|Year : 2017 | Volume
| Issue : 1 | Page : 20-25
Cerebral venous thrombosis in women from Indian subcontinent
Aralikatte Onkarappa Saroja, Chandrakanth Tapsi, Karkal Ravishankar Naik
Department of Neurology, KLES Dr. Prabhakar Kore Hospital and MRC, KLE University's Jawaharlal Nehru Medical College, Belagavi, Karnataka, India
|Date of Web Publication||20-Mar-2017|
Aralikatte Onkarappa Saroja
Department of Neurology, KLES Dr. Prabhakar Kore Hospital and MRC, KLE University's Jawaharlal Nehru Medical College, Nehru Nagar, Belagavi - 590 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Purpose: Cerebral venous thrombosis (CVT) is one of the common causes of stroke in women. The causes in pregnancy include acquired hypercoagulable state and are multifactorial in nonpregnant women. This study was conducted to evaluate clinical profile, risk factors, and outcome of cerebral venous sinus thrombosis in pregnant and nonpregnant women. Methods: Women with radiologically proven CVT admitted between 2001 and 2014 were included in the study. Data regarding demographic features, clinical profile, laboratory parameters, and follow-up at 1, 3, and 6 months were analyzed both prospectively and retrospectively. Results: During the study period, 150 women with CVT were admitted. Among them, 69 were related to pregnancy (antepartum 3 and postpartum 66). Eighty-one women had CVT unrelated to pregnancy. Patients with pregnancy-related CVT were younger (24.55 ± 4.16 years) with shorter duration of symptoms (4.97 ± 5.73 days), compared to nonpregnant women who were older (37.14 ± 12.85 years) with longer symptom duration (11.51 ± 18.96 days). There was no difference in the clinical presentation except for higher incidence of altered sensorium in pregnancy group and higher incidence of partial seizures in nonpregnant group. Pattern of venous sinus involvement and infarction was similar in the two groups. Nonpregnant patients had multiple risk factors, severe anemia being the most common followed by the use of oral contraceptives, hyperhomocysteinemia, protein C/S deficiency, malignancy, and psoriasis. Mortality and long-term outcome were similar. Conclusions: Our study reveals a higher proportion of nonpregnant women with CVT. Clinicoradiological profile and outcome did not differ between pregnant and nonpregnant states.
Keywords: Cerebral venous thrombosis, pregnancy, puerperium, women
|How to cite this article:|
Saroja AO, Tapsi C, Naik KR. Cerebral venous thrombosis in women from Indian subcontinent. J Sci Soc 2017;44:20-5
| Introduction|| |
Cerebral venous thrombosis (CVT) is characterized by thrombosis of intracranial venous sinuses or cortical veins and is less frequent than the thrombotic and embolic arterial infarctions. CVT accounts for 10%–20% of strokes in young persons and 0.5%–1% of all strokes. The reported incidence of CVT ranges from 0.22 to 1.32/100,000 person-years., An autopsy study from India revealed ten percent incidence of CVT in all patients with stroke. CVT affects persons of all ages and causes are multifactorial. Factors contributing to the occurrence of CVT differ between men and women. CVT is three times more common in women compared to men, and earlier studies reported the higher occurrence of CVT in relation to pregnancy and postpartum state., However, in the recent years, CVT is being reported with a higher incidence in nonpregnant states. Etiological factors contributing to CVT in nonpregnant women include the use of hormonal preparation, anemia, infections, inherited prothrombotic states, trauma, cancer, and hematological disorders occurring alone or in combination., Common presenting features of CVT are symptoms of raised intracranial pressure, seizures, focal neurological deficits, and altered sensorium.,, Outcome in CVT with early diagnosis and treatment with anticoagulation carries better prognosis in comparison.,,, Pregnancy-related CVT is reported to have a better prognosis than nonpregnant-related CVT and the risk factors in nonpregnant states are different. We intended to study these two groups of women with regard to their clinical profile and outcome.
