] StrokeCerebrovasc DIs 1992,2 34-39 © 1992 National Stroke Associanon
Aseptic Cerebral Venous Thrombosis: Proposed Prognostic Scale Fernando Barinagarrementeria, M.D., Carlos Cantu, M.D., and IHugo Arredondo, M.D.
Seventy-eight patients with aseptic cerebral venous thrombosis between 1966 and 1990 were reviewed In order to determine prognostic factors for this condition Sixty-eight patients were women. The average age of the patients was 30 5 years Fifty-two percent of patients developed the thrombosis dunng the postpartum or puerperal stage. The clinical manifestations that were associated with a poor prognosis were: stupor or coma, bilateral pyramidal tract signs, generalized seizures, meningeal signs, bilateral lesions on computed tomography, and hernorrhagrc cerebrospinal fluid USing these clinical features, a prognostic scale is proposed with a positive predictive value of 0.98 for a good prognosis and 0.96 for a poor prognosis. Key Words: Cerebral venous thrombosis-Dural sinuses-Pregnancy-Prognosis
Cerebral venous thrombosis (CVT) including dural sinus and cortical vein thrombosis was first described by Ribes in 1825 in a patient with metastatic carcinoma to the central nervous system. In 1828, Abercrombie described the first case related to the postpartum state. Since then, numerous causes of CVT have been identified. In recent years, the septic forms have become quite rare with the use of antibiotics. However, the morbidity and mortality continues to be high This study analyzes the clinical, radiological, and pathological characteristics of 78 cases in an attempt to discover the factors predictive for morbidity and mortahty in patients with CVT. From the Stroke Chmc and I Neuroimaglng Department, Nationallnstllute of Neurology and Neurosurgery, Mexico City, Mexico Address correspondence and reprint requests to Dr. F Barinagarrementena at Stroke Clmic, Instituto Nacional de Neurologia y Neurocirugia, Insurgentes sur 3877, Tlalp an 14410, Mexico OF, Mexico 34
J STROKE CEREBROVASC DIS, VOL
2, NO 1,1992
Material and Methods The clinical and radiological files of patients with the diagnosis of aseptic CVT admitted to our hospital between January 1966 and January 1990 were examined in order to determine prognostic factors The diagnosis of CVT was based on any of the following criteria. 1. Angiographic evidence of CVT a) Total or partial occlusion of any or some of the cerebral venous sinuses b) Occlusion of cerebral veins c) Delayed venous emptying and/or engorgement of superficial or deep cerebral veins 2. Evidence of CVT via neuropathological study a) Presence of thrombosis of cerebral veins or venous sinuses, with or without associated venous infarct 3. Presence of a compatible clinical picture and obvious predisposing factors, added to findings on imaging studies characteristic of CVT
ASEPTICCEREBRALVENOUS THROMBOSIS
a) Headache, seizures, disorder of consciousness, focal neurological deficit with or without intracranial hypertension b) History of recent or present use of an oral contraceptive, puerperal state or pregnancy c) Computed tomographic (CT) signs considered pathognomonic of the disease, such as the presence of a delta sign. The following were considered exclusion criteria: (a) incomplete radiological or clinical records; (b) inconclusive radiological studies for diagnosis of cerebral venous thrombosis; or (c) cavernous sinus thrombosis. Based on the abovementioned criteria, we obtained 94 patients of which 78 were finally accepted for analysis. Of the total series (78 cases), 57 were included on the basis of angiographic criteria, 14 on neuropathological criteria, and the remaining 7 on clinical-tomographic criteria (delta sign). Special emphasis was placed on the clinical outcome of the patients. We applied the following classifications arbitrarily: (a) complete recovery (those patients in whom there had not been any neurological deficit or any other sequelae); (b) partial recovery was divided in two groups-mild or moderate sequelae (the patient returned to his or her usual activities in spite of some neurological deficit) and serious sequelae (the patient required assistance due to severe disability); a1)9 (c) death. Later, we classified the patients into two large groups according to their final outcome. Group I included those patients who completely recovered and those who partially recovered with mild or moderate sequelae. Group II included those who partially recovered WIth serious sequelae or those who died. The clmical, radiological, and laboratory data obtained were correlated with the final outcome according to the above classification to determine the predictive factors of morbidity and mortality. A multi-varied statistical analysis was done via 2 X 2 contingency tables and statistical validation via chisquare test, and the exact Fisher test.
Results Of the 78 patients analyzed in this study, 68 were women (87.2%) with an average age of 31 years, and 10 were men (12.8%) with an average age of 30. Ages ranged from 15 to 77 years Eighty-five percent of the patients were under 40 years of age. Twenty-six patients (333%) had no predisposing history that could be related to venous thrombosis; 42 patients (52 5%) were in the postpartum or puerperal
Table 1.
CT filldlllgs ill 60 patients with
Direct signs of CVT Delta sIgn Dense sinus sign Intramedulary veins Total Parenchymatous changes Hemorrhagic infarction or unilateral hematoma BIlateral nonhemorrhagic infarction BIlateral hematoma or hemorrhagic infarction
cvr
11 cases 5 cases 3 cases 19 cases
(183%) (83%) (50%) (316%)
20 cases
(256%)
4 cases
(51%)
12 cases
(15.3%)
stage. Four patients (5.1%) were pregnant; four patients used oral contraceptives at the time of thrombosis. In one case, there was a recent history of cranial trauma, and, in another case, there was metastasic cancer of the breast without involvement of the central nervous system. The clinical manifestations appeared acutely in 30 cases (385%), subacutely in 28 cases (35.9%), and chronically in the remaining 20 (25.6%). The duration of symptoms to the time of diagnosis was less than 1 week in 47 patients (60.3%), 23 (29.5%) of which had had symptoms for less than 48 hand 24 patients (30.8%) who had had symptoms for more than 48 h but less than 7 days. The duration of symptoms until the time of diagnosis was from 1 to 3 weeks in 24 patients (30.8%), and more than 3 weeks in 7 patients (8.9%). The course of the illness was progressive in 60 patients (76.9%), intermittent or fluctuating in 10 patients (12.8%), and nonprogressive in 8 patients (10.3%). The most frequent initial clinical manifestation was headache, which appeared in 49 patients (628%). Other presenting symptoms included: partial motor seizures in seven patients, motor deficit in six patients, sensory deficits in six cases, generalized seizures in six patients, disorder of consciousness in two patients, and two patients with visual disturbances. Two patients had a hematocrit greater than 60%. Thrombocytosis (platelet count above 400,000/cu mm) was detected in six patients. We obtained a sample of the cerebrospinal fluid in 54 of th e 78 patients. In 14 pati ents (26%), the fluid was normal, including initial pressure. Sixteen (40%) patients had an elevated pressure without alteration in the cytochemistry studies. Contrast-enhanced cranial CT was done on 60 patients. The CT findings are summarized in Table 1. / STROKECEREBROVASCDIS, VOL.2, NO.1, 1992
35
F. BARINAGARREMENTERIA ET AL
Table 2.
