Seizures In Adults Research Articles

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). 2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Forty-two articles were included. The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month-16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6-17 years); oxcarbazepine for TRCFE (1 month-4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

Multimodal seizure detection: A review.

A review is given on the combined use of multiple modalities in non electroencephalography (EEG)-based detection of motor seizures in children and adults. A literature search of papers was done on multimodal seizure detection with extraction of data on type of modalities, study design and algorithm, sensitivity, false detection rate, and seizure types. Evidence of superiority was sought for using multiple instead of single modalities. Seven papers were found from 2010 to 2017, mostly using contact sensors such as accelerometers (n = 5), electromyography (n = 2), heart rate (n = 2), electrodermal activity (n = 1), and oximetry (n = 1). Remote sensors included video, radar, movement, and sound. All studies but one were in-hospital, with video-EEG as a gold standard. Algorithms were based on physiology and supervised machine learning, but did not always include a separate test dataset. Sensitivity ranged from 4% to 100% and false detection rate from 0.25 to 20 per 8hours. Tonic-clonic seizure detection performed best. False detections tended to be restricted to a minority (16%-30%) of patients. Use of multiple sensors increased sensitivity; false detections decreased in one study, but increased in another. These preliminary studies suggest that detection of tonic-clonic seizures might be feasible, but larger field studies are required under more rigorous design that precludes bias. Generic algorithms probably suffice for the majority of patients.

Psychogenic nonepileptic seizures in adults with epilepsy and intellectual disability: A neglected area

PurposeTo describe the main characteristics of psychogenic nonepileptic seizures (PNES) in adults with epilepsy and intellectual disability (ID), and to analyse the differences regarding psychosocial functioning, epilepsy severity and ID between patients with PNES and a control group without PNES. MethodsMedical records of adults with ID and epilepsy living at an epilepsy care facility (N = 240) were screened for PNES and evaluated by a neurologist. A control group consisting of patients with epilepsy and ID, without PNES, was matched according to age, sex and level of ID. Characteristics of PNES and epilepsy were provided by the subject’s nursing staff or retrieved from patient charts, psychosocial data were collected by standardised questionnaires and level of ID was individually assessed using psychometric instruments. ResultsThe point prevalence of PNES was 7.1%. The patients with PNES (n = 15) were most often female and had a mild or moderate level of ID. Compared to controls, they showed more depressive symptoms, experienced more negative life events and had more often an ID discrepancy (ID profile with one domain particularly more impaired than another). Stress-related triggers were recognised in a large majority by the nursing staff. ConclusionPNES appears to be a relatively rare diagnostic entity among inpatients with both epilepsy and ID. However, the complexity of diagnosing PNES in this population, and the similarities in stress-related triggers for PNES in patients with and without ID, suggest that PNES may be underdiagnosed in the ID population. Diagnostic challenges of PNES and, as subcategory, reinforced behavioural patterns are discussed.

Lacosamide: A Review in Focal-Onset Seizures in Patients with Epilepsy.

Lacosamide (Vimpat®) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged ≥4years with epilepsy. In adults and adolescents (aged ≥16years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18weeks) treatment, with efficacy sustained over the longer-term (up to 8years). Moreover, patients were effectively switched from adjunctive oral lacosamide to the same dosage of intravenous lacosamide. Oral lacosamide was an effective conversion to monotherapy agent in this patient population and as monotherapy demonstrated noninferiority to carbamazepine controlled release in terms of seizure freedom. Antiepileptic benefits were maintained during longer-term (≤2years) monotherapy. The antiepileptic efficacy of lacosamide in children aged ≥4years has been extrapolated from data from adults and adolescents, with a similar response expected provided paediatric dosage adaptations are used and safety is demonstrated. Indeed, preliminary data demonstrated the efficacy of short-term (16weeks) adjunctive lacosamide in patients aged ≥4 to <17years. Oral lacosamide was generally well tolerated over the short- and longer-term when administered as adjunctive therapy, a conversion to monotherapy agent and monotherapy in adults and adolescents and when administered as adjunctive therapy in children aged ≥4years. Thus, lacosamide is a useful option for the management of focal-onset seizures across a broad age range, starting as early as 4years of age.

