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Sample records for partial status epilepticus

  1. Complex partial status epilepticus: a recurrent problem.

    PubMed Central

    Cockerell, O C; Walker, M C; Sander, J W; Shorvon, S D

    1994-01-01

    Twenty patients with complex partial status epilepticus were identified retrospectively from a specialist neurology hospital. Seventeen patients experienced recurrent episodes of complex partial status epilepticus, often occurring at regular intervals, usually over many years, and while being treated with effective anti-epileptic drugs. No unifying cause for the recurrences, and no common epilepsy aetiologies, were identified. In spite of the frequency of recurrence and length of history, none of the patients showed any marked evidence of cognitive or neurological deterioration. Complex partial status epilepticus is more common than is generally recognised, should be differentiated from other forms of non-convulsive status, and is often difficult to treat. PMID:8021671

  2. [Simple partial frontal nonconvulsive status epilepticus].

    PubMed

    Thomas, P; Mottin, Y

    1997-07-01

    Non convulsive status epilepticus (NCSE) of frontal origin is a rare cause of mental confusion. The present case of possible frontal-onset NCSE proved to have a neuropsychological examination that was suggestive either of a disruption of attentional function or a left prefrontal dysfunction, exhibiting disturbances of immediate memory and logical programmation, perseverations and affective disinhibition. Vigilance was not impaired. This case was therefore, on a nosographic point of view, more consistent with a simple partial status epilepticus with cognitive and affective symptomatology rather than with a complex partial status epilepticus of extra-temporal origin. PMID:9684010

  3. [Nonconvulsive Status Epilepticus].

    PubMed

    Mizobuchi, Masahiro

    2016-04-01

    Nonconvulsive status epilepticus (NCSE) is a type of status epilepticus (SE) lacking a predominant motor manifestation. The annual prevalence of NCSE is estimated to reach 10 to 20 cases in every 100,000 people. While almost half of all SE cases are nonconvulsive, there are several different types of NCSE: 1) epileptic absence SE, 2) epileptic focal seizure SE with consciousness disturbance (complex partial SE), 3) de novo NCSE of late onset, 4) NCSE due to acute brain injury or prolonged consciousness disturbance after convulsive SE. An electroencephalography (EEG) evaluation is necessary to diagnose NCSE. However, continuous EEG (cEEG) monitoring over at least 24 hours is preferable to detect NCSE, as cognitive disturbances due to this condition may fluctuate over time. In addition, neuroimaging techniques, such as MRI with arterial spin labeled sequences or single photon emission computed tomography (SPECT) can demonstrate hyperperfused areas in cases of focal onset. Thus, patients presenting with alternative cognitive disturbance with or without mild confusion should be evaluated using cEEG monitoring or blood flow imaging so as not to overlook treatable NCSE. PMID:27056863

  4. Simple Partial Status Epilepticus Manifested as Homonymous Hemianopsia: A Rare Intracranial Recording

    PubMed Central

    Siatouni, Anna; Gatzonis, Stylianos; Alexopoulos, Andreas; Georgakoulias, Nikos; Papathanassiou, Mathildi; Korfias, Stefanos; Zisimopoulou, Vaso; Sakas, Damianos

    2016-01-01

    A 30-year-old woman with intractable seizures evaluated as surgical candidate. During presurgical evaluation an invasive electroencephalogram was recommended to define the location and extent of epileptogenic zone and relationship to epileptogenic lesion. On third monitoring night the patient complained of persistent homonymous hemianopsia following a habitual seizure. Concurrently, persistent epileptic activity was evident in a small, restricted area around the right calcarine fissure. The ictal discharges persisted for the next 30 h despite high-dose administration of intravenous antiepileptic drugs, until patient was taken to operating room. Simple partial status epilepticus presenting with pure visual symptoms is rare and difficult to diagnose, even more so when presenting with negative visual phenomena. Epileptic etiology of unexplained, paroxysmal negative visual symptoms should be considered in the differential diagnosis in patients with pre-existing epilepsy, as well as patients with no prior history of epilepsy. PMID:27162608

  5. 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

  6. Treatment of Established Status Epilepticus.

    PubMed

    Falco-Walter, Jessica J; Bleck, Thomas

    2016-01-01

    Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

  7. Treatment of Established Status Epilepticus

    PubMed Central

    Falco-Walter, Jessica J.; Bleck, Thomas

    2016-01-01

    Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

  8. Pharmacotherapy for Status Epilepticus.

    PubMed

    Trinka, Eugen; Höfler, Julia; Leitinger, Markus; Brigo, Francesco

    2015-09-01

    Status epilepticus (SE) represents the most severe form of epilepsy. It is one of the most common neurologic emergencies, with an incidence of up to 61 per 100,000 per year and an estimated mortality of 20 %. Clinically, tonic-clonic convulsive SE is divided into four subsequent stages: early, established, refractory, and super-refractory. Pharmacotherapy of status epilepticus, especially of its later stages, represents an "evidence-free zone," due to a lack of high-quality, controlled trials to inform clinical decisions. This comprehensive narrative review focuses on the pharmacotherapy of SE, presented according to the four-staged approach outlined above, and providing pharmacological properties and efficacy/safety data for each antiepileptic drug according to the strength of scientific evidence from the available literature. Data sources included MEDLINE and back-tracking of references in pertinent studies. Intravenous lorazepam or intramuscular midazolam effectively control early SE in approximately 63-73 % of patients. Despite a suboptimal safety profile, intravenous phenytoin or phenobarbital are widely used treatments for established SE; alternatives include valproate, levetiracetam, and lacosamide. Anesthetics are widely used in refractory and super-refractory SE, despite the current lack of trials in this field. Data on alternative treatments in the later stages are limited. Valproate and levetiracetam represent safe and effective alternatives to phenobarbital and phenytoin for treatment of established SE persisting despite first-line treatment with benzodiazepines. To date there are no class I data to support recommendations for most antiepileptic drugs for established, refractory, and super-refractory SE. Limiting the methodologic heterogeneity across studies is required and high-class randomized, controlled trials to inform clinicians about the best treatment in established and refractory status are needed. PMID:26310189

  9. [Differential diagnosis of status epilepticus].

    PubMed

    Navarro, V; Fischer, C; Convers, P

    2009-04-01

    The diagnosis of status epilepticus can be retained, wrongly, in several circumstances. Nonepileptic pseudoseizures from a psychiatric origin and some movement disorders can mimic convulsive status epilepticus. Encephalopathy of various causes (post-anoxic, metabolic, toxic, Creutzfeldt-Jakob disease) can be wrongly taken for non-convulsive status epilepticus, mainly due to inadequate interpretation of the electroencephalogram (EEG). In these encephalopathies, the existence of (non-epileptic) myoclonus and the abolition of the EEG abnormalities with the use of a benzodiazepine (without correction of the clinical symptoms) are additional confounding factors, leading to false diagnosis. Nevertheless, in general, the diagnosis of status epilepticus can be confirmed or rejected base on a combined analysis of the clinical data and the EEG. PMID:19217635

  10. Management of Status Epilepticus in Children

    PubMed Central

    Smith, Douglas M.; McGinnis, Emily L.; Walleigh, Diana J.; Abend, Nicholas S.

    2016-01-01

    Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children. PMID:27089373

  11. Management of Status Epilepticus in Children.

    PubMed

    Smith, Douglas M; McGinnis, Emily L; Walleigh, Diana J; Abend, Nicholas S

    2016-01-01

    Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children. PMID:27089373

  12. Management of Pediatric Status Epilepticus

    PubMed Central

    Loddenkemper, Tobias

    2014-01-01

    Opinion Statement Status epilepticus (SE) is a medical emergency consisting of persistent or recurring seizures without a return to baseline mental status. SE is not a single entity, but can be divided into subtypes based on seizure types and underlying etiologies. Management should be implemented rapidly and based on continuously reassessed care pathways. The aim is to terminate seizures while simultaneously identifying and managing precipitant conditions. Seizure management involves “emergent” treatment with benzodiazepines (lorazepam intravenously, midazolam intramuscularly, or diazepam rectally) followed by “urgent” therapy (phenytoin/fosphenytoin, phenobarbital, levetiracetam or valproate sodium). If seizures persist, “refractory” treatments include infusions of midazolam or pentobarbital. Prognosis is dependent on the underlying etiology and seizure persistence. This paper reviews the current management options and strategies for pediatric convulsive status epilepticus. PMID:24909106

  13. [Treatment of non-convulsive status epilepticus].

    PubMed

    Liimatainen, Suvi; Ollikainen, Jyrki; Peltola, Jukka

    2011-01-01

    Non-convulsive status epilepticus is an insidious condition and a challenging diagnosis for neurologists on call. The condition must, however, be recognized, since it constitutes a neurological emergency. Non-convulsive status epilepticus may also be associated as an additional complication with an acute neurologic disease, in which case an EEG recording is usually required. In addition, non-convulsive status epilepticus can be found in a significant proportion of patients with unconsciousness of unknown origin. PMID:21995129

  14. Genetic mutations associated with status epilepticus.

    PubMed

    Bhatnagar, M; Shorvon, S

    2015-08-01

    This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult

  15. Status Epilepticus Caused by Nefopam

    PubMed Central

    Kim, Young-baeg; Kim, Jeong-min

    2014-01-01

    Nefopam, a centrally acting analgesic, has been used to control postoperative pain. Reported adverse effects are anticholinergic, cardiovascular or neuropsychiatric. Neurologic adverse reactions to nefopam are confusion, hallucinations, delirium and convulsions. There are several reports about fatal convulsive seizures, presumably related to nefopam. A 71-year-old man was admitted for surgery for a lumbar spinal stenosis. He was administered intravenous analgesics : ketorolac, tramadol, orphenadrine citrate and nefopam HCl. His back pain was so severe that he hardly slept for several days; he even needed morphine and pethidine. At 4 days of administration of intravenous analgesics, the patient suddenly started generalized tonic-clonic seizures for 15 seconds, and subsequently, status epilepticus; these were not responsive to phenytoin and midazolam. After 3 days of barbiturate coma therapy the seizures were controlled. Convulsive seizures related to nefopam appear as focal, generalized, myoclonic types, or status epilepticus, and are not dose-related manifestations. In our case, the possibility of convulsions caused by other drugs or the misuse of drugs was considered. However, we first identified the introduced drugs and excluded the possibility of an accidental misuse of other drugs. Physicians should be aware of the possible occurrence of unpredictable and serious convulsions when using nefopam. PMID:25535527

  16. 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

  17. Transcranial Magnetic Stimulation for Status Epilepticus

    PubMed Central

    Zeiler, F. A.; Matuszczak, M.; Teitelbaum, J.; Gillman, L. M.; Kazina, C. J.

    2015-01-01

    Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted. PMID:26682065

  18. 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.

  19. 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. PMID:27215700

  20. Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports.

    PubMed

    Walker, Matthew; Cross, Helen; Smith, Shelagh; Young, Camilla; Aicardi, Jean; Appleton, Richard; Aylett, Sarah; Besag, Frank; Cock, Hannah; DeLorenzo, Robert; Drislane, Franck; Duncan, John; Ferrie, Colin; Fujikawa, Denson; Gray, William; Kaplan, Peter; Koutroumanidis, Micheal; O'Regan, Mary; Plouin, Perrine; Sander, Josemir; Scott, Rod; Shorvon, Simon; Treiman, David; Wasterlain, Claude; Wieshmann, Udo

    2005-09-01

    In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees. We present here the extended abstracts of the main talks with the points raised by the discussants. Despite disagreements on certain issues there was much in the way of consensus. First, it was agreed that nonconvulsive status epilepticus is a term that covers a range of disparate conditions with varying prognoses and treatments. The agreed definition was thus suitably vague, Astatus epilepticus is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in nonconvulsive clinical symptomsA>. Secondly, it was agreed that even within a specific condition (e.g. complex partial status epilepticus), the prognosis and treatment depends upon the context in which the condition occurs (e.g. in the critically ill, in coma, in the A and in people with prior epilepsy). Perhaps, most importantly it was agreed that we lacked good clinical data, and the challenge was to design good studies for a condition that is underrecognised and often difficult to diagnose. PMID:16162436

  1. The treatment of convulsive status epilepticus in children. The Status Epilepticus Working Party, Members of the Status Epilepticus Working Party.

    PubMed

    Appleton, R; Choonara, I; Martland, T; Phillips, B; Scott, R; Whitehouse, W

    2000-11-01

    There is currently little agreement between hospital protocols when treating convulsive status epilepticus in children, and a working party has been set up to produce a national evidence based guideline for treating this condition. This four step guideline is presented in this paper. Its effectiveness will be highlighted and its use audited in a number of centres. PMID:11040151

  2. Status epilepticus: An association with pyrethroid poisoning

    PubMed Central

    Panwar, Mamta; Usha, Ganapathy; Kumath, Manish

    2013-01-01

    This report describes a 35 year old male who presented with seizures after consuming 4-5 bottles of “ALL-OUT” a commercial composition of pyrethroid used as insecticides. Our case report supports authors reporting an association of pyrethroid poisoning with status epilepticus. PMID:23983421

  3. Therapeutic Hypothermia for Refractory Status Epilepticus in a Child with Malignant Migrating Partial Seizures of Infancy and SCN1A Mutation: A Case Report

    PubMed Central

    Shein, Steven L.; Reynolds, Thomas Q.; Gedela, Satyanarayana; Kochanek, Patrick M.

    2012-01-01

    Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children. PMID:23667778

  4. 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

  5. A Case of Phenytoin-induced Rhabdomyolysis in Status Epilepticus

    PubMed Central

    Kim, Hyunjin; Jo, Sungyang; Park, Kye Won; Han, Su-Hyun; Lee, Sang-Ahm

    2016-01-01

    Phenytoin is a commonly used antiepileptic drug, especially when treating status epilepticus. Here, we present a patient who suffered from status epilepticus and developed rhabdomyolysis after being treated with phenytoin. As multiple seizures itself can induce rhabdomyolysis, it is difficult to recognize that phenytoin can be the cause of rhabdomyolysis in status epilepticus patients. Even though phenytoin is a rare cause of rhabdomyolysis, we should discern that phenytoin can be a causative drug to bring about rhabdomyolysis. PMID:27390679

  6. Status epilepticus associated with borage oil ingestion.

    PubMed

    Al-Khamees, Wafa'a A; Schwartz, Michael D; Alrashdi, Saleh; Algren, Adam D; Morgan, Brent W

    2011-06-01

    The use of herbal and complementary medicine is common. Many herbal products are known to produce serious adverse effects. Borage oil is derived from the seeds of the borage plant (Borago officinalis) an abundant source of gamma-linolenic acid (GLA), and Borage oil has been promoted as a treatment for rheumatoid arthritis, atopic dermatitis, diabetic neuropathy, and menopause-related symptoms. We report a case of status epilepticus in a patient who consumed borage oil for one week. PMID:21387119

  7. Managing Status Epilepticus in the Older Adult.

    PubMed

    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

  8. 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

  9. Endocannabinoids block status epilepticus in cultured hippocampal neurons

    PubMed Central

    Deshpande, Laxmikant S.; Blair, Robert E.; Ziobro, Julie M.; Sombati, Sompong; Martin, Billy R.; DeLorenzo, Robert J.

    2008-01-01

    Status epilepticus is a serious neurological disorder associated with a significant morbidity and mortality. Antiepileptic drugs such as diazepam, phenobarbital and phenytoin are the mainstay of status epilepticus treatment. However, over 20% of status epilepticus cases are refractory to the initial treatment with two or more antiepileptic drugs. Endocannabinoids have been implicated as playing an important role in regulating seizure activity and seizure termination. This study evaluated the effects of the major endocannabinoids methanandamide and 2-arachidonylglycerol (2-AG) on status epilepticus in the low-Mg2+ hippocampal neuronal culture model. Status epilepticus in this model was resistant to treatment with phenobarbital and phenytoin. Methanandamide and 2-AG inhibited status epilepticus in a dose-dependent manner with an EC50 of 145±4.15 nM and 1.68±0.19 µM, respectively. In addition, the anti-status epilepticus effects of methanandamide and 2-AG were mediated by activation of the cannabinoid CB1 receptor since they were blocked by the cannabinoid CB1 receptor antagonist AM251. These results provide the first evidence that the endocannabinoids, methanandamide and 2-AG, are effective inhibitors of refractory status epilepticus in the hippocampal neuronal culture model and indicate that regulating the endocannabinoid system may provide a novel therapeutic approach for treating refractory status epilepticus. PMID:17174949

  10. Status Epilepticus in Adults: A Review of Diagnosis and Treatment.

    PubMed

    Lawson, Thomas; Yeager, Susan

    2016-04-01

    Status epilepticus is a medical emergency that requires rapid diagnosis and treatment. Nonconvulsive status epilepticus is frequently underdiagnosed and therefore undertreated, which can lead to permanent neuronal damage resulting in disability or death. Despite the frequent occurrence and morbidity associated with status epilepticus, this topic has received little attention within the literature. A systematic approach to treatment should start with management of airway, breathing, and circulation, followed by administration of benzodiazepines and intravenous antiepileptic drugs, and rapid escalation of therapy to prevent morbidity and mortality. Armed with the information in this article, nurses will have a higher-level understanding of what to do when encountering a patient in status epilepticus. PMID:27037340

  11. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    PubMed Central

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S.

    2015-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. PMID:25363147

  12. 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". PMID:25819797

  13. 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. PMID:26418265

  14. Cobalamin deficiency triggering de novo status epilepticus.

    PubMed

    Anastogiannis, Haralabos; Karanasios, Panagiotis; Makridou, Alexandra; Makris, Nicolaos; Argyriou, Andreas A

    2014-03-01

    Cobalamin deficiency is included in the spectrum of very uncommon underlying causes of status epilepticus (SE) and the literature contains very few such cases. We herein report a case of unusual presentation of cobalamin (vitamin B12) deficiency with de novo SE with the intention to bolster the argument that a de novo manifestation of SE due to cobalamin deficiency might not be that uncommon. We also support the importance of prompt identification and treatment of the underlying causes of SE, particularly those which are uncommon. PMID:24659635

  15. 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

  16. 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. PMID:25902572

  17. Valacyclovir and Acyclovir Neurotoxicity With Status Epilepticus.

    PubMed

    Hoskote, Sumedh S; Annapureddy, Narender; Ramesh, Atul K; Rose, Keith; Jones, James P

    2016-01-01

    We present the case of a 52-year-old man with hypertension, diastolic congestive heart failure, end-stage renal disease on hemodialysis 3 times a week and a remote history of a hemorrhagic stroke who presented to the emergency department with a vesicular rash on his left arm. The rash was observed to be in a dermatomal distribution, and a diagnosis of herpes zoster was made. The patient was discharged home on valacyclovir 1 g 3 times a day for a duration of 7 days. The patient took 2 doses of valacyclovir before presenting to the hospital again with irritability and hallucinations. Over the next several days, the patient's neurologic status declined and he became disoriented and increasingly somnolent. Because of a concern for varicella zoster virus (VZV) or herpes simplex virus (HSV) meningoencephalitis, acyclovir was initiated intravenously at 600 mg (10 mg/kg) for every 12 hours. Computed tomography and magnetic resonance imaging of the brain failed to reveal an acute process. Electroencephalogram was interpreted as seizure activity versus metabolic encephalopathy. Lumbar puncture was not suggestive for meningitis, subarachnoid hemorrhage, or HSV/VZV infection. The patient subsequently had a witnessed seizure during dialysis and was felt to have status epilepticus due to acyclovir and valacyclovir neurotoxicity. The patient underwent daily hemodialysis for removal of the drug and eventually made a full neurologic recovery. Our case highlights that acyclovir neurotoxicity can result in status epilepticus, hallucinations, and altered consciousness. Differentiating acyclovir neurotoxicity from HSV or VZV meningoencephalitis is of crucial importance because the symptoms are similar but the management is vastly different. PMID:24368610

  18. [Nonconvulsive status epilepticus: clinical practice and pathophysiology].

    PubMed

    Nagayama, Masao

    2013-05-01

    The clinical spectrum of nonconvulsive status epilepticus (NCSE) is rapidly expanding from classical manifestations, such as staring, repetitive blinking, chewing, swallowing, and automatism to novel manifestations, such as acute and protracted coma, apnea, cognitive impairment, higher brain dysfunction, and cardiac arrest. It is only in the last decade that these novel NCSE manifestations have been revealed, which is certainly reflective of modern advances in critical care neurology, such as the introduction and spread of continuous electroencephalography (cEEG) monitoring. Although NCSE is a relatively frequent, treatable condition but with a high mortality rate, physicians are still unfamiliar with its clinical manifestations, thus leading to underdiagnosis. In this review, the clinical manifestations, epidemiology, diagnosis, and management of NCSE are critically described using the best available evidence and perspectives, including my hypothesis on epileptic organ dysfunction; in particular, the possible causal relationship between NCSE and cardiac arrhythmia, such as atrial fibrillation is also discussed. PMID:23667121

  19. Status Epilepticus: Epidemiology and Public Health Needs.

    PubMed

    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

  20. 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

  1. Autoimmunity and inflammation in status epilepticus: from concepts to therapies.

    PubMed

    Holzer, Franz Josef; Seeck, Margitta; Korff, Christian M

    2014-10-01

    The understanding of immunological mechanisms underlying some forms of epilepsy and encephalitis has rapidly increased for the last 10 years leading to the concept of status epilepticus of autoimmune origin. Actual treatment recommendations regarding autoimmune status epilepticus are based on retrospective case studies, pathophysiological considerations and experts' opinion. In addition, there are no clear indicators to predict outcome. In situations where autoimmune mechanisms are suspected in patients with status epilepticus, there is evidence that earlier treatment is related to better outcome. Increased awareness is mandatory to decrease the number of patients with major neurological problems or fatal outcome, which is overall about 50%. We here summarize findings of all pediatric and adult patients reported to date, and review the current state of knowledge in the field of immune therapeutic approaches of status epilepticus. PMID:25201402

  2. Nonconvulsive status epilepticus in rats: impaired responsiveness to exteroceptive stimuli.

    PubMed

    Mikulecká, A; Krsek, P; Hlinák, Z; Druga, R; Mares, P

    2000-12-20

    An animal model of human complex partial status epilepticus induced by lithium chloride and pilocarpine administration was developed in our laboratory. The objective of the study was to provide a detailed analysis of both ictal and postictal behavior and to quantify seizure-related morphological damage. In order to determine the animal's responsiveness to either visual or olfactory stimuli, adult male rats were submitted to the following behavioral paradigms: the object response test, the social interaction test, and the elevated plus-maze test. The rotorod test was used to evaluate motor performance. Two weeks after status epilepticus, brains were morphologically examined and quantification of the brain damage was performed. Profound impairment of behavior as well as responsiveness to exteroceptive stimuli correlated with the occurrence of epileptic EEG activity. When the epileptic EEG activity ceased, responsiveness of the pilocarpine-treated animals was renewed. However, remarkable morphological damage persisted in the cortical regions two weeks later. This experimental study provides support for the clinical evidence that even nonconvulsive epileptic activity may cause brain damage. We suggest that the model can be used for the study of both functional and morphological consequences of prolonged nonconvulsive seizures. PMID:11099755

  3. Cost of status epilepticus: A systematic review.

    PubMed

    Kortland, Lena-Marie; Knake, Susanne; Rosenow, Felix; Strzelczyk, Adam

    2015-01-01

    The objective of this review is to give an overview of published cost of illness (COI) studies on status epilepticus (SE). For identifying COI studies that evaluated the direct and indirect costs of SE, a systematic literature review was performed. We used a standardized assessment form for extracting information on the study design, methodological framework, and data sources from each publication. The results were systematically reported. We identified only two studies worldwide, which included prevalence- or incidence-based data on the direct costs of SE: one from Germany and one from the USA. Both used a bottom-up approach and a prospective design. The estimated mean inpatient costs summed up to US$18,834 in the USA and to €8347 in Germany per admission with an average length of stay of 12.9 and 14.0 days. The mean annual direct costs for SE had been estimated at US$4 billion in the USA and at €83 million (adults only) in Germany. Both available studies indicate that SE is a cost-intensive disorder with an acute CNS aetiology as a cost-driving factor. In conclusion, there is a paucity of data on the costs of SE. Further studies are warranted to determine costs, its predictors, quality of life, mortality data due to SE and its sequelae and to provide a basis for further cost-effectiveness calculations for new drugs and other interventions in SE and prolonged seizures. PMID:25564314

  4. Unilateral brain oedema related to focal status epilepticus

    PubMed Central

    Ali, Noura Abdulwahid; Palat Chirakkara, Sudhir Kumar; Reddy, Jagan Jinna; Sinha, Shobhit

    2013-01-01

    We present a female patient in her late 30s, with baseline vegetative state following prior traumatic brain injury, who presented with prolonged right hemispheric status epilepticus. The neuroimaging revealed a striking right-sided pancortical oedema with left (crossed) cerebellar diaschisis and dilation of right hemispheric arteries. EEG was concordant and showed nearly continuous right hemispheric seizure discharges with suppressed background. Infective and vascular aetiologies were ruled out. The patient showed clinical and electrographic improvement following treatment with antiepileptic drugs. Unilateral cerebral oedema is a rare presentation of focal status epilepticus, and should be considered as a differential diagnosis in the appropriate clinical scenario. PMID:24334523

  5. 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". PMID:26189787

  6. Endotracheal Intubation in Patients Treated for Prehospital Status Epilepticus

    PubMed Central

    Miller, Joseph B.; Nicholas, Katherine S.; Varelas, Panayiotis N.; Harsh, Donna M.; Durkalski, Valerie; Silbergleit, Robert; Wang, Henry E.

