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D W Chadwick

Publications and source records attributed to D W Chadwick.

At least 37 records · Page 2Linked to original sources
PubMed2000

Carbamazepine versus valproate monotherapy for epilepsy.

BACKGROUND: Carbamazepine and valproate are drugs of first choice for epilepsy. Despite the lack of hard evidence from individual randomized controlled trials, there is strong clinical belief that valproate is the drug of choice for generalized epilepsies and carbamazepine for partial epilepsies. OBJECTIVES: To overview the best evidence comparing carbamazepine and valproate monotherapy SEARCH STRATEGY: Our search strategy included: (a) MEDLINE 1966-99, (b) The Cochrane Library 1999 issue 4, (c) The trial register of the Cochrane Epilepsy Group (d) the pharmaceutical industry. SELECTION CRITERIA: Randomized controlled trials comparing carbamazepine and valproate monotherapy for epilepsy. DATA COLLECTION AND ANALYSIS: This was an individual patient data review. Outcome measures were time to withdrawal of allocated treatment, time to 12 month remission, and time to first seizure post randomization. Data were analysed using the stratified Logrank test with results expressed as hazard ratios (HR) (95% CI), where HR>1 indicates an event is more likely on valproate. A test for an interaction between treatment and epilepsy type (partial versus generalized) was also undertaken. MAIN RESULTS: Results Data were available for 1265 patients from five trials, representing 85% of the patients recruited into the eight trials that met our inclusion criteria. The main overall results (HR 95% CI) were: Time to treatment withdrawal 0.97 (0.79-1.18), 12 month remission 0.87 (0.74-1.02), first seizure 1.09 (0.96-1.25) suggesting no overall difference for these outcomes. The test for an interaction between treatment and epilepsy type was non significant for time to treatment withdrawal and 12 month remission, but significant for time to first seizure. The age distribution of adults classified as having a generalized epilepsy indicate that significant numbers of patients may have had their epilepsy misclassified. REVIEWER'S CONCLUSIONS: We have found some evidence to support the policy of using carbamazepine as the first treatment of choice in partial epilepsies, but no evidence to support the choice of valproate in generalized epilepsies, but confidence intervals are too wide to confirm equivalence. Misclassification of patients may have confounded our results, and has important implications for the design and conduct of future trials.

Adult↗
PubMed2000

Gabapentin for drug-resistant partial epilepsy.

BACKGROUND: The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding a new antiepileptic drug, gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for patients with drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register of The Cochrane Library Issue 4, 1998. In addition, we contacted Parke Davis (manufacturers of gabapentin) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled double blind add-on trials of gabapentin in patients with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios were estimated for each outcome. Dose response was evaluated in regression models, and Number Needed to Treat (NNTs) were calculated for individual doses. MAIN RESULTS: Four trials were included representing 750 randomized patients. EFFICACY: Overall odds ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in seizure frequency compared to placebo 2.22 (1.49 - 3.32). Dose regression analysis shows increasing efficacy with increasing dose, with 28.5% (21.5 - 36.7) of patients responding to 1800mg of gabapentin compared to placebo, NNT 6.7 (3.0 - 10.5). Global effectiveness: treatment withdrawal OR (95% CI) compared to placebo 1.40 (0.76 - 2.55); Side effects: OR (99% CI) compared to placebo. dizziness 2.26 (1.28 - 3.99); fatigue 2.29 (1.11 - 4.74); somnolence 2.04 (1.21 - 3.45) were significanty associated with gabapentin. REVIEWER'S CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.

Acetates↗
PubMed2000

Zonisamide for drug-resistant partial epilepsy.

BACKGROUND: The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding a new antiepileptic drug, zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of zonisamide when used as an add-on treatment for patients with drug -resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (Cochrane Library Issue 4, 1999). In addition, we contacted Dianippon and Elan Pharma (makers and licensees of zonisamide) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of zonisamide in patients with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) adverse events. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. MAIN RESULTS: Three trials were included with 499 patients randomized. EFFICACY: Overall odds ratio (OR, 95% CI) for 50% reduction in seizure frequency compared to placebo was 2.07 (1.36,3.15) for a 400mg/day dose of zonisamide. When the full treatment period of 12 weeks was considered for all three trials including varied rates of titration to 400mg/day the OR compared to placebo was 2.72 (1.74,4. 25). There was insufficient evidence to support a dose response relationship between dose and responder rate. Tolerability: Treatment withdrawal OR compared to placebo was 1.74 (1.03,2.95). Adverse events: ataxia 3.94 (1.23,12.57), somnolence 2.11 (1.11, 3. 98), agitation 3.52 (1.26,9.68), agitation and irritability 2.43(1. 04,5.66) and anorexia 2.98(1.38,6.42) were significantly associated with zonisamide. REVIEWER'S CONCLUSIONS: Zonisamide has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy. Minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of 12 week duration and results cannot be used to conform longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes.

Anticonvulsants↗
PubMed2000

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy.

