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M Squier

Publications and source records attributed to M Squier.

16 recordsLinked to original sources
PubMed2000

Five cases of brain injury following amniocentesis in mid-term pregnancy.

This paper describes the neuroimaging and neuropathological findings in five cases of severe brain damage after traumatic mid-trimester amniocentesis, all performed between 1986 and 1994. Although fetal injury after amniocentesis has been reported, reports of brain injury are infrequent. Continuous ultrasound monitoring may reduce the risk of fetal injury but follow-up ultrasound scans can be falsely reassuring. Withdrawal of blood-stained fluid, particularly if it contains tissue fragments, should alert the operator to the possibility of fetal damage. Histological examination of such tissue fragments may confirm the nature of the fetal damage. The consequences of fetal brain injury are severe, all five of our cases showed evidence of disruption of brain development compatible with mid-term injury. Obstetricians and their patients should be aware of the small but significant risk of brain damage after mid-term amniocentesis.

Adult↗
PubMed1999

Characterization of nodular neuronal heterotopia in children.

Neuronal heterotopia are seen in various pathologies and are associated with intractable epilepsy. We examined brain tissue from four children with subcortical or periventricular nodular heterotopia of different aetiologies: one with severe epilepsy following focal brain trauma at 17 weeks gestation, one with hemimegalencephaly and intractable epilepsy, one with focal cortical dysplasia and intractable epilepsy, and one dysmorphic term infant with associated hydrocephalus and polymicrogyria. The connectivity of nodules was investigated using histological and carbocyanine dye (DiI) tracing techniques. DiI crystal placement adjacent to heterotopic nodules revealed numerous DiI-labelled fibres within a 2-3 mm radius of the crystals. Although we observed labelled fibres closely surrounding nodules, the majority did not penetrate them. Placement of DiI crystals within nodules also identified a limited number of projections out of the nodules and in one case there was evidence for connectivity between adjacent nodules. The cellular and neurochemical composition of nodules was also examined using immunohistochemistry for calretinin and neuropeptide Y (NPY), which are normally expressed in GABAergic cortical interneurons. Within heterotopic nodules from all cases, numerous calretinin-positive neurons were identified, along with a few cell bodies and many processes positive for NPY. Calretinin-positive neurons within nodules were less morphologically complex than those in the cortex, which may reflect incomplete differentiation into an inhibitory neuronal phenotype. There were also abnormal clusters of calretinin-positive cells in the overlying cortical plate, indicating that the migratory defect which produces heterotopic nodules also affects development of the cortex itself. Thus, heterotopic nodules consisting of multiple neuronal cell types are associated with malformation in the overlying cortical plate, and have limited connectivity with other brain regions. This abnormal development of connectivity may affect neuronal maturation and consequently the balance of excitation and inhibition in neuronal circuits, leading to their epileptogenic potential.

Brain Chemistry↗
PubMed1998

Relation of impaired energy metabolism to apoptosis and necrosis following transient cerebral hypoxia-ischaemia.

This study investigated whether both mild and severe hypoxia-ischaemia (HI) caused significant numbers of cells to die by apoptosis in the developing brain in vivo. Newborn piglets were subjected to transient global HI and the fraction of all cells in the cingulate gyrus that were apoptotic or necrotic counted 48 h after resuscitation. The mean (S.D.) proportion of apoptotic cells was 11.9% (6.7%) (sham operated controls 4.1% (2.7%)), while 11.4% (8.4%) were necrotic (controls 0.7% (1.3%)) (P<0.05). Apoptotic and necrotic cell counts were both linearly related to the severity of impaired cerebral energy metabolism measured by magnetic resonance spectroscopy (P<0.05), as shown by: (1) the decline in the ratio of nucleotide triphosphates to the exchangeable phosphate pool during HI; (2) the fall in the ratio of phosphocreatine to inorganic phosphate 8 - 48 h after HI; and (3) an increased ratio of lactate to total creatine at both these times. Thus both apoptosis and necrosis occurred in the cingulate gyrus after both severe and mild HI in vivo in proportion to the severity of the insult.

