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Biomedical subjects

J W Sander

Publications and source records attributed to J W Sander.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort.

The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy.

Adolescent↗
PubMed2000

Microdysgenesis with abnormal cortical myelinated fibres in temporal lobe epilepsy: a histopathological study with calbindin D-28-K immunohistochemistry.

Microdysgenesis is a microscopic cortical malformation reported to occur with varying incidence in surgical lobectomies from patients with temporal lobe epilepsy (TLE). It may act as a substrate for the seizures. Four patients are reported with TLE, hippocampal sclerosis and cortical microdysgenesis which was also characterized by the presence of abnormal myelinated fibres running tangentially in the superficial cortical laminae and closely associated with abnormal clusters of neurones. Similar abnormal cortical fibres have been described in other malformations of cortical development including polymicrogyria and focal cortical dysplasia and it is therefore likely that these fibres represent part of the microdysgenetic malformation not hitherto reported. The possibility is discussed that they may also be of functional significance in terms of influencing local seizure propagation and the secondary cortical neuronal loss observed, predominantly affecting layer II. Studies of calbindin interneuronal populations showed preservation of these cells in the microdysgenetic cortex, when compared with non-malformed temporal lobes, despite an overall reduction in cortical neuronal density. In addition, prominent numbers of neurogliaform calbindin-positive nerve cells were observed in the microdysgenesis cases and the nature of these cells is speculated upon.

Adult↗
PubMed2000

The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK.

Over an 18-month period, all incident cases of neurological disorders were ascertained prospectively in an unselected urban population based in 13 general practices in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery. In three of these practices, the lifetime prevalence of neurological disorders was also assessed. A population of 100 230 patients registered with participating general practices was followed prospectively for the onset of neurological disorders. Multiple methods of case finding were used to maintain accuracy. The age- and sex-adjusted incidence rates of neurological disorders were calculated. The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients. The age- and sex-adjusted incidence rates were calculated for major neurological conditions. [These are expressed as rates per 100 000 persons per annum, with 95% confidence intervals (CI) in parentheses]. The commonest of these were first cerebrovascular events, 205 (CI: 183, 230); shingles, 140 (CI: 104, 184); diabetic polyneuropathy, 54 (CI: 33, 83); compressive neuropathies, 49 (CI: 39, 61); epilepsy, 46 (CI: 36, 60); Parkinson's disease, 19 (CI: 12, 27); peripheral neuropathies, 15 (CI: 9, 23); CNS infections, 12 (CI: 5, 13); post-herpetic neuralgia, 11 (CI: 6, 17); and major neurological injuries, 10 (CI: 4, 11). Lifetime prevalence rates are also reported (expressed as rate per 1000 persons with 95% CI). The most prevalent conditions were: completed stroke, 9 (CI: 8, 11); transient ischaemic attacks, 5 (CI: 4, 6); active epilepsy, 4 (CI: 4, 5); congenital neurological deficit, 3 (CI: 3, 4); Parkinson's disease, 2 (CI: 1, 3); multiple sclerosis, 2 (CI: 2, 3); diabetic polyneuropathy, 2 (CI: 1, 3); compressive mononeuropathies, 2 (CI: 2, 3); and sub-arachnoid haemorrhage, 1 (CI: 0.8, 2). Overall, the onset of 625 neurological disorders was observed per 100 000 population annually. Six percent of the population had at some time had a neurological disorder. This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times; we found that these disorders give rise to significant morbidity in the community.

Adolescent↗
PubMed2000

Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy.

