lacosamide and Status-Epilepticus

Status epilepticus is defined as the situation resulting from the failure of the mechanisms responsible for terminating an epileptic seizure. In 2015, an operational concept was adopted internationally in which two times are identified: a first time, at which treatment must begin (five minutes for convulsive status, 10-15 minutes for focal and non-convulsive status); and a second time, after which there is considered to be a high risk of subsequent sequelae (30 minutes in the case of the convulsive). It occurs in 3-42/100,000 children per year, who are refractory or super-refractory in 10-40% of cases.. This article will review the different therapeutic options for status, from early treatment at home to the different first-line (benzodiazepines), second-line (phenobarbital, valproic acid, phenytoin, levetiracetam and lacosamide) or third-line treatments, which include both pharmacological (anaesthetics, propofol, ketamine, lidocaine, topiramate, brivaracetam or perampanel) and non-pharmacological (ketogenic diet, immunomodulatory treatments or epilepsy surgery) therapies.. Early identification and treatment of a prolonged crisis are essential to prevent progression to status. Although with fewer sequelae than in adults, status epilepticus in children represents a cause of mortality of up to 3-5%, while 25% of them will develop subsequent epilepsy, as well as a considerable percentage of neurological sequelae.. Estado epiléptico pediátrico.. Introducción. El estado epiléptico se define como la situación resultante del fallo de los mecanismos responsables de finalizar una crisis epiléptica. En 2015, se adoptó internacionalmente un concepto operativo en el que se identifican dos tiempos: un primer momento, en el que hay que comenzar un tratamiento (cinco minutos para los estados convulsivos, 10-15 minutos para los estados focales y no convulsivos); y un segundo tiempo, a partir del cual se considera que hay un riesgo elevado de secuelas posteriores (30 minutos en los convulsivos). Ocurre en 3-42/100.000 niños al año, y son refractarios o superrefractarios en el 10-40% de las ocasiones. Desarrollo. En este artículo se revisarán las diferentes opciones terapéuticas del estado, desde el tratamiento precoz domiciliario hasta los diferentes tratamientos de primera línea (benzodiacepinas), segunda línea (fenobarbital, ácido valproico, fenitoína, levetiracetam y lacosamida) o tercera línea, que incluyen tanto terapias farmacológicas (anestésicos, propofol, cetamina, lidocaína, topiramato, brivaracetam o perampanel) como no farmacológicas (dieta cetógena, tratamientos inmunomoduladores o cirugía de epilepsia). Conclusiones. Son fundamentales la identificación y el tratamiento precoz de una crisis prolongada para evitar la evolución a estado. Aunque con menores secuelas que en los adultos, el estado epiléptico en niños representa una causa de mortalidad hasta del 3-5%, al mismo tiempo que un 25% de ellos desarrollará una epilepsia posterior, así como un porcentaje considerable de secuelas neurológicas.

Topics: Adult; Anesthetics; Anticonvulsants; Benzodiazepines; Child; Epilepsy; Humans; Ketamine; Lacosamide; Levetiracetam; Lidocaine; Phenobarbital; Phenytoin; Propofol; Seizures; Status Epilepticus; Topiramate; Valproic Acid

A 14-year-old boy presented with a prodromal respiratory infection followed by super refractory status epilepticus. A diagnosis of Febrile Infection-Related Epilepsy Syndrome (FIRES) was made. Initial MRI study and CSF analysis were normal. He required multiple anticonvulsants owing to the refractory nature of the seizures. The course of the illness was rather stormy, laced with various medical problems viz. hepatic dysfunction, sepsis, hemodynamic, and hematological abnormalities which posed several challenges in the management. Hemophagocytic lymphocytic histiocytosis (HLH) was identified as the etiology of the illness and was treated but without success. The case report highlights the several immunomodulatory strategies that were employed to treat the disease, despite which the outcome was unfavorable.

Topics: Adolescent; Anti-Inflammatory Agents; Anticonvulsants; Epileptic Syndromes; Fatal Outcome; Histiocytosis; Humans; Immune System Diseases; Lacosamide; Male; Methylprednisolone; Status Epilepticus

To compare the evidence on efficacy, safety, tolerability, and impact on short term/long functional outcome of lacosamide (LCM) and phenytoin (PHT) in patients with status epilepticus.. We conducted a systematic literature search of relevant electronic databases using a suitable search strategy to identify studies directly comparing PHT and LCM, irrespective of dose and duration in patients with convulsive and/or nonconvulsive status epilepticus (SE). We used a standardized assessment form to extract information on the study design, data sources, methodologic framework, efficacy, and adverse events attributed to PHT and LCM from included studies and compared the efficacy and safety outcomes, using a fixed/random effect model.. Five studies were found to be eligible for inclusion out of 192 search items, enrolling a total of 115 and 166 participants (predominantly with SE) in LCM and PHT arm, respectively. Baseline characteristics were comparable between both arms. The proportion with seizure control was comparable between both arms (57.3% in LCM vs. 45.7% in PHT arm, p = 0.28) and even in the subgroup analysis separately for convulsive and non-convulsive SE. Proportion with treatment-emergent adverse events (TEAE) were comparable in both (17.6% vs. 12.2%, p = 0.20), but serious adverse events (SAE) were higher in PHT arm (5.1% vs. 0.8%, p = 0.049). The proportion with all-cause mortality and survival with moderate-severe disability were comparable between both arms (p = 0.23 and 0.37, respectively).. LCM has comparable efficacy with fewer SAEs as compared to PHT for achieving seizure control in patients with SE.

Topics: Anticonvulsants; Humans; Lacosamide; Phenytoin; Seizures; Status Epilepticus; Treatment Outcome

Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE).. Decision analysis model populated with effectiveness data from a systematic review and meta-analysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters.. VPA and PB were more effective than PHT for SE. There is substantial overlap in the cost-effectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.

Topics: Anticonvulsants; Benzodiazepines; Cost-Benefit Analysis; Decision Support Techniques; Humans; Lacosamide; Levetiracetam; Phenobarbital; Phenytoin; Status Epilepticus; Treatment Failure; Valproic Acid

Lacosamide, is one of the newer antiepileptic drug approved for focal drug-resistant epilepsy as an add-on treatment in patients older than 16 years. However, there is growing evidence of its use, safety and efficacy in children. We aim to evaluate efficacy and tolerability of lacosamide in focal and generalized drug-resistant epilepsy and refractory status epilepticus in the pediatric population.. We conducted a systematic review on MEDLINE, EMBASE, COCHRANE, Google Scholar and Scielo from January 2008 to January 2017. The primary outcome was the efficacy of lacosamide in children with drug-resistant epilepsy and refractory status epilepticus. Efficacy and adverse events attributed to lacosamide were extracted from each publication and systematically reported. We performed no meta-analyses due to limited available data.. Of 175 abstracts identified by the search, 82 were reviewed as full-text. Twenty-six articles fulfilled eligibility criteria and described outcomes in 797 patients (57% male). The majority of studies were retrospective (69%) small series (84%). On average 51% of patients had 50% or greater seizure reduction. The mean seizure freedom rate was 24%. Adverse effects occurred in 18-59% of patients. The main events were dizziness, sedation, gastrointestinal upset, mood and behavioral changes. Half of the patients with Lennox Gastaut syndrome showed 50% or greater seizure reduction, 32% did not response to lacosamide and 17% suffered seizure aggravation.. Current evidence shows lacosamide as a good option in pediatric patients with focal drug-resistant epilepsy and refractory status epilepticus as an add-on therapy given its efficacy on seizure control and safety profile. The use of lacosamide in Lennox-Gastaut syndrome shows conflicting data. Large randomized controlled studies in the pediatric population are necessary to substantiate these findings.

Topics: Acetamides; Adolescent; Anticonvulsants; Child; Drug Resistant Epilepsy; Humans; Lacosamide; Status Epilepticus

Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.

Topics: Acetamides; Anticonvulsants; Diet, Ketogenic; Hong Kong; Humans; Lacosamide; Levetiracetam; Magnesium; Midazolam; Piracetam; Practice Guidelines as Topic; Status Epilepticus; Treatment Outcome; Valproic Acid

Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus.. Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing. There remains a lack of prospective randomized controlled trials comparing different treatment regimens. Recent data support further study of intravenous lacosamide as an urgent-control therapy, and ketamine and clobazam for refractory status epilepticus. Recent data support the use of continuous EEG to help guide treatment for all patients with refractory status epilepticus and to better understand epileptic activity that falls on the ictal-interictal continuum. Recent data also improve our understanding of the relationship between periodic epileptic activity and brain injury.. Many treatments are available for status epilepticus and there are much new data guiding the use of specific agents. However, there continues to be a lack of prospective data supporting specific regimens, particularly in cases of refractory status epilepticus.

Topics: Acetamides; Administration, Intravenous; Anticonvulsants; Benzodiazepines; Clobazam; Critical Care; Electroencephalography; Humans; Infusions, Intravenous; Ketamine; Lacosamide; Randomized Controlled Trials as Topic; Status Epilepticus; Treatment Outcome

The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE.. We performed a systematic literature search of electronic databases using a combined search strategy from 2008 until October 2016. Using a standardized assessment form, information on the study design, methodologic framework, data sources, efficacy, and adverse events attributed to LCM were extracted from each publication and systematically reported.. In total, 522 SE episodes (51.7% female) in 486 adults and 36 children and adolescents were evaluated with an overall LCM efficacy of 57%. Efficacy was comparable between use in nonconvulsive (57%; 82/145) and generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The efficacy with later positioning of LCM decreased from 100% to 20%. The main adverse events during treatment of SE are dizziness, abnormal vision, diplopia, and ataxia. Overall, lacosamide is well tolerated and has no clinically relevant drug-drug interactions.. The available data regarding the use of LCM in SE are promising, with a success rate of 57%. The strength of LCM is the lack of interaction potential and the option for intravenous use in emergency situations requiring rapid uptitration.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Epilepsy, Partial, Motor; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Status Epilepticus; Treatment Outcome; Young Adult

Many patients with critical illness have been noted to have nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE). How aggressively these seizures should be treated is unclear. Many investigators feel that the morbidity of NCSs and NCSE is different from that of generalized convulsive status epilepticus (GCSE), so treatment should be less urgent. Consequently, many nonsedating AEDs have been used to treat NCSs and NCSE in patients with critical illness. Randomized, controlled trials demonstrating the efficacy of AEDs in NCSs and NCSE are lacking. The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) study compared lacosamide to fosphenytoin in the treatment of NCSs. An update of the study is presented. This article is part of a Special Issue entitled "Status Epilepticus".

