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  • Since the emergence of paediatric intensive care units the fatality rates associated with severe acute illness have declined dramatically. Most children admitted to PICU are now expected to make a complete medical recovery. However, considering the severity and life threat of medical illness necessitating PICU admission, the neuropsychological outcome of survivors has been an increasingly important area of research.
  • For example, a review conducted by Carter et al., (2001) assessed neurological impairment following CNS infections such as meningitis, encephalitis, tetanus or malaria in children. Most common impairments seen were in cognition or motor functions. Increased levels of impairment were seen after encephalitis and BM.
  • Whilst research suggests that neuropsychological sequelae are commonly evident following meningitis and encephalitis, most of this research has focused on illness onset in infants and young children and little is known about outcome in other age groups or in children with other types of critical illness.
  • A pilot study conducted by Imperial College at St Mary’s hospital sought to investigate the effect of acute severe illness on neuropsychological function in children aged 5-16 years old and explore associations between any identified impairments and psychological outcome measures.
  • However, need to be cautious when drawing conclusions from this study. Only a small sample. There were no patient controls and therefore it is difficult to attribute the source of this effect (i.e., Illness itself or the PICU admission more generally). Although some impairments were observed, the implications for a child’s future academic performance are as yet unknown. The persistence of the impairment is also unknown as there was no follow- up. A possible explanation for the association between emotional and memory impairment may lie in the marked biological stress associated with severe illness. Increased levels of cortisol have been associated with hippocampal damage. The hippocampus is implicated in learning and memory and is also connected to other regions in the limbic system, such as the amygdala, which is related to expression, recognition, and memory of emotions. Anomalous HPA axis reactivity and increased cortisol levels have been connected with stress disorders and memory impairment. SDQ Emotion and hyperactivity correlated with PRM. SDQ hyperactivity correlated with SWM & RVIP.
  • The present study aimed to replicate and extend the findings of the pilot study.
  • Neuropsychological Tests CANTAB The CANTAB is a computerised battery that utilises touch screen technology. The CANTAB is a well-standardised measure, which has been validated in adults and children and is differentially sensitive to dysfunction in brain regions . It was used to measure visual memory, learning, and attention. Specifically, PRM Test of visual pattern recognition memory. SWM Test of spatial working memory. SSP Test of spatial working memory capacity. RVIP Test of visual sustained attention PAL Test of visual memory and new learning. CMS Pen and paper based tasks. This scale is standardized for administration in children aged 5-16 yrs. Was used to assess Verbal learning and memory. Specifically. Stories Test of verbal learning and memory of semantically related material presented in a sequential format. Word Pairs Test of verbal learning and memory of a list of word pairs over three learning trials. IQ IQ was estimated using the WASI. This provides a brief measure of IQ, covering aspects of verbal and performance IQ.
  • Psychiatric outcome questionnaires The SDQ was employed to provide measures on emotional symptoms, conduct problems, hyperactivity, peer relationship problems, and pro-social behaviour. The impact of Events Scale was employed in order to provide an indication of PTSD symptoms associated with PICU admission. Psychological well-being The Chalder Fatigue Scale, provides a measurement of both physical fatigue and mental fatigue. The sleep scales provides a measurement of sleep disturbance. Academic Measures Dr Hawley and colleagues originally created a questionnaire to assess academic performance in children after traumatic brain injury. We have adapted the questionnaire slightly to make it more appropriate for our needs. Our questionnaire explores teachers knowledge of PICU admission, the child’s educational performance and special educational needs before and after admission. Teachers will also be asked to rate the child against the ability of his/her classroom peers on a number of cognitive domains e.g., executive function, memory, and attention.
  • The time-span was chosen to avoid short-term effects of PICU admission.