    2015-01-01

    Introduction Limited data describe the frequency, timing, or indications for endotracheal intubation (ETI) in patients with status epilepticus. A better understanding of the characteristics of patients with status epilepticus requiring airway interventions could inform clinical care. We sought to characterize ETI use in patients with prehospital status epilepticus. Methods This study was a secondary analysis of the Rapid Anticonvulsant Medication Prior to Arrival Trial, a multi-center, randomized trial comparing intravenous lorazepam to intramuscular midazolam for prehospital status epilepticus treatment. Subjects received ETI in the prehospital, Emergency Department (ED), or inpatient setting at the discretion of caregivers. Results Of 1023 enrollments, 218 (21 %) received ETI. 204 (93.6 %) of the ETIs were performed in the hospital and 14 (6.4 %) in the prehospital setting. Intubated patients were older (52 vs 41 years, p < 0.001), and men underwent ETI more than women (26 vs 21 %, p = 0.047). Patients with ongoing seizures on ED arrival had a higher rate of ETI (32 vs 16 %, p < 0.001), as did those who received rescue anti-seizure medication (29 vs 20 %, p = 0.004). Mortality was higher for intubated patients (7 vs 0.4 %, p < 0.001). Most ETI (n = 133, 62 %) occurred early (prior to or within 30 min after ED arrival), and late ETI was associated with higher mortality (14 vs 3 %, p = 0.002) than early ETI. Conclusions ETI is common in patients with status epilepticus, particularly among the elderly or those with refractory seizures. Any ETI and late ETI are both associated with higher mortality. PMID:25623785

  7. Adjunctive enteral phenobarbital for adult status epilepticus: a brief report

    PubMed Central

    Tiamkao, Somsak; Suttapan, Kornkanok; Pranbul, Sineenard; Tiamkao, Siriporn; Sawanyawisuth, Kittisak

    2013-01-01

    Background Status epilepticus (SE) is a neurological emergency condition. Intravenous phenobarbital (PB) is recommended for refractory SE treatment. However, intravenous PB is unavailable in Thailand. Enteral PB has been shown to be effective in SE children. Methods In adult SE patients, the efficacy of enteral PB as an adjunctive therapy has been reported. This is a case series of adult SE patients who were treated with enteral PB at Khon Kaen University Hospital, Thailand. The clinical features and clinical outcomes are reported. Results There were six patients; five patients had convulsive SE, and one patient had nonconvulsive SE. All patients received PB enterally, at dosages of 900 mg initially and repeated doses of 900 mg as needed. This was gradually reduced to a maintenance dosage of 180 mg/day. Three out of six patients were completely controlled, whereas the other three patients were partially controlled. Three out of six patients were seizure-free after the initial loading dose of PB. No adverse effects were found in this study. Conclusion In adult patients, enteral PB may be effective as an add-on for refractory SE therapy. PMID:24379674

  8. Supra-recommendation Treatment of Super-refractory Status Epilepticus

    PubMed Central

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    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. PMID:27390680

  9. 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

  10. New-Onset Refractory Status Epilepticus: More Investigations, More Questions

    PubMed Central

    Dillien, Philippe; Ferrao Santos, Susana; van Pesch, Vincent; Suin, Vanessa; Lamoral, Sophie; Hantson, Philippe

    2016-01-01

    A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine. PMID:27462243

  11. New-Onset Refractory Status Epilepticus: More Investigations, More Questions.

    PubMed

    Dillien, Philippe; Ferrao Santos, Susana; van Pesch, Vincent; Suin, Vanessa; Lamoral, Sophie; Hantson, Philippe

    2016-01-01

    A 27-year-old previously healthy woman was admitted to the hospital with recurrent seizures. Status epilepticus developed that became refractory to third-line therapy with propofol and barbiturates. The patient had a very extensive diagnostic workup including autoimmune, viral and genetic investigations. A tentative immune therapy was proposed with high doses of steroids and plasma exchanges. Our patient had an inherited heterozygous single nucleotide variant in the sequence c.1280A>G [p.Lys427Arg] of the SMC3 gene that was insufficient to explain the seizures. Surprisingly, IgM antibodies against Japanese encephalitis virus were positive on the serum drawn 11 days after symptom onset, as detected by ELISA and the immunofluorescence antibody (IFA) technique. IgG antibodies were also positive using the IFA technique, but not with ELISA. The same investigations as well as the detection of the viral genome by the q-RT-PCR technique were negative on cerebrospinal fluid. Despite the suspicion of a viral infection, we concluded that our patient had a new-onset refractory status epilepticus of cryptogenic origin. Termination of the status epilepticus was obtained after 47 days, with a possible benefit from the introduction of ketamine. PMID:27462243

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

    PubMed

    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

  13. Electroencephalographic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey.

    PubMed

    Sutter, Raoul; Kaplan, Peter W

    2012-08-01

    There have been many attempts at defining the electroencephalography (EEG) characteristics of nonconvulsive status epilepticus (NCSE) without a universally accepted definition. This lack of consensus arises because the EEG expression of NCSE does not exist in isolation, but reflects status epilepticus under the variety of pathologic conditions that occur with age, cerebral development, encephalopathy, and epilepsy syndrome. Current NCSE definitions include "boundary conditions," in which electroencephalographic seizure activity occurs without apparent clinical seizures. Furthermore, what appears to one interpreter as status epilepticus, is not to another reader, reflecting the "art" of EEG interpretation. Seizures and epilepsy syndromes have undergone an evolution that has moved beyond a classification of focal or generalized conditions into a syndromic approach. It seems appropriate to make similar changes in the EEG analysis of the syndromes of NCSE. In effect, the literature on epilepsy classification has progressed to incorporate the different NCSE types with clinical descriptions, but the specific EEG evidence for these types is found largely in individual reports, and often by description only. NCSE classification of EEG patterns should derive from the aggregate of published EEG patterns in the respective clinical subtype, supported by an analysis of these EEG studies. The analysis that follows presents clinical descriptions and EEG patterns of NCSE in the neonatal period, infancy, childhood, adulthood, and late adulthood from a syndromic perspective based on age, encephalopathy, cerebral development, etiology, and syndrome. Proceeding from the proposed classification of status epilepticus syndromes in "Status epilepticus: its clinical features and treatment in children and adults" (published in 1994 by Cambridge University Press, New York), we have performed a systematic search for reports presenting EEG patterns of NCSE using the online medical search

  14. Non-convulsive status epilepticus associated with glutamic acid decarboxylase antibody.

    PubMed

    Cikrikçili, Ugur; Ulusoy, Canan; Turan, Selin; Yildiz, Senay; Bilgiç, Basar; Hanagasi, Hasmet; Baykan, Betül; Tüzün, Erdem; Gürvit, Hakan

    2013-07-01

    Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis.  PMID:23820312

  15. 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. PMID:26878120

  16. Effect of music on the recovery of a patient with refractory nonconvulsive status epilepticus.

    PubMed

    Kuester, Gisela; Rios, Loreto; Ortiz, Armando; Miranda, Marcelo

    2010-08-01

    The effect of music in epilepsy has been reported as beneficial but mainly in the interictal condition. There are no reports of the effect of music in an acute condition such as status epilepticus. Herein, we report a remarkable response to music in a patient with medically refractory nonconvulsive status epilepticus. PMID:20637708

  17. Complete recovery after severe myxoedema coma complicated by status epilepticus.

    PubMed

    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

  18. Algorithm for the treatment of status epilepticus: an Australian perspective.

    PubMed

    Jones, C L; Koios, J

    2016-04-01

    Convulsive status epilepticus (SE) is a medical emergency where successful treatment is associated with timely intervention and the use of a protocol has been recommended to provide the highest quality of care. Despite this, there is no nationally available protocol for the treatment of SE in adults in Australia. Treatment is therefore variable and often based on international guidelines or familiarity with certain medications. We have developed an Australian-based algorithm for the treatment of SE, focusing on simplifying management while delivering the safest possible care. We believe this algorithm is suitable for all health practitioners, regardless of training or experience. PMID:27062207

  19. Mixed myoclonic-absence status epilepticus in juvenile myoclonic epilepsy.

    PubMed

    Gélisse, Philippe; Crespel, Arielle

    2015-03-01

    Myoclonic status epilepticus or mixed absence-myoclonic status is uncommon in juvenile myoclonic epilepsy (JME), often precipitated by sleep deprivation, withdrawal of medication, or inadequate antiepileptic drugs (Thomas et al., 2006; Crespel et al., 2013). Such episodes respond well to benzodiazepines or valproate (Crespel et al., 2013). We present the video-EEG of a 24-year-old woman with JME and bipolar disorder. She had a confusional state five days after withdrawal of clonazepam (14 mg/d) and introduction of oxazepam (200 mg/d), followed by catatonic stupor with subtle myoclonus of the face and the arms. The EEG showed absence status (figures 1, 2), which stopped after IV injection of clonazepam (1 mg) (figure 3). Consciousness returned to normal [Published with video sequence and figures (1)]. PMID:25644293

  20. Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan.

    PubMed

    Roberts, Darren M; Dissanayake, Wasantha; Rezvi Sheriff, M H; Eddleston, Michael

    2004-09-01

    We describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with the organochlorine insecticide endosulfan. Although rarely seen in developed countries, pesticide poisoning particularly with endosulfan is an important cause of difficult-to-manage seizures in Asian countries. In this case report, we discuss the management of status epilepticus and refractory status epilepticus. Further, we specifically discuss the clinical pharmacology and toxicology of endosulfan. PMID:15337143

  1. Ketogenic diet for adults in super-refractory status epilepticus

    PubMed Central

    Thakur, Kiran T.; Probasco, John C.; Hocker, Sara E.; Roehl, Kelly; Henry, Bobbie; Kossoff, Eric H.; Kaplan, Peter W.; Geocadin, Romergryko G.; Hartman, Adam L.; Venkatesan, Arun

    2014-01-01

    Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE. PMID:24453083

  2. Severe cefepime-induced status epilepticus treated with haemofiltration.

    PubMed

    Suarez-de-la-Rica, A; Hernández-Gancedo, C; López-Tofiño, A; Maseda, E; Gilsanz, F

    2016-01-01

    Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA. PMID:26633605

  3. 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". PMID:26148985

  4. A Comparison of Intravenous Levetiracetam and Valproate for the Treatment of Refractory Status Epilepticus in Children.

    PubMed

    İşgüder, Rana; Güzel, Orkide; Ceylan, Gökhan; Yılmaz, Ünsal; Ağın, Hasan

    2016-08-01

    Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer. PMID:27080042

  5. 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". PMID:25843343

  6. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    PubMed Central

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed. PMID:25674075

  7. Temporal lobe or psychomotor status epilepticus. A case report.

    PubMed

    Wieser, H G

    1980-05-01

    A 22-year-old female with a history of polymorphic and uncontrollable psychomotor seizures in association with unclear disturbances of perception, emotion and intellect is reported. During chronically performed SEEG studies the patient entered a psychomotor status epilepticus with transition from the discontinuous to the continuous type. The electrical findings at surface and depth indicated a primary epileptogenic area in the right hippocampal formation. The typical clinical signs were observed during depth recording. The anatomo-electroclinical correlations therefore could be studied with confidence. Good correlation could be established between distinct seizure patterns and predominant clinical signs. Especially long-lasting hallucinations of music were clearly linked to the ictal involvement of the right gyrus of Heschl, and clouded consciousness and/or memory disturbances were shown to be due to bilateral ictal discharges in the hippocampal formations. Attempts to control the status activity by diazepam intravenously were without striking effects, but very specific acoustic stimuli influenced the discharging pattern of the gyrus of Heschl. PMID:6153964

  8. Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus

    PubMed Central

    Silbergleit, Robert; Durkalski, Valerie; Lowenstein, Daniel; Conwit, Robin; Pancioli, Arthur; Palesch, Yuko; Barsan, William

    2012-01-01

    BACKGROUND Early termination of prolonged seizures with intravenous administration of benzodiazepines improves outcomes. For faster and more reliable administration, paramedics increasingly use an intramuscular route. METHODS This double-blind, randomized, noninferiority trial compared the efficacy of intramuscular midazolam with that of intravenous lorazepam for children and adults in status epilepticus treated by paramedics. Subjects whose convulsions had persisted for more than 5 minutes and who were still convulsing after paramedics arrived were given the study medication by either intramuscular autoinjector or intravenous infusion. The primary outcome was absence of seizures at the time of arrival in the emergency department without the need for rescue therapy. Secondary outcomes included endotracheal intubation, recurrent seizures, and timing of treatment relative to the cessation of convulsive seizures. This trial tested the hypothesis that intramuscular midazolam was noninferior to intravenous lorazepam by a margin of 10 percentage points. RESULTS At the time of arrival in the emergency department, seizures were absent without rescue therapy in 329 of 448 subjects (73.4%) in the intramuscular-midazolam group and in 282 of 445 (63.4%) in the intravenous-lorazepam group (absolute difference, 10 percentage points; 95% confidence interval, 4.0 to 16.1; P<0.001 for both noninferiority and superiority). The two treatment groups were similar with respect to need for endotracheal intubation (14.1% of subjects with intramuscular midazolam and 14.4% with intravenous lorazepam) and recurrence of seizures (11.4% and 10.6%, respectively). Among subjects whose seizures ceased before arrival in the emergency department, the median times to active treatment were 1.2 minutes in the intramuscular-midazolam group and 4.8 minutes in the intravenous-lorazepam group, with corresponding median times from active treatment to cessation of convulsions of 3.3 minutes and 1.6 minutes

  9. [FOCAL MOTOR SEIZURES AND STATUS EPILEPTICUS PROVOKED BY MIRTAZAPINE].

    PubMed

    Dömötör, Johanna; Clemens, Béla

    2015-07-30

    The seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non-epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case. PMID:26380424

  10. Acetazolamide for electrical status epilepticus in slow-wave sleep.

    PubMed

    Fine, Anthony L; Wirrell, Elaine C; Wong-Kisiel, Lily C; Nickels, Katherine C

    2015-09-01

    Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers. PMID:26230617

  11. High frequency oscillations can pinpoint seizures progressing to status epilepticus.

    PubMed

    Salami, Pariya; Lévesque, Maxime; Avoli, Massimo

    2016-06-01

    Status epilepticus (SE) is defined as a seizure lasting more than 5min or a period of recurrent seizures without recovery between them. SE is a serious emergency condition that requires immediate intervention; therefore, identifying SE electrophysiological markers may translate in prompt care to stop it. Here, we analyzed the EEG signals recorded from the CA3 region of the hippocampus and the entorhinal cortex in rats that responded to systemic administration of 4-aminopyridine (4AP) by generating either isolated seizures or seizures progressing to SE. We found that high frequency oscillations (HFOs) - which can be categorized as ripples (80-200Hz) and fast ripples (250-500Hz) - had different patterns of occurrence in the two groups (n=5 for each group). Specifically, fast ripples in CA3 and entorhinal cortex of the SE group occurred at higher rates than ripples, both during the ictal and post-ictal periods when compared to the HFOs recorded from the isolated seizure group. Our data reveal that different patterns of HFO occurrence can pinpoint seizures progressing to SE, thus suggesting the involvement of different neuronal networks at the termination of seizure discharges. PMID:27018321

  12. Clinical significance of treatment delay in status epilepticus

    PubMed Central

    2013-01-01

    Background Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE. Methods This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition. Results The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome. Conclusions The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE. PMID:23445821

  13. Local cerebral glucose utilization during status epilepticus in newborn primates

    SciTech Connect

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

    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 in 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.

  14. 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. PMID:21705280

  15. 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

  16. A case of recurrent acute encephalopathy with febrile convulsive status epilepticus with carnitine palmitoyltransferase II variation.

    PubMed

    Sakai, Eiko; Yamanaka, Gaku; Kawashima, Hisashi; Morishima, Yasuyuki; Ishida, Yu; Oana, Shingo; Miyajima, Tasuku; Shinohara, Mayu; Saitoh, Makiko; Mizuguchi, Masashi

    2013-08-01

    Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE. PMID:23450341

  17. 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. PMID:26187779

  18. [Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus].

    PubMed

    de Freitas, Rivelilson Mendes; de Sousa, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro Barros; Fonteles, Marta Maria de França

    2003-06-01

    High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.). Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in immature striatum. PMID:12894279

  19. 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

  20. 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. PMID:26518205

  1. Surgical treatment of focal symptomatic refractory status epilepticus with and without invasive EEG

    PubMed Central

    Oderiz, Carolina Cuello; Aberastury, Marina; Besocke, Ana Gabriela; Sinner, Jorge; Comas-Guerrero, Betiana; Ciraolo, Carlos Alberto; Pasteris, Maria Concepción; Silva, Walter Horacio; García, María del Carmen

    2015-01-01

    Purpose Neurosurgery appears to be a reasonable alternative in carefully selected patients with refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). We discuss the optimal timing of the surgery and the use of previous stereoelectroencephalography (SEEG) invasive evaluation. Methods We identified 3 patients (two pediatric and one adult) who underwent epilepsy surgery because of RSE or SRSE from our epilepsy surgery database, one of them with previous SEEG. Results Status epilepticus resolved acutely in all of them with no mortality and no substantial morbidity. At follow-up (median: 2 years), 1 patient was seizure-free, and 2 had significant improvement. Conclusion Surgery should be considered in all cases of RSE and SRSE early in the course of the evolution of the disease. PMID:26543817

  2. 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. PMID:27280723

  3. Levetiracetam versus phenytoin in management of status epilepticus.

    PubMed

    Chakravarthi, Sudheer; Goyal, Manoj Kumar; Modi, Manish; Bhalla, Ashish; Singh, Parampreet

    2015-06-01

    The purpose of this study was to compare safety and efficacy of intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) in management of status epilepticus (SE). The second-line treatment of SE is limited to a few drugs available in an IV formulation such as PHT, fosphenytoin and valproate. The relative lack of serious side effects and favourable pharmacokinetics of LEV made it a promising option in management of SE. Randomized trials comparing relative efficacy of second-line agents are remarkably lacking. In this study, consecutive patients of SE (n=44) were randomized to receive either IV PHT (20mg/kg) or IV LEV (20mg/kg). The primary end point was successful clinical termination of seizure activity within 30min after the beginning of the drug infusion. Secondary end points included recurrence of seizures within 24 hours, drug related adverse effects, neurological outcome at discharge, need for ventilatory assistance, and mortality during hospitalization. Both LEV and PHT were equally effective with regard to primary and secondary outcome measures. PHT achieved control of SE in 15 (68.2%) patients compared to LEV in 13 (59.1%; p=0.53). Both the groups showed comparable results with respect to recurrence of seizures within 24 hours (p=0.34), outcome at discharge as assessed by functional independence measure (p=0.68), need of ventilatory assistance (p=0.47) and death (p=1). From this study it can be concluded that LEV may be an attractive and effective alternative to PHT in management of SE. PMID:25899652

  4. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus.

    PubMed

    Reznik, Michael E; Berger, Karen; Claassen, Jan

    2016-01-01

    Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE), a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while providing an approach to their use in adult patients, along with possible associated complications. PMID:27213459

  5. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus

    PubMed Central

    Reznik, Michael E.; Berger, Karen; Claassen, Jan

    2016-01-01

    Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE), a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while providing an approach to their use in adult patients, along with possible associated complications. PMID:27213459

  6. Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review.

    PubMed

    Walli, Akil; Poulsen, Troels Dirch; Dam, Mette; Børglum, Jens

    2016-01-01

    Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812

  7. Nonconvulsive status epilepticus: An unusual cause of postoperative unresponsiveness following general anaesthesia

    PubMed Central

    Sudha, P; Koshy, Rachel Cherian

    2011-01-01

    Any altered behaviour or sensorium following general anaesthesia is of concern to the anaesthesiologist, as it could be attributed to the anaesthetic itself or to a hypoxic insult, both of which can have medicolegal implications. It is important to be aware of a relatively unfamiliar entity known as nonconvulsive status epilepticus in this context. We report two cases to highlight this condition. PMID:21712877

  8. 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". PMID:25952268

  9. Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and Topical Review

    PubMed Central

    Dam, Mette

    2016-01-01

    Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is not uncommon in patients with refractory status epilepticus (RSE). We describe a case of refractory status epilepticus complicated by propofol infusion syndrome and collect from 5 databases all reports of refractory status epilepticus cases that were treated by propofol and developed the syndrome and outline whether refractory status epilepticus treatment with propofol is standardized according to international recommendations, compare it with alternative medications, and discuss how this syndrome can be treated and prevented. A total of 21 patients who developed this syndrome reported arrhythmia in all cases (100%), rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6 cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher than what is internationally recommended, and new treatment modalities such as renal replacement therapy, blood exchange, and extracorporeal membrane oxygenation seem to be promising. In conclusion, propofol should be carefully titrated, the maximal infusion rate needs to be reassessed, and combination of different sedative agents may be considered. PMID:27493812

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

    PubMed Central

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

    2014-01-01

    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. PMID:22019057

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

    SciTech Connect

    Dhote, Franck; Carpentier, Pierre; Barbier, Laure; Peinnequin, André; Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie; and others

    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. 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 activation is

  12. 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". PMID:25960423

  13. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency

    PubMed Central

    Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker

    2016-01-01

    Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency. PMID:27606021

  14. 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. PMID:26492121

  15. Two Patients Diagnosed with Juvenile Myoclonic Epilepsy by First-Ever Status Epilepticus in Adult Life

    PubMed Central

    Jeong, Hye Seon; Moon, Jeong Soo; Oh, Eung Seok; Kim, Jae Moon

    2011-01-01

    Juvenile myoclonic epilepsy (JME) is an idiopathic, age-related generalized epileptic syndrome. Status epilepticus (SE) in JME is very rare, and little is known about its etiology. We report 2 cases of adult patients, retrospectively diagnosed as JME by non convulsive status epilepticus which occurred for the first time. One patient was a 52-year-old woman who was presented with confusion and brief generalized tonic-clonic seizure (GTCS) for the first time. The other patient, a 39 year-old woman, visited the ER with transient LOC following confused mental state. Electroencephalograms of both patients repetitively showed generalized polyspikes and slow waves which were disappeared after IV injection of lorazepam. With careful history taking, both of them the patients were diagnosed as JME, and the seizures stopped just after sodium valproate medication. NCSE in patients with JME is rare but detailed history taking and suspicion of the disorder is helpful for diagnosis. PMID:24649443

  16. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency.

    PubMed

    Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker

    2016-01-01

    Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency. PMID:27606021

  17. Frontal motor seizure following non-convulsive status epilepticus in ring chromosome 20 syndrome.

    PubMed

    Kamoun, Fatma F; Ellouz, Emna J; Hsairi, Ines G; Triki, Chahnez C

    2012-01-01

    The ring chromosome 20 syndrome is a rare syndrome characterized by intractable epilepsy with particular electro clinical features including episodes of prolonged confusional state and nocturnal frontal lobe seizures. We report a 17-year-old girl who had intractable epilepsy with frontal seizure and prolonged confusional state secondary to non-convulsive status epilepticus. The diagnosis of ring chromosome 20 was suspected and confirmed by karyotype. The cytogenetic study of CHRNA4 and KCNQ2 genes did not detect deletion in the ring chromosome 20. During video-EEG recording, this girl presented a non-convulsive status epilepticus that lasted more than 20 minutes followed by typical frontal lobe seizure. This association was not previously described, and was probably caused by chromosomal instability. PMID:22246017

  18. 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.

