levetiracetam and Epilepsy--Complex-Partial

Topics: Aged; Anticonvulsants; Atrioventricular Block; Bacterial Infections; Clonazepam; Epilepsy, Complex Partial; Female; Humans; Lacosamide; Levetiracetam; Propofol; Valproic Acid

To determine the effect of levetiracetam (LEV) on partial seizure subtypes (simple partial, complex partial, and secondarily generalized seizures) in patients with refractory epilepsy.. Pooled results from three placebo-controlled trials were analyzed.. A statistically significant reduction in the frequency of all partial seizures and all seizure subtypes was observed in the LEV group (p < 0.001 vs. placebo). The proportion of patients in whom secondarily generalized seizures could be prevented over and above the reduction of partial seizures was significantly greater in the LEV group as compared with placebo, with an odds ratio of 1.83 [95% confidence interval (CI), 1.10-3.05]. CONCLUSIONS; LEV reduces frequency of simple and complex partial seizures. In addition, it demonstrates a specific, independent reduction of secondarily generalized seizures.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Humans; Levetiracetam; Male; Meta-Analysis as Topic; Middle Aged; Outcome Assessment, Health Care; Piracetam; Randomized Controlled Trials as Topic

Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.. This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument.. Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05).. For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Psychometrics; Taiwan; Topiramate; Young Adult

Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model. Psychomotor seizures in male albino Swiss mice were evoked by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via corneal electrodes. Potential adverse effects produced by the antiepileptic drugs in combination with ACEA+PMSF were assessed using the chimney test (motor performance), passive avoidance task (remembering and acquisition of learning), and grip-strength test (muscular strength). Brain concentrations of antiepileptic drugs were measured by HPLC to exclude any pharmacokinetic contribution to the observed effect. ACEA (5 mg/kg, i.p.) + PMSF (30 mg/kg, i.p.) significantly potentiated the anticonvulsant potency of levetiracetam (P<0.05), but not that of clobazam, lacosamide, phenobarbital, tiagabine or valproate in the 6-Hz corneal stimulation model. Moreover, ACEA+PMSF did not significantly affect total brain concentrations of levetiracetam in mice. No behavioral side effects were observed in animals receiving combinations of the studied antiepileptic drugs with ACEA+PMSF. In conclusion, the combined administration of ACEA+PMSF with levetiracetam is associated with beneficial anticonvulsant pharmacodynamic interaction in the 6-Hz corneal stimulation model. The selective activation of cannabinoid CB1 receptor-mediated neurotransmission in the brain may enhance levetiracetam-related suppression of seizures in epilepsy patients, contributing to the efficacious treatment of epilepsy in future.

Topics: Acetamides; Animals; Anticonvulsants; Arachidonic Acids; Avoidance Learning; Benzodiazepines; Clobazam; Cornea; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Electroshock; Epilepsy, Complex Partial; Lacosamide; Levetiracetam; Male; Mice; Muscle Strength; Nipecotic Acids; Phenobarbital; Phenylmethylsulfonyl Fluoride; Piracetam; Psychomotor Performance; Receptor, Cannabinoid, CB1; Tiagabine; Valproic Acid

The aim of this observational study was to obtain information regarding efficacy and safety of add-on levetiracetam (LEV; n=32) in Japanese patients with refractory partial seizures in an everyday clinical setting, relative to control AEDs (n=30). This is the first study of LEV add-on therapy conducted in Japan since approval was made. The medical charts of patients were retrospectively reviewed. The efficacy variables were seizure freedom and ≥50% reduction in seizure frequency. A significantly higher response to LEV was demonstrated in patients with all seizure types at baseline, relative to control AEDs. In patients with a duration of epilepsy of at least 10 years, significant effects in response to LEV were demonstrated with regards to efficacy variables, relative to control AEDs, thus providing meaningful results. Only two patients (6.2%) discontinued LEV treatment due to worsening of seizures, but no discontinuation was reported due to adverse events. LEV as add-on therapy to other AEDs is a promising useful treatment option for patients with refractory partial seizures without notable effects on safety, indicating that this treatment regimen might be recommended for such patients.

Topics: Adult; Anticonvulsants; Benzodiazepines; Clobazam; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Female; Fructose; Humans; Japan; Lamotrigine; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Drug Rash (or Reaction) with Eosinophilia and Systemic Symptoms (DRESS) is a potentially life-threatening hypersensitivity reaction to drugs characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and involvement of internal organs. Initially coined in 1996, the term is used to refer to an idiosyncratic reaction to several drugs, the most common of which are carbamazepine, allopurinol, sulfasalazine, and phenobarbital. We report the first case of DRESS related to rufinamide in a ten year old boy with a history of a complex seizure disorder.

