Cerebral venous thrombosis after high-dose steroid in patient with multiple sclerosis: A case report.

RATIONALE: Multiple sclerosis (MS) is a central nervous system disease mainly mediated by immunity, which is one of the most common causes of neurological dysfunction in young people worldwide. In the acute phase, high-dose steroid therapy is effective. There are few reports about cerebral venous thrombosis (CVT) after high-dose steroid therapy. PATIENT CONCERNS: We present a case of a 19-year-old female diagnosed with MS who developed a headache after high-dose steroid therapy was diagnosed with CVT. Headache symptoms improved after anticoagulant treatment. DIAGNOSES: MS comorbid CVT. INTERVENTIONS: Anticoagulant therapy was added and hormone therapy was reduced. OUTCOMES: Clinical symptoms such as headache, limb numbness, and involuntary tremors in the right hand were improved, and the muscle strength of the right limb recovered to grade 4. The patient did not suffer from headaches after discharge and no abnormality in the computed tomography (CT) scan of the cephalic vein at the 5-months follow-up. LESSONS: High-dose steroid therapy may be a risk factor for CVT in patients with MS. MS patients who develop headaches during high-dose steroid therapy should undergo further cranial CTV to rule out CVT.

Cerebral venous thrombosis after ChAdOx1 nCoV-19 vaccination: a systematic review.

OBJECTIVE: To perform a systematic review of case reports or case series regarding thrombosis with thrombocytopenia syndrome (TTS) and cerebral venous thrombosis (CVT) related to ChAdOx1 nCoV-19 vaccination to address the clinical features, laboratory findings, treatment modalities, and prognosis related with CVT. SUBJECTS AND METHODS: We included 64 TTS patients from 19 articles, 6 case series and 13 case reports, in which thrombosis occurred after the first dose of ChAdOx1 nCoV-19 vaccination published up to 30 June 2021 in Embase, ePubs, Medline/PubMed, Scopus, and Web of Science databases. RESULTS: Of the 64 TTS patients, 38 (59.3%) had CVT. Patients with CVT were younger (median 36.5 vs. 52.5 years, p<0.001), had lower fibrinogen levels (130 vs. 245 mg/dL, p=0.008), had more frequent history of intracerebral hemorrhage (ICH), and had higher mortality rate (48.6% vs. 19.2%, p=0.020) than that of patients without CVT. In multivariable analysis, the possibility of presence of CVT was higher in younger age groups [odd ratio (OR): 0.91, 95% confidence interval (CI): (0.86-0.97, p<0.001)] and those with accompanying intracerebral hemorrhage (ICH) (OR: 13.60, 95% CI (1.28-144.12, p=0.045). CONCLUSIONS: Our study demonstrated that CVT related to ChAdOx1 nCoV-19 vaccination was associated with younger age, low levels of fibrinogen, presence of ICH and more frequent mortality compared to those of non-CVT. If TTS occurs after ChAdOx1 nCoV-19 vaccination, the presence of CVT in patients with young age or ICH should be considered.

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.

Retrospective review COVID-19 vaccine induced thrombotic thrombocytopenia and cerebral venous thrombosis-what can we learn from the immune response.

