice. We found that elimination of VSMC AT1A receptors in female mice reduced (≈8 mmHg) baseline BP without altering sodium sensitivity. The severity of ANG II-induced hypertension was diminished (≈33% reduction in BP), particularly during the last 2 wk of chronic ANG II infusion, compared with controls, but natriuresis was not altered during the first 5 days of ANG II infusion. Urinary norepinephrine levels were enhanced in female SMKO compared with control mice. There was a virtually complete elimination of ANG II-induced kidney hemodynamic responses with attenuation of acute vasoconstrictor responses in the systemic vasculature. These findings demonstrate that direct vascular actions of AT1A receptors play a prominent role in BP control and hypertension pathogenesis in female mice.

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control.