An unusual case of carotidynia preceding recurrent ischemic stroke with carotid thrombosis in a patient with systemic lupus erythematosus.

Carotid artery thrombosis following carotidynia is an uncommon manifestation of systemic lupus erythematosus. We report the case of a woman without evidence of a lupus flare-up who presented with the unusual clinical course of ipsilateral carotidynia and recurrent ischemic stroke due to carotid thrombosis. To our knowledge, this is the first case of such an unusual manifestation in lupus and highlights distinctive challenges in the diagnosis and management of carotid artery thrombosis following carotidynia.

Multiple Sites of Arterial Thrombosis in A 35-Year Old Patient after ChAdOx1 (AstraZeneca) Vaccination, Requiring Emergent Femoral and Carotid Surgical Thrombectomy.

BACKGROUND: Vaccine Induced Thrombotic Thrombocytopenia (VITT) is a rare complication following ChAdOx1 (AstraZeneca) vaccination. Venous thrombosis in unusual sites such as splachnic or intracranial thrombosis, is the commonest manifestation. CASE REPORT: We report a 35-year-old male patient who presented with acute left leg ischemia and thrombocytopenia 11-days after vaccination requiring emergent thrombectomy. During work-up, a localized thrombus was detected in the left carotid bifurcation mandating carotid thrombectomy. Localized right iliac thrombus causing a non-limiting flow stenosis was treated conservatively. The platelet aggregating capacity of patient's plasma was confirmed in a functional assay, thereby establishing VITT. CONCLUSION: To the best of our knowledge this is the first case presenting multiple arterial thromboses requiring surgical treatment after ChAdOx1 vaccination.

Successful Endovascular Therapy in COVID-19 Associated Pediatric Ischemic Stroke.

Cerebrovascular diseases attributed to coronavirus disease 2019 (COVID-19) are uncommon but can result in devastating outcomes. Pediatric acute ischemic strokes are themselves rare and with very few large vessel occlusion related acute ischemic strokes attributed to COVID-19 described in the literature as of date. COVID-19 pandemic has contributed to acute stroke care delays across the world and with pediatric endovascular therapy still in its infancy, it poses a great challenge in facilitating good outcomes in children presenting with acute ischemic strokes in the setting of COVID-19. We present a pediatric patient who underwent endovascular therapy for an internal carotid artery occlusion related acute ischemic stroke in the setting of active COVID-19 and had an excellent outcome thanks to a streamlined stroke pathway involving the vascular neurology, neuro-interventional, neurocritical care, and anesthesiology teams.

Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

BACKGROUND: CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored. We examined the role of indoleamine 2,3-dioxygenase-1 (IDO-1), a rate-limiting enzyme of kynurenine biogenesis, in CKD-associated thrombosis after vascular injury. METHODS: IDO-1 expression in mice and human vessels was examined. IDO-1-/- mice, IDO-1 inhibitors, an adenine-induced CKD, and carotid artery injury models were used. RESULTS: Both global IDO-1-/- CKD mice and IDO-1 inhibitor in wild-type CKD mice showed reduced blood Kyn levels, TF expression in their arteries, and thrombogenicity compared with respective controls. Several advanced IDO-1 inhibitors downregulated TF expression in primary human aortic vascular smooth muscle cells specifically in response to uremic serum. Further mechanistic probing of arteries from an IS-specific mouse model, and CKD mice, showed upregulation of IDO-1 protein, which was due to inhibition of its polyubiquitination and degradation by IS in vascular smooth muscle cells. In two cohorts of patients with advanced CKD, blood IDO-1 activity was significantly higher in sera of study participants who subsequently developed thrombosis after endovascular interventions or vascular surgery. CONCLUSION: Leveraging genetic and pharmacologic manipulation in experimental models and data from human studies implicate IS as an inducer of IDO-1 and a perpetuator of the thrombotic milieu and supports IDO-1 as an antithrombotic target in CKD.

Simultaneous bilateral mechanical thrombectomy in a patient with COVID-19.

