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Biomedical subjects

A Connelly

Publications and source records attributed to A Connelly.

At least 73 records · Page 4Linked to original sources
PubMed1994

Clinical diversity of pyruvate dehydrogenase deficiency.

Clinical features, magnetic resonance, and biochemical studies are reported in 7 children with pyruvate dehydrogenase (PDH) deficiency. These findings confirm the diverse clinical presentation of this condition, although neurological abnormalities are consistent features. Imaging results are also varied. Six of the children were investigated with proton magnetic resonance spectroscopy and lactate was demonstrated in brain in all patients. Regional variation in the lactate signal was observed in those patients in whom 2 regions were examined. Advances in molecular genetics have provided some explanations for the clinical variation in pyruvate dehydrogenase deficiency.

Brain↗
PubMed1994

Quantitative MR relaxometry study of effects of vigabatrin on the brains of patients with epilepsy.

Neurotoxic changes have been found in the brains of dogs and rats treated with the antiepileptic drug vigabatrin, and these can be demonstrated in vivo by MRI. Quantification of T2 signal by relaxometry is more sensitive than visual assessment of T2-weighted images in revealing changes in T2 signal. We have therefore undertaken a quantitative MR study of 45 patients with refractory partial seizures during a prospective, randomised, double-blind trial of vigabatrin (1.5 g twice daily), followed by open treatment. T2 relaxometry was performed during a baseline period, after 20 weeks vigabatrin or placebo treatment and again in those who continued the drug for at least 35 weeks. Twenty weeks' vigabatrin treatment was not associated with a significant change in T2 relaxation time in any brain area. There were no significant T2 signal changes in the follow-up study and no correlation between change in T2 and duration of vigabatrin treatment. There was no quantitative MR evidence of vigabatrin-related changes in the white matter of these patients similar to those which have been found in animals treated with the drug.

Adolescent↗
PubMed1994

1H magnetic resonance spectroscopy in the investigation of intractable epilepsy.

We have been using proton magnetic resonance spectroscopy (1H MRS) in the investigation of adults and children with intractable epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the epilepsy patients as a group show significant reductions in the NAA signal and in the NAA/Cho+Cr ratio, with increases in the Cho and Cr signals. The reduction in NAA is interpreted in terms of neuronal loss or damage, while the increase in Cr and Cho signals may be a reflection of reactive astrocytosis.

Adult↗
PubMed1994

Functional magnetic resonance imaging of focal seizures.

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. We aimed to establish whether this noninvasive technique could also map the cortical activation that occurs during focal seizures. In order to do this, we used a conventional 1.5-tesla clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. We acquired FLASH images (TE = 60 msec) every 10 seconds over intervals of 10 minutes and derived activation images by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. We concluded that functional MRI can provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure.

Brain↗
PubMed1994

Magnetic resonance spectroscopy in temporal lobe epilepsy.

We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the temporal lobes ipsilateral to the seizure focus showed a mean reduction of 22% in the NAA signal, with a 15% increase in the Cr signal and a 25% increase in the Cho signal. There were smaller effects in the contralateral temporal lobes. These spectral abnormalities may reflect neuronal loss or damage, together with reactive astrocytosis. The NAA/Cho+Cr ratio was abnormally low in 88% of the patients, 40% showing bilateral effects. On the basis of the NAA/Cho+Cr ratio, we correctly achieved lateralization in 15 cases, with three incorrect. Two of the incorrect lateralizations also had imaging abnormalities on the contralateral side, and the other had severe bilateral abnormalities on MRS. We conclude that 1H MRS provides useful information in the preoperative investigation of patients with temporal lobe epilepsy, contributing to lateralization and detecting bilateral abnormalities.

Adolescent↗
PubMed1994

MR detection of hippocampal disease in epilepsy: factors influencing T2 relaxation time.

PURPOSE: To assess the reproducibility and stability of hippocampal T2 relaxation times and examine the effects of patients' age, seizures, and duration of epilepsy on this measure. METHODS: Hippocampal T2 relaxation times were measured in 63 patients with chronic epilepsy (55 with partial and 8 with idiopathic generalized seizures) using a Carr-Purcell-Meiboom-Gill sequence, echo times 22 to 262 millisecond, on a 1.5-T clinical MR imaging system. Twenty-three patients on stable medication regimens underwent repeated T2 relaxometry after an interval of between 115 and 331 days. In 4 patients with partial seizures, hippocampal T2 relaxation times were measured interictally and again within 45 minutes of seizures. RESULTS: In the 55 patients with partial epilepsy, hippocampal T2 relaxation times did not correlate with seizure frequency, duration of epilepsy, or age, but they were significantly more abnormal in those patients with a history of prolonged (more than 30 minutes) early childhood seizures than in those without. Eight patients with idiopathic generalized epilepsy had normal MR and hippocampal T2 relaxation times. In the 23 patients who underwent repeated T2 relaxometry there was no evidence of qualitative changes in T2-weighted images of the hippocampi or systematic changes of hippocampal T2 relaxation times with time. In 4 patients recent complex partial or secondary generalized seizures did not acutely alter hippocampal T2 relaxation times. CONCLUSION: Hippocampal T2 relaxation time is a precise, reliable, stable, noninvasive measurement sensitive to hippocampal disease. These results do not suggest progression of hippocampal disease in patients with intractable partial seizures during periods of up to 331 days.

