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Biomedical subjects

P B Fenwick

Publications and source records attributed to P B Fenwick.

At least 19 recordsLinked to original sources

The relationship between mind, brain, and seizures.

The medical model of epilepsy suggests that seizures arise at random or in response to precise physiological events. Little weight is given to the part that ongoing brain activity may play in either precipitating or inhibiting seizures. In the focal epilepsies, the presence of damaged neurons that fire in the epileptic mode continuously and are called pacemaker cells has been demonstrated in both animal models and human epilepsy. If these pacemaker cells are firing all the time, why then do seizures arise only spasmodically? Behavior can be thought of as changes in the excitation and inhibition of populations of neurons. Therefore, it is likely that these excitatory and inhibitory waves will either increase or decrease the likelihood of seizures arising. The conditioning of the neurons to fire in volleys in a biofeedback paradigm, the conditioning of seizures in a classic Pavlovian sense, and the occurrence of seizures in response to behavioral changes has been shown in animal models of epilepsy and in humans. There is now evidence that children can both inhibit and generate their own seizures spontaneously. Many adult patients have behavioral strategies that they use either to inhibit or to stop the spreading seizures. In patients who have difficulties in coping with the stresses in their life, the voluntary generation of seizures may come to form a response to difficult situations. Thus, any complete epilepsy program must consider the patient, the behavior, and the relationship between seizures and behavior.

Animals

Antiepileptic drugs and their psychotropic effects.

Antiepileptic drugs (AEDs) are still the main treatment for epilepsy. The first drugs such as the bromides, phenobarbital (PB), and related barbituates were all found to be anticonvulsant by chance. They also all carried to some extent the disadvantages of slowing thinking and motor behavior. Bromides are now seldom used and (PB) is only used when other drugs fail, although it is an important drug in the third world because of its low cost. Carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) are the current first-line AEDs. All of these drugs vary in the extent of their effect on mood. These drugs have also all been used in the treatment of psychiatric disorders. CBZ has been used mainly as a mood normalizer and has had some success in treating hypermanic episodes. VPA has been used successfully in the treatment of cyclical psychoses, whereas PHT, although it had a vogue in the 1940s for the treatment of psychosis, is little used as a psychological treatment now.

Affect

Metabolic clearance rate of testosterone in male epileptic patients on anti-convulsant therapy.

There are several reports which state that male epileptics on anti-convulsant therapy have reduced sexual activity. We and others have shown that, although total testosterone is raised, the free testosterone concentration is reduced in this patient population. This could be a result of an increased metabolic clearance rate (MCR) of testosterone, inadequate secretion of LH to stimulate testosterone synthesis or inappropriately low testosterone production by the Leydig cells. We have examined these possibilities by measuring the MCR of testosterone in 15 male epileptics on anti-convulsant therapy. In this group of patients, the mean LH (9.3 +/- 5.9 IU/l) and sex-hormone binding globulin (SHBG) (54.5 +/- 22.9 nmol/l) concentrations were significantly greater than those of five normal control subjects (4.7 +/- 1.11 IU/l and 26.0 +/- 7.0 nmol/l respectively). Mean total testosterone concentrations of the two groups were not significantly different but the mean percentage of free testosterone and free testosterone concentration were significantly lower in the patient population (2.06 +/- 0.43 vs 2.98 +/- 0.27 and 0.56 +/- 1.1 vs 0.79 +/- 0.07 pmol/l). The MCR of testosterone was significantly lower in the patients (773 +/- 322 vs 1354 +/- 443 l/day) and showed a positive correlation with the percentage of free testosterone. Therefore, our results suggest that the lowered free testosterone in male epileptics on anti-convulsant therapy is not due to an increased MCR of testosterone. The increased LH concentration suggests primary hypogonadism. This, in turn, could be responsible for low free testosterone levels in the presence of normal testosterone.

Adult

Behavioural treatment of epilepsy.

