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(Stroke. 1995;26:496-497.)
© 1995 American Heart Association, Inc.

Articles

Superior Sagittal Sinus Thrombosis and Thyrotoxicosis

Possible Association in Two Cases

C.E.H. Siegert, MD, PhD; A.H.M. Smelt, MD, PhD T.W.A. de Bruin, MD, PhD

From the Departments of Internal Medicine, University Hospital Leiden and University Hospital Utrecht (T.W.A. de B.) (Netherlands).

	Abstract

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Background Superior sagittal sinus thrombosis is an uncommon cerebrovascular accident that is frequently associated with diseases that may contribute to the development of thrombosis through hypercoagulability, stasis of the local blood stream, and abnormalities of the vessel wall. In approximately 25% of cases underlying diseases remain unrecognized.

Case Descriptions Two patients with superior sagittal sinus thrombosis during a thyrotoxic phase of Graves' disease are described. Both patients presented with hemiplegia, seizures, and a large goiter.

Conclusions The development of superior sagittal sinus thrombosis is multifactorial. Patients with thyrotoxicosis and a large goiter may be predisposed to the development of superior sagittal sinus thrombosis through hypercoagulability and stasis of the local venous blood flow.

Key Words: Graves' disease • sinus thrombosis • thrombosis

	Introduction

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Superior sagittal sinus (SSS) thrombosis is an uncommon cause of stroke. Presenting symptoms of raised intracranial pressure may be followed by focal neurological deficits. The presence of headache, hemiparesis, and focal epilepsy in a relatively young patient is indicative of SSS thrombosis. The diagnosis is confirmed by angiography, computed tomography (CT) scan, or magnetic resonance imaging (MRI). The treatment of SSS thrombosis is not uniform, and the role of anticoagulants remains controversial for fear of provoking hemorrhagic cerebral infarctions.

A wide variety of diseases may be associated with thrombosis of SSS, including infectious diseases and noninfectious conditions such as vasculitis, hypercoagulable states, and pregnancy.^{1 2 3} Despite these associations, approximately 25% of the cases of SSS thrombosis are still considered to be idiopathic.⁴

In the present communication we describe two patients who presented with SSS thrombosis during a thyrotoxic phase of Graves' disease and propose a previously unrecognized association between these two conditions.

	Case Reports

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Case 1
A 24-year-old man was admitted because of frontal headache, nausea, seizures, and somnolence. For 1 year he had been treated for Graves' disease with a suboptimal dose of carbimazole 5 mg TID and thyroxine 87.5 µg daily. Despite treatment, thyrotoxic symptoms, including excessive sweating and weight loss, had persisted. At admission physical examination disclosed mild disorientation in time. During subsequent hours generalized seizures, right hemiplegia, and aphasia developed. In addition, a large diffuse goiter, approximately six times the normal size, and Graves' ophthalmopathy class 1 were observed.⁵

Laboratory investigations confirmed biochemical hyperthyroidism with the following values: T₄, 161 nmol/L (normal, 70 to 160 nmol/L); free T₄, 35.5 pmol/L (normal, 7.7 to 20.6 pmol/L); and thyroid-stimulating hormone, <0.05 mU/L (normal, 0.3 to 4.8 mU/L). Hematologic and coagulant parameters, including thrombocyte count, prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III activity, protein C activity, protein C antigen, protein S antigen, and factor VIII coagulant activity, were all normal. The lupus anticoagulant could not be demonstrated. An electrocardiogram revealed sinus rhythm. Magnetic resonance angiography demonstrated the absence of flow, indicating thrombosis, in the SSS. In addition, CT scanning demonstrated hemorrhagic infarctions in the frontal lobe and in the left precentral gyrus. After initiation of oral anticoagulant, prednisone, and phenytoin therapy the patient's neurological recovery was complete. One year after admission, the patient was clinically euthyroid. Laboratory investigations revealed a normal free T₄ level of 16.9 pmol/L.

