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                                                                                                                     The team:
                                                                                                                             Major David Baxter
BIOSAP: Blast Injury Outcome Study in                                                                                            Dr David Sharp (IC)

Armed forces Personnel
                                                                                                                                 Dr Tony Goldstone (IC)
                                                                                                                                 Dr Richard Greenwood (UCL)
                                                                                                                                 Mr Neil Kitchen (UCL)

                                                                                                                     Location:
                                                                                                                                 Computional, Clinical & Cognitive Neuroimaging Lab (C3NL) –
                                                                                                                                 The Hammersmith Hospital (IC)
                                                                                                                                 The Robert Steiner MRI Center – The Hammersmith Hospital (IC)
Major David Baxter RAMC
SSNP Conference                                                                                                                  Defence Medical Rehabilitation Centre - Headley Court
September 2012




Blast wave physics                                                                                                   Blast wave physics




Primary, secondary, tertiary and quaternary injury                                                                   Background


                                                                                                                     Background:

                                                                                                                     Civilian TBI – outcome is poorly understood. Because pathophysiology is
                                                                                                                     not well understood.

                                                                                                                     This is true (more so) for blast. Nevertheless…




Cernak et al Traumatic brain injury: an overview of pathobiology with emphasis on military populations. Journal of
Cerebral Blood Flow & Metabolism (2010) 30, 255–266




                                                                                                                                                                                                 1
Improvements in diagnosis of non-penetrating brain
    injury                                                                                                     Focal injury and white matter damage

                                                                                                                       Contusion location                           Diffuse axonal injury
               Conventional                     MRI; T1, T2, Flair              DTI, SWI, Gradient Echo
               imaging
               i.e. xray and CT




                                                                                                                                                                  Grade 2: lesions in corpus callosum




                                                                                                                                                                  Grade 3: lesions also in brainstem
                                                                                                                                                                                            Adams et al ‘85




    Hypothesis and Impact                                                                                      What is the BIOSAP project and what are its aims

    Aim:
                  1. To characterize the neuropsychological and endocrine
                  consequences of blast traumatic brain injury.
                                                                                                                                ADMEM database
                  2. To compare this to civilian traumatic brain injury.
                                                                                                                                                     Imaging                  Imaging
                                                                                                                                DMRC Headley
                                                                                                                                Court                studies                  studies
    Hypothesis:
                                                                                                                                                     Endocrine                Endocrine
            1. Blast causes a specific pattern of white matter damage,                                                          B’ham hospitals      assessment               assessment
            that can be assessed using MRI.                                                                    Blas
                                                                                                               t TBI                                 Psychologica             Psychologica
                                                                                                                                                     l assessment             l assessment
                                                                                                                                Clinician referral
    Impact:
                  1. Gives the capability of screening blast injured soldiers
                  2. Provide evidence about the mechanism of blast injury.




                                                                                                               MRI assessment
Criteria

Inclusion                                             Exclusion                                                Structural MRI
•   Moderate to severe traumatic brain injury         •      Cognitive impairment such that the subject will
•   GCS <14                                                  be unable to cooperate.
•   LOC >30mins                                                                                                          T1
•   PTA >24hrs                                        •      Significant language or visuo-spatial                       T2 Flair
                                                             impairments..
                                                                                                                         T2 FFE – Gradient Echo
•   History of Blast injury.
                                                      •      Penetrating head injury or neurosurgery.                    Diffusion tensor imaging - DTI
•   Persistent cognitive impairment.                                                                                     Susceptibility Weighted Imaging – SWI
                                                      •      Overt bleeding visible on CT (excluding the
                                                             presence of microbleeds – a marker of diffuse
•   No significant premorbid neurological or                 axonal injury).
    psychiatric illness.                                                                                       Functional MRI

•   Able to give informed consent.


•   Ability to perform the scanning paradigm.

•   Clinically stable.




                                                                                                                                                                                                              2
Neuropsychological & Psychiatric Test Battery                                    Endocrine Assessment

Cognitive: (developed with Professor Jane Powell - Goldsmiths)                   •   Traumatic brain injury produces significant dysfunction in the
                                                                                     hypothalamic-pituitary axis in a significant number of patients
Intellectual function - WASI similarities, WASI Matrix reasoning                     [Schneider et al., 2007]

Executive function - Trail Making Test, Inhibition/switching, Letter fluency     •   Impairments persisting in 15-50% of patients. E.g. severe growth
                                                                                     hormone deficiency is seen in 10-20% of patients following traumatic
Memory function and learning - People Test immediate recall                          brain injury.

Information processing speed - Colour naming (s), Word reading (s)
                                                                                 •   Limits brain recovery.