Topics: Anti-Inflammatory Agents; Anticonvulsants; Child; Drug Hypersensitivity Syndrome; Epilepsy, Complex Partial; Fructose; Humans; Levetiracetam; Male; Piracetam; Prednisone; Topiramate; Triazoles

The relationship between the older antiepileptic drugs (AEDs) and sexual dysfunction has long been known and it is likely to be related to sexual hormonal changes. Instead, rare reports on sexual disorders related to new AEDs suggest the possibility of complex and poorly understood mechanisms, mainly involving central nervous system neurotransmitters such as glutamate, serotonin, and dopamine. Herein, we describe two young men with epilepsy who experienced severe loss of libido and anhedonia after levetiracetam intake.

Topics: Adult; Anhedonia; Anticonvulsants; Brain; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Complex Partial; Erectile Dysfunction; Gonadal Steroid Hormones; Humans; Lamotrigine; Levetiracetam; Libido; Magnetic Resonance Imaging; Male; Piracetam; Triazines; Valproic Acid; Young Adult

Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies.. Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered.. Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation.. LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Drug Tolerance; Emergencies; Epilepsy; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Cell Phone; Clobazam; Electroencephalography; Epilepsy, Complex Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Piracetam; Status Epilepticus; Tomography, X-Ray Computed

Topics: Acetamides; Aged; Anti-Infective Agents; Epilepsy; Epilepsy, Complex Partial; Humans; Levetiracetam; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Piracetam; Staphylococcal Infections; Ulcer

The effects of nitric oxide-active drugs on the anticonvulsant action of the antiepileptic drug levetiracetam in an experimental model of partial complex seizures named maximal dentate gyrus activation were studied in rats. Levetiracetam was given alone or in combination with 7-nitroindazole, a preferential inhibitor of neuronal nitric oxide synthase, or with L: -arginine, the precursor of nitric oxide synthesis. The maximal dentate activation parameters were the time of latency and the durations of maximal dentate activation and afterdischarge responses. The administration of levetiracetam showed an anticonvulsant effect that was increased when given in combination with 7-nitroindazole. The co-administration of levetiracetam and L: -arginine, which is pro-convulsant, did not significantly modify all the parameters. The present results indicate that the acute administration of levetiracetam, at the lower effective dose, exerts an efficacious inhibitory effect on the severity of maximal dentate activation seizures. Levetiracetam-induced antiepileptic effect is significantly increased by the simultaneous inhibition of neuronal nitric oxide synthase.

Topics: Animals; Anticonvulsants; Arginine; Dentate Gyrus; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Epilepsy, Complex Partial; Indazoles; Levetiracetam; Male; Nitric Oxide; Nitric Oxide Synthase Type I; Piracetam; Rats; Rats, Wistar

Topics: Adult; Anticonvulsants; Cerebral Cortex; Electroencephalography; Epilepsy, Complex Partial; Face; Female; Fructose; Hallucinations; Humans; Illusions; Levetiracetam; Magnetic Resonance Imaging; Piracetam; Reflex; Topiramate; Valproic Acid

Topics: Aged; Anticonvulsants; Epilepsy, Complex Partial; Humans; Hyponatremia; Levetiracetam; Male; Piracetam; Water-Electrolyte Imbalance

In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Topics: Acute Disease; Adult; Dose-Response Relationship, Drug; Epilepsy; Epilepsy, Complex Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam

Topics: Adult; Anticonvulsants; Electroencephalography; Epilepsy, Complex Partial; Humans; Infusions, Intravenous; Levetiracetam; Lorazepam; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome

A 64-year-old patient with symptomatic epilepsy developed thrombocytopenia during treatment with levetiracetam (LEV). As no other medical reason could be evaluated, a medication side effect was postulated. The only new drugs were valproic acid (since 3 weeks) and levetiracetam (since 3 days). After valproic acid medication was ended, thrombocytopenia did not improve and even worsened further. Finally levetiracetam administration was ended and trombocytopenia resolved rapidly and completely within few days.

Topics: Anticonvulsants; Epilepsy, Complex Partial; Female; Humans; Levetiracetam; Middle Aged; Piracetam; Thrombocytopenia