  19. 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. PMID:26681545

  20. Pott puffy tumor in a 4-year-old boy presenting in status epilepticus.

    PubMed

    Strony, Robert J; Dula, David

    2007-11-01

    Pott puffy tumor is an osteomyelitis of the frontal bone with the development of a subperiosteal abscess manifesting as a puffy swelling of the forehead or scalp. It is believed to occur as a complication of frontal sinusitis. The modern antibiotic era has made it a rarely encountered entity. This case describes a 4-year-old boy who presented in status epilepticus secondary to Pott puffy tumor. PMID:18007214

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

    SciTech Connect

    Kaminski, Rafal M. . E-mail: kaminskr@mail.nih.gov; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.

    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 lithium 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.

  2. Emergency management of the paediatric patient with generalized convulsive status epilepticus

    PubMed Central

    Friedman, JN

    2011-01-01

    The present guideline paper addresses the emergency management of generalized convulsive status epilepticus (CSE) in children and infants older than one month of age. It replaces the previous statement from 1996, and includes a new treatment algorithm and table of recommended medications, reflecting new evidence and the evolution of clinical practice over the past 15 years. The document focuses on the acute pharmacological management of CSE, but some issues regarding supportive care, diagnostic approach and treatment of refractory CSE are discussed. PMID:22294869

  3. Tetramethylenedisulfotetramine contaminated milk powder induced status epilepticus in two siblings and two dogs.

    PubMed

    Intusoma, Utcharee; Sornsrivichai, Vorasith

    2009-10-01

    A cluster of patients with tetramethylenedisulfotetramine (TETS) intoxication was reported in Thailand. Two siblings, a-six-month-old boy and a-four-year-old girl, and their domestic dogs presented with status epilepticus within 10 minutes after ingesting milk prepared from the same tin container of milk powder. Although the cases showed normal neurodevelopment at one-year follow-up, physicians should be informed of this lethal neurotoxic agent, especially in an era of terroristic activity. PMID:19845251

  4. Depression and/or potentiation of cortical responses after status epilepticus in immature rats.

    PubMed

    Tsenov, G; Mares, P

    2007-01-01

    Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical interhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE. PMID:16925471

  5. Experimental Models of Status Epilepticus and Neuronal Injury for Evaluation of Therapeutic Interventions

    PubMed Central

    Reddy, Doodipala Samba; Kuruba, Ramkumar

    2013-01-01

    This article describes current experimental models of status epilepticus (SE) and neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. SE is an emergency condition associated with continuous seizures lasting more than 30 min. It causes significant mortality and morbidity. SE can cause devastating damage to the brain leading to cognitive impairment and increased risk of epilepsy. Benzodiazepines are the first-line drugs for the treatment of SE, however, many people exhibit partial or complete resistance due to a breakdown of GABA inhibition. Therefore, new drugs with neuroprotective effects against the SE-induced neuronal injury and degeneration are desirable. Animal models are used to study the pathophysiology of SE and for the discovery of newer anticonvulsants. In SE paradigms, seizures are induced in rodents by chemical agents or by electrical stimulation of brain structures. Electrical stimulation includes perforant path and self-sustaining stimulation models. Pharmacological models include kainic acid, pilocarpine, flurothyl, organophosphates and other convulsants that induce SE in rodents. Neuronal injury occurs within the initial SE episode, and animals exhibit cognitive dysfunction and spontaneous seizures several weeks after this precipitating event. Current SE models have potential applications but have some limitations. In general, the experimental SE model should be analogous to the human seizure state and it should share very similar neuropathological mechanisms. The pilocarpine and diisopropylfluorophosphate models are associated with prolonged, diazepam-insensitive seizures and neurodegeneration and therefore represent paradigms of refractory SE. Novel mechanism-based or clinically relevant models are essential to identify new therapies for SE and neuroprotective interventions. PMID:24013377

  6. Are Newer AEDs Better Than the Classic Ones in the Treatment of Status Epilepticus?

    PubMed

    Rossetti, Andrea O

    2016-02-01

    Several newer antiepileptic drugs have been increasingly used in patients with status epilepticus, especially levetiracetam and lacosamide, because of their intravenous availability. They may offer advantages in terms of tolerability; however, to date, no clear evidence suggests any advantage regarding efficacy after the use of newer antiepileptic drugs in this specific clinical setting. However, there has been a considerable revival of interest regarding some classic compounds, such as midazolam (MDZ), valproate (VPA), ketamine, or ketogenic diet. Awaiting comparative studies, which in part are ongoing, it seems reasonable, for the first choice, to rely on those agents that are best known and less expensive. PMID:26840872

  7. 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. PMID:26552284

  8. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    PubMed Central

    Shrestha, Gentle Sunder; Joshi, Pankaj; Chhetri, Santosh; Karn, Ragesh; Acharya, Subhash Prasad

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion. PMID:25983437

  9. 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

  10. Gabapentin Administration Reduces Reactive Gliosis and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

    PubMed Central

    Rossi, Alicia Raquel; Angelo, Maria Florencia; Villarreal, Alejandro; Lukin, Jerónimo; Ramos, Alberto Javier

    2013-01-01

    The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE) followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the latency period after SE

  11. 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

  12. 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

  13. Syndromes at risk of status epilepticus in children: genetic and pathophysiological issues.

    PubMed

    Neubauer, Bernd A; Hahn, Andreas

    2014-10-01

    Status epilepticus (SE) is a medical emergency with increased risk of morbidity and mortality in all age groups. Recent research has identified a variety of new genes implicated in disorders with severe epilepsies as a prominent feature. Autoimmune mechanisms have also been recently recognised as a cause of epilepsies with SE as a characteristic symptom. Knowledge about the aetiology potentially underlying SE may help to guide diagnostics and eventually influence treatment decisions. This review recapitulates, in brief, the risk of SE in specific clinical settings, provides an overview of paediatric epilepsy syndromes more commonly, or by definition, associated with SE, and summarizes some recent research data on genetic defects and disease mechanisms implicated in the pathogenesis of epilepsies frequently accompanied by SE. PMID:25323303

  14. 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. PMID:26980640

  15. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

    PubMed

    McCarren, Hilary S; McDonough, John H

    2016-06-01

    Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID:27258770

  16. 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. PMID:26979444

  17. [Use of benzodiazepines in prolonged seizures and status epilepticus in the community].

    PubMed

    Sánchez-Carpintero, R; Camino, R; Smeyers, P; Raspall-Chaure, M; Martínez-Bermejo, A; Ruiz-Falcó, M L; Verdú, A; Sanmarti, F X; Blanco, O; Santos Borbujo, J; Picó, G; Cebollero, M A

    2014-12-01

    Prolonged seizures and status epilepticus are common neurological medical emergencies. Early and appropriate treatment is essential to reduce morbidity and mortality. Most seizures occur in the community, so parents and caregivers must be prepared for their management. Benzodiazepines (BZD) are the first-line drugs used, with rectal diazepam (DZPr) being the most commonly used in pre-hospital treatment in Spain. In September 2011, the European Medicines Agency (EMA) authorized the use of oromucosal midazolam (MDZb) for the treatment of prolonged acute convulsive seizures in patients aged 3 months to <18 years. MDZb has a rapid onset, short duration of effect, and avoids first-pass hepatic metabolism. MDZb has shown to be at least as or more effective than DZPr to stop the seizures. Buccal administration is easier and more socially accepted, especially in adolescents and adults. It is a safe drug with similar effects to other BZD; MDZb improves the overall cost-effectiveness of seizures management. PMID:25441206

  18. 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. PMID:26773681

  19. Cortical gray matter lesions in acute encephalopathy with febrile convulsive status epilepticus.

    PubMed

    Sato, Atsushi; Mizuguchi, Masashi; Mimaki, Masakazu; Takahashi, Kan; Jimi, Hanako; Oka, Akira; Igarashi, Takashi

    2009-09-01

    In acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), subcortical white matter lesions on diffusion-weighted images are sometimes encountered on magnetic resonance imaging (MRI), such as in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). We report here a severe case of AEFCSE following respiratory syncytial virus infection, with emphasis on the cranial MRI findings. MRI in this patient showed widespread T2-hyperintensity along the cerebral cortical gray matter from day 3 to day 22. Lesions with reduced diffusion were noted on day 3 in the deep zone of gray matter of the left occipito-temporo-parietal cortex, but on day 7 they shifted to the subcortical white matter of both the cerebral hemispheres. These MRI findings provide radiologic evidence for damage to the cortical gray matter in AEFCSE. The serial change of diffusion-weighted images suggests that the cortical gray matter may be injured prior to the involvement of the subcortical white matter. PMID:18848752

  20. 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

  1. 22-year-old girl with status epilepticus and progressive neurological symptoms.

    PubMed

    Striano, Pasquale; Ackerley, Cameron A; Cervasio, Mariarosaria; Girard, Jean-Marie; Turnbull, Julie; Del Basso-De Caro, Maria Laura; Striano, Salvatore; Zara, Federico; Minassian, Berge A

    2009-10-01

    A 22-year-old girl presented with convulsive status epilepticus and a previous history of recurrent seizures, myoclonus, ataxia and impaired cognitive functions. Neurological examination revealed rest and action-induced myoclonus, pyramidal signs and opposition hypertonia. Testing revealed severe metabolic acidosis, elevated transaminases and creatine kinase, and respiratory insufficiency. After intubation and ventilation, thiopental was introduced but the patient's condition worsened dramatically with death in a few hours. Autopsy showed profuse periodic acid-Schiff (PAS) positive intracellular inclusions in the CNS (Lafora bodies), most abundant in thalamus, cerebellum, and brainstem, as well as in other organs. Genetic testing revealed a homozygous missense mutation (c.205C > G, P69A) in the EPM2B (NHLRC1) gene, confirming the diagnosis of progressive myoclonic epilepsy Lafora-type. PMID:19744044

  2. Treatment of convulsive status epilepticus in childhood: recommendations of the Italian League Against Epilepsy.

    PubMed

    Capovilla, Giuseppe; Beccaria, Francesca; Beghi, Ettore; Minicucci, Fabio; Sartori, Stefano; Vecchi, Marilena

    2013-10-01

    The Italian League Against Epilepsy Commission Guidelines Subcommittee on Status Epilepticus (SE) has published an article on the management of SE in adults, and now presents a report on the management of convulsive status epilepticus (CSE) in children, excluding the neonatal period. Children's greater susceptibility than adults to epileptic seizures results from many factors. Earlier maturation of excitatory than inhibitory synapses, increased susceptibility and concentration of receptors for excitatory neurotransmitters, peculiar composition of the receptor subunits resulting in slower and less effective inhibitory responses, all cause the high incidence of SE in the pediatric population. The related morbidity and mortality rates, although lower than in adults, require immediate diagnosis and therapy. The division into focal and generalized, nonconvulsive and convulsive SE is applied in children and adolescents, as is the distinction in the three different stages according to the time elapsed since the start of the event and the response to drugs (initial, defined, and refractory SE). In children and adolescents, an "operational definition" is also accepted to allow earlier treatment (starting at 5-10 min). Maintenance and stabilization of vital functions, cessation of convulsions, diagnosis, and initial treatment of potentially "life-threatening" causes are the objectives to be pursued in the management of children with CSE. The need for early pharmacologic intervention stresses the need for action in the prehospital setting, generally using rectal diazepam. In hospital, parenteral benzodiazepines are used (lorazepam, diazepam, or midazolam). When first-line drugs fail, sodium phenytoin and phenobarbital should be used. As alternatives to phenobarbital, the following can be considered for treatment of refractory CSE: valproate, levetiracetam, and lacosamide. In cases with refractory CSE, pharmacologic options can be thiopental, midazolam, or propofol in

  3. Electrographic seizures after convulsive status epilepticus in children and young adults. A retrospective multicenter study

    PubMed Central

    Fernández, Iván Sánchez; Abend, Nicholas S.; Arndt, Daniel H.; Carpenter, Jessica L.; Chapman, Kevin E; Cornett, Karen M.; Dlugos, Dennis J.; Gallentine, William B.; Giza, Christopher C; Goldstein, Joshua L; Hahn, Cecil D; Lerner, Jason T; Matsumoto, Joyce H; McBain, Kristin; Nash, Kendall B; Payne, Eric; Sánchez, Sarah M; Williams, Korwyn; Loddenkemper, Tobias

    2013-01-01

    Objectives To describe the prevalence, characteristics and predictors of electrographic seizures following convulsive status epilepticus (CSE). Study design Multicenter retrospective study describing clinical and electroencephalographic (EEG) features of children (1 month-21 years) with CSE who underwent continuous EEG monitoring. Results Ninety-eight children (53 males) with a median age of 5 years with CSE underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electro-clinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a prior diagnosis of epilepsy (p= 0.029) and the presence of interictal epileptiform discharges (p< 0.0005). The median (p25–p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures [9.5 (3–22.5) versus 2 (2–5) days, Wilcoxon test, Z=3.916, p=0.0001]. Four children (4.1%) died before leaving the hospital and we could not identify a relationship between death and the presence or absence of electrographic seizures. Conclusions Following CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A prior diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures. PMID:24161223

  4. Diabetic hyperglycemia aggravates seizures and status epilepticus-induced hippocampal damage.

    PubMed

    Huang, Chin-Wei; Cheng, Juei-Tang; Tsai, Jing-Jane; Wu, Sheng-Nan; Huang, Chao-Ching

    2009-01-01

    Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon. This study aimed to determine the acute behavioral, pathological, and electrophysiological effects of status epilepticus (SE) on diabetic animals. Adult male Sprague-Dawley rats were first divided into groups with and without streptozotocin (STZ)-induced diabetes, and then into treatment groups given a normal saline (NS) (STZ-only and NS-only) or a lithium-pilocarpine injection to induce status epilepticus (STZ + SE and NS + SE). Seizure susceptibility, severity, and mortality were evaluated. Serial Morris water maze test and hippocampal histopathology results were examined before and 24 h after SE. Tetanic stimulation-induced long-term potentiation (LTP) in a hippocampal slice was recorded in a multi-electrode dish system. We also used a simulation model to evaluate intracellular adenosine triphosphate (ATP) and neuroexcitability. The STZ + SE group had a significantly higher percentage of severe seizures and SE-related death and worse learning and memory performances than the other three groups 24 h after SE. The STZ + SE group, and then the NS + SE group, showed the most severe neuronal loss and mossy fiber sprouting in the hippocampal CA3 area. In addition, LTP was markedly attenuated in the STZ + SE group, and then the NS + SE group. In the simulation, increased intracellular ATP concentration promoted action potential firing. This finding that rats with DH had more brain damage after SE than rats without diabetes suggests the importance of intensively treating hyperglycemia and seizures in diabetic patients with epilepsy. PMID:19384590

  5. Current treatment of convulsive status epilepticus - a therapeutic protocol and review.

    PubMed

    Mazurkiewicz-Bełdzińska, Maria; Szmuda, Marta; Zawadzka, Marta; Matheisel, Agnieszka

    2014-01-01

    The management of status epilepticus (SE) has changed in recent years. Substantial differences exist regarding the definition and time frame of a seizure, which has been operationally defined as lasting for 5 min. Not only have many new intravenous drugs, such as levetiracetam and lacosamide been introduced but other routes of administration, such as intranasal or buccal administration for midazolam, are also being developed. Optimal and successful therapy initiated at the appropriate moment, adequately tailored to the clinical state of the patient, determines the first step in the normalisation of vital functions and leads to the restoration of the physiological homeostatic mechanisms of the organism. The aim of this review is to present the current treatment options for the management of convulsive status epilepticus (CSE) that have been widely confirmed as the most effective in clinical trials and approved by the international neurology authorities as the actual therapeutic standards. We also intend to indicate distinct and unequivocal differentiation and therapeutic indications for each phase of CSE, including the precise doses of the related medications, to present practical guidelines for clinicians. The treatment of patients with CSE requires emergency physicians, neurologists and specialists in intensive care to work together to provide optimal care that should be initiated as soon as possible and conducted as a unified procedure to improve neurocritical care in patients who are transferred from the ambulance service, through the emergency department and finally to the neurology department or ICU. Appropriate treatment also involves avoiding mistakes associated with inadequate doses of medications, overdosing a patient or choosing an inappropriate medication. PMID:25293482

  6. Effect of lithium-pilocarpine-induced status epilepticus on ultrasonic vocalizations in the infant rat pup.

    PubMed

    López-Meraz, Maria-Leonor; Medel-Matus, Jesus-Servando; Morgado-Valle, Consuelo; Beltrán-Parrazal, Luis; Pérez-Estudillo, César; Manzo, Jorge

    2014-02-01

    Evidence shows that febrile convulsions induced in rat pups increase ultrasonic vocalizations (USVs); however, the effect of status epilepticus (SE) induced in developing rats on USVs has not been fully investigated. The goal of this study was to analyze USVs following lithium-pilocarpine-induced SE in fourteen-day-old (P14) rat pups. The rat pups were given 3-mEq/kg lithium chloride i.p. on the day before the induction of SE, which was carried out at P14 by subcutaneous injection of 100-mg/kg pilocarpine hydrochloride; control animals were given an equal volume of lithium chloride and saline on P13 and P14, respectively. Ultrasonic vocalizations were monitored at P15, P16, and P21 with a Mini 3 Bat Detector Ultra Sound Advice (15kHz-160kHz) set at 40±4kHz and digitally recorded in WAV format using the Audacity 1.3 beta software. A clear box (60×40×30cm) split down the middle with a holed wall was used; each pup was placed alone in one compartment, whereas its dam was placed on the other cage side at room temperature. Vocalizations were recorded over a 5-minute period, converted to sonograms and spectrograms, and analyzed using the Raven software. Parameters evaluated were as follows: USV frequency, latency to the first USV, and mean USV duration. There was a significant decrease in the latency (35.5±6.9s) and duration (50.8±8.6s) of USVs after SE compared with the control group (81.9±10.8s and 78.1±9.9s, respectively). Status epilepticus affected male and female rats differentially. PMID:24230988

  7. Spatiotemporal profile of Map2 and microglial changes in the hippocampal CA1 region following pilocarpine-induced status epilepticus

    PubMed Central

    Schartz, Nicole D.; Herr, Seth A.; Madsen, Lauren; Butts, Sarah J.; Torres, Ceidy; Mendez, Loyda B.; Brewster, Amy L.

    2016-01-01

    Status epilepticus (SE) triggers pathological changes to hippocampal dendrites that may promote epileptogenesis. The microtubule associated protein 2 (Map2) helps stabilize microtubules of the dendritic cytoskeleton. Recently, we reported a substantial decline in Map2 that coincided with robust microglia accumulation in the CA1 hippocampal region after an episode of SE. A spatial correlation between Map2 loss and reactive microglia was also reported in human cortex from refractory epilepsy. New evidence supports that microglia modulate dendritic structures. Thus, to identify a potential association between SE-induced Map2 and microglial changes, a spatiotemporal profile of these events is necessary. We used immunohistochemistry to determine the distribution of Map2 and the microglia marker IBA1 in the hippocampus after pilocarpine-induced SE from 4 hrs to 35 days. We found a decline in Map2 immunoreactivity in the CA1 area that reached minimal levels at 14 days post-SE and partially increased thereafter. In contrast, maximal microglia accumulation occurred in the CA1 area at 14 days post-SE. Our data indicate that SE-induced Map2 and microglial changes parallel each other’s spatiotemporal profiles. These findings may lay the foundation for future mechanistic studies to help identify potential roles for microglia in the dendritic pathology associated with SE and epilepsy. PMID:27143585

  8. 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

  9. Does status epilepticus induced at early postnatal period change excitability after cortical epileptic afterdischarges?

    PubMed

    Mareš, Pavel; Kubová, Hana

    2016-08-01

    Possible changes of cortical excitability after status epilepticus (SE) elicited in 12-day-old rats were studied by means of paired cortical afterdischarges (ADs). Consequences of lithium-pilocarpine status were studied in animals with implanted electrodes 3, 6, 9, 13, and 26 days after SE. Paired low-frequency stimulation with a 1-min interval was repeated after 10 min, and duration of ADs was measured. Control rats received saline instead of pilocarpine; other treatments were the same as in SE group. Postictal refractoriness (i.e., the testing response significantly shorter than the conditioning one) appeared at the age of 18 days in lithium-paraldehyde controls, whereas SE animals exhibited this phenomenon since postnatal day 21. The only significant difference between SE and lithium-paraldehyde controls was found in the second conditioning AD in the oldest group studied-it was longer in 38-day-old SE animals. Our results demonstrated moderate signs of higher excitability of SE rats in comparison with control ones long before appearance of spontaneous seizures. PMID:27346862

  10. Clinical and EEG analysis of initial status epilepticus during infancy in patients with mesial temporal lobe epilepsy.

    PubMed

    Ohtsu, Mayu; Oguni, Hirokazu; Awaya, Yutaka; Osawa, Makiko

    2002-06-01

    This study investigated the clinical and EEG characteristics of initial status epilepticus (SE) during infancy in patients with mesial temporal lobe epilepsy (MTLE). The subjects were six patients who had been brought to our emergency clinic and treated for their initial SE between 1977 and 1988, and later developed MTLE. We reviewed the medical records and laboratory findings at the time of the initial SE, and the clinical evolution up to the development of MTLE. The six patients included four females and two males. The initial SE developed at ages ranging from 7 months to 2 years and 9 months with a mean of 1 year and 2 months. These episodes were characterized by an elevated temperature of more than 38 degrees C (4/6 cases), clusters of prolonged seizures during one episode of SE (4/6 cases), long-lasting SE (120-380 min, mean 227 min, 6/6 cases), postictal prolonged loss of consciousness (median 5 h, 6/6 cases), and the presence of Todd's paralysis (3/6 cases). The lateralization of the ictal or postictal EEGs of the SE in five of the six cases was identical to that of the hippocampal atrophy later confirmed by MRI. Follow-up EEG examinations at a 6 month interval demonstrated temporal spike discharges appearing only after the onset of complex partial seizures. Two patients, who had no fever at the initial SE, were characterized by a very early appearance of epileptic EEG abnormality and a short interval between the initial SE and the development of complex partial seizures, suggesting that the SE was the first epileptic manifestation. The result of this study showed that SE progressing to MTLE tends to have complicated clinical manifestations characterized by clusters of unilateral or generalized SE followed by prolonged postictal unconsciousness, generalized clinical manifestations despite lateralized ictal EEG discharges, and the Todd's paresis in addition to the prolonged seizure duration. PMID:12015166

  11. 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

  12. Outcome of status epilepticus. What do we learn from animal data?

    PubMed

    Auvin, Stéphane; Dupuis, Nina

    2014-10-01

    Status Epilepticus (SE) is a life-threatening neurologic disorder defined as 5 minutes or more of a continuous seizure. SE can represent an exacerbation of a preexisting seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder. In humans, there are several differences between SE that occurs in adults and children. In adult patients, the mortality is high but the incidence is lower than in childhood. Experimental studies have been essential in helping clinicians describe SE, and since these early initial studies, further experimental studies have helped us to better understand the consequences of SE. Animal models of SE support the notion that SE induces brain damage and contribute to epileptogenesis. Laboratory models of SE in developing animals demonstrate age- and model-dependent propensity for brain injury and for epileptogenesis. The use of models with a double hit including a clinical relevant component to seizures provides data that allows us to further understand the contribution of early-life events in the future development of epilepsy. Using this approach, it has been shown that inflammation or a preexisting brain lesion enhance epileptogenesis in the developing brain. The use of models of SE also permits to establish that treatment to stop the seizure and/or the duration of the SE results in a decrease of SE induced cell injury. Preventing epileptogenesis remains an important goal to modify the development of comorbidities, and it still represents an area of research in need of much progress. PMID:25322806

  13. Enhanced inositide turnover in brain during bicuculline-induced status epilepticus

    SciTech Connect

    Van Rooijen, L.A.; Vadnal, R.; Dobard, P.; Bazan, N.G.

    1986-04-29

    Because brain inositides are enriched in the 1-stearoyl-2-arachidonoyl species, they form a likely source for the tetraenoic free fatty acids (FFA) and diacylglycerols (DG) that are accumulated during seizures. To study inositide turnover during bicuculline-induced seizures, rats were injected intraventricularly and bilaterally with 10-20 microCi /sup 32/P, mechanically ventilated and sacrificed by 6.5 KW head-focused microwave irradiation. Seizure activity was recorded by electroencephalography. Bicuculline-induced seizure activity resulted in: a) almost 50% increase in /sup 32/P labeling of phosphatidic acid (PA); phosphatidylinositol (PI) and phosphatidylinositol 4,5-bisphosphate (PIP2) also increased (24% and 36%, respectively); b) no change in other lipids; and c) water-soluble phosphodiesteratic degradation products, analyzed by high voltage paper electrophoresis, increased 24% in the amount of radiotracer recovered as inositol 1,4-bisphosphate (IP2) and by 44% in the amount recovered as inositol 1,4,5-trisphosphate (IP3). These data indicate that during experimental status epilepticus the cerebral inositide cycle is accelerated: PIP2----(IP3----IP2----IP----I) + DG----PA----PI----PIP----PIP2.

