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Biomedical subjects

D R Fish

Publications and source records attributed to D R Fish.

At least 91 records · Page 5Linked to original sources

High resolution magnetic resonance imaging in adults with partial or secondary generalised epilepsy attending a tertiary referral unit.

In the past the underlying structural abnormalities leading to the development of chronic seizure disorders have usually only been disclosed by histological examination of surgical or postmortem material, due to their often subtle nature that was beyond the resolution of CT or early MRI. The MRI findings in 341 patients with chronic, refractory epilepsy attending The National Hospital for Neurology and Neurosurgery and Chalfont Centre for Epilepsy are reported. Studies were performed on a 1.5 Tesla scanner with a specific volumetric protocol, allowing the reconstruction of 1.5 mm contiguous slices throughout the whole brain. Direct visual inspection of the two dimensional images without the use of additional quantitative measures showed that 254/341 (74%) were abnormal. Twenty four (7%) patients had more than one lesion. The principal MRI diagnoses were hippocampal asymmetry (32%), cortical dysgenesis (12%), tumour (12%), and vascular malformation (8%). Pathological confirmation was available from surgical specimens in 70 patients and showed a very high degree of sensitivity and specificity for the different entities. The advent of more widely available high resolution MRI should make it possible to identify the underlying pathological substrate in most patients with chronic partial epilepsy. This will allow a fundamental reclassification of the epilepsies for both medical and surgical management, with increasing precision as new methods (both of acquisition and postprocessing) are added to the neuroimaging battery used in clinical practice.

Adolescent↗

Fractal description of cerebral cortical patterns in frontal lobe epilepsy.

The convoluted pattern of normal cerebral cortex resists description by Euclidean geometry. However, subtle abnormalities often unrecognised in vivo may underlie a wide range of neurological disorders. Abnormalities of cortical morphology frequently characterise these lesions, and we applied fractal geometry in an attempt to quantify these abnormalities. We have demonstrated typical fractal scaling properties for the cortical-white matter interface on axial and coronal MR images, with a fractal dimension (Df) of 1.45 +0.06 (mean +1 standard deviation) in normal subjects. We have also applied this to 16 patients with frontal lobe epilepsy, a condition associated with subtle disruptions of the cortical ribbon, all of whom had no obvious abnormality on visual inspection of the images. Nine of these 16 had a Df < 1.27 (mean -3 standard deviations). A control group of 10 patients with temporal lobe epilepsy with a focal foreign tissue lesion (vascular or tumoural) all had Df in the normal range. Analysis of shape using this method identifies subtle abnormalities of the cortical ribbon, and has potential application to images of the human brain in a wide range of clinical and pathophysiological settings.

Adolescent↗

Frequency and characteristics of dual pathology in patients with lesional epilepsy.

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

The effect of seizures on memory for recently learned material.

We gave 58 patients with refractory partial seizures who were undergoing video-EEG telemetry a variety of memory tests shortly after the telemetry commenced, and we reassessed memory for this material 48 hours later. Thirty patients had one or more seizures during this period; 22 of these had complex partial seizures, secondary generalized seizures, or both. Eighteen patients did not have any seizures during the study period. Patients who had seizures forgot no more than patients who did not have seizures. There was no correlation between memory performance and the timing of seizures or the number of seizures. These findings indicate that isolated seizures do not generally cause patients to forget material they have recently learned.

Adult↗

Demonstration of thalamic activation during typical absence seizures using H2(15)O and PET.

BACKGROUND: The EEG correlate of absence seizures is 3-Hz, generalized spike-wave activity. Depth electrode recordings in animal models suggest that spike-wave activity oscillates within thalamocortical circuits, but the site of the primary abnormality is uncertain. The aim of the present study was to determine whether there is a selective increase in blood flow in the thalamus during absence seizures and, if so, whether it precedes the appearance of spike-wave activity on scalp EEG. METHODS: Using PET, regional cerebral blood flow (rCBF) was measured in eight patients with idiopathic generalized epilepsy in whom typical absence seizures were induced by voluntary hyperventilation. Each patient was studied up to 12 times, with an intravenous bolus injection of H2(15)O followed by a 90-second scan. The distribution of rCBF during absence seizures and in the 30 seconds before an absence seizure were compared with the distribution of rCBF when absence seizures did not occur. RESULTS: There was a mean global 14.9% increase in blood flow in association with typical absence seizures and, on top of the global increase, a focal increase in thalamic blood flow of 3.9 to 7.8%. There were no significant focal changes in rCBF in the 30 seconds before the onset of spike-wave activity on the EEG. CONCLUSION: This study provides evidence for the key role of the thalamus in the pathogenesis of absence seizures but was unable to show that it is the site of initiation of the seizures.

