Safety and effectiveness of anticoagulation in the management of acute stroke and transient ischemic attack due to intracranial and extracranial non-occlusive thrombus.

INTRODUCTION: The awareness of nonocclusive thrombus has increased with the increasing frequency of imaging methods used for acute ischemic stroke; however, the best treatment for nonocclusive thrombi is still unknown. In this study, we examined how anticoagulants affect supra-aortic artery nonocclusive thrombus and clinical outcomes. MATERIALS AND METHODS: This study included 52 patients with transient ischemic attack or stroke who were diagnosed with nonocclusive thrombi on computed tomography angiography at admission. Patients were treated with anticoagulant treatment and grouped according to treatment modality (either unfractionated heparin or low molecular weight heparin) and treatment duration. Primary safety outcome was major bleeding defined as immediate and clnically significant hemorrhage. Anticoagulant treatment was continued until the thrombus was resolved as determined by consecutive weekly computed tomography angiography controls. After thrombus resolution, treatment was directed according to the underlying etiology. Antiaggregation treatment was the preferred treatment after thrombus resolution for patients with no observed etiology. RESULTS: The affected internal carotid arteries were most frequently located in the cervical segment (48 %). Complete resolution was achieved within 2 weeks in 50 patients (96 %). The involved vasculature included the following: the extracranial carotid artery segments (n = 26, 50 %), intracranial ICA segments (n = 10, 19 %), basilar artery segments (n = 8, 15 %) and MCA segments (n = 7, 13 %). The most common underlying pathologies were atherosclerosis (n = 17), atrial fibrillation (n = 17), undetermined embolic stroke (n = 8), dissection (n = 7), and malignancy (n = 2). No symptomatic intra- or extracranial bleeding complications due to anticoagulant use were observed in any patient during the study period. A good functional outcome (modified Rankin scale score 0-2) was achieved in 49 patients (94 %) at 3 months. There was no significant difference between treatment type and duration in terms of reinfarction (p = 0.97 and p = 0.78, respectively). CONCLUSION: Anticoagulant treatment is safe and effective in symptomatic patients with intracranial or extracranial artery nonocclusive thrombus, regardless of the anticoagulant type, thrombus location and size.

Cerebral venous thrombosis: a practical review.

The evolution of the Coronavirus Disease-2019 pandemic and its vaccination raised more attention to cerebral venous thrombosis (CVT). Although CVT is less prevalent than arterial stroke, it results in larger years of life lost. CVT is more common in women and young patients. Predisposing factors are categorized as transient factors such as pregnancy, puerperium, oral contraceptive pills, trauma, and dehydration; and permanent factors such as neoplastic, vasculitic, thrombophilic, hematologic conditions, infectious causes such as severe acute respiratory syndrome coronavirus-2 infection and HIV. The most common manifestations are headache, seizures, focal neurologic deficits, altered level of consciousness, and cranial nerve palsies. The most common syndromes are stroke-like, raised-intracranial-pressure (ICP), isolated-headache, and encephalopathy, which may have overlaps. Diagnosis is mostly based on computed tomography, magnetic resonance imaging, and their respective venous sequences, supported by blood results abnormalities such as D-dimer elevation. Treatment includes the prevention of propagation of current thrombus with anticoagulation (heparin, or low molecular weight heparinoids and then warfarin, or direct oral anticoagulants), decreasing ICP (even by decompressive craniotomy), and treatment of specific underlying diseases.

Diagnosis and Treatment of Cerebral Venous Thrombosis.

