Prevalence of cerebral vein thrombosis among patients with spontaneous intracranial hypotension

Background and purpose Cerebral venous sinus thrombosis (CVST) is a rare condition but an important complication of spontaneous intracranial hypotension (SIH). We reviewed our experience of patients with SIH and assessed for the presence of CVST. Methods We reviewed the medical records and imaging studies from our tertiary referral institution, assessing patients with clinically suspected SIH as well as imaging findings of intracranial hypotension. All relevant brain MRIs were reviewed for the presence of brain sag, pachymeningeal enhancement, and CVST. Results Among 563 patients with a clinical diagnosis of SIH, 431 (76%) demonstrated brain sag. In the overall patient cohort, a total of 5 patients had CVST (0.9%) and all 5 of these patients demonstrated findings of brain sag. Of the patients with CVST, 3 had significant complications, including dural arteriovenous fistulas (2 patients) and lobar hemorrhage with seizure (1 patient). Conclusion SIH is a risk factor for the development of CVST. In our review of 563 patients with clinical and/or imaging findings of SIH, 0.9% of patients were diagnosed with CVST and 3 of these patients (60%) had additional severe complications.

Cerebral Vein Thrombosis in the Antiphospholipid Syndrome: Analysis of a Series of 27 Patients and Review of the Literature

(1) Background: The Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, pregnancy morbidity and raised titers of antiphospholipid antibodies. Cerebral vein thrombosis (CVT) is a rare form of cerebrovascular accident and an uncommon APS manifestation; the information in the literature about this feature consists of case reports and small case series. Our purpose is to describe the particular characteristics of CVT when occurs as part of the APS and compare our series with the patients published in the literature. (2) Methods: We conducted a retrospective observational study collecting data from medical records in three referral centers for APS and CVT, and a systematic review of the literature for CVT cases in APS patients. (3) Results: Twenty-seven APS patients with CVT were identified in our medical records, the majority of them diagnosed as primary APS and with the CVT being the first manifestation of the disease; additional risk factors for thrombosis were identified. The review of the literature yielded 86 cases, with similar characteristics as those of our retrospective series. (4) Conclusions: To our knowledge, our study is the largest CVT series in APS patients published to date, providing a unique point of view in this rare thrombotic manifestation.

Evaluation of rivaroxaban versus warfarin for the treatment of cerebral vein thrombosis: A case-control blinded study

Background: Anticoagulation therapy following cerebral vein thrombosis (CVT) can improve mortality and morbidity. Vitamin K antagonists are currently the routine oral anticoagulant used for CVT; while by introduction of rivaroxaban, a direct factor Xa inhibitor, the attentions have been deviated toward novel agents, but the evidence is not strong. The current study is aimed to compare the efficacy and safety of rivaroxaban versus warfarin for anticoagulation therapy of CVT. Methods: The current randomized clinical trial has been conducted on 50 patients with CVT among which, 25 ones were randomly allocated to rivaroxaban treatment (20 mg per day for three months) and remained 25 ones to warfarin treatment [adjusted based on international normalized ratio (INR) of 2-3]. The Modified Rankin Scale (mRS) and clinical investigations, including the incidence of seizure, papilledema, intra/extra-cranial bleeding, blurred vision, headache, nausea and vomiting, and death were evaluated at discharge time and within 3 and 6 months following CVT incidence; eventually, two groups were compared. Results: Comparison of mRS scores between the groups revealed significant differences in none of the interval assessments, at the time of admission (P = 0.510), within three months (P = 0.630), and within six months (P = 0.990), while both of the approaches led to significant decrease in mRS scores following both of the treatments (P < 0.001). The comparison of drug-related adverse effects showed insignificant difference between warfarin versus rivaroxaban (P > 0.050). Conclusion: Based on this study, rivaroxaban is an efficacious agent for the treatment of CVT without remarkable adverse effects.

Diplegia nervi facialis paraesthesiával – ritka Guillain–Barré-szindróma-variáns, SARS-CoV-2-infekciót követően

