Two antiepileptic drugs for intractable epilepsy with complex-partial seizures

The value of adding a second antiepileptic drug in intractable epilepsy with complex-partial seizures was studied in a long-term prospective trial in 30 adult patients who failed to respond to the maximum use of carbamazepine, phenytoin, phenobarbital or primidone as the first drug. Based on the individual previous history of one-drug treatment, the most promising antiepileptic drug (carbamazepine, clobazam, clonazepam, phenobarbital, phenytoin, primidone, valproic acid) was added, if necessary until clinical toxicity occurred. A reduction of the seizure frequency by more than 75% was seen in only four patients (13%) exposed to a second drug in the event of failure of optimum one-drug treatment. The remaining majority of patients (87%) did not benefit from the second drug; in three patients the seizure frequency increased by more than 100%. The common practice of adding another drug in difficult-to-treat cases may need to be reconsidered until further evidence is presented that two drugs are more beneficial than one drug in the treatment of intractable epilepsy.     

Monotherapy in epilepsy: role of the newer antiepileptic drugs

BACKGROUND: Monotherapy is the goal for pharmacological treatment of epilepsy. Well-controlled trials have established the efficacy of some of the newer antiepileptic drugs (AEDs) as monotherapy. OBJECTIVE: To review clinical data and expert opinions pertinent to the evaluation of most of the newer AEDs as monotherapy for epilepsy. DATA SOURCES: The MEDLINE database was searched for clinical trials using newer AEDs. Reference sections of review articles were manually searched to identify relevant studies not retrieved in MEDLINE. STUDY SELECTION: The resulting list of references was manually reviewed to identify monotherapy studies. RESULTS: Lamotrigine and oxcarbazepine demonstrated efficacy in randomized active-control trials in patients with newly diagnosed epilepsy and in substitution trials in patients refractory to conventional AEDs. CONCLUSION: Lamotrigine and oxcarbazepine are as effective as conventional AEDs at controlling partial seizures and are better tolerated.     

Fractures, epilepsy, and antiepileptic drugs

The risk for skeletal fractures in patients with epilepsy is two to six times greater than in the general population. Fractures may be caused by seizures themselves or by falls, with or without seizures. Side effects of antiepileptic drugs (AEDs), such as ataxia, and coexisting neurological deficits contribute to the risk for falls. The effects of older AEDs on bone mineral density probably increase the risk for fractures associated with seizures and falls. Preventive measures include optimal control of seizures and supplementation with calcium and vitamin D. Whether newer AEDs prove to be without adverse effects on bone mineral metabolism remains to be determined.     

Effects of antiepileptic treatment on sleep and seizures in nocturnal frontal lobe epilepsy

ObjectiveTo study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE).MethodsTwenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects.ResultsAntiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness.ConclusionsResidual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy.     

Sleep complaints and disorders in residential home patients taking hypnotic drugs

Objective: To analyze sleep of residential home patients taking hypnotic drugs. Patients and method: This prospective, observational and multicentric study was performed a given day in nursing homes. Residents over than?65, having MMSE ≥?15 and coherence?A or?B (for the AGGIR scale) were included. Aphasic residents or having acute pathology were excluded. Sleep complain was expressed by the resident himself and sleep disorder was observed by care givers. Sleep qualitative (complain versus disorder, difficulty to fall asleep and night awakenings) and quantitative (sleep duration) aspects were compared to residents who take or not hypnotic treatments. Results: 635?residents were included. 28.2% of the residents expressed sleep complains whereas care givers reported that only 11.4% of resident presented real sleep disorders (p<0.001). Compared to the residents who take hypnotic drugs (55.6%), residents without such treatment had shown less sleep complaints (31.2 versus 24.8%; p<0.05), less difficulties to fall asleep (38.6 versus 26.5%; p<0.001), and less night awakenings (69.5 versus 60.9%; p<0.05). No sleep duration difference was found according to hypnotic drugs. Discussion: Institutionalized geriatric patients who take hypnotic drugs seem to have a significant lower quality of sleep.     

Refractory epilepsy: treatment with new antiepileptic drugs.

