DR PETA SHARPLES
UNIVERSITY OF BRISTOL
NEUROLOGICAL IMPACT OF MENINGITIS
Dr Sharples studied medicine at St Mary’s Hospital London. She trained in paediatric neurology in Great Ormond Street Hospital, Oxford and Newcastle where she was an Action Research Training Fellow and First Assistant in Paediatric Neuroscience. Her PhD, which described the relationship between clinical outcome and cerebral metabolism in children with severe traumatic brain injury, was awarded the Michael Blacow prize of the Royal College of Paediatrics and Child Health and the Ronnie McKeith Prize of the British Paediatric Neurology Association.
Dr Sharples is a Consultant Paediatric Neurologist at the Bristol Royal Hospital for Sick Children and a senior lecturer in the Institute of Child Health at Bristol. As well as leading the paediatric neuro-rehabilitation service at Frenchay Hospital, she heads a clinical and experimental program of research, funded by grants from national bodies including the Department of Health, the British Brain and Spine Foundation, the Royal College of Surgeons, and Cancer and Leukaemia in Childhood. She has developed the paediatric neurology department in Bristol
from a single handed unit to one of the largest regional units in the UK, with eight consultants.
new antimicrobial agents and vaccine advances, bacterial meningitis
remains an important cause of death and acquired disability in
childhood. Half of all cases of non-traumatic encephalopathy admitted to
the South West Regional PICU over a five year period were due to CNS
infection. Improvements in paediatric intensive care have led to a fall
in mortality rates from meningitis, leading to increased focus on
quality of outcome in survivors. Various studies have suggested that,
overall, 10-20% of survivors of meningitis are left with neurological
disability. Data from Bristol suggests outcome in children with
meningitis admitted to PICU is poor in 26% and that a further 15% have
moderate or mild disability.
damage in meningitis results from activation of host inflammatory
pathways, mediated by cytokines. Cytokine production activates a cascade
of destructive molecular events, including generation of excitatory
amino acids, generation of nitrous oxide and free radicals, and calcium
influx into neurons. These processes result in cellular energy
depletion, loss of cell membrane integrity, entry of fluid into cells,
cellular lysis and neuronal death by necrosis. Inflammatory processes,
including glutamate production, may also result in activation of enzymes
responsible for programmed cell death, leading to apoptotic neuronal
In experimental models of
meningitis, cerebral blood flow increases in the first 1-6 hours after
infection and is associated with raised intracranial pressure and brain
oedema formation. As infection progresses, cerebral blood flow decreases
in associated with increasing intracranial pressure. Cerebral oxygen
delivery becomes inadequate to meet the brain’s metabolic needs, leading
to ischaemic brain damage.
processes can also cause raised intracranial pressure by blocking
normal drainage pathways for cerebrospinal fluid, causing
ventriculomegaly with raised intracranial pressure (hydrocephalus).
Bacterial meningitis is the single largest cause of non-tumoural
hydrocephalus. Single hospital series suggest hydrocephalus complicates
1/7-2.8% of episodes of bacterial meningitis in children.
impact in any individual patient of an acquired brain injury such as
meningitis, depends on the areas of the brain involved. Damage to the
frontal lobes causes difficulties with attention, intellect, executive
function and the inhibitory aspects of behaviour, and higher aspects of
memory function, including working memory. Temporal lobe damage, for
example, by uncal herniation, causes problems with fundamental memory
functions such as encoding and retrieval, as well as language
dysfunction and behavioural and emotional difficulties. Parietal lobe
damage can cause problems with language and visuo-spatial functioning.
lobe damage can cause visual problems, such as cortical blindness or
visual field defects. Raised intracranial pressure can result in brain
stem dysfunction, leading to problems with arousal or attention, cranial
nerve palsies and motor dysfunction (spastic quadriparesis or ataxia).
is increasing recognition that neuronal plasticity does not necessarily
result in children doing better than adults following acquired brain
damage. Young children, in particular, may do worse. Early intensive
neurorehabilitation is indicated in cases with significant disability,
to optimise recovery. Cognitive and behavioural difficulties may not
become apparent until some years after the acute illness, emphasising
the need for long term monitoring, including of milder cases.
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