Összefoglaló. A COVID–19 világméretű járvány kapcsán már jól ismertek az általános akut tünetek, mint a láz, a száraz köhögés, a nehézlégzés, a tüdőgyulladás, a hasi panaszok, a hasmenés, az ízérzés- és szaglásvesztés. Talán kevésbé ismertek a betegség neurológiai szövődményei: az encephalitis, a fejfájás és szédülés, az ischaemiás stroke, az akut haemorrhagiás nekrotizáló encephalopathia, de agitáltság és exekutív funkciózavar is kialakulhat. Hosszabb távon az úgynevezett poszt-COVID-szindróma jelenhet meg, perzisztáló testi panaszokkal, krónikusfáradtság-érzéssel, depresszióval, mentális problémákkal. A perifériás idegrendszeri betegségek közül a Guillain–Barré-szindróma fordul elő gyakrabban. Jelen közleményünkben egy diplegia nervi facialis, dysarthria és négy végtagot érintő szubjektív paraesthesiák miatt hospitalizált 41 éves férfi betegünk esetét ismertetjük, akinek felső légúti tünetekkel és lázzal járó SARS-CoV-2-infekciót 10–14 nappal követően jelentek meg neurológiai tünetei. Elektrofiziológiai és liquor laboratóriumi vizsgálat során alátámasztott módon, ritka Guillain–Barré-szindróma-variáns – bifacialis paresis paraesthesiával – igazolódott. Fontos, hogy a vírus idegrendszeri szövődményeit is ismerjük, mert az esetszámok a jövőben várhatóan növekedni fognak. Orv Hetil. 2021; 162(45): 1803–1807. Summary. After the worldwide spread of COVID-19, common symptoms are already well known as fever, coughing, shortness of breath, pneumonia, abdominal pain and diarrhea, either loss of olfaction or sense of taste. Neurological complications are perhaps less known as headache, dizziness, agitation, executive dysfunction or, in particular cases, viral encephalitis and acute hemorrhagic necrotizing encephalitis may also occur. In COVID-19 patients, ischemic stroke or cerebral vein thrombosis are also more commonly related to the increased risk of thrombosis. In the long term, so called post-COVID syndrome can emerge in the form of fatigue, depression or many other mental disorders. The most common disease of the peripheral nervous system is Guillain–Barré syndrome. This chapter reviews a case of a 41-year-old man presented to the Department of Neurology with facial diplegia, dysarthria and intermittent paresthesia of the upper and lower extremities. 10–14 days before the onset of neurological symptoms, he has gone through COVID-19 infection that involved fever and upper respiratory tract symptoms. Electrophysiology and liquor samples showed typical signs of a rare Guillain–Barré syndrome subtype – bifacial weakness with paresthesias. We are reviewing the neurological complications of the virus due to the expected increase of case numbers. Orv Hetil. 2021; 162(45): 1803–1807.

JAK2 GGCC (46/1) Haplotype in Unprovoked Venous Thrombotic Events

Background: JAK2 GGCC 46/1 haplotype can be represented by four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) which replace one cytosine and three thymidines by two guanosines and two cytosines, generating a "GGCC" combination. These four SNPs located on JAK2 introns 10, 12, 14, and 15, respectively, and are always inherited together, being in complete linkage disequilibrium. The 46/1 component of the name came from Jones et al. study where the haplotype structure of the JAK2 gene was mapped using 14 SNPs genotyped by the Wellcome Trust Case Control Consortium (WTCCC) in 1500 healthy blood donors. Two haplotypes (numbers 46 and 1) were found to be identical except for one SNP, and they have a combined frequency of 0.24 in healthy individuals. Numerous observational studies associate this haplotype with myeloproliferative neoplasms (MPNs), as well as splanchnic vein thrombosis (SVT) and non-splanchnic vein thrombosis (non-SVT). In contrast to 24% frequency noted in healthy population, the frequency goes up to 40-80% in JAK2 V617F mutated MPN, and in 64% of those with JAK2 exon 12 mutations (Anelli et al. IJMS, 2018). We herein report our study of JAK2 GGCC (46/1) Haplotype in unprovoked Venous Thrombotic Events (VTE) in patients with negative thrombophilia workup, including negative JAK2 V617F mutation. Methods: We retrospectively identified patients positive for one of the two SNPs (rs12343867 and rs10974900) and unprovoked venous thrombotic among adult patients with negative thrombophilia workup (including JAK2 mutation) treated at tertiary care center from January 2018 to January 2021. Results: We have identified 8 patients, Table (1), that were positive for JAK2 46/1 haplotype SNPs, of whom 62.5% were homozygous 2/2, 25% heterozygous 1/2, while only 12.5% harbor homozygous 1/1 (a normal variant of JAK2 haplotype). The median age 48.5 years (23-65), and the majority (87.5%) were females. Thrombosis site was noted to be SVT in half of the patients, while non-SVT was noted in the other half (12.5% had cerebral vein thrombosis, 12.5% had deep venous thrombosis, 12.5% had a pulmonary embolism, and 12.5% had jugular vein thrombosis). Half of the patients had more than one site venous thrombosis and the other half had only one site. Around 37.50% of the patients had recurrent venous thrombosis on top of therapeutic anticoagulation. Two patients (25%) had high hemoglobin (17.4/16.7) g/dl, but did not fulfill the criteria for polycythemia vera diagnosis (of whom one is a male smoker and one was a female). None of the patients had leukocytosis or thrombocytosis. By imaging, one patient had mild splenomegaly which could be related to SVT. Conclusion: We report on a potential correlation between unprovoked thrombotic events, mainly venous thrombotic events, with JAK2 46/1 haplotype in patients with a negative thrombophilia workup, a finding that merit further investigation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia]. Methods: The study population included adults &gt;18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes. Results : Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR. Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT); and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to &gt;44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment. Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67; D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients. Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. Figure 1 Figure 1. Disclosures Carrier: Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria; Aspen: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria. Castellucci: BMS: Honoraria; Pfizer: Honoraria; Amag Pharmaceuticals: Honoraria; The Academy: Honoraria.

