Cessation Of Status Epilepticus Research Articles

Status epilepticus: Management and prognosis

Status epilepticus is one of the most common neurological emergencies. Its incidence in adults is 36.1/100.000 per year (Leitinger et al. Epilepsia 2019). Less than half of the patients had previous seizures. Mortality varies according to the type of SE: case fatality is lower in awake patients (8.2%) compared with patients with impaired consciousness (33%) (Leitinger et al. Epilepsia 2019). SE is defined as “a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures”. (Trinka et al. Epilepsia 2015). It is a highly dynamic condition, which requires early diagnosis and treatment to prevent long term consequences. About 60% of patients in Convulsive SE (CSE) will be controlled by first line treatment (Trinka et al. Expert Opin Pharmacother. 2016). Recent studies suggest, that there is significant undertreatment in the early stages of status: Up to 80% receive not the recommended dose of Benzodiazepines (Kellinghaus et al. Ann Neurol 2019). If treatment is delayed, or the patient does not respond to adequate Benzodiazepines the stage of refractory SE (RSE) is reached, where anaesthetic treatments are necessary. The causes of SE must be identified by all means [8]. Common causes should be established in the first hours and treated appropriately, if causes cannot be identified the term NORSE (New Onset RSE) is used. At this stage extensive investigations are necessary to identify (and treat) the cause. In nearly 50% of cases, the probable cause of NORSE can eventually be determined. (Gaspard et al. Neurology 2015). The most commonly identified etiologies include autoimmune (19%) and paraneoplastic encephalitis (18%) or infection-related (8%). Once the patient is under general anaesthesia, major complications, such as pneumonia, immunosuppression, acidosis, metabolic derangements, cardiac suppression, gastric paresis, and others have to be managed appropriately. Overall RSE and super-refractory SE (SRSE), which does not respond to > 24h of general anaesthesia, is rare (7.2 and 1.2 / 100.000 / year), but mortality is highest in this group (Leitinger et al. Epilepsia 2019). One of the main diagnostic challenges at this stage, which is still unsolved, is the distinction between coma due to SE and coma with SE like EEG patterns (Trinka and Bauer Epilepsia 2009). This presentation will give an up to date overview on management and prognosis of SE.[1Bauer G. Trinka E. Nonconvulsive status epilepticus and coma.Epilepsia. 2010; 51: 177-190Google Scholar, 2Gaspard N. Foreman B.P. Alvarez V. Cabrera Kang C. Probasco J.C. Jongeling A.C. Meyers E. Espinera A. Haas K.F. Schmitt S.E. Gerard E.E. Gofton T. Kaplan P.W. Lee J.W. Legros B. Szaflarski J.P. Westover B.M. LaRoche S.M. Hirsch L.J. Critical Care EEG Monitoring Research Consortium (CCEMRC). New-onset refractory status epilepticus: Etiology, clinical features, and outcome.Neurology. 2015; 85: 1604-1613Google Scholar, 3Hirsch L.J. Gaspard N. van Baalen A. Nabbout R. Demeret S. Loddenkemper T. Navarro V. Specchio N. Lagae L. Rossetti A.O. Hocker S. Gofton T.E. Abend N.S. Gilmore E.J. Hahn C. Khosravani H. Rosenow F. Trinka E. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.Epilepsia. 2018; 59: 739-744Google Scholar, 4Kellinghaus C. Rossetti A.O. Trinka E. Lang N. May T.W. Unterberger I. Rüegg S. Sutter R. Strzelczyk A. Tilz C. Uzelac Z. Rosenow F. Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).Ann Neurol. 2019; 85: 421-432Google Scholar, 5Leitinger M. Trinka E. Giovannini G. Zimmermann G. Florea C. Rohracher A. Kalss G. Neuray C. Kreidenhuber R. Höfler J. Kuchukhidze G. Granbichler C. Dobesberger J. Novak H.F. Pilz G. Meletti S. Siebert U. Epidemiology of status epilepticus in adults: A population-based study on incidence, causes, and outcomes.Epilepsia. 2019; 60: 53-62Google Scholar, 6Trinka E. Cock H. Hesdorffer D. Rossetti A.O. Scheffer I.E. Shinnar S. Shorvon S. Lowenstein D.H. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.Epilepsia. 2015; 56: 1515-1523Google Scholar, 7Trinka E. Höfler J. Leitinger M. Rohracher A. Kalss G. Brigo F. Pharmacologic treatment of status epilepticus.Expert Opin Pharmacother. 2016; 17: 513-534Google Scholar, 8Trinka E. Höfler J. Zerbs A. Causes of status epilepticus.Epilepsia. 2012; 53: 127-138Google Scholar]

