Nonconvulsive status epilepticus and neurodevelopmental delay.

PubMed

Dirik, Eray; Yiş, Uluç; Hüdaoglu, Orkide; Kurul, Semra

2006-09-01

Nonconvulsive status epilepticus is characterized by continuous or near continuous epileptiform discharges on electroencephalography without overt motor or sensory phenomena. It is a symptomatic condition related to a disease such as epileptic encephalopathy or a metabolic disorder. Children with isolated nonconvulsive status epilepticus rarely present with global neurodevelopmental delay. This report describes an 18-month-old male who presented with global neurodevelopmental delay and decreased alertness in whom electrical status epilepticus during sleep, which is a form of nonconvulsive status epilepticus, was determined. Metabolic investigations and cranial magnetic resonance imaging were normal. He began to achieve developmental milestones after treatment with valproic acid. Although rare, pediatric neurologists and pediatricians must be aware of this condition in making the differential diagnosis of global neurodevelopmental delay and decreased alertness.

Lorazepam v. diazepam for pediatric status epilepticus.

PubMed

Pinto, Rovina Fiona; Turnbull, Jennifer

2016-05-01

Clinical question Is intravenous (IV) lorazepam superior to IV diazepam in the treatment of pediatric status epilepticus? Article chosen Chamberlain JM, Okada P, Holsti M, et al. Lorazepam v. diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA 2014;311(16):1652-60. To determine whether lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus.

Advancements in the critical care management of status epilepticus.

PubMed

Bauerschmidt, Andrew; Martin, Andrew; Claassen, Jan

2017-04-01

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.

[Status epilepticus in childhood].

PubMed

Malagón Valdez, Jorge

2013-01-01

Status epilepticus is a medical emergency which presents seizures by 30 minutes or more of continuous activity, or two or more consecutive crises without full recovery of consciousness between them. Currently, it is considered that a seizure convulsive or not, that last more than 5 minutes should be considered a status epilepticus. Different drugs for the treatment of this disease have been used. There is a general consensus in an aggressive handling should be done to reduce their morbidity and mortality, without forgetting that the cause of status is important for its management, control, and its aftermath.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

PubMed

Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

2016-12-22

Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

Can anesthetic treatment worsen outcome in status epilepticus?

PubMed

Sutter, Raoul; Kaplan, Peter W

2015-08-01

Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Predicting outcome of status epilepticus.

PubMed

Leitinger, M; Kalss, G; Rohracher, A; Pilz, G; Novak, H; Höfler, J; Deak, I; Kuchukhidze, G; Dobesberger, J; Wakonig, A; Trinka, E

2015-08-01

Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

PubMed

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

Chlormethiazole in treatment of status epilepticus.

PubMed Central

Harvey, P K; Higenbottam, T W; Loh, L

1975-01-01

Chlormethiazole (Heminevrin) was successful in controlling fits in seven out of nine episodes of intractable status epilepticus. It was administered as a constant intravenous injection at rates of up to 0.7g/h. No serious side effects were encountered, and the drug deserves wider recognition as a useful therapeutic agent in the management of status epilepticus. PMID:1131633

Pyridoxine deficiency in adult patients with status epilepticus.

PubMed

Dave, Hina N; Eugene Ramsay, Richard; Khan, Fawad; Sabharwal, Vivek; Irland, Megan

2015-11-01

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 μg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrographic status epilepticus in children with critical illness: Epidemiology and outcome.

PubMed

Abend, Nicholas S

2015-08-01

Electrographic seizures and electrographic status epilepticus are common in children with critical illness with acute encephalopathy, leading to increasing use of continuous EEG monitoring. Many children with electrographic status epilepticus have no associated clinical signs, so EEG monitoring is required for seizure identification. Further, there is increasing evidence that high seizure burdens, often classified as electrographic status epilepticus, are associated with worse outcomes. This review discusses the incidence of electrographic status epilepticus, risk factors for electrographic status epilepticus, and associations between electrographic status epilepticus and outcomes, and it summarizes recent guidelines and consensus statements addressing EEG monitoring in children with critical illness. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Consensus guidelines on management of childhood convulsive status epilepticus.

PubMed

Mishra, Devendra; Sharma, Suvasini; Sankhyan, Naveen; Konanki, Ramesh; Kamate, Mahesh; Kanhere, Sujata; Aneja, Satinder

2014-12-01

Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. A 'Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India' was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Each institution should use a pre-determined protocol for management of status epilepticus; pre-hospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.

New-onset refractory status epilepticus

PubMed Central

Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.

2015-01-01

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517

Review and update of the Hong Kong Epilepsy Guideline on status epilepticus.

PubMed

Fung, E Lw; Fung, B Bh

2017-02-01

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.

Drug-induced status epilepticus.

PubMed

Cock, Hannah R

2015-08-01

Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon, probably accounting for less than 5% of all SE cases, although limitations in case ascertainment and establishing causation substantially weaken epidemiological estimates. Some antiepileptic drugs, particularly those with sodium channel or GABA(γ-aminobutyric acid)-ergic properties, frequently exacerbate seizures and may lead to SE if used inadvertently in generalized epilepsies or less frequently in other epilepsies. Tiagabine seems to have a particular propensity for triggering nonconvulsive SE sometimes in patients with no prior history of seizures. In therapeutic practice, SE is most commonly seen in association with antibiotics (cephalosporins, quinolones, and some others) and immunotherapies/chemotherapies, the latter often in the context of a reversible encephalopathy syndrome. Status epilepticus following accidental or intentional overdoses, particularly of antidepressants or other psychotropic medications, has also featured prominently in the literature: whilst there are sometimes fatal consequences, this is more commonly because of cardiorespiratory or metabolic complications than as a result of seizure activity. A high index of suspicion is required in identifying those at risk and in recognizing potential clues from the presentation, but even with a careful analysis of patient and drug factors, establishing causation can be difficult. In addition to eliminating the potential trigger, management should be as for SE in any other circumstances, with the exception that phenobarbitone is recommended as a second-line treatment for suspected toxicity-related SE where the risk of cardiovascular complications is higher anyways and may be exacerbated by phenytoin. There are also specific recommendations/antidotes in some situations. The outcome of drug-induced status epilepticus is mostly good when promptly identified and treated, though less so in the context of overdoses. This article is

Astroglial role in the pathophysiology of status epilepticus: an overview

PubMed Central

Vargas-Sánchez, Karina; Mogilevskaya, Maria; Rodríguez-Pérez, John; Rubiano, María G.; Javela, José J.; González-Reyes, Rodrigo E.

2018-01-01

Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.

Astroglial role in the pathophysiology of status epilepticus: an overview.

PubMed

Vargas-Sánchez, Karina; Mogilevskaya, Maria; Rodríguez-Pérez, John; Rubiano, María G; Javela, José J; González-Reyes, Rodrigo E

2018-06-01

Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.

[Severe pulmonary embolism revealed by status epilepticus].

PubMed

Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J

2016-12-01

High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chloral hydrate in intractable status epilepticus.

PubMed

Lampl, Y; Eshel, Y; Gilad, R; Sarova-Pinchas, I

1990-06-01

Five adult patients were admitted to the neurological department in a state of status epilepticus. All were treated unsuccessfully with IV diazepam and diphenylhydantoin. Administration of sodium valporate or phenobarbital also was ineffective. However, after treatment with intrarectal chloral hydrate, all seizures ceased. The excellent effect of this drug was proved both clinically and electrodiagnostically. Discussed is the possibility of using chloral hydrate to treat patients with status epilepticus in whom conventional treatment has failed.

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Infraslow status epilepticus: A new form of subclinical status epilepticus recorded in a child with Sturge-Weber syndrome.

PubMed

Bello-Espinosa, Luis E

2015-08-01

Analysis of infraslow EEG activity (ISA) has shown potential in the evaluation of patients with epilepsy and in the differentiation between focal and generalized epilepsies. Infraslow EEG activity analysis may also provide insights into the pathophysiology of refractory clinical and subclinical status epilepticus. The purpose of this report is to describe a girl with Sturge-Weber syndrome (SWS) who presented with a 96-h refractory encephalopathy and nonischemic hemiparesis and who was identified to have infraslow status epilepticus (ISSE), which successfully resolved after midazolam administration. The continuous EEG recording of a 5-year-old girl with known structural epilepsy due to Sturge-Weber syndrome is presented. The patient presented to the ED with acute confusion, eye deviation, and right hemiparesis similar to two previous admissions. Despite administration of lorazepam, fosphenytoin, phenobarbital, and valproic loads, the patient showed no improvement in the clinical condition after 48 h. The continuous video-EEG monitoring (VEM) showed continuous severe diffuse nonrhythmic asymmetric slowing but no apparent ictal activity on continuous conventional EEG recording settings. As brain CT, CTA, CTV, and complete MRI scans including DWI obtained within 72 h of presentation failed to demonstrate any ischemic changes, analysis of the EEG infraslow (ISA) activity was undertaken using LFF: 0.01 Hz and HFF: of 0.1 Hz, respectively. Continuous subclinical unilateral rhythmic ictal ISA was identified. This was only evident on the left hemisphere which correlated with the structural changes due to SWS. A trial of continuous 120 to 240 μg/kg/h of IV midazolam resulted in immediate resolution of the contralateral hemiparesis and encephalopathy. Continuous prolonged rhythmic ictal infraslow activity (ISA) can cause super-refractory subclinical focal status epilepticus. This has not been previously reported, and we propose that this be called infraslow status

Status Epilepticus and Refractory Status Epilepticus Management

PubMed Central

Abend, Nicholas S.; Bearden, David; Helbig, Ingo; McGuire, Jennifer; Narula, Sona; Panzer, Jessica A.; Topjian, Alexis; Dlugos, Dennis J.

2014-01-01

Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status, and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician’s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other anti-seizure medications. If seizures persist then refractory SE is diagnosed and management options include additional anti-seizure medications or infusions of midazolam or pentobarbital. This paper reviews the management of pediatric SE and RSE. PMID:25727508

Human Immunodeficiency Viral Infection and Status Epilepticus in United States (2002-2009).

PubMed

Chaudhry, Saqib A; Afzal, Mohammad Rauf; Rodriguez, Gustavo J; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E; Suri, M Fareed K; Qureshi, Adnan I

2015-07-01

To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002-2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%-0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8-2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes.

Clinical decision making in seizures and status epilepticus.

PubMed

Teran, Felipe; Harper-Kirksey, Katrina; Jagoda, Andy

2015-01-01

Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting.

New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and Outcomes.

PubMed

Jafarpour, Saba; Hodgeman, Ryan M; De Marchi Capeletto, Carolina; de Lima, Mateus Torres Avelar; Kapur, Kush; Tasker, Robert C; Loddenkemper, Tobias

2018-03-01

Many pediatric patients presenting with status epilepticus have no history of seizures. We retrospectively analyzed the clinical characteristics of patients aged one month to 21 years who presented during six consecutive years with convulsive status epilepticus and without a history of seizures. New-onset refractory status epilepticus was defined as status epilepticus refractory to two lines of treatment, without an identified cause in the first 48 hours. Of 460 patients with status epilepticus, 79 (17.2%) presented with new-onset status epilepticus, including four (0.9%) with new-onset refractory status epilepticus. Of those patients, 54.4% were female, and the median age was 3.5 years (IQR: 1.08 to 6.75). The median seizure duration was 20 minutes (IQR: 10 to 40 minutes). Etiology was unknown in 36.7%, symptomatic in 30.3%, provoked in 16.5%, and provoked with an existing symptomatic etiology in 16.5%. Patients were followed for a median duration of 63 months (IQR: 21 to 97). The mortality rate was 3.8%. Of 55 patients who were developmentally normal at baseline, 29.1% had a significant cognitive impairment at the last follow-up, and 20% had academic difficulties or behavioral problems. Patients with symptomatic etiology had greater odds of having cognitive and behavioral problems compared with patients with unknown etiology (odds ratio = 3.83, P = 0.012). Patients with new-onset status epilepticus are at risk for recurrent seizures, recurrent status epilepticus, death, and subsequent cognitive-behavioral impairment. Specific monitoring and care interventions might be required in this high-risk population. Copyright © 2017 Elsevier Inc. All rights reserved.

[Efficacy of intravenous phenobarbital treatment for status epilepticus].

PubMed

Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

2013-08-01

Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

Neuroprotective effect of lithium after pilocarpine-induced status epilepticus in mice.

PubMed

Hong, Namgue; Choi, Yun-Sik; Kim, Seong Yun; Kim, Hee Jung

2017-01-01

Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage. The present study was designed to investigate the effects of lithium post-treatment on seizure susceptibility and hippocampal neuropathological changes following pilocarpine-induced status epilepticus. Status epilepticus was induced by administration of pilocarpine hydrochloride (320 mg/kg, i.p.) in C57BL/6 mice at 8 weeks of age. Lithium (80 mg/kg, i.p.) was administered 15 minutes after the pilocarpine injection. After the lithium injection, status epilepticus onset time and mortality were recorded. Lithium significantly delayed the onset time of status epilepticus and reduced mortality compared to the vehicle-treated group. Moreover, lithium effectively blocked pilocarpine-induced neuronal death in the hippocampus as estimated by cresyl violet and Fluoro-Jade B staining. However, lithium did not reduce glial activation following pilocarpine-induced status epilepticus. These results suggest that lithium has a neuroprotective effect and would be useful in the treatment of neurological disorders, in particular status epilepticus.

Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study.

PubMed

Poddar, Karan; Sharma, Rohan; Ng, Yu-Tze

2016-08-01

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

Non-convulsive status epilepticus presenting as a psychiatric condition.

PubMed Central

Walker, M C; Cockerell, O C; Sander, J W

1996-01-01

Non-convulsive status epilepticus may present as confusion, behavioural disturbances and psychiatric conditions. We present the case of a 17-year-old man who had episodes of non-convulsive status epilepticus as his only manifestation of epilepsy which was mis-diagnosed as a psychiatric condition for over 10 years. He has had almost complete resolution of his symptoms with the introduction of carbamazepine. Non-convulsive status epilepticus is probably commoner than previously thought, and should be considered as a possible diagnosis in all patients presenting with prolonged episodes of altered consciousness even without other manifestations of epilepsy. PMID:8683509

Human Immunodeficiency Viral Infection and Status Epilepticus in United States (2002–2009)

PubMed Central

Chaudhry, Saqib A.; Afzal, Mohammad Rauf; Rodriguez, Gustavo J.; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E.; Suri, M. Fareed K.; Qureshi, Adnan I.

2015-01-01

Objective To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Methods Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002–2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. Results The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%–0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8–2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Conclusions Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes. PMID:26301033

Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.

PubMed

Holtkamp, Martin

2018-03-01

Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA) A receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABA A receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological

Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management

PubMed Central

Billington, Michael; Kandalaft, Osama R.; Aisiku, Imoigele P.

2016-01-01

Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents. PMID:27563928

Status epilepticus developing during lacosamide monotherapy

PubMed Central

Papacostas, Savvas S

2015-01-01

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. PMID:25628098

Top 100 cited articles on epilepsy and status epilepticus: A bibliometric analysis.

PubMed

Park, Kang Min; Kim, Sung Eun; Lee, Byung In; Kim, Hyung Chan; Yoon, Dae Young; Song, Hong Ki; Bae, Jong Seok

2017-08-01

The purpose of this study is to identify the top 100-cited articles dedicated to epilepsy and status epilepticus published in journals from January, 1950 through February, 2016 that have made key contributions in the field. We performed a search of journals and selected the top 100-cited articles on epilepsy and status epilepticus, respectively, by utilizing the Institute for Scientific Information database available under the banner of the Web of Science. The top-cited articles on epilepsy and status epilepticus were all published in 24 journals, respectively. In both fields of epilepsy and status epilepticus, the most frequently cited journal was Epilepsia (26 articles on epilepsy and 19 articles on status epilepticus). The 100 most-cited articles in the field of both epilepsy and status epilepticus mainly originated from institutions in the United States of America. The articles on epilepsy included 25 laboratory studies, 15 pharmacotherapy studies, 13 general review studies, 12 surgery studies, 11 neuroimaging studies, eight epidemiology studies, eight neuropsychiatry studies, six genetic studies, and two electrophysiology studies, whereas 41 laboratory studies, 21 epidemiology studies, 16 pharmacotherapy studies, nine electrophysiology studies, nine general review studies, and four neuroimaging studies were included in the field of status epilepticus. We demonstrate that neuroimaging, genetics, and surgery are emerging topics in the field of epilepsy over the past decades. Moreover, we found that the majority of top-cited articles on epilepsy and status epilepticus originated from institutions in the United States of America and most were published in Epilepsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

New experimental therapies for status epilepticus in preclinical development.

PubMed

Walker, Matthew C; Williams, Robin S B

2015-08-01

Starting with the established antiepileptic drug, valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum, and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaluated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproic acid in treating the status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.

PubMed

Sutter, Raoul; Dittrich, Tolga; Semmlack, Saskia; Rüegg, Stephan; Marsch, Stephan; Kaplan, Peter W

2018-01-01

Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. All identified studies were screened for eligibility by two independent reviewers. Key data were extracted using standardized data collection forms. Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.

Status epilepticus severity score (STESS): A useful tool to predict outcome of status epilepticus.

PubMed

Goyal, Manoj Kumar; Chakravarthi, Sudheer; Modi, Manish; Bhalla, Ashish; Lal, Vivek

2015-12-01

The treatment protocols for status epilepticus (SE) range from small doses of intravenous benzodiazepines to induction of coma. The pros and cons of more aggressive treatment regimen remain debatable. The importance of an index need not be overemphasized which can predict outcome of SE and guide the intensity of treatment. We tried to evaluate utility of one such index Status epilepticus severity score (STESS). 44 consecutive patients of SE were enrolled in the study. STESS results were compared with various outcome measures: (a) mortality, (b) final neurological outcome at discharge as defined by functional independence measure (FIM) (good outcome: FIM score 5-7; bad outcome: FIM score 1-4), (c) control of SE within 1h of start of treatment and (d) need for coma induction. A higher STESS score correlated significantly with poor neurological outcome at discharge (p=0.0001), need for coma induction (p=0.0001) and lack of response to treatment within 1h (p=0.001). A STESS of <3 was found to have a negative predictive value of 96.9% for mortality, 96.7% for poor neurological outcome at discharge and 96.7% for need of coma induction, while a STESS of <2 had negative predictive value of 100% for mortality, coma induction and poor neurological outcome at discharge. STESS can reliably predict the outcome of status epilepticus. Further studies on STESS based treatment approach may help in designing better therapeutic regimens for SE. Copyright © 2015 Elsevier B.V. All rights reserved.

Propofol Infusion Syndrome in Refractory Status Epilepticus

PubMed Central

Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won

2013-01-01

Background and Purpose: Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. Methods: This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. Results: There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. Conclusions: RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE. PMID:24649467

Status epilepticus in the elderly: epidemiology, clinical aspects and treatment

PubMed Central

de Assis, Telma M.R.; Costa, Gersonita; Bacellar, Aroldo; Orsini, Marco; Nascimento, Osvaldo J.M.

2012-01-01

The aim of the study was to review the epidemiology, clinical profile and discuss the etiology, prognosis and treatment options in patients aged 60 years or older presenting with status epilepticus. We performed a systematic review involving studies published from 1996 to 2010, in Medline/PubMed, Scientific Electronic Library on line (Scielo), Latin-American and Caribbean Center of Health Sciences Information (Lilacs) databases and textbooks. Related articles published before 1996, when relevant for discussing epilepsy in older people, were also included. Several population studies had shown an increased incidence of status epilepticus after the age of 60 years. Status epilepticus is a medical and neurological emergency that is associated with high morbidity and mortality, and is a major concern in the elderly compared to the general population. Prompt diagnosis and effective treatment of convulsive status epilepticus are crucial to avoid brain injury and reduce the fatality rate in this age group. PMID:23355930

Status epilepticus caused by a myxoedema coma.

PubMed

Jansen, H J; Doebé, S R Oedit; Louwerse, E S; van der Linden, J C; Netten, P M

2006-06-01

The case of a 63-year-old woman who presented with status epilepticus, coma and hypoventilation is reported. A primary neurological cause was considered. Hypothermia led to further investigations and a diagnosis of severe hypothyroidism. The neurological complications of hyperthyriodism include alteration in mental status with slowness, decreased concentration and lethargy, headache, cranial nerve palsies, dysarthria, hoarseness, myopathy, neuropathy, reflex changes, ataxia, and psychotic episodes. Our patient suffered from a rare consequence of severe hypothyroidism presenting with status epilepticus and she died despite treatment. To our knowledge this is the second patient to be reported with myxoedema coma with this kind of presentation. Despite therapeutic options, there is a high mortality rate.

Super-refractory status epilepticus in West China.

PubMed

Tian, L; Li, Y; Xue, X; Wu, M; Liu, F; Hao, X; Zhou, D

2015-07-01

This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An update in the initial management of paediatric status epilepticus.

PubMed

Lawton, Ben; Davis, Tessa; Goldstein, Henry; Tagg, Andrew

2018-06-01

Over the last 2 years, algorithms for the optimal management of status epilepticus have changed, as the medical community has recognized the need to terminate seizures in status in a timely manner. Recent research has evaluated the different choices of benzodiazepine and has given consideration to second-line treatment options. There has been a move to examine alternatives to phenytoin (such as levetiracetam and lacosamide) as second-line agents. Valproate should be used cautiously in view of the potential side effects. Three ongoing trials [Established Staus Epilepticus Treatment Trial (ESETT), Convulsive Status Epilepticus Paediatric Trial (ConSEPT), and emergency treatment with levetiracetam or phenytoin in status epilepticus in children (EcLiPSE)] are comparing the efficacy of levetiracetam and phenytoin. Benzodiazepines remain the first-line agent of choice, although there is ongoing discussion about the mode of administration and the best drug to choose. The results of ESETT, ConSEPT, and EcLiPSE will affect our future management of status, as we give consideration to levetiracetam as an alternative to phenytoin. Other medications such as lacosamide may emerge in future algorithms too.

Vagus Nerve Stimulation for Electrographic Status Epilepticus in Slow-Wave Sleep.

PubMed

Carosella, Christopher M; Greiner, Hansel M; Byars, Anna W; Arthur, Todd M; Leach, James L; Turner, Michele; Holland, Katherine D; Mangano, Francesco T; Arya, Ravindra

2016-07-01

Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep. We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail. After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement. Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic burst-suppression coma in pediatric febrile refractory status epilepticus.

PubMed

Lin, Jainn-Jim; Chou, Cheng-Che; Lan, Shih-Yun; Hsiao, Hsiang-Ju; Wang, Yu; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Lin, Kuang-Lin

2017-09-01

Evidence for the beneficial effect of therapeutic burst-suppression coma in pediatric patients with febrile refractory status epilepticus is limited, and the clinical outcomes of this treatment strategy are largely unknown. Therefore, the aim of this study was to explore the outcomes of therapeutic burst-suppression coma in a series of children with febrile refractory status epilepticus. We retrospectively reviewed consecutive pediatric patients with febrile refractory status epilepticus admitted to our pediatric intensive care unit between January 2000 and December 2013. The clinical characteristics were analyzed. Thirty-five patients (23 boys; age range: 1-18years) were enrolled, of whom 28 (80%) developed super-refractory status epilepticus. All of the patients received the continuous administration of intravenous antiepileptic drugs for febrile refractory status epilepticus, and 26 (74.3%) achieved therapeutic burst-suppression coma. All of the patients received mechanical ventilatory support, and 26 (74.3%) received inotropic agents. Eight (22.9%) patients died within 1month. The neurologically functional outcomes at 6months were good in six (27.3%) of the 22 survivors, of whom two returned to clinical baseline. The patients with therapeutic burst-suppression coma were significantly associated with hemodynamic support than the patients with electrographic seizures control (p=0.03), and had a trend of higher 1-month mortality rate, worse 6months outcomes, and a longer duration of hospitalization. Our results suggest that therapeutic burst-suppression coma to treat febrile refractory status epilepticus may lead to an increased risk of hemodynamic instability and a trend of worse outcomes. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Underestimated Rate of Status Epilepticus according to the Traditional Definition of Status Epilepticus.

PubMed

Ong, Cheung-Ter; Wong, Yi-Sin; Sung, Sheng-Feng; Wu, Chi-Shun; Hsu, Yung-Chu; Su, Yu-Hsiang; Hung, Ling-Chien

2015-01-01

Status epilepticus (SE) is an important neurological emergency. Early diagnosis could improve outcomes. Traditionally, SE is defined as seizures lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness. Some specialists argued that the duration of seizures qualifying as SE should be shorter and the operational definition of SE was suggested. It is unclear whether physicians follow the operational definition. The objective of this study was to investigate whether the incidence of SE was underestimated and to investigate the underestimate rate. This retrospective study evaluates the difference in diagnosis of SE between operational definition and traditional definition of status epilepticus. Between July 1, 2012, and June 30, 2014, patients discharged with ICD-9 codes for epilepsy (345.X) in Chia-Yi Christian Hospital were included in the study. A seizure lasting at least 30 min or repeated seizures over 30 min without recovery of consciousness were considered SE according to the traditional definition of SE (TDSE). A seizure lasting between 5 and 30 min was considered SE according to the operational definition of SE (ODSE); it was defined as underestimated status epilepticus (UESE). During a 2-year period, there were 256 episodes of seizures requiring hospital admission. Among the 256 episodes, 99 episodes lasted longer than 5 min, out of which 61 (61.6%) episodes persisted over 30 min (TDSE) and 38 (38.4%) episodes continued between 5 and 30 min (UESE). In the 38 episodes of seizure lasting 5 to 30 minutes, only one episode was previously discharged as SE (ICD-9-CM 345.3). Conclusion. We underestimated 37.4% of SE. Continuing education regarding the diagnosis and treatment of epilepsy is important for physicians.

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

PubMed

Chamberlain, James M; Okada, Pamela; Holsti, Maija; Mahajan, Prashant; Brown, Kathleen M; Vance, Cheryl; Gonzalez, Victor; Lichenstein, Richard; Stanley, Rachel; Brousseau, David C; Grubenhoff, Joseph; Zemek, Roger; Johnson, David W; Clemons, Traci E; Baren, Jill

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

Status Epilepticus

PubMed Central

Seinfeld, Syndi; Goodkin, Howard P.; Shinnar, Shlomo

2016-01-01

Although the majority of seizures are brief and cause no long-term consequences, a subset is sufficiently prolonged that long-term consequences can result. These very prolonged seizures are termed “status epilepticus” (SE) and are considered a neurological emergency. The clinical presentation of SE can be diverse. SE can occur at any age but most commonly occurs in the very young and the very old. There are numerous studies on SE in animals in which the pathophysiology, medication responses, and pathology can be rigorously studied in a controlled fashion. Human data are consistent with the animal data. In particular, febrile status epilepticus (FSE), a form of SE common in young children, is associated with injury to the hippocampus and subsequent temporal lobe epilepsy (TLE) in both animals and humans. PMID:26931807

Refractory status epilepticus complicated by drug-induced involuntary movements.

PubMed

Nair, Pradeep Pankajakshan; Wadwekar, Vaibhav; Murgai, Aditya; Narayan, Sunil K

2014-02-11

New onset refractory status epilepticus (NORSE) is a neurological emergency and difficult to treat condition. We report a case of involuntary movements resulting from thiopentone sodium infusion during the management of refractory status epilepticus. A young woman was admitted with fever and NORSE in the neurology intensive care unit. In addition to supportive measures, she was treated with intravenous lorazepam, phenytoin sodium, sodium valproate, midazolam and thiopentone sodium. While on thiopentone sodium, she developed involuntary twitches involving her upper limbs and face with EEG showing no evidence of ongoing status epilepticus. Because of the temporal relationship with thiopentone infusion, we tapered the dose of thiopentone sodium, which resulted in the disappearance of the movements. The patient recovered well with no recurrence of the seizures during the hospital stay.

Towards acute pediatric status epilepticus intervention teams: Do we need "Seizure Codes"?

PubMed

Stredny, Coral M; Abend, Nicholas S; Loddenkemper, Tobias

2018-05-01

To identify areas of treatment delay and barriers to care in pediatric status epilepticus, review ongoing quality improvement initiatives, and provide suggestions for further innovations to improve and standardize these patient care processes. Narrative review of current status epilepticus management algorithms, anti-seizure medication administration and outcomes associated with delays, and initiatives to improve time to treatment. Articles reviewing or reporting quality improvement initiatives were identified through a PubMed search with keywords "status epilepticus," "quality improvement," "guideline adherence," and/or "protocol;" references of included articles were also reviewed. Rapid initiation and escalation of status epilepticus treatment has been associated with shortened seizure duration and more favorable outcomes. Current evidence-based guidelines for management of status epilepticus propose medication algorithms with suggested times for each management step. However, time to antiseizure medication administration for pediatric status epilepticus remains delayed in both the pre- and in-hospital settings. Barriers to timely treatment include suboptimal preventive care, inaccurate seizure detection, infrequent or restricted use of home rescue medications by caregivers and pre-hospital emergency personnel, delayed summoning and arrival of emergency personnel, and use of inappropriately dosed medications. Ongoing quality improvement initiatives in the pre- and in-hospital settings targeting these barriers are reviewed. Improved preventive care, seizure detection, and rescue medication education may advance pre-hospital management, and we propose the use of acute status epilepticus intervention teams to initiate and incorporate in-hospital interventions as time-sensitive "Seizure Code" emergencies. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Intravenous Levetiracetam in the Rat Pilocarpine-Induced Status Epilepticus Model: Behavioral, Physiological and Histological Studies

PubMed Central

Zheng, Yi; Moussally, Jon; Cash, Sydney S.; Karnam, Havisha B.; Cole, Andrew J.

2010-01-01

Purpose Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality. Intravenous levetiracetam (LEV), an antiepileptic drug approved to treat partial seizures, has recently been introduced. We sought to determine the effect of LEV administered intravenously in a chemoconvulsant model of status epilepticus. Methods We examined the effect of intravenous LEV in the rat lithium-pilocarpine model of status epilepticus. Ten or 30 minutes after the onset of behavioral status epilepticus, animals were treated with LEV (200–1200 mg/kg i.v.) administered in a single bolus. Behavioral responses were recorded. Selected animals had continuous EEG recording before, during and after the administration of LEV. Some animals were sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury. Results When administered 30 minutes after the onset of behavioral epileptic seizures, transient attenuation of ictal behavior was observed in animals treated with 800 mg/kg or more of LEV. The duration of behavioral attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from a mean of 4 minutes to 23.6 minutes. When administered 10 minutes after seizure onset, 400 mg/kg of LEV resulted in transient ictal behavioral attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine also delayed the onset of seizures. EEG recordings, however, showed no significant attenuation of ictal discharge. By contrast, TUNEL staining demonstrated less neuronal injury in hippocampii and other limbic structures in animals that responded behaviorally to LEV. Conclusions Intravenous administration of LEV in a chemoconvulsant model of status epilepticus results in attenuation of behavioral manifestations of seizure discharge and in reduction of neuronal injury but does not significantly alter ictal discharge recorded by EEG

Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: behavioral, physiological and histological studies.

PubMed

Zheng, Yi; Moussally, Jon; Cash, Sydney S; Karnam, Havisha B; Cole, Andrew J

2010-01-01

Status epilepticus is a neurological emergency associated with neuronal injury, lasting behavioral disturbance, and a high rate of mortality. Intravenous levetiracetam (LEV), an anti-epileptic drug approved to treat partial seizures, has recently been introduced. We sought to determine the effect of LEV administered intravenously in a chemoconvulsant model of status epilepticus. We examined the effect of intravenous LEV in the rat lithium-pilocarpine model of status epilepticus. Ten or 30 min after the onset of behavioral status epilepticus, animals were treated with LEV (200-1200 mg/kg i.v.) administered in a single bolus. Behavioral responses were recorded. Selected animals had continuous EEG recording before, during and after the administration of LEV. Some animals were sacrificed 24 h after the experiment and processed for histochemical assessment of neuronal injury. When administered 30 min after the onset of behavioral epileptic seizures, transient attenuation of ictal behavior was observed in animals treated with 800 mg/kg or more of LEV. The duration of behavioral attenuation increased sharply as the dose rose to 1000 mg/kg or higher, from a mean of 4-23.6 min. When administered 10 min after seizure onset, 400 mg/kg of LEV resulted in transient ictal behavioral attenuation, and higher doses caused relatively longer periods of attenuation. Pretreatment with LEV prior to pilocarpine also delayed the onset of seizures. EEG recordings, however, showed no significant attenuation of ictal discharge. By contrast, TUNEL staining demonstrated less neuronal injury in hippocampii and other limbic structures in animals that responded behaviorally to LEV. Intravenous administration of LEV in a chemoconvulsant model of status epilepticus results in attenuation of behavioral manifestations of seizure discharge and in reduction of neuronal injury but does not significantly alter ictal discharge recorded by EEG. Copyright 2009 Elsevier Ltd. All rights reserved.

Managing Status Epilepticus in the Older Adult

PubMed Central

Legriel, Stephane; Brophy, Gretchen M.

2016-01-01

The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care. PMID:27187485

Neurodevelopmental delay associated with nonconvulsive status epilepticus in a toddler.

PubMed

Shinawi, M; Shahar, E

2001-03-01

Nonconvulsive status epilepticus is a prolonged and continuous state of increased unawareness without overt motor seizures linked with repetitive generalized epileptic discharges. In children, it may occur de novo but more commonly may complicate a preexisting epileptic disorder. We report on a 2-year-old female who presented with global developmental delay as the main manifestation of nonconvulsive status epilepticus. Following valproic acid treatment, her motor, cognitive, and speech delays had gradually subsided and nearly completely resolved, in concert with normalization of electroencephalography (EEG). Hence, given a possible, albeit rare, presentation of nonconvulsive status epilepticus with global developmental delay, we suggest that EEG should be recommended in any infant who manifests neurodevelopmental delay.

Copy number variations in patients with electrical status epilepticus in sleep.

PubMed

Kevelam, Sietske H G; Jansen, Floor E; Binsbergen, Ellen van; Braun, Kees P J; Verbeek, Nienke E; Lindhout, Dick; Poot, Martin; Brilstra, Eva H

2012-02-01

Electrical status epilepticus in sleep syndrome is the association of the electroencephalographic pattern and deficits in language or global cognitive function and behavioral problems. The etiology is often unknown, but genetic risk factors have been implicated. Array-based comparative genomic hybridization was used to identify copy number variations in 13 children with electrical status epilepticus in sleep syndrome to identify possible underlying risk factors. Seven copy number variations were detected in 4 of the 13 patients, which consisted of 6 novel gains and 1 loss, the recurrent 15q13.3 microdeletion. Two patients carried a probable pathogenic copy number variation containing a gene involved in the cholinergic pathway. Genetic aberrations in patients with electrical status epilepticus in sleep syndrome can provide an entry in the investigation of the etiology of electrical status epilepticus in sleep. However, further studies are needed to confirm our findings.

P2X receptors as targets for the treatment of status epilepticus

PubMed Central

Henshall, David C.; Diaz-Hernandez, Miguel; Miras-Portugal, M. Teresa; Engel, Tobias

2013-01-01

Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection. PMID:24324404

P2X receptors as targets for the treatment of status epilepticus.

PubMed

Henshall, David C; Diaz-Hernandez, Miguel; Miras-Portugal, M Teresa; Engel, Tobias

2013-11-26

Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection.

Pediatric intensive care treatment of uncontrolled status epilepticus.

PubMed

Wilkes, Ryan; Tasker, Robert C

2013-04-01

The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus. Copyright © 2013 Elsevier Inc. All rights reserved.

De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

PubMed

Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin

2016-08-01

To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

PubMed

Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

2016-03-01

Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital.

PubMed

Halawa, Eman F; Draz, Iman; Ahmed, Dalia; Shaheen, Hala A

2015-11-01

Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. © The Author(s) 2015.

Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus.

PubMed

Nakamura, Kensuke; Inokuchi, Ryota; Daidoji, Hiroaki; Naraba, Hiromu; Sonoo, Tomohiro; Hashimoto, Hideki; Tokunaga, Kurato; Hiruma, Takahiro; Doi, Kent; Morimura, Naoto

2017-06-01

Benzodiazepines are used as first-line treatments for status epilepticus. Fosphenytoin (FPHT) is recommended for second-line therapy; however, intravenous injection of levetiracetam (LEV) may also be effective against status epilepticus. Herein, we compared the efficacy and safety of LEV as a second-line treatment for status epilepticus with FPHT in Japanese patients.Patients with status epilepticus were selected from the database of the Emergency and Critical Care Center of Hitachi General Hospital. The subjects were patients whose status epilepticus was successfully stopped by diazepam, and in whom FPHT or LEV was administered after diazepam. As LEV injections recently became clinically available in Japan, the choice of drug was determined by the treatment period. Thus, 21 patients who were intravenously injected with LEV as a second-line therapy and 42 matched patients (historical controls) who were treated with FPHT (1:2) were selected.The subjects had a mean age of 64.0 ± 2.2 years, and included 48 males and 15 females. The status epilepticus control rates of the FPHT and LEV groups did not differ significantly (81.0% [34/42] vs 85.1% [18/21], respectively; P  =  .69). As for serious adverse events, a reduction in blood pressure was observed in the FPHT group, but not in the LEV group. The oral anticonvulsant switching rates of the 2 groups were similar, but the same-drug switching rates of the FPHT and LEV groups were 8.1% and 77.8%, respectively.The efficacy of intravenous LEV injections after status epilepticus was equivalent to that of FPHT, and the incidence of adverse events was lower in the LEV group. LEV is effective and safe at preventing recurrent seizures after status epilepticus following benzodiazepine treatment.

Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

PubMed

Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

2015-07-28

Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

PubMed

Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

2016-03-01

Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno- and chemotherapies, with eventual partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

Myxoedema coma presenting in status epilepticus.

PubMed Central

Woods, K. L.; Holmes, G. K.

1977-01-01

A 71-year-old woman with myxoedema coma presenting in status epilepticus is reported. Although this complication of myxoedema coma is considered to be fatal the patient described responded dramatically to treatment and remains in good health. PMID:876913

Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome.

PubMed

Legriel, Stephane; Bresson, Edouard; Deye, Nicolas; Grimaldi, David; Sauneuf, Bertrand; Lesieur, Olivier; Lascarrou, Jean-Baptiste; Argaud, Laurent; Chelly, Jonathan; Beuret, Pascal; Schnell, David; Chateauneuf, Anne-Laure; Holleville, Mathilde; Perier, François; Lemiale, Virginie; Bruel, Cedric; Cronier, Pierrick; Pichon, Nicolas; Mongardon, Nicolas; de-Prost, Nicolas; Dumas, Florence; Cariou, Alain

2018-05-08

Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus-related cardiac arrest. Retrospective multicenter study. Seventeen university or university affiliated participating ICUs in France and Belgium. Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. None. We included 49 cases with convulsive status epilepticus-cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5-85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03-7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27-13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67-34.69; p < 0.0001). Having at least one comorbidity among cardiac, respiratory, and neurologic (other than epilepsy) conditions predicted absence of cardiac arrest (odds ratio, 0.28; 95% CI, 0.10-0.80; p = 0.02). In patients managed for convulsive status epilepticus, relative hypoxemia, on-scene management complications, and drug poisoning as the cause of

P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus.

PubMed

Henshall, David C; Engel, Tobias

2015-08-01

There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Status epilepticus-induced changes in the subcellular distribution and activity of calcineurin in rat forebrain.

PubMed

Kurz, Jonathan E; Rana, Annu; Parsons, J Travis; Churn, Severn B

2003-12-01

This study was performed to determine the effect of prolonged status epilepticus on the activity and subcellular location of a neuronally enriched, calcium-regulated enzyme, calcineurin. Brain fractions isolated from control animals and rats subjected to pilocarpine-induced status epilepticus were subjected to differential centrifugation. Specific subcellular fractions were tested for both calcineurin activity and enzyme content. Significant, status epilepticus-induced increases in calcineurin activity were found in homogenates, nuclear fractions, and crude synaptic membrane-enriched fractions isolated from both cortex and hippocampus. Additionally, significant increases in enzyme levels were observed in crude synaptic fractions as measured by Western analysis. Immunohistochemical studies revealed a status epilepticus-induced increase in calcineurin immunoreactivity in dendritic structures of pyramidal neurons of the hippocampus. The data demonstrate a status epilepticus-induced increase in calcineurin activity and concentration in the postsynaptic region of forebrain pyramidal neurons.

Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats★

PubMed Central

Liang, Zhaoliang; Gao, Fei; Wang, Fajun; Wang, Xiaochen; Song, Xinyu; Liu, Kejing; Zhan, Ren-Zhi

2013-01-01

Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer. PMID:25206705

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

PubMed

Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M

2017-06-01

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Epilepsy is associated with ventricular alterations following convulsive status epilepticus in children.

PubMed

Ali, Wail; Bubolz, Beth A; Nguyen, Linh; Castro, Danny; Coss-Bu, Jorge; Quach, Michael M; Kennedy, Curtis E; Anderson, Anne E; Lai, Yi-Chen

2017-12-01

Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus. We conducted a 2-year retrospective, case-control study. Children between 1 month and 21 years of age were included if they were admitted to the pediatric intensive care unit with primary diagnosis of convulsive status epilepticus and had 12-lead electrocardiogram (ECG) within 24 hours of admission. Children with heart disease, ion channelopathy, or on vasoactive medications were excluded. Age-matched control subjects had no history of seizures or epilepsy. The primary outcome was ventricular abnormalities represented by ST segment changes, abnormal T wave, QRS axis deviation, and corrected QT (QTc) interval prolongation. The secondary outcomes included QT/RR relationship, beat-to-beat QTc interval variability, ECG interval measurement between groups, and clinical factors associated with ECG abnormalities. Of 317 eligible children, 59 met the inclusion criteria. History of epilepsy was present in 31 children (epileptic) and absent in 28 children (non-epileptic). Compared with the control subjects (n = 31), the status epilepticus groups were more likely to have an abnormal ECG with overall odds ratio of 3.8 and 7.0 for the non-epileptic and the epileptic groups respectively. Simple linear regression analysis demonstrated that children with epilepsy exhibited impaired dependence and adaptation of the QT interval on heart rate. Beat-to-beat QTc interval variability, a marker of ventricular repolarization instability, was increased in children with epilepsy. Convulsive status epilepticus can adversely affect ventricular electrical properties and stability in children

Status epilepticus due to acute encephalitis: NORSE does not necessarily mean worse.

PubMed

Holzer, Franz Josef; Rossetti, Andrea O

2018-06-25

Status epilepticus (SE), refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) are very severe medical conditions with high mortality and a potentially poor outcome in several surviving patients. Although SE, RSE and SRSE are primarily neurological affections, these patients will be admitted to an intensive care unit (ICU) for critical care, most often mechanical ventilation and general anesthesia. When a patient enters RSE or even SRSE, his/her stay in the ICU may become longer and neurologists and ICU specialists will have to agree on whether or not it is appropriate to continue critical care. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Non-convulsive status epilepticus resistant to benzodiazepines.

PubMed Central

Livingston, J H; Brown, J K

1987-01-01

We describe the failure of an intravenous benzodiazepine to control non-convulsive status epilepticus occurring in six patients with the Lennox-Gastaut syndrome. In one patient the benzodiazepine induced a paradoxical response with clinical and electroencephalographic seizures. PMID:3545098

Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and diagnosis.

PubMed

Blades Golubovic, Susan; Rossmeisl, John H

2017-05-01

To review current knowledge of the etiopathogenesis, diagnosis, and consequences of status epilepticus (SE) in veterinary patients. Human and veterinary literature, including clinical and laboratory research and reviews. Status epilepticus is a common emergency in dogs and cats, and may be the first manifestation of a seizure disorder. It results from the failure of termination of an isolated seizure. Multiple factors are involved in SE, including initiation and maintenance of neuronal excitability, neuronal network synchronization, and brain microenvironmental contributions to ictogenesis. Underlying etiologies of epilepsy and SE in dogs and cats are generally classified as genetic (idiopathic), structural-metabolic, or unknown. Diagnosis of convulsive SE is usually made based on historical information and the nature of the seizures. Patient specific variables, such as the history, age of seizure onset, and physical and interictal neurological examination findings can help hone the rule out list, and are used to guide selection and prioritization of diagnostic tests. Electroencephalographic monitoring is routinely used in people to diagnose SE and guide patient care decisions, but is infrequently performed in veterinary medicine. Nonconvulsive status epilepticus has been recognized in veterinary patients; routine electroencephalography would aid in the diagnosis of this phenomenon in dogs and cats. Status epilepticus is a medical emergency that can result in life-threatening complications involving the brain and systemic organs. Status epilepticus often requires comprehensive diagnostic testing, treatment with multiple anticonvulsant agents, and intensive supportive care. © Veterinary Emergency and Critical Care Society 2017.

