Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new keppra research articles will be listed here shortly after becoming available to us.
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Medical research on keppra
Zh Nevrol Psikhiatr Im S S Korsakova. 2008; 108(10): 31-36
Shershever AS, Bentsion DL, Lavrova SA, Sorokova EV
Efficacy of keppra was studied in 52 patients, aged 10-55 years, after the surgical treatment of gliomas of the brain hemispheres. The medication was used (in combination with other anticonvulsant drugs and hormones) during the radiotherapy. In 30 (57,8%) of cases epileptic seizures were before the surgery. In 22 (42,2%) of patients they developed during the radiotherapy. Keppra was used in the regiment of "urgent aid" in relation to the appearance of seizures and increase of their frequency during the radiotherapy. Doses of keppra varied from 500 to 2500 mg (30-50 mg/kg/day) in a single dose. Then patients received the drug 2 times daily under the control of clinical and EEG presentations. A clinical effect, including the decrease of seizures frequency by 48,3% (p
Antiemetic properties of the antiepileptic drug levetiracetam.
N Engl J Med. 2008 Oct 23; 359(17): 1853
Lee JW, Bromfield EB, Kesari S
Levetiracetam for stiff-person syndrome: report of 2 patients.
Clin Neuropharmacol. 2008 Sep-Oct; 31(5): 301-2
Shimberg WR, Patel NB, Sullivan KL, Hauser RA, Zesiewicz TA
We report 2 patients with stiff-person syndrome whose spasms were greatly relieved by levetiracetam (Keppra).
Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury.
Neurosurg Focus. 2008 Oct; 25(4): E3
Jones KE, Puccio AM, Harshman KJ, Falcione B, Benedict N, Jankowitz BT, Stippler M, Fischer M, Sauber-Schatz EK, Fabio A, Darby JM, Okonkwo DO
OBJECT: Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI. METHODS: Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency. RESULTS: Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003). CONCLUSIONS: Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis.
Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents.
Epilepsia. 2008 Aug; 49 Suppl 6: 47-9
Desai J
In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug-drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Sep 15; 873(1): 129-32
Contin M, Mohamed S, Albani F, Riva R, Baruzzi A
We present a simple, fast and validated method for the determination of the new generation antiepileptic drug (AED) levetiracetam (LEV) in plasma of patients with epilepsy using high performance liquid chromatography (HPLC) with UV detection. Plasma sample (500 microL) pretreatment was based on simple deproteinization by methanol spiked with the internal standard (I.S.). HPLC analysis was carried out on a Synergi 4-microm Hydro-RP, 150 mm x 4 mm I.D. column. The mobile phase was a mixture of potassium dihydrogen phosphate buffer (50 mM, pH 4.5) and acetonitrile (94:6, v/v) at an isocratic flow rate of 1.5 mL/min. The UV detector was set at 205 nm. Calibration curves were linear (mean correlation coefficient=0.999) over a range of 4-80 microg/mL. The quantitation limit was 2 microg/mL and the absolute recovery was >90% for LEV and the I.S. Both intra and interassay precision and accuracy were lower than 7.5%. The chromatographic run lasted 13 min. The present procedure omitting expensive solid phase or time-consuming liquid-liquid extraction and drying steps is cheaper, faster and simpler than mostly published analytical methods for levetiracetam. Applied to a large population of patients with epilepsy this assay proved very practical in our therapeutic drug monitoring setting (TDM).
Levetiracetam as a possible cause of fulminant liver failure.
Neurology. 2008 Aug 26; 71(9): 685-6
Tan TC, de Boer BW, Mitchell A, Delriviere L, Adams LA, Jeffrey GP, Macquillan G
Efficacy and tolerability of levetiracetam versus phenytoin after supratentorial neurosurgery.
Neurology. 2008 Aug 26; 71(9): 665-9
Milligan TA, Hurwitz S, Bromfield EB
BACKGROUND: Antiepileptic drugs are routinely given after craniotomy. Though phenytoin (PHT) is still the most commonly used agent, levetiracetam (LEV) is increasingly administered for this purpose. This retrospective study compared the use of LEV and PHT as monotherapy prophylaxis following supratentorial neurosurgery. METHODS: Patients receiving LEV monotherapy after supratentorial craniotomy were reviewed and compared to a control group of patients receiving PHT monotherapy. RESULTS: One of 105 patients taking LEV and 9/210 patients taking PHT had seizures within 7 days of surgery (p = 0.17). Adverse drug reactions requiring change in therapy during hospitalization occurred in 1/105 patients taking LEV and 38/210 patients taking PHT (p < 0.001). Among patients followed for at least 12 months, 11/42 (26%) treated with LEV vs 42/117 (36%) treated with PHT developed epilepsy (p = 0.34); 64% remained on LEV, while 26% remained on PHT (p = 0.03). CONCLUSIONS: Both levetiracetam (LEV) and phenytoin (PHT) were associated with a low risk of early postoperative seizures and a moderate risk of later epilepsy. LEV was associated with significantly fewer early adverse reactions than PHT and with a higher retention rate in patients who were followed for at least 1 year and developed epilepsy.
Brain Res Bull. 2008 Aug 20;
Margineanu DG, Matagne A, Kaminski RM, Klitgaard H
Levetiracetam (Keppra((R))) is a new generation antiepileptic drug characterized by a unique profile of activity in experimental models of epilepsy. It also has a distinct binding site in the brain, i.e. the synaptic vesicle protein type 2 (SV2A). Levetiracetam has been reported to have antiepileptogenic and disease-modifying properties. In the present study the effects of chronic treatment with levetiracetam were assessed in rats that sustained pilocarpine-induced status epilepticus (SE). Hippocampal field potentials were recorded in vivo in anesthetized animals after 3-day washout period that followed 21-day treatment with different doses of levetiracetam (50, 150 or 300mg/(kgday)) administered via ALZET((R)) osmotic mini-pumps. Vehicle treated rats together with naive animals (not subjected to SE) were used as control groups. Chronic treatment with levetiracetam yielded clinically relevant plasma concentrations throughout the experiment with complete washout of the drug 3 days after treatment cessation. At this point in time post-SE rats chronically treated with vehicle developed clear signs of hippocampal hyperexcitability, i.e. increased amplitude of population spike (PS) recorded in the dentate gyrus and reduced paired-pulse inhibition in the CA1 area. Levetiracetam treatment dose-dependently counteracted these long-term effects of pilocarpine-induced SE. Furthermore, at the dose of 300mg/(kgday) levetiracetam restored these parameters back to control level. The present results indicate that chronic treatment with levetiracetam completely inhibits the development of hippocampal hyperexcitability following pilocarpine-induced SE.
Visualization of SV2A conformations in situ by the use of Protein Tomography.
Biochem Biophys Res Commun. 2008 Oct 31; 375(4): 491-5
Lynch BA, Matagne A, Brännström A, von Euler A, Jansson M, Hauzenberger E, Söderhäll JA
The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography. We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicates that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins.