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Biomedical subjects

J W Sander

Publications and source records attributed to J W Sander.

At least 73 records · Page 4Linked to original sources
PubMed1999

Amygdala sclerosis in sudden and unexpected death in epilepsy.

Sclerosis of the amygdala is a not uncommon finding in patients with chronic epilepsy. The amygdala has efferent connections, via the central nuclei, to cardioregulatory centres in the medulla. Experimental studies have suggested that damage to the central nucleus may be of functional significance in patients with sudden and unexpected death in epilepsy (SUDEP) in particular with regard to their susceptibility to cardiac arrhythmias. We investigated this possibility by carrying out a quantitative immunohistochemical analysis of the patterns of neuronal loss and gliosis in three amygdala subnuclei (central, basal and lateral) in post mortem material from 15 SUDEP cases and seven normal controls. We identified significant neuronal loss in the medial division of the lateral amygdaloid nucleus in SUDEP cases but not in central or basal nuclei. These patterns of cell loss in the amygdala do not differ from previous studies in both humans and animal models of chronic epilepsy suggesting that there is not a specific pattern of amygdaloid sclerosis in SUDEP patients which could implicate a functional role for this nucleus in the mechanism of the sudden death.

Adolescent↗
PubMed1999

A descriptive survey of long-term residents with epilepsy and intellectual disability at the Chalfont Centre: is there a relationship between maladaptive behaviour and magnetic resonance imaging findings?

The advent of high-resolution magnetic resonance imaging (MRI) has facilitated the identification of subtle, aetiologically relevant structural brain abnormalities in a significant proportion of patients with epilepsy and negative standard neuro-imaging. In the present study of people with intellectual disability (ID), the authors show that a high frequency of cerebral structural abnormalities (72.4%) can be demonstrated by high-resolution MRI in patients with epilepsy and ID. Malformations of cortical development (MCD) were found in 8.7% of people without profound ID. An earlier age of onset of habitual seizures was associated with more severe ID and more severe seizures in adulthood. There was no obvious association between this finding and maladaptive behaviour, but a past history of febrile convulsions was associated with increased irritability and agitation. Since there was no obvious association between a history of febrile convulsions and MRI abnormalities, the reason for the above finding remains unclear. Inevitably, any residential epilepsy centre population is subject to selection biases. The population studied was highly skewed, with only one-third of the sample being female and 80% having mild ID. Thus, the findings of the present study cannot necessarily be generalized to all people with ID.

Adolescent↗
PubMed1999

The long-term use of gabapentin, lamotrigine, and vigabatrin in patients with chronic epilepsy.

PURPOSE: To compare the long-term retention of gabapentin (GBP), lamotrigine (LTG), and vigabatrin (VGB) by patients with chronic epilepsy and the reasons for treatment discontinuation. To assess the likelihood of seizure freedom, seizure-related injury/hospital admission and mortality after these drugs were commenced. METHODS: This was a retrospective case-records survey in five tertiary referral epilepsy centres in the U.K. The retention times on treatment (from initiation to discontinuation) for the different antiepileptic drugs (AEDs) were compared by using Kaplan-Meier survival analysis and Cox regression. Incidences of seizure freedom and seizure-related injury/hospital admissions and standardised mortality ratios were calculated. RESULTS: There were 1,375 patients with chronic epilepsy included; 361 were taking GBP, 1,050 LTG, and 713 VGB. The retention of GBP, LTG, or VGB was <40% at 6 years. Fewer than 4% of patients become seizure free while taking one of the drugs. There was no reduction in mortality or seizure-related injury/admission. CONCLUSIONS: The impact of these new AEDs on chronic epilepsy can be described only as modest. This view may be revised, however, as more experience is gained with new drugs in previously untreated patients.

Acetates↗
PubMed1999

Male monozygotic twins discordant for periventricular nodular heterotopia and epilepsy.

PURPOSE: To determine zygosity and study cerebral structure in apparently identical twins with discordant manifestation of focal epilepsy. METHODS: Male twins in their fifth decade were scanned by using magnetic resonance imaging (MRI) to detect structural abnormalities. Zygosity was determined by using 10 microsatellite markers. RESULTS: DNA analysis showed that the twins were >99.99% likely to be monozygous; they were discordant for bilateral symmetric periventricular nodular heterotopia (PNH) and epilepsy. CONCLUSIONS: The discordant occurrence of PNH and epilepsy in monozygotic male twins carries implications with respect to somatic mosaicism, currently held to be responsible for PNH in affected male subjects.

