Superior Sagittal Sinus Dennis M.
Gettelfinger, MD, Emre Kokmen,
\s=b\ Seven patients had superior sagittal sinus thrombosis diagnosed by cerebral arteriography. We recommend that anti-$ coagulants not be used in the therapy of this entity, but rather that one should rely on antiedematous agents and anticonvulsants. (Arch Neurol 34:2-6, 1977)
Gowers' suggested
in 1888 recognized aseptic intracranial venous thrombosis and its association with pregnancy, marasmus, and cachectic conditions. We present seven cases of superior sagittal sinus (SSS) throm¬ bosis in adults unrelated to intra¬ cranial infection or neoplasm in whom the diagnosis was made antemortem. REPORT OF CASES Case 1.—A 27-year-old woman, gravida 2, para 1, was admitted to hospital with pain in her left calf five days before delivering a normal infant. Thrombophlebitis was diag¬ nosed. Findings from coagulation studies were
platelets, 300,000/cu
mm;
prothrom-
bin time, 10.7 seconds (100%), thrombin time, 7.9 seconds (control, 8.3); and fibrinogen, 435 mg/100 ml. She was given heparin sodium, 5,000 units subcutaneously every eight hours, with improvement. Delivery was normal. Two days postpar-
Accepted for publication June 30,
1976. From the Department of Neurology, University of Michigan Medical Center, Ann Arbor. Reprint requests to Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI 48109 (Dr Kokmen).
Thrombosis
MD
turn, she complained of
severe bifrontal and left temporal headache and photopho¬ bia. Findings from neurologic examination were normal. The headache lessened with analgesics. Five days postpartum, she was
discharged, receiving heparin sodium, 8,000 units subcutaneously every 12 hours. Two days later, she was readmitted with worsening headache, nausea, vomiting, and unsteadiness of gait. Findings from physical examination were normal. He¬ moglobin level was 13.5 gm/100 ml; hematocrit reading, 40%; WBC count, 10,300/cu mm; platelet count, 41,000/cu mm; prothrombin time, 81%; thrombin time, 9.6 seconds; and partial thromboplastin time, 35.5 seconds. Opening pressure on lumbar puncture was 170 mm of CSF, and the protein level was 38 mg/100 ml. There were 1,380 RBCs per cubic millimeter in tube 1 and 936 RBCs per cubic millimeter in tube
Heparin-induced thrombocytopenia was suspected; consequently, heparin was dis¬ continued. Four days later, the platelet count was 115,000/cu mm, and findings from coagulation studies were normal. A 4.
brain
scan
was
normal. An EEG
was
moderately abnormal, with diffuse slowing and theta and delta bursts with a left-sided gradient. She continued to complain of headache and was intermittently confused. Four days after admission, the opening pressure on lumbar puncture was 270 mm of CSF; protein level, 43 mg/100 ml; and RBC count, 2/cu mm. Dexamethasone, 4 mg intramuscularly every six hours, was begun. On the eighth day of hospitalization, cerebral arteriography disclosed ex¬ tensive thrombosis of deep and superficial veins bilaterally, with occlusion of almost the entire SSS, left transverse sinus, left internal jugular vein, the proximal portion
right transverse sinus, the straight sinus, and the vein of Galen (Fig 1). On the ninth day, dexamethasone was increased to 6 mg intramuscularly every six hours, and phenytoin was begun prophylactically. Ex¬ amination disclosed early papilledema, of the
drift of the outstretched left arm, and bilateral extensor plantar reflexes. The platelet count was 205,000/cu mm; and fibrinogen level, 235 mg/100 ml. Heparin sodium was begun, 5,000 units every six hours by continuous intravenous infusion. The next day, the platelet count was 72,000/cu mm, and the fibrinogen level was 185 mg/100 ml. She was given 1.8 million units of urokinase intravenously in 30 minutes. A hematoma developed over a femoral artery puncture site, and blood oozed from antecubital venipuncture sites. Four hours later, the platelet count was 69,000/cu mm, and fibrinogen level was less than 45 mg/100 ml. Eight hours after the first dose, another 0.9 million units of urokinase were given. One hour later, she developed incoherent speech, a right hemi¬ paresis, a dilated left pupil, and labored respirations. Ventilatory assistance was begun, and she was given -aminolevulinic acid, fibrinogen, platelet concentrate, mannitol, and dexamethasone. Another left carotid arteriogram disclosed a large avas¬ allar left cerebral mass (Fig 2). She was given supportive treatment, but her condi¬ tion worsened, and she died six days later. Autopsy disclosed extensive thrombosis in the SSS and both transverse sinuses as well as in meningeal and cerebral veins. A large infarction was present in the right parietal area, and a swollen infarction was in the right occipital lobe. The left hemi¬ sphere contained a massive recent hemor-
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rhage in the internal capsule. The ventri¬ cles contained bloody fluid.