Allgiograplzic fllldillgs ill 57 cases of cvr Findings
Number (%)
I. Nonvisuahzation (complete or parllal) of venous sinus II Nonvisuahzation of cerebral veins III Delayed venous emptying or venous engorgement I + III I+II+III I + II
55 (965) 12 (21 1) 43 (754) 34 (596) 10 (175) 2 (36)
Cerebral angiography was done on 57 of the 78 patients. The angiographic findings are shown in Table
2. On analyzing the sites of thrombosis within the venous system, we found that the superior sagittal sinus was affected in 70 patients (89.7%), and in 28 it was the sole site of occlusion. The cortical cerebral veins were affected in 19 patients, and In only one case were they the sole site of occlusion The deep venous system was thrombosed in 14 patients and was the sole site of occlusion in six. Twenty patients had involvement of both the transverse sinus and the superior sagittal sinus. According to our classification with respect to outcome, 38 patients had complete recovery (48.7%), and 22patients had partial recovery (28.2%), 14 with slight or moderate sequelae {l7.7%}; and 8 with serious sequelae, including 5 in a vegetative state. Eighteen patients died (231%). In summary, the final outcome was favorable (Group I) in 52 patients (66.7%) and unfavorable (Group 11) in 26 patients
Table 3.
(33.3%). Table 3 shows the factors that correlated statistically with an unfavorable prognosis (Group 11). Based on their statistical significance value, a numerical value was assigned arbitrarily to each one of these factors as shown in Table 3, with the aim of developing a prognostic scale. We applied this scale blindly to all the patients and found a positive correlation with prognosis. Patients with a total of 0-5 points had a favorable prognosis with a sensitivity ofO.98; those with a total of 6 or more points had an unfavorable outcome with a sensitivity of 0.96. Figure 1 shows the prognostic correlation in detail. Other prognostic factors were related to the etiology of the CVT. Those with postpartum or puerperal etiology had a good prognosIs: 37 survived and 4 died (p < 0.05). The patients categorized as idiopathic had an unfavorable prognosIs: of20 patients, 8 died (p < 0.05).
Discussion Although CVT was first described at the end of the last century, its prevalence is not yet known. Earlier reports documented a predominance of CVT in women, especially related to the puerperal state and pregnancy (l,2-5,6). This information is corroborated in our series, in which 87% of the patients were women. The incidence of CVT in the puerperal state and associated with pregnancy is variable in different parts of the world Carroll et al. (7) state an incidence of 1 case per 2,500 deliveries; Cross et al. (4) state a ratio of 1 per 10,000 deliveries, and in India a rate of up to 4-5 cases per 1,000 deliveries is reported (2).
Prognostic factors
III
cvr
Group I (52 cases)
Group II (26 cases)
Findings
Number (%)
Number (%)
Stupor or com a Bilateral pyramidal tract signs Generalized seizures Meningeal signs Papill edema Hemorrhagic infarclIon or Unilateral hematoma BIlateral nonhemorrhagic infarction Bilateral hematoma or hemorrhagic Infarction Bilateral lesion (CT) Hemorrhagic cerebrospinal fluid
4 (8)
12 (23) 8 (15) 12 (23) 22 (42) 14/42 (33) 1/42 (2) 5/42 (12) 7/42 (16) 5/40 (13)
23 (88)24 (92) 16 (61)11 (42)10 (38) ~ 6/18 (33)~ 3/18 (17)7/18 (39)10/18 (55)7/14 (50)-
-p
< 005.
~NS.