  14. Structural alterations in the rat brain and behavioral impairment after status epilepticus: An MRI study.

    PubMed

    Suleymanova, E M; Gulyaev, M V; Abbasova, K R

    2016-02-19

    Temporal lobe epilepsy (TLE) is one of the most common neurologic disorders often associated with behavioral impairments and cognitive deficit. Lithium-pilocarpine model of seizures in rodents reproduces many features of human convulsive status epilepticus (SE) and subsequent TLE. In this study, we have investigated changes in the rat brain after lithium-pilocarpine SE using a high-field MRI system for small animals in early and chronic periods after SE. We have studied the relationship between T2 relaxation time measured in these periods and the development of behavioral exploratory response to novelty and habituation in the open field test. A significant increase in T2 in the hippocampus and associated structures was found 2 days after SE and practically resolved by day seven, while an increase in T2 in the parietal and prefrontal cortex appeared 30 days after SE. High T2 values in the parietal cortex and thalamus on day two after SE were associated with an increased mortality risk. A substantial variability in T2 relaxation time was observed in the hippocampus and amygdala 30 days after SE. Rats survived after SE showed locomotor hyperactivity and disruption of long-term habituation in the open field test carried out 5 weeks after the seizures. Interestingly, T2 in the amygdala 30 days after SE had a strong correlation with hyperactivity in the novel open field. Therefore, the amygdala damage may be an important factor in the development of hyperactivity in the chronic period after SE. PMID:26674057

  15. T2 relaxation time post febrile status epilepticus predicts cognitive outcome.

    PubMed

    Barry, Jeremy M; Choy, ManKin; Dube, Celine; Robbins, Ashlee; Obenaus, Andre; Lenck-Santini, Pierre Pascal; Scott, Rod C; Baram, Tallie Z; Holmes, Gregory L

    2015-07-01

    Evidence from animal models and patient data indicates that febrile status epilepticus (FSE) in early development can result in permanently diminished cognitive abilities. To understand the variability in cognitive outcome following FSE, we used MRI to measure dynamic brain metabolic responses to the induction of FSE in juvenile rats. We then compared these measurements to the ability to learn an active avoidance spatial task weeks later. T2 relaxation times were significantly lower in FSE rats that were task learners in comparison to FSE non-learners. While T2 time in whole brain held the greatest predictive power, T2 in hippocampus and basolateral amygdala were also excellent predictors. These signal differences in response to FSE indicate that rats that fail to meet metabolic and oxygen demand are more likely to develop spatial cognition deficits. Place cells from FSE non-learners had significantly larger firing fields and higher in-field firing rate than FSE learners and control animals and imply increased excitability in the pyramidal cells of FSE non-learners. These findings suggest a mechanistic cause for the spatial memory deficits in active avoidance and are relevant to other acute neurological insults in early development where cognitive outcome is a concern. PMID:25939697

  16. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

    PubMed

    Wang, N; Mi, X; Gao, B; Gu, J; Wang, W; Zhang, Y; Wang, X

    2015-02-26

    Mounting evidence suggests that brain inflammation mediated by glial cells may contribute to epileptogenesis. Minocycline is a second-generation tetracycline and has potent antiinflammatory effects independent of its antimicrobial action. The present study aimed to investigate whether minocycline could exert antiepileptogenic effects in a rat lithium-pilocarpine model of temporal lobe epilepsy. The temporal patterns of microglial and astrocytic activation were examined in the hippocampal CA1 and the adjacent cortex following pilocarpine-induced status epilepticus (SE). These findings displayed that SE caused acute and persistent activation of microglia and astrocytes. Based on these findings, Minocycline was administered once daily at 45 mg/kg for 14 days following SE. Six weeks after termination of minocycline treatment, spontaneous recurrent seizures (SRS) were recorded by continuous video monitoring. Minocycline inhibited the SE-induced microglial activation and the increased production of interleukin-1β and tumor necrosis factor-α in the hippocampal CA1 and the adjacent cortex, without affecting astrocytic activation. In addition, Minocycline prevented the SE-induced neuronal loss in the brain regions examined. Moreover, minocycline significantly reduced the frequency, duration, and severity of SRS during the two weeks monitoring period. These results demonstrated that minocycline could mitigate SE-induced brain inflammation and might exert disease-modifying effects in an animal model of temporal lobe epilepsy. These findings offer new insights into deciphering the molecular mechanisms of epileptogenesis and exploring a novel therapeutic strategy for prevention of epilepsy. PMID:25541249

  17. Pharmacological blockade of the calcium plateau provides neuroprotection following organophosphate paraoxon induced status epilepticus in rats.

    PubMed

    Deshpande, Laxmikant S; Blair, Robert E; Huang, Beverly A; Phillips, Kristin F; DeLorenzo, Robert J

    2016-01-01

    Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10mg/kg, i.m.) and carisbamate (90mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival. PMID:27224207

  18. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice.

    PubMed

    Sabilallah, Mounira; Fontanaud, Pierre; Linck, Nathalie; Boussadia, Badreddine; Peyroutou, Ronan; Lasgouzes, Thibault; Rassendren, François A; Marchi, Nicola; Hirbec, Helene E

    2016-01-01

    Kainic acid (KA) is routinely used to elicit status epilepticus (SE) and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN) remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%). Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1) and anti-inflammatory (M2) genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered. PMID:26963100

  19. 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

  20. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice

    PubMed Central

    Sabilallah, Mounira; Fontanaud, Pierre; Linck, Nathalie; Boussadia, Badreddine; Peyroutou, Ronan; Lasgouzes, Thibault; Rassendren, François A.

    2016-01-01

    Kainic acid (KA) is routinely used to elicit status epilepticus (SE) and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN) remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%). Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1) and anti-inflammatory (M2) genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered. PMID:26963100

  1. Venous stroke and status epilepticus due to milk-induced anemia in a child.

    PubMed

    Finkel, Leslie; Piantino, Juan; Goldstein, Joshua; Wainwright, Mark S

    2015-02-01

    The risk factors for cerebral sinus venous thrombosis include dehydration, infection, and anemia. The clinical presentation in children of venous strokes associated with cerebral venous thrombosis is variable and may include seizures. Acute management should focus on the treatment of the primary cause and anticoagulation or antiplatelet therapy if needed. Early recognition and targeted treatment is important because survivors are at increased risk for long-term neurologic complications. We report a case of a 4-year-old girl who presented with status epilepticus and was subsequently found to have a cerebral venous sinus thrombosis in the transverse and sigmoid sinus, with venous infarction in the temporal lobe. Laboratory results were significant for a microcytic anemia caused by excessive milk intake. Although iron deficiency anemia is a common pediatric disorder, this uncommon presentation demonstrates the potential for neurologic complications secondary to anemia, as well as the need for a high index of suspicion in order to identify venous stroke as a cause in children who present to the emergency department with seizures. PMID:25513978

  2. Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress.

    PubMed

    Si, Pei-Pei; Zhen, Jun-Li; Cai, Yun-Lei; Wang, Wen-Jing; Wang, Wei-Ping

    2016-04-01

    There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS. PMID:26940236

  3. Multi-omics profile of the mouse dentate gyrus after kainic acid-induced status epilepticus

    PubMed Central

    Schouten, Marijn; Bielefeld, Pascal; Fratantoni, Silvina A.; Hubens, Chantal J.; Piersma, Sander R.; Pham, Thang V.; Voskuyl, Rob A.; Lucassen, Paul J.; Jimenez, Connie R.; Fitzsimons, Carlos P.

    2016-01-01

    Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after a systemic injection of KA inducing status epilepticus (KA-SE), in mice. We performed a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques, detecting the expression of 2327 proteins, 13401 mRNAs and 311 microRNAs. We here present a description of how these data were obtained and make them available for further analysis and validation. Our data may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG. PMID:27529540

  4. Multi-omics profile of the mouse dentate gyrus after kainic acid-induced status epilepticus.

    PubMed

    Schouten, Marijn; Bielefeld, Pascal; Fratantoni, Silvina A; Hubens, Chantal J; Piersma, Sander R; Pham, Thang V; Voskuyl, Rob A; Lucassen, Paul J; Jimenez, Connie R; Fitzsimons, Carlos P

    2016-01-01

    Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after a systemic injection of KA inducing status epilepticus (KA-SE), in mice. We performed a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques, detecting the expression of 2327 proteins, 13401 mRNAs and 311 microRNAs. We here present a description of how these data were obtained and make them available for further analysis and validation. Our data may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG. PMID:27529540

  5. Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus.

    PubMed

    Strzelczyk, Adam; Klein, Karl Martin; Willems, Laurent M; Rosenow, Felix; Bauer, Sebastian

    2016-01-01

    Brivaracetam is the latest approved antiepileptic drug in focal epilepsy and exhibits high affinity as SV2A-ligand. More than two thousand patients have received brivaracetam within randomized placebo-controlled trials. Significant median seizure reduction rates of 30.5% to 53.1% for 50 mg/d, 32.5% to 37.2% for 100 mg/d and 35.6% for 200 mg/d were reported. Likewise, 50% responder rates were 32.7% to 55.8% for 50 mg/d, 36% to 38.9% for 100 mg/d and 37.8% for 200 mg/d. Overall, brivaracetam is well tolerated. The main adverse events are fatigue, dizziness, and somnolence. Immediate switch from levetiracetam to brivaracetam at a conversion ratio between 10:1 to 15:1 is feasible, and might alleviate the behavioral side effects associated with levetiracetam. Brivaracetam has the potential to perform as an important, possibly broad-spectrum AED, initially in patients with drug-refractory epilepsies. Its intravenous formulation may be a new and desirable alternative for status epilepticus, but there is so far no experience in these patients. PMID:26891946

  6. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    PubMed

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients. PMID:26834859

  7. Profiling status epilepticus-induced changes in hippocampal RNA expression using high-throughput RNA sequencing.

    PubMed

    Hansen, Katelin F; Sakamoto, Kensuke; Pelz, Carl; Impey, Soren; Obrietan, Karl

    2014-01-01

    Status epilepticus (SE) is a life-threatening condition that can give rise to a number of neurological disorders, including learning deficits, depression, and epilepsy. Many of the effects of SE appear to be mediated by alterations in gene expression. To gain deeper insight into how SE affects the transcriptome, we employed the pilocarpine SE model in mice and Illumina-based high-throughput sequencing to characterize alterations in gene expression from the induction of SE, to the development of spontaneous seizure activity. While some genes were upregulated over the entire course of the pathological progression, each of the three sequenced time points (12-hour, 10-days and 6-weeks post-SE) had a largely unique transcriptional profile. Hence, genes that regulate synaptic physiology and transcription were most prominently altered at 12-hours post-SE; at 10-days post-SE, marked changes in metabolic and homeostatic gene expression were detected; at 6-weeks, substantial changes in the expression of cell excitability and morphogenesis genes were detected. At the level of cell signaling, KEGG analysis revealed dynamic changes within the MAPK pathways, as well as in CREB-associated gene expression. Notably, the inducible expression of several noncoding transcripts was also detected. These findings offer potential new insights into the cellular events that shape SE-evoked pathology. PMID:25373493

  8. 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. PMID:26775897

  9. Rapid, Coordinate Inflammatory Responses after Experimental Febrile Status Epilepticus: Implications for Epileptogenesis

    PubMed Central

    Patterson, Katelin P.; Kinney-Lang, Eli; Dubé, Celine; Rashid, Faisal; Ly, Catherine; Obenaus, Andre

    2015-01-01

    Abstract Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy. PMID:26730400

  10. p75NTR, but not proNGF, is upregulated following status epilepticus in mice.

    PubMed

    VonDran, Melissa W; LaFrancois, John; Padow, Victoria A; Friedman, Wilma J; Scharfman, Helen E; Milner, Teresa A; Hempstead, Barbara L

    2014-01-01

    ProNGF and p75(NTR) are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75(NTR), sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that mature NGF, p75(NTR), and proBDNF were upregulated following SE, while proNGF was not altered, indicating potential mechanistic differences between rats and mice. ProBDNF was localized to mossy fibers and microglia following SE. p75(NTR) was transiently induced primarily in axons and axon terminals following SE, as well as in neuron and astrocyte cell bodies. ProBDNF and p75(NTR) increased independently of cell death and their localization was different depending on the severity of SE. We also examined the expression of proneurotrophin co-receptors, sortilin and sorCS2. Following severe SE, sorCS2, but not sortilin, was elevated in neurons and astrocytes. These data indicate that important differences exist between rat and mouse in the proneurotrophin response following SE. Moreover, the proBDNF and p75(NTR) increase after seizures in the absence of significant cell death suggests that proneurotrophin signaling may play other roles following SE. PMID:25290065

  11. Recurrent status epilepticus as the primary neurological manifestation of CADASIL: A case report.

    PubMed

    Haddad, Naim; Ikard, Catherine; Hiatt, Kim; Shanmugam, Vignesh; Schmidley, James

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) often presents with a history of migraine with aura and eventual manifestations of dementia with unrelenting, repeated cerebral vascular insults. Only 6-10% of patients with CADASIL have been reported to develop seizures, and status epilepticus (SE) is exceedingly rare. Here, we describe a patient who presented with recurrent SE, with eventual biopsy diagnosis of CADASIL. An 80-year-old woman presented to our hospital three times in two years with decreased level of consciousness and subtle intermittent right-sided upper extremity and facial twitching. There was no known significant family history and no past medical history for seizures, stroke, migraine headache, or overt dementia. Electroencephalography revealed recurrent focal seizures with left hemispheric onset and evolution, fulfilling the criteria for focal SE each time. All three admissions required sedation with midazolam to control seizure activity, in addition to high doses of multiple antiepileptic drugs. Brain MRI repeatedly showed extensive abnormalities in the periventricular and deep white matter, subcortical white matter, and bilateral basal ganglia. Skin biopsy was obtained on the third admission, and electron microscopy showed numerous deposits of granular osmiophilic material, which are pathognomonic for CADASIL. Detailed investigations failed to reveal any other etiology for the patient's condition. This case illustrates the potential for nonconvulsive SE to be the sole manifestation of CADASIL. With the appropriate brain MRI findings, CADASIL should be added to the list of rare causes of SE. PMID:25870789

  12. Lorazepam or diazepam for convulsive status epilepticus: A meta-analysis.

    PubMed

    Wu, Wei; Zhang, Liqun; Xue, Rong

    2016-07-01

    Convulsive status epilepticus (CSE) is a neurological emergency in adults and children. However, whether a particular benzodiazepine is of superior efficacy and safety in management of CSE is controversial. We performed a meta-analysis to compare the outcome of lorazepam and diazepam for treating CSE. We searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to February 2014. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional trials. Trial quality was assessed using the modified Jadad scale and the Consolidated Standards Of Reporting Trials (CONSORT) checklist. Two authors independently extracted data from all eligible studies, including study design, participants, interventions, and outcomes. The data was analyzed using fixed-effects or random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. A total of six studies involving 970 patients were included in this analysis. The majority of patients were children (n=574) and 396 patients were adults. Meta-analysis showed no significant difference between the two treatment groups regarding seizure control and adverse effects regardless of patient age. This meta-analysis demonstrates that diazepam and lorazepam have equal efficacy and side effects for treating CSE in adults and children, and either can be chosen as a reasonable first-line therapy. More high quality randomized controlled trials are needed to support this finding. PMID:27052258

  13. 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

  14. Psychiatric disorders secondary to nonconvulsive status epilepticus of frontal origin. Two clinical case reports.

    PubMed

    Chicharro-Ciuffardi, Ada; González-Silva, Mónica; de Marinis-Palombo, Alejandro; Gabler-Santalices, Guillermo

    2012-01-01

    Nonconvulsive status epilepticus (NCSE) is common but often under-diagnosed. Due to the absence of specific symptoms, it is frequently misdiagnosed as a psychiatric disorder, which delays treatment. The cases of two patients who exhibited psychiatric symptoms and subtle cognitive disturbances (without confusion) as the sole manifestation of frontal lobe NCSE are reported. Both patients were initially treated as psychiatric disorders (depression and anorexia nervosa). The correct diagnosis was established by the electroencephalographic study, in one case after the patient experienced a generalized tonic-clonic seizure and in the other, after failure to improve with supposedly adequate treatment. There are reports of patients with NCSE whose symptoms suggest a psychiatric disorder (inappropriate behavior, emotional disinhibition, perseveration, reduced speech and motivation). This can occur without altered consciousness and symptoms may fluctuate, making the correct diagnosis extremely difficult. This entity can occur at any age and without a previous history of seizures. A high level of suspicion is necessary for prompt electroencephalographic study to confirm the diagnosis. Early treatment will correct the symptoms and significantly improve quality of life for patients and their families. PMID:22723134

  15. Changes of cortical epileptic afterdischarges after status epilepticus in immature rats.

    PubMed

    Tsenov, Grygoriy; Kubová, Hana; Mares, Pavel

    2008-02-01

    Status epilepticus (SE) in developing rats leads to neuronal degeneration in many brain structures including neocortex but the functional consequences of cortical damage were studied only exceptionally. Lithium-pilocarpine SE was elicited in 12- (P12) and 25-day-old (P25) rats, convulsions were interrupted after 2h by paraldehyde. Cortical electrodes were implanted 3, 6, 9, 13 and/or 26 days after SE. Low-frequency stimulation of sensorimotor cortex was repeated with at least 10-min intervals with a stepwise increasing intensity (0.2-14 mA). Thresholds for movements elicited by stimulation, spike-and-wave afterdischarges (ADs), clonic seizures, mixed ADs (transition into a limbic type of ADs) and recurrent ADs as well as duration of ADs were evaluated. The first three phenomena were not influenced by SE with the exception of lower thresholds for movements during stimulation. Transition into limbic seizures and recurrent seizures were delayed in both age groups and threshold intensities for limbic ADs were at some intervals higher in SE than in control animals. Duration of ADs was changed only at short intervals after SE; it was shortened at 3 and 6 days in P25 and 3 days in P12 rats, respectively. P12 group then exhibited a transient increase in duration of ADs 6 days after SE. Our results did not prove a higher cortical excitability after SE in either age group. On the contrary, there were some signs of a decreased excitability. PMID:18178384

  16. Status Epilepticus in Immature Rats Is Associated with Oxidative Stress and Mitochondrial Dysfunction.

    PubMed

    Folbergrová, Jaroslava; Ješina, Pavel; Kubová, Hana; Druga, Rastislav; Otáhal, Jakub

    2016-01-01

    Epilepsy is a neurologic disorder, particularly frequent in infants and children where it can lead to serious consequences later in life. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of many neurological disorders including epilepsy in adults. However, their role in immature epileptic brain is unclear since there have been two contrary opinions: oxidative stress is age-dependent and does not occur in immature brain during status epilepticus (SE) and, on the other hand, evidence of oxidative stress in immature brain during a specific model of SE. To solve this dilemma, we have decided to investigate oxidative stress following SE induced in immature 12-day-old rats by three substances with a different mechanism of action, namely 4-aminopyridine, LiCl-pilocarpine or kainic acid. Fluoro-Jade-B staining revealed mild brain damage especially in hippocampus and thalamus in each of the tested models. Decrease of glucose and glycogen with parallel rises of lactate clearly indicate high rate of glycolysis, which was apparently not sufficient in 4-AP and Li-Pilo status, as evident from the decreases of PCr levels. Hydroethidium method revealed significantly higher levels of superoxide anion (by ∼60%) in the hippocampus, cerebral cortex and thalamus of immature rats during status. SE lead to mitochondrial dysfunction with a specific pronounced decrease of complex I activity that persisted for a long period of survival. Complexes II and IV activities remained in the control range. Antioxidant treatment with SOD mimetic MnTMPYP or peroxynitrite scavenger FeTPPS significantly attenuated oxidative stress and inhibition of complex I activity. These findings bring evidence that oxidative stress and mitochondrial dysfunction are age and model independent, and may thus be considered a general phenomenon. They can have a clinical relevance for a novel approach to the treatment of epilepsy, allowing to target the mechanisms which play a crucial or

  17. Status Epilepticus in Immature Rats Is Associated with Oxidative Stress and Mitochondrial Dysfunction

    PubMed Central

    Folbergrová, Jaroslava; Ješina, Pavel; Kubová, Hana; Druga, Rastislav; Otáhal, Jakub

    2016-01-01

    Epilepsy is a neurologic disorder, particularly frequent in infants and children where it can lead to serious consequences later in life. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of many neurological disorders including epilepsy in adults. However, their role in immature epileptic brain is unclear since there have been two contrary opinions: oxidative stress is age-dependent and does not occur in immature brain during status epilepticus (SE) and, on the other hand, evidence of oxidative stress in immature brain during a specific model of SE. To solve this dilemma, we have decided to investigate oxidative stress following SE induced in immature 12-day-old rats by three substances with a different mechanism of action, namely 4-aminopyridine, LiCl-pilocarpine or kainic acid. Fluoro-Jade-B staining revealed mild brain damage especially in hippocampus and thalamus in each of the tested models. Decrease of glucose and glycogen with parallel rises of lactate clearly indicate high rate of glycolysis, which was apparently not sufficient in 4-AP and Li-Pilo status, as evident from the decreases of PCr levels. Hydroethidium method revealed significantly higher levels of superoxide anion (by ∼60%) in the hippocampus, cerebral cortex and thalamus of immature rats during status. SE lead to mitochondrial dysfunction with a specific pronounced decrease of complex I activity that persisted for a long period of survival. Complexes II and IV activities remained in the control range. Antioxidant treatment with SOD mimetic MnTMPYP or peroxynitrite scavenger FeTPPS significantly attenuated oxidative stress and inhibition of complex I activity. These findings bring evidence that oxidative stress and mitochondrial dysfunction are age and model independent, and may thus be considered a general phenomenon. They can have a clinical relevance for a novel approach to the treatment of epilepsy, allowing to target the mechanisms which play a crucial or

  18. 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

  19. Rapid Diagnosis of Nonconvulsive Status Epilepticus Using Reduced-Lead Electroencephalography

    PubMed Central

    Brenner, Jay M.; Kent, Paul; Wojcik, Susan M.; Grant, William

    2015-01-01

    Introduction Electroencephalography (EEG) is indicated for diagnosing nonconvulsive status epilepticus (NCSE) in a patient who has altered level of consciousness after a motor seizure. A study in a neonatal population found 94% sensitivity and 78% specificity for detection of seizure using a single-lead device. This study aims to show that a reduced montage EEG would detect 90% of seizures detected on standard EEG. Methods A portable Brainmaster EEG device was available in the emergency department (ED) at all times. Patients presenting to the ED with altered mental status and known history of seizure or a witnessed seizure having a standard EEG were eligible for this study. The emergency physician obtained informed consent from the legally authorized representative (LAR), while an ED technician attached the electrodes to the patient, and a research associate attached the electrodes to the wiring routing to the portable EEG module. A board-certified epileptologist interpreted the tracings via the Internet. Simultaneously, the emergency physician ordered a standard 23-lead EEG, which would be interpreted by the neurologist on call to read EEGs. We compared the epileptologist’s interpretation of the reduced montage EEG to the results of the 23-lead EEG, which was considered the gold standard for detecting seizures. Results Twelve of 12 patients or 100% had the same findings on reduced-montage EEG as standard EEG. One of 12 patients or 8% had nonconvulsive seizure activity. Conclusion The results are consistent with prior studies which have shown that 8–48% of patients who have had a motor seizure continue to have nonconvulsive seizure activity on EEG. This study suggests that a bedside reduced-montage EEG can be used to make the diagnosis of NCSE in the ED. Further study will be conducted to see if this technology can be applied to the inpatient neurological intensive care unit setting. PMID:25987926

  20. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study

    PubMed Central

    Chin, Richard FM; Neville, Brian GR; Peckham, Catherine; Wade, Angie; Bedford, Helen; Scott, Rod C

    2008-01-01

    Summary Background Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE. Methods We collected data prospectively on children in north London, UK, who had episodes of CSE (ascertainment 62–84%). The factors associated with seizure termination after first-line and second-line therapies, episodes of CSE lasting for longer than 60 min, and respiratory depression were analysed with logistic regression. Analysis was per protocol, and adjustment was made for repeat episodes in individuals. Results 182 children of median age 3·24 years (range 0·16–15·98 years) were included in the North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) between May, 2002, and April, 2004. 61% (147) of 240 episodes were treated prehospital, of which 32 (22%) episodes were terminated. Analysis with multivariable models showed that treatment with intravenous lorazepam (n=107) in the accident and emergency department was associated with a 3·7 times (95% CI 1·7–7·9) greater likelihood of seizure termination than was treatment with rectal diazepam (n=80). Treatment with intravenous phenytoin (n=32) as a second-line therapy was associated with a 9 times (95% CI 3–27) greater likelihood of seizure termination than was treatment with rectal paraldehyde (n=42). No treatment prehospital (odds ratio [OR] 2·4, 95% CI 1·2–4·5) and more than two doses of benzodiazepines (OR 3·6, 1·9–6·7) were associated with episodes that lasted for more than 60 min. Treatment with more than two doses of benzodiazepines was associated with respiratory depression (OR 2·9, 1·4–6·1). Children with intermittent CSE arrived at the accident and

  1. Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus.