Brain Diseases↗
PubMed1999

Sudden unexpected death in epilepsy.

The majority of persons with epilepsy develop lasting remission from seizures, although mortality is significantly greater than that of the age-matched general population. Of the deaths that are thought to be directly related to seizures, sudden unexpected death in epilepsy is probably the commonest category; more so than status epilepticus or seizure-related accidents. Annual incidence rates vary from 1 in 200 patients with chronic epilepsy to about 1 in 1000 in more population-based studies. Young adults with severe, intractable epilepsy appear to be the most frequently affected group and may have even higher incidence rates. Other risk factors may also be important. An area of great research interest, several pathogenetic mechanisms have been postulated, centering mainly around cardiac rhythm and central hypoventilation. Given the frequent devastation caused by sudden unexpected death in epilepsy, the importance of seizure control is emphasised.

Death, Sudden↗
PubMed1999

An audit of the perceived efficacy and tolerability of gabapentin therapy in an out-patient cohort with chronic epilepsy.

A retrospective audit of the perceived efficacy and tolerability of adjunctive gabapentin (GBT) therapy in patients with intractable epilepsy was carried out. The case-notes of 263 consecutive patients attending a tertiary referral centre in whom GBT had been added to concomitant anti-epileptic drugs were reviewed. There were 119 males (45%); the median age was 35 years (range 15-81 years) and the median duration of epilepsy was 20 years. The median dose of GBT administered was 1,600 mg (range 300-4,800 mg). Twenty-nine patients (11%) had a reduction in seizure frequency of greater than 50% and 7 (3%) achieved seizure freedom of 6 months' duration at least while taking GBT. Side-effects were reported by 169 patients (61%) and in 40 (15%) an increase in seizure frequency of 50% occurred, this being the commonest reason for GBT withdrawal. The median duration of treatment was 4 months (range 0.03-47 months). Ten patients, in whom GBT therapy had proven ineffective in doses of 900-1,800 mg, were rechallenged with doses of 300-4,800 mg. One individual experienced a 50% reduction in seizure frequency and 1 an increase in seizures of at least 50%. GBT was generally well tolerated at high doses and rechallenge of a small number with GBT in doses up to 4,800 mg did not result in further improvement in seizure frequency in the majority.

Acetates↗
PubMed1999

Febrile convulsions in 220 children--neurological sequelae at 12 years follow-up.

We report a 12-year follow-up study of children with febrile convulsions (FCs). The National General Practice Study of Epilepsy (NGPSE) is a large prospective community-based cohort study of 1,195 patients of all ages from first presentation with an identified seizure. Two hundred and twenty children with a first febrile convulsion were identified from the above study between 1984 and 1987. Children were prospectively followed up to ascertain subsequent seizures, neurological problems and treatment. Two hundred and seven patients were followed for a minimum of 8.4 years (median 11.2 years). In the FC cohort, 6% of the children developed subsequent epilepsy, which compares with a population risk of about 1.4%. Ten percent had neurological sequelae. Eleven percent of the children had received medication to prevent recurrence of FC, and in one third of these cases, this was for simple FCs. Using a time-dependent covariate Cox proportional hazards model, the number of FCs was associated with an increased risk of epilepsy (hazard ratio 2.48; 95% confidence limits, CL 1.68, 3.65) up to a limit of 4. A statistically significant association between occurrence of complex FC and subsequent epilepsy was not found, but a review of other studies quantified the odds ratio for epilepsy after a complex first FC as 3.4 (95% CL 2.1, 5.4). Epilepsy is a significant if infrequent sequel to FCs. Factors associated with subsequent epilepsy are the number of FCs or a complex first FC. Overtreatment of this condition continues.

Child↗
PubMed1999

Classification of the epilepsies: time for a change? A critical review of the International Classification of the Epilepsies and Epileptic Syndromes (ICEES) and its usefulness in clinical practice and epidemiological studies of epilepsy.