Five antiepileptic drugs have been marketed in the last decade. We report here a retrospective study of patients attending our unit who were prescribed one of the new antiepileptic drugs. All these patients had refractory localization related epilepsy and had failed to respond to a first-line drug. The drugs had a different profile of side-effects but topiramate (42%) was the most common drug to be withdrawn due to side-effects as compared with tiagabine (26%), vigabatrin (16%), gabapentin (16%), and lamotrigine (15%). With regard to efficacy, 31% of the patients receiving gabapentin had a greater than 50% reduction in seizures compared with lamotrigine (25%), topiramate (20%), vigabatrin (19%) and tiagabine (11%). The number of patients remaining seizure free with gabapentin was 8% whilst for lamotrigine this was 5%, vigabatrin 5%, topiramate 1% and tiagabine 4%. In conclusion, all these five antiepileptic drugs are useful in treating refractory localization related epilepsy.     

Nitric oxide, epileptic seizures, and action of antiepileptic drugs

Nitric oxide (NO) plays a variety of physiological and pathological roles in mammalian cells. In the central nervous system NO may behave as a second messenger, neuromodulator, and neurotransmitter, which may suggest an essential role of this gaseous molecule in epilepsy and epileptogenesis. The aim of this review is to survey the current literature in terms of experimental and clinical evidence of anti- or proconvulsive properties of NO and its implications in the anticonvulsive action of antiepileptic drugs. Up-to-date multiple NO synthase (NOS) inhibitors and donors of NO were used in a plethora of seizure models (e.g. electrically and pharmacologically-evoked convulsions, amygdala-kindled seizures). Reported results vary depending on the seizure model, kind and doses of pharmacological tools used in experiments, and route of drug administration. The most thoroughly tested NOS inhibitor was 7- nitroindazole (7-NI), which presented anticonvulsive properties in most known models of seizures. The clear-cut proconvulsant action of 7-NI was observed only in kainate-, nicotine-, and soman-induced convulsions in rodents. This NOS inhibitor enhanced the anticonvulsant action of almost all available classic and second-generation antiepileptic drugs except tiagabine, felbamate, and topiramate. The effect of NG-nitro-L-arginine methyl ester was not so unambiguous. In pentylenetetrazole, pictotoxin, and N-methyl-Daspartate seizure models the inhibitor exhibited dose-dependent bidirectional action. NG-nitro-L-arginine methyl ester potentiated the efficacy of diazepam and clonazepam, diminished that of valproate and phenobarbital, but did not affect the anticonvulsant action of phenytoin and ethosuximide. On the other hand, NG-nitro-L-arginine, was anticonvulsant in nicotine-, glutamate-, and hyperbaric O2- evoked seizures, and proconvulsant in pilocarpine-, kainate-, bicuculline-, aminophylline-, and 4-aminopyridine-induced convulsions. NG-nitro-L-arginine remained without effect on the anticonvulsant action of both classic (valproate, phenobarbital, diazepam) and new generation (oxcarbazepine, felbamate, and ethosuximide) antiepileptic drugs. The action of ethosuximide was even impaired. Summing up, in the present state of knowledge the only reasonable conclusion is that NO behaves as a neuromodulator with dual - proconvulsive or anticonvulsive - action.     

Aggravation of epilepsy by antiepileptic drugs

Antiepileptic drugs may paradoxically worsen seizure frequency or induce new seizure types in some patients with epilepsy. The mechanisms of seizure aggravation by antiepileptic drugs are mostly unknown and may be related to specific pharmacodynamic properties of these drugs. This article provides a review of the various clinical circumstances of seizure exacerbation and aggravation of epilepsy by antiepileptic drugs as well as a discussion of possible mechanisms underlying the occasional paradoxical effect of these drugs. Antiepileptic drug-induced seizure aggravation can occur virtually with all antiepileptic medications. Drugs that aggravate seizures are more likely to have only one or two mechanisms of action, either enhanced gamma-aminobutyric acid-mediated transmission or blockade of voltage-gated sodium channels. Antiepileptic drug-induced seizure exacerbation should be considered and the accuracy of diagnosis of the seizure type should be questioned whenever there is seizure worsening or the appearance of new seizure types after the introduction of any antiepileptic medication.     

