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  1. 1. 1 Thrombosis: A Focus on the Neonate 05/21/10
  2. 2. 2 NOTHING TO DECLARE
  3. 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. 4 Case Presentation  DOL #2 patient developed  tremors concerning for seizure  Shrill cry  Unstable temp  Transfer to SLCH
  5. 5. 5 Case Imaging  Head US:  Grade I–II B/L subependymal hemorrhage.  Left thalamic intraparenchymal hemorrhage.
  6. 6. 6 Normal Cranial US Imaging cont’d
  7. 7. 7 Cranial US of patient Imaging cont’d
  8. 8. 8 US showing Grade IV IVH Imaging cont’d
  9. 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. 10 Imaging cont’d
  11. 11. 11 Questions??  How common is sinus venous thrombosis?  Should neonates with sinus venous thrombosis be anticoagulated?
  12. 12. 12 Venous Drainage of the Brain
  13. 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. 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. 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. 16 Age Distribution DeVeber et al, NEJM 2001
  17. 17. 17 Location DeVeber et al, NEJM 2001
  18. 18. 18DeVeber et al, NEJM 2001 Location
  19. 19. 19 Neurological manifestations DeVeber et al, NEJM 2001
  20. 20. 20 Risk Factors DeVeber et al, NEJM 2001
  21. 21. 21 Some Compounding Factors  Common events that may complicate CVST:  Ear infections  Meningitis  Anemia  Head injury
  22. 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. 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. 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. 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. 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. 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. 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. 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. 30 Treatment DeVeber et al, NEJM 2001
  31. 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. 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. 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. 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. 35 Follow-up 5/18/10
  36. 36. 36 Follow-up  MRI and US (10 weeks post Lovenox)  No subependymal  No intracranial hemorrhage  No intraventricular hemorrhage
  37. 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. 38 Thank you!!!

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