A 27-year-old female presents to the Emergency Department after a collapse at work that was followed by a brief tonic-clonic seizure. She is 30 weeks pregnant with no previous pregnancies or other significant medical history. She currently localises bilaterally to painful stimulus but does not open her eyes or vocalise.

Her blood pressure is 170/50 mmHg, her urine analysis is unremarkable, and the cardiotocogram (CTG) is ‘reassuring’. A CT brain scan shows a sigmoid and transverse venous sinus thrombosis, with some temporal lobe parenchymal haemorrhage.

a)    List the major risk factors, other than pregnancy, for this condition.    (30%    marks)
b)    Briefly outline the management priorities for this patient?    (70%    marks)

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College Answer

a)

Prothrombotic conditions – genetic or acquired Oral contraceptive

Malignancy

Parameningeal Infection e.g. ear, sinus

Head trauma

Surgery

Mechanical precipitant

Autoimmune disease e.g. SLE, antiphospholipid

Other drugs e.g. androgens

b)

Resuscitation:
o    Consider intubation
o    Check gas exchange (expect slight respiratory alkalosis)
o    BP currently a bit on the high side, maybe careful hydralazine to SBP 140-160?

Specific therapy for cerebral venous sinus thrombosis

o    Therapeutic anticoagulation
o    Can use LMWH or UFH
o    Intracranial haemorrhage with CVT is not a contraindication to anticoagulation
o    Continued for remainder of pregnancy and usually for further 6-12 weeks postpartum

o    Aspirin – no evidence of benefit. Occasionally used as alternative if firm CI to therapeutic anticoagulation

o    Potential therapies include thrombolysis (systemic or catheter-directed), mechanical clot extraction, decompressive craniectomy
o    Assess for underlying cause that may require specific therapy e.g.,

  •  Antiphosphoplipid syndrome
  • Sinus or parameningeal infection

o    May need an anticonvulsant; consider neurology input

Pregnancy related:

o    Involvement of obstetric service, regular CTG, ultrasound
o    ? steroids to allow for early delivery if needed
o    Shielding for X-ray and CT limit as able
o    Blood conservation given physiological anaemia of pregnancy
o    Need to keep family up to date

Discussion

a)

The following lisk of risk factors was compiled using UpToDate and Ferro et al (2004). The latter was a multinational multicentre observational study which identified 624 patients with confirmed CVT. Of this group, the following risk factors were observed:

  • Genetic thrombophilia (22.4% of cases)
  • Pregnancy during peripartum period or puerperium (13.8%)
  • Infection, be it CNS or ENT (12.3%)
  • Drugs (7.5%)
  • Malignancy (7.4%)
  • Pregnancy at any stage (6.3%)
  • Antiphospholipid syndrome (5.9%)
  • Trauma, neurosrugery or lumbar puncture (4.5%)
  • Vasculitis (3%)
  • Polycythaemia or thrombocytosis (2.8%)
  • Surgery (2.7%)
  • Vascular anomaly in the CNS like dural fistula, AVM, etc (1.9%)
  • Dehydration (1.9%)

b)

The major approaches to fixing this problem are anticoagulation, thrombolysis, endovascular thrombectomy and open clot retrieval.

