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Biomedical subjects

A Connelly

Publications and source records attributed to A Connelly.

At least 55 records · Page 3Linked to original sources
PubMed1997

The spectrum of hippocampal sclerosis: a quantitative magnetic resonance imaging study.

One hundred patients with intractable temporal lobe epilepsy and 22 control subjects were scanned on a 1.5-T Siemens SP63 Magnetom scanner. A combination of hippocampal T2 mapping, hippocampal volume measurement corrected for intracranial volume, and inspection of hippocampal morphology on a hippocampal volume distribution graph compared with a control graph revealed previously undetected forms of bilateral hippocampal sclerosis and four false-positive diagnoses of hippocampal sclerosis made on visual inspection of the scans. A physiological asymmetry in the position of the hippocampi in 41% of control subjects and focal hippocampal atrophies in patients made measurement of the whole length of the hippocampus mandatory. The extent of hippocampal damage in patients with hippocampal sclerosis correlated with the number of secondary generalized seizures during a patient's lifetime. In contrast to patients with unilateral hippocampal sclerosis, patients with severe bilateral hippocampal sclerosis had no history of febrile convulsions. Twenty-six patients with intractable temporal lobe epilepsy had normal hippocampal magnetic resonance imaging measures and as a group were significantly older at the onset of habitual epilepsy than were patients with hippocampal sclerosis. In conclusion, a combination of quantitative magnetic resonance imaging techniques revealed a spectrum of hippocampal sclerosis and optimally defined boundaries of hippocampal normality. The spectrum of hippocampal sclerosis is related to the etiology, the number of secondary generalized seizures, and the age at onset of habitual epilepsy.

Adolescent↗
PubMed1997

Quantitative neuropathology and quantitative magnetic resonance imaging of the hippocampus in temporal lobe epilepsy.

The aims of this study were to examine the relationships of hippocampal T2 (HCT2) relaxation time and magnetic resonance (MR)-based hippocampal volume (HCV) to neuronal (ND) and glial cell densities (GD) of hippocampal neuronal cell layers, and to obtain a better clinicopathological definition of hippocampal sclerosis (HS) and end folium sclerosis (EFS). Fifty-three hippocampi with HS, 6 with EFS, and 6 control hippocampi were studied. Pathologically, the HS group had a significantly higher logarithm (log) GD/ND than the controls in all hippocampal subregions, and than the EFS group in all subregions except the granule cell layer of the dentate gyrus (GCDG). The EFS group had a significantly higher log GD/ND than the control group only in the GCDG. Clinical correlations suggested that EFS may be the consequence of temporal lobe seizures and not an epileptogenic entity. Hippocampal atrophy in HS was associated with neuronal cell depletion and concomitant gliosis in the cornu Ammonis (CA) 1, CA2, CA3, and hilus. An increased HCT2 was associated with damage in the CA1 and also the hilus and has a different neuropathological basis than HCV loss. MR-based HCV measurement and HCT2 mapping, therefore, give complementary information in the presurgical evaluation of temporal lobe epilepsy and longitudinal studies.

Adolescent↗
PubMed1997

Localized q-space imaging of the mouse brain.

Localized q-space imaging was used to obtain water displacement profiles from mouse brain. These profiles take the form of unidirectional diffusive displacement probability distributions. Two groups of mice were studied, a normal group and a group in which surgery had been performed to produce a unilateral reduction in the supply of blood to the forebrain. q-Space measurements were made both in vivo and postmortem. The displacement profiles were characterized using the summary parameter prob[d < 10], which is the proportion of water molecules that undergo a net diffusive displacement that is less than +/-10 microm, during the diffusion period (50 ms). The range of prob[d < 10] values in the normal group was 0.71 to 0.77 in vivo compared with 0.78 to 0.87 in the impaired hemisphere of the surgically treated group. An increase in prob[d < 10] occurred postmortem to yield values in the range 0.79 to 0.81 and 0.80 to 0.89 in the normal and surgically treated group, respectively. These observations are consistent with the diffusion-weighted image intensity changes that occur after a period of ischemia.