  • We assessed neuropsychological sequelae in each of the illness groups in comparison to the healthy controls and compared the number of children performing at least 1SD below standard norms on each sub-test. I used crosstabs to perform analysis, with subsequent planned comparisons to see which groups differed significantly from controls (or patient controls in case of recognition memory as we had a specific prediction that the SI group would perform worse than non-septic PICU children). RESULTS: Significantly higher proportion of ME group performing below average on visual recall, working memory and working memory capacity than healthy controls Significantly higher proportion of SI group performing badly on working memory and recognition than healthy controls (and patient controls on recognition measure)
  • Proportions not as high in the PC group (but still significantly different from controls). E.g., Performing worse than usual = 16% Difficulties with school work = 25%
  • Sub-groups – HD – ME (10%) Vs. HC (0%) – P=0.028 - PC (7%) Vs. HC (0%) – P=0.029
  • Impairment was classed as either performing at least 1sd below norm standard scores on at least 3 tests, or performing 2sd below norms on 2 tests. When working this out, we did not include performance in IQ as indicator (we just used performance on verbal and visual memory and attention sub-tests), so maybe this is why SI do not appear to be sig. more impaired than healthy controls.
  • All families that took part in the study Miss Sau-Ming Hau, Miss Seray Vezir, Miss Serenia Yip, Mr Russell Pryce, Dr Lola Picouto, Miss Natasha Khalife, Mr Kieran O’Donnell Dr Simon Nadel (C.I. SMH), Dr Mehrengise Cooper, Dr Christine Pierce (C.I. GOSH), Dr Tami Kramer, Dr Julia Gledhill, Prof. Vivette Glover, Prof. Barbara Sahakian, Prof. Elena Garralda (P.I) Miss Sarah Elison, Dr Dan Shears


  • 1. The Psychological Consequences of Meningitis and Septicaemia
  • 2.  
  • 3. Acute illness
    • Research into the psychological effects of acute illness in children has almost exclusively focussed on the study of post-traumatic stress disorder (PTSD)
    • This has demonstrated the presence of PTSD, sometimes continuing into adulthood, in children who have experienced road traffic accidents or are following diagnosis of cancer
    • Also, the parents of children with cancer and other life-threatening conditions (e.g. serious burns) have also often been shown to experience PTSD
  • 4. Post-traumatic stress disorder (PTSD)
    • Initial responses to a stressful medical event are a normal and adaptive response.
    • However, some families show pathologic and chronic stress responses, resulting in “Acute Stress Disorder (ASD) and Post-traumatic stress disorder (PTSD).
    • ASD is defined pathologic stress responses in the first month following a stressful event; PTSD is defined if the duration of stress responses is > 3 months.
  • 5. Post-traumatic stress disorder (PTSD)
    • ASD and PTSD are primarily a dysregulation of the fear system
    • Fear is a necessary emotion in times of danger, followed by an acute stress response (fight, flight or freeze)
    • The system depends on appraisal of threat in order to initiate survival behaviour
    • Once threat has passed, the fear system usually resolves over a period of days/weeks
    • In PTSD the system fails to reset
  • 6. Post-traumatic stress disorder (PTSD)
    • PTSD is characterised by:
    • Re-experiencing symptoms: nightmares and flashbacks; intrusive thoughts
    • Avoidance symptoms: avoiding places of thoughts associated with the stressful event
    • Emotional numbing symptoms: restricted range of affect and diminished interest
    • Hyperarousal symptoms: sleep and concentration difficulties; irritibility
  • 7. Post-traumatic stress disorder (PTSD)
    • Probability of developing PTSD following a stressful event is:
    • In men: 8-13%
    • In women: 20-30%
    • 80-90% show remission at 9 months
    • About 33% will remain symptomatic for > 3 years, with an increased risk of secondary problems (NICE 2007)
  • 8. Post-traumatic stress disorder (PTSD) in children
    • Children show different responses to adults, depending on age and developmental stage
    • Younger children: generalised fears, separation anxiety, sleep disturbance, agitation and disturbed play. Younger children may lose acquired skills (i.e. toileting)
    • School-age children: may develop vivid memories of the stressful event and nightmares, as well as sleeping/concentration problems with physical symptoms
    • They may become socially withdrawn and depressed
    • Adolescents exhibit similar behaviour, but more likely to become impulsive and aggressive.
  • 9. Consequences of Post-traumatic stress disorder (PTSD)
    • If not properly diagnosed and treated, PTSD causes substantial impairment of social, psychological and academic functioning in both adults and children.