Case 2
A 32-year-old woman was admitted because of headache, vomiting, and aphasia. Graves' disease was diagnosed 6 years before admission and previously treated with carbimazole and thyroxine. At admission the patient was not taking any drugs. She was a gravida 3, para 2. During two pregnancies placental deficiency due to ischemic infarctions developed, which resulted in intrauterine fetal death 6 years before. Four months before admission a healthy girl had been delivered. For some time she had experienced thyrotoxic symptoms including palpitations and excessive sweating. Physical examination demonstrated right hemiplegia and a large diffuse goiter of approximately five times the normal size. During subsequent hours she developed generalized seizures, starting in the right leg, and respiratory failure.

Laboratory investigations confirmed biochemical hyperthyroidism with the following values: T₄, 310 nmol/L; free T₄, 80 pmol/L; and thyroid-stimulating hormone, <0.05 mU/L. Hematologic and coagulant parameters, including thrombocyte count, prothrombin time, fibrinogen, antithrombin III activity, protein C antigen, and protein S antigen, were all normal. The lupus anticoagulant could not be demonstrated. An electrocardiogram revealed sinus rhythm. MRI demonstrated thrombosis of the SSS and the left transverse sinus. CT scanning demonstrated hemorrhagic infarctions in the left occipital lobe and in the right parieto-occipital lobes. The patient was intubated and treated with phenytoin, propylthiouracil, prednisone, and propranolol. No anticoagulant therapy was instituted. The neurological recovery was nearly complete after 1 year of follow-up.

	Discussion

Top Abstract Introduction Case Reports Discussion References

 
In the presented cases SSS thrombosis developed during the overtly thyrotoxic phase of Graves' disease. Since SSS thrombosis is a rare disease, not previously described in association with thyroid disorders, we questioned whether this serious manifestation is merely coincidental or indeed associated with thyrotoxicosis.

Thrombotic events in thyrotoxic patients principally concern systemic and cerebral arterial infarctions and have been directly attributed to atrial fibrillation, suggesting emboli as the causative agent.^{6 7} Patients with thyrotoxicosis do not appear to be at increased risk of developing deep venous thrombosis.

In general, venous thrombosis can be promoted by three factors: hypercoagulability, stasis of the blood stream, and abnormalities of the vessel wall. Possible predisposing factors for the development of SSS thrombosis in our patients with thyrotoxicosis are also in line with this triad. We first hypothesize that hypercoagulability during thyrotoxicosis may promote the development of SSS thrombosis. Several authors who studied the clotting function of patients with thyrotoxicosis found factor VIII activity to be increased.^{8 9 10 11} In these reports normalization of factor VIII activity was described after reaching the euthyroid state. Increased factor VIII activity, resulting in hypercoagulability, in these patients may be caused by an increased adrenergic tone or increased protein synthesis. These phenomena are known to occur in thyrotoxicosis.^{9 12}

Both described patients presented with large goiters. We also hypothesize that a large thyrotoxic goiter may cause stasis of the venous blood flow from the central nerve system. This may occur through venous compression by the large goiter itself or as a result of the large blood flow (>500 mL/min) through the thyroid gland in hyperthyroidism.^{13 14} Local obstruction by large goiters of axillary and subclavian veins, resulting in thrombosis, has previously been reported.¹⁵ In addition, a hyperdynamic circulation is a characteristic feature of thyrotoxicosis.¹⁶ This may result in increased venous return from the arterial cerebral vascular bed, which may potentially result in a low-flow state in the SSS. These hemodynamic factors may contribute to the multifactorial pathogenesis of SSS thrombosis.

The association between SSS thrombosis and thyrotoxicosis in Graves' disease has not been reported before. We hypothesize that hypercoagulability and stasis of the venous blood flow from the central vascular bed may contribute to the development of SSS thrombosis in thyrotoxic patients.

	Footnotes

 
Reprint requests to C.E.H. Siegert, MD, PhD, Department of Internal Medicine, University Hospital, Building I, C1-R 41, PO Box 9600, 2300 RC Leiden, Netherlands.

Received October 21, 1994; accepted December 8, 1994.

	References

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