Adolescent↗
PubMed1993

Proton magnetic resonance spectroscopy studies in lactic acidosis and mitochondrial disorders.

Congenital lactic acidosis form a large group of disorders that are commonly associated with profound neurological dysfunction. Difficulties are frequently encountered in establishing a diagnosis, and the mechanisms underlying brain damage are poorly understood. We have performed proton magnetic resonance spectroscopy (1H-MRS) on 24 patients under investigation for suspected metabolic disorder, and have compared the MRS observations of brain lactate with measurements of cerebrospinal fluid (CSF) lactate. We have shown good concordance between the two types of observation, confirming the value of the CSF measurements. Regional variations in brain lactate are detected in some cases, and these may help to elucidate the mechanisms underlying selective brain damage.

Acidosis, Lactic↗
PubMed1993

Early detection of abnormalities in partial epilepsy using magnetic resonance.

The incidence of brain abnormalities determined by magnetic resonance in 30 consecutive children presenting with intractable complex partial seizures is reported. Images were optimised to visualise the hippocampus and cortical grey matter. Abnormalities of the hippocampus or temporal lobe were seen in all 19 children with clinical features of temporal lobe epilepsy and in six of the seven children with clinically unlocalised epilepsy. By contrast, in the four children with a clinical diagnosis of extratemporal epilepsy, no temporal or hippocampal abnormalities were seen. Generalised cortical abnormalities of uncertain significance were found in a total of 14 children from all groups. The identification of focal brain abnormalities using optimised magnetic resonance imaging enables early non-invasive assessment of children with intractable seizure disorders and the identification of patients for whom epilepsy surgery may be appropriate. It may also lead to a better understanding of the structural basis of intractable epilepsy, and thereby contribute to early treatment decisions.

Adolescent↗
PubMed1993

Functional mapping of activated human primary cortex with a clinical MR imaging system.

Functional activation of the human brain can be visualized with magnetic resonance (MR) imaging, but most studies so far have used echo-planar imaging or magnetic fields of 2 T and above, neither of which are at present widely available. The authors used a standard 1.5-T MR imaging system to map regions of the brain that are activated with visual and motor tasks, using a long echo time (60 msec) fast low-angle shot sequence. Eleven visual and 14 motor studies were performed, and activation was seen in all cases. Up to 15% signal intensity change was apparent in gray matter but not in white matter. The precise anatomic location and extent of activation were defined by reference to T1-weighted images acquired during the same examination. This method of relating brain structure to function uses equipment that is widely available, which has considerable implications for the investigation of many neurologic and neurosurgical diseases and for our understanding of brain function and dysfunction.

Adult↗
PubMed1993

Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency.

We have performed localized in vivo proton magnetic resonance spectroscopy on two females with ornithine carbamoyl transferase deficiency during episodes of acute hyperammonemic encephalopathy with focal neurologic abnormalities. Spectra obtained from 2 x 2 x 2 cm cubic volumes at relatively long (135-ms) echo times contain additional signals that are characteristic of glutamine and indicate that glutamine is present in very high concentrations in the brain. The findings are consistent with the hypothesis that intracerebral accumulation of glutamine contributes to the encephalopathy associated with hyperammonemia. In one of the children, spectra obtained after treatment showed a marked decrease in the glutamine signals.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Detection of hippocampal pathology in intractable partial epilepsy: increased sensitivity with quantitative magnetic resonance T2 relaxometry.

Abnormal T2-weighted signal intensity in the hippocampus may be difficult to detect visually, and T2 mapping provides an objective means of assessing signal abnormality. We investigated 50 adult outpatients suffering from intractable partial epilepsy with MRI optimized to detect hippocampal and cortical gray matter abnormalities, and with MR T2 relaxation mapping. The range of normal hippocampal T2 relaxation times is small (99 to 106 msec), and the measurements are reproducible between observers. There were abnormal hippocampal T2 relaxation times in the hippocampus ipsilateral to the site of seizure origin in 70% of patients studied, with the more severe abnormality in the ipsilateral hippocampus in all cases. All hippocampal T2 measurements greater than 116 msec were associated with temporal lobe epilepsy and pathologic or MRI evidence of hippocampal sclerosis, or both. Bilateral abnormalities were present in 29% of cases with hippocampal sclerosis.

