Demonstration of Superior Sagittal Sinus Thrombosis by Indium-111 Platelet Scintigraphy Samuel L. Bridgers, MD; Edward Strauss, MD; Eileen O. Smith; Douglas Reed, MD; Michael D. Ezekowitz, MD, PhD \s=b\ Superior sagittal sinus thrombosis, documented by cerebral angiography, was demonstrated by indium-111 platelet scintigraphy in a 40-year-old man presenting with seizures and intracerebral hematoma. Early scintigraphy demonstrated focal increased indium-111 activity at the two ends of the thrombus, while later scintigraphy showed diffuse increased activity in the area of the sinus. This initial experience suggests that platelet scintigraphy may provide unique information regarding the natural history of intracranial venous thrombosis. (Arch Neurol 1986;43:1079-1081) Tndium-111 platelet scintigraphy has been used successfully for the detection of peripheral and intracardiac thrombosis.1·2 There has been only limited experience, however, in the diagnosis of intracranial throm¬ bosis.35 We report the demonstration of superior sagittal sinus thrombosis by platelet scintigraphy in a case where contrast-enhanced computed tomography (CT) failed to yield the diagnosis. REPORT OF A CASE A 40-year-old man was transferred to the Veteran's Administration Medical Center, West Haven, Conn, after the dis¬ covery of a left parietal intracerebral hematoma on CT at another hospital, where he had been taken after a seizure earlier in the day. The patient suffered two more generalized seizures in the emergen¬ cy room of the first hospital, and was treated with intravenous phenytoin sodi¬ um and diazepam. Over the course of the day, he also reported a worsening bifrontal headache. The patient, a chronic alcoholic acknowl¬ edging consumption of a quart of whiskey daily for several months, had a history of lumbar radiculopathy but no other prior neurologic complaints. During an episode of bronchopneumonia treated at another hospital 2'/2 years earlier, a question of Accepted for publication June 23, 1986. From the Veterans Administration Medical Center, West Haven, Conn (Drs Bridgers, Strauss and Ezekowitz, and Ms Smith); the Departments of Neurology (Dr Bridgers), Medicine (Dr Ezekowitz and Ms Smith), and Diagnostic Radiology (Drs Strauss, Reed, and Ezekowitz), Yale University School of Medicine, New Haven, Conn. Reprint requests to Neurology Service (127), Veterans Administration Medical Center, West Spring street, West Haven, CT 06516 (Dr Bridgers). bilateral lower extremity deep-vein throm¬ bosis had been raised, but the diagnosis was never confirmed, and the patient's symptoms resolved without anticoagulant therapy. Neurologic examination on arrival at the Veteran's Administration Medical Center was remarkable only for right upper extremity apraxia unaccompanied by frank weakness, reflex changes, or sensory deficit. Cognitive and language functions were intact. Fundoscopic examination was unremarkable. The patient was mildly tremulous. The patient continued to receive pheny¬ toin, and was also given sedatives for incip¬ ient alcohol withdrawal. He persisted with headache during his early hospitalization and had several episodes of vomiting. On day 2, he underwent contrast-enhanced CT (Fig 1), which demonstrated the known hematoma and surrounding edema. No lucency was noted in the superior sagittal sinus. On day 4, the patient developed frank weakness of the right upper extrem¬ ity and a right Babinski's sign after an episode of vomiting. Repeat noncontrast CT showed a possible extension of the hemorrhage and more pronounced edema. Dexamethasone acetate therapy was initi¬ ated. On day 5, cerebral angiography was performed. Selective left internal carotid artery injection was remarkable in the arterial phase only for mass effect, while the venous phase revealed no filling of the superior sagittal sinus (Fig 2). The patient underwent two series of scintigraphic studies following injection of labeled autologous platelets on day 6 and day 14 (see below). The patient's subsequent hospital course unremarkable. He was not treated with antiplatelet or anticoagulant agents. His headache gradually resolved, as did his right upper extremity deficit. Repeated CT on day 29 showed some resolution of the hemorrhage and edema. Lumbar puncture performed on day 30 was remarkable only for an opening pressure of 270 mm cerebro¬ spinal fluid (CSF). On admission, the patient's platelet count, prothrombin time, and partial thromboplastin time were normal, and these remained so throughout the hospital¬ ization. In addition, bleeding time, thrombin time, antithrombin III activity, eryth¬ rocyte sedimentation rate, antinuclear antibody titer, complement levels, and was lipoprotein electrophoresis were unre¬ markable. Platelet Scintigraphy Platelets were labeled according to a previously described modification6 of the method of Heaton et al,7 which was derived from that of Thakur et al.8 The process involves separation of platelets from a Fig 1.