There is abundant evidence of the close interrelation between the induction and inhibition of seizure activity and the patient's thoughts, feelings and behaviour. The detailed knowledge that we now have of the epileptic focus and the way that it is connected to the surrounding cerebral mechanisms, makes it possible for many patients with focal epilepsy to establish a significant degree of seizure control by altering their thinking and behaviour.

Cognitive Behavioral Therapy

Evoked and psychogenic epileptic seizures. I. Precipitation.

The precipitation of seizures by external stimulation (evoked seizures) is well known. Less well known is the precipitation of seizures by a change in the patient's thinking or feelings. This artick uses Lockhart's monkey model of focal epilepsy to propose that there is a close relationship between seizures and ongoing brain activity. Thus, seizures precipitated by both voluntary and spontaneous changes in behaviour and thinking must commonly occur. Clinical examples of such seizure precipitation is described.

Adult

Evoked and psychogenic epileptic seizures: II. Inhibition.

The inhibition of seizure activity by behavioural methods is becoming more popular. Lockhart's monkey model of focal epilepsy suggests a theoretical approach to behavioural seizure inhibition. Behaviour, by changing the pattern of excitation and inhibition surrounding a focus, is thus able to inhibit seizure activity. This article describes single case studies in which the behavioural methods of cued arousal, covert desensitization and relaxation have brought about a decrease in seizure frequency.

Adult

Effects of nitrous oxide on auditory cortical evoked potentials and subjective thresholds.

This study has examined the effects of inhaled nitrous oxide on the N1 and P2 components of the cortical auditory evoked potentials (AEP) in the latency interval 80-300 ms after the stimulus. The amplitudes, latencies and thresholds of the AEP were measured at a range of end-tidal nitrous oxide concentrations (0%, 10%, 20%, 40%) in 10 subjects with normal hearing. Systematic decreases in amplitude and latency were observed with an increase in threshold. A study of the effect of stimulus intensity on AEP amplitude showed that the amplitude change with nitrous oxide was accounted for largely by systematic increase in evoked potential threshold. Subjective pure tone thresholds were not affected by the concentrations of nitrous oxide used, indicating that the AEP changes were independent of subjective hearing level.

Adolescent

The aetiology of aggression in temporal-lobe epilepsy.

A retrospective case-note survey was carried out on 31 subjects admitted with temporal-lobe epilepsy to the Maudsley hospital from 1974-1983 inclusive. Fourteen aggressive subjects were compared with the non-aggressive patients on 95 organic, developmental, and social variables. Aggressive behaviour was associated with male sex, early onset of seizures, and a history of long-standing behavioural problems. Aggressive subjects had lower mean IQ scores and poorer occupational records than controls. No relationship was found between aggression and the presence of specific EEG or CAT scan findings, or a history of psychosis. The results demonstrate the complex interplay between organic and socially mediated factors underlying aggressive behaviour in temporal-lobe epilepsy.

Adolescent

Effect of oestrogen and testosterone implants on psychological disorders in the climacteric.

In a double-blind trial oestradiol, oestradiol/testosterone, or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic. After two months, women receiving active treatment scored better than the placebo group on a self-rating scale of distress, on anxiety, and on depression (p less than 0.05). Postmenopausal but not perimenopausal women improved after placebo, and at 4 months the scores in the three groups no longer differed significantly.

Adult

Nocturnal penile tumescence and serum testosterone levels.

Ten patients with chronic epilepsy were selected; five had high and five had low total serum testosterone levels. Each patient slept for two nights in the sleep laboratory. EEG monitoring and measurements of nocturnal penile tumescence were carried out during sleep. A clear relationship between both total and free serum testosterone levels were found with nocturnal penile tumescence. FSH, LH, SHBG, and prolactin showed no relationship. The five patients with low serum testosterone levels all showed reduced sexual activity.

Adolescent

Epilepsy and handicap from birth to age 36.