INTRODUCTION: Cerebral Venous Thrombosis (CVT), prior to the COVID pandemic, was rare representing 0.5 of all strokes, with the diagnosis made by MRI or CT venography.1-,3 COVID-19 patients compared to general populations have a 30-60 times greater risk of CVT compared to non-affected populations, and up to a third of severe COVID patients may have thrombotic complications.4-8 Currently, vaccines are the best way to prevent severe COVID-19. In February 2021, reports of CVT and Vaccine-induced immune thrombotic thrombocytopenia (VITT) related to adenovirus viral vector vaccines including the Oxford-AstraZeneca vaccine (AZD1222 (ChAdOx1)) and Johnson & Johnson COVID-19 vaccine (JNJ-78436735 (Ad26.COV2·S)), were noted, with a 1/583,000 incidence from Johnson and Johnson vaccine in the United States.11, 12 This study retrospectively analyzed CVT and cross-sectional venography at an Eastern Medical Center from 2018 to 2021, and presents radiographic examples of CVT and what is learned from the immune response. METHODS: After IRB approval, a retrospective review of cross-sectional CTV and MRVs from January 1st 2018 to April 30th 2021, at a single health system was performed. Indications, vaccine status, patient age, sex, and positive finding incidence were specifically assessed during March and April for each year. A multivariable-adjusted trends analysis using Poisson regression estimated venogram frequencies and multivariable logistic regression compared sex, age, indications and vaccination status. RESULTS AND DISCUSSION: From January 1, 2018 to April 30, 2021, (Fig. 1), a total of n = 2206 in patient and emergency room cross-sectional venograms were obtained, with 322 CTVs and 1884 MRVs. In 2018, 2019, 2020, respective totals of cross-sectional venograms were 568, 657, 660, compared to 321 cross-sectional venograms in the first four months of 2021. CTV in 2018, 2019, 2020, respective totals were 51, 86, 97, MRV totals were 517, 571, 563, compared to the 2021 first four month totals of 88 CTVs and 233 MRVs. March, April 2018, 2019, 2020, CTVs respectively were 6, 17, 11, compared to the 2021 first four months of 59 CTVs, comprising 63% of the total 93 CTVs, respective MRVs were 79, 97, 52, compared to 143 MRVs in the first four months of 2021 for 39% of the total 371 MRVs. In March, April 2020 during the pandemic onset, cross-sectional imaging at the East Coast Medical Center decreased, as priorities were on maintaining patient ventilation, high level of care and limiting spread of disease. In March/April 2021, reports of VITT and CVT likely contributed to increased CTVs and MRVs, of 39.65% [1.20-1.63] increase (P < 0.001) from prior. In March, April 2021 of 202 venograms obtained, 158 (78.2.%) were unvaccinated patients, 16 positive for CVT (10.1%), 44 were on vaccinated patients (21.7%), 8 specifically ordered with vaccination as a clinical indication, 2 positive for CVT (4.5%), (odds ratio = 0.52 [0.12-2.38], p = 0.200). CONCLUSION: CTV prior to the COVID pandemic, was rare, responsible for 0.5 of all strokes, at the onset of the pandemic in the East Coast, overall cross-sectional imaging volumes declined due to maintaining ventilation, high levels of care and limiting disease spread, although COVID-19 patients have a 30-60 times greater risk of CVT compared to the general population, and vaccination is currently the best option to mitigate severe disease. In early 2021, reports of adenoviral vector COVID vaccines causing CTV and VITT, led to at 39.65% increase in cross-sectional venography, however, in this study unvaccinated patients in 2021 had higher incidence of CVT (10.1%), compared to the vaccinated patients (4.5%). Clinicians should be aware that VITT CVT may present with a headache 5-30 days post-vaccination with thrombosis best diagnosed on CTV or MRV. If thrombosis is present with thrombocytopenia, platelets <150 × 109, elevated D-Dimer >4000 FEU, and positive anti-PF4 ELISA assay, the diagnosis is definitive.13 VITT CVT resembles spontaneous autoimmune heparin induced thrombocytopenia (HIT), and is postulated to occur from platelet factor 4 (PF4) binding to vaccine adenoviral vectors forming a novel antigen, anti-PF4 memory B-cells and anti-PF4 (VITT) antibodies.14-17.

Cerebral vein thrombosis in a woman using oral contraceptive pills for a short period of time: a case report.

BACKGROUND: Cerebral vein thrombosis is increasing in young adults. Although oral contraceptive pills increase the risk of cerebral vein thrombosis, relatively high brain venous involvement is rare when oral contraceptive pills are consumed for a short duration. CASE PRESENTATION: A 31-year-old Asian woman was referred to Imam Reza Hospital with a headache complaint on 11 November 2020. The woman, who had a headache for the previous 11 days, went to the hospital. Owing to endometriosis involvement, she consumed Diane tablets. According to the imaging findings, three vein involvements were diagnosed. Anticoagulant therapy was started, and the symptoms disappeared. CONCLUSIONS: All cerebral vein thrombosis symptoms are variable, but new presentation of headache could be an early symptom of cerebral vein thrombosis.

