Authors: Morolayo Ilori, Saachi Mittal, Mousa Eissa
Categories: Article, Cerebral vein sinus thrombosis, First trimester of pregnancy, Thrombosis in pregnancy, Cerebral venous thrombosis, Anticoagulation in pregnancy, Severe headache
Source: Case Reports in Women's Health
Authors: Morolayo Ilori, Saachi Mittal, Mousa Eissa
Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening cause of stroke, with increased incidence in pregnancy due to hypercoagulability, particularly during the third trimester and the postpartum period. First-trimester presentations are exceedingly rare. A 37-year-old woman, gravida 2, para 0, at 7 weeks of gestation, presented with severe, progressive headache, nausea, and vomiting. Her obstetric history was significant for intrauterine fetal demise (IUFD) at 22 weeks of gestation. Neurologic examination was nonfocal. Computed tomography venography (CTV), performed because magnetic resonance imaging (MRI) was contraindicated, demonstrated thrombosis of the left transverse and sigmoid sinuses extending into the left internal jugular vein. Therapeutic low-molecular-weight heparin resulted in clinical improvement. Evaluation during pregnancy was negative for acquired and inherited thrombophilias. The patient underwent an uncomplicated suction dilation and curettage and remained clinically stable on anticoagulation. This case illustrates the diagnostic challenges of CVST in early pregnancy and highlights CTV as a reliable alternative to MRI. Additionally, this case is notable for CVST presenting in the first trimester, a rare occurrence, with few cases reported in the literature. The combination of early pregnancy, prior IUFD without a known thrombophilia represents a unique risk factor constellation for CVST. Clinicians should maintain a high index of suspicion for CVST in patients presenting with severe, atypical headache in the first trimester, to enable timely diagnosis, anticoagulation, and optimized maternal outcomes.
Cerebral venous sinus thrombosis (CVST) accounts for 0.5–1 % of all strokes and is characterized by thrombosis of the dural venous sinuses and/or cortical veins [1]. It can be life-threatening and requires rapid intervention to prevent morbidity and mortality, especially in at-risk patients. Women are three times more likely than men to be diagnosed with CVST, and 70–80 % of women with the condition are of reproductive age [1]. Pregnancy and the postpartum period are recognized risk factors due to a physiologic hypercoagulable state marked by increased procoagulant factors, decreased anticoagulant activity, and reduced fibrinolysis [2]. These changes, alongside venous stasis and vascular injury, undoubtedly predispose pregnant women to thrombotic complications.
The estimated incidence of CVST in pregnancy ranges from 1 to 12 cases per 100,000 deliveries, with 70–80 % of cases occurring in the third trimester or the postpartum period [3]. While outcomes have improved with earlier recognition and anticoagulation therapy, mortality remains between 5 % and 30 % in pregnancy-related cases [4].
Intrauterine fetal demise (IUFD) is defined by the American College of Obstetrics and Gynecology (ACOG) as the death of a fetus at or after 20 weeks of gestation [5]. Inherited and acquired thrombophilias are risk factors for both IUFD and CVST. Inherited conditions include factor V Leiden mutation, prothrombin 20210 A mutation, and anticoagulant deficiencies. Antiphospholipid syndrome, an acquired thrombophilia, has been strongly associated with IUFD [6]. Therefore, a history of IUFD may represent an underlying prothrombotic pathology that increases the risk for cerebrovascular complications in the already hypercoagulable state of pregnancy.
Several case reports have described CVST in pregnancy; however, most have occurred in patients in the second or third trimester of pregnancy or the early postpartum period (Table 1). There are few reports of CVST in early pregnancy in the context of a history of IUFD, as in the present case. This report highlights the intersection between pregnancy-related hypercoagulability, adverse pregnancy outcomes, and the incidence of cerebrovascular complications.Table 1Similar case reports of cerebral venous sinus thrombosis in pregnancy.Table 1Author / yearGestational agePresentationTreatmentZhang et al., 2025 [7]Early pregnancy (post-spontaneous abortion)Headache + vomitingMechanical thrombectomy and urokinaseShimizu et al., 2022 [8]8 weeksHeadache + seizuresThrombectomy with aspiration catheter + stent retrieverZhou et al., 2022 [9]Early 1st trimester (∼ 8 weeks)Persistent headache, vomitingTwo stent retrieversMahmoud et al., 2024 [10]10 weeksPersistent headache, nausea/vomiting, hemiplegiaLow-molecular-weight heparin anticoagulation
A 37-year-old woman, gravida 2, para 0, at 7 weeks of gestation presented to the emergency department (ED) with a chief complaint of severe headache. She described a two-day history of progressively worsening and pulsatile pain localized to the left frontal, retro-orbital, and occipital regions. The headache was associated with persistent nausea, vomiting, and inability to tolerate oral intake. She reported partial improvement of symptoms when standing upright and worsening in the supine position. The headache was refractory to acetaminophen. She denied any history of head trauma, falls, vision changes, shortness of breath, chest pain, extremity numbness, tingling, or weakness. The patient reported no personal history of venous thromboembolism (VTE) or stroke. She denied heavy menstrual bleeding, the use of assisted reproductive technology, and a family history of bleeding disorders. Her family history was notable for a stroke in her biological mother.