  • Anticoagulation has been the mainstay of treatment. Coutinho et al (2012) performed a systematic review of the practice and found it to be very helpful, with risk of death reduced by two thirds (ARR of 13%) and substantially improved neurological outcomes. As the patients usually have some sort of procoagulant state, you're going to end up anticoagulating them anyway.
  • Thrombolysis for CVT is a logical extension of the use of thrombolysis for ischaemic stroke (i.e. "if its good enough for arterial clots, why not try it with venous clots"). This is the topic of the TO-ACT trial (Coutinho et al, 2013) which appears to still be recruiting. Apart from this undertaking, evidence for the use of thrombolysis in CVT consists of case series only (Ciccone et al, 2004, and Canhão et al, 2003, with about 200 patients in total). Discouraging features included a high rate of extracranial (21%) and intracranial (17%) haemorrhage, which occured in spite of the fact that in the majority of cases (88%) the thrombolytic agent was administered directly into the thrombosed sinus
  • Endovascular clot retrieval is typically reserved for situations where there is significant thrombus burden, contraindication to anticoagulation or a lack of clinical improvement or worsening of symptoms despite systemic heparin. It is the new exciting thing on this scene, and also only known from case series.  As a representative example, Mokin et al (2015) report on the American experience. Thirteen patients were identified, of whom five had a favorable clinical outcome (defined as modified Rankin Scale score of 0–2) and three died.  A systematic review of such case series (Siddiqui et al, 2015) found a good outcome in 84% and a mortality of 12% among a total of 185 patients, even though they represented the more severe end of the CVT spectrum (60% were in a coma).
  • Open clot retrieval seems to be an end-of-the-line manoeuvre. It is known only from heroic case reports (eg. Persson et al, 1990 and Ekseth et al, 1998). In each case, the surgeons followed thrombectomy by an infusion of a thrombolytic agent.
  • Decompressive craniectomy for this condition is discussed elsewhere. In brief, the results have been encouraging and full systemic anticoagulation within 24 hours of surgery seems to be safe. A 2009 review from Stroke courageously asserted that the therapy is "lifesaving" and that the outcome can be "excellent", on the basis of three cases. The AHA/ASA gudelines recommend this as a viable option.

References

References

Roberts, Jonathan C., and Christopher M. Fischer. "Cerebral venous sinus thrombosis." Vascular Emergencies: Expert Management for the Emergency Physician (2013): 1.

Rothwell, P. M., et al. "Risk factors for cerebral venous thrombosis." Oxford Textbook of Stroke and Cerebrovascular Disease (2014): 14.

Bhogal, P., et al. "Cerebral Venous Sinus Thrombosis." Clinical Neuroradiology (2016): 1-6.

Ferro, José M., et al. "Prognosis of cerebral vein and dural sinus thrombosis results of the international study on cerebral vein and dural sinus thrombosis (ISCVT)." Stroke 35.3 (2004): 664-670.

Lee, Emil JY. "The Empty Delta Sign 1." Radiology 224.3 (2002): 788-789.Virapongse, Chat, et al. "The empty delta sign: frequency and significance in 76 cases of dural sinus thrombosis." Radiology 162.3 (1987): 779-785.

Virapongse, Chat, et al. "The empty delta sign: frequency and significance in 76 cases of dural sinus thrombosis.Radiology 162.3 (1987): 779-785.

Saposnik, Gustavo, et al. "Diagnosis and management of cerebral venous thrombosis a statement for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 42.4 (2011): 1158-1192.

Coutinho, Jonathan M., Sebastiaan FTM de Bruijn, and Jan Stam. "Anticoagulation for cerebral venous sinus thrombosis." Stroke 43.4 (2012): e41-e42.

Coutinho, Jonathan M., et al. "Thrombolysis or anticoagulation for cerebral venous thrombosis: rationale and design of the TO‐ACT trial." International Journal of Stroke 8.2 (2013): 135-140.

Canhão, Patricia, Filipa Falcão, and Jos&eacute M. Ferro. "Thrombolytics for cerebral sinus thrombosis.Cerebrovascular diseases 15.3 (2003): 159-166.

Ciccone, Alfonso, et al. "Thrombolysis for cerebral vein and dural sinus thrombosis." The Cochrane Library (2004).

Mokin, Maxim, et al. "Endovascular treatment of cerebral venous thrombosis: Contemporary multicenter experience." Interventional Neuroradiology (2015): 1591019915583015.

Siddiqui, Fazeel M., et al. "Mechanical Thrombectomy in Cerebral Venous Thrombosis Systematic Review of 185 Cases." Stroke 46.5 (2015): 1263-1268.

Persson, Lennart, and Anders Lilja. "Extensive dural sinus thrombosis treated by surgical removal and local streptokinase infusion." Neurosurgery 26.1 (1990): 117-121.

Ekseth, Kåre, Sverre Boström, and Magnus Vegfors. "Reversibility of severe sagittal sinus thrombosis with open surgical thrombectomy combined with local infusion of tissue plasminogen activator: technical case report." Neurosurgery 43.4 (1998): 960-964.