Cvt

Cerebral venous thrombosis

1. Cerebral Venous Thrombosis Dr SANJOG CHANDANA (MIND)

2. Introduction Cerebral venous thrombosis (CVT) is an uncommon condition T hat accounts for 0.5 to 1% of all strokes in the adult population It is frequently underdiagnosed, as clinical manifestations are not specific and include a wide range of symptoms such as headache, focal neurological deficits, Seizures and altered mental status. Therefore, high clinical suspicion is required to avoid misdiagnosis, and imaging is fundamental in accurately detecting CVT and possible associated complications that could modify the prognosis and the therapeutic approach.

3. Epidemiology Annual incidence – 0.22 – 1.57 per 1 lac population Women > Men (3:1) Increased risk due to – CVT associated with pregnancy, puerperium, Ocs . Adults – Younger > elder ( arterial Strokes ) ISCVT ( International study on cerebral vein and dural sinus thrombosis ) – Mean age 37 years. Mean age – Women – 34 , Men – 42

4. Pathogenesis Predisposing factors – multiple Risk factors in venous thrombosis – Virchow’s triad

5. Pathogenesis 1: Thrombosis of Cerebral veins or dural sinus  obstructs blood drainage from brain tissues  leading to Parenchymal lesions / dysfunction ( stroke ),  increased venous / capillary pressure with disruption of blood brain barrier. 2: Occlusion of Dural sinus  decreased CSF absorption  increased ICP. Early phase  dilatation of cerebral veins + collateral pathway.

6. PATHOGENESIS INTERSTITIAL SPACE DECREASED ENTRY OF WATER FROM FAILURE OF NA+/K+ ATPASE PUMP VENOUS HEMORRHAGIC INFARCTION

7. ADVANCE IN MRI DWI + PERFUSION COEXISTENCE OF BOTH CYTOTOXIC + VASOGENIC EDEMA

8. RISK FACTORS Transient / Permanent Prothrombic condition - Genetic / acquired OCs Pregnancy and Puerperium Malignancy Infection Trauma

9. COVID 19 + Vaccine  majority without predisposing factors 34,331 patients  0.08 % CVT Mortality rate  40 % Infections – 6-12 % Trauma -5-10 % Idiopathic children 10 % , Adult 13 %. Older patients – malignancy and idiopathic (higher)

10. Clinical Aspects Highly variable Onset – acute , subacute, chronic. Mostly presents with new headache, Additionally – focal neurological deficits, seizures and /or encephalopathy.

11. Symptoms and signs Isolated intracranial hypertension syndrome ( Headache with or without vomiting, Papilledema, Visual problems) FOCAL Syndromes (Focal deficits, Seizures, or Both) Encephalopathy ( multifocal signs, mental status changes, stupor, coma)

12. Headache – 90 % , may precede other symptoms and signs Vague – Severe – worsens on Valsalva maneuvers with recumbency Usually gradual. Sometimes – thunderclap After LP May be with Aura.

13. ISOLATED INTRACRANIAL HYPERTENSION SYNDROME I.e . Associated with papilledema, visual problems Coinciding with bouts of increasing headache intensitiy More in chronic presentation – Fundoscopy – Papilledema Acute – less common.

14. SEIZURES Around 35-40 % Supratentorial Parenchymal brain lesions, Sagittal Sinus and cortical vein involvement Motor deficits

15. ISOLATED SINUS and Vein Thrombosis Cavernous sinus thrombosis : Ocular signs predominate, Orbital pain, Chemosis , Ptosis, Palsies Cortical veins : Motor/ Sensory deficits , Seizures SSS- Motor , bilateral , Seizures – common. Presentation as isolated intracranial HTN syndrome – infrequent. Isolated lateral sinus thrombosis – Isolated headache/ Intracranial HTN syndrome Left transverse sinus – Aphasia

16. Jugular vein/ Lateral sinus – Isolated pulsating tinnitus Lateral / Jugular / posterior fossa vein – Multiple Cranial N palsies Deep Venous – Severe signs , coma , Mental status changes, Motor deficits, Bilateral .

