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Biomedical subjects

J W Sander

Publications and source records attributed to J W Sander.

At least 127 records · Page 7Linked to original sources
PubMed1995

The British Neurological Surveillance Unit: a nation-wide scheme for the ascertainment of rare neurological disorders.

The British Neurological Surveillance Unit was set up in January 1993 with the aim of co-ordinating and improving the ascertainment of rare neurological disorders in the United Kingdom by using a system of nation-wide active surveillance. The unit provides a service for individual investigators who must first submit possible studies to a scientific advisory committee. Once accepted the condition is listed on a report card which is sent to every member of the British neurological community every month. The cards are easy to use, and all the reporting neurologist has to do is tick a box indicating whether a case has (or has not been) seen. At the end of every month the individual investigators then initiate further follow-up by contacting the reporting neurologists. In the first year of operation the scheme has assisted in the surveillance of 6 disorders and the following number of verified cases have so far been ascertained: polio in adults (n = 0); acute psychological disorders in patients with epilepsy (n = 75); Guillain-Barré syndrome in the south of England (n = 32); epilepsia partialis continua (n = 40); amyloid neuropathy (n = 12), and agenesis of the corpus callosum (n = 24). The monthly response rates are between 65 and 75%, with the eventual aim of achieving over 90% after the scheme has become more established.

Amyloid Neuropathies↗
PubMed1995

Ictal ECG changes in temporal lobe epilepsy.

Changes in cardiac rhythm may occur during epileptic seizures and this has been suggested as a possible mechanism for sudden unexpected death amongst patients with chronic epilepsy (SUDEP). We have studied ECG changes during 61 complex partial seizures of temporal lobe origin in 20 patients. Tachycardia was observed in 24/61 (39%) and bradycardia in 3/61 (5%). The mean and median tachycardia rate was 139 and 140 beats/min (range 120-180). The longest R-R interval observed was 9 seconds. No difference was found in regard to the lateralisation of seizures and cardiac arrhytmia. One of the patients with bradycardia was fitted with a demand cardiac pacemaker, which appeared to decrease the number of his falls. In conclusion, ictal cardiac changes which may be seen in temporal lobe epilepsy (TLE) are sinus tachycardia and occasionally sinus bradycardia. Patients presenting vague complains suggestive of either TLE or cardiac dysrhythmia, simultaneous monitoring with EEG/ECG is required, and if the episodes are frequent, video-EEG should be considered. Further studies on this subject are warranted as this may shed some light on possible mechanisms for SUDEP.

Adolescent↗
PubMed1995

Myoclonic epilepsy of late onset in trisomy 21.

We report the case of a patient with trisomy 21 (T21) with late onset epilepsy. The electroclinical features were of myoclonic jerks on awakening and generalised tonic clonic seizures, with generalised spike and wave on EEG, and a progressive dementia. As familial Alzheimer's dementia and progressive myoclonic epilepsy (Unverricht-Lundborg type) are both linked to the chromosome 21, this case may represent a distinct progressive myoclonic epilepsy related to T21.

Down Syndrome↗
PubMed1994

Mortality from epilepsy: results from a prospective population-based study.

Patients with epilepsy may be subject to an increased risk of premature death from the underlying cause, or from the epilepsy itself. The extent and nature of this risk has been insufficiently investigated. Standard mortality ratios (SMRs) of patients with newly diagnosed epilepsy were determined in a prospective national population-based study. 1091 patients with newly diagnosed or suspected epilepsy were ascertained who were attending one of 275 UK general practices from 1984-1987. 1091 patients were classified after 6 months as definite epilepsy (564), possible epilepsy (228), febrile seizures (220), or not epilepsy (79). Over a median follow up of 6.9 years the SMR for patients with definite or possible epilepsy was 2.5 (95% CI 2.1-2.9), and 3.0 (2.5-3.7) for definite epilepsy. The SMR was highest during the first year after diagnosis 5.1 (3.8-6.5), declined to 2.5 (1.5-3.9) at 3 years, and 1.3 (0.7-2.0) at 5 years. The commonest causes of death were pneumonia (SMR 7.2), cancer (3.5), and stroke (3.7). The SMR for patients with idiopathic epilepsy was 1.6 (1.0-2.4), remote symptomatic epilepsy 4.3 (3.3-5.5), and acute symptomatic epilepsy 2.9 (1.7-4.5). Mortality in patients with newly-diagnosed epilepsy was high, mainly due to the underlying cause. The SMR for idiopathic epilepsy was also raised, suggesting that epilepsy per se may carry a small risk of death.

Adolescent↗
PubMed1994

The cost of epilepsy in the United Kingdom: an estimation based on the results of two population-based studies.

