M J Brodie

..These data support the use of zonisamide in combination with commonly used antiepileptic drugs to provide efficacious and well-tolerated treatment for patients with refractory partial seizures...

..001). LEV improved seizure control in the majority of patients with mental retardation and may also have enhanced their quality of life...

..Modern AEDs that do not possess this property have similar efficacy for the common epilepsies. Accordingly, perhaps consideration should be given to starting treatment with, or even switching patients to, non-enzyme-inducing AEDs...

..All these data predict a healthy future for phenobarbital, particularly in helping to close the treatment gap in low- and middle-income countries during its second century of clinical use...

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..Collectively, these findings corroborate those of US and Asian clinical trials, which also show that zonisamide is safe and effective for adjunctive therapy of partial seizures...

..This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures...

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..To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged > or = 16 years with refractory partial seizures...

..Both authors agree that additional studies into the pathophysiology and prevention of SUDEP are urgently needed...

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..Single dose and repeated levetiracetam treatments were without effect on all of the parameters investigated. The anticonvulsant action of levetiracetam is unlikely to be mediated via an action on the GABAergic system...

..Recent evidence has, however, suggested that the drug also increases brain GABA concentrations in humans. These studies were designed to investigate the neurochemical basis of this observation...

..This lends credence to the hypothesis in support of a mechanistic approach to the management of epilepsy...

..It is possible, then, that these drugs will have different spectra of activity and toxicity profiles in human epilepsy...

..In addition, the drug may also lower brain concentrations of the excitatory neurotransmitter glutamate and its precursor, glutamine. These effects may contribute to the antiepileptic action of retigabine...

..However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA...

..We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes...

..01) and a fall in DHAS (p less than 0.001). Basal LH was also elevated, but this just failed to reach statistical significance (p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)..

..This article discusses some of the pharmacologic strategies used in treating patients with refractory localization-related epilepsy...

..In general practice, the use of the SEALS Inventory to assess HRQOL has the potential to improve quality of care for people with epilepsy...

..In conclusion, LTG can be regarded as an acceptable choice as initial treatment for elderly patients with newly diagnosed epilepsy...

..This effect was seen for partial (VPA, 57%; CBZ, 39%; PHT, 39%; P < 0.02) as well as tonic-clonic seizures (VPA, 70%; CBZ, 53%; PHT, 50%; NS). These data lend credence to the suggestion of therapeutic synergy between LTG and VPA...

..Desglycinyl-remacemide may have an additional action on Na(+) homeostasis that merits further exploration...

..Sponsors should be able to seek a licence for their drug either as a first choice treatment in newly diagnosed epilepsy or as substitution monotherapy once treatment with at least one other AED has failed...

..Those who do not attain long-term seizure freedom with the first three treatment schedules are likely to have refractory epilepsy...

..No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP...

..002). CONCLUSIONS: Nearly 50% of newly diagnosed patients became seizure-free on the first-ever AED, with >90% doing so at moderate or even modest dosing. Tolerability was as important as efficacy in determining overall effectiveness...

..We investigated the pharmacokinetic and pharmacodynamic profiles of VGB and TGB in rat brain and eye...

..The aims of this study, therefore, were to identify reliable, epilepsy-specific predictors of psychiatric and behavioural disorder in these patients, and to investigate reliable predictors of carer stress...

..These findings suggest that AED therapy can result in seizure freedom in more than 40% of mentally retarded people with epilepsy without producing unacceptable toxicity...

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..These results indicate that pregabalin is highly effective as adjunctive therapy in the treatment of patients with partial seizures with or without secondary generalization...

..LEV is an effective adjunctive treatment for refractory idiopathic and localisation-related epilepsies. Many patients who responded optimally to LEV did so at 1000 mg per day or less...

..To evaluate the safety and efficacy of zonisamide (ZNS) as adjunctive treatment in patients with refractory localization-related epilepsy...

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..The majority of patients with newly diagnosed epilepsy responding to treatment did so rapidly and completely with moderate doses of AEDs, with no differences in time to first seizure...

..Two patients with symptomatic epilepsy secondary to underlying cortical dysplasias are presented to illustrate these different scenarios. Clinical observations can provide insights to the processes underlying pharmacoresistance...

..We investigated polymorphic variants in various genes involved in the pharmacokinetics and pharmacodynamics of carbamazepine in an effort to identify predictors of maintenance dose...

..We have investigated the prevalence of this polymorphism in a series of patients attending a specialist epilepsy clinic...

..We compared the concentration-related effects of VGB in rat brain and eye with those of gabapentin (GBP) and topiramate (TPM), both of which have been reported to elevate brain GABA concentrations in humans...

..However, this hypothesis does not explain the similarly questionable efficacy of RMD monotherapy in newly diagnosed epilepsy, an observation that may have wider pharmacological implications...

..Levetiracetam has specific characteristics that make it an optimal choice for many patient populations...

..This randomised, double-blind study compared the newer antiepileptic drugs (AEDs) gabapentin (GBP) and lamotrigine (LTG) as monotherapy in newly diagnosed epilepsy...

..These findings suggest that remacemide is not sufficiently potent at the Na(+) channel or NMDA receptor to attenuate epileptiform activity in this model and that the anticonvulsant effects of the drug may be mediated by DGR...

..To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy...

..Such an individualised approach to management will optimise the chance of attaining remission and help many more patients achieve a fulfilling life...

..In this review, we will attempt to introduce the concepts of ion channel and neurotransmitter modulation and, thereafter, group currently used antiepileptic drugs according to their principal mechanisms of action...

