Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

Pediatric frequent relapsing nephrotic syndrome with multiple cerebral infarctions accompanied by patent foramen ovale and cerebral venous sinus thrombosis: a case report.

BACKGROUND: Idiopathic nephrotic syndrome (NS) presents as a hypercoagulable state, of which thromboembolism (TE) is a well-known life-threatening complication. Although TE is more likely to occur in venous vessels than arterial vessels, arterial TE is important because it may cause after-effects, including tissue necrosis and cerebral infarction (CI); therefore, prompt diagnosis and appropriate treatment are required. We report a pediatric NS case with multiple CIs. CASE PRESENTATION: A 14-year-7-month-old Japanese girl was diagnosed with frequent relapsing NS, accompanied by headache and disturbance of consciousness during the second relapse. Brain magnetic resonance imaging (MRI) and four-dimensional computed tomography revealed multiple CIs, vasogenic edema, and cerebral venous sinus thrombosis (CVST). The patient had no underlying thrombophilia other than hypercoagulability due to NS and prednisolone (PSL), and no cardiac arrhythmia; however, a right-to-left shunt through the patent foramen ovale (PFO) was observed with the Valsalva maneuver by echocardiography. Therefore, we assumed that a potential cause of multiple CIs might be an embolic stroke, caused by thrombosis formed from a hypercoagulable state due to NS and PSL treatment and reached through PFO. Antiplatelet and anticoagulant therapies were administered for TE. She was treated with PSL and mycophenolate mofetil (MMF) for NS. Rituximab (RTX) was administered to prevent NS relapse after complete remission (CR). She underwent transcatheter PFO closure at age 14 years and 9 months because we considered that the right-to-left shunt through the PFO would be one of the risks for recurrent cerebral embolism when NS relapses. One year after the onset of CIs, an MRI indicated that the CVST had resolved, leaving no neurological sequelae due to CI; therefore, anticoagulant therapy was discontinued. And then she has been in CR for NS with only MMF therapy. CONCLUSIONS: CI is a serious complication in patients with NS. The pathogenesis of multiple CIs is various, including right-to-left shunt through PFO, in addition to the hypercoagulability due to NS. It is important to investigate and manage underlying risks such as PFO, besides preventing the relapses of NS by aggressive treatments using MMF and RTX, in patients with NS.

Anticoagulation strategies in patients with coexisting traumatic intracranial hematomas and cerebral venous sinus thrombosis: an observational cohort study.

PURPOSE: Post-traumatic cerebral venous sinus thrombosis (ptCVT) is a rare but serious complication of traumatic brain injury (TBI). Managing ptCVT is challenging due to the concurrent risk of traumatic intracranial hematoma (ICH) expansion. Limited data exists on the safety and efficacy of anticoagulation therapy (ACT) in these cases. METHODS: This single-center observational cohort study included adult TBI patients with concurrent ICH and ptCVT. Low-molecular-weight heparin (LMWH) or heparin infusion was used to treat all ptCVTs based on institutional protocols. The outcomes of interest were hemorrhagic and thrombotic complications. RESULTS: Out of 1,039 TBI-patients admitted between 2006 and 2020, 32 met the inclusion criteria. The median time from injury to ptCVT diagnosis was 24 h. ACT was initiated at a median of 9 h after ptCVT diagnosis. Patients were administered either heparin infusion (n = 8) or LMWH at dosages ranging from 28 to 72% of the therapeutic level (n = 24). There were no hemorrhagic complications, even in patients receiving LMWH at ≥ 50% of the therapeutic dose. Thrombotic complications occurred in 3 patients (9.4%) - two cases of thrombus progression and one venous infarct. The patients who developed thrombotic complications differed from those who did not by having a 17-h delay in ACT initiation after diagnosis or by receiving an initial LMWH dose at 28% of the therapeutic level. CONCLUSION: LMWH at approximately 50% of the therapeutic level was effective for managing ptCVT associated with TBI in our retrospective dataset, with no risk of hematoma expansion. Prospective trials are warranted to confirm these results.

Catastrophic antiphospholipid syndrome: a case report and literature review.

