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Biomedical subjects

D R Fish

Publications and source records attributed to D R Fish.

At least 19 recordsLinked to original sources

Sudden death in epilepsy: a study of incidence in a young cohort with epilepsy and learning difficulty.

Sudden death, often seizure related, may occur in patients with epilepsy. Population-based incidence is probably on the order of 1:1,000/year. The incidence is much higher in selected groups, however. We wished to establish the incidence of sudden unexpected death (SUD) in a young cohort with severe epilepsy and learning difficulties. The study cohort included 310 pupils with epilepsy enrolled at a special residential school between April 1970 and April 1993. The follow-up period totaling 4,135 person-years included a period of residence at the school as well as time after leaving. Age and sex standardized overall mortality ratio was 15.9 [95% confidence interval (CI) 10.6-23.0], with 20 of 28 deaths considered epilepsy related. An incidence of sudden death cases of 1:295/year was noted. All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.

Adolescent

Benzodiazepine-GABAA receptor binding during absence seizures.

The role of benzodiazepine (BZD)-gamma-aminobutyric acidA (GABAA) receptors in the pathogenesis of absence seizures is uncertain. In this study, we examined the effect of absence seizures on the binding of flumazenil to the BZD binding site of the GABAA receptor. Five patients with idiopathic generalized epilepsy (IGE) were studied at rest and during absence seizures with [11C]flumazenil and positron emission tomography (PET). Normalized regional cerebral time-activity curves from the resting and ictal scans were compared with each other and with computed simulations showing the effects of changes in cerebral blood flow (CBF) and [11C]flumazenil binding. No evidence was found for a change in [11C]flumazenil binding with absence seizures. This result, together with those of a recent study showing no abnormality of [11C]flumazenil binding interictally in patients with childhood and juvenile absence epilepsy (JAE) does not support a primary role for the BZD binding site of the GABAA receptor in the pathogenesis of absence seizures.

Adolescent

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

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

Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy?

The sex ratio, age at onset, and ictal features of nine patients with nocturnal paroxysmal dystonia were compared with those of eight patients with daytime frontal lobe seizures and eight patients with nocturnal motor attacks of known epileptic origin. All patients underwent video electroencephalography telemetry. There were no clinical features that would allow distinction between the groups and no single phenomenon was uniquely seen in nocturnal paroxysmal dystonia. This study provides no evidence that nocturnal paroxysmal dystonia is a separate diagnostic entity.

Adolescent

Open stereotactic selective amygdalo-hippocampectomy for drug resistant epilepsy.

Selective removal of the medio-basal temporal structures has been introduced as an alternative to standard temporal lobectomy in the treatment of intractable temporal lobe epilepsy not related to gross structural lesions. Various approaches have been described for the surgical excision of the amygdalo-hippocampal complex, each of them presenting advantages and limitations. The recently introduced computer-assisted technique of volumetric stereotactic excision of deep-seated intracerebral lesions combines precision of targeting with elimination of unnecessary cortical trauma and may potentially provide an alternative method in the treatment of temporal lobe epilepsy. We present our experience of stereotactic volumetric selective amygdalo-hippocampectomy in six patients with medically intractable temporal lobe epilepsy. The criteria for selection, the pre-operative evaluation and the operative technique are discussed. All patients had a cessation or considerable reduction in seizure frequency while the morbidity was minimal.

Adolescent

Very high-frequency rhythmic activity during SEEG suppression in frontal lobe epilepsy.

Intracerebral EEG (SEEG) recordings showing the development of fast rhythmic activity at seizure onset provide important evidence for the localisation of an epileptic focus. However, very high-frequency activity (greater than 50 Hz) of low amplitude relative to the background may not be apparent on the paper record due to the limited bandwidth and dynamic range of conventional SEEG recording and display methods. The use of a digital telemetry system with a fast sampling rate (400 Hz) and a wide dynamic range (1 microV resolution, 4 mV range) has allowed us to utilize expanded time scale SEEG plots and autoregressive spectral estimation to identify this activity in chronic SEEG studies. This may be particularly useful in frontal lobe epilepsy, where rapid propagation often prevents adequate localization using conventional methods of analysis.

Adult

Hippocampal volumetric and morphometric studies in frontal and temporal lobe epilepsy.