The patient's obstetric history was notable for an IUFD at 22 weeks and 3 days two years before her presentation to the ED for headache. That earlier pregnancy had been complicated by a finding of short cervix at 20 weeks of gestation, for which the patient had been treated with vaginal progesterone. During routine cervical length surveillance ultrasound, fetal demise was noted. She underwent induction of labor with subsequent vaginal delivery. During the labor and delivery (L&D) admission, the patient was diagnosed with gestational hypertension. Placental pathology from that pregnancy demonstrated a three-vessel cord with recent and remote placental infarcts and associated central hematomas, which may be explained by recently diagnosed gestational hypertension or an underlying thrombotic etiology. The patient had declined fetal autopsy and cytogenetic analysis at that time.
Based on ACOG's clinical criteria for diagnosis of antiphospholipid syndrome (APLS) following loss of a morphologically normal fetus, an APLS workup was completed and was negative [11]. Although the inherited thrombophilia workup is not recommended by ACOG for IUFD, the patient underwent a thrombophilia workup for the IUFD pregnancy during the L&D admission, and prothrombin (factor II) activity was elevated at 155 % (N = 108–144 %), possibly a false positive due to pregnancy.
Upon presentation to the ED, the patient's vital signs were stable and neurological examination demonstrated no focal neurologic deficits. Laboratory evaluation was unremarkable. Brain computed tomography venography (CTV) with contrast was ordered rather than magnetic resonance imaging venography (MRV) because the patient had a metal ankle implant. CTV demonstrated filling defects in the left transverse and sigmoid dural venous sinus and at the jugular foramen, as well as an intraluminal filling defect of the left internal jugular vein below the foramen (Fig. 1). Studies showed no evidence of mass effect, hydrocephalus, vasogenic edema, or intracranial hemorrhage. These findings were diagnostic for left transverse and sigmoid sinus thrombosis with extension into the internal jugular vein.Fig. 1Brain contrast-enhanced computed tomography venography (CTV) at admission. A, Sagittal brain contrast-enhanced CTV showing a thrombosis in the left transverse sinus (arrow). B, Brain contrast-enhanced CTV shows filling defects in the left transverse dural venous sinus (red arrow) compared to patent right transverse dural venous sinus (white arrow). C, Brain contrast-enhanced CTV showing left jugular vein thrombosis just below the skull base (red arrow) compared to patent right jugular vein (white arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)Fig. 1
Following this initial workup, the neurology service was consulted, and the patient was initiated on therapeutic anticoagulation with weight-based low-molecular-weight heparin (LMWH), considered safe during pregnancy due to its lack of placental transfer. A comprehensive inherited and acquired thrombophilia workup to evaluate the etiology of the CVST had negative results for lupus anticoagulant, anticardiolipin antibodies, and factor V Leiden mutation. Anti-β2 glycoprotein antibodies, antithrombin III activity and homocysteine levels were within normal limits. Prothrombin (factor II) activity was elevated at 147 % (N = 108–144 %); however, genetic testing was negative for the prothrombin 20210 A gene mutation.
The patient was admitted to the maternal-fetal medicine service for further management. During her three-day hospitalization, her symptoms improved with antiemetics and a migraine regimen including acetaminophen, prochlorperazine, and metoclopramide. Hematology confirmed the plan for therapeutic LMWH at 1 mg/kg twice daily, with therapeutic levels achieved by hospital day 2. By hospital day 3, her headache and nausea had significantly improved. The patient also expressed concern regarding the continuation of her pregnancy in the context of her thrombotic complications and requested termination. After multidisciplinary counselling, suction dilation and curettage (D&C) was recommended due to increased bleeding risk.