Catatrophic antiphospholipid syndrome (CAPS), a rare variant of antiphospholipid syndrome (APS), is associated with rapid multiorgan failure. While APS is associated with single medium-to-large blood vessel occlusions, CAPS is most often associated with several, concurrent vascular occlusions of small vessels, commonly of the kidneys, heart, skin and brain. We present a case of a 21-year-old female patient with a history of immune thrombocytopenia purpura and APS, who eventually developed concurrent cerebral venous sinus thrombosis, diffuse alveolar haemorrhage, renal thrombotic microangiopathy, and a necrotic, vasculitic wound on her forearm. Despite hospitalisation and treatment, her condition worsened and the patient eventually died after succumbing to suspected CAPS.

A Rare Intersection of Septic Cavernous Sinus Thrombosis and Subarachnoid Hemorrhage: Insights from the Case of a 70-Year-Old Patient.

We describe a rare and complex case of septic cavernous sinus thrombosis (SCST) in a 70-year-old patient who initially presented with ocular symptoms that rapidly progressed to severe intracranial vascular complications, including subarachnoid hemorrhage (SAH). Despite the use of broad-spectrum antibiotics and anticoagulants, the patient's condition deteriorated. SCST, often caused by sinus infections, presents a significant diagnostic and therapeutic dilemma, with mortality rates exceeding 20%. This report underscores the diversity of clinical presentations, ranging from mild headaches to severe cranial nerve deficits, that complicate diagnosis and treatment. The inability to detect any aneurysms in our patient using magnetic resonance imaging (MRI) and computed tomography angiography (CTA) may indicate an alternative pathogenesis. This could involve venous hypertension and endothelial hyperpermeability. This case illustrates the need for personalized treatment approaches, as recommended by the European Federation of Neurological Societies, and the importance of a multidisciplinary perspective when managing such intricate neurological conditions. Our findings contribute to the understanding of SCST coexisting with SAH.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis.

BACKGROUND: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. METHODS: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. RESULTS: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. CONCLUSIONS: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Cerebral venous sinus thrombosis cases detected in on-call CT venographies in Sweden, 2019-2022.

No well-established criteria exist for assessing the risk of cerebral venous sinus thrombosis (CVST). Here, we sought to gain an understanding of CVST cases and associated risk factors, based on the rates of emergency CT venographies (CTVs) performed after hours. Furthermore, we aimed to assess possible correlations between CVST rates and COVID-19, including at the start of the COVID-19 vaccination campaign. We collected reports of emergency CTVs performed after hours at 56 Swedish hospitals between 1/1/2019 and 12/31/2022, and divided them into five groups: (I) from 1/1/2019 to 1/31/2020, before the emergence of COVID-19 cases in Sweden; (II) from 2/1/2020 to 12/26/2020, after the emergence of COVID-19 but before vaccination rollout; (III) from 12/27/2020 to 7/28/2021, from the start of the COVID-19 vaccination campaign until 50% of the adult population in Sweden had been vaccinated; (IV) from 7/29/2021 to 2/1/2022, from when 50% of the adult population was vaccinated until restrictions were lifted; and (V) from 2/2/2022 to 12/31/2022, after restriction measures were suspended. For all included patients, we collected information on demographics and clinical history, including pregnancy, recent partum, and use of oral contraceptives or post-menopausal hormone replacement therapy. In total, we collected 430 reports (92% female, 8% male). The CVST positivity rate was 22.2% in men vs. 2.3% in women. None of the pregnant (n = 49) or postpartum (n = 12) women had CVST positivity. The frequency of CTV examinations was lowest in group 2; during this period, the average time between patients being imaged was 7 days. The frequency of CTV examinations was highest in group IV; during this period, a patient underwent this type of scan every 1.5 days, on average. The frequency of CVST-positive scans was lowest in group II; during this period, a positive case was found every 66 days, on average. The frequency of CVST-positive scans was highest in group IV; during this period, a positive case was found every 62 days, on average, and no statistical difference with respect to group II was observed. Pregnancy and recent partum were not significant risk factors for CVST. The elevated CVST positivity rate observed during the height of the COVID-19 pandemic suggested that patients with less likelihood for positive CVST had fewer emergency visits. The positivity rate did not increase with the start of the COVID-19 pandemic or the rollout of COVID-19 vaccination.

