Carolinas Research Day 2021

Dural Venous Sinus Thrombosis Austin Belfiori, OMS4, Andrew Arteaga, OMS4, Lynn Campbell, DO, FACOEP, FACEP Edward Via College of Osteopathic Medicine – Carolinas Campus, Emergency Medicine, Spartanburg, SC

Abstract CBR-12

Abstract

Diagnostic Assessment & Intervention

Follow-up & Discussion

Head Computed Tomography (CT) without contrast was ordered due to the 10 out of 10 severity headache that awoke her from her sleep and revealed no acute intracranial findings. However, due to this new sudden onset headache that awoke patient from sleep a Computed Tomography Angiography (CTA) of the head with contrast was performed to check for possible subarachnoid hemorrhage. It found delayed filling of the left transverse and sigmoid sinuses, but no intraluminal occlusive thrombus was demonstrated. A CT venogram of the head with contrast was recommended and identified a filling defect within the lateral left transverse and left sigmoid sinus extending to the jugular bulb. Findings consistent with dural venous sinus thrombosis involving those vessels (see Image 1). A complete blood count, comprehensive metabolic panel, prothrombin time, and activated partial thromboplastin were then ordered on the patient. These were unremarkable, except for an elevated hemoglobin of 15.1 and elevated serum glucose of 136. Diagnosing a cerebral venous thrombosis has its challenges even when the patient in question is alert, oriented, and able to complete a thorough evaluation. A CT of the head without contrast is often the first imaging modality performed to rule out acute cerebral disorders; however, it is found to be normal in up to 30% of CVT cases 3 . Diagnosing CVT is also challenging due to the high variability of its presentation. It can range from acute, subacute, to chronic onset. This patient presented with a new onset severe headache which warranted differential diagnoses of subarachnoid hemorrhage, viral and bacterial meningitis, acute complicated sinusitis, and migraine headache. The six-month prognosis for this patient is favorable compared to a poorer outcome of CVT when the patient presents with presence of malignancy, coma on admission, thrombosis involving the deep venous system, mental status disturbance on admission, male gender, and intracranial hemorrhage on admission 4 . Image 1 . CT Venography Image 2. Timeline

