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Biomedical subjects

D R Fish

Publications and source records attributed to D R Fish.

At least 37 records · Page 2Linked to original sources

Surgical outcome in patients with epilepsy and dual pathology.

High-resolution MRI can detect dual pathology (an extrahippocampal lesion plus hippocampal atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippocampal lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippocampal lesion); mesial temporal resection (removal of an atrophic hippocampus); and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippocampus). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible.

Adolescent↗

EEG-triggered functional MRI of interictal epileptiform activity in patients with partial seizures.

EEG-triggered functional MRI (fMRI) offers the potential to localize the generators of scalp EEG events, such as interictal epileptiform discharges, using a biological measurement as opposed to relying solely on modelling techniques. Although recent studies have demonstrated these possibilities in a small number of patients, wider application has been limited by concerns about patient safety, severe problems due to pulse-related artefact obscuring the EEG trace, and lack of reproducibility data. We have systematically studied and resolved the issues of patient safety and pulse artefact and now report the application of the technique in 24 experiments in 10 consecutive patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes or spike wave). At least two experiments were performed for each patient. In each experiment, 10- or 20-slice snapshot gradient-echo planar images were acquired approximately 3.5 s after a single typical epileptiform discharge (activation image) and in the absence of discharges (control image). Between 21 and 50 epileptiform discharges were sampled in each experiment. The significance of functional activation was tested using the t test at 95% confidence on a pixel-by-pixel basis. Six of the 10 patients showed reproducible focal changes of the blood oxygen level-dependent (BOLD) signal, which occurred in close spatial relationship to the maximum of the epileptiform discharges in the concurrent EEG. No reproducible focal BOLD signal changes were observed in the remaining four patients. In conclusion, EEG-triggered fMRI is now a sufficiently developed technique to be more widely used in clinical studies, demonstrating that it can reproducibly localize the brain areas involved in the generation of spikes and spike wave in epilepsy patients with frequent interictal discharges.

Adult↗

Analysis of temporal lobe resections in MR images.

PURPOSE: The nature of the resection in surgery for intractable medial temporal lobe epilepsy is likely to be a principal factor determining seizure and neuropsychological outcome. However, there is no universally accepted system for describing the characteristics of individual resections to allow comparison between patients and patient groups treated at different institutions. We therefore developed a technique of volumetric analysis of temporal lobe resections. METHODS: With comparison of coregistered pre- and postoperative, volumetric magnetic resonance imaging (MRI) scans in 10 subjects, the volumes of six temporal lobe substructures were determined by manual delineation in the pre- and post-operative images for each case, allowing the extent of resection to be determined. RESULTS: The substructures and their extent of resection were measured with acceptable repeatability in each case. CONCLUSIONS: We developed a reliable method for the quantitative description of temporal lobe resections. This will be of application in determining the relation between the anatomic nature of the resection in intractable epilepsy and the seizure and neuropsychological outcome.

Amygdala↗

Seizures during video-game play and other common leisure pursuits in known epilepsy patients without visual sensitivity.

PURPOSE: Some individuals who are negative to flash/pattern sensitivity have been reported to experience seizures while exposed to video games. This study seeks to examine systematically whether exposure to video-game material is a risk factor for seizures in patients with chronic epilepsy without visual sensitivity. METHODS: Two hundred and twelve chronic epilepsy patients participated in the study. All were negative to rigorous flash and pattern sensitivity testing. They were randomly allocated to a video game-playing session or to a period of leisure (involving reading, physical exercise, puzzles, etc.) and then alternated between these activities for a fixed total of eight 45-min periods while undergoing video-EEG monitoring. The study ceased if the participant experienced a clinical seizure. RESULTS: Twenty-five of 212 subjects experienced a seizure while participating in the study. Thirteen seizures occurred during periods of video-game play, and 12 during alternative leisure. CONCLUSIONS: We have not identified a greater risk of seizures in patients with (not visually sensitive) epilepsy during video-game play compared with other common leisure pursuits. Furthermore, we exposed a large population (212 patients) mostly with severe epilepsy, mainly drug reduced and some sleep deprived, to prolonged video game-playing without observing a significant excess number of seizures. This finding provides strong support for the hypothesis that seizures during video game play in the >95% of the epilepsy population without visual sensitivity are most likely to represent a chance occurrence, although, as always, each individual should be carefully assessed.