OBJECTIVE: Cerebral venous thrombosis (CVT), thrombosis of the dural sinus, cerebral veins, or both, is a rare cerebrovascular disease. Although mortality rates after CVT have declined over time, this condition can result in devastating neurologic outcomes. This article reviews the latest literature regarding CVT epidemiology, details new factors associated with the development of CVT, and describes advances in CVT treatment. It also contains a discussion of future directions in the field, including novel diagnostic imaging modalities, and potential strategies to reduce the risks associated with CVT. LATEST DEVELOPMENTS: The incidence of CVT may be as high as 2 per 100,000 adults per year. It remains a difficult condition to diagnose given its variable clinical manifestations and the necessity of neuroimaging for confirmation. The COVID-19 pandemic has revealed a novel CVT trigger, vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as an association between COVID-19 infection and CVT. Although VITT is a very rare event, timely diagnosis and treatment of CVT due to VITT likely improves patient outcomes. Direct oral anticoagulants are currently being used to treat CVT and emerging data suggest that these agents are as safe and effective as vitamin K antagonists. The role of endovascular therapy to treat CVT, despite a recent clinical trial, remains unproven. ESSENTIAL POINTS: The incidence of CVT has increased, outcomes have improved, and the use of direct oral anticoagulants to treat CVT represents an important advance in the clinical care of these patients. Rates of CVT as a complication of COVID-19 vaccines using adenoviral vectors are very low (<5 per million vaccine doses administered), with the benefits of COVID-19 vaccination far outweighing the risks.

Cerebral Venous Thrombosis With Topical Estrogen-Progesterone Use in a Young Heterosexual Male: A Case Report.

INTRODUCTION: Our report sheds light on the risk of topical hormonal use in relation to cerebral venous sinus thrombosis. We diagnosed our patient with cerebral venous thrombosis (CVT) using computed tomography venogram, then detailed history and examination were obtained, and thorough blood tests and imaging were done to exclude other causes of CVT like thrombophilias, infections, and malignancies. CASE REPORT: Our patient is a 37-year-old heterosexual male, presented with headache only. The computed tomography venogram showed extensive CVT in the right internal jugular vein, sigmoid, transverse, and straight cerebral venous; detailed history and investigations suggest that his use of crushed oral contraceptive pills mixed with water topically on the scalp is the most important predisposing factor. This patient was managed with anticoagulants and is being followed in the clinic. CONCLUSION: Oral hormonal use in contraceptives is a known risk factor for CVT. This case sheds light on the importance of topical hormonal use concerning CVT in females and males; it stresses the need for more studies in that area, as it is poorly studied.

Cerebral venous thrombosis following an immunoglobulin-E mediated anaphylactic reaction.

BACKGROUND: Prothrombotic and pro-inflammatory states are known cerebral venous thrombosis risk factors. To date, two cases of venous thrombotic events after immunoglobulin-E mediated anaphylaxis have been reported. Herein, we describe the first case of cerebral venous thrombosis in close temporal relation with an immunoglobulin-E mediated anaphylactic event. CASE DESCRIPTION: A 51-year-old female presented with headache, language, and mental disturbance lasting for two days. Two days before the onset, she had undergone a provocative test with deflazacort to study an allergy history; after the test she developed a severe anaphylactic reaction. There were no other comorbidities, and in addition to contraceptive pill, she did not take other medications. On admission the patient was drowsy, with anomic aphasia, inattention and memory impairment. Magnetic Resonance Imaging depicted a left caudate and lenticulo-capsulo-thalamic venous infarct and thrombosis in the deep venous system. The patient was treated with anticoagulation and showed progressive improvement. Neoplastic and pro-thrombotic diseases were excluded. CONCLUSION: The close temporal association between the anaphylactic reaction and cerebral venous thrombosis suggests that anaphylactic reaction could have been a cerebral venous thrombosis precipitating factor. Immunoglobulin-E have been suggested to have prothrombotic activity by stimulating the release of platelet activation factor, thromboxane A2 and serotonin. This case adds on to the available information on possible cerebral venous thrombosis associated conditions.

MRI-negative myelitis associated with cerebral venous thrombosis after COVID-19 infection.

Transverse myelitis and cerebral venous thrombosis represent some of the described neurological complications of coronavirus disease. A woman in her early 30s presented with headache, left-sided sensory symptoms and voiding difficulty. The patient also reported dry cough, fever, nasal congestion, anosmia and ageusia 2 weeks before presentation. The clinical examination showed sensory disturbances on the left side of the body, starting from the lower abdomen and extending to the left leg, which was consistent with transverse myelitis. The laboratory assessment confirmed a previous infection with coronavirus disease and excluded autoimmune entities. Radiological investigations revealed left transverse sinus thrombosis with no spinal cord abnormalities. The treatment was started with therapeutic anticoagulation and intravenous high-dose steroids. The patient showed significant improvement, and the neurological deficits resolved after 3 months. This is the first documented case of imaging-negative myelitis associated with cerebral venous thrombosis after coronavirus disease.