Animals↗
PubMed1998

Brain imaging in neonatal hypoglycaemia.

Magnetic resonance imaging studies in two cases of neonatal hypoglycaemia showed cortical and white matter cerebral damage that was most obvious in the occipital lobes. Both cases showed oedema in the parieto-occipital cortex and underlying white matter in the acute phase, with profound atrophy of these regions in the chronic phase. These findings support those of pathological studies which suggest that hypoglycaemia induces cerebral damage by a mechanism separate from the effects of cerebral hypoxia-ischaemia caused by secondary seizures.

Brain↗
PubMed1997

Effect of desferrioxamine cardioplegia on ischemia-reperfusion injury in isolated rat heart.

BACKGROUND: The protective effect of desferrioxamine against myocardial ischemia-reperfusion injury remains uncertain. In this study we examined a broad range of ischemia-reperfusion indices to determine the effect of desferrioxamine cardioplegia in a model that reflects surgical practice. METHODS: Isolated rat hearts were subjected to 90 minutes of ischemia with cold cardioplegia, with or without 0.5-mmol/L desferrioxamine. Left ventricular mechanical function and the levels of thiobarbituric acid-reactive substances and nonprotein thiol compounds were measured after reperfusion. Electron microscopic analysis of mitochondria was performed using diaminobenzidine staining, together with histochemical staining for glycogen and marker enzymes in left ventricular muscle and the atrioventricular node. RESULTS: The desferrioxamine group showed better preservation of diastolic function (chamber stiffness coefficient at 15 minutes and maximum rate of decrease of left ventricular pressure at 45 minutes of reperfusion). Histochemical analysis showed that mitochondria-specific succinate dehydrogenase and the nonspecific esterase of the atrioventricular node were better preserved in the desferrioxamine group. CONCLUSIONS: The findings from this study indicate that there is added protection against ischemia-reperfusion injury when desferrioxamine is added to the cardioplegic solution; however, the study also highlighted that, in this clinically applicable model, desferrioxamine is not universally protective against all aspects of ischemia-reperfusion injury.

Animals↗
PubMed1996

The post-irradiation lower motor neuron syndrome neuronopathy or radiculopathy?

It is not known whether the post-irradiation lower motor neuron syndrome results from radiation damage to motor neuron cell bodies or from damage to the nerve roots of the cauda equina. We studied six cases who had presented with testicular neoplasms, subsequently undergoing irradiation that encompassed inter alia para-aortic nodes with co-irradiation of the distal spinal cord and cauda equina. A predominantly motor disorder affecting the legs ensued after variable and often prolonged latencies (3-25 years). However, all patients also developed mild sensory features either initially or on prolonged follow-up. Sural sensory nerve action potentials (SNAPs) were normal in five. Mild sphincter symptoms occurred in three of five surviving cases after a mean of 7.9 years. MRI showed gadolinium enhancement of the cauda equina in two of three patients. The first reported neuropathological study, uncomplicated by metastatic disease, of the conus and cauda equina was performed in one patient who died. This showed a radiation-induced vasculopathy of the proximal spinal roots, with preservation of motor neuronal cell bodies and spinal cord architecture. These clinical, radiological, neurophysiological and pathological findings all point to a predominantly, but not exclusively, motor radiculopathy affecting the irradiated portion of the cauda equina proximal to the dorsal root ganglia. Radiation exposure exceeded 40 Gy both in our series and in previous reports. The natural history of this disorder is one of relentless deterioration occasionally punctuated by 1-2-year periods of stability. Post-irradiation lumbosacral radiculopathy is a more accurate name for this condition.

Adult↗
PubMed1995

Neonatal carnitine palmitoyltransferase-2 deficiency: a case presenting with myopathy.

