You are going to see it referred to by many names: Cerebral Venous Thrombosis (CVT), Venous Sinus Thrombosis (VST), Cavernous Sinus Venous Thrombosis (CSVT)–all a little bit different but within a spectrum of disease we will talk about today. This is a rare cause of headache, but if you do not have a disease script for this diagnosis, you will miss it! Without the right treatment the patient will get much worse, but if you do think about it and diagnose it, these patients can do very well.
To talk about CVT, I have brought on new EMCrit Team Member, Casey Albin.
Casey Albin MD
I first discovered Casey on Twitter where she does insanely good neuro-critical care tweetoriols. She is an Assistant Professor of Neurology and Neurosurgery in the Division of Neurocritical Care at Emory University School of Medicine.
Casey Wrote Up Her Own Shownotes (b/c she is Amazing!)
When should I think about Venous Sinus Thrombus?
- Understanding the presenting signs requires knowing a little bit about the pathophysiology
- Remember that the anatomy of the brain is quite different in that the arteries and veins do not run in parallel proximity or supply and drain the same territories.
- When we talk about Cerebral Venous Thrombosis we are talking about to subtypes that often coexist
- Cerebral Vein Thrombosis
- Venous Sinus Thrombosis
- Often the patient has both and colloquially these get interchanged to mean the same thing, but
- Cerebral veins drain the brain parenchymal and there are two systems – superficial and deep
- These are draining the brain parenchyma and are beneath the meninges
- These ultimately drain to venous sinuses which are venous channels that are between the layers of dura.
- The most important of these are the sagittal sinus, transverse sinuses, straight sinus and cavernous sinus.
The reason the distinction matters is the downstream consequence of a vein being occluded is going to be a little different than if a sinus is occluded.
- When a vein is occluded you get a downstream blockage to flow within the parenchymal (remember, that’s where the vein are!)
- this causes a build=up of pressure which leads vasogenic edema
- If the pressure is great enough that you don’t get forward flow à cytotoxic edema and cell death, a so-called “Venous Infarct”
- And if there is still pressure into the dying tissue you can get an intraparenchymal hemorrhage
This can also occur when a Sinus is occluded, but it may not, but if enough of the venous sinuses are occluded you can see a dramatic rise in intracranial pressure. Because not only are you impeding VENOUS drainage but also CSF is ultimately reabsorbed back into the sinuses through the arachnoid granulations.
So, the reason all of the pathophysiology matters is that the patient can have different symptoms depending on what is physiologically happening.
That’s what makes diagnosing this so tricky, because in many ways VST is a mimicker of other pathology and it’s a very rare etiology stroke (<1%)
There is a really broad spectrum of the way this can present.
- International Study on Cerebral Vein and Dural Sinus Thrombosis group found that almost 90% of patients had a headache and about a 1/3 had papilledema
- Headache was most commonly subacute and crescendo type, not sudden onset WHOL although that may happen especially with associated IPH
- Localizing signs like paresis, aphasia, neglect or visual loss was found in about a 3rd of patients
- And coma or obtundation was found in a little more than 10%
So which patients are at highest risk?
- Epidemiologically, I think about this in YOUNG patients without the traditional vascular risk factors
- I am especially concerned for peri-partum women, the first 6 weeks post-partum being the highest risk
- I also think about it for women on OCPs
- In general, there is a female predominance to this disease
- I also think about it in people who are known to have a genetic thrombophilia or in patients who have a condition associated with hypercoagulability like cancer, IBD, antiphospholipid syndrome, or nephrotic syndrome
- A whole separate group our trauma patients, post-operative neurosurgery patients, and patients with head and neck infections in places that abut the sinuses
When we talk about H&N infections it’s important to bring up cavernous sinus thrombosis, which I think of as it’s own subtype of venous thrombosis.
- CST is more commonly associated with severe facial infections like sinusitis, otitis media, or orbital cellulitis.
- Not going to spend a lot of time on this because it’s super rare, but you this needs to cross your mind in a patient that has a severe H&N infection or trauma and presents with ophthalmoplegia and periorbital swelling
In general, for patients with a cerebral venous thrombosis, many are discovered to have more than one risk factor.
And because it’s the COVID-era….
- The risk of COVID disease causing this is at this point still not known, certainly there are case series and it seems to be linked to a higher inflammatory burden, not just mildly symptomatic patients… again likely rare, not impossible
- Vaccine-induced immune thrombotic thrombocytopenia is incredibly rare and reported with adenoviral vector vacccines’s namely the AstraZeneca vaccine and the J&J vaccine.
- It got more attentions in the very rare cases of being associated with the J&J and AstraZeneca COVID vaccines, but it is an INCREDIBLY rare side effect (1:470K for J&J and 1:150k for astrazeneca)
- Patients had high antibody titers to platelet factor 4 polyanion, which is the same as the antibodies found in autoimmune heparin induced thrombocytopenia.
