- Recognizing cerebral venous thrombosis
- Differentiation of Transverse Sinus Thrombosis From Congenitally Atretic Cerebral Transverse Sinus With CT
- Patient Inclusion
- Sources of Funding
- Cerebral Venous Thrombosis (CVT): Symptoms and Treatment
- How to Spot and Treat Cerebral Venous Sinus Thrombosis
- Explore This Issue
- Natural Progression
- Case Resolution
Recognizing cerebral venous thrombosis
A cerebral venous thrombosis (CVT) is a rare form of stroke. It takes place when a blood clot is formed in the cerebral veins (small veins in the brain that collect blood) and in the dural venous sinuses (the large veins in which blood is drained from the cerebral veins).
The blood clot leads to an obstruction of the blood flow, which causes inflammation and damage to the brain tissue. The blood clot can be induced by infections (ear, mouth, face or neck), clotting disorders, oral contraceptive therapy or some drugs (such as tamoxifen or chemotherapy).
It can also occur during pregnancy and postpartum (or postnatal) period. However, sometimes the underlying cause is unknown.
Cerebral venous thrombosis is also known as:
- Cerebral vein thrombosis
- Cerebral venous and sinus thrombosis
- Cerebral venous sinus thrombosis (CVST)
- Cerebral sinovenous thrombosis (CSVT)
- Sinus and cerebral vein thrombosis
- Cerebral vein and dural sinus thrombosis
- Cortical cerebral venous thrombosis
According to a scientific statement from the American Heart Association and the American Stroke Association, cerebral venous thrombosis mainly affects young adults and children, and represents only 0.5 to 1% of all strokes. Nevertheless, it is still a significant cause of death and disability, and early detection can improve the outcome in most cases.
The American organization Johns Hopkins Medicine reports that CVT affects around 5 1 million people each year.
It is slightly more frequent in women, especially at the age of 20 to 35, as it is common for women to use the birth control pill, undergo pregnancy or be in the postnatal period at this age.
Newborns have a higher risk of suffering this type of stroke during their first month. In general, approximately 3 300,000 people under the age of 18 will have a stroke.
Even if it is a rare condition, it is potentially devastating. Therefore, it is important to know how to identify the signs and symptoms, in order to increase your chances of an early recovery.
Symptoms of a cerebral venous thrombosis vary depending on the thrombosis location, time since onset of the stroke and other related complications, such as brain bleeding (cerebral hemorrhage) or increased pressure in the brain (intracranial hypertension).
However, the most common symptom is a severe headache: usually patients refer to it as the worst headache they have ever had, typically described as diffuse and often progresses in severity over days to weeks.
It can appear suddenly, or develop over a few hours or days and may be the only symptom, presenting a significant diagnostic challenge.
Other symptoms usually include:
- Blurred vision
Signs and symptoms of CVT may vary depending on the location of the clot. Severe cases of cerebral venous thrombosis are also associated with stroke- signs and symptoms such as:
- Difficulty in speaking or understanding speech
- Paralysis, numbness and/or weakness, especially on one side of the body
- Fainting or loss of consciousness
- Problems with mobility
- Decreased level of alertness
- Pulsatile tinnitus (ringing in the ears)
- Unilateral hearing loss
- Delay in development in children
- Altered state of consciousness
- Scalp swelling and distended scalp veins
- Loss of vision
An extensive blood clot may ultimately lead to coma and death. In the past, most patients with CVT did not survive, and it was therefore considered a serious condition.
However, recent research has shown that the mortality rate of cerebral venous thrombosis has decreased over time, probably due to changes in risk factors, better diagnosis and improved treatment. Fortunately, patients with this disease currently show a good outcome in most cases.
Although patients can still have some headaches and seizures for a period of time, almost 80% of patients recover completely (data obtained from the University of Michigan Health System (UMHS).
The wide range of signs and symptoms is a challenge for both doctors and patients, so you must pay special attention if you recognize one of them. If this is the case, you must call the emergency telephone number immediately, as early treatment could improve your recovery.
