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Biomedical subjects

M Rutherford

Publications and source records attributed to M Rutherford.

At least 19 recordsLinked to original sources

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.

Cerebral Cortex↗

Sequential neurological examinations in infants with neonatal encephalopathy and low apgar scores: relationship with brain MRI.

OBJECTIVE: The aims of this study were to (a) describe the evolution of neurological signs after the neonatal period in infants with neonatal encephalopathy and abnormal outcome and (b) to establish the relationship between the evolution of neurological signs and patterns of lesions on brain MRI. PATIENTS: Fifteen children with low Apgar scores, abnormal neurological signs at the end of the neonatal period, and abnormal outcome were examined at 1 - 2 weeks, 5 - 7 weeks, and 6 months. All the infants had at least one MRI scan performed in the neonatal period. RESULTS: All infants had persistent abnormalities on all examinations performed but the severity of neurological impairment was variable and was related to the pattern of brain lesions. Infants with severe basal ganglia and white matter lesions showed abnormal axial and limb tone, movements, and visual function on all the examinations and none achieved independent sitting. In infants with moderate basal ganglia lesions and/or severe white matter changes, visual function and feeding improved by 5 - 7 weeks and were still normal at 6 months while limb tone, which was reduced in the first weeks, appeared to be normal at 5 - 6 weeks but was found to be increased at 6 months; all were able to sit unsupported at 2 years and most of them achieved the ability to walk with support. CONCLUSIONS: Our results suggest that the evolution of the neurological patterns after the neonatal period in infants with persisting neonatal abnormalities depends on their pattern of brain lesions.

Apgar Score↗

Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia.

The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.

Female↗

Smaller cerebellar volumes in very preterm infants at term-equivalent age are associated with the presence of supratentorial lesions.

BACKGROUND AND PURPOSE: Traditionally cerebellar functions are thought to be related to control of tone, posture, gait, and coordination of skilled motor activity. However, there is an increasing body of evidence implicating the cerebellum in cognition, language, memory, and motor learning. Preterm infants are at increased risk of neurodevelopmental delay, cognitive dysfunction, and behavioral and emotional disturbances. The role of the cerebellum in these adverse outcomes is unclear. OBJECTIVE: The objective of this study was to determine whether absolute cerebellar volumes differ between term-equivalent preterm infants and term-born control infants and to assess whether cerebellar volume is influenced by any possible antenatal, perinatal, and postnatal factors. METHODS: The study compared the MR imaging cerebellar volume by using a manual quantification program of 113 preterm infants at term-equivalent age and 15 term-born control infants. RESULTS: The median cerebellar volume of preterm at term-equivalent age was 25.4 cm3 and that of term-born control infants was 26.9 cm3. On initial analysis, there was a significant median difference of 2.0 cm3 (95% CI, 1.2 cm3 to 2.7 cm3) (2-sided P < .0001). However multiple regression analysis of perinatal variables showed that only infants with supratentorial lesions (P = .003) were significantly associated with the reduction in cerebellar volumes. The median cerebellar volumes were the following: supratentorial lesions, 18.9 cm3; no supratentorial lesions, 26.1 cm3; and term infants, 26.9 cm3 (analysis of variance, P < .0001). Hence, there was no significant difference in cerebellar volumes of preterm infants at term-equivalent age in the absence of supratentorial lesions. The median vermal volumes were 0.7 cm3 and were significantly related to cerebellar volumes both in preterm infants with and without lesions and in term-control infants. CONCLUSION: Premature infants at term-equivalent age have similar total cerebellar and vermal volumes compared with term infants in the presence of normal brain imaging. Reduced cerebellar volume in preterm infants at term-equivalent age is seen in association with supratentorial pathology such as hemorrhagic parenchymal infarction, intraventricular hemorrhage with dilation, and periventricular leukomalacia.

Cerebellum↗

Does cranial ultrasound imaging identify arterial cerebral infarction in term neonates?