    • May also cause debilitating physical symptoms – e.g. pain, GI, dermatologic and musculoskeletal disorders
    • If criteria for PTSD are only partially met, these patients exhibit clinically meaningful functional impairment (i.e. anxiety disorders are 2nd most common important cause of disease), and may increase risk of stroke, cancer, diabetes and depression
    • Estimated to have enormous personal and societal costs
  • 10. Admission to Paediatric Intensive Care
    • Major stressful event for child and their family
    • Families experience overwhelming shock and disbelief, accompanied by feelings of helplessness
    • Parents faced with worries about outcome of treatment and acute life-threatening illness in their child
    • PICU experience is intense - sights and sounds in the environment, and seeing other children undergo painful, distressing procedures or even death
    • PICU admission imposes an immense burden on critically ill children, their siblings, parents and other family members, thus increasing risk of adverse psychological outcomes
  • 11.
    • Our research is focussed on acute paediatric illness as a possible aetiological factor for child mental health problems
    • We have studied the psychiatric sequelae of admission to paediatric intensive care units (PICUs) and to general wards with meningococcal disease and other life-threatening illnesses
  • 12.
    • Meningitis has ~ 97% survival.
    • Case fatality in meningococcal disease fell from 23% in 1992 to ~ 5% in 1997 (Booy et al. 2001).
    • Mortality from paediatric septic shock is 15 - 20% in 2007-9
    • Most children make complete physical /medical recovery (Fellick et al. 2001).
    • About 5% suffer limb/skin loss
    • About 5% neurological sequelae
    Meningococcal disease outcome
  • 13. What is known about outcome of meningitis
    • CNS infections acquired in childhood lead to impairment in motor and cognitive functions (Carter et al. 2003).
    • 12-year follow-up of children with bacterial meningitis found general performance and executive function impairments in comparison to controls (Anderson et al. 2004).
    • Academic limitations identified in 32% children 4 -10 years following bacterial meningitis (Koomen et al. 2005).
    • Teenagers from national incidence study of infantile meningitis in England & Wales passed significantly fewer GCSE’s compared with controls (De Louvois et al. 2007).
  • 14. Typical responses of parents after critical illness
    • “I feel frightened”
    • “For the first 6 weeks he was very anxious and wanted to sleep in our bed” (parents of a 13 year old boy)
    • “If the school rings me for anything I start to panic”
    • “I look out of the window more when he is out and generally check on him more”
    • “She is more moody, wants things her way now’”
    • “wherever she goes, now she wants me to go with her” (mother of an 11 year old girl)
  • 15.
    • Issues to consider:
    • There is a lack of research providing a detailed insight into neuropsychological function after meningitis and septicaemia.
    • Focus on illness onset in infants and young children.
    • Focus on outcome following meningitis.
    • Little work on associations between meningococcal disease/sepsis and neuropsychological sequelae.
  • 16. Children with acute life-threatening illness
    • Paediatric Intensive Care delivers advanced technology that helps preserve life. Does this lead to neuro-psychological morbidity?
      • Does PICU admission result in increased risk of PTSD?
      • If so, what situations cause most stress and what is protective?
    • Do children admitted with severe acute disease have a greater risk of psychiatric sequelae?
    • What psychological interventions can be helpful for affected children and their families?
  • 17. Design
    • Cohort study of children aged 3-16 years with MD admitted to 3 PICUs and 22 general paediatric wards in the London area
    • Parents and children seen 2 - 5 days following hospital admission
    • Postal follow-up questionnaire 3 months following discharge to assess psychiatric risk in children (SDQ), parents (GHQ) and both (IES)
    • Follow-up interviews 12 months following discharge
  • 18. Sample:
    • 70/78 (89%) (36 boys; 34 girls) consecutive admissions for meningococcal disease.