36 JSTROKECEREBROVASCDIS, VOL.2, NO 1, 1992
ASEPTICCEREBRALVENOUS THROMBOSIS
Group I • Good Proqnosis Group II + Bad PrognosIs
o
2
3
4
5
POI
Figure 1. tic score
6
7 N
T
8
9
Predictive 0 98 096
10
Value
11
S
Dtsinbution of patients wlIll cvr relatnie toprogllos-
Postpartum thrombosis can occur from the first week (generally after the third day) to the fourth week postpartum. We calculate that 80% of cases in world literature occur during the second and third week (2,3,5). Of the 41 cases of postpartum thrombosis in our series, 63% occurred during the second and third weeks, and only 5% occurred during the fourth week. In addition, 29% occurred during the first week, with 15% occurring in the first 48 h. Three of the cases occurred in the immediate postpartum period and one case in the sixth week. Accordmg to our analysis, the time when venous thrombosis occurs does not influence the prognosis The cases of CVT reported during pregnancy generally occur in the third tnmester (3,5). Four of our cases occurred during pregnancy. One occurred during the first trimester, two occurred during the second trimester, and one occurred during the third trimester. In those regions in which the incidence of CVT is low, the illness tends to occur equally in both sexes (8,9). Multiple etiologies ofCVT have been described (10), and it seems that the etiologies vary in different regions of the world Thus, for example, Bousser et aI. (9) report in their series a considerable number of cases associated with Behcet's disease, whereas other series emphasize the relationship between venous thrombosis and cranial trauma (11-14), with systemic metastasic disease (15), with the use of oral contraceptives (11,16,17), and with pregnancy and puerperium (5,6,18). In our series, CVT was associated with a hypercoagulable state of pregnancy and puerperium in 57%, a hematological disturbance (thrombocytosis and polycythemia) in 8%, contraceptive use in 5%, and a para neoplastic hypercoagulable state in 1.2% . As in other series (8,9), a large proportion of cases (27~1o) were categorized as idiopathic. It is probable that some of these cases represent hypercoagulable states not identified by the available means, and, therefore, a more thorough hematological workup is required for
their identification (in particular, antithrombin III, proteins C and 5, and antiphospholipid antibodies) (19,20). Recently, antiphospholipid antibodies have been associated with hypercoagulable states with cerebral arterial, cerebral venous, and peripheral vascular thrombotic phenomena (21-23). These antibodies were tested in three of our patients and were positive in one patient with postpartum venous thrombosis. Cerebral venous thrombosis is a condition with great clinical pleomorphism (6,9,24-27). Tables 3 and 4 show the clinical manifestations in this series. There are marked differences between this series and that reported by Bousser et aI. (9). In our series, seizures and focal neurological signs predommate, and in the Bousser series it is the increased intracranial pressure syndrome that predominates. Bousser et aI. state that the low frequency of focal neurological signs is due to early diagnosis; however, we also made early diagnosis and, in addition, we found CT evidence of early vascular lesions. Angiography has traditionally been considered the most accurate method of diagnosing CVT. Our series does not show differences with other series in relation to the angiographic findings (8,28,29). It is interesting that six of our patients presented with isolated involvement of the deep venous system, a fact that has been occasionally described (30,31). Other diagnostic methods include CT and magnetic resonance imaging (MRI). Sixty of the 78 patients in our series underwent CT; the main findings are shown in Table 1 and are compared to those of other series (32-42). In our series, the frequency of venous infarction (72%), especially hemorrhagic infarction (52%), is much greater than that of other reports in the literature (43). LIkewise, we found a high frequency of bilateral lesions (28%), a finding that is virtually diagnostic of CVT. MRI has recently been used to establish the diagnosis ofCVT (29,43-47). Nine of our patients underwent MRI. In six of the nine patients, MRI showed Table 4.
Prognostic scale
III
cvra
Factor
Points
Stupor or coma Bilateral pyramidal tract signs Generalized seizures Meningeal signs Bilateral lesion by CT scan Hemorrhagic cerebrospinal fluid
3 3 2 1
1 1
'Score of prognostic factors In relation to stausuc value. ] STROKECEREBROVASCDIS, VOL 2, NO 1, 1992
37
F BARINAGARREMENfERlA IT AL
Table 5.
Interpretationofthe prognostic scale for patients toitli cvr
Number of points 0-3 4-5 6-8 9-11
Good prognosis (%) 100 85 10
o
Bad prognosIs (%)
o 15 90 100
venous infarctions (four of them hemorrhagic). Six of the nine cases showed flow alteration in the venous sinuses, a finding described previously (29,47). The main usefulness of MRI is that it permits noninvasive follow-up. The prognosis of patients with CVT is quite variable. If the patient survives, recovery will often be complete or the sequelae will not be incapacitating (8-10,25); on the other hand, CVTcan be a serious or fatal illness that leaves incapacitating consequences. In our series, 49% of the cases recovered completely, 18% had mild sequelae, 10% had serious sequelae, and 23% died. What are the clinical or paraclinical elements that will allow us to predict the outcome of this condition? The answer to this question can facilitate the decision regarding therapeutic measures (for example, antiplatelet agents, anticoagulants, or fibrinolytics). . Although we know that several clinical features are associated with a poor prognosis, it has been impossible to predict precisely the outcome of the patient with CVT. In this study, we identified some factors that correlated highly with the final prognosis It is obvious, however, that the isolated presence of any of these factors is of little value; it is the combination of these factors that affords prognostic value. Based on the statistical value obtained for each prognostic factor, we developed a prognostic scale from 0 to 11 points (the lower the number of points, the better the prognosis) (Table 4). We applied this scale to all the patients in our series. The correlation with morbidity and mortality has been notable, with a predictive value of 0.98 for a good prognosis and 0.96 for a poor prognosis. We propose this scale as a prognostic scale for the outcome of patients with CVT (Table 5).