Case 2.-A 33-year-old woman, with a diagnosis of paroxysmal nocturnal hemoglobinuria, had been followed up for six years. She had been hospitalized several times for anemia, hematuria, infections, and thrombophlebitis of the lower extrem¬ ities. Three days after being discharged, receiving heparin subcutaneously for pel¬ vic vein thrombosis, she was readmitted for abdominal pain diagnosed as endometritis. She was given antibiotics, while heparin was continued, with resolution of symptoms except for headache. Two days later, she was found unconscious, with a right hemiparesis and nonreactive pupils. Arteriography demonstrated a large avascular left temporoparietal mass with multi¬ ple arterial occlusions near the mass and occlusion of the SSS, both transverse sinuses, and left sigmoid sinus. Extensive collateral venous flow was present. After left temporal craniotomy, massive brain swelling, and a large intracerebral hema¬ toma were found. The patient died in the recovery room. The artériographie and surgical findings were confirmed at autop¬ sy· Case 3.—A 25-year-old woman, gravida 3, para 3, had been taking oral contraceptives for three years. She developed persistent right-sided head pain and left hemiparesis for two days. On admission, bilateral papil¬ ledema was noted. She had a generalized seizure during which the eyes and head turned to her left. Arteriography showed complete occlusion of the SSS from the coronal suture to the torcular, with throm¬ bosis of the right parietal cortical veins. She was given continuous heparin and
dexamethasone therapy intravenously. Subsequently, this was changed to heparin administered subcutaneously and then warfarin sodium. Two months later, she
asymptomatic, physical examination
was
and
findings
were
normal.
from
Case 4.-An obese 23-year-old woman had been taking oral contraceptives for two years. She developed severe bifrontal headaches and had several generalized seizures. Examination showed confusion, lethargy, and bilateral extensor plantar reflexes. On lumbar puncture, opening pressure was 490 mm of CSF; protein level, 59 mg/100 ml; RBC count, 13,600/cu mm in tube 1 and 11,000/cu mm in tube 4. Cere¬ bral arteriography showed no visualization of the SSS, and the cortical veins drained away from the cortex. She was treated with anticonvulsants, dexamethasone, and glycerin, 2 gm/kg/day. Her symptoms gradually improved, although she devel¬ oped mild papilledema and continued to have elevated CSF pressure. Medications
gradually stopped. One year later, she no symptoms, and findings from neurologic examination were normal.
generalized. At that time,
were
became
had
temperature
Case 5.—A 19-year-old woman taking oral contraceptives for four months devel¬ oped throbbing bifrontal headache with nausea and vomiting. The mental status
and findings from neurologic examina¬ tions were normal, except for weakness of the right lateral rectus muscle. Nuclear brain scan demonstrated a parasagittal increase in uptake in the anterior view.
Electroencephalogram was mildly abnor¬ mal, with generalized slowing and diffuse delta activity. On lumbar puncture, open¬ ing pressure was 450 mm of CSF; RBC count, 3/cu mm; WBC count, 2/cu mm; and protein level, 38 mg/100 ml. The impres¬ sion of SSS thrombosis was confirmed with angiography. She was given glycerin and dexamethasone orally, with lessening of headache and lateral rectus weakness. Dexamethasone treatment was tapered on an outpatient basis. She was readmitted ten months later because headache recur¬ red. Lumbar puncture showed an opening pressure of 290 mm of CSF. Cerebral angiography was normal. Glycerin given orally relieved her headache in 24 hours and was discontinued. Four days later, the CSF pressure was 110 mm. Ten weeks later, she was symptom-free, and findings from neurologic examination were nor¬ mal. Case 6.—A 20-year-old woman developed severe headache and confusion 12 hours after the birth of her first child. Cerebral angiography elsewhere was interpreted as normal. After ventriculography, pseudotumor cerebri was diagnosed and treated with corticosteroids administered orally. She was seen by us seven months later because of generalized headaches that persisted. On lumbar puncture, opening pressure was 270 mm of CSF; WBC count, 2/cu mm; and protein level, 18 mg/100 ml. Cerebral angiography demonstrated occlu¬ sion of the SSS and the right internal cerebral vein. She was given dexametha¬ sone, with improvement of headache and return of CSF pressure to normal; dexa¬ methasone therapy was then tapered. Three months later, she again had a dull headache. Fundus examination showed absent venous pulsations, but no papilled¬ ema. No treatment was initiated. One month later, she felt well, and findings from fundus examination were normal. Case 7.—A 35-year-old woman had an eight-week history of painful extensor spasms of the lower extremities. Examina¬ tion disclosed bilateral extensor plantar reflexes. Nuclear brain scan and EEG were normal. During hospitalization, she experi¬ enced a right-sided focal motor seizure that
her 40 C. Lumbar puncture opening pressure of 90 mm of was
disclosed an CSF; RBC count, 2,050/cu mm; mononu¬ clear WBC count, 43/cu mm; and protein level, 31 mg/100 ml. Despite treatment with anticonvulsants, she had seven similar seizures over 24 hours. Cerebral angiog¬ raphy showed occlusion of the anterior two thirds of the SSS and probable occlusion of several left frontal and anterior parietal cortical veins. She was treated with dexa¬ methasone, penicillin, and methicillin sodi¬ um. A mild right hemiparesis cleared over several days. Lumbar puncture 13 days later showed an opening pressure of 150 mm of CSF; RBC count, 39/cu mm; mono¬ nuclear WBC count, 11/cu mm; protein level, 45 mg/100 ml. Dexamethasone was stopped, but two months after discharge she was unsteady on her feet and tired easily. Four years later, findings from examination were normal.