Before the scheduled procedure, the patient re-presented twice to the ED. On the first occasion, she reported nausea and vomiting consistent with early pregnancy. Her symptoms resolved with intravenous fluids, diphenhydramine, famotidine, and metoclopramide. On the second occasion, three days later, she presented with transient left facial numbness and chest pain. The neurological examination was nonfocal without cranial nerve deficits. Repeat CT imaging was negative for hemorrhagic conversion and progression of the CVST. She was discharged with neurology follow-up.
She subsequently underwent an uncomplicated suction D&C. Three weeks later, the patient presented to the ED complaining of left-sided neck pain. Neurological exam was unremarkable for new deficits. Repeat head CTV demonstrated persistent thrombosis of the left internal jugular vein at the skull base and thrombus within the left sigmoid sinus. Clinically, her symptoms continued to improve with symptomatic management, and she remained on therapeutic anticoagulation and was discharged with neurology follow-up.
The differential diagnosis of headache in pregnancy is broad, encompassing primary and secondary causes. Primary headache disorders such as migraine and tension-type headaches are common and often exacerbated during pregnancy. Secondary causes of headache in pregnancy, such as pre-eclampsia/eclampsia, hyperemesis gravidarum, and thrombotic events, warrant careful consideration, particularly those unique to or more prevalent in pregnancy. CVST represents a particularly difficult diagnosis, as it is both rare and associated with a wide spectrum of clinical manifestations. A retrospective study on diagnosis and management of cerebrovascular disorders in pregnancy and puerperium found that presumption of eclampsia as the etiology of focal neurological deficits frequently delayed diagnosis [12]. Furthermore, many of the symptoms of CVST, such as nausea and vomiting, frequently overlap with the normal physiologic changes of pregnancy, which can obscure timely recognition.
The most common presenting symptom of a CVST is a severe, intractable headache, as was the case for the patient presented here [13]. CVST in pregnancy can also present with seizures (50 %), motor weakness (38 %), visual disturbances (27 %), and comatose/obtunded status (45 %) [13,14]. A systematic review of CVST in pregnant patients found that those presenting with headache alone at the time of treatment were nearly four times as likely to achieve favorable long-term outcomes. In contrast, patients treated after neurological decompensation were almost four times as likely to experience adverse clinical deficits [14]. These findings underscore the importance of maintaining CVST in the differential diagnosis of headache in pregnancy, as early recognition can significantly improve outcomes. This case highlights the need for a high index of suspicion and a systematic approach to evaluating headache in pregnancy to ensure timely diagnosis and optimal management.
A CVST diagnosis is confirmed via neuroimaging; MRI/MRV is the gold standard but CT/CTV is a reliable alternative when MRI is contraindicated, as was the case for the present patient. To diagnose CVST, the imaging modality chosen must detect radiological abnormalities such as intraluminal thrombi and differentiate from venous infarcts and intracerebral hemorrhage. Several previous studies have concluded that CTV is equivalent to MRV in the diagnosis of CVST [3,14]. CTV provides a quick and accessible imaging modality that allows for good visualization of the major venous sinuses. However, it is not without its limitations, which include concerns regarding the risk of maternal allergy to iodine contrast, reduced sensitivity for detecting small parenchymal lesions and cortical vein thrombi, and fetal exposure to ionizing radiation. However, according to a 2016 ACOG Committee Opinion, the radiation dose associated with CT imaging exposure is lower than the exposure associated with fetal harm [15]. In this case, CTV was chosen as the diagnostic modality, as its accessibility and demonstrated reliability in detecting CVST provided an evidence-based alternative to MRI/MRV, ultimately facilitating timely diagnosis and initiation of management. Furthermore, this case underscores the clinical utility of CTV as a practical option in pregnancy when MRI/MRV is not feasible.