..This review provides an update on the principal mechanisms of action of a range of established and modern antiepileptic drugs...

..Pregabalin (PGB) was licensed in Europe as an add-on antiepileptic drug (AED) for the treatment of partial-onset seizures in 2004. This audit assessed the response to adjunctive PGB in patients with uncontrolled seizures...

..Each person should be assessed individually with respect to factors unique to his or her seizure disorder and its treatment...

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..We present the cases of 5 men who reported mild to moderate erectile dysfunction or impotence for the first time when treated with the new antiepileptic drug pregabalin as add-on therapy...

..Mean carer scores did not worsen with TPM therapy. CONCLUSIONS: TPM was effective as add-on therapy in learning-disabled people with difficult-to-control epilepsy. Seizure freedom is a realistic goal in this population...

..0078) than those who did not obtain full seizure control. CONCLUSION: The prognosis in epilepsy may be better in older than younger people, perhaps reflecting lower lesional epileptogenicity and genetic predisposition...

..Assessment by conventional static perimetry may neither be sufficiently sensitive nor specific to reliably identify retinal toxicity associated with VGB...

..Further studies are required to investigate the effects of recurrent seizure activity and to characterise mdr expression in other experimental seizure models...

..Eight new antiepileptic drugs were licensed in the 1990s with more to come. These new drugs along with earlier resective surgery have led to a better outcome for many more people with this condition...

..To develop a measure for use with adults with epilepsy and mental retardation, capable of assessing both clinical and care concerns and of quantifying treatment outcomes...

..An efficient regulatory trial programme will ensure rapid availability of new AEDs for the many children and adults whose lives continue to be blighted by seizures...

..Around 80% of patients who became seizure free on ZNS or had the drug withdrawn did so on a dose 200mg. ZNS is an effective broad-spectrum AED that can also produce a range of dose-dependent and idiosyncratic side effects...

..Future studies of mortality should be prospective and follow agreed guidelines to better quantify risk and causation in individual populations...

..Treatment following a first seizure should balance risk factors for recurrence with the informed opinion of the patients and their family...

..There is an urgent need for a large-scale, prospective, international, community-based study of SUDEP to explore more closely the risk factors to plan preventive strategies...

..No difference in efficacy was found between VPA and LTG in our patients with newly diagnosed epilepsy. LTG appeared to be better tolerated. Neither drug appeared to alter the circulating levels of androgenic hormones...

..Data from regulatory trials should be complemented by postmarketing studies and longer term studies of outcome to help clinicians decide the best way of utilising new AEDs and establishing their role in the therapeutic armamentarium...

..Treatment with two or three but not four AEDs may be a useful therapeutic option for patients not responding to monotherapy. Further explorations of the best regimens for individual seizure types and epilepsy syndromes is required...

..A staged approach to the pharmacologic management and, when appropriate, surgical work-up for each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life...

..No significant age-related differences in issues were identified. A conceptual model representing these findings is presented and clinical implications and suggestions for future research are reported...

..These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise...

..For most of these individuals, combination therapy using AEDs with complementary modes of action is the recommended treatment approach...

..Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy. This study assesses the effects of different EEG protocols on the yield of EEG abnormalities in young people with possible new epilepsy...

..This has led to conflicting advice in guidelines. Recent developments in the understanding of pharmacoresistance may explain the relatively high incidence of refractory epilepsy...

..More than 50% of patients developing localization-related epilepsy during adolescence or in adulthood had a good outcome. Prognosis in those with underlying hippocampal atrophy or cortical dysplasia was not always bad...

..Choice of drug may depend on comorbidity and comedication, among other factors. Initial dosing should be low with a slow titration schedule. A holistic approach to care helps optimize the outcome for elderly people with epilepsy...

..In the past 20 years, the explosion of 13 new agents into the marketplace has greatly increased the potential for therapeutic intervention. This article explores the rationale for treatment selection in adults with epilepsy...

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..These findings reveal a differential expression of mdr1 genes in normal rodent brain tissue and suggest that P-gp may afford a broader protection of the hippocampus than other brain structures...

..The goal of the work described here was to develop and validate a measure of the impact of epilepsy on an adolescent's quality of life that is based on direct exploration of the adolescent's views...

..CONCLUSIONS: Epilepsy can be difficult to diagnose in adolescents. Outcomes were surprisingly poor suggesting the need for improved services for this patient population...

..Further randomized controlled trials of older antiepileptic drugs are recommended to solidify the evidence-based treatment of the idiopathic generalized epilepsies...

..INTERPRETATION: Mortality risks and preventive strategies should be discussed with patients with epilepsy when treatment fails or is refused despite recurrent seizures...

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..This multicenter, open-label study evaluated the short-term tolerability of intravenously (IV)-infused levetiracetam (LEV; 500-1,500 mg/100 ml, 15 min, b.i.d.) as a substitute for the same oral dose...

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..An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life...

..Lower incidence of adverse events and discontinuations were achieved in patients receiving pregabalin when dosing was individualized to optimize efficacy and tolerability...

..Further studies to delineate the exact role, if any, of P-gp and other efflux transporters in drug-resistant epilepsy are warranted...

..The PGB-AED combinations were generally well tolerated. PGB may be added to VPA, LTG, PHT, or CBZ therapy without concern for pharmacokinetic drug-drug interactions...

..The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals...

..043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being...

..Care should be taken to avoid excessive drug load, which is associated with increased toxicity.Bigger and better randomised, controlled studies are needed to determine the optimal time and way to combine AEDs...