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  • 1. 1 Thrombosis: A Focus on the Neonate 05/21/10
  • 2. 2 NOTHING TO DECLARE
  • 3. 3 Case Presentation  JS was born at 36 weeks gestation in a community hospital.  Maternal History:  Mother had a h/o ITP during all three of her pregnancies and was treated during this pregnancy with prednisone.  Patient had poor feeding hours after birth. Labs showed left shift NICU for septic work up.  Hb 20, WBC 40, plt 202K, Segs 45%, Band 20%
  • 4. 4 Case Presentation  DOL #2 patient developed  tremors concerning for seizure  Shrill cry  Unstable temp  Transfer to SLCH
  • 5. 5 Case Imaging  Head US:  Grade I–II B/L subependymal hemorrhage.  Left thalamic intraparenchymal hemorrhage.
  • 6. 6 Normal Cranial US Imaging cont’d
  • 7. 7 Cranial US of patient Imaging cont’d
  • 8. 8 US showing Grade IV IVH Imaging cont’d
  • 9. 9 Case  MRI:  Intraventricular hemorrhage involving bilateral lateral ventricles, third and fourth ventricles with mild ventricular dilation including temporal horns.  Diffusion restriction within bilateral internal capsules, periventricular areas and corpus callosum likely representing ischemic changes.  Thrombosis of the posterior aspect of the superior sagittal sinus. Also partial thrombosis of the straight sinus. Imaging cont’d
  • 10. 10 Imaging cont’d
  • 11. 11 Questions??  How common is sinus venous thrombosis?  Should neonates with sinus venous thrombosis be anticoagulated?
  • 12. 12 Venous Drainage of the Brain
  • 13. 13 Drainage System  Transverse Sinus:  Drains the temporal and occipital cortex  Sylvia Veins and Cavernous Sinus:  Drains central part of the convexity  Superior Sagittal Sinus:  Drains the remaining part of the cortex  Deep Venous System:  Deep basal ganglia veins - drain basal ganglia (and germinal matrix)  This drains into the vein of Galen and the straight sinus
  • 14. 14 Cerebral Veins  Sinuses:  Are fixed to an external structure to the brain - more rigid  This helps maintain patency  No valves in this system suggesting passive flow.  May not be very responsive to changes in systemic pressure
  • 15. 15 Epidemiology  Canadian Study:  Incidence was 0.67/100,000 children  43% of these were under a month of age  German Pediatric Thrombophilia Registry:  Incidence of 2.6/100,000 neonates/year  Incidence 0.35/100,000 children/year DeVeber et al, NEJM 2001
  • 16. 16 Age Distribution DeVeber et al, NEJM 2001
  • 17. 17 Location DeVeber et al, NEJM 2001
  • 18. 18DeVeber et al, NEJM 2001 Location
  • 19. 19 Neurological manifestations DeVeber et al, NEJM 2001
  • 20. 20 Risk Factors DeVeber et al, NEJM 2001
  • 21. 21 Some Compounding Factors  Common events that may complicate CVST:  Ear infections  Meningitis  Anemia  Head injury
  • 22. 22 Radiologic Evaluation  CT Scan:  The diagnosis of CVST is missed in up to 40% of cases. (Barron et al., 1992, DeVeber et al., 2001)  MRI:  Diffusion and perfusion MRI is helpful to differentiate cytotoxic and vasogenic edema.  Does not differentiate between arterial and venous infarcts. (Forbes et al. 2001)  MRA/MRV:  Workup method of choice to see flow through vasculature.
  • 23. 23 Outcome of Sinovenous Thrombosis  42 children  Ages 3 weeks – 13 months  Five hospitals with pediatric stroke registry  Patients enrolled had documented CVST (either by CT or MRI by a neuroradiologist).  The database was used to collect data on presenting symptoms, radiologic and laboratory results at presentation and long term clinical and radiological follow up. Sebire et al, Brain 2005
  • 24. 24 Outcomes  All patients had at least one follow up with a pediatric neurologist  Functions assessed:  Function in nursery school  Ongoing headaches  Epilepsy  Neurologic Exam done  Outcome classification:  Death  Cognitive sequelae  Motor sequelae  Visual sequelae  Pseudotumor cerebri  None of the above Sebire et al, Brain 2005
  • 25. 25  Anticoagulation:  18 (43%) were treated with anticoagulation  6 (33%) anticoagulated had hemorrhage at presentation.  None had extension of their bleed and all survived  6 children were not anticoagulated due to extent of hemorrhage Treatment Sebire et al, Brain 2005
  • 26. 26 Results  Location of thrombus  16 (38%) - Superior Sagittal Sinus  11 (26%) - Sigmoid sinus  20 (47%) - Transverse or Lateral  4 (9%) - either the cavernous or Straight sinus  Radiologic Findings:  4 (9%) - bilateral hemorrhagic infarcts  7 (16%) - unilateral infarcts Sebire et al, Brain 2005
  • 27. 27 Results cont'd  26 (62%) suffered sequelae  12 (28.5%) - chronic pseudotumor cerebri  14 (33%) – cognitive/behavioral disabilities  5 (12%) - died Sebire et al, Brain 2005
  • 28. 28 Predictors  Death was associated with GCS <12  Good outcomes:  Older age (P=0.008)  Lateral and sigmoid Sinus (P=0.02)  Lack of parenchymal abnormality (P=0.1)  Anticoagulation Sebire et al, Brain 2005
  • 29. 29 Clinical Setting of CVST  Clinical Risk factors were found in all patients observed in this study. (pre-existing condition, dehydration, infection)  Prothrombotic disorders were found in 62% of patients.  Elevated factor VIII and MTHFR most common  55% of children in this study had an recent infections Sebire et al, Brain 2005
  • 30. 30 Treatment DeVeber et al, NEJM 2001
  • 31. 31 Inherited Thrombophilia  Most common genetic disorder  Prothrombin gene mutation  Factor V Leiden gene mutation  DeVeber et al NEJM, 2001  Lussana et al Seminars in Thrombosis and Hemostasis, 2007  Most common acquired disorder  Antiphospholipid syndrome (Heller et al Circulation, 2003)
  • 32. 32 American College of Chest Physicians  Clinical Practice Guidelines 2008:  Neonates without significant intracranial hemorrhage - anticoagulation (unfractionated heparin followed by LMWH)  Minimum treatment is 6 weeks and maximum is 3 months  Re-imaging to assess thrombus should be done at the end of therapy.  If a thrombus still exists therapy with LMWH should be continued for 3 additional months
  • 33. 33 American College of Chest Physicians  Clinical Practice Guidelines 2008:  Neonates with significant intracranial hemorrhage.  Monitor thrombus 5-7 days to assess extension of thrombus  If propagating - anticoagulation  Patients with recurrent risk factors should receive prophylactic therapy at those times.
  • 34. 34 Case – F/U  JS was anticoagulated with Lovenox and serial imaging done to monitor thrombus  IVH led to increasing hydrocephalus requiring to shunt placement.  Patient was treated with AED for seizures.
  • 35. 35 Follow-up 5/18/10
  • 36. 36 Follow-up  MRI and US (10 weeks post Lovenox)  No subependymal  No intracranial hemorrhage  No intraventricular hemorrhage
  • 37. 37 Summary  Cerebral sinovenous thrombosis is more common in neonates  Etiology is unknown in most cases  Anticoagulation in neonates with CSVT though controversial, is safe and should be for a minimum of 6 weeks  In neonates with CSVT, about 70% would have some degree of impairment
  • 38. 38 Thank you!!!