COMMENT
The incidence of SSS thrombosis is difficult to determine. Most de¬ scriptions are of sporadic cases. In a study of 182 consecutive autopsies in a chronic care facility, 17 (9%) demon¬ strated durai sinus thrombosis.- In a series of 1,396 autopsies over five years, there were 21 cases of SSS thrombosis.1 Several large series sug¬ gest an incidence during pregnancy and the puerperium of about one in every 2,500 pregnancies.' Detailed pathologic studies are de¬ scribed by Kalbag and Woolf' in their extensive monograph. The SSS is occluded by thrombus, either partially or along its entire length. Other durai sinuses may also be occluded, and, typically, cortical veins draining into the thrombosed area are also thrombosed. The walls of the sinus may be necrotic. Red blood cells may leak into brain and CSF. Cerebral infarctions, often hemorrhagic, are common, usually corresponding to areas of cortical vein thrombosis. Evidence of severe cerebral edema is usual. Intra¬ cerebral and subdural hematomas are rare, except after anticoagulant ther¬ apy.
Superior sagittal sinus thrombosis has been associated with a wide variety of clinical entities: trauma,6"s pregnancy,'"" puerperium,'"'-' the use of oral contraceptives,'' '* dehy¬ dration and cachexia,--'-7 congestive
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Fig 1.—Case 1. Anteroposterior (top left) and lateral (top right) views of right carotid angiogram and anteroposterior (center left) and lateral (center right) views of left carotid angiogram obtained during venous phase. Note nonopacification of superior sagittal (large curved arrow), straight, and transverse sinuses. Sigmoid sinuses (open arrows) are patent (although only segmentally on left). Right jugular vein (crossed open arrows) is patent; left is presumably thrombosed. There is considerable drainage via emissary veins into paravertebral plexus (arrowheads). Internal cerebral veins (solid arrows) drain primarily by retrograde flow through basilar veins (small curved arrows) due to occlusion of vein of Galen. On oblique anteroposterior view (bottom left) obtained during venous phase of right carotid angiogram with cross-compression of the opposite carotid artery demonstrates to best advantage complete thrombosis of superior sagittal sinus from its anterior aspect (A) to torcular Herophili (T). Vertebral angiography (not shown) also demonstrated nonopacification of the straight and transverse sinuses.
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heart failure,-n cerebral arterial oc¬ clusions,5-7 hemolytic anemia,11 thrombocytopenia,1" sickle cell trait,'-'0 cryofibrinogenemia,-1 paroxysmal nocturnal hemoglobinuria,-- Budd-Chiari syn¬ drome, ulcerative colitis,11'23-4 dia¬ betes,"1 and idiopathic disease.5-7·1126 An association of SSS thrombosis with oral contraceptives was first noted in 1962.11 In initial cases, the diagnosis was made at autopsy in women with unexplained acute neuro¬ logic disease, often with evidence of peripheral thrombosis.1411 Subse¬ quently, cases have been reported in which specific therapeutic interven¬ tion was attempted.1617-7 This compli¬ cation often occurs early in the course of oral contraceptive therapy.1" The clinical features of SSS throm¬ bosis are variable, depending on the setting in which it occurs and the extent of associated occlusions of other cerebral vasculature. The most frequent complaint is headache, which may be localized to the side of cerebral damage. Presumably, headache often results from increased intracranial pressure. Focal or generalized seizures are common and can be the initial manifestation. Papilledema frequent¬ '
ly develops. Focal neurologic deficits, such as hemiparesis, may develop.
Progressive decrease in consciousness and death can occur. The pathogenesis of SSS thrombosis is undoubtedly variable, depending on the clinical setting. It seems reason¬ able that, in most cases, a coagulopathy is contributory. In pregnancy and the puerperium, there is increased platelet adhesiveness,-" increase in blood-clotting factors VII and X,-" hyperfibrinogenemia and decreased
fibrinolysis,"' and elevated levels of triglycérides, fatty acids, and phos¬ pholipids.11 ·" In puerperal cerebral
and durai sinus thrombosis, a notable rise in serum lipids and fall in blood fibrinolytic activity compared to the already altered values in healthy pregnant and puerperal women. '- In the use of oral contraceptive steroids, elevated levels of prothrombin, blood-clotting factors VII, IX, and X, plasminogen, and antifibrinolytic activity begin in a few days, and, after six months, platelet counts are elevated.33-34 In congestive heart failure and dehydra¬ tion, hemodynamic factors may be important. An anatomical feature may contribute to SSS thrombosis. Many trabeculae cross the SSS, and, in some cases, a continuous membrane divides it for a portion of its venous
there
was
length.1""16 Perhaps these cause hemodynamic alterations predisposing to thrombosis.
Laboratory studies are essential to establish the diagnosis. The spinal fluid is often increased in pressure and may be bloody.5 The EEG frequently shows diffuse slowing, and there may be focal abnormalities that are often paroxysmal.1 Radioisotope brain scanning has shown increased uptake in the parasagittal area and may show areas of infarction.17 Ven¬ triculography demonstrates normal or small ventricles suggesting edema.1 The definitive diagnosis of SSS thrombosis is made by angiography. Frenckner38 was the first to demon¬ strate the entity by direct sinography of the SSS through a drill hole in the skull. Demonstration by arterial injec¬ tion, including the use of oblique views, is now the indicated procedure in the diagnosis of durai sinus and cortical vein occlusions.1'7-3" The natural history and prognosis are highly variable. Experience at this hospital indicates the clinical course can be benign. It is reasonable to believe that these are patients in whom the diagnosis is not made and who have a mild course without treat¬ ment.