The Commission on Classification and Terminology of the International League against Epilepsy (ILAE) first devised a comprehensive classification for the epilepsies and epileptic syndromes nearly 30 years ago. Despite subsequent revisions, the classification remains too complicated to be of utility in clinical practice and epidemiological research. Recent developments in neuro-imaging and neurogenetics have also contributed to the limited usefulness of the current International Classification of the Epilepsies and Epileptic Syndromes (ICEES). This review examines the evolution, advantages, and notable disadvantages of the ICEES and assesses its previous application in several population-based studies of epilepsy. The important need for a new, simplified, and aetiologically orientated classification which is amenable to use outside of the tertiary epilepsy centre is discussed.

Epidemiologic Methods↗
PubMed1999

Factors influencing the incidence of lamotrigine-related skin rash.

OBJECTIVE: To determine the incidences of serious and nonserious lamotrigine-related rash, determine the risk factors for lamotrigine-related rash, and evaluate the impact on the incidence of rash of the manufacturer's recommendation to reduce the starting dose of lamotrigine. METHODS: This was a retrospective case record survey at five tertiary referral epilepsy centers in the UK. The risk factors for lamotrigine-related rash were identified by logistic regression. The independent factors tested were gender, age, epilepsy type, concurrent medication, and starting dose of lamotrigine. The incidences of rash before and after the recommendation of reduction in starting dose were compared by chi2 analysis. RESULTS: A total of 1050 patients were included. The incidences of serious and nonserious rash were 1.1% (95% CI 0.5% to 1.8%) and 7% (95% CI 5.5% to 8.6%), respectively. Females were at higher risk of developing rash than were males, with a relative risk of 1.8 (95% CI 1.2 to 2.8). The starting dose of lamotrigine was reduced in response to the manufacturer's recommendation, and there was a significant reduction (p = 0.045) in the incidence of serious rash, from 1.5% (12/805) to 0% (0/245). However, there was no reduction in the overall incidence of lamotrigine-related rash, with 63/805 (8%) before and 23/245 (9%) after the recommendation. CONCLUSIONS: Failure to detect a reduction in the incidence of lamotrigine-related rash since the new (reduced) recommended starting dose of lamotrigine may arise from failure to reduce the starting dose below a critical threshold level, incomplete compliance with current recommendations, or insufficient sample size. The results of this and other studies show that the starting dose of lamotrigine is a significant factor affecting the incidence of rash; furthermore, this study also shows that significant reduction in the incidence of serious rash can be achieved by reducing the starting dose. Therefore, clinicians should not deviate from the recommendations.

Adolescent↗
PubMed1999

Assessing the psychosocial consequences of epilepsy: a community-based study.

BACKGROUND: Few studies have measured, using validated scales, the psychosocial handicap of epilepsy in a general practice setting. AIM: To assess the prevalence of psychosocial problems associated with epilepsy. METHOD: A survey was undertaken of 309 subjects, with one or more non-febrile epileptic seizures, drawn from two general practices in the United Kingdom (UK). The outcome measures were the Subjective Handicap of Epilepsy Scale (SHE), the SF-36, and the Hospital Anxiety and Depression scale (HAD). RESULTS: One-third of persons with active epilepsy were significantly handicapped by their condition. The severity of subjective handicap was related to seizure frequency and to the duration of remission of seizures. Between one-third and one-half of subjects scored as 'cases' on the HAD scale and on the mental health subscale of the SF-36. Only one-third of the psychiatric morbidity revealed by the questionnaires had been recognized by the general practitioner (GP). Scores on the SF-36 indicated that people with active seizures perceived themselves as significantly less healthy than those in remission, and that, for persons in remission, drug treatment had a detrimental effect on certain aspects of well-being. CONCLUSIONS: The occurrence of seizures, even at low frequencies, is associated with psychosocial handicap, and this may remain covert in general practice.

Adolescent↗
PubMed1998

Using topiramate in patients with epilepsy: practical aspects.

Clinical trials are important in determining the relative efficacy and safety of a new antiepileptic drug (AED); however, experience acquired in clinical practice will eventually determine its position in the antiepileptic armamentarium. Topiramate (TPM), a new AED has been available in the United Kingdom since mid-1995 and a considerable number of patients have being treated. As a result of this experience, a number of changes have being made in the way TPM is used, particularly in the starting doses and titration rates. This seems to have improved patients' tolerability of treatment, an important consideration if a drug is to be used to its optimum level. In this article, practical tips for the use of TPM are given and these include starting doses, titration rates, options for managing side effects occurring early in treatment, advice concerning the withdrawal of concomitant AEDs and indications for discontinuation of TPM. The need for adequate patient counseling regarding potential side effects and expectations of treatment is also reviewed.

