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Septic cerebral venosinus thrombosis secondary to an odontogenic infection.

CASE DESCRIPTION

A 69-year-old man with a history of stroke without residual deficits, peripheral artery disease, hyperlipidemia, and prostate cancer was transferred from an outside facility for management of a right-sided odontogenic infection. The patient reported right jaw pain for nine days. Over the preceding three days, the patient developed fever, headaches, blurry vision, mid-facial pain and swelling around the eyes. Physical exam revealed right mandibular pain and swelling, bilateral chemosis, impairment of right eye abduction, and vertical gaze (Figure 1). Laboratory studies revealed a leukocytosis and increased band forms. Blood cultures were positive for gram positive cocci. Cerebrospinal fluid analysis demonstrated 405 white blood cells with eighty-nine percent segmented neutrophils. Computer tomography (CT) of the head and sinuses with intravenous contrast revealed a right multi-loculated mandibular abscess, paranasal sinusitis, and right internal jugular thrombus. Magnetic resonance imaging (MRI) of the brain demonstrated findings consistent with meningitis, a small right-sided subdural empyema and partial thrombosis of bilateral superior ophthalmic veins and cavernous sinus. Magnetic resonance venogram (MRV) revealed a right internal jugular and sigmoid sinus thrombosis. Final blood cultures recovered Streptococcus gordonii, Streptococcus intermedius, Peptostreptococcus anaerobius, and Mycobacterium mucogenicum.

INTRODUCTION

Cerebral venosinus thrombosis (CVT) is an uncommon, potentially fatal disease. Though initially thought to be rare, its incidence has increased with the advancement of modern imaging modalities. While CVT affects all age groups, it generally occurs in young adults with a mean age of 39. (1)

The most common risk factors identified in 624 CVT patients include underlying thrombophilia, elevated estrogenic states, and infections. (1) Patients with prothrombotic conditions, both genetic and acquired, are at increased risk of developing CVT. These prothrombotic conditions include but are not limited to Factor V Leiden mutation, protein C, S, or antithrombin deficiencies, antiphospholipid antibody, and hyperhomocysteinemia. (1,3) High estrogenic states due to oral contraceptive use, pregnancy and the immediate postpartum period are the most common predisposing factors in CVT cases amongst women. (1,2) Infection is also a major risk factor and a frequently documented cause of CVT. Infections of the ear, sinus, mouth, head and neck are responsible for over 60% of CVT cases of infectious origin. (1) Factors such as malignancy, injury ,and mechanical precipitants have been identified in less than 20% of CVT cases combined. (1) Notably, CVT patients often have more than one risk factor. (1) If CVT is clinically suspected, workup for predisposing factors and etiologies should be pursued.

DISCUSSION

Pathogenesis

The pathophysiology of CVT is not completely understood. However, coagulation derangements secondary to proinflammatory conditions such as infections and trauma have been implicated in the pathogenesis. Vascular endothelial cells are directly altered in pro-inflammatory events resulting in endothelial dysfunction. (4) Tissue factor (TF), expressed by dysfunctional endothelial cells and damaged tissues, acts as an activator of the coagulation pathway. (4,5) Inflammatory pathways mediated by complements and cytokines can also trigger and propagate the coagulation cascade. IL-1 and TNF-[alpha] are cytokines that have been shown to mediate coagulation by inducing TF expression. (4,6) It is thought that the interplay between these mechanisms may contribute to the establishment of a hypercoagulable state and consequently thrombus formation in the presence of pro-inflammatory stressors.

Occlusion of cerebral venous structures results in obstruction of flow, decreased cerebrospinal fluid absorption, and increased intracranial pressure. Increased venous pressure leads to blood-brain barrier (BBB) dysfunction. (7) Extravasation of blood plasma secondary to BBB disruption causes cerebral edema. Cytotoxic edema from intracellular shift of water has been proposed as part of the pathological mechanism of CVT. (8) Histological findings from rat models of CVT have revealed neuronal shrinkage and necrosis, cellular infiltration, capillary collapse, intravascular fibrin aggregation, and hemorrhages. (7,9) Parenchymal involvement accounts for many of the clinical features of the disease.