1. Anteroposterior (left) and lateral (right) views of left carotid angiogram demonstrate large, avascular frontoparietal intracerebral mass with associated depression of Sylvian branches of middle cerebral artery (open arrows) and displacement of anterior cerebral artery to right (solid arrows).
Fig 2.—Case
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No comparative studies in the effi¬ cacy of various types of therapy exist. Considering the low incidence, this is not surprising. Surgical thrombectomy with survival has been re¬ ported.1" Measures to reduce intra¬ cranial pressure include subtemporal decompression,11 therapeutic lumbar puncture,1-"-1 and agents to control edema, such as dexamethasone14 '" and mannitol.-3·27 Anticonvulsants are used when seizures develop.511 Many have used antibiotics, even though no evidence for infection is present.511 Heparin was first used in 1942 to treat a case of puerperal SSS thrombo¬
sis.41 Since then, the use of anticoagu¬ lants in durai sinus and cerebral vein thrombosis has been controversial. Some feel they prevent extension of thrombosis,5111417 while others believe
they may promote intracranial hemor¬ rhage.71116 The successful use of the fibrinolytic agent urokinase has been reported.1" However, in our first patient, its use may have been detri¬
mental. The most important therapeutic question in this entity is whether or not anticoagulants should be used. Patients collected from the literature cannot be compared in answering this, because of variations in underlying clinical conditions, other surgical or medical treatment, and type and method of administration of anticoag¬ ulants. In our series, two of the three patients receiving anticoagulants died of hemorrhagic intracranial complica¬ tions. These same two were already receiving anticoagulants for periph¬ eral venous occlusion at the time
central
nervous
system symptoms
developed. This is in comparison to four patients who were taking anti¬ coagulants who recovered completely
while receiving other forms of ther¬ apy. We believe that the evidence supporting the use of anticoagulants is sufficiently inconclusive and the risk of untoward complications great enough that one should rely on more conservative therapy with antiedematous agents and anticonvulsants. This investigation was supported in part by National Institutes of Health grant 5T01-
NSO5004-24.
Joachim F. Seeger, MD, provided assistance in the preparation of the roentgenographic materi¬ als.
Nonproprietary Name and Trademark of Drug Urokinase- Win-Kinase.
References 1. Gowers WR: A Manual of Diseases of the Nervous System. London, Churchill, 1888, p 416. 2. Towbin A: The syndrome of latent cerebral venous thrombosis: Its frequency and relation to age and congestive heart failure. Stroke 4:419\x=req-\ 430, 1973. 3. Reddy CRRM, Rao MS: Cerebral infarction due to intracranial venous thrombosis. J Indiana State Med Assoc 50:98-102, 1968. 4. Carrol JD, Leak D, Lee HA: Cerebral throm-$ bophlebitis in pregnancy and the puerperium. Q J Med 35:347-368, 1966. 5. Kalbag RM, Woolf AL: Cerebral Venous
Thrombosis. London, Oxford University Press, 1967. 6. Holmes
G, Sargent P: Injuries of the superior longitudinal sinus. Br Med J 2:493-498,
1915. 7. Barnett HJM, Hyland HH: Non-infective intracranial venous thrombosis. Brain 76:36-49, 1953. 8. Carrie AW, Jaffe FA: Thrombosis of superior sagittal sinus caused by trauma without penetrating injury. J Neurosurg 11:173-182, 1954. 9. Amias AG: Cerebral vascular disease in pregnancy. J Obstet Gynaecol Br Commonw 77:312-325, 1970. 10. Fishman RA, Cowen D, Silberman M: Intracranial venous thrombosis during the first trimester of pregnancy. Neurology 7:217-220, 1957. 11. Krayenbuhl HA: Cerebral venous and sinus thrombosis. Clin Neurosurg 14:1-24, 1966. 12. Martin JP, Sheehan HL: Primary thrombosis of the cerebral veins (following childbirth). Br Med J 1:349-353, 1941. 13. Lorentz IT: Parietal lesion and "enavid." Br Med J 1191, 1962. 14. Atkinson EA, Fairburn B, Heathfield KWG: Intracranial venous thrombosis as a complication of oral contraceptives. Lancet 1:914\x=req-\ 918, 1970. 15. Buchanan DS, Brazinsky JH: Dural sinus
and cerebral vein thrombosis: Incidence in young receiving oral contraceptives. Arch Neurol 22:440-444, 1970. 16. Dinder F, Platts ME: Intracranial venous thrombosis complicating oral contraception. Can Med Assoc J 111:545-548, 1974. 17. Fairburn B: Intracranial venous thrombosis complicating oral contraception: Treatment by anticoagulant drugs. Br Med J 2:647, 1973. 18. Poltera AA: The pathology of intracranial venous thrombosis in oral contraception. J Pathol 106:209-219, 1972. 19. Greitz T, Link H: Aseptic thrombosis of intracranial sinuses. Radiol Clin Biol 35:111-123, 1966. 20. Schenk EA: Sickle cell trait and superior longitudinal sinus thrombosis. Ann Intern Med 60:465-470, 1964. 21. Dunsker SB, Torres-Reyes E, Peden JC: Pseudotumor cerebri associated with idiopathic cryofibrinogenemia: Report of a case. Arch Neurol 23:120-127, 1970. 22. Johnson RV, Kaplan SR, Blailock ZR: Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria. Neurolgy 20:681-686, 1970. 