Mitochondria were isolated from liver, heart and skeletal muscle of a 34-day-old female infant who died from a myopathic illness. Muscle biopsy showed lipid accumulation and no obvious pathology in any other organ. Enzymatic analysis of skeletal muscle extracts revealed normal activities of the markers pyruvate dehydrogenase and citrate synthase. Malonyl-CoA-sensitive carnitine palmitoyltransferase (CPT1) was detected but malonyl-CoA-insensitive carnitine palmitoyltransferase (CPT2) appeared to be absent. Quantitative immunoblotting revealed the presence of a normal abundance of CPT2 protein in the patient's muscle. It is concluded that enzymically inactive CPT2 protein was present.

Carnitine O-Palmitoyltransferase↗
PubMed1994

Case-control study of intrapartum care, cerebral palsy, and perinatal death.

OBJECTIVE: To investigate the relation between suboptimal intrapartum obstetric care and cerebral palsy or death. DESIGN: Case-control study. SETTING: Oxford Regional Health Authority. SUBJECTS: 141 babies who subsequently developed cerebral palsy and 62 who died intrapartum or neonatally, 1984-7. All subjects were born at term of singleton pregnancies and had no congenital anomaly. Two controls, matched for place and time of birth, were selected for each index case. MAIN OUTCOME MEASURES: Adverse antenatal factors and suboptimal intrapartum care (by using predefined criteria). RESULTS: Failure to respond to signs of severe fetal distress was more common in cases of cerebral palsy (odds ratio 4.5; 95% confidence interval 2.4 to 8.4) and in cases of death (26.1; 6.2 to 109.7) than among controls. This association persisted even after adjustment for increased incidence of a complicated obstetric history in cases of cerebral palsy. Neonatal encephalopathy is regarded as the best clinical indicator of birth asphyxia; only two thirds (23/33) of the children with cerebral palsy in whom there had been a suboptimal response to fetal distress, however, had evidence of neonatal encephalopathy; these 23 formed 6.8% of all children with cerebral palsy born to residents of the region in the four years studied. CONCLUSION: There is an association between quality of intrapartum care and death. The findings also suggest an association between suboptimal care and cerebral palsy, but this seems to have a role in only a small proportion of all cases of cerebral palsy. The contribution of adverse antenatal factors in the origin of cerebral palsy needs further study.

Apgar Score↗
PubMed1994

Unusual magnetic resonance and neuropathological findings in hemimegalencephaly: report of a case following hemispherectomy.

Hemimegalencephaly is a rare disorder manifest by early epilepsy, mental retardation and hemiplegia. The neuropathology has been described in only 15 cases to date. The present case provides a further description of the pathology in a hemispherectomy specimen and shows unusual features, including cystic breakdown of the white matter possibly related to the long duration of the features, including cystic breakdown of the white matter possibly related to the long duration of the disease; the subject was 13 years older than previously documented cases. MRI findings were also unusual in showing mass effect and ventricular compression in the affected hemisphere, features not previously described in hemimegalencephaly.

Adolescent↗
PubMed1994

Cerebral palsy and neonatal encephalopathy.

A retrospective cohort study was carried out to test the hypothesis that children born at term with cerebral palsy with signs of neurological dysfunction preceded by depression at birth (termed neonatal encephalopathy) differ from those without such signs in the frequency of antenatal and perinatal factors, and in the severity and characteristics of their impairment and disability. The study was carried out in the area covered by Oxford Regional Health Authority. Antenatal, intrapartum, neonatal factors, and the later clinical status of the two groups of children were used as the main outcome measures. Although most maternal and antenatal characteristics were similar in the two groups, the mothers of children with a history of neonatal encephalopathy were more likely to be primigravidae (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.3) and to have a pregnancy of greater than 41 weeks' gestation (OR 3.5; 95% CI 1.0 to 12.1). Intrapartum complications were more frequent in the neonatal encephalopathy group: meconium staining of the amniotic fluid (OR 3.5; 95% CI 1.5 to 7.8), an ominous first stage cardiotocograph (OR 10.2; 95% CI 2.9 to 36.4), with a longer median duration of abnormality (200 v 48 minutes). At 5 years of age those with neonatal encephalopathy were more likely to have developed spastic quadriplegia (OR 4.8; 95% CI 2.2 to 10.5), to have visual impairment (OR 3.0; 95% CI 1.0 to 8.6), and to be non-walking (OR 4.0; 95% CI 1.8 to 8.8) than those without neonatal encephalopathy. Children with cerebral palsy who were born at term and have neonatal encephalopathy are more likely to have had signs of intrapartum asphyxia and are more likely to have a more severe form of cerebral palsy than those without a history of neonatal encephalopathy. Although this group represents only one in 10 of all cases of cerebral palsy, some of these may be obstetrically preventable.

