18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome

Cerebral Venous Sinus Thrombosis (CVST)

• Risk factors: oral contraceptives, pregnancy and the puerperium, thrombophilia (factor V Leiden, prothrombin gene mutation, antiphospholipid syndrome), malignancy, dehydration, head trauma, nephrotic syndrome, inflammatory bowel disease, paroxysmal nocturnal hemoglobinuria, and local infection (mastoiditis, sinusitis, meningitis). Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a specific, rare cause after adenoviral-vector vaccines.
• Presentation: it mimics many things.
  • Headache in most patients, sometimes thunderclap.
  • Seizures, which are far more common than in arterial stroke.
  • Raised intracranial pressure with papilledema and visual loss (an isolated intracranial hypertension syndrome).
  • Focal deficits and encephalopathy.
  • Cavernous sinus thrombosis: proptosis, chemosis, and palsies of cranial nerves III, IV, V1, V2, and VI.
• Imaging:
  • Non-contrast CT may show a dense triangle or cord sign; contrast CT shows the empty delta sign in the superior sagittal sinus.
  • CT venography or MR venography confirms the diagnosis; MRI shows the thrombus and venous infarction.
  • Venous infarcts cross arterial territories, are often bilateral and parasagittal, and are hemorrhagic in up to 40%.
• Treatment:
  • Anticoagulation, with therapeutic low-molecular-weight heparin preferred to unfractionated heparin, even in the presence of hemorrhage: the bleeding is a consequence of venous hypertension, and anticoagulation relieves it.
  • VITT is the exception to usual heparin use: give non-heparin anticoagulation and intravenous immunoglobulin, and avoid platelet transfusion.
  • Transition to a vitamin K antagonist for 3 to 12 months; direct oral anticoagulants are reasonable in many patients, but vitamin K antagonists are preferred in antiphospholipid syndrome.
  • Seizure control: treat clinical or electrographic seizures; prophylaxis is considered with supratentorial lesions.
  • Raised intracranial pressure: head elevation, osmotherapy, acetazolamide for isolated intracranial hypertension, serial lumbar punctures or shunt for refractory visual loss, and decompressive craniectomy for impending herniation from a large venous infarct, which can be life-saving even in severe cases.
  • Endovascular therapy: the TO-ACT trial found no benefit from thrombectomy, so it is reserved for selected patients who deteriorate despite anticoagulation.
  • Treat an infectious source with antibiotics and drainage.

Posterior Reversible Encephalopathy Syndrome (PRES)

• Mechanism: failure of cerebral autoregulation with endothelial dysfunction, producing vasogenic edema preferentially in the posterior circulation, where sympathetic innervation is sparse.
• Triggers:
  • Severe or rapidly rising hypertension.
  • Preeclampsia and eclampsia.
  • Calcineurin inhibitors (tacrolimus, cyclosporine) and sirolimus.
  • Cytotoxic and targeted agents (cisplatin, gemcitabine, bevacizumab, tyrosine kinase inhibitors), and CAR-T therapy.
  • Kidney failure, autoimmune disease, sepsis, and rapid correction of anemia with transfusion.
• Presentation: headache, seizures (often the presenting event, sometimes status epilepticus), visual disturbance including cortical blindness, and encephalopathy. Blood pressure can be only modestly elevated, particularly with calcineurin inhibitors.
• Imaging: symmetric parieto-occipital white-matter vasogenic edema, hyperintense on T2 and FLAIR, with no restricted diffusion in most cases (which distinguishes it from infarction). Atypical frontal, brainstem, or cerebellar involvement occurs, and hemorrhage is present in a minority.
• Management:
  • Lower blood pressure by about 20% to 25% in the first hour with a titratable agent (nicardipine, clevidipine, labetalol); avoid overshoot, which causes infarction.
  • Treat seizures with antiseizure medication; magnesium is the agent for eclampsia, along with delivery.
  • Stop or reduce the offending drug; for calcineurin inhibitors, switch agents or reduce the level.
  • Treat kidney failure and electrolyte disturbance.
• Prognosis: most patients recover within days to weeks. Hemorrhage, infarction, and severe edema predict permanent deficits; recurrence is uncommon.

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

• Hallmark: recurrent thunderclap headache over days to weeks, often triggered by exertion, Valsalva, sexual activity, or bathing.
• Triggers: vasoactive drugs (cocaine, amphetamines, triptans, SSRIs, nasal decongestants, cannabis), the postpartum state, blood products and immunoglobulin, and pheochromocytoma.
• Imaging: multifocal segmental narrowing of the circle of Willis and its branches, the string-of-beads appearance, which reverses within about 12 weeks. Complications include convexity (sulcal) subarachnoid hemorrhage early, then ischemic infarction and intracerebral hemorrhage later. CSF is typically near-normal, which helps distinguish it from vasculitis.
• Management:
  • Remove vasoactive triggers.
  • Nimodipine or verapamil for headache control, acknowledging limited outcome evidence.
  • Avoid blood pressure extremes; treat severe hypertension cautiously.
  • Avoid glucocorticoids, which are associated with worse outcomes.
  • Short-term rest and avoidance of Valsalva maneuvers.

Distinguishing the Three (and Their Mimics)

Mimics to exclude: aneurysmal subarachnoid hemorrhage (lumbar puncture with xanthochromia, CT angiography), cervical artery dissection, primary CNS vasculitis (abnormal CSF, non-reversing stenoses), pituitary apoplexy, and intracranial hypotension.