References 1. Kendall D. Thrombosis of intracranial veins -, Brain 1948;71:386-442 2 Srinivasan K. Cerebral venous and arterial thrombosis in pregnancy and pueperium A study of 135 patients. Angiology 1983;34:733-46. 38
J STROKE CEREBROVASCDIS, VOL 2, NO. 1, 1992
3 Donaldson JO. Cerebral venous thrombosis. In: Donaldson JO, ed Neurology of pregnancy. Philadelphia' W.B Saunders, 1978,7:135-56. 4 Cross IN, Castro PO, Jennett WB Cerebral strokes associated With pregnancy and puerperium Br Med I 1968;3'214-8 5. Srinivasan K Puerperal cerebral venous and arterial thrombosis. Sem NeuroI1988,8:222-5. 6. Dubois J. Les thromboflebues cerebrales du postpartum GynecolObstet 1956,55472-93 7. Carroll JD, Leak D, Lee HA. Cerebral thrombophlebitis in pregnancy and the puerperium Q J Med 1966;35 . 347-68. 8 Krayenbuhl HA Cerebral venous and sinus thrombosis . Cltn Neurosurg 1966,14:1-24 9 Bousser MG, Chiras J, Bones J, et al. Cerebral venous thrombosis A review of 38 cases. Stroke 1985,16: 199-213 10. Gates PC, Barnett HJM. Venous disease: cortical veins and Sinuses. In Barnett HJM, Mohr JP, Stein B, Yatsu FM, eds. Stroke. patllOpllyslOlogy, diagnosis and management, vol 2. New York: Churchill-Livmgstone, 1986 ' 731-46 11 Rousseaux P, Bernard MH, Sherpereel B,et al Thrombose des SinUS veineux mtra-craruene (a propos de 22 cas) . Neurochirugie 1978,24'197-203. 12 Kmal ME. Traumatic thrombosis of dural venous sinuses in closed head Injuries. I Neurosurg 1967;27: 142-5. 13 Stnnger WL, Peerless SJ Superior sagittal sinus thrombosis after closed head injunes Neurosurgenj 1983,12:95-7. 14 Crirnnuns TJ, Rokswold GL, Yock DH Progressive posttraumatic supenor sagutal.sinus thrombosis complicated by pulmonary embolism J Neurosurg 1984; 60:179-82 15. Sigsbee B, Deck M, Posner JB. Nonmctastasic supenor sagittal sinus thrombosis complicating systemic cancer. Neurology 1979,29.139-46 16. Buchanan DS, Brazomslu JH Dural sinus and cerebral venous thrombosis. Incidence in young women receiving oral contraceptives Arch Neurol 1970;22: 440-4 17 Atkinson WA, Farburn B, Heathfield KN Intracranial venous thrombosis as complication of oral contraception. Lancet 1970,1:914-8 18 Estanol B, Rodriguez A, Conte B, et al Intracranial venous thrombosis In young women Stroke 1979; 10 680-1. 19. Schaffer AL The hypercoagulable states Ann Intern Med 1985;102:814-28 20. KItchens CS. Concept of hypercoagulability- a review of the development, chrucal application and recent progress. Semin Thromb Hemost 1985;11:591-609. 21 Harris EN, Gharavi AE, Hughes GR. Anti-phospholipid antibodies. Clin Rheumunol Dis 1985;11:591609 22 Levine SR, Welch KM. The spectrum of neurologic disease associated With antiphospholipid antrbodies Arch NeuroI1987;44 :876-83. 23. Asherson RA, Khamashta MA Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erithematosus, lupus-like disease and the primary anti phospholipid syndrome Am J Med 1989,86. 391-9.
ASEPTICCEREBRALVENOUS THROMBOSIS 24. Kalbag RM Cerebral venous thrombosis. In' Kapp JP, Schmideck HH, eds. The cerebral venOl/S system and its disorders. Orlando, FL, Grune & Stratton, 1984:50536 25 Imai WK, Everhart FR, Sanders MG Cerebral venous sinus thrombosis' report of a case and review of the literature. Pedtalncs 1982;70:965-70 26. Averback P. Primary cerebral venous thrombosis m young adults: the diverse manifestations of an underrecognized disease. Ann Nel/roI1978;3:81-6 27. Gettelfmger OM, Kokmen E. Superior sagittal sinus thrombosis Arch Nel/roI1977;34:2-6 28 Vines FS, Davis DO Clmlcal-radrologlcal correlation in cerebral venous occlusive disease. RadIology 1971, 98.9-22. 29. Gabrielsen TU, Heinz E. Spontaneous aseptic thrombosis of the superior sagittal sinus and cerebral veins Am J RoentgenoI1969;107.579-88. 30. NIshimura RN, Stepanek 0, HowiesonJ Internal cerebral vein thrombosis. A case report Arch Nel/roI1982, 39.439-40. 31 Yanez Bana RM, ROSSI Lopez RE, Romero J, et al Trombosrs venosa profunda en relacion a traumatismo craneoencefalico Neurologta (SpaIII) 1989,7'256-9 32. Virapongse C, Cazenove C, Quishng R, et al. The empty delta sIgn : frequency and significance m 76 cases of dural sinus thrombosis. RadIOlogy 187;162' 779-85. 33. Buonanno FS, Moody OM. Computed cranial tomographic fmdings in cerebral sinovenous occlusion J Contpui ASSIst Tomogr 1979,2.281-90. 34 Goldberg HI, Lee SH. Cerebral venous thrombosis In: Lee SH, Rao K, eds Cmmal computed tomography and MRI New York: McGraw-Hill, 1983'693-9 35. Wendling LR Intracranial venous sinus thrombosis
36 37. 38
39 40. 41. 42. 43 44 45 46. 47.
diagnosis suggested by computed tomography. Am J RoeutgenoI1978;130:978-80 . Patronas MJ, Duda EE,Wollman RL,et al Sagittal sinus thrombosis diagnosed by computed tomography Surg NellroI1981;15:1l-4 Brant-Zawadsky, Chan M, McCarty GE. Computed tomography in dural sinus thrombosis Arch Nel/roI1982, 39446-7. Kmgley DP, Kendall BE,Moseley IF. Superior sagittal smus thrombosis: an evaluation of the changes demonstrated on computed tomography. J Neurol Neurosurg Psychiatry 1978,41 :1055-8. Roa KC, Knipp HC, Wagner EG. Computed tomographic findmgs in cerebral sinus and venous thrombosis. Radiology 1981;140'391-8 . Chiras J, Bousser MG, Meder JF, et al. CT m cerebral thrombophlebitis NellroradlOlogy 1985;27:145-54. Guldberg AL, Rosenbaum JF. Computed tomography of dural sinus thrombosis JComputAssistTomogr 1986; 10.16-20. Chiras J, Dubs M, Boris J. Venous infarctions. NeuroradIOlogy 1985;27:593-600. Gomon JM, Grossman RI Intracranial hematomas: imagmg by high-field M R. RadIOlogy 1985;157:8793. Ramadan NM, Deveshwar R, Levine S Magnetic resonance and clinical cerebrovascular disease: an update Stroke 1989;20'1279-83 Bradley WG, Waluch V. Blood flow: magnetic resonance imagmg RadIOlogy 1985;154.443-58 Baver WM, Einhaupl K. MR of venous smus thrombosis : a case report. Am J NellroradlO11987;8 713-5. McMurdo SI(, Brant-Zawadsky M Dural sinus thrombosis: study using Intermediate field strength MR imaging. RadIOlogy 1986;161:83-6
J STROKECEREBROVASCDIS, VOL 2, NO
1, 1992
39
Aseptic Cerebral Venous Thrombosis: Proposed Prognostic Scale Fernando Barinagarrementeria, M.D., Carlos Cantu, M.D., and IHugo Arredondo, M.D.