Epilepsy has important socio-economic costs to a population. It is important to assess these costs so that health care priorities can be set. We assessed the burden of illness of epilepsy at the community level, and from this we were able to estimate costs for an individual and the cost to the United Kingdom (UK) as a whole. Cost analysis was based on two different populations of patients with epilepsy, a prevalent and an incident population. Patients with established epilepsy (n = 1628), who were identified from general practices throughout the UK as part of the National Epilepsy Survey (NES), and patients with newly diagnosed epilepsy (n = 602), from the National General Practice Study of Epilepsy (NGPSE), which is a prospective longitudinal cohort study of epilepsy. Indirect and direct costs were assessed in the NES, and direct costs in the NGPSE. A longitudinal cost profile of epilepsy was calculated, with an average initial direct costs of 611 pounds (US$917) per patient per annum which decreased after eight years of follow up to 169 pounds (US$254) per patient per annum. The cost to the UK of newly diagnosed epilepsy in the first year of diagnosis was 18 million pounds (US$27 million). The total annual cost of established epilepsy to the UK was estimated at 1930 million pounds (US$2895 million), over 69% of which was due to indirect costs (unemployment and excess mortality). The cost of active epilepsy per patient was approximately 4167 pounds (US$6251), and of inactive epilepsy 1630 pounds (US$2445) per patient per annum. Methodological issues in cost studies of epilepsy are reviewed.

Adult↗
PubMed1994

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.

Adult↗
PubMed1994

Developments in antiepileptic drug therapy.

Development of new antiepileptic drugs has continued to progress, with both the evolution of new drugs, as well as new formulations of old drugs. It is hoped that, with advances in the understanding of the molecular basis of epilepsy, novel antiepileptic drugs will come about through design rather than serendipity. This article concentrates on a selection of the more promising antiepileptic drugs and reviews their recent progress. Felbamate, lamotrigine, vigabatrin, zonisamide, and gabapentin are already in clinical use in certain countries. Stiripentol and other potential antiepileptic drugs are also reviewed. In addition, there have been strategies to improve the pharmacokinetics of currently used antiepileptic drugs and we have concentrated on controlled-release carbamazepine and oxcarbazepine, both available in certain countries. It is, however, increasingly apparent that good comparative studies are needed before definitive advice can be given in the drug treatment of epilepsy.

Anticonvulsants↗
PubMed1994

The characteristics of epilepsy in a largely untreated population in rural Ecuador.

A house-to-house survey of epileptic seizures covering a population of 72,121 persons was carried out in a rural area of northern Ecuador. A cascade system of diagnosis was used to identify all cases of epileptic seizures in this population. 1029 cases were found, of whom 881 were considered to be definite cases and 148 were possible cases. Of the 1029 cases, 56% had active epilepsy. The lifetime prevalence rate was found to lie between 12.2 and 19.5/1000 and the prevalence of active cases between 6.7 and 8.0/1000. An annual incidence rate of between 122/100,000 and 190/100,000 was estimated. Seizure type was classified without EEG data and almost half of the cases had partial seizures. In 27% of cases an aetiology was proposed on clinical grounds. This is one of few reported studies of a population that has been largely unexposed to antiepileptic drugs, providing an opportunity to study the natural history of the untreated condition. It has been suggested that treatment in newly developing epilepsy will prevent its development to a chronic condition. Only 37% of the 1029 cases had ever received antiepileptic drugs, and only 12% of the cases were taking them at the time of the survey. Despite this, a high rate of inactivity was observed, with 44% of all cases free of seizures. Nearly two thirds of the inactive cases identified had never received treatment with antiepileptic drugs. In a subgroup of untreated cases with an active condition, treatment with antiepileptic drugs was initiated and was highly effective even in cases with a long previous history. Thus the findings from this study suggest that the development of epilepsy resistant to therapy is not always associated with a long duration of untreated epilepsy.

Adolescent↗
PubMed1994

Complex partial status epilepticus: a recurrent problem.

Twenty patients with complex partial status epilepticus were identified retrospectively from a specialist neurology hospital. Seventeen patients experienced recurrent episodes of complex partial status epilepticus, often occurring at regular intervals, usually over many years, and while being treated with effective anti-epileptic drugs. No unifying cause for the recurrences, and no common epilepsy aetiologies, were identified. In spite of the frequency of recurrence and length of history, none of the patients showed any marked evidence of cognitive or neurological deterioration. Complex partial status epilepticus is more common than is generally recognised, should be differentiated from other forms of non-convulsive status, and is often difficult to treat.

Adult↗
PubMed1994

Newer antiepileptic drugs. Towards an improved risk-benefit ratio.