    PubMed

    Hu, Ming; Zhu, Kun; Chen, Xin-Lin; Zhang, Yao-Jie; Zhang, Jian-Shui; Xiao, Xin-Li; Liu, Jian-Xin; Liu, Yong

    2015-11-01

    Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker bromodeoxyuridine (BrdU) or retroviral vector expressing green fluorescent protein 2 months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to CA3 area or integrated into memory circuits were visualized by cholera toxin B subunit retrograde tracing, and detecting activation of BrdU(+) cells following a recall of spatial memory test at the chronic stage of TLE. We found that the microenvironment was still able to sustain significant neuronal differentiation of newly generated cells at 2 months post-status epilepticus time-point, and newly added neurons into granular cell layer were still able to integrate into neuronal circuitry, both anatomically and functionally. Quantified analyses of BrdU(+) or Ki-67(+) cells demonstrated that there was a reduced proliferation of progenitor cells and diminished survival of newly generated cells in the epileptic hippocampus. Both decreased levels of neurotrophic factors in the surrounding milieu and cell loss in the CA3 area might contribute the decreased production of new cells and their survival following chronic epilepsy. These results suggest that decreased neurogenesis in the chronically epileptic hippocampus 2 months post status epilepticus is not associated with altered integration of newly generated neurons, and that developing strategies to augment hippocampal neurogenesis in chronic epilepsy might be protective. PMID:26384773

  2. 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

    2015-01-01

    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. PMID:25445051

  3. Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain.

    PubMed

    Hester, Michael S; Hosford, Bethany E; Santos, Victor R; Singh, Shatrunjai P; Rolle, Isaiah J; LaSarge, Candi L; Liska, John P; Garcia-Cairasco, Norberto; Danzer, Steve C

    2016-06-01

    Growing evidence implicates the dentate gyrus in temporal lobe epilepsy (TLE). Dentate granule cells limit the amount of excitatory signaling through the hippocampus and exhibit striking neuroplastic changes that may impair this function during epileptogenesis. Furthermore, aberrant integration of newly-generated granule cells underlies the majority of dentate restructuring. Recently, attention has focused on the mammalian target of rapamycin (mTOR) signaling pathway as a potential mediator of epileptogenic change. Systemic administration of the mTOR inhibitor rapamycin has promising therapeutic potential, as it has been shown to reduce seizure frequency and seizure severity in rodent models. Here, we tested whether mTOR signaling facilitates abnormal development of granule cells during epileptogenesis. We also examined dentate inflammation and mossy cell death in the dentate hilus. To determine if mTOR activation is necessary for abnormal granule cell development, transgenic mice that harbored fluorescently-labeled adult-born granule cells were treated with rapamycin following pilocarpine-induced status epilepticus. Systemic rapamycin effectively blocked phosphorylation of S6 protein (a readout of mTOR activity) and reduced granule cell mossy fiber axon sprouting. However, the accumulation of ectopic granule cells and granule cells with aberrant basal dendrites was not significantly reduced. Mossy cell death and reactive astrocytosis were also unaffected. These data suggest that anti-epileptogenic effects of mTOR inhibition may be mediated by mechanisms other than inhibition of these common dentate pathologies. Consistent with this conclusion, rapamycin prevented pathological weight gain in epileptic mice, suggesting that rapamycin might act on central circuits or even peripheral tissues controlling weight gain in epilepsy. PMID:26995324

  4. KCC2 activity is critical in limiting the onset and severity of status epilepticus.

    PubMed

    Silayeva, Liliya; Deeb, Tarek Z; Hines, Rochelle M; Kelley, Matt R; Munoz, Michaelanne B; Lee, Henry H C; Brandon, Nicholas J; Dunlop, John; Maguire, Jaime; Davies, Paul A; Moss, Stephen J

    2015-03-17

    The K(+)/Cl(-) cotransporter (KCC2) allows adult neurons to maintain low intracellular Cl(-) levels, which are a prerequisite for efficient synaptic inhibition upon activation of γ-aminobutyric acid receptors. Deficits in KCC2 activity are implicated in epileptogenesis, but how increased neuronal activity leads to transporter inactivation is ill defined. In vitro, the activity of KCC2 is potentiated via phosphorylation of serine 940 (S940). Here we have examined the role this putative regulatory process plays in determining KCC2 activity during status epilepticus (SE) using knockin mice in which S940 is mutated to an alanine (S940A). In wild-type mice, SE induced by kainate resulted in dephosphorylation of S940 and KCC2 internalization. S940A homozygotes were viable and exhibited comparable basal levels of KCC2 expression and activity relative to WT mice. However, exposure of S940A mice to kainate induced lethality within 30 min of kainate injection and subsequent entrance into SE. We assessed the effect of the S940A mutation in cultured hippocampal neurons to explore the mechanisms underlying this phenotype. Under basal conditions, the mutation had no effect on neuronal Cl(-) extrusion. However, a selective deficit in KCC2 activity was seen in S940A neurons upon transient exposure to glutamate. Significantly, whereas the effects of glutamate on KCC2 function could be ameliorated in WT neurons with agents that enhance S940 phosphorylation, this positive modulation was lost in S940A neurons. Collectively our results suggest that phosphorylation of S940 plays a critical role in potentiating KCC2 activity to limit the development of SE. PMID:25733865

  5. Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children.

    PubMed

    Buttram, Sandra D W; Au, Alicia K; Koch, Joshua; Lidsky, Karen; McBain, Kristin; O'Brien, Nicole; Zielinski, Brandon A; Bell, Michael J

    2015-12-01

    Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a

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

    PubMed Central

    Lee, Yun-Jeong; Yum, Mi-Sun; Kim, Eun-Hee

    2016-01-01

    Purpose This study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS). Methods The medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained. Results The records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10–20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20–30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50). Conclusion Intravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV. PMID:26893602

  7. Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population

    PubMed Central

    Welch, Robert D.; Nicholas, Katherine; Durkalski-Mauldin, Valerie L.; Lowenstein, Daniel H.; Conwit, Robin; Mahajan, Prashant V.; Lewandowski, Christopher; Silbergleit, Robert

    2015-01-01

    Summary Objective 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. Methods 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. Results 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. Significance 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. PMID:25597369

  8. Beneficial influence of physical exercise following status epilepticus in the immature brain of rats.

    PubMed

    Gomes, F G Novaes; Gomes Da Silva, S; Cavalheiro, E A; Arida, R M

    2014-08-22

    Studies in adult animals have demonstrated a beneficial effect of physical exercise on epileptic insults. Although the effects of physical exercise on the mature nervous system are well documented, its influence on the developing nervous system subjected to injuries in childhood has been little explored. The purpose of our study was to investigate whether a physical exercise program applied during brain development could influence the hippocampal plasticity of rats submitted to status epilepticus (SE) induced by pilocarpine model at two different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28 (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX), SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise program, histological and behavioral (water maze) analyses were performed. Our results showed that only animals subjected to pilocarpine-induced SE at P28 presented spontaneous seizures during the observational period. A significant reduction in seizure frequency was observed in the SE/EX group compared to the SE group. In adulthood, animals submitted to early-life SE displayed impairment in long-term memory in the water maze task, while the exercise program reversed this deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and reduced pro-apoptotic response (Bax staining) in animals of both ages of SE induction (P18/28). Exercise also modified the brain-derived neurotrophic factor (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals subjected to SE in the postnatal period a physical exercise program brings about beneficial effects on seizure frequency and hippocampal plasticity in later stages of life. PMID:24857853

  9. Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus?

    PubMed

    Chanson, Eve; Bicilli, Élodie; Lauxerois, Michel; Kauffmann, Sophie; Chabanne, Russell; Ducray, François; Honnorat, Jérome; Clavelou, Pierre; Rosenberg, Sarah

    2016-02-01

    Seizures are common clinical manifestations in anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis, among other neurological and psychiatric symptoms. During the course of the disease, some specific EEG patterns have been described: generalized rhythmic delta activity (GRDA) and extreme delta brush (EDB). In comatose patients, the association of these EEG abnormalities with subtle motor manifestations can suggest ongoing non-convulsive status epilepticus (NCSE). We report the case of a 28-year-old woman admitted for a clinical presentation typical of anti-NMDA-R encephalitis, which was confirmed by CSF analysis. She was rapidly intubated because of severe dysautonomia and disturbed consciousness. Clinical examination revealed subtle paroxysmal and intermittent myoclonic and tonic movements, correlated on video-EEG with GRDA and/or EDB. NCSE was then suspected, but electroclinical manifestations persisted despite many anti-epileptic drugs combinations, or reappeared when barbiturate anesthesia was decreased. In order to confirm or dismiss the diagnosis, intracranial pressure (ICP) and surface video-EEG monitoring were performed simultaneously and revealed no ICP increase, thus being strongly against a diagnosis of seizures. Sedation was progressively weaned, and clinical condition as well as EEG appearance progressively improved. Literature review revealed 11 similar cases, including 2 with focal NCSE. Of the nine other cases, NCSE diagnosis was finally excluded in 5 cases. NCSE diagnosis in association with anti-NMDA-R encephalitis is sometimes very difficult and its occurrence might be overestimated. Video-EEG is highly recommended and more invasive techniques may sometimes be necessary. PMID:26922283

  10. CONTRIBUTION OF PROTEASE-ACTIVATED RECEPTOR 1 IN STATUS EPILEPTICUS-INDUCED EPILEPTOGENESIS

    PubMed Central

    Isaev, D.; Lushnikova, I.; Lunko, O.; Zapukhliak, O.; Maximyuk, O.; Romanov, A.; Skibo, G.G.; Tian, C.; Holmes, G.L.; Isaeva, E.

    2015-01-01

    Clinical observations and studies on different animal models of acquired epilepsy consistently demonstrate that blood-brain barrier (BBB) leakage can be an important risk factor for developing recurrent seizures. However, the involved signaling pathways remain largely unclear. Given the important role of thrombin and its major receptor in the brain, protease-activated receptor 1 (PAR1), in the pathophysiology of neurological injury, we hypothesized that PAR1 may contribute to status epilepticus (SE)-induced epileptogenesis and that its inhibition shortly after SE will have neuroprotective and antiepileptogenic effects. Adult rats subjected to lithium-pilocarpine SE were administrated SCH79797 (a PAR1 selective antagonist) after SE termination. Thrombin and PAR1 levels and neuronal cell survival were evaluated 48 hr following SE. The effect of PAR1 inhibition on animal survival, interictal spikes (IIS) and electrographic seizures during the first two weeks after SE and behavioral seizures during the chronic period were evaluated. SE resulted in a high mortality rate and incidence of IIS and seizures in the surviving animals. There was a marked increase in thrombin, decrease in PAR1 immunoreactivity and hippocampal cell loss in the SE-treated rats. Inhibition of PAR1 following SE resulted in a decrease in mortality and morbidity, increase in neuronal cell survival in the hippocampus and suppression of IIS, electrographic and behavioral seizures following SE. These data suggest that the PAR1 signaling pathway contributes to epileptogenesis following SE. Because breakdown of the BBB occurs frequently in brain injuries, PAR1 inhibition may have beneficial effects in a variety of acquired injuries leading to epilepsy. PMID:25843668

  11. Rapamycin reverses status epilepticus-induced memory deficits and dendritic damage.

    PubMed

    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

  12. Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in a lithium-pilocarpine model.

    PubMed

    Córdova-Dávalos, Laura; Carrera-Calvo, Dulce; Solís-Navarrete, Jael; Mercado-Gómez, Octavio Fabián; Arriaga-Ávila, Virginia; Agredano-Moreno, Lourdes Teresa; Jiménez-García, Luis Felipe; Guevara-Guzmán, Rosalinda

    2016-07-01

    Many reports investigating the hippocampus have demonstrated an increase in neuronal damage, cellular loss, oxidative stress and mitochondrial DNA damage during status epilepticus (SE); however, information regarding alterations in mitochondrial fission and fusion events in SE is lacking. The aim of the present study was to examine the possible imbalance between mitochondrial fission and fusion in the hippocampus of male rats after acute seizure mediated by SE. In this study, we used ninety animals were randomly divided into control and SE groups and subjected to the lithium-pilocarpine model of epilepsy. Hippocampi were obtained at 3, 24 and 72h after SE, and the cytoplasmic and mitochondrial fractions of the cells were used to analyze changes in the Drp1 and Fis1 fission proteins and the Mfn1 and Opa1 fusion proteins by western blot analysis. Moreover, changes in the expression of fission and fusion mRNA transcripts were evaluated by real-time PCR. Mitochondrial morphology was also analyzed using standard transmission electron microscopy. Our data showed that the fission-related mRNA Drp1 was down-regulated rapidly after SE, while Fis1 did not show any significant changes in expression. Moreover, the mitochondrial fusion-associated proteins Mfn1 and Opa1 exhibited an increase in expression at 72h after SE. Electron microphotography revealed several morphological changes, such as swollen mitochondria and damage of the inner mitochondrial membrane, at 24h; at 72h elongation of some mitochondrial was also observed. Our results suggest that after the initiation of SE, the main regulator of the fission mRNA Drp1 is down-regulated, which in turn regulates mitochondrial fission and leads to an increase in the Mfn1 and Opa1 proteins to induce mitochondrial fusion, suggesting an imbalance of the fission and fusion processes. PMID:27045873

  13. Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats

    PubMed Central

    2013-01-01

    Background Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE). Methods SE was induced with pilocarpine in Sprague–Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining. Results After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895. Conclusions An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy. PMID:23339567

  14. 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

  15. Effects of ketogenic diets on the occurrence of pilocarpine-induced status epilepticus of rats.

    PubMed

    Gama, Iclea Rocha; Trindade-Filho, Euclides Marinho; Oliveira, Suzana Lima; Bueno, Nassib Bezerra; Melo, Isabelle Tenório; Cabral-Junior, Cyro Rego; Barros, Elenita M; Galvão, Jaqueline A; Pereira, Wanessa S; Ferreira, Raphaela C; Domingos, Bruna R; da Rocha Ataide, Terezinha

    2015-02-01

    Two sources of medium-chain triglycerides--triheptanoin with anaplerotic properties and coconut oil with antioxidant features--have emerged as promising therapeutic options for the management of pharmacoresistant epilepsy. We investigated the effects of ketogenic diets (KDs) containing coconut oil, triheptanoin, or soybean oil on pilocarpine-induced status epilepticus (SE) in rats. Twenty-four adult male Wistar rats were divided into 4 groups and fed a control diet (7% lipids) or a KD containing soybean oil, coconut oil, or triheptanoin (69.8% lipids). The ketogenic and control diets had a lipid:carbohydrate + protein ratio of 1:11.8 and 3.5:1, respectively. SE was induced in all rats 20 days after initiation of the dietary treatment, through the administration of pilocarpine (340 mg/kg; i.p.). The latency, frequency, duration, and severity of seizures before and during SE were observed with a camcorder. SE was aborted after 3 h with the application of diazepam (5 mg/kg; i.p.). The rats in the triheptanoin-based KD group needed to undergo a higher number of seizures to develop SE, as compared to the control group (P < 0.05). Total weight gain, intake, energy intake, and feed efficiency coefficient, prior to induction of SE, differed between groups (P < 0.05), where the triheptanoin-based KD group showed less weight gain than all other groups, less energy intake than the Control group and intermediate values of feed efficiency coefficient between Control and other KDs groups. Triheptanoin-based KD may have a neuroprotective effect on the establishment of SE in Wistar rats. PMID:25005004

  16. Silencing Status Epilepticus-Induced BDNF Expression with Herpes Simplex Virus Type-1 Based Amplicon Vectors

    PubMed Central

    Falcicchia, Chiara; Trempat, Pascal; Binaschi, Anna; Perrier-Biollay, Coline; Roncon, Paolo; Soukupova, Marie; Berthommé, Hervé; Simonato, Michele

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to produce pro- but also anti-epileptic effects. Thus, its validity as a therapeutic target must be verified using advanced tools designed to block or to enhance its signal. The aim of this study was to develop tools to silence the BDNF signal. We generated Herpes simplex virus type 1 (HSV-1) derived amplicon vectors, i.e. viral particles containing a genome of 152 kb constituted of concatameric repetitions of an expression cassette, enabling the expression of the gene of interest in multiple copies. HSV-1 based amplicon vectors are non-pathogenic and have been successfully employed in the past for gene delivery into the brain of living animals. Therefore, amplicon vectors should represent a logical choice for expressing a silencing cassette, which, in multiple copies, is expected to lead to an efficient knock-down of the target gene expression. Here, we employed two amplicon-based BDNF silencing strategies. The first, antisense, has been chosen to target and degrade the cytoplasmic mRNA pool of BDNF, whereas the second, based on the convergent transcription technology, has been chosen to repress transcription at the BDNF gene. Both these amplicon vectors proved to be effective in down-regulating BDNF expression in vitro, in BDNF-expressing mesoangioblast cells. However, only the antisense strategy was effective in vivo, after inoculation in the hippocampus in a model of status epilepticus in which BDNF mRNA levels are strongly increased. Interestingly, the knocking down of BDNF levels induced with BDNF-antisense was sufficient to produce significant behavioral effects, in spite of the fact that it was produced only in a part of a single hippocampus. In conclusion, this study demonstrates a reliable effect of amplicon vectors in knocking down gene expression in vitro and in vivo. Therefore, this approach may find broad applications in neurobiological studies. PMID:26954758

  17. Neuroethological study of status epilepticus induced by systemic pilocarpine in Wistar audiogenic rats (WAR strain).

    PubMed

    Garcia-Cairasco, Norberto; Rossetti, Franco; Oliveira, José A C; Furtado, Marcio de A

    2004-08-01

    The administration of pilocarpine (PILO) is widely recognized as resulting in an experimental model of temporal lobe epilepsy; it is characterized by induction of status epilepticus (SE) and spontaneous recurrent seizures after a latent period. We provide in this work a neuroethological description of the SE induced by PILO. Behavioral evaluations were made in Wistar Audiogenic Rats (WARs) and Wistar resistant (R) animals. The experimental group (R) and WARs were pretreated with methyl scopolamine (1mg/kg ip) and injected with PILO (R animals, 340-380 mg/kg ip; WARs, 240-280 mg/kg ip). Among R animals, 36% developed SE, and among WARs, 53%. The control group (R animals and WARs) was injected only with methyl scopolamine plus saline. The ETHOMATIC method was used for evaluation of seizures. Sequences included in the analysis were chosen using (1) fixed observation windows and (2) behavioral triggers. The R group showed that the threshold for seizure is variable, so seizure onset and behavioral evolution were better described using behavioral triggers than fixed observation windows. The observation windows selected in similar duration intervals do not characterize the seizures. Sequential analysis in the WAR group showed high mortality after SE and greater susceptibility to PILO, compared with R animals. We conclude that with neuroethological tools it is possible to better map the sequence and evolution of SE induced by PILO compared to only using behavioral and arbitrary seizure severity scales. This sequence is faster and stronger in severity when WARs are compared with R animals. Although the WARs underwent an evolution of SE in some way equivalent to that of R animals, some rats presented tonic-clonic convulsions after PILO injection, very similar to acute audiogenic seizures, a brainstem-dependent model. The current data also point to the PILO-plus-WAR combination as a suitable protocol to study the genetic-epilepsy connection in experimental temporal lobe

  18. KCC2 activity is critical in limiting the onset and severity of status epilepticus

    PubMed Central

    Silayeva, Liliya; Deeb, Tarek Z.; Hines, Rochelle M.; Kelley, Matt R.; Munoz, Michaelanne B.; Lee, Henry H. C.; Brandon, Nicholas J.; Dunlop, John; Maguire, Jaime; Davies, Paul A.; Moss, Stephen J.

    2015-01-01

    The K+/Cl– cotransporter (KCC2) allows adult neurons to maintain low intracellular Cl– levels, which are a prerequisite for efficient synaptic inhibition upon activation of γ-aminobutyric acid receptors. Deficits in KCC2 activity are implicated in epileptogenesis, but how increased neuronal activity leads to transporter inactivation is ill defined. In vitro, the activity of KCC2 is potentiated via phosphorylation of serine 940 (S940). Here we have examined the role this putative regulatory process plays in determining KCC2 activity during status epilepticus (SE) using knockin mice in which S940 is mutated to an alanine (S940A). In wild-type mice, SE induced by kainate resulted in dephosphorylation of S940 and KCC2 internalization. S940A homozygotes were viable and exhibited comparable basal levels of KCC2 expression and activity relative to WT mice. However, exposure of S940A mice to kainate induced lethality within 30 min of kainate injection and subsequent entrance into SE. We assessed the effect of the S940A mutation in cultured hippocampal neurons to explore the mechanisms underlying this phenotype. Under basal conditions, the mutation had no effect on neuronal Cl– extrusion. However, a selective deficit in KCC2 activity was seen in S940A neurons upon transient exposure to glutamate. Significantly, whereas the effects of glutamate on KCC2 function could be ameliorated in WT neurons with agents that enhance S940 phosphorylation, this positive modulation was lost in S940A neurons. Collectively our results suggest that phosphorylation of S940 plays a critical role in potentiating KCC2 activity to limit the development of SE. PMID:25733865

  19. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.

    PubMed

    Suchomelova, L; Lopez-Meraz, M L; Niquet, J; Kubova, H; Wasterlain, C G

    2015-10-01

    This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. PMID:26259902

  20. Are morphologic and functional consequences of status epilepticus in infant rats progressive?

    PubMed

    Kubová, H; Mareš, P

    2013-04-01

    The present study examined whether status epilepticus (SE) induced by LiCl-pilocarpine in immature rats (postnatal day [P]12) interferes with normal development; leads to progressive epileptogenesis, or cognitive decline and to pathology similar to that seen in human temporal lobe epilepsy. We correlated the extent of pathologic changes with the severity of functional alterations or epilepsy. SE-induced changes were compared with those of rats with SE induced at P25. Animals of both ages were exposed to a battery of behavioral tests for up to 3months after SE. Rats with SE at P12 showed mild retardation of psychomotor development and delayed habituation, whereas rats with SE at P25 showed no habituation. Assessment in adulthood using the Morris water maze test revealed that SE at both P12 and P25 led to cognitive impairment and that the severity of the impairment increased with age. A handling test revealed increased aggression in rats with SE at P25, but not in rats with SE at P12. Epilepsy was diagnosed with continuous video-electroencephalographic (EEG) monitoring for up to 7d. P25 rats were monitored at 5months after SE and seizures were detected in 83.3% of animals. P12 animals were divided into two groups and monitored at 5 or 7months after SE. Both the severity and incidence of spontaneous recurrent seizures tended to progress with time, and their incidence increased from 50% to 87.5% at 5 and 7months, respectively. Morphometric analysis and stereologic assessment of hilar neurons performed after video-EEG monitoring revealed atrophy of temporal brain structures, enlargement of lateral ventricles, and loss of hilar neurons in both age groups. In P12 rats, morphologic damage also tended to progress over time. Performance of animals in the Morris water maze correlated with the severity of damage, but not with seizure parameters. PMID:23305765

  1. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multi-center study

    PubMed Central

    Gaspard, Nicolas; Foreman, Brandon; Judd, Lilith M.; Brenton, James N.; Nathan, Barnett R.; McCoy, Blathnaid M.; Al-Otaibi, Ali; Kilbride, Ronan; Fernández, Ivan Sánchez; Mendoza, Lucy; Samuel, Sophie; Zakaria, Asma; Kalamangalam, Giridhar P.; Legros, Benjamin; Szaflarski, Jerzy P.; Loddenkemper, Tobias; Hahn, Cecil D.; Goodkin, Howard P.; Claassen, Jan; Hirsch, Lawrence J.; LaRoche, Suzette M.