References After pharmacological intervention, the patient’s headache had resolved and was no longer feeling nauseous. Prior to discharge, the patient was worked up for clotting factors and found to have decreased Protein S. Long-term anticoagulation is recommended to prevent the recurrence of CVT. At the time of discharge, the patient was on a therapeutic dose of warfarin with an INR in the target range of 2.0-3.0 and will continue for 6-12 months. Since hospitalization she has quit smoking and drinking. She follows up with her primary care physician who monitors her INR levels. She is also being followed by oncology due to her Protein S deficiency. According to ISCVT, two percent of patients had a recurrent CVT, and four percent had other thrombotic events during follow-up2. Long term complications of CVT include headaches, vision loss, seizures, and cognitive and psychiatric impairment 2,6 . Dural Venous Sinus Thrombosis is an uncommon disease that can be difficult to diagnose. It is far less frequent than other types of stroke and carries with it a wide range of clinical presentations. This case report showcases several key features of DVST, a subset of CVT, that may help improve clinical awareness. By highlighting our patient’s relatively young age, female gender, clinical presentation, and imaging studies we can focus on several unique features of CVT. As seen in our 48-year-old patient, CVT traditionally affects young adults to middle aged adults, a population that is much younger compared to other strokes. It has been reported that CVT has a median age of 37, with less than 10% of patients being older than 65 2 . The same study reported a female to male ratio of 3:1, which may be related to gender specific factors like pregnancy, oral contraceptive use, hormone replacement therapy, and puerperium. As our case exhibits, headache is the most common symptom. Almost 90% of patients present with headache 2 . Headache in CVT can present as chronic, gradual onset, or even as thunderclap headache. The next most common symptom is seizure, with 39% of patients experiencing either focal or generalized seizures 2 . However, paresis, encephalopathy, aphasia, papilledema, and visual disturbances may also be seen. Clinical presentation can vary greatly from patient to patient making the diagnosis difficult. Two different mechanisms have been proposed to explain the clinical presentation of CVT. (1) The occlusion of the dural sinus which limits the resorption of CSF leading to increased intracranial pressure 7 . (2) Obstruction of cerebral veins prevents adequate blood drainage from adjacent brain tissue. Depending on its extent and location there will be a subsequent increase in venous and capillary pressure and break down of the blood brain barrier 8 . Anatomical variance along with differing sizes and locations of thrombosis may account for the various clinical presentations. For example, isolated thrombosis of the cortical veins, cavernous sinus, sagittal sinus, jugular vein, lateral sinus, sigmoid sinus, and straight sinus can be associated with certain presentations. Cavernous sinus thrombosis is associated with ocular disturbances such as proptosis, oculomotor palsies, chemosis and pain 9 . Cortical vein thrombosis commonly exhibits seizures, motor, and sensory defects 10 . Sagittal sinus thrombosis similarly shows seizures, but often has bilateral motor/sensory changes. Jugular and lateral sinus thrombosis can both present with pulsating tinnitus 11 . Lateral sinus thrombosis can also present with headache, intracranial hypertension and even aphasia 12 . Sigmoid sinus, lateral sinus, jugular and posterior fossa vein occlusion can all be associated with cranial nerve palsies 13 . Lastly the straight sinus often presents with a more severe set of symptoms when thrombosed such as coma, altered mental status, and motor deficits 14 . However, it is important to remember that it is not uncommon for multiple of these venous structures to be concomitantly thrombosed often clouding the differential diagnosis. Imaging for CVT is best confirmed via CT venography or MR