Topics: Acetamides; Anticonvulsants; Critical Illness; Humans; Lacosamide; Phenytoin; Recurrence; Seizures; Status Epilepticus

Status epilepticus is among the most common neurologic emergencies, with a mortality rate of up to 20%. The most important therapeutic goal is fast, effective, and well-tolerated cessation of status epilepticus. Intravenous phenytoin/fosphenytoin, phenobarbital, or valproate is the current standard treatment after failure of benzodiazepines. Lacosamide as a new antiepileptic drug has been available as an intravenous solution since 2009. To date, PubMed lists 19 studies (10 single case reports and 9 case series), reporting a total of 136 episodes of refractory status epilepticus (50% nonconvulsive status epilepticus, 31% focal status epilepticus, and 19% convulsive status epilepticus) treated with lacosamide. The most often used bolus dose was 200-400 mg over 3-5 min. The overall success rate was 56% (76/136). Adverse events (AEs) were reported in 25% (34/136) of patients: mild sedation in 25 cases, 1 patient with possible angioedema, 2 with allergic skin reaction, 4 with hypotension, and 1 with pruritus. One patient developed a third-degree atrioventricular (AV) block and paroxysmal asystole. Overall, the rate of AEs was low. Current evidence on the use of intravenous lacosamide in acute seizures and status epilepticus is restricted to retrospective case reports and case series (class IV). Further prospective studies to inform clinicians are necessary.

Topics: Acetamides; Administration, Intravenous; Anticonvulsants; Humans; Lacosamide; Retrospective Studies; Status Epilepticus; Treatment Outcome

We will review all available studies on the use of lacosamide in the treatment of partial-onset seizures. The available evidence includes two open-label studies and three randomized controlled trials evaluating the safety and efficacy of oral lacosamide. One open-label study and one randomized controlled trial evaluating the safety and tolerability of intravenous lacosamide was also identified. Lacosamide was found to be efficacious with significant reduction in seizure frequency dosed 400-600 mg daily. Moreover, its adverse drug effects were mild and infrequently reported in the literature. Findings suggest that lacosamide is an effective agent for adjunctive treatment of refractory partial-onset seizures.

Topics: Acetamides; Administration, Oral; Animals; Anticonvulsants; Contraindications; Epilepsies, Partial; Epilepsy; Humans; Injections, Intravenous; Lacosamide; Randomized Controlled Trials as Topic; Status Epilepticus

Current standard treatment of established status epilepticus after failure of benzodiazepines is intravenous phenytoin/fosphenytoin, phenobarbital, or valproate. Since 2006 two new antiseizure drugs have become available as intravenous formulation: levetiracetam (2006) and lacosamide (2008). Both drugs have been taken up very rapidly by the clinicians to treat acute seizures and status epilepticus, despite lack of evidence from randomized controlled trials. The favorable pharmacokinetic profile and the good tolerability, especially the lack of sedating effects of both drugs make them promising potential alternatives to the standard antiseizure drugs. Future randomized controlled trials are needed to inform clinicians better about the best choice of treatment in established status epilepticus. The experimental evidence as well as the current clinical experience with levetiracetam and lacosamide are summarized in this review.

Topics: Acetamides; Humans; Injections, Intraventricular; Lacosamide; Levetiracetam; Lipoproteins; Piracetam; Status Epilepticus

To evaluate current evidence for the use of lacosamide in the treatment of refractory status epilepticus.. Literature was accessed via PubMed (through July 2011) using the terms lacosamide and status epilepticus.. All reports on the use of lacosamide in patients with status epilepticus were included for evaluation. Reviews and animal data were excluded.. Treatment of status epilepticus is challenging, and most patients fail to respond to initial treatment. Recently, several reports have been published on the use of lacosamide for status epilepticus. Eleven reports (5 case reports and 6 case series) were identified. Lacosamide was credited with successful termination of status epilepticus in a majority of these reports. However, the data are weakened by the heterogeneity of the reports, their descriptive nature, and the common divergence from current recommendations for the treatment of status epilepticus.. While lacosamide has been reported as an effective treatment for refractory status epilepticus, there is insufficient evidence for its routine use. For cases in which the risks associated with anesthetizing drugs are believed to outweigh the benefits, such as in complex partial status epilepticus, lacosamide may be a reasonable option after more established drug therapies fail.

Topics: Acetamides; Anticonvulsants; Humans; Lacosamide; Status Epilepticus

Topics: Acetamides; Animals; Anticonvulsants; Carbamates; Disease Models, Animal; Fructose; Humans; Lacosamide; Pyrroles; Pyrrolidinones; Rats; Receptors, AMPA; Status Epilepticus; Tetrahydroisoquinolines; Topiramate; Treatment Outcome

The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE.. Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE).. Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P=0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6).. In patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lacosamide; Lorazepam; Male; Middle Aged; Pilot Projects; Seizures; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

This non-interventional study was conducted to evaluate the efficacy and tolerability of intravenous lacosamide (LCM-iv) under routine conditions in daily clinical practice as a prospective registry.. Patients with any type of seizure or epilepsy syndrome were recruited in 16 neurological and neuropediatric centers in Germany if the treating physician decided to administer LCM-iv for any reason. Observation time per patient was 10 days with daily documentation of LCM-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events. Treatment efficacy, tolerability, and handling of LCM-iv were assessed using a five-step scale.. In 119 patients treating physicians classified epilepsies as focal in 66.1% and generalized in 17.4% (16.5% unclassifiable). Most common etiologies of seizures were tumors (36.1%) and cerebrovascular diseases (21.8%). Reasons for LCM-iv treatment included preparation for surgery (25.2%), convulsive (24.4%) and non-convulsive (18.5%) status epilepticus (SE), series of seizures (16.0%), gastrointestinal causes (5.9%), and acute seizures (4.2%). The median dose of LCM-iv was 300mg per day. In 45 of 64 patients (70.3%) with SE or series of seizures, epileptic activity ceased during observation time. Five patients showed abnormalities in ECG prior to the infusion and one patient afterwards, but during infusion no abnormalities were reported. Treating physicians rated efficacy and tolerability as very good or good in 77.6% and 93.1% of patients, respectively.. This large and independent multicenter registry on the use of LCM-iv in clinical practice demonstrates that LCM-iv is well-tolerated and highly efficacious when given in emergency situations, including patients experiencing SE. It is advisable to perform an electrocardiogram prior to LCM-iv administration.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Germany; Humans; Infant; Lacosamide; Male; Middle Aged; Outcome Assessment, Health Care; Registries; Seizures; Status Epilepticus; Young Adult

Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment.. We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM.. Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented.. Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Injections, Intravenous; Lacosamide; Male; Middle Aged; Status Epilepticus; Treatment Outcome; Young Adult

Status epilepticus (SE) and seizure clusters (SC) represent neurologic emergencies with a case fatality rate up to 34%, depending on cause and comorbidity. As SE becomes more refractory to treatment over time, appropriate medication is important. This study aimed to investigate efficacy and tolerability of intravenous (IV) lacosamide (LCM) in treatment of SC and SE. Data of patients with SE or SC who were treated with IV LCM between December 2009 and February 2011 in two Austrian centers were analyzed retrospectively. Clinical information was extracted from patients' charts. Forty-eight patients (26f/22m) aged median 62 years (range 17-95 years) were identified. Thirty-five percent of patients (17 of 48) had SC and 65% (31 of 48) had SE. SE was nonconvulsive in 10 (32%), convulsive in 11 (36%), and focal in 10 (32%) patients. SE was acute symptomatic in six (20%) and remote symptomatic in 11 (35%) patients. Fourteen (45%) had preexisting epilepsy. Median initial bolus dose was 200 mg (range 200-400 mg) in patients with SE and 200 mg in patients with SC. Maximum infusion rate was 60 mg/min. Cessation was observed in 42 patients (88%). Success rate in patients with SE receiving LCM as first or second drug was 100% (8 of 8), as third drug 81% (11 of 15), and as fourth or later drug 75% (6 of 8). There were no side effects observed except for pruritus and skin rash in two patients. These data support use of IV LCM as a potential alternative to standard antiepileptic drugs for acute treatment of seizure emergency situations, although randomized controlled studies are needed.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Seizures; Status Epilepticus; Treatment Outcome; Young Adult

Status epilepticus (SE) is a frequent neurological emergency, derived from the failure of mechanisms responsible for seizure termination. The present study aims to compare the efficacy of the most common antiseizure medications (ASMs) employed for the treatment of benzodiazepine-refractory SE.. We performed a retrospective cohort study of all SE episodes treated in our hospital between January 2016 and December 2020. Inclusion criteria were: age ≥ 18 years; a diagnosis of status epilepticus. Exclusion criteria were: status epilepticus resolved by initial therapy with benzodiazepines; impossibility to retrieve medical records. We considered as effective the ASM that was the last drug introduced or increased in dose before termination of SE and without changes in the co-medication.. A total of 244 episodes in 219 patients were included in the study. The mean age of the final study cohort was 63.6 ± 19.2, with 108 (49%) men. In the total cohort, phenytoin (PHT) showed the highest response rate (57.6%), followed by lacosamide (LCM) (40.7%) and valproate (VPA) (39.8%). The comparative efficacy among the different drugs was significantly different (p < 0.001). In the pairwise comparisons, VPA was superior to levetiracetam (LEV) (response rate: 39.75% vs 24.71%; p = 0.004), but not to LCM. Phenytoin had a significantly higher resolution rate compared to VPA (response rate: 57.63% vs 39.75%; p = 0.02) and LEV (response rate: 57.63% vs 24.71; p < 0.001). The clinical predictors of anaesthetics administration were a disorder of consciousness upon clinical presentation, previous diagnosis of epilepsy, and younger age.. In our cohort of SE, PHT showed higher effectiveness in terminating established SE, as well as refractory SE in the subgroup of patients treated with anaesthetics.