In-hospital mortality of generalized convulsive status epilepticus: a large US sample.

PubMed

Koubeissi, Mohamad; Alshekhlee, Amer

2007-08-28

To evaluate the in-hospital mortality associated with generalized convulsive status epilepticus (GCSE), and predictors of death in a large US cohort. We identified our cohort from the National Inpatient Sample for the years 2000 through 2004 by searching the International Classification of Diseases, Ninth Revision, code for GCSE. We excluded patients with partial status epilepticus, and assessed whether associated diagnoses including brain tumors, CNS infections, stroke, hypoxic-ischemic brain injury, metabolic derangements, and respiratory failure predicted mortality. We used logistic regression models to identify predictors of death. Eleven thousand five hundred eighty patients were included in this analysis. The mean age of the patients was 39 +/- 25.6 years, and the median duration of stay was 3 days. Male sex (53.4%) and white race (42.4%) were predominant. Overall in-hospital mortality was 399 in 11,580 (3.45%). Age was a significant predictor of death. Mortality tripled in those who received mechanical ventilation compared with those who did not (7.43% vs 2.22%, odds ratio [OR] 2.79, 95% CI 2.18 to 3.59). Other predictors of mortality included hypoxic-ischemic brain injury (OR 9.85, 95% CI 6.63 to 14.6), cerebrovascular diseases (OR 2.08, 95% CI 1.13 to 3.82), female sex (OR 1.34, 95% CI 1.04 to 1.73), and higher comorbidity index (OR 6.79, 95% CI 4.27 to 10.8). Overall in-hospital mortality from generalized convulsive status epilepticus is low, but remarkably increases in those treated with mechanical ventilation. Other predictors of mortality include older age, female sex, hypoxic-ischemic brain injury, and higher comorbidity index.

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

DTIC Science & Technology

2011-09-01

Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

Supra-recommendation Treatment of Super-refractory Status Epilepticus.

PubMed

Vyas, Devashish Dhiren; Dash, Gopal Krishna

2016-06-01

A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India.

Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

PubMed Central

Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

2014-01-01

Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

Status epilepticus as the only presentation of the neonatal Bartter syndrome.

PubMed

Patra, Soumya; Konar, Mithun C; Basu, Rajarshi; Khaowas, Ajoy K; Dutta, Soumyadeep; Sarkar, Debanjali

2012-03-01

Bartter syndrome is a rare hereditary (autosomal recessive) salt-losing tubulopathy characterized by hypokalemia, hypochloremia, metabolic alkalosis, and normal blood pressure with hyperreninemia, The underlying renal abnormality results in excessive urinary losses of sodium, chloride, and potassium. We report a case of a four-month-old infant with neonatal Bartter syndrome, who presented only with status epilepticus. To the best of our present knowledge, there is no reported case of Bartter syndrome who presented with status epilepticus.

Progranulin and Its Related MicroRNAs after Status Epilepticus: Possible Mechanisms of Neuroprotection.

PubMed

Körtvelyessy, Peter; Huchtemann, Tessa; Heinze, Hans-Jochen; Bittner, Daniel M

2017-02-24

The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus.

Progranulin and Its Related MicroRNAs after Status Epilepticus: Possible Mechanisms of Neuroprotection

PubMed Central

Körtvelyessy, Peter; Huchtemann, Tessa; Heinze, Hans-Jochen; Bittner, Daniel M.

2017-01-01

The current knowledge about neuroprotective mechanisms in humans after status epilepticus is scarce. One reason is the difficulty to measure possible mediators of these neuroprotective mechanisms. The dawn of microRNA detection in the cerebrospinal fluid (CSF) and the recent advancements in measuring proteins in the CSF such as progranulin, which is, e.g., responsible for neurite outgrowth and limiting exceeding neuroinflammatory responses, have given us new insights into putative neuroprotective mechanisms following status epilepticus. This should complement the animal data. In this review, we cover what is known about the role of progranulin as well as the links between microRNA changes and the progranulin pathway following status epilepticus in humans and animals hypothesizing neuroprotective and neurorehabilitative effects. Progranulin has also been found to feature prominently in the neuroprotective processes under hypoxic conditions and initiating neurorehabilitative processes. These properties may be used therapeutically, e.g., through drugs that raise the progranulin levels and therefore the cerebral progranulin levels as well with the goal of improving the outcome after status epilepticus. PMID:28245590

A Study of Super Refractory Status Epilepticus from India.

PubMed

Misra, Usha K; Kalita, Jayantee; Dubey, Deepanshu

2017-01-01

Super refractory status epilepticus (SRSE) is an important and recently recognized neurological emergency. In view of paucity of studies on SRSE, we report the frequency, etiology and outcome of SRSE. In a hospital-based observational study during 2013 to 2016, consecutive patients with SRSE [persistence of status epilepticus (SE) for 24 h or more, or recurrence of SE on weaning of intravenous anesthetic] were included. The demographic, clinical, and laboratory data were obtained and the severity of SE was defined using Status Epilepticus Severity Score (STESS). The outcome was defined as control of SE, hospital death, and functional status at the time of discharge. Fourteen (13%) patients developed SRSE. Their median age was 27.5 (2-70) years and four were below 18 years of age. The etiology of SRSE was metabolic encephalopathy and encephalitis in five patients each, cerebral venous sinus thrombosis in one and miscellaneous disorders in three patients. Six (43%) patients died. The patients with SRSE had higher admission STESS ( p  = 0.04), and longer intensive care unit ( p  < 0.01) and hospital ( p  = 0.004) stay compared to non-SRSE group. The patients with treatable etiology had better outcome. SRSE occurred in 13% patients with SE and 43% of them died. The SRSE patients with treatable etiology had a better outcome.

[Treatment of refractory status epilepticus with topiramate. Report of three cases].

PubMed

Soler, Bernardita; Godoy, Jaime; Mellado Talesnik, Patricio

2009-07-01

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50%. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Focal status epilepticus as a manifestation of idiopathic hypertrophic cranial pachymeningitis.

PubMed

Navalpotro-Gómez, Irene; Vivanco-Hidalgo, Rosa María; Cuadrado-Godia, Elisa; Medrano-Martorell, Santiago; Alameda-Quitllet, Francisco; Villalba-Martínez, Gloria; Roquer, Jaume

2016-08-15

Idiopathic hypertrophic cranial pachymeningitis (IHCP) is an uncommon disease of unknown etiology characterized by thickening of the cerebral dura mater with possible associated inflammation. The most frequently described clinical symptoms include headache, cranial nerve palsy, and cerebellar dysfunction. Epilepsy and/or status epilepticus as main presentation is very uncommon. Two consecutive cases are presented of patients manifesting focal status epilepticus secondary to IHCP, with clinical, laboratory [blood test and cerebrospinal fluid (CSF) analysis], neuroradiologic [magnetic resonance imaging (MRI) at 3 Tesla and digital subtraction angiography (DSA)], and therapeutic data. One patient underwent meningeal biopsy; pathology findings are also included. Corticosteroid therapy resulted in clinical improvement in both cases, and neuroimaging showed decreased abnormal morphology, compared to initial findings. In the diagnostic approach to focal status epilepticus or epilepsy, IHCP must be considered a potential, although extremely infrequent, cause. Anti-inflammatory treatment is an effective addition to antiepileptic drug therapy in patients with IHCP. Copyright © 2016 Elsevier B.V. All rights reserved.

Interleukin-18 Expression Increases in Response to Neurovascular Damage Following Soman-induced Status Epilepticus in Rats

DTIC Science & Technology

2015-07-22

CONTRACT NUMBER soman-induced status epilepticus in rats 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Johnson, EA, Guignet, MA, Dao...See reprint. 15. SUBJECT TERMS Interleukin 18, Status epilepticus , Soman (GD), Macrophage, T-cell, Neutrophil, Piriform cortex, Hippocampus...following soman-induced status epilepticus in rats Erik A. Johnson1*, Michelle A. Guignet1, Thuy L. Dao1, Tracey A. Hamilton2 and Robert K. Kan1 Abstract

Use of the EpiNet database for observational study of status epilepticus in Auckland, New Zealand.

PubMed

Bergin, Peter; Jayabal, Jayaganth; Walker, Elizabeth; Davis, Suzanne; Jones, Peter; Dalziel, Stuart; Yates, Kim; Thornton, Vanessa; Bennett, Patricia; Wilson, Kaisa; Roberts, Lynair; Litchfield, Rhonda; Te Ao, Braden; Parmer, Priya; Feigin, Valery; Jost, Jeremy; Beghi, Ettore; Rossetti, Andrea O

2015-08-01

The EpiNet project has been established to facilitate investigator-initiated clinical research in epilepsy, to undertake epidemiological studies, and to simultaneously improve the care of patients who have records created within the EpiNet database. The EpiNet database has recently been adapted to collect detailed information regarding status epilepticus. An incidence study is now underway in Auckland, New Zealand in which the incidence of status epilepticus in the greater Auckland area (population: 1.5 million) will be calculated. The form that has been developed for this study can be used in the future to collect information for randomized controlled trials in status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Nonconvulsive status epilepticus after cessation of convulsive status epilepticus in pediatric intensive care unit patients.

PubMed

Chen, Jin; Xie, Lingling; Hu, Yue; Lan, Xinghui; Jiang, Li

2018-05-01

Little is known about pediatric patients suffering from nonconvulsive status epilepticus (NCSE) after convulsive status epilepticus (CSE) cessation. The aim of this study was to identify in pediatric patients the clinical characteristics of NCSE after CSE cessation and the factors that contribute to patient outcomes. Data from clinical features, electroencephalography (EEG) characteristics, neuroimaging findings, treatments, and prognosis were systematically summarized, and the associations between clinical characteristics and prognosis were quantified. Thirty-eight children aged 51days-14years, 2months were identified in the Chongqing Medical University pediatric intensive care unit as having experienced NCSE after CSE cessation between October 1, 2014 and April 1, 2017. All patients were comatose, 15 of whom presented subtle motor signs. The most common underlying etiology was acute central nervous system (CNS) infection. Electroencephalography (EEG) data showed that, during the NCSE period, all patients had several discrete episodes (lasting from 30s to 6h long), and the most common duration was 1-5min. The ictal onset locations were classified as focal (16 patients, 42.1%), multiregional independent (10 patients, 26.3%), and generalized (12 patients, 31.6%). Wave morphologies varied during the ictal and interictal periods. Neuroimaging detected signal abnormalities in the cerebral cortex or subcortex of 33 patients with NCSE (87%), which were classified as either multifocal and consistent with extensive cortical edema (21 patients, 55.3%) or focal (12 patients, 31.6%). Twelve patients were on continuous intravenous phenobarbital, and 31 were on continuous infusion of either midazolam (27 patients) or propofol (4 patients). At least one other antiepileptic drug was prescribed for 32 patients. Three patients were on mild hypothermia therapy. The duration of NCSE lasted <24h for 20 patients and >24h for 18 patients. The mortality rate was 21.1%, and half of the

Risk of seizures and status epilepticus in older patients with liver disease.

PubMed

Alkhachroum, Ayham M; Rubinos, Clio; Kummer, Benjamin R; Parikh, Neal S; Chen, Monica; Chatterjee, Abhinaba; Reynolds, Alexandra; Merkler, Alexander E; Claassen, Jan; Kamel, Hooman

2018-06-06

Seizures can be provoked by systemic diseases associated with metabolic derangements, but the association between liver disease and seizures remains unclear. We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. The primary exposure variable was cirrhosis, and the secondary exposure was mild, noncirrhotic liver disease. The primary outcome was seizure, and the secondary outcome was status epilepticus. Diagnoses were ascertained using validated International Classification of Diseases, Ninth Edition, Clinical Modification codes. Survival statistics were used to calculate incidence rates, and Cox proportional hazards models were used to examine the association between exposures and outcomes while adjusting for seizure risk factors. Among 1 782 402 beneficiaries, we identified 10 393 (0.6%) beneficiaries with cirrhosis and 19 557 (1.1%) with mild, noncirrhotic liver disease. Individuals with liver disease were older and had more seizure risk factors than those without liver disease. Over 4.6 ± 2.2 years of follow-up, 49 843 (2.8%) individuals were diagnosed with seizures and 25 patients (0.001%) were diagnosed with status epilepticus. Cirrhosis was not associated with seizures (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.0-1.3), but there was an association with status epilepticus (HR = 1.9, 95% CI = 1.3-2.8). Mild liver disease was not associated with a higher risk of seizures (HR = 0.8, 95% CI = 0.6-0.9) or status epilepticus (HR = 1.1, 95% CI = 0.7-1.5). In a large, population-based cohort, we found an association between cirrhosis and status epilepticus, but no overall association between liver disease and seizures. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

The clinical outcome and neuroimaging of acute encephalopathy after status epilepticus in Dravet syndrome.

PubMed

Tian, Xiaojuan; Ye, Jintang; Zeng, Qi; Zhang, Jing; Yang, Xiaoling; Liu, Aijie; Yang, Zhixian; Liu, Xiaoyan; Wu, Xiru; Zhang, Yuehua

2018-06-01

To analyze the clinical outcome and neuroimaging over a long duration follow-up in the currently largest series of acute encephalopathy after status epilepticus in patients with Dravet syndrome. Clinical and neuroimaging data of patients with Dravet syndrome with a history of acute encephalopathy (coma >24h) after status epilepticus from February 2005 to December 2016 at Peking University First Hospital were reviewed retrospectively. Thirty-five patients (15 males, 20 females) with a history of acute encephalopathy were enrolled from a total of 624 patients with Dravet syndrome (5.6%). The median onset age of acute encephalopathy was 3 years 1 month. The duration of status epilepticus varied between 40 minutes to 12 hours. Thirty-four patients had a high fever when status epilepticus occurred, and only one had a normal temperature. Coma lasted from 2 to 20 days. Twelve patients died and 23 survived with massive neurological regression. The median follow-up time was 2 years 1 month. Neuroimaging of 20 out of 23 survivors during the recovery phase showed diverse degrees of cortical atrophy with or without subcortical lesions. Acute encephalopathy after status epilepticus is more prone to occur in patients with Dravet syndrome who had a high fever. The mortality rate is high in severe cases. Survivors are left with severe neurological sequelae but often with either no seizure or low seizure frequency. Acute encephalopathy is more prone to occur in patients with Dravet syndrome with a high fever. The mortality rate is high for acute encephalopathy after status epilepticus in patients with Dravet syndrome. Survivors have neurological sequelae. © 2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Management of refractory status epilepticus in adults

PubMed Central

Rossetti, Andrea O.; Lowenstein, Daniel H.

2011-01-01

Summary Refractory status epilepticus (RSE) can be defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and etiology (that should be actively targeted). Recent recommendations for adults, relying upon limited evidence, suggest that RSE treatment aggressiveness should be tailored to the clinical situation: to minimize ICU-related complications, focal RSE without major consciousness impairment might initially be approached more conservatively; conversely, early induction of pharmacological coma is advisable in generalized-convulsive forms. At this stage, midazolam, propofol or barbiturates represent the most used alternatives. Several other treatments, such as additional anesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (electroconvulsive treatment, hypothermia), have been used in protracted RSE. Treatment lasting weeks or months may sometimes result in a good outcome, as in selected cases after cerebral anoxia and encephalitis. Well-designed prospective studies of this condition are urgently needed. PMID:21939901

De novo status epilepticus with isolated aphasia.

PubMed

Flügel, Dominique; Kim, Olaf Chan-Hi; Felbecker, Ansgar; Tettenborn, Barbara

2015-08-01

Sudden onset of aphasia is usually due to stroke. Rapid diagnostic workup is necessary if reperfusion therapy is considered. Ictal aphasia is a rare condition but has to be excluded. Perfusion imaging may differentiate acute ischemia from other causes. In dubious cases, EEG is required but is time-consuming and laborious. We report a case where we considered de novo status epilepticus as a cause of aphasia without any lesion even at follow-up. A 62-year-old right-handed woman presented to the emergency department after nurses found her aphasic. She had undergone operative treatment of varicosis 3 days earlier. Apart from hypertension and obesity, no cardiovascular risk factors and no intake of medication other than paracetamol were reported. Neurological examination revealed global aphasia and right pronation in the upper extremity position test. Computed tomography with angiography and perfusion showed no abnormalities. Electroencephalogram performed after the CT scan showed left-sided slowing with high-voltage rhythmic 2/s delta waves but no clear ictal pattern. Intravenous lorazepam did improve EEG slightly, while aphasia did not change. Lumbar puncture was performed which likely excluded encephalitis. Magnetic resonance imaging showed cortical pathological diffusion imaging (restriction) and cortical hyperperfusion in the left parietal region. Intravenous anticonvulsant therapy under continuous EEG resolved neurological symptoms. The patient was kept on anticonvulsant therapy. Magnetic resonance imaging after 6 months showed no abnormalities along with no clinical abnormalities. Magnetic resonance imaging findings were only subtle, and EEG was without clear ictal pattern, so the diagnosis of aphasic status remains with some uncertainty. However, status epilepticus can mimic stroke symptoms and has to be considered in patients with aphasia even when no previous stroke or structural lesions are detectable and EEG shows no epileptic discharges. Epileptic origin is

Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation.

PubMed

Kowalski, Robert G; Ziai, Wendy C; Rees, Richard N; Werner, J Kent; Kim, Grace; Goodwin, Haley; Geocadin, Romergryko G

2012-09-01

To characterize associations between antiepileptic drugs with sedating or anesthetic effects (third-line antiepileptic drugs) vs. other antiepileptic agents, and short-term outcomes, in status epilepticus. Furthermore, to evaluate the role of adverse hemodynamic and respiratory effects of these agents in status epilepticus treatment. Retrospective comparative analysis. Tertiary academic medical center with two emergency departments and two neurologic intensive care units. Adults admitted with a diagnosis of status epilepticus defined as seizures lasting continuously >5 mins, or for discrete periods in succession. None. Of 126 patients with 144 separate status epilepticus admissions, 57 were female (45%) with mean age 54.7 ± 15.7 yrs. Status epilepticus was convulsive in 132 cases (92%). Status epilepticus etiologies included subtherapeutic antiepileptic drugs (43%), alcohol or other nonantiepileptic drug (13%), and acute central nervous system disease (12%). Third-line antiepileptic drugs were administered in 47 cases (33%). Seventy-eight status epilepticus episodes (54%) had good outcomes (Glasgow Outcome Score = 1, 2) at the time of hospital discharge. On univariate analysis, poor outcome (Glasgow Outcome Score > 2) was associated with older age (mean 59.8 ± 15.5 vs. 50.5 ± 13.8 yrs, p < .001), acute central nervous system disease (21% vs. 4%, p = .001), mechanical ventilation (76% vs. 53%, p = .004), longer duration of ventilation (median 10 days [range 1-56] vs. 2 days [range 1-10], p < .001), treatment with vasopressors (35% vs. 5%, p < .001), and treatment with third-line antiepileptic drugs (51% vs. 17%, p < .001). Death was associated with acute central nervous system disease, prolonged ventilation, treatment with vasopressors, and treatment with third-line antiepileptic drugs. Predictors of poor outcome among all status epilepticus episodes were older age (odds ratio 1.06; 95% confidence interval 1.03-1.09; p < .001), treatment with third

An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

PubMed

Hassan, Haseeb; Rajiv, Keni Ravish; Menon, Ramshekhar; Menon, Deepak; Nair, Muralidharan; Radhakrishnan, Ashalatha

2016-06-01

Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common

The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

PubMed

Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

2015-12-01

We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

Clinical utility of EMSE and STESS in predicting hospital mortality for status epilepticus.

PubMed

Zhang, Yu; Chen, Deng; Xu, Da; Tan, Ge; Liu, Ling

2018-05-25

To explore the applicability of the epidemiology-based mortality score in status epilepticus (EMSE) and the status epilepticus severity score (STESS) in predicting hospital mortality in patients with status epilepticus (SE) in western China. Furthermore, we sought to compare the abilities of the two scales to predict mortality from convulsive status epilepticus (CSE) and non-convulsive status epilepticus (NCSE). Patients with epilepsy (n = 253) were recruited from the West China Hospital of Sichuan University from January 2012 to January 2016. The EMSE and STESS for all patients were calculated immediately after admission. The main outcome was in-hospital death. The predicted values were analysed using SPSS 22.0 receiver operating characteristic (ROC) curves. Of the 253 patients with SE who were included in the study, 39 (15.4%) died in the hospital. Using STESS ≥4 points to predict SE mortality, the area under the ROC curve (AUC) was 0.724 (P < 0.05). Using EMSE ≥79 points, the AUC was 0.776 (P < 0.05). To predict mortality in NCSE, STESS ≥2 points was used and resulted in an AUC of 0.632 (P > 0.05), while EMSE ≥90 points gave an AUC of 0.666 (P > 0.05). The hospital mortality rate from SE in this study was 15.4%. Those with STESS ≥4 points or EMSE ≥79 points had higher rates of SE mortality. Both STESS and EMSE are less useful predicting in-hospital mortality in NCSE compared to CSE. Furthermore, the EMSE has some advantages over the STESS. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Treatment of Convulsive Status Epilepticus.

PubMed

Grover, Eric H; Nazzal, Yara; Hirsch, Lawrence J

2016-03-01

Convulsive status epilepticus (CSE) is a medical emergency with an associated high mortality and morbidity. It is defined as a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. Successful management of CSE depends on rapid administration of adequate doses of anti-epileptic drugs (AEDs). The exact choice of AED is less important than rapid treatment and early consideration of reversible etiologies. Current guidelines recommend the use of benzodiazepines (BNZ) as first-line treatment in CSE. Midazolam is effective and safe in the pre-hospital or home setting when administered intramuscularly (best evidence), buccally, or nasally (the latter two possibly faster acting than intramuscular (IM) but with lower levels of evidence). Regular use of home rescue medications such as nasal/buccal midazolam by patients and caregivers for prolonged seizures and seizure clusters may prevent SE, prevent emergency room visits, improve quality of life, and lower health care costs. Traditionally, phenytoin is the preferred second-line agent in treating CSE, but it is limited by hypotension, potential arrhythmias, allergies, drug interactions, and problems from extravasation. Intravenous valproate is an effective and safe alternative to phenytoin. Valproate is loaded intravenously rapidly and more safely than phenytoin, has broad-spectrum efficacy, and fewer acute side effects. Levetiracetam and lacosamide are well tolerated intravenous (IV) AEDs with fewer interactions, allergies, and contraindications, making them potentially attractive as second- or third-line agents in treating CSE. However, data are limited on their efficacy in CSE. Ketamine is probably effective in treating refractory CSE (RCSE), and may warrant earlier use; this requires further study. CSE should be treated aggressively and quickly, with confirmation of treatment success with epileptiform electroencephalographic (EEG), as a transition to non-convulsive status

Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus

PubMed Central

Zeiler, F. A.

2015-01-01

Refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA) receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE. PMID:25649724

Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

PubMed

Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

2015-04-01

A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

Preliminary results of the global audit of treatment of refractory status epilepticus.

PubMed

Ferlisi, M; Hocker, S; Grade, M; Trinka, E; Shorvon, S

2015-08-01

The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.

A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

PubMed

Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

2001-07-01

This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

Status epilepticus following intravenous N-acetylcysteine therapy.

PubMed

Hershkovitz, E; Shorer, Z; Levitas, A; Tal, A

1996-11-01

A previously healthy 2 1/2-year-old girl developed status epilepticus followed by cortical blindness during intravenous N-acetylcysteine therapy for paracetamol ingestion. The child's vision was almost completely recovered during the 18 months follow-up period. We assume that the cortical blindness was a postictal sequela after prolonged seizure episode, most probably due to respiratory depression induced by N-acetylcysteine.

Quantitative Evaluation of Medial Temporal Lobe Morphology in Children with Febrile Status Epilepticus: Results of the FEBSTAT Study.

PubMed

McClelland, A C; Gomes, W A; Shinnar, S; Hesdorffer, D C; Bagiella, E; Lewis, D V; Bello, J A; Chan, S; MacFall, J; Chen, M; Pellock, J M; Nordli, D R; Frank, L M; Moshé, S L; Shinnar, R C; Sun, S

2016-12-01

The pathogenesis of febrile status epilepticus is poorly understood, but prior studies have suggested an association with temporal lobe abnormalities, including hippocampal malrotation. We used a quantitative morphometric method to assess the association between temporal lobe morphology and febrile status epilepticus. Brain MR imaging was performed in children presenting with febrile status epilepticus and control subjects as part of the Consequences of Prolonged Febrile Seizures in Childhood study. Medial temporal lobe morphologic parameters were measured manually, including the distance of the hippocampus from the midline, hippocampal height:width ratio, hippocampal angle, collateral sulcus angle, and width of the temporal horn. Temporal lobe morphologic parameters were correlated with the presence of visual hippocampal malrotation; the strongest association was with left temporal horn width (P < .001; adjusted OR, 10.59). Multiple morphologic parameters correlated with febrile status epilepticus, encompassing both the right and left sides. This association was statistically strongest in the right temporal lobe, whereas hippocampal malrotation was almost exclusively left-sided in this cohort. The association between temporal lobe measurements and febrile status epilepticus persisted when the analysis was restricted to cases with visually normal imaging findings without hippocampal malrotation or other visually apparent abnormalities. Several component morphologic features of hippocampal malrotation are independently associated with febrile status epilepticus, even when complete hippocampal malrotation is absent. Unexpectedly, this association predominantly involves the right temporal lobe. These findings suggest that a spectrum of bilateral temporal lobe anomalies are associated with febrile status epilepticus in children. Hippocampal malrotation may represent a visually apparent subset of this spectrum. © 2016 by American Journal of Neuroradiology.

Mega-dose phenobarbital therapy for super-refractory status epilepticus.

PubMed

Byun, Jung-Ick; Chu, Kon; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Jun, Jin-Sun; Lee, Han Sang; Lee, Woo-Jin; Lee, Doo Young; Jeon, Daejong; Lee, Soon-Tae; Jung, Keun-Hwa; Jung, Ki-Young; Lee, Sang Kun

2015-12-01

To evaluate the efficacy and safety of mega-dose phenobarbital (MDPB; enteral or parenteral phenobarbital >10 mg/kg/day) for treating super-refractory status epilepticus (SRSE; continuous or recurrent status epilepticus for ≥24 hours after the onset of continuous anaesthetic treatment) in adult patients. Adult patients with SRSE who were treated with MDPB in our institution from March 2005 to September 2014 were reviewed. We collected data on basic demographics, clinical features, functional status, anticonvulsant treatment, and possible adverse events. SRSE outcome was divided into six categories: successful therapy, initial failure, breakthrough seizures, withdrawal seizures, intolerable side effects, and death during treatment. Ten adult patients with SRSE received MDPB. Median age at seizure onset was 38 years (range: 18-59), and half were male. All patients had no history of seizures and had symptoms suggestive of viral encephalitis. Median duration of status epilepticus was 17.5 days (range: 6-60) and anaesthetics were used for a median of 14.0 days (range: 2-54) before MDPB. Successful control of SRSE was achieved in half of the patients, however, only one of ten patients was able to fully recover at discharge. Median duration of the MDPB was 45.5 days and the maximum serum phenobarbital level reached a median of 151.5 μg/ml. Patients with successful MDPB therapy had normal brain imaging (80% vs. 0%; p=0.048) and better functional outcome at discharge and after three months of follow-up. Infection was the most critical complication, along with cardiorespiratory depression. MDPB is a therapeutic option for control of SRSE when other choices are exhausted.

Refractory status epilepticus in children with and without prior epilepsy or status epilepticus

PubMed Central

Sánchez Fernández, Iván; Jackson, Michele C.; Abend, Nicholas S.; Arya, Ravindra; Brenton, James N.; Carpenter, Jessica L.; Chapman, Kevin E.; Gaillard, William D.; Gaínza-Lein, Marina; Glauser, Tracy A.; Goldstein, Joshua L.; Goodkin, Howard P.; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L.; Mikati, Mohamad A.; Peariso, Katrina; Riviello, James; Tasker, Robert C.; Topjian, Alexis A.; Wainwright, Mark S.; Wilfong, Angus; Williams, Korwyn

2017-01-01

Objective: To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). Methods: This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month–21 years of age) with rSE. Results: We enrolled 189 participants (53% male) with a median (25th–75th percentile) age of 4.2 (1.3–9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5–60] vs 16.5 [5–42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46–190] vs 50.5 [28–116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5–22.3] vs 20 [5–60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3–124] vs 65 [32.5–156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Conclusions: Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. PMID:28011930

Refractory status epilepticus in children with and without prior epilepsy or status epilepticus.

PubMed

Sánchez Fernández, Iván; Jackson, Michele C; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Gaínza-Lein, Marina; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Helseth, Ashley; Kapur, Kush; McDonough, Tiffani L; Mikati, Mohamad A; Peariso, Katrina; Riviello, James; Tasker, Robert C; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

2017-01-24

To compare refractory convulsive status epilepticus (rSE) management and outcome in children with and without a prior diagnosis of epilepsy and with and without a history of status epilepticus (SE). This was a prospective observational descriptive study performed from June 2011 to May 2016 on pediatric patients (1 month-21 years of age) with rSE. We enrolled 189 participants (53% male) with a median (25th-75th percentile) age of 4.2 (1.3-9.6) years. Eighty-nine (47%) patients had a prior diagnosis of epilepsy. Thirty-four (18%) patients had a history of SE. The time to the first benzodiazepine was similar in participants with and without a diagnosis of epilepsy (15 [5-60] vs 16.5 [5-42.75] minutes, p = 0.858). Patients with a diagnosis of epilepsy received their first non-benzodiazepine (BZD) antiepileptic drug (AED) later (93 [46-190] vs 50.5 [28-116] minutes, p = 0.002) and were less likely to receive at least one continuous infusion (35/89 [39.3%] vs 57/100 [57%], p = 0.03). Compared to patients with no history of SE, patients with a history of SE received their first BZD earlier (8 [3.5-22.3] vs 20 [5-60] minutes, p = 0.0073), although they had a similar time to first non-BZD AED (76.5 [45.3-124] vs 65 [32.5-156] minutes, p = 0.749). Differences were mostly driven by the patients with an out-of-hospital rSE onset. Our study establishes that children with rSE do not receive more timely treatment if they have a prior diagnosis of epilepsy; however, a history of SE is associated with more timely administration of abortive medication. © 2016 American Academy of Neurology.

Ketamine infusion for refractory status epilepticus: A case report of cardiac arrest.

PubMed

Koffman, Lauren; Yan Yiu, Ho; Farrokh, Salia; Lewin, John; Geocadin, Romergryko; Ziai, Wendy

2018-01-01

Refractory status epilepticus (RSE) has a high mortality rate and is often difficult to treat. When traditional therapies fail ketamine may be considered. There are limited reports of adverse cardiac events with the use of ketamine for RSE and no reports of cardiac arrest in this context. Evaluate the occurrence of cardiac arrhythmias associated with the use of ketamine for RSE. Retrospective chart review of nine patients who underwent ketamine infusion for RSE. Etiology of refractory status epilepticus included autoimmune/infectious process (Zeiler et al., 2014), ischemic stroke (Bleck, 2005) and subarachnoid hemorrhage (Bleck, 2005). Of the nine patients who received ketamine, two had documented cardiac events; one remained clinically stable and the other developed multiple arrhythmias, including recurrent episodes of asystole. Once ketamine was discontinued the latter patient stabilized with the addition of anti arrhythmic therapy. Ketamine is utilized to treat refractory status epilepticus, but should be used with caution in patients with subarachnoid hemorrhage, as there may be an increased risk of life threatening arrhythmias and cardiac arrest. Copyright © 2017 Elsevier Ltd. All rights reserved.

Curcumin protects neuronal cells against status-epilepticus-induced hippocampal damage through induction of autophagy and inhibition of necroptosis.

PubMed

Wang, Jin; Liu, Yuan; Li, Xiao-Hui; Zeng, Xiang-Chang; Li, Jian; Zhou, Jun; Xiao, Bo; Hu, Kai

2017-05-01

Status epilepticus, the most severe form of epilepsy, is characterized by progressive functional and structural damage in the hippocampus, ultimately leading to the development and clinical appearance of spontaneous, recurrent seizures. Although the pathogenesis underlying epileptogenesis processes remains unclear, a substantial body of evidence has shown that status epilepticus acts as an important initial factor in triggering epileptogenesis. Notably, besides classical cell death mechanisms such as apoptosis and necrosis, 2 novel regulators of cell fate known as necroptosis and autophagy, are demonstrated to be involved in neuronal damage in various neurodegenerative and neuropsychiatric disorders. However, whether necroptosis and autophagy play a role in post-status-epilepticus rat hippocampus and other epilepsy mechanisms deserves further research effort. In addition, research is needed to determine whether compounds from traditional Chinese herbs possess antiepileptic effects through the modulation of necroptosis and autophagy. In this study, we found that curcumin, a polyphenolic phytochemical extracted from the Curcuma longa plant, protects neuronal cells against status-epilepticus-induced hippocampal neuronal damage in the lithium-pilocarpine-induced status epilepticus rat model through induction of autophagy and inhibition of necroptosis.

Metabolic injury in a variable rat model of post-status epilepticus.

PubMed

Pearce, Patrice S; Wu, Yijen; Rapuano, Amedeo; Kelly, Kevin M; de Lanerolle, Nihal; Pan, Jullie W

2016-12-01

In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation. The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining. A hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks. Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according

Epidemiology of Pediatric Convulsive Status Epilepticus With Fever in the Emergency Department: A Cohort Study of 381 Consecutive Cases.

PubMed

Hayakawa, Itaru; Miyama, Sahoko; Inoue, Nobuaki; Sakakibara, Hiroshi; Hataya, Hiroshi; Terakawa, Toshiro

2016-09-01

Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children's hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P < .001). These results provide for the first time the pretest probability of final diagnoses in children with convulsive status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever. © The Author(s) 2016.

The mast cell stabilizer sodium cromoglycate reduces histamine release and status epilepticus-induced neuronal damage in the rat hippocampus.

PubMed

Valle-Dorado, María Guadalupe; Santana-Gómez, César Emmanuel; Orozco-Suárez, Sandra Adela; Rocha, Luisa

2015-05-01

Experiments were designed to evaluate changes in the histamine release, mast cell number and neuronal damage in hippocampus induced by status epilepticus. We also evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible stabilizing effect on the membrane of neurons, was able to prevent the release of histamine, γ-aminobutyric acid (GABA) and glutamate during the status epilepticus. During microdialysis experiments, rats were treated with saline (SS-SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration of pilocarpine to induce status epilepticus. Twenty-four hours after the status epilepticus, the brains were used to determine the neuronal damage and the number of mast cells in hippocampus. During the status epilepticus, SS-SE group showed an enhanced release of histamine (138.5%, p = 0.005), GABA (331 ± 91%, p ≤ 0.001) and glutamate (467%, p ≤ 0.001), even after diazepam administration. One day after the status epilepticus, SS-SE group demonstrated increased number of mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group showed increased latency to the establishment of the status epilepticus (p = 0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate) release, lower number of mast cells (p = 0.008) and reduced neuronal damage in hippocampus. Our data revealed that histamine, possibly from mast cells, is released in hippocampus during the status epilepticus. This effect may be involved in the subsequent neuronal damage and is diminished with sodium cromoglycate pretreatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus.

PubMed

Risbud, Rashmi M; Lee, Carolyn; Porter, Brenda E

2011-11-18

Status epilepticus induces a cascade of protein expression changes contributing to the subsequent development of epilepsy. By identifying the cascade of molecular changes that contribute to the development of epilepsy we hope to be able to design therapeutics for preventing epilepsy. MicroRNAs influence gene expression by altering mRNA stability and/or translation and have been implicated in the pathology of multiple diseases. MiR21 and its co-transcript miR21, microRNAs produced from either the 5' or 3' ends of the same precursor RNA strand, are increased in the hippocampus following status epilepticus. We have identified a miR21 binding site, in the 3' UTR of neurotrophin-3 that inhibits translation. Neurotrophin-3 mRNA levels decrease in the hippocampus following SE concurrent with the increase in miR21. MiR21 levels in cultured hippocampal neurons inversely correlate with neurotrophin-3 mRNA levels. Treatment of hippocampal neuronal cultures with excess K(+)Cl(-), a depolarizing agent mimicking the episode of status epilepticus, also results in an increase in miR21 and a decrease in neurotrophin-3 mRNA. MiR21 is a candidate for regulating neurotrophin-3 signaling in the hippocampus following status epilepticus. Copyright © 2011 Elsevier B.V. All rights reserved.

Status epilepticus and cluster seizures.

PubMed

Patterson, Edward Ned E

2014-11-01

Status epilepticus (SE) is a medical emergency for companion animals, with significant associated morbidity and mortality. Therapy in companion animals and people has been largely with sedatives and anesthetics, many of which have gamma-aminobutyric acid receptor-mediated mechanisms. Early aggressive treatment includes staged first-line therapy with benzodiazepines, and second- and third-line protocols when needed. Recently, intravenous levetiracetam has also been used in for SE in dogs and people, and there are other human intravenous drug preparations that may hold promise for future use in companion animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Spectrum and Predictors of Refractory Status Epilepticus in a Developing Country.

PubMed

Dubey, Deepanshu; Bhoi, Sanjeev K; Kalita, Jayantee; Misra, Usha K

2017-09-01

Refractory status epilepticus (RSE) can influence the outcome of status epilepticus (SE). In the present study, we report the aetiology and predictors of outcomes of RSE in a developing country. This is a prospective hospital-based study of SE patients (continuous seizures for five minutes or more). Those who had SE persisting after two antiepileptic drugs were defined as having RSE. We present the demographic information, duration, and type of SE, and we note its severity using the status epilepticus severity score (STESS), its aetiology, comorbidities and imaging findings. The outcome of RSE was defined as cessation of seizures and the condition upon discharge, as assessed by the modified Rankin Scale. A total of 35 (42.5%) of our 81 patients had RSE. The median duration of SE before starting treatment was 2 hours (range=0.008-160 h). The most common causes of RSE were stroke in 5 (14.3%), central nervous system (CNS) infections in 12 (34.3%) and metabolic encephalopathies in 13 (37.1%) patients. Some 21 (60%) patients had comorbidities, and the STESS was favourable in 7 (20%) patients. A total of 14 (20%) patients died, but death was directly related to SE in only one of these. Some 10 patients had super-refractory status epilepticus, which was due to CNS infection in 5 (50%) and metabolic encephalopathy in 3 (30%). On multivariate analysis, an unfavourable STESS (p=0.05) and duration of SE before treatment (p=0.01) predicted RSE. Metabolic aetiology (p=0.05), mechanical ventilation (p60 years (p=0.003) were predictors of poor outcomes. RSE was common (42.5%) among patients with SE in a tertiary care center in India. It was associated with high mortality and poor outcomes. Age above 60 years and metabolic aetiology were found to be predictors of poor outcomes.

Epilepsy surgery in a liver-transplanted girl with temporal lobe epilepsy and hippocampal sclerosis following PRES with status epilepticus.

PubMed

Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura

2016-07-01

Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Dyke-Davidoff-Masson Syndrome. An unusual cause of status epilepticus.

PubMed

Zawar, Ifrah; Khan, Ashfa A; Sultan, Tipu; Rathore, Ahsan W

2015-10-01

The Dyke-Davidoff-Masson Syndrome (DDMS) results from an insult to the growing brain in utero or early infancy, which lead to loss of neurons compromising the growth of the brain. Clinical presentation includes seizures, hemiparesis, facial asymmetry, and learning disability. Radiological findings include cerebral atrophy on one side. Here, we present a case with status epilepticus who had underlying DDMS. It is a rare syndrome and uncommon cause for status epilepticus. Infections of CNS, hypoxic ischemic encephalopathy, intracranial bleed, trauma, congenital vascular malformations are the common causes of this syndrome. Diagnosis is established after clinical history, examination, and MRI. Intractable seizures can be controlled with appropriate anticonvulsants. Subsequently, these children may require physiotherapy, speech therapy, and occupational therapy in addition to the anticonvulsant medication. Outcome is better if the seizures are controlled.

Head turning as a prominent motor symptom in status epilepticus.

PubMed

Bauer, Gerhard; Broessner, Gregor; Unterberger, Iris; Walser, Gerald; Pfausler, Bettina; Trinka, Eugen

2008-06-01

Head and eye turning is frequently observed during seizures. Versions with tonic and/or clonic symptoms can be differentiated from smooth head deviations. Head turning as a prominent symptom of status epilepticus has not previously been reported. We present eight case reports, (7 women/1 man, mean age 41 years, median 41.5, range 10 to 74), of status epilepticus (SE), with head turning as a prominent motor symptom. Six were accompanied by continuous frontal, occipital and temporal ictal epileptiform discharges. Furthermore, two patients had absence status with rhythmic and clonic head versions. While the localizing significance of head turnings in SE is low, in our cases, the direction was away from the discharging hemisphere in all cases of focal SE regardless of whether the turning was classified as version (three cases) or deviation (three cases). In this small series of SE, the classical observation of a patient looking away from the discharging hemisphere is still valid.

Do not overlook acute isoniazid poisoning in children with status epilepticus.

PubMed

Caksen, Hüseyin; Odabas, Dursun; Erol, Mehmet; Anlar, Omer; Tuncer, Oguz; Atas, Bülent

2003-02-01

A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.

Medical management with diazepam for electrical status epilepticus during slow wave sleep in children.

PubMed

Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman

2014-03-01

Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej

2007-03-15

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithiummore » pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.« less

A one-year prospective study of refractory status epilepticus in Modena, Italy.

PubMed

Giovannini, Giada; Monti, Giulia; Polisi, Michela M; Mirandola, Laura; Marudi, Andrea; Pinelli, Giovanni; Valzania, Franco; Girardis, Massimo; Nichelli, Paolo F; Meletti, Stefano

2015-08-01

Refractory status epilepticus (RSE) is a particular critical condition characterized by seizures that continue despite the use of first- and second-line therapies and by high mortality. To date, only one prospective study investigated clinical features and prognostic factors in RSE. In this study, we performed a one-year prospective survey to identify clinical features, outcomes, and variables associated with the development of RSE in the adolescent and adult population of Modena, northern Italy. We observed 83 episodes of SE in 83 patients. In 31% of the cases, third-line therapy (anesthetic drug) was needed. Among this group, 14% resolved and were classified as RSE, while, in 17%, seizures recurred at withdrawal of anesthetics and were classified as super-RSE. The development of RSE/super-RSE was associated with a stuporous/comatose state at presentation and with the absence of a previous history of epilepsy. Refractory status epilepticus/super-refractory status epilepticus showed a worse outcome compared with responsive SE: 54% versus 21% for 30-day mortality; 19% versus 56% for a return to baseline condition. This prospective study confirms stupor/coma at onset as a relevant clinical factor associated with SE refractoriness. We observed a rate of RSE comparable with previous reports, with high mortality and morbidity. Mortality in the observed RSE was higher than in previous studies; this result is probably related to the low rate of a previous epilepsy history in our population that reflects a high incidence of acute symptomatic etiologies, especially the inclusion of patients with postanoxic SE who have a bad prognosis per se. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

PubMed

Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

2016-01-15

The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Intravenous lacosamide for treatment of absence status epilepticus in genetic generalized epilepsy: A case report and review of literature.