Seventy-eight patients with aseptic cerebral venous thrombosis between 1966 and 1990 were reviewed In order to determine prognostic factors for this condition Sixty-eight patients were women. The average age of the patients was 30 5 years Fifty-two percent of patients developed the thrombosis dunng the postpartum or puerperal stage. The clinical manifestations that were associated with a poor prognosis were: stupor or coma, bilateral pyramidal tract signs, generalized seizures, meningeal signs, bilateral lesions on computed tomography, and hernorrhagrc cerebrospinal fluid USing these clinical features, a prognostic scale is proposed with a positive predictive value of 0.98 for a good prognosis and 0.96 for a poor prognosis. Key Words: Cerebral venous thrombosis-Dural sinuses-Pregnancy-Prognosis
Cerebral venous thrombosis (CVT) including dural sinus and cortical vein thrombosis was first described by Ribes in 1825 in a patient with metastatic carcinoma to the central nervous system. In 1828, Abercrombie described the first case related to the postpartum state. Since then, numerous causes of CVT have been identified. In recent years, the septic forms have become quite rare with the use of antibiotics. However, the morbidity and mortality continues to be high This study analyzes the clinical, radiological, and pathological characteristics of 78 cases in an attempt to discover the factors predictive for morbidity and mortahty in patients with CVT. From the Stroke Chmc and I Neuroimaglng Department, Nationallnstllute of Neurology and Neurosurgery, Mexico City, Mexico Address correspondence and reprint requests to Dr. F Barinagarrementena at Stroke Clmic, Instituto Nacional de Neurologia y Neurocirugia, Insurgentes sur 3877, Tlalp an 14410, Mexico OF, Mexico 34
J STROKE CEREBROVASC DIS, VOL
2, NO 1,1992
Material and Methods The clinical and radiological files of patients with the diagnosis of aseptic CVT admitted to our hospital between January 1966 and January 1990 were examined in order to determine prognostic factors The diagnosis of CVT was based on any of the following criteria. 1. Angiographic evidence of CVT a) Total or partial occlusion of any or some of the cerebral venous sinuses b) Occlusion of cerebral veins c) Delayed venous emptying and/or engorgement of superficial or deep cerebral veins 2. Evidence of CVT via neuropathological study a) Presence of thrombosis of cerebral veins or venous sinuses, with or without associated venous infarct 3. Presence of a compatible clinical picture and obvious predisposing factors, added to findings on imaging studies characteristic of CVT
ASEPTICCEREBRALVENOUS THROMBOSIS
a) Headache, seizures, disorder of consciousness, focal neurological deficit with or without intracranial hypertension b) History of recent or present use of an oral contraceptive, puerperal state or pregnancy c) Computed tomographic (CT) signs considered pathognomonic of the disease, such as the presence of a delta sign. The following were considered exclusion criteria: (a) incomplete radiological or clinical records; (b) inconclusive radiological studies for diagnosis of cerebral venous thrombosis; or (c) cavernous sinus thrombosis. Based on the abovementioned criteria, we obtained 94 patients of which 78 were finally accepted for analysis. Of the total series (78 cases), 57 were included on the basis of angiographic criteria, 14 on neuropathological criteria, and the remaining 7 on clinical-tomographic criteria (delta sign). Special emphasis was placed on the clinical outcome of the patients. We applied the following classifications arbitrarily: (a) complete recovery (those patients in whom there had not been any neurological deficit or any other sequelae); (b) partial recovery was divided in two groups-mild or moderate sequelae (the patient returned to his or her usual activities in spite of some neurological deficit) and serious sequelae (the patient required assistance due to severe disability); a1)9 (c) death. Later, we classified the patients into two large groups according to their final outcome. Group I included those patients who completely recovered and those who partially recovered with mild or moderate sequelae. Group II included those who partially recovered WIth serious sequelae or those who died. The clmical, radiological, and laboratory data obtained were correlated with the final outcome according to the above classification to determine the predictive factors of morbidity and mortality. A multi-varied statistical analysis was done via 2 X 2 contingency tables and statistical validation via chisquare test, and the exact Fisher test.
Results Of the 78 patients analyzed in this study, 68 were women (87.2%) with an average age of 31 years, and 10 were men (12.8%) with an average age of 30. Ages ranged from 15 to 77 years Eighty-five percent of the patients were under 40 years of age. Twenty-six patients (333%) had no predisposing history that could be related to venous thrombosis; 42 patients (52 5%) were in the postpartum or puerperal
Table 1.
CT filldlllgs ill 60 patients with
Direct signs of CVT Delta sIgn Dense sinus sign Intramedulary veins Total Parenchymatous changes Hemorrhagic infarction or unilateral hematoma BIlateral nonhemorrhagic infarction BIlateral hematoma or hemorrhagic infarction
cvr
11 cases 5 cases 3 cases 19 cases
(183%) (83%) (50%) (316%)
20 cases
(256%)
4 cases
(51%)
12 cases
(15.3%)
stage. Four patients (5.1%) were pregnant; four patients used oral contraceptives at the time of thrombosis. In one case, there was a recent history of cranial trauma, and, in another case, there was metastasic cancer of the breast without involvement of the central nervous system. The clinical manifestations appeared acutely in 30 cases (385%), subacutely in 28 cases (35.9%), and chronically in the remaining 20 (25.6%). The duration of symptoms to the time of diagnosis was less than 1 week in 47 patients (60.3%), 23 (29.5%) of which had had symptoms for less than 48 hand 24 patients (30.8%) who had had symptoms for more than 48 h but less than 7 days. The duration of symptoms until the time of diagnosis was from 1 to 3 weeks in 24 patients (30.8%), and more than 3 weeks in 7 patients (8.9%). The course of the illness was progressive in 60 patients (76.9%), intermittent or fluctuating in 10 patients (12.8%), and nonprogressive in 8 patients (10.3%). The most frequent initial clinical manifestation was headache, which appeared in 49 patients (628%). Other presenting symptoms included: partial motor seizures in seven patients, motor deficit in six patients, sensory deficits in six cases, generalized seizures in six patients, disorder of consciousness in two patients, and two patients with visual disturbances. Two patients had a hematocrit greater than 60%. Thrombocytosis (platelet count above 400,000/cu mm) was detected in six patients. We obtained a sample of the cerebrospinal fluid in 54 of th e 78 patients. In 14 pati ents (26%), the fluid was normal, including initial pressure. Sixteen (40%) patients had an elevated pressure without alteration in the cytochemistry studies. Contrast-enhanced cranial CT was done on 60 patients. The CT findings are summarized in Table 1. / STROKECEREBROVASCDIS, VOL.2, NO.1, 1992
35
F. BARINAGARREMENTERIA ET AL
Table 2.
