Stewart, William

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  • PalmgrenAlso reduced incidence skull fracture and falls and increased RTA in DAI casesCallosal lesion few mm diameter but extends through levels30% incidence by palmgren. Universal by APP
  • confidential
  • confidential
  • Stewart, William

    1. 1. The Neuropathological Reality of Diffuse Axonal Injury<br />Dr Willie Stewart PhD FRCPath<br />Consultant and Lead Neuropathologist<br />Honorary Clinical Senior Lecturer<br />Southern General Hospital, UK<br />
    2. 2. The Glasgow TBI Archive<br />unique dataset consisting of:<br /><ul><li>Approx 2000 cases with history of TBI (hours to decades survival)
    3. 3. Accrued between 1970 and 2006
    4. 4. Standardised sampling protocols
    5. 5. Formalin fixed, paraffin embedded
    6. 6. Standardised reporting
    7. 7. Over 150 publications using variety of techniques
    8. 8. Approx 1200 DNA samples from (largely) non-fatal TBI cases in longitudinal studies
    9. 9. Approx 50 fresh frozen TBI cases + age matched controls</li></ul>Clinical cohorts in longitudinal studies of outcome (up to several decades)<br />
    10. 10. The Neuropathological Reality of Diffuse Axonal Injury<br /><ul><li>Historical perspective
    11. 11. Terminology
    12. 12. Pathology
    13. 13. Macroscopic appearances
    14. 14. Histology
    15. 15. Time course
    16. 16. Myths and misunderstandings
    17. 17. Knowledge gaps</li></ul>n = magic number<br />
    18. 18. Diffuse traumatic axonal injury<br /><ul><li>Shearing injury
    19. 19. Diffuse damage to white matter of immediate impact type
    20. 20. Diffuse white matter shearing injury
    21. 21. Inner cerebral trauma
    22. 22. Diffuse axonal injury (DAI)
    23. 23. Traumatic axonal injury (TAI)
    24. 24. Diffuse traumatic axonal injury (dTAI)</li></li></ul><li>Diffuse traumatic axonal injury<br />Diffuse damage to axons in cerebral hemispheres, corpus callosum, brainstem and cerebellum. May be focal (haemorrhagic) lesion in corpus callosum and/ or brainstem.<br />Multifocal rather than diffuse<br /><ul><li>assymetrical involvement
    25. 25. parasagittal white matter
    26. 26. corpus callosum
    27. 27. internal capsule
    28. 28. fornices
    29. 29. cerebellar peduncles
    30. 30. brainstem tracts</li></li></ul><li>Diffuse traumatic axonal injury<br />Grade 1: Widespread axonal damage (stereotypical distribution)<br />Grade 2: Above plus focal lesion in corpus callosum<br />Grade 3: Above plus focal lesion in rostral brainstem <br /><ul><li> Now recognised in majority fatal TBI
    31. 31. Pathology grading system questioned</li></ul> n lucid interval<br />Grade 1 10 2(6)<br />Grade 2 29 9(5)<br />Grade 3 83 6<br />No dTAI 312 ?<br />
    32. 32.
    33. 33. Diffuse traumatic axonal injury<br />Haematoxylin and eosin<br /> axonal swellings and bulbs<br />Silver impregnation (Palmgren)<br />15-18h survival<br />approx 30% fatal TBI<br />Amyloid precursor protein (APP)<br />anterograde transport. Accumulates proximal to injury<br /> sub 1h survival (?)<br /> range of axonal abnormalities (partially) described<br /> time course of pathology (partially) characterised<br /> in majority fatal TBI<br />Synaptophsin, ubiquitin, neurofilament, tau....<br />
    34. 34. H&E<br />
    35. 35. LFB/CV<br />
    36. 36. Palmgren<br />
    37. 37. APP<br />
    38. 38.
    39. 39. Single mTBI<br /><ul><li>69 male
    40. 40. altercation in house
    41. 41. fall
    42. 42. no LOC
    43. 43. lucid and mobile immediately after
    44. 44. next morning found unresponsive
    45. 45. Local hospital- GCS ??
    46. 46. no intervention
    47. 47. died 4/7 after admission
    48. 48. Cause of death ‘bronchopneumonia’</li></li></ul><li>
    49. 49. APP<br />H&E<br />H&E<br />APP<br />
    50. 50. Single mTBI<br />“The third case, which showed a mild degree of white matter change associated with congophilicangiopathy, also had one of the highest”<br />
    51. 51.
    52. 52. Time course axonal APP pathology<br />APP<br />
    53. 53.
    54. 54.
    55. 55.
    56. 56.
    57. 57. Approximately 30% of acute TBI cases have amyloid-βplaques<br /><ul><li>Observed within hours of injury
    58. 58. Observed across the age spectrum
    59. 59. Diffuse in nature
    60. 60. Transient or persist?</li></li></ul><li>Amyloid plaque and NFT pathology is greater in TBI cases w survival >1year v controls<br />Frequent<br />Moderate<br />Sparse<br />Extensive<br />Moderate<br />Minimal<br />P=0.019; ChiSq<br />TBI Control<br />
    61. 61. Multiple mTBI<br />“Punch Drunk Syndrome” /dementia pugilistica / chronic traumatic encephalopathy (CTE)<br />Martland (1928): <br /><ul><li> tremors slowed movement, confusion, and speech problems </li></ul>Corsellis et al (1973) 15 ex-boxers:<br /><ul><li>septal and hypothalamic</li></ul>cavum septum <br />fornix and mammillary bodies atrophied<br /><ul><li>cerebellar</li></ul>tonsillarscarring, <br />reduction in Purkinje cells<br /><ul><li>substantia nigra – loss of pigment
    62. 62. Neurofibrillarytangles (NFTs)
    63. 63. TDP-43 abnormalities</li></li></ul><li>The Neuropathological Reality of Diffuse Axonal Injury<br /><ul><li>Terminology confused
    64. 64. Present in vast majority fatal TBI
    65. 65. Pathology of dTAI in mild requires further work
    66. 66. May persist several years after injury
    67. 67. Association with neurdegenerative pathology
    68. 68. under-estimated by imaging studies (for debate)</li></li></ul><li>The Glasgow TBI Archive<br />unique dataset consisting of:<br /><ul><li>Approx 2000 cases with history of TBI (hours to decades survival)
    69. 69. Accrued between 1970 and 2006
    70. 70. Standardised sampling protocols
    71. 71. Formalin fixed, paraffin embedded
    72. 72. Standardised reporting
    73. 73. Over 150 publications using variety of techniques
    74. 74. Approx 1200 DNA samples from (largely) non-fatal TBI cases in longitudinal studies
    75. 75. Approx 50 fresh frozen TBI cases + age matched controls</li></ul>Clinical cohorts in longitudinal studies of outcome (up to several decades)<br />

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