Anticonvulsants↗
PubMed1998

The subjective handicap of epilepsy. A new approach to measuring treatment outcome.

It is now widely acknowledged that the impact of epilepsy on the individual extends beyond the occurrence of seizures, and that there is a need for outcome measures sensitive to these consequences. Until now these instruments have largely been developed within a 'quality of life' framework. The technical and conceptual difficulties that arise with measuring quality of life have led us to develop a more focused measurement model, the 'Subjective Handicap of Epilepsy' (SHE) scale, based on the World Health Organization's concept of handicap. The scale contains 32 items in six subscales: 'Work and activities' (eight items), 'Social and personal' (four items), 'Self-perception' (five items), 'Physical' (four items), 'Life-satisfaction' (four items) and a 'Change' scale (seven items); and it takes on average < 10 min to complete. The scale's test-retest reliability was found to be satisfactory (intra-class correlation coefficient was 0.8-0.9 in 110 subjects). The test-retest interval (24 h to 8 weeks) had no influence on the reliability. The reliability was also not affected by minor recent fluctuations in seizure frequency. The internal consistency of the scales was 0.8-0.9 (Cronbach's alpha). The construct validity of the scale was examined in a sample of 287 clinic attendees at a university neurology clinic in the UK. The scales were highly sensitive to the handicapping effects of increasing seizure frequency, employment status, the impact of epilepsy on career choice and the subject's own opinion as to the major determinant of their quality of life. The scales were also sensitive, retrospectively, to the benefits of successful epilepsy surgery in a cohort of 105 patients. Scales focusing specifically on handicap were more sensitive to group differences in seizure frequency in the clinic population, and to outcome after epilepsy surgery, than the 'Life-satisfaction' scale and the Epilepsy Surgery Inventory 55 (ESI-55) scales. This supports the contention that measuring 'subjective handicap' may be a more sensitive, and more useful, approach to assessing the impact of interventions on the long-term consequences of epilepsy than current methods.

Adult↗
PubMed1998

New drugs for epilepsy.

Seizure freedom with no side-effects is the aim of treatment, and new antiepileptic drugs have not lived up to expectations; only a few patients with chronic epilepsy have been rendered seizure-free. These treatments have side-effects but their safety profile may be better than older alternatives, although chronic effects have not yet been established. This article reviews newly marketed antiepileptic drugs. It concentrates on shortcomings of current antiepileptic treatment and on the way drugs are developed. A new approach to treatment is long overdue. The development of rational antiepileptic treatments should be strongly encouraged. More clinically relevant paradigms need to be developed and incorporated into clinical trial programmes as these are presently biased in their designs towards regulatory issues.

Animals↗
PubMed1998

An economic appraisal of carbamazepine, lamotrigine, phenytoin and valproate as initial treatment in adults with newly diagnosed epilepsy.

We undertook an economic appraisal of four drugs used in monotherapy during the first 2 years of treatment for newly diagnosed patients with epilepsy: carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), and valproate (VPA). We adopted the cost-minimization model because, although no single trial compares all four drugs directly, the clinical trials comparing two or more of these drugs in newly diagnosed cases show no significant difference in efficacy between the drugs in terms of seizure frequency. Considered in the cost analyses were frequency of side effects, retention rates, medical consultations, inpatient and accident and emergency costs, laboratory investigations, and drug changes. A Delphi panel provided the treatment pathways, including frequency of clinical consultations, second-line monotherapy, and side-effects management. A sensitivity analysis was performed, varying the assumptions on which the calculations were based. Analysis was completed for a prospective, intention-to-treat perspective and also for those patients continuing the initial drug. The direct medical costs of 2-years therapy (intention-to-treat analysis) calculated for each trial were pound sterling 795-829 for CBZ, pound sterling 1,525-2,076 for LTG, pound sterling 736-768 for PHT, and pound sterling 868-884 for VPA. A sensitivity analysis provided similar relative estimates. We found that LTG for newly diagnosed patients is significantly more expensive in direct health service costs incurred. This analysis incorporated seizure control, side effects, and tolerability. We recommend that a similar type of analysis be considered as part of all clinical trials of antiepileptic drugs in which efficacy of outcome is similar as a guide to assess optimal cost effectiveness.

Adult↗