Cerebral venous thrombosis without thrombocytopenia after a single dose of COVID-19 (Ad26.COV2.S) vaccine injection: a case report.

BACKGROUND: The coronavirus pandemic became the hard challenge for the modern global health system. To date, vaccination is the best strategy against Sars-Cov-2-related illness. About 3 billions of people received at least one of the approved vaccines. The related adverse events were reported during the various experimental phases, but newer and less common side effects are emerging post-marketing. Vaccine-induced thrombocytopenia with thrombosis (VITT) is one of these insidious adverse reactions and it is considered responsible of venous thrombosis, in both the splanchnic and the cerebral circulation. Although its mechanism has been presumably established, resembling that observed in heparin-induced thrombocytopenia, some venous thromboses seem not to recognize this etiology and their pathogenesis remains unknown. Here we described a case of cerebral venous thrombosis after administration of the Ad26.COV2.S, presenting without thrombocytopenia, paving the way for possible novel causes of this vaccine-induced pathological condition. CASE PRESENTATION: A 45-year-old woman came to our observation for bilateral periorbital headache associated with retro-orbital pain started 8 days after administration of COVID vaccine Jannsen. Ophthalmologic exam showing a bilateral papilledema raised the suspicion of intracranial hypertension. Cerebral magnetic resonance imaging revealed signal alteration with T1-positive contrast enhancement in the right temporal and insular lobes suggestive of cerebral venous thrombosis. The absence of thrombocytopenia and platelet factor 4 (PF-4) antibodies led the clinicians to rule out VITT. The patient was treated successfully with warfarin. CONCLUSION: Venous thrombosis occurring after COVID-19 vaccination represents an adverse event of special interest. Patients with thrombosis and thrombocytopenia appear to be affected by a general thrombophilic state, sustained by an autoimmune mechanism, and show a higher mortality. Thrombosis without thrombocytopenia's pathogenesis has not yet been clarified, but laboratory data and good response to vitamin K antagonists help clinicians in the differential diagnosis with VITT. Future research will allow us to discover other possible mechanisms and maybe identify a subgroup of patients with a higher risk of developing this medical complication.

Iron-deficiency anaemia in childhood: a risk factor for severe venous thrombosis?

Iron deficiency anaemia is a common disorder in the paediatric age-group. The association between iron deficiency and venous thrombosis in children without an underlying illness is rare. Two cases are described. A 17-year-old girl had been taking oestrogen-progestogen therapy for contraception for about 2 years and developed a lower-limb deep vein thrombosis associated with pulmonary embolism. A 3-year-old girl was admitted to the paediatric emergency department with pallor, weakness and vomiting, and a cerebral CT showed a recent cerebral venous thrombosis. Both cases had severe iron-deficiency anaemia which increases a thrombotic tendency and could be a further crucial trigger of venous thrombosis in patients at low risk; therefore, in cases of unexplained thrombosis, it must always be considered to be a risk factor.Abbreviations APCR: activated protein C resistance; CMV: cytomegalovirus; CT: computerised tomography; CVST: cerebral venous sinus thrombosis; CVT: cerebral venous thrombosis; DVT: deep vein thrombosis; DOACs: direct oral anticoagulants; EBV: Epstein-Barr virus; ID: iron deficiency; IDA: iron deficiency anaemia; LMWH: low molecular weight heparin; PE: pulmonary embolism; RDW: red blood cell distribution width; VT: venous thrombosis.

Middle-age Asian male with cerebral venous thrombosis after COVID-19 AstraZeneca vaccination.

Vaccine-associated cerebral venous thrombosis has become an issue following the extensive vaccination program of the Coronavirus Disease of 2019 (COVID-19) Vaccine AstraZeneca (ChAdOx1 vaccine). The importance of early diagnosis should be emphasized due to the high mortality rate without appropriate treatment. Young female populations in western countries have been reported to be at a greater risk of this vaccine related thrombotic event, but cases in East Asia are lacking. Herein, we present the first case of cerebral venous sinus thrombosis 10 days after ChAdOx1 vaccination in a middle-age Asian male in Taiwan.