OBJECTIVE: To evaluate the diagnostic accuracy of cranial ultrasound (CUS) for detection of neonatal arterial territory cerebral infarction in term infants. METHODS: CUS scans from term infants with neonatal magnetic resonance imaging (MRI) evidence of neonatal infarction were reviewed. The scans were grouped by acquisition time after birth: 1-3 days (early) or 4-14 days (late). RESULTS: Brain MRI showed infarction in the territory of the middle cerebral artery in 43 of 47 infants, anterior cerebral artery in one, and posterior cerebral artery in three. Twelve of the 47 had minor changes on MRI in the white matter in the contralateral hemisphere, and four infants had bilateral infarctions. The early CUS scans were abnormal in 68% of the infants; the late CUS scans were abnormal in 87%. The late CUS scans were correct for laterality and site of lesion in 25/47 (53%) infants. In six infants with smaller lesions of the cortical middle cerebral artery branch or lesions in the posterior cerebral artery territory, the CUS scans were persistently normal. CONCLUSION: Normal early CUS scans do not exclude a diagnosis of neonatal stroke, although most scans are abnormal. CUS scans performed after day 3 were abnormal in 87% of infants. CUS scan findings were accurate for lesion laterality and site in 53%, and, in 34%, the scans showed abnormality strongly suggestive of infarction but not always site specific. For optimal prognostic information, infants with clinical histories or CUS scan findings suggestive of infarction should have a neonatal brain MRI scan.

Age Factors↗

Visual function at school age in children with neonatal encephalopathy and low Apgar scores.

OBJECTIVE: To assess different aspects of visual function at school age in children who suffered from neonatal encephalopathy. METHOD: Thirty nine full term infants with neonatal encephalopathy, low Apgar scores, and early neonatal imaging were studied using a battery of tests assessing different aspects of visual function (crowding acuity, stereopsis, visual fields) at school age. The results were compared with brain magnetic resonance imaging (MRI) findings and, when possible, with the results of the assessment of visual function performed at 5 and 12 months, available in 24 of the 39 children examined at school age. RESULTS: Sixteen of the 39 children (41%) had abnormal results at school age in at least one of the visual tests used. Seven of these 16 were untestable on all tests. The remaining 23 children (59%) had normal results. CONCLUSIONS: The presence and severity of visual impairment was related to the severity of brain lesions. Moderate or severe basal ganglia lesions and severe white matter changes were always associated with abnormal visual function. Infants with normal MRI, minimal basal ganglia lesions, and minimal or moderate white matter involvement tended to have normal vision. It was also found that the assessment of visual function performed in the first year was a reliable indicator of visual function at school age. With two exceptions, the results on the 5 month visual assessment were predictive of visual outcome at school age. In the remaining two cases, a normal visual outcome at 5 years was associated with visual abnormalities at 5 months but these had already normalised by the age of 1 year.

Apgar Score↗

General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction.

Background. Studies have reported that infants with hemiplegia of congenital origin may have a period between birth and up to 12 months when clinical signs of hemiplegia are not evident. The aim of this study was to establish whether the assessment of general movements (GMs) may help in the earlier detection of signs of hemiplegia. Subjects and Methods. Eleven infants with cerebral infarction on brain MRI, and eleven normal controls were enrolled in the study. Quality of GMs was assessed from videotapes between 3 and 6 weeks and between 9 and 16 weeks. Neurological outcome was evaluated at least at two years. Results. Seven of the 11 infants had an assessment performed between 3 and 6 weeks: abnormal GMs were observed in all the infants who developed hemiplegia, but one child had abnormal GMs and a normal outcome. All 11 infants had a scorable assessment between 9 and 16 weeks. In all a specific type of GMs, fidgety movements (FMs), were predictive of neurological outcome. The presence of early asymmetries at both 3 - 6 and 9 - 16 weeks was also significantly associated with later signs of hemiplegia. Conclusions. The assessment of GMs after the neonatal period appears to be very useful in the early identification of hemiplegia in infants with cerebral infarction. Whilst the prediction of hemiplegia should be possible from early neonatal MRI brain scans, this facility is not always available. Observation of GMs is a bedside clinical approach that allows confirmation of early prediction from MRI, early rehabilitation if needed and reassurance that neurological outcome will be good where that is appropriate.