Intravenous Brivaracetam in the Treatment of Status Epilepticus: A Systematic Review.

Brivaracetam is a high-affinity synaptic vesicle glycoprotein 2A ligand with high brain permeability and rapid onset of action. These properties make brivaracetam potentially an ideal compound in the emergency setting. The objective of our study was to review the evidence about the clinical efficacy and tolerability of intravenous brivaracetam in the treatment of status epilepticus. We systematically searched MEDLINE, EMBASE, Google Scholar, ClinicalTrials.gov, and conference proceedings to identify studies evaluating intravenous brivaracetam as treatment for status epilepticus of any type in patients of any age. Searches were conducted on 3 December, 2018. Seven studies were included (37 patients; aged 22-85 years; 21 were female). The type and etiology of status epilepticus varied across studies. The number of drugs used prior to brivaracetam to treat status epilepticus ranged from 1 to 8. The time from status epilepticus onset to brivaracetam administration ranged from 0.5 h to 105 days. The initial brivaracetam dose ranged from 50 to 400 mg. In case series, the proportion of patients achieving clinical status epilepticus cessation when brivaracetam was administered as the last drug varied from 27 to 50%; in case reports, all patients had status epilepticus cessation. The time from brivaracetam administration to status epilepticus cessation ranged from 15min to 94h. No serious adverse effects were reported. The available data suggested that brivaracetam can be a safe treatment option in patients with status epilepticus. The current evidence is however hampered by several confounding factors, and controlled studies are warranted to define the actual benefit of brivaracetam for the treatment of status epilepticus.

Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE).

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.

Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome

To our knowledge, there are no reports of status epilepticus (SE) associated with mitochondrial diseases and treated with perampanel (PER). We present three cases of patients with refractory SE associated with MELAS syndrome who responded favorably to PER.All cases were diagnosed as non-convulsive SE (focal without impairment of level of consciousness). After an initial treatment with other anti-seizure drugs, PER was added in all cases (8, 16 and 12 mg) and cessation of SE was observed within the next 4-8 hours. All the cases involved a stroke-like lesion present on brain MRI.In our patients, PER was an effective option in SE associated with MELAS syndrome.

Levetiracetam circulating concentrations and response in status epilepticus

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

Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus.

The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice. A multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017. A total of 61 patients (mean age = 29.8, range = 9-90years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7days to 24months, with a mean retention time of 7.9months, resulting in a total exposure time to BRV of 483months. The retention rate was 82% at 3months and 69% at 6months. Efficacy at 3months was 36% (50% responder rate), with 25% seizure-free for 3months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long-term 50% responder rate was present in 17 patients (28%; 11 seizure-free [18%]) for >6months and in 14 patients (23%; 10 seizure-free [16%]) for >12months. Treatment-emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200-300mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus. Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV-induced adverse events.

T21. Status epilepticus cessation during pyridoxine infusion in an infant with delayed diagnosis of ALDH7A1 mutation