Owing to systemic inflammation and widespread vessel endotheliopathy, SARS-CoV-2 has been shown to confer an increased risk of cryptogenic stroke, particularly in patients without any traditional risk factors. In this report, we present a case of a 67-year-old female who presented with acute stroke from bilateral anterior circulation large vessel occlusions, and was incidentally found to be COVID-positive on routine hospital admission screening. The patient had a large area of penumbra bilaterally, and the decision was made to pursue bilateral simultaneous thrombectomy, with two endovascular neurosurgeons working on each side to achieve a faster time to recanalization. Our study highlights the utility and efficacy of simultaneous bilateral thrombectomy, and this treatment paradigm should be considered for use in patients who present with multifocal large vessel occlusions.

SARS-CoV-2, recurrent ischemic strokes and carotid macrothrombosis: the other face of the cytokine storm (a case report).

Since December 2019, the world has experienced the emergence in China of a new infection called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection quickly has progressed to a global pandemic since March 2020, with very high human-to-human transmission rate. Besides lung injury, COVID-19 is also associated with cardio and neurovascular complications. Herein, we report the case of a 77-year-old female who presented with non-severe COVID-19 and multiple ischemic strokes secondary to an extensive carotid thrombosis. The ischemic stroke was supposed to have been caused by the cytokine storm related to COVID-19. The possibility of hemorrhagic transformation, based on the assessment of bleeding score, limited the use of anticoagulation, and probably explained the stroke recurrence and poor outcome in our patient. The pathogenic mechanism and the management of this complex situation are still lacking and further studies are needed.

Left Carotid Artery Thrombosis Due to Thromboangiitis Obliterans.

ABSTRACT: Thromboangiitis obliterans (TAO, Buerger disease) is a segmental, non-atherosclerotic vasculitis that causes occlusion of the small and medium sized vessels of the distal extremities. In rare cases, it can affect vessels in the gastrointestinal, cerebrovascular, coronary, and renal systems. The etiology of thromboangiitis obliterans is unknown, but there is a strong association with smoking in the development and the progression of the disease. We present the case of a 42-year-old homeless female smoker, who was found dead outdoors. Although originally suspected to be a possible trauma-related death, autopsy revealed a thrombus in her left carotid artery, which caused an acute cerebral infarction. It was concluded that thromboangiitis obliterans, likely precipitated by smoking, was the cause of the thrombosis and subsequent death.

Common Carotid Artery Occlusion in a Young Patient: Can Large-Vessel Stroke Be the Initial Clinical Manifestation of Coronavirus Disease 2019?

BACKGROUND: The occurrence of large-vessel occlusion in young patients with coronavirus disease 2019 (COVID-19) infection has been exceedingly rare. An extensive review of reported studies revealed a few reported cases. In the present report, we have described the clinical presentation, radiological findings, and outcome of large-vessel occlusion in a young patient with COVID-19 and reviewed the pertinent reported data on this condition. CASE DESCRIPTION: A 31-year-old woman was in her usual state of health until she had presented with a 3-day history of right-sided weakness, slurred speech, and decreased vision. The patient had been taken to several hospitals where she had been treated conservatively with analgesics and discharged. Shortly thereafter, her weakness had become progressive. She had become severely dysarthric and unresponsive. On arrival to the emergency department, her physical examination revealed that she was stuporous, with a Glasgow coma scale of 10 (eye response, 3; verbal response, 2; motor response, 5). The National Institutes of Health Stroke Scale score was 19 on presentation. Brain computed tomography and computed tomography venography revealed an occluded left internal carotid artery and left middle cerebral artery with subacute left middle cerebral artery territory infarction and midline shift. Computed tomography angiography revealed complete occlusion of the left common carotid artery. An emergent decompressive craniectomy was successfully performed. The patient was shifted to the intensive care unit. She was later found to be positive for COVID-19. CONCLUSIONS: Although rare, patients with COVID-19 can present with large-vessel occlusion. Prompt identification of COVID-19-related coagulopathy is essential to assess young patients with clinical manifestations of infarction.