Addition of Cannabidiol to Current Antiepileptic Therapy Reduces Drop Seizures in Children and Adults With Treatment-Resistant Lennox-Gastaut Syndrome

This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy.This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2–14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989).Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with >50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, p < 0.0001). The proportion of children with 90% seizure reduction was also higher in the diet group (19.5% vs 2%, p = 0.09). Six children in the diet group were seizure free at 3 months compared with two in the control group (p = 0.26). At 3 months, 6 children had constipation and 5 had weight loss.A simplified version of the modified Atkins diet was developed for use by parents with low levels literacy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy.

Is levetiracetam more effective than carbamazepine for the long-term treatment of generalized tonic-clonic seizures in healthy adults?

EVIDENCE-BASED ANSWER Levetiracetam is as effective, but not more effective, than carbamazepine for monotherapy in patients with newly diagnosed focal or generalized epilepsy followed for up to 12 months. Similarly, the withdrawal rates for adverse events are not significantly different between the 2 treatments (SOR: A, 2 consistent RCTs).

Determination of topiramate by capillary electrophoresis with capacitively-coupled contactless conductivity detection: A powerful tool for therapeutic monitoring in epileptic patients.

Topiramate (TPM) is the main antiepileptic drug used for the control of partial and generalized seizures in both adults and children. In association with clinical observations, the analysis of plasmatic concentration of TPM is of utmost importance for the individual adjustment of the administered dose to the patient. In the present work, a bioanalytical method was developed and validated for TPM analysis in plasma samples by capillary electrophoresis with capacitively-coupled contactless conductivity detection (CE-C4 D). A simple background electrolyte composed of 15 mmol/L triethylamine, hydrodynamic injections (0.8 psi for 5 s) and a moderate separation voltage (20 kV) were used, rendering relatively short analysis times (<3 min). The sample pre-treatment was carried out by liquid-liquid extraction using methyl terc-butyl ether as solvent and 200 μL of plasma. The method was validated according to the official guidelines from the European Medicine Agency and showed linearity in plasmatic concentration range from 1 to 30μg/mL, which covers the clinically-relevant interval. The lower limit of quantification of 1 μg/mL obtained also allows following patients with low dosage of the drug. The method was successfully applied to analysis of plasma samples and allowed the identification of 80% under-medicated patients in the analyzed patient pool.

Teratogenic Effect of Levetiracetam Drug on the Development of the Kidney in Embryo Rat

The new antiepileptic drugs, levetiracetam (LEV), are used to treat tonic-clonic seizures and myoclonic seizures in adults and children. Thirty pregnant rats were enrolled, which were divided into two groups A control (10), B treated (20). Group (A) were given distilled water orally for 15 days of pregnancy period. The other group was subdivided into two subgroups B1, B2 (each with 10 rats), which were treated with LEV for 14 days for subgroup (B1) and 15 days for the other subgroup (B2). The drug (350 mg/kg/day) is administered orally. Based on our results there was damage in the kidney due to the toxicity of the drug. The histopathological effects is represented by damage of cortical glomeruli in which there were hemorrhage, shrinking, accumulation of glomerular cells, and enlargement of capsular space. Severe malformations in the kidney were observed when the drug is used constantly during the organogenesis stages of pregnancy.

The Burden of Seizures in Adults with Tuberous Sclerosis Complex (TSC) and Epilepsy: Data from a Specialized Center in Netherlands (P6.276)

The Burden of Seizures in Adults with Tuberous Sclerosis Complex (TSC) and Epilepsy: Data from a Specialized Center in Netherlands (P6.276)

Acute Treatment of Prolonged and Repetitive Seizures in Adults Using Sublingual Administration of Lorazepam Intensol 2 mg/ml Solution (P1.265)

Acute Treatment of Prolonged and Repetitive Seizures in Adults Using Sublingual Administration of Lorazepam Intensol 2 mg/ml Solution (P1.265)

Abstract #709 An Unusual Case of Digeorge Syndrome Presenting as Seizures in Adulthood

Abstract #709 An Unusual Case of Digeorge Syndrome Presenting as Seizures in Adulthood

Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures

ObjectiveTo evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. MethodsThis was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400mg (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. ResultsThe analysis population included 1447 patients (ESL, n=1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p=0.802). However, the incidence of depression and suicidality-related TEAEs was significantly higher for ESL (7.4%) vs. placebo (3.8%) (p=0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was significantly higher for ESL (7.1%) vs. placebo (4.0%) (p=0.023); incidences of memory impairment, attention disturbance, apathy, aphasia, and bradyphrenia were higher for ESL 1200mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs (SAEs) were 0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL, and 0.7% and 0.5% taking placebo, respectively. ConclusionsIn phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. However, the incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were significantly higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo.

