Levetiracetam In Status Epilepticus Research Articles

CHANTER Syndrome: A Rare Cause of Encephalopathy and Ischemic Lesions (P2-5.017)

<h3>Objective:</h3> To present a rare case of Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted Diffusion (CHANTER) Syndrome. <h3>Background:</h3> CHANTER syndrome is a recently recognized constellation of clinical and radiologic findings. The clinical features include acutely depressed consciousness with obstructive hydrocephalus secondary to cerebellar edema. MRI findings are restricted diffusion in the cerebellar cortex, hippocampi, and basal nuclei. CHANTER is distinguished from ischemic stroke by lack of distribution in a specific vascular territory or vascular occlusion present on angiographic imaging. Etiology may be a primary metabolic or mitochondrial failure of the gray matter with anoxic injury precipitated by opiates or other drugs of abuse. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 70-year-old right-handed hypertensive woman with HIV, end-stage renal failure, and lymphoma in remission was in respiratory distress. Seizures of unclear duration were noted on ambulance arrival and midazolam was administered. She was intubated and loaded with levetiracetam for status epilepticus. Norepinephrine was given during a hypotensive episode. Neurological examination was remarkable for lack of motor response to noxious stimuli and present brainstem reflexes consistent with coma. Opiates were detected in urine. MRI brain showed multiple small foci of restricted diffusion involving bilateral cerebellar hemispheres, hippocampi, basal ganglia, and in the right parietal cortex. MR angiography of the head and neck was normal. Video EEGs showed severe diffuse slowing, generalized periodic discharges that became blunted with triphasic morphology after lorazepam and levetiracetam administration. Cardiac monitoring and echocardiogram were unremarkable. Her alertness improved and withdrew minimally all extremities to painful stimuli. She was discharged to a long-term skilled nursing facility. <h3>Conclusions:</h3> This case highlights a rare clinical manifestation suggestive of CHANTER syndrome. Unlike other cases previously described, the cerebellar lesions were not sufficiently large to cause hydrocephalus. However, the clinical recovery was very limited. Status epilepticus and transient hypotension may have played a role in the poor recovery. <b>Disclosure:</b> Dr. Hiana has nothing to disclose. Dr. Soh has nothing to disclose. Dr. Marchidann has stock in Eli Lilly. Dr. Marchidann has stock in Pfizer. Dr. Marchidann has stock in Merck. Dr. Marchidann has stock in Illumina. Dr. Marchidann has stock in Aeterna Zentaris. Dr. Marchidann has stock in Abbot. Dr. Marchidann has received publishing royalties from a publication relating to health care. Dr. Marchidann has received publishing royalties from a publication relating to health care.

Levetiracetam circulating concentrations and response in status epilepticus

IntroductionIntravenous levetiracetam (LEV) is broadly used in the treatment of status epilepticus (SE). A loading dose is usually infused, aiming to reach quickly the range of plasma concentrations considered as therapeutic (12–46 mg/l). The aim of the study was to evaluate the response to LEV in SE, correlated exposure assessed by plasma concentration monitoring, as well as calculated exposure parameters. Materials & methodsWe retrospectively analyzed a SE registry, including patients since 2015 with at least one available LEV plasma level measured less than 36 h after loading. A Bayesian maximum likelihood approach based on a population pharmacokinetic model was used to estimate LEV exposure parameters. We compared plasma levels and pharmacokinetics parameter estimates between responders and nonresponders. Therapeutic response was defined as SE cessation within 24 h following LEV introduction without a need for additional antiepileptic drug (AED). ResultsWe included 29 patients (45 plasma levels). Variability was salient in LEV loading doses (ranging between 17 and 38 mg/kg) and monitoring practice. There was no difference in median plasma concentrations (19.5 versus 21.5 mg/l; p = 0.71), median estimated LEV exposure (25.8 versus 37.0 mg/l; p = 0.61), peak (30.4 versus 41.5 mg/l; p = 0.36), or residual levels after loading dose (14.4 versus 20.5 mg/l; p = 0.07) between responders and nonresponders. ConclusionsLevetiracetam exposure does not seem to differ significantly between responders and nonresponders; greater exposure was not associated with better outcome. Loading doses of 30 mg/kg seem, however, appropriate to quickly reach the target exposure level. The short LEV half-life makes standardized sampling measurement necessary to obtain directly interpretable LEV levels.

Loading doses of levetiracetam in status epilepticus result in higher rates of seizure control than standard dosing – A pooled analysis

Loading doses of levetiracetam in status epilepticus result in higher rates of seizure control than standard dosing – A pooled analysis

Intravenous levetiracetam versus phenobarbital in children with status epilepticus or acute repetitive seizures.

PurposeThis study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS).MethodsThe medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained.ResultsThe records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10–20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20–30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50).ConclusionIntravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV.

Epilepsy: recent advances

This short review summarizes epilepsy papers published in the Journal of Neurology in 2009, covering pathophysiology (inflammation; propagation pathways), new treatments (oxcarbazepine in paediatrics; levetiracetam in status epilepticus), and non-seizure outcomes (violence; foetal/pregnancy).

Experience with Intravenous Levetiracetam in Status Epilepticus

Status epilepticus is a medical emergency associated with significant morbidity and mortality. To report our experience with the use of intravenous (IV) levetiracetam in patients with status epilepticus who had not responded to IV benzodiazepines. A retrospective review of the clinical charts of patients with status epilepticus who were treated with IV levetiracetam from July 2007 to July 2008 in our department was performed. Data on demographics, epileptic syndrome, aetiology, treatment dosage and adverse effects were analysed. IV levetiracetam was administered over a period of 15-30 minutes; each 500 mg of levetiracetam was diluted in 100 mL of normal saline. Thirty-four patients (19 men and 15 women, 11-90 years old) with status epilepticus were treated with IV levetiracetam. Six patients (18%) had primarily generalized status epilepticus and 28 (82%) had focal status epilepticus. The aetiologies were: vascular (47%), cryptogenic (24%), tumours (12%), metabolic (12%) and brain anoxia (6%). The indications for administering IV levetiracetam were: no response to IV phenytoin and/or IV valproic acid (53% of patients) or to avoid adverse effects, contraindications or potential interactions (47% of patients). The median loading dose of IV levetiracetam was 1000 mg and the maintenance dosage ranged from 500 to 1500 mg/12 hours (median 1000 mg/12 hours). Status epilepticus stopped in a clear temporal relationship with IV levetiracetam in 71% of patients. IV levetiracetam was especially effective in older patients with vascular status epilepticus, while cryptogenic status epilepticus, primarily generalized status epilepticus, previous therapy with IV phenytoin and/or valproic acid and status epilepticus due to brain anoxia were associated with a poor response. There were no serious adverse events documented in the patients' charts. While waiting for large, controlled studies, our data suggest that IV levetiracetam might be an alternative for the treatment of status epilepticus, especially in elderly patients with vascular status epilepticus and concomitant medical conditions.

Intravenous levetiracetam as treatment for status epilepticus

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.) application. It could be an alternative when standard drugs fail or should be avoided. We retrospectively identified patients from two German teaching hospitals who were treated with LEV i.v. for SE. Their charts were reviewed regarding sociodemographic data, type, etiology, onset and duration of SE, dose of LEV, concurrent antiepileptic drugs (AED) treatment, tolerability, and outcome. Thirty-two patients (15 female) were found who were treated with i.v. LEV for SE (median age 71 years). Two patients were exclusively treated with LEV. Eight received a low and further 20 patients a high dose of benzodiazepines before LEV. Two patients were treated with LEV to enable discontinuation of narcosis. SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients. Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology. Therapy was initiated within a median time of 3 h and LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3,500 mg. Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min. LEV could not terminate SE in seven patients. We documented nausea and emesis in one and elevation of liver enzymes in another patient that were likely to be attributed to LEV. LEV i.v. seems to be safe with relevant efficiency for the treatment of SE in elderly and multimorbid patients when comorbidity and respiratory insufficiency precludes high doses of benzodiazepines or phenytoin.

Levetiracetam: Past, Present and Future

Levetiracetam is an antiepileptic drug approved for use as an adjunctive agent in partial-onset seizures in adults. This approval was recently extended to children over 4 years of age. Among the currently approved antiepileptic drugs, levetiracetam is unique in its mechanism of action. Its CNS binding site, the synaptic vesicle protein SV2A, was discovered recently. Binding at this site may be important for the antiseizure activity of levetiracetam and the role of this binding site and its modulation by levetiracetam is an area of active research in epilepsy. Levetiracetam is generally safe, has near to ideal pharmacokinetics and does not interact with other medications. The most serious adverse events are behavioral in nature. Recent studies suggest that levetiracetam may be effective in generalized epilepsies, status epilepticus, pain and selected movement disorders. Intriguing studies using the kindling model of epilepsy suggest that levetiracetam may protect against the development of kindling and chronic epilepsy. A parenteral formulation of levetiracetam may soon become available and may lead to larger studies of levetiracetam in status epilepticus.