PRIME: Cognitive Outcome Following Major Burns

Patients were matched with for age, sex and IQ (as determined by National Adult Reading Test scores) controlled volunteers.

Participants were assessed for the following domains: verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed. The domains were assessed with the following validated cognitive tests: The Hopkins Verbal Learning Test, Trail making parts A and B, phonemic, semantic and switching verbal fluency as well as the Cogstate computerised battery: Identification speed, Detection speed, One Card Learning accuracy, One Back test accuracy, Two Back test accuracy, International Shopping List total correct answers and Groton Maze Learning total errors. Evidence of neuroinflammation was assessed using an fMRI protocol (Resting state MRI, T1w-MPR, T2 Space, Diffusion Tensor Imaging with 30 directions, right frontal white matter and posterior cingulate gyrus Single Voxel Spectroscopy, and patient group Susceptibility Weighted Imaging.

Quality of life was measured using the EuroQoL 5 Dimensions and visual analogue scale. Independent Activities of Daily Living was also assessed. Mental Health (as a confounder) was measured using the Patient Health Questionnaire 9, the Beck Depression Index II, the Beck Anxiety Inventory and the Trauma Screening Questionnaire.

Statistical methods include significant differences between the patient and control group using the Student t test (parametric data), the Mann Witney U test (non parametric data) or the Fisher's Exact test (qualitative scoring systems). MELODIC in FSL software was used to decompose the rs-fMRI data into brain networks using independent component analysis (ICA) and connectivity in these networks patients and controls was compared using dual regression. FreeSurfer was used to extract brain regions from T1 images and compare the normalised volume of the hippocampus, amygdala and precuneus for patients and controls. DTI data were analysed using tract based spatial statistics (TBSS) in FSL and using FreeSurfer regions for the hippocampus, amygdala and precuneus. Cho/Cr, Cho/NAA and Ins/Cr ratios were extracted from MRS data using Tarquin. SWI images were reviewed for the presence of microbleeds by two Radiologists.

Primary outcomes

• Neurocognitive deficit [Within 10 years of injury]: Median T score of cognitive results (verbal ability, verbal and visual learning, short-term memory, working memory, executive function, attention and processing speed)

Secondary outcomes

• Quality of Life [Within 10 years of injury]: EuroQoL 5D score
• Neuroinflammation [Within 10 years of injury]: As per the functional Magnetic Resonance Imaging protocol

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Invasive ventilation on a Burns Intensive Care Unit (BICU) within the previous ten years
* Burn injuries greater than 15% total body surface area (TBSA)
* Adult

Exclusion Criteria:

* Admission to BICU for other illnesses that were not burn related (such as Toxic Epidermal Necrolysis Syndrome)
* Evidence of head trauma
* Known substance misuse or alcohol excess
* Inability to understand plain verbal or written English
* Severe mental health issues
* Receiving formal psychiatric treatment
* Currently held under the Mental Health Act
* If the subject's psychological health was deemed to be at risk from inclusion
* Imprisoned
* Contraindications to MRI
* non-compatible pacemakers
* surgical metalwork or foreign bodies
* severe claustrophobia

• Marcela P Vizcaychipi, MD PhD, Principal investigator, Anaesthetic and Intensive Care Consultant