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Cohort Studies; Female; Humans; Lacosamide; Levetiracetam; Male; Phenytoin; Retrospective Studies; Status Epilepticus; Treatment Outcome

Status epilepticus in poststroke epilepsy is a challenging condition because of multiple vascular comorbidities and the advanced age of patients. Data on third-generation antiseizure medication (ASM) in this condition are limited. The aim of this study was to evaluate the efficacy of third-generation ASMs in the second- or third-line therapy of benzodiazepine-refractory status epilepticus in poststroke epilepsy following acute ischemic stroke.. Data on the effectiveness of third-generation ASMs in patients with status epilepticus in poststroke epilepsy were gathered from two German Stroke Registries and the Mainz Epilepsy Registry. We included only cases with epilepsy remote to the ischemic event. No patients with acute symptomatic seizures were included. The following third-generation ASMs were included: brivaracetam, lacosamide, eslicarbazepine, perampanel, topiramate, and zonisamide. The assessment of effectiveness was based on seizure freedom within 48 h since the start of therapy with the respective ASM. Seizure freedom was evaluated both clinically (clinical evaluation at least three times per day) and by daily electroencephalogram records.. Of the 138 patients aged 70.8 ± 8.1 years with benzodiazepine-refractory status epilepticus in ischemic poststroke epilepsy, 33 (23.9%) were treated with lacosamide, 24 (17.4%) with brivaracetam, 23 (16.7%) with eslicarbazepine, 21 (15.2%) with perampanel, 20 (14.5%) with topiramate, and 17 (12.3%) with zonisamide. Seizure freedom within 48 h was achieved in 66.7% of patients with lacosamide, 65.2% with eslicarbazepine, 38.1% with perampanel, 37.5% with brivaracetam, 35.0% with topiramate, and 35.3% with zonisamide (p < 0.05 for comparison of lacosamide or eslicarbazepine to other ASMs).. Based on these data, lacosamide and eslicarbazepine might be more favorable in the treatment of refractory status epilepticus in poststroke epilepsy, when administered as second- or third-line ASMs before anesthesia. Because of the fact that these ASMs share the same mechanism of action (slow inactivation of sodium channels), our findings could motivate further research on the role that this pharmaceutical mechanism of action has in the treatment of poststroke epilepsy.. This study was registered at ClinicalTrials.gov (NCT05267405).

Topics: Aged; Anticonvulsants; Benzodiazepines; Epilepsy; Humans; Ischemic Stroke; Lacosamide; Middle Aged; Retrospective Studies; Seizures; Status Epilepticus; Topiramate; Zonisamide

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.. Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Child; Female; Hospitals, University; Humans; Lacosamide; Levetiracetam; Male; Medical Records; Midazolam; Middle Aged; Phenobarbital; Phenytoin; Propofol; Status Epilepticus; Valproic Acid

The effect of lacosamide, a new antiseizure medication, was investigated electrophysiologically and biochemically in the penicillin-induced status epilepticus model.. The study included seven groups of rats (control, penicillin and 1, 5, 10, 25 and 50 mg/kg lacosamide). The rats were anesthetized using urethane (1.25 mg/kg/i.p.). ECG recordings were taken for one minute before and during status epilepticus in all groups. Lacosamide was administered intraperitoneally 30 min after intracortical microinjection of penicillin (500-IU/2.5/μl) and ECoG recording was taken for 180 min. The brain tissue was evaluated by ELISA method.. Lacosamide (1, 5, 10 and 25 mg/kg) decreased spike frequency significantly, while 50 mg/kg lacosamide dose resulted in an increase in spike frequency. ST segment elevation and heart rate were higher in the penicillin group. Lacosamide doses of 1, 5, 10 and 25 mg/kg decreased ST-segment elevation to the level of the control group, but 50 mg/kg lacosamide increased ST-segment elevation, QT and PR-interval. TOS and TNF-alpha levels increased in the penicillin group compared to control group, while 10 mg/kg lacosamide dose limited this increase. 50 mg/kg lacosamide administration was found to decrease TAS level compared to control group.. Our findings indicated associations of the decrease in spike frequency with the reduction of oxidative stress and inflammation in rats treated with 10 mg/kg lacosamide. High doses of lacosamide for acute treatment may cause cardiac changes in ECG.

Topics: Animals; Anticonvulsants; Electrocardiography; Lacosamide; Penicillins; Rats; Status Epilepticus

Status epilepticus (SE) is a life-threatening medical emergency which is frequently encountered in the critical care setting and can be refractory to treatment. Refractory status epilepticus (RSE) is defined as SE that has failed to respond to adequately used first-line and second-line antiepileptic medications. Super refractory status epilepticus is defined as SE that persists for 24 hours or more after the use of an anaesthetic agent or recurs after its withdrawal.If SE persists beyond a period of 7 days it is referred to as prolonged, refractory status epilepticus (PRSE). There are limited data guiding treatment of RSE in the paediatric population.Lacosamide (LCM) is licensed as an adjunctive treatment for partial-onset seizures. Evidence for the efficacy of LCM in paediatric SE is scarce. This case report may suggest a synergistic effect of LCM on slow-activation sodium channels in conjunction with medications such as phenytoin that causes fast inactivation of sodium channels. The dual fast and slow inactivation of sodium channels may enhance the effectiveness in treatment of RSE. This is the first case report of PRSE in an infant, successfully treated with LCM. A brief review of literature is also a part of this report.

Topics: Anticonvulsants; Epilepsia Partialis Continua; Humans; Infant; Lacosamide; Seizures; Status Epilepticus

Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE.. Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus.. The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

Topics: Animals; Anticonvulsants; Biomarkers; Hippocampus; Inflammation; Interleukin-1beta; Lacosamide; Male; Motor Activity; Oxidative Stress; Pilocarpine; Rats, Wistar; Reactive Oxygen Species; Seizures; Status Epilepticus; Topiramate; Tumor Necrosis Factor-alpha

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antioxidants; Behavior, Animal; Disease Models, Animal; Epilepsy, Temporal Lobe; Hippocampus; Lacosamide; Male; Neurons; Neuroprotective Agents; Oxidative Stress; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus

Efficacy, safety and tolerability of lacosamide in the treatment of status epilepticus are well described. However, other evidence of its pharmacologic profile in elderly patients with other comorbidities seems warranted. We describe the case of an 80 year-old woman with an history of arterial hypertension, ischemic cardiomyopathy, COPD, CKD, previous laryngeal cancer, a stoma positioning for diverticular disease and previous surgery for a left frontal meningioma. Since then, the patient developed focal epilepsy and she was on levetiracetam and valproic acid therapy. The patient was admitted to our department for a focal status epilepticus characterized by non-fluent aphasia and right facio-brachial clonic movements. She also presented with aspiration pneumonia and started intravenous antibiotic treatment. After failure of a first-line antiepileptic drug, lacosamide intravenous treatment was started, with complete reversal of the clinical picture. EEG then showed focal slow waves mixed to interictal epileptiform discharges over the left fronto-temporal regions. The patient was then discharged home with an oral lacosamide treatment and at 3 months she was seizure-free. Our case report confirms the efficacy of lacosamide in status epilepticus, highlighting its safety and tolerability in an elderly and fragile patient with multiple comorbidities and drug therapy.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Comorbidity; Female; Humans; Lacosamide; Levetiracetam; Status Epilepticus

We report the case of a previously healthy newborn who developed super-refractory status epilepticus after Group B streptococcal meningoencephalitis. After administration of first-, second- and third-line anticonvulsants without resolution of status epilepticus, we started intravenous lacosamide as adjunctive therapy to phenobarbital, phenytoin and continuous infusion of ketamine and midazolam. After administration of lacosamide, we observed a clear-cut improvement in the neurological clinical condition coupled with seizure control on continuous video-EEG monitoring, even after suspension of all other medications except for phenobarbital. No adverse effects ascribable to lacosamide were reported. The available data regarding the use of lacosamide for status epilepticus in adults and children are promising, although there is as yet only anecdotal evidence for neonatal status epilepticus. Its lack of potential interactions, good tolerability and the option of intravenous use lend to its appeal as treatment for status epilepticus. To the best of our knowledge, this is one of the first reported cases of effective lacosamide infusion in neonatal-onset super-refractory status epilepticus. This evidence should prompt further investigation on efficacy and safety of lacosamide to support its use in this population.

Topics: Anticonvulsants; Humans; Infant, Newborn; Lacosamide; Phenobarbital; Seizures; Status Epilepticus

Lacosamide (LCM) is a well-tolerated and increasingly used second-generation AED, and side effects such as atrial fibrillation are rare and poorly characterized. Supported by a literature review, we share our experience of the management of the first reported case of cardioembolic cerebral infarcts in the context of de novo atrial fibrillation, which appeared following a 200-mg intravenous infusion of LCM for the treatment of non-convulsive status epilepticus. Case report and literature review using search items including "atrial fibrillation OR atrial flutter AND LCM" in the thesaurus of Medline. We found three cases of atrial fibrillation/atrial flutter secondary to LCM, one following a 200-mg intravenous infusion. In one patient, previous risk factors for atrial fibrillation were reported and another was started on warfarin; all required suspension of LCM for cessation of atrial fibrillation. Previous risk factors for atrial fibrillation in our patient were older age, male gender, obesity, hypertension, valvular disease, first-degree atrioventricular block and left anterior fascicle block. Atrial fibrillation appeared at the end of the infusion and ceased after a loading dose of amiodarone and suspension of LCM. Apixaban was initiated indefinitely five days later, and MRI showed four acute silent infarctions. The appearance of atrial fibrillation has severe therapeutic and clinical implications and the use of LCM might be reconsidered within a context of increased predisposition to developing atrial fibrillation. If atrial fibrillation appears, the drug should be discontinued and anticoagulation should be considered according to embolic risk. Further investigation is needed in order to better categorize the risk profile of lacosamide regarding atrial fibrillation.