Differentiation of Transverse Sinus Thrombosis From Congenitally Atretic Cerebral Transverse Sinus With CT
Thrombosis of the cerebral dural venous sinuses is an uncommon but potentially devastating cause of stroke, which has a predilection for women and the young. It occurs in 3 to 4 people per 1 000 000 population, and an estimated 86% of cases involve the transverse sinuses.
1 The diagnosis of transverse sinus venous thrombosis, however, can be difficult to make given its nonspecific clinical signs and the lack of specificity of MR venograms (MRVs) alone.
2 Autopsy and cerebral angiographic studies have consistently shown that a dominant transverse sinus is common, most commonly on the left.2–4 Only 37% to 50% of patients studied have equally sized transverse sinuses.
2–4 In 1 study, 22% of normal subjects had 1 transverse sinus, which did not opacify at all by conventional angiography.3 Therefore, it is not uncommon to see dropout on MRV of 1 transverse sinus, suggesting occlusion due to thrombus, when congenital atresia may instead exist.
Standard noncontrast CT of the brain can give a clue to whether a transverse sinus is occluded by clot. Narrowing of the sigmoid plate notch on CT can suggest congenital narrowing or sinus atresia as opposed to clot as a cause of decreased flow.
5 This asymmetry in sigmoid plate notches, however, has not been studied in any systematic way as a method to differentiate atretic from occluded sinuses.
We hypothesized that, among individuals with absent signal of a transverse sinus on MRV, comparison of the sigmoid notches on noncontrast brain CT can differentiate transverse sinus clot from a congenitally atretic sinus.
The Johns Hopkins Institutional Review Board approved this study.
Subjects were selected either a sequential review of MRV scans from stroke inpatients or selection by International Classification of Diseases, 9thRevision codes after hospital discharge from Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center from 2007 to 2010.
The final data set consisted of individuals with absent signal on MRV in 1 of the transverse sinuses. We oversampled individuals with transverse sinus clot, so our sample does not represent the true prevalence of transverse sinus thrombosis.
A total of 53 patients were included in the study. A blinded investigator (R.H.L.
) reviewed all available historical, diagnostic, and imaging studies and then classified each subject as either having clot in the transverse sinus (n=11) or having an atretic sinus (n=43).
This complete data review was considered the gold standard for adjudicating transverse sinus clot versus congenital sinus atresia.
A “positive” sigmoid notch sign was defined as an asymmetrically smaller sigmoid notch on the side of MRV loss of transverse sinus signal (Figure).
A single slice of each subject's brain CT scan at the level of the sigmoid plate with clear visualization of the bilateral sigmoid notches through which the transverse sinus runs (Figure) was selected and marked with the side of abnormal transverse sinus on MRV.
The blinded neurologists adjudicated each CT as having a negative (consistent with transverse sinus thrombosis) or positive sigmoid notch sign (sigmoid sinus congenital atresia) on the side of MRV signal dropout.
The blinded reviewers were not given access to any other imaging studies, and their assessment was entirely due to visual estimation from the image, but they could ask for an additional CT slice from the same scan if needed. In the case of disagreement, a consensus rating was made by the reviewers.
Figure. Both Subjects A and B had right transverse sinus MRV dropout. Subject A has a negative sigmoid notch sign suggesting right transverse sinus clot. Subject B has a positive sigmoid notch sign (the right notch is smaller than the left) suggesting right atretic sinus. Arrows identify the sigmoid notches. MRV indicates MR venography.
Interrater reliability was calculated using a κ statistic. Sensitivity and specificity were calculated relative to the gold standard as were false-positive and -negative rates. Secondary analyses repeated analyses for right versus left signal dropout.
Of the 53 subjects, 11 had venous clot and 42 had an atretic sinus by the gold standard. Of the 11 subjects with clot, 1 subject had a right-sided clot and an atretic left transverse sinus.
