Neuro-cognitive function in children following hospital admission with septic illness and meningo-encephalitis.
Dr Lorraine Als, Dr Simon Nadel, Prof Elena Garralda.
- Start Date:
01 January 2007
Imperial College, London, UK
Our research aimed to study neuropsychological sequelae following paediatric intensive care unit (PICU) admission for meningo-encephalitis and septic illness; to examine associations of neuropsychological function with academic performance, psychiatric outcome/well-being, and clinical features during the acute illness itself; to explore the persistence of any neuropsychological deficits at approximately one year following discharge; and to consider implications for clinical practice.
We collected data between April 2007 – July 2010 and our final sample was made up of 88 school-aged children admitted to the PICU’s at St Mary’s and GOSH and 100 matched controls. The patient group consisted of 21 children admitted with meningo-encephalitis (ME), 22 with septic illness (SI) and 45 patient controls (PC). None of the patients admitted had a prior history of neurological or psychiatric disorder. The inclusion of these three patient groups enabled us to explore the contribution of critical infection (neurologic and systemic) over and above critical illness in general. The sepsis group were the most severely ill (as measured by the Paediatric Index of Mortality 2 (PIM2) illness severity score) and spent more time in PICU and hospital overall. The meningo-encephalitis group experienced more neurological involvement, with higher rates of raised intra-cranial pressure and seizures. Significantly more children in the patient control group had a chronic paediatric illness, such as diabetes, sickle cell disease, or asthma prior to admission.
Children were mainly assessed at home a median of 5 months following PICU discharge. Neuropsychological function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB); the Children’s Memory Scale (CMS); and the Wechsler Abbreviated Scale of Intelligence (WASI) or Wide Range Intelligence Test (WRIT). Parents, teachers, and older children also completed standardised questionnaires to quantify educational and psychiatric outcome/well-being.
Our results show that difficulties in memory, attention, IQ function, and school performance were significantly increased in the PICU cohort when compared with healthy comparison children, and these problems were specially noted following meningo-encephalitis and sepsis. Moreover, significantly more children in the PICU cohort were at risk for psychiatric morbidity and poor well-being, with the meningo-encephalitis and sepsis groups at particularly high risk of hyperactivity or post-traumatic stress symptoms.
As planned, we also examined associations in the PICU group between neuropsychological function and academic performance, psychiatric outcome/well-being, and clinical features of critical illness. There were a number of associations (at p values between 0.005 and 0.05); however, these associations did not reach required significance levels when statistical corrections were made for multiple comparisons. The associations that remained significant after corrections were made identified a link between i) worse spatial working memory/sustained attention and a poor ability to focus at school, and ii) worse spatial working memory and post traumatic stress symptoms.
A one year follow-up of 24 critically ill children with signs of neuropsychological problems revealed that for a number of children the IQ and psychiatric/well-being problems present during the early months of recovery persist over time, with some psychiatric symptoms becoming significantly worse.
The nested biological stress marker study aimed to assess whether the high levels of physiological stress characteristic of critical illness would affect children’s regulation of the stress response following recovery, as measured through salivary cortisol and amylase (a putative measure of sympathetic function); whether anomalies would be associated with neuropsychological and psychiatric sequelae; and whether they would be specially marked in children with meningo-encephalitis and septic illness.
Of the 152 children approached, saliva samples were obtained from 119: 53 PICU patients (19 with septic illness, 11 with meningo-encephalitis and 23 patient controls) and 66 healthy controls. These children were comparable to those failing to provide samples on age, gender, socio-economic status, hospital source, and group membership. Samples were taken three times a day – on awakening, 30 minutes and 12 hours later – over two days. For this analysis we used average figures from the two consecutive collection days.
We did not find statistical differences in median cortisol or amylase levels (awaking, 30 minute or 12 hour post-waking samples) or in the cortisol awaking response (CAR) between PICU groups - either as a whole or by individual illness groups - and healthy controls. However, i) higher 12 hour post-waking cortisol levels were statistically significantly linked to enhanced risk for post traumatic stress disorder; and ii) lower amylase levels at awaking were statistically associated with more sleep problems and poorer sustained attention performance (sensitivity measure), and at 12 hrs post waking with poorer sustained attention (sensitivity and reaction times). There were a number of additional near significant associations between cortisol/amylase levels and clinical features during illness, neuropsychological and psychiatric measures, suggesting deregulations of biological stress responses following PICU admission, possibly affecting the psychological adjustment of children, but given that only some of findings reached full statistical significance (after corrections for multiple comparisons), they are in need of replication before their validity can be fully evaluated.
The findings from this project provide a detailed account of the potential neuropsychological/behavioural after-effects children experience in the early stages of recovery and provide insight into how these may develop in the year following their illness. These findings are important because they indicate that some children - although medically recovered - will be struggling to manage everyday life after their acute illness. This provides strong support for the NICE guidance that children should be reviewed 4-6 weeks following discharge with meningitis or septicaemia and also highlights the importance of work in prevention, and more specifically, vaccination uptake rates.
We are in the process of disseminating our findings to healthcare professionals through conference presentations and the publication of journal articles and leaflets. This will be of benefit to children affected as it will help to increase awareness of the morbidities associated with meningitis and septicaemia and thus healthcare professionals will be better equipped to put appropriate remedies in place and/or make the appropriate referrals.