Internal carotid artery thrombosis in COVID 19 / Trombosis de arteria carótida interna en COVID 19

Abstract Case description: 37-year-old female with PCR-RT swab for COVID-19 positive, with neurological manifestation as a result of internal carotid artery occlusion. Clinical findings: Nasal congestion and sneezing of 5 days duration; pulsatile headache in the left hemicranium 3 days prior to admission, with intensity 6/10 according to the visual analogue scale, accompanied by phosphenes, photophobia and diplopia; with subsequent developing right hemiparesis over a 26-hour period. Treatment and result: She was given medical management with oral antiplatelet agents and anticoagulants (subcutaneous and oral) during his hospitalization, it was not possible to perform thrombolysis and thrombectomy due to the high risk of complications. He was discharged at 14 days, without functional limitation, symmetrical strength in upper and lower limbs, bilateral visual acuity 20/20, denying headache. Clinical relevance: The case presented here describes a pattern in how data supporting an association between COVID-19 and stroke in young populations with or without typical vascular risk factors, sometimes with only mild respiratory symptoms, is increasing. Prospective studies are required to further evaluate this association, as well as anticoagulation studies to prevent these potentially life-threatening events.

Resumen Descripción del caso: Mujer de 37 años con hisopado PCR-RT para COVID-19 positivo, con manifestación neurológica por oclusión de la arteria carótida interna. Hallazgos clínicos: Congestión nasal y estornudos de 5 días de duración; cefalea pulsátil en hemicráneo izquierdo 3 días antes del ingreso, con intensidad 6/10 según la escala visual analógica, acompañada de fosfenos, fotofobia y diplopía; con posterior desarrollo de hemiparesia derecha durante un período de 26 horas. Tratamiento y resultado: Se le brindó manejo médico con antiagregantes plaquetarios orales y anticoagulantes (subcutáneos y orales) durante su internación, no fue posible realizar trombólisis y trombectomía por alto riesgo de complicaciones. Fue dado de alta a los 14 días, sin limitación funcional, fuerza simétrica en miembros superiores e inferiores, agudeza visual bilateral 20/20, negando cefalea. Relevancia clínica: Se describe un patrón que indica cómo están aumentando los datos que apoyan una asociación entre COVID-19 y el accidente cerebrovascular en poblaciones jóvenes con o sin factores de riesgo vascular típicos, a veces con solo síntomas respiratorios leves. Se requieren estudios prospectivos para evaluar más a fondo esta asociación, así como estudios de anticoagulación para prevenir estos eventos potencialmente mortales.

COVID-19-Associated Carotid Atherothrombosis and Stroke.

We present a radiology-pathology case series of 3 patients with coronavirus disease 2019 (COVID-19) with acute ischemic stroke due to fulminant carotid thrombosis overlying mild atherosclerotic plaque and propose a novel stroke mechanism: COVID-associated carotid atherothrombosis.

The JUUL E-Cigarette Elevates the Risk of Thrombosis and Potentiates Platelet Activation.

BACKGROUND: Smoking is the main preventable cause of death in the United States and worldwide and is associated with serious cardiovascular health consequences, including thrombotic diseases. Recently, electronic cigarettes (e-cigarettes) and, in particular JUUL, have attained wide popularity among smokers, nonsmokers, pregnant females, and even the youth, which is alarming. Interestingly, there is/are no information/studies regarding the effect of JUUL on cardiovascular diseases, specifically in the context of modulation of platelet activation. Thus, it is important to discern the cardiovascular disease health risks associated with JUUL. METHODS AND RESULTS: We used a passive e-vape vapor inhalation system where C57BL/6J mice (10-12 weeks old) were exposed to JUUL e-cigarette vape. Menthol flavored JUUL pods containing 5% nicotine by weight were used as the e-liquid. Mice were exposed to a total of 70 puffs daily for 2 weeks; 3-second puff duration, and 25-second puff interval. The effects of JUUL relative to clean air were analyzed, on mouse platelet function in vitro (eg, aggregation) and in vivo (eg, FeCl3-induced carotid artery injury thrombosis model). Our results indicate that short-term exposure to JUUL e-cigarette causes hyperactivation of platelets and shortens the thrombus occlusion as well as hemostasis/bleeding times, relative to clean air (medians of 14 vs. 200 seconds, P < .01 and 35 vs. 295 seconds, P < .001, respectively). CONCLUSION: Our findings document-for the first time-that short-term exposure to the JUUL e-cigarette increases the risk of thrombotic events, in part by modulating platelet function, such as aggregation and secretion, in mice.