PURPOSE: We sought to determine the long-term retention rates of lamotrigine (LTG), gabapentin (GBP), and topiramate (TPM) therapy for patients at a tertiary referral clinic for chronic, refractory epilepsy. METHODS: We analyzed 424 consecutive patients with chronic, refractory partial and/or generalized epilepsy who were started on LTG, 158 patients who were started on GBP, and 393 patients who were started on TPM. The percentages of patients who continued therapy with LTG, GBP, and TPM were estimated with the use of Kaplan-Meier survival analysis. Factors that influence retention were analyzed with the use of Cox regression analysis. RESULTS: Kaplan-Meier survival analysis showed that at 3 years, 30% continued therapy on TPM compared with 29% on LTG and fewer than 10% on GBP. Adverse events resulted in therapy withdrawal in 40% of patients on TPM compared with GBP (37%) and LTG (22%). Perceived lack of efficacy led to treatment withdrawal in 39% of patients on GBP compared with 34% on LTG and 19% on TPM. Cox regression estimated that a fourth or fewer of patients with chronic partial epilepsy are likely to continue therapy with a new antiepileptic drug beyond 5 years. CONCLUSIONS: The impact of these new antiepileptic drugs on the long-term course of chronic partial epilepsy is likely to be small, as approximately three of four patients will discontinue therapy. More patients appear to continue on TPM compared with LTG or GBP, with a possible reason being better perceived efficacy of TPM, despite having the highest incidence of adverse events.

Acetates↗
PubMed2000

Idiopathic generalized epilepsy presenting with hemiconvulsive seizures.

PURPOSE: Unilateral seizures, or hemiconvulsive attacks, are motor seizures with tonic and/or clonic phenomena that involve only one side of the body. METHODS: We describe three adolescents who presented with hemiconvulsive seizures and were found to have 3-cps generalized spike-and-wave discharges on ictal and/or interictal EEG. All had normal neuroimaging studies. Two patients had been previously treated with carbamazepine, which led to a partial response in one patient. RESULTS: All three patients, however, are now seizure free on either sodium valproate or a combination of sodium valproate and lamotrigine. We believe the electroclinical diagnosis is that of idiopathic generalized epilepsy. CONCLUSIONS: Idiopathic generalized epilepsy presenting with hemiconvulsive seizures has not, to our knowledge, been previously described. However, the correct diagnosis of an idiopathic generalized seizure disorder, as opposed to a partial seizure disorder, has important treatment implications. The possible mechanism of hemiconvulsive seizures in idiopathic generalized epilepsy is discussed.

Adolescent↗
PubMed2000

Prognostic factors affecting long-term retention of topiramate in patients with chronic epilepsy.

PURPOSE: To determine the long-term retention rate of topiramate (TPM) therapy in patients with chronic epilepsy and to identify the relevant prognostic factors that influence retention. METHODS: All patients with chronic epilepsy (n = 393) prescribed TPM between October 1, 1995, and December 31, 1998, at a tertiary referral centre for epilepsy were analysed. The retention rate for TPM was calculated by using Kaplan-Meier survival analysis, and the prognostic factors influencing retention were analysed by using Cox regression. RESULTS: Of patients prescribed TPM, 30% continued taking the drug beyond 3 years. Discontinuation was mainly due to adverse events and lack of efficacy. Use of more than one new concurrent antiepileptic drug (AED) and lower maximal daily doses were more likely to result in treatment discontinuation due to adverse events. Older age at onset of epilepsy, a history of having previously taken more than one new AED [lamotrigine (LTG), gabapentin (GBP), or vigabatrin (VGB)], and lower maximal daily doses were more likely to lead to discontinuation due to lack of efficacy. CONCLUSIONS: A third of patients with chronic epilepsy started on TPM therapy will continue on treatment for >3 years. Absence of learning disabilities, late age at onset of seizures, previous use of more than one new AED, two or more concurrent AED use, and low maximal daily doses of TPM are more likely to result in discontinuation of medication. These factors should be taken into account when considering the use of TPM for the treatment of chronic epilepsy.

Adolescent↗
PubMed2000

Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 12 European countries.

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Anticonvulsants↗
PubMed2000

Neurocysticercosis and epilepsy in developing countries.