Allgiograplzic fllldillgs ill 57 cases of cvr Findings
Number (%)
I. Nonvisuahzation (complete or parllal) of venous sinus II Nonvisuahzation of cerebral veins III Delayed venous emptying or venous engorgement I + III I+II+III I + II
55 (965) 12 (21 1) 43 (754) 34 (596) 10 (175) 2 (36)
Cerebral angiography was done on 57 of the 78 patients. The angiographic findings are shown in Table
2. On analyzing the sites of thrombosis within the venous system, we found that the superior sagittal sinus was affected in 70 patients (89.7%), and in 28 it was the sole site of occlusion. The cortical cerebral veins were affected in 19 patients, and In only one case were they the sole site of occlusion The deep venous system was thrombosed in 14 patients and was the sole site of occlusion in six. Twenty patients had involvement of both the transverse sinus and the superior sagittal sinus. According to our classification with respect to outcome, 38 patients had complete recovery (48.7%), and 22patients had partial recovery (28.2%), 14 with slight or moderate sequelae {l7.7%}; and 8 with serious sequelae, including 5 in a vegetative state. Eighteen patients died (231%). In summary, the final outcome was favorable (Group I) in 52 patients (66.7%) and unfavorable (Group 11) in 26 patients
Table 3.
(33.3%). Table 3 shows the factors that correlated statistically with an unfavorable prognosis (Group 11). Based on their statistical significance value, a numerical value was assigned arbitrarily to each one of these factors as shown in Table 3, with the aim of developing a prognostic scale. We applied this scale blindly to all the patients and found a positive correlation with prognosis. Patients with a total of 0-5 points had a favorable prognosis with a sensitivity ofO.98; those with a total of 6 or more points had an unfavorable outcome with a sensitivity of 0.96. Figure 1 shows the prognostic correlation in detail. Other prognostic factors were related to the etiology of the CVT. Those with postpartum or puerperal etiology had a good prognosIs: 37 survived and 4 died (p < 0.05). The patients categorized as idiopathic had an unfavorable prognosIs: of20 patients, 8 died (p < 0.05).
Discussion Although CVT was first described at the end of the last century, its prevalence is not yet known. Earlier reports documented a predominance of CVT in women, especially related to the puerperal state and pregnancy (l,2-5,6). This information is corroborated in our series, in which 87% of the patients were women. The incidence of CVT in the puerperal state and associated with pregnancy is variable in different parts of the world Carroll et al. (7) state an incidence of 1 case per 2,500 deliveries; Cross et al. (4) state a ratio of 1 per 10,000 deliveries, and in India a rate of up to 4-5 cases per 1,000 deliveries is reported (2).
Prognostic factors
III
cvr
Group I (52 cases)
Group II (26 cases)
Findings
Number (%)
Number (%)
Stupor or com a Bilateral pyramidal tract signs Generalized seizures Meningeal signs Papill edema Hemorrhagic infarclIon or Unilateral hematoma BIlateral nonhemorrhagic infarction Bilateral hematoma or hemorrhagic Infarction Bilateral lesion (CT) Hemorrhagic cerebrospinal fluid
4 (8)
12 (23) 8 (15) 12 (23) 22 (42) 14/42 (33) 1/42 (2) 5/42 (12) 7/42 (16) 5/40 (13)
23 (88)24 (92) 16 (61)11 (42)10 (38) ~ 6/18 (33)~ 3/18 (17)7/18 (39)10/18 (55)7/14 (50)-
-p
< 005.
~NS.