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder leading to neonatal intractable seizures and epileptic encephalopathy. Clinical seizures usually begin in the first hours of life, with poor response to anticonvulsants, evolving to refractory status epilepticus. Diagnostic assessment includes cerebrospinal fluid analysis, gene testing and clinical response to parenteral pyridoxine. Early recognition and treatment is highly desired to avoid unfavorable neurodevelopmental outcome. Electroencephalographic monitoring commonly reveals pretreatment multifocal epileptiform activity and burst suppression pattern; after pyridoxine injection, the incidence of sharp waves decreases and periods of suppression can occur. Case report of a 11-month-old girl with first seizure with 4 h after birth and delayed genetic confirmation of pyridoxine-dependent epilepsy due to the gene ALDH7A1. EEG monitoring was performed during pyridoxine infusion. A 11 month-old girl, with unremarkable gestational and delivery history, started seizures 4 h after birth. Initially treated with phenobarbital, she evolved to convulsive status epilepticus (CSE), leading to orotracheal intubation and continuous sedation for 5 days. At 3 months, she had a new CSE, being hospitalized for 4 months and started on sodium valproate, vigabatrin, clobazam and levetiracetam. Epileptic seizures remained weekly. Phenobarbital and cannabidiol were added, with no further benefit. At 9 months, seizures became daily and she had a new CSE. In the ICU, it was started midazolam, ketamine, topiramate and ketogenic diet. After 1 month, she was discharged and referred to a tertiary hospital. An exome sequencing revealed 2 copies in homozygosis in the gene ALDH7A1, variant Chr5:125.894.936 C > T, previously associated with PDE. While being admitted for pyridoxin treatment, she started a new CSE. EEG showed diffuse spikes, polyspikes and sharp waves at intervals of 1–2 s. Immediately after intravenous injection of pyridoxine 200 mg, epileptiform activity became progressively less frequent, alternating with periods of attenuattion lasting from 2 to 8 s, with no longer SE after 3 min. After 3 days, EEG showed moderate diffuse disorganization, with no epileptiform activity. Discharge was after 10 days. Outpatient EEG monitoring showed left centrotemporal sharp waves and mild disorganization of background activity. This case illustrates a clinical scenario of seizures starting in the neonatal period, with recurrent convulsive status epilepticus and little response to anticonvulsants and ketogenic diet. The delayed diagnosis can be explained by rarity of the condition and limited availability of gene testing in public health system in medium and low-income countries. It remarks the importance of empirical pyridoxine treatment in neonates with early beginning of refractory seizures and status epilepticus (SE). EEG evolution and SE cessation documents pyridoxine responsiveness.

Dexmedetomidine stops benzodiazepine-refractory nerve agent-induced status epilepticus

Nerve agents are highly toxic chemicals that pose an imminent threat to soldiers and civilians alike. Nerve agent exposure leads to an increase in acetylcholine within the central nervous system, resulting in development of protracted seizures known as status epilepticus (SE). Currently, benzodiazepines are the standard of care for nerve agent-induced SE, but their efficacy quickly wanes as the time to treatment increases. Here, we examine the role of the α2-adrenoceptor in termination of nerve agent-induced SE using the highly specific agonist dexmedetomidine (DEX). Adult male rats were exposed to soman and entered SE as confirmed by electroencephalograph (EEG). We observed that administration of DEX in combination with the benzodiazepine midazolam (MDZ) 20 or 40 min after the onset of SE stopped seizures and returned processed EEG measurements to baseline levels. The protective effect of DEX was blocked by the α2-adrenoceptor antagonist atipamezole (ATI), but ATI failed to restore seizure activity after it was already halted by DEX in most cases, suggesting that α2-adrenoceptors may be involved in initiating SE cessation rather than merely suppressing seizure activity. Histologically, treatment with DEX + MDZ significantly reduced the number of dying neurons as measured by FluoroJade B in the amygdala, thalamus, and piriform cortex, but did not protect the hippocampus or parietal cortex even when SE was successfully halted. We conclude that DEX serves not just as a valuable potential addition to the anticonvulsant regimen for nerve agent exposure, but also as a tool for dissecting the neural circuitry that drives SE.

Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity.

Cross-sensitivity of rash has been reported between various antiepileptic drugs (AEDs). However, few studies have determined the frequency and management of cross-sensitivity in patients with super-refractory status epilepticus (SRSE). To examine the optimal AED for treating SRSE with cross-sensitivity. We performed a retrospective review of adult patients with SRSE treated at Nagoya City University Hospital, in which we investigated the frequency of cross-sensitivity among patients with SRSE and their clinical and medical profiles. We identified 10 adult patients with SRSE, 5 of whom had cross-sensitivity. Stiripentol (STP) was administered when previously used AEDs had demonstrated cross-sensitivity and failed to control seizures. After initiation of STP, the dose of general anaesthetics was reduced, and status epilepticus (SE) eventually ceased with co-administered AEDs without additional adverse effects. The mean time to SE cessation after initiation of STP was 30.8days (range, 18-46days), mean duration of general anaesthesia was 101.2days (range, 74-128days), and mean number of AEDs was 9.0 (range, 6-11). This study suggests that cross-sensitivity between AEDs is common in adults with SRSE and that STP may be useful for treating SRSE with cross-sensitivity.

