1. The Neuropathological Reality of Diffuse Axonal Injury Dr Willie Stewart PhD FRCPath Consultant and Lead Neuropathologist Honorary Clinical Senior Lecturer Southern General Hospital, UK

3. Accrued between 1970 and 2006

4. Standardised sampling protocols

5. Formalin fixed, paraffin embedded

6. Standardised reporting

7. Over 150 publications using variety of techniques

8. Approx 1200 DNA samples from (largely) non-fatal TBI cases in longitudinal studies

9. Approx 50 fresh frozen TBI cases + age matched controlsClinical cohorts in longitudinal studies of outcome (up to several decades)

11. Terminology

12. Pathology

13. Macroscopic appearances

14. Histology

15. Time course

16. Myths and misunderstandings

17. Knowledge gapsn = magic number

19. Diffuse damage to white matter of immediate impact type

20. Diffuse white matter shearing injury

21. Inner cerebral trauma

22. Diffuse axonal injury (DAI)

23. Traumatic axonal injury (TAI)

25. parasagittal white matter

26. corpus callosum

27. internal capsule

28. fornices

29. cerebellar peduncles

31. Pathology grading system questioned n lucid interval Grade 1 10 2(6) Grade 2 29 9(5) Grade 3 83 6 No dTAI 312 ?

33. Diffuse traumatic axonal injury Haematoxylin and eosin axonal swellings and bulbs Silver impregnation (Palmgren) 15-18h survival approx 30% fatal TBI Amyloid precursor protein (APP) anterograde transport. Accumulates proximal to injury sub 1h survival (?) range of axonal abnormalities (partially) described time course of pathology (partially) characterised in majority fatal TBI Synaptophsin, ubiquitin, neurofilament, tau....

34. H&E

35. LFB/CV

36. Palmgren

37. APP

40. altercation in house

41. fall

42. no LOC

43. lucid and mobile immediately after

44. next morning found unresponsive

45. Local hospital- GCS ??

46. no intervention

47. died 4/7 after admission

49. APP H&E H&E APP

50. Single mTBI “The third case, which showed a mild degree of white matter change associated with congophilicangiopathy, also had one of the highest”

52. Time course axonal APP pathology APP

58. Observed across the age spectrum

59. Diffuse in nature

62. Neurofibrillarytangles (NFTs)

64. Present in vast majority fatal TBI

65. Pathology of dTAI in mild requires further work

66. May persist several years after injury

67. Association with neurdegenerative pathology

69. Accrued between 1970 and 2006

70. Standardised sampling protocols

71. Formalin fixed, paraffin embedded

72. Standardised reporting

73. Over 150 publications using variety of techniques

74. Approx 1200 DNA samples from (largely) non-fatal TBI cases in longitudinal studies

75. Approx 50 fresh frozen TBI cases + age matched controlsClinical cohorts in longitudinal studies of outcome (up to several decades)