Fifty-five subjects with epilepsy were identified in the first 36 years of the 1946 birth cohort study. In 37 cases there was neither evident cause for the epilepsy nor associated brain-damage and these are referred to as 'uncomplicated', the rest as 'complicated'. Subjects with epilepsy came from poorer social backgrounds than the rest of the cohort. Mortality for both the complicated and uncomplicated groups was high. The educational and occupational achievements, marriage and parenthood, self-esteem and psychiatric morbidity of those surviving to adult life were compared with individually matched controls drawn from the same population. For the uncomplicated group there was no evidence of handicap at age 26, but 10 years later handicap was evident in this group in the economic sphere and in self-esteem.

Adult

Sexual behaviour in a centre for epilepsy.

The sexual behaviour and hormonal profiles in 97 patients with chronic epilepsy from an epilepsy centre were studied. Sexual behaviour relating to numbers of sexual contacts, orgasms, spontaneous erections, and early morning erections, whether there was difficulty in obtaining or maintaining an erection, or in ejaculation, was assessed at interview. Hormonal profiles consisted of LH, FSH, prolactin, total testosterone, free testosterone, and SHBG. Information was obtained relating to type of seizure, seizure frequency, age of onset, likely pathology, IQ, and medication. The study showed that this patient group was profoundly hyposexual and had a high level of sexual dysfunction. Serum free testosterone levels were low, and it is suggested that the high level of sexual dysfunction and lack of sexual interest may well have a hormonal basis. The reasons for this are discussed.

Adolescent

Changes in the pattern reversal visual evoked potential as a function of inspired nitrous oxide concentration.

The VEP to pattern displacement was measured at different levels of inspired N2O concentrations in air in 10 normal subjects. The inspired concentrations were 10, 20, 30 and 40% N2O. Expired CO2 concentrations were also measured. Ten normal controls went through the same procedure but breathed air on each trial rather than N2O. The results showed a significant decrease at 10%, almost at 20% and again significant at 30% and 40% for the amplitude of the N65-P95 wave. The P95-N125 wave was more resistant--10% was not significant, 20% was again nearly significant and 30% and 40% were significant. There were no latency changes. Because of the wider variance between group comparisons there was a significant reduction at 40% only for the N65-P95 wave and no significant difference for the P95-N125 wave. There was some evidence that the amplitude of the early components was still significantly reduced after the end of the experiment.

Adult

Changes in the visual evoked potential to pattern reversal with lithium medication.

Previous reports in the literature have suggested that lithium medication does not affect the VEP to flash stimulation. It was predicted that this would not be true for pattern reversal stimulation. Seven patients had their pattern evoked potential measured using a 42' check to fractional pattern displacement of 1/4, 1/2, 3/4 and full square. The VEP was measured before, 1 week after and 5 weeks after the commencement of lithium medication. The results show that there is a significant increase in both the N65-P95 and P95-N125 amplitudes when the 'before lithium' sessions are compared to 'after lithium.' Seven normal subjects matched for the age and sex of the patient group were tested twice, once as a 'control' and a further 5 weeks after this. No significant differences were found in the 'control' sessions between patient and normal groups although a significant difference in both the N65-P95 and P95-N125 amplitude after the treatment of the patient group with lithium was found.

Adult

The visual evoked response to pattern reversal in 'normal' 6-11-year-old children.

The visual evoked response to a 7 mm (40') check using a pattern reversal stimulus was measured in 73 normal children, aged 6-11. Full pattern displacement for the right and left eye and 1/4 and 1/2 pattern displacement for the right eye were studied. The amplitudes of the N65-P95 and P95-N125 wave, together with the P95 latency, were measured. Analysis of the data showed that there was no clear relationship between the mean amplitude or latency of the evoked response and age. However, significant changes were found between linear displacement and linear age for the N65-P95 wave and there was a complex interaction for the same wave between age, sex and eye. There was a significant difference in latencies between right and left eye between the boys and the girls, with the boys having longer latencies. There are thus both age- and sex-related differences in the amplitude and latency of the N65-P95 wave in 6-11 year-old children.

Brain