17. Clinical features

18. Clinical Features

19. INVESTIGATIONS NON INVASIVE : CT, CTV,MRI , MRV, Ultrasound INVASIVE : Cerebral angiography, Direct cerebral venography

20. Diagnosis: Suspected: New onset Headache Headache that features that differs from usual pattern ( progression or change in attack frequency , severity) Symptoms of raised ICP Encephalopathy Focal neurological deficits ( esp , - not fitting vascular territory ) Seizures Atypical findings on routine Neuroimaging ( Cerebral infarction crossing typical arterial boundaries, Hemorrhagic infarction, Lobar ICH) With known risk factors

21. Urgent imaging with MRI brain with MRV CT head with CTV ( if not available ) Clear demonstration of absence of flow and intraluminal thrombus – confirm diagnosis. Fallacies

22. CT HEAD Head CT is normal - up to 30 percent of CVT cases, most of the findings are nonspecific. CT is often the first investigation to be performed in clinical practice, and it is useful to rule out other acute or subacute cerebral disorders. In one-third of cases, CT demonstrates direct signs of CVT.

23. NCCT Head Dense vein sign 7-14 days Accurate

24. Empty Delta Empty triangle / Negative delta CECT recanalization around an organizing clot enlargement of the peridural small veins: a vascular mesh ( dural cavernous spaces), and meningeal venous tributaries thickening of the dura with increased enhancement

25. CORD SIGN CURVILINEAR OR LINEAR HYPERDISITY DUE TO THROMBOSED CORTICAL VEINS

26. Indirect signs More frequent Intense contrast enhancement of falx and tentorium Dilated trans-cerebral veins. Hemorrhage SAH ( 1-2 % ) limited to convexity

27. CT Venography Filling defects Sinus wall enhancement Increased collaterals Combined with CT Accuracy 90-100 %. Major dural sinuses

28. Quicker than MRI IN Those contraindicated Low resolution of Deep vein and cortical veins Contrast reaction, Radiation.

29. MRI using GRE T2 SWAN + MRV – most sensitive Age of thrombus: First 5 days – Isointense on T1 and hypointense on T2 Beyond 5 days – hyperintense on both T1, T2 After 1 st month Variable – isointense.

30. da Day 5 Day 13

31. Vasogenic Cytotoxic Hemorrhage

32. MRV Absence of flo w ? Hypoplasia, assymetric flow Contrast MRV – better visualisation of Cerebral venous channels GRE / SWI – low signal in thrombus

33. Cerebral angiography Recommended – uncertainty of diagnosis Isolated cortical vein thrombosis CTV / MRV inconclusive High suspicious When intervention is planned Sudden termination of Cortical vein Surrounded by corkscrew / dilated / tortuous collaterals Reversal of blood flow Delayed venous emptying

34. Laboratory tests PT APTT D dimer – elevated support CVT. Normal doesn’t rule out. Homocysteine Thrombophilia profile Protein C, S – not useful in acute CVT – done after stoppage of anticoagulant ( warfarin ) Antithrombin – after stoppage of heparin Antiphospholipid syndrome - repeat after 12 weeks Paroxysmal nocturnal hematuria – Hemolytic anemia, iron deficiency , pancytopenia LP – Sepsis, fever , no obvious cause infection

35. Treatment Acute antithrombotic managmenet Long term ( subacute )

36. Overall AIM – improve outcome To recanalize the occluded sinus / vein To prevent propagation of thrombus, namely the bridging cerebral veins To treat the underlying prothrombotic state, in order to prevent venous thrombosis in other parts of the body ( PE / DVT). Main treatment option is anticoagulation.

37. For most patients with CVT, -recommended - anticoagulation with subcutaneous LMWH or intravenous heparin for adults with symptomatic CVT who have no contraindication. The presence of hemorrhagic venous infarction, intracerebral hemorrhage, or isolated subarachnoid hemorrhage are not contraindications for anticoagulant treatment in CVT. Subcutaneous LMWH is more effective than  unfractionated heparin  (UFH), and is at least as safe. Treatment for children during the acute phase of CVT is similar to that for adults, but the evidence is weaker since there are no randomized controlled trials in this age group.

