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Medical Consequences of Acquired Brain Injury: Making Things Better After ABI

This conference will focus on the medical consequences of acquired brain injury (ABI) and how to improve outcomes for patients. Topics include causes of ABI, importance of traumatic brain injury, brain damage after TBI, limbic memory system, deficits resulting from ABI, and quality of survival measures.

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Medical Consequences of Acquired Brain Injury: Making Things Better After ABI

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  1. MEDICAL CONSEQUENCES OF ACQUIRED BRAIN INJURY Making Things Better After ABI SHIPS Project Conference, Bristol Vassall Centre, Fishponds July 2 2015 Dr Peta Sharples Consultant Paediatric Neurologist

  2. CAUSES OF ACQUIRED BRAIN INJURY • Traumatic brain injury (TBI) • CNS infection • Acute Disseminated Encephalomyelitis (ADEM) • Autoimmune Encephalitis • Brain tumours • Cerebrovascular accidents • Hypoxic-ischaemic encephalopathy • Status epilepticus • Metabolic encephalopathy

  3. Importance of Traumatic Brain Injury • Traumatic Brain Injury (TBI) is the single major cause of death and hospital admission in Northern region, with admission rate of 1 in 200 children per year(Sharples et al, 1990) • 83% of children admitted > 24 hours for TBI have sustained mild TBI and 17% severe or moderate TBI(Hawley et al, 2003) • Epidemiological data from North America suggests disability rate on hospital discharge of TBI children to be 112/100,000 children, extrapolation to the UK suggesting 10,000 children per year might potentially benefit from rehabilitation(Kraus et al, 1990) • However, these figures are based on the assumption that the proportion of TBI children with disability is 100% for severe TBI, 90% for moderate TBI & 10% mild TBI (Sharples, 1998) • Severe TBI significantly more common in areas of socio-economic deprivation

  4. Aetiology of Non-traumatic coma n = 328 Admissions to BRHC PICU 1997-2001

  5. Non-traumatic coma in relation to age n = 328 median age = 2 years

  6. BRAIN DAMAGE AFTERTBI • Primary injury Contusions Diffuse axonal injury • Secondary hypoxic-ischaemia injury Intracranial Intracranial haematoma (extradural, subdural) Diffuse brain swelling Contusions Extracranial Systemic hypoxia / hypotension • Another dimension Endogenous cascade of auto-destructive events initiated by TBI

  7. Secondary Delayed Brain Damage NECROSIS IL-1 beta TNF-alpha Cytokines IL-1β, TNFα mitochondria NMDA ROS NO NMDA AMPA AMPA mitochondrium Necrotic cell death Endogenous repair mechanisms – nerve growth factors (neurotrophins)

  8. Mannitol Hypertonic saline Decompression Ventricular Drain Surgical evacuation Barbiturates Moderate hypothermia Hyperventilation

  9. Histological Studies – FPI in rat Grundy et al, 2003 Left hippocampus CA3/2 region Hilus of DG CA1 CA2 Sham DG CA3 FPI

  10. THE LIMBIC MEMORY SYSTEM Amygdala Basal forebrain Basal ganglia LIMBIC SYSTEM BASAL FOREBRAIN HIPPOCAMPUS BASAL FOREBRAIN CHOLINERGIC SYSTEM

  11. Statistical maps of significant FA group differences () (control > severe/moderate TBI, late post childhood injury) in sagittal, coronal and axial views overlaid on mean FA image & TBSS skeleton () Tziraki, Daskas et al 2013 • Significant differences between severe/moderate TBI and controls in : • Intra-hemispheric association fibres (external capsule, sagittal striatum, superior longitudinal fasiculus) • Commissural fibres (splenium of corpus callosum, uncinatefasiculus,) • Projection fibres (anterior & superior corona radiata, anterior & posterior thalamic radiation) • Corticospinal tract

  12. FRONTAL Attention Intellect (abstraction) Executive function, flexibility Behaviour (inhibition) Higher memory functions Motor function PARIETAL Language Sensory perception OCCIPITAL Cortical blindness Visual problems TEMPORAL Memory (encoding, retrieval) Language Behaviour/Emotion BRAIN STEM Wakefulness/arousal, attention Cranial nerves Motor function (spastic quadriparesis, ataxia)