The efficacy of different kinds of intravenously applied antiepileptic drugs in the treatment of status epilepticus. How can it be determined?

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 χ2-tests with the Yates adjustment for small samples to evaluate statistical differences between efficacy rates of different AEDs in the entire group and in subgroups of SE according to the second level of subdivisions in axis 1 and according to axis 2 of the new ILAE classification. A total of 145 treatment episodes in 124 patients (47 male, 77 female) were evaluated. There were 23 significant differences in efficacy according to the different criteria. Only criteria 1 and 3 led to significant results in our analysis. When incorporating theoretical considerations and the results of this study, criterion 3 seems to be the most appropriate measure for the evaluation of efficacy of an AED in the treatment of SE, because it seems to be more reasonable than criterion 1.

Treatment of refractory and super-refractory status epilepticus with brivaracetam: A cohort study from two German university hospitals.

We aimed to ascertain the possible use of brivaracetam (BRV) as an option for treatment of status epilepticus (SE). A review of medical records was carried out to detect BRV administration in SE patients treated in Frankfurt and Greifswald during the period February 2016 to January 2017. The primary outcome question concerned SE resolution after BRV initiation. During that period, BRV was started with eleven adult patients with SE. Five of these were female, and the median age was 64 (interquartile range [IQR] 21years). The median SE duration before BRV initiation was 5days (IQR 9days); the median number of previous anticonvulsants used was 4 (IQR 5). Initial BRV doses ranged between 50mg and 400mg (median 100mg), titrated to a daily dose of 100 to 400mg (median 200mg). There was a cessation of SE in the first 24h of BRV in three patients (27%). While taking BRV, no serious side effects were seen. Based on these cases and previous data from animal experiments, BRV may prove useful in SE treatment, and trials would be warranted to examine BRV's efficacy in treating SE and how this efficacy might be influenced by co-administration with levetiracetam.

The SAMUKeppra study in prehospital status epilepticus: lessons for future study.

In the Lancet Neurology article "Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial" the authors conducted a prehospital, randomized controlled study to determine which treatment is more effective for status epilepticus (SE): benzodiazepine alone, or in combination with levetiracetam (LEV). Although the study had negative results, several aspects of the trial design likely masked any added effect that LEV may have had in controlling SE, including: higher doses of benzodiazepines, lower thresholds for determining cessation of SE, and a smaller sample size. Regardless, the study reaffirms the effectiveness and importance of early and adequate benzodiazepine dosing and helps guide us in designing future studies for treatment of SE.

The Safety and Effectiveness of Intravenous Lacosamide for Refractory Status Epilepticus in the Critically Ill.

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/41M), 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 48h, 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.

(S)-Ketamine in Refractory and Super-Refractory Status Epilepticus: A Retrospective Study.

ObjectiveThe aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU).MethodsWe retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET. Outcomes were seizure control and death.ResultsA total of 42 patients (14 women) with RSE and SRSE were treated with (S)-KET. The median duration of status epilepticus (SE) was 10 days [first quartile (Q1) 5.0, Q3 21.0]; the median latency from SE onset to the first administration of (S)-KET was 3 days (Q1 2.0, Q3 6.8). Prior to (S)-KET administration, patients had received a median of two (Q1 2.0, Q3 3.0) anesthetics and three (Q1 2.0, Q3 4.0) antiepileptic drugs. Forty percent of patients (17/42) received propofol: 65 % prior to (S)-KET; 35 % at the same time with (S)-KET. Seven patients received a median bolus of (S)-KET of 200 mg (Q1 200, Q3 250) followed by a continuous infusion, while 35 started with a continuous infusion (maximum rate median 2.55 mg/kg/h; Q1 2.09, Q3 3.22). In 64 % of patients (27/42), (S)-KET was the last drug before SE cessation; in five patients, it was given with propofol at the same time. Median duration of administration was 4 days (Q1 2.0, Q3 6.8). Overall (S)-KET treatment was well tolerated, adverse effects were not observed, and overall mortality was 45.2 %.ConclusionsTreatment of SRSE in adult patients with (S)-KET led to resolution of status in 64 %. No adverse events were found, indicating a favorable safety profile.

