SELSEHCC

Fenella Kirkham

Professor Kirkham was an undergraduate at Girton College, Cambridge and followed up her 2nd MB with a BA in History and Philosophy of Science (1975). After clinical training at Kings’ College hospital (MB 1978 BChir 1979), where she particularly enjoyed Child Health and Neurology, she went straight into Paediatrics. From 1982, she undertook a research project on Coma in childhood at Guy’s hospital, supervised by Professor Brian Neville and funded by the British Heart Foundation, which formed the basis of her MD. She trained as a Paediatric Neurologist and has been Professor at UCL Institute of Child Health since 2006 (6PAs). She held an honorary clinical post at Great Ormond Street hospital until 1999, when she moved to Southampton University Hospitals Trust as a consultant paediatric neurologist (6PAs).

Professor Kirkham’s research focuses on the prediction and prevention of complications, particularly  but not exclusively stroke, in sickle cell disease. In building up a cohort with up to 20 years follow-up so far, she collaborates with haematologists and paediatricians with whom she established regular joint clinics. Professor Kirkham was the principal investigator on a pilot randomised controlled trial of overnight auto-adjusting CPAP, funded by the Stroke Association (UK), which suggested that some of the morbidity in this condition (pain and poor attention) is preventable. She was also the Chief Investigator for the London site on two international collaborative studies: a cohort study ‘Asthma and nocturnal hypoxemia in sickle cell anemia (National Heart Lung and Blood Institute, USA) and a randomised trial of blood transfusion-the ‘Silent Infarct Transfusion Trial’ (National Institute for Neurological Diseases and Stroke, USA). Dr Kirkham also continues to publish on the pathophysiology of childhood stroke, coma and complex epilepsy.

Abstract: Cognition in sickle cell disease

The association between covert (silent) and overt stroke, sickle cell disease (SCD) and impaired neurocognitive functioning is well established. However, recent evidence suggests that patients with no cerebral infarction also show cognitive deficits. Data, including magnetic resonance imaging, from the longitudinal East London cohort study have been used to explore whether there are potentially modifiable risk factors associated with impaired neurocognitive functioning. As in previous studies, growth is the strongest predictor of IQ in adolescents with SCD, and the East London study shows that this is independent of the presence of infarction (silent or overt strokes). Appropriate early nutrition may prevent cognitive impairment.

Executive function, verbal learning, long-term and working memory appear to be a problem in asymptomatic children with SCD without infarction. We have looked into the effects of nocturnal and daytime oxygen saturation on executive function and memory performance as part of the Sickle Cell Anaemia Sleep and Asthma Cohort study. 10 patients aged 6 to 16 with homozygous SCD, but normal MRI and without abnormal cerebral blood flow velocity had an overnight in-hospital sleep study and tests of intelligence and various domains of executive function and verbal memory. Decreases in hemoglobin oxygen saturation and/or increased sleep arousals were associated with reduced performance on cognitive assessment. Nocturnal hemoglobin oxygen desaturation and sleep fragmentation may be a contributing factor to executive and memory dysfunction in SCA which might be improved by effective strategies to improve sleep, including overnight auto-adjusting continuous positive airways pressure if there is intermittent desaturation.

Relatively little is known about any relationship between the chronic pain in SCD and cognitive abilities. Data regarding the severity and frequency of pain were collected from medical notes and by history from controls and participants with SCD, who also underwent neuropsychological testing, comprising a brief IQ test and a short battery of tests designed to assess a range of executive functions. Measures of pain severity on the day of testing, but not self-reported pain frequency or number of hospital visits for pain, were found to correlate with inhibition and working memory in the SCA group, and with switching attention in the control group. On the basis of these results, pain does not simply act as a general distractor, but has a selective effect on executive functions.

The Cooperative study in the USA found evidence for reduction in IQ over time in children with SCD but did not have a control group. Longitudinal IQ data obtained from the East London cohort revealed that only children with SCD and symptomatic stroke, with or without moyamoya, showed significant decline in both verbal and performance IQ between childhood and adolescence, whereas children who were neurologically asymptomatic, with or without silent infarction, showed no change in IQ when compared with age- and ethnic-similar controls. These data suggest a stable IQ profile in the majority of UK children with SCD.  Early identification of the minority of children who are at risk of recurrent stroke should permit targeted treatment strategies against infarction and intellectual decline.

 

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