    2013-01-01

    Summary Purpose To examine patterns of use, efficacy and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and EEG reports in ten academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key findings Permanent control of RSE was achieved in 57% (34/60) of episodes. Ketamine was felt to have contributed to permanent control (“possible” or “likely” responses) in 32% (19/60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with post-anoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9mg/kg/h; when ketamine was introduced at least eight days after SE onset; or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26/60), but was lower when SE was controlled within 24h of ketamine initiation (16% vs. 56%, p=0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE. PMID:23758557

  2. Clinical Significance of Human Metapneumovirus in Refractory Status Epilepticus and Encephalitis: Case Report and Review of the Literature

    PubMed Central

    Vehapoglu, Aysel; Turel, Ozden; Uygur Sahin, Turkan; Kutlu, Nurettin Onur; Iscan, Akın

    2015-01-01

    Encephalitis is a complex neurological disease that is associated with significant morbidity and mortality, and the etiology of the disease is often not identified. Human metapneumovirus (hMPV) is a common cause of upper and lower respiratory tract infections in children. Few reports are available showing possible involvement of hMPV in development of neurologic complications. Here, we describe an infant, the youngest case in literature, with refractory status epilepticus and severe encephalitis in whom hMPV was detected in respiratory samples and review diagnostic workup of patient with encephalitis. PMID:26664779

  3. Refractory status epilepticus, serious rhabdomyolysis, acute liver injury, and pancytopenia after a massive intake of ethyl methanesulfonate: a case report

    PubMed Central

    Yamazaki, Hiroyuki; Tajima, Shogo; Takeuchi, Takahiro

    2015-01-01

    Ethyl methanesulfonate is a mutagenic, alkylating agent and considered harmful to humans at levels greater than a certain threshold; however, the toxicity at high doses remains unclear. We report a case of a Japanese man who presented with status epilepticus, rhabdomyolysis, pancytopenia, and hair loss after accidental ingestion of a massive amount of ethyl methanesulfonate. The patient completely recovered with critical care, including multiple antiepileptic drugs, renal replacement therapy, blood transfusion, granulocyte colony-stimulating factor therapy, and antibacterial/fungal prophylaxis. The case indicates that ethyl methanesulfonate causes neurotoxicity, hepatotoxicity, hematotoxicity, and renal toxicity, which can be successfully treated with appropriate palliative therapies. PMID:26629236

  4. 76 FR 34968 - Notice of Availability for Exclusive, Non-Exclusive, or Partially-Exclusive Licensing of an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... of an Invention Concerning the Methods and Compositions for Treating Status Epilepticus and Seizures... ``Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus''...

  5. A rare case of neonatal sepsis/meningitis caused by Pasteurella multocida complicated with status epilepticus and focal cerebritis.

    PubMed

    Spadafora, R; Pomero, G; Delogu, A; Gozzoli, L; Gancia, P

    2011-01-01

    Pasteurella multocida is normally present in respiratory and digestive tract of many domestic and wild animals, but is a rare pathogen in neonatal infection. Here we describe for the first time a case of meningitis complicated by status epilepticus and right parietal lobe cerebritis. The patient showed a dramatic clinical onset characterized by septic appearance and prolonged seizures. Multidrug anticonvulsivant therapy was used to control the status epilepticus, but despite the aggressive treatment electrical crises were still evident 24 hours after the admission. Furthermore, a brain MRI, performed to investigate a persistent intermittent fever even if CSF became sterile, showed a focus cerebritis in the right parietal lobe, early stage of the cerebral abscess. Prolonged antibiotic therapy with steroids was requested to solve the cerebritis area. Interestingly, direct contact between the patient and domestic animals was denied by the family, but the father reported a contact with a rooster, killed and cooked few days before, suggesting, as previously described, that Pasteurella may also be transmitted through asymptomatic human carrier. The patient had a favourable outcome with no medium-term sequelae one month after discharge, but the severity of the clinical course and the unpredictable way of transmission highlight the importance of hygiene measures approaching infants. PMID:22423481

  6. Lithium/pilocarpine status epilepticus-induced neuropathology of piriform cortex and adjoining structures in rats is age-dependent.

    PubMed

    Druga, R; Kubová, H; Suchomelová, L; Haugvicová, R

    2003-01-01

    Distribution of LiCl/pilocarpine status epilepticus-induced neuronal damage was studied in the piriform cortex and in adjoining structures in 12-day-old, 25-day-old and adult rats. No distinct structural and neuronal alterations were detected in the basal telencephalon in 12-day-old rats surviving status epilepticus (SE) for one week or two months. In 25-day-old rats a decrease in Nissl staining was evident. There was also cell loss and gliosis in the caudal 2/3 of the piriform cortex, in the superficial amygdaloid nuclei, in the dorsal and ventral endopiriform nucleus and in the rostrolateral part of the entorhinal cortical area. In adult animals, the topography of neuropathological changes in the basal telencephalon was comparable to those in 25-day-old rats. The damage in the caudal 2/3 or caudal half of the piriform cortex in adult rats with survival times one week or two months was characterized by a marked loss of neurons and striking glial infiltration. The thickness of the piriform cortex and superficial amygdaloid nuclei was significantly reduced. In 25-day-old and in adult animals the sublayer IIb and layer III of the piriform cortex was more affected, while sublayer IIa was less damaged. Parvalbumin (PV) immunocytochemistry revealed a significant decrease in the number of PV-immunoreactive neurons in the rostral piriform cortex and in the dorsal claustrum in animals surviving for two months. PMID:12678669

  7. Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus – A MRI Study Using Susceptibility Weighted Imaging

    PubMed Central

    Verma, Rajeev Kumar; Abela, Eugenio; Schindler, Kaspar; Krestel, Heinz; Springer, Elisabeth; Huber, Adrian; Weisstanner, Christian; Hauf, Martinus; Gralla, Jan; Wiest, Roland

    2016-01-01

    Objective The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). Methods We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. Results Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. Conclusions SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions. PMID:27486662

  8. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus

    PubMed Central

    Tanaka, Tsukasa; Maruyama, Azusa; Nagase, Hiroaki

    2016-01-01

    Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy). Septic encephalopathy (SE) is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE) could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure. PMID:27051542

  9. Expression regulation and targeting of the peroxisome proliferator-activated receptor γ following electrically-induced status epilepticus.

    PubMed

    Boes, Katharina; Russmann, Vera; Ongerth, Tanja; Licko, Thomas; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2015-09-14

    The neuroprotective and anti-inflammatory effects of the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone are of particular interest for disease-modifying and antiepileptogenic approaches. We studied the expression of PPARγ and the impact of rosiglitazone on the consequences of status epilepticus (SE) in a rat post-SE model. Immunohistochemical analysis revealed a selective overexpression of PPARγ in the piriform cortex of rats with spontaneous seizures. Rosiglitazone administration initiated following SE failed to exert relevant effects on the development of spontaneous seizures and neuronal cell loss. Whereas spatial learning in the Morris water maze was delayed in SE animals with vehicle administration, the learning curve of rosiglitazone-treated SE rats showed no significant difference to that of controls. The study provides first evidence arguing against a robust antiepileptogenic effect. However, the findings in the spatial learning paradigm indicate disease-modifying effects. PMID:26259695

  10. Post-seizure α-tocopherol treatment decreases neuroinflammation and neuronal degeneration induced by status epilepticus in rat hippocampus.

    PubMed

    Ambrogini, Patrizia; Minelli, Andrea; Galati, Claudia; Betti, Michele; Lattanzi, Davide; Ciffolilli, Silvia; Piroddi, Marta; Galli, Francesco; Cuppini, Riccardo

    2014-08-01

    Vitamin E (as α-tocopherol, α-T) was shown to have beneficial effects in epilepsy, mainly ascribed to its antioxidant properties. Besides radical-induced neurotoxicity, neuroinflammation is also involved in the pathophysiology of epilepsy, since neuroglial activation and cytokine production exacerbate seizure-induced neurotoxicity and contribute to epileptogenesis. We previously showed that α-T oral supplementation before inducing status epilepticus, markedly reduces astrocytic and microglial activation, neuronal cell death and oxidative stress in the hippocampus, as observed 4 days after seizure. In order to evaluate the possibility that such a neuroprotective and anti-inflammatory effect may also provide a strategy for an acute intervention in epilepsy, in this study, seizures were induced by single intaperitoneal injection of kainic acid and, starting from 3 h after status epilepticus, rats were treated with an intraperitoneal bolus of α-T (250 mg/kg b.w.; once a day) for 4 days, that was the time after which morphological and biochemical analyses were performed on hippocampus. Post-seizure α-T administration significantly reduced astrocytosis and microglia activation, and decreased neuron degeneration and spine loss; these effects were associated with the presence of a lowered lipid peroxidation in hippocampus. These results confirm and further emphasize the anti-inflammatory and neuroprotective role of α-T in kainic acid-induced epilepsy. Moreover, the findings show that post-seizure treatment with α-T provides an effective secondary prevention against post-seizure inflammation-induced brain damages and possibly against their epileptogenic effects. PMID:24488645

  11. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis presenting to the emergency department with status epilepticus.

    PubMed

    Nolan, Brodie; Plenk, Katharina; Carr, David

    2014-09-01

    Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a recently described and underdiagnosed entity that typically affects young, previously healthy individuals. Patients usually present in phases, which may include refractory seizures, psychosis, unresponsiveness, and autonomic instability. The diagnosis of anti-NMDAR encephalitis is challenging; however, prompt diagnosis and early treatment can lead to complete recovery. The incidence of anti-NMDAR encephalitis may be as high as four times that of encephalitis from herpes simplex, varicella-zoster, and West Nile viruses; however, it remains an underrecognized disorder. Early initiation of immunotherapy in anti-NMDAR encephalitis has been found to improve patient outcomes. Because of this, emergency physicians must be vigilant and consider this diagnosis in patients with altered mental status in whom a toxicologic or other etiology is not suspected. Early consideration of this diagnosis can facilitate urgent neurology consultation and prevent diagnostic delays arising from psychiatric referrals. It is essential to consider this diagnosis in suspicious emergency department presentations, particularly young patients who present with altered mental status, psychosis, or new-onset seizure activity when other obvious causes are ruled out. Emergency physicians should discuss the possibility of empirical intravenous immunoglobulin administration with neurology consultants if anti-NMDAR encephalitis is suspected. We describe the case of a 20-year-old man with anti-NMDAR encephalitis who presented to the emergency department with status epilepticus. PMID:25227654

  12. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

    PubMed

    Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; Fernaud-Espinosa, Isabel; Rodriguez-Alvarez, Natalia; Reynolds, James; Reschke, Cristina R; Conroy, Ronan M; McKiernan, Ross C; deFelipe, Javier; Henshall, David C

    2015-07-01

    Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects. PMID:24874920

  13. Midazolam Versus Diazepam for the Treatment of Status Epilepticus in Children and Young Adults: A Meta-Analysis

    PubMed Central

    McMullan, Jason; Sasson, Comilla; Pancioli, Arthur; Silbergleit, Robert

    2014-01-01

    Background Rapid treatment of status epilepticus (SE) is associated with better outcomes. Diazepam and midazolam are commonly used, but the optimal agent and administration route is unclear. Objectives To determine by systematic review if non-intravenous midazolam is as effective as diazepam, by any route, in terminating SE seizures in children and adults. Time to seizure cessation and respiratory complications were examined. Methods Search of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, American College of Physicians Journal Club, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and International Pharmaceutical Abstracts for studies published January 1, 1950 through July 4, 2009. English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE, and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures, were eligible. Two reviewers independently screened studies for inclusion and extracted outcomes data. Administration routes were stratified as non-intravenous (buccal, intranasal, intramuscular, rectal) or intravenous (IV). Fixed-effects models generated pooled statistics. Results Six studies with 774 subjects were included. For seizure cessation, midazolam, by any route, was superior to diazepam, by any route, (RR 1.52; 95% CI = 1.27 to 1.82). Non-IV midazolam is as effective as IV diazepam (RR 0.79; 95% CI = 0.19 to 3.36), and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR 1.54; 95% CI = 1.29 to 1.85). Midazolam was administered faster than diazepam (mean difference 2.46 minutes; 95% CI = 1.52 to 3.39 min) and had similar times between drug administration and seizure cessation. Respiratory complications requiring intervention were similar, regardless of administration route (RR 1.49; 95% CI = 0

  14. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat.

    PubMed

    Modebadze, Tamara; Morgan, Nicola H; Pérès, Isabelle A A; Hadid, Rebecca D; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M; Morris, Christopher M; Jones, Roland S G; Whalley, Benjamin J; Woodhall, Gavin L

    2016-01-01

    Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model's features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles. PMID:26909803

  15. Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy.

    PubMed

    Agadi, Satish; Shetty, Ashok K

    2015-07-01

    Mononuclear cells (MNCs) and mesenchymal stem cells (MSCs) derived from the bone marrow and other sources have received significant attention as donor cells for treating various neurological disorders due to their robust neuroprotective and anti-inflammatory effects. Moreover, it is relatively easy to procure these cells from both autogenic and allogenic sources. Currently, there is considerable interest in examining the usefulness of these cells for conditions such as status epilepticus (SE) and chronic epilepsy. A prolonged seizure activity in SE triggers neurodegeneration in the limbic brain areas, which elicits epileptogenesis and evolves into a chronic epileptic state. Because of their potential for providing neuroprotection, diminishing inflammation and curbing epileptogenesis, early intervention with MNCs or MSCs appears attractive for treating SE as such effects may restrain the development of chronic epilepsy typified by spontaneous seizures and learning and memory impairments. Delayed administration of these cells after SE may also be useful for easing spontaneous seizures and cognitive dysfunction in chronic epilepsy. This concise review evaluates the current knowledge and outlook pertaining to MNC and MSC therapies for SE and chronic epilepsy. In the first section, the behavior of these cells in animal models of SE and their efficacy to restrain neurodegeneration, inflammation, and epileptogenesis are discussed. The competence of these cells for suppressing seizures and improving cognitive function in chronic epilepsy are conferred in the next section. The final segment ponders issues that need to be addressed to pave the way for clinical application of these cells for SE and chronic epilepsy. PMID:25851047

  16. Interleukin-1 receptor is a target for adjunctive control of diazepam-refractory status epilepticus in mice.

    PubMed

    Xu, Zheng-Hao; Wang, Yi; Tao, An-Feng; Yu, Jie; Wang, Xiao-Yu; Zu, Yun-Yun; Zhang, Shi-Hong; Chen, Zhong

    2016-07-22

    Proinflammatory cytokine interleukin-1 beta (IL-1β) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40min before diazepam administration). The expression level of IL-1β in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1β weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1β contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE. PMID:27133574

  17. Nonconvulsive status epilepticus--a possible cause of mental retardation in patients with Lennox-Gastaut syndrome.

    PubMed

    Hoffmann-Riem, M; Diener, W; Benninger, C; Rating, D; Unnebrink, K; Stephani, U; Ernst, H P; Korinthenberg, R

    2000-08-01

    Lennox-Gastaut syndrome (LGS) is one of the most severe types of childhood epilepsy. It is usually resistant to treatment and associated with mental retardation. To delineate the risk factors associated with the outcome of LGS, we evaluated, in a retrospective and multicentre study, the course of the disease, EEG tracings, and intellectual function in 101 patients. Inclusion criteria were the presence of tonic seizures as well as slow spike and wave complexes in the EEG. The average documented observation period was 16 years (range 4-31 years). Overall, the intellectual and neurological outcome was poor. At the last follow-up, 38% of the patients could not speak, 21% were unable to walk and only 4% were free of seizures. Four independent risk factors for severe mental retardation were identified by multivariate analysis. These were in a decreasing order of importance: nonconvulsive status epilepticus (NCSE), odds ratio (OR) 25.2, a previous diagnosis of West syndrome (OR 11.6), a symptomatic etiology of epilepsy (OR 9.5), and an early age at onset of epilepsy (OR 4.7). The results highlight the association between NCSE and the severity of mental retardation in patients with LGS; this association appears to be independent of symptomatic etiology. Our data provide an indirect evidence that, at least in some of the patients, NCSE is not only a concomitant feature, but also a cause of severe mental retardation. PMID:11071139

  18. Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation

    PubMed Central

    Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A.; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K.

    2015-01-01

    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. PMID:26639668

  19. The Differential DRP1 Phosphorylation and Mitochondrial Dynamics in the Regional Specific Astroglial Death Induced by Status Epilepticus

    PubMed Central

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

    2016-01-01

    The response and susceptibility to astroglial degenerations are relevant to the distinctive properties of astrocytes in a hemodynamic-independent manner following status epilepticus (SE). Since impaired mitochondrial fission plays an important role in mitosis, apoptosis and programmed necrosis, we investigated whether the unique pattern of mitochondrial dynamics is involved in the characteristics of astroglial death induced by SE. In the present study, SE induced astroglial apoptosis in the molecular layer of the dentate gyrus, accompanied by decreased mitochondrial length. In contrast, clasmatodendritic (autophagic) astrocytes in the CA1 region showed mitochondrial elongation induced by SE. Mdivi-1 (an inhibitor of mitochondrial fission) effectively attenuated astroglial apoptosis, but WY14643 (an enhancer of mitochondrial fission) aggravated it. In addition, Mdivi-1 accelerated clasmatodendritic changes in astrocytes. These regional specific mitochondrial dynamics in astrocytes were closely correlated with dynamin-related protein 1 (DRP1; a mitochondrial fission protein) phosphorylation, not optic atrophy 1 (OPA1; a mitochondrial fusion protein) expression. To the best of our knowledge, the present data demonstrate for the first time the novel role of DRP1-mediated mitochondrial fission in astroglial loss. Thus, the present findings suggest that the differential astroglial mitochondrial dynamics may participate in the distinct characteristics of astroglial death induced by SE. PMID:27242436

  20. Effect of Argemone mexicana (L.) against lithium-pilocarpine induced status epilepticus and oxidative stress in Wistar rats.

    PubMed

    Asuntha, G; Raju, Y Prasanna; Sundaresan, C R; Rasheed, Arun; Chowdary, V Harini; Vandana, K R; Babu, K Satish; Prasad, K V S R G

    2015-01-01

    Argemone mexicana (L.) has a role in the treatment of epileptic disorders in Indian traditional system of medicine. We studied its effect on induced status epilepticus (SE) and oxidative stress in rats. SE was induced in male albino rats by administration of pilocarpine (30 mg/kg, ip) 24 h after injection of lithium chloride (3 mEq/kg, ip). Different doses of the ethanol extract of A. mexicana were administered orally 1 h before the injection of pilocarpine. The severity of SE was observed and recorded every 15 min for 90 min and thereafter at every 30 min for another 90 min, using the Racine scoring system. In vivo lipid peroxidation of rat brain tissue was measured utilizing thiobarbiturate-reactive substances. Both in vitro free radical nitric oxide and 2,2-diphenyl-1-picryl hydrazyl scavenging activities of the extract were also determined. The SE severity was significantly reduced following oral administration of the extract at 250, 500 and 1000 mg/kg doses. None of the animals from groups 3 to 5 (with A. mexicana extract) have exhibited forelimb clonus of stage 4 seizure. The extract also exhibited both in vivo and in vitro antioxidant activities. PMID:25675709

  1. Time-course changes of hippocalcin expression in the mouse hippocampus following pilocarpine-induced status epilepticus

    PubMed Central

    Choi, Hee-Soo

    2016-01-01

    Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE. PMID:26435544

  2. Convulsive status epilepticus duration as determinant for epileptogenesis and interictal discharge generation in the rat limbic system

    PubMed Central

    Bortel, Aleksandra; Lévesque, Maxime; Biagini, Giuseppe; Gotman, Jean; Avoli, Massimo

    2016-01-01

    We analyzed with EEG-video monitoring the epileptic activity recorded during the latent and chronic periods in rats undergoing 30 or 120 min pilocarpine-induced convulsive status epilepticus (SE). Interictal discharges frequency in the entorhinal cortex (EC) of animals exposed to 120 min SE was significantly higher in the chronic than in the latent period. Following seizure appearance, interictal spikes diminished in duration in the CA3 of the 120 min SE group, and occurred at higher rates in the amygdala in all animals. Rats exposed to 120 min SE generated shorter seizures but presented twice as many non-convulsive seizures per day as the 30 min group. Finally, seizures most frequently initiated in CA3 in the 120 min SE group but had similar onset in CA3 and EC in the 30 min group. These findings indicate that convulsive SE duration influences the development of interictal and ictal activity, and that interictal discharges undergo structure-specific changes after seizure appearance. PMID:20682341

  3. A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat

    PubMed Central

    Pérès, Isabelle A. A.; Hadid, Rebecca D.; Amada, Naoki; Hill, Charlotte; Williams, Claire; Stanford, Ian M.; Morris, Christopher M.; Jones, Roland S. G.; Whalley, Benjamin J.; Woodhall, Gavin L.

    2016-01-01

    Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles. PMID:26909803

  4. Increased Histone H3 Phosphorylation in Neurons in Specific Brain Structures after Induction of Status Epilepticus in Mice

    PubMed Central

    Mori, Tetsuji; Wakabayashi, Taketoshi; Ogawa, Haruyuki; Hirahara, Yukie; Koike, Taro; Yamada, Hisao

    2013-01-01

    Status epilepticus (SE) induces pathological and morphological changes in the brain. Recently, it has become clear that excessive neuronal excitation, stress and drug abuse induce chromatin remodeling in neurons, thereby altering gene expression. Chromatin remodeling is a key mechanism of epigenetic gene regulation. Histone H3 phosphorylation is frequently used as a marker of chromatin remodeling and is closely related to the upregulation of mRNA transcription. In the present study, we analyzed H3 phosphorylation levels in vivo using immunohistochemistry in the brains of mice with pilocarpine-induced SE. A substantial increase in H3 phosphorylation was detected in neurons in specific brain structures. Increased H3 phosphorylation was dependent on neuronal excitation. In particular, a robust upregulation of H3 phosphorylation was detected in the caudate putamen, and there was a gradient of phosphorylated H3+ (PH3+) neurons along the medio-lateral axis. After unilateral ablation of dopaminergic neurons in the substantia nigra by injection of 6-hydroxydopamine, the distribution of PH3+ neurons changed in the caudate putamen. Moreover, our histological analysis suggested that, in addition to the well-known MSK1 (mitogen and stress-activated kinase)/H3 phosphorylation/c-fos pathway, other signaling pathways were also activated. Together, our findings suggest that a number of genes involved in the pathology of epileptogenesis are upregulated in PH3+ brain regions, and that H3 phosphorylation is a suitable indicator of strong neuronal excitation. PMID:24147063

  5. Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status Epilepticus.

    PubMed

    Wang, Cui; Xie, Nanchang; Wang, Yunlong; Li, Yulin; Ge, Xinjie; Wang, Menglu

    2015-08-01

    The mitochondrial calcium uniporter (MCU) is reportedly involved in oxidative stress, apoptosis, and many neurological diseases. However, the role of the MCU in epilepsy remains unknown. In this study, we found that the MCU inhibitor Ru360 significantly attenuated neuronal death and exerted an anti-apoptotic effect on rat hippocampal neurons after pilocarpine-induced status epilepticus (SE), while the MCU activator spermine increased seizure-induced neuronal death and apoptosis. In addition, Ru360 decreased the level of seizure-induced reactive oxygen species (ROS) in mitochondria isolated from rat hippocampi. Moreover, Ru360 restored the altered mitochondrial membrane potential and cytochrome c (CytC) release in epileptic hippocampi. However, spermine treatment exerted an opposite effect on seizure-induced ROS production and mitochondrial membrane potential alteration and CytC release compared with Ru360 treatment. Altogether, the findings of this study suggest that MCU inhibition exerts a neuroprotective effect on seizure-induced brain injury possibly through the mitochondria/ROS/CytC pathway. PMID:26148531

  6. Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala.