23. Borda IT, Southern RF, Brown WF: Cerebral venous thrombosis in ulcerative colitis. Gastroenterology 64:116-119, 1973. 24. Harrison MJG, Truelove SC: Cerebral venous thrombosis as a complication of ulcerative colitis. Am J Dig Dis 12:1025-1028, 1967. 25. Askanasy HM, Kosary IZ, Braham J: Thrombosis of the longitudinal sinus: Diagnosis by carotid arteriography. Neurology 12:288-292, 1962. 26. Silberman M, Fishman R: Primary (idiopathic) thrombosis of superior longitudinal sinus. Trans Am Neurol Assoc 76:164-167, 1951. 27. Gabrielsen TO, Heinz ER: Spontaneous aseptic thrombosis of the superior sagittal sinus and cerebral veins. Radiology 107:579-588, 1969. 28. Wright HP: Changes in adhesiveness of blood platelets following parturition and surgical operations. J Pathol Bacteriol 54:461-468, 1942. women
29. Pechet L, Alexander B: Increased clotting factors in pregnancy. N Engl J Med 265:1093\x=req-\ 1097, 1961. 30. Gillman T, Naidos SS, Hathorn M: Plasma fibrinogen activity in pregnancy. Lancet 2:70-71, 1959. 31. Russ EM, Eder HA, Barr DP: Protein-lipid relationships in pregnancy and the newborn. J Clin Invest 33:1662-1669, 1954. 32. Bansal BC, Prakash C, Gupta RR, et al: Study of serum lipid and blood fibrinolytic activity in cases of cerebral venous/venous sinus thrombosis during the puerperium. Am J Obstet Gynecol 119:1079-1082, 1974. 33. Rutherford RN, Hougie C, Banks AL, et al: The effects of sex steroids and pregnancy on blood coagulation factors. Obstet Gynecol 24:886\x=req-\ 892, 1964. 34. Ygge J, Brody S, Korsan-Bengtsen K, et al: Changes in blood coagulation and fibrinolysis in women receiving oral contraceptives. Am J Obstet Gynecol 104:87-98, 1969. 35. O'Connell JEA: Some observations on the cerebral veins. Brain 57:484-503, 1934. 36. Browder J, Browder A, Kaplan HA: The venous sinuses of the cerebral dura mater: I. Anatomical structures within the superior sagittal sinus. Arch Neurol 26:175-180, 1972. 37. Go RT, Chin CL, Neuman LA: Diagnosis of superior sagittal sinus thrombosis by dynamic and sequential brain scanning. Neurology
23:1199-1204, 1973.
38. Frenckner P: Sinography, a method of radiography in the diagnosis of sinus thrombosis. J
Laryngol Otol 52:350-361, 1937. 39. Vines FS, Davis DO: Clinical-radiological
correlation in cerebral
venous
occlusive disease.
Radiology 98:9-22, 1971. 40. Ray BS, Dunbar HS: Thrombosis of the superior sagittal sinus as a cause of pseudotumor
cerebri. Trans Am Neurol Assoc 75:12-17, 1950. 41. Stansfield FR: Puerperal cerebral venous thrombosis treated with heparin. Br Med J 1:436\x=req-\ 438, 1942.
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/08/2015
Gettelfinger, MD, Emre Kokmen,
\s=b\ Seven patients had superior sagittal sinus thrombosis diagnosed by cerebral arteriography. We recommend that anti-$ coagulants not be used in the therapy of this entity, but rather that one should rely on antiedematous agents and anticonvulsants. (Arch Neurol 34:2-6, 1977)
Gowers' suggested
in 1888 recognized aseptic intracranial venous thrombosis and its association with pregnancy, marasmus, and cachectic conditions. We present seven cases of superior sagittal sinus (SSS) throm¬ bosis in adults unrelated to intra¬ cranial infection or neoplasm in whom the diagnosis was made antemortem. REPORT OF CASES Case 1.—A 27-year-old woman, gravida 2, para 1, was admitted to hospital with pain in her left calf five days before delivering a normal infant. Thrombophlebitis was diag¬ nosed. Findings from coagulation studies were
platelets, 300,000/cu
mm;
prothrom-
bin time, 10.7 seconds (100%), thrombin time, 7.9 seconds (control, 8.3); and fibrinogen, 435 mg/100 ml. She was given heparin sodium, 5,000 units subcutaneously every eight hours, with improvement. Delivery was normal. Two days postpar-
Accepted for publication June 30,
1976. From the Department of Neurology, University of Michigan Medical Center, Ann Arbor. Reprint requests to Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI 48109 (Dr Kokmen).
Thrombosis
MD
turn, she complained of
severe bifrontal and left temporal headache and photopho¬ bia. Findings from neurologic examination were normal. The headache lessened with analgesics. Five days postpartum, she was
discharged, receiving heparin sodium, 8,000 units subcutaneously every 12 hours. Two days later, she was readmitted with worsening headache, nausea, vomiting, and unsteadiness of gait. Findings from physical examination were normal. He¬ moglobin level was 13.5 gm/100 ml; hematocrit reading, 40%; WBC count, 10,300/cu mm; platelet count, 41,000/cu mm; prothrombin time, 81%; thrombin time, 9.6 seconds; and partial thromboplastin time, 35.5 seconds. Opening pressure on lumbar puncture was 170 mm of CSF, and the protein level was 38 mg/100 ml. There were 1,380 RBCs per cubic millimeter in tube 1 and 936 RBCs per cubic millimeter in tube
Heparin-induced thrombocytopenia was suspected; consequently, heparin was dis¬ continued. Four days later, the platelet count was 115,000/cu mm, and findings from coagulation studies were normal. A 4.