Anticoagulant Treatment for Pediatric Infection-Related Cerebral Venous Thrombosis.

BACKGROUND: We aimed to describe the clinical presentation, risk of bleeding and recurrent thrombosis, and perioperative anticoagulant management of children with cerebral venous thrombosis (CVT) and an associated head or neck infection. METHODS: In this subgroup analysis of the EINSTEIN-Jr study, we included children with CVT and an associated head or neck infection who received therapeutic anticoagulants with either low-molecular-weight heparin (with or without subsequent vitamin K antagonists) or rivaroxaban for a period of 3 months. Analyses are descriptive. RESULTS: Of 74 included children, 59 (80%) had otomastoiditis, 21 (28%) a central nervous system infection, 18 (24%) sinusitis, and 9 (12%) another upper respiratory tract infection; 29 (39%) had infection of multiple regions of the head or neck. All 74 children received antibiotics and therapeutic anticoagulants; 41 (55%) underwent surgery, of whom 34 were diagnosed with CVT preoperatively. Anticoagulation was started before surgery in 12 children and interrupted 0-1 days prior to surgery. Anticoagulation was (re)started in all 34 children at a median of 1 day (interquartile range: 0-1) postoperatively, in therapeutic doses in 94%. Overall, one child (1%, 95% confidence interval: 0-7) had recurrent thrombosis, and one (1%, 95% confidence interval: 0-7) had major bleeding; neither was associated with surgery. At 3 months, no children had died, 3 (4%) had persistent focal neurologic deficits, and 2 (3%) had impaired vision. CONCLUSIONS: Children with CVT and an associated head or neck infection administered therapeutic anticoagulants generally had low risks of bleeding and thrombotic complications, including those who had surgical interventions with delay or interruption of anticoagulation.

The Gliopeptide ODN, a Ligand for the Benzodiazepine Site of GABAA Receptors, Boosts Functional Recovery after Stroke.

Following stroke, the survival of neurons and their ability to reestablish connections is critical to functional recovery. This is strongly influenced by the balance between neuronal excitation and inhibition. In the acute phase of experimental stroke, lethal hyperexcitability can be attenuated by positive allosteric modulation of GABAA receptors (GABAARs). Conversely, in the late phase, negative allosteric modulation of GABAAR can correct the suboptimal excitability and improves both sensory and motor recovery. Here, we hypothesized that octadecaneuropeptide (ODN), an endogenous allosteric modulator of the GABAAR synthesized by astrocytes, influences the outcome of ischemic brain tissue and subsequent functional recovery. We show that ODN boosts the excitability of cortical neurons, which makes it deleterious in the acute phase of stroke. However, if delivered after day 3, ODN is safe and improves motor recovery over the following month in two different paradigms of experimental stroke in mice. Furthermore, we bring evidence that, during the subacute period after stroke, the repairing cortex can be treated with ODN by means of a single hydrogel deposit into the stroke cavity.SIGNIFICANCE STATEMENT Stroke remains a devastating clinical challenge because there is no efficient therapy to either minimize neuronal death with neuroprotective drugs or to enhance spontaneous recovery with neurorepair drugs. Around the brain damage, the peri-infarct cortex can be viewed as a reservoir of plasticity. However, the potential of wiring new circuits in these areas is restrained by a chronic excess of GABAergic inhibition. Here we show that an astrocyte-derived peptide, can be used as a delayed treatment, to safely correct cortical excitability and facilitate sensorimotor recovery after stroke.

The clinical characteristic, diagnosis, treatment, and prognosis of cerebral cortical vein thrombosis: a systematic review of 325 cases.