Animals↗
PubMed1997

Guanidinoacetate methyltransferase deficiency: new clinical features.

Guanidinoacetate methyltransferase deficiency is a recently described inborn error of creatine biosynthesis that responds to treatment with oral creatine supplementation. The previously reported clinical features consist of developmental arrest and an extrapyramidal movement disorder. We describe a patient who presented with epilepsy, global developmental delay, and a persistently low plasma creatinine level. The diagnosis was established by measuring urinary guanidinoacetate and by demonstrating absence of the creatine/phosphocreatine peak in the patient's basal ganglia in 1H magnetic resonance spectroscopy. The clinical and biochemical abnormalities responded to creatine replacement.

Amino Acid Metabolism, Inborn Errors↗
PubMed1997

Interictal 99Tc(m) HMPAO SPECT and 1H MRS in children with temporal lobe epilepsy.

PURPOSE: To understand the pathological basis of focal hypoperfusion seen on interictal 99Tc(m) hexamethylpropyleneamine oxime (HMPAO) single-photon-emission computed tomography (SPECT) in intractable temporal lobe epilepsy, and to determine why the technique may be misleading in the localization and lateralization of the seizure focus in some cases. METHODS: Interictal 99Tc(m) HMPAO SPECT and proton magnetic resonance spectroscopy (1H MRS) of the mesial temporal regions were performed in 14 children with intractable temporal lobe epilepsy not caused by a foreign tissue lesion. RESULTS: Hypoperfusion of one temporal lobe ipsilateral to the seizure focus was demonstrated in 10 (71%) of the children; 1H MRS correctly lateralised in eight of these 10. No asymmetry of perfusion of the anterior temporal regions was seen in the remaining four children; on 1H MRS, three of these were bilaterally abnormal but nonlateralising. Repeated SPECT and 1H MRS in three children demonstrated changes over time, the findings from the two techniques being consistent with each other on both the initial and the repeated scans. CONCLUSIONS: Abnormalities demonstrated by 1H MRS correlate well with those seen on interictal SPECT and can help to understand the pathologic basis of these SPECT abnormalities. Furthermore, the presence of bilateral damage can result in an absence of perfusion asymmetry on interictal SPECT.

Adolescent↗
PubMed1997

The relation between quantitative MRI measures of hippocampal structure and the intracarotid amobarbital test.

PURPOSE: The increasing sophistication of quantitative magnetic resonance imaging (MRI) techniques has generated hopes that they may eventually supersede the intracarotid amobarbital procedure (IAP) in the presurgical screening for bilateral abnormalities in prospective candidates for temporal lobe epilepsy surgery. As the first step toward this aim, the purpose of this study was to examine the relationship between these measures of structural and functional integrity. METHODS: We examined the relation between memory performance and pass/fail rates on the IAP and two MRI measures of hippocampal integrity: hippocampal volumes, adjusted for intracranial volume (HCvol) and hippocampal T2 relaxometry (HCT2), in 48 patients with medically intractable temporal lobe epilepsy, who underwent the IAP as part of their presurgical evaluation for temporal lobectomy. RESULTS: The unilateral memory scores from the IAP were not significantly correlated with the corresponding HCvol or HCT2 measures in the right- and left-temporal-lobe groups. However, the MRI measures of hippocampal asymmetry (right minus left HCvol, right minus left HCT2) were significantly correlated with our measure of functional asymmetry, the right minus left hemisphere memory score from the IAP, supporting the role of the IAP in lateralising temporal lobe dysfunction. Forty-six patients with unilateral hippocampal sclerosis and concordant EEG studies passed the IAP. Two patients failed the memory component of the IAP. In both cases, other presurgical investigations suggested bilateral abnormalities. CONCLUSIONS: We conclude that patients with unilateral hippocampal sclerosis, established by a rigorous quantitative MRI protocol, and concordant ictal and interictal EEG findings may not be at risk for postoperative amnesia, despite baseline neuropsychological deficits suggestive of bilateral disturbance.