Aims and objectives
This study was undertaken to compare clinical profile, risk factors, and radiological patterns of cerebral venous sinus thrombosis in pregnant and nonpregnant women. Their immediate in-hospital and long-term outcomes with treatment were evaluated.
| Methods|| |
Women with cerebral venous sinus thrombosis admitted under neurological services of the university teaching hospital over 13 years from July 2001 to July 2014 were studied both prospectively and retrospectively after institutional ethical clearance. All the women with clinical features and radiologically confirmed CVT were included in the study. These women were classified into two groups as pregnancy-related (antepartum and postpartum) and nonpregnancy-related CVT. Women who had delivered up to 6 weeks before the onset of neurological symptoms were included in the postpartum group. A detailed history of symptomatology in relation to mode of onset, underlying risk factors, previous history of thromboembolism, and family history of hypercoagulable states was obtained. Details of clinical examination, complete hemogram, cerebral imaging, coagulation profile, blood sugar, and renal and liver profiles were obtained for all the patients at admission. Cranial imaging consisted of cranial multislice computerized tomography performed before and after intravenous contrast. Magnetic resonance imaging including venography was performed using 1.5 Tesla system.
Course in the hospital, complications, treatment modality, and outcome at discharge were documented. Treatment modality consisted of anticoagulation, antiedema measures, and supportive therapy. Antiepileptic medication was instituted when required. Patients with large infarctions with increasing mass effect and impending herniation were subjected to decompressive craniectomy. Patients were followed up in the outpatient department with regular monitoring of the international normalized ratio. Data regarding their clinical status during follow-up at 1, 3, and 6 months after discharge were analyzed. Their functional outcome was measured using modified Rankin scale (mRS) at discharge and during follow-up. Thrombotic profile was done 6–12 months after the initial presentation after confirming recanalization of the venous sinuses. Anticoagulation was stopped for at least 1 month before the thrombotic profile evaluation. Data were entered in Microsoft Excel 2010 and subsequently analyzed using IBM SPSS Statistics for Windows, Version 20.0, Armonk, NY: IBM Corporation. Unpaired Student's t-test, Chi-square test, and ANOVA were used to analyze the data and level of significance was kept at 0.05.
| Results|| |
Total number of patients admitted to neurological services during the study period was 13,187. Among them, there were 405 patients with CVT of whom 150 were women with male to female ratio of 1.7:1. There were 69 women (46%) in pregnancy-related CVT group including three in antepartum state and 66 in postpartum period. Eighty-one women belonged to nonpregnancy CVT group (54%). Their baseline characteristics are given in [Table 1]. Women with pregnancy-related CVT were younger (24.55 ± 4.16 years) in comparison with nonpregnancy-related CVT (37.14 ± 12.85 years). The symptom duration was longer (11.51 ± 18.96) in the nonpregnancy-related group in comparison with pregnancy-related CVT (4.97 ± 5.73 days). Interval between delivery and symptoms onset was 10.23 ± 6.46 days in the 66 patients with postpartum CVT. Symptoms began within 1 week from delivery in 22 patients (33.3%) and within 2 weeks in sixty patients (99.9%).
|Table 1: The clinical features in 150 women with cerebral venous thrombosis|
Click here to view
Headache was the most common presenting symptom (82.76%), followed by seizures (60%), vomiting (56%), altered consciousness (52%), and limb weakness (48.6%). More number of pregnancy CVT group were in altered sensorium (P = 0.008) with lower Glasgow coma scale score than the nonpregnant group. Duration of hospitalization did not differ between the two groups [Table 1]. Women with pregnancy-related CVT had statistically nonsignificant higher incidence of seizures and status epilepticus. Incidence of partial seizures was higher in nonpregnant women with CVT.
