Dominic Upton

The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy

The amino acids L-glutamate and L-aspartate have been shown to be excitatory neurotransmitters in mammalian central nervous systems. Antagonists acting selectively at excitatory amino acid receptors have shown antiepileptic properties in several animal models. We report the results of the first therapeutic trial of the competitive NMDA antagonist, D-CPP-ene (SDZ EAA-494), in eight patients with intractable complex partial seizures. All patients withdrew prematurely because of side-effects, including poor concentration (8), sedation (7), ataxia (6), depression (3), dysarthria (2), amnesia (2) and unilateral choreo-athetosis in a patient with contralateral Sturge-Weber syndrome. Seizures were unchanged in four patients and worse in three. A further patient with apparent improvement in seizures in the first week developed complex partial status epilepticus on withdrawal of DCPP-ene. EEG on treatment (5) or in the immediate post-treatment period (2) showed slowing of background activity and, in five cases, an increase in epileptiform activity. Serum concentrations of DCPP-ene were found to be unpredictable and higher than expected from pharmacokinetic data on normal subjects. There was no clear relationship between serum concentrations and the severity of side-effects. Preliminary experience with DCPP-ene in patients with refractory partial seizures is not promising. Evaluation of related compounds is warranted.

A Role for the Hippocampus in Card Sorting

This study examines the performance of three groups of patients with epilepsy on three measures typically used to assess the integrity of the frontal lobes: the Modified Wisconsin Card Sorting Test (MWCST), verbal fluency and the Stroop test. The groups comprised sixteen patients with clearly defined hippocampal sclerosis, thirteen patients with unilateral temporal lobe seizure onset and eighteen patients with unilateral frontal lobe onset. Results demonstrated that performance on the MWCST was most compromised by hippocampal sclerosis. These patients took longer to complete the task, achieved fewer categories and made more perseverative errors than patients in the other groups. In contrast, verbal fluency and performance on the Stroop test were less affected by the presence of hippocampal sclerosis. These results have both clinical and theoretical significance. It is argued that patients with hippocampal damage perform poorly on the MWCST because of the heavy working memory requirements of the test. Cautious use of this test as a tool to localise seizure origin in patients with complex partial seizures is therefore recommended. The findings are discussed in terms of Grays (1982) model of the hippocampus as a comparator of actions.

Epilepsy and the family: a review of current literature.

Although the negative effect of epilepsy on patients psychosocial well-being has been increasingly documented in the last decade, the influence of the condition on the family has attracted much less interest. This paper reviews the present state of family research, examining the influence of both childhood and adulthood epilepsy on the psychological and social well-being of family members. Studies indicate that epilepsy may cause high levels of psychosocial difficulties for all family members, including stigmatization, stress, psychiatric morbidity, marital problems, poor self esteem and restriction of social activities. Studies also suggest that the family environment may be an important intervening factor between the condition and the outcome for the family unit, and a number of family factors are reviewed which have been suggested to mediate this relationship, with recommendations being made for their use in intervention studies. Shortcomings of the family studies to date are discussed and these include: concentration on examination of issues around family life, studies being based on reports from single members of the family and the selection of subjects from clinical populations. Recommendations are made concerning methodological and conceptual issues that need addressing for future research.

The impact of chronic epilepsy on the family

The emotional impact of intractable epilepsy on family members is a neglected topic, with the majority of studies confined to childhood epilepsy. Our clinical experience suggests that family members, particularly parents, may at times be under considerable emotional strain, especially when seizures are frequent and accompanied by injury. The purpose of this study was to explore the psychological and physical well-being, satisfaction with social circumstances and perceived level of support in families with an adult member with intractable epilepsy. Forty-four families were administered rating scales of mood and answered questions relating to their social situation and physical health. Levels of stress and dissatisfaction with their social situation was high, particularly in primary carers (the mother in most instances). Respite periods away from their caring role were few and the perceived level of support was low. Poor emotional adjustment was associated with severity of tonic and atonic seizures and episodes of status. Additionally, perceived low levels of support were associated with depression.

The psychological impact of exposure to floods

A number of studies have shown a range of symptoms resulting from exposure to natural disasters such as flooding. Among these consequences, individuals may experience symptoms of post-traumatic stress disorder (PTSD), depression and anxiety. The aim of this study was to examine the psychological impact of flooding in the UK. A cross-sectional survey was used to investigate the psychological symptoms associated with the aftermath of the flood amongst adults living in the affected communities. A questionnaire battery including the Harvard Trauma Questionnaire (trauma and symptoms associated with PTSD), Hopkins Symptom Checklist (anxiety and depression), Coping Strategies Questionnaire and a range of questions addressing sociodemographic characteristics and factors relating to the flood was administered to households in flood-affected areas. Four hundred and forty four completed questionnaires were returned. 27.9% of participants met criteria for symptoms associated with PTSD, 24.5% for anxiety and 35.1% for depression. Females had higher mean scores on PTSD, anxiety and depression than males. Most frequently reported coping strategies were rational, detached and avoidant, with the least frequent being emotional coping. Having to vacate home following flood, previous experience of flooding and poor health were associated with greater psychological distress. Detached coping appeared to be related to less distress. Although it is not possible to determine whether the symptoms were a direct consequence of the flood, symptoms of distress are a significant issue amongst communities affected by environmental events warranting further attention to prevent chronic distress.

