levetiracetam and Chronic-Disease

Murine typhus is a systemic febrile illness caused by Rickettsia typhi, a gram-negative, obligate intracellular bacterium. It is found worldwide, including in the United States, where cases are concentrated in suburban areas of Texas and California. The disease manifests with fever, headache, and rash. Central nervous system involvement is rare in both adults and children. Aseptic meningitis and meningoencephalitis are the most common neurological presentations, occurring in 2% to 5% of cases. Neurological dysfunction, including memory impairment and behavioral alterations, can occur and usually are reversible. Long-term deficits are considered rare even in untreated cases and have not been described in the pediatric population.. Single case report.. We describe a previously healthy 17-year-old girl infected with R. typhi who developed meningoencephalitis that resulted in chronic cognitive impairment despite treatment.. Murine typhus should be considered in the differential diagnosis of aseptic meningitis and meningoencephalitis. Early diagnosis and treatment can prevent death and long-term morbidity.

Topics: Acetazolamide; Adolescent; Anticonvulsants; Brain; Chronic Disease; Cognition Disorders; Diagnosis, Differential; Electroencephalography; Female; Humans; Levetiracetam; Neuropsychological Tests; Piracetam; Typhus, Endemic Flea-Borne

Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of levetiracetam for relief of neuropathic pain has not previously been reviewed.. To assess the analgesic efficacy and adverse events of levetiracetam in chronic neuropathic pain conditions in adults.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6) (via the Cochrane Library), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 3 July 2014, together with reference lists of retrieved papers and reviews.. We included randomised, double-blind studies of two weeks duration or longer, comparing levetiracetam with placebo or another active treatment in adults with chronic neuropathic pain conditions. Studies had to have a minimum of 10 participants per treatments arm.. Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction; intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison; 8 to 12 weeks duration; parallel design); second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with at least 200 participants in the comparison; and third tier evidence from data involving fewer than 200 participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.. We included six studies: five small, cross-over studies with 174 participants, and one parallel group study with 170 participants. Participants were treated with levetiracetam (2000 mg to 3000 mg daily) or placebo for between four and 14 weeks. Each study included participants with a different type of neuropathic pain; central pain due to multiple sclerosis, pain following spinal cord injury, painful polyneuropathy, central post-stroke pain, postherpetic neuralgia, and post-mastectomy pain.None of the included studies provided first or second tier evidence. The evidence was very low quality, downgraded because of the small size of the treatment arms, and because studies reported results using last observation carried forward (LOCF) imputation for withdrawals or using only participants who completed the study according to the protocol, where there were greater than 10% withdrawals. There were insufficient data for a pooled efficacy analysis in particular neuropathic pain conditions, but individual studies did not show any analgesic effect of levetiracetam compared with placebo. We did pool results for any outcome considered substantial pain relief (≥ 50% pain intensity reduction or 'complete' or 'good' responses on the verbal rating scale) for four studies with dichotomous data; response rates across different types of neuropathic pain was similar with levetiracetam (10%) and placebo (12%), with no statistical difference (risk ratio 0.9; 95% confidence interval (CI) 0.4 to1.7).We pooled data across different conditions for adverse events and withdrawals. Based on very limited data, significantly more participants experienced an adverse event with levetiracetam than with placebo (number needed to treat for an additional harmful event (NNH) 8.0 (95% CI 4.6 to 32)). There were significantly more adverse event withdrawals with levetiracetam (NNH 9.7 (6.7 to 18)).. The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.