Progressive thrombosis of cervical and intracranial arteries related to Ponatinib treatment for Chronic Myeloid Leukemia.

Ponatinib is a third-generation Tyrosine Kinase Inhibitor (TKI), approved as first-line treatment for Chronic Myeloid Leukaemia (CML) chronic phase. Here we describe a CML patient with a history of subsequent TIAs and an ischemic stroke during Ponatinib treatment. Patient was admitted for a 3-day history of sudden onset left hemiparesis due to an acute ischemic stroke. MRI showed bilaterally the almost total absence of signal in the intracranial tract of anterior circulation and low signal of cerebral posterior circulation. Digital Subtraction Angiography showed multiple steno-occlusions of both anterior and posterior circulation large vessels. The association between cerebrovascular events and TKIs of second and third-generation has been widely described. So Ponatinib was stopped. To our knowledge, this is the first case of multiple ischemic strokes and recurrent TIAs during treatment with Ponatinib, pointing out the importance of accurate quantification of cardiovascular risk before starting Ponatinib.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Menopausal hormone therapy, blood thrombogenicity, and development of white matter hyperintensities in women of the Kronos Early Estrogen Prevention Study.

OBJECTIVE: Development of white matter hyperintensities (WMH) in the brain is associated with blood thrombogenicity in recently menopausal women. This study examined the influence of menopausal hormone treatments (MHTs) on this association. METHODS: Measures of blood thrombogenicity were examined in women of the Kronos Early Estrogen Prevention Study (n = 95) who had brain magnetic resonance imaging before and during the 48 months of randomization to transdermal 17ß-estradiol (n = 30), oral conjugated equine estrogen (n = 29) both with progesterone for 12 days per month or placebo pills and patch (n = 36). Principal components (PCs) analysis was used to reduce the dimensionality of 14 markers of platelet activation and blood thrombogenicity. The first 5 PCs were assessed for association with treatment and changes in WMH. Within-person slopes were obtained to capture the extent of WMH change for each woman. RESULTS: WMH increased in all groups over the 48 months (P = 0.044). The partial effect of PC1, representing an average of six thrombogenicity variables (microvesicles derived from endothelium, leukocytes, and monocytes, and positive for tissue factor and adhesion molecules) on WMH was significant (P = 0.003). PC3, reflecting a contrast of platelet microaggregates and adenosine triphosphate secretion versus total platelet count, differed across groups (P = 0.006) with higher scores in the oral conjugated equine estrogen group. The global association between PCs and WMH increase, however, did not differ significantly by MHT (P = 0.207 for interaction between MHT and PC's). CONCLUSION: In recently menopausal women, the type of MHT did not significantly influence the association of markers of blood thrombogenicity with development of WMH in the brain.

Cocaine as a rare cause of locked-in syndrome: a case report.

INTRODUCTION: In the United States, cocaine is a commonly used drug of abuse. It is also a recognized contributing factor for both hemorrhagic and ischemic strokes. However, cocaine-induced basilar artery thrombosis has rarely been reported in the literature. CASE PRESENTATION: Our patient was a 51-year-old African American woman with a history of polysubstance abuse who presented to the emergency department for acute behavior changes. Later, during admission, she had a dramatic decrease in motor strength in all extremities and a positive Babinski reflex bilaterally. The results of her toxicology reports were positive for cocaine; in addition, results of magnetic resonance angiography and magnetic resonance imaging were consistent with acute thrombosis and subsequent infarction of the basilar artery. Her mental status improved, but she was only able to communicate via movements of her eyes. CONCLUSION: Our patient developed locked-in syndrome after use of cocaine. Given the prevalence of its use in the United States, cocaine use should be included among the potential causes of locked-in syndrome.

Risk of Adverse Vascular Events in Patients with Malignant Glioma Treated with Bevacizumab Plus Irinotecan: A Systematic Review and Meta-Analysis.