Cerebral Infarction↗

Occipito-temporal polymicrogyria and subclinical muscular dystrophy.

We report a two-year-old Caucasian boy who had neonatal seizures and was found to have bilateral occipito-temporal polymicrogyria on neonatal brain MRI. The child had no additional neurological abnormality other than the neonatal seizures, but serum CK was found to be elevated (5 - 7 times normal values) and the muscle biopsy showed evidence of early muscular dystrophy. Detailed protein and genetic studies did not allow the identification of a known form of muscular dystrophy. The boy has been followed regularly and he currently has mild global developmental delay but no clinical signs of muscle involvement. The association of polymicrogyria and muscular dystrophy is known to occur in Fukuyama and Walker Warburg muscular dystrophies, in muscle-eye-brain disease and in some patients with merosin deficient CMD. However the absence of weakness and of eye involvement, the normal expression of merosin and alpha dystroglycan and the pattern of brain involvement make it very unlikely that the child is affected by one of these forms. As the pattern of brain involvement and the muscle pathology is not typical of one of the forms of neuronal migration disorders secondary to a known gene defect, we suspect that the combination of muscle and brain involvement found in this child is not coincidental. Our findings suggest that serum CK should be determined in children with undiagnosed polymicrogyria, even in the absence of weakness. This may lead to an expansion of our understanding of muscle dystrophies and cortical dysplasias.

Child, Preschool↗

Neonatal cerebral infarction and visual function at school age.

OBJECTIVE: To assess various aspects of visual function at school age in children with neonatal cerebral infarction. PATIENTS AND METHODS: Sixteen children born at term, who had cerebral infarction of perinatal onset on neonatal magnetic resonance imaging (MRI) were assessed using a battery of visual tests. This included measures of crowding acuity (Cambridge Crowding Cards), stereopsis (TNO test), and visual fields. The results of the visual assessment were compared with the type and the extent of the lesion observed on neonatal MRI. RESULTS: Only six of the 16 children (28%) had some abnormalities of visual function on these tests. Visual abnormalities were more common in children with more extensive lesions involving the main branch of the middle cerebral artery and were less often associated with lesions in the territory of one of the cortical branches of the middle cerebral artery. The presence of visual abnormalities was not always associated with the involvement of optic radiations or occipital primary visual cortex. Abnormal visual fields were only found in children who also developed hemiplegia. CONCLUSIONS: Abnormality of visual function is not common in children who had neonatal infarction and, when present, tends to be associated with hemiplegia and more extensive lesions.

Cerebral Infarction↗

Anti-D (WinRho SD) treatment of children with chronic autoimmune thrombocytopenic purpura stimulates transient cytokine/chemokine production.

Intravenous anti-D is often used in the treatment of autoimmune thrombocytopenic purpura (AITP), but little is known about its mechanisms of action. To investigate anti-D's potential in vivo mechanism(s) of action, a small group (N = 7) of children with chronic AITP was studied. The children initially received either 25 or 50 microg/kg of WinRho-SD in a four-cycle cross-over trial, and peripheral blood samples from the first and third cycles were assessed for cytokine levels at pre-treatment, 3 hr, 1 day, and 8 days post-treatment. Results showed that platelet counts significantly increased in all the children by day 8 post-treatment. Analysis of serum by ELISA showed that there was a significant but transient rise in both pro- and anti-inflammatory cytokine/chemokine levels (e.g., IL1RA, IL6, GM-CSF, MCP-1 alpha, TNF-alpha and MCP-1) by 3 hr post-treatment in both cycles which returned to baseline levels by 8 days post-treatment. These results suggest that anti-D administration may initially activate the RES in the form of cytokine/chemokine secretion, which is subsequently followed by an increase in platelet counts. It is possible that the induced cytokine/chemokine storm may have an effect on several physiological processes such as those mediating either adverse effects or potentially RES phagocytic activity.

