A venous thrombus is when a blood clot (known as a thrombus) forms within a vein. Thrombosis is a more general term for blood clotting within a blood vessel. A common type of venous thrombosis is a deep vein thrombosis (DVT), which is a blood clot in the deep veins of the leg. Cerebral venous thrombosis, a clot within a vein in the brain, is a relatively rare event. In this article I will describe such a case and hopefully reflect the fascinating journey that both the practitioner and patient were taken through.
Case: Cerebral Vein Thrombosis
A 23-year-old male had noticed a ‘transient black-out of vision’ in both eyes. Possessing a free eye test voucher from a multiple, he decided to have his eyes tested. A vigilant young optometrist noticed papilloedema of both the optic discs and referred the patient urgently to St Mary’s Hospital in London. The patient was seen by the accident and emergency team, and brain scans revealed a cerebral vein thrombosis together with intracranial hypertension. The MRI scans revealed thrombosis of the superior sagittal sinus vein (figure 1).
The consultant wrote a summary note explaining to the patient that he had suffered a blood clot in one of the collecting venous sinuses inside the head. This is a rare finding in a young, healthy male and the consultants comforting words were: ‘You are showing great resilience in your recovery and I can reassure you that you are going to make a full recovery with rehabilitation and continued treatment.’ He was prescribed Diamox (2000mg), warfarin, vitamin D and omeprazole. The hospital team were surprised that our patient had not suffered headaches, seizures or some form of symptoms of a debilitating stroke.
Figure 1: Three views using MRI venography showing venous sinuses (superior sagittal sinus – SSS; straight sinus – STS; inferior sagittal sinus – ISS), vein of Galen (VOG), basal vein (BV), and internal cerebral vein (ICV) with convergence upon the confluence of sinuses (CON). From the confluence, the transverse sinus (TS) routes right and left and curves into the sigmoid sinus (SIG) to meet the internal jugular vein (IJAG). Similarly, the ophthalmic veins which drain into the cavernous sinus (CS) also drain blood via the superior petrosal veins (IP) into the internal jugular vein. Note, in all three scans (a, b and c), the superior sagittal sinus occlusion is seen at the top of the head, and in 1b it is possible to see narrowing of the vein (red arrows)
The MRI findings seen in October 2017 showed a flattening of the globe and tortuosity of the optic nerves due to the cerebral hypertension (figure 2). Three months later, there was less tortuosity and the flattening of the globe had improved, especially in the right eye (figure 3).
Figure 2 a: right eye in 2016 (on left) appears normal and perfuse, and a year later (on right) swollen with tortuous veins and some haemorrhages. b: left eye in 2016 (on left) appears normal and a year later (on right) looks raised due to papilloedema, with splinter haemorrhages and exudates also visible. C; MRI scan shows both globes flattened (dashed line) and with optic nerve tortuosity (red arrows)
Figure 3 a: October 2017, dark fluid MRI shows flattening of both globes (blue arrows) and tortuosity of the optic nerves. The left globe appears more distorted than the right. b: February 2018, an improvement in the right eye with a more rounded globe, straightening of the optic nerve (red line), and more clearly defined disc margins. The left globe still appears flattened (blue dashed line) and the optic nerve tortuous (red arrow), and this corresponds with the fundus appearance
Ocular examination
Here is a summary of my clinical findings from the period October 2017 to February 2018.
- Vision 6/6 R and L
- Colour vision – no defect on Ishihara
- Ocular motility – no signs of incomitancy
- Pupil reactions –normal responses and no defect detected
- Fundus examination (figures 2 and 3) – bilateral papilloedema was seen, with that of the left eye worse than the right. Disc margins were blurred all round, but after three months there was a reduction in the papilloedema. Retinal veins exhibit tortuosity due to increased pressure on the globe.
- OCT angiography of the discs confirmed the swelling and RNFL analysis showed very thick nerve fibre layers in both eyes due to the disc oedema (the apparent thickening therefore artefactual). The capillary network on the optic discs appeared raised and prominent, and the optic disc cupping was not visible (figures 4 and 5).
- Assessment of the visual evoked response (VEP) showed that the amplitudes were within normal limits (figure 6). Amplitudes indicate the number of healthy retinal ganglion cells that respond to a stimulus. Latency also appeared to be within normal limits, though latency to high contrast in the right eye was definitely delayed (124milliseconds). This is related to the parvocellular pathway and indicates some sort of central vision issue. It may be that the macular folds seen on the OCT were evidence that the retinal ganglion cells at the macula were affected. A normal response of the optic nerve is 100ms for the signal to transfer from the optic nerve to the striate cortex. Note the recovery of the VEP latency three months later.
- The electroretinogram (ERG) appeared normal with contrast sensitivity. This measures diffuse retinal ganglion cell response and is especially important for assessing glaucoma and peripheral diabetic retinopathy. Pattern ERG measurement for concentric field stimuli (figure 7) showed an outside normal response in both eyes. Concentric field stimuli is important for assessing macula function, and in this instance showed that, in both eyes, the macular ganglion cells were not in a healthy state. The right eye response was worse compared to the left eye, and hence the VEP high contrast latency (parvocellular pathway) was affected. Note that three months later there was recovery of the macula ganglion cell function.
Figure 4: Right retinal nerve fibres and ganglion cells showing substantial thickening due to papilloedema. There is a dramatic drop in thickness as the swelling subsides over the subsequent three months. The OCT angiography (central column images) show the swelling of the disc improving revealing the capillary and vascular networks in sharper detail (red arrow)
Discussion of Cerebral Vein Thrombosis
What is it?