BACKGROUND: Bevacizumab plus irinotecan is a new beneficial chemotherapy strategy for patients with malignant glioma. The purpose of this systematic review and meta-analysis was to comprehensively assess the risk of adverse vascular events in adults with malignant glioma treated with bevacizumab plus irinotecan. METHODS: The Cochrane Library, Embase and PubMed were searched, and relevant trials were identified up to June 2018. Two investigators screened all titles and abstracts for possible inclusion and extracted data independently. Six studies were included, and 5 of them in the control group using bevacizumab alone or bevacizumab with temozolomide. Three systems were used to assess the quality of evidence and the level of recommendation. The Oxford Centre for Evidence-Based Medicine Levels of Evidence (2009) system was used to classify the evidence into 5 levels (classes I-V). The star system from the Newcastle-Ottawa Scale was used to assess methodological quality. The GRADE profiler was used to evaluate the overall body of evidence. RESULTS: Our data show that bevacizumab plus irinotecan therapy does not significantly affect the risk of systemic adverse events (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.43-3.18). Patients treated with bevacizumab plus irinotecan had a similar risk of hematotoxicity (OR, 1.06; 95% CI, 0.26-4.38), thrombocytopenia (OR, 1.07; 95% CI, 0.25-4.63), and hypertension (OR, 1.34; 95% CI, 0.28-6.36) compared with the control group (those treated without irinotecan). Thrombosis occurred more frequently in patients treated with bevacizumab plus irinotecan compared with the control group (OR, 3.23; 95% CI, 1.47-7.12). CONCLUSIONS: The risk of systemic adverse events was not significantly different between patients with malignant glioma treated with bevacizumab plus irinotecan and the control group. The risks of hematotoxicity, thrombocytopenia, and hypertension were similar in the 2 groups. The risk of thrombosis was higher in patients treated with bevacizumab plus irinotecan. Monitoring for thrombosis and administering anticoagulant therapy as necessary merit promotion for patients with malignant glioma receiving treatment with bevacizumab plus irinotecan.

Pulmonary exposure to silver nanoparticles impairs cardiovascular homeostasis: Effects of coating, dose and time.

Pulmonary exposure to silver nanoparticles (AgNPs) revealed the potential of nanoparticles to cause pulmonary toxicity, cross the alveolar-capillary barrier, and distribute to remote organs. However, the mechanism underlying the effects of AgNPs on the cardiovascular system remains unclear. Hence, we investigated the cardiovascular mechanisms of pulmonary exposure to AgNPs (10 nm) with varying coatings [polyvinylpyrrolidone (PVP) and citrate (CT)], concentrations (0.05, 0.5 and 5 mg/kg body weight), and time points (1 and 7 days) in BALB/C mice. Silver ions (Ag+) were used as ionic control. Exposure to AgNPs induced lung inflammation. In heart, tumor necrosis factor α, interleukin 6, total antioxidants, reduced glutathione and 8-isoprostane significantly increased for both AgNPs. Moreover, AgNPs caused oxidative DNA damage and apoptosis in the heart. The plasma concentration of fibrinogen, plasminogen activation inhibitor-1 and brain natriuretic peptide were significantly increased for both coating AgNPs. Likewise, the prothrombin time and activated partial thromboplastin time were significantly decreased. Additionally, the PVP- and CT- AgNPs induced a significant dose-dependent increase in thrombotic occlusion time in cerebral microvessels at both time points. In vitro study on mice whole blood exhibited significant platelet aggregation for both particle types. Compared with AgNPs, Ag+ increased thrombogenicity and markers of oxidative stress, but did not induce either DNA damage or apoptosis in the heart. In conclusion, pulmonary exposure to AgNPs caused cardiac oxidative stress, DNA damage and apoptosis, alteration of coagulation markers and thrombosis. Our findings provide a novel mechanistic insight into the cardiovascular pathophysiological effects of lung exposure to AgNPs.