Seventy-three patients had limb weakness with 68 having hemiplegia (right side 40; left side 28) and five had quadriplegia without difference between the groups. Two patients had isolated aphasia and three had ataxia. Eight had other deficits such as ocular palsies, dysphonia, and dysarthria. Sixty-four women had no neurological deficits and had presented with isolated intracranial hypertension. Neurological deficits could not be determined in the two patients who were in deep coma. Laboratory data of the patients are shown in [Table 2].
|Table 2: The laboratory and radiological findings in women with cerebral venous thrombosis|
Click here to view
Cerebral imaging revealed venous infarction in 127 patients and isolated CVT without infarction in 23 patients. Infarctions were unilateral in 87 patients (left side 54; 42.51% and right side 33; 25.98%). Bilateral infarctions were seen in 42 (33.07%) women. Hemorrhagic infarctions (57.47%) were more frequent than pale infarctions (42.51%). Five patients had subarachnoid hemorrhage and two had a subdural hematoma. Fifty-eight patients had single sinus thrombosis (38.66%) and 87 had multiple sinus thrombosis (58%). Isolated superficial venous system thrombosis was seen in 114 (76%), deep venous system involvement in 22 (14.66%), and both deep and superficial venous sinuses were involved in 9 (6%) women. Three had cavernous sinus thrombosis and two had isolated cortical vein thrombosis. Superior sagittal sinus was the most common site of thrombosis (n = 86; 57.33%) followed by sigmoid and transverse sinuses.
Anemia was present in 115 women (76.67%) among whom 57 were in pregnancy-related CVT and 58 had to nonpregnancy-related CVT. Peripheral smear revealed microcytic hypochromic picture in 66 (57.39%) and dimorphic picture in 35 (30.43%) and normal blood picture in 14 (12.17%) patients with anemia. Severe anemia defined as hemoglobin <80 g/L was seen among 44 women and was more frequent among nonpregnant group (n = 34; 41.97%) than the pregnancy-related CVT group (n = 10; 14.49%).
Fifteen nonpregnant CVT women had used oral contraceptives and five of them also had anemia. Hyperhomocysteinemia was seen in 11 out of 48 patients tested, among them nine were nonpregnant and two were postpartum women. Protein C/S deficiency was seen in 12 (16 tested) nonpregnant and 2 (5 tested) in postpartum patients. In the nonpregnant group, one each had psoriasis and malignancy. Family history of venous thrombosis was documented in two women.
Four women underwent craniectomy for large cerebral infarction, of whom three were in the pregnancy-related group (one antepartum and two postpartum). One patient died following decompressive surgery. Sixteen women (10.67%) died during hospital stay, of whom nine were in pregnant group and seven in nonpregnant group. Among those who succumbed eight had severe anemia, one had sepsis, and another had thrombotic thrombocytopenic purpura.
Serial mRS data of the discharged patients are shown in [Table 3]. All the patients showed gradual improvement and none deteriorated or died during the follow-up. There was no difference in the mRS scores between the two groups at discharge or follow-up. Three patients had recurrent CVT (one in pregnant and two in nonpregnant group). Seizures recurred after tapering antiepileptic drug in 12 women (four in pregnant group and eight in nonpregnant group).
|Table 3: Serial modified Rankin scale scores of the women with cerebral venous thrombosis from the time of discharge|
Click here to view
| Discussion|| |
CVT was first described in postpartum women by Abercrombie in 1828. Since then pregnancy-related CVT has been described in various studies. CVT is reported to be much more common in women and has been attributed to gender-specific risk factors. In our series, CVT was more in men than women (63% vs. 37%), ratio of 2.7:1.
Cerebral venous sinus thrombosis is one of the leading causes of stroke in young women. Pregnancy and puerperium are common causes of transient prothrombotic states in women. The frequency of CVT in the puerperium is estimated at 12/100,000 deliveries, only slightly lower than puerperal arterial stroke. In a Mexican study, 50% of CVT occurred during pregnancy or puerperium. During pregnancy and postpartum period, women are at increased risk of venous thromboembolic events. Pregnancy induces several prothrombotic changes in the coagulation system and persists during early postpartum period. Hypercoagulability worsens after delivery as a result of volume depletion, dehydration, and consumption of high-fat food in developing countries during peripartum period.
Physiological changes during pregnancy include increase in red cell mass and plasma volume with dilutional anemia. The plasma levels of protein S decline progressively during pregnancy while protein C levels remain unchanged. Antithrombin III levels are stable during pregnancy and rise after delivery. Acquired protein C resistance, high factor VIII, and factor V activity are found during pregnancy. There is also increase in D-dimer levels in late pregnancy due to increased thrombin generation and fibrinolysis. Coagulation factors may be elevated during postpartum state up to 12 weeks, hence may not be reliable indicators of venous thrombosis. These changes during pregnancy and postpartum period confer a higher risk of venous thrombosis.