venography 15 . With, noncontrast CT is often ordered first. As this case highlights, noncontrast CT can be normal in up to 30% of CVT cases 3 . Follow up imaging to a normal findings on noncontrast CT should be considered in patients presenting with new onset headache, headache with patterns that vary with respect to past headaches, signs of intracranial hypertension, seizure, encephalopathy, focal neurologic deficits that do not follow traditional vascular territories. Such findings should raise clinical suspicion of CVT. This case report is limited in its ability to showcase all the possible hallmark clinical presentations of isolated lateral and sigmoid sinus thrombosis. Our patient presented with new, sudden-onset headache and nausea; however, she lacked the other common clinical presentations associated with isolated lateral and sigmoid sinus thrombosis, which include pulsating tinnitus, aphasia, or cranial nerve palsies 11,12,13 . CVT has an annual incidence of less than 1.5 per 100,000 with some sources finding evidence of markedly lower incidence making CVT very uncommon 1 . Furthermore, its range of possible clinical presentations often make it difficult to identify. The rarity and host of clinical presentations associated with CVT make clinical awareness, high degree of suspicion, and imaging instrumental in successful diagnosis and treating cerebral venous thrombosis . 1. Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The Incidence of Cerebral Venous Thrombosis. Stroke . 2012;43(12):3375-3377. doi:10.1161/strokeaha.112.671453 2. Ferro José M., Canhão Patrícia, Stam J, Bousser M-G, Barinagarrementeria F. Prognosis of Cerebral Vein and Dural Sinus Thrombosis. Stroke . 2004;35(3):664-670. doi:10.1161/01.str.0000117571.76197.26. 3. Bousser MG, Russell RR. Cerebral venous thrombosis. In: Major Problems in Neurology, Warlow CP, Van Gijn J (Eds), WB Saunders, London 1997. p.27, 104. 4. Ferro JM, Bacelar-Nicolau H, Rodrigues T, et al. Risk score to predict the outcome of patients with cerebral vein and dural sinus thrombosis. Cerebrovasc Dis . 2009;28(1):39 - 44. doi:10.1159/000215942 5. Einhäupl K, Stam J, Bousser MG, et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol . 2010;17(10):1229 - 1235. doi:10.1111/j.1468- 1331.2010.03011 6. de Bruijn SF, Budde M, Teunisse S, de Haan RJ, Stam J. Long-term outcome of cognition and functional health after cerebral venous sinus thrombosis. Neurology . 2000;54(8):1687 - 1689. doi:10.1212/wnl.54.8.1687 7. Coutinho JM. Cerebral venous thrombosis. J Thromb Haemost . 2015;13 Suppl 1:S238 - S244. doi:10.1111/jth.12945 8. Ungersböck K, Heimann A, Kempski O. Cerebral blood flow alterations in a rat model of cerebral sinus thrombosis. Stroke . 1993;24(4):563 - 570. doi:10.1161/01.str.24.4.563 9. Smith DM, Vossough A, Vorona GA, Beslow LA, Ichord RN, Licht DJ. Pediatric cavernous sinus thrombosis: A case series and review of the literature. Neurology . 2015;85(9):763 - 769. doi:10.1212/WNL.0000000000001886 10. Jacobs K, Moulin T, Bogousslavsky J, et al. The stroke syndrome of cortical vein thrombosis. Neurology . 1996;47(2):376 - 382. doi:10.1212/wnl.47.2.376 11. Waldvogel D, Mattle HP, Sturzenegger M, Schroth G. Pulsatile tinnitus--a review of 84 patients. J Neurol . 1998;245(3):137 - 142. doi:10.1007/s004150050193 12. Damak M, Crassard I, Wolff V, Bousser MG. Isolated lateral sinus thrombosis: a series of 62 patients. Stroke . 2009;40(2):476 - 481. doi:10.1161/STROKEAHA.107.509711 13. Kuehnen J, Schwartz A, Neff W, Hennerici M. Cranial nerve syndrome in thrombosis of the transverse/sigmoid sinuses. Brain . 1998;121 ( Pt 2):381 - 388. doi:10.1093/brain/121.2.381 14. Crawford SC, Digre KB, Palmer CA, Bell DA, Osborn AG. Thrombosis of the deep venous drainage of the brain in adults. Analysis of seven cases with review of the literature. Arch Neurol . 1995;52(11):1101 - 1108. doi:10.1001/archneur.1995.00540350095021 15. Khandelwal N, Agarwal A, Kochhar R, et al. Comparison of CT venography with MR venography in cerebral sinovenous thrombosis. AJR Am J Roentgenol . 2006;187(6):1637 - 1643. doi:10.2214/AJR.05.1249