brain
scan
was
normal. An EEG
was
moderately abnormal, with diffuse slowing and theta and delta bursts with a left-sided gradient. She continued to complain of headache and was intermittently confused. Four days after admission, the opening pressure on lumbar puncture was 270 mm of CSF; protein level, 43 mg/100 ml; and RBC count, 2/cu mm. Dexamethasone, 4 mg intramuscularly every six hours, was begun. On the eighth day of hospitalization, cerebral arteriography disclosed ex¬ tensive thrombosis of deep and superficial veins bilaterally, with occlusion of almost the entire SSS, left transverse sinus, left internal jugular vein, the proximal portion
right transverse sinus, the straight sinus, and the vein of Galen (Fig 1). On the ninth day, dexamethasone was increased to 6 mg intramuscularly every six hours, and phenytoin was begun prophylactically. Ex¬ amination disclosed early papilledema, of the
drift of the outstretched left arm, and bilateral extensor plantar reflexes. The platelet count was 205,000/cu mm; and fibrinogen level, 235 mg/100 ml. Heparin sodium was begun, 5,000 units every six hours by continuous intravenous infusion. The next day, the platelet count was 72,000/cu mm, and the fibrinogen level was 185 mg/100 ml. She was given 1.8 million units of urokinase intravenously in 30 minutes. A hematoma developed over a femoral artery puncture site, and blood oozed from antecubital venipuncture sites. Four hours later, the platelet count was 69,000/cu mm, and fibrinogen level was less than 45 mg/100 ml. Eight hours after the first dose, another 0.9 million units of urokinase were given. One hour later, she developed incoherent speech, a right hemi¬ paresis, a dilated left pupil, and labored respirations. Ventilatory assistance was begun, and she was given -aminolevulinic acid, fibrinogen, platelet concentrate, mannitol, and dexamethasone. Another left carotid arteriogram disclosed a large avas¬ allar left cerebral mass (Fig 2). She was given supportive treatment, but her condi¬ tion worsened, and she died six days later. Autopsy disclosed extensive thrombosis in the SSS and both transverse sinuses as well as in meningeal and cerebral veins. A large infarction was present in the right parietal area, and a swollen infarction was in the right occipital lobe. The left hemi¬ sphere contained a massive recent hemor-
Downloaded From: http://archneur.jamanetwork.com/ by a University of California - San Diego User on 06/08/2015
rhage in the internal capsule. The ventri¬ cles contained bloody fluid.
Case 2.-A 33-year-old woman, with a diagnosis of paroxysmal nocturnal hemoglobinuria, had been followed up for six years. She had been hospitalized several times for anemia, hematuria, infections, and thrombophlebitis of the lower extrem¬ ities. Three days after being discharged, receiving heparin subcutaneously for pel¬ vic vein thrombosis, she was readmitted for abdominal pain diagnosed as endometritis. She was given antibiotics, while heparin was continued, with resolution of symptoms except for headache. Two days later, she was found unconscious, with a right hemiparesis and nonreactive pupils. Arteriography demonstrated a large avascular left temporoparietal mass with multi¬ ple arterial occlusions near the mass and occlusion of the SSS, both transverse sinuses, and left sigmoid sinus. Extensive collateral venous flow was present. After left temporal craniotomy, massive brain swelling, and a large intracerebral hema¬ toma were found. The patient died in the recovery room. The artériographie and surgical findings were confirmed at autop¬ sy· Case 3.—A 25-year-old woman, gravida 3, para 3, had been taking oral contraceptives for three years. She developed persistent right-sided head pain and left hemiparesis for two days. On admission, bilateral papil¬ ledema was noted. She had a generalized seizure during which the eyes and head turned to her left. Arteriography showed complete occlusion of the SSS from the coronal suture to the torcular, with throm¬ bosis of the right parietal cortical veins. She was given continuous heparin and
dexamethasone therapy intravenously. Subsequently, this was changed to heparin administered subcutaneously and then warfarin sodium. Two months later, she
asymptomatic, physical examination
was
and
findings
were
normal.
from
Case 4.-An obese 23-year-old woman had been taking oral contraceptives for two years. She developed severe bifrontal headaches and had several generalized seizures. Examination showed confusion, lethargy, and bilateral extensor plantar reflexes. On lumbar puncture, opening pressure was 490 mm of CSF; protein level, 59 mg/100 ml; RBC count, 13,600/cu mm in tube 1 and 11,000/cu mm in tube 4. Cere¬ bral arteriography showed no visualization of the SSS, and the cortical veins drained away from the cortex. She was treated with anticonvulsants, dexamethasone, and glycerin, 2 gm/kg/day. Her symptoms gradually improved, although she devel¬ oped mild papilledema and continued to have elevated CSF pressure. Medications
gradually stopped. One year later, she no symptoms, and findings from neurologic examination were normal.
generalized. At that time,
were
became
had
temperature
Case 5.—A 19-year-old woman taking oral contraceptives for four months devel¬ oped throbbing bifrontal headache with nausea and vomiting. The mental status
and findings from neurologic examina¬ tions were normal, except for weakness of the right lateral rectus muscle. Nuclear brain scan demonstrated a parasagittal increase in uptake in the anterior view.