The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and several different imaging techniques have been utilized to detect this with varying success. We describe the clinical application of magnetic resonance imaging (MRI) using a three-dimensional volume technique which allows total hippocampal volume to be measured and symmetry evaluated. Hippocampal surface area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC workstation. Total volumes and surface areas were calculated. The cross-sectional surface area at 1.5 mm intervals was displayed graphically, permitting morphometric analysis of the hippocampus throughout its length. Focal atrophy within any part of the hippocampal formation (HF) and its extent could thus be assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20) and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes compared with normal values derived from 10 neurologically normal controls. Asymmetric hippocampal volume loss was demonstrated in all 20 patients with clinically typed TLE, but not in normal controls or patients with FLE. Volume loss distribution was anterior in 12 patients, posterior in one patient and widespread in seven patients. Secondarily generalized seizures were strongly associated with widespread loss. This method of surface area and volumetric analysis of the hippocampus in TLE can demonstrate asymmetry and focal involvement, and help distinguish between hippocampal and frontal pathologies.

Adult

Effect of a single 30-minute treatment of high voltage pulsed current on edema formation in frog hind limbs.

The purpose of this study was to investigate the effect of a single treatment of high voltage pulsed current (HVPC) on edema formation. Twenty-four frogs were anesthetized, and both hind limbs of each frog were traumatized by impact. Limb volumes were measured by water displacement immediately before and after trauma and at predetermined intervals for 24.0 hours posttrauma. One limb of each frog was randomly selected to receive 30 minutes of continuous, 120-pulse per second, cathodal HVPC at voltages 10% less than motor threshold levels. Data were analyzed by an analysis of variance for repeated measures. Sources of significant differences were determined by paired t tests (probability values determined by Bonferroni adjustment). A single 30-minute application of HVPC significantly curbed edema formation for between 4.0 and 7.5 hours following treatment (ie, volumes of treated limbs were significantly less than those of untreated limbs). These results suggest that regimens currently applied to humans (ie, one treatment per day or three times per week) may be insufficiently aggressive to provide sustained treatment effects.

Animals

Effect of electrically induced muscle contractions on posttraumatic edema formation in frog hind limbs.

We tested the hypothesis that repeated muscle contractions induced by high voltage pulsed current (HVPC) would limit volume increases in traumatized frog hind limbs. Twelve frogs were anesthetized, and both hind limbs of each frog were traumatized by impact. Limb volumes were measured via water displacement over a 24-hour period. Four 30-minute treatments of continuous 1-pulse per second HVPC were applied to one limb selected randomly. Stimulation produced muscle contractions that resulted in minimal joint movements. Volume changes from pretrauma limb volumes (in milliliters per kilogram) were analyzed by an analysis of variance for repeated measures. Our hypothesis was rejected (ie, repeated muscle contractions, as induced in this study, did not limit posttraumatic edema formation in frogs). Further investigation of the relative influences of limb position and varying pulse rates, pulse durations, and intensities of HVPC on edema formation may provide valuable insights on effective treatment of edema in humans.

Animals

Effects of low voltage pulsed current on edema formation in frog hind limbs following impact injury.

The purpose of this study was to test the effect of low voltage pulsed current (LVPC) on posttraumatic edema formation in frog hind limbs. Feet of 26 anesthetized bullfrogs were systematically injured by weight drop. One hind limb of each animal was randomly selected to receive continuous 100-pps LVPC at 90% of motor threshold; the opposite hind limb served as a control. A series of four 30-minute treatments (interrupted by 30-minute rests) was begun minutes after injury. Changes from pretrauma limb volumes were determined before and after each treatment and at 8, 17, 20, and 24 hours posttrauma. Analysis of variance revealed no significant treatment effect. Similar studies utilizing high voltage pulsed current (HVPC) at 90% of motor threshold revealed significant curbing of edema formation in frogs. Waveform (LVPC versus HVPC) seems to influence the efficacy of electrotherapy for edema control.

Analysis of Variance

Influence of high voltage pulsed current on edema formation following impact injury in rats.

High voltage pulsed current (HVPC) has been shown to be effective in curbing posttraumatic edema formation in frogs. The purpose of this study was to establish the utility of HVPC in controlling edema formation in a mammalian model. Both feet of 20 anesthetized rats were traumatized following initial determination of hind-limb volumes. Four 30-minute cathodal HVPC treatments at 120 pulses per second and 90% of visible motor threshold interspersed with 30-minute rest periods were applied to one randomly selected hind limb of each rat via the immersion technique. The other hind limb served as a control. Limb volumes were measured after each treatment and rest period. All data were expressed as changes from pretrauma limb volumes in milliliters per kilogram of body weight; these data were analyzed by repeated-measures analyses of variance and post hoc paired t tests. Volumes of untreated limbs were significantly greater than volumes of treated limbs after the second treatment. Evidence of significant treatment effects in frogs, and now rats, provides a compelling rationale for initiating trials of efficacy of cathodal HVPC in inhibiting acute edema formation in humans.