38. Management for patients with COVID-19 vaccine-associated thrombosis Treatment with intravenous  immune globulin  and a non-heparin anticoagulant has been suggested.

39. Risk of new intracranial hemorrhage  Anticoagulants appear to be safe to use in adult patients with CVT who have associated intracranial hemorrhage, either intracerebral or subarachnoid. In the Berlin and Dutch trials, 34 of 79 patients (43 percent) included in the Berlin and Dutch trials had an intracerebral hemorrhage at baseline . None of the patients randomized to heparin developed a new intracerebral hemorrhage. In contrast, a new intracerebral hemorrhage developed in three patients randomized to placebo.

40. Case series have also reported relatively low risks of intracranial hemorrhage (<5 percent) and systemic hemorrhage (<2 percent), and such hemorrhages did not influence outcome. These findings are in accordance with the hypothesis that hemorrhage in CVT is caused by the probable mechanism of venous outflow blockage and very high intradural and intravenous pressure, leading to both rupture of venules and to hemorrhagic transformation of venous infarctions.

41. Systemic Thrombolytics Thrombolytic agents such as Streptokinase, Urokinase and rTPA has been used in case reports and small series. Major risk – GI , Intracranial hemorrhage. CI – Recent child birth, history of bleeding disorder, recent major surgery, IBD. Some suggestion – local delivery of thrombolytic agents – reduce systemic effects.

42. Endovascular treatment Recommended for adults and children who develop progressive neurologic worsening despite adequate anticoagulation with SC LMWH or IV heparin. Endovascular thrombolysis Mechanical thrombectomy Balloon angioplasty

43. Justification: Poor GCS, lack of adequate response to Anticoagulant therapy, rapid neurological worsening , altered mental status, deep sinus thrombosis, large strokes Locally infusing thrombolytics minimizes systemic effects and facilitates local clot lysis with high concentration of thrombolytic agents. Routes of access : Transfemoral , Transjugular , Direct puncture of dural sinuses.

44. Surgery Indicated : malignant intracranial hypertension, Acute visual loss, intracranial hemorrhage , edema with mass effect. Ventriculostomy – with CSF diversion and ICP monitoring Craniectomy ( Decompression) Craniotomy + thrombectomy.

45. Guideline recommendations The 2017 European Stroke Organization guidelines for the diagnosis and treatment of cerebral venous thrombosis, endorsed by the European Academy of Neurology , recommend heparin at therapeutic dosage to treat adult patients with acute CVT, including those with an intracerebral hemorrhage at baseline . The guidelines suggest using LMWH instead of UFH . No recommendation is made regarding thrombolysis for acute CVT E xcept that patients who have a pretreatment low risk of poor outcome ( absence of coma, mental status disturbance, thrombosis of the deep venous system, intracranial hemorrhage, and malignancy) should not be exposed to aggressive treatments such as thrombolysis.

46. The 2014 American Heart Association/American Stroke Association (AHA/ASA) guidelines A nticoagulation is reasonable for patients with acute CVT, even in patients with intracranial hemorrhage . The 2011 AHA/ASA guidelines for the diagnosis and management of CVT conclude that initial anticoagulation with adjusted-dose UFH or weight-based LMWH in full anticoagulant doses is reasonable, followed by vitamin K antagonists, regardless of the presence of intracerebral hemorrhage 

47. American Academy of Chest Physicians (ACCP) issued in 2012 suggest anticoagulation over no anticoagulation during the acute and chronic phases of CVT.

48. Guidelines for children Children without significant intracerebral hemorrhage, the ACCP recommends initial anticoagulation with UFH or LMWH, followed by LMWH or vitamin K antagonist treatment ( warfarin ) for a minimum of three months. Anticoagulation for an additional three months is suggested if there is still cerebral sinus-venous occlusion or ongoing symptoms after three months of therapy.