Cerebral cortical vein thrombosis (CCVT) is a rare type of cerebral venous thrombosis, which is frequently combined with cerebral venous sinus thrombosis (CVST). We aimed to compare the difference of clinical features between the isolated and the combined subtypes of CCVT. A literature search was conducted utilizing the PubMed Central and EMBASE databases to identify studies up to Dec 2019. Clinical manifestations, presumable risk factors, imaging modalities, radiological findings, treatment, and prognosis in patients with CCVT were recorded. 335 publications were identified (n = 325, 141 males and 184 females, mean age 40.24 ± 16.26 years). Headaches (46.8%), motor/sensory disorders (43.3%), and seizures (42.5%) were commonly seen. Pregnancy/postpartum (n = 29), oral contraception use (n = 15), fertility drug use (n = 4) ranked the top three comorbidities of CCVT in female patients, while for general populations, thrombophilia, invasive interventions in the cerebrospinal system, as well as malignancy, would be the common risk factors. MRV and DSA were more likely to confirm diagnosis. More than 30% of CCVT presented brain lesions, including infarction (6.5%) and hemorrhage (24.0%). Isolated CCVT was prone to develop hemorrhagic infarction while combined CCVT was more likely to have ischemic lesions. More than 90% of the patients acquired good outcomes at discharge or short-term follow-up (within one year). There is a difference between Isolated CCVT and CCVT combined CVST on the sites and types of brain lesions. MRV and DSA may contribute to the final diagnosis. Most patients acquired complete or partial recovery of clinical symptoms or imaging presentations after long-term anticoagulation (3-6 months).

Cerebral venous thrombosis in Argentina: clinical presentation, predisposing factors, outcomes and literature review.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare medical condition that primarily affects young adults. The clinical spectrum is broad and its recognition remains a challenge for clinicians. Limited information is available on CVT in Argentina. Our goal was to report the results of the first National registry on CVT in Argentina and to compare clinical presentation, predisposing factors and outcomes with other international registries. MATERIAL AND METHOD: The Argentinian National Registry on CVT (ANR-CVT) is a multicenter retrospective cohort study comprising patients aged 18 and older with a diagnosis of CVT from January 2015 to January 2019. We evaluated demographics, predisposing factors, clinical presentation, and radiological characteristics (e.g. number of involved sinuses, venous infarction or hemorrhage on CT and MRI scans at admission), therapeutic interventions and functional outcomes at discharge and at 90 days. Our results were compared to a literature review of CVT registries. RESULTS: Overall, one hundred and sixty-two patients met the inclusion criteria. The mean age was 42 (±17) years; 72% were women. Seventy percent of patients were younger than 50 years. The most common presenting symptom was headache (82%). The transverse sinus was the most common site of thrombosis (70%) followed by the sigmoid sinus (46%). The main predisposing factor in women was contraceptive use (44%), 3% of the events occurred during pregnancy and 9% during the puerperium. Participants 50 years and older had a higher frequency on malignancy related (7.5% vs. 30%, p = 0.0001) and infections (2% vs. 11%, p = 0.001). The modified Rankin Scale (mRS) ≤2 at discharge was 81% and the rate of mortality at discharge was 4%. At 90 days, the mRS≤2 was 93%. When the ANR-CVT was compared with larger registries from Europe and Asia, the prevalence of cancer among patients with CVT was two to five-fold higher (15% vs. 7% and 3%, respectively; p = 0.002 and p < 0.001). Anticoagulation rates at discharge were also higher (94%) compared to registries from Asia (ASCVT - 68%) or Turkey (VENOST - 67%). CONCLUSION: Participants in the first ANR-CVT had a low mortality and disability at 90 days. Clinical and radiological characteristics were similar to CVT from other international registries with a higher prevalence of cancer. There was a high variability in treatment adherence to guidelines as reflected by anticoagulation rates (range 54.5%-100%) at discharge.

Preliminary findings regarding the use of direct oral anticoagulants in cerebral venous thrombosis.