PubMed

Reif, P S; Männer, A; Willems, L M; Kay, L; Zöllner, J P; Klein, K M; Rosenow, F; Strzelczyk, A

2018-04-06

Nearly 10 years after its introduction into the market, the significance of lacosamide in genetic generalized epilepsies is still unclear. Its new mode of action may qualify lacosamide as a therapeutic agent in this entity, but only a limited number of cases have been published so far. To describe the efficacy of lacosamide as treatment in a patient with the absence status epilepticus. We report on a 28-year-old woman with genetic generalized epilepsy who suffered recurrent absence status epilepticus during video-EEG-monitoring. After treatment failure of first- and second-line medication, lacosamide was administered. The outcome in this patient was evaluated, and a systematic literature review was performed for the use of lacosamide in the absence status epilepticus. After application of 400 mg lacosamide intravenously, the absence status epilepticus terminated within 30 minutes. No further seizures or epileptiform discharges reoccurred until the end of video-EEG-Monitoring 3 days later. The role of lacosamide as a therapeutic option in patients with the absence status epilepticus is unclear. Only two cases have been reported so far with conflicting results. Further randomized controlled studies are required to validate the relevance of lacosamide as treatment for status epilepticus in genetic generalized and the absence epilepsy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Short-term outcomes and major barriers in the management of convulsive status epilepticus in children: a study in Georgia.

PubMed

Shatirishvili, Teona; Kipiani, Tamar; Lomidze, Giorgi; Gabunia, Maia; Tatishvili, Nino

2015-09-01

Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second-line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. A prospective, hospital-based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Forty-eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre-hospital intervention. Moreover, patients with appropriate pre-hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow-up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource-limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.

Lidocaine for Status Epilepticus in Pediatrics.

PubMed

Zeiler, Frederick A; Zeiler, Kaitlin J; Teitelbaum, Jeanne; Gillman, Lawrence M; West, Michael; Kazina, Colin J

2015-11-01

Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in pediatrics for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and Grading of Recommendations Assessment, Development, and Evaluation methodologies by two independent reviewers. Overall, 20 original studies were identified, with 19 manuscripts and one meeting abstract. Two hundred and thirty-five pediatric patients were treated for 252 episodes of SE/RSE. Patients had varying numbers of antiepileptic drugs (two to eight) on board before lidocaine therapy. During 20 of the 252 (7.9%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some using bolus dosing alone; others used a combination of bolus and infusion therapy. Overall, 60.0% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 57.6% and 12.3%, respectively. Patient outcomes were sparingly reported. There currently exists Oxford level 2b, Grading of Recommendations Assessment Development, and Evaluation C evidence to support the consideration of lidocaine for SE and RSE in the pediatric population. Further prospective studies of lidocaine administration in this setting are warranted.

Does semiology of status epilepticus have an impact on treatment response and outcome?

PubMed

Baysal-Kirac, Leyla; Feddersen, Berend; Einhellig, Marion; Rémi, Jan; Noachtar, Soheyl

2018-06-01

This study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. Two hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18-97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). The most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). Status epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE. Copyright © 2018 Elsevier Inc. All rights reserved.

Non-convulsive status epilepticus in a patient with carbon-monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Marziali, Simone; Di Giuliano, Francesca; Picchi, Eliseo; Natoli, Silvia; Leonardis, Carlo; Leonardis, Francesca; Garaci, Francesco; Floris, Roberto

2016-12-01

The presentation of carbon monoxide poisoning is non-specific and highly variable. Hyperbaric oxygen therapy is used for the treatment of this condition. Various reports show the occurrence of self-limiting seizures after carbon monoxide poisoning and as a consequence of hyperbaric oxygen therapy. Contrary to the seizures, status epilepticus has been rarely observed in these conditions. The exact pathophysiology underlying seizures and status epilepticus associated with carbon monoxide poisoning and hyperbaric oxygen therapy is not really clear, and some elements appear to be common to both conditions. We describe a case of non-convulsive status epilepticus in a patient with carbon monoxide poisoning treated with hyperbaric oxygen therapy. The mechanism, MRI findings and implications are discussed. © The Author(s) 2016.

Relationship between cortex and pulvinar abnormalities on diffusion-weighted imaging in status epilepticus.

PubMed

Nakae, Yoshiharu; Kudo, Yosuke; Yamamoto, Ryoo; Dobashi, Yuichi; Kawabata, Yuichi; Ikeda, Shingo; Yokoyama, Mutsumi; Higashiyama, Yuichi; Doi, Hiroshi; Johkura, Ken; Tanaka, Fumiaki

2016-01-01

The aim of this study was to analyze the pattern of magnetic resonance diffusion-weighted imaging (DWI) findings in status epilepticus in terms of clinical characteristics. Participants comprised 106 patients with status epilepticus who were admitted to our hospital and underwent DWI. Forty-five patients (42.5 %) showed abnormal findings on DWI and were divided into two groups, comprising 26 patients (24.5 %) with cortex lesions alone and 19 patients (17.9 %) with cortex and pulvinar lesions in the same hemisphere. A long duration of status epilepticus (>120 min) tended to be more prevalent among patients with cortex and pulvinar lesions (57.9 %) than among patients with cortex lesions alone (30.8 %) by univariate and multivariate analyses. Todd's palsy tended to be more frequent in patients with abnormalities on DWI (24/45, 53.3 %) than in patients with normal DWI (21/61, 34.4 %). Six of the 26 patients with cortex lesions alone (23.1 %) had taken anti-epileptic drugs before the attack compared to none of the 19 patients with both cortex and pulvinar lesions. The trend toward a longer duration of status epilepticus in patients with both cortex and pulvinar lesions favors a spreading pattern of seizure discharge from cortex to pulvinar via cortico-pulvinar pathways, and anti-epileptic drugs might, to some extent, prevent spreading of seizure discharge from cortex to pulvinar. In addition, existence of high-intensity areas on DWI at the onset of epilepsy may be a predictive factor for the occurrence of Todd's palsy.

Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

PubMed Central

Vieira, Michele Juliane; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, José Antônio; Cavalheiro, Esper Abrão; da Graça Naffah-Mazzacoratti, Maria

2014-01-01

OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. PMID:25318094

Extreme delta brush evolving into status epilepticus in a patient with anti-NMDA encephalitis.

PubMed

Herlopian, Aline; Rosenthal, Eric S; Chu, Catherine J; Cole, Andrew J; Struck, Aaron F

2017-01-01

Extreme delta brush (EDB) is an EEG pattern unique to anti-NMDA encephalitis. It is correlated with seizures and status epilepticus in patients who have a prolonged course of illness. The etiology of the underlying association between EDB and seizures is not understood. We present a patient with anti-NMDA encephalitis who developed status epilepticus evolving from the high frequency activity of the extreme delta brush. This case demonstrates that EDB is not only a marker for a greater propensity for seizures but also directly implicated in seizure generation.

Mortality, morbidity and refractoriness prediction in status epilepticus: Comparison of STESS and EMSE scores.

PubMed

Giovannini, Giada; Monti, Giulia; Tondelli, Manuela; Marudi, Andrea; Valzania, Franco; Leitinger, Markus; Trinka, Eugen; Meletti, Stefano

2017-03-01

Status epilepticus (SE) is a neurological emergency, characterized by high short-term morbidity and mortality. We evaluated and compared two scores that have been developed to evaluate status epilepticus prognosis: STESS (Status Epilepticus Severity Score) and EMSE (Epidemiology based Mortality score in Status Epilepticus). A prospective observational study was performed on consecutive patients with SE admitted between September 2013 and August 2015. Demographics, clinical variables, STESS-3 and -4, and EMSE-64 scores were calculated for each patient at baseline. SE drug response, 30-day mortality and morbidity were the outcomes measure. 162 episodes of SE were observed: 69% had a STESS ≥3; 34% had a STESS ≥4; 51% patients had an EMSE ≥64. The 30-days mortality was 31.5%: EMSE-64 showed greater negative predictive value (NPV) (97.5%), positive predictive value (PPV) (59.8%) and accuracy in the prediction of death than STESS-3 and STESS-4 (p<0.001). At 30 days, the clinical condition had deteriorated in 59% of the cases: EMSE-64 showed greater NPV (71.3%), PPV (87.8%) and accuracy than STESS-3 and STESS-4 (p<0.001) in the prediction of this outcome. In 23% of all cases, status epilepticus proved refractory to non-anaesthetic treatment. All three scales showed a high NPV (EMSE-64: 87.3%; STESS-4: 89.4%; STESS-3: 87.5%) but a low PPV (EMSE-64: 40.9%; STESS-4: 52.9%; STESS-3: 32%) for the prediction of refractoriness to first and second line drugs. This means that accuracy for the prediction of refractoriness was equally poor for all scales. EMSE-64 appears superior to STESS-3 and STESS-4 in the prediction of 30-days mortality and morbidity. All scales showed poor accuracy in the prediction of response to first and second line antiepileptic drugs. At present, there are no reliable scores capable of predicting treatment responsiveness. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

PubMed

Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

2016-05-01

Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. © The Author(s) 2015.

Propofol effectively inhibits lithium-pilocarpine- induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

PubMed Central

Wang, Henglin; Wang, Zhuoqiang; Mi, Weidong; Zhao, Cong; Liu, Yanqin; Wang, Yongan; Sun, Haipeng

2012-01-01

Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine. The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior, electroencephalography and 24-hour survival rate. Propofol (12.5–100 mg/kg) improved status epilepticus in a dose-dependent manner, and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection. Western blot results showed that, 24 hours after induction of status epilepticus, the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus. Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels, but not the increase in N-methyl-D-aspartate receptor 2A subunit levels. The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine. This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures. PMID:25737709

Midazolam fails to prevent neurological damage in children with convulsive refractory febrile status epilepticus.

PubMed

Nagase, Hiroaki; Nishiyama, Masahiro; Nakagawa, Taku; Fujita, Kyoko; Saji, Yohsuke; Maruyama, Azusa

2014-07-01

We conducted a retrospective study to compare the outcome of intravenous midazolam infusion without electroencephalography or targeted temperature management and barbiturate coma therapy with electroencephalography and targeted temperature management for treating convulsive refractory febrile status epilepticus. Of 49 consecutive convulsive refractory febrile status epilepticus patients admitted to the pediatric intensive care unit of our hospital, 29 were excluded because they received other treatments or because of various underlying illnesses. Thus, eight patients were treated with midazolam and 10 with barbiturate coma therapy using thiamylal. Midazolam-treated patients were intubated only when necessary, whereas barbiturate coma therapy patients were routinely intubated. Continuous electroencephalography monitoring was utilized only for the barbiturate coma group. The titration goal for anesthesia was clinical termination of status epilepticus in the midazolam group and suppression or burst-suppression patterns on electroencephalography in the barbiturate coma group. Normothermia was maintained using blankets and neuromuscular blockade in the barbiturate coma group and using antipyretics in the midazolam group. Prognoses were measured at 1 month after onset; children were classified into poor and good outcome groups. Good outcome was achieved in all the barbiturate coma group patients and 50% of the midazolam group patients (P = 0.02, Fisher's exact test). Although the sample size was small and our study could not determine which protocol element is essential for the neurological outcome, the findings suggest that clinical seizure control using midazolam without continuous electroencephalography monitoring or targeted temperature management is insufficient in preventing neurological damage in children with convulsive refractory febrile status epilepticus. Copyright © 2014 Elsevier Inc. All rights reserved.

Study of Refractory Status Epilepticus from a Tertiary Care Center.

PubMed

Kohli, Sahil; Pasangulapati, Suresh Babu; Yoganathan, Sangeetha; Rynjah, Gideon Lyngsyun; Prabhakar, A T; Aaron, Sanjith; Alexander, Mathew; Mathew, Vivek

2017-01-01

To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15-65 years 52.8%, preexisting seizures were present in 34.4% ( n = 75). Nearly 77.1% had NRSE ( n = 168) and 22.9% had RSE ( n = 50). This included 17 patients with SRSE ( n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures ( P = 0.007), low sensorium at admission ( P = 0.001), low albumin at admission ( P = 0.002), and first EEG being abnormal ( P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE ( P = 0.001). On multivariate analysis, de novo seizures ( P = 0.009) and abnormal EEG at admission ( P = 0.03) were predictive for RSE. Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE.

Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

PubMed

Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E

2017-07-01

Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132

PubMed Central

Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

2011-01-01

When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804

Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.

PubMed

Leitinger, M; Beniczky, S; Rohracher, A; Gardella, E; Kalss, G; Qerama, E; Höfler, J; Hess Lindberg-Larsen, A; Kuchukhidze, G; Dobesberger, J; Langthaler, P B; Trinka, E

2015-08-01

Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false

Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions.

PubMed

Hirsch, Lawrence J; Gaspard, Nicolas; van Baalen, Andreas; Nabbout, Rima; Demeret, Sophie; Loddenkemper, Tobias; Navarro, Vincent; Specchio, Nicola; Lagae, Lieven; Rossetti, Andrea O; Hocker, Sara; Gofton, Teneille E; Abend, Nicholas S; Gilmore, Emily J; Hahn, Cecil; Khosravani, Houman; Rosenow, Felix; Trinka, Eugen

2018-04-01

We convened an international group of experts to standardize definitions of New-Onset Refractory Status Epilepticus (NORSE), Febrile Infection-Related Epilepsy Syndrome (FIRES), and related conditions. This was done to enable improved communication for investigators, physicians, families, patients, and other caregivers. Consensus definitions were achieved via email messages, phone calls, an in-person consensus conference, and collaborative manuscript preparation. Panel members were from 8 countries and included adult and pediatric experts in epilepsy, electroencephalography (EEG), and neurocritical care. The proposed consensus definitions are as follows: NORSE is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause. FIRES is a subcategory of NORSE, applicable for all ages, that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus. Proposed consensus definitions are also provided for Infantile Hemiconvulsion-Hemiplegia and Epilepsy syndrome (IHHE) and for prolonged, refractory and super-refractory status epilepticus. This document has been endorsed by the Critical Care EEG Monitoring Research Consortium. We hope these consensus definitions will promote improved communication, permit multicenter research, and ultimately improve understanding and treatment of these conditions. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhote, Franck, E-mail: franck.dhote@irba.fr; Carpentier, Pierre; Barbier, Laure

2012-03-01

Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation.more » When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial

Novel clinical features of nonconvulsive status epilepticus

PubMed Central

Nagayama, Masao; Yang, Sunghoon; Geocadin, Romergryko G.; Kaplan, Peter W.; Hoshiyama, Eisei; Shiromaru-Sugimoto, Azusa; Kawamura, Mitsuru

2017-01-01

Nonconvulsive status epilepticus (NCSE) has rapidly expanded from classical features such as staring, repetitive blinking, chewing, swallowing, and automatism to include coma, prolonged apnea, cardiac arrest, dementia, and higher brain dysfunction, which were demonstrated mainly after the 2000s by us and other groups. This review details novel clinical features of NCSE as a manifestation of epilepsy, but one that is underdiagnosed, with the best available evidence. Also, we describe the new concept of epilepsy-related organ dysfunction (Epi-ROD) and a novel electrode and headset which enables prompt electroencephalography. PMID:28979770

Effect of diet with omega-3 in basal brain electrical activity and during status epilepticus in rats.

PubMed

Pessoa, Daniella Tavares; da Silva, Eva Luana Almeida; Costa, Edbhergue Ventura Lola; Nogueira, Romildo Albuquerque

2017-11-01

Western diets are high in saturated fat and low in omega-3. Certain animals cannot produce omega-3 from their own lipids, making it necessary for it to be acquired from the diet. However, omega-3s are important components of the plasma membrane, and altering their proportions can promote physical and chemical alterations in the membranes, which may modify neuronal excitability. These alterations occur in healthy individuals, as well as in patients with epilepsy who are more sensitive to changes in brain electrical activity. This study evaluated the effect of a diet supplemented with omega-3 on the basal brain electrical activity both before and during status epilepticus in rats. To evaluate the brain electrical activity, we recorded electrocorticograms (ECoG) of animals both with and without omega-3 supplementation before and during status epilepticus induced by pilocarpine. Calculation of the average brain wave power by a power spectrum revealed that omega-3 supplementation reduced the average power of the delta wave by 20% and increased the average power of the beta wave by 45%. These effects were exacerbated when status epilepticus was induced in the animals supplemented with omega-3. The animals with and without omega-3 supplementation exhibited increases in basal brain electrical activities during status epilepticus. The two groups showed hyperactivity, but no significant difference between them was noted. Even though the brain activity levels observed during status epilepticus were similar between the two groups, neuron damage to the animals supplemented with omega-3 was more slight, revealing the neuroprotective effect of the omega-3. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus

PubMed Central

Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

2013-01-01

Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator. PMID:24130206

Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus.

PubMed

Sharma, Sushma; Nair, Pradeep P; Murgai, Aditya; Selvaraj, Raja J

2013-10-15

Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator.

Non-convulsive status epilepticus.

PubMed Central

Stores, G; Zaiwalla, Z; Styles, E; Hoshika, A

1995-01-01

The clinical, electrographic and reported neuropsychological features of 50 children with non-convulsive status epilepticus (NCSE) were reviewed and the children's progress followed for one to five years. NCSE occurred in a variety of epilepsies, especially the Lennox-Gastaut syndrome. Clinical manifestations ranged from obvious mental deterioration to subtle changes. The condition had often been overlooked or misinterpreted and many children had experienced repeated episodes over long periods. Following diagnosis, immediate treatment was often not attempted or was not successful. Further episodes of NCSE occurred in the majority of children during the follow up period. Failure to recognise NCSE and to treat episodes promptly, and the high rate of recurrence, is of particular concern in view of fears that repeated exposure to this condition might be brain damaging. At least 28 children in the present series showed evidence of intellectual or educational deterioration over the period during which NCSE had occurred, although the exact cause was difficult to determine. PMID:7574851

miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132.

PubMed

Jimenez-Mateos, Eva M; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A; Simon, Roger P; Stallings, Raymond L; Henshall, David C

2011-11-01

When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

PubMed

Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

2015-02-01

Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

High dose phenobarbitone coma in pediatric refractory status epilepticus; a retrospective case record analysis, a proposed protocol and review of literature.

PubMed

Gulati, Sheffali; Sondhi, Vishal; Chakrabarty, Biswaroop; Jauhari, Prashant; Lodha, Rakesh; Sankar, Jhuma

2018-04-01

Ongoing refractory status epilepticus is associated with significant morbidity and mortality. Therapeutic coma induction with midazolam, thiopentone, phenobarbitone or propofol is indicated when conventional antiepileptics fail to abort seizure. Of these, the most extensively studied is midazolam. Amongst the remaining three, phenobarbitone has the most favourable pharmacological profile, but has not been studied adequately, more so in the pediatric age group. The current retrospective case records analysis is an attempt to describe use of phenobarbitone coma in pediatric refractory status epilepticus. Case records of patients, admitted with status epilepticus to the pediatric inpatient services of a tertiary care teaching hospital of North India between January 2014 and December 2016 were reviewed. Those with refractory status epilepticus who failed to respond to midaolam infusion and phenobarbitone coma was used were included for analysis. Overall, 108 children presented in status, of which 34 developed refractory status epilepticus. Of these 34, 21 responded to midazolam infusion and in 13 high dose phenobarbitone coma following a standardised protocol was used. Amongst these 13 (8 males and 5 females, median age 6 years, IQR: 2.5-9.5), 12 responded and 1 succumbed. The median time to clinical seizure resolution and desired electroencephalographic changes post phenobarbitone initiation were 16 (IQR: 12-25) and 72 h (IQR: 48-120) respectively. High dose phenobarbitone appears to be an effective therapeutic modality in pediatric refractory status epilepticus. The current study provides a protocol for its use which can be validated in future studies with larger sample size. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

VGKC antibodies in pediatric encephalitis presenting with status epilepticus.

PubMed

Suleiman, J; Brenner, T; Gill, D; Brilot, F; Antony, J; Vincent, A; Lang, B; Dale, R C

2011-04-05

Voltage-gated potassium channel antibodies (VGKC Ab) are associated with limbic encephalitis and neuromyotonia in adults. There have been no systematic investigations in children to date. We looked for antibodies that are associated with CNS syndromes in adults including antibodies to VGKCs, NMDARs, glutamic acid decarboxylase (GAD), and glycine receptor (GlyR) in the stored acute serum from 10 children with unexplained encephalitis presenting with encephalopathy and status epilepticus. We also looked for antibodies to leucine-rich glioma-inactivated 1 (Lgi1) and contactin-associated protein-like 2 (Caspr2), which are now known to be tightly complexed with VGKCs in vivo. Sixty-nine pediatric controls were used for comparison. An elevated VGKC Ab (>100 pM) was detected in 4/10 patients with encephalitis compared to only 1/69 controls (p < 0.001). The outcome in the 4 VGKC Ab-positive patients with encephalitis was variable including good recovery (n = 1), cognitive impairment (n = 3), temporal lobe epilepsy (n = 2), and mesial temporal sclerosis (n = 1). No other antibodies were detected, including those to Lgi1 and Caspr2. Encephalitis associated with VGKC Ab occurs in children and presents with status epilepticus and focal epilepsy. These antibodies are not directed against Lgi1 or Caspr2.

Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms.

PubMed

van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

2016-01-01

Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activity during the chronic epileptic phase. Given rapamycin's role in growth and immune response, the potential therapeutic effects of rapamycin after status epilepticus with emphasis on brain inflammation and brain vasculature were investigated. Seven weeks after kainic acid-induced status epilepticus, rats were perfusion fixed and (immuno)histochemistry was performed using several glial and vascular markers. In addition, an in vitro model for the human BBB was used to determine the effects of rapamycin on transendothelial electrical resistance as a measure for BBB integrity. (Immuno)histochemistry showed that local blood vessel density, activated microglia, and astrogliosis were reduced in rapamycin-treated rats compared to vehicle-treated rats. In vitro studies showed that rapamycin could attenuate TNFα-induced endothelial barrier breakdown. These data suggest that rapamycin improves BBB function during the chronic epileptic phase by a reduction of local brain inflammation and blood vessel density that can contribute to a milder form of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

PubMed Central

Shinnar, Shlomo; Gloss, David; Alldredge, Brian; Arya, Ravindra; Bainbridge, Jacquelyn; Bare, Mary; Bleck, Thomas; Dodson, W. Edwin; Garrity, Lisa; Jagoda, Andy; Lowenstein, Daniel; Pellock, John; Riviello, James; Sloan, Edward; Treiman, David M.

2016-01-01

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events

Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases.

PubMed

Myers, Kenneth A; McMahon, Jacinta M; Mandelstam, Simone A; Mackay, Mark T; Kalnins, Renate M; Leventer, Richard J; Scheffer, Ingrid E

2017-04-01

Dravet syndrome (DS) is a well-recognized developmental and epileptic encephalopathy associated with SCN1A mutations and 15% mortality by 20 years. Although over half of cases succumb to sudden unexpected death in epilepsy, the cause of death in the remainder is poorly defined. We describe the clinical, radiologic, and pathologic characteristics of a cohort of children with DS and SCN1A mutations who developed fatal cerebral edema causing mass effect after fever-associated status epilepticus. Cases were identified from a review of children with DS enrolled in the Epilepsy Genetics Research Program at The University of Melbourne, Austin Health, who died after fever-associated status epilepticus. Five children were identified, all of whom presented with fever-associated convulsive status epilepticus, developed severe brain swelling, and died. All had de novo SCN1A mutations. Fever of 40°C or greater was measured in all cases. Signs of brainstem dysfunction, indicating cerebral herniation, were first noted 3 to 5 days after initial presentation in 4 patients, though were apparent as early as 24 hours in 1 case. When MRI was performed early in a patient's course, focal regions of cortical diffusion restriction were noted. Later MRI studies demonstrated diffuse cytotoxic edema, with severe cerebral herniation. Postmortem studies revealed diffuse brain edema and widespread neuronal damage. Laminar necrosis was seen in 1 case. Cerebral edema leading to fatal brain herniation is an important, previously unreported sequela of status epilepticus in children with DS. This potentially remediable complication may be a significant contributor to the early mortality of DS. Copyright © 2017 by the American Academy of Pediatrics.

Status Epilepticus Impairs Synaptic Plasticity in Rat Hippocampus and Is Followed by Changes in Expression of NMDA Receptors.

PubMed

Postnikova, T Y; Zubareva, O E; Kovalenko, A A; Kim, K K; Magazanik, L G; Zaitsev, A V

2017-03-01

Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Real-time PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

PubMed

Zaccara, G; Giorgi, F S; Amantini, A; Giannasi, G; Campostrini, R; Giovannelli, F; Paganini, M; Nazerian, P

2018-06-01

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats I: Magnetic resonance imaging.

PubMed

van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

2016-01-01

The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session. Gadobutrol leakage was widespread and extensive in both rapamycin and vehicle-treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin-treated rats 4 and 8 days after status epilepticus compared to vehicle-treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin-treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen. The initial slow recovery of BBB function in rapamycin-treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post-status epilepticus rats treated with rapamycin. Furthermore, the data show that CE-MRI (using step-down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

PubMed

Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-10-01

To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

PubMed

Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

2012-09-01

Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright �

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus.

PubMed

Erklauer, Jennifer; Graf, Jeanine; McPherson, Mona; Anderson, Anne; Wilfong, Angus; Minard, Charles G; Loftis, Laura

2018-03-26

Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite

Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

PubMed Central

Alford, Elizabeth L.; Wheless, James W.

2015-01-01

Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID:26380568

Induction of burst suppression or coma using intravenous anesthetics in refractory status epilepticus.

PubMed

Kang, Bong Su; Jung, Keun-Hwa; Shin, Jeong-Won; Moon, Jang Sup; Byun, Jung-Ick; Lim, Jung-Ah; Moon, Hye Jin; Kim, Young-Soo; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun

2015-05-01

General anesthetic-induced coma therapy has been recommended for the treatment of refractory status epilepticus (RSE). However, the influence of electroencephalographic (EEG) burst suppression (BS) on outcomes still remains unclear. This study investigated the impact of intravenous anesthetic-induced BS on the prognosis of RSE using a retrospective analysis of all consecutive adult patients who received intravenous anesthetic treatment for RSE at the Seoul National University Hospital between January 2006 and June 2011. Twenty-two of the 111 episodes of RSE were enrolled in this study. Of the 22 RSE patients, 12 (54.5%) were women and 18 (81.4%) exhibited generalized convulsive status epilepticus. Sixteen patients (72.7%) were classified as having acute symptomatic etiology, including three patients with anoxic encephalopathy, and others with remote symptomatic etiology. Only two patients (9.1%) had a favorable Status Epilepticus Severity Score (0-2) at admission. All patients received midazolam (MDZ) as a primary intravenous anesthetic drug for RSE treatment; three (13.6%) received MDZ and propofol, and one (4.5%) received MDZ and pentobarbital. The rates of mortality and poor outcome at discharge were 13.6% (n=3) and 54.5% (n=12), respectively. While BS was achieved in six (27.5%) patients, it was not associated with mortality or poor outcome. Induced BS was associated with prolonged hospital stay in subgroup analysis when excluding anoxic encephalopathy. Our results suggest that induction of BS for treating RSE did not affect mortality or outcome at discharge and may lead to an increased length of hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid attenuates spontaneous recurrent seizures and vasogenic edema following lithium-pilocarpine induced status epilepticus.

PubMed

Yang, Tingting; Lin, Zhenzhou; Xie, Ling; Wang, Yao; Pan, Suyue

2017-07-13

Vasogenic edema induced by blood brain barrier disruption and neuronal loss play an important role in the epileptogenic process. 4,4'- diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) is a commonly used anion channel inhibitor that has been reported to exert an anticonvulsant effect in rat hippocampus in vitro. The present study aimed to investigate whether DIDS could prevent epileptogenic process in rat lithium-pilocarpine model of temporal lobe epilepsy. The tight junction proteins and serum extravasation were examined in the piriform cortex 3days after status epilepticus. The findings showed that status epilepticus induced vasogenic edema. Based on these findings, rats were intracerebroventricularly infused with saline and DIDS 1 week after surgery, DIDS reduced vasogenic edema and prevented neuronal loss following status epilepticus in the piriform cortex. Moreover, spontaneous recurrent seizures were recorded by continuous video monitoring. DIDS significantly reduced the frequency and duration of spontaneous recurrent seizures from day 28 to day 42 post status epilepticus. These findings demonstrated that DIDS attenuated vasogenic edema and neuronal apoptosis and might exert disease-modifying effect in animal model of temporal lobe epilepsy. These results explored a novel therapeutic strategy for treatment of epilepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

A prospective study of diffusion weighted magnetic resonance imaging abnormalities in patients with cluster of seizures and status epilepticus.

PubMed

Jabeen, S A; Cherukuri, Pavankumar; Mridula, Rukmini; Harshavardhana, K R; Gaddamanugu, Padmaja; Sarva, Sailaja; Meena, A K; Borgohain, Rupam; Jyotsna Rani, Y

2017-04-01

To study the frequency, imaging characteristics, and clinical predictors for development of periictal diffusion weighted MRI abnormalities. We prospectively analyzed electro clinical and imaging characteristic of adult patients with cluster of seizures or status epilepticus between November 2013 and November 2015, in whom the diffusion weighted imaging was done within 24h after the end of last seizure (clinical or electrographic). There were thirty patients who fulfilled the inclusion and exclusion criteria. Twenty patients (66%) had periictal MRI abnormalities. Nine patients (34%) did not have any MRI abnormality. All the patients with PMA had abnormalities on diffusion weighted imaging (DWI). Hippocampal abnormalities were seen in nine (53%), perisylvian in two (11.7%), thalamic in five (30%), splenium involvement in two (11.7%) and cortical involvement (temporo-occipital, parieto-occipital, temporo-parietal, fronto-parietal and fronto-temporal) in sixteen (94.1%) patients. Complete reversal of DWI changes was noted in sixteen (80%) patients and four (20%) patients showed partial resolution of MRI abnormalities. Mean duration of seizures was significantly higher among patients with PMA (59.11+20.97h) compared to those without MRI changes (27.33+9.33h) (p<0.001). Diffusion abnormalities on MRI are common in patients with cluster of seizures and status epilepticus and were highly concordant with clinical semiology and EEG activity. Patients with longer duration of seizures/status were more likely to have PMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG).

PubMed

Sánchez Fernández, Iván; Abend, Nicholas S; Agadi, Satish; An, Sookee; Arya, Ravindra; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, David B; Goldstein, Joshua L; Goodkin, Howard P; Hahn, Cecil D; Heinzen, Erin L; Mikati, Mohamad A; Peariso, Katrina; Pestian, John P; Ream, Margie; Riviello, James J; Tasker, Robert C; Williams, Korwyn; Loddenkemper, Tobias

2014-02-01

Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG). A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Different as night and day: Patterns of isolated seizures, clusters, and status epilepticus.

PubMed

Goldenholz, Daniel M; Rakesh, Kshitiz; Kapur, Kush; Gaínza-Lein, Marina; Hodgeman, Ryan; Moss, Robert; Theodore, William H; Loddenkemper, Tobias

2018-05-01

Using approximations based on presumed U.S. time zones, we characterized day and nighttime seizure patterns in a patient-reported database, Seizure Tracker. A total of 632 995 seizures (9698 patients) were classified into 4 categories: isolated seizure event (ISE), cluster without status epilepticus (CWOS), cluster including status epilepticus (CIS), and status epilepticus (SE). We used a multinomial mixed-effects logistic regression model to calculate odds ratios (ORs) to determine night/day ratios for the difference between seizure patterns: ISE versus SE, ISE versus CWOS, ISE versus CIS, and CWOS versus CIS. Ranges of OR values were reported across cluster definitions. In adults, ISE was more likely at night compared to CWOS (OR = 1.49, 95% adjusted confidence interval [CI] = 1.36-1.63) and to CIS (OR = 1.61, 95% adjusted CI = 1.34-1.88). The ORs for ISE versus SE and CWOS versus SE were not significantly different regardless of cluster definition. In children, ISE was less likely at night compared to SE (OR = 0.85, 95% adjusted CI = 0.79-0.91). ISE was more likely at night compared to CWOS (OR = 1.35, 95% adjusted CI = 1.26-1.44) and CIS (OR = 1.65, 95% adjusted CI = 1.44-1.86). CWOS was more likely during the night compared to CIS (OR = 1.22, 95% adjusted CI = 1.05-1.39). With the exception of SE in children, our data suggest that more severe patterns favor daytime. This suggests distinct day/night preferences for different seizure patterns in children and adults. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Google search behavior for status epilepticus.

PubMed

Brigo, Francesco; Trinka, Eugen

2015-08-01

Millions of people surf the Internet every day as a source of health-care information looking for materials about symptoms, diagnosis, treatments and their possible adverse effects, or diagnostic procedures. Google is the most popular search engine and is used by patients and physicians to search for online health-related information. This study aimed to evaluate changes in Google search behavior occurring in English-speaking countries over time for the term "status epilepticus" (SE). Using Google Trends, data on global search queries for the term SE between the 1st of January 2004 and 31st of December 2014 were analyzed. Search volume numbers over time (downloaded as CSV datasets) were analyzed by applying the "health" category filter. The research trends for the term SE remained fairly constant over time. The greatest search volume for the term SE was reported in the United States, followed by India, Australia, the United Kingdom, Canada, the Netherlands, Thailand, and Germany. Most terms associated with the search queries were related to SE definition, symptoms, subtypes, and treatment. The volume of searches for some queries (nonconvulsive, focal, and refractory SE; SE definition; SE guidelines; SE symptoms; SE management; SE treatment) was enormously increased over time (search popularity has exceeded a 5000% growth since 2004). Most people use search engines to look for the term SE to obtain information on its definition, subtypes, and management. The greatest search volume occurred not only in developed countries but also in developing countries where raising awareness about SE still remains a challenging task and where there is reduced public knowledge of epilepsy. Health information seeking (the extent to which people search for health information online) reflects the health-related information needs of Internet users for a specific disease. Google Trends shows that Internet users have a great demand for information concerning some aspects of SE

Brexanolone as adjunctive therapy in super‐refractory status epilepticus

PubMed Central

Claassen, Jan; Wainwright, Mark S.; Husain, Aatif M.; Vaitkevicius, Henrikas; Raines, Shane; Hoffmann, Ethan; Colquhoun, Helen; Doherty, James J.; Kanes, Stephen J.

2017-01-01

Objective Super‐refractory status epilepticus (SRSE) is a life‐threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE‐547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open‐label evaluation of brexanolone response during and after anesthetic third‐line agent (TLA) weaning. Methods Patients receiving TLAs for SRSE control were eligible for open‐label, 1‐hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow‐up. Results Twenty‐five patients received open‐label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty‐two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. Interpretation In an open‐label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342–352 PMID:28779545

Prognosis of status epilepticus in elderly patients.

PubMed

Vilella, L; González Cuevas, M; Quintana Luque, M; Toledo, M; Sueiras Gil, M; Guzmán, L; Salas Puig, J; Santamarina Pérez, E

2018-03-01

To evaluate the clinical features and prognosis of status epilepticus (SE) in patients above 70 years old. Retrospective analysis of all patients ≥70 years old with SE registered prospectively during 4 years. Follow-up after discharge was performed. Ninety patients were evaluated. Acute symptomatic etiology was the most prevalent. The mean number of antiepileptic drugs (AEDs) used was 2.7 ± 1.2, and 21% of the patients required sedation. A poor outcome was considered when death (31.1%) or developing of new neurological impairment at discharge (32.2%) occurred. After multivariate analysis, four variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95% CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482-33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P = .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031). Independent predictive factors of mortality were SE duration >12 hours (OR: 4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4 (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There was no association between sedation and the number of AEDs used with outcome at discharge or long-term mortality (P > .05). SE above 70 years old has a high morbimortality. Prognosis is not related to treatment aggressiveness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perioperative management of massive fat embolism syndrome presenting as refractory status epilepticus

PubMed Central

Watson, William; Louro, Jack; Dudaryk, Roman

2018-01-01

Fat embolism syndrome (FES) most commonly can occur after trauma in patients with long bone fractures. While the majority of FES cases present as a mild decrease in mental status, some may manifest as seizure activity. We describe a case of a young patient with traumatic fractures who developed FES leading to refractory status epilepticus and simultaneously required damage controlled orthopedic surgery. The role of imaging modalities including magnetic resonance imaging, transcranial Doppler, and transesophageal echocardiography in diagnosis is discussed, and a multidisciplinary approach to successful perioperative management is described.

Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus

PubMed Central

Ogutu, Bernhards R; Newton, Charles R J C; Muchohi, Simon N; Otieno, Godfrey O; Edwards, Geoffrey; Watkins, William M; Kokwaro, Gilbert O

2003-01-01

Aims Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water-soluble prodrug, fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and fosphenytoin sodium in children with severe falciparum malaria and status epilepticus. Methods Children received intravenous (i.v.) phenytoin as a 18 mg kg−1 loading dose infused over 20 min followed by a 2.5 mg kg−1 12 hourly maintenance dose infused over 5 min (n = 11), or i.v. fosphenytoin, administered at a rate of 50 mg min−1 phenytoin sodium equivalents (PE; n = 16), or intramuscular (i.m.) fosphenytoin as a 18 mg kg−1 loading dose followed by 2.5 mg kg−1 12 hourly of PE (n = 11). Concentrations of phenytoin in plasma and cerebrospinal fluid (CSF), frequency of seizures, cardiovascular effects (respiratory rate, blood pressure, trancutaneous oxygen tension and level of consciousness) and middle cerebral artery (MCA) blood flow velocity were monitored. Results After all routes of administration, a plasma unbound phenytoin concentration of more than 1 µg ml−1 was rapidly (within 5–20 min) attained. Mean (95% confidence interval) steady state free phenytoin concentrations were 2.1 (1.7, 2.4; i.v. phenytoin, n = 6), 1.5 (0.96, 2.1; i.v. fosphenytoin, n = 11) and 1.4 (0.5, 2.4; i.m. fosphenytoin, n = 6), and were not statistically different for the three routes of administration. Median times (range) to peak plasma phenytoin concentrations following the loading dose were 0.08 (0.08–0.17), 0.37 (0.33–0.67) and 0.38 (0.17–2.0) h for i.v. fosphenytoin, i.v. phenytoin and i.m. fosphenytoin, respectively. CSF: plasma phenytoin concentration ratio ranged from 0.12 to 0.53 (median = 0.28, n = 16). Status epilepticus was controlled in only 36% (4/11) following i.v. phenytoin, 44% (7/16), following i.v. fosphenytoin and 64

Setting the scene: definition of prolonged seizures, acute repetitive seizures, and status epilepticus. Do we know why seizures stop?

PubMed

Cross, J Helen

2014-10-01

Status epilepticus is recognised as an acute emergency requiring urgent intervention. The optimal timing of such an intervention during a prolonged seizure, and the reasons for such, have provided much discussion. For operational purposes, a definition of a prolonged seizure of ≥5 minutes requiring intervention appears justified. However, a definition of status epilepticus of ≥30 minutes should stand, with the proportion of seizures proceeding to this clinical state remaining small. The reasons for this may be inherent to an individual, but an understanding of the mechanisms underlying the predisposition may lead to improved management pathways in the future.

A national database of incidence and treatment outcomes of status epilepticus in Thailand.

PubMed

Tiamkao, Somsak; Pranbul, Sineenard; Sawanyawisuth, Kittisak; Thepsuthammarat, Kaewjai

2014-06-01

Status epilepticus (SE) is a serious neurological condition. The national database of SE in Thailand and other developing countries is limited in terms of incidence and treatment outcomes. This study was conducted on the prevalence of status epilepticus (SE). The study group comprised of adult inpatients (over 18 years old) with SE throughout Thailand. SE patients were diagnosed and searched based on ICD 10 (G41) from the national database. The database used was from reimbursement documents submitted by the hospitals under the three health insurance systems, namely, the universal health coverage insurance, social security, and government health welfare system during the fiscal year 2010. We found 2190 SE patients receiving treatment at hospitals (5.10/100 000 population). The average age was 50.5 years and 1413 patients were males (64.5%). Mortality rate was 0.6 death/100 000 population or 11.96% of total patients. Significant factors associated with death or a nonimproved status at discharge were type of insurance, hospital level, chronic kidney disease, having pneumonia, having shock, on mechanical ventilator, and having cardiopulmonary resuscitation. In conclusion, the incidence of SE in Thailand was 5.10/100 000 population with mortality rate of 0.6/100 000 population.

Reversible postoperative blindness caused by bilateral status epilepticus amauroticus following thoracolumbar deformity correction: case report.

PubMed

Ibrahim, Tarik F; Sweis, Rochelle T; Nockels, Russ P

2017-07-01

Postoperative vision loss (POVL) is a devastating complication and has been reported after complex spine procedures. Anterior ischemic optic neuropathy and posterior optic neuropathy are the 2 most common causes of POVL. Bilateral occipital lobe seizures causing complete blindness are rare and have not been reported as a cause of POVL after spine surgery with the patient prone. The authors report the case of a 67-year-old man without a history of seizures who underwent a staged thoracolumbar deformity correction and developed POVL 6 hours after surgery. Imaging, laboratory, and ophthalmological examination results were nonrevealing. Routine electroencephalography study results were negative, but continuous electroencephalography captured bilateral occipital lobe seizures. The patient developed nonconvulsive status epilepticus despite initial treatment with benzodiazepines and loading doses of levetiracetam and lacosamide. He was therefore intubated for status epilepticus amauroticus and received a midazolam infusion. After electrographic seizure cessation for 48 hours, the patient was weaned off midazolam. The patient was maintained on levetiracetam and lacosamide without seizure recurrence and returned to his preoperative visual baseline status.

Anti-retroviral therapy-induced status epilepticus in "pseudo-HIV serodeconversion".

PubMed

Etgen, Thorleif; Eberl, Bernhard; Freudenberger, Thomas

2010-01-01

Diligence in the interpretation of results is essential as information gained from the psychiatric patient's history might often be restricted. Nonobservance of established guidelines may lead to a wrong diagnosis, induce a false therapy and result in life-threatening situations. Communication errors between hospitals and doctors and uncritical acceptance of prior diagnoses add substantially to this problem. We present a patient with alcohol-related dementia who received anti-retroviral therapy that promoted a non-convulsive status epilepticus. HIV serodeconversion was considered after our laboratory result yielded a HIV-negative status. Critical review of previous diagnostic investigations revealed several errors in the diagnosis of HIV infection leading to a "pseudo-serodeconversion." Finally, anti-retroviral therapy could be discontinued. Copyright © 2010 Elsevier Inc. All rights reserved.

Status Epilepticus: Epidemiology and Public Health Needs

PubMed Central

Sánchez, Sebastián; Rincon, Fred

2016-01-01

Status epilepticus (SE) is defined as a continuous clinical and/or electrographic seizure activity lasting five minutes or more or recurrent seizure activity without return to baseline. There is a paucity of epidemiological studies of SE, as most research is derived from small population studies. The overall incidence of SE is 9.9 to 41 per 100,000/year, with peaks in children and the elderly and with febrile seizures and strokes as its main etiologies. The etiology is the major determinant of mortality. Governments and the academic community should predominantly focus on the primary prevention of etiologies linked to SE, as these are the most important risk factors for its development. This review describes the incidence, prevalence, etiology, risk factors, outcomes and costs of SE and aims to identify future research and public health needs. PMID:27537921

Monitor for status epilepticus seizures

NASA Technical Reports Server (NTRS)

Johnson, Mark; Simkins, Thomas

1994-01-01

This paper describes the sensor technology and associated electronics of a monitor designed to detect the onset of a seizure disorder called status epilepticus. It is a condition that affects approximately 3-5 percent of those individuals suffering from epilepsy. This form of epilepsy does not follow the typical cycle of start-peak-end. The convulsions continue until medically interrupted and are life threatening. The mortality rate is high without prompt medical treatment at a suitable facility. The paper describes the details of a monitor design that provides an inexpensive solution to the needs of those responsible for the care of individuals afflicted with this disorder. The monitor has been designed as a cooperative research and development effort involving the United States Army Armament Research, Development, and Engineering Center's Benet Laboratories (Benet) and the Cerebral Palsy Center for the Disabled (Center), in association with the Department of Neurology at Albany Medical College (AMC). Benet has delivered a working prototype of the device for field testing, in collaboration with Albany Medical College. The Center has identified several children in need of special monitoring and has agreed to pursue commercialization of the device.