This is a case report detailing the importance of clinical awareness in the diagnosis of Dural Venous Sinus Thrombosis (DVST), a subset of Cerebral Venous Thrombosis (CVT) in the setting of a small community hospital emergency department. A 48-year-old female presented to the emergency department with a chief complaint of sudden onset headache, with 10/10 pain at its worse but was ranking the pain 5/10 upon arrival to the ER. PT states her pain was a pressure sensation and localized posteriorly. She stated that it woke her from sleep and worsened with cough and head movement. She also reported photophobia and nausea. Pt had been seen the day prior by her PCP and dx with sinus infection and bronchitis. The patient’s Neurologic, HEENT, and MSK exams were all benign. A non-contrast CT was ordered and came back negative. A CTA was then done and revealed findings that raised suspicion for CVT. CT venography was used to confirm the diagnosis of CVT and heparin therapy was initiated. The neurological consult and neurosurgery guided the remainder of the patient’s care. Patients with accurately diagnosed and correctly treated CVT typically have good outcomes. CVT has an annual incidence of less than 1.5 per 100,000, making it very uncommon 1 . Furthermore, its range of possible clinical presentations often make it difficult to identify. The rarity and host of clinical presentations associated with CVT make clinical awareness and imaging instrumental in a successful diagnosis. Cerebral venous thrombosis poses many unique challenges to physicians compared to other strokes. The remarkably low annual incidence and inconsistent clinical presentations make clinical awareness crucial for identifying the disease. CVT occurs with thrombosis and occlusion of the cerebral venous system, which leads to various clinical presentations. These various clinical presentations can often be attributed to isolated thrombosis. For example, our patient was diagnosed with DVST, a subset of CVT, after finding isolated thrombosis of the lateral left transverse and left sigmoid sinus on CT venography. Isolated sinus and vein thrombosis can also be found in cortical veins, cavernous sinus, sagittal sinus, jugular vein, and straight sinus. CVT, traditionally affects a younger population with a mean age of 39 2 . It also exhibits a 3:1 female to male ratio 2 . Often patients have some form of acquired or inherited hypercoagulability state. The low annual incidence has made CVT a difficult disease to study on a large scale. However, some studies have made great strides in identifying common symptoms, appropriate imaging, and treatment methods. We now know to have a higher degree of clinical suspicion for CVT in patients that present with new onset headache, headache with patterns that vary with respect to past headaches, signs of intracranial hypertension, seizure, encephalopathy, or focal neurologic deficits that don’t follow traditional vascular territories. Physicians armed with this clinical awareness will be better equipped to recognize and correctly work up CVT in the future. This case of a 48-year- old female with a primary complaint of rapid onset headache that woke her from sleep will showcase some key learning points for raising clinical awareness of CVT. A 48-year-old female with a history of COPD presented to the ED complaining of a headache that came on suddenly last night while she was sleeping. She described her left posterior headache as a pressure sensation. The patient ranked the pain as a 10 out of 10 at its worst but was currently at a 5 out of 10. She reported her pain was worse with coughing and certain head movements. She denied any fever, chills, or vomiting, but was experiencing some nausea. She expressed some sensitivity to light but denied any changes in vision. She denied any numbness, tingling, loss of sensation or weakness in her extremities. She denied any recent trauma. She was seen by her primary care physician two days prior for complaints of cough and sore throat and was started on Augmentin and steroids for pharyngitis, sinus infection, and bronchitis. She had been coughing up yellow/green colored sputum and was continuing to have ear pain, rhinorrhea, sinus pain, and sore throat. She denied any chest pain or changes in her shortness of breath. She also denied any abdominal pain but was experiencing some diarrhea since starting the antibiotics. The patient’s past medical history included COPD, anemia, hereditary spherocytosis, irritable bowel syndrome, arthritis, irregular menstrual cycles, anxiety, and depression. Her family history included COPD and osteoporosis in her mother and alcohol abuse in her father. Her maternal grandmother had diabetes and arthritis. Her maternal grandfather had colon cancer, heart disease, skin cancer, and stroke. Her sister had breast cancer at age 40. The patient was a current smoker of 1PPD for the past 33 years and consumed 6 standard drinks of alcohol per week. Patient’s surgical history included breast biopsy excision (benign), appendectomy, colonoscopy, endometrial ablation, squamous cell carcinoma excision from nose, and cyst removal. Her initial vital signs showed a blood pressure of 128/72 mmHg, heart rate of 54 bpm, respiratory rate of 19 breaths/min, oxygen saturation of 97% on room air, and a temperature of 98.1 °F. Physical exam revealed a well-appearing female who was in no acute distress. She was awake, alert, and oriented and had CNII-XII intact, strength 5 out of 5 throughout, and no loss of sensation. Her pupils were equal, round, and reactive to light with extraocular muscles intact and no papilledema. Inspection of her ear, nose, and throat found tympanic membranes to be clear bilaterally, clear drainage in her nostrils with some erythema, and no tonsillar erythema or exudate noted. Her neck was supple with full range of motion, no jugular venous distention or lymphadenopathy, and negative Brudzinski’s and Kernig's sign. Her heart sounds were normal, and her lungs had some scattered wheezing in the bases. She had no edema in her extremities and had full range of motion. Her skin was warm and dry with no visible rashes present. Introduction & Patient Presentation

The patient was initially given Compazine IV 10mg and 1L 0.9 Normal Saline which improved her nausea and her headache to a 3 out of 10 pain. After the CTA came back negative, she was administered Toradol IV 30mg along with Phenergan 12.5mg, which almost completely rid her of her headache. The patient was admitted and started on Heparin gtt for treatment of the DVST. After a period of observation to ensure no progression of neurologic involvement pt was then bridged to a therapeutic dose of warfarin. The therapeutic dose of warfarin was achieved through measurements of INR levels targeted toward the range of 2.0-3.0. Anticoagulants appear to be safe to use in adult patients with DVST 5 . Endovascular intervention can be initiated in patients that present with worsening neurological deficits despite adequate coagulation. The goal of this intervention is to recanalize the occluded sinus.

Acknowledgements

Special thanks to Pelham Medical Center.

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