Macrothrombosis and stroke in patients with mild Covid-19 infection.

Coronavirus disease 2019 (COVID-19) is a pandemic disease currently affecting millions of people worldwide. Its neurological implications are poorly understood, and further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID-19, but nothing is known about coagulopathy in patients with milder disease. We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID-19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID-19. Our cases suggest that even in the absence of severe disease, patients with COVID-19 may be at increased risk of thrombus formation leading to stroke, perhaps resulting from viral involvement of the endothelium. Further systematic study is needed because this may have implications for primary and secondary stroke prevention in patients with COVID-19.

Atherosclerotic plaque injury-mediated murine thrombosis models: advantages and limitations.

In spite of current treatment strategies, myocardial infarction and stroke are still major causes of death worldwide. These events are triggered by damage of an atherosclerotic plaque, resulting in occlusive thrombus formation. Mouse studies have significantly contributed to our understanding of the mechanisms of atherogenesis and of thrombosis following plaque injury, but the extent to which the mouse serves as an accurate model of human disease is open to discussion. In this review, we provide a detailed overview and comparison of the described mouse models for atherothrombosis including their (dis)advantages. Herein guidance is provided on how to select a suitable atherothrombosis model for research questions primarily relevant to the field of thrombosis.

Internal carotid artery thrombosis in COVID 19.

CASE DESCRIPTION: 37-year-old female with PCR-RT swab for COVID-19 positive, with neurological manifestation as a result of internal carotid artery occlusion. CLINICAL FINDINGS: Nasal congestion and sneezing of 5 days duration; pulsatile headache in the left hemicranium 3 days prior to admission, with intensity 6/10 according to the visual analogue scale, accompanied by phosphenes, photophobia and diplopia; with subsequent developing right hemiparesis over a 26-hour period. TREATMENT AND RESULT: She was given medical management with oral antiplatelet agents and anticoagulants (subcutaneous and oral) during his hospitalization, it was not possible to perform thrombolysis and thrombectomy due to the high risk of complications. He was discharged at 14 days, without functional limitation, symmetrical strength in upper and lower limbs, bilateral visual acuity 20/20, denying headache. CLINICAL RELEVANCE: The case presented here describes a pattern in how data supporting an association between COVID-19 and stroke in young populations with or without typical vascular risk factors, sometimes with only mild respiratory symptoms, is increasing. Prospective studies are required to further evaluate this association, as well as anticoagulation studies to prevent these potentially life-threatening events.

DESCRIPCIÓN DEL CASO: Mujer de 37 años con hisopado PCR-RT para COVID-19 positivo, con manifestación neurológica por oclusión de la arteria carótida interna. HALLAZGOS CLÍNICOS: Congestión nasal y estornudos de 5 días de duración; cefalea pulsátil en hemicráneo izquierdo 3 días antes del ingreso, con intensidad 6/10 según la escala visual analógica, acompañada de fosfenos, fotofobia y diplopía; con posterior desarrollo de hemiparesia derecha durante un período de 26 horas. TRATAMIENTO Y RESULTADO: Se le brindó manejo médico con antiagregantes plaquetarios orales y anticoagulantes (subcutáneos y orales) durante su internación, no fue posible realizar trombólisis y trombectomía por alto riesgo de complicaciones. Fue dado de alta a los 14 días, sin limitación funcional, fuerza simétrica en miembros superiores e inferiores, agudeza visual bilateral 20/20, negando cefalea. RELEVANCIA CLÍNICA: Se describe un patrón que indica cómo están aumentando los datos que apoyan una asociación entre COVID-19 y el accidente cerebrovascular en poblaciones jóvenes con o sin factores de riesgo vascular típicos, a veces con solo síntomas respiratorios leves. Se requieren estudios prospectivos para evaluar más a fondo esta asociación, así como estudios de anticoagulación para prevenir estos eventos potencialmente mortales.