Peroxisome proliferator-activated receptors γ/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus

PubMed Central

2012-01-01

Background Status epilepticus induces subcellular changes that may lead to neuronal cell death in the hippocampus. However, the mechanism of seizure-induced neuronal cell death remains unclear. The mitochondrial uncoupling protein 2 (UCP2) is expressed in selected regions of the brain and is emerged as an endogenous neuroprotective molecule in many neurological disorders. We evaluated the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal cell death under experimental status epilepticus. Methods In Sprague–Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Oxidized protein level, translocation of Bcl-2, Bax and cytochrome c between cytosol and mitochondria, and expression of peroxisome proliferator-activated receptors γ (PPARγ) and UCP2 were examined in the hippocampal CA3 subfield following KA-induced status epilepticus. The effects of microinjection bilaterally into CA3 area of a PPARγ agonist, rosiglitazone or a PPARγ antagonist, GW9662 on UCP2 expression, induced superoxide anion (O2· -) production, oxidized protein level, mitochondrial respiratory chain enzyme activities, translocation of Bcl-2, Bax and cytochrome c, and DNA fragmentation in bilateral CA3 subfields were examined. Results Increased oxidized proteins and mitochondrial or cytosol translocation of Bax or cytochrome c in the hippocampal CA3 subfield was observed 3–48 h after experimental status epilepticus. Expression of PPARγ and UCP2 increased 12–48 h after KA-induced status epilepticus. Pretreatment with rosiglitazone increased UCP2 expression, reduced protein oxidation, O2· - overproduction and dysfunction of mitochondrial Complex I, hindered the translocation of Bax and cytochrome c, and reduced DNA fragmentation in the CA3 subfield. Pretreatment with GW9662 produced opposite effects. Conclusions Activation of PPARγ upregulated mitochondrial UCP2 expression

Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

NASA Astrophysics Data System (ADS)

El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

2015-01-01

Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

Complete recovery after severe myxoedema coma complicated by status epilepticus

PubMed Central

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-01-01

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. PMID:25809434

Complete recovery after severe myxoedema coma complicated by status epilepticus.

PubMed

Fjølner, Jesper; Søndergaard, Esben; Kampmann, Ulla; Nielsen, Søren

2015-03-25

We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as a differential diagnosis in medical emergencies. 2015 BMJ Publishing Group Ltd.

Costs and cost-driving factors for acute treatment of adults with status epilepticus: A multicenter cohort study from Germany.

PubMed

Kortland, Lena-Marie; Alfter, Anne; Bähr, Oliver; Carl, Barbara; Dodel, Richard; Freiman, Thomas M; Hubert, Kristina; Jahnke, Kolja; Knake, Susanne; von Podewils, Felix; Reese, Jens-Peter; Runge, Uwe; Senft, Christian; Steinmetz, Helmuth; Rosenow, Felix; Strzelczyk, Adam

2016-12-01

To provide first data on inpatient costs and cost-driving factors due to nonrefractory status epilepticus (NSE), refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). In 2013 and 2014, all adult patients treated due to status epilepticus (SE) at the university hospitals in Frankfurt, Greifswald, and Marburg were analyzed for healthcare utilization. We evaluated 341 admissions in 316 patients (65.7 ± [standard deviation]18.2 years; 135 male) treated for SE. Mean costs of hospital treatment were €14,946 (median €5,278, range €776-€152,911, €787 per treatment day) per patient per admission, with a mean length of stay (LOS) of 19.0 days (median 14.0, range 1-118). Course of SE had a significant impact on mean costs, with €8,314 in NSE (n = 137, median €4,597, €687 per treatment day, 22.3% of total inpatient costs due to SE), €13,399 in RSE (n = 171, median €7,203, €638/day, 45.0% of total costs, p < 0.001), and €50,488 in SRSE (n = 33, median €46,223, €1,365/day, 32.7% of total costs, p < 0.001). Independent cost-driving factors were SRSE, ventilation, and LOS of >14 days. Overall mortality at discharge was 14.4% and significantly higher in RSE/SRSE (20.1%) than in NSE (5.8%). Acute treatment of SE, and particularly SRSE and ventilation, are associated with high hospital costs and prolonged LOS. Extrapolation to the whole of Germany indicates that SE causes hospital costs of >€200 million per year. Along with the demographic change, incidence of SE will increase and costs for hospital treatment and sequelae of SE will rise. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Status epilepticus in pregnancy: Etiology, management, and clinical outcomes.

PubMed

Rajiv, Keni Ravish; Radhakrishnan, Ashalatha

2017-11-01

Status epilepticus (SE) in pregnancy carries significant risk to both mother and fetus. There is limited literature available on SE occurring in pregnancy world-over, with majority being from obstetric centers. All women who developed SE related to pregnancy (gestation, labor, or puerperium) between January 2000 and December 2016 were included in the study. Data were collected from our SE registry, maintained, and archived in the institute. The variables influencing the maternal and fetal outcome were compared using Student's t-test for continuous variables and Fisher's exact test for discrete variables. During the 16-year study period, a total of 348 SE events were recorded in 294 patients. Among these, there were 138 women, of which 17 had SE related to pregnancy. The etiology of SE was remote symptomatic in two and acute symptomatic in 15 patients. The various causes detected after initial evaluation for acute symptomatic SE were eclampsia (n=4), posterior reversible encephalopathy syndrome due to various causes other than eclampsia (n=6), cortical venous thrombosis (n=3), subarachnoid hemorrhage (n=1), and NMDA receptor antibody-mediated encephalitis (n=1).13 of 17 women with SE (76%) had good outcome. Majority of the fetuses had good outcomes, i.e., Category 1 (n=9, 57%). Duration of intensive care unit stay (p=0.029) and Status Epilepticus Severity Score (p=0.0324) at admission, were found to be significantly associated with poor outcomes. In any patient presenting with SE occurring in pregnancy, though eclampsia is presumed to be the most common overall cause; it is relevant to consider other etiologies such as posterior reversible encephalopathy syndrome, cortical venous thrombosis, and autoimmune encephalitis especially in cases presenting with refractory SE. Posterior reversible encephalopathy may occur in pregnancy due to diverse etiologies other than eclampsia. Copyright © 2017 Elsevier Inc. All rights reserved.

Nonconvulsive status epilepticus due to ifosfamide.

PubMed

Kilickap, Saadettin; Cakar, Mustafa; Onal, Ibrahim K; Tufan, Abdurrahman; Akoglu, Hadim; Aksoy, Sercan; Erman, Mustafa; Tekuzman, Gulten

2006-02-01

To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide. Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy. The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration. Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

PubMed

Imran, Imran; Hillert, Markus H; Klein, Jochen

2015-12-01

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by

Suppressing cAMP response element-binding protein transcription shortens the duration of status epilepticus and decreases the number of spontaneous seizures in the pilocarpine model of epilepsy.

PubMed

Zhu, Xinjian; Dubey, Deepti; Bermudez, Camilo; Porter, Brenda E

2015-12-01

Current epilepsy therapies directed at altering the function of neurotransmitter receptors or ion channels, or release of synaptic vesicles fail to prevent seizures in approximately 30% of patients. A better understanding of the molecular mechanism underlying epilepsy is needed to provide new therapeutic targets. The activity of cyclic AMP (cAMP) response element-binding protein (CREB), a major transcription factor promoting CRE-mediated transcription, increases following a prolonged seizure called status epilepticus. It is also increased in the seizure focus of patients with medically intractable focal epilepsy. Herein we explored the effect of acute suppression of CREB activity on status epilepticus and spontaneous seizures in a chronic epilepsy model. Pilocarpine chemoconvulsant was used to induce status epilepticus. To suppress CREB activity, a transgenic mouse line expressing an inducible dominant negative mutant of CREB (CREB(IR) ) with a serine to alanine 133 substitution was used. Status epilepticus and spontaneous seizures of transgenic and wild-type mice were analyzed using video-electroencephalography (EEG) to assess the effect of CREB suppression on seizures. Our findings indicate that activation of CREB(IR) shortens the duration of status epilepticus. The frequency of spontaneous seizures decreased in mice with chronic epilepsy during CREB(IR) induction; however, the duration of the spontaneous seizures was unchanged. Of interest, we found significantly reduced levels of phospho-CREB Ser133 upon activation of CREB(IR) , supporting prior work suggesting that binding to the CRE site is important for CREB phosphorylation. Our results suggest that CRE transcription supports seizure activity both during status epilepticus and in spontaneous seizures. Thus, blocking of CRE transcription is a novel target for the treatment of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy.

PubMed

Ylikotila, Pauli; Ketola, Raimo A; Timonen, Susanna; Malm, Heli; Ruuskanen, Jori O

2015-11-01

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. Copyright © 2015 Elsevier Inc. All rights reserved.

[Management of pediatric status epilepticus].

PubMed

Vargas L, Carmen Paz; Varela E, Ximena; Kleinsteuber S, Karin; Cortés Z, Rocío; Avaria B, María de Los Ángeles

2016-01-01

Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patient’s evolution.

Refractory Convulsive Status Epilepticus in Children: Etiology, Associated Risk Factors and Outcome

PubMed Central

BARZEGAR, Mohammad; MAHDAVI, Mohammad; GALEGOLAB BEHBEHANI, Afshin; TABRIZI, Aidin

2015-01-01

Objective Refractory status epilepticus (RSE) is a life-threatening disease in children wherein the patient’s convulsive seizures do not respond to adequate initial anticonvulsants. RSE is associated with high rate of mortality and morbidity. This study was aimed to survey the risk factors leading status epilepticus (SE) to RSE in children, and their early outcome. Materials & Methods Patients with SE hospitalized in Tabriz Children’s Hospital, Iran were studied during the years 2007 and 2008 with regard to their clinical profile, etiology, the treatment methods available to them and their outcome upon release from the hospital. Results Among 132 patients with SE, 53 patients (40.15%) suffered from RSE. Acute symptomatic etiology was a risk factor responsible for developing RSE in the patient (P=0.004). Encephalitis was the most common etiology of acute symptomatic SE. There was no significant relationship observed between RSE and the patients’ age, gender, date of initial drug intake and type of seizure. The mortality rate was 8.3% and a new neurological deficit occurred in 25.7% of cases. None of RSE with encephalitis returned to the baseline status. Mortality and morbidity rates were significantly higher in children with RSE than in those with SE (P=0.006). Conclusion Etiology of SE significantly influenced prognosis of it with significant incidence of RSE in acute symptomatic group. Because acute neurological insult such as encephalitis and meningitis are common causes of RSE in children, properly management of them is necessary to avoid permanent brain damage. PMID:26664438

A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

PubMed

Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O; Scheffer, Ingrid E; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H

2015-10-01

The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is 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. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor

Electrical status epilepticus during sleep: a study of 22 patients.

PubMed

Değerliyurt, Aydan; Yalnizoğlu, Dilek; Bakar, Emel Erdoğan; Topçu, Meral; Turanli, Güzide

2015-02-01

The aim of this study was to evaluate the clinical and imaging characteristics, treatment results, and prognosis of patients with electrical status epilepticus during sleep (ESES). A total of 22 patients with ESES pattern on EEG were retrospectively studied. The first neurological symptoms were seen at a mean age of 4.4years. The first symptoms in 77% of the patients were seizures. Other symptoms were hyperactivity, restlessness, insomnia, disinhibition, autistic behavior, speech retardation and deterioration in school performance. Diagnosis of ESES was made at a mean age of 7.45years, approximately 3years after the first symptom. Magnetic resonance imaging (MRI) was abnormal in 36% of the patients. Single photon emission computed tomography (SPECT) showed focal hypoperfusion after resolution of ESES involving left temporoparietal and right posterior temporal areas in four patients including three with normal MRI, and one with periventricular leukomalacia without focal cortical lesion. First line treatment with valproic acid monotherapy was not effective. Electrical status epilepticus during sleep disappeared in 82% of the patients on clobazam and 70% of the patients on clonazepam in combination with valproic acid within a few months. Topiramate was not found to be effective. A significant decrease in intelligence quotient (IQ) scores was found in 66% of the patients compared to the baseline. ESES should be considered in children with new onset behavioral, cognitive, and speech problems with or without seizures. The high frequency of focal seizures and focal findings on SPECT suggest a focal origin. Clonazepam and clobazam were most effective in our cohort. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies.

PubMed

Petit-Pedrol, Mar; Armangue, Thaís; Peng, Xiaoyu; Bataller, Luis; Cellucci, Tania; Davis, Rebecca; McCracken, Lindsey; Martinez-Hernandez, Eugenia; Mason, Warren P; Kruer, Michael C; Ritacco, David G; Grisold, Wolfgang; Meaney, Brandon F; Alcalá, Carmen; Sillevis-Smitt, Peter; Titulaer, Maarten J; Balice-Gordon, Rita; Graus, Francesc; Dalmau, Josep

2014-03-01

and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients' antibodies caused a selective reduction of GABAA receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABAA receptor). High titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundació la Marató de TV3, the Netherlands Organisation for Scientific Research (Veni-incentive), the Dutch Epilepsy Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Landau-Kleffner Syndrome, Electrical Status Epilepticus in Slow Wave Sleep, and Language Regression in Children

ERIC Educational Resources Information Center

McVicar, Kathryn A.; Shinnar, Shlomo

2004-01-01

The Landau-Kleffner syndrome (LKS) and electrical status epilepticus in slow wave sleep (ESES) are rare childhood-onset epileptic encephalopathies in which loss of language skills occurs in the context of an epileptiform EEG activated in sleep. Although in LKS the loss of function is limited to language, in ESES there is a wider spectrum of…

Pharmacokinetics of rectal levetiracetam as add-on treatment in dogs affected by cluster seizures or status epilepticus.

PubMed

Cagnotti, Giulia; Odore, Rosangela; Gardini, Giulia; Amedeo, Stefano; Bertone, Iride; Guerriero, Giulia; Lentini, Laura; Dappiano, Elena; D'Angelo, Antonio

2018-06-18

Levetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported. Eight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 μg/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2 ± 15.5 μg/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as "responders". Minimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.

Outcome following postanoxic status epilepticus in patients with targeted temperature management after cardiac arrest.

PubMed

Dragancea, Irina; Backman, Sofia; Westhall, Erik; Rundgren, Malin; Friberg, Hans; Cronberg, Tobias

2015-08-01

Postanoxic electrographic status epilepticus (ESE) is considered a predictor of poor outcome in resuscitated patients after cardiac arrest (CA). Observational data suggest that a subgroup of patients may have a good outcome. This study aimed to describe the prevalence of ESE and potential clinical and electrographic prognostic markers. In this retrospective single study, we analyzed consecutive patients who suffered from CA, and who received temperature management and were monitored with simplified continuous EEG (cEEG) during a five-year period. The patients' charts and cEEG data were initially screened to identify patients with clinical seizures or ESE. The cEEG diagnosis of ESE was retrospectively reanalyzed according to strict criteria by a neurophysiologist blinded to patient outcome. The EEG background patterns prior to the onset of ESE, duration of ESE, presence of clinical seizures, and use of antiepileptic drugs were analyzed. The results of somatosensory-evoked potentials (SSEPs) and neuron-specific enolase (NSE) at 48 h after CA were described in all patients with ESE. Antiepileptic treatment strategies were not protocolized. Outcome was evaluated using the Cerebral Performance Category (CPC) scale at 6 months, and good outcome was defined as CPC 1-2. Of 127 patients, 41 (32%) developed ESE. Twenty-five patients had a discontinuous EEG background prior to ESE, and all died without regaining consciousness. Sixteen patients developed a continuous EEG background prior to the start of ESE, four of whom survived, three with CPC 1-2 and one with CPC 3 at 6 months. Among survivors, ESE developed at a median of 46 h after CA. All had preserved N20 peaks on SSEP and NSE values of 18-37 μg/l. Electrographic status epilepticus is common among comatose patients after cardiac arrest, with few survivors. A combination of a continuous EEG background prior to ESE, preserved N20 peaks on SSEPs, and low or moderately elevated NSE levels may indicate a good outcome. This

The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

PubMed Central

Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

2014-01-01

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

Status epilepticus in scrub typhus.

PubMed

Kalita, Jayantee; Mani, Vinita E; Bhoi, Sanjeev K; Misra, Usha K

2016-07-01

Scrub typhus is an emerging infection, and there is little information about status epilepticus (SE) in scrub typhus. We report the clinical spectrum and outcome of SE in scrub typhus. In a 3-year prospective hospital-based observational study, all scrub typhus patients with SE were included. Scrub typhus was diagnosed by immunochromatography assay. SE was defined if convulsions lasted longer than 5 min. The patients' demographic, clinical, computed tomography (CT), magnetic resonance imaging (MRI), and electroencephalography (EEG) findings were noted. Response to antiepileptic drugs (AEDs) and outcome at 1 month and 1 year were recorded. Between 2012 and 2014, there were 66 patients with scrub typhus admitted with central nervous system (CNS) involvement, 10 (15.2%) of whom had SE (generalized convulsions in 5, secondary generalized in one). The median age of the patients was 34 (range 18-71) years and seven were female. The duration of SE ranged between 10 min and 48 h. SE responded to one AED in five patients, two AEDs in three patients, and more than two AEDs in two patients. Cranial MRI findings were normal. All patients recovered completely with doxycycline by 1 month and AED was withdrawn by 8 months in all. Although 15% patients with scrub typhus may have SE, they have good outcome. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Which EEG patterns in coma are nonconvulsive status epilepticus?

PubMed

Trinka, Eugen; Leitinger, Markus

2015-08-01

Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma. Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary. The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015. Published by Elsevier Inc.

Epilepsy surgery in the elderly: an unusual case of a 75-year-old man with recurrent status epilepticus.

PubMed

Tellez-Zenteno, Jose F; Sadanand, Venkatraman; Riesberry, Martha; Robinson, Christopher A; Ogieglo, Lissa; Masiowski, Paul; Vrbancic, Mirna

2009-06-01

Epilepsy surgery is increasingly well-supported as an effective treatment for patients with intractable epilepsy. It is most often performed on younger patients and the safety and efficacy of epilepsy surgery in elderly patients are not frequently described. We report a case of a 75-year-old right-handed man who underwent a left fronto-temporal craniotomy for resection of a suprasellar meningioma in 2002. Immediately following hospital discharge, he began to experience complex partial seizures. He continued to have frequent seizures despite treatment with multiple combinations of antiepileptic medications. He presented with status epilepticus every two or three months, and required long periods of hospitalization on each occasion for post-ictal confusion and aphasia. Scalp EEG showed continuous spikes and polyspikes and persistent slowing in the left temporal area, as well as spikes in the left frontal area. EEG telemetry recorded multiple seizures, all with a clear focus in the left temporal area. MRI scan showed an area of encephalomalacia in the left temporal lobe, as well as post-surgical changes in the left frontal area. Neuropsychological testing showed bilateral memory impairment with no significant cognitive decline expected after unilateral temporal lobe resection. A left anteromesial temporal lobectomy was performed with intraoperative electrocorticography. Since surgery, the patient was not seizure-free (Engel class II-b), but had no further episodes of status epilepticus in one year and two months of follow-up. This is one of the oldest patients reported in the literature with epilepsy surgery and supports the possibility of epilepsy surgery in elderly patients for particular cases. In addition, few cases with such a malignant evolution of temporal lobe epilepsy have been described in this age group.

Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

PubMed

Fernández-Torre, José L; Burgueño, Paula; Ballesteros, María A; Hernández-Hernández, Miguel A; Villagrá-Terán, Nuria; de Lucas, Enrique Marco

2015-08-01

Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition

Predictors of outcomes and refractoriness in status epilepticus: A prospective study.

PubMed

Atmaca, Murat Mert; Bebek, Nerses; Baykan, Betül; Gökyiğit, Ayşen; Gürses, Candan

2017-10-01

The objective of this study was to determine the predictors of outcomes and refractoriness in status epilepticus (SE). This is a prospective study of 59 adult patients with SE who were admitted to the Emergency Department between February 2012 and December 2013. The effects of clinical, demographic, and electrophysiologic features of patients with SE were evaluated. To evaluate outcome in SE, STESS, mSTESS, and EMSE scales were used. Logistic regression analysis showed that being aged ≥65years (p=0.02, OR: 17.68, 95% CI: [1.6-198.4]) for the short term and having potentially fatal etiology (p=0.027, OR: 11.7, 95% CI: [1.3-103]) for the long term were the only independent predictors of poor outcomes; whereas, the presence of periodic epileptiform discharges (PEDs) in EEG was the only independent predictor of refractoriness (p=0.032, OR: 13.7, 95% CI: [1.3-148.5]). The patients with ≥3 Status Epilepticus Severity Score (STESS) did not have poorer outcomes in the short- (p=0.157) and long term (p=0.065). There was no difference between patients with 0-2, 3-4, and ≥4 mSTESS in the short- and long term in terms of outcome (p=0.28 and 0.063, respectively). Also, there was no difference between subgroups (convulsive SE [CSE], nonconvulsive SE [NCSE], and epilepsia partialis continua [EPC]) in terms of STESS and mSTESS. When patients with EPC were excluded, both STESS and mSTESS scores of the patients correlated with poorer long-term outcomes (p=0.025 and 0.017, respectively). The patients with ≥64 points in the Epidemiology-based Mortality in SE-Etiology, age, comorbidity, EEG (EMSE-EACE) score and those with ≥27 points in EMSE-Etiology, age, comorbidity (EMSE-EAC) score did not have poorer outcomes in the short term (p=0.06 and 0.274, respectively) while they had significantly poorer outcome in the long term (p<0.001 and 0.002, respectively). In subgroup analysis, patients with CSE with ≥64 points in EMSE-EACE had significantly poorer outcome in the both

Temporal seizure focus and status epilepticus are associated with high-sensitive troponin I elevation after epileptic seizures.

PubMed

Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

2015-09-01

Postictal elevation of high-sensitive troponin I (TNI), a highly specific biomarker for myocardial ischemia, has been reported. We aimed at evaluating its association of high-sensitive troponin I (TNI) with seizure type and focus, as well as vascular risk factors. TNI was measured in 247 patients admitted to our clinic via the emergency room with an acute epileptic seizure. TNI control measurements were performed in 61.5% of cases. All patients underwent electroencephalography and cerebral imaging. Seizure focus - when possible - was determined using results from these examinations as well as clinical data. Of 247 patients, 133 (53.8%) were men, the mean age was 59 ± 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05 ± 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus and temporal seizure focus were significantly associated with TNI elevation in multivariate analysis. In 21 (13.8%) of the patients with TNI control measurement, TNI was continuously elevated. Higher age and temporal seizure focus were significantly associated with continuously high TNI. Coronary heart disease and vascular risk factors were significantly associated with high TNI only in univariate analysis. No patient had a symptomatic myocardial ischemia. Postictal TNI elevation is relatively common in older patients with status epilepticus or temporal seizure focus. These data support the concept of relevant and possibly dangerous ictal effects on cardiac function especially in temporal lobe seizures. Although the risk of manifest postictal myocardial infarction seems to be very low, selected patients could profit from closer monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Progranulin levels in status epilepticus as a marker of neuronal recovery and neuroprotection.

PubMed

Huchtemann, T; Körtvélyessy, P; Feistner, H; Heinze, H J; Bittner, D

2015-08-01

Recently, a mouse model showed that progranulin, a mediator in neuroinflammation and a neuronal growth factor, was elevated in the hippocampus after status epilepticus (SE). This elevated level might mirror compensating neuronal mechanisms after SE. Studies concerning neuronal recovery and neuroprotective mechanisms after SE in humans are scarce, so we tested for progranulinin the cerebrospinal fluid (CSF) after various types of SE. We performed a retrospective analysis of progranulin levels in CSF in patients (n = 24) who underwent lumbar puncture as part of diagnostic workup after having SE and in patients after having one single tonic-clonic seizure who comprised the control group (n = 8). In our group with SE, progranulin levels in CSF were not significantly elevated compared to our control group. Furthermore, there was no correlation between progranulin levels and the time interval between lumbar puncture and SE. Additionally, in cases of higher CSF progranulin levels, we found no impact on the clinical outcome after SE. Although our cohort is heterogeneous and not fully sufficient, we conclude that progranulin in CSF is not elevated after SE in our cohort. Therefore, our results do not suggest a change in cerebral progranulin metabolism as a possible neuroregenerative or neuroprotective mechanism in humans after SE in acute and subacute phases. A larger cohort study is needed to further strengthen this result. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.

Convulsive status epilepticus and health-related quality of life in children with epilepsy.

PubMed

Ferro, Mark A; Chin, Richard F M; Camfield, Carol S; Wiebe, Samuel; Levin, Simon D; Speechley, Kathy N

2014-08-19

The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p < 0.001). Controlling for clinical, demographic, and family characteristics, CSE was significantly associated with poorer HRQL (β = -4.65, p = 0.031). The final model explained 47% of the variance in QOLCE scores. The findings suggested that not only do children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. © 2014 American Academy of Neurology.

Convulsive status epilepticus and health-related quality of life in children with epilepsy

PubMed Central

Chin, Richard F.M.; Camfield, Carol S.; Wiebe, Samuel; Levin, Simon D.; Speechley, Kathy N.

2014-01-01

Objectives: The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Methods: Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Results: Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p < 0.001). Controlling for clinical, demographic, and family characteristics, CSE was significantly associated with poorer HRQL (β = −4.65, p = 0.031). The final model explained 47% of the variance in QOLCE scores. Conclusions: The findings suggested that not only do children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. PMID:25037204

Refractory status epilepticus and autoimmune encephalitis with GABAAR and GAD65 antibodies: A case report.

PubMed

Gagnon, Maude-Marie; Savard, Martin; Mourabit Amari, Karim

2016-04-01

Autoimmune encephalitis is an inflammatory disorder of the brain that may be associated with different neuronal antibodies. Recently, an increasing number of valuable autoantibodies have been identified, including GABAAR antibodies, which appear to be associated with a severe form of encephalitis with refractory status epilepticus. We report here on a patient with encephalitis associated with GAD65 and GABAAR antibodies, an entity that remains an understudied topic, with an unanticipated clinical presentation and we describe the longitudinal follow-up. We report a case of encephalitis associated with GAD65 and GABAAR antibodies; we describe clinical and paraclinical features and the longitudinal follow-up. Our case presented with dysgueusia, dysosmia and episodes of hyperventilation that evolved into a refractory status epilepticus. Multiple anticonvulsant drugs were required. An aggressive immunotherapy was associated with a relative favorable outcome, in regard of epilepsy and cognitive functions. However, a relapse occurred and a full recovery was not observed at the last follow-up visit. There was no correlation between GAD65 antibodies titers and disease activity. Autoimmune encephalitis associated with GABAAR and GAD65 antibodies might be a severe and refractory disease. The appropriate treatment is currently unknown for those patients. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Anti‐flatulence treatment and status epilepticus: a case of camphor intoxication

PubMed Central

Guilbert, J; Flamant, C; Hallalel, F; Doummar, D; Frata, A; Renolleau, S

2007-01-01

We describe a case of a young child who lived in Hong Kong who presented with a severe epilepticus status after a return flight to Paris. Routine laboratory tests failed to establish a cause. Upon further questioning, the parents reported that the nanny had given an abdominal massage to the child with an unlabelled solution reported to have anti‐flatulence effects. Toxicological analysis of this solution revealed the presence of camphor. Although the highly toxic effects of camphor have long been established, the present case illustrates that camphor continues to be a source of paediatric exposure. This case highlights the importance of systematic questioning and recalls the extreme danger associated with camphor even when administered transcutaneously. PMID:18029526

Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

PubMed

Coppola, Giangennaro; Operto, Francesca Felicia; Auricchio, Gianfranca; D'Amico, Alessandra; Fortunato, Delia; Pascotto, Antonio

2007-06-01

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring. Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].

Efficacy of lacosamide in children and adolescents with drug-resistant epilepsy and refractory status epilepticus: A systematic review.

PubMed

Ortiz de la Rosa, Johann Sebastián; Ladino, Lady Diana; Rodríguez, Paula Juliana; Rueda, María Camila; Polanía, Juan Pablo; Castañeda, Angie Catalina

2018-03-01

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. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[A case of non-convulsive status epilepticus worsened Wernicke's aphasia reversely].

PubMed

Ueki, Y; Terada, K; Otsuka, A; Kanda, M; Akiguchi, I

2000-04-01

A 62-year-old right-handed woman had presented progressive speech impediment over 4 months. She was alert without any convulsions or involuntary movements. Neurological examination showed Wernicke's aphasia, constructional apraxia. Her magnetic resonance imaging (MRI) showed an old cerebral infarction in the left parieto-occipital area, in addition to ischemic changes in the bilateral deep white matter. Electroencephalography (EEG) revealed periodic lateralized epileptiform discharges (PLEDs) predominant in the posterior left hemisphere. The PLEDs as well as the cortical symptoms improved after an administration of anti-convulsive agents, thus establishing the diagnosis of non-convulsive status epilepticus (NSE). It should be emphasized that NSE manifesting as Wernicke's aphasia should be distinguished from dementia syndrome because it is a treatable disorder.

Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

PubMed

Bradley, Lucas; Bahgat, Diaa; Sharp, Gregory; Willis, Erin; Ocal, Eylem; Albert, Gregory; Serletis, Demitre

2015-10-01

We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies.

Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model.

PubMed

Shao, Yi-Ye; Li, Bing; Huang, Yong-Mei; Luo, Qiong; Xie, Yang-Mei; Chen, Ying-Hui

2017-01-01

Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

PubMed

Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

2012-05-02

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Nonintravenous rescue medications for pediatric status epilepticus: A cost-effectiveness analysis.

PubMed

Sánchez Fernández, Iván; Gaínza-Lein, Marina; Loddenkemper, Tobias

2017-08-01

To quantify the cost-effectiveness of rescue medications for pediatric status epilepticus: rectal diazepam, nasal midazolam, buccal midazolam, intramuscular midazolam, and nasal lorazepam. Decision analysis model populated with effectiveness data from the literature and cost data from publicly available market prices. The primary outcome was cost per seizure stopped ($/SS). One-way sensitivity analyses and second-order Monte Carlo simulations evaluated the robustness of the results across wide variations of the input parameters. The most cost-effective rescue medication was buccal midazolam (incremental cost-effectiveness ratio ([ICER]: $13.16/SS) followed by nasal midazolam (ICER: $38.19/SS). Nasal lorazepam (ICER: -$3.8/SS), intramuscular midazolam (ICER: -$64/SS), and rectal diazepam (ICER: -$2,246.21/SS) are never more cost-effective than the other options at any willingness to pay. One-way sensitivity analysis showed the following: (1) at its current effectiveness, rectal diazepam would become the most cost-effective option only if its cost was $6 or less, and (2) at its current cost, rectal diazepam would become the most cost-effective option only if effectiveness was higher than 0.89 (and only with very high willingness to pay of $2,859/SS to $31,447/SS). Second-order Monte Carlo simulations showed the following: (1) nasal midazolam and intramuscular midazolam were the more effective options; (2) the more cost-effective option was buccal midazolam for a willingness to pay from $14/SS to $41/SS and nasal midazolam for a willingness to pay above $41/SS; (3) cost-effectiveness overlapped for buccal midazolam, nasal lorazepam, intramuscular midazolam, and nasal midazolam; and (4) rectal diazepam was not cost-effective at any willingness to pay, and this conclusion remained extremely robust to wide variations of the input parameters. For pediatric status epilepticus, buccal midazolam and nasal midazolam are the most cost-effective nonintravenous rescue

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2011-06-15

... Status Epilepticus and Seizures Causing Status Epilepticus AGENCY: Department of the Army, DoD. ACTION... PCT/US2009/060091, entitled ``Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus'' filed on October 9, 2009. The United States Government, as represented by the...

Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma

PubMed Central

Engel, Tobias; Murphy, Brona M.; Hatazaki, Seiji; Jimenez-Mateos, Eva M.; Concannon, Caoimhin G.; Woods, Ina; Prehn, Jochen H. M.; Henshall, David C.

2010-01-01

The functional significance of neuronal death for pathogenesis of epilepsy and the underlying molecular mechanisms thereof remain incompletely understood. The p53 transcription factor has been implicated in seizure damage, but its target genes and the influence of cell death under its control on epilepsy development are unknown. In the present study, we report that status epilepticus (SE) triggered by intra-amygdala kainic acid in mice causes rapid p53 accumulation and subsequent hippocampal damage. Expression of p53-up-regulated mediator of apoptosis (Puma), a proapoptotic Bcl-2 homology domain 3-only protein under p53 control, was increased within a few hours of SE. Induction of Puma was blocked by pharmacologic inhibition of p53, and hippocampal damage was also reduced. Puma induction was also blocked in p53-deficient mice subject to SE. Compared to Puma-expressing mice, Puma-deficient mice had significantly smaller hippocampal lesions after SE. Long-term, continuous telemetric EEG monitoring revealed a ∼60% reduction in the frequency of epileptic seizures in the Puma-deficient mice compared to Puma-expressing mice. These are the first data showing genetic deletion of a proapoptotic protein acting acutely to influence neuronal death subsequently alters the phenotype of epilepsy in the long-term, supporting the concept that apoptotic pathway activation is a trigger of epileptogenesis.—Engel, T., Murphy, B. M., Hatazaki, S., Jimenez-Mateos, E. M., Concannon, C. G., Woods, I., Prehn, J. H. M., Henshall, D. C. Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma. PMID:19890018

Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study.

PubMed

Gujjar, Arunodaya R; Nandhagopal, Ramachandiran; Jacob, Poovathoor C; Al-Hashim, Abdulhakeem; Al-Amrani, Khalfan; Ganguly, Shyam S; Al-Asmi, Abdullah

2017-07-01

Status Epilepticus (SE) is a common medical emergency carrying a high morbidity and mortality. Levetiracetam (LEV) is a novel anticonvulsant effective against varied seizures. Few prospective studies have addressed its use in SE. We aimed to examine the efficacy of intravenous LEV in controlling SE and cluster attacks of seizures (CS), in comparison with IV phenytoin (DPH), using a prospective, randomized study design. Adult patients with SE or CS, following an initial dose of IV benzodiazepine to control ongoing seizure, were randomized to receive either medication. Rates of seizure control over 24h, adverse effects and outcomes were compared. A logistic regression model was used to identify outcome predictors. 52 patients with SE and 63 with CS received either LEV or DPH. In the SE group, LEV was effective in18/22(82%) and DPH in 22/30(73.3%) patients in controlling seizures. Among patients with CS, LEV was effective in 31/38(81.6%) and DPH in 20/25(80%). With the use of LEV, DPH or both, SE and CS were controlled among 92% and 96% of patients respectively. Adverse events included hypotension (in 2 on DPH) and transient agitation (2 on LEV). IV Levetiracetam controls status epilepticus or cluster seizures with an efficacy comparable to that of phenytoin. Use of these two agents consecutively may control >90% of all such conditions without resort to anaesthetic agents. Further studies should explore its efficacy in larger cohorts of epileptic emergencies. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

PubMed

Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

2009-08-04

Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats

PubMed Central

Meade, Seth M.; Smith, Cara S.; Chen, Keying; Kleinman, Nanette; Capadona, Jeffrey R.

2017-01-01

Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225–250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg) dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP) slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose). Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol. PMID:28785508

Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats.

PubMed

Ereifej, Evon S; Meade, Seth M; Smith, Cara S; Chen, Keying; Kleinman, Nanette; Capadona, Jeffrey R

2017-01-01

Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225-250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg) dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP) slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose). Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol.

Developmental outcome after a single episode of status epilepticus.

PubMed

Roy, Hélène; Lippé, Sarah; Lussier, Francine; Sauerwein, Hannelore Catherine; Lortie, Anne; Lacroix, Jacques; Lassonde, Maryse

2011-08-01

Consequences of status epilepticus (SE) on psychomotor development and the specific impact of the convulsive event on emerging executive functions remain controversial. Infants treated for a single episode of SE, those treated for a single febrile seizure, and healthy infants were tested with respect to motor development, language, personal, and social skills and self-regulation. The children were divided into two age groups to investigate the impact of the convulsive event at different windows of brain maturation. We found that infants who had had SE were inferior to healthy controls on the development scales. Age differentiated SE impact on visuomotor development versus sociolinguistic development. Children who had been treated for SE had significantly more difficulties delaying a response to an attractive stimulus in one of the long-delay conditions. A single episode of SE can interfere with psychomotor and cognitive development in children without previous developmental delay, and it seems that the functions that are emerging at the time of insult are most vulnerable. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Super-Refractory Status Epilepticus: Report of a Case and Review of the Literature.

PubMed

Lapenta, Leonardo; Frisullo, Giovanni; Vollono, Catello; Brunetti, Valerio; Giannantoni, Nadia Mariagrazia; Sandroni, Claudio; Di Lella, Giuseppe; Della Marca, Giacomo

2015-10-01

Super-refractory status epilepticus (SE; ie, SE continuing or recurring despite 24 hours of general anesthesia) is a severe condition with high percentage of mortality and morbidity. Usually, this condition occurs because of serious brain damage; nevertheless, some patients develop super-refractory SE without identifiable etiology. Although not uncommonly encountered in neurointensive care, scientific data on this condition are still lacking in terms of treatment and prognosis. Herein, we report a case of super-refractory SE with recovery after 50 days, despite electroencephalographic (EEG) and magnetic resonance imaging (MRI) signs traditionally related to poor prognosis. A review of the literature on super-refractory SE is also presented. © EEG and Clinical Neuroscience Society (ECNS) 2014.

Pediatric status epilepticus: improved management with new drug therapies?

PubMed

Verrotti, Alberto; Ambrosi, Michela; Pavone, Piero; Striano, Pasquale

2017-06-01

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.

Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

PubMed Central

Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

2007-01-01

The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology. PMID:17971868

Considerations in prophylaxis for tumor-associated epilepsy: prevention of status epilepticus and tolerability of newer generation AEDs.

PubMed

Wychowski, Thomas; Wang, Hongyue; Buniak, Liana; Henry, J Craig; Mohile, Nimish

2013-11-01

To identify risk factors for the development of tumor-associated epilepsy (TAE) and potential benefit of newer generation AEDs in seizure prevention. We performed an IRB approved retrospective study of newly diagnosed GBM patients at the University of Rochester between 1/1/05 and 5/13/11. Records were reviewed to describe demographics, seizure incidence, occurrence of status epilepticus, and AED use and toxicity. 172 patients with newly diagnosed GBM were included in the study. 53.4% developed TAE. 31.4% had seizure prior to diagnosis. 118 patients were seizure-free at diagnosis: 32.2% developed post-diagnosis TIE (PostTAE) and 60.2% remained seizure-free. 70 seizure-free patients received an AED peri-operatively. 36 were weaned off AEDs and 31 were continued. Incidence of PostTAE and time to first seizure were comparable in AED-treated and untreated patients. 4 PostTAE patients presented with status epilepticus (SE), all were not AED treated. AEDs were withdrawn in 10 patients due to toxicity: 9 from phenytoin and 1 from levetiracetam. There is a high incidence of PostTAE in GBM. Prophylactic AED therapy did not reduce PostTAE but may have prevented SE. Minimal toxicity was observed on 2nd generation AEDs. The high burden of epilepsy in this population and tolerability of newer AEDS suggest that AAN guidelines should be revisited. Copyright © 2013 Elsevier B.V. All rights reserved.

Nonconvulsive status epilepticus: the encephalopathic pediatric patient.

PubMed

Greiner, Hansel M; Holland, Katherine; Leach, James L; Horn, Paul S; Hershey, Andrew D; Rose, Douglas F

2012-03-01

A high prevalence of nonconvulsive status epilepticus (NCSE) has been reported in critically ill adults and neonates. Recent prospective pediatric studies focus on critically ill children and show wide variability in the frequency of NCSE. This study examines prevalence of pediatric NCSE regardless of inpatient setting and retrospectively identifies risk factors indicating a need for urgent continuous EEG. Medical records from patients aged 3 months to 21 years were identified either by (1) searching a clinical EEG database (n = 18) or (2) consecutive inpatient EEG referrals for NCSE over an 8-month period (n = 57). Seventy-five children, mean age of 7.8 years, were studied. NCSE was identified in 26 patients (35%) and in 8 of 57 (14%) patients referred for possible NCSE. More than half of the patients referred were outside of the ICU. A witnessed clinical seizure was observed in 24 of 26 (92%) patients with NCSE. Acute cortical neuroimaging abnormalities were significantly more frequent in patients with NCSE. The presence of clinical seizures and acute neuroimaging abnormality was associated with an 82% probability of NCSE. All but 1 patient with NCSE had electrographic or electroclinical seizures within the first hour of monitoring. A high prevalence of NCSE was observed, comparable to adult studies, but within a wider range of inpatient settings. Children with acute encephalopathy should undergo continuous EEG. This evaluation is more urgent if certain clinical risk factors are present. Optimal duration of monitoring and the effect of NCSE on prognosis should be studied.

Tonic Seizure Status Epilepticus Triggered by Valproate in a Child with Doose Syndrome.

PubMed

Grande-Martín, Alberto; Pardal-Fernández, José Manuel; Carrascosa-Romero, María Carmen; De Cabo, Carlos

2016-06-01

Antiepileptic drugs may occasionally increase seizure frequency or eliciting de novo seizure occurrence; the underlying mechanism of these effects is not known. The potential adverse effects of valproic acid in myoclonic astatic epilepsy have been noted by experienced clinicians in various different regions of the world, but this important observation has not been sufficiently reported. We present the case of tonic status epilepticus in an 8-year-old boy with Doose syndrome related to valproic acid. Valproic acid, such as others antiepileptic drugs, is liable to produce paradoxical effects such as the atypical seizures we report. We emphasize the importance for the management of acute seizures in an intensive care unit setting and increase awareness of the acute toxic effects of antiepileptic drugs. Georg Thieme Verlag KG Stuttgart · New York.

Bayesian adaptive trials offer advantages in comparative effectiveness trials: an example in status epilepticus.

PubMed

Connor, Jason T; Elm, Jordan J; Broglio, Kristine R

2013-08-01

We present a novel Bayesian adaptive comparative effectiveness trial comparing three treatments for status epilepticus that uses adaptive randomization with potential early stopping. The trial will enroll 720 unique patients in emergency departments and uses a Bayesian adaptive design. The trial design is compared to a trial without adaptive randomization and produces an efficient trial in which a higher proportion of patients are likely to be randomized to the most effective treatment arm while generally using fewer total patients and offers higher power than an analogous trial with fixed randomization when identifying a superior treatment. When one treatment is superior to the other two, the trial design provides better patient care, higher power, and a lower expected sample size. Copyright © 2013 Elsevier Inc. All rights reserved.

Treatment of Focal Status Epilepticus plus Epileptic Spasms with Leukotomy in an Infant with TSC 1 Mutation: A Case Study.

PubMed

Park, Jun T; Shahid, Asim M; Miller, Jonathan P; Lüders, Hans O

2015-12-01

Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy. We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives. Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10-20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip. The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue. We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.

Age dependent mortality in the pilocarpine model of status epilepticus

PubMed Central

Blair, Robert E.; Deshpande, Laxmikant S.; Holbert, William H.; Churn, Severn B.; DeLorenzo, Robert J.

2010-01-01

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death. PMID:19429042

Age-dependent mortality in the pilocarpine model of status epilepticus.

PubMed

Blair, Robert E; Deshpande, Laxmikant S; Holbert, William H; Churn, Severn B; DeLorenzo, Robert J

2009-04-10

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 and 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week-old animals, mortality due to SE increased progressively with age and reached 90% in 28-week-old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.

Utility of Lumbar Puncture in Children Presenting With Status Epilepticus.