Adolescent↗

Multimodal MR imaging: functional, diffusion tensor, and chemical shift imaging in a patient with localization-related epilepsy.

PURPOSE: To demonstrate the integration of complementary functional and structural data acquired with magnetic resonance imaging (MRI) in a patient with localization-related epilepsy. METHODS: We studied a patient with partial and secondarily generalized seizures and a hemiparesis due to a malformation of cortical development (MCD) in the right hemisphere by using EEG-triggered functional MRI (fMRI), diffusion tensor imaging (DTI), and chemical shift imaging (CSI). RESULTS: fMRI revealed significant changes in regional blood oxygenation associated with interictal epileptiform discharges within the MCD. DTI showed a heterogeneous microstructure of the MCD with reduced fractional anisotropy, a high mean diffusivity, and displacement of myelinated tracts. CSI demonstrated low N-acetyl aspartate (NAA) concentrations in parts of the MCD. CONCLUSIONS: The applied MR methods described functional, microstructural, and biochemical characteristics of the epileptogenic tissue that cannot be obtained with other noninvasive means and thus improve the understanding of the pathophysiology of epilepsy.

Adult↗

Presurgical evaluation of patients with epilepsy and normal MRI: role of scalp video-EEG telemetry.

When considering surgery for intractable partial seizures, even with high resolution MRI, some patients do not show structural abnormalities. The aim was to consider whether these patients were likely to proceed to surgical treatment after scalp video-EEG telemetry. All patients undergoing presurgical evaluation at the National Hospital for Neurology and Neurosurgery between 1995 and 1997 were reviewed and 40 were identified without definite MRI abnormalities. None of 40 disclosed a well localised epileptogenic zone concordant with other tests that would have allowed the patient to proceed directly to surgery. In five of the 40, evaluation led to a hypothesis that could be tested by intracranial studies; three proceeded to surgery. It is suggested that high quality MRI is performed first when surgical evaluation is undertaken and if negative the patient carefully counselled before proceeding with any investigations, as successful resective surgery is an unlikely outcome in such MRI negative cases.

Adolescent↗

Supratentorial cavernous haemangiomas and epilepsy: a review of the literature and case series.

OBJECTIVES: To characterise the clinical features and response to treatment of supratentorial cavernomas associated with epilepsy. METHODS: A systematic review of the literature was carried out and a retrospective case series of patients with cavernoma diagnosed by MRI and/or histology was compiled. Patient selection biases in the literature review were reduced as far as possible by selection of unbiased publications. RESULTS: In the literature, cavernomas were relatively less common in the frontal lobes. There were multiple cavernomas in 23% of cases. The main clinical manifestations were seizures (79%) and haemorrhage (16%). The annual haemorrhage rate was 0.7%. The outcome after excision was good with improvement in seizures in 92% of patients. In the case series the surgical outcome was less favourable, reflecting inclusion of a higher proportion of patients with intractable epilepsy. In both the literature review and the case series, outcome was poorer in cases with a longer duration of seizures at the time of surgery. CONCLUSIONS: The good surgical results, particularly in cases treated earlier, and the significant cumulative haemorrhage rate, suggest that excision is the optimum treatment. However, these factors have not been examined prospectively and, despite the availability of several retrospective studies, the optimum treatment, particularly for non-intractable cases, will only be determined by a prospective study.

Adolescent↗

Video-EEG telemetry: apparent manifestation of both epileptic and non-epileptic attacks causing potential diagnostic pitfalls.

Video-EEG telemetry is often used to support the diagnosis of non-epileptic seizures (NES). Although rare, some patients may have both epileptic seizures (ES) and NES. It is crucially important to identify such patients to avoid the hazards of inappropriate anticonvulsant withdrawal. To delineate the electroclinical characteristics and diagnostic problems in this group of patients, we studied the clinical, EEG and MRI features of 14 consecutive patients in whom separate attacks, considered to be both NES and ES were recorded using video-EEG telemetry. Only two patients were drug-reduced during the telemetry. Most patients had their first seizure (ES or NES) in childhood (median age 7 years; range: 6 months-24 years); 8/14 patients were female. Brain MRI was abnormal in 10/14 patients. Interictal EEG abnormalities were present in all patients; 13/14 had epileptiform and 1/14 only background abnormalities. Over 70 seizures were recorded in these 14 patients: in 12/14 patients, the first recorded seizure was a NES (p < 0.001), and 7 of these patients had at least one more NES before an ES was recorded. Only 3/14 patients had more than 5 NES before an ES was recorded. Recording a small number of apparently NES in an individual by no means precludes the possibility of additional epilepsy. Particular care should be taken, and multiple (> 5) seizure recording may be advisable, in patients with a young age of seizure onset, interictal EEG abnormalities, or a clear, potential aetiology for epilepsy.