Adult↗

Methods for normalization of hippocampal volumes measured with MR.

PURPOSE: To investigate the use of six cerebral measures as correlates for hippocampal volumes and, therefore, to enable normalized absolute hippocampal volumes to be calculated via two correction processes. METHODS: Hippocampal volumes and six cerebral measures were estimated from MR data in 20 control subjects. Three of these measures (the cranial volume, the cerebral volume, and the midsagittal cranial area) were then applied to a group of 32 control subjects, and regression analysis was performed to investigate the linear relationship between hippocampal volume and each measure. Division of hippocampal volume by cerebral measure and correction via a covariance calculation enabled corrected absolute hippocampal volumes to be determined for 32 control subjects and 23 patients with temporal lobe epilepsy. RESULTS: Correction processes reduced the variance in absolute hippocampal volumes in control subjects and enabled abnormally small absolute volumes to be defined. Of 11 patients with unilateral volume ratio abnormalities, 8 had unilateral abnormally small absolute hippocampal volumes. Of 12 patients with normal volume ratios, 4 had bilateral abnormally small absolute hippocampal volumes. CONCLUSION: Correction processes can define absolute hippocampal volumes for correlation studies and may enable identification of unsuspected bilateral hippocampal volume loss.

Adult↗

Management and outcome of severe Guillain-Barré syndrome.

Seventy-nine patients with Guillain-Barré syndrome admitted to a neurological intensive therapy unit (ITU) between 1985 and 1992 were studied retrospectively. The mean age was 49.8 years (range 16-86) and the time between the first neurological symptom and admission to ITU was 10.2 days (0-62). Admission was precipitated by a combination of respiratory failure requiring ventilatory support (73.4%), bulbar weakness (57.0%), autonomic features (11.4%) and general medical factors (10.1%). Specific treatments included plasma exchange (65.8%), intravenous immunoglobulin (13.9%) and methylprednisolone/placebo (12.7%). Significant complications included lower respiratory tract infections (45.6%), hyponatraemia (25.3%), dysautonomia (19.0%), urinary tract infection (12.7%) and cognitive disturbances (8.9%). Four patients (5.1%) died during the acute illness. Duration of nadir correlated with duration of ventilation, duration of ITU stay and outcomes at 3 months, 6 months and 1 year. However, time to nadir, an indicator of rapidity of deterioration, did not correlate with any outcome. The low mortality in this series of acutely ill and severely disabled patients suggests that specialized intensive therapy units continue to have an important role in the management of acutely ill patients with Guillain-Barré syndrome.

Acute Disease↗

Estimation of resection volumes in lesional epilepsy surgery.

An MR-based method for measuring resection volumes in lesional epilepsy surgery is described. The volume of the preoperative lesion, the resection cavity and, as a result, the volume of the brain surrounding the lesion resected during surgery have been calculated in 13 patients.

Adolescent↗

Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder.

We describe a distinctive epilepsy syndrome in six families, which is the first partial epilepsy syndrome to follow single gene inheritance. The predominant seizure pattern had frontal lobe seizure semiology with clusters of brief motor attacks occurring in sleep. Onset was usually in childhood, often persisting through adult life. Misdiagnosis as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia was common, and the inheritance pattern was often not appreciated. This autosomal dominant epilepsy syndrome is ideal for identification of partial epilepsy genes.

Adolescent↗

Opiate receptors in idiopathic generalised epilepsy measured with [11C]diprenorphine and positron emission tomography.

