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BIOSAP: Blast Injury Outcome Study in

Armed forces Personnel

Major David Baxter RAMC

SSNP Conference

September 2012

Aim of this presentation

The team:

Major David Baxter

Dr David Sharp (IC)

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)

Defence Medical Rehabilitation Centre - Headley Court

Blast wave physics Blast wave physics

Primary, secondary, tertiary and quaternary injury

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

Background

Background:

Civilian TBI – outcome is poorly understood. Because pathophysiology is

not well understood.

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

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Improvements in diagnosis of non-penetrating brain

injury

Conventional

imaging

i.e. xray and CT

MRI; T1, T2, Flair DTI, SWI, Gradient Echo

Focal injury and white matter damage

Contusion location Diffuse axonal injury

Grade 2: lesions in corpus callosum

Grade 3: lesions also in brainstem

Adams et al ‘85

Hypothesis and Impact

Aim:

1. To characterize the neuropsychological and endocrine

consequences of blast traumatic brain injury.

2. To compare this to civilian traumatic brain injury.

Hypothesis:

1. Blast causes a specific pattern of white matter damage,

that can be assessed using MRI.

Impact:

1. Gives the capability of screening blast injured soldiers

2. Provide evidence about the mechanism of blast injury.

What is the BIOSAP project and what are its aims

Blast TBI

Imaging studies Endocrine assessment Psychological assessment

Imaging studies Endocrine assessment Psychological assessment

ADMEM database

DMRC Headley Court

B’ham hospitals

Clinician referral

Criteria

Inclusion • Moderate to severe traumatic brain injury

• GCS <14

• LOC >30mins

• PTA >24hrs

• History of Blast injury.

• Persistent cognitive impairment.

• No significant premorbid neurological or

psychiatric illness.

• Able to give informed consent.

• Ability to perform the scanning paradigm.

• Clinically stable.

Exclusion • Cognitive impairment such that the subject will

be unable to cooperate.

• Significant language or visuo-spatial

impairments..

• Penetrating head injury or neurosurgery.

• Overt bleeding visible on CT (excluding the

presence of microbleeds – a marker of diffuse

axonal injury).

MRI assessment

Structural MRI

T1

T2 Flair

T2 FFE – Gradient Echo

Diffusion tensor imaging - DTI

Susceptibility Weighted Imaging – SWI

Functional MRI

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Neuropsychological & Psychiatric Test Battery

Cognitive: (developed with Professor Jane Powell - Goldsmiths)

Intellectual function - WASI similarities, WASI Matrix reasoning

Executive function - Trail Making Test, Inhibition/switching, Letter fluency

Memory function and learning - People Test immediate recall

Information processing speed - Colour naming (s), Word reading (s)

Psychiatric:

Including: AGHDA, Beck Depression Inventory, Epworth Sleepiness, Nottingham

Health Profile, SF-36

PTSD

Mood disturbance

Anxiety

Endocrine Assessment

• Traumatic brain injury produces significant dysfunction in the

hypothalamic-pituitary axis in a significant number of patients

[Schneider et al., 2007]

• Impairments persisting in 15-50% of patients. E.g. severe growth

hormone deficiency is seen in 10-20% of patients following traumatic

brain injury.

• Limits brain recovery.

• Important therapeutic opportunity.

Case 1: History

28yo male

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: Structural imaging findings

T2Flair Gradient Echo

Case 1: Outcome

Returned to work in a limited capacity but struggling…

Case 2: History

27yo. Male

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

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Case 2: Structural imaging findings

T2Flair Gradient Echo

Case 2: Outcome

Currently studying for Msc.

Case summary

Conventional imaging

1. Gradient echo imaging is more sensitive than standard T1 and Flair to

the changes associated with diffuse axonal injury

2. But…the presence of microbleeds can still be associated with very

variable clinical outcome.

Results

• 20 blast injured soldiers

• 40 age matched civilians with moderate

to severe TBI

• 40 uninjured civilian controls

Study participant demograhics

Controls Military Civilian Difference

Age 30.6 yrs (SD

6.7)

29.4 yrs (SD

5.8)

30.3 yrs (SD

7.6)

No

difference

Time since

injury

n/a 14.6 mnths

(SD 5.9)

12 mnths

(SD 12.7)

No

difference

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

difference

Microbleeds n/a 5 (25%) 5 (25%) No

difference

Diffusion tensor imaging

Mori et al Neur

Cortex

White matter - TBI

Low fractional anisotropy

& High mean diffusivity

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DTI Results TBSS Pattern analysis

Pattern analysis results Now focus on the bTBI group

Endocrine assessment results Region of Interest analysis

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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