Conversion to brivaracetam monotherapy for the treatment of patients with focal seizures: Two double-blind, randomized, multicenter, historical control, Phase III studies

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) approved for monotherapy (in the USA) and adjunctive treatment of focal (partial-onset) seizures in adults, at a dose range of 50–200 mg/day taken in two equal doses, with a recommended starting dose of 100 mg/day. Two Phase III, randomized, double-blind, multicenter, historical-controlled, conversion-to-monotherapy studies (N01276, NCT00698581; N01306, NCT00699283) were conducted to evaluate the efficacy, safety, and tolerability of conversion to BRV 50 mg/day monotherapy in adults with uncontrolled focal seizures. Patients aged 16–75 years, with 2–40 focal seizures per 4 weeks during an 8-week baseline, and on stable doses of 1–2 AEDs were enrolled. Patients were randomized to BRV 50 or 100 mg/day (3:1) in two equal doses without titration. The treatment period comprised 1-week BRV add-on, 8-week baseline AED tapering, and 8-week BRV monotherapy periods. Primary efficacy endpoint was Kaplan-Meier estimate of the cumulative exit rate due to pre-defined exit criteria at Day 112 (50 mg/day, efficacy population). The upper 95% confidence interval (CI) was compared with the historical control threshold (0.722). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs; intent-to-treat population). After randomization of 150 patients (N01276: 88; N01306: 62), both studies were terminated due to the confounding effects of a higher-than-expected discontinuation rate. For BRV 50 mg/day, ≥1 exit criterion was met by 26/67 (38.8%) patients (study N01276) and 18/45 (40.0%) patients (study N01306). In both studies, the cumulative exit rate was lower than the historical control threshold (N01276: 0.487, 95% CI 0.347, 0.626; N01306: 0.474, 95% CI 0.310, 0.638). However, with maximum 10% censoring due to early withdrawal (sensitivity analysis), cumulative exit rates were above historical control (N01276: 0.652, 95% CI 0.532, 0.772; N01306: 0.704, 95% CI 0.563, 0.844). Overall incidence of TEAEs was 110/150, 73.3% (treatment period); 78/147, 53.1% (baseline AED tapering period); 41/84, 48.8% (BRV monotherapy period). In conclusion, BRV 50 mg/day monotherapy demonstrated an exit rate lower than historical control. Results should be interpreted with caution as, following termination of both studies, patient numbers were too low to evaluate the efficacy of BRV monotherapy. These are the first published safety and tolerability data for BRV monotherapy. Monotherapy was well tolerated, with a relatively low incidence of TEAEs, though this should be interpreted with the caveat that the majority of common TEAEs were likely to have occurred earlier in the course of treatment with BRV. No new safety concerns were identified, supporting the favorable safety profile of BRV observed in adjunctive studies.

A review of the pharmacology and clinical efficacy of brivaracetam.

Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg) and multiple (200–800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.

Status epilepticus as a presenting feature of bilateral paramedian thalamic and midbrain infarct—Artery of percheron infarct?

Abstract Seizures in stroke account for 11% cases of new onset seizure in adults. Risk factors for stroke associated seizures are cortical involvement, anterior hemisphere lesion, cardioembolic etiology. Seizure in case of thalamic or brainstem infarcts have rarely been described in literature and status epilepticus is very rare in these infarcts. Here we report a case of 40 years male patient who presented to emergency room with history of sudden onset vertigo and vomiting, followed by generalised tonic clonic seizures which evolved into status epilepticus. His magnetic resonance imaging of brain with diffusion weighted image (DWI) revealed acute infarct involving bilateral paramedian thalamic and midbrain region. Emergency physician should be aware of this atypical clinical scenario which can facilitate early diagnosis and treatment and thereby improve disease prognosis.