Epilepsy is one of the most common neurological disorders. Even though existing antiepileptic drugs can render 80% of newly diagnosed patients seizure free, a significant number of patients have chronic intractable epilepsy causing disability with considerable socioeconomic implications. There is, therefore, a need for more potent and effective antiepileptic drugs and drugs with fewer adverse effects, particularly CNS effects. Drugs for the treatment of partial seizures are particularly needed. With major advances in our understanding of the basic neuropathology, neuropharmacology and neurophysiology of epilepsy, numerous candidate novel antiepileptic drugs have been developed in recent years. This review comparatively evaluates the pharmacokinetics, efficacy and adverse effects of 12 new antiepileptic drugs namely vigabatrin, lamotrigine, gabapentin, oxcarbazepine, felbamate, tiagabine, eterobarb, zonisamide, remacemide, stiripentol, topiramate and levetiracetam (ucb-L059). Of the 12 drugs, vigabatrin, lamotrigine and gabapentin have recently been marketed in the UK. Five of these new drugs have known mechanisms of action (vigabatrin, lamotrigine, tiagabine, oxcarbazepine and eterobarb), which may provide for a more rational approach to the treatment of epilepsy. Oxcarbazepine, remacemide and eterobarb are prodrugs. Vigabatrin, gabapentin and topiramate are more promising on the basis of their pharmacokinetic characteristics in that they are excreted mainly unchanged in urine and not susceptible to significant pharmacokinetic interactions. In contrast, lamotrigine, felbamate and stiripentol exhibit significant drug interactions. Essentially, all the drugs are effective in partial or secondarily generalised seizures and are effective to varying degrees in other seizure types. Particularly welcome is the possible effectiveness of zonisamide in myoclonus and felbamate in Lennox-Gastaut syndrome. In relation to adverse effects, CNS effects are observed with all drugs, however, gabapentin, remacemide and levetiracetam appear to exhibit least. There is also the possibility of rational duotherapy, using drugs with known mechanisms of action, as an additional therapeutic approach. The efficacy of these 12 antiepileptic drug occurs despite the fact that candidate antiepileptic drugs are evaluated under highly unfavourable conditions, namely as add-on therapy in patients refractory to drug management and with high seizure frequency. Thus, whilst candidate drugs which do become licensed are an advance in that they are effective and/or are associated with less adverse effects than currently available antiepileptic drugs in these patients, it is possible that these drugs may exhibit even more improved risk-benefit ratios when used in normal clinical practice.

Acetamides↗
PubMed1993

The effect of oral flumazenil on interictal epileptic activity: results of a double-blind, placebo-controlled study.

The effect on interictal EEG epileptic activity (IEA) of oral flumazenil, a benzodiazepine antagonist and potential antiepileptic drug, was studied in 12 adults with refractory epilepsy. Comparisons were made with placebo and 15 mg diazepam using a double-blind, randomised, cross-over design. A significant reduction in IEA from the baseline epileptic discharges was observed after flumazenil administration (at a dose of 30 or 100 mg) with a low incidence of adverse events. In patients who achieved > 50% reduction in the frequency of IEA, the median duration and extent of action of flumazenil (at either dose) were greater than for diazepam 15 mg or placebo. The frequency of response and duration of action with oral flumazenil were comparable to those obtained via the intravenous route. These results suggest that oral flumazenil may have an intrinsic antiepileptic activity and provide a rationale for a new approach in the treatment of intractable epilepsy.

Administration, Oral↗
PubMed1993

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.

Adult↗
PubMed1993

Antiepileptic drug treatment in a community health care setting in northern Ecuador: a prospective 12-month assessment.

The results of a prospective assessment of antiepileptic drug treatment carried out over a 12-month period, in the context of existing community health care in a rural area of a developing country (a highland region of northern Ecuador), are reported. A house to house survey defined all patients in the area with a history of epileptic seizures, and 192 patients with active epilepsy were recruited into the programme. These patients were randomised to treatment with carbamazepine or phenobarbital, and 139 completed the assessment. Treatment was carried out by health visitors and rural doctors, monitored by a team of neurologists, and standard treatment regimens were used. Treatment was effective in controlling seizures, 53% of the patients were rendered entirely seizure free in the second 6 months of therapy, and a further 14% had a 50% or more reduction in seizures. These results were similar to those reported in hospital based studies in developed countries. No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine. Antiepileptic drug levels were monitored during the study, and ranges similar to those found in developed countries were recorded. Compliance was good. In view of the successful treatment in this community control programme, we would recommend that community programmes for the control of epilepsy in rural settings should be given a higher priority in the planning of health care provision than is commonly the case. Finally, the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-standing epilepsy, who had not been previously treated, and the results of this treatment were good.

Adolescent↗