The cerebral veins are responsible for carrying deoxygenated blood from the brain tissue, along with cerebrospinal fluid, to the dural venous sinuses. There are 11 venous sinuses in total, converging at the confluence of sinuses (see figure 1). From the confluence, the transverse sinus curve into the sigmoid sinus and blood flows out through the internal jugular veins. Blood from the ophthalmic veins drain into the cavernous sinus and this blood returns to the internal jugular veins via the superior and inferior petrosal veins. The venous walls are extremely thin due to no muscular tissue in the walls and there are no valves.
Figure 5: As figure 4 but for the left eye and showing the papilloedema to be worse in this eye. The left eye retinal nerve fibres show an increase in swelling indicating swelling from behind the optic disc. The ganglion cell layer is showing a loss and hence an improvement in the macular swelling (red arrow)
Cerebral venous sinus thrombosis describes a blood clot (thrombus) within one of the dural venous sinuses. The thrombus occludes venous return through the sinuses, so causing an accumulation of deoxygenated blood within the brain tissue. This reduced or obstructed blood flow through veins is termed venous infarction. Further complication arises due to cerebrospinal fluid drainage through the sinuses being impeded, leading to CSF accumulation and raised intracranial pressure.
Figure 6: Visual evoked potential on the left shows a latency delay with high contrast stimuli for the right eye (OD), suggesting compromise of the parvocellular pathway which represents the centrally located macular cells. The VEP on the right shows good recovery for each eye after three months
Epidemiology
Cerebral vein thrombosis (CVT) is very rare, occurring in three cases per million in adults and seven cases per million in children. Seventy-five percent of affected adults are female, with a male to female ratio of 1:3. The most common CVT occurs in the superior sagittal sinus (62%) followed by the transverse sinus (42%), straight sinus (18%) and then the internal jugular vein (12%).
Symptoms and prognosis
Headaches are the most common symptoms in young patients, and occur in 90% of cases. They are usually dull, diffuse and gradual in onset, especially if they are due to intracranial hypertension. The headaches would also worsen with exercise and Valsalva reflex movement. Seizures (37% of cases), vomiting and focal neurological signs (such as motor and sensory deficits) may be present. Double vision due to a nerve palsy, vision disturbances and, in some cases, hemianopia may also be observed.
Figure 7: Initial pattern ERG (left side) suggested the retinal ganglion cells at the macula (parvocellular) were under distress and not firing efficiently. The right eye was worst affected, and this was reflected in the VEP plot where there is latency to high contrast stimuli. The later pattern (right side) showed that the macular ganglion cells have bounced back to show a normal response to visual stimuli
The prognosis in 80% of cases is good, with complete recovery or just minor residual signs and symptoms. However, 5% of patients die in the acute phase due to brain herniation and 10% of patients suffer longer-term mortality.
Pathogenesis
The main risk factors for venous thrombosis are linked to what is described as Virchow’s Triad, namely:
1 Stasis of blood flow
2 Changes in the vessel wall
3 Changes in the composition of the blood
The most important risk factor is when prothrombotic conditions exist. Other risks include:
- Dehydration
- Head trauma
- Neurological surgical procedures
- Sinus infections
- Use of some contraceptives
- Corticosteroids
- High altitude
- Systemic inflammatory conditions (such as sarcoidosis)
- Obstetrical delivery (accounting for 12 per 100,000 cases)
The mechanisms involved in the development of CVT are two-fold:
1 Thrombosis – of the cerebral vein which leads to brain haemorrhages, causing localised cytotoxic and vasogenic oedema and venous infarction. This in turn would cause cerebral tissue lesions and dysfunction.
2 Occlusion – of the dural sinus which leads to decreased CSF drainage. CSF therefore accumulates and raises intracranial pressure.
Treatment
Anticoagulant use, especially warfarin, is the main line of treatment for three to six months, but in cases of severe thrombophilia (an abnormal tendency to develop blood clots) and recurrent CVT, indefinite anticoagulant use is recommended. Testing for prothrombotic conditions should only be undertaken some two to four weeks after completion of warfarin therapy. Acetazolamide (Diamox) is indicated in cases of CSF accumulation and intracerebral hypertension. Pregnant women with CVT should be continued with low-molecular weight heparin to minimise foetal adverse effects. Vitamin K facilitates clotting, so a vitamin K antagonist is prescribed to prevent this.
Our patient’s haematologist was planning to undertake prothrombin checks to see if there were any hereditary issues. This was pencilled in after six months from the episode and withdrawal of warfarin. The results of the prothrombin tests were inconclusive, but the haematologist was confident that there was a 95% certainty that our patient had a genetic predisposition to sticky blood on the basis there was no other reason for him to have a CVT. His warfarin was changed to a milder anti-coagulant called edoxaban.
Due to the papilloedema still being present, he was put on a reduced dose of acetazolamide (1000mg instead of 2000mg) and told to reduce it further as time goes. In fact, he did try to reduce his dosage down further, but felt his vision was affected so he has since stuck to 1000mg and aims to reduce it further at a future date.
Thrombus and Prothrombin
When a blood vessel is damaged, platelets (thrombocytes) and fibrin combine to form a blood clot and so prevent blood loss. Even when a blood vessel is not damaged, a blood clot may form under certain conditions. Prothrombotic describes a state where there is an increased risk of blood clotting or thrombosis. Prothrombotic conditions include the presence of protein C, protein S or antithrombin deficiency (an inherited condition).
Eye care in the community
1 Optic disc drusen
2 Vein thrombosis
3 Sports injuries
4 Ehlers-Danlos syndrome
5 Myasthenia gravis
6 Total sight loss
7 Shingles, molluscum contagiosum and VKC
8 Field loss
9 Sjögren’s disease
10 Optic neuritis
11 Glaucoma monitoring
12 Iris melanoma
Kirit Patel is an optometrist in independent practice in Radlett, Hertfordshire.