The neurochemical basis of absence seizures is uncertain. A previous PET study has provided evidence for release of endogenous opioids from cerebral cortex at the time of absence seizures, but it is has not yet been established whether there is an abnormality of opiate receptor numbers interictally. In the present study, the non-specific opiate receptor ligand, [11C]diprenorphine, was used to measure cerebral opiate receptors interictally in patients with childhood and juvenile absence epilepsy. Eight patients and eight normal controls had a single scan after a high specific activity injection of [11C]diprenorphine. The cerebral volume of distribution (Vd) of [11C]diprenorphine relative to plasma was calculated on a pixel-by-pixel basis. There were no significant differences in [11C]diprenorphine Vd between patients and control subjects in either cortex or thalamus, structures thought to be involved in the pathogenesis of absence seizures. The results suggest that there is no overall abnormality of opioid receptors in patients with childhood and juvenile absence epilepsy. Studies with specific ligands may provide information about the different receptor subtypes.

Adult↗

Dysembryoplastic neuroepithelial tumor. Features in 16 patients.

Dysembryoplastic neuroepithelial tumour (DNT) is a newly recognized brain mass lesion with distinctive pathological features and a favourable prognosis. We reviewed the clinical, electroencephalographic, neuroimaging and pathological features of 16 patients with DNT who underwent surgery; only one patient did not have epilepsy. Mean age at seizure onset was 9.5 years (range: 1 week to 30 years) and surgery 17 years (range: 7 months to 37 years). The mean verbal IQ was 94.6 (range: 79-110) and performance IQ 105 (range: 79-130) (n = 10). The EEG was abnormal in all cases reviewed (n = 13): localized slow activity was seen in 12 and interictal spiking in 10 patients, being less extensive than or concordant with the lesion in three and more extensive than or distant to the lesion in seven. X-ray CT was normal in three out of 11 patients. Magnetic resonance imaging provided detailed anatomical information: the lesion was predominantly intracortical, although in six patients, there was also white matter involvement. The lesion involved the temporal lobe in all but one patient where it was in the cingulate gyrus. Of the temporal lobe cases, MRI showed that the lesion involved, or was in close proximity to, mesial temporal structures in 11 out of 14 patients. Other magnetic resonance features included: circumscribed hyperintensity on long TE/TR images (10 patients), hypointensity on short TR images (12 patients), and cyst formation (five patients). Calcification was seen on CT in four patients. Post surgical follow-up ranged from 8 to 30 months (mean 16.2 months): 12 patients are seizure free and two have a > 80% reduction in seizure frequency (n = 14). Histopathological characteristics included a heterogeneous composition in all cases, calcification (13 cases), dysplastic features (12 cases) and isolated foci of subpial spread (five cases). The presence of occasional mitoses in 12 cases and immunoreactivity to the proliferating cell nuclear antigen in six cases indicate that these lesions have cellular proliferative activity and that there may be a need to follow these patients postoperatively.

Adolescent↗

MRI in focal lesions.

The advent of modern, high resolution MRI and post-processing techniques allows the identification of the underlying structural abnormalities in most (> 80%) patients with partial epilepsy undergoing presurgical evaluation. This information is crucially important for case selection, and the prediction of post-operative seizure control. In consequence, the whole agenda of pre-operative assessment should change, with increasing emphasis on high quality neuroimaging.

Brain↗

A patient-to-computed-tomography image registration method based on digitally reconstructed radiographs.

An automatic method for the accurate registration of computed tomography (CT) data with two camera-calibrated radiographs is presented. The registration is based on the skull as visualized both in the plain radiographs and in radiographs digitally reconstructed from CT. A reference coordinate system is established based on the radiographic projection parameters obtained using an angiographic stereotactic localizer. The CT-derived reconstructed radiographs are aligned iteratively at multiple resolutions until a best match is found by adjusting the position and orientation of the CT data set relative to the reference coordinate system. The results of experiments with a skull phantom performed under stereotactic control which show that reliable registration is possible with an accuracy better than 1 mm are presented. Possible applications include intraoperative patient-to-CT frameless registration and registration of radiographic data with frameless CT for depth electroencephalogram electrode position confirmation.