Another subject had both atresia and clot on the left. Seven of the 11 subjects with clot had right-sided clot. Overall MRV signal dropout was identified on the right for 19 (35.
9%) of the 53 patients and the majority of atretic sinuses occurred on the left.
Each blinded neurologist had a sensitivity of 91% (detecting 10 of 11 clots a negative sigmoid notch sign). Specificity was 71% for 1 reviewer (identifying a positive sign in 30 of 42 atretic sinus cases) and 81% for the other (a positive sign in 34 of 42 cases). Cohen κ was 0.60. The consensus sensitivity was 91% and specificity was 86%.
The false-positive rate was 14.3% (proportion of individuals with atretic sinus who had a negative sigmoid notch sign, suggesting presence of a thrombus), and the false-negative rate was 9.1% (Table 1). Sensitivity and specificity improved to 100% and 92%, respectively, in the 19 cases in which MRV dropout was on the right side (Table 2).
|Transverse sinus thrombosis||1||10||11||9.1% (false–negative rate)||−9.2% to 27.3%||90.9% (sensitivity)||72.7%–109.2%|
|Congenitally atretic sinus||36||6||42||85.7% (specificity)||74.7%–96.7%||14.3% (false-positive rate)||3.3%–25.3%|
|MRV dropout left side (N=34)||75%||83%|
|MRV dropout right side (N=19)||100%||92%|
The diagnosis of cerebral sinus thrombosis can be difficult given its nonspecific clinical presentation. Due to the potential seriousness of this diagnosis, a screening tool that is both rapid and highly sensitive to the presence of venous clot is needed.
MRV flow studies often overcall occlusion, and a congenitally atretic transverse sinus may appear identical in appearance to a transverse sinus thrombosis.
Four-vessel cerebral angiography, the current gold standard in diagnosing thrombosis, can be time-consuming and carries potential risk.
The sigmoid notch sign, as described in this study, is a highly sensitive and specific measure of differentiating clot from atretic sinus when drop the transverse sinus is visualized on MRV.
With the addition of the sigmoid notch sign on CT (which was ly already obtained, so is cost-effective) to the rest of the clinical presentation, an immediate decision can be made as to whether this is ly a clot requiring anticoagulation or simply an atretic sinus.
This technique can be used by specialist or nonspecialist neurologists.
This study is limited by our relatively small sample size, because true transverse clot thrombosis is a relatively rare finding. In addition, our gold standard was review of all available records but in the majority of cases did not include cerebral angiography.
However, we are confident that our final gold standard classifications were accurate because they were the entire set of brain MR images and medical records available. In addition, although the number of patients with thrombosis was especially low, the sample used to calculate specificity is larger with a narrower CI.
This allows a clinician to “rule out” a clot with fairly high confidence if there is an asymmetrically smaller sigmoid notch on the same side as absent signal on an MRV.
The sigmoid notch sign, a simple and quick tool, is highly sensitive and specific. This makes it potentially useful to neurologists, in conjunction with clinical judgment, for diagnosis of transverse sinus venous thrombosis when drop flow is seen on MRV. Further studies are needed to evaluate its use prospectively and in comparison with conventional angiography.
Sources of Funding
Dr Gottesman is supported by the National Institute on Aging (National Institute of Neurological Disorders and Stroke)RO1 AG040282-01.
- 1. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005; 352:1791–1798.CrossrefMedlineGoogle Scholar
- 2. Leach JL, Fortuna RB, Jones BV, Shipley G. Imaging of cerebral venous thrombosis: current techniques, spectrum of findings, and diagnostic pitfalls. Radiographics. 2006; 26:S19–S43.CrossrefMedlineGoogle Scholar
- 3. Morris L. Angiography of the superior sagittal and transverse sinuses. Br J Radiol. 1960; 33:606–613.CrossrefMedlineGoogle Scholar
- 4. Oka K, Rhonton LA, Barry M, Rodrequez R. Microsurgical anatomy of the superficial veins of the cerebrum. Neurosurgery. 1985; 17:711–748.CrossrefMedlineGoogle Scholar
- 5. Connor EJ, Siddiqui MA, Stewart VR, O'Flynn EAM. The relationship of transverse sinus stenosis to bony groove dimensions provides an insight into the aetiology of idiopathic intracranial hypertension. Neuroradiology. 2008; 50:999–1004.CrossrefMedlineGoogle Scholar
Cerebral Venous Thrombosis (CVT): Symptoms and Treatment
Cerebral venous thrombosis (CVT) is a blood clot of a cerebral vein in the brain. This vein is responsible for draining blood from the brain. If blood collects in this vein, it will begin to leak into brain tissues and cause a hemorrhage or severe brain swelling.