Electroencephalogram was mildly abnor¬ mal, with generalized slowing and diffuse delta activity. On lumbar puncture, open¬ ing pressure was 450 mm of CSF; RBC count, 3/cu mm; WBC count, 2/cu mm; and protein level, 38 mg/100 ml. The impres¬ sion of SSS thrombosis was confirmed with angiography. She was given glycerin and dexamethasone orally, with lessening of headache and lateral rectus weakness. Dexamethasone treatment was tapered on an outpatient basis. She was readmitted ten months later because headache recur¬ red. Lumbar puncture showed an opening pressure of 290 mm of CSF. Cerebral angiography was normal. Glycerin given orally relieved her headache in 24 hours and was discontinued. Four days later, the CSF pressure was 110 mm. Ten weeks later, she was symptom-free, and findings from neurologic examination were nor¬ mal. Case 6.—A 20-year-old woman developed severe headache and confusion 12 hours after the birth of her first child. Cerebral angiography elsewhere was interpreted as normal. After ventriculography, pseudotumor cerebri was diagnosed and treated with corticosteroids administered orally. She was seen by us seven months later because of generalized headaches that persisted. On lumbar puncture, opening pressure was 270 mm of CSF; WBC count, 2/cu mm; and protein level, 18 mg/100 ml. Cerebral angiography demonstrated occlu¬ sion of the SSS and the right internal cerebral vein. She was given dexametha¬ sone, with improvement of headache and return of CSF pressure to normal; dexa¬ methasone therapy was then tapered. Three months later, she again had a dull headache. Fundus examination showed absent venous pulsations, but no papilled¬ ema. No treatment was initiated. One month later, she felt well, and findings from fundus examination were normal. Case 7.—A 35-year-old woman had an eight-week history of painful extensor spasms of the lower extremities. Examina¬ tion disclosed bilateral extensor plantar reflexes. Nuclear brain scan and EEG were normal. During hospitalization, she experi¬ enced a right-sided focal motor seizure that
her 40 C. Lumbar puncture opening pressure of 90 mm of was
disclosed an CSF; RBC count, 2,050/cu mm; mononu¬ clear WBC count, 43/cu mm; and protein level, 31 mg/100 ml. Despite treatment with anticonvulsants, she had seven similar seizures over 24 hours. Cerebral angiog¬ raphy showed occlusion of the anterior two thirds of the SSS and probable occlusion of several left frontal and anterior parietal cortical veins. She was treated with dexa¬ methasone, penicillin, and methicillin sodi¬ um. A mild right hemiparesis cleared over several days. Lumbar puncture 13 days later showed an opening pressure of 150 mm of CSF; RBC count, 39/cu mm; mono¬ nuclear WBC count, 11/cu mm; protein level, 45 mg/100 ml. Dexamethasone was stopped, but two months after discharge she was unsteady on her feet and tired easily. Four years later, findings from examination were normal.
COMMENT
The incidence of SSS thrombosis is difficult to determine. Most de¬ scriptions are of sporadic cases. In a study of 182 consecutive autopsies in a chronic care facility, 17 (9%) demon¬ strated durai sinus thrombosis.- In a series of 1,396 autopsies over five years, there were 21 cases of SSS thrombosis.1 Several large series sug¬ gest an incidence during pregnancy and the puerperium of about one in every 2,500 pregnancies.' Detailed pathologic studies are de¬ scribed by Kalbag and Woolf' in their extensive monograph. The SSS is occluded by thrombus, either partially or along its entire length. Other durai sinuses may also be occluded, and, typically, cortical veins draining into the thrombosed area are also thrombosed. The walls of the sinus may be necrotic. Red blood cells may leak into brain and CSF. Cerebral infarctions, often hemorrhagic, are common, usually corresponding to areas of cortical vein thrombosis. Evidence of severe cerebral edema is usual. Intra¬ cerebral and subdural hematomas are rare, except after anticoagulant ther¬ apy.
Superior sagittal sinus thrombosis has been associated with a wide variety of clinical entities: trauma,6"s pregnancy,'"" puerperium,'"'-' the use of oral contraceptives,'' '* dehy¬ dration and cachexia,--'-7 congestive
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Fig 1.—Case 1. Anteroposterior (top left) and lateral (top right) views of right carotid angiogram and anteroposterior (center left) and lateral (center right) views of left carotid angiogram obtained during venous phase. Note nonopacification of superior sagittal (large curved arrow), straight, and transverse sinuses. Sigmoid sinuses (open arrows) are patent (although only segmentally on left). Right jugular vein (crossed open arrows) is patent; left is presumably thrombosed. There is considerable drainage via emissary veins into paravertebral plexus (arrowheads). Internal cerebral veins (solid arrows) drain primarily by retrograde flow through basilar veins (small curved arrows) due to occlusion of vein of Galen. On oblique anteroposterior view (bottom left) obtained during venous phase of right carotid angiogram with cross-compression of the opposite carotid artery demonstrates to best advantage complete thrombosis of superior sagittal sinus from its anterior aspect (A) to torcular Herophili (T). Vertebral angiography (not shown) also demonstrated nonopacification of the straight and transverse sinuses.