Psychiatric:
                                                                                 •   Important therapeutic opportunity.
Including: AGHDA, Beck Depression Inventory, Epworth Sleepiness, Nottingham
Health Profile, SF-36
PTSD
Mood disturbance
Anxiety




Case 1: History
                                                                               Case 1: Structural imaging findings

28yo male                                                                      T2Flair                                    Gradient Echo
Top cover
Wearing Helmet and eye protection
50 Kg IED.
Multiple fractures. Superficial lacerations. Left sided pneumothorax.

Initial GCS 12/15
2 weeks of retrograde amnesia
6 weeks of post-traumatic amnesia
On neuropsychological assessment;
          Impaired executive function, memory and processing speed




Case 1: Outcome                                                                  Case 2: History



                                                                                 27yo. Male
          Returned to work in a limited capacity but struggling…                 Passenger in vehicle
                                                                                 Wearing body armour and Helmet
                                                                                 IED of unknown size
                                                                                 Multiple fractures and lacerations. Left sided pneumothorax.

                                                                                 Initial GCS 13/15
                                                                                 1 day retrograde amnesia
                                                                                 4 days post traumatic amnesia
                                                                                 On neuropsychological assessment;
                                                                                          Impaired memory




                                                                                                                                                            3
Case 2: Outcome
Case 2: Structural imaging findings

T2Flair                                Gradient Echo
                                                                                        Currently studying for Msc.




  Case summary                                                                 Results


  Conventional imaging
                                                                               • 20 blast injured soldiers
  1. Gradient echo imaging is more sensitive than standard T1 and Flair to
  the changes associated with diffuse axonal injury
                                                                               • 40 age matched civilians with moderate
                                                                                 to severe TBI
  2. But…the presence of microbleeds can still be associated with very
  variable clinical outcome.                                                   • 40 uninjured civilian controls




  Study participant demograhics                                              Diffusion tensor imaging


                 Controls       Military       Civilian       Difference           Cortex


   Age           30.6 yrs (SD   29.4 yrs (SD   30.3 yrs (SD   No
                 6.7)           5.8)           7.6)           difference

   Time since    n/a            14.6 mnths     12 mnths       No
   injury                       (SD 5.9)       (SD 12.7)      difference                                                White matter - TBI




   Contusion     n/a            9 (45%)        10 (50%)       No
                                                              difference

   Microbleeds   n/a            5 (25%)        5 (25%)        No
                                                              difference                                              Low fractional anisotropy
                                                                                                                         Mori et al Neur
                                                                                                                      & High mean diffusivity




                                                                                                                                                  4
DTI Results TBSS               Pattern analysis




Pattern analysis results       Now focus on the bTBI group




Endocrine assessment results   Region of Interest analysis




                                                             5
Neuropsychological and QoL assessment results   Summary


                                                1. MRI changes following blast traumatic brain injury are associated with,
                                                   neuropsychological, neuropsychiatric and endocrine changes.

                                                2. Blast traumatic brain injury produces a hetreogenous white matter
                                                   injury pattern, however some regions appear to particularly vulnerable
                                                   to injury from blast.

                                                3. We will attempt to use this research to identify patients who will go on
                                                   to have a poor clinical outcome, and provide information about the
                                                   mechanism of blast.




BIOSAP


Thanks to;
        DPMD       Prof M Midwinter
                   Dr A K Samra
                   Mjr C Lethbridge
      DMRC         Col Etherington
                   Wng Cmdr A Bennett
                   Kit Malia
                   Doreen Rowland
                   Ronel Terblanche
                   Alison Lutte-Elliott
      Goldsmiths   Prof Jane Powell