Chemokines↗

Visual function and EEG reactivity in infants with perinatal brain lesions at 1 year.

The aim of this study was to examine the correlation between EEG, visual, and brain MRI findings in 19 term infants with perinatal brain lesions. All 19 had their visual acuity and visual fields assessed and had an EEG and a brain MRI performed at 1 year of age. Four of the five infants with normal optic radiations and occipital cortices on MRI had normal vision. Involvement of optic radiations and occipital cortices was only associated with visual abnormalities in eight of 14 infants. The correlation between visual abnormalities and EEG findings was stronger. All infants with a completely normal EEG from the posterior regions had normal vision and all those with an EEG non-reactive to eye closure had visual abnormalities, irrespective of MRI data. A reactive EEG with other abnormal features (such as spikes, rapid or slow activities) was accompanied by abnormal vision in five of eight participants. Results suggest that there is a better correlation between visual function and EEG activity than between visual function and involvement of the classical visual areas of the occipital cortex and optic radiations on brain MRI at 1 year of age.

Action Potentials↗

MRI lesions and infants with neonatal encephalopathy. Is the Apgar score predictive?

OBJECTIVE: The aim of this study was to establish whether, in full-term infants presenting with neonatal encephalopathy, the 1 minute Apgar score gives an indication of the presence, site or type of lesions observed on brain MRI in the neonatal period. PARTICIPANTS AND METHODS: The study cohort included 157 full-term infants who had neurological abnormalities during the first 48 hours after delivery. Infants with developmental, genetic, infective or metabolic diagnoses were excluded from the study. The infants were subdivided according to their 1 minute Apgar score into three groups as follows: Apgar score 0 - 3 (n = 108/157, 69 %), 4 - 7 (n = 29, 19 %), 8 - 10 (n = 21, 12 %). Results. Severe and moderate basal ganglia and thalamic (BGT) lesions, with one exception, were only observed in the group with an Apgar score of 3 or below. Minimal BGT lesions were, with one exception, associated with scores below 7 and mainly below 3. However, not all the infants with low Apgar scores had BGT lesions and 28 % of the patients with Apgar scores below 3 had normal scans or only minimal white matter changes. White matter lesions without BGT involvement were equally distributed in the cohort, irrespective of the Apgar scores. Cerebral infarction and scattered white matter haemorrhages were the most common findings in infants with Apgar scores of 4 and above. The Apgar scores were not always predictive of motor outcome at 2 years but the presence and severity of the sequelae mainly reflected the site and severity of MRI findings. CONCLUSIONS: These findings stress the importance of subdividing neonatal encephalopathy into diagnostic categories according to brain lesions if one wishes to study either causative factors or outcome.

Apgar Score↗

Neurological and perceptual-motor outcome at 5 - 6 years of age in children with neonatal encephalopathy: relationship with neonatal brain MRI.

OBJECTIVE: The aims of this study were 1) to determine the incidence of minor neurological dysfunction and perceptual-motor difficulties in children aged 5-1/2 -- 6-1/2, who had been born full-term but presented with neonatal encephalopathy (NE) and low Apgar scores and 2) to examine the relationships between the presence/absence of these difficulties with neonatal brain MRI. PARTICIPANTS AND METHODS: Sixty-eight full-term infants with one minute Apgar scores less than or equal to 5 and neurological abnormalities during the first 48 hours after birth were included in the study. All children had a neonatal MRI brain scan. Surviving infants were assessed between the age of 5 and 6 years using the Touwen Examination, the Movement ABC and the WPPSI-R. RESULTS: Fifteen of the 68 infants (22 %) died in the neonatal period. Of the 53 surviving infants, 19 (36 %) had cerebral palsy. The remaining 34 were considered normal at 2 years of age but, when assessed at school age, 8 (15 %) had minor neurological dysfunction and/or perceptual-motor difficulties, 1 (2 %) had only cognitive impairment and 25 (47 %) were normal. The outcome largely reflected the pattern of lesions on brain imaging. While 83 % of those with a normal outcome had normal scans or minimal white matter lesions, 80 % of those with minor neurological dysfunction and/or perceptual-motor difficulties had mild or moderate basal ganglia or more marked white matter lesions. CONCLUSION: Continued surveillance is recommended for children with apparently normal outcome at two years of age after NE, particularly when abnormalities are detected on brain MRI.