Topics: Aged, 80 and over; Anticonvulsants; Atrial Fibrillation; Cerebral Infarction; Embolism; Humans; Infusions, Intravenous; Lacosamide; Male; Status Epilepticus

The lithium-pilocarpine model in rats is commonly used to study the characteristic events of acute status epilepticus (SE), epileptogenesis and temporal lobe epilepsy (TLE). Here we investigated the impact of lacosamide alone and in combination with other drugs (pregabalin, piracetam and scopolamine) on spontaneous recurrent seizures (SRSs) and behavioral parameters during the time frame of 6 weeks after SE. In addition, the level of oxidative stress in the hippocampus was accessed by real-time microdialysis study (8-isoprostanes) and antioxidants enzymes in the homogenate. Results revealed severe behavioral deficits with the control epileptic group and animals displayed hyperexcitability, aggression apprehension and memory insufficiency. Pharmacological manipulation for 6 weeks with lacosamide (L) - 80 mg/kg; in polypharmacy with pregabalin (L/P) - 50/50 mg/kg and piracetam (L/Pi) - 50/140 mg/kg significantly (P < 0.05) ameliorated the anxiety-related behavior (open filed, elevated plus maze, light/dark tests), depression (forced swim test) and improved spatial/reference memory (Morris water maze). There were low incidences of seizures in L, L/P and L/Pi groups revealing disease-modifying effects of employed drugs. Furthermore, the chronic use of scopolamine (L/P/S; 50/50/2 mg/kg) as polypharmacy with the concept of antagonizing the cholinergic inputs in the epileptogenic phase aberrated the behavioral situation further worse. Treatments with L/P and L/Pi significantly attenuated (P < 0.05) the oxidative stress by reducing 8-isoprostanes and malondialdehyde (MDA) levels. Furthermore, superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in the L/P group were significantly (P < 0.05) improved. Overall, our findings support the use of a combination of drugs (L/P and L/Pi) in lithium-pilocarpine model which remarkably ameliorated SRSs, reduced anxiety-related behaviors, retention of spatial/reference memory and lowered oxidative stress in a time-course evaluation 6 weeks post- SE insult.

Topics: Animals; Anticonvulsants; Behavior, Animal; Biomarkers; Brain; Disease Models, Animal; Drug Therapy, Combination; Lacosamide; Male; Maze Learning; Motor Activity; Open Field Test; Oxidative Stress; Pilocarpine; Rats, Sprague-Dawley; Status Epilepticus; Swimming; Time Factors

Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients.. The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus.. Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test.. The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats.. Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment.

Topics: Animals; Anticonvulsants; Cognition; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Emotional Regulation; Follow-Up Studies; Lacosamide; Male; Pilocarpine; Rats; Rats, Wistar; Status Epilepticus; Time Factors; Topiramate

Recently, we have reported that while agomelatine (Ago) is unable to prevent development of epilepsy it exerts a strong neuroprotective and anti-inflammatory response in the KA post-status epilepticus (SE) rat model. In the present study, we aimed to explore whether the brain-derived neurotrophic factor (BDNF) in the hippocampus is involved in the neuroprotective effect of Ago against the KA-induced SE and epileptiform activity four months later in rats. Lacosamide (LCM) was used as a positive control. The EEG-recorded seizure activity was also evaluated in two treatment protocols. In Experiment#1, Ago given repeatedly at a dose of 40 mg/kg during the course of SE was unable neither to modify EEG-recorded epileptiform activity nor the video- and EEG-recorded spontaneous seizures four months later compared to LCM (50 mg/kg). However, both Ago and LCM inhibited the expression of BDNF in the mossy fibers and also prevented neuronal loss in the dorsal hippocampal and the piriform cortex after SE. In Experiment#2, acute injection of Ago and LCM on epileptic rats, characterized by high seizure rates, did not prevent EEG-recorded paroxysmal events while only LCM decreased either absolute or relative powers of gamma (28-60 Hz) and high (HI) (60-120 Hz) frequency bands to baseline in the frontal and parietal cortex, respectively. Our results suggest that the protection against neuronal loss in specific limbic regions and overexpressed BDNF in the mossy fibers resulting from the repeated treatment with Ago and LCM, respectively, during SE is not a prerequisite for alleviation of epileptogenesis and development of epilepsy. In addition, a reduction of gamma and HI bands in the frontal and parietal cortex is not associated with EEG-recorded paroxysmal events after acute injection of LCM.

Topics: Acetamides; Animals; Brain-Derived Neurotrophic Factor; Disease Models, Animal; Electroencephalography; Epilepsy, Temporal Lobe; Hippocampus; Kainic Acid; Lacosamide; Male; Neurons; Neuroprotective Agents; Rats; Rats, Wistar; Seizures; Signal Transduction; Status Epilepticus

Since lacosamide was approved as an adjuvant agent for the treatment of medically refractory focal epilepsy over ten years ago, it is becoming more widely used for the treatment of idiopathic (genetic) generalized epilepsies. Several studies have demonstrated efficacy in reducing primary generalized tonic-clonic seizures (GTCS), but efficacy is less well-characterized for myoclonic and absence seizures. A 29-year-old man with juvenile myoclonic epilepsy and medically refractory GTCS on a combination of levetiracetam and topiramate was started on lacosamide adjunctive therapy with the plan to replace topiramate. While his GTCS became controlled, he was witnessed to have confusional episodes, with waxing and waning responsiveness, lasting a few days, several times a month. After eight months of adjunctive lacosamide therapy, he was admitted to the epilepsy monitoring unit, where paroxysms of generalized spike-and-wave complexes, lasting for 30-90 minutes, were recorded, interrupted only by sleep. During these periods, he demonstrated psychomotor slowing and disorientation on examination. The absence status was successfully broken by lorazepam, and lacosamide was discontinued. The patient had no further confusional episodes at the most recent follow-up visit, four months after discharge.

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Humans; Lacosamide; Male; Myoclonic Epilepsy, Juvenile; Seizures; Status Epilepticus

Generalized tonic status epilepticus (TSE) is a rare epileptic condition. It occurs usually in the context of symptomatic generalized epilepsy, in particular, in subjects with a diagnosis of Lennox-Gastaut syndrome, atypical forms of idiopathic (genetic) generalized epilepsy, or as a paradoxical effect during treatment with diverse antiepileptic drugs. Herein, we describe the case of an elderly woman on chronic treatment with psychotropic drugs who developed an episode of generalized TSE. Motor manifestations were subtle and difficult to recognize as seizures, and a detailed video-EEG importantly contributed to accurate and prompt diagnosis. TSE was initially refractory to conventional anti-seizure drug therapy including levetiracetam and valproate but was finally controlled with lacosamide. Our case indicates a potential therapeutic effect of lacosamide on TSE in the elderly after treatment failure with first-line anti-seizure drugs. [Published with video sequence on www.epilepticdisorders.com].

Topics: Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsy, Generalized; Female; Humans; Lacosamide; Status Epilepticus

Lacosamide is a new-generation antiepileptic drug (AED) that is eliminated by both hepatic and renal mechanisms. Lacosamide elimination by continuous renal replacement therapy (CRRT) has never been studied. The objective of this case report was to describe lacosamide pharmacokinetics in the setting of CRRT. We describe a single patient admitted to the study center with status epilepticus and multiorgan failure. The patient required both continuous venovenous hemofiltration (CVVH) and several AEDs. He was receiving intravenous lacosamide 200 mg twice/day at steady state prior to sampling. Plasma lacosamide concentrations were derived using a validated high-performance liquid chromatography method. Parameters were calculated using Phoenix WinNonlin 7.1 software. The peak concentration at steady state was 7.7 mg/L, the trough concentration was 5.9 mg/L (goal 5-12 mg/L). The volume of distribution was 0.7 L/kg, the elimination half-life was 21 hours, and the sieving coefficient was 0.8 (± 0.06). Lacosamide was cleared by CVVH as demonstrated by the sieving coefficient, but plasma concentrations remained within goal range throughout the dosing interval. These results may suggest that lacosamide 200 mg twice/day is a useful dosing strategy for critically ill patients who require CVVH.

Topics: Anticonvulsants; Critical Illness; Hemofiltration; Humans; Lacosamide; Male; Middle Aged; Status Epilepticus

Some studies suggest higher efficacy of lacosamide (LCM) in status epilepticus (SE) with higher loading doses; however, this weight-adjusted dose has not been evaluated.. The objective was to evaluate the relationship between loading weight-adjusted dose and efficacy of LCM in SE.. A group of patients with SE treated with LCM from Spanish hospitals was examined retrospectively. Demographic data, type of SE, etiology, response rate, last antiepileptic drug (AED) used, treatment line in which LCM was used, total loading dose, and weight-adjusted dose were collected.. One hundred sixty-five cases of SE were collected; 87 (52.7%) patients had nonconvulsive SE. Mean age was 64.2 ± 17.2 and 60.6% (n = 100) were men. Regarding etiology, SE was considered as acute symptomatic in 85 (51.5%), remote symptomatic in 51 (30.9%), progressive symptomatic in 10 (6.1%), and cryptogenic in 19 (11.5%). Lacosamide was used as the third drug in 46.1%, and as a second option in 28%. In 115 patients, clonazepam had been used as the first option, and no benzodiazepines had been administered in the remaining 50. The median loading dose was 400 mg (100-600 mg), and the weight-adjusted dose was 5 mg/kg (3-6 mg/kg). The response rate was 63.3%, and 55.1% responded within the first 12 h. Efficacy was significantly higher in patients who had taken benzodiazepines at LCM loading doses >5.3 mg/kg (p = 0.006). This relationship was maintained independent of using other concomitant AEDs. However, if benzodiazepines were not taken, this relationship was not found.. In adults with benzodiazepine-resistant SE, the response rate to LCM was higher, with weight-adjusted doses above 5.3 mg/kg.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Lacosamide; Male; Middle Aged; Retrospective Studies; Spain; Status Epilepticus; Treatment Outcome; Young Adult

Currently, lacosamide (LCM) is not approved for use in status epilepticus (SE) but several shreds of evidence are available to support its use. The present study was, therefore, undertaken to evaluate the effect of LCM on pilocarpine (PILO) induced SE and neurodegeneration in C57BL/6 mice and to ascertain the involvement of CRMP-2 in mediating above effect.. Pilocarpine-induced SE model was developed to explore the effect of LCM 20, 40 and 80 mg/kg in mice. We assessed the seizure severity, seizure latency, spontaneous alternation behavior (SAB) and motor coordination by behavioral observation. Histopathological evaluation and measurement of the levels of CRMP-2, reduced glutathione (GSH) and malondialdehyde (MDA) were carried out in mice hippocampus.. LCM exhibited a biphasic effect i.e., protection against SE at 20 mg/kg and 40 mg/kg dose whilst aggravated seizure-like behavior and mortality at 80 mg/kg. Further, it increased percentage alternation (i.e., restored spatial memory) in SAB and elevated motor impairment with increasing dose. Histologically, LCM 20 mg/kg and 40 mg/kg (but not 80 mg/kg) reduced neurodegeneration. LCM 20 mg/kg and 40 mg/kg reversed the elevated MDA and GSH levels while 80 mg/kg showed a tendency to increase oxidative stress. In contrast, LCM (at all doses) reversed the pilocarpine-induced elevation of collapsin response mediator protein-2 (CRMP-2).. LCM protected against pilocarpine-induced SE, associated neurodegeneration and improved pilocarpine-associated impairment of spatial memory. The study reveals that CRMP-2 may not be mediating the inverted-U-response of LCM at least in pilocarpine model. Therefore, the anti-oxidant effect of LCM (and not its ability to modulate CRMP-2) was anticipated as the mechanism underlying neuroprotection.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Glutathione; Hippocampus; Intercellular Signaling Peptides and Proteins; Lacosamide; Lipid Peroxidation; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Motor Activity; Muscarinic Agonists; Nerve Tissue Proteins; Oxidative Stress; Pilocarpine; Status Epilepticus