—Computed tomography. Contrastenhanced computed tomographic scan per¬ formed on day 2 shows left parietal hemor¬ rhage and surrounding edema, but there is no lucency or "open delta" sign in superior sagittal sinus (arrow) to suggest thrombosis. citrated 43-mL sample of autologous blood, incubation with indium-lll-oxine complex (Amersham) for labeling, and resuspension in platelet-poor plasma for reinjection. After provision of informed consent, this patient underwent two labeled plate¬ let injections, as previously noted, both involving approximately 200 microcuries of indium-Ill activity. Following both injections, ten-minute images were ob¬ tained at 24 and 48 hours, using a smallfield gamma camera with medium-energy parallel-hole collimator set on both energy peaks of indium-Ill with 20% windows (Fig 3). Lateral and posterior images obtained 24 hours after the injection on day 6 showed two foci of intense indiumIll activity in the area of the superior sagittal sinus, presumed to represent the two ends of the thrombus, while a 48-hour posterior image revealed a diffuse increase in activity in the sinus. A similar, but less pronounced, diffuse increase in activity was seen following the second labelled platelet injection on both 24- and 48-hour images. COMMENT In this case, platelet scintigraphy, while not used to make the diagnosis, provided a dramatic demonstration of the superior sagittal sinus thrombo¬ sis. Two previous reports have sug¬ gested that this diagnosis could be made using platelet scintigraphy, but neither provided confirmation by angiography, computed tomography, Downloaded From: http://archneur.jamanetwork.com/ by a University of Pennsylvania User on 06/12/2015 or Fig 2.—Cerebral angiography. Lateral view In venous phase after transfemoral left internal carotid artery contrast injection shows no filling of superior sagittal sinus (large arrows). Marked enlargement of deep medullary veins (area demarcated by small arrows) represents collateral flow due to sinus occlusion. Fig 3.—Platelet scintigraphy. Top left, Right lateral ten-minute image obtained on day 7 of patient's illness, 24 hours after injection of indium-111 labeled autologous platelets. Occiput Is on left side of ¡mage. Two foci of intense indium-111 activity are seen, posterior to vertex and near region of torcular Herophili (connected arrows). Less intense but still increased activity extending forward in superior sagittal sinus (unconnected arrows) could represent less active thrombosis or blood pooling. Halo surrounding ¡mage in this and subsequent scintigraphs is "edge-packing" artifact, consequence of physical characteristics of collimator shielding and duration of imaging. Total counts equal 34K. Top right, Corresponding posterior ten-minute ¡mage. Intense foci are indicated by connected arrows, and less clearly abnormal but increased activity in sinus are indicated by upper unconnected arrows. Similar moderately increased activity is noted in right transverse sinus (lower unconnected arrows). Again, this may represent extension of thrombus. Total counts equal 37K. Bottom left, Posterior ten-minute ¡mage obtained 48 hours after first injection. Diffuse increased activity is evident in region of superior sagittal sinus (connected arrows). Total counts equal 27K. Bottom right, Posterior ten-minute ¡mage obtained on day 15, 24 hours after second injection of labeled platelets. Now, only slight diffuse increase in activity is evident in region of superior sagittal sinus between connected arrows. Total counts equal 29K. autopsy.3·4 In our case, angiography established the existence of sinus occlusion. In both of the previous cases, apparent diffuse increase in indium-Ill activity in the sinus was seen, similar to the second sequence of images obtained in our patient; both