Topics: Adult; Analgesics; Chronic Disease; Humans; Levetiracetam; Neuralgia; Piracetam; Randomized Controlled Trials as Topic

Levetiracetam (LEV) is the most recently licensed antiepileptic drug (AED) for adjunctive therapy of partial seizures. Its mechanism of action is uncertain but it exhibits a unique profile of anticonvulsant activity in models of chronic epilepsy. Three randomised, double-blind, placebo-controlled trials enrolling 904 patients with refractory partial epilepsy have demonstrated the efficacy of LEV as adjunctive therapy, with a responder rate (> or = 50% reduction in seizure frequency) of 28-41%. Long-term efficacy studies suggest retention rates of 60% after one year, with 13% of patients seizure-free for six months of the study and 8% seizure-free for one year. Adverse effects of LEV, including somnolence, lethargy and dizziness, were generally mild and the frequency of incidents was not significantly different between the active treatment and placebo groups in clinical trials. LEV has no clinically significant pharmacokinetic interactions (PKI) with other AEDs, or with commonly prescribed medications. Preliminary data suggest that LEV has efficacy in primary generalised epilepsy and further randomised trials are under way. The combination of potent antiepileptic properties with a relatively mild adverse effect profile makes LEV an attractive adjunctive therapy for partial seizures.

Topics: Animals; Anticonvulsants; Chronic Disease; Drug Evaluation; Drug Interactions; Epilepsy; Humans; Levetiracetam; Long-Term Care; Piracetam; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome

Migraine is not curable, but preventive treatments are usually used to decrease the intensity and frequency of headache attacks. Different therapeutic options are widely studied for chronic migraine (CM), but all of them have different inefficacies.. The aim of this study was to compare the efficacy of levetiracetam versus sodium valproate in the treatment of CM.. A randomized controlled clinical trial was conducted on 62 patients with chronic migraine (30 patients in intervention group-treated with levetiracetam and 32 patients in control group- treated with sodium valproate). The treatment regimen consisted of initial dose of levetiracetam or sodium valproate 500 mg daily which increased to 500 mg two times a day after two weeks. The treatment response was evaluated by measuring pain frequency, pain severity, and the MIDAS (migraine disability assessment) score over three months follow-up.. During a three-month follow-up, the mean of headache frequency, severity, and MIDAS score were changed significantly. The rate of decrease in headache frequency was higher in control group than intervention group ((6.7±2.7 and 14.4±5.3 day/month, respectively) (P<0.001). Also, headache severity and MIDAS score significantly decreased in the control group than intervention group (3.4±1.1 and 5.7±1.6, respectively P<0.001, 16.7 ± 6.1 and 30.2±9.8, respectively (P<0.001).. According to our findings, levetiracetam offered improvement in headache frequency, severity, and MIDAS score in patients with CM. However, levetiracetam was not effective enough for chronic migraine as valproate, despite some significant effect. Thus levetiracetam can be one of the choices for limited chronic migraine subjects who are in contraindication of Valproate.

Topics: Adolescent; Adult; Analgesics; Chronic Disease; Disability Evaluation; Double-Blind Method; Female; Humans; Iran; Levetiracetam; Male; Middle Aged; Migraine Disorders; Pain Measurement; Piracetam; Severity of Illness Index; Time Factors; Treatment Outcome; Valproic Acid; Young Adult

Levetiracetam was recently approved as adjunctive therapy for partial onset seizures. The authors conducted an open-label trial of levetiracetam in eight patients with chronic myoclonus. Patients were assessed by using the Unified Myoclonus Rating Scale. Levetiracetam was well tolerated. Three of five patients with cortical myoclonus experienced reductions in their myoclonus scores, providing support for a larger, placebo-controlled trial in cortical myoclonus.

Topics: Adult; Aged; Anticonvulsants; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Myoclonic; Female; Humans; Levetiracetam; Male; Middle Aged; Pilot Projects; Piracetam; Treatment Outcome

Levetiracetam was initially developed as a nootropic drug, although since 2002 it has been used as anticonvulsant for the treatment of partial and generalized epilepsy syndromes. The purpose of the research was to investigate anti-paroxysmal activity of levetiracetam (LEV) on the model of cobalt-induced chronic epilepsy caused by the application of cobalt to the sensorimotor area of the rat cortex to evaluate LEV impact on the different stages of epileptogenesis. LEV effects were studied at the initial stage of the epileptogenesis (2nd day after the cobalt application) and at the stage of generalized paroxysmal activity (6th day after the cobalt application). The research showed that levetiracetam administration (dosages 50 mg/kg and 200 mg/kg) at the early stage of the epileptogenesis had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic areas: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. LEV administration on 6th day (dosage 50 mg/kg) did not have statistical effect on the epileptogenesis, while at a dosage of 200 mg/kg on 6th day LEV significantly suppressed paroxysmal activity in the studied structures of rats with cobalt epilepsy. The strongest anti-paroxysmal effect was detected in hippocampus and was expressed as the normalization of bioelectrical activity and the appearance of a regular theta rhythm. Thus, LEV effects are mostly directed to the hippocampal area of epileptiform activity and, to a lesser extent, to the cortical area.