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS. The results of the quantitative MRI were compared with the results of conventional diagnostic MRI, foramen ovale (FO) recording and the WADA test. Thirty-one patients were found to have unilateral MTS (17 left and 14 right) and 7 bilateral MTS. No evidence of MTS was detected in 16 patients. Of the 31 patients diagnosed with unilateral MTS on the basis of hippocampal volume and T2 measurement, 74% and 77% would respectively have received the same diagnosis on the basis of hippocampal volume and T2 measurements alone. In comparison to FO recording, quantitative MRI has a sensitivity of 55% and a specificity of 86%, while conventional diagnostic MRI has a sensitivity of 42% and a specificity of 80% for detection of MTS. Unilateral abnormalities were detected by FO recording in 30% cent of patients who appeared normal on quantitative MRI. WADA test results were available for 40 patients. The findings were consistent with quantitative MRI showing reduced memory function ipsilateral to unilateral MTS in 18 patients, but reduced memory function contralateral to unilateral MTS in two patients, and reduced memory function without MR abnormality in seven patients. WADA testing revealed unilateral memory impairments where MRI found bilateral pathology in 4 patients and in 4 patients in whom quantitative MRI detected unilateral MTS there was no evidence of reduced memory during WADA testing of the corresponding cerebral hemisphere. In the patients with unilateral right MTS a highly significant negative correlation (p = 0.0003) was observed between age of onset and the volume of the contralateral temporal lobe. Quantitative MR imaging of the hippocampus (i.e. volume and T2 measurement) is preferable to conventional radiological reporting for providing objective evidence of the presence of MTS on which to base the referral of patients for surgery, and since it has associated morbidity FO recording is now only being used in selected patients. Furthermore, stereology provides a convenient method for estimating the volume of other brain structures, which is relevant to obtaining a better understanding of the effects of laterality and age of onset of TLE.

Adolescent↗
PubMed2000

Seizures provoked by blows to the head.

The nonepileptic nature of convulsions occurring within seconds of head injury has been commented on. However, we have recently seen a patient in whom relatively trivial blows to the head did seem to give rise to epileptic seizures.

Arachnoid Cysts↗
PubMed1999

Improvement in adult-onset Rasmussen's encephalitis with long-term immunomodulatory therapy.

OBJECTIVE: To study the immediate and chronic effects of high-dose, long-term human i.v. immunoglobulin (h i.v.Ig) therapy in two patients with advanced adult-onset Rasmussen's encephalitis (RE). BACKGROUND: Despite advances in our understanding of the autoimmune pathogenesis of RE, medical options for chronic treatment are limited. METHODS: In an open-label treatment trial, treatment started with monthly cycles of high-dose h i.v.Ig (0.4 g/kg/d for 5 days) followed by maintenance therapy (0.4 g/kg 1 day each month) after the patients' conditions began to improve. Outcome measures included clinical, psychological, functional, and laboratory assessments before and at relevant intervals throughout 1 year of treatment. RESULTS: In both patients, unrelenting pretreatment deterioration halted, and after this they displayed striking improvements in seizure control, hemiparesis, and cognition that produced useful recovery of function. Improvements were delayed until after 2 to 4 monthly cycles of high-dose h i.v.Ig and continued when patients switched to maintenance treatment. Their recoveries were accompanied by increased cerebral perfusion on interictal SPECT and suppression of inflammatory markers in CSF. CONCLUSIONS: h i.v.Ig can be a useful, possibly disease-modifying, long-term therapy for adult-onset RE that should be considered before radical surgery is performed. Because improvements can be delayed, we propose guidelines for intensive and prolonged trials of immunomodulatory therapy in adults with this syndrome.

Adult↗
PubMed1999

The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic.

We assessed the frequency, causes and consequences of erroneous diagnosis of epilepsy, and the outcome of patients referred with 'refractory epilepsy', by retrospective analysis of the case records of 324 patients. The sample was divided into those exposed to anti-epileptic drugs (n = 184), of whom 92 were said to have refractory seizures, and those who had not received treatment (n = 140). The latter group is reported elsewhere. The overall misdiagnosis rate was 26.1% (46/184), with incomplete history-taking and misinterpretation of the EEG equally responsible. Side-effects were reported by 19/40, while unnecessary driving restrictions and employment difficulties were encountered by 12/33 and 5/33, respectively. Of those labelled 'refractory epilepsy', 12 did not have epilepsy. Sixteen were rendered seizure-free and 25 significantly improved by the optimal use of anti-epileptic drugs or surgery. Diagnostic and management services for patients with suspected and established epilepsy are suboptimal, with psychological and socio-economic consequences for individual patients. The resulting economic burden on the health and welfare services is probably substantial.

Ambulatory Care↗
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

Topiramate in clinical practice: first year's postlicensing experience in a specialist epilepsy clinic.