Levetiracetam-treated patients commonly report daytime drowsiness, fatique, asthenia and decreasing of motor activity. However the origin of these reported side effects are still debated, we aimed to clarify effect of levetiracetam on sleep. Therefore this prospective study was conducted to evaluate the effects of levetiracetam on motor activity, amount and continuity of sleep and napping.. Various tests were performed on twenty two patients treated with levetiracetam (10 monotherapy, 12 add-on therapy) at least three days before the initiation of treatment, and consecutively for five to eight days at the third week of treatment. These tests included sleep logs, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Modified Maintenance of Wakefulness Test and actimetric measurements. In order to evaluate the sleep behavior of these patients the following sleep parameters were estimated: bedtime, wake-up time, sleep-onset time, sleep-offset time, sleep latency, total sleep time, wake time after sleep onset, fragmentation index, total activity score, nap episodes, total nap duration and sleep efficiency. Twenty members of staff from our hospital (Doctor, nurse, secretary, civil servant etc.) were evaluated as control subjects in the study.. After three-week treatment with levetiracetam (in particular with add-on therapy), Epworth Sleepiness Scale scores, napping episodes and total nap durations increased and sleep latencies decreased. While durations of Modified Maintenance of Wakefulness Test and total activity scores decreased. However the total sleep time and the sleep efficiency did not show any difference from the pre-treatment values.. Our results suggest that levetiracetam leads to drowsiness by decreasing the daily motor activity and increasing the naps; however this agent does not have any major effects on total sleep time and sleep efficiency during night. Actimetric analyses give information about continuity of sleep and sleep/wake states however does not give satisfactory information about architecture of sleep. In order to determine the effects of levetiracetam on the sleep architecture we need similiar protocol studies by full night polysomnography.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Disorders of Excessive Somnolence; Electroencephalography; Epilepsy, Complex Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Motor Activity; Piracetam; Prospective Studies; Severity of Illness Index; Sleep; Sleep Stages; Surveys and Questionnaires; Wakefulness

Topics: Anticonvulsants; Carbamazepine; Child; Drug Eruptions; Eosinophilia; Epilepsy, Complex Partial; Female; Humans; Levetiracetam; Piracetam; Syndrome; Time Factors

Based on blood sampling in a formula-fed pair of twins, the estimated serum half-life of levetiracetam (LEV) at birth is 16-18 h.

Topics: Amniotic Fluid; Anticonvulsants; Epilepsy, Complex Partial; Female; Fetal Blood; Half-Life; Humans; Infant, Newborn; Levetiracetam; Maternal-Fetal Exchange; Piracetam; Pregnancy; Pregnancy Complications; Twins

Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the effects of NEF in amygdala-kindled seizures and its potential for antiepileptic therapy.. Effects of NEF on fully amygdala-kindled seizures and development of amygdala-kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone-type antiepileptic drug (AED).. In fully amygdala-kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose-dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala-kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala-kindled seizures. As well as fully amygdala-kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration.. Although NEF possesses potent anticonvulsant effects on fully amygdala-kindled seizures, it has few or no effects on the development of amygdala-kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala-kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.

Topics: Administration, Oral; Amygdala; Animals; Anticonvulsants; Behavior, Animal; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; Electroencephalography; Epilepsy, Complex Partial; Humans; Kindling, Neurologic; Levetiracetam; Male; Nootropic Agents; Piracetam; Pyrrolidinones; Rats; Rats, Wistar; Seizures

1. The tetanus toxin seizure model, which is associated with spontaneous and intermittent generalized and non-generalized seizures, is considered to reflect human complex partial epilepsy. The purpose of the present study was to investigate and compare the anticonvulsant effects of carbamazepine with that of levetiracetam, a new anti-epileptic drug in this model. 2. One microl of tetanus toxin solution (containing 12 mLD(50) microl(-1) of tetanus toxin) was placed stereotactically into the rat left hippocampus resulting in generalized and non-generalized seizures. 3. Carbamazepine (4 mg kg(-1) h(-1)) and levetiracetam (8 and 16 mg kg(-1) h(-1)) were administered during a 7 day period via an osmotic minipump which was placed in the peritoneal cavity. Carbamazepine (4 mg kg(-1) h(-1)) exhibited no significant anticonvulsant effect, compared to control, when the entire 7 day study period was evaluated but the reduction in generalized seizures was greater (35.5%) than that for non-generalized seizures (12.6%). However, during the first 2 days of carbamazepine administration a significant reduction in both generalized seizure frequency (90%) and duration (25%) was observed. Non-generalized seizures were unaffected. This time-dependent anticonvulsant effect exactly paralleled the central (CSF) and peripheral (serum) kinetics of carbamazepine in that steady-state concentrations declined over time, with the highest concentrations achieved during the first 2 days. Also there was a significant 27.3% reduction in duration of generalized seizures during the 7 day study period (P=0.0001). 4. Levetiracetam administration (8 and 16 mg kg(-1) h(-1)) was associated with a dose-dependent reduction in the frequency of both generalized (39 v 57%) and non-generalized (36 v 41%) seizures. However, seizure suppression was more substantial for generalized seizures. Also a significant dose-dependent reduction in overall generalized seizure duration was observed. 5. These data provide experimental evidence for the clinical efficacy of levetiracetam for the management of patients with complex partial seizures. Furthermore, levetiracetam probably does not act by preventing ictogenesis per se but acts to reduce seizure severity and seizure generalization.

Topics: Animals; Anticonvulsants; Carbamazepine; Epilepsy, Complex Partial; Levetiracetam; Male; Piracetam; Rats; Rats, Sprague-Dawley; Tetanus Toxin