Topics: Animals; Anticonvulsants; Chronic Disease; Cobalt; Dose-Response Relationship, Drug; Electroencephalography; Electrophysiological Phenomena; Epilepsy; Levetiracetam; Male; Rats; Rats, Wistar

Zolpidem is an imidazopyridine nonbenzodiazepine hypnotic drug with a high affinity to the α1 subunit of the gamma amino butyric acid A receptor It is the first pharmacological option in the short-term management of sleep-onset insomnia. Initially considered a safer drug compared to benzodiazepines because of lower liability for abuse and dependence, recently, an increasing body of reports has questioned zolpidem's proneness to misuse. In this report, we describe a case of serious zolpidem abuse requiring pharmacological washout during hospitalization because of previous withdrawal seizures in a patient with chronic sleep-onset and maintenance insomnia.

Topics: Aged; Anticonvulsants; Chronic Disease; Clonazepam; Female; Hospitalization; Humans; Levetiracetam; Pregabalin; Seizures; Selective Serotonin Reuptake Inhibitors; Sertraline; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Zolpidem

To clarify the effect of levetiracetam (LEV) for acute and chronic seizure control in acute encephalitis with refractory, repetitive partial seizures (AERRPS).. We retrospectively reviewed the clinical course of six AERRPS cases treated with LEV, and explored the acute phase termination by withdrawal from barbiturate-induced coma under artificial ventilation, and the reduction in seizure frequency during the chronic phase. LEV was administrated orally or via nasogastric tubes as an add-on agent during acute (n=3; age 8-10 years) and chronic (n=3; age 19-30 years) AERRPS.. In the acute phase, administration of LEV (50-60 mg/kg/d) in combination with phenobarbital (n=3; peak 57.9-76.1 μg/ml) and potassium bromide (n=2; 30-36 mg/kg/d)) resulted in successful reduction of intravenous barbiturate dosage and withdrawal from artificial ventilation. In the chronic phase, seizure frequency reduced by >75% for 5-18 months with LEV 750-1500 mg/d.. LEV may affect seizure control in AERRPS, particularly during the chronic phase, through its unique action of inhibition of excitatory neurotransmitter release. The regimen of oral barbiturate, potassium bromide and LEV would be worth for trial during the acute phase of AERRPS.

Topics: Acute Disease; Adolescent; Adult; Anticonvulsants; Bromides; Child; Chronic Disease; Encephalitis; Female; Humans; Levetiracetam; Male; Phenobarbital; Piracetam; Potassium Compounds; Retrospective Studies; Seizures; Status Epilepticus; Young Adult

To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats.. Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump. Seizure activity was recorded by video-EEG monitoring with 2h of recording per day at the same time of day. We also performed western blot after EEG analysis.. Compared to control animals, PGP, ETB receptor and p38MAPK expression was increased in the hippocampus of epileptic animals. Neither SB202190 nor BQ788 affected the spontaneous seizure activity in epileptic rats. Three of ten rats were responders and achieved complete seizure control or significant reduction in seizure activity by LEV. In four of ten rats, seizure frequency was unaltered by LEV (non-responders). LEV + SB202190 reduced seizure duration, but not seizure frequency, in both responders and non-responders. LEV + BQ788 alleviated seizure frequency and seizure duration in both responders and non-responders. Compared to responders, PGP and ETB receptor expression was enhanced in the hippocampus of non-responders.. To the best of our knowledge, these findings are the first indications of the role of ETB receptor in pharmacoresistant epilepsy. Therefore, the present data suggest that the regulation of the ETB receptor-mediated signaling pathway may be important for identification of new therapeutic strategies for improving antiepileptic drug efficacy.