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heart failure,-n cerebral arterial oc¬ clusions,5-7 hemolytic anemia,11 thrombocytopenia,1" sickle cell trait,'-'0 cryofibrinogenemia,-1 paroxysmal nocturnal hemoglobinuria,-- Budd-Chiari syn¬ drome, ulcerative colitis,11'23-4 dia¬ betes,"1 and idiopathic disease.5-7·1126 An association of SSS thrombosis with oral contraceptives was first noted in 1962.11 In initial cases, the diagnosis was made at autopsy in women with unexplained acute neuro¬ logic disease, often with evidence of peripheral thrombosis.1411 Subse¬ quently, cases have been reported in which specific therapeutic interven¬ tion was attempted.1617-7 This compli¬ cation often occurs early in the course of oral contraceptive therapy.1" The clinical features of SSS throm¬ bosis are variable, depending on the setting in which it occurs and the extent of associated occlusions of other cerebral vasculature. The most frequent complaint is headache, which may be localized to the side of cerebral damage. Presumably, headache often results from increased intracranial pressure. Focal or generalized seizures are common and can be the initial manifestation. Papilledema frequent¬ '
ly develops. Focal neurologic deficits, such as hemiparesis, may develop.
Progressive decrease in consciousness and death can occur. The pathogenesis of SSS thrombosis is undoubtedly variable, depending on the clinical setting. It seems reason¬ able that, in most cases, a coagulopathy is contributory. In pregnancy and the puerperium, there is increased platelet adhesiveness,-" increase in blood-clotting factors VII and X,-" hyperfibrinogenemia and decreased
fibrinolysis,"' and elevated levels of triglycérides, fatty acids, and phos¬ pholipids.11 ·" In puerperal cerebral
and durai sinus thrombosis, a notable rise in serum lipids and fall in blood fibrinolytic activity compared to the already altered values in healthy pregnant and puerperal women. '- In the use of oral contraceptive steroids, elevated levels of prothrombin, blood-clotting factors VII, IX, and X, plasminogen, and antifibrinolytic activity begin in a few days, and, after six months, platelet counts are elevated.33-34 In congestive heart failure and dehydra¬ tion, hemodynamic factors may be important. An anatomical feature may contribute to SSS thrombosis. Many trabeculae cross the SSS, and, in some cases, a continuous membrane divides it for a portion of its venous
there
was
length.1""16 Perhaps these cause hemodynamic alterations predisposing to thrombosis.
Laboratory studies are essential to establish the diagnosis. The spinal fluid is often increased in pressure and may be bloody.5 The EEG frequently shows diffuse slowing, and there may be focal abnormalities that are often paroxysmal.1 Radioisotope brain scanning has shown increased uptake in the parasagittal area and may show areas of infarction.17 Ven¬ triculography demonstrates normal or small ventricles suggesting edema.1 The definitive diagnosis of SSS thrombosis is made by angiography. Frenckner38 was the first to demon¬ strate the entity by direct sinography of the SSS through a drill hole in the skull. Demonstration by arterial injec¬ tion, including the use of oblique views, is now the indicated procedure in the diagnosis of durai sinus and cortical vein occlusions.1'7-3" The natural history and prognosis are highly variable. Experience at this hospital indicates the clinical course can be benign. It is reasonable to believe that these are patients in whom the diagnosis is not made and who have a mild course without treat¬ ment.
1. Anteroposterior (left) and lateral (right) views of left carotid angiogram demonstrate large, avascular frontoparietal intracerebral mass with associated depression of Sylvian branches of middle cerebral artery (open arrows) and displacement of anterior cerebral artery to right (solid arrows).
Fig 2.—Case
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No comparative studies in the effi¬ cacy of various types of therapy exist. Considering the low incidence, this is not surprising. Surgical thrombectomy with survival has been re¬ ported.1" Measures to reduce intra¬ cranial pressure include subtemporal decompression,11 therapeutic lumbar puncture,1-"-1 and agents to control edema, such as dexamethasone14 '" and mannitol.-3·27 Anticonvulsants are used when seizures develop.511 Many have used antibiotics, even though no evidence for infection is present.511 Heparin was first used in 1942 to treat a case of puerperal SSS thrombo¬
sis.41 Since then, the use of anticoagu¬ lants in durai sinus and cerebral vein thrombosis has been controversial. Some feel they prevent extension of thrombosis,5111417 while others believe
they may promote intracranial hemor¬ rhage.71116 The successful use of the fibrinolytic agent urokinase has been reported.1" However, in our first patient, its use may have been detri¬
mental. The most important therapeutic question in this entity is whether or not anticoagulants should be used. Patients collected from the literature cannot be compared in answering this, because of variations in underlying clinical conditions, other surgical or medical treatment, and type and method of administration of anticoag¬ ulants. In our series, two of the three patients receiving anticoagulants died of hemorrhagic intracranial complica¬ tions. These same two were already receiving anticoagulants for periph¬ eral venous occlusion at the time
central
nervous
system symptoms
developed. This is in comparison to four patients who were taking anti¬ coagulants who recovered completely
while receiving other forms of ther¬ apy. We believe that the evidence supporting the use of anticoagulants is sufficiently inconclusive and the risk of untoward complications great enough that one should rely on more conservative therapy with antiedematous agents and anticonvulsants. This investigation was supported in part by National Institutes of Health grant 5T01-
NSO5004-24.
Joachim F. Seeger, MD, provided assistance in the preparation of the roentgenographic materi¬ als.
Nonproprietary Name and Trademark of Drug Urokinase- Win-Kinase.
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