First-line management of CVST in pregnancy and non-pregnant patients is anticoagulation to prevent thrombosis expansion, facilitate recanalization, and prevent deep vein thrombosis or pulmonary embolism [3]. For non-pregnant patients, LWMH is preferred over unfractionated heparin (UFH); however, both are first-line treatments for CVST [3]. LMWH is the first-line treatment in pregnant and postpartum patients because it has a comparable safety profile, does not cross the placenta, and is not excreted through breastmilk [3]. Current guidelines from the American Society of Hematology recommend treatment throughout the pregnancy with adjusted weight-based dosing and continuation of treatment for a minimum of 6 weeks postpartum [16]. Close outpatient follow-up with maternal-fetal medicine (MFM), vascular neurology, and hematology would be recommended throughout pregnancy. Therapeutic dose LMWH should be discontinued 24 h prior to induction of labor or cesarean section but can be resumed 4–6 h after vaginal delivery or 6–12 h after cesarean section [17].
The prognosis following a CVST is variable in pregnant and postpartum populations; however, patients presenting with headache alone, as in the present case, have good long-term outcomes. Additionally, a systematic review has concluded that the risk of CVST recurrence in future pregnancies is low, and the frequency of spontaneous abortion is comparable to that of pregnancies in patients without a history of CVST [18]. Therefore, pregnancy is not contraindicated in patients who have a history of CVST. However, given the compounding risk that pregnancy poses in patients with a history of CVST, prophylaxis with LMWH during future pregnancies is recommended [3,14,18]. Additionally, in subsequent pregnancies, the present patient would not require aspirin prophylaxis for preeclampsia prevention solely based on her history of IUFD and a previous pregnancy complicated by CVST. These pregnancy complications without other high-risk factors for preeclampsia (e.g., prior history of preeclampsia, chronic hypertension, renal disease, APLS) are not established indications for aspirin prophylaxis according to current guidelines from ACOG, the Society for Maternal-Fetal Medicine, and the US Preventive Services Task Force [19]. Aspirin prophylaxis beginning at 12 weeks of gestation in subsequent pregnancies would only be indicated in cases such as that reported here based on advanced maternal age and ethnicity.
Pregnancy and advanced maternal age were risk factors for CVST present in this case. It is well known that maternal thrombophilia is strongly associated with an increased risk of thromboembolic events. An epidemiologic study of pregnancy-related stroke found that thrombophilia conferred 16 times the odds of maternal stroke (95 % CI 9.4–27.2) [17]. Additionally, APLS is a strongly associated risk factor for IUFD; a review article on thrombophilias and stillbirth detailed a study that found APLS conferred over 3 times the odds of stillbirth (95 % CI 1.62–6.7) [6]. The workups during the IUFD and CVST pregnancies yielded elevated prothrombin (factor II) activity, a finding often associated with the mutation but not diagnostic for a prothrombin 20210 A mutation [20]. Genetic testing for factor V Leiden and prothrombin 20210 A mutations were negative, and APLS antibodies were within normal limits; therefore, the patient did not have a thrombophilia, and the elevated prothrombin (factor II) activity was likely a result of pregnancy state. Overall, this is a unique case that documents a patient notable for pregnancies complicated by IUFD and CVST in the absence of a thrombophilia, a major risk factor for both these complications during pregnancy.
This case illustrates a presentation of CVST in the first trimester of pregnancy in a patient with a history of IUFD. It underscores the importance of maintaining a high index of suspicion for CVST in pregnant patients presenting with severe, intractable headache, particularly during the first trimester, when such presentations are exceedingly rare. Furthermore, this case is proof that timely recognition and management of CVST are critical for favorable outcomes. CTV proved to be a reliable diagnostic alternative when MRI/MRV was contraindicated, and the safety and efficacy of LMWH in early pregnancy were reinforced. The occurrence of a CVST in a patient with a prior IUFD in the absence of an identifiable thrombophilia represents a unique clinical scenario that expands the current understanding of the risk factors for cerebrovascular complications in pregnancy. Continued reporting of such cases will enhance awareness and guide future evaluation, management, and counselling for pregnant patients with similar presentations.
Morolayo Ilori contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript, undertaking the literature review and revising the article critically for important intellectual content.
Saachi Mittal contributed to patient care, conception of the case report, acquiring and interpreting the data, drafting the manuscript, undertaking the literature review and revising the article critically for important intellectual content.
Mousa Eissa contributed to patient care, acquiring and interpreting the data, drafting the manuscript and revising the article critically for important intellectual content.
Written informed consent was obtained from the patient for publication of the case report and accompanying images.
This article was not commissioned and was peer reviewed.
This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
The authors declare that they have no competing interest regarding the publication of this case report.