Adult↗
PubMed1997

Diffusion weighted magnetic resonance imaging of compromised tissue in stroke.

Diffusion weighted imaging (DWI) and T2 weighted magnetic resonance imaging were performed on at least two occasions in 28 children presenting with stroke. In previous reports of DWI in human stroke, eventual infarction was observed (with only one exception) in all regions in which early DWI hyperintensity occurred. In the present report, two children had regions of DWI hyperintensity which did not progress to infarction. One patient who presented with right hemiplegia showed extensive high signal on DWI, with T2 evidence of tissue swelling but without hyperintensity. DWI changes persisted over weeks, with no imaging indication of infarction. This child recovered completely. A second child who had a major vessel infarct with concomitant regions of hyperintensity on T2 weighted imaging and DWI, also had DWI hyperintensity in an adjacent territory which did not develop any subsequent evidence of infarction. Thus in clinical practice DWI can demonstrate tissue which is compromised but not irreversibly so.

Brain↗
PubMed1997

Etiology and early prognosis of newly diagnosed partial seizures in adults: a quantitative hippocampal MRI study.

Sixty-three adult patients with newly diagnosed partial seizures underwent MRI of the brain including hippocampal quantitation. Seventy-six percent of patients had normal MRI findings, 10% had hippocampal sclerosis (HS), and 14% had MRI abnormalities other than HS. Patients with HS had a worse early prognosis than patients with other MRI findings with respect to seizures. The extent of hippocampal damage appeared to be an important mediating factor in frequency of seizures, secondary generalization, and resistance to antiepileptic drug treatment. Because MRI provides prognostic information and can alter management for the individual patient, high-resolution MRI should be performed in all patients with newly diagnosed partial seizures.

Adult↗
PubMed1996

Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy.

We performed proton magnetic resonance spectroscopy of the mesial temporal regions in 20 children with intractable temporal lobe epilepsy and compared results with those from 13 normal subjects. Abnormalities of the ratio of N-acetylaspartate to choline plus creatine (NAA/[Cho+Cr]) were seen in 15 patients (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side), suggesting neuronal loss or dysfunction. There was also a bilateral increase in creatine and choline (mean 18%), consistent with reactive astrocytosis. We conclude that proton magnetic resonance spectroscopy can contribute to lateralization of the seizure focus, and by detection of bilateral abnormalities, can contribute to the understanding of the underlying pathophysiology in temporal lobe epilepsy.

Adolescent↗
PubMed1996

Quantitative comparison of functional magnetic resonance imaging with positron emission tomography using a force-related paradigm.

The intention of our study was to compare functional magnetic resonance imaging (fMRI) with positron emission tomography (PET). We used the same force-related motor paradigm for both techniques, which allows for quantification of stimulus intensity. Regional cerebral blood flow (rCBF) was determined with PET in six male subjects (age 30 +/- 3) using the slow bolus injection technique and oxygen-15-labeled water. Scans were collected during six different conditions: at rest and during repetitive Morse key press at 1 Hz, with the right index finger at a range of different forces. In a second series of experiments fMRI data were acquired under similar conditions in six volunteers in a single slice parallel to and 51 +/- 3 mm dorsal to the anterior and posterior commissure (AC-PC). A conventional 1.5-T clinical magnetic resonance (MR) system and the FLASH technique were used. The data obtained in both series of experiments were subjected to the same statistical analyses. Statistical parametric maps (SPM) were generated by two different approaches: a correlation between peak force and rCBF or fMRI signal and using a categorical comparison of force exerted with rest. SPMs were coregistered with anatomical MR images. PET and fMRI measurements demonstrated activation in the primary motor cortex (M1) and posterior supplementary motor cortex in all subjects. Correlation analysis demonstrated foci in the M1 in four subjects with PET and in only one subject with fMRI. Locations of activation peaks differed by 2 to 8 mm between imaging methods. The relationship between fMRI signal or rCBF and peak force was logarithmic. The maximum increase in fMRI signal was 5.0% +/- 0.9 at 60% of the maximum voluntary contraction while the corresponding increase in rCBF was 13.7% +/- 1.2. The ratio of percentage rCBF change to percentage fMRI signal change was very similar across all force levels. The high degree of correspondence between PET and fMRI data provides good cross-validation for the two techniques.

