A Woman With Worsening Headache and Signs of Stroke: What’s the Cause?
Andrew Henn, DO; Aaron Wolfe, DO; and Vikas Jain, MD
Henn A, Wolfe A, Jain V. A woman with worsening headache and signs of stroke: What’s the cause? Consultant. 2017;57(4):221-224.
A 24-year-old woman presented to the emergency department (ED) after having had a headache for 3 days. She described a constant, gradually worsening headache that was worse when she was recumbent and was improved by nothing. She rated the pain as 7.5 on a 10-point scale. She associated the headache with “out of body” dizziness, diffuse areas of subjective numbness and weakness, and an unstable gait.
The patient denied a recent history of fever, vomiting, syncope, changes in vision, head trauma, or history of similar headaches. She reported a past medical history significant for an emergency cesarean delivery at 26 weeks’ gestation 2 weeks before presentation. Review of her outside medical records revealed that she also had a mutation of MTHFR, which codes for methylenetetrahydrofolate reductase, an enzyme in the pathway for processing homocysteine, and that she had been on enoxaparin prior to delivery but had not been on any anticoagulants since delivery.
On physical examination, the patient was alert and oriented to person, place, and time and was in no acute distress. She was afebrile (temperature, 36.8°C). Cardiac evaluation found her to be mildly tachycardic (heart rate, 120 beats/min) but normotensive (blood pressure, 126/85 mm Hg). Her pupils were equal, round, and reactive to light. Mucous membranes were moist. There was no nuchal rigidity, with Kernig and Brudzinski signs negative for meningitis. Her lungs were clear to auscultation, and abdominal examination findings were normal.
Initial neurologic examination revealed subjective left-sided numbness, normal muscle strength bilaterally, and normal finger-nose-finger and heel-knee-shin test results, but she required significant coaching and reported confusion when asked to perform tests despite receiving visual cues. The patient’s initial National Institutes of Health Stroke Scale (NIHSS) score in the ED was 2 (suggesting a minor stroke), with 1 point scored for mild to moderate aphasia and 1 point scored for mild to moderate sensory loss, but she had dynamic neurologic examination results, developing expressive aphasia, and with symptoms waxing and waning significantly.
Magnetic resonance imaging (MRI)/magnetic resonance venography (MRV) scans were ordered, the results of which are shown in Figures 1-3.
Answer: Cerebral Venous Thrombosis
Computed tomography (CT) scans of the head showed a hyperdense tubular structure perpendicular to the superior sagittal sinus, possibly representing a thrombosed vein, but no acute intracranial hemorrhage (ICH). MRI/MRV scans (Figures 1-3) showed bilateral frontoparietal cytotoxic and vasogenic edema, with thrombosis in the superior sagittal sinus and the superficial cortical veins. The patient received a diagnosis of cerebral venous thrombosis (CVT).
Figure 1. An MRV showed the absence of flow in the superior sagittal sinus and bilateral cortical veins (arrow).
Figure 2. A gradient recalled echo MRI sequence showed prominent abnormally hypointense cortical veins bilaterally near the vertex (arrow), a finding suggestive of thrombosed veins.
Figure 3. A diffusion-weighted MRI showed abnormal hyperintensity in the bilateral frontoparietal lobes (arrows), suggestive of venous infarcts.
A consulting neurologist recommended therapeutic enoxaparin and levetiracetam. In the ED, the neurologist reassessed the patient’s NIHSS score at 8 points—2 points in the right arm motor category, and 1 point for each of the following categories: level of consciousness (LOC) responsiveness, LOC questions, LOC commands, right leg motor, sensory, and language.
Upon admission to the neurointensive care unit, her NIHSS was scored at 10 points—3 points for right arm motor, 2 points for LOC commands, and 1 point in each of the categories of LOC responsiveness, right arm motor, right leg motor, left leg motor, and language. While in the neurointensive care unit, the patient’s electroencephalogram showed moderate diffuse encephalopathy and epileptiform activity.
After 4 days, her NIHSS score had improved to 0, and she was discharged on day 8 on a regimen of antiepileptic medications. She was lost to follow-up 3 months from presentation.
CVT is the formation of a thrombus in the cerebral veins and in the venous sinuses. As a result of the increased use of MRI and increasing clinical awareness, the frequency of CVT diagnosis is increasing.1 CVT is a relatively rare condition with an approximate worldwide incidence of 5 people per million per year,1 and it accounts for 0.5% to 3% of all strokes.2,3
CVT is a multifactorial condition with a female predominance of 3 to 1.2 It is most common in persons younger than age 50 years.3,4 The risk factors include oral contraceptive use, genetic prothrombotic tendencies (eg, factor V Leiden), pregnancy, postpartum, infection, malignancy, and trauma.2 Approximately 80% to 85% of patients who develop CVT have an identifiable risk factor.5
Several different mutations of MTHFR have been identified that cause a variety of clinical manifestations including hyperhomocysteinemia. Hyperhomocysteinemia increases the risk of venous thromboembolic disease but has no clear association with CVT.3,6 Some authors suggest that a MTHFR mutation is not an independent risk factor for thromboembolic complications during pregnancy.7 Further studies of genetic testing for a MTHFR mutation in pregnant and postpartum women with CVT are needed to determine the clinical significance of the mutation.