Intravenous (IV) lacosamide use for status epilepticus has increased in recent years and is recommended for refractory status epilepticus by current guidelines. Per the lacosamide package labeling, the preferred route of administration is diluted and infused over 30-60 min; however, administration undiluted is also acceptable and recent literature demonstrated safety at a maximum rate of 80 mg per minute (Kellinghaus et al. in Acta Neurol Scand 123:137-141, 2011). Undiluted administration as an IV push has potential to increase efficiency of administration to patients needing urgent seizure control since it may be dispensed from automatic dispensing cabinets in patient care areas. This study aims to compare safety outcomes and efficiency of administration in patients receiving lacosamide IV push compared to IV piggyback.. We present a single-center, retrospective cohort study of patients receiving lacosamide via IV piggyback or IV push from June 2016 to July 2017. Baseline characteristics, data related to potential safety concerns and timing of ordering, verification, and administration were collected. The primary safety outcomes were incidence of infusion site reactions, hypotension (systolic blood pressure [SBP] < 90 mm Hg), and bradycardia (heart rate [HR] < 50 beats per minute) documented within 2 h of each lacosamide dose. Secondary safety outcomes included the incidence of PR interval prolongation in patients with at least one electrocardiogram measured. The primary efficiency outcome was the time between order verification and administration.. Patients in the IV piggyback (n = 88) and IV push (n = 78) groups had similar baseline characteristics, initial dose, SBP, and HR. Hypotension (8 vs. 10.3%) and bradycardia (2.3 vs. 2.6%) rates were similar among both groups (p > 0.05). Only one patient in each group had documented PR prolongation, and no documented infusion reactions occurred. Median time from order verification to administration was significantly reduced in the IV push group (35 min vs. 1 h 49 min; p < 0.001).. Administration of lacosamide via IV push results in similar adverse effect rates to IV piggyback preparations with more efficient time to administration.

Topics: Aged; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus

Mossy fiber sprouting (MFS) and neuronal loss are important pathological features of chronic epilepsy closely related to the development of spontaneous recurrent seizures. However, the pathological mechanism of MFS remains unclear. Collapsin response mediator protein 2 (CRMP2) is a cytoplasmic protein highly expressed in the nervous system and is involved in axon/dendrite specification and axonal growth. It is possibly associated with the development of MFS. Lacosamide (LCM), a novel antiepileptic drug, was recently found to inhibit the CRMP2-mediated neurite outgrowth. Therefore, we studied the relationships between LCM, CRMP2, and MFS, seeking potential therapeutic targets for epileptogenesis and a better understanding of the mechanism of action of LCM. We used kainic acid to induce status epilepticus in an animal model and examined the resultant changes in protein expression by Western blot and changes in histology by specific staining for cell death and MFS. Our results showed that the expression level of CRMP2 was elevated and the expression level of phosphorylated CRMP2 (p-CRMP2) was reduced following status epilepticus. Administration of LCM not only reversed this effect but also suppressed spontaneous recurrent seizures and reduced MFS and loss of hippocampal neurons. This study reveals that, in addition to its antiseizure efficacy, LCM has a neuroprotective effect and inhibits the development of epilepsy. CRMP2 is possibly involved in the mechanism by which LCM suppresses MFS and is expected to be a new therapeutic target for treating epileptogenesis.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Fluoresceins; Intercellular Signaling Peptides and Proteins; Kainic Acid; Lacosamide; Male; Mice; Mossy Fibers, Hippocampal; Nerve Tissue Proteins; Rats, Wistar; Status Epilepticus; Time Factors

We explored the influence of four different efficacy criteria on the results of observational studies concerning the treatment of status epilepticus (SE) and its subtypes. We compared and contrasted the results of four different efficacy criteria for the effectiveness of phenytoin, valproate, levetiracetam, and lacosamide. Criterion 1=the last antiepileptic drug (AED) administered before SE termination. Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication. Criterion 3=the last drug introduced into the antiepileptic therapy or increased in dose within 24h before termination of the SE without changes in the co-medication. Criterion 4=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE even allowing changes in the co-medication. We used two-tailed χ

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Health Behavior; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

Intravenous lacosamide (LCM) is increasingly used in the treatment of status epilepticus (SE), but optimal loading dose and target serum levels are unclear. We analysed the correlation between LCM serum levels after intravenous loading dose and clinical response.. Retrospective study in two centres from December 2014 to May 2016 including consecutive SE patients treated with LCM, in which trough serum levels after intravenous loading dose were available. Trough levels were correlated with the loading dose and the clinical response, defined as LCM introduction terminating SE without the need of further treatment. Correlations were adjusted for other SE characteristics.. Among 40 patients, 16 (40%) responded to LCM. LCM serum concentrations within the reference interval (10-20mg/l) were associated with loading doses of >9mg/kg (p=0.003; χ2). However, we observed no difference between LCM serum levels in responders (median 10.4mg/l) versus non-responders (median 9.5mg/l; p=0.36; U test), even after adjusting for other predictors of clinical outcome (SE severity, aetiology, and number of previous treatment).. High intravenous LCM loading doses (>9mg/kg) were associated with serum levels within the reference interval, there was however no correlation with the clinical response. Prospective studies are needed to evaluate the benefit of increasing the LCM loading dose in SE.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Female; Humans; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Treatment Outcome

Status epilepticus (SE) often does not respond to initial treatment. A second-line agent with a less established safety and efficacy profile is then required. This study examined the safety of intravenous (IV) lacosamide (LCM) in a critically ill population and obtained an estimate of effectiveness in patients with refractory SE on continuous video EEG monitoring (cEEG).. Retrospective review of critically ill patients in SE on cEEG treated with IV LCM from June 2009 to April 2011.. Eighty-four patients in SE (43 F/41 M), mean age 59.6 years, were identified; and 59.5 % had nonconvulsive SE. The most common etiologies were ischemic and hemorrhagic strokes. There were no significant changes in serial blood pressure monitoring, PR prolongation, aspartate aminotransferase (AST), or creatinine pre- and post-LCM. There was a significant increase in alanine aminotransferase (ALT) from days 1-7 (p = 0.031). Fifty-one patients were LCM-naïve. In these patients, cessation of SE on cEEG after LCM occurred in 15.7, 25.5, 58.8, and 82.4 % by 4, 12, 24, and 48 h, respectively.. IV LCM appears safe short term in critically ill patients with SE. The retrospective estimate of effectiveness for LCM appears promising for management in SE. Prospective, randomized controlled studies are needed to better determine the role of LCM in treating SE.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Critical Illness; Drug Resistant Epilepsy; Female; Humans; Lacosamide; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Status Epilepticus; Young Adult

Topics: Acetamides; Aged; Anticonvulsants; Humans; Lacosamide; Male; Status Epilepticus; Stevens-Johnson Syndrome

Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus.. Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide.. Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient.. In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg.

Topics: Acetamides; Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Lacosamide; Male; Retrospective Studies; Status Epilepticus; Treatment Outcome

to evaluate the efficacy and safety of intravenous (IV) lacosamide (LCM) in the treatment of seizure clusters (SC) and status epilepticus (SE) in hospitalized adult patients.. we prospectively analyzed treatment response, seizure outcome, and adverse effects of IV LCM in 38 patients with seizure emergencies (15 with SC, 23 with SE) during a hospital stay. The loading dose of IV LCM was 200-400mg and the maintenance dose was 200-400mg daily. Response to IV LCM was evaluated within 20min, 4h and 24h of LCM infusion.. an acute anti-seizure effect after IV LCM was especially evident when it was first used - (SC) or second line (established SE) treatment. In particular, 87% of SC patients (13/15) and 80% of established SE (8/10) demonstrated response to LCM treatment, while no patients with super-refractory SE (0/8) responded to IV LCM according to our criteria. The loading of IV LCM was well tolerated, with mild adverse effects (2/38 temporary dizziness). In most patients, during and after administration of the loading dose of IV LCM a temporary (30min-1h) sedation was observed. No ECG and laboratory values-changes were documented in any of the patients.. LCM is an effective and well-tolerated treatment when used to treat SC in hospitalized adult patients. As add-on therapy, it may be useful to stop seizure activity in patients with focal SE not responding to first/second-line intravenous AEDs.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain; Electroencephalography; Female; Hospitalization; Humans; Inpatients; Lacosamide; Male; Middle Aged; Prospective Studies; Seizures; Status Epilepticus; Treatment Outcome

Two cases with partial onset epilepsy who developed status epilepticus (SE) on lacosamide (LCM) monotherapy are reported. LCM is an effective adjunctive antiepileptic drug (AED) for partial-onset epilepsy and as infusion in SE. It has also shown efficacy in monotherapy. The reported cases achieved control of seizures with adjunctive LCM treatment and were afterwards converted to monotherapy. Both patients subsequently developed SE while on LCM monotherapy. They were on monotherapy for at least 2 months after withdrawal of concomitant AEDs precluding the possibility of withdrawal-induced SE. Pharmacovigilance is indicated when LCM is administered in monotherapy in order to assess its proper therapeutic potential and its putative limitations especially in cases where it may prove ineffective. Moreover, vigilance is necessary whenever any concomitant antiepileptic is tapered regardless of the substances used. Higher doses may be needed when an AED is used in monotherapy.