Apgar Score↗
PubMed1993

Molecular genetic characterization of an X-linked form of Leigh's syndrome.

We report a patient with necrotizing encephalomyelopathy (Leigh's syndrome) associated with a deficiency of pyruvate dehydrogenase complex activity. The underlying mutation is an A to C transversion in the pyruvate dehydrogenase complex E1 alpha subunit gene. As the E1 alpha subunit is encoded on the X chromosome, this observation confirms that some patients with Leigh's syndrome may potentially exhibit X-linked inheritance.

Amino Acid Sequence↗
PubMed1993

Acute myopathy associated with large parenteral dose of corticosteroid in myasthenia gravis.

A 13 year old Greek girl with myasthenia gravis developed widespread muscle paralysis and atrophy after large parenteral doses of corticosteroids (5.48 g methylprednisolone). An electromyogram showed myopathy, creatine kinase concentration below normal, and a muscle biopsy showed severe myopathy with selective loss of the thick filaments (myosin). Previous reports of myopathy associated with large steroid doses have mostly been in patients who were also receiving non-depolarising neuromuscular blocking drugs. This patient is unique in that severe myopathy was associated with neuromuscular blockade caused by antibodies to acetylcholine receptors. The findings in this case suggest that high doses of parenteral corticosteroids in patients with myasthenia gravis may be dangerous and that blocking the neuromuscular junction with drugs or antibodies predisposes skeletal muscles to the injurious effects of corticosteroids.

Adolescent↗
PubMed1991

Type 2 fiber predominance in Lambert-Eaton myasthenic syndrome.

Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) have shown progressive atrophy and loss of type 1 fibers, resulting in overwhelming type 2 predominance. A similar abnormality was found in a single biopsy from a second case of LEMS without associated carcinoma. Review of the literature suggests that type 2 fiber predominance has been observed in at least one other biopsied case. Interference with transmitter release caused by anti-voltage-gated calcium channel antibodies may deprive type 1 muscle fibers of the low frequency discharge necessary to maintain their metabolic properties.

Adolescent↗
PubMed1991

The incidence of prenatal brain injury.

Recent epidemiological studies have shown that cerebral palsy is only rarely associated with birth asphyxia and that there may be more important causative factors in the prenatal period. For this reason a series of 165 brains of infants who were stillborn or died in the early neonatal period was examined in order to identify the incidence and nature of prenatal brain damage. Seventeen (44%) of the stillborn infants showed evidence of brain damage thought to be related to circulatory disorders. The most frequent abnormality, widespread ischaemic damage to the white matter of the cerebral hemispheres, occurred in 10 (26%). Criteria for white matter ischaemia were reactive astrocytosis, macrophage infiltration, karyorrhexis and endothelial swelling or reduplication. This abnormality was only seen after 27 weeks gestation. In five (13%) of the stillborn infants, haemorrhage was seen in association with ischaemic damage and in only two (5%) did brain haemorrhage occur in utero without evidence of co-existing ischaemic damage. Of the 90 live-born infants, 12 (16%) of those surviving less than 3 days and three (20%) of 15 infants who lived between 3 and 7 days after birth showed ischaemic damage which was of prenatal origin. The most frequent pathological change in the infants studied was white matter gliosis occurring in infants who survived into or beyond the last trimester. This may interfere with normal myelination by diverting glial stem cells into reactive astrocytes and thus reduce the population of oligodendrocytes available to synthesize myelin and so cause permanent neurological damage.

Abortion, Spontaneous↗