Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review.

Importance: The COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST. Observations: VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk. Conclusions and Relevance: Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

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).

IgM nephropathy complicated by cerebral venous sinus thrombosis: a case study.

BACKGROUND: IgM nephropathy is a rare disease with variable clinical presentations and is an unusual cause of nephrotic syndrome. Histopathological findings typically include mesangial hypercellularity with IgM and complement deposition, though the spectrum may range from normal glomeruli through to focal and segmental glomerulosclerosis. Thromboembolism is a well recognised complication of nephrotic syndrome, but cerebral venous sinus thrombosis is rarely described. CASE PRESENTATION: This is the case of a 23-year-old male presenting with the nephrotic syndrome, whose initial renal biopsy was consistent with minimal change disease. Complete remission was achieved with prednisone, however multiple relapses and steroid dependence prompted re-biopsy, the results of which were more consistent with IgM nephropathy. His last relapse was complicated by cerebral venous sinus thrombosis. He then received rituximab and a weaning course of prednisone to again enter remission. CONCLUSIONS: This case highlights the need to consider IgM nephropathy in the differential diagnosis of nephrotic syndrome. Additionally, it emphasises the risk of thrombosis in patients with severe nephrosis.

Chemotherapy associated dural sinus thrombosis presenting as a cerebrospinal fluid leak.

Despite the well documented increased risk of thrombosis in patients with cancer and during chemotherapy, cerebral venous sinus thrombosis (CVT) remains a rare entity. We present a rare case of cerebrospinal fluid (CSF) rhinorrhoea secondary to a left transverse sinus thrombus which occurred 2 years previously during chemotherapy for breast cancer. The patient underwent a three-layer repair using Neuro-Patch, septal cartilage and middle turbinate pedicle flap and was started on acetazolamide. There was no recurrence at 1-year follow-up. Raised intracranial pressure secondary to cerebral venous occlusion can erode the base of skull and predispose to CSF leaks. Despite the theoretical risk, there have been no cases reported where CSF leaks have occurred following chemotherapy induced CVT. We describe the first case and discuss pathophysiology and management.

Recurrent intracranial hemorrhage and cerebral venous sinus thrombosis: an atypical case of Neuro-Behçet's Syndrome.

We report the case of a 22-year-old man with an history of headaches, seizures, cognitive impairment associated with recurrent intracranial hemorrhage (ICH), acute ischemic stroke (AIS), worsened over the last eighteen months for a new onset of uveitis and cerebral venous sinus thrombosis (CVST). After excluding common causes of lobar ICH, and some rare ones according to the diagnostic protocol proposed by Beuker et al, in the suspicion of Primary Angiitis of the Central Nervous System (PACNS), the gradual development of a low-grade fever, a cutaneous rash, and a papulopustular manifestation on lower back after rachicentesis (pathergy phenomenon), allowed us to make a diagnosis of Neuro-Behçet's Syndrome (NBS) without oral/genital aphthous ulcerations, according to the International Study Group for Behçet's Disease classification criteria for BD (ICBD).

A clinical research on the potential pathogenesis of somatic cancer related cerebral venous sinus thrombosis.

To investigate the pathogenesis of somatic solid cancer-related cerebral venous sinus thrombosis (CVST).A total of 174 patients with CVST were recruited from the hospital between January 2006 and December 2017 and divided into two groups: (1) somatic cancer-related CVST group, defined as active somatic solid cancer patients with acute CVST; (2) cancer group (CG), defined as active somatic solid cancer patients without CVST. The cancer group patients were age and gender-matched somatic cancer-related CVST group patients. In addition, the types and amount distribution of cancer in cancer group were also matched with somatic cancer-related CVST group patients.Compared to cancer group patients, somatic cancer-related CVST group patients had more intracranial metastasis, a higher platelet count, higher plasma D-dimer, carcinoembryonic antigen (CEA) and cancer antigen (CA) 125 levels, a greater platelet to lymphocyte ratio (PLR), and a greater platelet to neutrophil ratio (PNR). The risk for CVST in somatic cancer-related CVST group patients increased independently by 0.7% (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.000, 1.015; P = .047) with a 1 ng/ml increase in D-dimer levels, by 4.6% (OR 1.046; 95% CI 1.011, 1.083; P = .010) with a 1 U/ml increase in CEA, by 2.7% (OR 1.027; 95% CI 1.003, 1.051; P = .025) with a 1 U/ml increase in CA125, and by 10.6% (OR 1.106; 95% CI 1.002, 1.220; P = .045) with a 1 unit increase in PNR.It was suggested that together impacts of elevated plasma D-dimer, CA125, CEA levels, and a greater PNR may lead to hypercoagulability and to trigger the development of cancer-related CVST.