BACKGROUND: Direct oral anticoagulants (DOACs) have entered the treatment paradigms of various conditions based upon large randomized controlled trials. However, use of DOACs for thrombosis at unusual sites, such as cerebral venous thrombosis (CVT), is less clear as the ability to conduct large randomized controlled trials is limited by its rarity. Furthermore, its use in the setting of malignancy or in the elderly remains an area of ongoing research. OBJECTIVE: Our aim was to assess the outcomes in CVT patients treated with DOACs compared to warfarin. We also sought to elucidate whether its use was safe in the setting of malignancy or in the elderly. METHODS: Retrospectively assess the differences in clinical outcomes in patients hospitalized with CVT in the Lifespan Health System. RESULTS: Between 1 July 2004 and 1 March 2020, 46 adult patients with CVT fulfilled inclusion criteria. No significant differences in outcomes were observed between the DOAC (N = 8) and vitamin K antagonist (VKA) (N = 38) cohorts. The use of DOACs did not result in an increased rate of acute complications, recurrent venous thromboembolism (VTE) and/or CVT, World Health Organization (WHO) grade 3 or 4 bleeding rates, or differences in clinical improvement per the modified Rankin scale. Furthermore, in patients with underlying metastatic cancer (N = 2) or in patients > 80 (N = 1) who received a DOAC, there was no increase in adverse events or significant differences in outcome when compared to warfarin. CONCLUSION: Patients who received a DOAC in the treatment of CVT demonstrated no differences in outcomes when compared to warfarin.

Rapidly progressive cognitive impairment: an unusual presentation of cerebral venous thrombosis caused by JAK2 V617F-positive primary myelofibrosis: A case report.

RATIONALE: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition, which mainly manifests as headaches, seizures, and focal neurological deficits. JAK2 mutation in myeloproliferative diseases increases the risk of CVT. PATIENT CONCERNS: This 40-year-old woman suffered from rapidly progressive cognitive impairment and limb weakness. Her symptoms worsened while being treated with mannitol with the diagnose of cerebral hemorrhage. DIAGNOSIS: The patient was diagnosed with CVT and multiple intracranial hemorrhage caused by JAK2 V617F mutation-positive primary myelofibrosis by neuroimage and whole-exome sequencing. INTERVENTION: She received low-molecular-weight heparin sodium 3800 IU twice a day followed by oral anticoagulant therapy. OUTCOMES: The patient showed full recovery from limb weakness and in the follow-up period she noticed no change in her memory. LESSONS: Clinicians should be aware of the possibility of the JAK2 V617F mutation in CVT patients without known causes or risk factors.

Thromboembolic events in inflammatory bowel disease.

GOAL OF THE STUDY: Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolic events (TEE) during outbreaks, increasing morbidity and mortality. The aim of our study was to specify the prevalence of TEE in IBD patients and to determine their epidemiological, clinical and evolutionary characteristics. MATERIEL AND METHODS: This is a retrospective study collecting all patients with IBD, who had a thromboembolic complication confirmed by imagery, between January 2012 and December 2018. RESULTS: One hundred patients with IBD were diagnosed during the study period. A TEE occurred in 6 patients (5.9%). These patients had an average age of 41 years, divided into 4 women and 2 men. Five patients had Crohn's disease and one patient had ulcerative colitis. The IBD was active in all patients. Five patients were already hospitalized and under preventive heparin therapy. Patients had deep venous thrombosis of the lower limbs in 3 cases, associated with pulmonary embolism in 1 case, cerebral venous thrombosis in 2 cases and pulmonary embolism isolated in 1 case. Thrombophilia investigations were negative in all patients. Evolution under medical treatment was favorable in 4 patients and fatal in 2 patients. CONCLUSION: In our study, the prevalence of TEE in patients with IBD was 5.9%. Thrombosis occurred during the active phase of IBD in all cases.

Cerebral Venous Thrombosis in Hematological Malignancy: Balancing the Risks.

BACKGROUND AND AIM: The coexistence of cerebral venous thrombosis (CVT) and hematological neoplasms is rare. Currently available therapeutic options raise problems concerning the balance of thrombotic and hemorrhagic risks. Our purpose is to characterize a series of cases of CVT and concomitant hematological malignancy, focusing on predisposing factors and treatment strategies. METHODS: We performed a descriptive retrospective analysis of the cases of CVT and hematological neoplasms diagnosed in a tertiary center from 2006 to 2015. RESULTS: From the 111 CVT cases diagnosed, only 7 coexisted with hematological malignancy (lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes). These included 4 women; median age was 44 years old. Median follow-up time was 72 days. The hematological condition was already known in 5 cases. Besides malignancy, we identified other prothrombotic conditions in all cases. Several anticoagulant strategies were used during the acute phase, after which 5 patients remained on warfarin indefinitely. One patient died due to cerebral hemorrhage during the acute phase. In the remaining 6 patients, there was no recurrence of CVT or other complications of anticoagulation. CONCLUSIONS: Although these results reiterate the role of hematological malignancy as predisposing factor to CVT, in all cases other factors contributed to CVT etiology, potentiating the risk. We report 1 death directly attributable to a fatal hemorrhagic complication of anticoagulation, evidencing the delicate balance of thrombotic and hemorrhagic risk. Nevertheless, most patients benefited of long-term anticoagulation, which proved a reasonable option. A multidisciplinary approach is paramount in making decisions regarding the time and type of anticoagulation.