Presentation

Patients with CVT may have variable clinical presentations, and onset can be subacute, acute or chronic. Factors that affect the spectrum of clinical manifestations and course include extent and duration of venous thrombosis, territories of the involved vessels, establishment of venous collaterals, presence of parenchymal lesions (i.e. cerebral edema, cerebral hemorrhage), gender, and age. (1,10) The three major presenting syndromes of CVT are isolated intracranial hypertension syndrome, focal cerebral syndrome (including cavernous sinus syndrome) and encephalopathy. (11) Isolated intracranial hypertension syndrome consists of headache, vomiting and/or papilledema. (1) Focal cerebral syndrome consists of focal motor and sensory deficits. Paresis is the most frequent focal deficit associated with CVT. (1) Ocular manifestations are the dominant signs and symptoms seen in cavernous sinus syndrome. Cranial nerves III and IV, as well as the ophthalmic and maxillary branches of cranial nerve V, are located along the lateral wall of the cavernous sinus. Cranial nerve VI and the internal carotid artery are located medially within the cavernous sinus. Given the anatomic relationships, thrombosis of the cavernous sinus can result in ophthalmoplegia, chemosis, periorbital swelling, proptosis, Horner's syndrome, diplopia and decreased visual acuity. Patients with CVT may also present with encephalopathy, multifocal deficits and seizures. Altered level of consciousness may range from coma or stupor to delirium, with coma being a poor prognostic factor for morbidity and mortality. (1,10) In a multicenter, prospective, observational study thirty nine percent of patients had seizure at presentation and seven percent had a seizure within two weeks of presentation. (12) Overall, the most common presenting symptom is headache, which can be the only presenting symptom of CVT. (1,13,14)

Diagnosis

Given the nonspecific clinical presentations in patients with CVT, neuroimaging is essential.

Non-contrast CT of the head is an early imaging modality employed to rule out other acute or subacute cerebral causes. Head CT, however, may be normal in approximately 20% of CVT cases. (15) Features of CVT include the dense triangle sign and cord sign seen on nonenhanced CT and the empty delta sign seen on contrasted CT. (14,16) Indirect signs of CVT on CT consist of cerebral edema and hemorrhages and mass defects. (14) CT venography can be useful in confirming a diagnosis of CVT and is comparable to magnetic resonance (MR) venography. In addition to good visualization of the cerebral venous system, the advantages of CT venography include cost effectiveness and the availability and rapidity of CT scan in hospital settings. Similar to MR venography, CT venography is also limited by anatomic variability. (17)

When available, MRI with MR venography remains the current standard for CVT diagnosis. Variations in blood flow and blood breakdown products produce signal changes on MRI. (15) Initially, thrombus formation is visualized as area of isointensity and hypointensity in T1- and T2- weighted images, respectively. Over time, the thrombus becomes hyperintense on both T1- and T2weighted images. (18,20) MR venography can demonstrate absence of flow in occluded sinus and vessels, and contrast-enhanced MR venography can further differentiate venous thrombosis from normal anatomic variants such as a hypoplastic sinus. (14,15)

Conventional cerebral angiography is invasive and not commonly used for diagnosing CVT as CT and MR venography are safer diagnostic options. In the event that MR and CT venography are inconclusive, conventional cerebral angiography may be performed as it offers superior spatial resolution of the cerebral arteriovenous circulation. (21,22)

Management and Treatment

Once CVT is confirmed, treatment should be implemented as early as possible. Treatment should focus on addressing the underlying cause, prompt anticoagulation, and controlling seizures and intracranial hypertension. In CVT patients with known or suspected infection, appropriate antibiotics should be administered. Surgical drainage of associated infectious fluid collections is recommended. (21)

Anticoagulation is considered a cornerstone in the treatment of acute and subacute CVT. The goal of anticoagulation therapy is to reestablish blood flow, prevent subsequent venous thromboembolic events, and improve outcome. (23) Studies have shown that unfractionated heparin or low molecular weight heparin (LMWH) may be safely used in patients without contraindications. (24,26) In the acute phase, current guidelines recommend anticoagulation with adjusted dose unfractionated heparin or weight-based LMWH at full anticoagulation doses. (21) Continuation of anticoagulation after the acute phase may be necessary to prevent future thrombotic events including recurrent CVT and systemic VTE, which occur in 2% and 5.8% of patients respectively. (27) Based on evidence and recommendations for systemic deep venous thrombosis, oral anticoagulation in provoked CVT should be continued for 3-6 months and 6-12 months in unprovoked CVT with a target INR between 2 and 3. Indefinite anticoagulation should be considered in patients with recurrent CVT and in patients with CVT and severe thrombophilia. (21) In cases with contraindications to anticoagulants, antiplatelet drugs may be considered though there are no data on their efficacy or safety in CVT.