Neurocysticercosis is a disease of poverty and underdevelopment. Little is known about the natural history of the infection in humans, but some of the mechanisms whereby the parasite remains silent and evades the host immune response are understood. Symptomatic neurocysticercosis usually results from host inflammatory response after parasite death, and the clinical manifestations can be diverse. There is no evidence that cysticidal treatment does more good than harm in addition to conventional antiepileptic treatment. Population control measures involving immunisation or mass treatment have not shown long term effectiveness.Epilepsy, similarly to neurocysticercosis, is a largely unrecognised but increasing burden on the welfare and economies of developing countries. The technology of drug treatment and psychosocial rehabilitation is well known but requires widespread and effective dissemination at low cost. There is little epidemiological data on risk factors for epilepsy in developing countries on which to base prevention strategies. The public health prioritisation of chronic disorders such as epilepsy remains a challenge for policy and practice in developing countries. For both neurocysticercosis and epilepsy, there is a dilemma about whether limited public resources would better be spent on general economic development, which would be expected to have a broad impact on the health and welfare of communities, or on specific programmes to help individual affected people with neurocysticercosis and epilepsy. Either approach requires detailed economic evaluation.

Cost of Illness↗
PubMed2000

Sudden unexpected death in epilepsy: a series of witnessed deaths.

OBJECTIVES: Sudden unexpected death in epilepsy (SUDEP) represents a significant category of mortality in the population with chronic epilepsy. A consistent feature is that most of these deaths are unwitnessed. The aim was to identify witnessed deaths, examine the circumstances, and relate these findings to the proposed mechanisms for SUDEP. METHODS: During the course of case ascertainment for a control study on SUDEP, witnessed deaths were identified and the circumstances examined in detail. Cases were notified by coroners, neurologists, and bereaved families. The findings were related to the proposed mechanisms for SUDEP which include central and obstructive apnoea and cardiac arrhythmia. RESULTS: One hundred and thirty five SUDEP cases have been identified to date, of which 15 were witnessed deaths. Twelve deaths were associated with convulsive seizures, one collapse occurred 5 minutes after a generalised seizure, another collapse occurred after an aura and one patient died while in a probable post ictal state. Witnesses reported that 12 of the 15 cases experienced respiratory difficulty. CONCLUSIONS: Most sudden epilepsy deaths are unwitnessed. Where witnessed most occur in association with a seizure and respiratory compromise is a prominent feature. Positioning or stimulation of respiration may be important in the prevention of these deaths.

Adolescent↗
PubMed2000

Effects of topiramate on cognitive function.

OBJECTIVE: To explore the impact of topiramate on tests of intellect and other cognitive processes. METHODS: This was a retrospective study. The neuropsychological test scores of 18 patients obtained before and after the introduction of treatment with topiramate (median dose 300 mg) were compared with changes in test performance of 18 patients who had undergone repeat neuropsychological assessments at the same time intervals. Complaints of cognitive decline precipitated referral for reassessment in five cases in the topiramate treated group. The groups were matched for age and intellectual level at the time of the first assessment. Patients were assessed using the WAIS-R, tests of verbal and non-verbal memory, language, and perceptual processing. A subgroup of patients underwent a brief reassessment after the withdrawal or substantial reduction of topiramate. RESULTS: Repeat assessments in those taking topiramate were associated with a significant deterioration in many domains, which were not seen in the comparison group. The greatest changes were for verbal IQ, verbal fluency, and verbal learning (p<0. 001). Improvements in verbal fluency (p<0.05), verbal learning (p<0. 01), and digit span (p<0.001) were recorded in those patients who had topiramate withdrawn or reduced. CONCLUSIONS: In our patient group topiramate had a negative impact on cognition which was consistent with subjective complaints of patients. Tests requiring verbal processing seemed especially sensitive to the drug. A decline in verbal intellect (VIQ), a measure which has been considered by some to be insensitive to antiepileptic drug effects, was particularly striking. Caution is warranted in the interpretation of the findings due to methodological limitations of the study design. Further investigation of mediating factors such as serum concentrations, comedication, and other potential risk factors, however, is needed to enable appropriate targeting of treatment with this effective antiepileptic agent.