A comparison of four antiepileptic drugs in status epilepticus: experience from India

Purpose: We report the efficacy and safety of lorazepam (LOR), phenytoin (PHT), valproate (VPA) and levetiracetam (LEV) as first and second choice antiepileptic drug (AED) in status epilepticus (SE) and their combinations in preventing refractory SE. Materials and methods: The results of our two earlier trials on SE were compared; one evaluated VPA versus PHT (group I) and the other LOR versus LEV (group II). In group I, additional patients were recruited in addition to published data. The primary outcome was cessation of SE after first and second AEDs and secondary outcome was mortality and side effects. The efficacy of these four drugs as first and second choice was compared. The frequency of refractory seizure in groups I and II and their contributing factors were analyzed. Results: One hundred and seventeen patients were in group I and 79 in group II. The baseline characteristics of the patients were similar in LOR, LEV, VPA and PHT groups. As a first choice, LOR controlled SE in 75.1%, LEV in 76.3%, VPA in 55.4% and PHT in 44.2% patients. As a second choice, LEV was effective in 88.9%, LOR in 70%, VPA in 74.1% and PHT in 25% patients. Refractory SE was more frequent in group I than group II (29.9% versus 10.5%), however, complications and mortality were higher in group II. Conclusion: LOR and LEV combination was superior in reducing refractory SE but at the cost of higher complications and death.

Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial.

Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication. To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam. Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered. The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration. Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%). Among pediatric patients with convulsive status epilepticus, treatment with lorazepam did not result in improved efficacy or safety compared with diazepam. These findings do not support the preferential use of lorazepam for this condition. clinicaltrials.gov Identifier: NCT00621478.

Use of oxcarbazepine for treatment of refractory status epilepticus

PurposeOxcarbazepine (OXC) is an effective anticonvulsant used for treatment of partial and secondarily generalized seizures. However, there is almost no data regarding its effectiveness and tolerability when used for treatment of status epilepticus (SE). MethodsWe retrospectively identified all patients who received OXC for treatment of SE in our hospital between July 2008 and December 2010 in our hospital and analyzed all available data. ResultsWe identified 13 patients (median age 79 years) who were treated with OXC for refractory SE after failure of first- and second-line therapy in our institution. In the majority of patients, etiology was remote symptomatic (10/13), and semiology was nonconvulsive (10/13). OXC was initiated as third or later agent in almost all patients after median latency of 81h with a median maximum daily dose of 1800mg. OXC was the last drug before SE cessation in 8/13 patients. Relevant hyponatriemia <125mmol/l was seen in 3 patients. ConclusionOXC may be an effective alternative in refractory SE, but patients need to be monitored closely for hyponatriemia. Practice implicationsOXC could be used for refractory SE under close electrolyte monitoring when standard agents fail or are unsuitable.

Usefulness of intravenous lacosamide in status epilepticus

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.

Pediatric Seizures

On the basis of strong evidence, treatment is highly dependent on the seizure semiology results, electroencephalography (EEG) findings, and origin. • On the basis of moderate evidence and consensus, vigorous use of video EEG recordings and home video cameras should be used to delineate the epileptic syndromes. • On the basis of strong evidence, pediatric epilepsy syndromes have common comorbidities. As a consensus, some pediatric epilepsy centers consider referral to a neuropsychologist to be first-line care in these patients. • On the basis of strong evidence and consensus, antiepileptic drug therapy has its own complications and should be discontinued after an appropriate treatment course. • On the basis of moderate evidence and consensus, uncontrolled seizures put patients at risk for significant morbidity and mortality.

Lacosamide as a new treatment option in 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.