Animals

The effect of sleep on the dyskinetic movements of Parkinson's disease, Gilles de la Tourette syndrome, Huntington's disease, and torsion dystonia.

The effect of sleep on the involuntary movements or dyskinesias in Parkinson's disease, Huntington's disease, primary and secondary torsion dystonia, and Gilles de la Tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry. Movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies, and in each condition reappeared under similar circumstances. The movements were most likely to occur after awakenings or lightenings of sleep, or in stage one sleep. The movements were very rare during the deeper phases of sleep. Those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and, rarely, by sleep spindles or slow waves. The control group showed normal "semipurposeful" movements under the same conditions during sleep. The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.

Brain

Effect of anodal high voltage pulsed current on edema formation in frog hind limbs.

We have recently demonstrated that some forms of cathodal high voltage pulsed current (HVPC) curb posttraumatic edema formation in frog hind limbs. The purpose of this study was to determine, by assessing the capacity of anodal HVPC to curb posttraumatic edema formation, whether polarity is an important variable. Fourteen anesthetized bullfrogs were placed on large dispersive electrodes lining body slings that maintained the frogs' limbs in a dependent position throughout data collection. The frogs' feet were traumatized by impact following initial measurement of limb volumes. At the commencement of each of four 30-minute treatments, hind limbs were immersed in separate beakers and briefly stimulated until motor threshold was determined. One limb, randomly selected, received anodal HVPC at 90% of motor threshold and 120 pulses per second; the other limb served as a control. Treatments were followed by 30-minute rests. Limb volumes were measured by water displacement immediately after trauma and following each treatment and rest period. Data were expressed as changes from pretrauma volumes in milliliters per kilogram of body weight. A repeated-measures analysis of variance was used to test for treatment effect. Despite an aggressive series of treatments, virtually symmetrical bilateral edema occurred; therefore, no treatment effect was evident. This result contrasts with treatment effects previously reported for cathodal HVPC.

Analysis of Variance

Motor inhibition from the brainstem is normal in torsion dystonia during REM sleep.

The maintenance of axial atonia during REM sleep was monitored in 14 patients with primary torsion dystonia, 10 patients with secondary torsion dystonia, and 10 normal subjects using submental EMG and video EEG telemetry. The excitability of the corticospinal tract during REM sleep was also assessed using scalp magnetic stimulation in seven patients and three controls. During REM sleep dystonic patients had well maintained atonia evidenced by infrequent bursts of submental activity, no episodes of complex semi-purposeful behaviour and reduced motor responses to magnetic stimulation. These findings suggest that the inhibitory centres in the region of the locus coeruleus and their descending pathways to the spinal alpha motor neurons are intact in torsion dystonia.

Adolescent

Sleep spindles in torsion dystonia.

Quantitative analysis of overnight sleep spindles was performed in 14 patients with primary generalized torsion dystonia, 10 patients with secondary torsion dystonia, 10 normal subjects, and 39 patients with other neurological disorders. Only 4 patients with torsion dystonia had increased numbers of sleep spindles, and only one of these had sleep spindles of an abnormal amplitude or duration. Sleep spindle abnormalities do not appear to be common in torsion dystonia, and are unlikely to be of pathophysiological significance in this condition.

Adolescent

The clinical differentiation of seizures arising in the parasagittal and anterolaterodorsal frontal convexities.

The ictal clinical manifestations of 40 patients with frontal lobe epilepsy who became and remained seizure free after selective removal of the parasagittal or anterolaterodorsal convexities were studied. Seizures arising from the parasagittal region were characterized by a high incidence of somatosensory auras (60%) and by tonic and/or clonic motor behavior (100%) and never exhibited automatisms. Conversely, the anterolaterodorsal convexity group never showed somatosensory auras but often had warnings more typical of temporal lobe seizures, only displayed partial motor seizure activity in half the cases, and included a relatively high incidence of automatisms (30%). These clinical differences may be useful in the localization of frontal lobe epileptogenic foci. The manifestations of anterolaterodorsal convexity seizures may reflect frequent spread to the temporal lobe, whereas parasagittal convexity seizures often show initial ictal behavior, in keeping with seizure activity in that region. Early ictal unilateral head turning without other motor manifestations was seen in 3 of 10 patients in the parasagittal convexity group and in 9 of 30 patients in the anterolaterodorsal convexity group. In 11 of these 12 cases, the head turning was contralateral to the surgical removal.

Adolescent