studies were performed approximate¬ ly two weeks after ictal events. Since labeled platelets not incorporated into thrombus or sequestered in the spleen remain in the blood pool, the interpretation of diffuse increased activity in a large vascular structure such as the superior sagittal sinus must be approached with caution when dual-isotope subtraction tech¬ niques are not used. By obtaining platelet scintigraphy earlier in the patient's course, we successfully dem¬ onstrated active focal platelet uptake at the two ends of the thrombus. The later demonstration of diffuse uptake may imply patency of the sinus inapparent at angiography. Clarification of the role of blood-pool activity in such situations can be achieved with dual-isotope scintigraphy using technetium-99m-labeled red blood cells as well as labeled platelets.5 Subtraction of the technetium-99m scintigram allows correction for the blood pool's influence on indium-Ill activity. The described CT signs of sagittal sinus occlusion, while useful when present, are too frequently absent to allow CT to be used in isolation for exclusion of this diagnostic possibili¬ ty.9·10 Our experience suggests that platelet scintigraphy could join digi¬ tal intravenous angiography11 and magnetic resonance imaging12 as an alternative means to diagnose cere¬ bral venous occlusion, as well as an ancillary procedure to differentiate new thrombosis from either older thrombus or nonthrombotic occlusion. Clearly, more experience will be nec¬ essary to determine just what the role of this technique should be. Sagittal sinus thrombosis is an uncommon entity, and little is known about the temporal evolution of the thrombotic process. Our experience suggests that platelet scintigraphy can provide unique information regarding natural history. Without antithrombotic therapy, labelled platelet uptake declined markedly over the two weeks after this patient's original presentation, suggesting that active thrombosis likewise declined in the interval. In light of continuing controversy concerning the use of anticoagulants in the treatment of this disorder,10 such information may eventually prove useful in determin¬ ing the need for therapy. Downloaded From: http://archneur.jamanetwork.com/ by a University of Pennsylvania User on 06/12/2015 Supported by the Medical Research Service, US Veterans Administration. References 1. Ezekowitz MD, Wilson DA, Smith EO, et al: Comparison of indium-111 platelet scintigraphy and two-dimensional echocardiography in the diagnosis of left ventricular thrombi. N Engl J Med 1982;306:1509-1513. 2. Powers WJ, Siegel BA: Thrombus imaging with indium-111 platelets. Semin Thromb Hemost 1983;9:115-131. 3. Kessler C, Kniffert T, Botsch H: Der Nutzen der Plattchenszintigraphie zur Aufklarung intrakranieller vaskularer Prozesse. Aktuel Neurol 1980;7:27-29. 4. Kessler C, Trabant R: Thromboszintigraphie mit 111-Indium. Arch Psychiatric Nervenkr 1982;231:449-457. 5. Sutherland GR, King ME, Peerless SJ, et al: Platelet interaction with giant intracranial aneurysms. J Neurosurg 1982;56:53-61. 6. Ezekowitz MD, Leonard JC, Smith EO, et al: Identification of left ventricular thrombi in man using indium-111 labeled autologous platelets. Circulation 1981;63:803-810. 7. Heaton WA, Davis HH, Welch MJ, et al: Indium-111: A new radionuclide label for studying human platelet kinetics. Br J Haematol 1979; 42:613-622. 8. Thakur ML, Welch MJ, Joist JH, et al: Indium-111 labeled platelets: Studies on prepara- tion and evaluation of in vitro and in vivo functions. Thromb Res 1976;9:345-357. 9. Rao KCVG, Knipp HC, Wagner EJ: CT findings in cerebral sinus and venous thrombosis. Radiology 1981;140:391-398. 10. Bousser M, Chiras J, Bories J, et al: Cerebral venous thrombosis: A review of 38 cases. Stroke 1985;16:199-213. 11. Barnes BD, Brant-Zawadzki M, Mentzer W: Digital subtraction angiography in the diagnosis of superior sagittal sinus thrombosis. Neu- rology 1983;33:508-510. 