Venous collateral drainage patterns predict clinical worsening in dural venous sinus thrombosis.

BACKGROUND: Dural venous sinus thrombosis (DVST) is an increasingly recognized cause of a wide array of neurological symptoms, with outcomes that range from complete recovery to death. The condition of approximately 23% of patients with DVST will worsen after initial presentation, as a result of restricted venous outflow and venous hypertension, but early identification of this subset is challenging. A venous collateral scale (VCS) that grades alternative drainage routes may improve prediction of clinical deterioration. OBJECTIVE: To examine the ability of the VCS system to accurately identify patients with DVST who will experience clinical worsening, based on their imaging at presentation. METHODS: From our institutional database, we identified patients with DVST on dedicated venous imaging between January 2010 and July 2016. A VCS was created and calculated from venous imaging at presentation by two reviewers blinded to subsequent data. RESULTS: The 27 patients who met the inclusion criteria for this study had a median age of 42 years and 14 (52%) were female. Initial symptoms included headache without hemorrhage in 30% and focal deficit in 30%. Transverse sinus occlusion was present in 70% and superior sagittal sinus occlusion in 41%. VCS was 0 in 11%, 1 in 37%, and 2 in 52%. A lower VCS was significantly associated with clinical worsening both from time of initial symptom onset (77% vs 29%, VCS 0-1 vs 2, p<0.05) and during hospitalization (62% vs 0%, VCS 0-1 vs 2, p<0.01). In multivariate analysis, VCS but no other presenting features was significantly associated with in-hospital worsening (OR=2, p<0.01). CONCLUSIONS: The type and quality of venous collaterals influence outcome in DVST. VCS helps to identify patients whose condition is likely to deteriorate and may need additional aggressive interventions.

Frosted branch angiitis and cerebral venous sinus thrombosis as an initial onset of neuro-Behçet's disease: a case report and review of the literature.

BACKGROUND: Frosted branch angiitis is a rare, severe condition. It can be either a primary or a secondary condition and is characterized by rapid deterioration of vision and fulminant retinal vasculitis that manifests as diffuse sheathing of retinal vessels, macular edema, papillitis, vitritis and anterior uveitis. We aimed to describe a case of frosted branch angiitis and cerebral venous sinus thrombosis as an initial neuro-Behçet's disease onset. Diagnosis of Behçet's disease was based on the current 2014 International Criteria for Behçet's Disease and the International consensus recommendation criteria for neuro-Behçet's disease. In addition, a literature review using search parameters of "frosted branch angiitis", "Behçet" and "neuro-Behçet" in the PubMed database is presented. CASE PRESENTATION: A 28-year-old Brazilian pardo woman presented to our hospital with abrupt bilateral vision loss associated with recurrent aphthous oral ulcers 6 months before visual symptom onset. A fundus examination showed bilateral widespread retinal vasculitis with venous and arterial white sheathing, optic disc swelling, macular edema, and retinal hemorrhages, leading to the diagnosis of frosted branch angiitis. An extensive systemic workup for retinal vasculitis was uneventful, except for brain magnetic resonance imaging demonstrating cerebral venous sinus thrombosis and lymphocytic aseptic meningitis. A diagnosis of neuro-Behçet's disease was made, and treatment was started with methylprednisolone therapy 1 g/day for 5 consecutive days, followed by oral mycophenolate mofetil and infliximab 5 mg/kg infusion. The patient's response was rapid, with improvement of visual acuity to hand movement and counting fingers by day 7 and final visual acuity of counting fingers and 20/130. CONCLUSIONS: Frosted branch angiitis may be associated with infectious, noninfectious, or idiopathic causes. An extensive workup should be done to exclude systemic vasculitis such as Behçet's disease. Treatment with systemic steroids must be promptly initiated in association with specific treatment aimed at inflammation control and blindness risk reduction.