Topics: Animals; Anticonvulsants; Brain; Chronic Disease; Disease Models, Animal; Endothelin B Receptor Antagonists; Enzyme Inhibitors; Epilepsy; Imidazoles; Levetiracetam; Male; Oligopeptides; p38 Mitogen-Activated Protein Kinases; Piperidines; Piracetam; Pyridines; Rats, Sprague-Dawley; Receptor, Endothelin B; Seizures; Treatment Outcome

Levetiracetam (LEV, 2S-(oxo-1-pyrrolidinyl)butanamide, Keppra, UCB Pharma) is a new anti-epileptic drug used to treat certain types of seizures in epilepsy patients. However, the pharmacodynamics of LEV is still controversial. Recently, interleukin-1 beta (IL-1 beta) has been reported to involve in epileptic phenomena. Therefore, we investigated the effects of LEV on IL-1 beta system in the hippocampus and piriform cortex of chronic epileptic rats. As compared to controls, typical reactive astrogliosis and microgliosis were observed in the hippocampus and piriform cortex of epileptic animals. In addition, both reactive astrocytes and reactive microglia showed strong IL-1 beta and interleukin-1 receptor subtype 1 (IL-1R1) immunoreactivities. LEV reduced reactive gliosis and expression levels of IL-1 beta system in the hippocampus and the piriform cortex, while valproic acid did not. These findings suggest that the LEV may have, at least in part, anti-inflammatory effect, particularly against IL-1 beta system in neuroglia within epileptic brains.

Topics: Animals; Anticonvulsants; Astrocytes; Chronic Disease; Epilepsy; Gliosis; Hippocampus; Interleukin-1beta; Levetiracetam; Male; Microglia; Olfactory Pathways; Pilocarpine; Piracetam; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 Type I; Valproic Acid

To investigate the effects of different levetiracetam (LEV) doses on urodynamic parameters in an animal model of neurogenic detrusor overactivity (NDO).. A total of 54 female rats were studied. Of the 54 rats, 6 served as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic control and treatment groups were further subdivided (n = 6), and cystometry was performed at 3 and 4 weeks after SCT, respectively.. All paraplegic controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/- 0.2/min. The contraction amplitude and bladder capacity were not significantly different. After 1 week of LEV treatment, these urodynamic parameters improved significantly in a dose-dependent manner, and the changes were more striking at 2 weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/- 0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01). The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P = .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P = .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002).. The results of our study have shown that LEV is an effective treatment of NDO after SCT in rats. It might prove to be a novel, alternative therapeutic approach to NDO. The follow-up of these experimental results with a clinical trial is warranted.

Topics: Animals; Anticonvulsants; Chronic Disease; Dose-Response Relationship, Drug; Female; Levetiracetam; Paraplegia; Piracetam; Rats; Rats, Sprague-Dawley; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

Compared with traditional antiepileptic drugs, levetiracetam has a unique mechanism of action and unique properties, including predominant renal excretion and lack of drug-drug interactions. In the elderly, depression associated with levetiracetam has not been reported.. A 73-year-old black man (height, 172.7 cm; weight, 92.7 kg; body mass index [BMI], 31 kg/m(2)) with stage 4 kidney disease was taking levetiracetam 500 mg BID for partial complex seizures. After 5 months of taking medication, new-onset depression, evidenced by depressed mood, weight loss, fatigue, and appearing withdrawn, was noted in this patient. Levetiracetam was discontinued by order of the patient's primary care physician. At a follow-up appointment 4 weeks later, the depressive symptoms had nearly resolved. The patient's Naranjo Adverse Drug Reaction Probability Scale score was 6, indicating levetiracetam to be a probable cause of depression in this patient. In a second case, a 92-year-old white woman (height, 154.9 cm; weight, 54.5 kg; BMI, 22.7 kg/m(2)) with existing chronic kidney disease and new-onset partial seizure, likely due to a meningioma, was initiated on levetiracetam 500 mg once daily. Depressive symptoms (eg, anhedonia, hypersomnolence, decreased appetite) were noted within 5 weeks. Cessation led to improvement in mood and cognition within 8 days. Based on this patient's Naranjo Adverse Drug Reaction Probability Scale score of 6, levetiracetam was a probable cause of depression in this patient.. Levetiracetam was a probable cause of depression in these 2 elderly patients. Cautious use and additional monitoring may be necessary when prescribing levetiracetam to elderly patients, especially when prescribing to those with a history of renal impairment.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Chronic Disease; Depression; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Kidney Diseases; Levetiracetam; Male; Piracetam