PubMed

Michelson, Kenneth A; Lyons, Todd W; Johnson, Kara B; Nigrovic, Lise E; Harper, Marvin B; Kimia, Amir A

2017-08-01

Because meningitis may trigger seizures, we sought to determine its frequency in children with first-time status epilepticus (SE). We performed a retrospective cross-sectional study of children aged 1 month to 21 years who presented to a single pediatric emergency department between 1995 and 2012 with SE and who had a lumbar puncture (LP) performed as part of the diagnostic evaluation. We defined bacterial meningitis as a cerebrospinal fluid (CSF) culture positive for a bacterial pathogen or CSF pleocytosis (CSF white blood cells ≥10 cells/mm) with a blood culture positive for a bacterial pathogen. We defined viral meningitis or encephalitis using a positive enterovirus or herpes simplex virus polymerase chain reaction test. Among 126 children with SE who had an LP performed, 8 (6%) had CSF pleocytosis. Of these, 5 had received antibiotics before performance of a diagnostic LP. One child in the cohort was proven to have bacterial meningitis (0.8%; 95% confidence interval [CI], 0%-6%). Two other children had enteroviral meningitis (2/13 tested, 15%; 95% CI, 3%-51%), and 1 had a herpes simplex virus infection (1/47, 2%; 95% CI, 0%-15%). Bacterial meningitis is an uncommon cause of SE.

A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus.

PubMed

Kurz, Jonathan E; Moore, Bryan J; Henderson, Scott C; Campbell, John N; Churn, Severn B

2008-10-01

Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE); however, the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN-dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE. SE was induced by pilocarpine injection, and seizure activity was monitored by video-EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a paranitrophenol phosphate (pNPP) assay protocol. Cofilin phosphorylation was assessed using phosphocofilin-specific antibodies. Cofilin-actin binding was determined by coimmunoprecipitation, and actin polymerization was measured using a triton-solubilization protocol. Spines were visualized using a single-section rapid Golgi impregnation procedure. The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE-induced cofilin dephosphorylation could be partially blocked by the preinjection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin-cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN-dependent loss of dendritic spines histologically. The data demonstrate a CaN-dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms.

Role of lidocaine (lignocaine) in managing status epilepticus.

PubMed

Pascual, J; Ciudad, J; Berciano, J

1992-01-01

Lidocaine (lignocaine) was given in 42 episodes of status epilepticus (SE) in 36 patients either because of limited pulmonary reserve (22 patients) or because of lack of response to diazepam (14 patients). Lidocaine (1.5-2 mg/kg) was given intravenously in two minutes. A further identical bolus was infused if no response had occurred or if seizures recurred. With the first bolus 11 episodes of SE did not stop, but 31 responded, always in less than one minute. In 19 episodes, however, this response lasted less than 30 minutes. Twelve episodes did not recur, but 30 needed a second bolus because of recurrence. Of these, 19 episodes responded at once but SE reappeared in seven. In these seven episodes the mean control time with the second dose was 102 minutes. Five of these subsequently responded to a continuous infusion of lidocaine. Eleven patients, who had not responded to the first bolus, had no response to the second. Lidocaine is a drug that may be epileptogenic at high doses. At the doses used here, however, lidocaine seems to be a rapid acting anticonvulsant, useful in the short term management of SE and may be indicated in patients in whom respiratory or consciousness depression is undesirable and in those with no response to diazepam. The absence of response to lidocaine indicates SE resistant to treatment and poor prognosis. These data show that prompt lidocaine administration may be worthwhile when management of respiratory depression is not possible.

Role of lidocaine (lignocaine) in managing status epilepticus.

PubMed Central

Pascual, J; Ciudad, J; Berciano, J

1992-01-01

Lidocaine (lignocaine) was given in 42 episodes of status epilepticus (SE) in 36 patients either because of limited pulmonary reserve (22 patients) or because of lack of response to diazepam (14 patients). Lidocaine (1.5-2 mg/kg) was given intravenously in two minutes. A further identical bolus was infused if no response had occurred or if seizures recurred. With the first bolus 11 episodes of SE did not stop, but 31 responded, always in less than one minute. In 19 episodes, however, this response lasted less than 30 minutes. Twelve episodes did not recur, but 30 needed a second bolus because of recurrence. Of these, 19 episodes responded at once but SE reappeared in seven. In these seven episodes the mean control time with the second dose was 102 minutes. Five of these subsequently responded to a continuous infusion of lidocaine. Eleven patients, who had not responded to the first bolus, had no response to the second. Lidocaine is a drug that may be epileptogenic at high doses. At the doses used here, however, lidocaine seems to be a rapid acting anticonvulsant, useful in the short term management of SE and may be indicated in patients in whom respiratory or consciousness depression is undesirable and in those with no response to diazepam. The absence of response to lidocaine indicates SE resistant to treatment and poor prognosis. These data show that prompt lidocaine administration may be worthwhile when management of respiratory depression is not possible. PMID:1548499

Treatment of Refractory and Super-refractory Status Epilepticus.

PubMed

Rai, Samhitha; Drislane, Frank W

2018-06-19

Refractory and super-refractory status epilepticus (SE) are serious illnesses with a high risk of morbidity and even fatality. In the setting of refractory generalized convulsive SE (GCSE), there is ample justification to use continuous infusions of highly sedating medications-usually midazolam, pentobarbital, or propofol. Each of these medications has advantages and disadvantages, and the particulars of their use remain controversial. Continuous EEG monitoring is crucial in guiding the management of these critically ill patients: in diagnosis, in detecting relapse, and in adjusting medications. Forms of SE other than GCSE (and its continuation in a "subtle" or nonconvulsive form) should usually be treated far less aggressively, often with nonsedating anti-seizure drugs (ASDs). Management of "non-classic" NCSE in ICUs is very complicated and controversial, and some cases may require aggressive treatment. One of the largest problems in refractory SE (RSE) treatment is withdrawing coma-inducing drugs, as the prolonged ICU courses they prompt often lead to additional complications. In drug withdrawal after control of convulsive SE, nonsedating ASDs can assist; medical management is crucial; and some brief seizures may have to be tolerated. For the most refractory of cases, immunotherapy, ketamine, ketogenic diet, and focal surgery are among several newer or less standard treatments that can be considered. The morbidity and mortality of RSE is substantial, but many patients survive and even return to normal function, so RSE should be treated promptly and as aggressively as the individual patient and type of SE indicate.

Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus

PubMed Central

Naylor, David E.; Liu, Hantao; Niquet, Jerome; Wasterlain, Claude G.

2017-01-01

After 1 h of lithium-pilocarpine status epilepticus (SE), immunocytochemical labeling of NMDA receptor NR1 subunits reveals relocation of subunits from the interior to the cell surface of dentate gyrus granule cells and CA3 pyramidal cells. Simultaneously, an increase in NMDA-miniature excitatory postsynaptic currents (mEPSC) as well as an increase in NMDA receptor-mediated tonic currents is observed in hippocampal slices after SE. Mean-variance analysis of NMDA-mEPSCs estimates that the number of functional postsynaptic NMDA receptors per synapse increases 38% during SE, and antagonism by ifenprodil suggests that an increase in the surface representation of NR2B-containing NMDA receptors is responsible for the augmentation of both the phasic and tonic excitatory currents with SE. These results provide a potential mechanism for an enhancement of glutamatergic excitation that maintains SE and may contribute to excitotoxic injury during SE. Therapies that directly antagonize NMDA receptors may be a useful therapeutic strategy during refractory SE. PMID:23313318

Non-convulsive status epilepticus and consciousness disturbance after star fruit (Averrhoa carambola) ingestion in a dialysis patient.

PubMed

Chang, Chung-Hsin; Yeh, Jiann-Horng

2004-12-01

Star fruit ingestion may induce severe neurological complications in chronic renal failure patients. We present a case on maintenance dialysis therapy who developed a consciousness disturbance without convulsion after eating star fruit. The symptoms became aggravated after haemodialysis. The brain computed tomography scan showed no abnormal findings, but the electroencephalogram found active focal sharp waves in the left central regions and diffusion-weighted magnetic resonance imaging also showed hyperintense lesions in the left central regions that were compatible with non-convulsive status epilepticus. His condition improved dramatically after anticonvulsant therapy and regular haemodialysis. The patient was discharged 20 days later without neurological sequela.

Intentional intra-arterial injection of midazolam in a patient with status epilepticus in the Intensive Care Unit

PubMed Central

Ali, Muhammad Asghar; Yahya, Muhammad

2017-01-01

Fundamental medical care includes intravenous (IV) access which provides prompt resuscitation and reliable delivery of analgesics, antibiotics, and vasoactive medication. Difficult access populations, especially in critical area, continue to challenge providers to consider and utilize alternative means to provide IV access. Potential options under such circumstances include intramuscular, intraosseous, and intratracheal drug administration, but in extreme cases where no other options are available, intra-arterial route might be considered. We present a case where midazolam was intentionally injected intra-arterially to abort seizure activity in a patient with status epilepticus in the Intensive Care Unit. PMID:29033730

Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus.

PubMed

Arya, Ravindra; Peariso, Katrina; Gaínza-Lein, Marina; Harvey, Jessica; Bergin, Ann; Brenton, J Nicholas; Burrows, Brian T; Glauser, Tracy; Goodkin, Howard P; Lai, Yi-Chen; Mikati, Mohamad A; Fernández, Iván Sánchez; Tchapyjnikov, Dmitry; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2018-04-27

To describe the efficacy and safety of ketogenic diet (KD) for convulsive refractory status epilepticus (RSE). RSE patients treated with KD at the 6/11 participating institutions of the pediatric Status Epilepticus Research Group from January-2011 to December-2016 were included. Patients receiving KD prior to the index RSE episode were excluded. RSE was defined as failure of ≥2 anti-seizure medications, including at least one non-benzodiazepine drug. Ketosis was defined as serum beta-hydroxybutyrate levels >20 mg/dl (1.9 mmol/l). Outcomes included proportion of patients with electrographic (EEG) seizure resolution within 7 days of starting KD, defined as absence of seizures and ≥50% suppression below 10 μV on longitudinal bipolar montage (suppression-burst ratio ≥50%); time to start KD after onset of RSE; time to achieve ketosis after starting KD; and the proportion of patients weaned off continuous infusions 2 weeks after KD initiation. Treatment-emergent adverse effects (TEAEs) were also recorded. Fourteen patients received KD for treatment of RSE (median age 4.7 years, interquartile range [IQR] 5.6). KD was started via enteral route in 11/14 (78.6%) patients. KD was initiated a median of 13 days (IQR 12.5) after the onset of RSE, at 4:1 ratio in 8/14 (57.1%) patients. Ketosis was achieved within a median of 2 days (IQR 2.0) after starting KD. EEG seizure resolution was achieved within 7 days of starting KD in 10/14 (71.4%) patients. Also, 11/14 (78.6%) patients were weaned off their continuous infusions within 2 weeks of starting KD. TEAEs, potentially attributable to KD, occurred in 3/14 (21.4%) patients, including gastro-intestinal paresis and hypertriglyceridemia. Three month outcomes were available for 12/14 (85.7%) patients, with 4 patients being seizure-free, and 3 others with decreased seizure frequency compared to pre-RSE baseline. This series suggests efficacy and safety of KD for treatment of pediatric RSE. Copyright © 2018

Acquisition and retrieval of conditioned taste aversion is impaired by brain damage caused by two hours of pilocarpine-induced status epilepticus.

PubMed

Sroubek, J; Hort, J; Komárek, V; Langmeier, M; Brozek, G

2001-01-01

The effect of Cavalheiro's pilocarpine model of epileptogenesis upon conditioned taste aversion (CTA), an important example of nondeclarative memory, was studied in adult Long Evans rats. Deterioration of CTA was studied during the silent period between pilocarpine-induced status epilepticus (SE) and delayed spontaneous recurrent seizures. SE was elicited by i.p. injection of pilocarpine (320 mg/kg ) and interrupted after 2 hours by clonazepame (1 mg/kg i.p.). Peripheral cholinergic symptoms were suppressed by methylscopolamine (1 mg/kg i.p.), administered together with pilocarpine. CTA was formed against the salty taste of isotonic LiCl. In the experiment of CTA acquisition, the CTA was formed and tested during the silent period after SE. In the experiment of CTA retrieval, the CTA was acquired before SE and the retrieval itself was tested during the silent period. Retrieval of CTA acquired before SE was impaired more than the retrieval of CTA formed during the silent period. Our findings indicate that epileptic seizures can disrupt even non-declarative memory but that CTA formed by the damaged brain can use its better preserved parts for memory trace formation. Ketamine (50 mg/kg i.p.) applied 2 min after the onset of pilocarpine-induced status epilepticus protected memory deterioration.

Status epilepticus associated with acute encephalitis: long-term follow-up of functional and cognitive outcomes in 72 patients.

PubMed

Chen, Weibi; Su, Yingying; Jiang, Mengdi; Liu, Gang; Tian, Fei; Ren, Guoping

2018-05-11

Continued care in patients with encephalitis and prolonged status epilepticus (SE) is controversial. Limited data is available on the functional and cognitive outcomes. In a prospective cohort study from 2007 to 2016, patients with acute encephalitis and SE were reviewed. Long-term outcomes including motor disability (modified Rankin Scale, mRS), daily living skills (activities of daily living, ADL), cognitive ability (modified Telephone Interview for Cognitive Status, TICS-M) and epilepsy sequelae, were evaluated in those survivors at 12-month follow-up. At the 12-month follow-up, 72 patients were recruited, who got a median score of 14 on the total ADL. 68% patients remained independent in their daily activities (mRS≤2). Post-SE symptomatic epilepsy was observed in 49% patients. 62 patients achieved a median score of 40 on the TICS-M and 14 on the TICS-M memory. Patients with autoimmune encephalitis were less prone to post-SE symptomatic epilepsy (18% vs. 58%, P=0.005) but lower TICS-M memory score than those with viral encephalitis (8.5 vs. 15, P=0.017). Compared to non-refractory status epilepticus (RSE), patients with RSE had a longer stay in NCU (39 vs. 26, P=0.002), more in-hospital complications and post-SE symptomatic epilepsy (67% vs. 33%, P=0.005). Long-term outcomes including ADL, mRS, and TICS-M were not significantly different between patients with RSE and non-RSE or between patients with long (≥4h) and short duration (<4h) of SE. Survival with favorable functional recovery was promising after prolonged RSE in patients with acute encephalitis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Factors associated with occurrence and outcome of super-refractory status epilepticus.

PubMed

Madžar, Dominik; Knappe, Ruben U; Reindl, Caroline; Giede-Jeppe, Antje; Sprügel, Maximilian I; Beuscher, Vanessa; Gollwitzer, Stephanie; Hamer, Hajo M; Huttner, Hagen B

2017-11-01

Super-refractory status epilepticus (SRSE) represents a challenging medical condition with high morbidity and mortality. In this study, we aimed to establish variables related to SRSE development and outcome. We retrospectively screened our databases for refractory SE (RSE) and SRSE episodes between January 2001 and January 2015. Baseline demographics, SE characteristics, and variables reflecting the clinical course were compared in order to identify factors independently associated with SRSE occurrence. Within the SRSE cohort, predictors of in-hospital mortality as well as good functional outcome in survivors to discharge were established through univariate and multivariable analyses. A total of 131 episodes were included, among those 46 (35.1%) meeting the criteria of SRSE. Comparison of RSE and SRSE episodes revealed a lower premorbid mRS score (odds ratio (OR) per mRS point, 0.769; p=0.039) and non-convulsive SE (NCSE) in coma (OR, 4.216; p=0.008) as independent predictors of SRSE. SRSE in-hospital mortality was associated with age (OR, 1.091 per increasing year; p=0.020) and worse premorbid functional status (OR, 1.938 per mRS point; p=0.044). Good functional outcome in survivors was independently related to shorter SRSE duration (OR, 0.714 per day; p=0.038). Better premorbid functional status and NCSE in coma as worst seizure type indicate a role of acute underlying etiologies in the development of SRSE. In-hospital mortality in SRSE is determined by nonmodifiable factors, while functional outcome in survivors depends on seizure duration underscoring the need of achieving rapid seizure termination. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Refractory and severe status epilepticus in a patient with ring chromosome 20 syndrome.

PubMed

Hirano, Yoshiko; Oguni, Hirokazu; Nagata, Satoru

2016-09-01

Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder that is characterized by the development of refractory epilepsy during childhood with gradual declines in cognitive performance and behavior. Although the prognoses of seizures and intellectual disability associated with this condition are poor, life-threatening complications have rarely been described. We herein presented a case of a 17-year-old female with [r(20)] syndrome who developed recurrent status epilepticus (SE) at 14years of age that evolved into unremitting SE in spite of vigorous antiepileptic treatments. She was administered thiopental anesthesia for 1year, and was subsequently left in severe neurological sequelae. It is important to note that patients with this syndrome not only have severe epileptic encephalopathy persisting into adulthood, but are also at risk of fatal SE. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application

PubMed Central

Vezzani, Annamaria; Dingledine, Raymond; Rossetti, Andrea O

2016-01-01

Status epilepticus (SE) is a life-threatening neurological emergency often refractory to available treatment options. It is a very heterogeneous condition in terms of clinical presentation and causes, which besides genetic, vascular and other structural causes also include CNS or severe systemic infections, sudden withdrawal from benzodiazepines or anticonvulsants and rare autoimmune etiologies. Treatment of SE is essentially based on expert opinions and antiepileptic drug treatment per se seems to have no major impact on prognosis. There is, therefore, urgent need of novel therapies that rely upon a better understanding of the basic mechanisms underlying this clinical condition. Accumulating evidence in animal models highlights that inflammation ensuing in the brain during SE may play a determinant role in ongoing seizures and their long-term detrimental consequences, independent of an infection or auto-immune cause; this evidence encourages reconsideration of the treatment flow in SE patients. PMID:26312647

Self-induced drug intoxication in baclofen: of the calm hypotonic coma in the status epilepticus.

PubMed

Thill, Chloé; Di Constanzo, Laurence; Pessey, François; Aries, Philippe; Montelescaut, Étienne; Sapin, Jeanne; Vaillant, Catherine; Drouillard, Isabelle

2016-06-01

Baclofen is an agonist of peripheral and central B gamma-aminobutyric acid receptors, whose activation causes a myorelaxation and a powerfull depression of the central nervous system. Moreover, it has an action against addiction, in reducing craving. Commercialized since 1975 in France, to control muscle spasticity due to medullar affection or multiple sclerosis, it receives a temporary recommendation of use in march 2014, as a last-line adjuvant treatment in alcohol withdrawal. Beyond its therapeutic use, baclofen is involved in many self-induced intoxications. We report the case of a patient who develops, after a massive ingestion of baclofen (supposed dose ingested: 1 200 mg), a hypotonic and calm coma, requiring her admission in our intensive care unit, and then a status epilepticus.

Mitogen- and Stress-Activated Protein Kinase 1 Regulates Status Epilepticus-Evoked Cell Death in the Hippocampus

PubMed Central

Choi, Yun-Sik; Horning, Paul; Aten, Sydney; Karelina, Kate; Alzate-Correa, Diego; Arthur, J. Simon C.; Hoyt, Kari R.; Obrietan, Karl

2017-01-01

Mitogen-activated protein kinase (MAPK) signaling has been implicated in a wide range of neuronal processes, including development, plasticity, and viability. One of the principal downstream targets of both the extracellular signal-regulated kinase/MAPK pathway and the p38 MAPK pathway is Mitogen- and Stress-activated protein Kinase 1 (MSK1). Here, we sought to understand the role that MSK1 plays in neuroprotection against excitotoxic stimulation in the hippocampus. To this end, we utilized immunohistochemical labeling, a MSK1 null mouse line, cell viability assays, and array-based profiling approaches. Initially, we show that MSK1 is broadly expressed within the major neuronal cell layers of the hippocampus and that status epilepticus drives acute induction of MSK1 activation. In response to the status epilepticus paradigm, MSK1 KO mice exhibited a striking increase in vulnerability to pilocarpine-evoked cell death within the CA1 and CA3 cell layers. Further, cultured MSK1 null neurons exhibited a heighted level of N-methyl-D-aspartate-evoked excitotoxicity relative to wild-type neurons, as assessed using the lactate dehydrogenase assay. Given these findings, we examined the hippocampal transcriptional profile of MSK1 null mice. Affymetrix array profiling revealed that MSK1 deletion led to the significant (>1.25-fold) downregulation of 130 genes and an upregulation of 145 genes. Notably, functional analysis indicated that a subset of these genes contribute to neuroprotective signaling networks. Together, these data provide important new insights into the mechanism by which the MAPK/MSK1 signaling cassette confers neuroprotection against excitotoxic insults. Approaches designed to upregulate or mimic the functional effects of MSK1 may prove beneficial against an array of degenerative processes resulting from excitotoxic insults. PMID:28870089

Anesthetic drugs in status epilepticus: Risk or rescue?

PubMed Central

Marsch, Stephan; Fuhr, Peter; Kaplan, Peter W.; Rüegg, Stephan

2014-01-01

Objective: To evaluate the risks of continuously administered IV anesthetic drugs (IVADs) on the outcome of adult patients with status epilepticus (SE). Methods: All intensive care unit patients with SE from 2005 to 2011 at a tertiary academic medical care center were included. Relative risks were calculated for the primary outcome measures of seizure control, Glasgow Outcome Scale score at discharge, and death. Poisson regression models were used to control for possible confounders and to assess effect modification. Results: Of 171 patients, 37% were treated with IVADs. Mortality was 18%. Patients with anesthetic drugs had more infections during SE (43% vs 11%; p < 0.0001) and a 2.9-fold relative risk for death (2.88; 95% confidence interval 1.45–5.73), independent of possible confounders (i.e., duration and severity of SE, nonanesthetic third-line antiepileptic drugs, and critical medical conditions) and without significant effect modification by different grades of SE severity and etiologies. As IVADs were used after first- and second-line drugs failed, there was a correlation between treatment-refractory SE and the use of IVADs, leading to insignificant results regarding the risk of IVADs and outcome after additional adjustment for refractory SE. Conclusion: Our findings heighten awareness regarding adverse effects of IVADs. Randomized controlled trials are needed to further clarify the association of IVADs with outcome in patients with SE. Classification of evidence: This study provides Class III evidence that patients with SE receiving IVADs have a higher proportion of infection and an increased risk of death as compared to patients not receiving IVADs. PMID:24319039

Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat.

PubMed

Singleton, Michael W; Holbert, William H; Ryan, Matthew L; Lee, Anh Tuyet; Kurz, Jonathan E; Churn, Severn B

2005-04-21

This study was conducted to characterize the post-pubertal developmental aspects on seizure susceptibility and severity as well as calcium/calmodulin protein kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to ninety-day-old rats, in 10-day increments, were studied. This corresponds to a developmental age group that has not received thorough attention. The pilocarpine model of SE was characterized both behaviorally and electrographically. Seven criteria were analyzed for electrographical characterization: seizure severity, SE susceptibility, the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death. After 1 h of SE, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. There was no developmental effect on the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death; however, there was a significant effect on SE probability and seizure severity. Once SE was expressed, all animals showed a decrease in both cortical and hippocampal CaM kinase II activities. Conversely, seizure activity in the absence of SE did not result in a decrease in CaM kinase II activity. The data suggest that there is a gradual age-dependent modulation of SE susceptibility and seizure severity within the developmental stages studied. Additionally, once status epilepticus is observed at any age, there is a corresponding SE-induced inhibition of CaM kinase II.

Decreased allopregnanolone levels in cerebrospinal fluid obtained during status epilepticus.

PubMed

Meletti, Stefano; Lucchi, Chiara; Monti, Giulia; Giovannini, Giada; Bedin, Roberta; Trenti, Tommaso; Rustichelli, Cecilia; Biagini, Giuseppe

2017-02-01

Neuroactive steroids are increasingly considered as relevant modulators of neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS) have been shown to possess, respectively, anticonvulsant or proconvulsant properties. In view of the potential role of these steroids, we aimed at evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples obtained from patients with status epilepticus (SE). To this purpose, we enrolled 41 patients affected by SE and 41 subjects investigated for nonepileptic neurologic disorders. Liquid chromatographic procedures coupled with electrospray tandem mass spectrometry and routine laboratory investigations were performed. Significantly lower AP levels were found in the CSF of patients affected by SE (-30%; p < 0.05, Mann-Whitney test). Notably, AP was not detectable in 28 of 41 patients affected by SE (p < 0.01 vs. controls, Fisher's exact test). In serum, AP levels did not differ in the two considered groups. Conversely, PS was present at similar levels in the investigated groups. Finally, differences in AP levels could not be explained by a variation in CSF albumin content. These findings indicate that AP is defective in the CSF of patients affected by SE. This phenomenon was not dependent on carriers for steroids, such as albumin. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

A Cellular Mechanism for Dendritic Spine Loss in the Pilocarpine Model of Status Epilepticus

PubMed Central

Kurz, Jonathan E.; Moore, Bryan J.; Henderson, Scott; Campbell, John N.; Churn, Severn B.

2013-01-01

Purpose Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE), however the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN-dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE. Methods SE was induced by pilocarpine injection, and seizure activity was monitored by video-EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a para-nitrophenol phosphate assay protocol. Cofilin phosphorylation was assessed using phosphocofilin-specific antibodies. Cofilin-actin binding was determined by co-immunoprecipitation, and actin polymerization was measured using a triton-solubilization protocol. Spines were visualized using a single-section rapid Golgi impregnation procedure. Results The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE-induced cofilin dephosphorylation could be partially blocked by the pre-injection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin-cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN-dependent loss of dendritic spines histologically. Discussion The data demonstrate a CaN-dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms. PMID:18479390

Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus.

PubMed

Naylor, David E; Liu, Hantao; Niquet, Jerome; Wasterlain, Claude G

2013-06-01

After 1h of lithium-pilocarpine status epilepticus (SE), immunocytochemical labeling of NMDA receptor NR1 subunits reveals relocation of subunits from the interior to the cell surface of dentate gyrus granule cells and CA3 pyramidal cells. Simultaneously, an increase in NMDA-miniature excitatory postsynaptic currents (mEPSC) as well as an increase in NMDA receptor-mediated tonic currents is observed in hippocampal slices after SE. Mean-variance analysis of NMDA-mEPSCs estimates that the number of functional postsynaptic NMDA receptors per synapse increases 38% during SE, and antagonism by ifenprodil suggests that an increase in the surface representation of NR2B-containing NMDA receptors is responsible for the augmentation of both the phasic and tonic excitatory currents with SE. These results provide a potential mechanism for an enhancement of glutamatergic excitation that maintains SE and may contribute to excitotoxic injury during SE. Therapies that directly antagonize NMDA receptors may be a useful therapeutic strategy during refractory SE. Copyright © 2013 Elsevier Inc. All rights reserved.

Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis.

PubMed

Jaques, Léonore; Rossetti, Andrea O

2012-05-01

Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory. Copyright © 2012 Elsevier Inc. All rights reserved.

Lacosamide in status epilepticus: Systematic review of current evidence.

PubMed

Strzelczyk, Adam; Zöllner, Johann Philipp; Willems, Laurent M; Jost, Julie; Paule, Esther; Schubert-Bast, Susanne; Rosenow, Felix; Bauer, Sebastian

2017-06-01

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. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

PubMed

Sutter, R; Semmlack, S; Spiegel, R; Tisljar, K; Rüegg, S; Marsch, S

2017-09-01

The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE. © 2017 EAN.

Challenges in the treatment of convulsive status epilepticus.

PubMed

Zaccara, Gaetano; Giannasi, Gianfranco; Oggioni, Roberto; Rosati, Eleonora; Tramacere, Luciana; Palumbo, Pasquale

2017-04-01

Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts. Copyright © 2017. Published by Elsevier Ltd.

Pilocarpine-Induced Status Epilepticus Increases the Sensitivity of P2X7 and P2Y1 Receptors to Nucleotides at Neural Progenitor Cells of the Juvenile Rodent Hippocampus.

PubMed

Rozmer, Katalin; Gao, Po; Araújo, Michelle G L; Khan, Muhammad Tahir; Liu, Juan; Rong, Weifang; Tang, Yong; Franke, Heike; Krügel, Ute; Fernandes, Maria José S; Illes, Peter

2017-07-01

Patch-clamp recordings indicated the presence of P2X7 receptors at neural progenitor cells (NPCs) in the subgranular zone of the dentate gyrus in hippocampal brain slices prepared from transgenic nestin reporter mice. The activation of these receptors caused inward current near the resting membrane potential of the NPCs, while P2Y1 receptor activation initiated outward current near the reversal potential of the P2X7 receptor current. Both receptors were identified by biophysical/pharmacological methods. When the brain slices were prepared from mice which underwent a pilocarpine-induced status epilepticus or when brain slices were incubated in pilocarpine-containing external medium, the sensitivity of P2X7 and P2Y1 receptors was invariably increased. Confocal microscopy confirmed the localization of P2X7 and P2Y1 receptor-immunopositivity at nestin-positive NPCs. A one-time status epilepticus in rats caused after a latency of about 5 days recurrent epileptic fits. The blockade of central P2X7 receptors increased the number of seizures and their severity. It is hypothesized that P2Y1 receptors after a status epilepticus may increase the ATP-induced proliferation/ectopic migration of NPCs; the P2X7 receptor-mediated necrosis/apoptosis might counteract these effects, which would otherwise lead to a chronic manifestation of recurrent epileptic fits. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spatiotemporal characterization of mTOR kinase activity following kainic acid induced status epilepticus and analysis of rat brain response to chronic rapamycin treatment.

PubMed

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain.

Spatiotemporal Characterization of mTOR Kinase Activity Following Kainic Acid Induced Status Epilepticus and Analysis of Rat Brain Response to Chronic Rapamycin Treatment

PubMed Central

Macias, Matylda; Blazejczyk, Magdalena; Kazmierska, Paulina; Caban, Bartosz; Skalecka, Agnieszka; Tarkowski, Bartosz; Rodo, Anna; Konopacki, Jan; Jaworski, Jacek

2013-01-01

Mammalian target of rapamycin (mTOR) is a protein kinase that senses nutrient availability, trophic factors support, cellular energy level, cellular stress, and neurotransmitters and adjusts cellular metabolism accordingly. Adequate mTOR activity is needed for development as well as proper physiology of mature neurons. Consequently, changes in mTOR activity are often observed in neuropathology. Recently, several groups reported that seizures increase mammalian target of rapamycin (mTOR) kinase activity, and such increased activity in genetic models can contribute to spontaneous seizures. However, the current knowledge about the spatiotemporal pattern of mTOR activation induced by proconvulsive agents is rather rudimentary. Also consequences of insufficient mTOR activity on a status epilepticus are poorly understood. Here, we systematically investigated these two issues. We showed that mTOR signaling was activated by kainic acid (KA)-induced status epilepticus through several brain areas, including the hippocampus and cortex as well as revealed two waves of mTOR activation: an early wave (2 h) that occurs in neurons and a late wave that predominantly occurs in astrocytes. Unexpectedly, we found that pretreatment with rapamycin, a potent mTOR inhibitor, gradually (i) sensitized animals to KA treatment and (ii) induced gross anatomical changes in the brain. PMID:23724051

Local cerebral glucose utilization during status epilepticus in newborn primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujikawa, D.G.; Dwyer, B.E.; Lake, R.R.

1989-06-01

The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-(/sup 14/C)-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc inmore » frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.« less

Nonconvulsive Status Epilepticus After Electroconvulsive Therapy: A Review of Literature.

PubMed

Aftab, Awais; VanDercar, Ashley; Alkhachroum, Ayham; LaGrotta, Christine; Gao, Keming

The clinical presentation and risk factors of nonconvulsive status epilepticus (NCSE) in the context of electroconvulsive therapy (ECT) are poorly understood, and guidance regarding diagnosis and management remains scarce. In this article, we identify case reports of ECT-induced NCSE from literature, and discuss the presentation, diagnosis, and management of these cases in the context of what is known about NCSE from the neurology literature. A literature search on PubMed for case reports of NCSE after ECT. We identified 13 cases for this review. Diagnosis in all cases was based on clinical features and electroencephalogram (EEG) findings. Clinical presentation was altered mental status or unresponsiveness, with subtle motor phenomena in some cases. All cases had nonspecific risk factors that have been associated with prolonged seizures and convulsions, such as recent discontinuation/reduction of benzodiazepines or anticonvulsants, and concurrent use of antipsychotics and antidepressants. All patients were treated with either benzodiazepines or antiepileptic agents. Outcomes in these post-ECT NCSE cases were generally favorable. Although rare, post-ECT NCSE should be kept in mind by physicians when confusion or unresponsiveness develops and continues after ECT; multilead EEG is gold standard for diagnosis. An intravenous (IV) antiepileptic drug (AED) challenge can help clarify the diagnosis. Initial treatment is recommended with IV benzodiazepines, with a repeat dose if necessary. If seizures persist, IV AEDs are warranted. NCSE refractory to this treatment should be treated with a scheduled IV or oral AED. Serial multilead EEGs should be used to monitor resolution of symptoms. NCSE after ECT is a rare but recognizable clinical event. A high clinical suspicion and low threshold for EEG is necessary for prompt diagnosis. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus☆

PubMed Central

Duffy, B.A.; Chun, K.P.; Ma, D.; Lythgoe, M.F.; Scott, R.C.

2014-01-01

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10 mg/kg or 2 mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2 mg/kg and 10 mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus. PMID:24333865

Infodemiology of status epilepticus: A systematic validation of the Google Trends-based search queries.

PubMed

Bragazzi, Nicola Luigi; Bacigaluppi, Susanna; Robba, Chiara; Nardone, Raffaele; Trinka, Eugen; Brigo, Francesco

2016-02-01

People increasingly use Google looking for health-related information. We previously demonstrated that in English-speaking countries most people use this search engine to obtain information on status epilepticus (SE) definition, types/subtypes, and treatment. Now, we aimed at providing a quantitative analysis of SE-related web queries. This analysis represents an advancement, with respect to what was already previously discussed, in that the Google Trends (GT) algorithm has been further refined and correlational analyses have been carried out to validate the GT-based query volumes. Google Trends-based SE-related query volumes were well correlated with information concerning causes and pharmacological and nonpharmacological treatments. Google Trends can provide both researchers and clinicians with data on realities and contexts that are generally overlooked and underexplored by classic epidemiology. In this way, GT can foster new epidemiological studies in the field and can complement traditional epidemiological tools. Copyright © 2015 Elsevier Inc. All rights reserved.

Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

PubMed Central

Wong-Goodrich, Sarah J. E.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

2008-01-01

Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a Control or SUP diet on embryonic days 12–17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function. PMID:18353663

Status epilepticus in the elderly patients: A national data study in Thailand.

PubMed

Tiamkao, Somsak; Pranboon, Sineenard; Thepsuthammarat, Kaewjai; Sawanyawisuth, Kittisak

2017-01-15

There are limited data in terms of incidence, clinical features, and outcomes in elderly patients with status epilepticus (SE) in national level. We retrospectively explored national data in Thailand for reimbursement of all SE in elderly patients admitted in the fiscal year 2004-2012. SE in elderly patients (age>60years old) were diagnosed and searched based on ICD 10 (G41) from the national database of from the National Health and Security Office. There were 3326 SE in elderly patients. The national incidence of SE was highest at 8.78patients/100,000/year in 2012. The average age was 72.02years and most were males (1379 patients; 58.8%). At discharge, 66% of patients had improved and in-hospital mortality rate was 14.5%. Predictors of poor outcomes were older age≥80years, being female, hospital levels, chronic renal failure, central nervous system infection, respiratory failure, pneumonia, septicemia, shock, acute renal failure, and hyperkalemia. In conclusion, the number of cases of SE in elderly patients in Thailand has been increasing annually. Increasing age was associated with poor outcome in admitted elderly SE patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Review article: Paediatric status epilepticus in the pre-hospital setting: An update.

PubMed

Furyk, Jeremy; Watt, Kerriane; Emeto, Theophilus I; Dalziel, Stuart; Bodnar, Daniel; Riney, Kate; Babl, Franz E

2017-08-01

Paediatric status epilepticus (SE) is a medical emergency and a common critical condition confronting pre-hospital providers. Management in the pre-hospital environment is challenging but considered extremely important as a potentially modifiable factor on outcome. Recent data from multicentre clinical trials, quality observational studies and consensus documents have influenced management in this area, and is important to both pre-hospital providers and emergency physicians. The objective of this review was to: (i) present an overview of the available evidence relevant to pre-hospital care of paediatric SE; and (ii) assess the current pre-hospital practice guidelines in Australia and New Zealand. The review outlines current definitions and guidelines of SE management, regional variability in pre-hospital protocols within Australasia and aspects of pre-hospital care that could potentially be improved. Contemporary data is required to determine current practice in our setting. It is important that paediatric neurologists, emergency physicians and pre-hospital care providers are all engaged in future endeavours to improve clinical care and knowledge translation efforts for this patient group. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model

PubMed Central

Sato, Satoru M; Woolley, Catherine S

2016-01-01

Status epilepticus (SE) is a common neurological emergency for which new treatments are needed. In vitro studies suggest a novel approach to controlling seizures in SE: acute inhibition of estrogen synthesis in the brain. Here, we show in rats that systemic administration of an aromatase (estrogen synthase) inhibitor after seizure onset strongly suppresses both electrographic and behavioral seizures induced by kainic acid (KA). We found that KA-induced SE stimulates synthesis of estradiol (E2) in the hippocampus, a brain region commonly involved in seizures and where E2 is known to acutely promote neural activity. Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE. DOI: http://dx.doi.org/10.7554/eLife.12917.001 PMID:27083045

The management of Convulsive Refractory Status Epilepticus in adults in the UK: No consistency in practice and little access to continuous EEG monitoring.

PubMed

Patel, Mitesh; Bagary, Manny; McCorry, Dougall

2015-01-01

Convulsive Status Epilepticus (CSE) is a common neurological emergency with patients presenting with prolonged epileptic activity. Sub-optimal management is coupled with high morbidity and mortality. Continuous electroencephalogram (EEG) monitoring is considered essential by the National Institute for Health and Care Excellence (NICE) in the management of Convulsive Refractory Status Epilepticus (CRSE). The aim of this research was to determine current clinical practice in the management of CRSE amongst adults in intensive care units (ICU) in the UK and establish if the use of a standardised protocol requires re-enforcement within trusts. 75 randomly selected UK NHS Trusts were contacted and asked to complete a questionnaire in addition to providing their protocol for CRSE management in ICU. 55 (73%) trusts responded. While 31 (56% of responders) had a protocol available in ICU for early stages of CSE, just 21 (38%) trusts had specific guidelines if CRSE occurred. Only 23 (42%) trusts involved neurologists at any stage of management and just 18 (33%) have access to continuous EEG monitoring. This study identifies significant inconsistency in the management of CSE in ICU's across the UK. A minority of ICU units have a protocol for CRSE or access to continuous EEG monitoring despite it being considered fundamental for management and supported by NICE guidance. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Long-term outcome of refractory status epilepticus in adults: A retrospective population-based study.

PubMed

Kantanen, Anne-Mari; Reinikainen, Matti; Parviainen, Ilkka; Kälviäinen, Reetta

2017-07-01

Refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality. We aimed to analyze the long-term outcome of intensive care unit (ICU)-treated RSE and super-refractory status epilepticus (SRSE) patients in a population based cohort. A retrospective study of ICU- and anesthesia-treated RSE patients in Kuopio University Hospital's (KUH) special responsibility area hospitals in the central and eastern part of Finland from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH's catchment area consists of five hospitals-one university hospital and four central hospitals-and covers a population of 840 000. We included all consecutive adult (16 years or older) RSE patients admitted in the participating ICUs during the 3-year period and excluded patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a long-term (1-year) outcome measure: good (mRS 0-3, recovered to baseline function) or poor (mRS 4-6, major functional deficit or death). We identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an annual incidence of 3.0 (95% confidence interval (CI) 2.4-3.8). 21% of the patients were classified as SRSE, with the annual incidence being 0.6/100 000 (95% CI 0.4-1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7% (95% CI 1.2%-12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%-32.5%) (n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed neurological deficit at 1year. Poor outcome (mRS 4-6) was recorded for 52% (n=39) of the patients. Older age was associated with poorer outcome at 1year (p=0.03). For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3) (95%CI 0%-38.2%). During 1-year follow-up, nearly 50% of the ICU-treated RSE patients recovered to baseline function, whereas 30% showed new functional defects and 20% died. SRSE does not have a necessarily poorer outcome. The outcome is worse in older patients and in patients with

Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany.

PubMed

Strzelczyk, Adam; Ansorge, Sonja; Hapfelmeier, Jana; Bonthapally, Vijayveer; Erder, M Haim; Rosenow, Felix

2017-09-01

Super-refractory status epilepticus (SRSE) is a severe condition in which a patient in status epilepticus (SE) for ≥24 h does not respond to first-, second-, or third-line therapy. The economic impact of SRSE treatment remains unclear. A health insurance research database was used for a population-based estimation of SRSE-associated inpatient costs, length of stay, and mortality in Germany. An algorithm using International Classification of Diseases, 10th Edition coding and treatment parameters identified and classified patients in a German statutory health insurance database covering admissions from 2008 to 2013 as having refractory SE (RSE) or SRSE. Admissions data in our study refer to these classifications. Associated patient data included costs, procedures, and demographics. The algorithm identified 2,585 (all type) SE admissions, classified as 1,655 nonrefractory SE (64%), 592 (22.9%) RSE, and 338 (13.1%) SRSE, producing database incidence rates of 15.0 in 100,000, 5.2 in 100,000, and 3.0 in 100,000 per year, respectively. Median cost per admission was €4,063 for nonrefractory SE, €4,581 (p < 0.001) for RSE, and €32,706 (p < 0.001) for SRSE. Median length of stay varied significantly between 8 days (mean = 13.6) in nonrefractory SE, 14 days in RSE, and up to 37 days in SRSE. Discharge mortality increased from 9.6% in nonrefractory SE to 15.0% (p < 0.001) in RSE and 39.9% (p < 0.001) in SRSE. This study evaluated the hospital treatment costs associated with admissions classified by the algorithm as SRSE in Germany. SRSE represented 13% of all SE admissions, but resulted in 56% of all SE-related costs. The lack of approved treatments and limited number of evidence-based treatment guidelines highlight the need for further evaluations of the SRSE burden of illness and the potential for further optimization of treatments for SRSE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China.

PubMed

Su, Yingying; Liu, Gang; Tian, Fei; Ren, Guoping; Jiang, Mengdi; Chun, Brian; Zhang, Yunzhou; Zhang, Yan; Ye, Hong; Gao, Daiquan; Chen, Weibi

2016-12-01

Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, evidence-based data to guide initial drug treatment choices are lacking in the Chinese population. We conducted this prospective, randomized, controlled trial to evaluate the relative efficacy and safety of intravenous phenobarbital and valproate in patients with GCSE. After the failure of first-line diazepam treatment, Chinese adult patients with GCSE were randomized to receive either intravenous phenobarbital (standard doses, low rate) or valproate (standard). Successful treatment was considered when clinical and electroencephalographic seizure activity ceased. Adverse events following treatment, as well as the neurological outcomes at discharge and 3 months later, were also evaluated. Overall, 73 cases were enrolled in the study. Intravenous phenobarbital was successful in 81.1% of patients, and intravenous valproate was successful in 44.4% of patients (p < 0.05). The relapse rate of status epilepticus within 24 h of receiving phenobarbital (6.7%) was significantly lower than that in patients receiving valproate (31.3%), and the total number of adverse events did not differ significantly between the two groups (p > 0.05). In the phenobarbital group, two patients (5.4%) required ventilation and two patients (5.4%) developed serious hypotension. The neurological outcomes of the phenobarbital group were generally better than those of the valproate group; however, no significant differences were observed between phenobarbital and valproate with respect to mortality (8.1 vs. 16.6%) at discharge, or mortality (16.2 vs. 30.5%) and post-symptomatic epilepsy (26.3 vs. 42.8%) at 3-month follow-up. Intravenous phenobarbital appears to be more effective than intravenous valproate for Chinese adult patients with GCSE. The occurrence of serious respiratory depression and hypotension caused by phenobarbital was reduced by decreasing the intravenous infusion rate; however, even at a

Convulsive status epilepticus in a quaternary hospital paediatric intensive care unit (PICU) in South Africa: An 8 year review.