12. Cascino TL, Wiebers DO, Forbes GS: Digital subtraction angiography and NMR scanning for diagnosing dural sinus thrombosis in tumor patients. Neurology 1984;34(suppl 1):85. High-Field Magnetic Resonance Imaging in the Diagnosis of Cavernous Sinus Thrombosis Peter J. Savino, MD; Robert I. Grossman, MD; Norman J. Schatz, MD; Robert C. Sergott, MD; Thomas M. Bosley, MD sinus thrombosis is Cavernous important but difficult clinical an diagnosis to confirm by most imaging modalities.1,2 Until the advent of highfield magnetic resonance imaging (MRI), the imaging method of choice for evaluating thrombus formation in the cavernous sinus was transarterial or intravenous digital subtraction angiography. This article discusses the MRI findings in the diagnosis of cavernous sinus thrombosis. REPORT OF A CASE A 73-year-old woman noticed pain around her left eye ten days before examination. Over the next four days, her left upper eyelid drooped, and she experienced double vision. She was hospitalized elsewhere, and computed tomography (CT) showed a mass in the left anterior cavernous sinus. A cerebral arteriogram was normal. The patient was treated with systemic corticosteroids (prednisone, 80 mg/d), with no resolution of the pain or ocular motility disturbance. Five years prior to admission, the patient had an episode of painful ophthalmoplegia that was described as a partial third and total sixth cranial nerve palsy on the left side. She had 3 mm of left ptosis, absent left medial and lateral rectus func¬ tion, but good vertical movement and pre¬ served intorsion on attempted downward Accepted for publication May 19,1986. From the Neuro-Ophthalmology Service, Wills Eye Hospital, Thomas Jefferson University (Drs Savino, Schatz, Sergott, and Bosley), and the Department of Radiology, Hospital of the University of Pennsylvania (Dr Grossman), Phila- delphia. Reprint requests to Wills Eye Hospital, Ninth and Walnut streets, Philadelphia, PA 19107 (Dr Savino). COMMENT gaze. The pupil was normal. This gradually several months, and the patient's final resolution was described as a 14-prism-diopter esotropia in extreme left and right gaze. She stated that she had had four of these episodes prior to the present one, with resolution of each within days to weeks. The patient's visual acuity was 6/7.5 OD and 6/9+1 OS. Results of exophthalmometry at base 103 were 15 OD and 16 OS. She had complete immobility of the left eye except for intorsion on attempted down¬ ward gaze. The left pupil was dilated and did not react to light, but there was no relative afferent pupillary defect. Fundus examination showed no abnormality, and visual fields were full. Neurologic exami¬ nation showed only decreased corneal sen¬ sation on the left side. Further investigation included a search for collagen vascular as well as metastatic disease. Findings from a mammography and two lumbar punctures were normal. A CT scan with intravenous contrast enhancement revealed bulging of the later¬ al margin of the left cavernous sinus, sug¬ gesting a mass lesion (Fig 1). The MRI scan, performed the day after the CT scan, showed a serpiginous struc¬ ture with hyperintensity on Tl- and T2weighted images (WI) representing the thrombosed posterior portion of the supe¬ rior ophthalmic vein (Fig 2). Thrombus formation was also demonstrated as highsignal abnormality on T1WI in the anteri¬ or portion of the cavernous sinus (Fig 3). The specific findings of cavernous sinus thrombosis on MRI permitted corticoste¬ roid therapy to be discontinued. The patient was discharged without medication with a diagnosis of thrombosis in the left anterior cavernous sinus and superior oph¬ thalmic vein, most likely from a durai vascular malformation. When last exam¬ ined four months after the present episode, there was no change in ocular findings. resolved over This patient presented with dys¬ function of cranial nerves III, IV, V„ and VI, indicating a lesion of the cavernous sinus or superior orbital fissure. Pathologic conditions that produce this syndrome may be intrin¬ sic cavernous sinus mass lesions (an¬ eurysm or meningioma) or masses from adjacent structures (pituitary adenoma or chordoma).3 Metastatic lesions may also produce a cavernous sinus syndrome.4 Inflammation in this area (Tolosa-Hunt syndrome) may be indistinguishable from mass lesions but usually produces more pain. These inflammatory processes typically re¬ spond dramatically to systemic corti¬ costeroid therapy.5 Our patient had no history of neoplastic disease, and none was detected on evaluation. The lack of response to Fig 1.—Contrast-enhanced coronal computed tomographic scan demonstrating bulging of left cavernous sinus by nonenhancing mass (arrow). Downloaded From: http://archneur.jamanetwork.com/ by a University of Pennsylvania User on 06/12/2015