Divergent effects of levetiracetam and tiagabine against spontaneous seizures in adult rats following neonatal hypoxia

Animal models are valuable tools for screening novel therapies for patients who suffer from epilepsy. However, a wide array of models are necessary to cover the diversity of human epilepsies. In humans, neonatal hypoxia (or hypoxia-ischemia) is one of the most common causes of epilepsy early in life. Hypoxia-induced seizures (HS) during the neonatal period can also lead to spontaneous seizures in adulthood. This phenomenon, i.e., early-life hypoxia leading to adult epilepsy − is also seen in experimental models, including rats. However, it is not known which anti-seizure medications are most effective at managing adult epilepsy resulting from neonatal HS. Here, we examined the efficacy of three anti-seizure medications against spontaneous seizures in adult rats with a history of neonatal HS: (1) phenobarbital (PHB), the oldest epilepsy medicine still in use today; (2) levetiracetam (LEV); and (3) tiagabine (TGB). Both LEV and TGB are relatively new anticonvulsant drugs that are ineffective in traditional seizure models, but strikingly effective in other models. We found that PHB and LEV decreased seizures in adult rats with a history of HS, whereas TGB exacerbated seizures. These divergent drug effects indicate that the HS model may be useful for differentiating the clinical efficacy of putative epilepsy therapies.

New onset seizures an etiological study

Background:Seizures are common disorders found all over the world and are encountered frequently during medical practice in variety of settings. Etiological spectrum of acute symptomatic seizures in developing countries is different from developed countries. So, this study was done to know the various etiologies of new onset seizures in adults in this region.Methods: Consecutive 100 Cases of new onset seizures from the Bhagwan Mahaveer Jain hospital, Bengaluru, were included in the study. The etiology was determined by neuroimaging and appropriate investigations including cerebrospinal fluid examination.Results: Of 100 patients 89% were acute symptomatic seizures. The seizure types were GTCS in 71% and 29% had simple or complex partial seizure (s) with or without secondary generalization. 8 (8%) patients had status epilepticus (SE). 40% 0f SE were caused by neuroinfections. Neuroinfection was the leading cause of seizure, which accounted for 34%, followed by Cerebrovascular accidents (29%) and metabolic (9%). Neurocysticercosis is most common cause in neuroinfection (35%), followed by meningitis (29%) and cerebral malaria (17%). 8% of seizures were because of CNS Tuberculosis. 55% of the CVA were due stroke and 34% due to CVT. 14% of seizures were pregnancy related.Conclusions: This study illustrates that the etiological spectrum of seizures in this part of the world is different from that described from developed countries and CNS infections account for a significant number of cases.

Human abuse potential of brivaracetam in healthy recreational central nervous system depressant users

BackgroundBrivaracetam is a new antiepileptic drug indicated for adjunctive treatment of focal seizures in adults at a dose of 50–200mg/day taken in two equal doses. The objective of this study was to evaluate the abuse potential of brivaracetam compared with alprazolam (positive control), placebo, and levetiracetam. MethodsThis was a randomized, double-blind, triple-dummy, crossover study in healthy male and female recreational central nervous system (CNS) depressant users aged 18–55years, who could distinguish between the subjective effects of alprazolam 2mg and placebo. All participants received single doses of brivaracetam (50 [therapeutic dose], 200, 1000mg [supratherapeutic doses]), alprazolam (1.5, 3mg), placebo, and levetiracetam (4000mg) in random order each separated by 7–10days. Subjective Visual Analogue Scales (VAS) and Addiction Research Center Inventory (ARCI) scales were completed at intervals up to 24h postdose. Primary endpoints were Drug Liking (at this moment) VAS, Overall Drug Liking VAS, Feeling High VAS, and ARCI Pentobarbital Chlorpromazine Alcohol Group (PCAG, sedation) maximum effect (Emax). Maximum effect values on each scale were analyzed using a mixed-effect model (per protocol population, N=44). ResultsThe maximum effect for both alprazolam doses was significantly greater versus placebo for six designated endpoints, confirming study validity. Drug Liking (at this moment) VAS Emax was significantly lower for brivaracetam 50mg than alprazolam (both doses); there were no significant differences between brivaracetam 200mg and alprazolam (both doses), and brivaracetam 1000mg and alprazolam 1.5mg. Brivaracetam 1000mg (supratherapeutic single dose) had significantly higher Drug Liking (at this moment) VAS Emax than alprazolam 3mg. Overall, Drug Liking VAS Emax for brivaracetam 50 and 200mg was not significantly different from alprazolam (both doses). Brivaracetam 1000mg had significantly higher Overall Drug Liking VAS Emax than alprazolam 1.5mg, but was not significantly different from alprazolam 3mg. Feeling High VAS Emax was lower versus alprazolam with brivaracetam 50 and 200mg, while brivaracetam 1000mg was comparable with alprazolam (both doses). Addiction Research Center Inventory PCAG Emax for brivaracetam (all doses) was significantly lower than alprazolam (both doses). On the secondary/supportive endpoints, compared with alprazolam, brivaracetam had fewer positive effects (ARCI Morphine Benzedrine Group [euphoria]; Good Drug Effects VAS [50mg]) and fewer negative effects (Bad Drug Effects VAS; ARCI Lysergic Acid Diethylamide [dysphoria]). Brivaracetam was not significantly different from alprazolam for Take Drug Again VAS (50, 200mg). For most endpoints, brivaracetam (50–200mg) was not significantly different from levetiracetam (4000mg). ConclusionThis study in healthy recreational CNS depressant users showed that single doses of brivaracetam 50mg (therapeutic single dose) had lower sedative, positive, and negative drug effects than alprazolam, while brivaracetam 200 and 1000mg (supratherapeutic single doses) were more similar to alprazolam. The subjective profile of brivaracetam appeared to be similar to that of levetiracetam, but further evaluation using a range of levetiracetam doses would be needed to confirm similar abuse potential.