Adolescent↗

Identification of EEG events in the MR scanner: the problem of pulse artifact and a method for its subtraction.

Triggering functional MRI (fMRI) image acquisition immediately after an EEG event can provide information on the location of the event generator. However, EEG artifact associated with pulsatile blood flow in a subject inside the scanner may obscure EEG events. This pulse artifact (PA) has been widely recognized as a significant problem, although its characteristics are unpredictable. We have investigated the amplitude, distribution on the scalp, and frequency of occurrence of this artifact. This showed large interindividual variations in amplitude, although PA is normally largest in the frontal region. In five of six subjects, PA was greater than 50 microV in at least one of the temporal, parasagittal, and central channels analyzed. Therefore, we developed and validated a method for removing PA. This subtracts an averaged PA waveform calculated for each electrode during the previous 10 s. Particular attention has been given to reliable ECG peak detection and ensuring that the average PA waveform is free of other EEG artifacts. Comparison of frequency spectra for EEG recorded outside and inside the scanner, with and without PA subtraction, showed a clear reduction in artifact after PA subtraction for all four frequency ranges analyzed. As further validation, lateralized epileptiform spikes were added to recordings from inside and outside the scanner: PA subtraction significantly increased the proportion of these spikes that were correctly identified and decreased the number of false spike detections. We conclude that in some subjects, EEG/fMRI studies will be feasible only using PA subtraction.

Adult↗

Photosensitivity--better informing patients with epilepsy of their individual risk.

Photosensitive epilepsy is relatively rare. However, a large proportion of individuals with epilepsy perceive that they are at an increased risk of a seizure whilst exposed to specific photic material. The difference between perceived and real risk may be due to inadequate education and misinformation. One half of the participants in the present survey could not recall being informed of the result of the 'gold standard' test for photosensitivity--intermittent photic stimulation during an electroencephalogram. Furthermore, approximately one-third of our sample were apparently given inaccurate and overcautious advice about their everyday exposure to photic material. Better information and advice is crucial to improve this situation in the future. The majority of people with epilepsy (>95%) who are not photosensitive can pursue activities that involve flickering or patterned light, encompassing educational, employment and leisure opportunities, without undue concern.

Adolescent↗

The detection and significance of subtle changes in mixed-signal brain lesions by serial MRI scan matching and spatial normalization.

The purpose of this work is to detect and assess the significance of subtle signal changes in mixed-signal lesions based on serial MRI scan matching. Pairs of serially acquired T1-weighted volume MR images from 20 normal controls and seven patients with epilepsy were matched and difference images obtained. The precision and consistency of the registration were evaluated. The Gaussian noise level in the difference images was determined automatically. A structured difference filter was then used to segment structured (changed) voxels from the Gaussian noise. In the controls, the structured difference images were normalized into Talairach space, resulting in a structured noise map. The significance of changes in patients was assessed by spatial normalization and comparison with the structured noise map. The precision and consistency of the co-registration were < or = 0.06 mm with a registration success rate of 100%. The Gaussian noise level in the difference images was in the range 3.0-6.9. In the controls, an average of 1.6% of the brain voxels were classified as structured. Sine-based registration resulted in a reduction of < 1% in the amount of structure compared to linear interpolation. The structured noise map in controls showed high noise density in areas affected by image artefacts. We show examples of significant changes found in lesions which had been reported as unchanged on visual inspection. A novel quantitative approach has been presented for the detection and quantification of subtle signal changes in lesions. This method is of potential clinical value in the non-invasive characterization of signal change and biological behaviour of neoplastic lesions.

Adult↗

Identifying homologous anatomical landmarks on reconstructed magnetic resonance images of the human cerebral cortical surface.

