Headache post AZ vaccine. How do we spot cerebral venous thrombosis?

Whilst debate continues to revolve around the association between the Covid-19 AZ vaccine and rare but serious thromboembolic events including cerebral venous thrombosis, patients have been advised by the MHRA to contact their doctor if they have a headache post-vaccine that persists for more than 4 days. This is because of the reports of extremely rare cases of cerebral venous thrombosis (CVT) that have been reported soon after vaccination, often in association with low platelets. Patients have also been advised to report persistent bruising due to the link with thrombocytopaenia, thought to be due to an immune-driven adverse reaction to the vaccine similar to that seen with heparin-induced thrombocytopaenia.

Well, if you’re anything like me, you have probably never seen a case of CVT and your memory of it from medical school may be a bit hazy at best. So, let’s ‘keep it simple’ and have a bit of revision. Fortunately, there was an excellent recent evidence review in Practical Neurology 2020 from which we can learn the following:

·     Cerebral venous thrombosis (CVT) is a rare but important cause of stroke in younger adults

·     It is caused by complete or partial occlusion of the cerebral major venous sinuses (hence also called cerebral venous sinus thrombosis CVST) and the smaller feeding cortical veins (cortical vein thrombosis)

·     The mean age of onset is 33 and there is a two-thirds female preponderance, thought to be due to its association with pregnancy, the puerperium, and oestrogen containing contraceptives.

·     Other risk factors include any other pro-thrombotic condition including inherited thrombophilia (e.g. antiphospholipid syndrome, protein C and S deficiency, etc), acquired thrombophilia (e.g. myeloproliferative conditions), inflammatory disease and infection (NB including of course COVID-19 itself)

·     Over the age of 55 CVT is equally prevalent between men and women and malignancy is a major cause

·     It is a difficult clinical diagnosis, as not only is it incredibly rare it has varying clinical manifestations which are different from a ‘conventional’ stroke

·     CVT will obviously increase venous pressure and therefore decrease cerebral perfusion and will block CSF absorption; this results in raised intracranial pressure, meaning that the clinical manifestations of CVT tend to be more gradual onset and less well-defined in their vascular territory than in a ‘conventional’ arterial stroke

·     CVT will most commonly present with a headache due to raised intracranial pressure and this is present in 90% of cases. It may be the only manifestation in 25% of cases. Unfortunately, CVT related headache does not have specific diagnostic features, although it is usually gradual onset and progressive. It worsens over hours or days and may have features of raised intracranial pressure (e.g. worse in the morning, worse with Valsalva manoeuvre or coughing or straining), improve with standing, nausea, feeling sleepy and visual changes. Less often it may come on suddenly with a thunderclap headache by triggering a secondary sub-arachnoid bleed. The headache may be localised or diffuse.

·     Stroke like focal neurological symptoms occur in up to 40% of patients with CVT. These are also more gradual in onset, and a broad range of possible focal neurological defects (e.g. hemisensory loss, hemiparesis, hemianopia, visual impairment, etc) may occur although motor symptoms are most common.

·     CVT may present with other symptoms of raised ICP such as altered consciousness, confusion, and seizures.

·     D-dimer can be normal, however, it has a high negative predictive value for excluding CVT in patients with isolated headache and therefore has been suggested as a component for pre-imaging probability testing.

·     The MHRA statement April 7^th 2021 report that so far there have been 79 cases of thromboembolism associated with thrombocytopaenia following the COVID-19 AZ vaccine (51 women and 28 men) and of these 44 have been cerebral venous thrombosis, and 35 have been other types of VTE including DVT, PE and splanchnic vein thrombosis (causes persistent abdominal pain). 19 of the 79 cases have died, and 11 of those who died were under the age of 50. All cases occurred after the first dose.

·     Guidance from the UK Expert Haematology Panel April 7^th 2021 report that cases may occur 5 to 28 days after vaccination and are characterised by thrombocytopaenia (platelets < 150), raised D-Dimers (> 2,000) and progressive thrombosis with a high preponderance of CVT but PE and arterial ischaemia may also occur.

In conclusion, we should consider CVT as a possible diagnosis and refer for imaging in a patient post AZ vaccination who presents with a headache that is new onset, persistent and progressive especially if they have other risk factors for thromboembolism, and certainly if they have any other neurological symptoms or signs including features of raised intracranial pressure (e.g. positional and worse with Valsalva manoeuvre). Look for signs of bleeding, petechiae, or bruising, and if immediate referral is not deemed clinically necessary check a FBC to look for low platelets (< 150) and consider a D-dimer test (a D-dimer > 2000 is considered a probable case).