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections.

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST. METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated. RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications. CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

A neonatal case of cerebral venous sinus thrombosis with intrauterine onset after COVID-19 infection during pregnancy: Cause or coincidence?

Coronavirus 19 disease (COVID-19) is known to predispose patients to increased thrombotic events and the risk is higher in pregnancy which is already a hypercoagulable state. Vertical transmission of the disease during pregnancy was neglected according to data early in the pandemic, however, despite conflicting results from different studies, there is an increasing suspicion of vertical transmission with the rise of new fetal and neonatal cases and perinatal transmission can be higher than expected. An early term neonate, with the history of maternal COVID-19 infection in the start of third trimester, was diagnosed as cerebral venous sinus thrombosis and chronic hemorrhagic ischemia, with intrauterine onset.

Cerebral Venous Sinus Thrombosis in Preterm Infants.

BACKGROUND: Neonatal cerebral venous sinus thrombosis (CVST) can lead to brain injury and neurodevelopmental impairments. Previous studies of neonatal CVST have focused on term infants, and studies of preterm infants are lacking. In this study, we examined the clinical and radiological features, treatment and outcome of CVST in preterm infants. METHODS: This was a retrospective, consecutive cohort study of preterm infants (gestational age <37 weeks) with radiologically confirmed CVST. All magnetic resonance imaging/MRV and CT/CTV scans were re-reviewed to study thrombus characteristics and pattern of brain injury. Outcome was assessed by the validated pediatric stroke outcome measure at the most recent clinic visit. RESULTS: Twenty-six preterm infants with CVST were studied. Of these, 65% were moderate-late preterm (32-37 weeks), 27% very preterm (28-32 weeks), and 8% extreme preterm (<28 weeks). Most (73%) were symptomatic at presentation with seizures or abnormal exam. Transverse (85%) and superior sagittal (42%) sinuses were common sites of thrombosis. Parenchymal brain injury was predominantly periventricular (35%) and deep white matter (31%) in location. Intraventricular hemorrhage occurred in 46%. Most infants (69%) were treated with anticoagulation. No treated infant (including eleven with pretreatment hemorrhage) had new or worsening post-treatment hemorrhage. Outcomes ranged from no deficits (50%), mild-moderate (25%), and severe (25%) impairment. CONCLUSIONS: In our sample of preterm infants with CVST, more than one-quarter were asymptomatic. White matter brain lesions predominated and one-half had neurological deficits at follow-up. Anticoagulation of preterm CVST in this small cohort appeared to be safe. Larger studies of preterm CVST are needed.

Fatal invasive aspergillosis in a child with chronic granulomatous disease.

Patients with chronic granulomatous disease, a primary immunodeficiency, experience granulomatous complications and recurrent life-threatening opportunistic bacterial and fungal infections. In this article, we report on a case of invasive aspergillosis in an eight-year-old boy with chronic granulomatous disease, who presented with pleural effusion and pneumonia, cerebral venous sinus thrombosis, and unusual skin lesions caused by Aspergillus fumigatus. Antifungal treatment with itraconazole and other antifungal agents, along with interferon-γ, was ineffective and the patient eventually died from cerebral venous sinus thrombosis, and intracerebral haemorrhage following increased intracranial pressure after one month. The diagnosis of invasive aspergillosis should be considered early in children presenting with invasive fungal infections, particularly those involving the central nervous system.

Downregulation of NF-κB by Shp-1 Alleviates Cerebral Venous Sinus Thrombosis-Induced Brain Edema Via Suppression of AQP4.