General neuropsychological characteristics of frontal lobe epilepsy

The neuropsychological characteristics of frontal lobe epilepsy have rarely been reported, with neuropsychological indicators usually being related to subjects with other forms of neurological damage. In this study we assessed the performance of 74 subjects with frontal lobe epilepsy (42 with left, 32 with right frontal epileptic foci) on a series of measures thought to be sensitive to frontal lobe dysfunction and compared to 57 subjects with temporal lobe epilepsy (31 with left, 26 with right epileptic foci). The results indicated a number of measures that could be considered sensitive to frontal lobe epileptic dysfunction. However, the pattern of results did not indicate consistent deficits to be associated with frontal lobe epileptic dysfunction. There are a number of unique factors associated with epilepsy that need to be considered, and these may account for the variable pattern of results obtained. In particular, the rapid propagation of frontal lobe seizures both bilaterally and to other cortical regions has to be considered.

Neuropsychological effects of tiagabine, a potential new antiepileptic drug

The neuropsychological effects of the GABA-reuptake blocker, tiagabine-HCl, were tested in an open trial of 22 adult patients with refractory partial epilepsy followed by a double-blind, placebo-controlled, cross-over trial in 12 subjects. Nineteen patients completed the initial open titration and fixed-dose phase of the study and 11 patients completed the double-blind phase. The median daily tiagabine dose was 32 mg during the open fixed dose and 24 mg during the double-blind periods. Neuropsychological evaluation did not show any significant effect on cognitive function in the open or double-blind phases. In this group of patients no statistically significant difference in the frequency of the total number of seizures or complex partial seizures was found in the open or double-blind stages. Seizure severity was significantly less in the open fixed dose than in the baseline period, but was not significantly different between the two double-blind periods. Reported side effects were transient, most commonly aggression/irritability, lethargy, headache and drowsiness. No significant EEG changes were observed.

Effectiveness of Coping Strategies Employed by People with Chronic Epilepsy.

Psychological adjustment to a chronic illness, such as epilepsy, is not merely a function of severity or duration of the disorder. Several psychological factors have been identified as having an influential effect. We report here a study that explores one such variable, namely use of coping strategy. A total of 137 people with intractable epilepsy participated in the study. The duration of the epilepsy ranged from 1 to 51 years with a mean of 18.5 years. Seventy percent were experiencing at least weekly seizures. Coping style was measured using a questionnaire that tapped six different coping strategies. Psychological adjustment was assessed via measures of anxiety, depression, self-esteem, social avoidance, and acceptance of epilepsy. Few significant relationships were observed between seizure-related variables and psychological adjustment. The most consistent finding was between poor emotional adjustment and the coping strategy, “wish fulfillment.” A relationship between better adjustment and the strategy, “cognitive restructuring,” was also found. The implications of these results for psychotherapeutic interventions in epilepsy will be considered.

Knowledge and use of evidence‐based practice of GPs and hospital doctors

Rationale, aims and objectives  Clinical effectiveness and evidence-based practice (EBP) are the cornerstone of modern day health care. Although many studies have explored attitudes and perceived knowledge of individual professions few have compared the factors between professional groups and in particular in the medical profession. We report a study comparing the views, knowledge and practice of hospital doctors with their general practitioner (GP) counterparts in terms of EBP and clinical effectiveness. In this way it was hoped to highlight not only any differences between these groups but also the needs of these groups and suggest some ways of fulfilling these. Methods  A postal questionnaire survey was completed by a random sample of 500 GPs and 500 hospital medics. Results  There was a significant difference between the groups with the GPs rating their skill level as lower that their medical doctor counterparts. Similarly, GPs reported using EBP steps less frequently than hospital doctors. Barriers to implementing EBP differed between the groups with GPs reporting difficulty with accessing a library and making time available. Conclusion  A number of differences between GPs and their hospital counterparts were recorded which highlights the difference in educational and policy approach required for greater uptake of EBP.

Age at Onset and Neuropsychological Function in Frontal Lobe Epilepsy

Summary: Purpose: Previous studies into the cognitive consequences of frontal lobe epileptic dysfunction may have proved inconclusive, due to a factor not commonly accounted for: Damage or disturbance during different epochs of development may give rise to different levels of neuropsychological dysfunction. In this study, we investigated the influence of age at onset on cognitive performance in a group of subjects with frontal lobe epilepsy (FLE).