Topics: Acetamides; Adult; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsies, Partial; Humans; Lacosamide; Male; Middle Aged; Seizures; Status Epilepticus; Treatment Outcome

Status epilepticus (SE) is an important emergency situation associated with high morbidity and mortality. The goal of pharmacological therapy-rapid seizure termination-is only achieved in just over half of patients with first-line anti-epileptic drug (AED) therapy and many patients require second and higher lines of AEDs to achieve seizure termination; therefore, there is a clear need for more effective treatment options. Lacosamide is a relatively new AED and the intravenous formulation has shown promise for treatment of SE. The aim of the current study was to compare electroencephalographic (EEG) response and seizure termination with intravenous lacosamide (±other AEDs) in patients with convulsive versus non-convulsive SE, in a Spanish intensive care setting.. In this prospective, observational study, patients with convulsive or non-convulsive SE who received intravenous lacosamide 400 mg/day for 8 days were compared in terms of EEG response and seizure termination. Adverse events were not specifically assessed.. Fifty-three patients (69.8 % male; mean age 55.2 years) were treated with lacosamide (mean dose 390.6 mg) as first- (20.8 %), second- (34 %), third (22.6 %) or fourth-line (22.6 %) treatment for convulsive (n = 23, 43.4 %) or non-convulsive (n = 30, 56.6 %) SE. The majority of patients (73.6 %) had a comorbid condition, predominantly hypertension (35.8 %), and most (79.2 %) received at least one concomitant AED, including midazolam (54.7 %), valproic acid (52.8 %), and levetiracetam (30.2 %). Patient characteristics and treatment received did not differ significantly between the convulsive and non-convulsive SE groups. EEG recordings following lacosamide treatment demonstrated the elimination of paroxysmal activity (disappearance and/or attenuation of epileptiform activity in >60 % of recording time) in 56.6 % of patients; 69.6 % of convulsive and 46.7 % of non-convulsive SE groups. Among all patients, 90.6 % showed some EEG improvement (disappearance of epileptiform activity in <30 % total recording time or disappearance and/or attenuation of epileptiform activity in 30-60 % total recording time); and there was no significant between-group difference for achievement of seizure termination (90.0 vs. 91.3 % for non-convulsive vs. convulsive SE).. Intravenous lacosamide (±other AEDs) was similarly effective in patients with convulsive or non-convulsive SE. Further investigation into the use of lacosamide in the treatment of SE is warranted.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Anticonvulsants; Electroencephalography; Female; Humans; Lacosamide; Male; Middle Aged; Prospective Studies; Status Epilepticus

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy. A male infant was born on pregnancy week 36, weighing 2.2kg. Both levetiracetam and and lacosamide were present in cord blood in levels similar to those in maternal blood. The infant was partially breast-fed and experienced poor feeding and sleepiness, starting to resolve after two first weeks. Milk samples were drawn 5 days after the delivery and a blood sample from the infant 3 days later. Lacosamide level in milk was low, resulting in an estimated relative infant dose of 1.8% of the maternal weight-adjusted daily dose in a fully breast-fed infant. This is the first case describing lacosamide use during pregnancy and lactation.

Topics: Acetamides; Adult; Anticonvulsants; Female; Fetal Blood; Humans; Infant, Newborn; Lacosamide; Levetiracetam; Male; Milk, Human; Piracetam; Pregnancy; Status Epilepticus; Venous Thrombosis

A restrospective review of patients treated in the ICU for refractory status epilepticus who had received an initial IV loading dose of lacosamide (LCS) was performed. A total of 142 patients were identified. The first 34 patients received 400mg which by weight-based measurement ranged from 2 to 11 mg/kg. Higher mg/kg dosing had been used subsequently with doses up to 13 mg/kg. No patient required reduction in rate or cessation of infusion. Initiation of pressor agents was not needed during the infusion of the loading dose. Postinfusion LCS blood levels were drawn, and dosing of 10-12 mg/kg and higher resulted in blood levels above 15 μg/ml while doses of 2-6 mg/kg resulted in levels below 10 μg/ml. We conclude that a weight-based loading dose of 10-12 mg/kg at an infusion rate of 0.4 mg/kg/min is safe and will produce levels of 15 μg/ml and higher. This article is part of a Special Issue entitled "Status Epilepticus".

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Resistant Epilepsy; Electroencephalography; Female; Humans; Intensive Care Units; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Young Adult

Nearly one third of patients presenting with mesial temporal lobe epilepsy (MTLE), the most prevalent lesion-related epileptic disorder in adulthood, do not respond to currently available antiepileptic medications. Thus, there is a need to identify and characterize new antiepileptic drugs. In this study, we used the pilocarpine model of MTLE to establish the effects of a third generation drug, lacosamide (LCM), on seizures, interictal spikes and high-frequency oscillations (HFOs, ripples: 80-200 Hz, fast ripples: 250-500 Hz).. Sprague-Dawley rats (250-300 g) were injected with pilocarpine to induce a status epilepticus (SE) that was pharmacologically terminated after 1h. Eight pilocarpine-treated rats were then injected with LCM (30 mg/kg, i.p.) 4h after SE and daily for 14 days. Eight pilocarpine-treated rats were used as controls and treated with saline. Three days after SE, all rats were implanted with bipolar electrodes in the hippocampal CA3 region, entorhinal cortex (EC), dentate gyrus (DG) and subiculum and EEG-video monitored from day 4 to day 14 after SE.. LCM-treated animals showed lower rates of seizures (0.21 (± 0.11) seizures/day) than controls (2.6 (±0.57), p<0.05), and a longer latent period (LCM: 11 (± 1) days, controls: 6.25 (± 1), p<0.05). Rates of interictal spikes in LCM-treated rats were significantly lower than in controls in CA3 and subiculum (p<0.05). Rates of ripples and fast ripples associated with interictal spikes in CA3 and subiculum as well as rates of fast ripples occurring outside of interictal spikes in CA3 were also significantly lower in LCM-treated animals. In controls, interictal spikes and associated HFOs correlated to seizure clustering, while this was not the case for isolated HFOs.. Our findings show that early treatment with LCM has powerful anti-ictogenic properties in the pilocarpine model of MTLE. These effects are accompanied by decreased rates of interictal spikes and associated HFOs. Isolated HFOs were also modulated by LCM, in a manner that appeared to be unrelated to its antiictogenic effects. These results thus suggest that distinct mechanisms may underlie interictal-associated and isolated HFOs in the pilocarpine model of MTLE.

Topics: Acetamides; Animals; Anticonvulsants; Disease Models, Animal; Electrocorticography; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Hippocampus; Lacosamide; Male; Pilocarpine; Rats, Sprague-Dawley; Seizures; Status Epilepticus; Treatment Outcome; Video Recording

The treatment of refractory status epilepticus (RSE) remains largely empirical. Lacosamide (LCM) is a new anticonvulsant available in intravenous (IV) form, but its optimal dosing regimen for the treatment of RSE is unknown. We compared safety and efficacy of two loading doses: 200 and 400 mg.. Prospective observational study of all patients who received IV LCM for RSE or seizure clusters between October 2010 and December 2012. A first group received an IV load of 200 mg of LCM. After the initial part of the study, and due to poor results with this dosage, a second group received a loading dose of 400 mg. Outcome measures included response rate, time to response, and adverse events.. There was a trend in favor of a higher response rate to LCM in the 400 mg group [7/14 (50 %) vs. 2/11 (18 %), respectively; p = 0.2]. Early responses (occurring within 3 h of initiation of LCM) were significantly more frequent in the 400 mg group [4/14 (28 %) vs. 0/11 (0 %); p = 0.026]. Overall, 9/25 patients (36 %) responded to LCM and seizures were terminated in eight more patients (32 %), by adding other anticonvulsants. The following adverse events were attributed to LCM: myoclonus and confusion, increase in seizure frequency, vertigo, ataxia, and an asymptomatic increase in liver enzymes level. All occurred in the 200 mg group. No skin rash, renal, cardiac, or hemodynamic side effects were observed in any group.. In this small prospective observational study, an initial dose of 400 mg of IV LCM was associated with a higher proportion of early termination of RSE and with a trend toward a higher response rate.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Critical Care; Dose-Response Relationship, Drug; Drug Resistance; Female; Humans; Lacosamide; Male; Middle Aged; Prospective Studies; Status Epilepticus; Treatment Outcome; Young Adult

To compare intravenous phenytoin (PHT) and intravenous lacosamide (LCM) for treatment of status epilepticus after failure of the first and second drug.. We retrospectively identified patients from a large community hospital in northern Germany who had been diagnosed with SE between August 2008 and December 2010. Patients who had failed to respond to the first two drugs were selected for this analysis.. Forty-six patients (23 female, median age 68 years) were identified. LCM was used as third drug in 21 patients (median bolus 400 mg) and PHT in 15 patients (median bolus 1500 mg). Pretreatment was similar regarding substance groups (benzodiazepine as first line, levetiracetam as second line drug) and bolus doses. Status epilepticus was terminated in six patients (40%) of the PHT group and in seven patients (33%) of the LCM group. Four patients (27%) of the PHT group and no patient of the LCM group suffered from a relevant, treatment-related side effect during administration of the third drug.. Lacosamide and PHT showed similar success rates for treatment of SE when used after failure of benzodiazepines and levetiracetam. However, PHT was associated with relevant side effects that were not seen with LCM.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Female; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retreatment; Retrospective Studies; Status Epilepticus; Treatment Outcome; Young Adult

Topics: Acetamides; Electroencephalography; Female; Humans; Lacosamide; Middle Aged; Status Epilepticus; Treatment Outcome

Status epilepticus (SE) is considered a life-threatening medical emergency. First-line treatment with antiepileptic drugs (AEDs) consists of intravenous benzodiazepines followed by phenytoin. SE is considered refractory (RSE) when unresponsive to standard doses of the first two AEDs. Scarce evidence is available to support specific guidelines for the management of RSE in either adults or children. This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in children affected by RSE.. Children with RSE who were treated with ivLCM were included in the study. Efficacy was defined as the cessation of seizures after administration of ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following standard protocols before ivLCM was administered.. Eleven children entered the study (mean age: 9.4 years). Etiology was symptomatic in 7 patients (63%). RSE was convulsive (focal or generalized) in 6 patients and nonconvulsive in 5. The mean initial bolus dose of LCM was 8.6 mg/kg. The drug, which was used as a fourth or later option, was effective in stopping RSE in 45% of patients, with seizures terminating within 12 h in three children. No serious adverse events attributable to LCM were reported.. LCM might be an effective and well-tolerated AED in children with RSE.