    PubMed

    Pitkänen, A; Tuunanen, J; Halonen, T

    1996-05-01

    The present study compares the efficacy of carbamazepine (20 mg/kg/day) and vigabatrin (250 mg/kg/day) in preventing hippocampal and amygdaloid damage in the perforant pathway stimulation model of status epilepticus in the rat. One group of rats received a combination of the drugs. Drug treatments were started one week before the stimulation and continued for two weeks thereafter. Gallyas silver impregnation and somatostatin immunohistochemistry were used to detect neuronal damage. All drug treatments were equally effective in decreasing the number and severity of seizures during electrical stimulation. In the vigabatrin group, the damage to the hilar somatostatin-immunoreactive (SOM-ir) neurons and hippocampal CA3c pyramidal cells was less severe than in the vehicle (SOM-ir, P < 0.01; CA3c, P < 0.05) and carbamazepine (SOM-ir, P < 0.01; CA3c, P < 0.05) groups. In the carbamazepine and combination groups, the severity of neuronal damage in the hippocampus did not differ from that in vehicle-treated animals. The amygdaloid neurons were not protected by any of the treatments. Our results show that even though vigabatrin and carbamazepine treatments had similar anticonvulsant efficacy during the perforant pathway stimulation, only vigabatrin but not carbamazepine decreased seizure-induced neuronal damage. Vigabatrin decreased neuronal damage in the hippocampus but not in the amygdala. These results demonstrate that different brain regions and neuronal networks may be protected unequally by different anticonvulsants. PMID:8800633

  7. Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

    SciTech Connect

    Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.; Braitman, D.J.

    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 and 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.

  8. Proepileptic Influence of a Focal Vascular Lesion Affecting Entorhinal Cortex-CA3 Connections After Status Epilepticus

    PubMed Central

    Biagini, Giuseppe; Baldelli, Enrica; Longo, Daniela; Contri, Miranda Baccarani; Guerrini, Uliano; Sironi, Luigi; Gelosa, Paolo; Zini, Isabella; Ragsdale, David S.; Avoli, Massimo

    2016-01-01

    In limbic seizures, neuronal excitation is conveyed from the entorhinal cortex directly to CA1 and subicular regions. This phenomenon is associated with a reduced ability of CA3 to respond to entorhinal cortex inputs. Here, we describe a lesion that destroys the perforant path in CA3 after status epilepticus (SE) induced by pilocarpine injection in 8-week-old rats. Using magnetic resonance imaging, immunohistochemical, and ultrastructural analyses, we determined that this lesion develops after 30 minutes of SE and is characterized by microhemorrhages and ischemia. After a longer period of SE, the lesion invariably involves the upper blade of the dentate gyrus. Adult rats treated with subcutaneous diazepam (20 mg kg−1 for 3 days) did not develop the dentate gyrus lesion and had less frequent spontaneous recurrent seizures (p < 0.01). Young (3-week-old) rats rarely (20%) developed the CA3 lesion, and their spontaneous seizures were delayed (p < 0.01). To investigate the role of the damaged CA3 in seizure activity, we reinduced SE in adult and young epileptic rats. Using FosB/ΔFosB markers, we found induction of FosB/ΔFosB immunopositivity in CA3 neurons of young but not in adult rats. These experiments indicate that SE can produce a focal lesion in the perforant path that may affect the roles of the hippocampus in epileptic rats. PMID:18596544

  9. Time course of neuronal damage in the hippocampus following lithium-pilocarpine status epilepticus in 12-day-old rats.

    PubMed

    Druga, Rastislav; Mares, Pavel; Kubová, Hana

    2010-10-01

    Status epilepticus (SE) leads to serious damage in hippocampus of the adult brain. Much less is known about immature brain where neuronal degeneration may have different localization and time course. Lithium-pilocarpine SE was induced in 12-day-old male Wistar rats. Six different intervals after SE (from 4 h to 1 week) were studied using Fluoro-Jade B staining. Three to four animals were used for every interval. Severity of damage in individual parts of hippocampal formation was semi-quantified. A consistent neuronal damage occurred in all hippocampal fields (CA 1, CA 3, dentate gyrus) at all survival intervals. Hippocampal fields CA 1 and CA 3 exhibited degeneration of interneurons located mainly in stratum oriens and pyramidale at shorter intervals (4-12h). Massive degeneration of pyramidal cells started at 24h in CA 1 and at 48 h in CA 3. Dentate gyrus exhibited degenerating neurons in granular layer with a peak at short intervals (4-8 h), and molecular layer was spared. The lower blade of dentate gyrus was more affected than the upper blade. Damage of hilar neurons was negligible. Our results demonstrate that SE elicited in immature rats causes acute neurodegeneration in the hippocampus. Time course of this degeneration is different for individual parts of hippocampal formation and for individual cell types. PMID:20673826

  10. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Kourdougli, Nazim; Varpula, Saara; Chazal, Genevieve; Rivera, Claudio

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20–30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine-treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down-regulation and pathological distribution of the K+-Cl− cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE. PMID:26557054

  11. Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus

    PubMed Central

    Deshpande, Laxmikant S.; Blair, Robert E.; Nagarkatti, Nisha; Sombati, Sompong; Martin, Billy R.; DeLorenzo, Robert J.

    2007-01-01

    Status epilepticus (SE) is a life-threatening neurological disorder associated with a significant morbidity and mortality. Benzodiazepines are the initial drugs of choice for the treatment of SE. Despite aggressive treatment, over 40% of SE cases are refractory to the initial treatment with two or more medications. It would be a major advance in the clinical management of SE to identify novel anticonvulsant agents that do not lose their ability to treat SE with increasing seizure duration. Cannabinoids have recently been demonstrated to regulate seizure activity in brain. However, it remains to be seen whether they develop pharmacoresistance upon prolonged SE. In this study we used low-Mg2+ to induce SE in hippocampal neuronal cultures and in agreement with animal models and human SE confirm the development of resistance to benzodiazepine with increasing durations of SE. Thus, lorazepam (1 μM) was effective in blocking low-Mg2+ induced high frequency spiking for up to 30-mins into SE. However, by 1-hr and 2-hr of SE onset it was only 10–15% effective in suppressing SE. In contrast, the cannabinoid type-1 (CB1) receptor agonist, WIN 55,212-2 (1 μM) in a CB1 receptor dependent manner completely abolished SE at all the time points tested even out to 2 hr after SE onset, a condition where resistance developed to lorazepam. Thus, the use of cannabinoids in the treatment of SE may offer a unique approach to controlling SE without the development of pharmacoresistance observed with conventional treatments. PMID:17289026

  12. Detrimental effect of post Status Epilepticus treatment with ROCK inhibitor Y-27632 in a pilocarpine model of temporal lobe epilepsy.

    PubMed

    Kourdougli, Nazim; Varpula, Saara; Chazal, Genevieve; Rivera, Claudio

    2015-01-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults where 20-30% of the patients are refractory to currently available anti-epileptic drugs. The RhoA/Rho-kinase signaling pathway activation has been involved in inflammatory responses, neurite outgrowth and neuronal death under pathological conditions such as epileptic insults. Acute preventive administration of ROCK inhibitor has been reported to have beneficial outcomes in Status Epilepticus (SE) epilepsy. In the present study, we evaluate the effect of chronic post SE treatment with the ROCK inhibitor Y-27632 in a rat pilocarpine model of TLE. We used chronic i.p. injections of Y-27632 for 5 days in 6 week old control rats or rats subjected to pilocarpine treatment as a model of TLE. Surprisingly, our findings demonstrate that a systemic administration of Y-27632 in pilocarpine-treated rats increases neuronal death in the CA3 region and ectopic recurrent mossy fiber sprouting (rMFS) in the dentate gyrus of the hippocampal formation. Interestingly, we found that chronic treatment with Y-27632 exacerbates the down-regulation and pathological distribution of the K(+)-Cl(-) cotransporter KCC2, thus providing a putative mechanism for post SE induced neuronal death. The involvement of astrogliosis in this mechanism appears to be intricate as ROCK inhibition reduces reactive astrogliosis in pilocarpine rats. Conversely, in control rats, chronic Y-27632 treatment increases astrogliosis. Together, our findings suggest that Y-27632 has a detrimental effect when chronically used post SE in a rat pilocarpine model of TLE. PMID:26557054

  13. Development of a Prolonged Calcium Plateau in Hippocampal Neurons in Rats Surviving Status Epilepticus Induced by the Organophosphate Diisopropylfluorophosphate

    PubMed Central

    Deshpande, Laxmikant S.; Carter, Dawn S.; Blair, Robert E.; DeLorenzo, Robert J.

    2010-01-01

    Organophosphate (OP) compounds are among the most lethal chemical weapons ever developed and are irreversible inhibitors of acetylcholinesterase. Exposure to majority of OP produces status epilepticus (SE) and severe cholinergic symptoms that if left untreated are fatal. Survivors of OP intoxication often suffer from irreversible brain damage and chronic neurological disorders. Although pilocarpine has been used to model SE following OP exposure, there is a need to establish a SE model that uses an OP compound in order to realistically mimic both acute and long-term effects of nerve agent intoxication. Here we describe the development of a rat model of OP-induced SE using diisopropylfluorophosphate (DFP). The mortality, behavioral manifestations, and electroencephalogram (EEG) profile for DFP-induced SE (4 mg/kg, sc) were identical to those reported for nerve agents. However, significantly higher survival rates were achieved with an improved dose regimen of DFP and treatment with pralidoxime chloride (25 mg/kg, im), atropine (2 mg/kg, ip), and diazepam (5 mg/kg, ip) making this model ideal to study chronic effects of OP exposure. Further, DFP treatment produced N-methyl-D-aspartate (NMDA) receptor–mediated significant elevation in hippocampal neuronal [Ca2+]i that lasted for weeks after the initial SE. These results provided direct evidence that DFP-induced SE altered Ca2+ dynamics that could underlie some of the long-term plasticity changes associated with OP toxicity. This model is ideally suited to test effective countermeasures for OP exposure and study molecular mechanisms underlying neurological disorders following OP intoxication. PMID:20498005

  14. Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.

    PubMed

    González-Reyes, Susana; Santillán-Cigales, Juan Jair; Jiménez-Osorio, Angélica Saraí; Pedraza-Chaverri, José; Guevara-Guzmán, Rosalinda

    2016-10-01

    Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and neuroprotective effects. Recently, it was demonstrated that GL produced neuroprotective effects on the postischemic brain as well as on the kainic acid injury model in rats. In addition to this, GL also prevented excitotoxic effects on primary cultures. The aims of the present study were to evaluate GL scavenging properties and to investigate GL's effect on oxidative stress and inflammation in the lithium/pilocarpine-induced seizure model in two cerebral regions, hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before pilocarpine administration significantly suppressed oxidative stress. Moreover, malondialdehyde levels were diminished and glutathione levels were maintained at control values in both cerebral regions at 3 and 24 after SE. At 24h after SE, glutathione S-transferase and superoxide dismutase activity increased in the hippocampus, while both glutathione reductase and glutathione peroxidase activity were unchanged in the olfactory bulb at that time. In addition, GL suppressed the induction of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in both cerebral regions evaluated. These results suggest that GL confers protection against pilocarpine damage via antioxidant and anti-inflammatory effects. PMID:27490898

  15. Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.

    PubMed

    Laurén, Hanna B; Lopez-Picon, Francisco R; Brandt, Annika M; Rios-Rojas, Clarissa J; Holopainen, Irma E

    2010-01-01

    Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA)-induced status epilepticus (SE) in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed), and long-term potentiation (LTP; 18 genes changed). Also genes involved in Ca(2+) homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP), apolipoprotein E (apo E), cannabinoid type 1 receptor (CB1), Purkinje cell protein 4 (PEP-19), and interleukin 8 receptor (CXCR1), with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE). However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the juvenile age

  16. Development of status epilepticus, sustained calcium elevations and neuronal injury in a rat survival model of lethal paraoxon intoxication.

    PubMed

    Deshpande, Laxmikant S; Carter, Dawn S; Phillips, Kristin F; Blair, Robert E; DeLorenzo, Robert J

    2014-09-01

    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 (4mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6-8min. The EEG profile for POX induced SE was characterized and showed clinical and electrographic seizures with 7-10Hz spike activity. Treatment of 100% lethal POX intoxication with an optimized three drug regimen (atropine, 2mg/kg, i.p., 2-PAM, 25mg/kg, i.m. and diazepam, 5mg/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 [Ca(2+)]i (Ca(2+) plateau) and significant multifocal neuronal injury. POX SE induced Ca(2+) plateau had its origin in Ca(2+) release from intracellular Ca(2+) stores since inhibition of ryanodine/IP3 receptor lowered elevated Ca(2+) levels post SE. POX SE induced neuronal injury and alterations in Ca(2+) dynamics may underlie some of the long term morbidity associated with OP toxicity. PMID:24785379

  17. Cocaine-induced status epilepticus and death generate oxidative stress in prefrontal cortex and striatum of mice.

    PubMed

    Macêdo, Danielle Silveira; Vasconcelos, Silvânia Maria Mendes; Andrade-Neto, Manoel; Belchior, Luciana Dias; Honório Júnior, José Eduardo Ribeiro; Gonçalves, Danilo Oliveira; Fonteles, Marta Maria França; Silva, Maria Izabel Gomes; Aguiar, Lissiana Magna Vasconcelos; Viana, Glauce Socorro Barros; de Sousa, Francisca Cléa Florenço

    2010-01-01

    Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) with cocaine 90 mg/kg and observed during 1h. After this cocaine overdose some animals presented status epilepticus (SE) while some died after seizures. These animals were divided in two groups, SE and death. A group with an association of the antioxidant Vitamin E (Vit E, 400mg/kg, i.p.) plus Coc 90 (Vit E plus Coc 90) was undertaken to assess the neuroprotective effect of Vit E. Neurochemical analyses were carried out in prefrontal cortex (PFC) and striatum (ST). GSH levels increased only after cocaine-induced death in both areas studied. Cocaine-induced SE has increased nitrite/nitrate content in PFC and ST, while after death the increase was only in PFC. MDA (the lipid peroxidation marker) was elevated after SE and death in ST and only after death in PFC. Antioxidant treatment significantly reduced the GSH, nitrite/nitrate in ST and MDA levels. Only nitrite/nitrate content in PFC has not been decreased by Vit E pretreatment. The results relate that oxidative stress occurs after cocaine-induced toxicity mainly after death indicating that probably the increase of OS in the animal's brain leads to seizures and death, also showing a protective effect of Vit E in this process. Together with previous results this study contributes to the knowledge of cocaine-induced toxicity and possible in the near future to the use of antioxidants in the prevention of cocaine-induced CNS toxicity. PMID:19822180

  18. Sequential prefrontal lobe volume changes and cognitive dysfunctions in children with Panayiotopoulos syndrome presenting with status epilepticus.

    PubMed

    Kanemura, Hideaki; Sano, Fumikazu; Ohyama, Tetsuo; Aoyagi, Kakuro; Sugita, Kanji; Aihara, Masao

    2015-05-01

    Panayiotopoulos syndrome (PS) is usually not associated with neurodevelopmental problems. However, neuropsychological impairments may also be present in at least some of the patients with PS. On the other hand, several degrees of neuronal damage due to status epilepticus (SE) may occur in the cortex. We prospectively measured frontal and prefrontal lobe volumes using three-dimensional magnetic resonance imaging (3D-MRI)-based volumetry in patients with PS with and without SE. Moreover, the neuropsychological outcome in relation to the presence of SE in children with PS is also discussed. We studied six patients with a final diagnosis of PS, including three cases with SE and cognitive impairments/behavioral problems (SE group) and three cases without SE (non-SE group). Serial 3D-MRI studies were performed five times (at onset of clinical symptoms and 1-4 years after onset) in both the SE and non-SE patients. All patients were studied with a set of Wechsler Intelligence Scale for Children, version III (WISC-III) or Wechsler Preschool and Primary Scale of Intelligence tests and the Kaufman Assessment Battery for Children (K-ABC). Growth of the frontal and prefrontal lobes was slightly decreased for some time after SE episodes in the SE patients. Moreover, the prefrontal-to-frontal lobe volume ratio was stagnant for some time after SE in the SE patients. The scores on the neuropsychological tests were decreased in the SE patients. Moreover, the average WISC and K-ABC scores in the SE group remained low and did not reach the levels of the initial examinations. Occurrence of SE in patients with PS at least in some patients may be associated with retarded prefrontal lobe growth, which was related to neuropsychological problems and ultimately, neuropsychological outcomes. Treatment management may be required to prevent SE as much as possible to achieve optimal prognosis in PS at least in some patients. PMID:25847347

  19. Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus.

    PubMed

    Lee, Chun-Yao; Jaw, Thomas; Tseng, Huan-Chin; Chen, I-Chun; Liou, Horng-Huei

    2012-01-01

    This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis. PMID:22761705

  20. The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.

    PubMed

    Grabenstatter, H L; Del Angel, Y Cruz; Carlsen, J; Wempe, M F; White, A M; Cogswell, M; Russek, S J; Brooks-Kayal, A R

    2014-02-01

    Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE affects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EEG monitored during SE and for one month to assess seizure frequency over time. Protein and/or mRNA levels for pSTAT3, and STAT3-regulated genes including: ICER, Gabra1, c-myc, mcl-1, cyclin D1, and bcl-xl were evaluated in WP1066 and vehicle-treated rats during stages of epileptogenesis to determine the acute effects of WP1066 administration on SE and chronic epilepsy. WP1066 (two 50mg/kg doses) administered within the first hour after onset of SE results in transient inhibition of pSTAT3 and long-term reduction in spontaneous seizure frequency. WP1066 alters the severity of chronic epilepsy without affecting SE or cell death. Early WP1066 administration reduces known downstream targets of STAT3 transcription 24h after SE including cyclin D1 and mcl-1 levels, known for their roles in cell-cycle progression and cell survival, respectively. These findings uncover a potential effect of the JAK/STAT pathway after brain injury that is physiologically important and may provide a new therapeutic target that can be harnessed for the prevention of epilepsy development and/or progression. PMID:24051278

  1. Dendritic morphology, synaptic transmission, and activity of mature granule cells born following pilocarpine-induced status epilepticus in the rat

    PubMed Central

    Gao, Fei; Song, Xueying; Zhu, Dexiao; Wang, Xiaochen; Hao, Aijun; Nadler, J. Victor; Zhan, Ren-Zhi

    2015-01-01

    To understand the potential role of enhanced hippocampal neurogenesis after pilocarpine-induced status epilepticus (SE) in the development of epilepsy, we quantitatively analyzed the geometry of apical dendrites, synaptic transmission, and activation levels of normotopically distributed mature newborn granule cells in the rat. SE in male Sprague-Dawley rats (between 6 and 7 weeks old) lasting for more than 2 h was induced by an intraperitoneal injection of pilocarpine. The complexity, spine density, miniature post-synaptic currents, and activity-regulated cytoskeleton-associated protein (Arc) expression of granule cells born 5 days after SE were studied between 10 and 17 weeks after CAG-GFP retroviral vector-mediated labeling. Mature granule cells born after SE had dendritic complexity similar to that of granule cells born naturally, but with denser mushroom-like spines in dendritic segments located in the outer molecular layer. Miniature inhibitory post-synaptic currents (mIPSCs) were similar between the controls and rats subjected to SE; however, smaller miniature excitatory post-synaptic current (mEPSC) amplitude with a trend toward less frequent was found in mature granule cells born after SE. After maturation, granule cells born after SE did not show denser Arc expression in the resting condition or 2 h after being activated by pentylenetetrazol-induced transient seizure activity than vicinal GFP-unlabeled granule cells. Thus our results suggest that normotopic granule cells born after pilocarpine-induced SE are no more active when mature than age-matched, naturally born granule cells. PMID:26500490

  2. Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus.

    PubMed

    Vinet, Jonathan; Vainchtein, Ilia D; Spano, Carlotta; Giordano, Carmela; Bordini, Domenico; Curia, Giulia; Dominici, Massimo; Boddeke, Hendrikus W G M; Eggen, Bart J L; Biagini, Giuseppe

    2016-08-01

    Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS-based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine-treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen-presenting cell phenotype correlated with the presence of CD4(pos) T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL-1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL-1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)-9 and 12 while microglia only expressed MMP-12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350-1362. PMID:27246930

  3. Squamous Cell Lung Carcinoma Presenting With Refractory Status Epilepticus: A Case Report of Paraneoplastic Limbic Encephalitis.

    PubMed

    Hurley, Killian; Herron, Malcolm; McDermott, Sean; Farrell, Terence; O'Riordan, Deirdre

    2015-08-01

    Lung cancer-associated paraneoplastic syndromes affecting the central nervous system present significant diagnostic and treatment challenges. In this case, the patient presented with personality change, cognitive impairment, complex partial seizures, ataxia, dyspraxia, and dysphasia. Shortly after admission, the patient suffered refractory generalized tonic-clonic seizures and a decreased level of consciousness and required intubation, ventilation, and admission to the ICU. He was subsequently diagnosed with paraneoplastic limbic encephalitis based on recognized criteria, including a compatible clinical picture, elevated protein content in his cerebrospinal fluid with negative cytology, a positive positron emission tomography-computed tomography scan showing a right upper lobe tumor, and the exclusion of other neuro-oncological complications. Histopathology confirmed the tissue diagnosis as squamous cell cancer. Initial immunotherapy with steroids and intravenous immunoglobulin and subsequent lobectomy and adjuvant chemotherapy were partially successful, leading to partial resolution of his cognitive impairment. This report highlights the diagnostic and therapeutic challenges of lung-related paraneoplastic syndromes. In addition, it illustrates the poor outcomes for patients and identifies squamous cell cancer as an extremely rare cause of paraneoplastic limbic encephalitis. PMID:25784771

  4. Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus.

    PubMed

    Betti, Michele; Minelli, Andrea; Ambrogini, Patrizia; Ciuffoli, Stefano; Viola, Valentina; Galli, Francesco; Canonico, Barbara; Lattanzi, Davide; Colombo, Evelin; Sestili, Piero; Cuppini, Riccardo

    2011-10-01

    Vitamin E (as α-tocopherol, α-T) is proposed to alleviate glia-mediated inflammation in neurological diseases, but such a role in epilepsy is still elusive. This study investigated the effect of α-T supplementation on glial activation, neuronal cell death and oxidative stress of rat brain exposed to kainate-induced seizures. Animals were fed for 2 weeks with a α-T-enriched diet (estimated intake of 750 mg/kg/day) before undergoing status epilepticus. Compliance to supplementation was demonstrated by the remarkable increase in brain α-T. Four days after seizure, brain α-T returned to baseline and lipid peroxidation markers decreased as compared to non-supplemented rats. Status epilepticus induced a lower up-regulation of astrocytic and microglial antigens (GFAP and MHC II, respectively) and production of pro-inflammatory cytokines (IL-1β and TNF-α) in supplemented than in non-supplemented animals. This anti-inflammatory effect was associated with a lower neuronal cell death. In conclusion, α-T dietary supplementation prevents oxidative stress, neuroglial over-activation and cell death occurring after kainate-induced seizures. This evidence paves the way to an anti-inflammatory and neuroprotective role of α-T interventions in epilepsy. PMID:21749318

  5. 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. PMID:24968009

  6. Pilocarpine-induced status epilepticus in mice: A comparison of spectral analysis of electroencephalogram and behavioral grading using the Racine scale.

    PubMed

    Phelan, Kevin D; Shwe, U T; Williams, David K; Greenfield, L John; Zheng, Fang

    2015-11-01

    Pilocarpine-induced status epilepticus (SE) is a widely used seizure model in mice, and the Racine scale has been used to index seizure intensity. The goal of this study was to analyze electroencephalogram (EEG) quantitatively using fast Fourier transformation (FFT) and statistically evaluate the correlation of electrographic seizures with convulsive behaviors. Simultaneous EEG and video recordings in male mice in a mixed genetic background were conducted and pilocarpine was administered intraperitoneally to induce seizures. The videos were graded using the Racine scale and the root-mean-square (RMS) power analysis of EEG was performed with Sirenia Seizure Pro software. We found that the RMS power was very weakly correlated with convulsive behavior induced by pilocarpine. Convulsive behaviors appeared long before electrographic seizures and showed a strong negative correlation with theta frequency activity and a moderate positive correlation with gamma frequency activity. Racine scores showed moderate correlations with RMS power across multiple frequency bands during the transition from first electrographic seizure to SE. However, there was no correlation between Racine scores and RMS power during the SE phase except a weak correlation with RMS power in the theta frequency. Our analysis reveals limitations of the Racine scale as a primary index of seizure intensity in status epilepticus, and demonstrates a need for quantitative analysis of EEG for an accurate assessment of seizure onset and severity. PMID:26432759

  7. Behavioral and Movement Disorders due to Long-Lasting Myoclonic Status Epilepticus Misdiagnosed as ADHD in a Patient With Juvenile Myoclonic Epilepsy: Electroclinical Findings and Related Hemodynamic Changes.