Abstract 1122‐000160: Transvenous Embolization Technique: A Modern Strategy for Anterior Ethmoidal Dural Arteriovenous Fistulas

Introduction : Ethmoidal dural arteriovenous fistulae (AVF) are rare intracranial lesions and account for 2–3% of all dAVF. They are often supplied by the ethmoidal or falcine branches of the ophthalmic artery and typically drain into a cortical vein then into the superior sagittal sinus (SSS). Current available treatment options include surgical resection and endovascular embolization via transarterial and transvenous routes. Prior studies have solely compared surgical and transarterial endovascular treatment approaches. Reports of the transvenous approach remain scarce in the literature. Methods : We performed a retrospective review for anterior ethmoidal (AE)‐dAVFs treated with transvenous embolization by our practice between August 2018 and August 2021. Four patients with 5 dAVFs were identified. We describe the presentation, treatment, and outcome of these cases. Results : We describe four patients with AE‐dAVF. Case 1 is a 33‐year‐old man with a previously treated basal ganglia arteriovenous malformation achieving cure. He was lost for follow up for three years and returned with symptoms of peri‐orbital headache and blurry vision. Diagnostic angiography revealed a dAVF arising from the cribriform plate with arterial supply derived from bilateral AE arteries and venous drainage via a common cortical frontal interhemispheric vein to the anterior third of the SSS. Transvenous embolization was achieved and liquid embolic was injected into the vein with retrograde penetration to the fistulous point. Follow‐up angiography revealed obliteration of the dAVF. Case 2 is a 23‐year‐old man with chronic headache who was found to have a right sided ethmoidal dAVF arising from the right ophthalmic artery for which he underwent successful embolization through a transarterial approach. Follow‐up angiography demonstrated occlusion of the treated fistula and new left sided ethmoidal AVF arising from the left ophthalmic artery with a single draining cerebral vein which drains into the anterior third of the SSS. Transvenous embolization was achieved via coiling. Follow up angiography also showed complete occlusion of the dAVF. Case 3 was a 67‐year‐old woman who presented with a Cognard type III right ethmoidal dAVF with arterial feeders through surpra‐orbital branches of the right ophthalmic artery, draining into a frontal cortical vein leading to the SSS. The patient underwent transvenous embolization using coils. Case 4 was a 64‐year‐old woman who presented with scalp tenderness. Diagnostic angiography revealed a left AE‐dAVF. Transvenous embolization with complete occlusion was achieved using a combination of liquid embolic and coil embolization. No adverse events were encountered during or after embolization, but long‐term outcome has yet to be collected for cases 3 and 4. There were no neurologic procedural complications. Conclusions : This small case series shows that transvenous embolization is a feasible, effective, and safe alternative to surgery. Larger prospective studies are needed to further validate this treatment approach in patients with ethmoidal dAVF.

Dramatic demise of a pregnant woman in third trimester after presenting with persistent headache: An iatrogenic

A 31-years-old patient, pregnant at 32 weeks of gestation presented to our triage unit with complaint of gradually progressive persistent headache that started 1 day earlier and was unresponsive to all analgesics. Her history was insignificant for any major medical or surgical events and the pregnancy course was smooth as well. Her lab results and obstetric ultrasound were reassuring. During magnetic resonance imaging examination, the patient suddenly deteriorated after giving her an inhalational anaesthesia for sedation. She became unconscious. She was intubated, mechanically ventilated, and put-on cardiovascular support. Brain imaging then revealed Brain Stem (BS) herniation and diffuse brain oedema. She was announced dead with intrauterine foetal death. A late diagnosis of cerebral venous thrombosis was established. This caused BS herniation through increased intracranial pressure, which was iatrogenically augmented by administering inhalation anaesthesia. Keywords: cerebral vein; thrombosi; thrombophilia; pregnancy; headache; magnetic resonance imaging; brain stem herniation.

Acquired pial arteriovenous fistula secondary to cerebral cortical vein thrombosis: A case report and review of the literature

Pial arteriovenous fistulas (AVFs) are rare neurovascular malformations. They differ from arteriovenous malformations (AVMs) in that they involve single or multiple feeding arteries, draining directly into a dilated cortical vein with no intervening nidus. Pial and dural AVFs differ in blood supply, as the first originate from pial or cortical arteries and the latter from outside the dural leaflets. Unlike dural AVFs, most of the pial AVFs are supratentorial. The vast majority are congenital, manifesting during infancy. Acquired pial AVFs are significantly rarer and occur after vasculopathy, head trauma, brain surgery, or cerebral vein thrombosis. We describe a unique case of an acquired pial AVF in a 50-year-old man secondary to a cortical vein thrombosis manifesting as a focal-onset seizure with secondary generalization. A cerebral digital subtraction angiography revealed a low-flow pial AVF fed by a postcentral branch of the left middle cerebral artery draining to the superior sagittal sinus via a cortical vein. It also showed a collateral venous circulation adjacent to the previously thrombosed left parietal vein. There was no evidence of an associated dural AVF or venous varix. Endovascular treatment was scheduled three months later, but the angiogram preceding the embolization showed spontaneous and complete closure of the malformation. To our knowledge, this is the first case illustrating acquired pure pial AVF unaccompanied by a dural component following cortical vein thrombosis, eventually resulting in an unprompted closure.