Pharmacoresistance is a major problem in the treatment of epilepsy. We showed previously that pharmacoresistance, at least partially, is due to an up-regulation of the multidrug transporter (MDT) P-glycoprotein (P-gp): inhibition of P-gp improves seizure control in phenytoin-treated epileptic rats (poststatus epilepticus rat model for temporal lobe epilepsy). Since it has been suggested that levetiracetam (LEV) is no substrate for MDTs, we hypothesized that LEV would more adequately control seizures in this rat model.. Chronic epileptic rats were treated repeatedly with LEV (2-week interval; different dosages) via continuous infusion using osmotic minipumps, 5-6 months after electrically induced status epilepticus. The anticonvulsive effects were determined by video-EEG monitoring and the concentration of LEV was measured in plasma and brain homogenates using gas chromatography.. LEV adequately entered the epileptic brain and dose-dependently suppressed spontaneous seizures in chronic epileptic rats for 3-4 days. Hereafter, seizure frequency increased, while LEV plasma levels did not change. Seizure behavior was less severe throughout the whole treatment. LEV did not affect seizure duration. After a withdrawal period of 2 weeks all rats initially responded again to LEV.. The initial seizure control by LEV supports the observation that LEV is not impeded by MDTs. However, the failure to control seizures for a longer period of time indicates the development of tolerance to this drug. This poses another problem in the treatment of this kind of epilepsy. Whether tolerance may be prevented by intermittent administration of LEV should be further investigated.

Topics: Animals; Anticonvulsants; Chromatography, Gas; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Tolerance; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Infusion Pumps; Levetiracetam; Male; Phenytoin; Piracetam; Rats; Rats, Sprague-Dawley; Temporal Lobe; Videotape Recording

The purpose of this study was to assess, in rats, the antinociceptive effects of levetiracetam (i.p.), a novel antiepileptic drug, in acute pain tests and in two models of human neuropathic pain. Levetiracetam and carbamazepine contrasted morphine by an absence of effect in the tail flick and hot plate tests. In normal rats, carbamazepine failed to modify the vocalisation thresholds to paw pressure whereas levetiracetam slightly increased this threshold only at the highest dose (540 mg/kg) for 30 min. In the sciatic nerve with chronic constriction injury model, the highest dose of levetiracetam (540 mg/kg) and carbamazepine (30 mg/kg) reversed the hyperalgesia. In streptozocin-induced diabetic rats, levetiracetam dose-dependently increased the vocalization threshold from 17 to 120 mg/kg reaching a similar effect as 10 mg/kg of carbamazepine. These results indicate that levetiracetam induces an antihyperalgesic effect in two models of human neuropathic pain, suggesting a therapeutic potential in neuropathic pain patients.

Topics: Acute Disease; Analgesics; Animals; Carbamazepine; Chronic Disease; Constriction, Pathologic; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hyperalgesia; Injections, Intraperitoneal; Levetiracetam; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Piracetam; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Vocalization, Animal

Topics: Adrenergic alpha-Agonists; Anticonvulsants; Antidepressive Agents; Chronic Disease; Clonidine; Depression; Dyskinesia, Drug-Induced; Female; Humans; Hypotension; Levetiracetam; Lithium Carbonate; Middle Aged; Piracetam