Cerebral Venous Sinus Thrombosis From a Tertiary Care Teaching Hospital in India.

OBJECTIVE: The prognosis of cerebral venous sinus thrombosis (CVST) may be dependent on underlying causes and magnetic resonance imaging findings. We report the clinical, laboratory, and radiologic spectrum, and outcome of consecutive patients with CVST. METHODS: Consecutive patients with CVST over the last 15 years were subjected to detailed history, clinical examination, and laboratory tests as per fixed protocol. The diagnosis of CVST was based on MR venography. The magnetic resonance imaging findings and the sinuses involved were noted. The patients were treated with low-molecular-weight heparin or unfractionated heparin for 14 days, followed by oral anticoagulation. Hospital mortality and 3-month outcome (good or poor) were recorded and correlated with various clinical and laboratory parameters. RESULTS: There were 86 patients whose median age was 30 (6 to 76) years; 47 of them were females. Headache was present in 91.9%, vomiting in 68.6%, focal weakness in 53.5%, seizure in 51.2%, and altered sensorium in 53.5%. Female-specific etiology was present in 34%, prothrombotic condition in 62.8%, infections in 19.8%, and malignancy in 2.8%; no cause could be established in 25.6% of patients. Hyperhomocystinemia was present in 45.9% of patients. Five patients died in the unfractionated heparin group. At 3 months, 77 patients were followed up, of whom 68 had complete, 3 had partial, and 6 had poor recovery. The 3-month outcome was related to Glasgow Coma Scale score and type of heparin used. CONCLUSIONS: In our study multiple prothrombotic conditions were common, and low-molecular-weight heparin reduces mortality and results in good outcome.

Different gestational ages and changing vulnerability of the premature brain.

In recent decades, there has been a general increase in survival rates of preterm and low birth weight infants, but this overall decrease in perinatal mortality has not been accompanied by a decrease in long-term physical and mental disability. In order to reduce the long-term sequelae of prematurity and to establish preventive measures, it is important to identify risk factors since the main determinant of specific vulnerability to different types of lesions is gestational age. The regional tissue vulnerability at a given gestational age is probably determined by the local metabolic requirements together with specific cell characteristics and their level of maturation. In this article, we discuss the most common neonatal cerebral lesions (cerebellar haemorrhage, germinal matrix intraventricular haemorrhage, periventricular leukomalacia, arterial ischaemic stroke, cerebral vein sinus thrombosis and hypoxic-ischaemic encephalopathy) related to the gestational age-dependent vulnerability of the premature brain.

[Clinical characteristics and prognosis of patients with cerebral venous sinus thrombosis in southwest China].

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a rare cerebral vascular disease. Early diagnosis and treatments are crucial for a better prognosis. This study investigated the clinical characteristics and risk factors associated with the prognosis of patients with CyST. METHODS: From Jan 2009 to Jan 2013, patients who were admitted to the Department of Neurology of West China Hospital with confirmed CVST (according to the 2006 guideline of European neurology with neuroimaging when necessary) were consecutively recruited. Their medical records including demographic information and detailed clinical data were analyzed. The functional outcome of CVST was assessed 12 months after discharge using the modified Rankin Scale (mRS). RESULTS: A total of 73 patients were enrolled in this study. Acute and chronic onset of illness accounted for 13.7% and 35.6% of all patients, respectively. The earliest common symptom was headache (90.4%). Other initial symptoms included decreased visual acuity or blurred vision (2.7%), unilateral limb weakness (2.7%), diplopia (1. 4 9/o) and seizure (1.4%). CT scan was conducted in 46 patients (63.3%), which revealed 8 (17.4%) cases of cerebial hemorrhagic infarction. Delta sign and cord sign was shown in 34.8% and 30.4% CT imaging, respectively. The MRI scan confirmed that 27. 5% of those patients had encephaledema, 55% had delta sign and 45% had cord sign. The commonly involved location of CVST was right lateral sinus (68.5%), left lateral sinus (57.5%), ongitudinal sinus (53. 4%), left sigmoid sinus (50.7%), right sigmoid sinus (47.8%), confluence sinuum (32.9%), nferior sagittal sinus (21.900), sinus rectus (20.5%), jugular vein (12. 3%) and cerebral vein (9.6%). During the 12-month follow-up, 6.8% patients died, 72.6% had good mRS outcome (<2) and 27.4% had poor mRS outcome (> OR =2). The regression analysis identified epilepsy and papilledma as independent predictors of poor prognosis of CyST. CONCLUSION: It is difficult to recognize CVST at an early stage due to its diverse clinical presentations. Neuroimaging may be helpful for the diagnosis. Epilepsy and papilledema are potentially independent predictors for the 12-month functional outcome of patients with CVST.