PubMed

Reddy, Yavini; Balakrishna, Yusentha; Mubaiwa, Lawrence

2017-10-01

Convulsive status epilepticus (CSE) is associated with a high morbidity and mortality. This study aimed to describe the clinical profile, aetiology, neuroimaging and EEG findings as well as outcome of children with CSE in Sub-Saharan Africa. This was a retrospective analysis of electronic records of children with CSE admitted to the Paediatric Intensive Care Unit (PICU) over an 8-year period from January 2007 to December 2014. Seventy six patients were admitted to the PICU with CSE and 55(72%) had refractory status epilepticus. The median age at presentation was 15 months (IQR 6-37 months). The main aetiologies were meningoencephalitis and gastroenteritis in 33(43%) and 19(25%) patients respectively. The most frequently used antiepileptic drugs for CSE in PICU consisted of infusions of midazolam (96%) and thiopentone (22%). Neuroimaging findings were abnormal in 53(75%) patients with hypoxic changes in 17 patients. On multivariable regression, the predictors of poor outcome included the use of more than 3 antiepileptic drugs in PICU(RR-1.41(1.12-1.78), p=0.003), duration of mechanical ventilation for more than 3days (RR 1.98(1.22-3.20), p=0.005) and abnormal neuroimaging findings (RR 3.21(1.53-6.72), p=0.002). The mortality rate was 24%(n=18). Persistent seizures or a new neurological deficit occurred in 58%(n=44). The main cause of mortality was CSE related diffuse cortical and brainstem injury. Predominant neurological sequelae were cerebral palsy and persistent epilepsy. The high burden of infection related CSE is associated with high morbidity and mortality rates in contrast to the rates in developed countries. This highlights the need for early recognition and treatment of underlying conditions. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Neonatal status epilepticus alters prefrontal-striatal circuitry and enhances methamphetamine-induced behavioral sensitization in adolescence.

PubMed

Lin, Tzu-Chao; Huang, Li-Tung; Huang, Ya-Ni; Chen, Gunng-Shinng; Wang, Jia-Yi

2009-02-01

Neonatal seizures may alter the developing neurocircuitry and cause behavioral abnormalities in adulthood. We found that rats previously subjected to lithium-pilocarpine (LiPC)-induced neonatal status epilepticus (NeoSE) exhibited enhanced behavioral sensitization to methamphetamine (MA) in adolescence. Neurochemically, dopamine (DA) and metabolites were markedly decreased in prefrontal cortex (PFC) and insignificantly changed in striatum by NeoSE, but were increased in both PFC and striatum by NeoSE+MA. Glutamate levels were increased in both PFC and striatum in the NeoSE+MA group. DA turnover, an index of utilization and activity, was increased by NeoSE but reversed by MA in PFC. Gene expression of the regulator of G-protein signaling 4 (RGS4) was downregulated in PFC and striatum by NeoSE and further suppressed by MA. These findings suggest NeoSE affects both dopaminergic and glutamatergic systems in the prefrontal-striatal circuitry that manifests as enhanced behavioral sensitization to MA in adolescence.

Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus.

PubMed

Chamberlain, Daniel B; Chamberlain, James M

2017-01-01

We demonstrate the application of a Bayesian approach to a recent negative clinical trial result. A Bayesian analysis of such a trial can provide a more useful interpretation of results and can incorporate previous evidence. This was a secondary analysis of the efficacy and safety results of the Pediatric Seizure Study, a randomized clinical trial of lorazepam versus diazepam for pediatric status epilepticus. We included the published results from the only prospective pediatric study of status in a Bayesian hierarchic model, and we performed sensitivity analyses on the amount of pooling between studies. We evaluated 3 summary analyses for the results: superiority, noninferiority (margin <-10%), and practical equivalence (within ±10%). Consistent with the original study's classic analysis of study results, we did not demonstrate superiority of lorazepam over diazepam. There is a 95% probability that the true efficacy of lorazepam is in the range of 66% to 80%. For both the efficacy and safety outcomes, there was greater than 95% probability that lorazepam is noninferior to diazepam, and there was greater than 90% probability that the 2 medications are practically equivalent. The results were largely driven by the current study because of the sample sizes of our study (n=273) and the previous pediatric study (n=61). Because Bayesian analysis estimates the probability of one or more hypotheses, such an approach can provide more useful information about the meaning of the results of a negative trial outcome. In the case of pediatric status epilepticus, it is highly likely that lorazepam is noninferior and practically equivalent to diazepam. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Rapamycin Reverses Status Epilepticus-Induced Memory Deficits and Dendritic Damage

PubMed Central

Brewster, Amy L.; Lugo, Joaquin N.; Patil, Vinit V.; Lee, Wai L.; Qian, Yan; Vanegas, Fabiola; Anderson, Anne E.

2013-01-01

Cognitive impairments are prominent sequelae of prolonged continuous seizures (status epilepticus; SE) in humans and animal models. While often associated with dendritic injury, the underlying mechanisms remain elusive. The mammalian target of rapamycin complex 1 (mTORC1) pathway is hyperactivated following SE. This pathway modulates learning and memory and is associated with regulation of neuronal, dendritic, and glial properties. Thus, in the present study we tested the hypothesis that SE-induced mTORC1 hyperactivation is a candidate mechanism underlying cognitive deficits and dendritic pathology seen following SE. We examined the effects of rapamycin, an mTORC1 inhibitor, on the early hippocampal-dependent spatial learning and memory deficits associated with an episode of pilocarpine-induced SE. Rapamycin-treated SE rats performed significantly better than the vehicle-treated rats in two spatial memory tasks, the Morris water maze and the novel object recognition test. At the molecular level, we found that the SE-induced increase in mTORC1 signaling was localized in neurons and microglia. Rapamycin decreased the SE-induced mTOR activation and attenuated microgliosis which was mostly localized within the CA1 area. These findings paralleled a reversal of the SE-induced decreases in dendritic Map2 and ion channels levels as well as improved dendritic branching and spine density in area CA1 following rapamycin treatment. Taken together, these findings suggest that mTORC1 hyperactivity contributes to early hippocampal-dependent spatial learning and memory deficits and dendritic dysregulation associated with SE. PMID:23536771

A girl with tuberous sclerosis complex presenting with severe epilepsy and electrical status epilepticus during sleep, and with high-functioning autism and mutism.

PubMed

Pacheva, Iliyana; Panov, Georgi; Gillberg, Christopher; Neville, Brian

2014-06-01

Most patients with tuberous sclerosis complex (TSC) suffer from epilepsy, and many have cognitive and behavioral problems like severe intellectual disability, autism, and hyperactivity. Only rare patients with TSC and autism have a normal intelligence quotient. We report a 13-year-old girl with definite TSC who had early-onset severe epilepsy, autistic behavior, and moderate developmental delay. By school age, however, she had normal intelligence; her intelligence quotient was at least 70 based on a Stanford-Binet test that she refused to complete. She showed good reading, writing, and language comprehension skills, and the special abilities of hyperlexia, hypermnesia, and hypercalculia. However, she did not speak. Criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and her Childhood Autism Rating Scale score of 36 indicated mild to moderate autism. She had severe electroencephalographic abnormalities: hypsarrhythmia, multifocal or generalized epileptiform discharges, and electrical status epilepticus during sleep, with a continuous left temporal focus. Magnetic resonance imaging showed many cortical tubers in all brain lobes, and subependymal nodules. We discuss possible explanations for her lack of speech. Considered as speech apraxia, her mutism could be either a symptom of her TSC or a component of her autism. Another possibility is that long-lasting electrical status epilepticus during sleep led to her autistic behavior and language arrest. Still another possibility is that a disinhibited mammalian target of rapamycin (mTOR) pathway was at the root of all of her neuropsychiatric symptoms.

From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

PubMed

Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

2016-11-01

Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

A KCNQ channel opener for experimental neonatal seizures and status epilepticus

PubMed Central

Raol, YogendraSinh H.; Lapides, David A.; Keating, Jeffery; Brooks-Kayal, Amy R.; Cooper, Edward C.

2009-01-01

Objective Neonatal seizures occur frequently, are often refractory to anticonvulsants, and are associated with considerable morbidity and mortality. Genetic and electrophysiological evidence indicates that KCNQ voltage-gated potassium channels are critical regulators of neonatal brain excitability. This study tests the hypothesis that selective openers of KCNQ channels may be effective for treatment of neonatal seizures. Methods We induced seizures in postnatal day 10 rats with either kainic acid or flurothyl. We measured seizure activity using quantified behavioral rating and electrocorticography. We compared the efficacy of flupirtine, a selective KCNQ channel opener, with phenobarbital and diazepam, two drugs in current use for neonatal seizures. Results Unlike phenobarbital or diazepam, flupirtine prevented animals from developing status epilepticus (SE) when administered prior to kainate. In the flurothyl model, phenobarbital and diazepam increased latency to seizure onset, but flupirtine completely prevented seizures throughout the experiment. Flupirtine was also effective in arresting electrographic and behavioral seizures when administered after animals had developed continuous kainate-induced SE. Flupirtine caused dose-related sedation and suppressed EEG activity, but did not result in respiratory suppression or result in any mortality. Interpretation Flupirtine appears more effective than either of two commonly used anti-epileptic drugs, phenobarbital and diazepam, in preventing and suppressing seizures in both the kainic acid and flurothyl models of symptomatic neonatal seizures. KCNQ channel openers merit further study as potential treatments for seizures in infants and children. PMID:19334075

Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus

PubMed Central

Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong

2016-01-01

Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339

Encephalopathy with status epilepticus during sleep (ESES) induced by oxcarbazepine in idiopathic focal epilepsy in childhood

PubMed Central

Pavlidis, Elena; Rubboli, Guido; Nikanorova, Marina; Kölmel, Margarethe Sophie; Gardella, Elena

2015-01-01

Summary Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin, carbamazepine and phenobarbital have been reported. We describe a child with benign epilepsy with centrotemporal spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The patient was studied through repeated clinical-neuropsychological evaluations and 24-hour EEG recordings. He was treated with OXC two months after epilepsy onset. One month after starting OXC, he developed an abrupt and severe cognitive deterioration. A 24-hour EEG and neuropsychological tests showed an electro-clinical picture compatible with ESES. Withdrawal of OXC and introduction of other drugs were followed by a prompt improvement. Five months after ESES onset, a 24-hour EEG was normal. Our report indicates that OXC can induce ESES in BECTS. PMID:26415787

Evaluation of a clinical tool for early etiology identification in status epilepticus

PubMed Central

Alvarez, Vincent; Westover, M. Brandon; Drislane, Frank W.; Dworetzky, Barbara A.; Curley, David

2016-01-01

Summary Objectives Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. Methods This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. Results Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4–89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4–96) (κ = 0.81). Significance This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment. PMID:25385281

Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

PubMed Central

Bertoglio, Daniele; Amhaoul, Halima; Van Eetveldt, Annemie; Houbrechts, Ruben; Van De Vijver, Sebastiaan; Ali, Idrish; Dedeurwaerdere, Stefanie

2017-01-01

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Kalaivani, Mani

2017-02-03

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 6, 2015).Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcomes. To compare the efficacy, adverse effects, and short- and long-term outcomes of refractory status epilepticus (RSE) treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (16 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 16 August 2016), MEDLINE (Ovid, 1946 to 16 August 2016), ClinicalTrials.gov (16 August 2016), and the South Asian Database of Controlled Clinical Trials (16 August 2016). Previously we searched IndMED, but this was not accessible at the time of the latest update. All randomised controlled trials (RCTs) or quasi-RCTs (regardless of blinding) assessing the control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6

Management of convulsive status epilepticus in children: an adapted clinical practice guideline for pediatricians in Saudi Arabia

PubMed Central

Bashiri, Fahad A.; Hamad, Muddathir H.; Amer, Yasser S.; Abouelkheir, Manal M.; Mohamed, Sarar; Kentab, Amal Y.; Salih, Mustafa A.; Nasser, Mohammad N. Al; Al-Eyadhy, Ayman A.; Othman, Mohammed A. Al; Al-Ahmadi, Tahani; Iqbal, Shaikh M.; Somily, Ali M.; Wahabi, Hayfaa A.; Hundallah, Khalid J.; Alwadei, Ali H.; Albaradie, Raidah S.; Al-Twaijri, Waleed A.; Jan, Mohammed M.; Al-Otaibi, Faisal; Alnemri, Abdulrahman M.; Al-Ansary, Lubna A.

2017-01-01

Objective: To increase the use of evidence-based approaches in the diagnosis, investigations and treatment of Convulsive Status Epilepticus (CSE) in children in relevant care settings. Method: A Clinical Practice Guideline (CPG) adaptation group was formulated at a university hospital in Riyadh. The group utilized 2 CPG validated tools including the ADAPTE method and the AGREE II instrument. Results: The group adapted 3 main categories of recommendations from one Source CPG. The recommendations cover; (i)first-line treatment of CSE in the community; (ii)treatment of CSE in the hospital; and (iii)refractory CSE. Implementation tools were built to enhance knowledge translation of these recommendations including a clinical algorithm, audit criteria, and a computerized provider order entry. Conclusion: A clinical practice guideline for the Saudi healthcare context was formulated using a guideline adaptation process to support relevant clinicians managing CSE in children. PMID:28416791

Neuroprotective effect of pyruvate and oxaloacetate during pilocarpine induced status epilepticus in rats.

PubMed

Carvalho, Andrezza Sossai Rodrigues; Torres, Laila Brito; Persike, Daniele Suzete; Fernandes, Maria José Silva; Amado, Debora; Naffah-Mazzacoratti, Maria da Graça; Cavalheiro, Esper Abrão; da Silva, Alexandre Valotta

2011-02-01

Recent research data have shown that systemic administration of pyruvate and oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased release of glutamate during epileptic seizures can lead to excitotoxicity and neuronal cell death, we tested the hypothesis that glutamate scavenging mediated by pyruvate and oxaloacetate systemic administration could have a neuroprotective effect in rats subjected to status epilepticus (SE). SE was induced by a single dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was quantitatively determined five hours after SE onset, using the optical fractionator method for stereological cell counting. Apoptotic cascade in the hippocampus was also investigated seven days after SE using caspase-1 and -3 activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was significantly reduced when rats were treated with oxaloacetate or pyruvate plus oxaloacetate. The treatment with pyruvate and oxaloacetate caused a neuroprotective effect in rats subjected to pilocarpine-induced SE. Copyright © 2010 Elsevier Ltd. All rights reserved.

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

An update on the recognition and treatment of non-convulsive status epilepticus in the intensive care unit.

PubMed

Kinney, Michael O; Kaplan, Peter W

2017-10-01

Non-convulsive status epilepticus (NCSE) is a complex and diverse condition which is often an under-recognised entity in the intensive care unit. When NCSE is identified the optimal treatment strategy is not always clear. Areas covered: This review is based on a literature review of the key literature in the field over the last 5-10 years. The articles were selected based on their importance to the field by the authors. Expert commentary: This review discusses the complex situations when a neurological consultation may occur in a critical care setting and provides an update on the latest evidence regarding the recognition of NCSE and the decision making around determining the aggressiveness of treatment. It also considers the ictal-interictal continuum of conditions which may be met with, particularly in the era of continuous EEG, and provides an approach for dealing with these. Suggestions for how the field will develop are discussed.

Mannitol induces selective astroglial death in the CA1 region of the rat hippocampus following status epilepticus

PubMed Central

Ko, Ah-Reum; Kang, Tae-Cheon

2015-01-01

In the present study, we addressed the question of whether treatment with mannitol, an osmotic diuretic, affects astrogliovascular responses to status epilepticus (SE). In saline-treated animals, astrocytes exhibited reactive astrogliosis in the CA1-3 regions 2-4 days after SE. In the mannitol-treated animals, a large astroglial empty zone was observed in the CA1 region 2 days after SE. This astroglial loss was unrelated to vasogenic edema formation. There was no difference in SE-induced neuronal loss between saline- and mannitol-treated animals. Furthermore, mannitol treatment did not affect astroglial loss and vasogenic edema formation in the dentate gyrus and the piriform cortex. These findings suggest that mannitol treatment induces selective astroglial loss in the CA1 region independent of vasogenic edema formation following SE. These findings support the hypothesis that the susceptibility of astrocytes to SE is most likely due to the distinctive heterogeneity of astrocytes independent of hemodynamics. [BMB Reports 2015; 48(9): 507-512] PMID:25703536

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

PubMed

Dalziel, Stuart R; Furyk, Jeremy; Bonisch, Megan; Oakley, Ed; Borland, Meredith; Neutze, Jocelyn; Donath, Susan; Sharpe, Cynthia; Harvey, Simon; Davidson, Andrew; Craig, Simon; Phillips, Natalie; George, Shane; Rao, Arjun; Cheng, Nicholas; Zhang, Michael; Sinn, Kam; Kochar, Amit; Brabyn, Christine; Babl, Franz E

2017-06-22

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom

Inhibition of the prostaglandin EP2 receptor is neuroprotective and accelerates functional recovery in a rat model of organophosphorus induced status epilepticus

PubMed Central

Rojas, Asheebo; Ganesh, Thota; Lelutiu, Nadia; Gueorguieva, Paoula; Dingledine, Raymond

2015-01-01

Exposure to high levels of organophosphorus compounds (OP) can induce status epilepticus (SE) in humans and rodents via acute cholinergic toxicity, leading to neurodegeneration and brain inflammation. Currently there is no treatment to combat the neuropathologies associated with OP exposure. We recently demonstrated that inhibition of the EP2 receptor for PGE2 reduces neuronal injury in mice following pilocarpine-induced SE. Here, we investigated the therapeutic effects of an EP2 inhibitor (TG6-10-1) in a rat model of SE using diisopropyl fluorophosphate (DFP). We tested the hypothesis that EP2 receptor inhibition initiated well after the onset of DFP-induced SE reduces the associated neuropathologies. Adult male Sprague-Dawley rats were injected with pyridostigmine bromide (0.1 mg/kg, sc) and atropine methylbromide (20 mg/kg, sc) followed by DFP (9.5 mg/kg, ip) to induce SE. DFP administration resulted in prolonged upregulation of COX-2. The rats were administered TG6-10-1 or vehicle (ip) at various time points relative to DFP exposure. Treatment with TG6-10-1 or vehicle did not alter the observed behavioral seizures, however six doses of TG6-10-1 starting 80-150 min after the onset of DFP-induced SE significantly reduced neurodegeneration in the hippocampus, blunted the inflammatory cytokine burst, reduced microglial activation and decreased weight loss in the days after status epilepticus. By contrast, astrogliosis was unaffected by EP2 inhibition 4 d after DFP. Transient treatments with the EP2 antagonist 1 h before DFP, or beginning 4 h after DFP, were ineffective. Delayed mortality, which was low (10%) after DFP, was unaffected by TG6-10-1. Thus, selective inhibition of the EP2 receptor within a time window that coincides with the induction of cyclooxygenase-2 by DFP is neuroprotective and accelerates functional recovery of rats. PMID:25656476

Morpho-physiological Characteristics of Dorsal Subicular Network in Mice after Pilocarpine Induced Status Epilepticus

PubMed Central

He, De Fu; Ma, Dong Liang; Tang, Yong Cheng; Engel, Jerome; Bragin, Anatol; Tang, Feng Ru

2010-01-01

The goal of this study was to examine morpho-physiological changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV), and immunopositive interneurons, was found at 2 months after pilocarpine-induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates were increased significantly in SE mice compared to the control group. Fast irregular discharge neurons were PV-immunopositive interneurons, and had less dendritic spines in SE mice when compared to control mice. When LEnt was stimulated, bursting and fast irregular discharge neurons had much shorter latency and stronger excitatory response in SE mice compared to the control group. Our results illustrate that morpho-physiological changes in the dorsal subiculum could be part of a multilevel pathological network that occurs simultaneously in many brain areas to contribute to the generation of epileptiform activity. PMID:19298597

Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy

PubMed Central

Kakooza-Mwesige, Angelina; Wagner, Ryan G.; Chengo, Eddie; White, Steven; Kamuyu, Gathoni; Ngugi, Anthony K.; Sander, Josemir W.; Neville, Brian G.R.; Newton, Charles R.J.

2015-01-01

Objective: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. Methods: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. Results: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. Conclusions: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE. PMID:25841025

Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus.

PubMed

Varvel, Nicholas H; Neher, Jonas J; Bosch, Andrea; Wang, Wenyi; Ransohoff, Richard M; Miller, Richard J; Dingledine, Raymond

2016-09-20

The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs. brain-infiltrating monocytes. Chemokine receptor 2 (CCR2(+)) monocytes invade the hippocampus between 1 and 3 d after SE. In contrast, only an occasional CD3(+) T lymphocyte was encountered 3 d after SE. The initial cellular sources of the chemokine CCL2, a ligand for CCR2, included perivascular macrophages and microglia. The induction of the proinflammatory cytokine IL-1β was greater in FACS-isolated microglia than in brain-invading monocytes. However, Ccr2 knockout mice displayed greatly reduced monocyte recruitment into brain and reduced levels of the proinflammatory cytokine IL-1β in hippocampus after SE, which was explained by higher expression of the cytokine in circulating and brain monocytes in wild-type mice. Importantly, preventing monocyte recruitment accelerated weight regain, reduced BBB degradation, and attenuated neuronal damage. Our findings identify brain-infiltrating monocytes as a myeloid-cell subclass that contributes to neuroinflammation and morbidity after SE. Inhibiting brain invasion of CCR2(+) monocytes could represent a viable method for alleviating the deleterious consequences of SE.

Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus

PubMed Central

Varvel, Nicholas H.; Neher, Jonas J.; Bosch, Andrea; Wang, Wenyi; Ransohoff, Richard M.; Miller, Richard J.; Dingledine, Raymond

2016-01-01

The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood–brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs. brain-infiltrating monocytes. Chemokine receptor 2 (CCR2+) monocytes invade the hippocampus between 1 and 3 d after SE. In contrast, only an occasional CD3+ T lymphocyte was encountered 3 d after SE. The initial cellular sources of the chemokine CCL2, a ligand for CCR2, included perivascular macrophages and microglia. The induction of the proinflammatory cytokine IL-1β was greater in FACS-isolated microglia than in brain-invading monocytes. However, Ccr2 knockout mice displayed greatly reduced monocyte recruitment into brain and reduced levels of the proinflammatory cytokine IL-1β in hippocampus after SE, which was explained by higher expression of the cytokine in circulating and brain monocytes in wild-type mice. Importantly, preventing monocyte recruitment accelerated weight regain, reduced BBB degradation, and attenuated neuronal damage. Our findings identify brain-infiltrating monocytes as a myeloid-cell subclass that contributes to neuroinflammation and morbidity after SE. Inhibiting brain invasion of CCR2+ monocytes could represent a viable method for alleviating the deleterious consequences of SE. PMID:27601660

Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy.

PubMed

Kariuki, Symon M; Kakooza-Mwesige, Angelina; Wagner, Ryan G; Chengo, Eddie; White, Steven; Kamuyu, Gathoni; Ngugi, Anthony K; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J

2015-05-05

We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p < 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE. © 2015 American Academy of Neurology.

Outcomes of deviation from treatment guidelines in status epilepticus: A systematic review.

PubMed

Uppal, Preena; Cardamone, Michael; Lawson, John A

2018-04-16

Due to a gap between published clinical guidelines on status epilepticus SE and clinician management of SE, a systematic review was performed to investigate treatment adherence to SE guidelines and its impact on patient outcomes. Medline and Embase searches were conducted for studies appraising adherence to SE guidelines (from 1970 and 1st April 2018). The quality of eligible studies was assessed by QUADAS- 2 criteria. Comparison was made between patients where guidelines were followed and not followed. Various patient outcomes including intubation, ICU admission, morbidity and mortality were compared. A Forest plot was used to investigate the effect of adherence on outcome. A total of 3424 titles and abstracts were screened from the initial search after removal of duplicates. A total of 441 full text articles were reviewed in detail, and 22 articles were included in this study. The proportion of deviations ranged from 10.7% to 66.1%. Four studies were descriptive. Eighteen studies looked at the adverse effects of non-adherence. Eight studies showed respiratory depression and intubation were associated with excessive benzodiazepine use. A subset analysis showed 5.79 times higher odds of respiratory depression and intubation], if excessive benzodiazepines were given. The next most common variations were delayed management and insufficient treatment. These variations from the guidelines were associated with prolonged seizures. This review provides preliminary evidence that non-adherence to SE guidelines negatively impacts on patient outcomes. Appropriate and timely treatment is imperative for rapid seizure termination and improving outcomes. Copyright © 2018 British Epilepsy Association. All rights reserved.

Beneficial effects of enriched environment following status epilepticus in immature rats.

PubMed

Faverjon, S; Silveira, D C; Fu, D D; Cha, B H; Akman, C; Hu, Y; Holmes, G L

2002-11-12

There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.

New onset status epilepticus in older patients: Clinical characteristics and outcome.

PubMed

Malter, M P; Nass, R D; Kaluschke, T; Fink, G R; Burghaus, L; Dohmen, C

2017-10-01

We here evaluated (1) the differential characteristics of status epilepticus (SE) in older (≥60 years) compared to younger adults (18-59 years). In particular, we were interested in (2) the proportion and characteristics of new onset SE in patients with no history of epilepsy (NOSE) in older compared to younger adults, and (3) predictive parameters for clinical outcome in older subjects with NOSE. We performed a monocentric retrospective analysis of all adult patients (≥18years) admitted with SE to our tertiary care centre over a period of 10 years (2006-2015) to evaluate clinical characteristics and short-time outcome at discharge. One-hundred-thirty-five patients with SE were included in the study. Mean age at onset was 64 years (range 21-90), eighty-seven of the patients (64%) were older than 60 years. In 76 patients (56%), SE occurred as NOSE, sixty-seven percent of them were aged ≥60 years. There was no age-dependent predominance for NOSE. NOSE was not a relevant outcome predictor, especially regarding age-related subgroups. Older patients with NOSE had less frequently general tonic clonic SE (GTCSE; p=0.001) and were more often female (p=0.01). Regarding outcome parameters and risk factors in older patients with NOSE, unfavourable outcome was associated with infections during in-hospital treatment (0.04), extended stay in ICU (p=0.001), and generally in hospital (p<0.001). In our cohort, older patients represented the predominant subgroup in patients with SE. Older patients suffered more often from non-convulsive semiology and had a less favourable short-time outcome. NOSE was not a predictive outcome parameter in older patients. Data suggest that avoiding infections should have a priority because higher infection rates were associated with unfavourable outcome. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Time from convulsive status epilepticus onset to anticonvulsant administration in children

PubMed Central

Sánchez Fernández, Iván; Abend, Nicholas S.; Agadi, Satish; An, Sookee; Arya, Ravindra; Brenton, James Nicholas; Carpenter, Jessica L.; Chapman, Kevin E.; Gaillard, William D.; Glauser, Tracy A.; Goodkin, Howard P.; Kapur, Kush; Mikati, Mohamad A.; Peariso, Katrina; Ream, Margie; Riviello, James; Tasker, Robert C.; Jackson, Michele

2015-01-01

Objective: To describe the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration of antiepileptic drug (AED). Methods: This was a prospective observational cohort study performed from June 2011 to June 2013. Pediatric patients (1 month–21 years) with convulsive SE were enrolled. In order to study timing of AED administration during all stages of SE, we restricted our study population to patients who failed 2 or more AED classes or needed continuous infusions to terminate convulsive SE. Results: We enrolled 81 patients (44 male) with a median age of 3.6 years. The first, second, and third AED doses were administered at a median (p25–p75) time of 28 (6–67) minutes, 40 (20–85) minutes, and 59 (30–120) minutes after SE onset. Considering AED classes, the initial AED was a benzodiazepine in 78 (96.3%) patients and 2 (2–3) doses of benzodiazepines were administered before switching to nonbenzodiazepine AEDs. The first and second doses of nonbenzodiazepine AEDs were administered at 69 (40–120) minutes and 120 (75–296) minutes. In the 64 patients with out-of-hospital SE onset, 40 (62.5%) patients did not receive any AED before hospital arrival. In the hospital setting, the first and second in-hospital AED doses were given at 8 (5–15) minutes and 16 (10–40) minutes after SE onset (for patients with in-hospital SE onset) or after hospital arrival (for patients with out-of-hospital SE onset). Conclusions: The time elapsed from SE onset to AED administration and escalation from one class of AED to another is delayed, both in the prehospital and in-hospital settings. PMID:25948729

Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus.

PubMed

Gonzalez, Daniel; Chamberlain, James M; Guptill, Jeffrey T; Cohen-Wolkowiez, Michael; Harper, Barrie; Zhao, Jian; Capparelli, Edmund V

2017-08-01

Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE. We developed a population pharmacokinetic model for lorazepam using the NONMEM software. We then assessed exploratory exposure-response relationships using the overall efficacy and safety study endpoints, and performed dosing simulations. A total of 145 patients contributed 439 pharmacokinetic samples. The median (range) age and dose were 5.4 years (0.3-17.8) and 0.10 mg/kg (0.02-0.18), respectively. A two-compartment pharmacokinetic model with allometric scaling described the data well. In addition to total body weight (WT), younger age was associated with slightly higher weight-normalized clearance (CL). The following relationships characterized the typical values for the central compartment volume (V1), CL, peripheral compartment volume (V2), and intercompartmental CL (Q), using individual subject WT (kg) and age (years): V1 (L) = 0.879*WT; CL (L/h) = 0.115*(Age/4.7) 0.133 *WT 0.75 ; V2 (L) = 0.542*V1; Q (L/h) = 1.45*WT 0.75 . No pharmacokinetic parameters were associated with clinical outcomes. Simulations suggest uniform pediatric dosing (0.1 mg/kg, to a maximum of 4 mg) can be used to achieve concentrations of 50-100 ng/mL in children with SE, which have been previously associated with effective seizure control. The population pharmacokinetics of lorazepam were successfully described using a sparse sampling approach and a two-compartment model in pediatric patients with active SE.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus.

PubMed

Sánchez Fernández, I; Gaínza-Lein, M; Abend, N S; Anderson, A E; Arya, R; Brenton, J N; Carpenter, J L; Chapman, K E; Clark, J; Gaillard, W D; Glauser, T A; Goldstein, J L; Goodkin, H P; Helseth, A R; Jackson, M C; Kapur, K; Lai, Y-C; McDonough, T L; Mikati, M A; Nayak, A; Peariso, K; Riviello, J J; Tasker, R C; Tchapyjnikov, D; Topjian, A A; Wainwright, M S; Wilfong, A; Williams, K; Loddenkemper, T

2018-05-08

To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. We studied 219 patients (53% males) with a median (25th-75th percentiles [p 25 -p 75 ]) age of 3.9 (1.2-9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p 25 -p 75 ) time from seizure onset to treatment was 16 (5-45) minutes to first benzodiazepine (BZD), 63 (33-146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107-539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14-2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11-2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32-2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67-3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment. © 2018 American Academy of Neurology.

Status epilepticus induction has prolonged effects on the efficacy of antiepileptic drugs in the 6-Hz seizure model.

PubMed

Leclercq, Karine; Kaminski, Rafal M

2015-08-01

Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks

Effects of protease-activated receptor 1 inhibition on anxiety and fear following status epilepticus.

PubMed

Bogovyk, Ruslan; Lunko, Oleksii; Fedoriuk, Mihail; Isaev, Dmytro; Krishtal, Oleg; Holmes, Gregory L; Isaeva, Elena

2017-02-01

Protease-activated receptor 1 (PAR1) is an important contributor to the pathogenesis of a variety of brain disorders associated with a risk of epilepsy development. Using the lithium-pilocarpine model of temporal lobe epilepsy (TLE), we recently showed that inhibition of this receptor during the first ten days after pilocarpine-induced status epilepticus (SE) results in substantial anti-epileptogenic and neuroprotective effects. As PAR1 is expressed in the central nervous system regions of importance for processing emotional reactions, including amygdala and hippocampus, and TLE is frequently associated with a chronic alteration of the functions of these regions, we tested the hypothesis that PAR1 inhibition could modulate emotionally driven behavioral responses of rats experiencing SE. We showed that SE induces a chronic decrease in the animals' anxiety-related behavior and an increase of locomotor activity. PAR1 inhibition after SE abolished the alteration of the anxiety level but does not affect the increase of locomotor activity in the open field and elevated plus maze tests. Moreover, while PAR1 inhibition produces an impairment of memory recall in the context fear conditioning paradigm in the control group, it substantially improves contextual and cued fear learning in rats experiencing SE. These data suggest that PAR1-dependent signaling is involved in the mechanisms underlying emotional disorders in epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus

PubMed Central

Kong, Qiongman; Takahashi, Kou; Schulte, Delanie; Stouffer, Nathan; Lin, Yuchen; Lin, Chien-liang Glenn

2013-01-01

Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased glial glutamate transporter EAAT2, the major glutamate transporter, could prevent seizure activity and reduce epileptogenic processes. EAAT2 transgenic mice, which have a 1.5-2 fold increase in EAAT2 protein levels as compared to their non-transgenic counterparts, were tested in a pilocarpine-induced status epilepticus (SE) model. Several striking phenomena were observed in EAAT2 transgenic mice compared with their non-transgenic littermates. First, the post-SE mortality rate and chronic seizure frequency were significantly decreased. Second, neuronal degeneration in hippocampal subfields after SE were significantly reduced. Third, the SE-induced neurogenesis and mossy fiber sprouting were significantly decreased. The severity of cell loss in epileptic mice was positively correlated with that of mossy fiber sprouting and chronic seizure frequency. Our results suggest that increased EAAT2 expression can protect mice against SE-induced death, neuropathological changes, and chronic seizure development. This study suggests that enhancing EAAT2 protein expression is a potential therapeutic approach. PMID:22513140

Endothelial NOS activation induces the blood-brain barrier disruption via ER stress following status epilepticus.

PubMed

Ko, Ah-Reum; Kim, Ji Yang; Hyun, Hye-Won; Kim, Ji-Eun

2015-10-05

The blood-brain barrier (BBB) maintains the unique brain microenvironment, which is separated from the systemic circulating system. Since the endoplasmic reticulum (ER) is an important cell organelle that is responsible for protein synthesis, the correct folding and sorting of proteins contributing to cell survivals, ER stress is a potential cause of cell damage in various diseases. Therefore, it would be worthy to explore the the relationship between the ER stress and BBB disruption during vasogenic edema formation induced by epileptogenic insults. In the present study, we investigated the roles of ER stress in vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced status epilepticus (SE). SE-induced eNOS activation induces BBB breakdown via up-regulation of GRP78 expression and dysfunction of SMI-71 (an endothelial BBB marker) in the piriform cortex (PC). In addition, caveolin-1 peptide (an eNOS inhibitor) effectively attenuated GRP78 expression and down-regulation of SMI-71. Taken together, our findings suggest that eNOS-mediated ER stress may participate in SE-induced vasogenic edema formation. Therefore, the modulation of ER stress may be a considerable strategy for therapy in impairments of endothelial cell function. Copyright © 2015 Elsevier B.V. All rights reserved.

Strain-dependent effects of long-term treatment with melatonin on kainic acid-induced status epilepticus, oxidative stress and the expression of heat shock proteins.

PubMed

Atanasova, Milena; Petkova, Zlatina; Pechlivanova, Daniela; Dragomirova, Petya; Blazhev, Alexander; Tchekalarova, Jana

2013-10-01

Oxidative stress is implicated in the pathogenesis of both hypertension and epileptogenesis, therefore it could be used as a tool for studying co-morbidity of hypertension and epilepsy. Clinical data suggest that melatonin is a potent antioxidant that is effective in the adjunctive therapy of hypertension and neurodegenerative diseases. The present study aimed to explore and compare the efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed higher lipid peroxidation (LP) in the frontal cortex and hippocampus and decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg, i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus of the two strains and increased SOD/CuZn production in the frontal cortex of SHRs. Melatonin failed to suppress seizure incidence and intensity though the latency for seizure onset was significantly increased in SHRs. Melatonin attenuated the KA-induced increase in the level of LP in the hippocampus both in SHRs and Wistar rats. However, an increased activity in SOD/CuZn and mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus was observed only in Wistar rats pretreated with melatonin. Taken together, the observed strain differences in the efficacy of chronic melatonin exposure before SE suggest a lack of a direct link between the seizure activity and the markers of oxidative stress and neurotoxicity. © 2013.

Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study.

PubMed

Misra, U K; Kalita, J; Maurya, P K

2012-04-01

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.

Status epilepticus during early development disrupts sexual behavior in adult female rats: recovery with sexual experience.

PubMed

Coria-Avila, Genaro Alfonso; Paredes-Ramos, Pedro; Galán, Ricardo; Herrera-Covarrubias, Deissy; López-Meraz, Maria-Leonor

2014-05-01

Female sexual behavior is sensitive to stress and diseases. Some studies have shown that status epilepticus (SE) can affect sexual proceptivity and receptivity in female rats and also increases reject responses towards males. However, epidemiologic studies indicate that SE is more frequent in young individuals. Herein, we assessed the effects of SE in infant females on their sexual behavior during adulthood. Thirteen-day-old (P13) rat pups received intraperitoneal injections of lithium chloride (3 mEq/kg). Twenty hours later, at P14, SE was induced by subcutaneous injection of pilocarpine hydrochloride (100 mg/kg s.c.). Control animals were given an equal volume of saline subcutaneously. The animals were weaned at P21 and, later in adulthood, were ovariectomized and hormone-primed with estradiol+progesterone, and their sexual behavior assessed during 4 separate trials of 30 min each with a stud male. Our results indicate that proceptive behaviors (solicitations and hops and darts) were impaired during the first trial, but no alterations were observed for receptivity and attractivity. By trial 3, all SE females displayed normal proceptivity. These results indicate that SE in infancy readily affects proceptivity in a reversible manner. We discuss the role of sexual experience in recovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Somatostatin type-2 receptor activation inhibits glutamate release and prevents status epilepticus

PubMed Central

Kozhemyakin, Maxim; Rajasekaran, Karthik; Todorovic, Marko S.; Kowalski, Samuel L.; Balint, Corinne; Kapur, Jaideep

2013-01-01

Summary Newer therapies are needed for the treatment of status epilepticus (SE) refractory to benzodiazepines. Enhanced glutamatergic neurotransmission leads to SE, and AMPA receptors are modified during SE. Reducing glutamate release during SE is a potential approach to terminate SE. The neuropeptide somatostatin (SST) is proposed to diminish presynaptic glutamate release by activating SST type-2 receptors (SST2R). SST exerts an anticonvulsant action in some experimental models of seizures. Here, we investigated the mechanism of action of SST on excitatory synaptic transmission at the Schaffer collateral-CA1 synapses and the ability of SST to treat SE in rats using patch-clamp electrophysiology and video-EEG monitoring of seizures. SST reduced action potential-dependent EPSCs (sEPSCs) at Schaffer collateral-CA1 synapses at concentrations up to 1 μM; higher concentrations had no effect or increased the sEPSC frequency. SST also prevented paired-pulse facilitation of evoked EPSCs and did not alter action-potential-independent miniature EPSCs (mEPSCs). The effect of SST on EPSCs was inhibited by the SST2R antagonist cyanamid-154806 and was mimicked by the SST2R agonists, octreotide and lanreotide. Both SST and octreotide reduced the firing rate of CA1 pyramidal neurons. Intraventricular administration of SST, within a range of doses, either prevented or attenuated pilocarpine-induced SE or delayed the median time to the first grade 5 seizure by 11 min. Similarly, octreotide or lanreotide prevented or attenuated SE in more than 65% of animals. Compared to the pilocarpine model, octreotide was highly potent in preventing or attenuating continuous hippocampal stimulation-induced SE in all animals within 60 min of SE onset. Our results demonstrate that SST, through the activation of SST2Rs, diminishes presynaptic glutamate release and attenuates SE. PMID:23473742

Hyperforin attenuates microglia activation and inhibits p65-Ser276 NFκB phosphorylation in the rat piriform cortex following status epilepticus.

PubMed

Lee, Sang-Kyu; Kim, Ji-Eun; Kim, Yeon-Joo; Kim, Min-Ju; Kang, Tae-Cheon

2014-08-01

Hyperforin, a lipophilic constituent of medicinal herb St. John's Wort, has neurobiological effects including antidepressant activity, antibiotic potency, anti-inflammatory activity and anti-tumoral properties. Furthermore, hyperforin activates transient receptor potential conical channel-6 (TRPC6), a nonselective cation channel. To elucidate the roles of hyperforin and TRPC6 in neuroinflammation in vivo, we investigated the effect of hyperforin on neuroinflammatory responses and its related events in the rat piriform cortex (PC) following status epilepticus (SE). Hyperforin attenuated microglial activation, p65-serine 276 NFκB phosphorylation, and suppressed TNF-α expression in the PC following SE. Hyperforin also effectively alleviated SE-induced vasogenic edema formation, neuronal damage, microglial TRPC6 induction and blood-derived monocyte infiltration. Our findings suggest that hyperforin may effectively attenuate microglia-mediated neuroinflammation in the TRPC6-independent manner. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new-onset super-refractory status epilepticus (NORSE) in a deployed U.S. soldier.

PubMed

Hainsworth, Jeffrey Brian; Shishido, Akira; Theeler, Brett James; Carroll, Craig Grason; Fasano, Rebecca Ellen

2014-12-01

A 23-year-old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti-seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti-GABA(B)-receptor. This case is noteworthy for being the first reported case of anti-GABA(B)-receptor limbic encephalitis presenting with new-onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA-receptor autoantibodies and the upfront use of multi-modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2012-08-15

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE

Canine status epilepticus treated with fosphenytoin: A proof of principle study.

PubMed

Patterson, Edward E; Leppik, Ilo E; Coles, Lisa D; Podell, Michael; Vite, Charles H; Bush, William; Cloyd, James C

2015-06-01

There are a limited number of marketed intravenous antiepileptic drugs (AEDs) available to treat status epilepticus (SE). All were first developed for chronic therapy of epilepsy, not specifically for SE. Epilepsy and canine SE (CSE) occur naturally in dogs, with prevalence, presentation, and percentage of refractory cases similar to human epilepsy. The objective of this study was to determine if CSE treated with fosphenytoin (FOS) results in a similar responder rate as for people. A randomized clinical trial was performed for dogs with CSE. Dogs who presented during a seizure or who had additional seizures after enrolling received intravenous (i.v.) benzodiazepine (BZD) followed immediately by intravenous infusion of 15 mg/kg phenytoin equivalent (PE) of fosphenytoin (FOS) or saline placebo (PBO). If seizures continued, additional AEDs were administered per the standard of care for veterinary patients. Total and unbound plasma phenytoin (PHT) concentrations were measured. Consent was obtained for 50 dogs with CSE. Thirty-one had additional motor seizures and were randomized to the study intervention (22 FOS and 9 PBO). There was a statistically significant difference in the 12 h responder rate, with 63% in the FOS group versus 22% in the placebo group (p = 0.043) having no further seizures. The unbound PHT concentrations at 30 and 60 min were within the therapeutic concentrations for people (1-2 μg/ml) with the exception of one dog. There was mild vomiting in 36% of the FOS group (7/22) within 20 min of FOS administration and none of the placebo group (0/9) (p = 0.064). This proof of concept study provides the first evidence that FOS is tolerated and effective in canine SE at PHT concentrations clinically relevant for human SE. Furthermore, naturally occurring CSE can be utilized as a translational platform for future studies of novel SE compounds. © 2015 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against

Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus.

PubMed

Gaínza-Lein, Marina; Sánchez Fernández, Iván; Jackson, Michele; Abend, Nicholas S; Arya, Ravindra; Brenton, J Nicholas; Carpenter, Jessica L; Chapman, Kevin E; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua L; Goodkin, Howard P; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Tasker, Robert C; Tchapyjnikov, Dmitry; Topjian, Alexis A; Wainwright, Mark S; Wilfong, Angus; Williams, Korwyn; Loddenkemper, Tobias

2018-04-01

Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11

A follow-up ¹⁸F-FDG brain PET study in a case of Hashimoto's encephalopathy causing drug-resistant status epilepticus treated with plasmapheresis.