  13. Some of the deficits resulting from acquired brain injury BSRM & RCP Working Party, 2003

  14. Quality of Survival Measures

  15. DISCHARGE KOSCHI CATEGORY n = 81 (29 severe, 15 moderate, 37 mild) Calvert et al, DMCN 2008

  16. COGNITIVE FUNCTION OVER TIME (24 MONTHS) POST-TBI Verbal IQ Performance IQ VIQ PIQ Controls Controls Mild TBI Mild TBI Severe/moderate TBI Severe/moderate TBI General Memory Index GENERAL MEMORY INDEX Controls MildTBI Severe/moderateTBI Miller, 2009

  17. Mild TBI and Outcome • Short term (1-2 years) follow up studies of paediatric mild TBI not demonstrated cognitive deficit but have shown behavioural problems • Uncertainty expressed as to extent emotional and behavioural problems reported in mild TBI children are due to: - injury - pre-morbid status - and/or familial dysfunction • In 2004, the WHO Collaborating Centre for Neurotrauma Task Force on Mild TBI critically reviewed 428 studies related to prognosis • On the basis of 120 papers considered methologically sound, they concluded that “children’s prognosis after mild TBI is good, with quick resolution of symptoms and little evidence of residual cognitive, academic or behavioural deficits” • Similar conclusions were reached for mild TBI in adults

  18. Health Related Quality of Life (HRQL) 12 months after severe/moderate & mild TBI p < 0.001 p < 0.001 Severe/Moderate Severe/Moderate Mild Control Mild Control PedsQL™ Total Scale Score PedsQL™ Psychosocial Health Summary Score

  19. PedsQL scores 12 months post TBI Severe/Moderate Mild Control

  20. Overall QoL (PedsQL total score) vs. Verbal IQ & Performance IQ in severe/moderate TBI 12 months post injury r=0.45; p= 0.03 r=0.56; p= 0.01

  21. * * * * * * 60 severe/moderate 50 mild * * control 40 30 * p < 0.001 20 10 0 Internalising Externalising Total Competence Total problem CBCL INDICES: TBI vs. CONTROLS AT 6 MONTHS POST-TBI

  22. Overall QoL (PedsQL total score) vs. Child Behaviour Checklist (CBCL) at 12 months after TBI r = -0.63; p < 0.0001 r = -0.66; p < 0.0001 r = -0.47; p < 0.0001

  23. Family Burden of Injury (FBII) vs. CBCL FBII vs. CBCL Externalizing Index FBII vs. CBCL Internalizing Index 3 3 t= 0.18; p = 0.038 t= 0.17; p = 0.05 2 2 FBII rating score FBII rating score 1 1 0 0 0 10 20 30 40 50 20 0 10 30 40 50 CBCL Ext Index CBCL Int. Index FBII vs. CBCL Total Problem Score FBII vs. CBCL Total Competence 3 3 2 2 FBII rating score t = - 0.19; p = 0.008 t = 0.22; p = 0.011 FBII rating score 1 1 0 0 0 10 20 30 0 50 100 CBCL Social competence CBCL Total Problem Score

  24. THE LIMBIC MEMORY SYSTEM Amygdala Basal forebrain Basal ganglia LIMBIC SYSTEM BASAL FOREBRAIN HIPPOCAMPUS BASAL FOREBRAIN CHOLINERGIC SYSTEM

  25. EXECUTIVE FUNCTION • Executive function encompasses a range of interrelated abilities that direct, guide and regulate cognitive, emotional and behavioural functions and provide ability to engage in complex activities, such as multitasking • Psychologists often describe the frontal lobe as the ‘control’ centre for executive functioning, due to the dense connectivity of this region with other brain regions. • Damage to frontal and prefrontal areas and their connections often results in executive dysfunction • Executive function is difficult to assess in a structured cognitive test situation, as this often does not place sufficient demand on regulatory abilities • Standardised questionnaires e.g. the Behaviour Rating Inventory of Executive Function (BRIEF) can give more insight

  26. BEHAVIOURAL PATHOLOGY & NEUROANATOMY • Late development of frontal lobes • Late emergence of functional competence (Chelune & Baer, 1986; Passler et al, 1985; Welsh, Pennington, & Groisser, 1991) • Late emergence of behavioural dysfunction secondary to executive function deficits

  27. Traumatic Brain Injury: deficits in relation to time after injury

  28. BRIEF: Behavioural Regulation Index 24 months post-TBI * * 70 Severe 60 Moderate 50 Mild Control 40 T Score 30 * p < 0.05 20 10 0 Severe Moderate Mild Control Severity