Aquaporin 4 (AQP4), a water channel protein, has been well studied in arterial stroke-induced brain edema. However, the role of AQP4 in cerebral venous sinus thrombosis (CVST) has not been reported. Here, we showed that AQP4 expression was increased in the brain of a rat CVST model, whereas inhibition of AQP4 decreased cerebral edema. Subsequent experiments showed that Shp-1 (Src homology 2-containing phosphatase-1) expression and NF-κB phosphorylation were upregulated after CVST. We found that Shp-1 inhibition resulted in enhancement of NF-κB activation and increased AQP4 expression accompanied by aggravated brain edema. We further showed that NF-κB inhibition led to decreased AQP4 expression and subsequent attenuation of brain edema but had no significant effect on Shp-1 expression. These results provide the first evidence suggesting that downregulation of NF-κB by Shp-1 alleviates CVST-induced brain edema through suppression of AQP4.

Late-Onset Vaccine-Induced Immune Thombotic Thrombocytopenia (VITT) with Cerebral Venous Sinus Thrombosis.

OBJECTIVES: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication after adenoviral vector vaccination against COVID-19 reported up to 24 days after ChAdOx1 nCOV-19 (AZD1222) vaccination. This report describes a case with a significantly later onset of VITT with cerebral venous sinus thrombosis. CASE DESCRIPTION: We report a 42-year-old woman presenting to the emergency department 53 days after AZD1222 vaccination with sudden onset sensory aphasia and an 18-day history of headache. Cranial computed tomography (CT) showed acute intracranial hemorrhage and CT venogram demonstrated thrombosis of the left vein of Labbé and transverse and sigmoid sinus. D-dimers were elevated and despite a normal platelet count, platelet-activating anti-PF4 antibody testing was positive, confirming the diagnosis of VITT. The patient was treated with intravenous immunoglobulins and argatroban, and was discharged without any neurological deficit on day 12. CONCLUSION: Our report of VITT with symptom onset on day 35 and diagnosis of cerebral sinuous thrombosis on day 53 after AZD1222 vaccination significantly enhances the time window during which VITT may occur.

Characteristics and outcomes of postpartum cerebral venous sinus thrombosis: A subgroup analysis of the ACTION-CVT study.

BACKGROUND AND PURPOSE: There is a relative paucity of data regarding long-term outcomes and treatment-related complications in women of childbearing age with cerebral venous sinus thrombosis (CVST). We sought to determine whether outcomes differ in women of childbearing age with versus without postpartum CVST. METHODS: We retrospectively analysed 373 non-pregnant females of childbearing age (18-45 years) included in the multicenter observational Anticoagulation in the Treatment of Cerebral Venous Thrombosis study (ACTION-CVT). Comparisons were made between postpartum (first 12 weeks from delivery, n=38 [10.2%]) versus non-postpartum women (n=335 [89.8%]). The primary outcomes of interest were one-year risk of all-cause death, venous thromboembolism (VTE) recurrence, and major hemorrhage (i.e., new or worsening intracranial hemorrhage or major extracranial hemorrhage). Secondary outcomes were the discharge disposition and modified Rankin Scale (mRS) score at discharge and 90 days. RESULTS: Postpartum status was associated with greater risk of seizures (42.1% versus 20.9%, p=0.003), venous infarction (47.4% versus 29.5%, p=0.025), intracranial hemorrhage (55.3% versus 36.1%, p=0.022), and requirement for neurosurgical treatment (13.2% versus 3.6%, p=0.021). There was no significant association with one year all cause death (N=373 HR=1.35, 95%-CI=0.15-11.87, p=0.784), VTE recurrence (N=373, HR=1.27, 95%-CI=0.45-3.59, p=0.648), major hemorrhage (N=373, HR=1.36, 95%-CI=0.46-4.0, p=0.581) as well as excellent (mRS[0-1]: OR=1.58, 95%-CI=0.4-7.1, p=0.554) and good (mRS[0-2]: OR=0.92, 95%-CI=0.2-4.27, p=0.918) 90-day mRS. Results were similar after adjustment for potential confounders. CONCLUSIONS: Although CVST in the 12-week postpartum period was more frequently associated with early complications, 90-day functional disability and one-year outcomes were similar to women with CVST unrelated to pregnancy.

Behcet's Disease (BD) Presenting as a Cerebral Venous Sinus Thrombosis (CVST).