        • 52 PICU
        • 18 Non-PICU
    • Median age at follow-up: 6.8 years (IQR: 4 – 12)
  • 19. 3-month follow-up
    • Meningococcal disease was associated with significant increases in emotional and hyperactivity symptoms in the child
      • 11% had PTSD
    • Parental mental distress was high during admission and decreased thereafter
      • nearly half the mothers and a quarter of fathers had PTSD symptoms at 3 months
      • Psychological symptoms in the child were linked to PICU admission and to illness severity, to similar symptoms in parents, and to pre-morbid psychological symptoms in the child
  • 20. 12 month follow up study
    • 56 children aged 3 - 16 years
    • The most significant change was an increase in impact on daily living scores.
    • 6 (11%) children were at risk for PTSD
    • The strongest correlations of child psychological symptoms were illness-related changes in parenting,
    • Parental outcomes:
    • 24% of mothers and 15% fathers were high risk for PTSD.
    • The strongest correlation of maternal PTSD symptoms was paternal PTSD symptoms.
  • 21. Diagnoses in children > 6 years of age, 12 months post-discharge
    • At least one disorder 50%
    • Major Depression 16%
    • Minor Depression 10%
    • Adjustment disorder 8%
    • Oppositional defiant 8%
    • disorder
    • Phobic Disorder 2%
    • Panic Disorder 2%
    • Organic Psychotic Disorder 2%
  • 22. Diagnoses in children < 6 years, 12 months post-discharge
    • 22% scored above cut-off for psychiatric disorder
    • Problems: tantrums, difficult to manage, sleep problems, fears and feeding problems. One child developed PTSD
  • 23. Summary
    • 50% of children develop mostly new psychopathology following meningococcal disease.
    • These were primarily depressive and anxiety related disorders
    • In 25% this persisted at one year
  • 24. Cognitive outcome following critical illness
    • Survivors of PICU:
      • reduced performance on spatial working memory, visual sustained attention, verbal recognition memory, and IQ 3-9 months after PICU admission (Elison et al., 2008).
        • With specific deficits in children admitted with sepsis.
    • Survivors of septic shock:
      • reduced performance on visual motor integration and executive function measures, but not IQ 4-16 years following illness (Vermunt et. al., 2009).
    • Survivors of infantile meningitis:
      • less likely to achieve 5 GCSE passes at grade A-C compared with controls (25% VS. 47%) (De Louvois et. al., 2007).
  • 25. Behavioural outcome following critical illness
    • Survivors of PICU:
      • Increased PTSD symptoms in children 6-12 months following PICU admission when compared to children admitted to a general paediatric ward (GPW) (Rees et al., 2004).
      • Delusional memories reported by 1/3 children admitted to PICU, which were found to be associated with increased risk of post traumatic stress disorder (Colville et al., 2008).
    • Survivors of Meningococcal Disease (MD):
      • High levels of hyperactivity, emotional, and PTSD symptoms in 3 month follow-up of children admitted to PICU with MD (Judge et al., 2002; Shears et al., 2005).
      • Psychiatric disorders present in 57% of children during the year after hospital admission with MD, which persisted in 32% at 12 month follow-up (Shears et al., 2007).
        • Shock linked to greater likelihood of psychiatric disorder.
  • 26. Neuropsychological function in children following admission to paediatric intensive care: a pilot investigation. (Elison et. al. Intensive Care Med. 2008 Jul;34(7):1289-93)
    • Examined neuropsychological performance in 16 children aged 5-16 years 3 - 9 months post discharge from PICU
    • Explored associations between identified impairments, psychological outcome and illness severity.
  • 27.
    • PICU admitted children displayed poorer performance on tests of spatial working memory; visual sustained attention; verbal learning and recognition memory.
    • Sepsis was specifically associated with poorer pattern recognition memory.
    • Significant correlations between neuropsychological functioning and emotional / hyperactivity scores and post traumatic stress symptoms.
    • Illness severity measures were not associated with neuropsychological performance.
  • 28.
    • Most research has focused on outcome of illness in infants and young children and little is known about outcome in school-aged children.
    • Unclear from this research if outcome is due to critical illness in general, or if it is related to specific critical illnesses, such as meningitis and/or septicaemia.
  • 29. Objectives of our latest project
    • To study neuropsychological function in children aged 5-16 yrs following admission to PICU.
    • Examine associations of neuropsychological function with academic performance, psychological outcome, and illness severity.