OBJECTIVE: Topiramate became available for use in October 1995. Meta-analysis of its randomised controlled data suggested that it may be the most potent of the new antiepileptic drugs. The aim of this study was to assess the first year's postlicensing experience in a specialist regional epilepsy clinic. METHODS: The case notes of 174 of 178 patients who were prescribed topiramate in the 12 months between November 1995 and October 1996 were retrospectively reviewed. Data were collected on seizure type, classification of epilepsy, presence or absence of learning difficulties, depression, or behavioural problems, co-medication, dosage escalation, efficacy, adverse events, whether or not the patient was still on topiramate and, if not, the reason for withdrawal. Kaplan-Meier survival analysis was used to estimate the overall retention rate and log rank tests were used to determine factors associated with stopping topiramate. RESULTS: Overall 90 of 174 patients had ceased taking topiramate at the end of the study. The median "survival time" was 427 days (95% CI 362.9-491.1). The cumulative probability for remaining on topiramate at 1 year was 0.549 (95% CI 0.475-0.623). The retention rate in patients in whom topiramate was substituted for another drug was significantly higher than in those in whom it was added to current therapy. Adverse events (CNS related) were the most common reason for stopping topiramate. Eight patients with partial and one patient with juvenile myoclonic epilepsy became seizure free. CONCLUSIONS: There is a significant (20-25%) chance of being intolerant to topiramate at relatively low doses. Substituting topiramate for another antiepileptic drug may reduce the chances of drug withdrawal. If topiramate is tolerated there is a good chance of worthwhile improvement in seizure control. These data, although not derived from randomised controlled trials, represent pragmatic use of novel antiepileptic drugs in "real life" and may be helpful to non-specialists when prescribing topiramate.

Anticonvulsants↗
PubMed1999

Principles of treatment of epilepsy.

Epilepsy is a common chronic neurological condition with a prevalence of 4-8 per 1000. The present classification of epilepsy is based on: 1) the etiology, which distinguishes symptomatic epilepsies from those that are idiopathic and cryptogenic, and 2) the localization of the disorder in the brain, separating the generalized seizures from epilepsies with partial or focal onset. The majority of patients with epilepsy will go into remission and two-thirds will remain so 2 years after drug withdrawal. The impact of epilepsy on individual patients varies. Employment, driving and learning may constitute major problems. There is a small but definite increase in mortality in patients suffering from epilepsy. Treatment of epilepsy usually involves long-term medical treatment, with the ultimate aim being no seizures and no drugs. Before starting treatment, the diagnosis of epilepsy should be assured. Initiation of antiepileptic drug therapy needs a full and adequate discussion with the patient and the choice of the minimum effective dose of an appropriate monotherapy. Nonpharmacological treatments may be necessary at a relatively early stage if pharmacologic treatment is ineffective. In choosing between different anti-epileptic drugs, consideration should be given to the efficacy of the drug for an individual patient and the tolerability of the drug. There is good evidence from many studies that the chief factor determining relative effectiveness is likely to be the spectrum and incidence of adverse effects of antiepileptic drugs. Some 20% of patients developing epilepsy have a chronic disorder uncontrolled by drugs. In patients receiving and complying with optimal doses of a single antiepileptic drug, the addition of further agents is likely to result in a significant improvement in seizure control in only about 10% of patients, but inevitably it increases the risks of dose-related, idiosyncratic and chronic toxicity due to both pharmacokinetic and pharmacodynamic drug interactions. For this group of patients an appropriate aim may not be complete remission of seizures but a compromise of reduced seizure frequency with less severe seizures, to be achieved with one or, at most, two drugs. The management of these patients with unremitting seizures constitutes a treatment challenge for epileptologists.

Journal Article↗
PubMed1998

Liverpool Seizure Severity Scale revisited.

The purpose of the study was to examine the psychometric properties of the revised Liverpool Seizure Severity Scale. The scale has been adapted to increase its content validity and its potential for detecting change attributable to antiepileptic drug treatment. Ninety-seven patients completed the revised scale of which 32 completed it for both major and minor seizures. Reliability of the revised scale was conducted using assessment of internal consistency and test-retest. T-tests were conducted to assess the ability of patients to differentiate between major and minor seizures on scores of the seizure-severity scale. The psychometric properties of the scale were not adversely affected by either the increase in the number of items or the additional response scores. Patients completing the two scales of major and minor seizures were able to reliably differentiate between the two. We have attempted to improve the Liverpool Seizure Severity Scale in order to enhance its reliability, validity and sensitivity to change. The amendments we have made have not adversely affected its psychometric properties and we hope that it will make it more acceptable for use in clinical trials of new antiepileptic drug treatment. The revised scale is currently being applied to a number of clinical trials.

Adolescent↗
PubMed1998

Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards.

PURPOSE: To systematically review the methodology and use of neuropsychological tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: Trial reports were found by searching Medline 1966-1996 and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and neuropsychological test data was extracted by using a proforma. RESULTS: 43 reports met our inclusion criteria, representing 40 RCTs. as three RCTs had generated two reports. Twenty-two were actively controlled, and 18 were placebo-controlled studies. Reporting of basic methods such as randomization method was poor. There has been no uniform approach to the use of neuropsychological tests, and a total of 87 has been used. The Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at 13 times each, but were not used or reported in a uniform manner. CONCLUSIONS: Poor reporting of methods and the use of a plethora of neuropsychological tests create great difficulties for anyone wishing to make sense of currently available data. If we are better to understand the neuropsychological effects of AEDs, a more rational approach is needed, for which recommendations are made.

Adult↗