Increasing maternal age, increased duration of hospital stay, cesarean delivery, instrument-assisted delivery, hypertension, infections, and excessive vomiting in pregnancy increase the risk of developing CVT. Cultural practices such as water deprivation, unhygienic home deliveries, anemia, and malnutrition have been proposed to promote pregnancy-related CVT in India. In the recent years with improving health-care system, there is a reduction in the pregnancy-related CVT. The occurrence of pregnancy-related venous thrombosis has been reported to be 9.8% to 17% of all the CVT ,,, In the present study, pregnancy-related CVT was 17.03% of the CVT patients.
The risk factors among nonpregnant CVT patients are multifactorial and included anemia, use of oral contraceptives, genetically determined prothrombotic states, dehydration, hyperhomocysteinemia, infection, trauma, carcinoma, and systemic causes such as renal failure and hematological disorders. Risk factors among nonpregnant CVT patients were severe anemia, consumption of oral contraceptives, protein C/S deficiency, hyperhomocysteinemia, psoriasis, and malignancy. Pregnancy-related CVT patients were younger, similar to published studies. The duration of symptoms was longer among nonpregnant women. Shorter duration of symptoms in the postpartum CVT is likely to be due to rapid evolution of the thrombosis and its resultant consequences.
Most common presentation of CVT is due to raised intracranial pressure secondary to venous sinus occlusion. Focal neurological deficits and seizures occur due to parenchymal involvement. In the present study, the incidence of raised intracranial pressure, seizures, and focal neurological deficits were similar to earlier studies. Although the incidence did not differ between the two groups in our study, partial onset seizures were frequent in nonpregnant CVT group. There was no difference between the two groups in relation to neurological symptoms, level of consciousness, and focal deficits. Eight among 11 patients who underwent decompression survived and three succumbed. In our study, four women underwent craniectomy among them one died probably due to delayed surgery. One patient had minimal residual disability and had a successful second pregnancy and delivery.
Lower limb and pelvic vein thrombosis incidence was reported as 2.5% during follow-up. Five women (3.33%) had venous thrombosis of lower limbs during hospital stay (two in pregnant group and three in nonpregnant group). None of our patients had symptoms of pulmonary embolism. Recurrent CVT is reported to occur in 2%–5%., In our series, three women had recurrent CVT (one in pregnant group and two in nonpregnant group). Twelve women (8%) had a recurrence of seizures after tapering of antiepileptic medications (four in pregnant group and eight in nonpregnant group) which is lower compared to published literature. All the patients with recurrent seizures had hemorrhagic infarctions.
The overall mortality in CVT is reported to be 3%–15%. Coutinho et al. documented complete recovery in 81% of women, dependency or death in 12%, and mortality in 6% of women with CVT. Higher mortality (32.6% versus 9.7%) was reported in nonpregnancy-related CVT group compared to pregnancy-related venous thrombosis. In our study, 89.33% of our patients had total recovery and mortality was 10.67%. Poorer outcome in these patients probably is related to large cerebral infarction, multiple sinus involvement, poor Glasgow coma score, and presence of severe anemia.
| Conclusions|| |
In the present study of women with CVT, proportion of pregnancy-related CVT was lower than nonpregnancy-related CVT. Anemia was the most common risk factor in both groups and other factors in the nonpregnant CVT patients were oral contraceptives, hyperhomocysteinemia, and protein C/S deficiency. There was no difference in clinical profile and outcome except in the younger age of onset in pregnancy group and seizure type. Mortality was marginally higher in pregnancy group.
Complete workup for prothrombotic states could not be done in a systematic manner.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y, Haapaniemi E, et al.
Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: The Helsinki young stroke registry. Stroke 2009;40:1195-203.
Srinivasan K. Ischemic cerebrovascular disease in the young. Two common causes in India. Stroke 1984;15:733-5.
Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-70.
Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: A cross-sectional study. Stroke 2012;43:3375-7.