Algorithms↗

Subependymal heterotopia: a distinct neuronal migration disorder associated with epilepsy.

Subependymal heterotopia has recently been recognised as a cause of epilepsy, but the clinical and investigational features have not been fully described. The clinical, psychometric, imaging, and electroencephalographic features of 13 adult patients with subependymal heterotopia and epilepsy have been reviewed. Age at seizure onset ranged from 18 months to 20 years (median 13 years). There were significantly more female (12) than male (1) patients (p < 0.01). Diagnosis of subependymal heterotopia was made by MRI in 11 patients and CT in two. The heterotopic grey matter was nodular in 11 patients and diffuse in two; bilateral in eight and unilateral in five. There were significantly more patients with predominant right than left cerebral hemisphere involvement (p < 0.01). The most commonly involved site was the occipital horn of the lateral ventricles (10 of 13 patients). Eleven patients presented with partial epilepsy, 10 of whom also had secondarily generalised seizures. The clinical description of the seizures often suggested either an occipital (four patients) or temporal (five patients) onset. Two patients presented with absence attacks without clear focal features. Patients demonstrated normal early milestones (12 of 13 patients), including normal motor development (all patients) and average or above average intelligence (10 of 13 patients). An EEG examination showed normal background activity in all but two patients, one of whom had large intracranial haematomas. Epileptiform activity was usually widespread (10 of 13 patients) and in three patients, there was generalised 3-Hz spike and wave activity that had previously led to an erroneous diagnosis of concomitant primary generalised epilepsy. Onset of epilepsy in the second decade of life, normal developmental milestones and intelligence, and the finding of an overwhelming female preponderance differentiates subependymal heterotopia from other cortical dysgeneses. The female preponderance supports the importance of the X chromosome and sex steroids in the maturation and development of the cerebral cortex.

Adult↗

Image guided audit of surgery for temporal lobe epilepsy.

Studies on surgery for temporal lobe epilepsy are hampered by lack of information about the actual surgery that has taken place. A method is described for accurately measuring the volumes of resection by MRI after surgery. Ten cases of surgically treated temporal lobe epilepsy (nine non-tailored resections, one selective amygdalohippocampectomy) are presented to show the technique. Indices of extent of resection in both the mesiobasal and lateral temporal lobe compartments have been measured, compared, and evaluated. By comparison with identical preoperative volumetric MRI the hippocampal resections have been correlated with the demonstrated hippocampal volume loss, thought to be of relevance in the aetiology of temporal lobe epilepsy. Detailed postoperative audit in this manner is vital in providing a rational basis for follow up studies of outcome.

Adolescent↗

Association of hippocampal sclerosis with cortical dysgenesis in patients with epilepsy.

The possible dual occurrence of hippocampal sclerosis (HS) and other structural lesions (especially cortical dysgenesis [CD]) is well established in patients with chronic partial epilepsy. We describe the frequency of additional CD in a series of 100 patients with evidence of HS, using volumetric MRI. Additional, often subtle, CD was present in 15 patients: subependymal heterotopia (six), forme fruste of tuberous sclerosis (two), focal macrogyria (two), focal cortical dysplasia (one), laminar heterotopia (one), bilateral schizencephaly (one), and simplified gyral patterns (two). In contrast, in 46 healthy volunteers, only one had possible CD (p < 0.05). Only 2 of 15 patients had a history of childhood febrile convulsions. HS is a heterogeneous condition; patients being evaluated for temporal lobe surgery should be carefully screened for additional CD using appropriate MR techniques.

Adolescent↗

Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients.

We treated 19 patients with Rasmussen's syndrome (chronic encephalitis and epilepsy)--a rare progressive disorder of unknown etiology causing focal epilepsy, hemiparesis, and intellectual deterioration--with intravenous immunoglobulins, high-dose steroids, or both, to control seizures and improve the end point of the disease. Ten of 17 patients receiving steroids, and eight of nine patients receiving immunoglobulins, had some reduction of seizure frequency in the short term. Improvement in hemiparesis was slight. The effect of these drugs in ameliorating the end point of the disease in the long term remains unknown, and further multicenter studies with standardized protocols are warranted.

Adolescent↗