Adolescent↗
PubMed1993

Placental microvascular changes in twin pregnancies with abnormal umbilical artery waveforms.

OBJECTIVE: To determine whether there is a relationship between umbilical artery Doppler waveforms and placental histology in twin pregnancies. METHODS: The placental vasculature was examined histologically in 41 cases of twin pregnancy in women who had undergone antenatal Doppler umbilical artery waveform analysis. RESULTS: Those fetuses with abnormal systolic-diastolic ratios (S/Ds) showed a reduction in the placental tertiary stem villi arterial vessels compared with fetuses with normal S/Ds. The mean count of small arterial vessels (diameter less than 90 mu) in the placentas from cases with normal S/Ds (below the 95th percentile) was 5.6, whereas the mean arterial count for those with high S/Ds (above the 99th percentile) was 3.9 (P = .039). CONCLUSIONS: In twin pregnancies complicated by placental insufficiency, there is microvascular disease restricted to the placenta of the affected fetus. This suggests that the placental vascular lesion originates in the fetal circulation rather than in the uteroplacental vasculature.

Birth Weight↗
PubMed1991

Localized 1H NMR spectroscopy in Canavan's disease: a report of two cases.

Two children with Canavan's Disease, an autosomal recessive leukodystrophy, were studied by localized 1H spectroscopy. The N-acetylaspartate (NAA) signal intensity was high relative to other metabolite signals, and the signal intensity from choline-containing compounds was low. These findings are discussed in relation to a possible role for NAA in normal myelination.

Aspartic Acid↗
PubMed1991

Approaches to editing, assignment and interpretation of proton spectra.

Clinical 1H spectroscopy of the brain is complemented by parallel analyses of biopsy specimens and by studies of animal models of disease. 1H spectroscopy has been carried out on perchloric acid extracts of biopsy specimens from patients with intracranial tumours. The data suggest that clinical spectroscopy may be useful in the identification and grading of these tumours. In addition, the spectra from extracts derived from normal white matter add weight to the possibility that acetyl-containing compounds other than N-acetylaspartate may make a significant contribution to the signal at 2.0 ppm in vivo. Edited 1H spectra of brain metabolites in rats with acute liver failure demonstrate an elevation of glutamine and of lactate, suggesting a role for 1H spectroscopy in clinical investigations of metabolic encephalopathies. However, the observation and resolution of signals from glutamate and glutamine is more difficult at the lower fields that are available for clinical spectroscopy. Finally, some studies of patients with inborn errors of metabolism are described. It is shown that in a disorder of oxidative metabolism, brain lactate can be detected without the need for complex spectral editing techniques. Investigations of the metabolic abnormalities associated with Canavan's disease have shed further light on a possible role for N-acetylaspartate.

Animals↗
PubMed1991

Fetal umbilical artery velocity waveforms and subsequent neonatal outcome.

Flow velocity waveforms (FVWs) from the fetal umbilical artery were recorded from 2178 pregnant women over a 6-year period. All of them had an obstetric factor indicating increased risk of fetal compromise. A total of 6749 studies was recorded. The systolic diastolic (AB) ratio was measured and classified as normal (less than 95th centile), elevated (95-99th centile), high (greater than 99th centile) or extreme (absent diastolic flow). The results of these studies have been related to subsequent fetal and neonatal outcome. An abnormal umbilical artery FVW was associated with shorter gestation and infants with lower birthweight, shorter length and lower ponderal index. There was a highly significant association between an abnormal FVW and the birth of an infant small for gestational age. The significance of the association increased with the increased abnormality of the umbilical artery FVW and this was independent of gestational age. Preterm infants associated with high or extreme AB ratios spent twice as long in the neonatal nursery than those with normal AB ratios. Analysis of 794 pregnancies studies serially indicated that an abnormal FVW in which the AB ratio was increasing, in contrast to a decreasing AB ratio, predicted a poor outcome for both size at birth and duration of neonatal intensive care. We conclude that in high risk pregnancy Doppler umbilical artery FVW studies predict the most compromised fetuses in terms of growth retardation and requirements for neonatal intensive care.

Adult↗
PubMed1988

High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease.

Chronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 microns and the inplane resolution was 40 X 40 microns. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.

Animals↗