Adult↗
PubMed1996

Magnetic resonance imaging and spectroscopy.

In the past year, magnetic resonance has assumed an increasingly important role in the study of patients with epilepsy that now extends beyond its demonstration of neuroanatomy and neuropathology into the fields of neurochemistry, neurometabolism and neurophysiology. For proper use of this information, epileptologists, neurologists and neuroradiologists need to understand the limitations as well as the strengths of this technology. Magnetic resonance literacy will increasingly become an essential part of all of these disciplines.

Child, Preschool↗
PubMed1996

Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.

We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.

Adolescent↗
PubMed1996

The amygdala and intractable temporal lobe epilepsy: a quantitative magnetic resonance imaging study.

OBJECTIVE: To establish a quantitative MRI technique using T2 relaxation time mapping to study systematically the amygdala in patients with intractable temporal lobe epilepsy (TLE). BACKGROUND: Identification of a focal abnormality on MRI in patients with intractable TLE is important, because outcome from surgery depends largely on the removal of the underlying pathology. Hippocampal sclerosis (HS) is the most common cause of intractable TLE, but epileptogenic lesions can be confined to the amygdala. METHODS: Twenty control subjects and 82 patients with intractable TLE were studied. Patients who had foreign tissue lesions visible on routine MRI were excluded. All subjects had a hippocampal T2 map and volumetry and an amygdala T2 (AT2) map. RESULTS: Forty-four of the 82 patients (54%) had an abnormal AT2, which was bilateral in 18. Forty-four patients (54%) had unilateral HS on MRI, 25 (57%) of whom had an abnormal AT2. Seven patients (8%) had bilateral HS, four of whom had an abnormal AT2. Thirty-one patients (38%) had normal quantitative hippocampal measures, 15 of whom had an abnormal AT2, which was bilateral in seven. Fluid attenuated inversion recovery (FLAIR) imaging, where appropriate, confirmed that the increased AT2 signal was due to parenchymal changes. Neuropathologic correlates of an increased AT2 included microdysgenesis in one and gliosis in three patients. Patients with an isolated AT2 abnormality were significantly older at the onset of habitual epilepsy and rarely had a history of febrile convulsions, in comparison with patients who had HS. An isolated AT2 abnormality correlated well with interictal EEG findings. CONCLUSIONS: The combination of AT2 mapping and FLAIR is a sensitive method to detect lesions that are not seen on routine MRI in the amygdalae of patients with intractable TLE. Further correlational studies will be required to define the role of this technique in the presurgical evaluation of patients with intractable TLE.

Adolescent↗
PubMed1995

Ictal imaging using functional magnetic resonance.

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. This noninvasive technique can also map the cortical activation that occurs during focal seizures, as demonstrated here by the results obtained using a conventional 1.5 T clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. FLASH images (TE = 60 ms) were acquired every 10 s over a period of 25 min, and activation images derived 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 detectable clinical seizure. The activated regions included gyri that were structurally abnormal. These results demonstrate (a) that functional MRI can potentially provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure; and (b) that there is the possibility of obtaining similar information in the absence of clinical seizures, suggesting the potential for studies in patients were interictal electrical disturbances.

Brain Damage, Chronic↗
PubMed1995

Quantitative hippocampal MRI and intractable temporal lobe epilepsy.

