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Biomedical subjects

G D Jackson

Publications and source records attributed to G D Jackson.

At least 73 records · Page 4Linked to original sources

Optimised interictal HMPAO-SPECT in the evaluation of partial epilepsies.

Interictal blood flow single photon emission computed tomography (SPECT) has been considered to be of limited value in the investigation of patients with partial epilepsies. Newer SPECT technologies using brain dedicated multiple detector systems have not been fully evaluated. To study the usefulness of an optimized SPECT technique, we scanned 40 epilepsy patients and ten normal subjects. Interictal [99mTc]hexamethylpropylene amine oxime (HMPAO) SPECT scans were acquired using the GE/CGR Neurocam triple-headed brain-dedicated system. The results of a qualitative analysis of the scans were compared to EEG and optimised MRI findings. Eight of the normal subjects and one of 40 patients had normal SPECT scans. There was a comparable concordance of lateralization between SPECT, MRI and EEG. The majority of our patients had mesial temporal pathology on MRI. Perfusion abnormalities extending beyond the mesial temporal area were common and did not simply relate to structural abnormalities. Quantification of blood flow in multiple brain regions revealed that hypoperfusion did not occur at random. Perfusion in the mesial temporal lobe was related to perfusion in anatomically and functionally related ipsilateral and contralateral brain regions. These hypoperfused areas probably reflect dysfunctioning areas which are related to the epileptogenic process.

Adult↗

Children with intractable focal epilepsy: ictal and interictal 99TcM HMPAO single photon emission computed tomography.

Fourteen children with intractable complex partial seizures underwent ictal and interictal 99TcM HMPAO single photon emission computed tomography (SPECT) scans. Abnormalities concordant with clinical and/or EEG localisation were present in 13 of 14 ictal and/or interictal scans. Focal hyperperfusion was seen at the seizure focus on ictal scans and focal hypoperfusion was seen on interictal scans. The timing of the injection in relation to the start of the seizure was crucial for reliable localisation. While recognisable patterns of regional cerebral blood flow (rCBF) were seen on either interictal or ictal scans, marked changes in the patterns of rCBF between the ictal study and interictal study provided the most reliable information about seizure localisation. Using both ictal and interictal studies, 99TcM HMPAO SPECT may provide data about both the seizure origin and its relationship to structurally abnormal regions of the brain.

Adolescent↗

Posterior agyria-pachygyria with polymicrogyria: evidence for an inherited neuronal migration disorder.

We describe two brothers with mental retardation and refractory epilepsy. MRI revealed symmetrical agyria-pachygyria of the temporo-occipito-parietal regions, areas of deeply infolded polymicrogyric parietal cortex, and dilated occipital horns (colpocephaly). The stereotyped clinical, EEG, and MRI findings suggest that this may be a distinct inherited condition and imply that agyria-pachygyria with polymicrogyria is not always sporadic.

Brain↗

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↗

Preoperative MRI predicts outcome of temporal lobectomy: an actuarial analysis.

We used actuarial methods to study outcome after temporal lobectomy in 135 consecutive patients classified into subgroups according to preoperative MRI findings. Sixty months after surgery, 69% of patients with foreign tissue lesions, 50% with hippocampal sclerosis, and 21% with normal MRIs had no postoperative seizures. An eventual seizure-free state of 2 years or more, whether the patient was seizure-free since surgery or not, was achieved by 80% of patients with foreign tissue lesions, 62% of those with hippocampal sclerosis, and 36% of those with normal MRIs. Outcome was worse in those with normal MRIs than in the other two groups. Early postoperative seizures with later remission (the "running down" phenomenon) occurred in all groups. Late seizure recurrence was present only in the hippocampal sclerosis group. These data show that preoperative MRI is a useful predictor of outcome and that actuarial analysis provides insight into different longitudinal patterns of outcome in MRI subgroups. This information can now be used in preoperative counseling.

Actuarial Analysis↗

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↗

Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging.