Presentation 20 year old Caucasian male presented to eye casualty 4 weeks post initial diagnosis of bilateral acute anterior uveitis (AAU), with a three-week history of a progressively worsening headache associated with nausea and vomiting. Diagnosis Non-contrast Computed Topography of the head and Magnetic Resonance venogram revealed a cerebral venous sinus thrombosis (CVST). He had a long-standing history of intermittent oral ulceration, and was diagnosed with Neuro Behcet's Disease (NBD). Treatment The patient was commenced on a therapeutic dose of enoxaparin and prednisolone, and was discharged on enoxaparin, warfarin, tapering prednisolone and azathioprine. Discussion/Conclusion NBD is a rare, but serious manifestation of BD. BD is an important differential diagnosis in a young patient presenting with CVST or bilateral AAU.

Clinical characteristics of cerebral venous sinus thrombosis in childhood-onset systemic lupus erythematosus patients: a single-centre study from China.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) is a rare complication of childhood-onset SLE (cSLE) and is potentially fatal to the patient. In order to better define the characteristics of CVST in cSLE, we analysed a single-centre study of cSLE presenting with CVST. METHODS: Clinical characteristics and laboratory findings of cSLE patients complicated with CVST from January 2006 to December 2019 were analysed through this retrospective, single-centre study. RESULTS: A total of 1395 records of cSLE patients were reviewed. Five patients (0.36%) had CVST. Headache (80%) was the most frequent symptom. The transverse sinus (45%) was the most frequent location of thrombus, followed by the sigmoid sinus (27%). The SLE disease activity index (SLEDAI) at the time of CVST was 11±3. The D-dimer was elevated in all 5 cases, only one patient was positive for ACL and anti-ß2GP-I IgM. All the patients underwent MRV screen to confirm the diagnosis. All the patients had a favourable outcome after receiving glucocorticoid and immunosuppressant treatment, as well as anticoagulant therapy. CONCLUSIONS: CVST is relatively rare in cSLE and tends to occur in active lupus patients. Severe and persistent headache is an index of CVST. Early diagnosis and more intensive therapy for SLE, combined with anticoagulation therapy, could significantly improve the prognosis of CVST in cSLE.

Early Outcomes of Bivalirudin Therapy for Thrombotic Thrombocytopenia and Cerebral Venous Sinus Thrombosis After Ad26.COV2.S Vaccination.

Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin in patients suspected of having vaccine-induced thrombotic thrombocytopenia. At this time there have been no reported outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. We describe the early outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. A 40-year-old Caucasian woman was found to have thrombocytopenia, cerebral venous sinus thrombosis, and pulmonary embolism following vaccination for COVID-19 with Ad26.COV2.S. She exhibited a steady rise in platelet count: 20×109/L at hospital day 0, 115×109/L at discharge on hospital day 6, and 182×109/L on outpatient follow-up on day 9. While the patient exhibited a transient drop in hemoglobin, there was no clinical evidence of bleeding. This patient did not demonstrate any clinical sequelae of thrombosis, and she reported resolution of her headache. Vaccination with Ad26.COV2.S appears to be associated with a small but significant risk for thrombotic thrombocytopenia within 13 days of receipt. The Centers for Disease Control and Prevention guidance to consider an alternative to heparin was not accompanied by specifically recommended alternatives. A single patient treated with bivalirudin for suspected vaccine-induced thrombotic thrombocytopenia subsequently experienced symptom improvement and a rise in platelet count and did not demonstrate any immediate negative outcomes. A provider may consider bivalirudin as an alternative to heparin in patients with suspected vaccine-induced thrombotic thrombocytopenia following Ad26.COV2.S vaccination, pending more definitive research.

Dural arteriovenous fistula following cerebral venous sinus thrombosis in a patient with minimal change disease: A case report.