PubMed

Pari, Elisa; Rinaldi, Fabrizio; Premi, Enrico; Codella, Maria; Rao, Renata; Paghera, Barbara; Panarotto, Maria Beatrice; De Maria, Giovanni; Padovani, Alessandro

2014-04-01

Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with antithyroid antibodies. It may have an acute onset (episodes of cerebral ischemia, seizure, and psychosis) or it may present as an indolent form (depression, cognitive decline, myoclonus, tremors, and fluctuations in level of consciousness). We here describe a case of encephalopathy presenting as non-convulsive status epilepticus associated with Hashimoto's thyroiditis (HT), unresponsive to corticosteroid therapy, with improvement after plasma exchange treatment. A previously healthy 19-year-old woman, presented generalized tonic-clonic seizures. About a month later, she manifested a speech disorder characterized by difficulties in the production and comprehension of language. Within a few days she also developed confusion and difficulties in recognizing familiar places, with gradual worsening over time. EEG revealed a non-convulsive status epilepticus (NCSE). CSF examination showed slightly elevated cell count and four oligoclonal bands. MRI was unremarkable, and (18)F-FDG brain PET showed widespread hypometabolism, mostly in posterior regions bilaterally. Laboratory and ultrasound findings showed signs of HT. Treatment with steroid was introduced without any improvement. After five sessions of plasma exchange there was a decrease of antithyroid antibodies, as well as EEG and clinical improvement. Three months after discharge (18)F-FDG brain PET showed a complete normalization of the picture, and the patient was asymptomatic. This report emphasizes the successful treatment of HE with plasma exchange in a patient who presented with NCSE. Based on the actual evidence, the term "Encephalopathy associated with Hashimoto's thyroiditis" may be the most proper. Furthermore, to our knowledge, this is the first case of an adult patient studied twice with an (18)F-FDG brain PET: prior to treatment with plasma exchange, and at 3 months follow-up when the patient was clinically completely

Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

PubMed

Chan, D W S; Thomas, T; Lim, M; Ling, S; Woodhall, M; Vincent, A

2017-03-01

Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABA B receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Neurocognitive and neurobehavioral disabilities in Epilepsy with Electrical Status Epilepticus in slow sleep (ESES) and related syndromes.

PubMed

Raha, Sarbani; Shah, Urvashi; Udani, Vrajesh

2012-11-01

The aims of this study were to assess the cognitive and behavioral problems of patients with Epilepsy with Electrical Status Epilepticus in slow sleep (ESES) and related syndromes and to review their EEG (electroencephalography) findings and treatment options. Fourteen patients with ESES were evaluated and treated in 2010. Nine children had continuous spike and wave during slow-wave sleep (CSWS)/ESES syndrome, 3 had Atypical BECTS (benign epilepsy with centrotemporal spikes), 1 had Opercular syndrome, and 1 had Landau-Kleffner syndrome. The duration of ESES ranged from 6 to 52 months. Eleven (91%) children had behavioral issues, most prominent being hyperactivity. Seven of the 13 children (53%) showed evidence of borderline to moderate cognitive impairment. A total of 28 EEG findings of ESES were analyzed for SWI (spike-wave index). Antiepileptic drugs received by the patients included valproate, clobazam, levetiracetam, and others. Eleven patients had been treated with oral steroids and it was found to be efficacious in seven (63%). Disabilities caused by ESES affect multiple domains. Patients with an SWI>50% should be followed up frequently with neuropsychological assessments. Steroids appear to be effective, although there is a need to standardize the dose and duration of treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

The Acute and Chronic Effects of the Novel Anticonvulsant Lacosamide in an Experimental Model of Status Epilepticus

PubMed Central

Wasterlain, Claude G.; Stöhr, Thomas; Matagne, Alain

2011-01-01

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 50 mg/kg) either 10 minutes (early treatment) or 40 minutes (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 towards 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 (50 mg/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 (30–50 mg/kg) reduced the number of animals that developed spontaneous recurrent seizures (33% vs 100% in controls, P <0.05), 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. PMID:21277168

Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation.

PubMed

Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K

2015-12-07

Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.

Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

PubMed

Itakura, Ayako; Saito, Yoshiaki; Nishimura, Yoko; Okazaki, Tetsuya; Ohno, Koyo; Sejima, Hitoshi; Yamamoto, Toshiyuki; Maegaki, Yoshihiro

2016-08-01

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The relevance of timing in nonconvulsive status epilepticus: A series of 38 cases.

PubMed

Gutiérrez-Viedma, Álvaro; Parejo-Carbonell, Beatriz; Cuadrado, María-Luz; Serrano-García, Irene; Abarrategui, Belén; García-Morales, Irene

2018-05-01

Timing in the management of nonconvulsive status epilepticus (NCSE) seems to be one of the most important modifiable prognostic factors. We aimed to determine the precise relationship between timing in NCSE management and its outcome. We performed a cross-sectional study in which clinical data were prospectively obtained from all consecutive adults with NCSE admitted to our hospital from 2014 to 2016. Univariate and multivariable regression analyses were performed to identify clinical and timing variables associated with NCSE prognosis. Among 38 NCSE cases, 59.9% were women, and 39.5% had prior epilepsy history. The median time to treatment (TTT) initiation and the median time to assessment by a neurologist (TTN) were 5h, and the median time to first electroencephalography assessment was 18.5h; in the cases with out-of-hospital onset (n=24), the median time to hospital (TTH) arrival was 2.8h. The median time to NCSE control (TTC) was 16.5h, and it positively correlated with both the TTH (Spearman's rho: 0.439) and the TTT (Spearman's rho: 0.683). In the multivariable regression analyses, the TTC was extended 1.7h for each hour of hospital arrival delay (p=0.01) and 2.7h for each hour of treatment delay (p<0.001). Recognition delay was more common in the episodes with in-hospital onset, which also had longer TTN and TTC, and increased morbidity. There were pervasive delays in all phases of NCSE management. Delays in hospital arrival or treatment initiation may result in prolonged TTC. Recognition of in-hospital episodes may be more delayed, which may lead to poorer prognosis in these cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus (Review).

PubMed

Prabhakar, Hemanshu; Bindra, Ashish; Singh, Gyaninder Pal; Kalaivani, Mani

2013-07-01

Failure to respond to antiepileptic drugs in uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (10 May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov, The South Asian Database of Controlled Clinical Trials, and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol. Two review authors screened the search results and reviewed abstracts of relevant and eligible trials before retrieving the full text publications. One study was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE and receiving either propofol or thiopental sodium for the control of seizure activity (Rossetti 2011). This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. There was no evidence of a difference between the drugs with respect to the outcome measures such as control of seizure activity and functional outcome at three months. There is lack of robust and randomised controlled evidence that can clarify the efficacy of propofol and thiopental sodium over each other in the treatment of RSE. There

CRE-Mediated Transcription and COX-2 Expression in the Pilocarpine Model of Status Epilepticus

PubMed Central

Lee, Boyoung; Dziema, Heather; Lee, Kyu Hyun; Choi, Yun-Sik; Obrietan, Karl

2007-01-01

Status epilepticus (SE) triggers neuronal death, reactive gliosis and remodeling of synaptic circuitry, thus leading to profound pathological alterations in CNS physiology. These processes are, in part, regulated by the rapid upregulation of both cytotoxic and cytoprotective genes. One pathway that may couple SE to transcriptionally-dependent alterations in CNS physiology is the CREB (cAMP response element-binding protein)/CRE (cAMP response element) cascade. Here, we utilized the pilocarpine model of SE on a mouse strain transgenic for a CRE-reporter construct (β-galactosidase) to begin to characterize how seizure activity regulates the activation state of the CREB/CRE pathway in both glia and neurons of the hippocampus. SE triggered a rapid (4–8 hrs post SE) but transient increase in CRE-mediated gene expression in the neuronal sublayers. In contrast to neurons, SE induced a lasting increase (up to 20 days) in CRE-mediated transcription in both reactive astrocytes and microglia. CRE-mediated gene expression correlated with expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2). To examine the role of CREB in SE-induced COX-2 expression, we generated a transgenic mouse strain that expresses A-CREB, a potent repressor of CREB-dependent transcription. In these animals, the capacity of SE to stimulate COX-2 expression was markedly attenuated, indicating that CREB is a key intermediate in SE-induced COX-2 expression. Collectively these data show that SE triggers two waves of CREB-mediated gene expression, a transient wave in neurons and a long-lasting wave in reactive glial cells, and that CREB couples SE to COX-2 expression. PMID:17029965

Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice

PubMed Central

Engelmann, Robby; Sellmann, Tina; Köhling, Rüdiger; Müller-Hilke, Brigitte

2017-01-01

Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4–5 weeks old C57BL/6 mice. Brains were removed at days 1–4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0–3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention. PMID:29182639

Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation

PubMed Central

Chak, Kayam; Roy-Chaudhuri, Biswajoy; Kim, Hak Kyun; Kemp, Kayla C; Kay, Mark A

2016-01-01

MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3′UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 following SE. Polysome profiling reveals co-localization of pre-miR-21 in the ribosome fraction with translating mRNAs in U-87 cells. The current work suggests that pre-miR-21 may post-transcriptionally counteract miR-21-mediated suppression following SE and could potentially lead to prolonged TGF-β receptor expression impacting epileptogenesis. The study further supports that the ratio of the pre to mature miRNA may be important in determining the regulatory effects of a miRNA gene. PMID:27725160

Posterior reversible encephalopathy syndrome with status epilepticus following surgery for lumbar stenosis and spondylolisthesis: case report.

PubMed

Delgado-López, Pedro David; Garcés-Pérez, Gloria; García-Carrasco, Juan; Alonso-García, Esther; Gómez-Menéndez, Ana Isabel; Martín-Alonso, Javier

2018-06-01

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological condition encountered in many different clinical settings, generally occurring in the context of hypertensive crisis, immunosuppressive therapy or autoimmune diseases. It is characterized by headache, stupor, seizures and visual alterations. MRI findings include white matter changes preferentially in the parieto-occipital regions. Although pathogenesis is not fully elucidated, vasoconstriction and brain hypoperfusion seem to be the cause of brain ischemia and vasogenic edema. CSF hypotension is also a reported plausible pathogenic mechanism. We present a unique case of PRES following laminectomy and fixation for L4-5 lumbar stenosis and spondylolisthesis. The patient presented with a 5-day duration status epilepticus immediately after surgery. Brain MRI showed FLAIR and T2 hyperintensities in the bilateral parietal and occipital lobes and external capsules. On the basis of her postoperative lumbar images, we hypothesize that an unnoticed CSF leak might have contributed to develop PRES in this case. The patient developed multiple postoperative complications. Following treatment for severe hypertension and seizures she ultimately recovered. Prompt recognition and treatment of this potentially life-threatening syndrome is necessary in order to increase the likelihood of favorable outcome. Spinal surgeons need to be aware of the possibility of neurological deterioration following spinal surgery and be alert about the occurrence of a dural leak, either recognized or unnoticed, as the plausible mechanism triggering PRES. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of tooth replacement on the nutritional status of partially dentate elders.

PubMed

McKenna, Gerald; Allen, P Finbarr; O'Mahony, Denis; Cronin, Michael; DaMata, Cristiane; Woods, Noel

2015-11-01

The aim of this study was to compare the impact of two different tooth replacement strategies on the nutritional status of partially dentate older patients. Nutritional status was measured using the full version of the Mini Nutritional Assessment (MNA) and the short form of the Mini Nutritional Assessment (MNA-SF). A randomised controlled clinical trial was conducted (Trial Registration no. ISRCTN26302774). Partially dentate patients aged 65 years and older were recruited and randomly allocated to the two different treatment groups: the removable partial dentures (RPD) group and the shortened dental arch (SDA) group. Nutritional status was measured using the MNA and MNA-SF administered at baseline and 1, 6 and 12 months after treatment intervention by a research nurse blinded to the treatment group allocation of all participants. Data collected using the full version of the MNA showed significant improvements in mean MNA scores over the length of the study (p < 0.05). For the entire patient group, there was a mean increase of 0.15 points at 6 months and a further increase of 0.19 points at 12 months. These increases were similar within the treatment groups (p > 0.05). For MNA-SF, the analysis showed that there were no significant differences recorded over the data collection points after treatment intervention (p < 0.05). Tooth replacement using conventional and functionally orientated treatment for the partially dentate elderly showed significant improvements in MNA score 12 months after intervention. Prosthodontic rehabilitation may play an important role in the nutritional status of partially dentate elders.

Non-convulsive seizures and non-convulsive status epilepticus monitoring in the intensive care unit. A real need for the Gulf Cooperation Council countries.

PubMed

Mesraoua, Boulenouar; Wieser, Heinz G

2009-10-01

Continuous EEG (cEEG) monitoring in the intensive care unit (ICU) is essential for detecting non-convulsive seizures/status epilepticus (NCSs, NCSE). Currently there exist a number of continuous EEG monitoring systems adapted for use in the ICU. However, these systems have been trained using EEG data collected from healthy, neurologically intact patients with epileptic seizures, a very different patient population from ICU patients. The review consists of 2 parts, clinical and technological aspects. In the first one, we summarize the electroencephalographic aspects of NCSs/NCSE and other EEG patterns encountered in the ICU. In the second part, we explain how to develop a novel cEEG monitoring system to be used in Hamad Medical Corporation ICUs, Doha, Qatar, that is able to detect pathological EEG patterns commonly occurring in the critically ill patient. Real-time monitoring of seizure discharges, and other pathological EEG patterns will allow correct diagnosis and adequate treatment in a timely fashion.

Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.

PubMed

Scorza, Carla A; Marques, Marcia J G; Gomes da Silva, Sérgio; Naffah-Mazzacoratti, Maria da Graça; Scorza, Fulvio A; Cavalheiro, Esper A

2018-03-06

Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and VEGF remained unchanged 24h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys. Copyright © 2017 Elsevier B.V. All rights reserved.

A case of Cefepime encephalopathy, being difficult to distinguish from non-convulsive status epilepticus during the treatment of bacterial meningitis.

PubMed

Toda, Yusuke; Yamazaki, Mineo; Ota, Tomohiro; Fujisawa, Yosuke; Kimura, Kazumi

2016-10-28

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

Estimating intracranial volume using intracranial area in healthy children and those with childhood status epilepticus

PubMed Central

Piper, Rory J; Yoong, Michael M; Pujar, Suresh; Chin, Richard F

2014-01-01

Background Correcting volumetric measurements of brain structures for intracranial volume (ICV) is important in comparing volumes across subjects with different ICV. The aim of this study was to investigate whether intracranial area (ICA) reliably predicts actual ICV in a healthy pediatric cohort and in children with convulsive status epilepticus (CSE). Methods T1-weighted volumetric MRI was performed on 20 healthy children (control group), 10 with CSE with structurally normal MRI (CSE/MR-), and 12 with CSE with structurally abnormal MRI (CSE/MR+). ICA, using a mid-sagittal slice, and the actual ICV were measured. Results A high Spearman correlation was found between the ICA and ICV measurements in the control (r = 0.96; P < 0.0001), CSE/MR− (r = 0.93; P = 0.0003), and CSE/MR+ (r = 0.94; P < 0.0001) groups. On comparison of predicted and actual ICV, there was no significant difference in the CSE/MR− group (P = 0.77). However, the comparison between predicted and actual ICV was significantly different in the CSE/MR+ (P = 0.001) group. Our Bland–Altman plot showed that the ICA method consistently overestimated ICV in children in the CSE/MR+ group, especially in those with small ICV or widespread structural abnormalities. Conclusions After further validation, ICA measurement may be a reliable alternative to measuring actual ICV when correcting volume measurements for ICV, even in children with localized MRI abnormalities. Caution should be applied when the method is used in children with small ICV and those with multilobar brain pathology. PMID:25365798

Modulation of CaM kinase II activity is coincident with induction of status epilepticus in the rat pilocarpine model.

PubMed

Singleton, Michael W; Holbert, William H; Lee, Anh Tuyet; Bracey, James M; Churn, Severn B

2005-09-01

This study was conducted to characterize the early cellular changes in CaM kinase II activity that occur during the induction of status epilepticus (SE). The pilocarpine model of SE was characterized both behaviorally and electrographically. At specific time points after the first discrete seizure, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. After the development of SE, the data show an immediate inhibition of both cortical and hippocampal CaM kinase II activity in homogenate, but a delayed inhibition in synaptic kinase activity. The maintenance of synaptic kinase activity was due to a translocation of CaM kinase II protein to the synapse. However, despite the translocation of functional kinase, CaM kinase II activity was not maintained, membrane potential was not restored, and the newly translocated CaM kinase II did not terminate the SE event. Unlike the homogenate samples, in the crude synaptoplasmic membrane (SPM) subcellular fractions, a positive correlation is found between the duration of SE and the inhibition of CaM kinase II activity in both the cortex and hippocampus. The data support the hypothesis that alterations of CaM kinase II activity are involved in the early events of SE pathology.

Chemokine CCL2–CCR2 Signaling Induces Neuronal Cell Death via STAT3 Activation and IL-1β Production after Status Epilepticus

PubMed Central

Tian, Dai-Shi; Feng, Li-Jie; Liu, Jun-Li

2017-01-01

Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2–CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1GFP/+:CCR2RFP/+ double-transgenic mice, we demonstrated that CCL2–CCR2 signaling has a role in resident microglial activation and blood-derived monocyte infiltration. Moreover, seizure-induced degeneration of neurons in the hippocampal CA3 region was attenuated in mice lacking CCL2 or CCR2. We further showed that CCR2 activation induced STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL-1β production, which are critical for promoting neuronal cell death after status epilepticus. Consistently, pharmacological inhibition of STAT3 by WP1066 reduced seizure-induced IL-1β production and subsequent neuronal death. Two weeks after KA-induced seizures, CCR2 deficiency not only reduced neuronal loss, but also attenuated seizure-induced behavioral impairments, including anxiety, memory decline, and recurrent seizure severity. Together, we demonstrated that CCL2–CCR2 signaling contributes to neurodegeneration via STAT3 activation and IL-1β production after status epilepticus, providing potential therapeutic targets for the treatment of epilepsy. SIGNIFICANCE STATEMENT Epilepsy is a global concern and epileptic seizures occur in many neurological conditions. Neuroinflammation associated with microglial activation and monocyte infiltration are characteristic of epileptic brains. However, molecular mechanisms underlying neuroinflammation in neuronal death following epilepsy remain to be elucidated. Here we demonstrate that CCL2–CCR2 signaling is

Risk Factors Associated with Death in In-Hospital Pediatric Convulsive Status Epilepticus

PubMed Central

Ramgopal, Sriram; Gulati, Deepak; Thanaviratananich, Sikawat; Kothare, Sanjeev V.; Alshekhlee, Amer; Koubeissi, Mohamad Z.

2012-01-01

Objective To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. Patients and Methods We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. Results We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE. Conclusion Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management. PMID:23110074

Perceived challenges to obtaining informed consent for a time-sensitive emergency department study of pediatric status epilepticus: results of two focus groups.

PubMed

Chamberlain, James M; Lillis, Kathleen; Vance, Cheryl; Brown, Kathleen M; Fawumi, Olubunmi; Nichols, Shari; Davis, Colleen O; Singh, Tasmeen; Baren, Jill M

2009-08-01

The objective was to describe the perspective of research personnel on issues of informed consent in a time-sensitive clinical study under emergency circumstances. The authors convened concurrent focus groups of research staff and investigators involved in a pharmacokinetic study of lorazepam for status epilepticus (SE). Moderators led discussion with open-ended questions on selected issues of parental consent, communication and understanding, patient assent, and comparison to other types of studies. Focus group transcripts were analyzed to identify themes and subthemes from the discussions. Most themes and subthemes were identified in both research staff and investigator focus groups. Focus group discussion points were categorized into three main themes: barriers to and enablers of informed consent, barriers to and enablers of actual enrollment, and overall ethical concerns about the research. Many of the issues identified were unique to emergency research. From the perspectives of research staff and investigators enrolling patients in a time-sensitive emergency department study, the authors identified several areas of concern that should be addressed when planning future emergency studies.

Status Epilepticus Secondary to Pseudonodular Hemorragic Occipital Lesion with Edema: "Non Semper Ea Sunt, Quae Videntur, Decipit Frons Prima Multos" (Things Are Not Always What They Seem; The First Appearance Deceives Many).

PubMed

Nasi, Davide; Servadei, Franco; Romano, Antonio

2017-08-01

We report a case in which common radiologic images masked a rare case of supratentorial hemangioblastoma (HBL). Other peculiarities of this case are the clinical presentation with status epilepticus and the occurrence of a supratentorial HBL unrelated to von Hippel-Lindau syndrome. Based on clinical and radiologic findings, including massive cerebral edema and hemorrhagic presentation, our preoperative diagnosis was a cerebral metastasis. In this scenario, physicians must take into account the words of the Roman fabulist Phaedrus: "Non semper ea sunt, quae videntur, decipit frons prima multos" (things are not always what they seem; the first appearance deceives many). Copyright © 2017 Elsevier Inc. All rights reserved.

Emergency electroencephalogram: Usefulness in the diagnosis of nonconvulsive status epilepticus by the on-call neurologist.

PubMed

Máñez Miró, J U; Díaz de Terán, F J; Alonso Singer, P; Aguilar-Amat Prior, M J

2018-03-01

We aim to describe the use of emergency electroencephalogram (EmEEG) by the on-call neurologist when nonconvulsive status epilepticus (NCSE) is suspected, and in other indications, in a tertiary hospital. Observational retrospective cohort study of emergency EEG (EmEEG) recordings with 8-channel systems performed and analysed by the on-call neurologist in the emergency department and in-hospital wards between July 2013 and May 2015. Variables recorded were sex, age, symptoms, first diagnosis, previous seizure and cause, previous stroke, cancer, brain computed tomography, diagnosis after EEG, treatment, patient progress, routine control EEG (rEEG), and final diagnosis. We analysed frequency data, sensitivity, and specificity in the diagnosis of NCSE. The study included 135 EEG recordings performed in 129 patients; 51.4% were men and their median age was 69 years. In 112 cases (83%), doctors ruled out suspected NCSE because of altered level of consciousness in 42 (37.5%), behavioural abnormalities in 38 (33.9%), and aphasia in 32 (28.5%). The EmEEG diagnosis was NCSE in 37 patients (33%), and this was confirmed in 35 (94.6%) as the final diagnosis. In 3 other cases, NCSE was the diagnosis on discharge as confirmed by rEEG although the EmEEG missed this condition at first. EmEEG performed to rule out NCSE showed 92.1% sensitivity, 97.2% specificity, a positive predictive value of 94.6%, and a negative predictive value of 96%. Our experience finds that, in an appropriate clinical context, EmEEG performed by the on-call neurologist is a sensitive and specific tool for diagnosing NCSE. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

5% Carbon Dioxide is safe but of limited efficacy as a treatment for paediatric non-convulsive status epilepticus: An open label observational study.

PubMed

Forsyth, Rob; Martland, Tim; Lai, Ming; Vadlamani, Gayatri; Hogan, Vanessa

2016-07-01

To establish the efficacy and tolerability of inhaled 5% carbon dioxide/95% oxygen as a treatment for paediatric non-convulsive status epilepticus (NCSE). In an open label clinical trial, children in NCSE were given high flow inhaled 5% carbon dioxide/95% oxygen by face mask for 120 s under EEG control. Six children (five male; ages 3-13; all with severe underlying epilepsy and disability) were recruited. Inhalation was well tolerated in all cases. Capillary blood gasses showed no significant derangements at the end of the inhalation. Effects on EEG normalisation were limited and transient, and no clinical improvements were noted. No adverse effects occurred. Inhaled 5% carbon dioxide/95% oxygen has been suggested as a potent, well tolerated anticonvulsant. An anticonvulsant without sedating and respiration-depressing effects would be particularly welcome in the management of NCSE where the justification for aggressive anticonvulsant therapy is often uncertain, however it appears that 5% carbon dioxide is of limited efficacy in this context. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Resistance of neurofilaments to degradation, and lack of neuronal death and mossy fiber sprouting after kainic acid-induced status epilepticus in the developing rat hippocampus.

PubMed

Lopez-Picon, Francisco; Puustinen, Niina; Kukko-Lukjanov, Tiina-Kaisa; Holopainen, Irma E

2004-12-01

Neurofilament (NF) proteins, the major constituent of intermediate filaments in neurons, have an important role in cellular stability and plasticity. We have now studied the short-term (hours) and long-term (up to 1 week) effects of kainic acid (KA)-induced status epilepticus (SE) on the reactivity of NF proteins, and mossy fiber (MF) sprouting and neuronal death up to 4 weeks in 9-day-old rats. In Western blotting, the expression of the phosphorylation-independent epitopes of NF-L, NF-M, and NF-H rapidly but transiently increased after the treatment, whereas the phosphorylated NF-M remained elevated for 7 days. However, the treatment did not change the immunoreactivity of NF proteins, and no neuronal death or mossy fiber sprouting was detected at any time point. Our findings indicate seizure-induced reactivity of NF proteins but their resistance to degradation, which could be of importance in neuronal survival and may also prevent MF sprouting in the developing hippocampus.

Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

PubMed

Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

2015-01-05

In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population.

PubMed

Welch, Robert D; Nicholas, Katherine; Durkalski-Mauldin, Valerie L; Lowenstein, Daniel H; Conwit, Robin; Mahajan, Prashant V; Lewandowski, Christopher; Silbergleit, Robert

2015-02-01

To examine the effectiveness of intramuscular (IM) midazolam versus intravenous (IV) lorazepam for the treatment of pediatric patients with status epilepticus (SE) in the prehospital care setting. This multicenter clinical trial randomized patients diagnosed with SE to receive either IM midazolam or IV lorazepam administered by paramedics in the prehospital care setting. Included in this secondary analysis were only patients younger than 18 years of age. Evaluated were the associations of the treatment group (IM vs. IV) with the primary outcome, defined as seizure cessation prior to emergency department (ED) arrival, and with patient characteristics, time to important events, and adverse events. Descriptive statistics and 99% confidence intervals (CIs) were used for the analysis. Of 893 primary study subjects, 120 met criteria for this study (60 in each treatment group). There were no differences in important baseline characteristics or seizure etiologies between groups. The primary outcome was met in 41 (68.3%) and 43 (71.7%) of subjects in the IM and IV groups, respectively (risk difference [RD] -3.3%, 99% CI -24.9% to 18.2%). Similar results were noted for those younger than 11 years (RD -1.3%, 99% CI -25.7% to 23.1%). Time from initiating the treatment protocol was shorter for children who received IM midazolam, mainly due to the shorter time to administer the active treatment. Safety profiles were similar. IM midazolam can be rapidly administered and appears to be safe and effective for the management of children with SE treated in the prehospital setting. The results must be interpreted in the context of the secondary analysis design and sample size of the study. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

PubMed

Prabhakar, Hemanshu; Kalaivani, Mani

2015-06-25

This is an updated version of the original Cochrane review published in Issue 8, 2012.Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcome. To compare the efficacy, adverse effects, and short- and long-term outcomes of RSE treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (26 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, February 2015) and MEDLINE (1946 to 26 March 2015). We also searched ClinicalTrials.gov (26 March 2015), the South Asian Database of Controlled Clinical Trials and IndMED (a bibliographic database of Indian Medical Journals). All randomised or quasi-randomised controlled studies (regardless of blinding) of control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study cannot be considered of high methodological quality. This study was terminated early due to recruitment problems. This study showed a wide confidence interval suggesting that the drugs may differ in efficacy up to more than two-fold. Days of mechanical ventilation were more in patients

Differential changes in mGlu2 and mGlu3 gene expression following pilocarpine-induced status epilepticus: A comparative real-time PCR analysis

PubMed Central

Ermolinsky, Boris; Pacheco Otalora, Luis F.; Arshadmansab, Massoud F.; Zarei, Masoud; Garrido-Sanabria, Emilio R.

2008-01-01

Group II metabotropic glutamate (mGlu II) receptors subtype 2 and 3 (mGlu2 and mGlu3) are subtle regulators of neuronal excitability and synaptic plasticity in the hippocampus. In recent years, researchers have investigated the potential neuroprotective and anticonvulsant effects of compounds acting on mGlu II receptors. However, abnormal expression and function of mGlu2 and mGlu3 have been reported in temporal lobe epilepsy, a phenomena that may limit the therapeutic effectiveness of these potentially new antiepileptic drugs. Here, we investigated seizure-induced changes in mGlu2 and mGlu3 mRNA following pilocarpine-inducted status epilepticus (SE) and subsequent epileptogenesis. Relative changes in gene expression were assessed by comparative analysis of quantitative real-time PCR (qrtPCR) by the delta-delta CT method. Pilocarpine-treated and control rats were sacrificed at different periods (24h, 10 days, one month and more than two months) following SE. Total RNA was isolated from microdissected dentate gyrus and processed for RT-PCR and qrtPCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an endogenous control gene. Analysis of relative quantification (RQ) ratios of mGlu2 and mGlu3 mRNA expression revealed a significant down-regulation of both targets at 24h after SE. Gene expression partially recovered at 10 days following SE reaching control levels at one month after SE. Two month after SE, mGlu2 mRNA expression was significantly down-regulated to ~41% of control expression whereas mGlu3 mRNA was comparable to control levels. Our data indicate that mGlu2 and mGlu3 expression is dynamically down-regulated or selectively enhanced during critical periods of epileptogenesis. Seizure-induced differential dysregulation of mGlu2 and mGlu3 receptors may affect the availability of these molecular targets for therapeutic compounds in epilepsy. PMID:18585369

Upregulation of Krüppel-like factor 6 in the mouse hippocampus after pilocarpine-induced status epilepticus.

PubMed

Jeong, K H; Lee, K-E; Kim, S Y; Cho, K-O

2011-07-14

Krüppel-like factor 6 (KLF6) is a transcriptional regulator involved in a broad range of cellular processes. To date, however, the expression of KLF6 in brains with pathophysiological conditions, such as epilepsy, has not been reported. Therefore, the present study investigated the temporal pattern of KLF6 expression in the mouse hippocampus and identified cell types expressing KLF6 after pilocarpine-induced status epilepticus (SE). Seizures were induced by administrating pilocarpine hydrochloride (280 mg/kg, i.p.) 30 min after an injection of atropine methyl nitrate (3 mg/kg, i.p.). Pilocarpine- and saline-injected animals were sacrificed 1, 3, 7, 14, or 28 days after the onset of SE. Immunohistochemistry showed that the proportion of KLF6-positive cells increased in the hippocampus 1 day after SE onset, peaked at 3 days after SE, and then gradually decreased until 28 days after SE, consistent with the results from our immunoblot analysis. Cells expressing increased levels of KLF6 following pilocarpine-induced SE also expressed GFAP and Ox-42, markers for astrocytes and microglia, respectively. Quantitative analysis revealed that astrocytes were the major type of KLF6-expressing glial cells. These cells also expressed heat shock protein 47 (HSP47), a collagen-specific molecular chaperone. This is the first report showing that KLF6 is inducible in the hippocampus and may be associated with glial responses, especially HSP47-related tissue remodeling after pilocarpine-induced SE. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

TRPC3- and ETB receptor-mediated PI3K/AKT activation induces vasogenic edema formation following status epilepticus.

PubMed

Kim, Ji-Eun; Kang, Tae-Cheon

2017-10-01

Status epilepticus (SE, a prolonged seizure activity) is a high risk factor of developing vasogenic edema, which leads to secondary complications following SE. In the present study, we investigated whether transient receptor potential canonical channel-3 (TRPC3) may link vascular endothelial growth factor (VEGF) pathway to NFκB/ET B receptor axis in the rat piriform cortex during vasogenic edema formation. Following SE, TRPC3 and ET B receptor independently activated phosphatidylinositol 3 kinase (PI3K)/AKT/eNOS signaling pathway. SN50 (a NFκB inhibitor) attenuated the up-regulations of eNOS, TRPC3 and ET B receptor expressions following SE, accompanied by reductions in PI3K/AKT phosphorylations. Inhibition of SE-induced VEGF over-expression by leptomycin B also abrogated PI3K and AKT phosphorylations, but not TRPC3 expression. Wortmannin (a PI3K inhibitor) and 3CAI (an AKT inhibitor) effectively inhibited up-regulation of eNOS expressions and vasogenic edema lesion following SE. These findings indicate that PI3K/AKT may be common down-stream molecules for TRPC3- and ET B receptor signaling pathways during vasogenic edema formation. In addition, the present data demonstrate for the first time that TRPC3 may integrate VEGF- and NFκB-mediated vasogenic edema formation following SE. Thus, we suggest that PI3K/AKT signaling pathway may be one of considerable therapeutic targets for vasogenic edema. Copyright © 2017 Elsevier B.V. All rights reserved.

TRPC3 channels play a critical role in the theta component of pilocarpine-induced Status Epilepticus in mice

PubMed Central

Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2016-01-01

Summary Objective Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the BDNF/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced Status Epilepticus (SE). Methods The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and EEG recording of pilocarpine-induced seizures were performed. Results We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity which dominates both the pre-ictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anti-convulsive drugs. PMID:28012173

Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.

1992-12-31

The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions andmore » electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.« less

Association of Physical and Technical Activities With Partial Match Status in a Soccer Professional Team.

PubMed

Moalla, Wassim; Fessi, Mohamed Saieffedin; Makni, Emna; Dellal, Alexandre; Filetti, Cristoforo; Di Salvo, Valter; Chamari, Karim

2018-06-01

Moalla, W, Fessi, MS, Makni, E, Dellal, A, Filetti, C, Di Salvo, V, and Chamari, K. Association of physical and technical activities with partial match status in a soccer professional team. J Strength Cond Res 32(6): 1708-1714, 2018-The purpose of this study was to examine the association between physical and technical activities and partial match status (winning, drawing, or losing) in a professional soccer team over 2 seasons. Physical and technical activities of 52 official matches were collected and analyzed at each 15-minute interval, for each half (45 minutes), and full match (90 minutes) using a multiple-camera computerized tracking system. The results indicated that according to full match outcome: winning status was characterized by players covering more total distance (p ≤ 0.05) and low-intensity running (<14.4 km·h) (p ≤ 0.05), whereas, losing status induced more sprinting (≥25.2 km·h) (p < 0.01) and high-intensity running (≥19.8 km·h) (p ≤ 0.05). However, according to partial match status (i.e., 15 minutes and half time), players covered more distance for all running intensities while winning (p < 0.01). Technical match performance scores were not influenced by match status. In conclusion, the present study showed that the physical activities including high-intensity running and total distance covered were related to the match status, whereas technical activities were not. The overall outcome shows that higher physical activity was associated with winning partial match periods. This approach highlights the importance of physical fitness in soccer and may help coaches to better modulate players' roles and team tactical organization throughout the match.

In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy.

PubMed

van Eijsden, Pieter; Otte, Wim M; van der Hel, W Saskia; van Nieuwenhuizen, Onno; Dijkhuizen, Rick M; de Graaf, Robin A; Braun, Kees P J

2011-04-01

Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine-induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ₁) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ₁ decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ₁ and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Impact of tooth replacement strategies on the nutritional status of partially-dentate elders.

PubMed

McKenna, Gerald; Allen, Patrick Finbarr; Flynn, Albert; O'Mahony, Denis; DaMata, Cristiane; Cronin, Michael; Woods, Noel

2012-06-01

To investigate the impact of tooth replacement on the nutritional status of partially dentate older patients, and, to compare two different tooth replacement strategies; conventional treatment using removable partial dentures and functionally orientated treatment based on the shortened dental arch. Amongst older patients, diet plays a key role in disease prevention, as poor diets have been linked to numerous illnesses. Poor oral health and loss of teeth can have very significant negative effects on dietary intake and nutritional status for elderly patients. There is evidence that good oral health generally, has positive effects on the nutritional intake of older adults. A randomised, controlled clinical trial was designed to investigate the impact of tooth replacement on the nutritional status of partially dentate elders. Forty-four patients aged over 65 years completed the trial, with 21 allocated to conventional treatment and 23 allocated to functionally orientated treatment. Nutritional status was accessed at baseline and after treatment using the Mini Nutritional Assessment (MNA) and a range of haematological markers. At baseline, relationships were observed between the number of occluding tooth contacts and some measures of nutritional status. As the number of contacts increased, MNA scores (R = 0.16), in addition to vitamin B12 (R = 0.21), serum folate (R = 0.32) and total lymphocyte count (R = 0.35), also increased. After treatment intervention, the only measure of nutritional status that showed a statistically significant improvement for both treatment groups was MNA score (p = 0.03). No significant between group differences were observed from analysis of the haematological data. In this study, prosthodontic rehabilitation with both conventional treatment and functionally orientated treatment resulted in an improvement in MNA score. Haematological markers did not illustrate a clear picture of improvement in nutritional status for either treatment group. �

Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus.

PubMed

Brigo, Francesco; Bragazzi, Nicola; Nardone, Raffaele; Trinka, Eugen

2016-11-01

The aim of this study was to conduct a meta-analysis of published studies to directly compare intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) or IV valproate (VPA) as second-line treatment of status epilepticus (SE), to indirectly compare intravenous IV LEV with IV VPA using common reference-based indirect comparison meta-analysis, and to verify whether results of indirect comparisons are consistent with results of head-to-head randomized controlled trials (RCTs) directly comparing IV LEV with IV VPA. Random-effects Mantel-Haenszel meta-analyses to obtain odds ratios (ORs) for efficacy and safety of LEV versus VPA and LEV or VPA versus PHT were used. Adjusted indirect comparisons between LEV and VPA were used. Two RCTs comparing LEV with PHT (144 episodes of SE) and 3 RCTs comparing VPA with PHT (227 episodes of SE) were included. Direct comparisons showed no difference in clinical seizure cessation, neither between VPA and PHT (OR: 1.07; 95% CI: 0.57 to 2.03) nor between LEV and PHT (OR: 1.18; 95% CI: 0.50 to 2.79). Indirect comparisons showed no difference between LEV and VPA for clinical seizure cessation (OR: 1.16; 95% CI: 0.45 to 2.97). Results of indirect comparisons are consistent with results of a recent RCT directly comparing LEV with VPA. The absence of a statistically significant difference in direct and indirect comparisons is due to the lack of sufficient statistical power to detect a difference. Conducting a RCT that has not enough people to detect a clinically important difference or to estimate an effect with sufficient precision can be regarded a waste of time and resources and may raise several ethical concerns, especially in RCT on SE. Copyright © 2016 Elsevier Inc. All rights reserved.

An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome.

PubMed

Kim, Tae-Kyoung; Jung, Eui Sung; Park, Jong-Moo; Kang, Kyusik; Lee, Woong-Woo; Lee, Jung-Ju

2016-06-01

Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion.

A rare cause of status epilepticus; alpha lipoic acid intoxication, case report and review of the literature.

PubMed

Tolunay, Orkun; Çelik, Tamer; Kömür, Mustafa; Gezgin, Ali Emre; Kaya, Musa Soner; Çelik, Ümit

2015-11-01

Alpha lipoic acid is a powerful antioxidant widely used for the supplementary treatment of diabetic neuropathy. Intoxication with alpha lipoic acid is very rare. There is no reported dose of safety in children. A 14-month-old previously healthy girl was referred to our hospital with the diagnosis of drug intoxication. She was admitted to the emergency department with lethargy and continuing involuntary movements for several hours after she had ingested an unknown amount of alpha lipoic acid. On admission she was lethargic and had myoclonic seizures involving all extremities. She had no fever and laboratory examinations were normal except for mild metabolic acidosis. The seizures were unresponsive to bolus midazolam, phenytoin infusion and levetiracetam infusion. She was taken to the pediatric intensive care unit with the diagnosis of status epilepticus. After failure of the treatment with midazolam infusion she was intubated and thiopental sodium infusion was started. Her myoclonic seizures were controlled with thiopental sodium infusion. After 48 h intubation and mechanical ventilation thiopental sodium was gradually reduced and then stopped. Following the withdraw of thiopental sodium, she was seizure free on her discharge on the 8th day. Alpha lipoic acid and derivatives cause side effects in children like refractory convulsions. They are frequently rendered as vitamins by diabetic patients and are left at places where children can easily access them. Therefore, when faced with refractory convulsions in children who have had no disease before, intoxication by medicaments with alpha lipoic acid should be taken into consideration. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Incidence of status epilepticus in southern Europe: a population study in the health district of Ferrara, Italy.

PubMed

Govoni, Vittorio; Fallica, Elisa; Monetti, Vincenza Cinzia; Guerzoni, Franco; Faggioli, Raffaella; Casetta, Ilaria; Granieri, Enrico

2008-01-01

The epidemiologic features of status epilepticus (SE) are still in the course of definition. We carried out an intensive survey of multiple sources of case material in the resident population of the health district of Ferrara, Italy, in 2003. Information was collected on age, gender, duration, seizure type and etiology of SE. The age- adjusted annual incidence rate of SE was 27.2/100,000 (95% CI = 19.4-36.9) and it was higher in men (41.7/100,000, 95% CI = 26.9-61.7) than in women (12.3/100,000, 95% CI = 6.9-20.4). The incidence was higher in the elderly (older than 60 years, 39.2/100,000) than in younger adults in the age group 20-59 years (14.7/100,000). The age-specific incidence showed a bimodal distribution peaking in the youngest (0-4 years) and in the oldest age group (75+ years). Cerebrovascular disease was the most frequent etiologic factor (45%). Epilepsy had previously been diagnosed in 40% of the patients. The case fatality was 5%. The study found a higher incidence of SE than that expected on the basis of the previous European studies suggesting that the risk of SE in southern Europe is higher and more similar to that estimated in population studies in the United States. The case fatality was lower than that reported in previous South-European population studies despite the similar clinical features of the patients. Indirect evidence suggests that several factors related to the SE management could have positively influenced the outcome. Copyright 2007 S. Karger AG, Basel.

The efficacy of intravenous sodium valproate and phenytoin as the first-line treatment in status epilepticus: a comparison study

PubMed Central

2013-01-01

Background Status epilepticus (SE) is a serious neurological condition and requires prompt treatment. Sodium valproate has been used to treat SE successfully but its role as the first-line antiepileptic drug (AED) is still controversial. This study evaluated the efficacy of intravenous sodium valproate to determine if it is non-inferior to intravenous phenytoin in SE treatment. Methods Patients diagnosed as SE during 2003–2010 who were of an age of more than 15 years and received either intravenous sodium valproate or intravenous phenytoin as the first-line treatment were enrolled. Clinical characteristics and outcomes of SE were recorded and analyzed. The differences of outcomes between sodium valproate and phenytoin group were determined by descriptive statistics. Results During the study period, there were 37 and 17 SE patients who received intravenous phenytoin and intravenous sodium valproate as the first-line treatment, respectively. All patients received diazepam 10 mg intravenously as a rescue medication before starting the antiepileptic agents if uncontrolled except one patient in the sodium valproate group. There were no significant differences between the phenytoin and sodium valproate groups in all outcome variables including numbers of patients with clinically-controlled seizures, non-dependent patients, time to seizure control, and duration of hospitalization, and death. No serious cardiovasculars event such as hypotension occurred in either group. Conclusion Intravenous sodium valproate is non-inferior to intravenous phenytoin as the first-line treatment in SE with no significant cardiovascular compromises. PMID:23889906

Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway.

PubMed

Xu, Kai-Liang; Liu, Xin-Qiu; Yao, Yu-Long; Ye, Ming-Rong; Han, Yao-Guo; Zhang, Tao; Chen, Gang; Lei, Ming

2018-01-01

Convulsive status epilepticus (CSE) is a neurological disease with contraction and extension of limbs, leading to damage of hippocampus and cognition. This study aimed to explore the effects of dexmedetomidine (DEX) on the cognitive function and neuroinflammation in CSE rats. All rats were divided into control group, CSE group and DEX group. Morris water maze test was used to measure cognitive function. Acute hippocampal slices were made to detect long-term potentiation (LTP). Immunohistochemistry was used to determine the expression of α7-nicotinic acetylcholine receptor (α7-nAChR) and interleukin-1β (IL-1β). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of IL-1β, tumor necrosis factor-α (TNF-α), S-100β and brain-derived neurotrophic factor (BDNF). Our results showed that DEX improved the memory damage caused by CSE. DEX reduced seizure severity and increased the amplitudes and sustainable time of LTP, and also inhibited the hippocampal expression of α7-nAChR and IL-1β in CSE rats. DEX treatment decreased serum IL-1β, TNF-α and S-100β levels and increased BDNF levels. The effects of DEX on seizure severity and LTP could be simulated by nicotine or attenuated by concurrent α-bungarotoxin (α-BGT) treatment. In conclusions, DEX significantly improved spatial cognitive dysfunction, reduced seizure severity and increased LTP in CSE rats. Improvements by DEX were closely related to enhancement of cholinergic anti-inflammatory pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Refractory Status Epilepticus in Children: intention-to-treat with continuous infusions of midazolam and pentobarbital

PubMed Central

Tasker, Robert C; Goodkin, Howard P; Fernández, Iván Sánchez; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-01-01

Objective To describe pediatric patients with convulsive refractory status epilepticus (RSE) in whom there is intention-to-use an intravenous anesthetic for seizure control. Design Two-year prospective observational study evaluating patients (age range one month to 21 years) with RSE not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Setting Nine pediatric hospitals in the United States. Patients In a cohort of 111 patients with RSE (median age 3.7 years, 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. Main Results The median (interquartile range, IQR) intensive care unit length-of-stay was 10 (3–20) days. Up to four ‘cycles’ of serial anesthetic therapy were used and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9–34) hours for the first cycle, and longer when a second cycle was required (30 [4,−120] hours, p=0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam non-responders, transition to a second agent occurred after a median of one day. Most patients (94%) experienced seizure termination with these two therapies. Conclusions Midazolam and pentobarbital remains the mainstay of continuous infusion therapy for RSE in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure

The role of necroptosis in status epilepticus-induced brain injury in juvenile rats.

