Treatment of hypoxic-ischaemic brain damage by moderate hypothermia

Edwards, AD; Wyatt, John; Thoresen, Marianne

doi:10.1136/fn.78.2.f85

Cited by 65 publications

(25 citation statements)

References 55 publications

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“…There is an agreement concerning the opportunity of therapeutic neuroprotective possibilities after birth asphyxia (9,10,43). After the start of the neurotoxic cascade, there is a therapeutic window, before the secondary energy failure starts and the more permanent brain injury is established (9).…”

Section: Discussionmentioning

confidence: 99%

S100 Protein in Serum as a Prognostic Marker for Cerebral Injury in Term Newborn Infants with Hypoxic Ischemic Encephalopathy

et al. 2004

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The astroglial protein S100 is an established biochemical marker for CNS injury in the adult. The aim was to investigate whether S100 in serum is a prognostic marker of cerebral injury in term newborn infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. Serum S100 was measured on postnatal days 1-4 in 62 term infants with birth asphyxia. The infants were classified for HIE and had follow-up for at least 18 mo. Infants with moderate and severe HIE had significantly higher S100 levels on postnatal day 1 (p ϭ 0.031) and day 2 (p ϭ 0.008) than infants with mild or no HIE. The levels of S100 decreased on days 2 and 3 in all infants with HIE. The median S100 level on postnatal day 1 was higher in nine infants who died neonatally and in 10 infants who developed cerebral palsy (CP), compared with 43 infants with no signs of impairment at follow up, 14.0 (0.5-60.0) g/L, 20.7 (0.2-64.0) g/L and 5.5 (0.7-120.0) g/L, respectively. A level of S100 above 12 g/L the first day of life was significantly more frequent in infants who died or developed CP than in infants with no impairment at follow up (p ϭ 0.02). Increased S100 levels were significantly inversely correlated with perinatal pH in the infants and associated with abnormal CTG at admission to the labor ward. Early determination of serum S100 may reflect the extent of brain damage in infants with HIE after asphyxia. Abbreviations CP, cerebral palsy CSF, cerebrospinal fluid CTG, cardiotocography FHR, fetal heart rate HIE, hypoxic ischemic encephalopathy S100, S100 protein including the subunits ␣␤ and ␤␤ aEEG, amplitude integrated EEG GFAP, glial fibrillary acidic protein Birth asphyxia remains a considerable problem in perinatal medicine with an incidence around 0.6 -0.8% of births (1-3). About half of these infants develop hypoxic ischemic encephalopathy (HIE) (2, 4). Those with moderate and severe HIE are at high risk of developing cerebral palsy (CP) (5-8). Prognostic assessment of brain injury after perinatal asphyxia will become essential for proper selection concerning early cerebroprotective treatment, which might be a likely option in the near future (9, 10). Several biochemical markers in cerebrospinal fluid (CSF) have been associated with cerebral complications in infants after perinatal asphyxia (11-14) and recently also S100 in CSF (15). A prognostic marker in serum would be of great value. S100 is a calcium binding protein present in the CNS. The dimers ␣␤ and ␤␤ of S100 are mainly specific for the nervous system and present chiefly in the astroglial cells of the CNS (16,17). S100 ␣␣ is present in many organs outside the CNS and will not be discussed in this report, where S100 will be used for the brain-specific S100 with subunits ␣␤ and ␤␤.The astroglial protein S100 is an established biochemical marker for CNS injury in the adult, in whom increased levels of S100 in CSF have been reported after cerebral insults (18,19). S100 in blood has been shown to be a marker of brain damage in adult stroke (20, 21) and a potential marker for c...

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Section: Discussionmentioning

confidence: 99%

S100 Protein in Serum as a Prognostic Marker for Cerebral Injury in Term Newborn Infants with Hypoxic Ischemic Encephalopathy

et al. 2004

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“…We have recently shown that CMRgl is significantly lower in asphyxiated full-term infants who die or develop CP than in asphyxiated infants with no signs of impairment at follow up (7). To select infants for early cerebroprotective treatment, which is a likely option in the near future (8), specific methods are required for very early identification of the infants who are at the highest risk of becoming disabled. aEEG has been used for very early prediction of outcome in full-term infants after birth asphyxia.…”

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confidence: 99%

Cerebral Glucose Metabolism and Early EEG/aEEG in Term Newborn Infants with Hypoxic-Ischemic Encephalopathy

et al. 2003

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The objective was to investigate how early electrocortical background pattern, as recorded with amplitude integrated EEG (aEEG), correlates with global and regional cerebral glucose metabolism (CMRgl) measured by positron emission tomography during the subacute phase after birth asphyxia. Nineteen term infants with hypoxic-ischemic encephalopathy were investigated. The aEEG background was evaluated at 0 -6, 6 -12, 12-24, 24 -48, and 48 -72 h postnatal age, and classified into four categories according to increasing degree of abnormality. The aEEG were also evaluated for sleep-wake cycling and epileptic seizure activity. CMRgl was measured by positron emission tomography with 2-( 18 F) fluoro-2-deoxy-D-glucose at a median (range) postnatal age 10 (4 -24) d. Increasing degree of abnormality in aEEG correlated significantly with decreasing CMRgl: at 6 -12 h (Ϫ0.593; 0.012) (r value; p value), 12-24 h (Ϫ0.669; 0.003), and 24 -48 h (Ϫ0.569; 0.014) postnatal age. Presence of sleep-wake cycling at 0 -6 h (0.697; 0.012), 6 -12 h (0.668; 0.003), and 12-24 h (0.612; 0.009) of age correlated with increased CMRgl. Delayed seizure activity at 12-24 h correlated with decreased CMRgl (Ϫ0.661; 0.004). Infants with abnormal aEEG at 6 -12 h had lower CMRgl in all regions of the brain compared with infants with normal aEEG. CMRgl of any specific region of the brain was not significantly more correlated to aEEG than CMRgl of other regions. Early electrocortical background patterns, early presence of sleep-wake cycling, and delayed seizure activity were highly correlated with global CMRgl measured during the subacute phase after asphyxia, but did not correlate with any specific pattern of regional uptake. Abbreviations aEEG, amplitude integrated EEG BS, burst-suppression aEEG CMRgl, cerebral metabolic rate of glucose CP, cerebral palsy FDG, fluoro-deoxyglucose HIE, hypoxic-ischemic encephalopathy OM, orbito-meatal PET, positron emission tomography rCMRgl, regional cerebral metabolic rate of glucose ROI, region of interest SWC, sleep-wake cycling in aEEG SZA, epileptic seizure activity in aEEG Birth asphyxia in term newborn infants remains a considerable problem in perinatal medicine, with high risk of mortality and disability (1-3). To predict outcome, the clinical neurologic assessment in grading HIE has proved to be of great value during the first days of life (4 -6). We have recently shown that CMRgl is significantly lower in asphyxiated full-term infants who die or develop CP than in asphyxiated infants with no signs of impairment at follow up (7). To select infants for early cerebroprotective treatment, which is a likely option in the near future (8), specific methods are required for very early identification of the infants who are at the highest risk of becoming disabled. aEEG has been used for very early prediction of outcome in full-term infants after birth asphyxia. There is a high risk for neurologic injury when the background aEEG is abnormal during the first hours of life (9, 10).On postmortem examinations of newborn in...

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“…Several recent animal studies have suggested that selective (cerebral) hypothermia of the asphyxiated infant may protect against subsequent brain injury. [27][28][29] Although this was felt to be a promising area of research, there was consensus that no recommendation for routine implementation could be made until appropriate controlled studies in humans have been performed.…”

Section: Environmentmentioning

confidence: 99%