Rats treated with 250 mg/kg/day vigabatrin showed lesions detected by magnetic resonance imaging (MRI) in the cerebellar white matter in vivo. No lesions were seen in any control animal. As well as these visually apparent lesions, quantitative T2 relaxation time measurements showed a 12 ms increase in cerebellar white matter from 66 +/- 4 ms (SD, n = 5) to 78 +/- 2 ms (SD, n = 7). This region, as expected from previous studies, showed microvacuolation on post-mortem pathology. Additionally, significant increases in T2 relaxation times of 4-9 ms were found in the cerebral cortex, thalamus and hippocampus. Microvacuolation was not detected by post-mortem histopathology in the cerebral cortex or hippocampus, however, immunohistochemical staining for glial fibrillary acidic protein and for macrophages (ED1) showed reactive astrocytes (gliosis) and in more severe cases, microglial proliferation in these regions; such changes were also seen in association with the microvacuoles. No T2 increase was found in the cerebellar grey matter or olfactory bulbs. MRI techniques, including T2 relaxometry, are therefore sensitive for detecting vigabatrin-induced changes, including reactive astrocytosis, microglial proliferation and vacuolation in the rat brain. These results suggest that quantitative MRI should be a useful method for evaluating whether vigabatrin has neuropathological effects when given to patients.

Animals↗

New techniques in magnetic resonance and epilepsy.

Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epileptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years.

Adult↗

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↗

Role of bile in non-specific defence mechanisms of the gut.

The effect of depriving the intestine of bile for 48 hours was studied to determine any influence on various parameters of innate immunity in the gastrointestinal tract. Groups of rats were prepared by bile duct cannulation (with or without fluid replacement) or bile duct ligation. Normal and sham operated animals were used for comparing the thickness of the mucus layer and the cells contained therein, enumeration of goblet cells, and measurement of villus size. Histological examination indicated that the intestinal tissues of treated and control rats were similar. Though villus size and numbers of goblet cells were unaffected, a significant reduction occurred in the thickness of the mucus blanket in the duodenal regions of rats deprived of bile, and there were significantly lower numbers of mucus associated enterocytes and lymphocytes, suggesting a lower turnover rate of the epithelium. The balance of the bacterial populations in the caecum and intestine was altered by bile deprivation-increased numbers of coliform organisms were found in both regions. The range of factors, including antibodies and other known constituents, present in bile may contribute to the maintenance of tissue integrity and influence the balance in indigenous bacterial populations in the intestine. Disturbance of the host's biliary system and concomitant effects on the microbial flora may weaken the overall processes of defence in the intestine.

Animals↗

Effects of vigabatrin on partial seizures and cognitive function.

Forty five patients with refractory partial seizures were studied in a prospective, randomised, placebo controlled, add on, parallel group, double blind trial of the new antiepileptic drug vigabatrin (1.5 g twice daily) followed by open treatment. Seizure frequency was monitored throughout an eight week baseline, 20 weeks double blind, and up to 18 months of open vigabatrin treatment. Cognitive function, including measures of memory and concentration, mood, and behaviour were assessed at baseline and again during the 20th week of treatment. Vigabatrin was associated with a significant reduction in a measure of motor speed and overall score on a design learning test in the first 20 weeks of treatment. In comparison with the baseline period, vigabatrin treatment was associated with a significant reduction in median complex partial seizure frequency four to 12 and 12 to 20 weeks after commencing vigabatrin (-66% and -69% in the vigabatrin group, +50% and +25% in the placebo group). Ten of 20 patients on vigabatrin and four of 23 on placebo showed a > 50% reduction in complex partial seizure frequency in the last eight weeks of double blind treatment. At least 60% of responders had maintained the response to vigabatrin when assessed during the open phase of the trial at 44 weeks. Two patients discontinued vigabatrin because of depression, which resolved on drug withdrawal.

Adolescent↗

Hippocampal sclerosis without detectable hippocampal atrophy.

Six patients from three centers had MRI and pathologic evidence of hippocampal sclerosis but no detectable hippocampal atrophy. Loss of normal internal structure and T1- and T2-weighted signal abnormalities allowed the MRI diagnosis of unilateral hippocampal sclerosis when hippocampal volume measurements were normal and symmetric. Although accurate hippocampal volume measurements will determine the most severely affected side in most cases, volume measurements or atrophy alone will not always detect all MRI-visible pathology. Additional detailed MRI assessment is required before structural abnormality of the hippocampus is excluded on the basis of volume measurements.

Adolescent↗

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↗

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↗

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↗

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↗