Adolescent↗
PubMed2000

Stopping drug therapy in epilepsy.

In most of the epilepsies and epileptic syndromes, the decision to initiate antiepileptic drug (AED) therapy is often a far simpler one than the decision to stop it. The primary factor that drives a patient to want to discontinue therapy, and a doctor to endorse or recommend this, is a fear of long-term adverse events, a consideration that may be entirely justified as the side effects of vigabatrin and felbamate have proved. On the other hand, seizure recurrence with the attendant implications in employment, driving regulations and social stigmatization is a strong deterrent that discourages withdrawal of therapy. The absence of a clearer understanding of the natural history and prognosis of many individual epilepsy syndromes somewhat hampers the resolution of this dilemma. Hopefully, as our understanding of the epilepsies grows and the prediction of the chances of seizure relapse becomes a more precise science, stopping medication will become a less fraught exercise for both the patient and the doctor.

Animals↗
PubMed2000

Factors predicting prognosis of epilepsy after presentation with seizures.

The objective of this study was to identify the factors, at the time of diagnosis, that determine the prognosis for remission of epilepsy. A prospective community-based cohort study of 792 patients recruited at the time of their first diagnosis of epileptic seizures was undertaken; in those classified 6 months after presentation, the median follow-up period was 7.2 years (quartiles at 6.2 and 8.2 years) after presentation. We analyzed data from 6 months after the first identified seizure, which prompted the diagnosis of epilepsy, to allow us to factor in those aspects contingent on a diagnostic assessment Baseline clinical and demographic data were analyzed using the Cox proportional hazards regression model with remission of epilepsy for 1, 2, 3, and 5 years as outcome measures. The dominant clinical feature predicting remission was the number of seizures in the 6-month diagnostic assessment period. Thus, the chance of entering 1 year of remission by 6 years for a patient who had 2 seizures during this initial 6 months was 95%; for 5 years of remission, it was 47% as opposed to 75% for 1 year of remission and 24% for 5 years of remission if there had been 10 or more seizures during this period. The number of seizures in the early phase of epilepsy (here, taken as the first 6 months after presentation) is the single most important predictive factor for both early and long-term remission of seizures.

Child↗
PubMed1999

Carbamazepine in comparative trials: pharmacokinetic characteristics too often forgotten.

OBJECTIVES: To compare the use of carbamazepine (CBZ) in comparative monotherapy trials with its use in practice. BACKGROUND: CBZ is often the drug of first choice for partial onset seizures and is frequently used as the reference drug in comparative trials with newly developed antiepileptic compounds. There are several issues related to CBZ that may have an impact on the final outcome of these trials. CBZ has nonlinear time-dependent kinetics due to autoinduction, and this may cause adverse reactions on starting treatment; somnolence and rash usually occur in the first weeks and may be related to the dose and titration schedule. Total daily dose or the serum levels of the drug do not correlate with therapeutic efficacy. METHODS: Review of the current literature on the pharmacokinetics properties of CBZ and of comparative trials of new antiepileptic drugs that used CBZ as the reference drug. CONCLUSIONS: The use of CBZ differed in comparative clinical trials and in clinical practice, with slower and lower titration rates used in the latter. This may be disadvantageous for CBZ because its pharmacokinetics peculiarities are ignored. If CBZ is to be used in these trials, titration rates and dosages should resemble those used in clinical practice because this is likely to improve efficacy and tolerability. Otherwise, the results of these trials may support regulatory applications but have little relevance to clinical practice. We suggest an initial CBZ dose of 100 mg/d and a slow titration schedule with dose incremental steps of 100 mg/d every week up to 600 mg/d. Blood levels should determine the initial target dose, but after this has been achieved titration should be based on seizure control and tolerability rather than by blood levels.

Carbamazepine↗