                                                                                                                              6

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David Baxter - Biosap

  • 1. Aim of this presentation The team: Major David Baxter BIOSAP: Blast Injury Outcome Study in Dr David Sharp (IC) Armed forces Personnel Dr Tony Goldstone (IC) Dr Richard Greenwood (UCL) Mr Neil Kitchen (UCL) Location: Computional, Clinical & Cognitive Neuroimaging Lab (C3NL) – The Hammersmith Hospital (IC) The Robert Steiner MRI Center – The Hammersmith Hospital (IC) Major David Baxter RAMC SSNP Conference Defence Medical Rehabilitation Centre - Headley Court September 2012 Blast wave physics Blast wave physics Primary, secondary, tertiary and quaternary injury Background Background: Civilian TBI – outcome is poorly understood. Because pathophysiology is not well understood. This is true (more so) for blast. Nevertheless… Cernak et al Traumatic brain injury: an overview of pathobiology with emphasis on military populations. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 255–266 1
  • 2. Improvements in diagnosis of non-penetrating brain injury Focal injury and white matter damage Contusion location Diffuse axonal injury Conventional MRI; T1, T2, Flair DTI, SWI, Gradient Echo imaging i.e. xray and CT Grade 2: lesions in corpus callosum Grade 3: lesions also in brainstem Adams et al ‘85 Hypothesis and Impact What is the BIOSAP project and what are its aims Aim: 1. To characterize the neuropsychological and endocrine consequences of blast traumatic brain injury. ADMEM database 2. To compare this to civilian traumatic brain injury. Imaging Imaging DMRC Headley Court studies studies Hypothesis: Endocrine Endocrine 1. Blast causes a specific pattern of white matter damage, B’ham hospitals assessment assessment that can be assessed using MRI. Blas t TBI Psychologica Psychologica l assessment l assessment Clinician referral Impact: 1. Gives the capability of screening blast injured soldiers 2. Provide evidence about the mechanism of blast injury. MRI assessment Criteria Inclusion Exclusion Structural MRI • Moderate to severe traumatic brain injury • Cognitive impairment such that the subject will • GCS <14 be unable to cooperate. • LOC >30mins T1 • PTA >24hrs • Significant language or visuo-spatial T2 Flair impairments.. T2 FFE – Gradient Echo • History of Blast injury. • Penetrating head injury or neurosurgery. Diffusion tensor imaging - DTI • Persistent cognitive impairment. Susceptibility Weighted Imaging – SWI • Overt bleeding visible on CT (excluding the presence of microbleeds – a marker of diffuse • No significant premorbid neurological or axonal injury). psychiatric illness. Functional MRI • Able to give informed consent. • Ability to perform the scanning paradigm. • Clinically stable. 2
  • 3. Neuropsychological & Psychiatric Test Battery Endocrine Assessment Cognitive: (developed with Professor Jane Powell - Goldsmiths) • Traumatic brain injury produces significant dysfunction in the hypothalamic-pituitary axis in a significant number of patients Intellectual function - WASI similarities, WASI Matrix reasoning [Schneider et al., 2007] Executive function - Trail Making Test, Inhibition/switching, Letter fluency • Impairments persisting in 15-50% of patients. E.g. severe growth hormone deficiency is seen in 10-20% of patients following traumatic Memory function and learning - People Test immediate recall brain injury. Information processing speed - Colour naming (s), Word reading (s) • Limits brain recovery. Psychiatric: • Important therapeutic opportunity. Including: AGHDA, Beck Depression Inventory, Epworth Sleepiness, Nottingham Health Profile, SF-36 PTSD Mood disturbance Anxiety Case 1: History Case 1: Structural imaging findings 28yo male T2Flair Gradient Echo Top cover Wearing Helmet and eye protection 50 Kg IED. Multiple fractures. Superficial lacerations. Left sided pneumothorax. Initial GCS 12/15 2 weeks of retrograde amnesia 6 weeks of post-traumatic amnesia On neuropsychological assessment; Impaired executive function, memory and processing speed Case 1: Outcome Case 2: History 27yo. Male Returned to work in a limited capacity but struggling… Passenger in vehicle Wearing body armour and Helmet IED of unknown size Multiple fractures and lacerations. Left sided pneumothorax. Initial GCS 13/15 1 day retrograde amnesia 4 days post traumatic amnesia On neuropsychological assessment; Impaired memory 3
  • 4. Case 2: Outcome Case 2: Structural imaging findings T2Flair Gradient Echo Currently studying for Msc. Case summary Results Conventional imaging • 20 blast injured soldiers 1. Gradient echo imaging is more sensitive than standard T1 and Flair to the changes associated with diffuse axonal injury • 40 age matched civilians with moderate to severe TBI 2. But…the presence of microbleeds can still be associated with very variable clinical outcome. • 40 uninjured civilian controls Study participant demograhics Diffusion tensor imaging Controls Military Civilian Difference Cortex Age 30.6 yrs (SD 29.4 yrs (SD 30.3 yrs (SD No 6.7) 5.8) 7.6) difference Time since n/a 14.6 mnths 12 mnths No injury (SD 5.9) (SD 12.7) difference White matter - TBI Contusion n/a 9 (45%) 10 (50%) No difference Microbleeds n/a 5 (25%) 5 (25%) No difference Low fractional anisotropy Mori et al Neur & High mean diffusivity 4
  • 5. DTI Results TBSS Pattern analysis Pattern analysis results Now focus on the bTBI group Endocrine assessment results Region of Interest analysis 5
  • 6. Neuropsychological and QoL assessment results Summary 1. MRI changes following blast traumatic brain injury are associated with, neuropsychological, neuropsychiatric and endocrine changes. 2. Blast traumatic brain injury produces a hetreogenous white matter injury pattern, however some regions appear to particularly vulnerable to injury from blast. 3. We will attempt to use this research to identify patients who will go on to have a poor clinical outcome, and provide information about the mechanism of blast. BIOSAP Thanks to; DPMD Prof M Midwinter Dr A K Samra Mjr C Lethbridge DMRC Col Etherington Wng Cmdr A Bennett Kit Malia Doreen Rowland Ronel Terblanche Alison Lutte-Elliott Goldsmiths Prof Jane Powell 6