Thrombolytic therapy is a treatment option in CVT cases with neurologic deterioration despite anticoagulation treatment. (28) Local thrombolysis employs urokinase or recombinant tissue plasminogen activator directly administered into the site of occlusion with or without mechanical disruption of the thrombus. (29,30) High success rate of rapid recanalization and significant improvement in morbidity and mortality have been noted in clinically severe CVT cases in which local thrombolysis was performed. (28,w30) Additional studies are still needed in order to determine the definitive role of thrombolytics in the management of CVT and the patient population that would ultimately benefit from the therapy.

In addition to treatment of CVT, therapy frequently involves management of early complications. Early complications resulting from CVT include seizures, hydrocephalus, and isolated intracranial hypertension. Antiepileptic drugs (AED's) may be considered in patients with CVT who have a supratentorial lesion and who present with seizure. (12) Initiation of AED's may also be reasonable for all patients who present with seizure, as they have a higher risk of recurrent early seizures. Hydrocephalus can be communicating, secondary to decreased CSF outflow, or non-communicating, from hemorrhage into the ventricular system. Neurosurgical consultation is recommended and treatment options include invasive procedures such as ventriculostomy or ventriculoperitoneal shunt. Management of isolated intracranial hypertension includes serial lumbar puncture and acetazolamide. Ophthalmologic consultation is recommended to assist with monitoring of visual fields and papilledema, as prolonged pressure on the optic discs may result in permanent blindness. (21)

Follow up

Our patient was started on appropriate antibiotics upon admission. After imaging studies demonstrated cerebral venosinus thrombosis, anticoagulation with un-fractionated heparin was initiated. The patient's symptoms improved rapidly after initiation of anti-coagulation, including resolution of chemosis (Figure 2). The patient was transitioned to warfarin prior to discharge. Mild impairment of right eye abduction (Figure 2) was present and visual acuity was normal.

Conclusion

CVT remains a clinical diagnosis though advances in neuroimaging have greatly improved its recognition and detection. Acutely, head CT may rule out acute and subacute cerebral causes that share similar presentations. Definitive diagnosis of CVT can be made using MRI in conjunction with MR venography. CT with CT venography is a comparable diagnostic option. If MR and CT venography proves equivocal, cerebral angiography may be considered. Treatment should be promptly initiated once CVT is diagnosed. Anticoagulation is should be recommended in patients without specific contraindications and likely improves clinical outcome. Similar to recommendations for other thrombotic events, continued anticoagulation after the acute phase should be considered to prevent recurrence.

REFERENCES

(1.) Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004; 35:664

(2.) De Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP. Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in carriers of hereditary prothrombotic conditions. The Cerebral Venous Sinus Thrombosis Study Group. BMJ 1998; 316:589.

(3.) Hillier CE, Collins PW, Bowen DJ, et al. Inherited prothrombotic risk factors and cerebral venous thrombosis. QJM 1998; 91:677.

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(15.) Selim M, Fink J, Linfante I, Kumar S, Schlaug G, Caplan LR. Diagnosis of cerebral venous thrombosis with echo-planar T2-weighted magnetic resonance imaging. Arch Neurol 2002; 59(6):1021-6.

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Hongvan Le, MD; Shane Prejean, MD; Madeleine Heck, MD

Dr. Le is currently a second year ophthalmology resident at the University of Alabama Birmingham School of Medicine; Dr. Prejean is a first year cardiology fellow at the University of Alabama at Birmingham School of Medicine; Dr. Heck is associate professor of clinical medicine at LSUHSC in Baton Rouge and is an infectious disease specialist affiliated with the Baton Rouge General Medical Center and Our Lady of the Lake Regional Medical Center.

Acknowledgments

The authors would like to thank Dr. Diana Hamer for her editorial assistance.

Caption: FIGURE 1: Chemosis and Abducens Nerve (CN VI) Palsy. Significant peri-orbital swelling and scleral edema is seen (Top). Right sixth nerve paralysis is demonstrated by the absence of right eye abduction when the patient was asked to look to the right (Bottom).

Caption: FIGURE 2: Treatment with Anti-coagulation. Improvement in peri-orbital swelling 48 hours after initiation of anticoaulation (top). Exam demonstrates residual CN VI palsy (bottom).
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Author:Le, Hongvan; Prejean, Shane; Heck, Madeleine
Publication:The Journal of the Louisiana State Medical Society
Article Type:Case study
Date:Mar 1, 2017
Words:2777
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