Autoimmune heparin-induced thrombocytopenia of delayed onset: a clinical challenge.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) usually appears at 5 to 10 days after initiation of heparin. Autoimmune HIT can arise after discontinuation of heparin treatment (delayed-onset HIT) or without any preceding heparin exposure (spontaneous HIT syndrome). CASE REPORT: This case presents a course of autoimmune HIT with delayed onset. The patient was hospitalized due to influenza pneumonia and received low-molecular-weight heparin thromboprophylaxis for 9 days. Seven days after discharge, she was readmitted because of a cerebral sinus vein thrombosis and severe thrombocytopenia. Intracranial bleeding and brain infarction caused her death. DISCUSSION: Autoimmune HIT was confirmed by functional heparin-induced platelet (PLT) activation test. Intracranial bleeding prevented continuous and effective anticoagulation. PLT transfusions were given, although they are generally advised against in HIT patients due to potential risk of thromboembolic events. CONCLUSION: This case presents that testing PLT-activating antibodies both in the presence and in the absence of current heparin treatment helps to diagnose patients with autoimmune HIT. There is conflicting evidence to refuse PLT transfusion when HIT is complicated with life-threatening bleeding.

Cerebral venous thrombosis requiring invasive treatment for elevated intracranial pressure in women with combined hormonal contraceptive intake: risk factors, anatomical distribution, and clinical presentation.

OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population. METHODS The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher's exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05. RESULTS Of the 168 patients, 57 (age range 16-49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.

CO poisoning as an associated risk factor for CVT.

We report a 24year old female who presented with sudden and severe headaches after recent carbon monoxide poisoning. Imaging revealed an acute cerebral venous thrombosis. Prior studies have suggested that carbon monoxide is a risk factor for an acute hypercoagulable state (i.e. DVT). However, little data is available regarding the correlation between carbon monoxide poisoning and cerebral venous thrombosis. This case demonstrates that such a correlation should be considered in acute intracerebral thrombotic events.

Thrombosis and systemic and cardiac oxidative stress and DNA damage induced by pulmonary exposure to diesel exhaust particles and the effect of nootkatone thereon.

Adverse cardiovascular effects of particulate air pollution persist even at lower concentrations than those of the current air quality limit. Therefore, identification of safe and effective measures against particle-induced cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit with diverse bioactivities including anti-inflammatory and antioxidant effects. However, its protective effect on the cardiovascular injury induced by diesel exhaust particles (DEPs) has not been studied before. We assessed the possible protective effect of nootkatone (90 mg/kg) administered by gavage 1 h before intratracheal instillation of DEPs (30 µg/mouse). Twenty-four hours after the intratracheal administration of DEPs, various thrombotic and cardiac parameters were assessed. Nootkatone inhibited the prothrombotic effect induced by DEPs in pial arterioles and venules in vivo and platelet aggregation in whole blood in vitro. Also, nootkatone prevented the shortening of activated partial thromboplastin time and prothrombin time induced by DEPs. Nootkatone inhibited the increase of plasma concentration of fibrinogen, plasminogen activator inhibitor-1, interleukin-6, and lipid peroxidation induced by DEPs. Immunohistochemically, hearts showed an analogous increase in glutathione and nuclear factor erythroid-derived 2-like 2 expression by cardiac myocytes and endothelial cells after DEP exposure, and these effects were enhanced in mice treated with nootkatone + DEPs. Likewise, heme oxygenase-1 was increased in mice treated with nootkatone + DEPs compared with those treated with DEPs or nootkatone + saline. The DNA damage caused by DEPs was prevented by nootkatoone pretreatment. In conclusion, nootkatoone alleviates DEP-induced thrombogenicity and systemic and cardiac oxidative stress and DNA damage, at least partly, through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 activation. NEW & NOTEWORTHY Nootkatoone, a sesquiterpenoid found in grapefruit, alleviates the thrombogenicity and systemic and cardiac oxidative stress and DNA damage in mice exposed to diesel exhaust particles. Nootkatone-induced boosting of nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 levels in the heart of mice exposed to diesel exhaust particles suggests that its protective effect is, at least partly, mediated through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 activation.