Guided by a review of the anatomical literature, 36 sulci on the human cerebral cortical surface were designated as homologous. These sulci were assessed for visibility on 3-dimensional images reconstructed from magnetic resonance imaging scans of the brains of 20 normal volunteers by 2 independent observers. Those sulci that were found to be reproducibly identifiable were used to define 24 landmarks around the cortical surface. The interobserver and intraobserver variabilities of measurement of the 24 landmarks were calculated. These reliably reproducible landmarks can be used for detailed morphometric analysis, and may prove helpful in the analysis of suspected cerebral cortical structured abnormalities in patients with such conditions as epilepsy.

Anatomy, Regional↗

Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24.

Autosomal dominant nocturnal frontal-lobe epilepsy (ADNFLE) is a recently identified partial epilepsy in which two different mutations have been described in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4). An additional seven families are presented in which ADNFLE is unlinked to the CHRNA4 region on chromosome 20q13.2. Seven additional sporadic cases showed no evidence of defective CHRNA4. One of the families showed evidence of linkage to 15q24, close to the CHRNA3/CHRNA5/CHRNB4 cluster (maximum LOD score of 3.01 with D15S152). Recombination between ADNFLE and CHRNA4, linkage to 15q24 in one family, and exclusion from 15q24 and 20q13.2 in others demonstrate genetic heterogeneity with at least three different genes for ADNFLE. The CHRNA4 gene and the two known CHRNA4 mutations are responsible for only a minority of ADNFLE. Although the ADNFLE phenotype is clinically homogeneous, there appear to be a variety of molecular defects responsible for this disorder, which will provide a challenge to the understanding of the basic mechanism of epileptogenesis.

Chromosome Mapping↗

Cerebral activation in malformations of cortical development.

Malformations of cortical development (MCD) are an important aetiology of localization-related epilepsy. Previous MRI and [11C]flumazenil PET studies have demonstrated widespread structural and neuroreceptor abnormalities beyond the region of MCD that is visually apparent on MRI. We investigated the ability of brain regions affected by MCD to participate in normal cognitive and motor tasks and compared the responses seen in such patients with those in normal subjects. We studied five patients known to have MCD affecting the occipital region and seven normal subjects using H2 (15)O PET whilst they were performing a visual attention task. We also studied five right-handed patients known to have MCD affecting the left frontal lobe and seven right-handed normal subjects, using H2 (15)O PET whilst they were performing a motor learning task with the right hand. The patient and normal control data were examined using statistical parametric mapping to determine the ability of the brain region affected by MCD to participate in the task and also to detect evidence for atypical organization of cortical function in association with the MCD. Eight of the ten patients with MCD showed significant alteration of relative regional cerebral blood flow during the task compared with 'rest' in the affected brain region. These regions included focally dysgenetic cortex, the cortex lining schizencephalic clefts, heterotopic bands, subependymal grey matter heterotopia, and the cortex overlying band and subependymal heterotopia. In addition there was a significant alteration in the overall activation pattern in five patients compared with the normal control groups; in all five patients this atypical organization involved regions of cortex that appeared entirely normal on MRI. We conclude that regions of MCD may participate in normal cognitive functions but widespread cortical atypical organization may be seen. These findings have implications for surgical planning in any such patients.

Adolescent↗

Effects of electrical stimulation on edema formation in different strains of rats.

BACKGROUND AND PURPOSE: Although electrical stimulation (ES) is commonly used to curb edema formation, efficacy has been demonstrated in only one species of frog and one strain of rat. The purpose of this study was to determine whether different strains of rats respond differently to ES. SUBJECTS AND METHODS: Feet of Sprague-Dawley, Zucker-Lean, and Brown Norway rats were injured in a uniform manner. One foot served as a control, and the other foot received four 30-minute exposures to cathodal high-voltage pulsed current at amplitudes 10% less than those required to induce visible muscle activity. Each treatment period was followed by a 30-minute rest period. Limb volumes were measured before and after trauma and after each treatment and rest period. Changes from pretrauma volumes were analyzed by repeated-measures analysis of variance. RESULTS: Edema formation was curbed in Zucker-Lean and Brown Norway rats but not in Sprague-Dawley rats. CONCLUSION AND DISCUSSION: The finding that two of the three strains of rats responded to ES suggests that some strains of rats may be suitable models for the study of edema. That frogs and rats respond to high-voltage pulsed current suggests that humans might respond similarly.

Animals↗