36 JSTROKECEREBROVASCDIS, VOL.2, NO 1, 1992
ASEPTICCEREBRALVENOUS THROMBOSIS
Group I • Good Proqnosis Group II + Bad PrognosIs
o
2
3
4
5
POI
Figure 1. tic score
6
7 N
T
8
9
Predictive 0 98 096
10
Value
11
S
Dtsinbution of patients wlIll cvr relatnie toprogllos-
Postpartum thrombosis can occur from the first week (generally after the third day) to the fourth week postpartum. We calculate that 80% of cases in world literature occur during the second and third week (2,3,5). Of the 41 cases of postpartum thrombosis in our series, 63% occurred during the second and third weeks, and only 5% occurred during the fourth week. In addition, 29% occurred during the first week, with 15% occurring in the first 48 h. Three of the cases occurred in the immediate postpartum period and one case in the sixth week. Accordmg to our analysis, the time when venous thrombosis occurs does not influence the prognosis The cases of CVT reported during pregnancy generally occur in the third tnmester (3,5). Four of our cases occurred during pregnancy. One occurred during the first trimester, two occurred during the second trimester, and one occurred during the third trimester. In those regions in which the incidence of CVT is low, the illness tends to occur equally in both sexes (8,9). Multiple etiologies ofCVT have been described (10), and it seems that the etiologies vary in different regions of the world Thus, for example, Bousser et aI. (9) report in their series a considerable number of cases associated with Behcet's disease, whereas other series emphasize the relationship between venous thrombosis and cranial trauma (11-14), with systemic metastasic disease (15), with the use of oral contraceptives (11,16,17), and with pregnancy and puerperium (5,6,18). In our series, CVT was associated with a hypercoagulable state of pregnancy and puerperium in 57%, a hematological disturbance (thrombocytosis and polycythemia) in 8%, contraceptive use in 5%, and a para neoplastic hypercoagulable state in 1.2% . As in other series (8,9), a large proportion of cases (27~1o) were categorized as idiopathic. It is probable that some of these cases represent hypercoagulable states not identified by the available means, and, therefore, a more thorough hematological workup is required for
their identification (in particular, antithrombin III, proteins C and 5, and antiphospholipid antibodies) (19,20). Recently, antiphospholipid antibodies have been associated with hypercoagulable states with cerebral arterial, cerebral venous, and peripheral vascular thrombotic phenomena (21-23). These antibodies were tested in three of our patients and were positive in one patient with postpartum venous thrombosis. Cerebral venous thrombosis is a condition with great clinical pleomorphism (6,9,24-27). Tables 3 and 4 show the clinical manifestations in this series. There are marked differences between this series and that reported by Bousser et aI. (9). In our series, seizures and focal neurological signs predommate, and in the Bousser series it is the increased intracranial pressure syndrome that predominates. Bousser et aI. state that the low frequency of focal neurological signs is due to early diagnosis; however, we also made early diagnosis and, in addition, we found CT evidence of early vascular lesions. Angiography has traditionally been considered the most accurate method of diagnosing CVT. Our series does not show differences with other series in relation to the angiographic findings (8,28,29). It is interesting that six of our patients presented with isolated involvement of the deep venous system, a fact that has been occasionally described (30,31). Other diagnostic methods include CT and magnetic resonance imaging (MRI). Sixty of the 78 patients in our series underwent CT; the main findings are shown in Table 1 and are compared to those of other series (32-42). In our series, the frequency of venous infarction (72%), especially hemorrhagic infarction (52%), is much greater than that of other reports in the literature (43). LIkewise, we found a high frequency of bilateral lesions (28%), a finding that is virtually diagnostic of CVT. MRI has recently been used to establish the diagnosis ofCVT (29,43-47). Nine of our patients underwent MRI. In six of the nine patients, MRI showed Table 4.
Prognostic scale
III
cvra
Factor
Points
Stupor or coma Bilateral pyramidal tract signs Generalized seizures Meningeal signs Bilateral lesion by CT scan Hemorrhagic cerebrospinal fluid
3 3 2 1
1 1
'Score of prognostic factors In relation to stausuc value. ] STROKECEREBROVASCDIS, VOL 2, NO 1, 1992
37
F BARINAGARREMENfERlA IT AL
Table 5.
Interpretationofthe prognostic scale for patients toitli cvr
Number of points 0-3 4-5 6-8 9-11
Good prognosis (%) 100 85 10
o
Bad prognosIs (%)
o 15 90 100
venous infarctions (four of them hemorrhagic). Six of the nine cases showed flow alteration in the venous sinuses, a finding described previously (29,47). The main usefulness of MRI is that it permits noninvasive follow-up. The prognosis of patients with CVT is quite variable. If the patient survives, recovery will often be complete or the sequelae will not be incapacitating (8-10,25); on the other hand, CVTcan be a serious or fatal illness that leaves incapacitating consequences. In our series, 49% of the cases recovered completely, 18% had mild sequelae, 10% had serious sequelae, and 23% died. What are the clinical or paraclinical elements that will allow us to predict the outcome of this condition? The answer to this question can facilitate the decision regarding therapeutic measures (for example, antiplatelet agents, anticoagulants, or fibrinolytics). . Although we know that several clinical features are associated with a poor prognosis, it has been impossible to predict precisely the outcome of the patient with CVT. In this study, we identified some factors that correlated highly with the final prognosis It is obvious, however, that the isolated presence of any of these factors is of little value; it is the combination of these factors that affords prognostic value. Based on the statistical value obtained for each prognostic factor, we developed a prognostic scale from 0 to 11 points (the lower the number of points, the better the prognosis) (Table 4). We applied this scale to all the patients in our series. The correlation with morbidity and mortality has been notable, with a predictive value of 0.98 for a good prognosis and 0.96 for a poor prognosis. We propose this scale as a prognostic scale for the outcome of patients with CVT (Table 5).