Cerebral sinovenous thrombosis associated with mastoiditis due to recurrent otitis media.

Cerebral sinovenous thrombosis (CSVT) in childhood is a rare reported. In this era of widespread antibiotic use for acute otitis media, the incidence of otogenic CSVT has markedly declined but has not been completely prevented. The current therapies for CSVT include anticoagulation, thrombolysis, hydration, surgery, and supportive care that were based on adult studies, pediatric case studies, and expert opinion. We describe the case of a 3-year-old boy who presented with manifestations of CSVT associated with mastoiditis secondary to otitis media. He completed a 3-month course of combination antibiotic and anticoagulation therapy; the CSVT was recanalized, and the mastoiditis had partially improved.

The entire dural sinus tree is compressed in patients with idiopathic intracranial hypertension: a longitudinal, volumetric magnetic resonance imaging study.

INTRODUCTION: The objective of this study was to explore the volumetric alterations of dural sinuses in patients with idiopathic intracranial hypertension (IIH). METHODS: Standardized cranial magnetic resonance imaging (MRI) was used in 17 patients prior to and following treatment of IIH and in seven controls. Magnetic resonance venographies (MRV) were employed for (a) judgement of circumscript dural sinus stenoses and (b) computation of sinus volumes. Cross-sectional areas (CSA) of the superior sagittal sinuses (SSS) were measured on T2-weighted images. Results of the initial MRIs were compared to those on follow-up MRIs and to results of controls. RESULTS: Stenoses of the transverse sinuses (TS) resulting in cranial venous outflow obstruction (CVOO) were present in 15/17 (88%) patients, normalizing in 7/15 cases (47%) after treatment of IIH. CVOO was not detected in the control group. Segmentation of MRV revealed decreased dural sinus volumes in patients with IIH as compared to controls (P = 0.018). Sinus volumes increased significantly with normalization of intracranial pressure independent from disappearing of TS stenoses (P = 0.007). The CSA of the SSS were normal on the initial MRIs of patients with IIH and increased on follow-up after treatment (P < 0.001). However, volumetries displayed overlap in patients and controls. CONCLUSIONS: Patients with IIH not only exhibit bilateral stenoses of the TS as has been reported, but volume changes of their entire dural sinus system also occur. The potential etiopathological and diagnostic roles of these changes are discussed.

Establishing a new rat model of central venous sinus thrombosis and analyzing its pathophysiological and apoptotic changes.

This study aims to establish a new animal model of cerebral venous sinus thrombosis (CVST) and to investigate the pathophysiological and apoptotic changes of CVST. Fifty-eight adult Sprague-Dawley rats were used in the present study. They were randomized into three groups, namely control (n=6), embolism (n=26) and sham-operated (n=26) groups. In the embolism group, a self-made plastic graft was inserted in the superior sagittal sinus of each rat during the operation. Each plastic graft had a total length of 0.4 cm, its conical anterior segment had the largest diameter of 0.12 cm and its posterior segment became gradually thin and flat with a width of 0.2 cm and length of 0.1cm. In both the embolism and the sham-operation groups, the rat brains were resected at 6h, 1, 3, and 5 days post-surgery. Gross observation and water content of samples were assessed. Immunohistochemistry for caspase 3, Bcl-2 and Bax were also performed. In the embolism group, cerebral edema reached a peak level at 6h after surgery and then gradually recovered. Significant elevated positive rates of caspase 3, Bcl-2 and Bax after embolism operation were observed, reaching peaks at 1 day time point. Yet, Bcl-2/Bax decrease significantly during the follow-up, indicating apoptosis induction in embolism operation group. The new rat CVST model made by inserting a solid graft into the superior sagittal sinus is reproducible and reliable. Apoptosis plays a crucial role during the development of CVST pathophysiology.