Cerebral Venous Thrombosis after Red Blood Cell Transfusion for the Treatment of Iron Deficiency Anemia.

A 57-year-old male presented with generalized seizure who received red blood cell (RBC) transfusion for the treatment of iron deficiency anemia (IDA). Neuroradiological findings revealed cerebral venous thrombosis (CVT) on the left frontal vein. He received anticoagulants, anticonvulsants, and iron supplements. He discharged without any neurological deficit. It should be noted that RBC transfusion might increase the risk of CVT in patients with IDA.

Thrombosis of Large Aneurysm Induced by Flow-Diverter Stent and Dissolved by Direct Factor Xa Inhibitor.

BACKGROUND: Antiplatelet agents are typically administered before and after treatment using flow-diverter stents (FDS) to prevent thrombotic complications, but the effects of anticoagulants are unclear. We present a patient with a giant aneurysm treated with an FDS. The thrombus within the aneurysm was dissolved when a direct factor Xa inhibitor was administered to treat lower limb venous thrombosis that occurred secondary to steroid use. CASE DESCRIPTION: A 60-year-old woman with a 30-mm giant thrombosed aneurysm in the cavernous segment of the right internal carotid artery presenting with headache and right abducens nerve palsy was treated by placing an FDS. Diplopia and increased pain in her right eye appeared on postoperative day 7, and both were alleviated by continuous oral administration of prednisolone. Angiography 3 months postoperatively revealed that the aneurysm thrombosis had progressed, and there were signs of healing. However, at the same time, lower limb venous thrombosis occurred, which was treated by continuous edoxaban. Six months after surgery, her headaches worsened and angiography showed that the aneurysm was again contrast enhanced and that the thrombus within the aneurysm had dissolved. After discontinuing edoxaban 9 months after surgery, the aneurysmal thrombosis had again rapidly progressed. CONCLUSIONS: Administration of a direct factor Xa inhibitor during healing after placing an FDS may cause dissolution of an existing thrombus; therefore factor Xa inhibitors must be used with caution.

Deep Venous Thrombosis with Decreased Cerebral Blood Flow to the Thalamus was Completely Restored by Factor Xa Inhibitor.

BACKGROUND: Cerebral venous thrombosis is rare and an uncommon cause of stroke and has diverse etiologies and varied clinical presentations. Here, we report 2 cases of deep cerebral venous thrombosis. CASE DESCRIPTION: A 64-year-old woman presented with cerebral venous thrombosis due to a hypercoagulable state associated with ovarian tumor. On initial fluid-attenuated inversion recovery and diffusion-weighted imaging, there was a diffuse high-intensity lesion in the bilateral thalamus. Computed tomography angiography showed occlusion of the straight sinus, vein of Galen, and internal cerebral vein. Single-photon emission computed tomography showed decreased cerebral blood flow in the bilateral thalamus. After 3 weeks of factor Xa inhibitor therapy, the patient's consciousness gradually improved and eventually became clear enough to leave the hospital. She had no neurological deficit. Another patient was a 47-year-old man who presented with splitting headache and drowsiness. Magnetic resonance venography confirmed deep thrombosis of the vein of Galen. He completely recovered after 4 weeks of factor Xa inhibitor therapy. CONCLUSIONS: This study reports on 2 rare cases of decreased cerebral blood flow in the bilateral thalamus on single-photon emission computed tomography, which improved following the administration of factor Xa inhibitor.