References 1. Kendall D. Thrombosis of intracranial veins -, Brain 1948;71:386-442 2 Srinivasan K. Cerebral venous and arterial thrombosis in pregnancy and pueperium A study of 135 patients. Angiology 1983;34:733-46. 38
J STROKE CEREBROVASCDIS, VOL 2, NO. 1, 1992
3 Donaldson JO. Cerebral venous thrombosis. In: Donaldson JO, ed Neurology of pregnancy. Philadelphia' W.B Saunders, 1978,7:135-56. 4 Cross IN, Castro PO, Jennett WB Cerebral strokes associated With pregnancy and puerperium Br Med I 1968;3'214-8 5. Srinivasan K Puerperal cerebral venous and arterial thrombosis. Sem NeuroI1988,8:222-5. 6. Dubois J. Les thromboflebues cerebrales du postpartum GynecolObstet 1956,55472-93 7. Carroll JD, Leak D, Lee HA. Cerebral thrombophlebitis in pregnancy and the puerperium Q J Med 1966;35 . 347-68. 8 Krayenbuhl HA Cerebral venous and sinus thrombosis . Cltn Neurosurg 1966,14:1-24 9 Bousser MG, Chiras J, Bones J, et al. Cerebral venous thrombosis A review of 38 cases. Stroke 1985,16: 199-213 10. Gates PC, Barnett HJM. Venous disease: cortical veins and Sinuses. In Barnett HJM, Mohr JP, Stein B, Yatsu FM, eds. Stroke. patllOpllyslOlogy, diagnosis and management, vol 2. New York: Churchill-Livmgstone, 1986 ' 731-46 11 Rousseaux P, Bernard MH, Sherpereel B,et al Thrombose des SinUS veineux mtra-craruene (a propos de 22 cas) . Neurochirugie 1978,24'197-203. 12 Kmal ME. Traumatic thrombosis of dural venous sinuses in closed head Injuries. I Neurosurg 1967;27: 142-5. 13 Stnnger WL, Peerless SJ Superior sagittal sinus thrombosis after closed head injunes Neurosurgenj 1983,12:95-7. 14 Crirnnuns TJ, Rokswold GL, Yock DH Progressive posttraumatic supenor sagutal.sinus thrombosis complicated by pulmonary embolism J Neurosurg 1984; 60:179-82 15. Sigsbee B, Deck M, Posner JB. Nonmctastasic supenor sagittal sinus thrombosis complicating systemic cancer. Neurology 1979,29.139-46 16. Buchanan DS, Brazomslu JH Dural sinus and cerebral venous thrombosis. Incidence in young women receiving oral contraceptives Arch Neurol 1970;22: 440-4 17 Atkinson WA, Farburn B, Heathfield KN Intracranial venous thrombosis as complication of oral contraception. Lancet 1970,1:914-8 18 Estanol B, Rodriguez A, Conte B, et al Intracranial venous thrombosis In young women Stroke 1979; 10 680-1. 19. Schaffer AL The hypercoagulable states Ann Intern Med 1985;102:814-28 20. KItchens CS. Concept of hypercoagulability- a review of the development, chrucal application and recent progress. Semin Thromb Hemost 1985;11:591-609. 21 Harris EN, Gharavi AE, Hughes GR. Anti-phospholipid antibodies. Clin Rheumunol Dis 1985;11:591609 22 Levine SR, Welch KM. The spectrum of neurologic disease associated With antiphospholipid antrbodies Arch NeuroI1987;44 :876-83. 23. Asherson RA, Khamashta MA Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erithematosus, lupus-like disease and the primary anti phospholipid syndrome Am J Med 1989,86. 391-9.
ASEPTICCEREBRALVENOUS THROMBOSIS 24. Kalbag RM Cerebral venous thrombosis. In' Kapp JP, Schmideck HH, eds. The cerebral venOl/S system and its disorders. Orlando, FL, Grune & Stratton, 1984:50536 25 Imai WK, Everhart FR, Sanders MG Cerebral venous sinus thrombosis' report of a case and review of the literature. Pedtalncs 1982;70:965-70 26. Averback P. Primary cerebral venous thrombosis m young adults: the diverse manifestations of an underrecognized disease. Ann Nel/roI1978;3:81-6 27. Gettelfmger OM, Kokmen E. Superior sagittal sinus thrombosis Arch Nel/roI1977;34:2-6 28 Vines FS, Davis DO Clmlcal-radrologlcal correlation in cerebral venous occlusive disease. RadIology 1971, 98.9-22. 29. Gabrielsen TU, Heinz E. Spontaneous aseptic thrombosis of the superior sagittal sinus and cerebral veins Am J RoentgenoI1969;107.579-88. 30. NIshimura RN, Stepanek 0, HowiesonJ Internal cerebral vein thrombosis. A case report Arch Nel/roI1982, 39.439-40. 31 Yanez Bana RM, ROSSI Lopez RE, Romero J, et al Trombosrs venosa profunda en relacion a traumatismo craneoencefalico Neurologta (SpaIII) 1989,7'256-9 32. Virapongse C, Cazenove C, Quishng R, et al. The empty delta sIgn : frequency and significance m 76 cases of dural sinus thrombosis. RadIOlogy 187;162' 779-85. 33. Buonanno FS, Moody OM. Computed cranial tomographic fmdings in cerebral sinovenous occlusion J Contpui ASSIst Tomogr 1979,2.281-90. 34 Goldberg HI, Lee SH. Cerebral venous thrombosis In: Lee SH, Rao K, eds Cmmal computed tomography and MRI New York: McGraw-Hill, 1983'693-9 35. Wendling LR Intracranial venous sinus thrombosis
36 37. 38
39 40. 41. 42. 43 44 45 46. 47.
diagnosis suggested by computed tomography. Am J RoeutgenoI1978;130:978-80 . Patronas MJ, Duda EE,Wollman RL,et al Sagittal sinus thrombosis diagnosed by computed tomography Surg NellroI1981;15:1l-4 Brant-Zawadsky, Chan M, McCarty GE. Computed tomography in dural sinus thrombosis Arch Nel/roI1982, 39446-7. Kmgley DP, Kendall BE,Moseley IF. Superior sagittal smus thrombosis: an evaluation of the changes demonstrated on computed tomography. J Neurol Neurosurg Psychiatry 1978,41 :1055-8. Roa KC, Knipp HC, Wagner EG. Computed tomographic findmgs in cerebral sinus and venous thrombosis. Radiology 1981;140'391-8 . Chiras J, Bousser MG, Meder JF, et al. CT m cerebral thrombophlebitis NellroradlOlogy 1985;27:145-54. Guldberg AL, Rosenbaum JF. Computed tomography of dural sinus thrombosis JComputAssistTomogr 1986; 10.16-20. Chiras J, Dubs M, Boris J. Venous infarctions. NeuroradIOlogy 1985;27:593-600. Gomon JM, Grossman RI Intracranial hematomas: imagmg by high-field M R. RadIOlogy 1985;157:8793. Ramadan NM, Deveshwar R, Levine S Magnetic resonance and clinical cerebrovascular disease: an update Stroke 1989;20'1279-83 Bradley WG, Waluch V. Blood flow: magnetic resonance imagmg RadIOlogy 1985;154.443-58 Baver WM, Einhaupl K. MR of venous smus thrombosis : a case report. Am J NellroradlO11987;8 713-5. McMurdo SI(, Brant-Zawadsky M Dural sinus thrombosis: study using Intermediate field strength MR imaging. RadIOlogy 1986;161:83-6
J STROKECEREBROVASCDIS, VOL 2, NO
1, 1992
39