PubMed

Cai, Qianyun; Gan, Jing; Luo, Rong; Qu, Yi; Li, Shiping; Wan, Chaomin; Mu, Dezhi

2017-10-01

To study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction. The lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons. Western blot and immunofluorescence (IF) staining were used to investigate the expression of receptor interacting protein kinase-3 (RIP3), mixed lineage kinase domain-like (MLKL), and p-MLKL after SE. EEG was monitored during the chronic epileptic period. The Morris water maze test was performed to evaluate spatial learning and memory in juvenile rats after SE. Massive PI-positive (PI + ) neurocytes were observed mainly in the amygdala and piriform cortex 24h to 7days after SE, with the most prominent changes observed after 72h. Injured neurons observed via TEM exhibited necroptotic morphological features, including loss of ribosomes, autophagosome formations, deformed nuclei with condensed and marginated chromatin, and disruptive cell membranes. The expression of RIP3 and p-MLKL increased after 24h, peaked at 72h, and decreased 7days after SE. In addition, IF staining revealed that MLKL was expressed in cell plasma membranes present in the amygdala and piriform cortex. This finding was concomitant with the fact that MLKL is involved in executing necroptosis by binding and disrupting the plasma membrane. During the chronic epileptic period, spontaneous recurrent seizures were observed behaviorally and interictal spikes and sharp waves were recorded by EEG in the SE group. The Morris water maze test revealed that in the place navigation test, the escape latency of the SE group was longer than that of the control group (p<0.05). In the spatial probe test, the number of times the rats in the SE group passed through the

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2012-07-01

2012.235820. Third goal was to test whether drugs that open M channels wouterminate status epilepticus induced by an organophosphate and cholinergic...agonist (Li/Pilocarpine). Two modelof organophasphate-induced seizures were characterized and published: Characterization of status epilepticus induced...terminates refractory status epilepticus in two models. . 15. SUBJECT TERMS- Seizures, status epilepticus Cholinergic, M Current, Synaptoic

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

PubMed Central

Carter, Dawn S.; Harrison, Anne J.; Falenski, Katherine W.; Blair, Robert E.; DeLorenzo, Robert J.

2010-01-01

Summary Acquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca2+ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca2+ homeostasis is the neuronal calcium binding protein, calbindin-D28k that serves to buffer and transport Ca2+ ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca2+ homeostasis associated with AE. PMID:18394865

Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.

PubMed

Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

2015-05-22

The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events. Copyright © 2015 Elsevier B.V. All rights reserved.

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2015-07-01

susceptibility of mouse strain to pilocarpine-induced status epilepticus and seizure-induced excitotoxic cell death[1]. Therefore, we optimized and fully...University). For the induction of status epilepticus animals received methylscopolamine nitrate (0.1 mg/kg in saline, s.c.) thirty minutes before...animals entering status epilepticus and 80% survival rate. After animals entered status epilepticus , a second dose of methylscopolamine was

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2015-07-01

mouse strain to pilocarpine-induced status epilepticus and seizure- induced excitotoxic cell death [1]. Therefore, in close collaboration with the...Laboratory (kind gift of Dr. Venkatesh Murthy, Harvard University). For the induction of status epilepticus animals received methylscopolamine nitrate...The dose used was most efficient, yielding 90% of animals entering status epilepticus and 80% survival rate. After animals entered status epilepticus

Uppermost synchronized generators of spike-wave activity are localized in limbic cortical areas in late-onset absence status epilepticus.

PubMed

Piros, Palma; Puskas, Szilvia; Emri, Miklos; Opposits, Gabor; Spisak, Tamas; Fekete, Istvan; Clemens, Bela

2014-03-01

Absence status (AS) epilepticus with generalized spike-wave pattern is frequently found in severely ill patients in whom several disease states co-exist. The cortical generators of the ictal EEG pattern and EEG functional connectivity (EEGfC) of this condition are unknown. The present study investigated the localization of the uppermost synchronized generators of spike-wave activity in AS. Seven patients with late-onset AS were investigated by EEG spectral analysis, LORETA (Low Resolution Electromagnetic Tomography) source imaging, and LSC (LORETA Source Correlation) analysis, which estimates cortico-cortical EEGfC among 23 ROIs (regions of interest) in each hemisphere. All the patients showed generalized ictal EEG activity. Maximum Z-scored spectral power was found in the 1-6 Hz and 12-14 Hz frequency bands. LORETA showed that the uppermost synchronized generators of 1-6 Hz band activity were localized in frontal and temporal cortical areas that are parts of the limbic system. For the 12-14 Hz band, abnormally synchronized generators were found in the antero-medial frontal cortex. Unlike the rather stereotyped spectral and LORETA findings, the individual EEGfC patterns were very dissimilar. The findings are discussed in the context of nonconvulsive seizure types and the role of the underlying cortical areas in late-onset AS. The diversity of the EEGfC patterns remains an enigma. Localizing the cortical generators of the EEG patterns contributes to understanding the neurophysiology of the condition. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Development of status epilepticus, sustained calcium elevations and neuronal injury in a rat survival model of lethal paraoxon intoxication

PubMed Central

Deshpande, Laxmikant S.; Carter, Dawn S.; Phillips, Kristin F.; Blair, Robert E.; DeLorenzo, Robert J.

2014-01-01

Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague-Dawley rats injected with POX (4 mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6–8 min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7–10 Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2 mg/kg, i.p., 2-PAM, 25 mg/kg, i.m. and diazepam, 5 mg/kg, i.p.) promptly stopped SE and reduced acute mortality to 12% and chronic mortality to 18%. This model is ideally suited to test effective countermeasures against lethal POX exposure. Animals that survived the POX SE manifested prolonged elevations in hippocampal [Ca2+]i (Ca2+ plateau) and significant multifocal neuronal injury. POX SE induced Ca2+ plateau had its origin in Ca2+ release from intracellular Ca2+ stores since inhibition of ryanodine/ IP3 receptor lowered elevated Ca2+ levels post SE. POX SE induced neuronal injury and alterations in Ca2+ dynamics may underlie some of the long term morbidity associated with OP toxicity. PMID:24785379

HMGB1 regulates P-glycoprotein expression in status epilepticus rat brains via the RAGE/NF-κB signaling pathway

PubMed Central

Xie, Yuan; Yu, Nian; Chen, Yan; Zhang, Kang; Ma, Hai-Yan; Di, Qing

2017-01-01

Overexpression of P-glycoprotein (P-gp) in the brain is an important mechanism involved in drug-resistant epilepsy (DRE). High-mobility group box 1 (HMGB1), an inflammatory cytokine, significantly increases following seizures and may be involved in upregulation of P-gp. However, the underlying mechanisms remain elusive. The aim of the present study was to evaluate the role of HMGB1 and its downstream signaling components, receptor for advanced glycation end-product (RAGE) and nuclear factor-κB (NF-κB), on P-gp expression in rat brains during status epilepticus (SE). Small interfering RNA (siRNA) was administered to rats prior to induction of SE by pilocarpine, to block transcription of the genes encoding HMGB1 and RAGE, respectively. An inhibitor of NF-κB, pyrrolidinedithiocarbamic acid (PDTC), was utilized to inhibit activation of NF-κB. The expression levels of HMGB1, RAGE, phosphorylated-NF-κB p65 (p-p65) and P-gp were detected by western blotting. The relative mRNA expression levels of the genes encoding these proteins were measured using reverse transcription-quantitative polymerase chain reaction and the cellular localization of the proteins was determined by immunofluorescence. Pre-treatment with HMGB1 siRNA reduced the expression levels of RAGE, p-p65 and P-gp. PDTC reduced the expression levels of P-gp. These findings suggested that overexpression of P-gp during seizures may be regulated by HMGB1 via the RAGE/NF-κB signaling pathway, and may be a novel target for treating DRE. PMID:28627626

Early life status epilepticus and stress have distinct and sex-specific effects on learning, subsequent seizure outcomes, including anticonvulsant response to phenobarbital.

PubMed

Akman, Ozlem; Moshé, Solomon L; Galanopoulou, Aristea S

2015-02-01

Neonatal status epilepticus (SE) is often associated with adverse cognitive and epilepsy outcomes. We investigate the effects of three episodes of kainic acid-induced SE (3KA-SE) and maternal separation in immature rats on subsequent learning, seizure susceptibility, and consequences, and the anticonvulsant effects of phenobarbital, according to sex, type, and age at early life (EL) event. 3KA-SE or maternal separation was induced on postnatal days (PN) 4-6 or 14-16. Rats were tested on Barnes maze (PN16-19), or lithium-pilocarpine SE (PN19) or flurothyl seizures (PN32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury. 3KA-SE or separation on PN4-6 caused more transient learning delays in males and did not alter lithium-pilocarpine SE latencies, but aggravated its outcomes in females. Anticonvulsant effects of phenobarbital were preserved and potentiated in specific groups depending on sex, type, and age at EL event. Early life 3KA-SE and maternal separation cause more but transient cognitive deficits in males but aggravate the consequences of subsequent lithium-pilocarpine SE in females. In contrast, on flurothyl seizures, EL events showed either beneficial or no effect, depending on gender, type, and age at EL events. © 2014 John Wiley & Sons Ltd.

Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy After Traumatic Brain Injury

DTIC Science & Technology

2014-10-01

developed status epilepticus (Figure 1) which continued for 3 days resulting in the animal’s death. Spontaneous recurrent seizures were recorded in 3...recording of a CCI-injured mouse in status epilepticus . Upper trace is an EEG recording of 4 h of status epilepticus while the lower traces...seizure (b) and the continuous spiking evident of status epilepticus (c). * represents movement artifact from the seizure motor activity. Although we

Observational study of intravenous lacosamide in patients with convulsive versus non-convulsive status epilepticus.

PubMed

Moreno Morales, Eros Yamel; Fernandez Peleteiro, Manuel; Bondy Peña, Ernesto Carlo; Domínguez Lorenzo, Jose Maria; Pardellas Santiago, Elva; Fernández, Anxo

2015-07-01

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

Determinants and predictors of outcome in super refractory status epilepticus--a developing country perspective.

PubMed

Jayalakshmi, Sita; Ruikar, Devashish; Vooturi, Sudhindra; Alladi, Suvarna; Sahu, Sambit; Kaul, Subhash; Mohandas, Surath

2014-11-01

Super refractory status epilepticus (SRSE) is a recent entity. There is limited information about the etiology and outcome of SRSE from developing countries. We evaluated determinants and predictors of outcome in patients with convulsive SRSE in Indian population. In this open cohort study, data of patients with convulsive SE admitted in neurointensive care unit (NICU) from 2005 to 2013 was retrospectively analyzed. Regression and survival analysis was done for outcome of patients divided into non refractory SE (NRSE), refractory SE (RSE), and SRSE groups. The primary outcome for analysis was in hospital mortality. Also functional outcome at 6 months was graded according to the Glasgow outcome scale (GOS), and classified as good (GOS 4 and 5) and poor (GOS 1, 2 and 3) outcome groups. Out of 177 patients with SE, 105 (59.3%) had NRSE; 72 (40.7%) had RSE of which 30 (16.9% of 177) were sub-classified as SRSE. SRSE was frequent (39%) in children (p<0.01), elderly (21.7%; p<0.003), and in incident SE (82.1%, p=0.05). Encephalitis was the commonest etiology in RSE (30.9%, p=0.015), SRSE (66.7%, p<0.001) than NRSE (12.3%). Encephalitis (β=8.250 (1.8-37.82); p=0.007) was the determinant of the progression of SE to SRSE. Overall mortality was 19.2%, highest in SRSE (40.0%) followed by RSE (35.7%), both significantly (p<0.001) higher than NRSE (6.7%). Mortality was high in patients with encephalitis than other etiologies (39.1% vs. 12.1%; p=0.001). Acidosis predicted mortality in the entire cohort (β=7.313 (1.6-32.58); p=0.009); however none of the variables predicted mortality in SRSE patients. At 6 months follow up only 33.3% of patients with SRSE were in GOS good outcome group when compared to RSE (33.3% vs. 57.1%; p=0.055), and NRSE (33.3% vs. 79.1%; p<0.0001). SRSE is common in children, elderly, and incident SE. Encephalitis was the determinant of progression of SE to SRSE. None of the variables predicted mortality in SRSE patients. Sixty percent of patients with

The Synergistic Effect of Raloxifene, Fluoxetine, and Bromocriptine Protects Against Pilocarpine-Induced Status Epilepticus and Temporal Lobe Epilepsy.

PubMed

Pottoo, Faheem Hyder; Tabassum, Nahida; Javed, Md Noushad; Nigar, Shah; Rasheed, Rouqia; Khan, Ayash; Barkat, Md Abul; Alam, Md Sabir; Maqbool, Amir; Ansari, Mohammad Azam; Barreto, George E; Ashraf, Ghulam Md

2018-06-07

The present antiepileptic drugs pose several problems in the management of seizures owing to their meager neuroprotective potential, adverse effects on bone, detrimental effects on cognitive function, chronic toxicity, drug interactions, side effects including aggression, agitation, and irritability and sometimes exacerbation of seizures. We followed up progressive preclinical investigation in mice against pilocarpine (PILO)-induced status epilepticus (SE) and temporal lobe epilepsy (TLE). To determine the response of raloxifene (RF) (4 and 8 mg/kg), fluoxetine (FT) (14 and 22 mg/kg), bromocriptine (BC) (6 and 10 mg/kg), and their low-dose combinations, oral treatment was scheduled for 28 days followed by PILO (300 mg/kg, i.p). The response was stalked for intensive behavioral monitoring of convulsions, hippocampal neuropeptide Y (NPY), and oxidative stress discernment along with histomorphological studies. The resultant data confirmed the therapeutic potential of triple drug combination of raloxifene (4 mg/kg) with fluoxetine (14 mg/kg) and bromocriptine (6 mg/kg) compared to monotherapy with raloxifene (4 mg/kg), and bromocriptine (6 mg/kg) as otherwise monotherapy with fluoxetine (14 mg/kg) was ineffective to suppress convulsions; an effect better than sodium valproate (300 mg/kg), a standard AED, was validated. Most profoundly, PILO-induced compensatory increases in hippocampal NPY levels (20.01%), which was escalated (100%) with the triple drug combination. The same pattern of results was superseded for oxidative stress indices and neuronal damage. The results for the first time demonstrate the propitious role of triple drug combination in the management of SE and TLE. Therapeutically, this enhancing profile of drugs fosters a safer and more effective drug-combination regimen. Graphical abstract ᅟ.

[Change of hippocampal NMDA receptor and emotional behavior and spatial learning and memory in status epilepticus rat model].

PubMed

Wang, Wei-Ping; Lou, Yan; Li, Zhen-Zhong; Li, Pan; Duan, Rui-Sheng

2007-02-01

SD rats were utilized for the purpose of the exploration of effects of status epilepticus (SE) on their emotional behavior, spatial learning and memory, and explorating its molecular mechanism. Forty maturity male SD rats, weighing (200 +/- 20) g were divided randomly and equally into SE group (SG) and normal control group (NG). The SG rats were induced by Pentylenetetrazole (PTZ) and the control animals received a saline (0.9%) solution. The change of emotional behavior in two groups were tested in elevated plus maze. Furthermore, Morris water maze was applied to evaluate the effects by SE on spatial learning and memory in rats. At the same time, N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA in the hippocampus was determined by reverse transcription polymerase chain reaction (RT-PCR). In elevated plus test, SE rats increased the times of visits as well as the time spent on the open arms of the elevated plus maze (P < 0.01). In Morris water maze, the mean escape latency for the SE rats looking for hidden platform in the place navigation test prolonged (P < 0.01). The efficiency of their search strategy was poor (P < 0.05). The swimming time in platform region and the percentage of their swimming time decreased (P < 0.01). The number of times they crossed the platform area decreased (P < 0.01). Meanwhile the expression of NR1 subunit mRNA in hippocampus was lower (P < 0.01). The experimental results showed that SE could result in the change of emotional behavior and damage of spatial learning and memory in rats. NR1 might be involved in the patho- and physiological process in causing these behavioral changes.

Comparison of functionally orientated tooth replacement and removable partial dentures on the nutritional status of partially dentate older patients: a randomised controlled clinical trial.

PubMed

McKenna, Gerald; Allen, P Finbarr; O'Mahony, Denis; Flynn, Albert; Cronin, Michael; DaMata, Cristiane; Woods, Noel

2014-06-01

The aims of this study were to conduct a randomised controlled clinical trial (RCT) of partially dentate older adults comparing functionally orientated treatment based on the SDA concept with conventional treatment using RPDs to replace missing natural teeth. The two treatment strategies were evaluated according to their impact on nutritional status measured using haematological biomarkers. A randomised controlled clinical trial (RCT) was conducted of partially dentate patients aged 65 years and older (Trial Registration no. ISRCTN26302774). Each patient provided haematological samples which were screened for biochemical markers of nutritional status. Each sample was tested in Cork University Hospital for serum Albumin, serum Cholesterol, Ferritin, Folate, Vitamin B12 and 25-hydroxycholecalciferol (Vitamin D). A mixed model analysis of covariance (ANCOVA) indicated that for Vitamin B12 (p=0.9392), serum Folate (p=0.5827), Ferritin (p=0.6964), Albumin (p=0.8179), Serum Total Cholesterol (p=0.3670) and Vitamin D (p=0.7666) there were no statistically significant differences recorded between the two treatment groups. According to the mixed model analysis of covariance (ANCOVA) for Vitamin D there was a significant difference between levels recorded at post-operative time points after treatment intervention (p=0.0470). There was an increase of 7% in 25-hydroxycholecalciferol levels recorded at 6 months compared to baseline (p=0.0172). There was no further change in recorded levels at 12 months (p=0.6482) and these increases were similar within the two treatment groups (p>0.05). The only measure which illustrated consistent significant improvements in nutritional status for either group were Vitamin D levels. However no significant difference was recorded between the two treatment groups. Functionally orientated prosthodontic rehabilitation for partially dentate older patients was no worse than conventional removable partial dentures in terms of impact on nutritional

Prophylactic treatment with levetiracetam after status epilepticus: lack of effect on epileptogenesis, neuronal damage, and behavioral alterations in rats.

PubMed

Brandt, Claudia; Glien, Maike; Gastens, Alexandra M; Fedrowitz, Maren; Bethmann, Kerstin; Volk, Holger A; Potschka, Heidrun; Löscher, Wolfgang

2007-08-01

Levetiracetam (LEV) is a structurally novel antiepileptic drug (AED) which has demonstrated a broad spectrum of anticonvulsant activities both in experimental and clinical studies. Previous experiments in the kindling model suggested that LEV, in addition to its seizure-suppressing activity, may possess antiepileptogenic or disease-modifying activity. In the present study, we evaluated this possibility by using a rat model in which epilepsy with spontaneous recurrent seizures (SRS), behavioral alterations, and hippocampal damages develop after a status epilepticus (SE) induced by sustained electrical stimulation of the basal amygdala. Two experimental protocols were used. In the first protocol, LEV treatment was started 24h after onset of electrical amygdala stimulation without prior termination of the SE. In the second protocol, the SE was interrupted after 4h by diazepam, immediately followed by onset of treatment with LEV. Treatment with LEV was continued for 8 weeks (experiment #1) or 5 weeks (experiment #2) after SE, using continuous drug administration via osmotic minipumps. The occurrence of SRS was recorded during and after treatment. In addition, the rats were tested in a battery of behavioral tests, including the elevated-plus maze and the Morris water maze. Finally, the brains of the animals were analyzed for histological lesions in the hippocampal formation. With the experimental protocols chosen for these experiments, LEV did not exert antiepileptogenic or neuroprotective activity. Furthermore, the behavioral alterations, e.g., behavioral hyperexcitability and learning deficits, in epileptic rats were not affected by treatment with LEV after SE. These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats.

Febrile Infection-Related Epilepsy Syndrome (FIRES): An Overview of Treatment and Recent Patents.

PubMed

Hon, Kam Lun E Lun; Leung, Alexander K C; Torres, Alcy R

2018-05-08

New-onset refractory status epilepticus (NORSE) refers to a clinical presentation in a patient without active epilepsy or other existing relevant neurological disorder, with new onset of refractory status epilepticus in the absence of a clear acute or active structural, metabolic, or toxic cause. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE that requires a febrile infection between 24 hours and 2 weeks prior to the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus, and with no restriction to the age of the patient. The literature on FIRES is scarce. This article reviews the pathophysiology, clinical features, and various treatment modalities in the treatment of FIRES. A Medline/Pubmed search was conducted using Clinical Queries with the key terms "febrile infection-related epilepsy syndrome", "FIRES", "new-onset refractory status epilepticus" and "NORSE". The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "FIRES", "NORSE" and "febrile epilepsy syndrome" from www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com. FIRES almost invariably begins with a mild nonspecific febrile illness in an otherwise healthy individual. Twenty four hours to two weeks later, seizures begin and quickly become very frequent and worsen, becoming status epilepticus. Seizures can be simple motor, complex partial or secondary generalized. The exact etiology is no known. It is possible that the syndrome is caused by an inflammatory or autoimmune mechanism. Seizures in FIRES are notoriously very difficult to treat. Treatment modalities include, among others, various antiepileptic drugs, ketogenic diet, intravenous corticosteroids, intravenous immunoglobulin, and burst-suppression coma. Outcome is poor; most children are left with significant cognitive disability

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2013-05-01

resistance to enter status epilepticus in contrast to colonies established at Dr. Stanton’s laboratories based in animals originally provided by Dr...of SV2A proteins by Western Blotting at 10 days following status epilepticus (Fig. 8C). At 1 month after status epilepticus , SV2A protein levels were... status epilepticus . Reduction of SV2A transcripts in qPCR was not as dramatic when compared to changes in protein expression (Fig. 8D) but this may

Advanced Clinical Decision Support for Transport of the Critically Ill Patient

DTIC Science & Technology

2013-12-01

algorithms, status asthmaticus and status epilepticus , are to "go live" for use on pediatric critical care transport by the end of October. (Appendices 5...additional algorithms ( status asthmaticus and status epilepticus , Appendices 5 and 6). 8) Plans for validation testing to other transport teams...Practice Guideline Status Epilepticus Clinical Practice Guideline 17 d .s:. ... > 0 Cf :~f t t) ’ U t I .!! ~ .. z ~ i ~ t 0 - : i l

Alpha-Linolenic Acid Confers Neuroprotection and Improves Behavioral Deficits After Soman Exposure: Involvement of Neurogenesis Through an mTOR-Mediated Pathway

DTIC Science & Technology

2015-01-15

chemical warfare agent that irreversibly inhibits acetylcholinesterase in the periphery and central nervous system. Soman induces status epilepticus ...of signs and symptoms including status epilepticus and death. The neuropathology leads to severe cognitive performance, including long-term cognitive... status epilepticus and excessive synaptic accumulation of acetylcholine affects other organ systems beside the brain causing hypersecretions

M Current-Based Therapies for Nerve Agent Seizures

DTIC Science & Technology

2013-07-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS Seizures, status epilepticus Cholinergic, M Current...Channel openers in cholinergic overstimulation-induced status epilepticus . Body: We proposed to study the effects of organophosphates and muscarinic...test whether drugs that open M channels would terminate status epilepticus induced by an organophosphate and cholinergic agonist (Li/Pilocarpine). Two

Novel Therapeutic Approaches for the Treatment of Depression and CognitiveDeficits in a Rodent Model of Gulf War Veterans’ Illness

DTIC Science & Technology

2016-10-01

elevated hippocampal neuronal [Ca2+]i following DFP exposures We have demonstrated that Status Epilepticus leads to development of sustained neuronal Ca2...Pharmacological blockade of the calcium plateau provides neuroprotection following organophosphate paraoxon induced status epilepticus in rats...2010) Development of a prolonged calcium plateau in hippocampal neurons in rats surviving status epilepticus induced by the organophosphate

Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.

PubMed

Drion, Cato M; Borm, Lars E; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J; Hartog, Aloysius F; van Vliet, Erwin A; Gorter, Jan A

2016-05-01

Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post-status epilepticus (SE) rat model. Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) "stop-treatment"-post-SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) "pretreatment"-rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) "chronic phase-treatment"-5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video-electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC). Stop-treatment led to a strong reduction of seizures during the 3-week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5-day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight. The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post-SE rat model but has seizure-suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic

Protective effects of S+ ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs.

PubMed

Dorandeu, Frederic; Baille, Valerie; Mikler, John; Testylier, Guy; Lallement, Guy; Sawyer, Thomas; Carpentier, Pierre

2007-05-20

Soman poisoning is known to induce full-blown tonic-clonic seizures, status epilepticus (SE), seizure-related brain damage (SRBD) and lethality. Previous studies in guinea-pigs have shown that racemic ketamine (KET), with atropine sulfate (AS), is very effective in preventing death, stopping seizures and protecting sensitive brain areas when given up to 1h after a supra-lethal challenge of soman. The active ketamine isomer, S(+) ketamine (S-KET), is more potent than the racemic mixture and it also induces less side-effects. To confirm the efficacy of KET and to evaluate the potential of S-KET for delayed medical treatment of soman-induced SE, we studied different S-KET dose regimens using the same paradigm used with KET. Guinea-pigs received pyridostigmine (26 microg/kg, IM) 30min before soman (62 microg/kg, 2 LD(50), IM), followed by therapy consisting of atropine methyl nitrate (AMN) (4 mg/kg, IM) 1min following soman exposure. S-KET, with AS (10mg/kg), was then administered IM at different times after the onset of seizures, starting at 1h post-soman exposure. The protective efficacy of S-KET proved to be comparable to KET against lethality and SRBD, but at doses two to three times lower. As with KET, delaying treatment by 2h post-poisoning greatly reduced efficacy. Conditions that may have led to an increased S-KET brain concentration (increased doses or number of injections, adjunct treatment with the oxime HI-6) did not prove to be beneficial. In summary, these observations confirm that ketamine, either racemic or S-KET, in association with AS and possibly other drugs, could be highly effective in the delayed treatment of severe soman intoxication.

Status epilepticus in the elderly: Prognostic implications of rhythmic and periodic patterns in electroencephalography and hyperintensities on diffusion-weighted imaging.

PubMed

Yoshimura, Hajime; Matsumoto, Riki; Ueda, Hiroyuki; Ariyoshi, Koichi; Kawamoto, Michi; Ishii, Junko; Ikeda, Akio; Takahashi, Ryosuke; Kohara, Nobuo

2016-11-15

To delineate the clinical characteristics and functional outcome of status epilepticus (SE) in elderly people, and elucidate prognostic implications of SE-associated rhythmic and periodic patterns (RPPs) in electroencephalography and hyperintensities on diffusion-weighted imaging. We retrospectively investigated 107 consecutive patients with SE aged≥65years in a comprehensive community hospital. RPPs were classified using the 2012 American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. Poor outcome was defined as an increase in modified Rankin Scale (mRS) score at discharge compared with that at baseline, including death. Median age of patients was 80.0years. Median mRS score at baseline was 3. Thirty-four patients (31.8%) had a previous diagnosis of epilepsy. Cerebrovascular disease and dementia were major etiologies. Poor outcome occurred in 41 (38.3%). In electroencephalography, periodic discharges (PDs) were present in 21.0% (22/105), rhythmic delta activity (RDA) in 10.5% (11/105), and conventional seizure patterns in 9.5% (10/105). Diffusion-weighted hyperintensities associated with SE were observed in 28.0% (26/93). With univariate analysis, poor outcome was significantly associated with no previous diagnosis of epilepsy, etiology, refractory SE, specific electroencephalographic patterns (PDs and conventional seizure patterns, but not RDA), and diffusion-weighted hyperintensities. With multivariate logistic regression analysis, diffusion-weighted hyperintensities (OR 6.13 [95% CI 1.72-21.9]) and refractory SE (OR 5.36 [95% CI 1.28-22.4]) were independently associated with poor outcome. SE often occurred as the first seizure in already disabled elderly people, further worsening their functional disabilities. Diffusion-weighted hyperintensities and refractory SE, but not RPPs in electroencephalography, were independent functional prognostic factors. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling.

PubMed

Tchekalarova, Jana; Atanasova, Dimitrinka; Kortenska, Lidia; Atanasova, Milena; Lazarov, Nikolai

2018-07-01

Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT 1 and MT 2 receptor agonist and serotonin 5HT 2C receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and maintained for a period of 10 weeks in Wistar rats. Registration of spontaneous motor seizures was performed through a video (24 h/day) and EEG monitoring. Antidepressant activity of agomelatine was explored in the splash test, sucrose preference test (SPT) and forced swimming test (FST) while anxiolytic effect was observed through the novelty suppression-feeding test (NSFT) during chronic phase in epileptic rats. The frequency of motor seizures detected by video and EEG recording did not differ between vehicle and Ago group. Rats with registered spontaneous motor seizures showed symptoms typical for depressive behavior that included decreased grooming, anhedonia during the dark period and hopeless-like behavior. Epileptic rats exhibited also anxiety with novelty-induced hypophagia. This behavioral deficit correlated with increased signal markers of inflammation (plasma levels of interleukin (IL)-1β and activated glia in brain), while plasma corticosterone levels were not changed. Agomelatine treatment during epileptogenesis exerted a clear antidepressant effect by suppressing all behavioral hallmarks, reducing plasma IL-1β levels and preventing microgliosis and astrogliosis in specific limbic regions. The present results suggest that agomelatine treatment starting after SE can provide an effective therapy of comorbid depression in chronic epileptic condition through suppression of inflammatory signaling

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2012-05-01

mouse strain to pilocarpine-induced status epilepticus and seizure- induced excitotoxic cell death (Schauwecker, 2012). Therefore, in close...kind gift of Dr. Venkatesh Murthy, Harvard University). For the induction of status epilepticus animals received methylscopolamine nitrate (0.1 mg...weight, 5 animals per group). The dose used was most efficient, yielding 90% of animals entering status epilepticus and 80% survival rate. After

Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

DTIC Science & Technology

2014-12-01

poisoning can result in status epilepticus (SE), which can become pharmacoresistant if treatment is delayed. Virtually no data exist on OP-induced...are needed to characterize models of P7 and P14 DFP-induced SE. 15. SUBJECT TERMS Status Epilepticus , seizure, organophosphate, DFP, pediatric...5 Introduction Organophosphate (OP) exposure can lead to continuous, repetitive seizures (i.e., status epilepticus , SE), which are

Efficacy of the GluK1/AMPA Receptor Antagonist LY293558 Against Seizures and Neuropathology in a Soman-Exposure Model without Pretreatment and its Pharmacokinetics after Intramuscular Administration

DTIC Science & Technology

2012-10-01

Introduction: 519 Number of words in the Discussion: 1,175 Non-standard abbreviations: SE, status epilepticus ; BLA, basolateral amygdala; GluK1Rs...cardiorespiratory depression and intense seizure activity ( status epilepticus , SE), which are due to the elevated acetylcholine in the peripheral and central nervous...2010) Diazepam administration after prolonged status epilepticus reduces neurodegeneration in the amygdala but not in the hippocampus during

The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302

DTIC Science & Technology

2014-11-01

to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the cur- rent US Food and Drug... status epilepticus (SE), which are initiated by the excessive stimulation of cholinergic receptors. If immediate death is prevented by adequate...5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid; PBS, phosphate-buffered saline; SE, status epilepticus ; UBP302, (S)-3-(2-carboxybenzyl

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2013-05-01

induced status epilepticus persistently increases size, vesicular release rate and endocytosis of mossy fiber boutons in SpH-expressing mice Size... status epilepticus rats We also examined the effects of LEV on miniature excitatory postsynaptic currents (mEPSCs) evoked by spontaneous release...Pilocarpine vs. lithium-pilocarpine for induction of status epilepticus in mice: development of spontaneous seizures, behavioral alterations and

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2016-09-01

sustains seizures. It is instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke...onset of chronic seizures that define epileptic progression. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY...availability of experimental models to molecularly dissect a disease sub-type. In this grant, we will investigate the mechanisms of Status Epilepticus

Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice.

PubMed

Reynolds, Conner D; Nolan, Suzanne O; Huebschman, Jessica L; Hodges, Samantha L; Lugo, Joaquin N

2017-07-01

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups. The present study extends these findings by spectrographic characterization of USVs following neonatal seizures. On PD10, male C57BL/6 pups were administered intraperitoneal injections of kainic acid or physiological saline. On PD12, isolation-induced recordings were captured using a broad-spectrum ultrasonic microphone. Status epilepticus significantly suppressed USV quantity (p=0.001) and total duration (p<0.05). Seizure pups also utilized fewer complex calls than controls (p<0.05). There were no changes in call latency or inter-call intervals. Spectrographic analysis revealed increased peak amplitude for complex, downward, short, two-syllable, and upward calls, as well as reduced mean duration for short and two-syllable calls in seizure mice. This investigation provides the first known spectrographic characterization of USVs following early-life seizures. These findings also enhance evidence for USVs as an indicator of select communicative impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death.

PubMed

Auzmendi, Jerónimo; Buchholz, Bruno; Salguero, Jimena; Cañellas, Carlos; Kelly, Jazmín; Men, Paula; Zubillaga, Marcela; Rossi, Alicia; Merelli, Amalia; Gelpi, Ricardo J; Ramos, Alberto J; Lazarowski, Alberto

2018-02-16

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures increase P-gp expression in the brain, which is associated with membrane depolarization in the hippocampus, and in the heart, which is associated with fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and severe arrhythmias, and both are related with SUDEP. Here, we investigate whether SE induces the expression of hypoxia-inducible transcription factor (HIF)-1α and P-gp in cardiomyocytes, which is associated with altered heart rhythm, and if these changes are related with the spontaneous death rate. SE was induced in Wistar rats once a week for 3 weeks, by lithium-pilocarpine-paradigm. Electrocardiograms, HIF-1α, and P-gp expression in cardiomyocytes, were evaluated in basal conditions and 72 h after SE. All spontaneous deaths occurred 48 h after each SE was registered. We observed that repeated SE induced HIF-1α and P-gp expression in cardiomyocytes, electrocardiographic (ECG) changes, and a high rate of spontaneous death. Our results suggest that the highly accumulated burden of convulsive stress results in a hypoxic heart insult, where P-gp expression may play a depolarizing role in cardiomyocyte membranes and in the development of the ECG changes, such as QT

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2013-06-01

instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke). This is followed by a...in two different models of temporal lobe epilepsy. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY CLASSIFICATION...disease sub-type. In this grant, we will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2016-08-01

instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke). This is followed by a...that define epileptic progression. 15. SUBJECT TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY CLASSIFICATION OF: U 17...grant, we will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal lobe epilepsy (TLE), a

The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

DTIC Science & Technology

2012-01-01

progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats

Caramiphen edisylate as Adjunct to Standard Therapy attenuates soman-induced Seizures and Cognitive Deficits in Rats

DTIC Science & Technology

2014-06-16

exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus ...activity level ( status epilepticus [SE]) result in severe and extensive neuropatholog- ical damage (de Araujo Furtado et al., 2010; de Araujo Furtado et...following exposure to GD and status epilepticus . Lesions to the mediodorsal thalamus result in the perseverance of edge swim (thigmotaxis) and a

Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

DTIC Science & Technology

2013-10-01

SUPPLEMENTARY NOTES 14. ABSTRACT Organophosphate (OP) poisoning can result in status epilepticus (SE), a medical emergency which can become...Introduction Organophosphate (OP) poisoning can result in status epilepticus (SE), a medical emergency which can become pharmacoresistant if...P28 rat pups. Figure 1. DFP-induced status epilepticus in a P28 rat. Animals were treated with 0.026 mg/kg pyridostigmine bromide (i.p.) 30 min

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2012-05-01

susceptibility of mouse strain to pilocarpine-induced status epilepticus and seizure- induced excitotoxic cell death (Schauwecker, 2012). Therefore, in...Stanton’s Laboratory (kind gift of Dr. Venkatesh Murthy, Harvard University). For the induction of status epilepticus animals received methylscopolamine...380 mg/kg of body weight, 5 animals per group). The dose used was most efficient, yielding 90% of animals entering status epilepticus and 80% survival

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2015-06-01

transforms into one that sustains seizures. It is instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury...Surprisingly, the combination attenuates seizures in two different models of temporal lobe epilepsy. 15. SUBJECT TERMS Status Epilepticus , Wnt...will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of temporal lobe epilepsy (TLE), a disease

Neuroprotection and Anti-Epileptogenesis with Mitochondria-Targeted Antioxidant

DTIC Science & Technology

2016-06-01

antioxidant, SS-31 in the pilocarpine (PILO) model of status epilepticus (SE), the kindling seizure model and the tetanus toxin (Tx) model of epilepsy...neuroprotective and antiepileptogenic agent in three experimental models of epilepsy. The pilocarpine-induced model of status epilepticus (PILO) was...neuroprotection, seizures, status epilepticus OVERALL PROJECT SUMMARY: SS-31 was created by Dr. Szeto but the rights to the drug are controlled by Stealth

New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

DTIC Science & Technology

2014-05-01

in control versus pilocarpine-treated (suffering status epilepticus ) group of animals that were injected with saline instead of levetiracetam for 1...month (Figure 1A). As previously reported we detected a significant 4.4% increase in normalized peak fluorescence in status epilepticus (SE) group...slices) (Figure A, b3). These data is consistent with our previous findings that status epilepticus induce an abnortmal increase in presynaptic

Seizures and epilepsy in hypoglycaemia caused by inborn errors of metabolism.

PubMed

Gataullina, Svetlana; Delonlay, Pascale; Lemaire, Eric; Boddaert, Nathalie; Bulteau, Christine; Soufflet, Christine; Laín, Gemma Aznar; Nabbout, Rima; Chiron, Catherine; Dulac, Olivier

2015-02-01

The aim of the study was to characterize seizures and epilepsy related to hypoglycaemia. We analyzed the files of 170 consecutive patients referred for hypoglycaemia (onset 1h to 4y) caused by inborn errors of metabolism (glycogen storage disease type I, fatty acid β-oxidation disorders, and hyperinsulinism). Ninety patients (42 males and 48 females; 38 neonates and 52 infants/children) had brief hypoglycaemic seizures (68%) or status epilepticus (32%). Status epilepticus occurred earlier (mean 1.4d) than brief neonatal seizures (4.3d, p=0.02). Recurrent status epilepticus followed initial status epilepticus and was often triggered by fever. Epilepsy developed in 21 patients. In 18 patients, epilepsy followed hypoglycaemic status epilepticus and began with shorter delay when associated with grey matter lesions (1.9mo, standard error of the mean [SEM] 1mo) than with white matter damage (3.3y [SEM 1y], p=0.003). Three patients with hyperinsulinism developed idiopathic epilepsy following brief neonatal seizures. Brief neonatal hyperinsulinaemic hypoglycaemic seizures have characteristics of idiopathic neonatal seizures. Neonatal status epilepticus should be prevented by the systematic measurement of glucose blood level. Recurrent seizures never consist of status epilepticus when following brief initial seizures. Epilepsy is symptomatic of brain damage with shorter delay in the case of grey rather than white matter lesions, except in a few idiopathic cases in which epilepsy and hyperinsulinism may share a common genetic background. © 2014 Mac Keith Press.

Interleukin-1β increases neuronal death in the hippocampal dentate gyrus associated with status epilepticus in the developing rat.

PubMed

Rincón-López, C; Tlapa-Pale, A; Medel-Matus, J-S; Martínez-Quiroz, J; Rodríguez-Landa, J F; López-Meraz, M-L

Interleukin-1β (IL-1β) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1β has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1β on 14-day-old Wistar rats experiencing DG neuronal death induced by SE. SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1β (at 0, 0.3, 3, 30, or 300ng/μL) in the right ventricle; another group was injected with IL-1β receptor (IL-1R1) antagonist (IL-1Ra, at 30ng/μL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30ng/μL of IL-1Ra plus 3ng/μL of IL-1β. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei. We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/μL and 300ng/μL of IL-1β in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3ng/μL of IL-1β. Administration of both of IL-1β and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. Our data suggest that IL-1β increases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Early Post Traumatic Seizures in Military Personnel Result in Long Term Disability

DTIC Science & Technology

2013-10-01

contusional versus non-contusional). The seizures occurred repeatedly in nearly ¼ of patients are 1/3 of those with seizures had status epilepticus . In...a seizure or status epilepticus occurs within the initial 3 days. Electrographic epileptiform activity will be categorized as follows: Type of...increases of 50% above the baseline value of any of these quantitative measures. A standardized protocol to treat status epilepticus as well as dosage

Human iPSC-Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

DTIC Science & Technology

2015-10-01

1) Induction of status epilepticus (SE) in young rats through kainic acid injections to generate rats exhibiting chronic TLE typified by SRS. (2...of status epilepticus (SE) via graded kainic acid injections, termination of acute seizures 2 hours after SE onset via diazepam injections and...injections to these rats to induce acute seizures or status epilepticus (SE) in 11 separate experimental sessions (n=8-12/session). These experiments

Jak/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2012-07-01

display different cellular responses n status epilepticus models (Schauwecker and Steward, 1997), nd/or are often used in transgenic studies. Severe brain...after status epilepticus (SE). This study investigated changes in these pathways after experimental TBI in the rat using a lateral fluid percussion... status epilepticus (SE) (Choi et al., 2003, Lund et al., 2008). Following SE, the JaK/STAT pathway has been shown to regulate the γ-aminobutyric acid

Mechanism and Therapy for the Shared Susceptibility to Migraine and Epilepsy after Traumatic Brain Injury (TBI)

DTIC Science & Technology

2013-10-01

injured mice. Nine hours post-injury, one mouse developed status epilepticus (Figure 1) which continued for 3 days resulting in the animal’s death...seizures per day. 6 Figure 1: Electrographic recording of a CCI-injured mouse in status epilepticus . Upper trace is an EEG recording of...4 h of status epilepticus while the lower traces represent portions of the EEG within the dashed boxes at an expanded timescale. The recordings

Epilepsy and the Wnt Signaling Pathway

DTIC Science & Technology

2015-06-01

status epilepticus (SE), head injury, infection or stroke). This is followed by a variable (months to years in humans) “latent period” followed by the...TERMS Status Epilepticus , Wnt Signaling, Epileptogenesis 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACTU U 18. NUMBER OF PAGES 4...disease sub-type. In this grant, we will investigate the mechanisms of Status Epilepticus (SE) and the ensuing latent period in animal models of

JaK/STAT Inhibition to Prevent Post-Traumatic Epileptogenesis

DTIC Science & Technology

2012-07-01

necessary because, although global pSTAT upregulation has been identified after status epilepticus following pilocarpine treatment in rats (Kim et...100 mg/kg, i.p.) in pilocarpine-treated rats indicated that it was able to suppress pSTAT3 upregulation after status epilepticus , this procedure had...cellular responses n status epilepticus models (Schauwecker and Steward, 1997), nd/or are often used in transgenic studies. Severe brain injury was