When caught early, CVT can be treated without causing life-threatening complications.
Blood clots are more ly to occur in your body when there is an interruption in regular blood flow. While CVT is an uncommon condition, it can be triggered by a number of factors.
Some of the most common risk factors include:
Less common risk factors for CVT include pregnancy and other blood clotting disorders. Both conditions can make blood clot more easily, affecting proper blood flow throughout the body and the brain.
In infants, the most common cause of CVT is infection, specifically in the ear.
In some cases of CVT, the cause is unknown.
If left untreated, CVT can have life-threatening consequences.
When diagnosing cerebral venous thrombosis, doctors will evaluate the symptoms you experience and will also take into account your medical and family history. However, a final diagnosis depends on checking the blood circulation in your brain. To check the blood flow, doctors can use imaging tests to detect blood clots and swelling.
A doctor can misdiagnose a CVT if they use the wrong test. While there are a number of imaging tests available, some aren’t as helpful in diagnosing this condition, such as a simple X-ray of the skull.
The two best imaging tests to help detect CVT are:
- MRI venogram. An MRI venogram, also referred to as an MRV, is an imaging test that produces images of the blood vessels in the head and neck area. It can help to evaluate blood circulation, irregularities, strokes, or brain bleeds. During this MRI, doctors will inject a special dye into your bloodstream to display blood flow and to help determine if blood is clotting in order to diagnose thrombosis. This test is typically used to clarify images from a CT scan.
- CT venogram. CT scans use X-ray imaging to show your doctor your bones and arterial vessels. Combined with a venogram, doctors will inject a dye into the veins to produce images of blood circulation and help detect blood clotting.
CVT treatment options depend on the severity of the condition. Primary treatment recommendations focus on preventing or dissolving blood clots in the brain.
Doctors may prescribe anticoagulants, or blood thinners, to help prevent blood clotting and any further growth of the clot. The most commonly prescribed drug is heparin, and it’s injected directly into the veins or under the skin.
Once your doctor thinks you’re stable, they may recommend an oral blood thinner warfarin as a periodic treatment. This can help to prevent recurrent blood clots, specifically if you have a diagnosed blood clotting disorder.
Other than helping to prevent blood clots, doctors will also address symptoms of CVT. If you’ve experienced a seizure from this condition, doctors will prescribe anti-seizure medication to help control the episode. Similarly, if you begin to experience stroke- symptoms, a doctor will admit you into a stroke or intensive care unit.
In all cases of CVT, doctors will monitor brain activity. Follow-up venograms and imaging tests are recommended to assess thrombosis and to ensure there are no additional clots.
Follow-ups are also crucial to make sure you don’t develop clotting disorders, tumors, or other complications from cerebral venous thrombosis.
The doctors will ly run additional blood tests to see if you have any clotting disorders that may have increased your risk of developing CVT.
In more severe cases of cerebral venous thrombosis, doctors may recommend surgery to remove the blood clot, or thrombi, and to fix the blood vessel. This procedure is referred to as thrombectomy. In some thrombectomy procedures, doctors may insert a balloon or similar device to prevent blood vessels from closing.
While uncommon, cerebral venous thrombosis can become a life-threatening condition if left untreated. When caught early, CVT can be treated noninvasively using medication.
If you begin experiencing irregular headaches or corresponding symptoms, notify your doctor immediately.