OBJECTIVES: To evaluate and compare T2 relaxometry and volumetrics of hippocampus in the presurgical evaluation of patients with intractable temporal lobe epilepsy (TLE), and to correlate these quantitative MRI measures with the pathology of the resected hippocampus. PATIENTS: Forty patients with intractable TLE who underwent presurgical evaluation and subsequent temporal lobe surgery. MAIN OUTCOME MEASURES: Hippocampal T2 (HCT2), volumes of hippocampi and hippocampal volume ratio (HCVR) (volume of hippocampus with higher HCT2 divided by volume of hippocampus with lower HCT2), and qualitative pathology. RESULTS: Thirty-two patients had hippocampal sclerosis, three patients had end-folium sclerosis, one patient had amygdala sclerosis, and four patients had a foreign tissue lesion in the temporal lobe. HCT2 (R/L) correlated inversely with the ratio of hippocampal volumes (R/L) (r = -0.91; p < 0.0001). A high T2 signal in an atrophic hippocampus was characteristic of hippocampal sclerosis. All patients with hippocampal sclerosis had an HCVR below control values, and only one of these had an HCT2 in the normal range. HCVR produced one false-positive result. The patients with end-folium sclerosis had normal HCT2 and HCVR. The patient with amygdala sclerosis had a normal hippocampus on qualitative and quantitative assessment. Of the four patients with a lesion, one had a mildly increased HCT2 and one had mild volume asymmetry. Hippocampal volume asymmetry could be reliably detected on visual inspection of the MRI with an HCVR of 0.85 or less, and an increase of HCT2 with a T2 of 115 msec or higher. CONCLUSION: Quantitative MRI combining HCT2 and HCVR is a reliable method for diagnosing hippocampal sclerosis noninvasively. End-folium sclerosis and amygdala sclerosis should be considered in patients with intractable TLE and negative findings on MRI studies, including quantitative measures of the hippocampus.

Adolescent↗
PubMed1995

Verbal memory impairment after right temporal lobe surgery: role of contralateral damage as revealed by 1H magnetic resonance spectroscopy and T2 relaxometry.

We assessed performance on selected tests of verbal memory in 48 patients who had undergone either anterior temporal lobectomy or selective amygdalo-hippocampectomy for the relief of pharmacologically intractable epilepsy. We related performance both to the side of surgical excision and to the presence or absence of abnormalities in the contralateral, unoperated, temporal lobe, as revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry. There were abnormalities on the unoperated side detected by 1H MRS in 50% of the 34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33% of the complete series of 48 patients. There was no systematic relationship between seizure outcome and the presence or absence of abnormalities on the unoperated side. Verbal memory deficits were present in patients with left-sided excision, regardless of whether there were abnormalities on the unoperated side. The patients with right-sided excision also had verbal memory deficits, but only in the group with magnetic resonance abnormalities on the contralateral (ie, left) side and only on delayed recall. The study extends previous findings on the role of the temporal lobes in memory and highlights the role of these new magnetic resonance techniques in relating cognitive processes to brain structures.

Adult↗
PubMed1995

Functional MR imaging correlations with positron emission tomography. Initial experience using a cognitive activation paradigm on verbal working memory.

The most established functional MR imaging technique for activation studies relies on a T2*-weighted contrast. This signal arises primarily from a blood oxygen level dependent contrast generated by an imbalance between the increase in regional cerebral blood flow and oxygen metabolism in the brain during activation. As predicted by theory, the percentage signal changes observed in functional MR imaging experiments are considerably smaller than those detected by positron emission tomography, which directly measures regional cerebral blood flow as an index of neuronal activity. Cross-validation of functional MR imaging with an established technique such as positron emission tomography would be extremely valuable for determining the correlation between functional MR image signal change and regional cerebral blood flow change and for assessing the sensitivity of the functional MR imaging technique. The authors report on such cross-validation experiments in three subjects challenged with a verbal working memory task and show that satisfactory replication of positron emission tomography results with functional MR imaging was achieved in two subjects. Limitations owing to magnetic field strength used and single-slice sampling may have contributed to the lack of signal detection in the case where no reliable activation pattern was detected with functional MR imaging.

Adult↗