49. Children who have significant intracerebral hemorrhage, the ACCP suggests either initial anticoagulation as for children without hemorrhage, or radiologic monitoring of the thrombosis at five to seven days and anticoagulation if thrombus extension is noted at that time. The ACCP suggests thrombolysis, thrombectomy, or surgical decompression only in children with severe CVT in whom there is no improvement with initial anticoagulation therapy.

50.   AHA Stroke Council state that it is reasonable to institute either UFH or LMWH in children with CVT, whether or not there is secondary hemorrhage . This is followed by  warfarin  therapy for three to six months.

51. Other acute management issues Elevated intracranial pressure and herniation : In early stage – cerebral edema , hemorrhage , herniation – lead to death. General recommendation – followed for control of ICP Elevation of head end, Intensive care unit admission, Osmotic therapy Hyperventilation to target PaCO2 – 30-35 mmhg ICP monitoring Impending herniation due to unilateral lesion – hemicraniectomy . Ventricular shunting – No conclusive evidence for acute phase.

52. For patients with sustained ICP elevation - successful treatment - prevents visual failure and resolve headache. Glucocorticoids – not recommended Seizures - for supratentorial lesions , having seizures – antiepileptic prophylaxis is recommended – Levetiracetam / Sodium valproate., Infection / Inflammation : appropriated antibiotics for Meningitis , otitis, mastoiditis, Glucocorticoids for inflammatory diseases.

53. Management after acute phase Decision regarding the duration of anticoagulant and AEDs. Long term anticoagulants – aim is to prevent recurrence, extracerebral venous thrombosis. Warfarin – INR - 2-3 Dabigatran (150 mg twice daily ) ( Less blood monitoring and dose adjustments ).

54. Special population Malignancy : long term anticoagulant , if no renal insufficiency – LMWH. Renal insufficiency – Warfarin Pregnancy – Heparin safer.

55. Duration of anticoagulant Minimum – 3 months after acute phase of CVT. There is no definitive optimum duration. For patients with a provoked CVT associated with a transient risk factor, anticoagulation is continued for three to six months. For patients with an unprovoked CVT, anticoagulation is continued for 6 to 12 months. For patients with recurrent CVT, venous thromboembolism after CVT, or a first CVT with a severe thrombophilia ( ie , homozygous prothrombin  G20210A  mutation, homozygous factor V Leiden mutation, deficiencies of protein C, protein S, or antithrombin, combined thrombophilia defects, or antiphospholipid syndrome), anticoagulation may be continued indefinitely .

56. Aspirin – No evidence Seizure – at least 1 year of seizure free episode. Headache – Acetazolamide / Furosemide. Visual loss – optic sheath fenestration.

57. Cognitive / psychiatric complication : Rehabilitation / Antidepressents Subsequent pregnancy : UFH, Oral contraceptives – NOT Used

58. Prognosis CVT can results in death / permanent disability. Usually has a favourable prognosis. 5 % die during acute phase. Main COD – Transtentorial herniation secondary to large hemorrhagic lesion Herniation due to multiple lesions, diffuse brain edema , status epilepticus, medical complications, PE.

59. Neurological deterioration occurs in approx 23 % Overall 15 % death or dependency rate 78 months. ( ISCVT + other meta- analysis )

60. Predictors of mortality at 30 days in ISCVT Depressed consciousness Altered mental status Thrombosis of deeper system Right hemispheric damage Posterior fossa lesions.

61. Predictors of poor long term outcomes in ISCVT CNS infection Any malignancy Deep Venous system involvement Hemorrhage on CT / MRI GCS < 9 on admission Mental status changes Age > 37 years Male gender

62. CVT risk score Designed to estimate the functional prognosis after CVT onset. Prescence of malignancy . 2 points Coma on admission , 2 points Thrombosis involving deep venous system , 2 points Mental status disturbances on admission, 1 point Male gender , 1 point Intracranial hemorrhage on admission , 1 point. >= 3. , >2 MRS

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