CVT is a difficult diagnosis to make, partly because of its varied presenting symptoms, and also because of its relative rarity; therefore, clinicians must maintain a high level of suspicion for CVT. The most common complaint of a patient with CVT is headache (> 90%), but other symptoms can include nausea, vomiting, visual disturbance, papilledema, focal or generalized seizures (40%), focal neurologic deficit, altered mental status, and coma.4,5 This variety of symptoms is a result of multiple pathologic processes occurring simultaneously, which are a result of the location of the thrombus. Thrombosis can occur in the cerebral veins and in the venous sinuses. A thrombus in the cerebral veins causes obstruction of the normal venous drainage, leading to venous congestion, which causes edema, ischemia/infarction, and hemorrhage. A thrombus in the venous sinuses causes elevated intracranial pressure by impairing drainage and absorption of cerebrospinal fluid.2 ICH is found at presentation in 30% to 40% of patients with CVT.3
Neuroimaging is the only way to definitively diagnose CVT, but other diagnostic considerations are worth mentioning. The usefulness of a D-dimer test in CVT is similar to when it is used for pulmonary embolism and deep vein thrombosis, if one has a high clinical suspicion; a negative D-dimer test result does not rule out CVT.3 Lumbar puncture may be done in the ED, especially if there is a concern for subarachnoid hemorrhage or meningitis. A lumbar puncture most commonly will show an elevated opening pressure, but there are no specific cerebrospinal fluid findings to diagnose CVT.3
CT of the head is often the initial test ordered in the ED because it is readily available. Unfortunately, only 40% to 50% of CT scans will have abnormalities in cases of CVT.3,4 The preferred method for diagnosis is MRI/MRV, although CT venography is a good option for patients with a contraindication to MRI, such as those with a pacemaker.
The primary treatment is anticoagulation, which can be a very uncomfortable decision given the high incidence of associated ICH. However, studies have shown that patients treated with heparin or enoxaparin had an absolute risk reduction of 13% for death or dependence compared with placebo.8 Furthermore, no new symptomatic ICHs occurred in the anticoagulation group, while the placebo group had further thrombotic complications including one death from pulmonary embolism.8
If symptoms continue to worsen, or the patient shows signs of brain herniation, more drastic options such as thrombolytic therapy or decompressive hemicraniectomy have been attempted, but limited data are available regarding these options.
CVT is a relatively rare diagnosis but is one that must be considered in the appropriate clinical context. This case illustrates why it is essential to consider a broad differential diagnosis and maintain a high index of suspicion. It would have been easy to discount this patient’s symptoms or attribute them to complex migraine, considering that she was a young and otherwise healthy patient with vague symptoms and no objective findings on examination. Nevertheless, patients with CVT are very sick and have the potential to decompensate quickly, so once the diagnosis is made, timely initiation of treatment and admission to a high level of care is essential. Starting anticoagulation in a patient with ICH may be uncomfortable for the treating clinician and should be done under the guidance of the consulting service. Treating the underlying hypercoagulable state is the key to preventing further thromboembolic complications in cases of CVT.
Andrew Henn, DO, is in the Emergency Medicine Residency Program at Case Western Reserve University School of Medicine, MetroHealth Medical Center, in Cleveland, Ohio.
Aaron Wolfe, DO, is an assistant clinical professor and is the codirector of Emergency Medicine Simulation at Case Western Reserve University School of Medicine, MetroHealth Medical Center, in Cleveland, Ohio.
Vikas Jain, MD, is an assistant clinical professor in the Department of Radiology at Case Western Reserve University School of Medicine, MetroHealth Medical Center, in Cleveland, Ohio.
- Ferro JM, Canhão P. Etiology, clinical features, and diagnosis of cerebral venous thrombosis. UpToDate. http://www.uptodate.com/contents/etiology-clinical-features-and-diagnosis-of-cerebral-venous-thrombosis. Updated December 13, 2016. Accessed April 3, 2017.
- Alvis-Miranda HR, Castellar-Leones SM, Alcala-Cerra G, Moscote-Salazar LR. Cerebral sinus venous thrombosis. J Neurosci Rural Pract. 2013;4(4):427-438.
- Saposnik G, Barinagarrementeria F, Brown RD Jr, et al; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(4):1158-1192.
- Fischer C, Goldstein J, Edlow J. Cerebral venous sinus thrombosis in the emergency department: retrospective analysis of 17 cases and review of the literature. J Emerg Med. 2010;38(2):140-147.
- Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005;352(17):1791-1798.
- Ünlü Y, Keleş S, Becit N, Koçoğulları CU, Koçak H, Bakan E. Hyperhomocysteinaemia as a risk factor for deep-vein thrombosis. Eur J Vasc Endovasc Surg. 2005;30(3):315-318.
- Ziakas PD, Poulou LS, Pavlou M, Zintzaras E. Thrombophilia and venous thromboembolism in pregnancy: a meta-analysis of genetic risk. Eur J Obstet Gynecol Reprod Biol. 2015;191:106-111.
- Coutinho J, de Bruijn SFTM, deVeber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev. 2011;(8):CD002005. doi:10.1002/14651858.CD002005.pub2