    • Explore persistence of neuropsychological deficits at 12 months in sub-sample.
    • Explore if children with psychopathology have anomalies in their biological stress response.
  • 30. Design
    • Prospective case-control study of children aged 5-16 yrs admitted to the PICU’s with:
      • Meningo-encephalitis (ME)
      • Septicaemia (SI)
      • Other critical illnesses (also known as patient controls: PC)
      • Main Patient Exclusion Criteria:
        • Pre-morbid neurological/neuromuscular illness
        • Pre-morbid psychiatric disorders
        • Global developmental delay
        • Neurological admissions (apart from meningo-encephalitis)
        • Severe disease sequelae
        • Overseas address
        • Discharged for palliative care
        • No discharge summary available
  • 31.
      • IQ:
        • Wechsler Abbreviated Scale of Intelligence (WASI; The Psychological Corporation, 1999) – 6 yrs and older.
        • Wide Range Intelligence Test (WRIT; Glutting et al) – 5 yr olds.
        • Verbal memory and learning:
          • Children’s Memory Scale (CMS; Cohen, 1997).
        • Visual memory, learning, and attention:
        • Cambridge Neuropsychological Test Automated Battery (CANTAB; Cambridge Cognition, 2006).
    Neuropsychological Tests © Copyright 2011 Cambridge Cognition Limited. All rights reserved.
  • 32. Neuropsychological Battery
      • Cambridge Neuropsychological Test Automated Battery (CANTAB; Cambridge Cognition, 2006).
      • Children’s Memory Scale (CMS; Cohen, 1997).
        • Stories
        • Word Pairs
      • Wechsler Abbreviated Scale of Intelligence (WASI; The Psychological Corporation, 1999).
      • (PRM - Pattern Recognition Memory; SWM - Spatial Working memory; SSP - Spatial Span; RVIP - Rapid Visual Information Processing; PAL - Paired Associates Learning)
  • 33. Questionnaires
      • Psychiatric adjustment:
      • Strength and Difficulties Questionnaire (SDQ; Goodman, 1997).
      • Impact of Events Scale (IES-8; Yule, 1997).
    • Psychological well-being measures:
      • Chalder Fatigue Scale (FS; Chalder, 1993).
      • Child Sleep Habits Questionnaire/ Sleep Self Report (CSHQ/SSR; Owens et al., 2000) .
    • Academic measures:
      • Academic performance Questionnaire (AQ; Hawley, 2004).
    • Other:
      • Case Note questionnaire (CNQ)
        • Paediatric Index of Mortality (PIM2).
        • Total days in PICU.
        • Presence of Shock.
        • Neurological involvement.
  • 34. Methods
    • Healthy comparison children were nominated by patient families (e.g., siblings and/or friends of the family) or recruited from local schools.
    • The PICU group were children admitted to St Mary’s or Great Ormond Street Hospitals.
    • PICU Children were invited to take part in the study 3-6 months following their hospital discharge.
  • 36. Participants PICU 125 Healthy Controls 100 PICU 88 SI 22 ME 21 Healthy Controls 100 PC 45 ME = Meningo-Encephalitis SI = Sepsis PC = Patient Controls
  • 37. Disease Type
  • 39. Cognitive Assessment
    • The PICU group were seen a median of 155 days (approximately 5 months) after discharge from hospital.
    • 80/88 PICU completed 9 sub-test battery:
      • 4 x participant refusal
      • 3 x technical issues
      • 1 x failure to pass first stage of sub-test
    • 100/100 HC completed 9 sub-test battery.
    • If a participant did not complete 3 or more sub-tests, their results were not included in the analysis (n=3).