So clinically –
- Diverse range of presentations ranging from headache to coma and focal neurologic findings.
- Have a high index of suspicion for new headaches or focal findings in younger patients without traditional stroke risk factors, especially women.
The other way this tends to get diagnosed is that a patient comes in with new headaches / focal weakness and they get a CT scan. So, I think it’s incredibly important to be familiar with some of the findings that point you in the direction of doing further evaluation for VST.
On a Non-Contrast CT Scan:
- Always on my differential for a cortically based bleed, especially if it’s abutting a sinus either that or a complication of bacterial endocarditis
- Cord sign – hyperdense blood filling one of the sinuses
- Bear Claw or Garlic Clove sign, where it looks like the intraparenchymal hemorrhage is clawing into the brain
- Or vasogenic edema that is dramatically out of proportion to the hemorrhage
- Or crossing arterial territories
- If it appears that the patient has diffuse cerebral edema I also tend to be worried about this if it’s the right patient population
- Finally, and this is super important, can’t miss – if there is bilateral edema / hypodensity of the thalami, that patient needs a VST workup (vein of Galen / straight sinus pathology)
And, because these patients are often treated as a stroke alert, they get contrast for a CTA which may show:
- Empty delta sign
- Or lack of opacification in any of the sinuses
You have suspicion of a cerebral venous thrombosis – how to confirm?
- Couple ways:
- CTV = fastest, requires contrast, pretty good sensitivity
- MRI w/ contrast if you get a volumetric 3D T1 image highest sensitivity, specificity and accuracy, especially if it can then be paired with a non-contrasted t1 sequence / t2 sequence which can help in dating blood
- MRV – can be done with contrast or TOF, also very sensitive, may overcall and there is artifact if just TOF
Once diagnosed …then what?
- Ask “could this be HIT or is this one of the vary rare cases of a vaccine-associated VST?”
- If yes to either of those questions == do not use heparin
- Use argatroban or bivalirudin and you can certainly consider or entertain giving IVIG although where I’ve practiced this is not routinely done, but has certainly been described
If this is not HIT or a vaccine complication
- Start a heparin gtt (or an alternative a/c to get them to a therapeutic anticoagulated state)
- Even if IPH
- We scan frequently.. but not to stop the heparin drip because if the IPH is getting worse then its probably that the clotting is getting worse
- Neurologists in general tend to not like blousing heparin but this is a condition where it really is important to get them therapeutic quickly, and to pivot to a different agent if you are running into heparin resistance
When to consider interventional thrombectomy?
- Probably institution dependent, where I’ve practiced theres always been a high bar to do this
- Because the TO-ACT published in JAMA in 2020 showed that in a small group showed that the addition of intraventional therapy to medical therapy standard of care did not appear to improve functional outcomes so the trial was halted for futility at the first interim analysis.
- Might this be something to think about in a patient that is getting profoundly worse despite medical therapy or in a patient that because of systemic factors cannot safely be a/c’ed — sure.
- But not part of the standard treatment
What to worry about in these patients?
- Elevated Intracranial pressure
Seizures = can complicate up to 40% of patients. No guideline on using prophylactic AEDs, if they seize one, definitely start an AED. If the patient is altered, low threshold to get cEEG
Elevated ICP == certainly be a major issue in patient with a heavy burden of venous sinus occlusion or in patient that have suffered an IPH.
- Usual management although invasive monitoring has a higher risk given the patient is on a/c, probably a good time for pupillometry or using ultrasound to do optic nerve sheath diameter measurements if that’s something you do frequently enough to have comfort with it
- Can use an invasive monitor if a/c is held around the time of insertion. Careful and monitoring for hemorrhage
- These patients may actually progress to needing a decompressive hemicraniectomy
- Which is of course terrifying – no one is going to feel at ease with having a freshly decompressed patient on therapeutic a/c
- So you would think that if it gets to that point then things are going to go really badly, but actually in small cohort studies these patients do quite well, the reason being that often it is edema more than true infarction that is leading to this ICP crisis and that’s reversible.
- Should be considered in patients with rapid deterioration, with mass effect, significant midline shift and obliterations of the basal cisterns.
Hydrocephalus == pretty rare, not commonly encountered but can happen because of occlusions around the arachnoid granulations or because of diffuse edema / hemorrhage causing an obstructive pathology
- Treatment the same way as if you didn’t have a VST except that more risk with EVD given the a/c problem
Long term… historically treated with warfarin, RESPECT open-label, randomized trial comparing dabigatran to warfarin and demonstrated similarly low rates of recurrence and similar rates of bleeding. American Society of Hematology actually now favors the use of DOACs. … shared decision making with patient re warfarin or DOAC.
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