Interventional recanalization as a treatment of carotid stump syndrome caused by right internal carotid artery occlusion: A case report.

RATIONALE: Carotid stump syndrome is a cerebral infarction caused by an embolus formed subsequent to the vortex of blood flow from the occluded stump, which then moves through the collateral vessels into the brain. The covered stent and stent-assisted coil embolization stump are the effective interventions for the carotid artery stump. PATIENT CONCERNS: A 71-year-old man twice experienced left limb weakness; diffusion weighted imaging confirmed the diagnosis of cerebral infarction. Cervical computed tomography angiography, intracranial magnetic resonance angiography, and digital subtraction angiography were conducted to evaluate collateral circulation, intraluminal composition, and shape of the carotid stump. DIAGNOSES: The patient was diagnosed with cerebral infarction and right carotid stump syndrome. INTERVENTION: The patient underwent interventional recanalization of the occluded internal carotid artery, which relieved his symptoms and led to satisfactory therapeutic outcomes during the clinical follow-up. OUTCOMES: A 9-month clinical follow-up revealed no stroke recurrence. LESSONS: Interventional recanalization for the carotid artery stump syndrome is feasible. Accurate preoperative evaluation including collateral circulation, intraluminal composition, and shape of the carotid stump can assure a successful vascularization and guided management.

Nix-mediated mitophagy regulates platelet activation and life span.

Platelet activation requires fully functional mitochondria, which provide a vital energy source and control the life span of platelets. Previous reports have shown that both general autophagy and selective mitophagy are critical for platelet function. However, the underlying mechanisms remain incompletely understood. Here, we show that Nix, a previously characterized mitophagy receptor that plays a role in red blood cell maturation, also mediates mitophagy in platelets. Genetic ablation of Nix impairs mitochondrial quality, platelet activation, and FeCl3-induced carotid arterial thrombosis without affecting the expression of platelet glycoproteins (GPs) such as GPIb, GPVI, and αIIbß3 Metabolic analysis revealed decreased mitochondrial membrane potential, enhanced mitochondrial reactive oxygen species level, diminished oxygen consumption rate, and compromised adenosine triphosphate production in Nix -/- platelets. Transplantation of wild-type (WT) bone marrow cells or transfusion of WT platelets into Nix-deficient mice rescued defects in platelet function and thrombosis, suggesting a platelet-autonomous role (acting on platelets, but not other cells) of Nix in platelet activation. Interestingly, loss of Nix increases the life span of platelets in vivo, likely through preventing autophagic degradation of the mitochondrial protein Bcl-xL. Collectively, our findings reveal a novel mechanistic link between Nix-mediated mitophagy, platelet life span, and platelet physiopathology. Our work suggests that targeting platelet mitophagy Nix might provide new antithrombotic strategies.

Emergent Rescue Extracranial-Intracranial Bypass for Acute Carotid Stent Thrombosis Report.

BACKGROUND: Acute stent thrombosis is a rare adverse event following endovascular treatment of carotid artery. Experience on the topic is scarce, making the therapeutic approach a clinical challenge. In cases of intraprocedural acute carotid stent thrombosis, thromboaspiration, thrombectomy, and thrombolysis have been used as successful modalities for achieving recanalization. CASE DESCRIPTION: We describe a case of carotid artery dissection treated endovascularly and complicated by intraprocedural stent thrombosis, which was ultimately managed by emergent extracranial-intracranial bypass with radial artery graft connecting the external carotid artery to the ipsilateral middle cerebral artery. CONCLUSIONS: Neurosurgical management may represent a rescue option for otherwise unmanageable acute carotid stent thrombosis.