Banerjee AK, Varma M, Vasista RK, Chopra JS. Cerebrovascular disease in North-West India: A study of necropsy material. J Neurol Neurosurg Psychiatry 1989;52:512-5.
Lipska K, Sylaja PN, Sarma PS, Thankappan KR, Kutty VR, Vasan RS, et al.
Risk factors for acute ischaemic stroke in young adults in South India. J Neurol Neurosurg Psychiatry 2007;78:959-63.
Nagaraja D, Sarma GR. Treatment of cerebral sinus/venous thrombosis. Neurol India 2002;50:114-6.
] [Full text]
Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke 2000;31:1274-82.
Saadatnia M, Mousavi SA, Haghighi S, Aminorroaya A. Cerebral vein and sinus thrombosis in Isfahan-Iran: A changing profile. Can J Neurol Sci 2004;31:474-7.
Martinelli I, Battaglioli T, Pedotti P, Cattaneo M, Mannucci PM. Hyperhomocysteinemia in cerebral vein thrombosis. Blood 2003;102:1363-6.
Narayan D, Kaul S, Ravishankar K, Suryaprabha T, Bandaru VC, Mridula KR, et al.
Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral sinus venous thrombosis: Insights from Nizam's Institute Venous Stroke Registry, Hyderabad (India). Neurol India 2012;60:154-9. [Full text]
de Bruijn SF, de Haan RJ, Stam J. Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients. For the Cerebral Venous Sinus Thrombosis Study Group. J Neurol Neurosurg Psychiatry 2001;70:105-8.
Cantú C, Barinagarrementeria F. Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 1993;24:1880-4.
Wasay M, Saadatnia M, Venketasubramanian N, Kaul S, Menon B, Gunaratne P, et al.
Predictors of cerebral venous thrombosis and arterial ischemic stroke in young Asian women. J Stroke Cerebrovasc Dis 2012;21:689-94.
Einhäupl K, Bousser MG, de Bruijn SF, Ferro JM, Martinelli I, Masuhr F, et al.
EFNS guideline on the treatment of cerebral venous and sinus thrombosis. Eur J Neurol 2006;13:553-9.
Nagaraja D, Taly AB, Haridas VT, Veerendrakumar M, Subbakrishna DK. Heparin in haemorrhagic infarction in cerebral venous sinus thrombosis. J Assoc Physicians India 1998;46:706-7.
Nagaraja D, Haridas T, Taly AB, Veerendrakumar M, SubbuKrishna DK. Puerperal cerebral venous thrombosis: Therapeutic benefit of low dose heparin. Neurol India 1999;47:43-6.
] [Full text]
Bansal BC, Gupta RR, Prakash C. Stroke during pregnancy and puerperium in young females below the age of 40 years as a result of cerebral venous/venous sinus thrombosis. Jpn Heart J 1980;21:171-83.
Pabinger I, Grafenhofer H, Kyrle PA, Quehenberger P, Mannhalter C, Lechner K, et al.
Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002;100:1060-2.
Ruíz-Sandoval JL, Cantú C, Barinagarrementeria F. Intracerebral hemorrhage in young people: Analysis of risk factors, location, causes, and prognosis. Stroke 1999;30:537-41.
Davie CA, O'Brien P. Stroke and pregnancy. J Neurol Neurosurg Psychiatry 2008;79:240-5.
Chandra S, Tripathi AK, Mishra S, Amzarul M, Vaish AK. Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus 2012;28:144-6.
Aaron S, Alexander M, Maya T, Mathew V, Goel M, Nair SC, et al
. Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis. Neurol India 2010;58:555-9.
] [Full text]
Biousse V, Bousser MG. Cerebral venous thrombosis. Neurologist 1999;5:326-49.
Lath R, Kumar S, Reddy R, Boola GR, Ray A, Prabhakar S, et al
. Decompressive surgery for severe cerebral venous sinus thrombosis. Neurol India 2010;58:392-7.
] [Full text]
Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Cantú C, Bousser MG, et al
. Cerebral venous and sinus thrombosis in women. Stroke 2009;40:2356-61.
[Table 1], [Table 2], [Table 3]