How to Spot and Treat Cerebral Venous Sinus Thrombosis
We were wrapping up a peaceful shift, as peaceful as it can be for a Level 1 trauma center, when we heard the dreaded overhead page, “Medical alert to red 3.”
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We entered the room to find a 52-year-old female with the chief complaint of posterior headache for one week, migrating, variable in intensity, but constant and associated with nausea.
Well, why was this a medical alert again? The triage nurse added, “Weakness, numbness and tingling to the left upper extremity, onset yesterday morning; dropped tea cup from left hand; slight unsteadiness in left leg, onset yesterday.
” The patient added, “I have numbness around my mouth, and I think my vision is off, but that’s been forever! It’s probably nothing. I don’t want to waste your time.”
Cerebral venous sinus thrombosis (CVST) is a type of stroke in which the venous channels of the brain become thrombosed, resulting in cerebral infarction in the areas corresponding to the thrombosis. CVST is uncommon. However, the epidemiology is difficult to determine.
One consensus opinion indicates that there is approximately one CVST stroke to every 62.5 arterial thrombotic strokes, while another states that CVST constitutes 0.5 percent to 1 percent of all strokes in young or middle-aged adults.
1,2 It is more common in neonates and young persons, with the incidence decreasing as age increases.
3 There is a female predominance, with roughly a 3:1 female-to-male ratio, which is influenced by gender-specific factors such as oral contraceptive use, pregnancy, puerperium, and hormonal replacement therapy. Also, women have a better prognosis when CVST is attributable to those factors.3,4
MRI of the 52-year-old female patient with cerebral venous sinus thrombosis.
Source: Dr. Anumeha Singh
Presentation can vary greatly depending on the location and extent of the thrombosis. It can present just with findings suggesting increased intracranial pressure (eg, idiopathic intracranial hypertension), such as headache, vomiting, papilledema, and visual disturbances.
Cranial nerve involvement may also be present and include such findings as facial weakness; deafness; visual deficits; or oculomotor, abducens, or trochlear nerve palsies with paralysis of extraocular muscles or ptosis.1 Headache is the most common presenting symptom and is usually localized and gradual in onset.
Focal deficits may occur bilaterally, and seizures may occur.3
CVST can also present similarly to encephalopathy with multifocal signs, mental status change, stupor, coma, cognitive dysfunction, frontal lobe syndrome, etc.3
Parenchymal brain lesions depend upon the location and number of occluded sinuses or veins. This can lead to cerebral edema, infarction, or hemorrhagic infarction, which may manifest with motor and sensory deficits, cranial nerve palsy, aphasia, and seizures.3
American Heart Association/American Stroke Association 2011 guidelines recommend cerebral venous imaging in cases of lobar intracerebral hemorrhage of otherwise unclear origin, cerebral infarction that crosses typical arterial boundaries, and clinical features consistent with idiopathic intracranial hypertension.2 MRI plus magnetic resonance venography is considered the most sensitive modality. CT venography can be considered when MRI is unavailable or contraindicated. If diagnosed, screening for prothrombotic conditions is suggested as well. This typically prompts both neurology and hematological evaluation.3,5,6
Approximately 5 percent of patients die during the acute phase (interval from symptom onset to diagnosis fewer than 48 hours).7,8 Predictors of mortality at 30 days are depressed consciousness, altered mental status, thrombosis of the deep venous system, right hemispheric hemorrhage, and posterior fossa lesions.
The primary cause of death is transtentorial herniation. The following are also predictive of poor outcomes: central nervous system infection, malignancy, hemorrhage, Glasgow Coma Scale score less than 9 on admission, age greater than 37 years, and male gender.
Complete recovery is expected in 79 percent of the entire cohort.7
Recanalization occurs in 40 percent to 90 percent of cases, most within four months. The highest rates are in deep cerebral veins and cavernous sinuses.
The lowest rates are seen in the transverse or lateral sinuses.