Age Factors↗

Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy.

In 1996 we reported sequential magnetic resonance imaging study in an infant with merosin-deficient congenital muscular dystrophy with normal brain magnetic resonance imaging at 3 weeks and white matter changes by 6 months. We now report an infant with merosin-deficient congenital muscular dystrophy with a mild degree of white matter changes already present on brain magnetic resonance imaging at 5 days of age. The difference may be due to a difference in the T2 sequences used. The images in this present case were obtained with a fast spin echo sequence (echo time: 210 ms). The increased T2 weighted may be responsible for a better detection of the white matter changes at an early stage, when they can be missed on conventional, less weighting T2 sequences. These results suggest that, by using appropriate sequences, mild white matter changes may be detectable on brain magnetic resonance imaging in the first days of life in infants with merosin-deficient congenital muscular dystrophy.

Age of Onset↗

Neurologic examination in infants with hypoxic-ischemic encephalopathy at age 9 to 14 months: use of optimality scores and correlation with magnetic resonance imaging findings.

OBJECTIVES: To evaluate whether a structured and scorable neurologic examination (The Hammersmith Infant Neurological Examination) correlates with early magnetic resonance imaging findings in a group of infants with hypoxic-ischemic encephalopathy (HIE) and whether the scores of this assessment can predict the locomotor function in these children. STUDY DESIGN: A total of 53 term infants fulfilling the criteria for HIE underwent scanning within 4 weeks from delivery with a 1 Tesla HPQ magnet. The scores from the neurologic examination performed between 9 to 14 months were correlated to the neonatal magnetic resonance imaging findings and to the maximal locomotor function defined at the ages of 2 and 4 years. RESULTS: The scores were always optimal in the infants with normal or minor neonatal magnetic resonance imaging findings. The lowest scores were associated with severe basal ganglia and white matter lesions. All the infants who had a global score between 67 and 78 at 1 year were able to walk independently at 2 years and without restrictions at 4 years. Scores between 40 and 67 were associated with restricted mobility and scores <40 with severely limited self-mobility at 2 and 4 years. CONCLUSIONS: The use of a standardized neurologic optimality scoring system gives additional prognostic information, easily available in the clinic, on the severity of the functional motor outcome in infants with HIE.

Female↗

The effects of repeated antenatal glucocorticoid therapy on the developing brain.

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.

Betamethasone↗

Combined use of electroencephalogram and magnetic resonance imaging in full-term neonates with acute encephalopathy.

OBJECTIVE: The electroencephalogram (EEG) is widely used in full-term infants with acute neonatal encephalopathy, and its prognostic value has been confirmed by several studies. Magnetic resonance imaging (MRI) of the brain has also been applied in these patients, and increasing numbers of reports affirm its prognostic reliability. The aim of this study has been to investigate the correlation between an early EEG and MRI findings in infants with acute neonatal encephalopathy and to assess the prognostic value of a combination of EEG and MRI findings. PARTICIPANTS AND METHODS: Twenty-five full-term infants had an EEG recorded within the first 72 hours after birth and a neonatal brain MRI scan after the end of the first week. RESULTS: Both EEG and MRI were predictive of outcome. A normal MRI was always associated with normal EEG background activity and normal outcome and severe abnormalities on MRI with marked EEG abnormalities and an abnormal outcome. When the MRI showed moderate abnormalities, the EEG in all cases but one identified patients with normal and abnormal outcome.EEG, MRI, HIE, neurodevelopment.

Brain↗