Association of non-adherence to antiepileptic drugs and seizures, quality of life, and productivity: survey of patients with epilepsy and physicians

Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical outcomes, although few studies have examined this relationship. This study assessed barriers and drivers to adherence, its impact on quality of life, and the importance of the patient–physician relationship to adherence. Two cross-sectional online surveys were conducted among 408 adult patients with epilepsy and 175 neurologists who treat epilepsy patients. Twenty-nine percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents. Patient-oriented epilepsy treatment programs and clear communication strategies to promote self-management and patients’ understanding of epilepsy are essential to maximizing treatment and quality of life outcomes while also minimizing economic costs.     

Idiopathic generalized epilepsy and choice of antiepileptic drugs

The authors reviewed 58 patients with EEG-confirmed idiopathic generalized epilepsy (IGE). When initially seen, 17 (29%) were on broad-spectrum (adequate) antiepileptic drugs (AED) only, 28 (48%) on ill-advised AED only, and 13 (22%) on a combination of both. Thus, a majority of patients with IGE initially receive ill-advised AED, which cause IGE to appear intractable.     

Prognosis of epilepsy withdrawn from antiepileptic drugs

Abstract Antiepileptic drugs (AED) were discontinued in 55 epileptics who had been free from seizures treated with AED, in accordance with the following criteria and procedures. (i) A reduction in AED commences when patients have been free from seizures for at least 2 years and epileptic discharges have also disappeared in repeated electroencephalogram (EEG) recordings during that period. (ii) AED are gradually reduced if no relapse is seen in clinical seizures and epileptic discharges in EEG. (iii) As a rule at least 2 years are required as the interval from the onset of a reduction to the withdrawal of AED. Forty-three patients were followed up by a questionnaire and/or by telephone and the follow-up period from the withdrawal of AED to the survey ranged from 0.9 to 8.8 years; in 38 patients (88.4%) the period was longer than 2 years. No relapse of seizures was found in any of the 43 patients. The severity of epilepsy judged by the total number and frequency of seizures, the presence of neuropsychiatric complications, the combination of different types of seizures, and the duration of epilepsy from the seizure onset to the last seizure appeared not to be risk factors for the recurrence of seizure. Normal EEG was, however, considered to be an important prerequisite for a good prognosis.     

Sleep,sleep disorders and inflammation in children

Sleep-disordered breathing (SDB) and, more specifically, obstructive sleep apnea (OSA), can lead to significant morbidities including cardiovascular morbidity and neurocognitive dysfunction in children. Oxidative stress and increased inflammatory process activity are thought to be linked to the morbid consequences of OSA. Clinical and laboratory-based approaches have shown that oxidative stress and inflammation may be further modulated by genetic, lifestyle and environmental factors. Surgical treatment for OSA in children has been shown to be at least partially effective at normalizing endothelial function, reducing levels of inflammatory markers, and improving lipid profile, the apnea–hypopnea index and sleep fragmentation.     

The comparative efficacy of antiepileptic drugs for partial and tonic-clonic seizures.

Studies of the efficacy of anticonvulsant drugs are difficult to undertake and historically have been of poor quality. Randomised comparisons of drugs are few in number, and have failed to detect significant differences between drugs. This is surprising in view of the strong feelings that many clinicians have about the relative efficacy of the drugs they use. A review of the literature emphasises the need for further studies in this field.     

Stopping antiepileptic drugs after epilepsy surgery: a survey of U.S. epilepsy center neurologists

One hundred fifty-one neurologists at U.S. epilepsy centers responded to a survey on stopping medications in patients following successful resective epilepsy surgery. Sixty-two percent said patients should be > or = 2 years seizure-free before stopping medication. Although respondents tended to agree about the importance of many of the queried factors (e.g., focal pathology in favor of and persistent auras against stopping antiepileptic drugs), it is unclear how well these factors determine seizure outcome in this setting.