Recurrence rates for CVST are 2 percent to 4 percent, with increased risk in males, prothrombotic states, thrombophilia, polycythemia, and patients with previous venous thromboembolism.7
The main treatment for CVST is anticoagulation. Unfractionated heparin and low-molecular-weight heparin are most commonly used. Patients will also require long-term anticoagulation with an oral anticoagulant, such as warfarin, with a goal international normalized ratio of 2.5.
Recommendations include treatment for three months in patients whose CVST was due to a transient risk factor, six to 12 months in those with idiopathic CVST or mild thrombophilia (eg, heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII), and indefinitely in those with recurrent CVST or severe thrombophilia (eg, antithrombin, protein C, or protein S deficiency; homozygous factor V Leiden or prothrombin G20210A mutation; antiphospholipid antibodies; or combined prothrombotic conditions). Endovascular mechanical disruption of clots and direct thrombolysis are usually reserved for patients failing anticoagulation. Symptomatic treatment of elevated intracranial pressure and herniation can be approached with traditional methods. There has been no evidence to support glucocorticoid use. Symptomatic and prophylactic usage of antiepileptics are recommended in patients with higher risk of seizure (eg, supratentorial lesion involvement) and seizure on presentation. Valproic acid is commonly used due to fewer drug-to-drug interaction with anticoagulants.7
Our patient was started on a heparin drip of 25,000 units in 500 mL 0.45% NaCl continuous infusion via our low-dose protocol without bolus and admitted to the neurology ICU, where she was bridged to warfarin and discharged five days later.
On the evening of her discharge, the patient developed an acute five- to 10-minute episode of transient left arm stiffening, paresthesias, uncontrolled cramping of her left fingers, and worsening of her left facial droop, which were thought to be focal seizures due to the location of her CVST in combination with a family history of seizure disorder. She was admitted to the neurology service overnight for observation and discharged on levetiracetam 750 mg every 12 hours. At three months postevent, the patient had no recurrence of seizures or stroke- symptoms and remained compliant with her coumadin and levetiracetam.
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Keynote speaker, James Williams, PhD, MHS, serves as the senior director for Global Networks – Medical Evidence, Research, and Innovation at Biogen.
The day also includes a panel discussion featuring: Ellen Mowry, MD Associate Professor of Neurology Johns Hopkins School of Medicine Peter Zandi, PhD, MPH, MH Professor Johns Hopkins Bloomberg School of Public Health Diana Gumas, […]
Posted by: Crystal Williams on: January 24, 2020
Co-Sponsored by the Johns Hopkins & University of Maryland Baltimore Institutes for Clinical & Translational Research To attend, contact Molly Lutz at 410-328-2488 or firstname.lastname@example.org. Links: CATALiST Seminar Series University of Maryland Baltimore Institute for Clinical and Translational Research
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In 2008, Johns Hopkins professor of pediatrics and medicine Neil Goldenberg, MD, PhD (at the time, a faculty member of University of Colorado School of Medicine) submitted an investigator-initiated trial (IIT) award application to the pharmaceutical company that oversaw research and development of the low […]
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There are four award opportunities: Research Education Core Funding for Junior Faculty ($35,000 direct costs) Pilot/Exploratory Studies Core Funding ($30,000 direct costs) Biostatistics Core Development Project Funding ($35,000 direct costs) Biological Mechanisms Development Project Funding ($35.
000 direct costs) Successful applicants will receive salary, research core support, […]
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Posters and exhibits by rare disease groups and researchers. Artwork and tours of the NIH Clinical Center and the National Library of Medicine. Admission is free, and the event is open to the public, including patients, patient advocates, health care providers, researchers, industry representatives and government employees.
In association with Global Genes®, participants are encouraged to wear their favorite […]
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Lili Portilla, director of the NCATS Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, will provide insights to help biotech researchers and entrepreneurs understand intellectual property (IP) protection and navigate the Federal Drug Administration (FDA) regulatory approval pathways, which are steps required for the commercialization of new promising […]
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