  29. LATE EMOTIONAL & BEHAVIOURAL OUTCOME POST CHILDHOOD TBITBI and controls Daskas et al, 2013

  30. LATE COGNITIVE FUNCTIONING (7 YEARS+) POST CHILDHOOD TBI Daskas et al, 2013 p=0.005 p=0.016 HUI3 single-attribute self-report scores for cognition in TBI and control groups

  31. Outcome of mild TBI in children:a prospective UK cohort study • Data analysed from the Avon Longitudinal Study of Parents and Children (ALSPAC) • TBI cases (n=410) defined as any head injury resulting in loss of consciousness and/or skull fracture before age 11 • Comparison group (n=1819) created from children who suffered traumatic orthopaedic injuries (fractures, excluding of skull) • Control group (n=8770) consisted of children without TBI or orthopaedic injury

  32. Outcome of mild TBI in children:a prospective UK cohort study • TBI children more likely than controls to live in SE adversity • TBI children more likely than controls (but not orthopaedic group) to have high hyperactivity and conduct scores age 42 months • Outcomes at ages 13 and 16 yrs associated with mild TBI were: - SDQ total behavioural problem score - SDQ hyperactivity score - SDQ conduct problems - Increased anxiety levels - Increased depressive symptomatology • Adjustment for pre-injury SDQ scores attenuated the TBI SDQ scores, but they remained significantly different from controls • Weak associations observed between orthopaedic injuries and later conduct problems • We conclude that mild TBI in childhood is associated with increased behavioural problems up to age 16 years, not explained by pre-injury characteristics, and with increased levels of depression and anxiety

  33. Long term outcome after mild TBI • Anstey et al, 2004 • Three age cohorts (20-44, 40-44, 60-64) randomly sampled from two Australian cities, yielding 7,485 participants. 5.7% reported history of TBI involving loss of consciousness >15 min, mean 22 years previously. • TBI associated with increased symptoms of depression, anxiety, negative affect and suicidal ideation. Effect size greatest in young adults. • Timonan et al, 2002 • General population birth cohort (n=12,058) in Northern Finland, followed up prospectively until age 31 years. • Data on TBIs obtained from hospital notes and Finnish Hospital Discharge Registers (FHDR), mental disorders incl. alcohol from FHDR, criminal offences from Justice Ministry • Controlling for confounders, TBI increased the risk of developing mental disorders two fold. • TBI significantly related to later mental disorder with coexisting criminality in males. • Williams et al, 2010 • Investigated rate of self-reported TBI in a male adolescent youth offending population. • TBI with loss of consciousness reported by 46% of 186 subjects (29.6% mild TBI). • Frequency of self reported TBI associated with more convictions, greater mental health problems and greater misuse of cannabis • > 3 TBIs associated with greater violence in offences

  34. MEASURES OF INJURY SEVERITY Glasgow Coma Scale (GCS) Designed to measure depth and duration of impaired consciousness in comatose patients. Accepted as a universal benchmark for classifying injury severity, esp. in acute period following head injury Post-traumatic amnesia (PTA) PTA is a transient state of altered cognition and behaviour associated with concussive type injuries. Duration of PTA has been used as an index of injury severity in head injured patients in follow up setting

  35. Less than 5 mins 5 mins to 1 hour 1 hour to 24 hours 24 hours to 2 weeks 2 to 4 weeks Greater than 4 weeks Minor Mild Moderate Severe Very severe Extremely severe PTA: INDEX OF TBI SEVERITYClassifications of TBI severity based on length of PTA(Jennett & Teasdale, 1981)

  36. SEVERITY OF INJURY Severity by admission GCS Severity by duration of PTA N = 33 N = 15 N = 8 35 N = 24 N = 15 N = 13 N = 4 35 30 30 25 25 20 No. of children 20 No. of children 15 15 10 10 5 5 0 0 Severe 3-8 Moderate 9-12 Mild 13-15 GCS moderate severe very severe extremely severe severity category severity category Miller et al, 2008

  37. INJURY SEVERITY IN RELATION TO PERFORMANCE IQ PTA vs. PIQ at 1 month PTA vs. PIQ at 12 months 150 150 rs = - 0.49: p = 0.001 N = 41 rs = - 0.48: p = 0.001 N = 56 125 125 PIQ PIQ 100 100 75 75 50 50 0 25 50 75 100 0 25 50 75 100 Duration PTA (days) Duration PTA (days) There was no significant relationship between admission GCS and Performance IQ at 1 month (rs= 0.15: p = 0.13) or 12 months post TBI (rs = 0.18: p = 0.12)