Topics: Acetamides; Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Humans; Italy; Lacosamide; Male; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤ 24 h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose >200mg versus ≤ 200 mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cohort Studies; Emergency Service, Hospital; Factor Analysis, Statistical; Female; Humans; Lacosamide; Logistic Models; Male; Middle Aged; Observation; Reaction Time; Status Epilepticus; Time Factors; Treatment Outcome; Young Adult

Topics: Acetamides; Anticonvulsants; Electroencephalography; Humans; Lacosamide; Male; Middle Aged; Status Epilepticus

Refractory status epilepticus (RSE) is an emergency with high mortality requiring neurointensive care. Treatment paradigms include first-generation antiepileptic drugs (AEDs) and anesthetics. Lacosamide (LCM) is a new AED, holding promise as a potent treatment option for RSE. High-level evidence regarding safety and efficacy in the treatment of RSE is lacking.. The objective of the study was to evaluate the safety profile and efficacy of intravenous (i.v.) LCM as an add-on treatment in adult RSE patients.. All consecutive RSE patients treated in the intensive care units (ICUs) of an academic tertiary care center between 2005 and 2011 were included. Severity of status epilepticus (SE) was graded by the SE Severity Scale (STESS), and SE etiology was categorized according to the guidelines of the International League Against Epilepsy (ILAE). Outcomes were seizure control, RSE duration, and death.. Of 111 RSE patients, 53 % were treated with LCM. Twenty-five patients with hypoxic-ischemic encephalopathy were excluded. Mortality was 30 %. Mean number of AEDs, duration, severity, and etiology of SE, as well as critical medical conditions did not differ between patients with and without LCM. While age tended to be higher, critical interventions, such as the use of anesthetics and mechanical ventilation, tended to be less frequent in patients with LCM. Seizure control tended to be achieved more frequently in patients with LCM (odds ratio, OR 2.34, 95 % CI 0.5-10.1, p = 0.252). Among patients with LCM, 51 % received LCM as the last AED (including hypoxic-ischemic encephalopathy), allowing the reasonable assumption that LCM was responsible for seizure control, which was achieved in 91 %. Multivariable analysis revealed a decreased mortality in patients with LCM (OR 0.34, 95 % CI 0.1-0.9, p = 0.035). A possible confounder in this context was the implementation of continuous video-electroencephalography (EEG) monitoring 6 months prior to the first use of i.v. LCM. There were no serious LCM-related adverse events.. LCM had a favorable safety profile as adjunctive treatment for RSE. Its use was associated with decreased mortality of RSE-a finding that might have been confounded by the implementation of continuous video-EEG monitoring in the ICU prior to the use of i.v. LCM, leading to heightened awareness as well as earlier diagnosis and treatment of SE. Randomized trials are warranted to further strengthen the evidence of efficacy of LCM for RSE treatment.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Anticonvulsants; Cohort Studies; Electroencephalography; Female; Humans; Intensive Care Units; Lacosamide; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Severity of Illness Index; Status Epilepticus; Tertiary Care Centers; Treatment Outcome; Video Recording

To evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients.. We enrolled 16 patients (7 M/9 F; 77 ± 7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400 mg over 30 min, followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24 h following treatment, as evaluated by EEG recording and clinical observation.. LCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45-60 min after administration. None of these patients relapsed in the following 24 h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six.. This pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data.

Topics: Acetamides; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Lacosamide; Male; Status Epilepticus; Stroke; Treatment Outcome

Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are electrographic seizures (ESz) that are not associated with overt clinical seizure activity. NCS are distinct ESz, whereas NCSE has ongoing, continuous electrographic seizure activity. Both are common in critically ill patients admitted to hospital intensive care units (ICUs), and studies have shown that about 20% of ICU patients undergoing continuous electroencephalography (cEEG) monitoring will have NCS/NCSE. Although the treatment for convulsive SE is well established, there is no clear consensus for the treatment of NCS/NCSE. Antiepileptic drugs (AEDs), such as phenytoin (PHT) and fosphenytoin (fPHT), used in convulsive SE are also used to treat NCS/NCSE despite lack of data for their appropriateness for these conditions. Recent studies have shown that very aggressive treatment of NCSss/NCSE can lead to worse outcomes because the AEDs used can have significant adverse effects. Recently, several intravenous (IV) AEDs have become available for substitution therapy when their oral use is not possible. There are retrospective case reports and case series that suggest that these AEDs may be beneficial for treatment of NCS/NCSE. The Treatment of Recurrent Electrographic Nonconvulsive Seizures (TRENdS) Study will compare the efficacy and tolerability of fPHT and lacosamide in patients having NCS as noted by cEEG monitoring. The study is currently open to recruitment and has 13 sites in the United States. A total of 200 subjects will be randomized, 100 to each treatment arm.

Topics: Acetamides; Anticonvulsants; Electroencephalography; Humans; Lacosamide; Monitoring, Physiologic; Phenytoin; Retrospective Studies; Secondary Prevention; Status Epilepticus; Treatment Outcome

Lacosamide (LCM) is a treatment option for status epilepticus (SE) described in several series. We therefore proposed to describe its use in status epilepticus patients in our hospital. All patients admitted to our hospital for SE from September 2010 to April 2012 were evaluated. We collected related variables including the type of SE, etiology, antiepileptic drugs (AEDs) used, loading dose of AEDs, cessation of SE after AEDs, ICU admission and mortality. In those patients receiving LCM, we reviewed the infusion rate and time to response. We compared patients receiving LCM with patients in whom it was not used. This was a retrospective and uncontrolled study. A total of 92 patients were included; 67.7 % of SE patients who received LCM responded to treatment. The vast majority of the patients presented non-convulsive and motor focal SE. When we selected patients to receive four or more AEDs, the LCM efficacy was 55.6 %, a very similar result compared to when it was not used. Subsequently, we analyzed the sample regarding the AED administered as the second or third line of treatment, and the responder rate was significantly higher when LCM was used (84.6 vs. 47.8 %, p 0.041). After an adjusted regression analysis, the use of LCM was independently associated with cessation of SE. The total percentage of undesirable effects was very low (12 %), and they were all mild. No relationship was found between a specific etiology and better response. LCM is a useful drug that represents an alternative in the treatment of non-convulsive or focal motor SE. Its efficacy might be more important when it is administered as a second or third option after benzodiazepines. A randomized trial is required to confirm these results.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Treatment Outcome; Young Adult

Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE.. Patients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added.. Thirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported.. LCM might be a fast, effective and safe add-on treatment in RSE.

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Therapy, Combination; Female; Humans; Lacosamide; Male; Middle Aged; Prospective Studies; Spain; Status Epilepticus; Treatment Outcome; Young Adult

Seizures are common in critically ill patients and can impact morbidity and mortality. Traditional anti-epileptic drugs (AEDs) in this setting are not always effective and are associated with adverse events and drug interactions. Lacosamide (LCM) is a new AED which is available in parental form although few studies have evaluated the safety and efficacy of LCM in critically ill patients.. Critically ill patients at Emory University Hospital who received LCM from April 1, 2009 to February 1, 2010 were retrospectively reviewed. Primary outcome measure was incidence and time to seizure cessation. Adverse effects were also recorded.. LCM was administered in 24 patients including 13 episodes of refractory status epilepticus (RSE) occurring in 10 patients and for treatment of isolated seizures or following resolution of RSE in an additional 14 patients. Seizure cessation was achieved in 5/13 (38%) episodes of RSE (mean 11.2 h) while there was at least a 50% decrease in seizure frequency in 7/13 (54%). 11/14 patients (76%) who received LCM for treatment of isolated seizures or prevention of seizure recurrence remained seizure free. Three patients experienced a decline in systolic blood pressure (> 20 mmHg) while one patient experienced unexplained fever and one patient had elevation of liver function tests.. This preliminary data suggests that LCM may be a safe and effective alternative for treatment of seizures in critically ill patients. Further prospective, randomized controlled trials are needed to confirm these findings and further explore the incidence of adverse effects.

Topics: Acetamides; Adult; Aged; Aged, 80 and over; Anticonvulsants; Critical Illness; Female; Humans; Hypotension; Intensive Care Units; Lacosamide; Male; Middle Aged; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

Many patients present with refractory Status epilepticus (SE) despite multiple anti-epileptic drugs (AEDs). Lacosamide (LCM) was recently approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. LCM has demonstrated efficacy in animal models of pharmacoresistant seizures. To date, there are isolated anecdotal reports of LCM use in SE.. To report a single center experience with IV Lacosamide in patients with NCSE.. Pharmacy records were reviewed to identify patients with SE who received IV LCM in our institution. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring.. 10 patients (4 men, 6 women), age 16-90 years with refractory SE were given LCM. Eight patients were in focal non-convulsive SE (NCSE), 2 were in generalized non-convulsive SE. The etiologies included anoxic brain injury, idiopathic, encephalitis, tumor, posterior reversible encephalopathy syndrome (PRES), stroke, and AVM. IV LCM was added after traditional AEDs, including drug-induced coma in some, failed to control the SE. NCSE resolved in 7/10 patients whereas 1/10 patient showed partial response with cessation of NCSE but still frequent electrographic seizures and 2/10 patients were resistant to therapy.. LCM is a useful adjunct in refractory NCSE. The IV formulation allows prompt administration in the intensive care unit setting. Response was seen especially in focal SE. Similar to other AEDs, response was poor in patients with postanoxic injury. Our data is limited by the small number of patients. Larger controlled studies are necessary to assess accurately the efficacy of IV LCM as an early treatment of SE.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Young Adult

Topics: Acetamides; Anticonvulsants; Drug Resistance; Humans; Lacosamide; Status Epilepticus

Lacosamide has been reported to have been successfully used for non-convulsive status epilepticus after benzodiazepine failure, and convulsive status epilepticus after benzodiazepine and levetiracetam failure. We report a case of simple motor status epilepticus refractory to benzodiazepines and multiple anti-epileptic medications (AEDs) over 4 days. The addition of lacosamide in combination with existing levetiracetam aborted the continuous seizure with maintenance of seizure freedom through the most recent follow-up at 4 weeks.