A 78-year-old man presented with nephrotic syndrome and new-onset disorientation. Plasma D-dimer level was increased, and a lower leg deep vein thrombosis was identified on ultrasound. Histopathologic analysis of percutaneous renal biopsy samples confirmed the diagnosis of minimal change disease. Treatment with prednisone (20 mg/day), cyclosporine (50 mg/day), and anticoagulant therapy with edoxaban tosylate hydrate led to the complete resolution of nephrotic syndrome after 4 weeks. Despite this, his disorientation persisted. Head CT and MRI have revealed cerebral venous sinus thrombosis and dural arteriovenous fistula, which was considered a possible complication of nephrotic syndrome. Embolization dramatically improved his disorientation. This paper highlights that cerebral venous sinus thrombosis and dural arteriovenous fistula should always be considered in patients with nephrotic syndrome and new-onset disorientation.

HIT in the head: a systematic review of cerebral venous sinus thrombosis in classical and autoimmune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) causes thrombosis and thrombocytopenia, usually due to prior heparin exposure, so-called classical HIT. However, in the autoimmune form, the signs and symptoms of HIT occur without prior heparin exposure. Development of cerebral venous sinus thrombosis (CVST) secondary to HIT is a rare occurrence, with relatively few reports in the literature. There is a need to better understand the clinical presentation and treatment paradigms in these rare cases. Therefore, we present the first systematic review of CVST occurring in classical and autoimmune HIT. Cases of HIT-induced CVST were identified through a systematic search of Pubmed from the date of inception to March 2021. Literature search revealed 21 cases of HIT and associated CVST with six cases (28.6%) of autoimmune HIT. Patients presented with signs and symptoms consistent with increased intracranial pressure, intracerebral hemorrhage (ICH), and/or focal neurologic deficits. Headache was the most common symptom with 12 patients (60.0%) presenting as such. 10 patients (47.6%) included in the study developed ICH. Non-heparin anticoagulants, especially direct thrombin inhibitors, were the first-line treatment for the majority of patients (55.6%). Intravenous immunoglobulin (IVIG) was used as treatment for select patients (16.7%) with autoimmune HIT. Few patients received surgical intervention for CVST (14.3%) or ICH (30.0%). Four patients had a full recovery, four patients had residual deficits, and seven patients ultimately expired. Symptoms of HIT-induced CVST are often related to CNS dysfunction. Non-heparin anticoagulants are important to treat CVST, even when patients have concomitant ICH, and may be supplemented with IVIG if treating autoimmune HIT. Rapid identification and treatment of HIT-induced CVST is imperative in order to prevent morbidity and mortality.

Sigmoid Sinus Thrombosis Followed by Splenic Infarction Due to Imatinib Therapy in a Patient with Gastrointestinal Stromal Tumor; Hematological Side Effects of Imatinib.

Imatinib has an important place as an adjuvant therapy as well as in the treatment of metastatic disease caused by gastrointestinal stromal tumor (GIST), which is one of the common mesenchymal tumors of the gastrointestinal tract. Imatinib is a tyrosine kinase inhibitor and is generally well tolerated. However, it can cause some serious adverse effects. The most common of these are edema on the face and legs, headache, fatigue, nausea, vomiting, and rash on the skin. The most serious side effects, albeit less common, are gastrointestinal or intraabdominal bleeding. However, thrombotic events such as sigmoid sinus thrombosis and splenic infarction are extremely rare. The current report presents a patient with GIST who is treated with imatinib 400 mg/day. The patient presented with edema on the face and headache in the second month of imatinib therapy, after which she was diagnosed with sigmoid sinus thrombosis. The patient who presented with abdominal pain approximately three months later developed splenic infarction. She was administered acetylsalicylic acid, supplemental oxygen (O2) in the first episode of thrombosis, and imatinib therapy was discontinued. The patient's complaints and thrombus regressed, after which imatinib therapy was resumed. She was administered intravenous hydration, supplemental oxygen, analgesics, and imatinib therapy was discontinued after the patient sustained splenic infarction. After resolution of sigmoid sinus thrombosis and the regression of splenic infarction area, the patient was switched to sunitinib therapy. She is attending routine control visits. Sigmoid sinus thrombosis and splenic infarction should be kept in mind as a rare cause of headache and abdominal pain in patients treated with imatinib, and detailed neurological and gastrointestinal evaluation should be performed.