  38. INJURY SEVERITY IN RELATION TO SPEED OF INFORMATION PROCESSING PTA vs. Processing Speed at 1 month PTA vs. Processing Speed at 12 month 150 150 rs = - 0.32: p = 0.03 rs = - 0.51: p = 0.005 125 125 Speed information Speed information processing processing 100 100 75 75 50 50 0 25 50 75 100 0 25 50 75 100 Duration PTA (days) Duration PTA (days) There was no significant relationship between admission GCS and Speed Information Processing at 1 month (rs = 0.19: p = 0.14 ) or 12 months post TBI (rs = 0.14: p = 0.23)

  39. Health Related Quality of Life in the First Year After Diagnosis – Brain Tumour vs. Controls Penn et al, 2008

  40. Performance and Verbal IQ Performance IQ Verbal IQ

  41. Behaviour Problems: CBCL Parent Report

  42. Adaptive Behaviour: Parent Report Vineland Adaptive Behaviour Composite

  43. Education after ABI • Severe and moderate ABI is highly likely to lead to educational problems due to neurocognitive sequelae • Such difficulties typically increase with progression through education, esp. to secondary level • Mild ABI, esp. TBI, may also cause educational difficulties, but these may not emerge for years • Post-ABI children are at significant risk of behavioural problems, depression, anxiety, low self esteem, educational failure and social isolation

  44. Special educational needs of ABI children • Medical needs Epilepsy care plan (approx 7% of cases TBI) Management of fatigue Neuroendocrine sequelae • Rehabilitation needs • Physiotherapy /occupational therapy • Speech and Language therapy • Cognitive, psychological and social rehabilitation • School enacting the rehabilitation prescription

  45. Management of fatigue post-ABI • Graded return to school after injury • Timetable most demanding at optimum performance times e.g. morning • Provide rest / break periods • A “buddy” to carry books and equipment between classroom changes • Reduce demands when appropriate – individualised curriculum • Do not necessarily insist on completion of tasks • Develop a strategy to use when fatigue is obvious (e.g. designated quiet area for 10 mins) • Discuss management of homework – try to limit • Consider extra time in examinations

  46. DEFINITIONS OF REHABILITATION • The use of all means aimed at reducing the impact of disabling and handicapping conditions and at enabling disabled people to achieve social integration World Health Organisation1980 • A process of active change by which a person who has become disabled acquires the knowledge and skills needed for optimal physical, psychological and social function British Society of Rehabilitation Medicine 1997 • Rehabilitation aims to reduce the impact of (brain) injury by restoration of damaged function, or compensation for lost function, within the limitations of underlying disease, to optimise physical, cognitive, psychological and social function Seeley & Hutchinson, 2006

  47. National Standards for Paediatric ABI Neurorehab. centre Outreach Community disability Reports: Children’s Neurosurgical Specification Standards, 2011 Management of Children with Major Trauma NHS CAG Report, 2011 BPNA/BACCH Moving Forward - Services for Neurorehabilitation following ABI, 2006 Children’s NSF 2004, 2005 (Acquired Brain Injury Exemplar “Jack’s Journey”) NSF for Long Term Conditions, 2004 BRSM & RCP National Clinical Guidelines Rehabilitation following ABI, 2003 Aspects covered: Acute in-patient neuro-rehabilitation Post-acute in-patient neuro-rehabilitation Early management post-discharge Later management post-discharge Themes: Early intervention, on HDU and even ICU Timely access to expert rehabilitation treatment and services Specialist co-ordinated interdisciplinary in-patient rehabilitation team with ABI expertise Outreach from specialist in-patient centre into community Appropriate level of therapy/support - tailored to need and to individual child and family Access to educational provision Psychological needs children and their families, key worker Interdisciplinary working Co-ordinated care (NHS, education, social services) Framework of assessment Goal setting and assessment Outcome assessment (impairment, functional, emotional/behavioural, QoL, participation, family burden) Transition points, re-access to specialist service as required

  48. The “slinky” model of the phases of ABI rehabilitation Neurorehabilitation centre Outreach team Community Disability team BSRM, 2003

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