  • 40. Visual Memory and Attention
      • Reduced visual memory function in comparison to healthy controls
          • Specifically in ME and SI children
  • 41. Verbal Memory
      • Reduced verbal memory function
          • Specific incidence in ME & SI children
  • 42. IQ
      • Below average IQ
        • Most pronounced in SI children
  • 44. Academic performance Questionnaire
    • 82/88 PICU teachers were sent the AQ; 68 returned (83%)
    • 96/100 HC teachers; 89 returned (93%)
    • Sig. ↑ proportion of PICU children rated as performing “worse than usual” than healthy controls
    • Sig. ↑ proportion of PICU children rated as having “difficulties keeping up with work” than healthy controls
    • The presence of problem behaviors as identified by teacher ratings were sig. associated with sub-optimal performance on some of the neuropsychological measures:
      • Poor ability to focus linked to worse sustained attention
      • Poor recall of earlier events associated with worse verbal and visual recall,
      • Poor ability to break task down into component parts linked to worse spatial working memory strategy and capacity
  • 46. Psychiatric Disorder
    • Scores on the SDQ from 3 informants (i.e., parent, child, teacher) were used to predict risk for psychiatric disorder.
    • Trend associated with high risk for ANY DISORDER, caused by higher rates in ME and SI children in comparison to healthy controls.
    • Sig. difference in proportion of ME and PC children at high risk of HYPERACTIVITY DISORDER in comparison to healthy controls.
    • Larger proportion of ME and SI children at high risk for BEHAVIOURAL and EMOTIONAL disorder, but these differences did not reach significance.
  • 47. Post Traumatic Stress Disorder
    • Rates of probable PTSD were sig. higher in SI and ME patient groups in comparison to control sample
    • Analysis within the patient group showed a sig. effect of illness group on post-traumatic symptoms and rates of probable PTSD.
      • The SI children were the source of these effects, scoring sig. higher than the PC children on all measures.
  • 49. Fatigue
    • Sig. differences between all three illness groups and HC’s on symptoms of fatigue (physical and mental) and rates of probable fatigue disorder.
  • 50. Sleep Disturbance
    • Sig. differences between PC and HC’s on symptoms of sleep disturbance and rates of probable sleep disorder.
    • Tendency for more sleep disturbance in SI in comparison to HC.
  • 51. Results ONE YEAR FOLLOW-UP
  • 52. Follow-up
    • We identified PICU children performing poorly on some of the neuropsychological tests and re-assessed them approximately one year after discharge.
    • Sig. more of the PICU children were classified as poor performers in comparison to healthy controls
    • 24 PICU children were re-assessed (65% of those approached).
      • significant improvements in most neuropsychological measures, but problems in visual recognition, attention, and IQ were sustained.
      • The proportion of children reported to have difficulties with school work also remained similar across time-points.
      • These children showed high levels of psychiatric symptoms and reduced well-being at baseline, which appeared unabated at follow-up.
      • In some instances (i.e., for emotional, behavioural, and hyperactivity disorder), the risk became significantly higher at follow-up.
  • 53. Summary
    • Some children admitted to PICU recover with no after-effects, but for some they are likely to experience :
      • Reduced neuropsychological function
      • Worse educational status
      • Poorer psychiatric function and well being
    • In some areas of functioning these problems were specially noted following meningo-encephalitis and sepsis.
    • These after effects apparent as early as 3 months post discharge.
    • For a number of children the neuropsychological and psychiatric problems at short-term follow-up persist, with some children showing increased risk for psychiatric morbidity over time.
  • 54. Conclusions
    • PICU admission leads to an increase in child psychopathology persisting at 12 months
    • Children with more severe illness and septic shock, and those with impairing pre-morbid emotional and behavioural problems have the highest risk
    • Changes in parenting and maternal mental health may contribute to the persistence of the psychological morbidities and may be potentially treatable
  • 55. Why the findings are important
    • They indicate that a significant number of children - although medically recovered - will be struggling to manage everyday life after their acute illness.
    • Provides strong support for the NICE guidance that children should be reviewed 4-6 weeks following discharge with meningitis or septicaemia.
    • Highlights the importance of work in prevention of psychiatric and psychological sequelae, and vaccination.
  • 56.
    • Parents most value:
        • communication
        • participation
        • information about the child’s condition
        • support from ward staff
        • consistency of care
        • facilities for parents and children
    • Future work might address ways of decreasing PICU parents’ stress by enhancing parental coping during admission and following discharge
  • 57. Acknowledgements - Particularly Lorraine Als/Elena Garralda
  • 58. Thank-you