Topics: Acetamides; Anticonvulsants; Humans; Lacosamide; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Status Epilepticus

Lacosamide (LCM) is a novel antiepileptic drug (AED) recently approved as an adjunctive therapy in the treatment of partial seizures in adults. LCM is available in oral and intravenous formulations, has linear pharmacokinetics and a unique mechanism of action.. To evaluate the safety and efficacy of intravenous LCM in the treatment of nonconvulsive status epilepticus (NCSE) after failure of conventional therapy.. We retrospectively reviewed all patients with NCSE treated with LCM. We reviewed the clinical and electrographic changes before and after LCM administration. We also noted any reported side effects including electrocardiographic changes.. We report four cases of NCSE that were refractory to conventional treatment, but readily responsive to LCM. No side effects attributable to LCM were identified.. Intravenous LCM may be safe and efficacious as an add-on AED for the treatment of NCSE when standard therapy fails.

Topics: Acetamides; Aged; Anticonvulsants; Electroencephalography; Female; Humans; Injections, Intravenous; Lacosamide; Middle Aged; Retrospective Studies; Single-Blind Method; Status Epilepticus; Treatment Outcome

Case reports suggest lacosamide may have a role in status epilepticus (SE). The purpose of this case series is to describe the use of lacosamide in refractory SE (RSE) at our institution.. Observational study of all patients admitted to the neurosciences intensive care unit with RSE who received at least one dose of lacosamide from October 2009 to September 2010.. Nine patients received lacosamide after failure of at least two other agents. Lacosamide was started a median of 2 days (range: 0-14 days) after the onset of SE. The most frequently used dosing regimen was an initial intravenous dose of 200 mg followed by 200 mg every 12 h. Most patients had received 3 (range: 2-5) AEDs prior to lacosamide. Levetiracetam was used prior to lacosamide in all cases. No patients evaluated responded to lacosamide according to our predefined criteria. One patient developed angioedema after receiving two doses; another patient developed angioedema where timing in relation to the lacosamide was unclear. Care was withdrawn in three of the nine patients for reasons unrelated to lacosamide. Lacosamide was continued at discharge on all surviving patients except in one case of angioedema.. This is the largest case series to date describing the use of lacosamide in patients with RSE. Despite the novel mechanism of action, we observed no evidence that lacosamide is effective in RSE; however, our sample size was small. Further study is needed to determine the role of lacosamide in SE, especially early in the treatment course.

Topics: Acetamides; Aged; Aged, 80 and over; Angioedema; Anticonvulsants; Drug Administration Schedule; Drug Eruptions; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intensive Care Units; Lacosamide; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus

The effective management of status epilepticus (SE) continues to be a therapeutic challenge. The aim of this study was to investigate the efficacy of lacosamide treatment in an experimental model of self-sustaining SE. Rats were treated with lacosamide (3, 10, 30 or 50mg/kg) either 10 min (early treatment) or 40 min (late treatment) after the initiation of perforant path stimulation. Early lacosamide treatment significantly and dose-dependently reduced acute SE seizure activity; late treatment showed only a non-significant trend toward reduced seizure activity. Early lacosamide treatment also dose-dependently reduced the number of spontaneous recurrent seizures following a 6-week waiting period, with 70% reduction at the highest dose tested (50mg/kg); there was also a significant reduction in the number of spikes and the cumulative time spent in seizures. Late treatment with high-dose lacosamide (30-50mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P<.05), but did not significantly reduce seizure severity or frequency in rats that developed spontaneous recurrent seizures. The results presented here suggest that lacosamide deserves investigation for the clinical treatment of SE. Potential for disease modification in this rat model of self-sustaining SE will require further studies.

Topics: Acetamides; Analysis of Variance; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Lacosamide; Rats; Self Administration; Status Epilepticus; Time Factors

Status epilepticus (SE) is a frequent neurological emergency requiring immediate treatment. Therapy usually requires intravenous anticonvulsive medication. Lacosamide is a novel anticonvulsant drug that is available as infusion solution. We describe seven patients with focal SE who were treated with intravenous Lacosamide. All patients in our case series were unsuccessfully treated with other antiepileptic drugs before Lacosamide i.v. was added. In all cases, SE was terminated within 24 h after Lacosamide. There were no serious side effects or adverse events attributable to Lacosamide i.v. Our data suggest that Lacosamide might be an effective add-on treatment, if standard drugs fail or are unsuitable.

Topics: Acetamides; Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Lacosamide; Male; Middle Aged; Status Epilepticus; Treatment Outcome

Subacute encephalopathy with seizures in chronic alcoholism (SESA) was first described in 1981 by Niedermeyer who reported alcoholic patients presenting with confusion, seizures and focal neurological deficits and is quite distinct from patients presenting with typical alcohol withdrawal seizures. EEG often reveals periodic discharges and spikes, but SESA presenting with non-convulsive status epilepticus has rarely been described. We report a case of SESA with non-convulsive status epilepticus in a patient who was initially suspected of having a typical alcohol withdrawal seizure. A 61 year old woman with a history of chronic alcoholism was admitted at an outside hospital for confusion thought to be secondary to an alcohol withdrawal seizure. She had right hemiparesis and later developed right facial twitching that did not respond to intravenous fosphenytoin and levetiracetam. She was transferred for further management. Upon arrival, lorazepam and fosphenytoin were given and right face clonic movements resolved. However, continuous EEG monitoring revealed ongoing non-convulsive status epilepticus (NCSE). Following treatment with IV valproate and lacosamide, there was resolution of NCSE. SESA is likely an under recognized clinical syndrome that is quite distinct from typical alcohol withdrawal seizures and requires a different diagnostic and management approach. NCSE is likely to account for the encephalopathy and focal neurological deficits seen in patients presenting with the clinical syndrome of SESA. Therefore, a high degree of suspicion is warranted and continuous EEG monitoring is recommended for alcoholic patients with encephalopathy and focal neurological deficits.

Topics: Acetamides; Alcohol Withdrawal Seizures; Alcoholism; Anticonvulsants; Brain Diseases; Confusion; Diffusion Magnetic Resonance Imaging; Electroencephalography; Female; Humans; Lacosamide; Lorazepam; Middle Aged; Neurologic Examination; Paresis; Patient Compliance; Phenytoin; Seizures; Status Epilepticus; Tomography, X-Ray Computed; Valproic Acid

Prolonged, refractory status epilepticus is a rare clinical syndrome that is associated with severe morbidity and mortality. Lacosamide is a newly approved medication for treatment of partial onset seizures in adults, which has a novel mechanism of action. Experimental data and recent reports suggest that lacosamide could be effective in status epilepticus. We report a child with prolonged, refractory status epilepticus that persisted for 10 weeks despite treatment with multiple anti-epileptics and anesthetics and was then aborted with lacosamide. This is the first report of the effect of lacosamide in prolonged refractory status epilepticus, and the first report of lacosamide efficacy in status epilepticus in a child.

Topics: Acetamides; Anticonvulsants; Child; Humans; Lacosamide; Male; Status Epilepticus; Treatment Outcome

Nonconvulsive status epilepticus (NCSE) and epilepsia partialis continua (EPC) are common epileptic conditions for which straightforward recommendations based on controlled randomized trials for treatment in therapy refractory courses are lacking. In a large retrospective study on drug efficacy in status epilepticus (SE) we identified the patients treated in our department by searching for the term "status epilepticus" in the electronic archive of medical reports of our clinic. Here we present the subset of data concerning the patients treated with lacosamide (LCM). Ten episodes of SE in nine patients could be analyzed. To control for age dependency of results at discharge we calculated a Spearman correlation coefficient with age as independent variable and return to baseline Modified Rankin Score (mRS) at discharge=1, worsening of condition at discharge (i.e. new neurological deficit or worsening of mRS)=2 and death in hospital=3 as dependent variables. LCM was given in dosages of 50-100mg. It was not earlier administered than as fourth drug. Nevertheless it seemed to be effective for termination of status epilepticus in 20% of the episodes. But the outcome at discharge seemed considerably to depend on age of patients (r=0.94, explaining 89% of variance).

Topics: Acetamides; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Injections, Intravenous; Lacosamide; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Treatment Outcome

Topics: Acetamides; Anticonvulsants; Electroencephalography; Female; Humans; Lacosamide; Middle Aged; Status Epilepticus

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.

Topics: Acetamides; Adult; Anticonvulsants; Diazepam; Drug Resistance; Drug Therapy, Combination; Epilepsy; Etomidate; Humans; Lacosamide; Levetiracetam; Male; Midazolam; Piracetam; Practice Guidelines as Topic; Status Epilepticus; Treatment Outcome

Treatment of status epilepticus usually requires intravenous anticonvulsant therapy. Lacosamide is a novel anticonvulsant drug that is available as infusion solution. We describe a patient with nonconvulsive status epilepticus who was successfully treated with intravenous lacosamide.

Topics: Acetamides; Adult; Anticonvulsants; Electroencephalography; Female; Humans; Injections, Intravenous; Lacosamide; Status Epilepticus; Treatment Outcome

This paper comprises a series of experiments in rodent models of partial and generalized epilepsy which were designed to describe the anti-convulsant profile of the functionalized amino acid lacosamide. Lacosamide was effective against sound-induced seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced seizures in rats and mice, in the rat hippocampal kindling model of partial seizures, and in the 6Hz model of psychomotor seizures in mice. The activity in the MES test in both mice (4.5mg/kg i.p.) and rats (3.9 mg/kg p.o.) fell within the ranges previously reported for most clinically available anti-epileptic drugs. At both the median effective dose for MES protection, as well as the median toxic dose for rotorod impairment, lacosamide elevated the seizure threshold in the i.v. pentylenetetrazol seizure test, suggesting that it is unlikely to be pro-convulsant at high doses. Lacosamide was inactive against clonic seizures induced by subcutaneous administration of the chemoconvulsants pentylenetetrazol, bicuculline, and picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full efficacy in the homocysteine model of epilepsy. In summary, the overall anti-convulsant profile of lacosamide appeared to be unique, and the drug displayed a good margin of safety in those tests in which it was effective. These results suggest that lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset epilepsies, and support ongoing clinical trials in these indications.

Topics: Acetamides; Animals; Anticonvulsants; Bicuculline; Cobalt; Convulsants; Electroshock; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Epilepsy, Reflex; Excitatory Amino Acid Agonists; GABA Antagonists; Homocysteine; Kindling, Neurologic; Lacosamide; Male; Mice; N-Methylaspartate; Neurotoxicity Syndromes; Pentylenetetrazole; Picrotoxin; Rats; Rats, Sprague-Dawley; Status Epilepticus