Hemispheric Cerebral Oximetry Monitoring During Pediatric Seizure Activity in a Pediatric Emergency Department.

Sustained neuronal activity during seizures causes cellular perturbations, alterations in cerebral physiology, and potentially neurological injury, a neurological emergency. With variable clinical manifestations of seizures, frequent failure of seizure recognition by providers in pediatric and developmentally challenged patients can increase seizure complications. Neuroresuscitation should include rapid cerebral physiology assessment for increased seizure recognition and optimal neurological outcomes. In neurological emergencies, cerebral oximetry has demonstrated its utility in altered cerebral physiology and a standard combat neurological assessment tool. During adult seizures, cerebral oximetry (regional cerebral oxygen saturation [rcSO2]) has been shown as a useful neurological assessment tool, but research is lacking in pediatric emergency department (PED) seizure patients. The aim of this study was to identify trends in rcSO2 readings for patients presenting to the PED with seizure activity and in the postseizure state in order to evaluate usefulness of rcSO2 as a neurological assessment tool in pediatric seizure patients. This was a PED observational case series comparing hemispheric rcSO2 readings in first-time clinically evident generalized and focal seizure patients to first-time postseizure patients with no PED seizures. Generalized or focal seizure (n = 185) hemispheric rcSO2 revealed significant differences compared with nonseizure and controls' rcSO2 readings (n = 115) (P < 0.0001). Generalized and focal seizure rcSO2's were either less than 60% or greater than 80% compared with nonseizure rcSO2 (P < 0.0001). Ipsilateral focal seizure rcSO2 correlated to seizure side (P < 0.0001) and was less than the contralateral rcSO2 (P < 0.0001), with interhemispheric rcSO2 discordance greater than 16 (P < 0.0001). Seizure to preseizure rcSO2 discordance was as follows: generalized 15.2, focal: left 19.8, right 20.3 (P < 0.0001). Hemispheric during-seizure rcSO2 readings significantly correlated with generalized and focal seizures and reflected altered cerebral physiology. Ipsilateral focal seizure rcSO2 readings correlated to the focal side with wide interhemispheric rcSO2 discordance. All postseizure rcSO2 readings returned to preseizure readings, showing altered cerebral physiology resolution. Overall, in generalized or focal seizure, rcSO2 readings were less than 60% or greater than 80%, and in focal seizure, interhemispheric rcSO2 discordance was greater than 10. During seizures, hemispheric rcSO2 readings demonstrated its potential pediatric seizure utility. Utilizing rcSO2 readings related to seizure activity could expedite pediatric and developmentally challenged patients' seizure recognition, cerebral assessment, and interventions especially in pharmacoresistant seizures.

Intravenous Carbamazepine for Adults With Seizures.

To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.