An update on idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often encountered in neurologic practice. It produces nonlocalizing symptoms and signs of raised intracranial pressure and, when left untreated, can result in severe irreversible visual loss. It most commonly occurs in obese women of childbearing age, but it can also occur in children, men, nonobese adults, and older adults. Although it is frequently associated with obesity, it can be associated with other conditions, such as obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identification of subgroups at high risk for irreversible visual loss, including black patients, men, and patients with fulminant forms of IIH, help guide the optimal management and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as well as a recently begun randomized clinical treatment trial, should provide further insight into this common yet poorly understood syndrome.

Dural arteriovenous fistula associated with superior sagittal sinus occlusion secondary to invasion by a parafalcine meningioma: case report.

OBJECTIVE: We report a rare case of thrombosis of the superior sagittal sinus associated with a parafalcine meningioma resulting in a superior sagittal sinus dural arteriovenous fistula (dAVF). We conclude that dural sinus thrombosis is a significant predisposing factor for development of a dAVF. CLINICAL PRESENTATION: A 60-year-old man had a left parietal parafalcine meningioma that invaded the posterior third of his superior sagittal sinus, leading to its occlusion and presumably resulting in an associated dAVF. The fistula was fed by the middle meningeal and superficial temporal arteries on both sides and drained through a superior interhemispheric cortical vein into the vein of Galen and straight sinus. INTERVENTION AND TECHNIQUE: The parafalcine mass, which involved the sagittal sinus, was excised via a left parieto-occipital craniotomy. It was decided to resect the dAVF at a later date. Seven days after the original operation, the patient underwent a parietal interhemispheric approach for occlusion of the dAVF. Dissection proceeded until a large arterialized vein and venous pouch with multiple feeders from both external carotid arteries were observed. The vein, which was partially embedded within the falx cerebri, was collapsed, and a second indocyanine green injection confirmed cessation of blood flow. CONCLUSION: This report supports that dAVFs are acquired lesions and that venousoutflow obstruction is a significant contributing factor to their development. In meningiomas associated with the dural sinuses, diagnostic evaluation for possible dAVFs should be considered. Treatment of these lesions should be based on risk factors because spontaneous resolution after tumor excision has been reported.

Continuous thrombolysis and repeated thrombectomy with the Penumbra System in a child with hemorrhagic sinus thrombosis: technical note.

UNLABELLED: Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially lethal event. When showing a malignant clinical course despite anticoagulant therapy, new endovascular techniques and technology allow the possibility of more aggressive thrombolysis and thrombectomy. The authors present a case of recanalization of an extensive cerebral thrombosis using a new endovascular thromboaspiration device, the Penumbra System. BACKGROUND AND PURPOSE: CVST in children is a rare but potentially lethal disorder. When showing a malignant progression despite anticoagulant therapy, the use of local thrombolytics and thrombectomy procedures might provide therapeutic solution. METHODS: A 16-year-old girl presented with signs and symptoms of a hemorrhagic cerebral sinus thrombosis and showed progression despite full dose anticoagulant therapy. The evolution being attributed to increasing mass effect, decompressive surgery was performed without clinical improvement. Further brain imaging demonstrated progression of the sinus thrombosis. Repeated local thrombectomy with the Penumbra thrombectomy system and continuous, relatively low dose local thrombolysis was performed during a period of 60 h, resulting in recanalization and clinical improvement. The methodology of combined thromboaspiration and thrombolysis is described. CONCLUSIONS: We present a novel method for revascularization using the Penumbra System in combination with long-term, relatively low dose thrombolysis, in the setting of both clinically and morphologically progressive, hemorrhagic sinus thrombosis. The procedure proved to be both safe and effective and may be considered in the future for patients with progressive sinovenous thrombosis despite adequate medical therapy.