    PubMed

    Fanella, Martina; Carnì, Marco; Morano, Alessandra; Albini, Mariarita; Lapenta, Leonardo; Casciato, Sara; Fattouch, Jinane; Di Castro, Elisabetta; Colonnese, Claudio; Vaudano, Anna Elisabetta; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2016-01-01

    Epilepsy and attention-deficit/hyperactivity disorder (ADHD) likely share common underlying neural mechanisms, as often suggested by both the evidence of electroencephalography (EEG) abnormalities in ADHD patients without epilepsy and the coexistence of these 2 conditions. The differential diagnosis between epilepsy and ADHD may consequently be challenging. In this report, we describe a patient presenting with a clinical association of "tics" and behavioral disorders that appeared 6 months before our first observation and had previously been interpreted as ADHD. A video-EEG evaluation documented an electroclinical pattern of myoclonic status epilepticus. On the basis of the revised clinical data, the EEG findings, the good response to valproate, the long-lasting myoclonic status epilepticus, and the enduring epileptic abnormalities likely causing behavioral disturbances, the patient's symptoms were interpreted as being the expression of untreated juvenile myoclonic epilepsy. The EEG-functional magnetic resonance imaging study revealed, during clinical generalized spike-and-wave and polyspike-and-wave discharges, positive blood oxygen level-dependent (BOLD) signal changes bilaterally in the thalamus, the prefrontal cortex (Brodmann area 6, supplementary motor area) and the cerebellum, and negative BOLD signal changes in the regions of the default mode network. Such findings, which are typical of BOLD changes observed in idiopathic generalized epilepsy, may also shed light on the anatomofunctional network underlying ADHD. PMID:25733678

  8. Comparison of status epilepticus models induced by pilocarpine and nerve agents - a systematic review of the underlying aetiology and adopted therapeutic approaches.

    PubMed

    Tang, F R; Loke, W K; Ling, E A

    2011-01-01

    Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its combination of high lethality, demonstrated use and relative abundance of un-destroyed stockpiles in various militaries around the world. While current fielded antidotes are able to mitigate acute poisoning, effective neuroprotection in the field remains a challenge amongst subjects with established status epilepticus following nerve agent intoxication. Due to ethical, safety and surety issues, extensive preclinical and clinical research on cholinergic nerve agents is not possible. This may have been a contributory factor for the slow progress in uncovering new neuroprotectants for nerve agent casualties with established status epilepticus. To overcome this challenge, comparative research with surrogate chemicals that produce similar hypercholinergic toxicity but with less security concerns would be a useful approach forward. In this paper, we will systemically compare the mechanism of seizure generation, propagation and the subsequent clinical, hematologic, and metabolic, biochemical, neuroinflammatory changes and current therapeutic approaches reported in pilocarpine, soman, and sarin models of seizures. This review will be an important first step in closing this knowledge gap among different closely related models of seizures and neurotoxicity. Hopefully, it will spur further efforts in using surrogate cholinergic models by the wider scientific community to expedite the development of a new generation of antidotes that are better able to protect against delayed neurological effects inflicted by nerve agents. PMID:21182477

  9. Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.

    PubMed

    Malkin, Sergey L; Amakhin, Dmitry V; Veniaminova, Ekaterina A; Kim, Kira Kh; Zubareva, Olga E; Magazanik, Lev G; Zaitsev, Aleksey V

    2016-07-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions. PMID:27109923

  10. Independent impact of infections on the course and outcome of status epilepticus: a 10-year cohort study.

    PubMed

    Semmlack, Saskia; Tschudin-Sutter, Sarah; Widmer, Andreas F; Valença, Martina; Rüegg, Stephan; Marsch, Stephan; Sutter, Raoul

    2016-07-01

    Infections are frequent in patients with status epilepticus (SE). It remains unclear if infections merely reflect severity of the underlying illness or if they independently predict unfavourable course and outcome. We sought to determine if infections diagnosed within 48 h from SE onset are independent predictors of poor course and outcome and if their effect is modified by clinical characteristics. From 2005 to 2014, pertinent clinical data, microbiology, death, return to functional baseline, and unfavourable outcome in survivors were assessed in SE patients treated in the intensive care units (ICU) of an academic medical care center. Among 352 consecutive patients, 81 (23 %) were diagnosed with infections at SE onset. In-hospital mortality was higher in patients with infections (26 %) compared to 10 % in patients without infections (p < 0.001). Infections at SE onset increased the odds ratios (OR) for prolonged ICU (OR = 4.1, 95 %CI 1.87-6.74) and hospital stay (OR = 5.4, 95 %CI 1.24-9.63), refractory SE (OR = 3.1, 95 %CI 1.79-5.34), prolonged mechanical ventilation (OR = 3.8, 95 %CI 2.15-6.79), no return to functional baseline (OR = 2.1, 95 %CI 1.10-4.02), unfavourable outcome in survivors (OR = 2.0, 95 %CI 1.02-3.81), and death (OR = 2.5, 95 %CI 1.28-4.99). All associations were independent of confounders and without significant effect modification by age, level of consciousness, types and severity of SE, and etiologies. In addition, the number of infections increased the probability of unfavourable course and outcome. Infections at SE onset are frequent and associated with prolonged medical care, treatment refractory SE, higher morbidity and mortality independently of potential confounders calling for the evaluation of treatment strategies. PMID:27142712

  11. Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampus.

    PubMed

    Melo, Igor S; Santos, Yngrid M O; Costa, Maísa A; Pacheco, Amanda L D; Silva, Nívea K G T; Cardoso-Sousa, L; Pereira, U P; Goulart, L R; Garcia-Cairasco, Norberto; Duzzioni, Marcelo; Gitaí, Daniel L G; Tilelli, Cristiane Q; Sabino-Silva, Robinson; Castro, Olagide W

    2016-08-01

    Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as status epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na(+)/glucose cotransporters (SGLTs) on hippocampus during SE is still unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after pilocarpine (PILO)-induced SE. Vehicle (VEH, 1μL) or phlorizin, a specific SGLT inhibitor (PZN, 1μL, 50μg/μL), was administered in the hippocampus of rats 30min before PILO (VEH+PILO or PZN+PILO, respectively). The limbic seizures were classified using the Racine's scale, and the amount of wet dog shakes (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade C (FJ-C), and FJ-C-positive neurons (FJ-C+) were counted 24h and 15days after SE. The PZN-treated rats showed higher (p<0.05) number of WDS when compared with VEH+PILO. There was no difference in seizure severity between PZN+PILO and VEH+PILO groups. However, the pattern of limbic seizures significantly changed in PZN+PILO. Indeed, the class 5 seizures repeated themselves more times (p<0.05) than the other classes in the PZN group at 50min after SE induction. The PZN+PILO animals had a higher (p<0.05) number of FJ-C+ cells in the dentate gyrus (DG), hilus, and CA3 and CA1 of hippocampus, when compared with VEH+PILO. The PZN+PILO animals had a decreased number (p<0.05) of FJ-C+ cells in CA1 compared with VEH+PILO 15days after SE induction. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures during SE and increased neurodegeneration in hippocampus 24h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stages of epileptogenic processes. PMID:27429292

  12. Epileptogenesis following Kainic Acid-Induced Status Epilepticus in Cyclin D2 Knock-Out Mice with Diminished Adult Neurogenesis.

    PubMed

    Kondratiuk, Ilona; Plucinska, Gabriela; Miszczuk, Diana; Wozniak, Grazyna; Szydlowska, Kinga; Kaczmarek, Leszek; Filipkowski, Robert K; Lukasiuk, Katarzyna

    2015-01-01

    The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). Cyclin D2 knockout (cD2 KO) mice, which lack adult neurogenesis almost entirely, were used as a model. First, we examined whether status epilepticus (SE) evoked by an intra-amygdala injection of KA induces cell proliferation in cD2 KO mice. On the day after SE, we injected BrdU into mice for 5 days and evaluated the number of DCX- and DCX/BrdU-immunopositive cells 3 days later. In cD2 KO control animals, only a small number of DCX+ cells was observed. The number of DCX+ and DCX/BrdU+ cells/mm of subgranular layer in cD2 KO mice increased significantly following SE (p<0.05). However, the number of newly born cells was very low and was significantly lower than in KA-treated wild type (wt) mice. To evaluate the impact of diminished neurogenesis on epileptogenesis and early epilepsy, we performed video-EEG monitoring of wt and cD2 KO mice for 16 days following SE. The number of animals with seizures did not differ between wt (11 out of 15) and cD2 KO (9 out of 12) mice. The median latency to the first spontaneous seizure was 4 days (range 2-10 days) in wt mice and 8 days (range 2-16 days) in cD2 KO mice and did not differ significantly between groups. Similarly, no differences were observed in median seizure frequency (wt: 1.23, range 0.1-3.4; cD2 KO: 0.57, range 0.1-2.0 seizures/day) or median seizure duration (wt: 51 s, range 23-103; cD2 KO: 51 s, range 23-103). Our results indicate that SE-induced epileptogenesis is not disrupted in mice with markedly reduced adult neurogenesis. However, we cannot exclude the contribution of reduced neurogenesis to the chronic epileptic state. PMID:26020770

  13. Antagonist Targeting microRNA-155 Protects against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor

    PubMed Central

    Cai, Zhengxu; Li, Song; Li, Sheng; Song, Fan; Zhang, Zhen; Qi, Guanhua; Li, Tianbai; Qiu, Juanjuan; Wan, Jiajia; Sui, Hua; Guo, Huishu

    2016-01-01

    Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings. The expression of brain-derived neurotrophic factor (BDNF) and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and Western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study. PMID:27303295

  14. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

    PubMed Central

    2014-01-01

    Introduction Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. Methods We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. Results Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5

  15. Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium-Pilocarpine Model of Status Epilepticus in Rats.

    PubMed

    García-García, Luis; Shiha, Ahmed Anis; Bascuñana, Pablo; de Cristóbal, Javier; Fernández de la Rosa, Rubén; Delgado, Mercedes; Pozo, Miguel A

    2016-05-01

    It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, has neuroprotective properties in the lithium-pilocarpine model of status epilepticus (SE) in rats. The aim of the present study was to investigate the effect of 5-HT depletion by short-term administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute phase of this SE model. Our results show that 5-HT depletion did modify neither the brain basal metabolic activity nor the lithium-pilocarpine-induced hypometabolism when evaluated 3 days after the insult. In addition, hippocampal neurodegeneration and astrogliosis triggered by lithium-pilocarpine were not exacerbated by PCPA treatment. These findings point out that in the early latent phase of epileptogenesis, non-5-HT-mediated actions may contribute, at least in some extent, to the neuroprotective effects of fluoxetine in this model of SE. PMID:26208805

  16. Status epilepticus and cardiopulmonary arrest in a patient with carbon monoxide poisoning with full recovery after using a neuroprotective strategy: a case report

    PubMed Central

    2012-01-01

    Introduction Carbon monoxide poisoning can be associated with life-threatening complications, including significant and disabling cardiovascular and neurological sequelae. Case presentation We report a case of carbon monoxide poisoning in a 25-year-old Saudi woman who presented to our facility with status epilepticus and cardiopulmonary arrest. Her carboxyhemoglobin level was 21.4 percent. She made a full recovery after we utilized a neuroprotective strategy and normobaric oxygen therapy, with no delayed neurological sequelae. Conclusions Brain protective modalities are very important for the treatment of complicated cases of carbon monoxide poisoning when they present with neurological toxicities or cardiac arrest. They can be adjunctive to normobaric oxygen therapy when the use of hyperbaric oxygen is not feasible. PMID:23241416

  17. Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala kainic acid model of status epilepticus in mice.

    PubMed

    Diviney, Mairead; Reynolds, James P; Henshall, David C

    2015-10-01

    Benzodiazepines remain as the first-line treatment for status epilepticus (SE), but debate continues as to the choice and delivery route of pharmacotherapy. Lorazepam is currently the preferred anticonvulsant for clinical use, but midazolam has become a popular alternative, particularly as it can be given by nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in animal models. Here, we aimed to compare the efficacy of midazolam with that of lorazepam in an experimental model of focal-onset SE. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6 mice. Forty minutes later, mice were treated with an intraperitoneal injection of either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity, histology, and behavioral tests assessing recovery of function were evaluated and compared between groups. Intraperitoneal injection of either lorazepam or midazolam resulted in similar patterns of reduced EEG epileptiform activity during 1-hour recordings. Damage to the hippocampus and presentation of postinsult anxiety-related behavior did not significantly differ between treatment groups at 72h. However, return of normal behaviors such as grooming, levels of activity, and the evaluation of overall recovery of SE mice were all superior at 24h in animals given midazolam compared with lorazepam. Our results indicate that midazolam is as effective as lorazepam as an anticonvulsant in this model while also providing improved animal recovery after SE. These data suggest that midazolam might be considered by researchers as an anticonvulsant in animal models of SE, particularly as it appears to satisfy the requirements of refining procedures involving experimental animals at early time-points after SE. PMID:26291773

  18. Transcranial focal electrical stimulation reduces the convulsive expression and amino acid release in the hippocampus during pilocarpine-induced status epilepticus in rats.

    PubMed

    Santana-Gómez, César E; Alcántara-González, David; Luna-Munguía, Hiram; Bañuelos-Cabrera, Ivette; Magdaleno-Madrigal, Víctor; Fernández-Mas, Rodrigo; Besio, Walter; Rocha, Luisa

    2015-08-01

    The aim of the present study was to evaluate the effects of transcranial focal electrical stimulation (TFS) on γ-aminobutyric acid (GABA) and glutamate release in the hippocampus under basal conditions and during pilocarpine-induced status epilepticus (SE). Animals were previously implanted with a guide cannula attached to a bipolar electrode into the right ventral hippocampus and a concentric ring electrode placed on the skull surface. The first microdialysis experiment was designed to determine, under basal conditions, the effects of TFS (300 Hz, 200 μs biphasic square pulses, for 30 min) on afterdischarge threshold (ADT) and the release of GABA and glutamate in the hippocampus. The results obtained indicate that at low current intensities (<2800 μA), TFS enhances and decreases the basal extracellular levels of GABA and glutamate, respectively. However, TFS did not modify the ADT. During the second microdialysis experiment, a group of animals was subjected to SE induced by pilocarpine administration (300 mg/kg, i.p.; SE group). The SE was associated with a significant rise of GABA and glutamate release (up to 120 and 182% respectively, 5h after pilocarpine injection) and the prevalence of high-voltage rhythmic spikes and increased spectral potency of delta, gamma, and theta bands. A group of animals (SE-TFS group) received TFS continuously during 2h at 100 μA, 5 min after the establishment of SE. This group showed a significant decrease in the expression of the convulsive activity and spectral potency in gamma and theta bands. The extracellular levels of GABA and glutamate in the hippocampus remained at basal conditions. These results suggest that TFS induces anticonvulsant effects when applied during the SE, an effect associated with lower amino acid release. This article is part of a Special Issue entitled "Status Epilepticus". PMID:26006058

  19. 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

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

    PubMed

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

    2015-06-01

    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

  1. New-onset refractory status epilepticus in an adult with an atypical presentation of cat-scratch disease: successful treatment with high-dose corticosteroids.

    PubMed

    Laswell, Emily M; Chambers, Kasandra D; Whitsel, Danielle R; Poudel, Kiran

    2015-06-01

    New-onset refractory status epilepticus (NORSE) is defined as a sudden onset of refractory status epilepticus in patients who do not have a history of epilepsy. It is a neurologic emergency, and determining the underlying etiology is an important factor for effectively managing and predicting the prognosis of NORSE. We describe the case of a 28-year-old woman who was hospitalized with NORSE secondary to an unknown etiology. She did not respond to traditional anticonvulsant therapy, including benzodiazepines, fosphenytoin, propofol, and levetiracetam. The patient was placed on continuous electroencephalography (EEG) monitoring and was treated further with multiple antiepileptics, which were titrated aggressively based on EEG readings and therapeutic drug levels; despite this treatment, EEG monitoring revealed continued seizures. Thus, high-dose corticosteroids were started for seizure control. Her workup included computed tomography and magnetic resonance imaging of the head, a lumbar puncture, toxicology screening, and extensive testing for multiple infectious and inflammatory etiologies. The patient's history revealed recent exposure to a new cat. Serologic results were positive for Bartonella henselae, and she was diagnosed with cat-scratch disease (CSD). She did not have the typical presentation of symptoms of lymphadenopathy, however, which is common in CSD. Doxycycline 100 mg and rifampin 300 mg twice daily were added to the patient's anticonvulsant and corticosteroid therapy. She was hospitalized for a total of 26 days and discharged with only minor neurologic impairment (short-term memory deficits and minor cognitive problems). The patient was discharged receiving antiepileptics, antibiotics, and a corticosteroid taper. To our knowledge, this is the first clinically known case of NORSE secondary to CSD without typical CSD symptoms in the adult population. The patient failed to respond to traditional anticonvulsant therapy alone. With the addition of high

  2. Prophylactic treatment with melatonin after status epilepticus: effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy.

    PubMed

    Tchekalarova, Jana; Petkova, Zlatina; Pechlivanova, Daniela; Moyanova, Slavianka; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Atanasova, Dimitrina; Lazarov, Nikolai; Stoynev, Alexander

    2013-04-01

    Melatonin is a potent antioxidant which showed anticonvulsant activities both in experimental and clinical studies. In the present study, we examined the effect of melatonin treatment (10mg/kg/day, diluted in drinking water, 8 weeks) during epileptogenesis on the consequences of a kainate (KA)-induced status epilepticus (SE) in rats. Melatonin increased the latency in the appearance of spontaneous recurrent seizures (SRSs) and decreased their frequency only during the treatment period. The behavioral alterations associated with hyperactivity, depression-like behavior during the light phase, and deficits in hippocampus-dependent working memory were positively affected by melatonin treatment in rats with epilepsy. Melatonin reduced the neuronal damage in the CA1 area of the hippocampus and piriform cortex and recovered the decrease of hippocampal serotonin (5-HT) level in rats with epilepsy. Taken together, long-term melatonin treatment after SE was unable to suppress the development of epileptogenesis. However, it showed a potential in reducing some of the deleterious alterations that develop during the chronic epileptic state in a diurnal phase-dependent mode. PMID:23435277

  3. Hippocampal distribution of IL-1β and IL-1RI following lithium-pilocarpine-induced status epilepticus in the developing rat.

    PubMed

    Álvarez-Croda, Dulce-Mariely; Santiago-García, Juan; Medel-Matus, Jesús S; Martínez-Quiroz, Joel; Puig-Lagunes, Angel A; Beltrán-Parrazal, Luis; López-Meraz, María-Leonor

    2016-01-01

    The contribution of Interleukin-1β (IL-1β) to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1β and its type 1 receptor (IL-1RI) following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1β and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1β and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1β mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1β and IL-1RI immunoreactivity was not detected in control animals. IL-1β and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1β and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat. PMID:27168372

  4. Lovastatin decreases the synthesis of inflammatory mediators in the hippocampus and blocks the hyperthermia of rats submitted to long-lasting status epilepticus.

    PubMed

    Gouveia, Telma Luciana Furtado; Scorza, Fulvio Alexandre; Silva, Michele Juliana Vieira; Bandeira, Tatiane de Aquino; Perosa, Sandra Regina; Argañaraz, Gustavo Adolfo; Silva, Marcelo de Paula; Araujo, Thiago Rodrigues; Frangiotti, Maria Isabel Berzaghi; Amado, Débora; Cavalheiro, Esper Abrão; Silva, José Antonio; Naffah-Mazzacoratti, Maria da Graça

    2011-01-01

    Statins may act on inflammatory responses, decreasing oxidative stress and also reducing temperature after a brain ischemic insult. Previous data have indicated that statins protect neurons from death during long-lasting status epilepticus (SE) and attenuate seizure behaviors in animals treated with kainic acid. In this context, the study described here aimed to investigate the effect of lovastatin on body temperature and on mRNA expression levels of hippocampal cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 and B2 receptors of rats submitted to pilocarpine-induced SE. Quantitative real-time polymerase chain reaction showed a significant decrease in mRNA expression of interleukin-1β, interleukin-6, tumor necrosis factor α, and kinin B1 receptor in animals with SE treated with lovastatin, compared with untreated animals with SE (P<0.001). Lovastatin also reduced SE-induced hyperthermia, indicating that mechanisms related to brain protection are triggered by this drug under conditions associated with acute excitotoxicity or long-lasting SE. PMID:21130693

  5. The Effects of Quinacrine, Proglumide, and Pentoxifylline on Seizure Activity, Cognitive Deficit, and Oxidative Stress in Rat Lithium-Pilocarpine Model of Status Epilepticus

    PubMed Central

    Abu-Taweel, Gasem M.; Aboshaiqah, Ahmad E.; Ajarem, Jamaan S.

    2014-01-01

    The present data indicate that status epilepticus (SE) induced in adult rats is associated with cognitive dysfunctions and cerebral oxidative stress (OS). This has been demonstrated using lithium-pilocarpine (Li-Pc) model of SE. OS occurring in hippocampus and striatum of mature brain following SE is apparently due to both the increased free radicals production and the limited antioxidant defense. Pronounced alterations were noticed in the enzymatic, glutathione-S transferase (GST), catalase (CAT), and superoxide dismutase (SOD), as well as in the nonenzymatic; thiobarbituric acid (TBARS) and reduced glutathione (GST), indices of OS in the hippocampus and striatum of SE induced animals. Quinacrine (Qcn), proglumide (Pgm), and pentoxifylline (Ptx) administered to animals before inducing SE, were significantly effective in ameliorating the seizure activities, cognitive dysfunctions, and cerebral OS. The findings suggest that all the drugs were effective in the order of Ptx < Pgm < Qcn indicating that these drugs are potentially antiepileptic as well as antioxidant; however, further studies are needed to establish this fact. It can be assumed that these antiepileptic substances with antioxidant properties combined with conventional therapies might provide a beneficial effect in treatment of epilepsy through ameliorating the cerebral OS. PMID:25478062

  6. Expressions of tumor necrosis factor alpha and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy.

    PubMed

    Ashhab, Muhammad Usman; Omran, Ahmed; Kong, Huimin; Gan, Na; He, Fang; Peng, Jing; Yin, Fei

    2013-11-01

    Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE. PMID:23636891

  7. Efficacy of ketamine in refractory convulsive status epilepticus in children: a protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

    PubMed Central

    Rosati, Anna; Ilvento, Lucrezia; L'Erario, Manuela; De Masi, Salvatore; Biggeri, Annibale; Fabbro, Giancarlo; Bianchi, Roberto; Stoppa, Francesca; Fusco, Lucia; Pulitanò, Silvia; Battaglia, Domenica; Pettenazzo, Andrea; Sartori, Stefano; Biban, Paolo; Fontana, Elena; Cesaroni, Elisabetta; Mora, Donatella; Costa, Paola; Meleleo, Rosanna; Vittorini, Roberta; Conio, Alessandra; Wolfler, Andrea; Mastrangelo, Massimo; Mondardini, Maria Cristina; Franzoni, Emilio; McGreevy, Kathleen S; Di Simone, Lorena; Pugi, Alessandra; Mirabile, Lorenzo; Vigevano, Federico; Guerrini, Renzo

    2016-01-01

    Introduction Status epilepticus (SE) is a life-threatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as ‘refractory’ (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-d-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences. Trial registration number NCT02431663; Pre-results. PMID:27311915

  8. Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.

    PubMed

    Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Pereira, Letícia Meier; de Oliveira, Clarissa Vasconcelos; Grigoletto, Jéssica; Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2014-12-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na(+),K(+)-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na(+),K(+)-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis-Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na(+),K(+)-ATPase activity, however no changes in expression or phosphorylation state at Ser(943) were found. Further studies are necessary define the potential of nitrated Na(+),K(+)-ATPase as a new therapeutic target for seizure disorders. PMID:25311690

  9. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    PubMed

    Minge, Daniel; Bähring, Robert

    2011-01-01

    Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP) dynamics immediately following status epilepticus (SE) in mice. SE was induced by intraperitoneal (i.p.) injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+) imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV). No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst) firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP), was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP)-induced Ca(2+) signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+) and K(+) current components. PMID:22039527

  10. Acute Alterations of Somatodendritic Action Potential Dynamics in Hippocampal CA1 Pyramidal Cells after Kainate-Induced Status Epilepticus in Mice

    PubMed Central

    Minge, Daniel; Bähring, Robert

    2011-01-01

    Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP) dynamics immediately following status epilepticus (SE) in mice. SE was induced by intraperitoneal (i.p.) injection of kainate, and behavioral manifestation of SE was monitored for 3–4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2–5 mV). No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst) firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP), was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP)-induced Ca2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na+ and K+ current components. PMID:22039527